Divergent amplifications of CYP9A cytochrome P450 genes provide two noctuid pests with differential protection against xenobiotics.
Here, we provide mechanistic support for the involvement of the CYP9A subfamily of cytochrome P450 monooxygenases in the detoxification of host plant defense compounds and chemical insecticides in Spodoptera exigua and Spodoptera frugiperda. Our comparative genomics shows that a large cluster of CYP9A genes occurs in the two species but with significant differences in its contents, including several species-specific duplicates and substantial sequence divergence, both between orthologs and between duplicates. Bioassays of CRISPR-Cas9 knockouts of the clusters show that, collectively, the CYP9As can detoxify two furanocoumarin plant defense compounds (imperatorin and xanthotoxin) and insecticides representing three different chemotypes (pyrethroids, avermectins, and oxadiazines). However, in vitro metabolic assays of heterologously expressed products of individual genes show several differences between the species in the particular CYP9As with activities against these compounds. We also find that the clusters show tight genetic linkage with high levels of pyrethroid resistance in field strains of the two species. We propose that their divergent amplifications of the CYP9A subfamily have not only contributed to the development of the broad host ranges of these species over long evolutionary timeframes but also supplied them with diverse genetic options for evolving resistance to chemical insecticides in the very recent past.


Cortical Sensitivity to Guitar Note Patterns: EEG Entrainment to Repetition and Key.
Music is ubiquitous throughout recent human culture, and many individual's have an innate ability to appreciate and understand music. Our appreciation of music likely emerges from the brain's ability to process a series of repeated complex acoustic patterns. In order to understand these processes further, cortical responses were measured to a series of guitar notes presented with a musical pattern or without a pattern. ERP responses to individual notes were measured using a 24 electrode Bluetooth mobile EEG system (Smarting mBrainTrain) while 13 healthy non-musicians listened to structured (i.e., within musical keys and with repetition) or random sequences of guitar notes for 10 min each. We demonstrate an increased amplitude to the ERP that appears ~200 ms to notes presented within the musical sequence. This amplitude difference between random notes and patterned notes likely reflects individual's cortical sensitivity to guitar note patterns. These amplitudes were compared to ERP responses to a rare note embedded within a stream of frequent notes to determine whether the sensitivity to complex musical structure overlaps with the sensitivity to simple irregularities reflected in traditional auditory oddball experiments. Response amplitudes to the negative peak at ~175 ms are statistically correlated with the mismatch negativity (MMN) response measured to a rare note presented among a series of frequent notes (i.e., in a traditional oddball sequence), but responses to the subsequent positive peak at ~200 do not show a statistical relationship with the P300 response. Thus, the sensitivity to musical structure identified to 4 Hz note patterns appears somewhat distinct from the sensitivity to statistical regularities reflected in the traditional "auditory oddball" sequence. Overall, we suggest that this is a promising approach to examine individual's sensitivity to complex acoustic patterns, which may overlap with higher level cognitive processes, including language.


Partial trisomy 7p associated with familial 7p;22q translocation.
A newly described partial trisomy of the short arm of chromosome number 7 is reported in a familial translocation between 7 and 22. The unbalanced translocation was found in one family member, the propositus, and the balanced form in 5 other members. The possibility of this translocation being a rare telomeric attachment previously undescribed in humans is discussed. Prominent clinical features include general mental and motor retardation, microbrachycephaly, and cardiac and oral abnormalities.


Time-dependent inhibition by glyceryl trinitrate of platelet aggregation caused by U46619 (a thromboxane/endoperoxide receptor agonist).
Glyceryl trinitrate is a weak inhibitor of platelet aggregation in vitro. Its effect on platelet aggregation in response to U46619 (a thromboxane/endoperoxide receptor agonist) was studied turbidometrically in platelet-rich plasma from healthy volunteers. The object was to determine whether inhibition was influenced by a period of preincubation between preparation of platelet-rich plasma and addition of glyceryl trinitrate. Incubation was performed at 37 degrees C and 22 degrees C. Samples were removed at intervals and transferred to an aggregometer cuvette at 37 degrees C. Glyceryl trinitrate (100 microM) or an equal volume of distilled water was added 5 min before U46619 (2 microM), and aggregation recorded as change in light transmission. Inhibition by glyceryl trinitrate was markedly time and temperature dependent, with a progressive increase in inhibitory potency between 120 and 300 min preincubation at 37 degrees C but not at 22 degrees C. The explanation of this is unknown but the effect was not influenced by lipopolysaccharide or by cycloheximide, so it does not appear to be due to exposure to endotoxin or to enzyme induction in vitro.


Salt sensitivity and insulin resistance: Is there a link?
Salt sensitivity is not only found in patients with essential hypertension but also in normotensive individuals. These salt-sensitive normotensives are believed to be genetically predisposed to the development of hypertension. In this paper we present data from our studies in such normotensive salt-sensitive individuals, thereby focusing on the relationship between salt sensitivity and familial history of hypertension and on insulin sensitivity. Salt-sensitivity was associated with a positive familial history of hypertension, a finding that supports the hypothesis that salt sensitivity in normotensive individuals points to a genetic predisposition for the development of hypertension. Also, salt-sensitive subjects displayed a hyperinsulinaemic response to an oral glucose load and a decreased insulin-mediated glucose disposal, as assessed by the insulin suppression test. The latter finding implies that insulin resistance is present in otherwise healthy, hypertension-prone individuals before overt hypertension develops. Assuming that there is a pathophysiological relationship between insulin resistance and salt sensitivity, our findings suggest that early recognition of insulin resistance and the implementation of measures aimed at improving insulin sensitivity could contribute to the prevention of cardiovascular disease in these individuals.


Pigmented lesion of the middle ear: report of a case.
Melanotic lesions of the mucosal membranes of the head and neck have been reported infrequently. Malignant melanomas are reported with much more frequency than benign nevi in this region. The first reported case of a nevus of the middle ear mucosa is presented. The distinctions between this lesion, nevus of Ota, meningioma, Schwannoma, and hematoma are discussed. The malignant potential for this lesion is not known, but it appears low enough to obviate interval tympanotomy.


Decreased serum choline concentrations in humans after surgery, childbirth, and traumatic head injury.
The serum levels of choline decreased by approximately 50% in patients having a surgery under general as well as epidural anesthesia. The decrease is lasts for two days after surgery. Intravenous administration of succinylcholine, either by a single bolus injection or by a slow continuous infusion, increased the serum choline levels several folds during surgery. In these patients, a significant decrease in the serum choline levels was observed one and two days after surgery. In 16 pregnant women at the term, serum choline levels were higher than the value observed in 19 nonpregnant women. The serum choline levels decreased by about 40% or 60% after having a childbirth either by vaginal delivery or caesarean section, respectively. Serum choline levels in blood obtained from 9 patients with traumatic head injury were significantly lower than the observed levels in blood samples obtained from healthy volunteers. These observations show that serum choline levels increase during pregnancy and decrease during stressful situations in humans.


An efficient and general enantioselective synthesis of sphingosine, phythosphingosine, and 4-substituted derivatives.
A general and efficient protocol for the enantioselective synthesis of sphingosine, phythosphingosine, and 4-substituted derivatives was established. These compounds were obtained from a common intermediate prepared from butadiene monoepoxide by a synthetic sequence involving enantioselective allylic substitution, cross-metathesis, and dihydroxylation.


Thoracoscopic Resection in the Treatment of Spontaneous Pneumothorax.
We retrospectively evaluated the patients with primer spontaneous pneumothorax (PSP) who were treated with thoracoscopic resection. We retrospectively collected the data of the patients with a spontaneous pneumothorax who were operated with video-assisted thoracoscopic surgery (VATS) between 2010 and 2016. During the study period, 10 patients applied to our hospital with spontaneous pneumothorax. Five children (three boys, two girls) with a mean age of 16.6 (16-17) were selected with VATS. Three of the patients had bleb, one of the patients had Congenital Cystic Adenomatoid Malformation (CCAM) type 2, and the last one had chronic emphysematous tissue on pathological analyses. Post-operative follow-up time was 2.2 (1-4) years without any complication. Spontaneous pneumothorax is a disease especially seen in puberty. The main reasons are apical segment bullae formation and blebs. VATS is especially advantageous to reach apical segments and for easy resections. Blebs, CCAM and emphysematous lung tissue may cause spontaneous pneumothorax.


Dopaminergic modulation of cognitive control: distinct roles for the prefrontal cortex and the basal ganglia.
Evidence from psychopharmacological functional neuroimaging begins to elucidate the neurochemical mechanisms of cognitive control. The role of dopamine in two subcomponent processes of cognitive control is discussed: the active maintenance and the flexible updating of goal-relevant representations. A range of studies have highlighted a role for the prefrontal cortex (pFC) and its modulation by dopamine in the active maintenance of distractor-resistant goal-relevant representations. This work suggests that dopamine might modulate top-down signals from the pFC, thereby increasing the activity of posterior cortical regions that process goal-relevant representations and rendering them distractor-resistant. Conversely, other studies highlight a role for dopamine in the basal ganglia in cognitive switching, which might reflect a modulation of the selective gating of cortical cognitive and motor programs. We present a working hypothesis that integrates these two disparate literatures and states that the flexible adaptation of current goal-relevant representations is mediated by modulatory influences of activity in the dopamine-sensitive basal ganglia on connectivity between the prefrontal cortex and posterior cortex.


A Randomized Double-Blind Clinical Trial Evaluates the Efficacy of Alternative Herbal Mouthwashes.
The removal of dental plaque is the primary step in achieving good oral hygiene. Mechanical plaque removal measures have questionable efficacy in inaccessible areas and proximal aspects of the oral cavity. Out of the several types of mouthwash available, chlorhexidine (CHX) is regarded as the gold standard, but considering its adverse effects, herbal alternatives are being sought after. So, the aim of the study was to evaluate the efficacy of alternative herbal mouthwashes. In this randomized, double-blind study, 125 selected patients were divided into five groups. Group 1: negative control - distilled water (DW); group 2: positive control - hexidine mouthwash (ICPA, Gujarat, India); group 3: FeelFresh Herbal Mouthcare Gargle (Able Exports, Gujarat, India); group 4: HiOra mouthwash (Himalaya Wellness Company, Bengaluru, India); group 5: Colgate MaxFresh Fresh Tea mouthwash (Colgate-Palmolive, India). Plaque index (PI), gingival index (GI), and microbial count (CFU) were evaluated before and after the intervention. The difference among the three types of herbal mouthwash was statistically non-significant. The lowest PI, GI, and CFU values were obtained in the subjects of group 4. Herbal mouthwashes are a promising alternative and are effective in maintaining oral hygiene.


Comparative efficacy and safety of cefprozil versus penicillin, cefaclor and erythromycin in the treatment of streptococcal pharyngitis and tonsillitis.
Cefprozil is a new oral cephalosporin with an enhanced in vitro spectrum of activity that includes group A beta-hemolytic streptococci (GABHS). Four multicenter randomized clinical trials were conducted to compare the clinical efficacy and safety of cefprozil administered once or twice a day for the treatment of mild to moderate GABHS tonsillitis and pharyngitis. A total of 1597 patients were enrolled in the trials. Patient demographics and severity of infection were similar for all treatment groups. In Study 1, cefprozil administered at 20 mg/kg once daily was clinically, in 68 of 76 patients (89%) and bacteriologically, in 66 of 74 patients (89%) superior to penicillin -51 of 69 (74%) and 46 of 69 (67%)--administered three times a day in patients of two to 12 years of age. In Study 2, the patients enrolled were 13 years of age and older, and cefprozil administered at 20 mg/kg once a day had similar clinical (93% vs. 90%) and bacteriological (95% vs. 94%) response rates as cefaclor administered three times a day. Study 3 demonstrated that cefprozil administered twice daily was similar to penicillin given three times a day, the clinical satisfactory response being 164 of 175 (94%) for cefprozil and 146 of 165 (88%) for penicillin. In Study 4, identical clinical and bacteriologic responses (95%) were observed for cefprozil administered once a day and erythromycin ethylsuccinate administered four times a day in children over two years of age. There were no significant differences in the incidence or severity of drug-related adverse events, which, when reported, were mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)


Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2.
Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer-associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario.


Nonsteroidal anti-inflammatory drug gastropathy: new avenues for safety.
Chronic oral or systemic nonselective nonsteroidal anti-inflammatory drug (NSAID) therapy, ubiquitously used by physicians to treat osteoarthritis-associated pain, is associated with a wide range of symptomatic adverse events, the most frequent and serious of which is gastropathy. Although cardiovascular and renal problems are a very real concern, they are significantly less frequent. These complications can be life-threatening in at-risk populations such as older adults, who are common users of long-term oral systemic NSAID therapy. Topical NSAID formulations deliver effective doses of analgesics directly to the affected joints, thereby limiting systemic exposure and potentially the risk of systemic adverse events, such as gastropathy and serious cardiovascular events. There are currently two topical NSAIDs approved by the US Food and Drug Administration for osteoarthritis-associated pain, as well as for the signs and symptoms of osteoarthritis. This review discusses the relative safety, and the gastrointestinal, cardiovascular, and renal risks of chronic oral or systemic NSAID therapy and topical NSAID formulations in patients with osteoarthritis.


Isolated Unilateral Abducens Nerve Palsy Manifesting as a Rare Complication of Idiopathic Pituitary Apoplexy: A Case Report.
Pituitary apoplexy (PA) is an expansion of a pituitary adenoma due to infarction or hemorrhage of the gland. The term apoplexy usually describes larger bleeds leading to a sudden onset of symptoms. Although it is a rare condition, it can be a life-threatening emergency. PA usually presents with severe headache, nausea, vomiting, visual acuity, and field defects, frequently involving the cranial nerves directly adjacent to the pituitary gland, including third (oculomotor) cranial nerve, fourth (trochlear) cranial nerve, ophthalmic and maxillary branches of the fifth (trigeminal) cranial nerve, and, less commonly, the sixth (abducens) cranial nerve. Here, we present the case of a 36-year-old male who presented with a one-week history of worsening headache associated with double vision. On physical examination, the patient was noted to have left abducens nerve palsy. MRI brain showed anterior right T1 hyperintensity in the pituitary representing blood products. The patient was treated with analgesics and hormonal therapy with improvement in symptoms and eventual resolution of PA without the need for surgical intervention. PA is an unusual cause of acute isolated abducens nerve palsy which should be identified promptly as it is a life-threatening emergency that can be treated immediately with hormonal replacement followed by a decision to manage conservatively or surgically. The long-term follow-up includes endocrine assessment, visual assessment, and imaging surveillance.


SMARCA4-Deficient Undifferentiated Tumor of Lung Mass-A Rare Tumor With the Rarer Occurrence of Brain Metastasis: A Case Report and Review of the Literature.
Among thoracic tumors, these include subsets of a relatively newly described and yet to be fully characterized tumor entity: SMARCA4-deficient Undifferentiated Tumor (SMARCA4-dUT). Mutations of SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and loss of BRG1 (Brahma-related gene-1) is the underlying molecular hallmark of SMARCA4-dUT. They mostly involved the mediastinum, lung, and/or pleura showing undifferentiated round cell or rhabdoid morphology associated with aggressive clinical behavior. The pathogenesis of these tumors is still not clear. Morphologically, SMARAC4-dUT is differentiated from SMARCA4-dNSCLC by the presence of squamous and solid components in the latter. Immunohistochemically SMARC4-dUT has characteristic loss of SMARCA4 and SMARCA2 and strong expression of SOX2, CD34, and SALL4. Common sites of metastasis include lymph nodes, bones, and adrenal glands but rarely brain metastasis. We present a unique and rare case of a 76-year-old male with a right lung mass with documented pathology of SMARCA4-dUT and was found to have multiple brain metastases.


Effect of Alteration in Precipitation Amount on Soil Microbial Community in a Semi-Arid Grassland.
Climate models predict significant changes in precipitation magnitude in semi-arid grasslands, so it is vital to improve our understanding of how changing precipitation affects microbial communities in grassland ecosystems. Using a long-term field manipulation experiment, we evaluated the responses of microbial communities to a decrease (DP) and an increase (IP) in precipitation on a semi-arid grassland in northern China. The results showed that bacterial species richness decreased significantly with DP but remained stable under IP. Relative abundance of oligotrophic, slow-growing bacterial phyla (e.g., Chloroflexi and Acidobacteria) increased with DP but decreased with IP, whereas the relative abundance of copiotrophic, fast-growing bacterial phyla (e.g., Proteobacteria and Bacteroidetes) decreased with DP but increased with IP. In contrast, diversity, species composition, and relative abundance of different fungal phyla change little with DP or IP. These results indicate a greater sensitivity of bacteria to precipitation changes than fungi, and the sensitivity of bacteria to DP was higher than IP. Our findings are important for understanding soil microbial dynamics under future climate change scenarios.


The acoustic correlates of stress and tone in Chácobo (Pano): A production study.
This paper investigates the acoustic correlates of word initial prominence and tone in Chácobo, a southern Pano language of the northern Bolivian Amazon. This paper reports the results of a production study with five speakers producing trisyllabic words with a word final high tone. It tests a claim found in the literature that there is an additional word-initial prominence in such forms and determines its acoustic correlates compared with high tone. This study used trisyllabic forms in morphophonological contexts where these forms would appear with a final high tone. In such forms, high tone and word-initial prominence do not overlap (e.g., "panaß̞í" "asaí"). The paper takes into account five acoustic correlates across the three syllables of these words: F1, F2, F0, duration, intensity. The paper finds that the initial syllable in these words shows a statistically significant increase in intensity. There is significant speaker variation with respect to whether duration is a correlation of initial stress and the results do not provide clear evidence that initial stress is marked with duration. The final high-tone marked syllables are distinguished based on an increase in F0 and secondarily with vowel duration. Whether pitch is also a correlate of stress requires future research. The paper interprets these results as suggesting that Chácobo is a language in which tone and stress co-exist. The study thus provides instrumental evidence for a phenomenon suggested to occur in some Pano languages. The limitations of this study, including the fact the results have more than one interpretation in light of current discussions concerning stress and tone, are also discussed.


Cross-Electrophile C-PIII Coupling of Chlorophosphines with Organic Halides: Photoinduced PIII and Aminoalkyl Radical Generation Enabled by Pnictogen Bonding.
Pnictogen bonding (PnB) has gained recognition as an appealing strategy for constructing novel architectures and unlocking new properties. Within the synthetic community, the development of a straightforward and much simpler protocol for cross-electrophile C-PIII coupling remains an ongoing challenge with organic halides. In this study, we present a simple strategy for photoinduced PnB-enabled cross-electrophile C-PIII couplings using readily available chlorophosphines and organic halides via merging single electron transfer (SET) and halogen atom transfer (XAT) processes. In this photomediated transformation, the PnB formed between chlorophosphines and alkyl amines facilitates the photogeneration of PIII radicals and α-aminoalkyl radicals through SET. Subsequently, the resulting α-aminoalkyl radicals activate C-X bonds via XAT, leading to the formation of carbon radicals. This methodology offers operational simplicity and compatibility with both aliphatic and aromatic chlorophosphines and organic halides.


[Thyroid disease].
The incidence of pregnant women with thyroid dysfunction has been reported to be around 0.1-0.4%. Graves' disease accounts for more than half of these disorders. The main cause of thyroid disease in pregnancy and puerperium is autoimmune dysfunction. Whether there may be goitre or exophthalmus present, clinical signs as inappropriate weight gain, high systolic pressure, palpitation (greater than or equal to 110/min), emotional lability, fatigue, acceleration of suppression of the Achilles' tendon reflex should induce changes in the biochemical thyroid function tests. Parameters for the diagnosis and management for hyperthyroidism are serum levels of free T4 and TSH, while those of T3, reverse T3, and TSH are for hypothyroidism. Serum anti-microsomal antibodies and anti-thyroglobulin antibodies which have no effect on the fetus are also good markers for severity. The transplacental transfer of maternal TSH receptor antibodies consisting of stimulatory and inhibitory immunoglobulins and maternal thyroid-binding inhibiting immunoglobulins play roles in the development of transient neonatal hyper- or hypothyroidism. Fetal control is achieved by optimal maternal management. Untreated hyperthyroidism may be associated with fetal malformations. This risk may be reduced by antithyroid drug treatment of up to 150 mg/day of propylthiouracil which has less chance of placental passage and less secretion into the mother's milk than methyl-mercapto-imidazol. Maternal thyroid function should be kept in the upper limit of normal range, taking into consideration the fetal dysfunction induced by over-administration of the drug which passes through placenta. Children of hypothyroid women taking inadequate replacement therapy manifested lower IQ values compared to the progeny of euthyroid or hypothyroid women taking adequate therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


Scrutinizing the Emotional Nature of Intuitive Coherence Judgments.
Dual-system models propose that cognitive processing can occur either intuitively or deliberately. Unlike deliberate decision strategies, intuitive ones are assumed to have an emotional component attached to the decision process. We tested if intuitive decisions are indeed accompanied by an emotional response while deliberate decisions are not. Specifically, we conducted a psychophysiological study in which participants were instructed to decide either intuitively or deliberately if three simultaneously presented words were semantically coherent or incoherent (triad task). The degree of emotionality of these two decision strategies (intuitive vs. deliberate) was compared using changes in electrodermal activity (EDA) and the reaction time (RT) effect of an affective priming paradigm as primary measurements. Based on a valence-arousal model, our results revealed that intuitive and deliberate judgments do not differ as to their emotional valence but that they do differ in emotional arousal. Most notably, sympathetic activation during intuitive judgments was significantly lower compared to sympathetic activation during deliberate judgments. Our results reflect that a relaxed state of mind-manifested in low sympathetic activity-could underlie the holistic processing that is assumed to facilitate the proliferation of semantic associations during coherence judgments. This suggests that coherence judgments made under an (instructed) intuitive decision mode have a specific psychophysiological signature and that arousal is the differentiating component between intuitive and deliberate decision strategies.


Self-Powered Intelligent Water Meter for Electrostatic Scale Preventing, Rust Protection, and Flow Sensor in a Solar Heater System.
Triboelectric nanogenerators (TENGs) have been investigated for mechanical energy harvesting because of their high-energy conversion efficiency, low cost, ease of manufacturing, and so on. This paper deals with designing a kind of water-fluid-driven rotating TENG (WR-TENG) inspired by the structure of a water meter. The designed WR-TENG is effectively integrated into a self-powered electrostatic scale-preventing and rust protection system. The WR-TENG can generate a constant DC voltage up to about 7.6 kV by using a voltage-doubling rectifier circuit (VDRC) to establish a high-voltage electrostatic field in the water tank. A WR-TENG, a VDRC, and an electric water heating tank are the components of the whole system. The system is convenient to be installed in any waterway system, effectively preventing the rusting of stainless steel and restraining the formation of scale when the water is heated to 65 ± 5 °C. Moreover, the approximately linear relationship between the short-circuit current and the rotation rate of the WR-TENG makes employing it as a self-powered water flow sensor possible. This work enables a facile, safe, and effective approach for electrostatic scale prevention, rust protection, and flow sensing in solar heaters, which will enrich the high-voltage applications of TENGs.


[On excellent education mode of biomedical engineering in USA].
Based on the rankings of the best undergraduate/graduate biomedical engineering programs from the USA News & World Report, we have made a comprehensive analysis on the excellent education mode in USA 2002. It is hoped that the results as reference materials will be useful to our biomedical education at home.


Differential nitric oxide levels in the blood and skeletal muscle of type 2 diabetic subjects may be consequence of adiposity: a preliminary study.
Nitric oxide (NO·) exerts key regulatory functions including vasodilation and glucose uptake. Thus reduced NO· levels are associated with insulin resistance and hypertension. In this preliminary work we aimed to measure the levels of NO· metabolites in serum and skeletal muscle of obese and non-obese subjects, with or without type 2 diabetes mellitus (T2DM). Fifteen sedentary male participants [7 obese controls (C) vs 5 obese and 3 non-obese T2DM; age 54±9 years] were selected according to their BMI (>30 kg/m(2) for obese and 23-27 kg/m(2) for non-obese participants) and evaluated for fasted values of blood glucose, HbA1c, lipid profile, serum CRP (C-reactive protein), erythrocyte glutathione (GSH) metabolism, plasma adiponectin, leptin and cytokines (TNF-α and INFγ), serum and skeletal muscle nitric oxide metabolites (nitrite and nitrates; tNOx) and skeletal muscle nNOS and iNOS expression. Body composition was measured by whole body DEXA and muscle microbiopsy was performed in the vastus lateralis. We found that serum tNOx (total nitrite/nitrate; μmol/L) was lower in obese T2DM group (12.7±3.5) when compared with their controls (21.1±2.4), although the non-obese group presented higher concentration of tNOx (33.8±7.2). Skeletal muscle nNOS was higher in obese controls, lower in non-obese T2DM and undetected in obese T2DM. On the other hand, expression of iNOS had an inverse relationship with nNOS, showing higher expression in obese T2DM, decrease in non-obese T2DM and absence in obese control group. tNOx levels (μmol/mg protein) were decreased in the non-obese T2DM group (12.07±0.59) when compared with the obese control (21.68±6.2) and the obese T2DM group (26.3±7.26). We conclude that the decreased serum NO∙ production in obese T2DM patients seems to be associated with adipose mass as lower adiposity was associated with normal NO∙ which was reduced in the skeletal muscle of the non-obese T2DM patients. We suggest that the lower adiposity (and higher adiponectin) in non-obese T2DM could be responsible for differential levels of NO∙ production and insulin resistance.


Streaked x-ray backlighting with twin-slit imager for study of density profile and trajectory of low-density foam target filled with deuterium liquid.
Low-density plastic foam filled with liquid deuterium is one of the candidates for inertial fusion target. Density profile and trajectory of 527 nm laser-irradiated planer foam-deuterium target in the acceleration phase were observed with streaked side-on x-ray backlighting. An x-ray imager employing twin slits coupled to an x-ray streak camera was used to simultaneously observe three images of the target: self-emission from the target, x-ray backlighter profile, and the backlit target. The experimentally obtained density profile and trajectory were in good agreement with predictions by one-dimensional hydrodynamic simulation code ILESTA-1D.


Construction of expression systems for flaA and flaB genes of Helicobacter pylori and determination of immunoreactivity and antigenicity of recombinant proteins.
To clone flagellin genes A (flaA) and B (flaB) from a clinical strain of Helicobacter pylori (H pylori) and to construct prokaryotic expression systems of the genes and identify immunity of the fusion proteins. The flaA and flaB genes from a clinical H pylori isolate Y06 were amplified by high fidelity PCR. The nucleotide sequences of target DNA amplification fragments from the two genes were sequenced after T-A cloning. The recombinant expression vector pET32a inserted with flaA and flaB genes was constructed, respectively. The expressions of FlaA and FlaB fusion proteins in E. coli BL21DE3 induced by isopropylthio-beta-D-galactoside (IPTG) at different concentrations were examined by SDS-PAGE. Western blot using commercial antibodies against whole cell of H pylori and immunodiffusion assay using self-prepared rabbit antiserum against FlaA (rFlaA) or FlaB (rFlaB) recombinant proteins were applied to the determination of the fusion proteins immunity. ELISA was used to detect the antibodies against rFlaA and rFlaB in sera of 125 H pylori infected patients and to examine rFlaA and rFlaB expression in 98 clinical isolates of H pylori, respectively. In comparison with the reported corresponding sequences, the nucleotide sequence homologies of the cloned flaA and flaB genes were from 96.28-97.13% and 96.31-97.73%, and their putative amino acid sequence homologies were 99.61-99.80% and 99.41-100% for the two genes, respectively. The output of rFlaA and rFlaB expressed by pET32a-flaA-BL21DE3 and pET32a-flaB-BL21DE3 systems was as high as 40-50% of the total bacterial proteins. Both rFlaA and rFlaB were able to combine with the commercial antibodies against whole cell of H pylori and to induce rabbits to produce specific antibodies with the same 1:2 immunodiffusion titers after the animals were immunized with the two recombinant proteins. Ninety-eight and zero point 4 and 92.80% of the serum samples from 125 patients infected with H pylori were positive for rFlaA and rFlaB antibodies, respectively. One hundred percent and 98.98% of the 98 tested isolates of H pylori were detectable for rFlaA and rFlaB epitopes, respectively. Two prokaryotic expression systems with high efficiency of H pylori flaA and flaB genes were successfully established. The expressed rFlaA and rFlaB showed satisfactory immunoreactivity and antigenicity. High frequencies of FlaA and FlaB expression in different H pylori clinical strains and the general existence of specific antibodies against FlaA and FlaB in H pylori infected patients strongly indicate that FlaA and FlaB are excellent antigen candidates for developing H pylori vaccine.


Studies on the biosynthesis of rabbit haptoglobin.
Rabbit haptoglobin is a tetrameric protein consisting of two nonglycosylated alpha and two glycosylated beta chains, the latter being joined to the former and the former to each other by disulfide linkages. We describe here the results of studies that analyzed the biosynthetic pathway of rabbit haptoglobin by using cultured hepatocytes incubated with L-[35S]cysteine. The initial form of haptoglobin detected in hepatocytes exhibited Mr = 46,000, was glycosylated, and corresponded in migration to the initial species formed when the mRNA for rabbit haptoglobin was translated using the reticulocyte lysate system coupled with dog pancreatic microsomes. This one-chain intermediate was rapidly cleaved into a glycosylated form of the beta chain and into the mature alpha chain, these chains being joined by disulfide linkages. Dimerization also occurred rapidly, forming a tetrameric precursor of haptoglobin. Several other intracellular glycosylated forms of the beta chain were detected subsequently, representing intermediates formed during oligosaccharide processing prior to secretion of mature haptoglobin. Addition of tunicamycin (5 micrograms/ml) inhibited glycosylation of the initial form of haptoglobin detected, but subsequent proteolytic processing into alpha and beta chains still occurred. Our results showed that the pathway of biosynthesis of rabbit haptoglobin closely resembles that reported for rat haptoglobin ( Hanley , J. M., Haugen , T. H., and Heath, E. C. (1983) J. Biol. Chem. 258, 7858-7869).


Effect of composite type, light intensity, configuration factor and laser polymerization on polymerization contraction forces.
To investigate the effect of composite type, light intensity, configuration factor and laser polymerization on polymerization contraction force. Glass rods (10 pairs/group) were etched with HF acid, silanated, unfilled resin applied and light cured for 20 s. Rods were held vertically in chucks on a Zwick machine. A cylindrical matrix was filled with Silar chemical cure, Silux Plus microfill or Z-100 hybrid composite and the crosshead of the UTM positioned at an inter-rod distance corresponding to a specific ratio of bound to unbound composite surface area (configuration factor or C). Exposure time with the Demetron 401 conventional visible light curing unit (D401) was 40 s/side (80 s total). Exposure times for the ILT Model D5500 air cooled laser (LAC) and Model 5500ABL water cooled laser (LWC) was 20 s/side (40 s total). Experimental groups, n = 10 with constant factors in parentheses, included: (1) Silar chemical-cured (C = 3); (2) Z-100 hybrid (C = 3, D401, 100% intensity); (3) Silux Plus microfill (C = 3, D401, 100% intensity); (4) D401 100% light intensity = 476 mW (Z-100, C = 3, D401); (5) D401 50% intensity = 238 mW (Z-100, C = 3, D401); (6) D401 25% intensity = 119 mW (Z-100, C = 3, D401); (7-9) C = 5, 3 & 1 respectively (Z-100, D401, 100% intensity); (10) D401 with 13 mm tip = 391 mW/cm2 (Z-100, C = 3; D401); (11) D401 with Turbo Tip = 811 mW/cm2 (Z-100, C = 3; D401); (12) LAC = 265 mW, 689 mW/cm2 (Z-100, C = 3); (13) LWC = 365 mW, 1100 mW/cm2 (Z-100, C = 3). One Way ANOVA and Duncan's Multiple Range Test (alpha = 0.05) were performed separately for each variable. Homogeneous subsets by variable were: composite type Group 1 (25N) < Group 3 (65.8N) < Group 2 (90.4N); intensity Group 6 (73.9N) = Group 5 (77.7N) < Group 4 (90.4N); C-Factor Group 7 (81.8N) < Group 8 (90.4N) < Group 9 (103.4N); light source Group 12 (77.4N) = Group 13 (79.1N) < Group 10 (90.4N) = Group 11.(89.4N). The chemical-cured composite had the lowest maximum polymerization contraction force, the microfill was intermediate and the hybrid composite had the highest recorded force. Increases in light intensity increased the maximum force on the force/time curve. Maximum forces were inversely related to C-factor (C5 < C3 < C1) and directly related to composite volume in a non-rigid system which allowed compliance. Maximum force was not significantly different with the two tips tested on the conventional curing light. Forces obtained with laser polymerization were similar for the two laser groups, which were both statistically lower than the conventional light tested.


Effects of amino acids and amino acid analogues on lysosomal protein degradation in isolated rat hepatocytes.
An amino acid mixture, specially designed to improve the protein balance in isolated hepatocytes, inhibited lysosomal (propylamine-sensitive) degradation of endogenous proteins by 80-90%. The amino acids had no effect on the degradation of the endocytosed protein asialofetuin, the conclusion being that amino acids are involved in the regulation of autophagy. Furthermore, the effect of two amino acids was tested individually, at high concentrations, in an electron microscopic analysis. Leucine caused a 79% decrease in the early forms of autophagic vacuoles, while asparagine had no effect. Leucine appears to be important in the regulation of the bulk autophagy observable in the electron microscope but this type of autophagy possibly contributes only about one-half of the total amount of protein degraded in lysosomes, since leucine only inhibits some 30% of the lysosomal protein degradation. Certain branched-chain amino acids related to leucine inhibited lysosomal protein degradation to the same extent as did leucine.


Direct electrochemistry of cytochrome c at a glassy carbon electrode modified with single-wall carbon nanotubes.
The electrochemistry of horse heart cytochrome c was studied by cyclic voltammetry at a glassy carbon electrode modified with single-wall carbon nanotubes (SWNTs). A pair of well-defined redox waves was obtained in cytochrome c aqueous solution at an activated SWNT film-modified electrode. The optimal conditions for activating the SWNT film-modified electrode has been determined. The electrode reaction of cytochrome c is a diffusion-controlled process. The peak current increases linearly with the concentration of cytochrome c in the range from 3.0 x 10(-5)-7.0 x 10(-4) M. The detection limit is 1.0 x 10(-5) M. The activated SWNT film was characterized by scanning electron microscopy. Furthermore, interaction of cytochrome c with adenine was characterized by electrochemical and spectral methods.


Comparative efficacy of anthelmintics and their effects on hemato-biochemical changes in fasciolosis of goats of South Gujarat.
Fasciolosis is a parasitic disease caused by Fasciola spp. of the family Fasciolidae (trematodes) characterized by bottle jaw, anemia, progressive debility, and potbelly condition. There are many aspects of fasciolosis remaining unknown thus hemato-biochemical alterations in closantel, triclabendazole + ivermectin, and oxyclozanide + levamisole treated goats were studied. A total of 40 naturally fasciolosis infected goats having egg per gram more than 100 were randomly divided into four groups. Goats of Group I-III were treated with three different anthelmintics, whereas, goats of Group-IV were kept as control or untreated. Whole blood, serum, and fecal samples were collected on 0, 7(th), and 30(th) day of treatment. During the study, values of hemoglobin, total erythrocyte count, pack cell volume, and total protein were significantly elevated to their normal levels in anthelmintics treated groups. Whereas, values of total leukocyte count, aspartate transaminase (AST), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) were significantly reduced to their normal level in anthelmintics treated groups. The efficacy of closantel (T1), triclabendazole + ivermectin (T2), and oxyclozanide + levamisole (T3) was 99.63%, 100%, and 94.74% and 100%, 100%, and 97.38% on 7(th) and 30(th) day of treatment, respectively. Fasciolosis in goats can be diagnosed on the basis of fecal sample examination, but alterations in important biomarkers such as AST, GGT, and LDH are also helpful for early diagnosis. The use of newer anthelmintic either alone or in combination showed a higher therapeutic response in fasciolosis of goats.


[Medium-term efficacy and safety analysis of Ex-PRESS shunt implantation for the treatment of secondary glaucoma in Sturge-Weber syndrome].
Objective: To evaluate the medium-term efficacy and safety of Ex-PRESS shunt implantation in the treatment of secondary glaucoma associated with Sturge-Weber Syndrome (SWS). Methods: This was a retrospective case series study. Medical records of patients diagnosed with secondary glaucoma due to SWS who underwent Ex-PRESS shunt implantation at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, between January 2013 and February 2020 were collected. Only the right eye were included in the analysis when both eyes were affected. Follow-up visits were scheduled at postoperative week 1, 3 months, 6 months, 1 year, 2 years, and 3 years. Clinical data including intraocular pressure (IOP), vertical cup-to-disc (C/D) ratio, corneal horizontal diameter, visual field, anterior chamber condition, anti-glaucoma medication usage, and additional surgeries were evaluated and analyzed before and after the procedure. Surgical success rates and procedure-related complications at each follow-up time point were assessed. Statistical analyses were performed using t-test, Mann-Whitney U test, and χ2 test. Results: A total of 21 patients (21 eyes) were included in the study, comprising 10 females and 11 males. Among them, 15 eyes were on the right side, and 6 eyes were on the left side. The patients' ages ranged from 3 to 51 years, with a median age of 8.1 (6.3, 11.9) years. The follow-up period ranged from 3 to 53 months, with a median of 11 (6, 24) months. Preoperatively, the IOP in the 21 operated eyes was (32.9±9.1) mmHg (1 mmHg=0.133 kPa), significantly higher than the IOP in the 19 healthy eyes, which was (17.1±4.3) mmHg (t=5.80, P<0.001). The C/D ratio in the operated eyes was (0.75±0.13), also significantly higher than that in the healthy eyes, which was (0.32±0.10) (t=11.22, P<0.001). At the 1-year, 2-year, and 3-year follow-up, 8 eyes out of 16 operated eyes, 6 eyes out of 9 operated eyes, and 7 eyes out of 10 operated eyes achieved overall surgical success (complete success+conditional success), respectively. The number of eyes with complete success at the three follow-up time points was 3, 2, and 4, respectively. The IOP in the operated eyes was significantly reduced at all follow-up time points compared to preoperative values (all P<0.05), while there was no statistically significant difference in C/D ratio before and after surgery (all P>0.05). Two operated eyes experienced retinal detachment or choroidal leakage postoperatively, both of which recovered after conservative treatment. One eye developed postoperative degree Ⅰ shallow anterior chamber, and it resolved spontaneously on the third day after surgery. No serious surgical complications, such as bleb-related complications, malignant glaucoma, expulsive choroidal hemorrhage, or endophthalmitis, were observed postoperatively. Conclusions: Ex-PRESS shunt implantation for the treatment of secondary glaucoma in SWS demonstrated a relatively high level of safety. The medium-term IOP in the operated eyes significantly decreased compared to preoperative values. However, the majority of operated eyes did not achieve complete surgical success.


Study on effects of p-phenylbenzoic acid on change of sulfation and glucuronidation in rats.
The effects of p-phenylbenzoic acid (PPBA) on sulfation and glucuronidation was studied in rats. Following intravenous injection of 14C-p-tert-butylphenol (14C-TB, 50 micromol/kg) with PPBA (50 micromol/kg), the sulfation of 14C-TB was decreased by 38.8% and its glucuronidation increased by 62.3%. In a system of isolated hepatocytes, the sulfation of 14C-TB increased and its glucuronidation decreased following the addition of 100 microM of PPBA, suggesting competitive inhibition by the glucuronidation of PPBA. On the other hand, the sulfation of 14C-TB decreased and its glucuronidation increased following the addition of 400 microM of PPBA, which represents the plasma concentration of PPBA in vivo. At this concentration, significant leakage of GOT, GPT and LDH into the medium was observed, whereas, no significant change in the ATP synthesis was noted. Microsomes preincubated with 60 microM of PPBA, which represents the intracellular concentration of PPBA in the liver in vivo, showed no change in the level of glucuronidation of 14C-TB. These results suggest that PPBA in the plasma injures cell membranes and causes a leakage of cytosolic sulfotransferase, whereas UDPGT, embedded in the microsomal membrane, does not leak from the injured cell membrane, resulting in the decrease in sulfation and increase in glucuronidation. Similar in vivo effects on the sulfation/glucuronidation ratio were observed for benzoic acids substituted with benzoyl and phenoxy groups.


Canadian health measures survey: brief overview.
The Canadian Health Measures Survey (CHMS) was developed to address important data gaps and limitations in existing health information by collecting directly measured indicators of health and wellness on a representative sample of approximately 5,000 Canadians aged 6-79 years. The CHMS includes an in-home general health interview and a subsequent clinic visit where direct physical measures of health are taken (anthropometry, spirometry, blood pressure, fitness, physical activity, oral health examination, blood and urine specimens) in mobile clinics. Reference laboratories are used to analyze biological specimens for indicators of general health, chronic disease, infectious disease and environmental biomarkers and to store biospecimens for future research. This paper provides a brief overview of the survey sampling, methodological, operational, logistical, ethical, legal and social issues and procedures related to the CHMS.


The Parkinson's disease-related protein DJ-1 protects dopaminergic neurons in vivo and cultured cells from alpha-synuclein and 6-hydroxydopamine toxicity.
Dopaminergic degeneration is a major finding in brains of patients with Parkinson's disease (PD), together with Lewy bodies, intraneuronal inclusions mainly composed of the fibrillogenic protein α-synuclein (α-syn). The familial-PD-related protein DJ-1 was reported to reduce dopaminergic degeneration triggered by α-syn or by the dopaminergic-selective neurotoxin 6-hydroxydopamine (6-OHDA). The aim was to further investigate the role of DJ-1 in dopaminergic degeneration and to see whether a cell-permeable recombinant form of DJ-1 (TAT-DJ-1) could restore dopamine depletion in vivo, thus representing an innovative therapeutic approach. We developed in vitro (PC12/TetOn cells and mouse primary mesencephalic neurons) and in vivo models [including DJ-1 knockout (-/-) mice] to investigate DJ-1 in dopaminergic degeneration. We found that in PC12/TetOn cells overexpressing α-syn with the familial-PD linked mutation A30P, DJ-1 silencing increased α-syn (A30P) toxicity. Primary mesencephalic neurons from DJ-1 (-/-) mice were more vulnerable to a cell-permeable form of α-syn (TAT-α-syn) and to 6-OHDA. Intrastriatally administered TAT-DJ-1 reduced 6-OHDA toxicity in vivo in C57BL/6 mice. Finally, when we injected TAT-α-syn (A30P) in the striatum of DJ-1 (-/-) animals, dopamine was depleted more than in the control strain. DJ-1 appears to have a protective role against dopaminergic degeneration triggered by α-syn or 6-OHDA, reinforcing the possible therapeutic importance of this protein in PD.


Kinetic study for the inclusion complex of carboxylic acids with cyclodextrin by the ultrasonic relaxation method.
Ultrasonic absorption coefficients in the frequency range of 0.8-95 MHz were measured in aqueous solutions containing both beta-cyclodextrin (beta-CD) (host) and butanoic acid (in its dissociated form and undissociated one) (guest). A single relaxational phenomenon was observed only when the solutes were coexisting, although no relaxation was found in the beta-CD solution or in the acid solutions. The absorption was also measured in a solution of pentanoic acid (dissociated form) with beta-CD, and single relaxation was detected. The ultrasonic relaxation observed in these solutions was due to a perturbation of a chemical equilibrium related to a reaction of an inclusion complex formed by the host and guest. The equilibrium constant was obtained from the dependence of the maximum absorption per wavelength on the guest concentration. The rate constant for the inclusion process of the guest into a cavity of beta-CD and that for the leaving process from the cavity were determined from the obtained relaxation frequency and the equilibrium constant. The standard volume change of the reaction was also computed from the maximum absorption per wavelength. These results were compared with those in solutions containing both beta-CD and different guest molecules. It was found that the hydrophobicity of guest molecules played an important role in the formation of the inclusion complex and also that the charge on the carboxylic group had a considerable effect on the kinetic characteristics of the complexation reaction.


Regulation of IFN-Is by MEF2D Promotes Inflammatory Homeostasis in Microglia.
Microglia play an essential role in the central nervous system immune response. The transcription factor myocyte enhancer factor-2 D (MEF2D) is known to participate in stress regulation in various cell types and is easily activated in microglia. MEF2D has been shown to transcriptionally regulate several cytokine genes in immune cells and directly regulates the inflammatory response, suggesting that MEF2D may act as a key stimulus response regulator of microglia and is involved in the regulation of brain microhomeostasis. To uncover the molecular mechanism of MEF2D in the inflammatory system, in the present study, we investigated the global effect of MEF2D in activated microglia and explored its potential regulatory network. Experiments with a recombinant lentiviral vector containing either shRNA or overexpressing MEF2D were performed in the murine microglial BV2 cell line. Transcriptome sequencing and global gene expression patterns were analysed in lipopolysaccharide-stimulated shMEF2D BV2 cells. Pro- and anti-inflammatory factors were assessed by Western blot, qPCR or ELISA, and microglial activity was assessed by phagocytosis and morphologic analysis. The direct binding of MEF2D to the promoter region of interferon regulatory factor 7 (IRF7) was tested by ChIP-qPCR. The interferon-stimulated genes (ISGs) were tested by qPCR. MEF2D actively participated in the inflammatory response of BV2 microglial cells. Stably expressed RNAi-induced silencing of MEF2D disrupted the microglial immune balance in two ways: (1) the expression of proinflammatory factors, such as NLRP3, IL-1β, and iNOS was promoted; and (2) the type-I interferon signalling pathway was markedly inhibited by directly modulating IRF7 transcription. In contrast, overexpression of MEF2D significantly reduced the expression of NLRP3 and iNOS under LPS stimulation and alleviated the level of immune stress in microglia. These findings demonstrate that MEF2D plays an important role in regulating inflammatory homeostasis partly through transcriptional regulation of the type-I interferon signalling pathway.


Bisphenol a Exposure in Utero Disrupts Hypothalamic Gene Expression Particularly Genes Suspected in Autism Spectrum Disorders and Neuron and Hormone Signaling.
Bisphenol A (BPA) is an endocrine-disrupting compound detected in the urine of more than 92% of humans, easily crosses the placental barrier, and has been shown to influence gene expression during fetal brain development. The purpose of this study was to investigate the effect of in utero BPA exposure on gene expression in the anterior hypothalamus, the basal nucleus of the stria terminalis (BNST), and hippocampus in C57BL/6 mice. Mice were exposed in utero to human-relevant doses of BPA, and then RNA sequencing was performed on male PND 28 tissue from whole hypothalamus (n = 3/group) that included the medial preoptic area (mPOA) and BNST to determine whether any genes were differentially expressed between BPA-exposed and control mice. A subset of genes was selected for further study using RT-qPCR on adult tissue from hippocampus to determine whether any differentially expressed genes (DEGs) persisted into adulthood. Two different RNA-Seq workflows indicated a total of 259 genes that were differentially expressed between BPA-exposed and control mice. Gene ontology analysis indicated that those DEGs were overrepresented in categories relating to mating, cell-cell signaling, behavior, neurodevelopment, neurogenesis, synapse formation, cognition, learning behaviors, hormone activity, and signaling receptor activity, among others. Ingenuity Pathway Analysis was used to interrogate novel gene networks and upstream regulators, indicating the top five upstream regulators as huntingtin, beta-estradiol, alpha-synuclein, Creb1, and estrogen receptor (ER)-alpha. In addition, 15 DE genes were identified that are suspected in autism spectrum disorders.


Effect of body mass index on quality of life in allergic/asthmatic patients.
Evaluation of quality of life (QoL) is of particular interest in patients suffering from chronic diseases. Although studies have shown an association between QoL and obesity and allergy/asthma, the effect of obesity on QoL is not well known. The aim of this study was to assess the impact of body mass index (BMI) as a contributory factor on QoL in patients with a diagnostic label of allergy/asthma. We surveyed 100 patients (69 F/31 M) (age 34.15+/-13.32 years), and 65 healthy controls (42 F/23 M) (age 35.45 +/-8.96 years). QoL was determined by SF-36. BMI > or = 25 kg/m(2) was accepted as overweight/obesity. Forty-five percent of the patients had BMI > or = 25 kg/m(2) with no difference between the genders. They were significantly older and more likely to have less education level than those with BMI < 25 kg/m(2). Quality-of-life scores among patients with allergy/asthma were lower than those in the control group, irrespective of BMI. However, increased BMI was found to be related with improved quality of life among controls. Pearson's analysis showed that BMI was inversely correlated with physical functioning among patients (r = -0.229, p = 0.034), but in the control group it was positively correlated with QoL. All the domains of SF-36, except role-physical ones, among female subjects were significantly impaired more than those of male patients. It has been shown that the major determinants of impaired QoL are female sex, older age, and less educational status in patients with allergic/asthmatic symptoms. The impact of BMI on QoL could be undermined, because it seems to play a minor role.


Utilization of Recycled Egg Carton Pulp for Nitrocellulose as an Accelerant in Briquette Production.
Nitrocellulose (NC) is a conservative material that is used in a variety of applications, such as coating agents, biodegradable plastics, and propellant main charge. Nitrocellulose raw materials are easily obtained from lignocellulose sources, most notably cotton and wood pulp. The egg carton, a recycled paper waste designed for packaging and transporting eggs, is used in this study to make nitrocellulose in pulp form. The effects of different nitration durations (40, 50, and 60 min) from egg carton pulp bleached with various KOH concentrations (0.6 M, 1.0 M, and 1.5 M) on NC properties were evaluated. The accelerant properties of the NC of nitration time in 50 min were studied in a rice husk charcoal briquette. Rice husk charcoal briquettes are made in various ratios with nitrocellulose as an accelerant (97:3, 96:4, and 95:5). The NC was characterized using Fourier transform infrared (IR) spectroscopy and thermogravimetric (TG) analysis. 1.0 M of bleached egg carton pulp has the highest cellulose content (86.94%) with the presence of crystalline structure of cellulose at peak 1430 cm-1 after the bleaching process. Meanwhile, different nitration times revealed that 50 min had the highest nitrogen content (7.97%) with a 1.23 degree of substitution (DS) value. Based on its TG analysis, NC 50 has met the requirements for use as an accelerant for briquettes, with an onset temperature of 91.60 °C and a weight loss of 62.60%. Infrared at peak 1640 cm-1 confirmed the presence of NO2 groups in nitrocellulose successfully formed by nitration. After the addition of nitrocellulose, the calorific value of the briquette increased from 13.54% to 15.47%. Fixed carbon and volatile matter showed the same pattern. The combustion of nitrocellulose-briquette has also been demonstrated by Td10% of degradation, which degraded between 310 and 345 °C.


Treatment of experimentally induced Pasteurella multocida infections in broilers and turkeys: comparative studies of different oral treatment regimens.
Experimental fowl cholera was induced in 60 healthy 10-week-old broiler chickens and 8-week-old turkeys by intramuscular inoculation with approximately 80 colony-forming units (cfu) of Pasteurella multocida X-73 strain and with approximately 70 cfu of P. multocida P-1059 strain, respectively. This method of infection proved to be useful for evaluating the efficacy of anti-microbial medication, by measuring mortality, weight gain, pathological responses and frequency of re-isolation of P. multocida. The efficacies of two different dosing methods, continuous and pulse dosing, were compared. Using the continuous-dosing method, norfloxacin was administered to drinking water at 100 mg/l for 5 days in chickens. Efficacies were slightly improved compared with pulse dosing at 15 mg/kg bodyweight for the same length of time. The opposite was observed in turkeys, to the degree of control of mortality and maintenance of weight gain.


A human pathogenic bacterium Shigella proliferates in plants through adoption of type III effectors for shigellosis.
Shigella, which infects primates, can be transmitted via fresh vegetables; however, its molecular interactions with plants have not been elucidated. Here, we show that four Shigella strains, Shigella boydii, Shigella sonnei, Shigella flexneri 2a, and S. flexneri 5a, proliferate at different levels in Arabidopsis thaliana. Microscopic studies revealed that these bacteria were present inside leaves and damaged plant cells. Green fluorescent protein (GFP)-tagged S. boydii and S. flexneri 5a colonized leaves only, whereas S. flexneri 2a colonized both leaves and roots. Using Shigella mutants lacking type III secretion systems (T3SSs), we found that T3SSs that regulate the pathogenesis of shigellosis in humans also play a central role in bacterial proliferation in Arabidopsis. Strikingly, the immunosuppressive activity of two T3S effectors, OspF and OspG, was required for proliferation of Shigella in Arabidopsis. Of note, delivery of OspF or OspG effectors inside plant cells upon Shigella inoculation was confirmed using a split GFP system. These findings demonstrate that the human pathogen Shigella can proliferate in plants by adapting immunosuppressive machinery used in the original host human.


Allogeneic bone marrow transplantation for acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma following preparation with busulfan and cyclophosphamide (BuCy2).
The combination of busulfan (Bu) and cyclophosphamide (Cy) has been found to be effective preparative therapy for patients treated with allogeneic bone marrow transplantation (BMT). We developed the BuCy2 regimen, which contains a lower dose of cyclophosphamide than the original BuCy regimen, in the hope of reducing regimen-related toxicities. We have studied the use of BuCy2 as preparation for allogeneic BMT in patients with acute myelogenous leukemia, acute lymphocytic leukemia, and multiple myeloma. In patients with acute myelogenous leukemia, the leukemia-free survival and regimen-related toxicity rates obtained in our study appear similar to those achieved with other preparative regimens, including those containing Cy and total body irradiation (TBI). BuCy2 is also an effective BMT preparative regimen in patients with acute lymphocytic leukemia and multiple myeloma. Treatment with BuCy2 results in a lower incidence of severe stomatitis and probably of interstitial pneumonia than does treatment with Cy/TBI, but hepatic veno-occlusive disease occurs more frequently in BuCy-treated patients. The incidence of veno-occlusive disease appears to be affected by agents used as prophylaxis for graft-versus-host disease. Compared with Cy/TBI regimens, BuCy treatment is likely to result in fewer delayed effects of treatment, such as impairment of fertility and second malignancies. Current clinical efforts are focusing on ways to improve the antileukemic activity of the BuCy preparative regimen and to reduce regimen-related toxicities.


Molecular prognostic prediction in liver cirrhosis.
The natural history of cirrhosis varies and therefore prognostic prediction is critical given the sizable patient population. A variety of clinical prognostic indicators have been developed and enable patient risk stratification although their performance is somewhat limited especially within relatively earlier stage of disease. Molecular prognostic indicators are expected to refine the prediction, and potentially link a subset of patients with molecular targeted interventions that counteract poor prognosis. Here we overview clinical and molecular prognostic indicators in the literature, and discuss critical issues to successfully define, evaluate, and deploy prognostic indicators as clinical scores or tests. The use of liver biopsy has been diminishing due to sampling variability on fibrosis assessment and emergence of imaging- or lab test-based fibrosis assessment methods. However, recent rapid developments of genomics technologies and selective molecular targeted agents has highlighted the need for biopsy tissue specimen to explore and establish molecular information-guided personalized/stratified clinical care, and eventually achieve "precision medicine".


A common region of deletion on chromosome 17q in both sporadic and familial epithelial ovarian tumors distal to BRCA1.
Linkage analysis in familial breast and ovarian cancer and studies of allelic deletion in sporadic ovarian tumors have identified a region on chromosome 17q containing a candidate tumor-suppressor gene (referred to as BRCA1) of likely importance in ovarian carcinogenesis. We have examined normal and tumor DNA samples from 32 patients with sporadic and 8 patients with familial forms of the disease, for loss of heterozygosity (LOH) at 21 loci on chromosome 17 (7 on 17p and 14 on 17q). LOH on 17p was 55% (22/40) for informative 17p13.1 and 17p13.3 markers. When six polymorphic markers flanking the familial breast/ovarian cancer susceptibility locus on 17q12-q21 were used, LOH was 58% (23/40), with one tumor showing telomeric retention. Evaluation of a set of markers positioned telomeric to BRCA1 resulted in the highest degree of LOH, 73% (29/40), indicating that a candidate locus involved in ovarian cancer may reside distal to BRCA1. Five of the tumors demonstrating allelic loss for 17q markers were from individuals with a strong family history of breast and ovarian cancer. More important, two of these tumors (unique patient number [UPN] 57 and UPN 79) retained heterozygosity for all informative markers spanning the BRCA1 locus but showed LOH at loci distal to but not including the anonymous markers CMM86 (D17S74) and 42D6 (D17S588), respectively. Deletion mapping of seven cases (two familial and five sporadic) showing limited LOH on 17q revealed a common region of deletion, distal to GH and proximal to D17S4, that spans approximately 25 cM. These results suggest that a potential tumor-suppressor gene involved in both sporadic and familial ovarian cancer may reside on the distal portion of chromosome 17q and is distinct from the BRCA1 gene.


[On "the heart also governs Qi"].
As the organ of supreme superiority over any other organ of the body, the heart controls the function of the whole body. The lung governs the motions of Qi(vital energy), as have long been established in the basic theories in traditional Chinese medicine, but in this paper, the authors attempt to define the close relations between the heart and Qi by proposing that the heart also governs Qi, through either immediate and indirect actions. The heart plays an important role in the motion, generation and function regulation of Qi, with also impact on the changes of Qi ji, it is therefore of great importance to obtain a thorough comprehension of the associations between the two facets of Qi government by the lung and the heart, for the purpose of accurate clinical identification of the diseases and consequently appropriate treatment.


Development and Application of Genomic Resources in an Endangered Palaeoendemic Tree, Parrotia subaequalis (Hamamelidaceae) From Eastern China.
Parrotia subaequalis is an endangered palaeoendemic tree from disjunct montane sites in eastern China. Due to the lack of effective genomic resources, the genetic diversity and population structure of this endangered species are not clearly understood. In this study, we conducted paired-end shotgun sequencing (2 × 125 bp) of genomic DNA for two individuals of P. subaequalis on the Illumina HiSeq platform. Based on the resulting sequences, we have successfully assembled the complete chloroplast genome of P. subaequalis, as well as identified the polymorphic chloroplast microsatellites (cpSSRs), nuclear microsatellites (nSSRs) and mutational hotspots of chloroplast. Ten polymorphic cpSSR loci and 12 polymorphic nSSR loci were used to genotype 96 individuals of P. subaequalis from six populations to estimate genetic diversity and population structure. Our results revealed that P. subaequalis exhibited abundant genetic diversity (e.g., cpSSRs: Hcp = 0.862; nSSRs: HT = 0.559) and high genetic differentiation (e.g., cpSSRs: RST = 0.652; nSSRs: RST = 0.331), and characterized by a low pollen-to-seed migration ratio (r ≈ 1.78). These genetic patterns are attributable to its long evolutionary histories and low levels of contemporary inter-population gene flow by pollen and seed. In addition, lack of isolation-by-distance pattern and strong population genetic structuring in both marker systems, suggests that long-term isolation and/or habitat fragmentation as well as genetic drift may have also contributed to the geographic differentiation of P. subaequalis. Therefore, long-term habitat protection is the most important methods to prevent further loss of genetic variation and a decrease in effective population size. Furthermore, both cpSSRs and nSSRs revealed that P. subaequalis populations consisted of three genetic clusters, which should be considered as separated conservation units.


Clinical use of pentoxifylline in haemorrhagic disorders of the retina.
The clinical effect of pentoxifylline, given orally at doses of 300 mg to 600 mg for 3 months, was studied in 20 patients (23 eyes) with retinal haemorrhage caused by disturbances of retinal circulation, i.e. branch and/or total obstruction of the central retinal vein, obstruction of the central retinal artery, diabetic retinopathy and polycytaemic retinopathy. Twenty-two similar patients (27 eyes) formed a control group and were treated primarily with conventional fibrinolytic agents only. It was found that in the group treated with pentoxifylline, there was significantly earlier absorption of the haemorrhage and significantly less appearance of neovascularization. In some cases, prominent improvement of the arm-to-retina circulation time and a marked decrease in avascular areas were obtained. The difference in the improvement of visual acuity between the group treated with pentoxifylline and controls was less pronounced. Screening tests for haemorrhagic disorders were carried out in the group treated with pentoxifylline before and after administration. No side-effects causing haemorrhagic disorders were found. These results suggest that pentoxifylline is effective in preventing retinal or intra-vitreal neovascularization caused by retinal ischaemia and in hastening recovery from these diseases.


Evaluation of the role of routine melan-A immunohistochemistry for exclusion of microinvasion in 120 cases of lentigo maligna.
To assess the usefulness of routine melan-A immunohistochemistry (IHC) for exclusion of microinvasion in lentigo maligna (LM). One hundred and twenty cases of LM from our archives were reviewed by 2 authors with S100 protein and melan-A IHC using a red chromogen. Melan-A was useful to confirm the diagnosis of LM in early lesions and to differentiate these from chronically sun-damaged skin. The presence of scattered melan-A-positive cells was noted in the dermis in 72 of 120 cases (melanophages in 36 cases, nonspecific cells different to melanophages in 16 cases, and a dual cell population in 20 cases). The significance of these cells was uncertain. Only 3 cases suspicious for microinvasion were identified: 2 on haematoxylin and eosin and 1 on S100. We recommend use of melan-A to confirm the diagnosis in early lesions of LM and in the differential diagnosis from melanocytic hyperplasia in chronically sun-exposed skin. We do not recommend routine use of melan-A to identify or exclude microinvasion. However, it may have a role, in conjunction with S100, in cases with suspicious features for early invasion on haematoxylin and eosin sections.


The effect of the essential oil of Eugenia caryophyllata in animal models of depression and locomotor activity.
The essential oil of Eugenia caryophyllata (clove oil; Family: Myrtaceae) is used in dental care as an antiseptic and analgesic. The present study investigates the effect of clove oil on animal models of depression and locomotion. Clove oil was administered in doses of 0.025, 0.05, and 0.1 ml/kg/day, intraperitoneally (i.p.) for 3 weeks. The forced swim test (FST) and the tail suspension test (TST) were used to assess depression. To evaluate locomotor activity, the rota rod test and the photoactometer procedure were performed. In the FST, it was observed that the duration of immobility was significantly decreased (P < 0.01) in animals treated with clove oil (0.05 and 0.1 ml/kg); however, the clove oil dose of 0.025 ml/kg showed an insignificant increase in the immobile period. The TST demonstrated that pretreatment with clove oil decreases (P < 0.01) the immobile period significantly at all the three administered doses. Similarly, the photoactometer procedure showed increased locomotor activity at all the three doses, although significant (P < 0.05) only at 0.1 ml/kg. In addition, the rota rod test showed that animals treated with clove oil (0.1 ml/kg) enhanced muscle coordination as demonstrated by a significant increase (P < 0.05) in the latency to fall from the rota rod as compared to the control. However, the lowest administered dose (0.025 ml/kg, i.p.) decreased the latency to fall from the rota rod significantly (P < 0.05) compared to the control. Clove oil (0.05 ml/kg) also showed a decrease in the latency to fall from the rota rod although the result was not statistically significant. Thus, it can be concluded that pretreatment with clove oil decreases depression and enhances locomotor activity similar to that exhibited by psychostimulants.


Forms of Folate in the Monkey.
The predominant forms of folate found in monkey liver three days after parenteral administration of 3H pteroylglutamate contained five and six glutamyl residues and were primarily the 5-methyl, with lesser quantities of 5- and 10-formyl tetrahydro derivatives. Formation of polyglutamate forms occurred more slowly in kidney. A complex mixture of the polyglutamates was also found in intestinal mucosal cells.


Metabolism of cysteine, cysteinesulfinate and cysteinesulfonate in rats fed adequate and excess levels of sulfur-containing amino acids.
The oxidation of cysteine, cysteinesulfinate and cysteinesulfonate labeled with 14C in the 1- and 3-positions was studied in rats that had been fed diets with adequate or excess cysteine. Consumption of excess cysteine for 5 or 10 days resulted in an increase in hepatic cysteine dioxygenase activity and a decrease in hepatic cysteinesulfinate decarboxylase activity but had no effect on the oxidation of the C-1 or C-3 of cysteine, cysteinesulfinate or cysteinesulfonate. When the labeled compounds were administered by intraperitoneal injection, 41% of cysteine, 100% of cysteinesulfinate and 37% of cysteinesulfonate were oxidized over an 8-hour period. The percentage of the oxidized cysteine, cysteinesulfinate and cysteinesulfonate that was converted to taurine was calculated to be 83, 70 and 100%, respectively. When these same compounds were administered intragastrically, the relative flux to taurine was lower for all compounds; 41% of the oxidized cysteine, none of the cysteinesulfinate and 11% of the oxidized cysteinesulfonate appeared to be converted to taurine. Metabolism of intragastrically administered cysteine may be more indicative of what happens to dietary cysteine, whereas metabolism of intraperitoneally administered cysteine and cysteinesulfinate may be more indicative of liver metabolism and of the metabolism of endogenous cysteine and cysteinesulfinate.


Mesoscale Block Copolymers.
Materials composed of well-defined mesoscale building blocks are ubiquitous in nature, with noted ability to assemble into hierarchical structures possessing exceptional physical and mechanical properties. Fabrication of similar synthetic mesoscale structures will offer opportunities for precise conformational tuning toward advantageous bulk properties, such as increased toughness or elastic modulus. This requires new materials designs to be discovered to impart such structural control. Here, the preparation of mesoscale polymers is achieved by solution fabrication of functional polymers containing photoinduced chemical triggers. Subsequent photopatterning affords mesoscale block copolymers composed of distinct segments of alternating chemical composition. When dispersed in appropriate solvents, selected segments form helices to generate architectures resembling block copolymers, but on an optically observable size scale. This approach provides a platform for producing mesoscale geometries with structural control and potential for driving materials assembly comparable to examples found in nature.


Enhancer signatures stratify and predict outcomes of non-functional pancreatic neuroendocrine tumors.
Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered 'non-functional'1-3. As clinical behaviors vary widely and distant metastases are eventually lethal2,4, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major subtypes, with epigenomes and transcriptomes that partially resemble islet α- and β-cells. Transcription factors ARX and PDX1 specify these normal cells, respectively5,6, and 84% of 142 non-functional PNETs expressed one or the other factor, occasionally both. Among 103 cases, distant relapses occurred almost exclusively in patients with ARX+PDX1- tumors and, within this subtype, in cases with alternative lengthening of telomeres. These markedly different outcomes belied similar clinical presentations and histology and, in one cohort, occurred irrespective of MEN1 mutation. This robust molecular stratification provides insight into cell lineage correlates of non-functional PNETs, accurately predicts disease course and can inform postoperative clinical decisions.


An axial periodic fibrillar arrangement of antigenic determinants for fibronectin and procollagen on ascorbate treated human fibroblasts.
Fibronectin and collagens are major constituents of the cell matrix of fibroblasts. Fibronectin is a 220,000 dalton glycoprotein that mediates a variety of adhesive functions of cells examined in vitro. Fibronectin is secreted in a soluble form and interacts with collagen to form extracellular filaments. Fibronectin and procollagen type I were localized using the peroxidase anti-peroxidase method. Under standard culture conditions, fibronectin and procollagen were localized to non-periodic 10 nm extracellular fibrils, the cell membrane and plasma membrane vesicles. Ascorbate treatment of cells leads to a new larger fibril with a diameter of approximately 40 nm. Antibodies to fibronectin and procollagen I react to these native collagen fibrils with an axial periodicity of approximately 70 nm. Fibronectin is clearly associated with native collagen fibrils produced by ascorbate treated cells and there is an asymetric distribution or segregation of fibronectin on these collagen fibrils with a 70 nm axial repeat.


Neuroimaging strategies for three types of Horner syndrome with emphasis on anatomic location.
The purposes of this study were to review the anatomy of the oculosympathetic pathway, to describe the clinical characteristics of the three types of Horner syndrome, and to illustrate underlying pathologic features with an emphasis on neuroimaging strategies based on three symptom complexes. Horner syndrome results from interruption of the oculosympathetic pathway and is usually associated with unique clinical features classified into central, preganglionic, and postganglionic types according to the anatomic location of the underlying pathologic process.


Chlamydophila (Chlamydia) pneumoniae induces histidine decarboxylase production in the mouse lung.
Chlamydophila (Chlamydia) pneumoniae (C. pneumoniae) is the third most common cause of community-acquired pneumonia and is probably involved in the development of certain chronic inflammatory diseases, including atherosclerosis and adult-onset asthma. Histamine, synthesized by histidine decarboxylase (HDC) from L-histidine, plays an essential role in allergic and inflammatory processes and in cell differentiation. The effect of C. pneumoniae infection on the expression of HDC has not been examined. In the present study, normal Balb/c mice and HDC knockouts, and control mice with a CD1 background were infected intranasally with C. pneumoniae. On days 1, 3, 7, 16 and 31 after infection, the normal Balb/c mice were sacrificed and divided into three groups. In the homogenized lungs of the first group, C. pneumoniae titres were determined and demonstrated peak levels on day 7. HDC production was revealed by a Western blot assay throughout the observation period of 1-16 days, and cytokine concentrations were determined by ELISA. The interleukin-3 (IL-3) and interleukin-6 (IL-6) levels were highest on day 1 and on days 1-3, respectively; the interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels reached the maximum on day 7, but the quantity of IL-4 was still three times higher than that in the control group 16 days after infection. The lungs of the mice in the second group were processed for the in situ demonstration of HDC activity, while the lungs in the third group were stained for C. pneumoniae antigen. The HDC activity was increased predominantly in the bronchial epithelial cells, while C. pneumoniae antigens were expressed especially in the interstitial macrophages. The HDC knockout mice exhibited a higher survival rate after C. pneumoniae infection than did the control mice. These results point to a strong association between local histamine production and other inflammatory mediators and are novel in demonstrating the role of histamine in the pathomechanism of C. pneumoniae infections.


Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch.
In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).


[Effect of NK4 gene transfection on tumor growth of human pancreatic cancer xenograft in nude mice].
NK4 is not only an antagonist of hepatocyte growth factor but also an angiogenesis inhibitor. Studies have confirmed that NK4 can inhibit tumor growth and metastasis, but its effect on pancreatic cancer remains unknown. This study was designed to observe the effect of NK4 gene on human pancreatic cancer in nude mice and the possible mechanisms. The nude mouse model of pancreatic cancer was established with human pancreatic cancer cell line SW1990. The eukaryotic expression vector of NK4 gene was constructed and transfected into the tumors. The mice weight, tumor size and volume were measured before and after transfection. The apoptotic cells, microvessel density (MVD), and the expression of proliferating cell nuclear antigen (PCNA) in the tumors were observed using immunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. Four weeks after NK4 gene transfection, the tumor volume and weight was significantly smaller in NK4-transfected group than in PBS control group and empty vector group [(1.39+/-0.33) cm(3) vs. (2.06+/-0.55) cm(3) and (1.90+/-0.36) cm(3), P<0.01; (1.30+/-0.81) g vs. (3.45+/-1.88) g and (3.14+/-1.51) g, P<0.01]; the inhibition rate was 62.29%. The tumor cell apoptotic index was significantly higher in NK4-transfected group than in the rest 2 groups (9.34+/-0.91 vs. 4.13+/-0.79 and 3.94+/-1.03, P<0.001); the MVD was significantly lower in NK4-transfected group than in the rest 2 groups (12.24+/-4.63 vs. 20.13+/-7.00 and 19.70+/-6.15, P<0.05); the expression of PCNA in NK4-transfected group was not different from those of the rest 2 groups (53.88+/-4.30 vs. 56.24+/-4.03 and 54.33+/-5.41,P>0.05). NK4 gene transfection may inhibit the growth of human pancreatic cancer in mouse model through suppressing angiogenesis and enhancing the apoptosis of pancreatic cancer cells.


Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance.
Melatonin has been shown to protect against oxidative stress in various, highly divergent experimental systems. There are many reasons for its remarkable protective potential. Signaling effects comprise the upregulation of antioxidant enzymes, such as superoxide dismutases, peroxidases, and enzymes of glutathione supply, down-regulation of prooxidant enzymes, such as nitric oxide synthases and lipoxygenases, and presumably also the control of quinone reductase 2. Other mechanisms are based on direct interactions with several reactive oxygen and nitrogen species. Among these reactions, the capacity of easily undergoing single-electron transfer reactions is of particular importance. Electron donation by melatonin is not only an aspect of direct radical scavenging, but additionally represents the basis for formation of the protective metabolites AFMK (N1-ace-tyl-N2-formyl-5-methoxykynuramine) and AMK (N1-acetyl-5-methoxykynuramine). Recent investigations on mitochondrial metabolism indicate that melatonin as well as AMK are capable of supporting the electron flux through the respiratory chain, of preventing the breakdown of the mitochondrial membrane potential, and of decreasing electron leakage, thereby reducing the formation of superoxide anions. Radical avoidance is a new line of investigation, which exceeds mitochondrial actions and also comprises antiexcitatory effects and contributions to the maintenance of internal circadian phase relationships.


Adhesion-dependent interactions between eosinophils and cholinergic nerves.
Eosinophils adhere to airway cholinergic nerves and influence nerve cell function by releasing granule proteins onto inhibitory neuronal M(2) muscarinic receptors. This study investigated the mechanism of eosinophil degranulation by cholinergic nerves. Eosinophils were cocultured with IMR32 cholinergic nerve cells, and eosinophil peroxidase (EPO) or leukotriene C(4) (LTC(4)) release was measured. Coculture of eosinophils with nerves significantly increased EPO and LTC(4) release compared with eosinophils alone. IMR32 cells, like parasympathetic nerves, express the adhesion molecules vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 (ICAM-1). Inhibition of these adhesion molecules alone or in combination significantly inhibited eosinophil degranulation. IMR32 cells also significantly augmented the eosinophil degranulation produced by formyl-Met-Leu-Phe. Eosinophil adhesion to IMR32 cells resulted in an ICAM-1-mediated production of reactive oxygen species via a neuronal NADPH oxidase, inhibition of which significantly inhibited eosinophil degranulation. Additionally, eosinophil adhesion increased the release of ACh from IMR32 cells. These neuroinflammatory cell interactions may be relevant in a variety of inflammatory and neurological conditions.


Endothelial cellular senescence is inhibited by liver X receptor activation with an additional mechanism for its atheroprotection in diabetes.
Senescence of vascular endothelial cells leads to endothelial dysfunction and contributes to the progression of atherosclerosis. Liver X receptors (LXRs) are nuclear receptors whose activation protects against atherosclerosis by transcriptional regulation of genes important in promoting cholesterol efflux and inhibiting inflammation. Here we found that LXR activation with specific ligands reduced the increase in senescence-associated (SA) β-gal activity, a senescence marker, and reversed the decrease in telomerase activity, a replicative senescence marker, in human endothelial cells under high glucose. This effect of LXR activation was associated with reduced reactive oxygen species and increased endothelial NO synthase activity. A series of experiments that used siRNAs indicated that LXRβ mediates the prevention of endothelial cellular senescence, and that sterol regulatory element binding protein-1, which was up-regulated as a direct LXRβ target gene, may act as a brake of endothelial cellular senescence. Although oral administration of the LXR ligand led to severe fatty liver in diabetic rats, concomitant therapy with metformin avoided the development of hepatic steatosis. However, the preventive effect of the LXR ligand on SA β-gal-stained cells in diabetic aortic endothelium was preserved even if metformin was coadministered. Taken together, our studies demonstrate that an additional mechanism, such as the regulation of endothelial cellular senescence, is related to the antiatherogenic properties of LXRs, and concomitant treatment with metformin may provide a clinically useful therapeutic strategy to alleviate an LXR activation-mediated adverse effects on liver triglyceride metabolism.


IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells.
Recent studies into the pathogenesis of airway disorders such as asthma have revealed a dynamic role for airway smooth muscle cells in the perpetuation of airway inflammation via secretion of cytokines and chemokines. In this study, we evaluated whether IL-17 could enhance IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells (HASMC) and investigated the upstream and downstream signaling events regulating the induction of CXCL-8. CXCL-8 mRNA and protein induction were assessed by real-time RT-PCR and ELISA from primary HASMC cultures. HASMC transfected with site-mutated activator protein (AP)-1/NF-kappaB CXCL-8 promoter constructs were treated with selective p38, MEK1/2, and phosphatidylinositol 3-kinase (PI3K) inhibitors to determine the importance of MAPK and PI3K signaling pathways as well as AP-1 and NF-kappaB promoter binding sites. We demonstrate IL-17 induced and synergized with IL-1beta to upregulate CXCL-8 mRNA and protein levels. Erk1/2 and p38 modulated IL-17 and IL-1beta CXCL-8 promoter activity; however, IL-1beta also activated the PI3K pathway. The synergistic response mediating CXCL-8 promoter activity was dependent on both MAPK and PI3K signal transduction pathways and required the cooperation of AP-1 and NF-kappaB cis-acting elements upstream of the CXCL-8 gene. Collectively, our observations indicate MAPK and PI3K pathways regulate the synergy of IL-17 and IL-1beta to enhance CXCL-8 promoter activity, mRNA induction, and protein synthesis in HASMC via the cooperative activation of AP-1 and NF-kappaB trans-acting elements.


Minimally invasive approach for redo mitral valve surgery: a true benefit for the patient.
Redo mitral valve surgery via sternotomy is associated with a substantial morbidity and mortality. This study evaluated a minimally invasive technique for mitral valve redo procedures. Out of a series of 394 patients undergoing mitral valve repair or replacement via a right minithoracotomy, 39 patients underwent redo mitral valve surgery (59+/-13 years, 23 female). Previous cardiac surgeries included 17 patients with mitral valve repair, 6 patients with mitral valve replacement, 3 patients with aortic valve replacement, 2 patients with atrial septal defect closure, and 11 patients with coronary artery bypass grafting (CABG). In all cases, femoro-femoral cannulation was performed. The port access technique was applied in patients undergoing redo valve surgery. In patients with prior CABG, the operation was performed using deep hypothermia and ventricular fibrillation. In all cases, sternotomy was avoided. The mitral valve was replaced in 20 patients and repaired in 19. Time of surgery and cross-clamp time were comparable with the overall series (168+/-73 [redo] vs 168+/-58 min and 52+/-21 [redo] vs 58+/-25 min). Mortality was 5.1%. One patient had transient hemiplegia due to the migration of the endoclamp. All other patients had uneventful outcomes and normal mitral valve function at 3-month's follow-up. Redo mitral valve surgery can be performed safely using a minimally invasive approach in patients with a previous sternotomy. The right lateral minithoracotomy offers excellent exposure. It minimizes the need for cardiac dissection, and thus, the risk for injury. Avoiding a resternotomy increases patient comfort of redo mitral valve surgery.


Therapeutic angiogenesis: a complex problem requiring a sophisticated approach.
Blood and vascular disorders underlie a plethora of pathologic conditions and are the single most frequent cause of human disease. Ischemia, involving restricted blood flow to tissues is the most common consequence of vessel dysfunction resulting in the disruption of oxygen and nutrient delivery and the accumulation of waste metabolites. Cells cannot survive extended severe ischemia but may be able to adapt to a moderate condition where diffusion to and from bordering nonischemic regions sustains vital functions. Under this condition, the secondary functions of effected cells are likely to be impaired, and a new metabolic equilibrium is established, determined by the level of cross-diffusion and degree of hypoxia. In tissues with a normally high metabolic turnover such as skeletal and cardiac muscle, even mild ischemia causes hypoxia, acidosis, and depressed function (contractility) and eventually threatens myocyte viability and organ function. Ischemic cardiac muscle is additionally vulnerable because reperfusion is essential for survival but reperfusion itself poses additional stress principally from increased production of free radicals during reoxygenation. The latter effect is called reperfusion injury and can cause as much damage as the ischemia. The treatment possibilities for ischemia-related vascular disease are limited. Lipid/cholesterol-lowering agents, diet and antiplatelet adherence (aspirin) therapy may help slow the progression of vessel disease in some instances; but surgical reconstruction may be the only option in advanced stages, and even this is not always an option. An alternative and rather obvious strategy to treat ischemia is to activate endogenous angiogenic or arteriogenic pathways to stimulate revascularization of the tissue. The feasibility of such a strategy has now been established through the results of studies over the past decade, and a new discipline called therapeutic angiogenesis has emerged. This review focuses on the application of therapeutic angiogenesis for treating ischemic muscle disease and includes a critical evaluation of the parameters and limitations of current procedures. The development of this technology has benefited from its application to both peripheral and coronary artery disease and results from both are reviewed here.


The digestive behavior of pectin in human gastrointestinal tract: a review on fermentation characteristics and degradation mechanism.
Pectin is widely spread in nature and it develops an extremely complex structure in terms of monosaccharide composition, glycosidic linkage types, and non-glycosidic substituents. As a non-digestible polysaccharide, pectin exhibits resistance to human digestive enzymes, however, it is easily utilized by gut microbiota in the large intestine. Currently, pectin has been exploited as a novel functional component with numerous physiological benefits, and it shows a promising prospect in promoting human health. In this review, we introduce the regulatory effects of pectin on intestinal inflammation and metabolic syndromes. Subsequently, the digestive behavior of pectin in the upper gastrointestinal tract is summarized, and then it will be focused on pectin's fermentation characteristics in the large intestine. The fermentation selectivity of pectin by gut bacteria and the effects of pectin structure on intestinal microecology were discussed to highlight the interaction between pectin and bacterial community. Meanwhile, we also offer information on how gut bacteria orchestrate enzymes to degrade pectin. All of these findings provide insights into pectin digestion and advance the application of pectin in human health.