Gain modulation and odor concentration invariance in early olfactory networks.
The broad receptive field of the olfactory receptors constitutes the basis of a combinatorial code that allows animals to detect and discriminate many more odorants than the actual number of receptor types that they express. One drawback is that high odor concentrations recruit lower affinity receptors which can lead to the perception of qualitatively different odors. Here we addressed the contribution that signal-processing in the antennal lobe makes to reduce concentration dependence in odor representation. By means of calcium imaging and pharmacological approach we describe the contribution that GABA receptors play in terms of the amplitude and temporal profiles of the signals that convey odor information from the antennal lobes to higher brain centers. We found that GABA reduces the amplitude of odor elicited signals and the number of glomeruli that are recruited in an odor-concentration-dependent manner. Blocking GABA receptors decreases the correlation among glomerular activity patterns elicited by different concentrations of the same odor. In addition, we built a realistic mathematical model of the antennal lobe that was used to test the viability of the proposed mechanisms and to evaluate the processing properties of the AL network under conditions that cannot be achieved in physiology experiments. Interestingly, even though based on a rather simple topology and cell interactions solely mediated by GABAergic lateral inhibitions, the AL model reproduced key features of the AL response upon different odor concentrations and provides plausible solutions for concentration invariant recognition of odors by artificial sensors.


Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease.
Dendritic cells (DCs) are composed of a family of cells, now recognized to be essential for innate and acquired immunity. DCs at mucosal surfaces have a particular capacity to induce the differentiation of regulatory T cells producing interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in the steady state (non-infected, non-immunized), yet they retain the capacity to induce effector T cells in response to invasive pathogens. This decision between the induction of active immunity and tolerance will depend on the subpopulation of DC involved and the surface receptors engaged during DC activation and T-cell priming. The local microenvironment will likely play an important role both in defining the DC phenotype and in providing direct signals to responding T cells. Furthermore, DCs in organized mucosal lymphoid tissues preferentially induce the expression of CCR9 and alpha4beta7 on T cells, which results in T-cell homing to the intestinal lamina propria. Finally, DCs may play an important role in the maintenance of abnormal intestinal inflammation either by driving pathogenic T-cell responses in mesenteric lymph nodes or by acting to expand or maintain pathogenic T cells locally at sites of inflammation. In this review, a brief discussion of general issues of DC biology that are pertinent to mucosal immunity is followed by a more in-depth discussion of the phenotype and function of DC populations in the intestine.


[Comparison of the effect of eight kinds of volatile oil of Chinese material medica on percutaneous absorption of ibuprofen in vitro].
To compare the permeation-enhancing effect of the volatile oil of eight kinds of Chinese material medica including Fructus Evodia, Radix Saposhnikoviae, Rhizoma Atractylodes lancea Radix Aucklandiae, Radix Curcuma wenyujin, Rhizoma et Radix Notopterygii, Lignum Aquilariae Resinatum, Herba Schizonepetae on the model drug of ibuprofen in order to provide theoretic foundation for the selection and application of natural penetration enhancer. The permeation flux of ibuprofen was determined using the penetration experiment apparatus in vitro. The content of ibuprofen was measured by HPLC. All the above mentioned volatile oil showed permeation enhancing effect on ibuprofen in different degrees, and the enhancive permeation multiple was 3.46, 3.00, 2. 36, 2.32, 2.28, 2.01, 1.37 and 1.29. All eight kinds of volatile oil can enhance the percutaneous absorption of ibuprofen in vitro, among which the volatile oil of Fructus Evodia and Radix Saposhnikoviae showed significant penetration enhancing effect.


Increasing cardiac rate by tracking the respiratory rate.
The rate responsive pacemaker using respiratory rate as a sensor was implanted in 22 patients, 19 patients for ventricular pacing and three for atrial pacing. The level of exercise achieved with this system was consistently higher than with a fixed ventricular pacing rate. In addition, no special chemical or mechanical sensors are required; the sensor itself is simple, long-lasting, and energy efficient. Thus, this system adapts easily to the individual patient.


Air pollution exposure and the risk of macrosomia: Identifying specific susceptible months.
Birth weight is an important indicator of future growth and development for newborns. Few studies investigated the potential effects of air pollutants on macrosomia and their susceptible windows. We included 38,971 singleton full-term births from Beijing HaiDian Maternal and Child Health Hospital between 2014 and 2018, and assessed the associations of air pollutants exposure during preconception and pregnancy with macrosomia as well as the corresponding susceptible windows. The concentrations of air pollutants (PM2.5, PM10, SO2, NO2, CO and O3) for participants were calculated by the data from the nearest monitoring stations. Distributed lag models (DLM) incorporating logistic regression models were used to estimate the associations between air pollutants exposure during the 3 months before conception and pregnancy period and the risk of macrosomia, identifying susceptible windows of air pollutants. Weighted quantile sum (WQS) regression was applied to estimate the joint effect of air pollutants. A 10 μg/m3 increase in PM2.5 exposure from 3rd to 8th gestational month was positively associated with the risk of macrosomia, with the strongest effect in the 6th month (OR = 1.010, 95 % CI: 1.002-1.019). For a 10 μg/m3 increase in SO2, the windows of significant exposure were from the 1st preconception month to the 3rd gestational month, with the strongest effect in the 2nd month (OR = 1.030, 95 % CI: 1.010-1.049). We also observed the significant positive associations were in the 5th-8th gestational months for PM10, the 8th-9th gestational months for NO2 and the 3rd-7th gestational months for CO respectively. WQS regression also indicated a positive association between co-exposure to air pollutants and macrosomia. Our results suggest air pollution exposure is associated with increased risk of macrosomia. The windows of exposure for susceptibility to the risk of macrosomia vary between air pollutants. The susceptible exposure windows were middle and late pregnancy for PM, CO and NO2, while for SO2, early pregnancy is the window of vulnerability. Our findings provide the evidence that air pollution exposure is an independent risk factor for macrosomia and a basis for targeted environment policy.


Binding properties of a mannose-specific lectin from the snowdrop (Galanthus nivalis) bulb.
Carbohydrate binding properties of a new plant lectin (GNA) isolated from snowdrop bulbs were studied using the technique of quantitative precipitation, hapten inhibition, and affinity chromatography on immobilized lectin. Purified GNA precipitated highly branched yeast mannans but did not react with most glucans. Hapten inhibition experiments showed that D-mannose is an inhibitor of GNA-mannan interaction but neither N-acetyl-D-mannosamine nor D-glucose is an inhibitor. Hapten inhibition with various sugars showed that GNA requires the presence of equatorial hydroxyl groups at the C-3 and C-4 positions and an axial group at the C-2 position of the D-pyranose ring. A nonreducing terminal D-mannose residue is necessary for the interaction of oligosaccharides, and oligosaccharides with terminal Man(alpha-1-3)Man units showed the highest inhibitory potency (10-30 times greater than D-mannose) among the manno-oligosaccharides tested. The presence of the hydrophobic p-nitrophenyl aglycone increased the affinity of D-mannose only slightly. Immobilized GNA bound yeast mannan but did not bind glycogen. The behavior of glycoproteins with high mannose type glycan chains depended on the density and the structure of their glycan chains. Glycopeptides which carry Man(alpha 1-3)Man units were retarded on the immobilized GNA column whereas those lacking this unit or with hybrid type glycan chains were not retarded on the column.


Irradiation therapy for gallbladder carcinoma: recent advances.
Gallbladder carcinomas were usually considered to be radioresistant. So far, the role of radiotherapy has not been adequately evaluated. The aim of this report is to assess the value of radiotherapy in carcinoma of the gallbladder. We reviewed publications concerning the role of radiation therapy in gallbladder carcinoma from 1974 to 2000. External radiation therapy, intraoperative radiation therapy, and brachytherapy were evaluated in two different groups: one group of patients underwent surgery, with apparently complete resection of the tumor; and another group underwent palliative treatment. Local control of the tumor and reduction of tumor size were reported in several publications. Collected data suggested a slight improvement in survival after adjuvant or palliative radiotherapy. The best benefit was obtained in tumors resected with only microscopic residual tissue. If possible an intraoperative "boost" (15 Gy) is recommended on the gross lesion, residual lesion, or tumor bed. Additional postoperative external radiotherapy (45-50 Gy) must be delivered. Radiotherapy appears to be a safe procedure that slightly improves the survival time of patients treated for gallbladder carcinoma. Further trials are needed to assess the role of combined radiotherapy and chemotherapy.


Antioxidation, anti-hyperlipidaemia and hepatoprotection of polysaccharides from Auricularia auricular residue.
As hyperlipidemia was a pathological progress by lipid dysfunctions, the present object was to investigate the hypolipidemic and hepatoprotective effects of Auricularia auricular residue polysaccharides (RPS) against HFE (high-fat emulsion) toxicities in mice. The structure analysis showed that the RPS was pyranose-polysaccharides mainly composed of glucose with the weight-average molecular weight of 2.00 × 105 Da. The in vivo experiments demonstrated that the RPS had potential hepatoprotections by enhancing the antioxidant and anti-hyperlipidaemia status, and could inhibit the increasing body weights. Besides, the RPS could improve the glucose utilization with the oral glucose tolerance test (120 min) of 5.04 ± 0.12 mmol/L at the dose of 400 mg/kg bw. The results in present study demonstrated that RPS could be used as a functional foods and natural medicines against the HFE-induced hyperlipidemia and its complications.


COD::CIF::Parser: an error-correcting CIF parser for the Perl language.
A syntax-correcting CIF parser, COD::CIF::Parser, is presented that can parse CIF 1.1 files and accurately report the position and the nature of the discovered syntactic problems. In addition, the parser is able to automatically fix the most common and the most obvious syntactic deficiencies of the input files. Bindings for Perl, C and Python programming environments are available. Based on COD::CIF::Parser, the cod-tools package for manipulating the CIFs in the Crystallography Open Database (COD) has been developed. The cod-tools package has been successfully used for continuous updates of the data in the automated COD data deposition pipeline, and to check the validity of COD data against the IUCr data validation guidelines. The performance, capabilities and applications of different parsers are compared.


High Patient Satisfaction for up to 6 Months With OnabotulinumtoxinA Treatment for Upper Facial Lines.
OnabotulinumtoxinA safety and efficacy are well established for upper facial lines (UFL), including forehead lines (FHL), glabellar lines (GL), and crow's feet lines (CFL). To investigate the association of onabotulinumtoxinA efficacy with patient-reported psychological impacts and satisfaction in UFL. A pooled analysis of data from 4 pivotal Phase 3 trials (onabotulinumtoxinA vs placebo in FHL ± GL, FHL + GL ± CFL, CFL, and CFL + GL for ≤180 days) evaluated investigator-assessed ≥1-grade severity improvement on the Allergan Facial Wrinkle Scale at Day 30 (responders). Facial Line Outcomes (FLO-11) Questionnaire, Facial Line Satisfaction Questionnaire (FLSQ), and Subject Assessment of Satisfaction of Appearance (SASA) were used to evaluate responder appearance-related psychological impacts and satisfaction. OnabotulinumtoxinA patients, by primary study focus (FHL, GL, or CFL), totaled 921, 921, and 833, respectively; 786 patients received placebo. Most patients were female, White, and aged 45 to 50 years (median). Through 150 days, >42% FHL, >43% GL, and ≥32% CFL patients were onabotulinumtoxinA responders. Responders reported improvements in appearance-related psychological impacts (FLO-11) and high satisfaction (FLSQ and SASA), sustained through ≥150 days. A ≥1-grade improvement with onabotulinumtoxinA is a clinically meaningful outcome in UFL, associated with long-lasting improved patient-reported psychological impacts and high satisfaction.


Classification of ultrasonographic images of small hepatocellular carcinoma using galactose-based contrast agent: relation between image patterns and histologic features.
The aim of this study was to establish the relation between observed ultrasonographic (US) images produced with a galactose-based contrast agent and histologic characteristics of small hepatocellular carcinomas (HCCs). A total of 64 nodules in 64 patients, 22 well differentiated and 42 moderately differentiated with a histologically proven HCC, smaller than 3.0 cm in diameter and who had undergone hepatectomy were consecutively examined by contrast-enhanced US using a galactose-based contrast agent. Perfusion images were acquired by intermittent high-intensity, harmonic power Doppler sonography using a high pulse-repetition frequency and high-pass filter setting. Perfusion images of the arterial and late phases were classified into several patterns and compared with the histologic findings obtained from resected specimens. Most of the well- and moderately differentiated resected HCCs showed hyperechoic change during the arterial phase. However, 13 (59%) of the well-differentiated HCCs showed isoechoic change and 27 (64%) of the moderately differentiated HCCs showed hypoechoic change during the late phase. The difference is statistically significant (P < 0.0001). In a comparison of microscopic portal invasion (vp) of HCCs using enhanced US patterns, both vp(-) and vp(+) groups showed a high incidence of the hypervascular pattern during the arterial phase; in contrast, during the late phase 11 (73%) of 15 vp(+) nodules showed hypoechoic change with spotty signals. This difference is statistically significant (P < 0.0001) when compared with a high incidence (52%) of signal defect in the vp(-) group. The existence of well-differentiated components associated with the periphery of moderately differentiated HCCs also correlated closely with patterns during the late phase (P < 0.01). Late-phase contrast-enhanced US images of small HCCs with a galactose-based contrast agent are useful for predicting specific histologic characteristics.


Battle tactics against MMP-9; discovery of novel non-hydroxamate MMP-9 inhibitors endowed with PI3K/AKT signaling attenuation and caspase 3/7 activation via Ugi bis-amide synthesis.
Matrix metalloproteinases (MMPs) are major modulators of the tumor microenvironment. They participate in extracellular matrix turnover, tumor growth, angiogenesis and metastasis. Accordingly, MMPs inhibition seems to be ideal solution to control cancer. Many MMPs inhibitors have been introduced ranging from hydroxamate-based peptidomimetics to the next generation non-hydroxamate inhibitors. Among MMPs, MMP-9 is attractive druggable anticancer target. Studies showed that inhibiting AKT, the central signaling node of MMP-9 upregulation, provides additional MMP-9 blockade. Furthermore, caspase-dependent AKT cleavage leads to cell death. Herein, Ugi MCR was utilized as a rapid combinatorial approach to generate various decorated bis-amide scaffolds as dual MMP-9/AKT inhibitors endowed with caspase 3/7 activation potential. The target adducts were designed to mimic the thematic structural features of non-hydroxamate MMP inhibitors. p-Nitrophenyl isonitrile 1 was utilized as structure entry to Ugi products with some structural similarities to amide-based caspase 3/7 activators. Besides, various acids, amines and aldehydes were employed as Ugi educts to enrich the SAR data. All adducts were screened for cytotoxicity against normal fibroblasts and three cancer cell lines; MCF-7, NFS-60 and HepG-2 utilizing MTT assay. 8, 11 and 28 were more active and safer than doxorubicin with single-digit nM IC50 and promising selectivity. Mechanistically, they exhibited dual MMP-9/AKT inhibition at single-digit nM IC50 with excellent selectivity over MMP-1,-2 and -13, and induced >51% caspase 3/7 activation. Consequently, they induced >49% apoptosis as detected by flow cytometric analysis, and inhibited cell migration (metastasis) up to 97% in cancer cells. Docking simulations were nearly consistent with enzymatic evaluation, also declared possible binding modes and essential structure features of active compounds. In silico physicochemical properties, ligand efficiency and drug-likeness metrics were reasonable for all adducts. Interestingly, 8 and 28 can be considered as drug-like candidates.


Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.
Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.


A comparison of two procedures for labelling the surface of the hydatid disease organism, Echinococcus granulosus, with 125I.
Living, intact protoscoleces of the British horse and sheep strains of Echinococcus granulosus were subjected to surface radioiodination procedures using 125I and Iodogen and 125I-Bolton Hunter reagent. Subsequent combined electron microscopy and autoradiography revealed specific surface membrane labelling with the Iodogen procedure, but significant tegumental labelling with the Bolton-Hunter reagent. The two parasite strains yielded different profiles of electrophoretically separated labelled proteins; the Iodogen method, not surprisingly, resulted in a less complex pattern of labelled polypeptides than the Bolton and Hunter reagent.


A community-based survey to assess risk for one health challenges in rural Philippines using a mobile application.
Recent emerging and re-emerging diseases in animals and humans show the vulnerability of humans, animals, and crops to disease outbreaks and the large potential impact on health, food security, and economies worldwide. A technology-enabled One Health (OH) surveillance program offers an opportunity for early detection and response as well as prevention of disease outbreaks in resource-limited settings. As an initial step toward developing the surveillance program, we aimed to identify at-risk groups of households for potential shared health challenges at the human-animal-environmental interface in a rural community of the Philippines. A cross-sectional household survey was conducted in the municipality of Los Baños in proximity (63 kilometers south) to Metro Manila by enumerators living in the same community. Twenty-four enumerators conducted household interviews asking a) household characteristics including ownership of animals and crops; b) awareness, beliefs and knowledge about OH; c) family-level health practices related to sanitation, hygiene, and food safety; and d) risk factors for potential OH issues. All data collection and transferring process were streamlined using a mobile application. Of 6,055 participating households, 68% reported having one or more of gardens, farms, and animals for various reasons. While only 2% of the households have heard about OH, 97% believed they can get disease from animals, plants or the environment. A latent class analysis with nine risk factors for potential OH issues suggested that 46% of the households were at moderate to high risk for exposure to zoonotic pathogens and environmental contaminants. Our findings indicate that there are unaddressed threats to human, animal, and plant health. Given the importance of the interconnections between the health of humans, animals, and plants, further evaluations of the at-risk households would be necessary to mitigate potential shared health threats in the community. Further, our study demonstrates that mHealth technology can provide an opportunity to systematically assess potential one health problems in the rural communities with limited internet connection.


Phasic changes in upper airway impedance.
To identify within breath variations in the mechanical properties of the isolated upper airway, we examined changes in impedance spectra over the course of the respiratory cycle. Changes were evaluated with a modified forced oscillation technique applied to the isolated, sealed upper airways of nine anesthetized mongrel dogs. Upper airway impedance spectra were studied during sequential 350 msec epochs. We found spectral changes which were reproducible within the respiratory cycle. Impedance spectra revealed that during mid-inspiration at the point of peak upper airway muscle activity, the low frequency real part decreased and the imaginary part was less negative and less steep. During late inspiration and early expiration the impedance values returned to their end-expiratory values. The only significant change in parameter estimates from a three-parameter model indicated an increase in compliance. Since these changes correlated not only with tidal flow through the lower trachea and lung but also with upper airway muscle activation, we reasoned that changes in impedance could have resulted from an increase in upper airway size. Therefore, we used a sealed speaker system and, while the animal was apnoeic, evaluated impedance at two different airway pressures and the resultant volumes. The changes in impedance spectra with a volume increase were similar to those seen during spontaneous breathing efforts. We conclude that the mechanical properties of the upper airway change during the respiratory cycle and that these changes correlate with the respiratory activation of upper airway muscles. We suspect that these changes in input impedance could reflect a change in the size of the airway rather than a true increase in elasticity.


Detection of Aeromonas hydrophila DNA oligonucleotide sequence using a biosensor design based on Ceria nanoparticles decorated reduced graphene oxide and Fast Fourier transform square wave voltammetry.
A new strategy was introduced for ssDNA immobilization on a modified glassy carbon electrode. The electrode surface was modified using polyaniline and chemically reduced graphene oxide decorated cerium oxide nanoparticles (CeO2NPs-RGO). A single-stranded DNA (ssDNA) probe was immobilized on the modified electrode surface. Fast Fourier transform square wave voltammetry (FFT-SWV) was applied as detection technique and [Ru(bpy)3](2+/3+) redox signal was used as electrochemical marker. The hybridization of ssDNA with its complementary target caused a dramatic decrease in [Ru(bpy)3](2+/3+) FFT-SW signal. The proposed electrochemical biosensor was able to detect Aeromonas hydrophila DNA oligonucleotide sequence encoding aerolysin protein. Under optimal conditions, the biosensor showed excellent selectivity toward complementary sequence in comparison with noncomplementary and two-base mismatch sequences. The dynamic linear range of this electrochemical DNA biosensor for detecting 20-mer oligonucleotide sequence of A. hydrophila was from 1 × 10(-15) to 1 × 10(-8) mol L(-1). The proposed biosensor was successfully applied for the detection of DNA extracted from A. hydrophila in fish pond water up to 0.01 μg mL(-1) with RSD of 5%. Besides, molecular docking was applied to consider the [Ru(bpy)3](2+/3+) interaction with ssDNA before and after hybridization.


Genetic and other influences on red-cell flavin enzymes, pyridoxine phosphate oxidase and glutathione reductase in families with beta-thalassaemia.
In 18 beta-thalassaemia families from the Ferrara area the incidence of an inherited low flavin mononucleotide (FMN)-dependent pyridoxine phosphate (PNP) oxidase activity, a sensitive indicator of red-cell FMN deficiency, is higher in related members in these families than in the unrelated spouses and controls subjects without family history of thalassaemia. This suggests slower red-cell riboflavin metabolism in thalassaemia families, which may have resulted from selection in combination with thalassaemia by malaria. However, there was a markedly higher incidence of red-cell flavin adenine dinucleotide (FAD) deficiency in thalassaemia heterozygotes than in their normal relatives. This was indicated by higher stimulation of FAD-dependent glutathione reductase (GR) activity by FAD and lower GR activity per red cell, and suggests a marked additive effect by thalassaemia on the red cell FAD deficiency that results from the inherited slow riboflavin metabolism. There is evidence that diversion of FAD to other FAD-dependent enzymes might be an important factor.


Dermal absorption and skin damage following hydrofluoric acid exposure in an ex vivo human skin model.
The wide industrial use of hydrofluoric acid (HF) poses a high risk for accidental dermal exposure. Despite local and systemic hazards associated with HF, information on percutaneous penetration and tissue damage is rare. In the present ex vivo study, the dermal absorption of HF (detected in terms of fluoride ions) was quantified and the skin damaging potential as a function of concentration and exposure duration was assessed. Percutaneous penetration of HF (c=5, 30, and 50%) at 3 exposure durations (3, 5, and 10 min) was investigated in a static diffusion cell model using freshly excised human skin. Alterations of skin were histologically evaluated. HF rapidly penetrated through skin under formation of a considerable intradermal reservoir (∼ 13-67% of total absorbed fluoride). Histologically, epidermal alterations were detected already after exposure to 5% HF for 3 min. The degree of skin damage increased with rising concentration and exposure duration leading to coagulation necrosis. For HF concentrations of ≥ 30%, skin damage progressed into deeper skin layers. Topically applied HF concentration was the principal parameter determining HF induced skin effects. The intradermal HF retention capacity associated with progression and prolongation of HF induced skin effects must be considered in the review of skin decontamination procedures.


Q455V mutation in COL8A2 is associated with Fuchs' corneal dystrophy in Korean patients.
To investigate the possibility of collagen type VIII alpha2 (COL8A2) as a potential susceptibility gene for Korean patients with Fuchs' corneal dystrophy (FECD), we performed mutation screening of the COL8A2 gene. A total of 25 FECD patients were screened, including 15 patients from six pedigrees with early onset FECD and an additional 10 unrelated patients, all of Korean ancestry. Seventy-three control individuals without corneal disease were selected from the general population. PCR-SSCP and direct sequencing were used to screen genetic variations in COL8A2. The pathogenic impact of these sequence variants was evaluated through the SIFT and PolyPhen algorithms. We have identified a novel heterozygous mutation, Q455V, in exon 2 of COL8A2. All patients of Korean pedigrees with FECD had the Q455V mutation, and two out of nine unrelated cases also had this mutation. But it was not present in unaffected individuals from these pedigrees or from control groups. Two heterozygous missense mutations, R155Q and T502M, were also observed, but, they showed no significant difference between FECD patients and controls. The allele frequencies of A35A and G495G, which were synonymous substitutions, were significantly associated with FECD. Both Q455V and T502M were predicted as deleterious mutations by computational methods using PolyPhen and SIFT. Our data constitute the first report of a heterozygous Q455V mutation of the COL8A2 gene in Korean patients with FECD. Q455V may be the causative defect in the development and progression of Korean FECD patients.


Theoretical evaluation of peak capacity improvements by use of liquid chromatography combined with drift tube ion mobility-mass spectrometry.
In the domain of liquid phase separations, the quality of separation obtainable is most readily gauged by consideration of classical chromatographic peak capacity theory. Column-based multidimensional strategies for liquid chromatography remain the most attractive and practical route for increasing the number of spatially resolved components in order to reduce stress on necessary mass spectrometric detection. However, the stress placed on a chromatographic separation step as a second dimension in a comprehensive online methodology (i.e. online LC×LC) is rather high. As an alternative to online LC×LC combinations, coupling of HPLC with ion mobility spectrometry hyphenated to mass spectrometry (IMS-MS) has emerged as an attractive approach to permit comprehensive sampling of first dimension chromatographic peaks and subsequent introduction to an orthogonal IMS separation prior to measurement of ions by a mass spectrometer. In the present work, utilization of classical peak capacity and ion mobility theory allows theoretical assessment of the potential of two- (LC×IMS-MS) or even three-dimensional (LC×LC×IMS-MS) experimental setups to enhance peak capacity and, therefore, the number of correctly annotated features within the framework of complex, non-targeted analysis problems frequently addressed using HPLC-MS strategies. Theoretical calculations indicate that newly-available drift tube IMS-MS instrumentation can yield peak capacities of between 10 and 40 using nitrogen drift gas for typical non-targeted metabolomic, lipidomic and proteomic applications according to the expected reduced mobilities of components in the respective samples. Theoretically, this approach can significantly improve the overall peak capacity of conventional HPLC-(MS) methodologies to in excess of 10(4) depending upon the column length and gradient time employed. A more elaborate combination of LC×LC×IMS-MS would improve the ion suppression limitation and possibly allow access to theoretically even higher peak capacities, but such a combination may render the IMS separation practically redundant as well as imparting the well-known dilution problems associated with LC×LC. Finally, some predictions for the separation of co-eluted isobaric compounds can also be made by considering the required peak-to-peak resolution for acceptable IMS separation. The here-described theoretical predication approach can be used to aid method development for HPLC×IMS-MS and is also accompanied by some practical considerations that should be contemplated in associated non-targeted analysis workflows.


(2-Thienylmethyl)ammonium trichlorostannate(II): a hybrid salt.
The structure of the title hybrid salt, (C(5)H(8)NS)[SnCl(3)], is built up from segregated layers of organic cations and Sn polyhedra. [SnCl(3)](-) groups are linked together by weak Sn...Cl interactions to form a one-dimensional polymeric chain of anions.


Molecular endocrine changes of Gh/Igf1 axis in gilthead sea bream (Sparus aurata L.) exposed to different environmental salinities during larvae to post-larvae stages.
The influence of acclimation of the euryhaline gilthead sea bream (Sparus aurata) larvae/post-larvae to brackish water on growth, energetic contents, and mRNA levels of selected hormones and growth-regulating hypothalamic neurohormones was assessed. Specimens from 49 days post-hatching were acclimated during 28 days to two different environmental salinities: 38 and 20 psu (as brackish water). Both groups were then transferred to 38 psu and acclimated for an additional week. Early juveniles were sampled after 28 days of acclimation to both salinities and one week after transfer to 38 psu. Pituitary adenylate cyclase-activating peptide (adcyap1; pacap), somatostatin-I (sst1), growth hormone (gh1), insulin-like growth factor-I (igf1), and prolactin (prl) mRNA expression were all studied by QPCR. Post-larvae acclimated to 20 psu showed better growth performance and body energetic content than post-larvae maintained at 38 psu. prl, adcyap1, and igf1 mRNA expression levels increased in 20-psu-acclimated post-larvae but decreased upon transfer to 38 psu. GH1 expression did not show significant changes under both experimental conditions. Our results suggested an enhanced general performance for post-larvae in brackish water, supported by the actions of adcyap1, igf1, and prl.


Characterization of a ferredoxin:NADP+ oxidoreductase from a nonphotosynthetic plant tissue.
A flavoprotein with properties similar to those of ferredoxin:NADP+ oxidoreductases found in the leaves of higher plants has been purified to apparent homogeneity from bean sprouts, a nonphotosynthetic plant tissue. The absorbance and circular dichroism spectra of the bean sprout protein are similar to those of spinach leaf ferredoxin:NADP+ oxidoreductase and an antibody raised against the spinach enzyme recognized the bean sprout enzyme. The bean sprout enzyme catalyzed ferredoxin-dependent electron transfer from NADPH to equine cytochrome c at a high rate but, unlike the spinach enzyme, exhibited little NADPH to 2,6-dichlorophenol indophenol diaphorase activity. The bean sprout enzyme forms a 1:1 electrostatically stabilized complex with ferredoxins isolated from either bean sprouts or spinach leaves.


Evidence for the existence of alpha-adrenoceptors in the rat lung.
Isolated rat lung parenchymal strips responded to carbachol, 5-HT and phenylephrine (PE) with contractions. Bradykinin (BK), histamine, PGF2 alpha, PGE1, PGE2 and dimaprit were either inactive or produced weak relaxations. Isoproterenol, noradrenaline (NA) and epinephrine (E) relaxed lung strips. The further increase in their concentrations produced contractions of varying magnitudes. The lung strips contracted to 5-HT or carbachol, responded to isoproterenol and E and NA with relaxations. Metiamide and cimetidine (selective histamine H2-receptor antagonists) did not alter responses to histamine and carbachol. Propranolol (a beta-adrenoceptor blocker) antagnoized or reversed relaxations to E and isoproterenol, and markedly enhanced contractions to NA, PE and E. Atropine and phentolamine or dibenzyline antagonized contractions to carbachol and sympathomimetic agents, respectively. From study it may be concluded that there are alpha- and beta-adrenergic receptors mediating contractions and relaxations in the peripheral airways of rat.


Asymmetric one-dimensional exclusion processes: a two-parameter exactly solvable example.
We consider a two-parameter family of asymmetric exclusion processes for particles living on a continuous one-dimensional space. Using the Bethe ansatz, the exact solution to the master equation, and from that the drift and the diffusion rate in the two particle sector, are obtained.


Central effects of the beta-adrenergic blocking agent acebutolol. A quantitative EEG study using normalised slope descriptors.
The effects of acute intravenous injection of acebutolol 25 mg on the EEG were investigated in 5 normal subjects. On-line EEG analysis was carried out by a special purpose mini-computer using normalised slope descriptors (hjorth parameters). No significant changes were found apart from those due to drowsiness in 2 subjects, although minute to minute ECG frequency was significantly lowered (p = 0.031). The EEG, which is considered to be a sensitive tool, failed to show any conclusive evidence of any central action of the drug. The effects of beta-adrenergic blockers on the CNS are not yet fully understood.


Extrapancreatic perineural invasion in pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma continues to be a highly lethal disease, despite advances in modern medicine. Curative surgical options continue to carry significant morbidity and offer little improvement in overall 5-year survival. Currently, imaging plays an essential role in the pre-operative evaluation of patients who are undergoing evaluation for resection. However, some pancreatic cancers have particularly aggressive biology, despite appearing resectable by conventional imaging criteria. Imaging biomarkers that serve as surrogates for tumors with such aggressive phenotype have been recently described, namely duodenal invasion and extrapancreatic perineural invasion. In this pictorial review, we will summarize key concepts of extrapancreatic perineural invasion, describe its association with a poor prognosis, and highlight the role of imaging in its detection.


First-year college students' weight change is influenced by their randomly assigned roommates' BMI.
There is ongoing debate about whether friends' greater similarity in Body Mass Index (BMI) than non-friends is due to friend selection, shared environments, or peer influence. First-year college students (n = 104) from a southwestern U.S. university were randomly assigned roommates during the university's housing process, effectively removing friend selection effects. Participant BMI was measured up to four times (T1-T4) across 2015-2016. The influence of roommate baseline BMI (T1) on change in participant BMI over time (T2-T4) was analyzed using a linear mixed effects model adjusted for individual socio-demographics, linear time trends, baseline BMI, and physical clustering of students. A sensitivity analysis examining floormates was also conducted. Consistent with roommate influence, participants randomized to roommates with a higher BMI gained more weight between times T2 and T4 (β = 0.06; 95% CI = 0.02, 0.10). No shared environment effects (shared campus or floor) were found. Randomly assigned roommates influenced each other's weight trajectories. This clarifies that BMI convergence can occur outside of friend selection or shared environments mechanisms.


Inflammatory markers are elevated in early pregnancy, but not late pregnancy, in women with overweight and obesity that later develop preeclampsia.
Obesity and preeclampsia both involve a pathological inflammatory response, which may be how obesity increases preeclampsia risk. Previous studies have failed to assess robust measurements of inflammatory markers across gestation, specifically in overweight/ obese women in the context of preeclampsia. We measured 20 inflammatory markers in plasma via multiplex assay (ThermoFisher Inflammation 20 plex Human ProcartaPlex Panel) across the three trimesters of pregnancy in an existing cohort of overweight and obese women who developed preeclampsia (n = 37) and without preeclampsia (n = 74). Mann-Whitney U tests examined differences in inflammatory marker concentrations between cases and controls. Repeated measures ANOVA tests were used to explore differences in inflammatory marker concentrations over time within cases and controls. Pro-inflammatory markers (IL-1α, IL-1β, IL-6, IFN-α, IFN-γ, GM-CSF, IL-12p70, IL-17α, TNF-α, IL-8) and anti-inflammatory markers (IL-4, IL-10, IL-13) were higher in the first and second trimester in participants who later developed preeclampsia compared to those who did not (p < .05). Only TNF-α and IL-8 remained elevated in the third trimester. Inflammatory markers did not change across pregnancy in preeclampsia cases but did increase across pregnancy in controls. Our findings diverge from prior studies, predominantly of non-obese women, that report lower circulating concentrations of anti-inflammatory cytokines in preeclampsia versus normotensive pregnancy, particularly by late pregnancy. We posit that women with overweight and obesity who develop preeclampsia entered pregnancy with a heightened pro-inflammatory state likely related to obesity, which increased risk for preeclampsia. Further studies are needed to investigate if inflammatory maker profiles differ between obese and non-obese women.


Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat.
Following a cortical injury, neurons in areas near and connected to the site of injury begin to degenerate. The observed neuronal death may contribute to the severity of the observed behavioral impairments. The purpose of the present study was to examine if progesterone, a hormone known for its effectiveness at reducing cerebral edema, could protect against secondary neuronal death and facilitate the acquisition of an avoidance learning task in an ablation model of cortical injury. Rats served as sham controls or received bilateral ablation of the medial prefrontal cortex followed by a 10-day regimen of progesterone (4 mg/kg) or oil vehicle (1 ml/kg) beginning 1 h after cortical lesions. Progesterone-treated lesion rats showed a significant facilitation of avoidance learning compared to oil-treated lesion controls. In addition, progesterone-treated lesion animals did not differ from either progesterone- or oil-treated sham controls in avoidance learning. Anatomical analysis revealed that progesterone treatment decreased the amount of neuronal death seen in the striatum and the mediodorsal nucleus of the thalamus. The findings are consistent with the notion that progesterone is an effective neuroprotective agent and suggest that the hormone can reduce the behavioral impairments associated with frontal cortical ablation injury.


Quadruplex-Templated and Catalyzed Ligation of Nucleic Acids.
Template-guided chemical reactions between nucleic acid strands are an important process in biomedical research. However, almost all of these reactions employ an oligonucleotide-templated approach that is based on the double-helix alignment. The moderate stability of the double helix makes this approach unsuitable for many chemical reactions, so alternative nucleic acid alignment mechanisms, demonstrating higher thermal and chemical stability, are desirable. Earlier, we described a noncovalent coupling mechanism between DNA strands through a quadruplex-and-Mg2+ connection (QMC). QMC is based on G-quadruplexes and allows unusually stable and specific interactions. Herein, a novel catalytic nucleic acid reaction, based on QMC, is described. This approach uses G-tetrads as a structural and recognition element without employing Watson-Crick complementarity rules at any stage of substrate/catalyst formation or interaction between them. Quadruplex-templated ligation can be achieved through the self-ligation of two nucleic acid strands, or through a quadruplex catalyst, which forms a G-triplex and specifically connects the strands. The process is extraordinarily robust and efficient. For instance, the ligation of carbodiimide-activated substrates can proceed in boiling solutions, and complete ligation is demonstrated within a minute. The quadruplex-templated and catalyzed reactions will create new opportunities for chemical reactions requiring harsh experimental conditions.


The role of attentional slippage in Stroop dilution.
The present study examined the cognitive locus of Stroop dilution using a psychological refractory period (PRP) paradigm. Participants were asked to perform a tone discrimination task via a bimanual keypress response and a modified Stroop task via a vocal response serially as Task 1 and Task 2, respectively. In Task 2, a neutral word was added on half of the trials and no neutral word on the other half of the trials to observe the Stroop dilution effect. The amount of Stroop dilution, as well as the Stroop effect, was relatively constant across different stimulus-onset asynchronies (SOAs), which implies that Stroop dilution occurs due to the competition between a neutral word and a color word after a target color bar is selected to be processed further. These results indicate that focused attention plays an important role in the modulation of Stroop interference by the presence of a neutral word.


Cdx regulates gene expression through PRC2-mediated epigenetic mechanisms.
The extra-embryonic yolk sac contains adjacent layers of mesoderm and visceral endoderm. The mesodermal layer serves as the first site of embryonic hematopoiesis, while the visceral endoderm provides a means of exchanging nutrients and waste until the development of the chorioallantoic placenta. While defects in chorioallantoic fusion and yolk sac hematopoiesis have been described in Cdx mutant mouse models, little is known about the gene targets and molecular mechanisms through which Cdx members regulate these processes. To this end, we used RNA-seq to examine Cdx-dependent gene expression changes in the yolk sac. We find that loss of Cdx function impacts the expression of genes involved in yolk sac hematopoiesis, as previously described, as well as novel Cdx2 target genes. In addition, we observed Cdx-dependent changes in PRC2 subunit expression accompanied by altered H3K27me3 deposition at a subset of Cdx target genes as early as E7.5 in the embryo proper. This study identifies additional Cdx target genes and provides further evidence for Cdx-dependent epigenetic regulation of gene expression in the early embryo, and that this regulation is required to maintain gene expression programs in the extra-embryonic yolk sac at later developmental stages.


Enhanced adsorption of Cd (II) from aqueous solution by a shrimp bran modified Typha orientalis biochar.
The biochar which was characterized with well-developed facial structure and O-/N-containing functional groups could effectively remove Cd (II) from water. In this paper, Typha orientalis-based biochar (BCS) with well-developed N containing functional groups was modified with shrimp bran which was rich in crude protein for the first time. There are more well-developed O-/N-containing functional groups in the structure of BCS than that of pure Typha orientalis-based biochar without any modification (BC), and this conclusion was depended on their comparisons of Brunauer-Emmett-Teller (BET), X-ray diffraction (XRD), scanning electron microscopy (SEM), elemental analysis (EA), Boehm titration, Fourier transform infrared (FTIR), and other characterization techniques. Moreover, according to the experiment, the phenomenon that the adsorption capacity of Cd(II) on these two adsorbents (BCs) decreased with the increase of solution ionic strength could be carried out. The Cd(II) adsorption studies combined with X-ray photoelectron spectroscopy (XPS) analysis revealed that the adsorption mechanism was mainly attributed to physical microporous filtration and chemical interaction between Cd(II) and the surface functional groups (surface complexation, ion exchange, and electrostatic attraction).


Cladribine tablets in people with relapsing multiple sclerosis: A real-world multicentric study from southeast European MS centers.
Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS). To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS). A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries. We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment. Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals.


Genotypic variation in the tolerance to moderate cadmium toxicity among 20 maize genotypes with contrasting root systems.
Cadmium (Cd) contamination in farmland is a serious environmental and safety issue affecting plant growth, crop productivity, and human health. This study aimed to investigate genotypic variation in root morphology and Cd accumulations under moderate Cd stress among diverse maize genotypes. Twenty maize genotypes with contrasting root systems were assessed for Cd tolerance 39 days after transplanting (V6, six-leaf stage) under 20 μmol L-1 CdCl2 using a semi-hydroponic phenotyping platform in a glasshouse. Cadmium stress significantly inhibited plant growth across all genotypes. Genotypic variation in response to Cd toxicity was apparent: shoot dry weight varied from 0.13 (genotype NS2020) to 0.35 g plant-1 (Dongke301) with deductions up to 63% compared with non-Cd treatment (CK). Root dry weight of 20 genotypes ranged from 0.06 (NS2020) to 0.18 g plant-1 (Dongke301) with a deduction up to 56%. Root length ranged from 2.21 (NS590b) to 9.22 m (Dongke301) with a maximal decline of 76%. Cadmium-treated genotypes generally had thicker roots and average diameter increased by 34% compared with CK. Genotypes had up to 3.25 and 3.50 times differences in shoot and root Cd concentrations, respectively. Principal component and cluster analyses assigned the 20 genotypes into Cd-tolerant (five genotypes) and Cd-sensitive (15 genotypes) groups. Maize genotypes varied significantly in response to moderate Cd stress. Cadmium-tolerant genotypes optimized root morphology and Cd accumulation and distribution. This study could assist in the selection and breeding of new cultivars with improved adaptation to Cd-contaminated soil for food and feed or land remediation purposes. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Does Pulmonary Hamartoma Increase the Risk of Lung Cancer? Outcomes of 38 Pulmonary Hamartoma Cases.
Hamartomas are common benign tumors of the lung. Rarely, lung cancer coincidence may occur at the time of diagnosis or in the follow-up period. Between 2016 and 2019, 38 patients who underwent a surgical procedure and diagnosed with lung hamartoma were retrospectively evaluated regarding clinicopathological features. Cases were analyzed according to age, sex, radiological findings, localization of nodules, surgical methods, and the coincidence of lung cancer. The mean age was 50.2±11.1 (range 28-76 years). There were 23 male (60.5%) and 15 female (39.5%) patients. Mean size was 2.7±1.8 (range 0.8-10 cm). In 28 patients, hamartoma was <3 cm in diameter (73.6%). Eighteen hamartomas were localized in the upper lobe (47.4%). Only 6 cases (15.8%) were localized at the central part of the lung. Multiple nodules were reported in 10 cases (26.3%). In 4 cases (10.5%), lung carcinoma and hamartoma were seen together at the time of diagnosis. Video-assisted thoracoscopic surgery (VATS) has been performed in 29 cases (76.3%). As a surgical method, enucleation was performed in 4 cases (10.5%), wedge resection in 28 cases (73.7%), and lobectomy in 6 cases (15.8%). No post-operative mortality appeared in the early follow-up. Pulmonary hamartomas are usually present as solitary pulmonary nodules with benign radiological findings. VATS wedge resection is a method that can be used safely in diagnosis and treatment. Hamartomas may be associated with lung cancer at the time of diagnosis or follow-up, so it should be kept in mind that a different nodule seen in patients diagnosed with hamartoma may be associated with lung cancer.


Investigating the Integrity of Graphene towards the Electrochemical Hydrogen Evolution Reaction (HER).
Mono-, few-, and multilayer graphene is explored towards the electrochemical Hydrogen Evolution Reaction (HER). Careful physicochemical characterisation is undertaken during electrochemical perturbation revealing that the integrity of graphene is structurally compromised. Electrochemical perturbation, in the form of electrochemical potential scanning (linear sweep voltammetry), as induced when exploring the HER using monolayer graphene, creates defects upon the basal plane surface that increases the coverage of edge plane sites/defects resulting in an increase in the electrochemical reversibility of the HER process. This process of improved HER performance occurs up to a threshold, where substantial break-up of the basal sheet occurs, after which the electrochemical response decreases; this is due to the destruction of the sheet integrity and lack of electrical conductive pathways. Importantly, the severity of these changes is structurally dependent on the graphene variant utilised. This work indicates that multilayer graphene has more potential as an electrochemical platform for the HER, rather than that of mono- and few-layer graphene. There is huge potential for this knowledge to be usefully exploited within the energy sector and beyond.


A new era for steroid-resistant nephrotic syndrome in childhood.
Among youth with incident nephrotic syndrome, those with steroid-resistant nephrotic syndrome (SRNS) often have an ominous clinical course. Identifying them at or shortly after diagnosis would potentially prevent substantial morbidity and even mortality. For those with a specific monogenic form, targeted therapy might be possible, as is the case presently for CoQ10 insufficiency cases. Further, dissecting specific causes and pathways that lead to SRNS may lead to other targeted, potentially highly effective treatments.


Expectant management of severe preterm preeclampsia: a comparison of maternal and fetal indications for delivery.
To examine the delivery indication (maternal or fetal) for patients with preterm preeclampsia and assess whether disease characteristics at presentation are predictive of delivery indication. We conducted a retrospective cohort study at a tertiary hospital in Melbourne, Australia (Mercy Hospital for Women). We assessed indication for delivery for participants presenting with preeclampsia from 23(+0) to 32(+6) weeks gestation. We compared baseline disease characteristics, disease features at delivery and postnatal outcomes between those delivered for maternal or fetal indications, or for both maternal and fetal indications. Two hundred sixty six participants presented with preterm preeclampsia and 108 were eligible for inclusion in our study. More participants were delivered for maternal indications at 65.7% compared to those requiring delivery on fetal grounds at 19.4% or for both indications at 14.8% (p < 0.0001). Maternal disease characteristics at presentation were similar between groups; however, there was a higher proportion of growth restriction and abnormal Dopplers among those delivered on fetal grounds. Participants delivered on maternal grounds gained less gestation, had higher blood pressure and higher incidence of abnormal liver function tests than those delivering for fetal indications at delivery. Participants with preterm preeclampsia were predominantly delivered due to maternal disease progression compared to fetal compromise.


Ethanol and current thresholds for brain self-stimulation in the lateral hypothalamus of the rat.
Two groups of animals were implanted with stimulating electrodes in the lateral hypothalamus for intracranial self-stimulation (ICSS). Following surgery these animals were trained in the auto-titration, brain self-stimulation procedure which measured both the rate of responding and the reinforcement threshold for electrical stimulation. When behavior was stable, one group was given saline or ethanol (0.1-1.7 g/kg) administered intraperitoneally (IP) either 15 or 60 min before testing. The other group was given saline or ethanol (1.0-4.5 g/kg) administered intragastrically (IG) 15 or 60 min before testing. With IP administration, there was a graded decrease in lever-pressing at 15 min but the effect was less obvious at 60 min. There were no changes in threshold except at the highest dose when behavior was disrupted. With IG administration, a reduction in the rate of responding occurred at 15 min only. No changes in thresholds were observed at any dose level or injection-test interval. Thus, administration of ethanol either by the IP or IG route did not affect the reinforcement thresholds for ICSS in the lateral hypothalamus, and these results contrasted with those of other drugs of abuse such as amphetamine or morphine.


Enzymically attaching oligosaccharide-linked 'cargoes' to cellulose and other commercial polysaccharides via stable covalent bonds.
The Equisetum enzyme hetero-trans-β-glucanase (HTG) covalently grafts native plant cellulose (donor-substrate) to xyloglucan (acceptor-substrate), potentially offering a novel 'green' method of cellulose functionalisation. However, the range of cellulosic and non-cellulosic donor substrates that can be utilised by HTG is unknown, limiting our insight into its biotechnological potential. Here we show that HTG binds all celluloses tested (papers, tissues, hydrogels, bacterial cellulose) to radioactively- or fluorescently-labelled xyloglucan-heptasaccharide (XXXGol; acceptor-substrate). Glycol-chitin, glycol-chitosan and chitosan also acted as donor substrates but less effectively than cellulose. Cellulose-XXXGol conjugates were formed throughout the volume of a block of hydrogel, demonstrating penetration. Plant-derived celluloses (cellulose Iβ) became more effective donor-substrates after 'mercerisation' in ≥3 M NaOH; the opposite was true for bacterial cellulose Iα. Cellulose-XXXGol bonds resisted boiling 6 M NaOH, demonstrating strong glycosidic bonding. In conclusion, HTG stably grafts native and processed celluloses to xyloglucan-oligosaccharides, which may carry valuable 'cargoes', exemplified by sulphorhodamine. We thus demonstrate HTG's biotechnological potential to modify various cellulose-based substrates such as textiles, pulps, papers, packaging, sanitary products and hydrogels.


New Horizons in the development of antiepileptic drugs: Innovative strategies.
The past decades have brought many advances to the treatment of epilepsy. However, despite the continued development and release of new antiepileptic drugs, many patients have seizures that do not respond to drug therapy or have related side effects that preclude continued use. Even in patients in whom pharmacotherapy is efficacious, current antiepileptic drugs do not seem to affect the progression or the underlying natural history of epilepsy. Furthermore, there is currently no drug available which prevents the development of epilepsy, e.g. after head trauma or stroke. Thus, there are at least four important goals for the future: (1) development of better antiepileptic ("anti-ictal") drugs with higher efficacy and tolerability to stop seizures compared to current medications; (2) better understanding of processes leading to epilepsy, thus allowing to create therapies aimed at the prevention of epilepsy in patients at risk; (3) development of disease-modifying therapies, interfering with progression of epilepsy, and (4) improved understanding of neurobiological mechanisms of pharmacoresistance, allowing to develop drugs for reversal or prevention of drug resistance. The third Workshop on New Horizons in the Development of Antiepileptic Drugs explored these four goals for improved epilepsy therapy, with a focus on innovative strategies in the search for better anti-ictal drugs, for novel drugs for prevention of epilepsy or its progression, and for drugs overcoming drug resistance in epilepsy. In this conference review, the current status of antiepileptic therapies under development is critically assessed, and innovative approaches for future therapies are highlighted.


Chemoselection as a strategy for organ preservation in advanced oropharynx cancer: response and survival positively associated with HPV16 copy number.
To test induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CRT) or surgery/radiotherapy (RT) for advanced oropharyngeal cancer and to assess the effect of human papilloma virus (HPV) on response and outcome. Sixty-six patients (51 male; 15 female) with stage III to IV squamous cell carcinoma of the oropharynx (SCCOP) were treated with one cycle of cisplatin (100 mg/m(2)) or carboplatin (AUC 6) and with fluorouracil (1,000 mg/m(2)/d for 5 days) to select candidates for CRT. Those achieving a greater than 50% response at the primary tumor received CRT (70 Gy; 35 fractions with concurrent cisplatin 100 mg/m(2) or carboplatin (AUC 6) every 21 days for three cycles). Adjuvant paclitaxel was given to patients who were complete histologic responders. Patients with a response of 50% or less underwent definitive surgery and postoperative radiation. Pretreatment biopsies from 42 patients were tested for high-risk HPV. Fifty-four of 66 patients (81%) had a greater than 50% response after IC. Of these, 53 (98%) received CRT, and 49 (92%) obtained complete histologic response with a 73.4% (47 of 64) rate of organ preservation. The 4-year overall survival (OS) was 70.4%, and the disease-specific survival (DSS) was 75.8% (median follow-up, 64.1 months). HPV16, found in 27 of 42 (64.3%) biopsies, was associated with younger age (median, 55 v 63 years; P = .016), sex (22 of 30 males [73.3%] and five of 12 females [41.7%]; P = .08), and nonsmoking status (P = .037). HPV titer was significantly associated with IC response (P = .001), CRT response (P = .005), OS (P = .007), and DSS (P = .008). Although the numbers in this study are small, IC followed by CRT is an effective treatment for SCCOP, especially in patients with HPV-positive tumors; however, for patients who do not respond to treatment, alternative treatments must be developed.


Enhanced potassium-stimulated gamma-aminobutyric acid release by astrocytes derived from rats with early hepatogenic encephalopathy.
Bulk-isolated astrocytes from rats with early hepatogenic encephalopathy (HE) induced with thioacetamide responded to the increase of potassium in the incubation medium from 5 mM to 75 mM with a markedly enhanced release of previously taken up [14C]gamma-aminobutyric acid ([14C]GABA). The process was not affected by omission of calcium and/or addition of EGTA to the incubation medium. Only a slight stimulation of GABA release by high potassium was observed in astrocytes from control rats. In contrast, histamine and histidine were vigorously released from control astrocytes in high-potassium medium, and their release was not enhanced by HE, indicating that the observed phenomenon is specific for GABA.


Hypoxia causes reductions in birth weight by altering maternal glucose and lipid metabolism.
Hypoxia of residence at high altitude (>2500 m) decreases birth weight. Lower birth weight associates with infant mortality and morbidity and increased susceptibility to later-in-life cardiovascular and metabolic diseases. We sought to determine the effects of hypoxia on maternal glucose and lipid metabolism and their contributions to fetal weight. C57BL6/NCrl mice, housed throughout gestation in normobaric hypoxia (15% oxygen) or normoxia, were studied at mid (E9.5) or late gestation (E17.5). Fetal weight at E17.5 was 7% lower under hypoxia than normoxia. The hypoxic compared with normoxic dams had ~20% less gonadal white adipose tissue at mid and late gestation. The hypoxic dams had better glucose tolerance and insulin sensitivity compared with normoxic dams and failed to develop insulin resistance in late gestation. They also had increased glucagon levels. Glucose uptake to most maternal tissues was ~2-fold greater in the hypoxic than normoxic dams. The alterations in maternal metabolism in hypoxia were associated with upregulation of hypoxia-inducible factor (HIF) target genes that serve, in turn, to increase glycolytic metabolism. We conclude that environmental hypoxia alters maternal metabolism by upregulating the HIF-pathway, and suggest that interventions that antagonize such changes in metabolism in high-altitude pregnancy may be helpful for preserving fetal growth.


Inhibition of microRNA-222 up-regulates TIMP3 to promotes osteogenic differentiation of MSCs from fracture rats with type 2 diabetes mellitus.
Type 2 diabetes mellitus (T2DM) is the most common diabetes and has numerous complications. Recent studies demonstrated that T2DM compromises bone fracture healing in which miR-222 might be involved. Furthermore, tissue inhibitor of metalloproteinase 3 (TIMP-3) that is the target of miR-222 accelerates fracture healing. Therefore, we assume that miR-222 could inhibit TIMP-3 expression. Eight-week-old rats were operated femoral fracture or sham, following the injection of streptozotocin (STZ) to induce diabetes one week later in fractured rats, and then, new generated tissues were collected for measuring the expression of miR-222 and TIMP-3. Rat mesenchymal stem cells (MSCs) were isolated and treated with miR-222 mimic or inhibitor to analyse osteogenic differentiation. MiR-222 was increased in fractured rats and further induced in diabetic rats. In contrast, TIMP-3 was reduced in fractured and further down-regulated in diabetic rats. Luciferase report assay indicated miR-222 directly binds and mediated TIMP-3. Furthermore, osteogenic differentiation was suppressed by miR-222 mimic and promoted by miR-222 inhibitor. miR-222 is a key regulator that is promoted in STZ-induced diabetic rats, and it binds to TIMP3 to reduce TIMP-3 expression and suppressed MSCs' differentiation.


Mechanisms of post-synaptic excitation in amphibian motoneurones.
1. Post-synaptic excitation produced in motoneurones of the isolated perfused frog spinal cord by different monosynaptic inputs and by ionophoretically applied glutamate was analysed with intracellular recording technique. 2. Ca2+-deficient, high Mg2+ (5--20 mM) media or addition of Mn2+ (2mM) or Co2+ (5 mM) reversibly abolished chemically mediated e.p.s.p.s derived from medullary reticular formation, ventral and lateral columns, but not the short-latency, rapidly rising e.p.s.p.s derived from dorsal roots or muscle nerves, suggesting electric coupling between some primary afferents and spinal motoneurones. This conclusion is consistent with the dynamic properties of dorsal root e.p.s.p.s, their small sensitivity to cooling, and with results of correction of intracellular records made for contribution of extracellular field potential. E.p.s.p.s evoked by ventral root stimulation were also insensitive to Ca2+-lack and presence of 5--10 mM-Mg2+. 3. As the post-synaptic membrane was made more negative the amplitude of electrotonic dorsal root e.p.s.p.s was increased, and it was decreased by depolarizing currents. No reversal of the early part of the electrotonic e.p.s.p. was observed, although the presence of the local response would account for the occasional reversal of its later phase seen with depolarization. 4. When hyperpolarizing and depolarizing currents were applied to motoneurones in which chemically mediated e.p.s.p.s of the reticular cells, the ventral and lateral columns, were evoked, the actual reversal of the early part of e.p.s.p. was not observed, and there was no correlation between the sensitivity of the e.p.s.p.s to injected currents and their time course. The positive values of the extrapolated reversal potentials and the effects of changes in ionic content of perfusing media suggest that synaptically released transmitter triggers off the Na permeability of the subsynaptic membrane. 5. The amplitude of depolarization produced by ionophoretically applied glutamate depends non-linearly on membrane potential and the curvature of this dependence differs from that seen with chemically mediated s.p.s.p.s. The asymptotic nature of this relationship is explicable by a dependence of the membrane conductance change upon the membrane voltage. 6. The results of conductance measurements during the glutamate induced depolarization, the values of apparent reversal potentials and their dependence on external Na+ and K+ and internal Cl- is explicable by the opening post-synaptic channel gates for Na+ and closing post-synaptic channel gates for K+. 7. Chemical and electrical transmission in the amphibian cord is discussed in relation to recent anatomical findings.


Comprehensive insights into antibiotic resistance gene migration in microalgal-bacterial consortia: Mechanisms, factors, and perspectives.
With the overuse of antibiotics, antibiotic resistance gene (ARG) prevalence is gradually increasing. ARGs are considered emerging contaminants that are broadly concentrated and dispersed in most aquatic environments. Recently, interest in microalgal-bacterial biotreatment of antibiotics has increased, as eukaryotes are not the primary target of antimicrobial drugs. Moreover, research has shown that microalgal-bacterial consortia can minimize the transmission of antibiotic resistance in the environment. Unfortunately, reviews surrounding the ARG migration mechanism in microalgal-bacterial consortia have not yet been performed. This review briefly introduces the migration of ARGs in aquatic environments. Additionally, an in-depth summary of horizontal gene transfer (HGT) between cyanobacteria and bacteria and from bacteria to eukaryotic microalgae is presented. Factors influencing gene transfer in microalgal-bacterial consortia are discussed systematically, including bacteriophage abundance, environmental conditions (temperature, pH, and nutrient availability), and other selective pressure conditions including nanomaterials, heavy metals, and pharmaceuticals and personal care products. Furthermore, considering that quorum sensing could be involved in DNA transformation by affecting secondary metabolites, current knowledge surrounding quorum sensing regulation of HGT of ARGs is summarized. In summary, this review gives valuable information to promote the development of practical and innovative techniques for ARG removal by microalgal-bacterial consortia.


Transcranial electrical stimulation of the occipital cortex during visual perception modifies the magnitude of BOLD activity: A combined tES-fMRI approach.
The aim of this study was to investigate if the blood oxygenation level-dependent (BOLD) changes in the visual cortex can be used as biomarkers reflecting the online and offline effects of transcranial electrical stimulation (tES). Anodal transcranial direct current stimulation (tDCS) and 10Hz transcranial alternating current stimulation (tACS) were applied for 10min duration over the occipital cortex of healthy adults during the presentation of different visual stimuli, using a crossover, double-blinded design. Control experiments were also performed, in which sham stimulation as well as another electrode montage were used. Anodal tDCS over the visual cortex induced a small but significant further increase in BOLD response evoked by a visual stimulus; however, no aftereffect was observed. Ten hertz of tACS did not result in an online effect, but in a widespread offline BOLD decrease over the occipital, temporal, and frontal areas. These findings demonstrate that tES during visual perception affects the neuronal metabolism, which can be detected with functional magnetic resonance imaging (fMRI).


Radiation dose evaluations during radiological contrast studies in patients with morbid obesity.
The purpose of this study was to evaluate the radiation dose to patients during radiological contrast studies performed after vertical banded gastroplasty (VBG) or Roux-en-Y gastric bypass (RYGBP) surgery in patients with morbid obesity. Dose evaluations were performed on a sample of 39 patients (32 women and 7 men) with a mean weight of 117 kg (range 68-175 kg) and a mean body mass index (BMI) of 43.7 (range 22.2-54.9). Between the second and seventh postoperative day, patients underwent radiological follow-up after oral administration of approximately 70 ml of water-soluble iodinated contrast material (Gastrografin) and images acquired in anteroposterior, right and left oblique projections with the patient upright and then supine. Exposure conditions, dose-area product (DAP) and entrance skin dose (ESD) were recorded for each procedure. On the basis of these data, the effective dose (ED) was calculated using simulation software based on the Monte Carlo method for determining the absorbed dose to organs. To assess the optimal exposure conditions and the dose contributions of fluoroscopy and radiography, the effective dose rates were also evaluated using Plexiglas phantoms of different thickness to simulate different patient sizes. The phantom measurements showed a fourfold dose increase when passing from normal-sized patients to obese patients. Mean DAP value obtained from in-vivo measurements was 70 Gy cm(2) (range 17-147 Gy cm(2)), and mean effective dose was 21 mSv (range 5-45 mSv). When performing radiological contrast studies in patients with morbid obesity, every possible precaution should be taken to minimise patient dose. Special care should be taken to evaluate justification of the radiological procedure.


CpG-ODN enhances ingestion of apoptotic neutrophils by macrophages.
The clearance of apoptotic neutrophils by macrophages plays an important role in the process of inflammatory response. In the present study, we examined the ability of macrophages to ingest apoptotic neutrophils after activated by synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) in vitro. The results showed that, while CpG-ODN at the experimental concentration had no cytotoxic effect on the viability of macrophages, the percentage of macrophages with ingested apoptotic neutrophils was increased from 23.6 to 42.30% by CpG-ODN stimulation. This effect was silenced when macrophages were treated with the mutation of CpG-ODN motifs. Both the total and cell surface protein of Toll-like receptor 9 (TLR9) expression in macrophages was up-regulated after CpG-ODN stimulation. While chloroquine (CHQ) had no effect on TLR9 expression in macrophages, it abolished the enhanced uptake of apoptotic neutrophils by macrophages. Although CpG-ODN had no significant effect on the IL-6 production, it was able to induce the increase of TNF-alpha protein expression and this effect was inhibited by CHQ pretreatment. Increased TNF-alpha production from macrophages induced by CpG-ODN stimulation was down-regulated after phagocytosis of apoptotic neutrophils. In conclusion, CpG-ODN could enhance the ingestion of apoptotic neutrophils by macrophages via TLR9 accompanied with an increasing in the level of TNF-alpha. After phagocytosis of apoptotic neutrophils, the increased TNF-alpha production from macrophages induced by CpG-ODN stimulation was down-regulated which the implications in the immune response remains for the further study.


16,16-Dimethyl prostaglandin E2 induces villus contraction in rats without affecting intestinal restitution.
In a previous study we found that 16,16-dimethyl prostaglandin E2 protects the small intestine against chenodeoxycholic acid injury in the rat. One possible explanation for prostaglandin's protective action may be that prostaglandin-induced villus contraction accelerates mucosal restitution. This hypothesis was tested in rats by perfusing intestinal segments in vivo in a single-pass fashion with 0.125-0.5 micrograms/L of 16,16-dimethyl prostaglandin E2. These studies showed a dose-dependent, reversible contraction of intestinal villi and crypts. To test the effect of this contraction on mucosal restitution, standardized intestinal injury was produced in indomethacin-pretreated rats perfused in vivo with 5 mmol/L chenodeoxycholic acid. The rats were then perfused with bile acid-free buffer containing either 0.5 microgram/mL of 16,16-dimethyl prostaglandin E2 or vehicle. This study showed that despite decreasing villus height after bile acid injury, 16,16-dimethyl prostaglandin E2 did not significantly affect the rate of morphologic (assessed by villus denudation) or functional (assessed by mannitol and water absorption) restitution of the injured intestinal mucosa. Thus, although 16,16-dimethyl prostaglandin E2 causes villus contraction, this effect does not result in more rapid restitution of the injured intestinal mucosa and is not a likely mechanism for prostaglandin-mediated protection of the intestinal mucosa.


Green "turn-off" luminescent nanosensors for the sensitive determination of desperately fluorescent antibacterial antiviral agent and its metabolite in various matrices.
Nitazoxanide (NTX) is an antimicrobial drug that was used for the treatment of various protozoa. However, during the coronavirus pandemic, NTX has been redirected for the treatment of such virus that primarily infect the respiratory tract system. NTX is now used as a broad-spectrum antiviral agent. In this study, a highly sensitive and green spectrofluorometric method was developed to detect NTX in various dosage forms and its metabolite, tizoxanide (TX), in human plasma samples using nitrogen and sulfur co-doped carbon quantum dots nanosensors (C-dots). A simple and eco-friendly hydrothermal method was used to synthetize water soluble C-dots from citric acid and l-cysteine. After excitation at 345 nm, the luminescence intensity was measured at 416 nm. Quenching of C-dots luminescence occurred upon the addition of NTX and was proportional to NTX concentration. Assessment of the quenching mechanism was performed to prove that inner filter effect is the underlying molecular mechanism of NTX quenching accomplished. After optimizing all experimental parameters, the analytical procedure was evaluated and validated using the ICH guidelines. The method linearity, detection and quantification limits of NTX were 15 × 10-3-15.00 µg/mL, 56.00 × 10-4 and 15 × 10-3 µg/mL, respectively. The proposed method was applied for the determination of NTX in its commercial pharmaceutical products; Nanazoxid® oral suspension and tablets. The obtained % recovery, relative standard deviation and % relative error were satisfactory. Comparison with other reported spectrofluorimetric methods revealed the superior sensitivity of the proposed method. Such high sensitivity permitted the selective determination of TX, the main metabolite of NTX, in human plasma samples making this study the first spectrofluorimetric method in literature that determine TX in human plasma samples. Moreover, the method greenness was assessed using both Eco-Scale and AGREE approaches to prove the superiority of the proposed method greenness over other previously published spectrofluorimetric methods for the analysis of NTX and its metabolite, TX, in various dosage forms and in human plasma samples.


Poverty and maternal mortality in Nigeria: towards a more viable ethics of modern medical practice.
Poverty is often identified as a major barrier to human development. It is also a powerful brake on accelerated progress toward the Millennium Development Goals. Poverty is also a major cause of maternal mortality, as it prevents many women from getting proper and adequate medical attention due to their inability to afford good antenatal care. This Paper thus examines poverty as a threat to human existence, particularly women's health. It highlights the causes of maternal deaths in Nigeria by questioning the practice of medicine in this country, which falls short of the ethical principle of showing care.Since high levels of poverty limit access to quality health care and consequently human development, this paper suggests ways of reducing maternal mortality in Nigeria. It emphasizes the importance of care ethics, an ethical orientation that seeks to rectify the deficiencies of medical practice in Nigeria, notably the problem of poor reproductive health services.Care ethics as an ethical orientation, attends to the important aspects of our shared lives. It portrays the moral agent (in this context the physician) as a self who is embedded in webs of relations with others (pregnant women). Also central to this ethical orientation is responsiveness in an interconnected network of needs, care and prevention of harm.This review concludes by stressing that many human relationships involve persons who are vulnerable, including pregnant women, dependent, ill and or frail, noting that the desirable moral response is that prescribed by care ethics, which thus has implications for the practice of medicine in Nigeria.


Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota.
Gut microbiota dysbiosis is closely involved in intestinal carcinogenesis. A marked reduction in butyrate-producing bacteria has been observed in patients with colorectal cancer (CRC); nevertheless, the potential benefit of butyrate-producing bacteria against intestinal tumor development has not been fully investigated. We found that Clostridium butyricum (C. butyricum, one of the commonly used butyrate-producing bacteria in clinical settings) significantly inhibited high-fat diet (HFD)-induced intestinal tumor development in Apcmin/+ mice. Moreover, intestinal tumor cells treated with C. butyricum exhibited decreased proliferation and increased apoptosis. Additionally, C. butyricum suppressed the Wnt/β-catenin signaling pathway and modulated the gut microbiota composition, as demonstrated by decreases in some pathogenic bacteria and bile acid (BA)-biotransforming bacteria and increases in some beneficial bacteria, including short-chain fatty acid (SCFA)-producing bacteria. Accordingly, C. butyricum decreased the fecal secondary BA contents, increased the cecal SCFA quantities, and activated G-protein coupled receptors (GPRs), such as GPR43 and GPR109A. The anti-proliferative effect of C. butyricum was blunted by GPR43 gene silencing using small interfering RNA (siRNA). The analysis of clinical specimens revealed that the expression of GPR43 and GPR109A gradually decreased from human normal colonic tissue to adenoma to carcinoma. Together, our results show that C. butyricum can inhibit intestinal tumor development by modulating Wnt signaling and gut microbiota and thus suggest the potential efficacy of butyrate-producing bacteria against CRC.


Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats.
Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats' livers. STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR. Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P < 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P < 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P < 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P < 0.05) and decrease MDA levels (P < 0.001) compared to diabetic control group. Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.


Efficient electrochemical generation of ferrate(VI) by iron coil anode imposed with square alternating current and treatment of antibiotics.
Anode passivation is still a main challenge for the electrochemical generation of ferrate(VI, Fe(VI)), leading to the reduction of Fe(VI) production efficiency. In this study, cyclic voltammetry, scanning electronic microscopy, and electrochemical impedance spectroscopy were used to select better anode electrode configurations (iron wire, iron gauze, and iron coil). The results indicate that iron coil had the least degree of passivation. Different imposed current waveforms during the electrochemical generation of Fe(VI) were also investigated, and the iron coil imposed with square alternating current (AC) wave can mitigate the anode passivation, resulting in higher Fe(VI) production efficiency. The optimum conditions for the electrochemical generation of Fe(VI) were evaluated and the optimum temperature (40 ℃), current density (10 mA/cm2), AC cycle period (15 s) and electrolyte concentrations (14 M NaOH) were identified. As a result, 0.12 mol/L Fe(VI) concentration and over 50% of current efficiency can be achieved after 3 h electrolysis. The generated Fe(VI) solution was further applied to oxidize doxycycline(DOX) and sulfadiazine(SDZ) as typical antibiotics. Over 80% of DOX can be removed at a Fe(VI) to DOX molar ratio of 5:1 (pH = 4-9), whilst a higher Fe(VI) to SDZ molar ratio of 20:1 (pH = 7) was needed to obtain 75% SDZ removal.


Galectins in the Tumor Microenvironment: Focus on Galectin-1.
In the last decades, the focus of cancer research has moved from epithelial cells to the tumor milieu, in an effort to better understand tumor development and progression, and with the important end goal of translating this knowledge into effective therapies. The galectin family of glycan-binding proteins displays important functions in cancer development and progression. Numerous groups have made outstanding contributions to deepen our knowledge about the role of galectins in the tumor-stroma crosstalk, defining them as key players in modulating interactions between tumor cells and the extracellular matrix, fibroblasts, endothelium, and the immune system. While several members of the family have been of particular interest until now, others are still considered as future exploding stars. This chapter provides an overview for galectin-1, the first identified and still one of the most well-studied galectins, and highlights the very important implications in its regulation of the tumor microenvironment in many different tumor types. Besides, a glimpse of the role of other galectins in the tumor milieu is also provided. Gaining a deeper understanding about the numerous roles of galectin-1 will not only help us to better understand other galectins but also is likely to result in the development of more effective cancer therapies.


Spermiogenesis in Platichthys flesus.
Early spermatids of Platichthys flesus (flounder) have a central spherical nucleus and cytoplasm with numerous dispersed mitochondria and a pair of peripheral centrioles. One of the centrioles acts as a kinetosome for axoneme formation. After the start of chromatin condensation the centrioles and developing axoneme migrate to adopt a tangential orientation adjacent to a flattened, lateral margin of the nucleus. During migration, pericentriolar material becomes reorganised. The proximal centriole becomes surrounded by nine fibres, and the distal centriole by a complex collar. As the nucleus condenses it undergoes a rotation which shifts it to the anterior of the centrioles and deepens the articular fossa which houses, and is connected to, the two centrioles and their associated structures. This rotation also results in the mitochondria becoming relocated to form a ring around the proximal region of the axoneme to give the cell its mature ultrastructure.


Activities of enzymes associated with phosphoenolpyruvate metabolism in the mudskippers, Boleophthalmus boddaerti and Periophthalmodon schlosseri.
1. PK and LDH activities in the muscle of Periophthalmodon schlosseri and Boleophthalmus boddaerti were at least 100-fold higher than their respective activities in the liver. 2. The ratio of PK:PEPCK in liver of B. boddaerti was smaller than that of P. schlosseri. 3. PK:PEPCK ratios in both fishes were intermediate between those of aerobic and anaerobic organisms. 4. MDH activity was higher than other enzymes assayed in the liver of both fishes. 5. The ratios of LDH:MDH in the liver of both mudskippers were comparable to those of anaerobic organisms. 6. AST was at least eight times more active than ALT in the liver of both fishes. 7. In the muscle of these mudskippers, the aspartate content was significantly less than that of alanine. 8. Exposure of these fishes to various experimental conditions led to changes in specific activities of PEPCK, LDH, AST and ALT.


An uvsB mutant of Aspergillus nidulans with high variable spontaneous mutation and intergenic mitotic recombination frequencies.
An UV-sensitive mutant has been isolated with a new technique which allows isolation of UV-sensitive and UV-non-mutable mutants in Aspergillus nidulans. This mutant is an allele of the known uvsB gene but shows some features not previously described in the alleles so far isolated. Its more important characteristics are: (1) Frequency of mitotic intergenic recombination is strongly increased in uvs/uvs diploids and it is highly variable in different clones: it varies from a minimum of 40-fold to a maximum of about 1000-fold in comparison with uvs+/uvs+ strains. (2) The frequency of mitotic intergenic recombination is increased also in the heterozygous diploids. (3) The frequency of spontaneous mutation is higher and highly variable in different subclones: it may be increased up to 1000-fold.


Decrease in stereoacuity in the seventh decade of life.
We measured stereoacuity in 41 subjects with normal Snellen acuity in each eye, and normal ocular health. Patients were measured in each of the age ranges 21-28, 41-49, 51-59 and 60-70 years. Stereoacuity was reduced from about 16 sec arc for the three younger groups to about 27 sec arc for the older subjects. Since stereopsis has a cortical neural substrate, these data suggest that there may be cortical changes affecting the interaction of information from the two eyes with advancing age, but whether these changes result from loss of contrast sensitivity, instability of ocular alignment or binocular stress, all of which have been reported in elderly subjects, is not known.


Quantitative Assessment of Myocardial Edema by MR T2 Mapping in Children With Kawasaki Disease.
Few studies assessed myocardial inflammation using Cardiovascular Magnetic Resonance Imaging in Kawasaki disease (KD) patients. To quantify myocardial edema in KD patients using T2 mapping and explore the independent predictors of T2 values. Prospective. Ninety KD patients including 40 in acute phase (26 males, 65.0%) and 50 in chronic phase (34 males, 68.0%). Thirty-one healthy volunteers (21 males, 70.0%). 3.0 T T2-weighted Turbo Spin Echo-Short Time of Inversion Recovery sequence, True fast imaging with steady precession flash sequence and fast low-angle shot 3D spoiled gradient echo sequence. T2 values were compared among KD groups and controls. Student's t test and Fisher's exact test; One-way analysis of variance; Pearson correlation analysis; Receiver operating curve analysis; Multivariable linear regression. Global T2 value of KD patients in acute phase was the highest, followed by those of chronic-phase patients and controls (38.83 ± 2.41 msec vs. 37.55 ± 2.28 msec vs. 36.05 ± 1.64 msec). Regional T2 values showed a same trend. There were no significant differences in global and regional T2 values between KD patients with and without coronary artery (CA) dilation, no matter in acute or chronic phase (all KD patients: P = 0.51, 0.51, 0.53, 0.72; acute KD: P = 0.61, 0.37, 0.33, 0.83; chronic KD: P = 0.65, 0.79, 0.62, 0.79). No significant difference was observed in global T2 values between KD patients with Z score > 5.0 and 2.0 < Z score ≤ 5.0 (P = 0.65). Multivariate analysis demonstrated that stage of disease (β = -0.123) and heart rate (β = 0.280) were independently associated with global T2 values. The degree of myocardial edema was more severe in acute-phase than in chronic-phase KD patients. Myocardial edema persists in patients regardless of the existence or degree of CA dilation. 2 TECHNICAL EFFICACY: Stage 2.


Modeling of gas emission in coal mine excavation workface: a new insight into the prediction model.
Coalbed methane (CBM) is a clean energy source, but its utilization is inefficient due to the complexity and low accuracy of its emission prediction model. In this research, we constructed a mathematical model of gas emission from the excavation workface, and combined the experimental results to propose a new model for accurate and concise prediction. The new model was validated in the field workface and compared with the traditional prediction model. Moreover, the sensitivity of gas emission parameters and the participation ratio of gas emission sources were analyzed. The study results show that the new model has higher calculation accuracy than the old model prediction, with an average error reduction of 4.693%. In the excavation workface, the coal fall gas emission conforms to the negative power function equation, and the coal wall gas emission conforms to the negative exponential function equation. In the early stage of excavation, the proportion of coal fall gas emission is higher than that of coal wall gas emission, and the peak proportion reaches 58.5%. In the later stage, the proportion of coal fall gas emission gradually decreases to below 30%. The order of the sensitivity of gas emission parameters is coal wall gas initial velocity > coal fall gas decay coefficient > coal fall gas initial velocity > coal wall gas decay coefficient. The new model is successfully applied in engineering, which helps to improve the efficiency of coal mine gas disaster control and utilization.


Anti-metastatic action of non-steroidal anti-inflammatory drugs.
Epidemiological studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of several types of human cancer. However, the molecular mechanisms by which NSAIDs exert their chemopreventive and anticancer effects are not fully understood. Cyclooxygenase 1 (COX-1) and COX-2 are the main targets for NSAIDs. Recent studies demonstrate that COX-2 is overexpressed in many human cancers and may promote tumorigenesis via: (1) stimulation of cancer cell proliferation; (2) increase of tumor angiogenesis; (3) prevention of cancer cell apoptosis; (4) modulation of immunoregulatory reactions; and (5) enhancement of tumor metastasis. NSAIDs may target the signaling molecules (from upstream activators to downstream effectors) involved in these mechanisms to attenuate the development and progression of cancer. In this review, we discuss the recent findings with regard to the mechanisms by which NSAIDs inhibit tumorigenesis and will specifically focus on the elucidation of NSAID-induced inhibition of tumor metastasis.