A highly efficient dioxo(mu-oxo)molybdenum(VI) dimer catalyst for olefin epoxidation.
The oxo-bridged dimer [Mo(2)O(4)(mu(2)-O)Cl(2)(pzH)(4)] (1; pzH = pyrazole) exhibits unusually high activity in the liquid-phase catalytic epoxidation of the cyclic olefins cyclooctene and (R)-(+)-limonene under mild conditions and in the absence of additional organic solvents, using tert-butyl hydroperoxide as the oxidant. The complex is stable under the reaction conditions and can be used in further catalytic runs without significant loss of performance. An X-ray crystallographic investigation reveals that 1 has an unprecedented and extremely rare all-cis configuration at each of the MoO(2)-(mu(2)-O)Cl(pzH)(2) cores, which can be understood by considering supramolecular contacts and geometric factors.


Diabetes mellitus and Degos disease.
We present the case of a 75-year-old man who was diagnosed with Degos disease (DD) in the context of type 2 diabetes mellitus. The cutaneous lesions of DD were located at the trunk as well as in the proximal parts of the arms. He presented with positive laboratory test for lupic anticoagulant, but other rheumatologic parameters of interest were within normal limits. The skin biopsy corroborated the diagnosis of DD, and also showed morphologic features traditionally associated to hyaline diabetic microangiopathy. Since the latter has recently been atributted to C5b-9 deposit in the vessel wall, we discuss if both conditions are pathogentically connected or just coincidental (Fig. 3, Ref. 32). Full Text (Free, PDF) www.bmj.sk.


Touch satiety: differential effects of stroking velocity on liking and wanting touch over repetitions.
A slow, gentle caress of the skin is a salient hedonic stimulus. Low threshold, unmyelinated C-tactile afferents fire preferentially to this type of touch, where slow (<1 cm/s) and fast (>10 cm/s) stroking velocities produce lower firing frequencies and are rated as less pleasant. The current aim was to investigate how the experience of tactile pleasantness changes with repeated exposure (satiety to touch). A further aim was to determine whether tactile satiety varied with different stroking velocities. The experimental paradigm used a controlled brush stroke to the forearm that was delivered repeatedly for ∼ 50 minutes. In Experiment 1, brush strokes were administered at three different velocities (0.3 cm/s, 3 cm/s and 30 cm/s), which were presented in a pseudo-randomised order. In Experiment 2, brush strokes were applied using only one velocity (either 3 or 30 cm/s). After each stroke, the participants rated both subjective pleasantness (liking) and wanting (the wish to be further exposed to the same stimulus) for each tactile sensation. In Experiment 1, both pleasantness and wanting showed a small, but significant, decrease over repetitions during stroking at 3 cm/s only, where the mean values for pleasantness and wanting were similar. Conversely, slower (0.3 cm/s) and faster (30 cm/s) stroking showed no decrease in ratings over time, however pleasantness was rated higher than wanting. In Experiment 2, both pleasantness and wanting showed a significant decrease over repetitions for both applied velocities, with a larger decrease in ratings for stroking at 3 cm/s. In conclusion, satiety to touch occurred with a slow onset and progression, where pleasantness and wanting ratings to stroking at 3 cm/s were affected more than at the slower or faster velocities. Tactile satiety appears to differ compared to appetitive and olfactory satiety, because the hedonic and rewarding aspects of touch persist for some time.


In vivo quantification of hyperoxic arterial blood water T1.
Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O2 (pO2) and increased oxygen bound to hemoglobin in arteries (Ya) and veins (Yv). The dependence of T1a on Ya and Yv has been elegantly characterized ex vivo; however, the combined influence of pO2, Ya and Yv on T1a in vivo under normal ventilation has not been reported. Here, T1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T1 -dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O2/79% N2), hypercapnic normoxic (HN; 5% CO2/21% O2/74% N2) and hypercapnic hyperoxic (HH; 5% CO2/95% O2) gas administration. HH T1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O2) 3-T arterial blood T1aHH = 1.49 ± 0.07 s relative to a normoxic T1a of 1.65 s.


Ciliate species from tank-less bromeliads in a dry tropical forest and their geographical distribution in the Neotropics.
The study of ciliate diversity in tropical environments remains scarce. In Neotropical forests, bromeliads are a common component of the vascular flora; bromeliads with tank morphology intercept rain water and detritus, resulting in the formation of a phytotelm, where heterotrophic protist communities like ciliates can establish. However, it is not known if ciliates inhabit tank-less bromeliads. For this reason, the goal of the present study was to investigate if ciliates can establish between the leaf axils of five terrestrial and epiphytic tank-less bromeliad species in a dry tropical forest in west Mexico. We collected samples of rain water and detritus from the leaf axils during the humid season of years 2015 and 2016. For ciliate taxonomical identification, we used optical microscopy, in vivo observation, and silver impregnation techniques. To summarize information about geographical distribution of ciliates identified at species level in the Neotropics, we provided their records from previous works, at country level with locality and georeferenciation. We recorded 27 taxa of ciliates, where the class Oligohymenophorea contained the largest richness of taxa. Drepanomonas revoluta, Leptopharynx bromeliophilus, and Tetrahymena sp. were recorded from all the species of bromeliads. Bromelia karatas was the species that hosted the largest number of ciliate taxa (22). Our results indicated that Glaucomides bromelicola, Gonostomum bromelicola, Leptopharynx bromelicola and L. bromeliophilus, species which are considered endemic to tank bromeliads, can also inhabit tank-less bromeliads. We provided previous records of 19 ciliate species from eleven countries within the Neotropical region, and Bromeliothrix metopoides was the species most frequently recorded in Neotropical countries (9). Therefore, tank-less bromeliads can constitute a temporal habitat for ciliates, and function as cysts reservoirs in environments with a pronounced seasonality like dry tropical forests.


Inhaled corticosteroids for subacute cough in children.
Cough is the most common symptom presenting to primary healthcare services. Cough in children is associated with significant morbidity for both children and their parents. While inhaled corticosteroids (ICS) can potentially reduce cough associated with airway inflammation and airway hyper-reactivity, use of ICS in children is not without potential adverse effects. Therefore, it would be beneficial to clinical practice to evaluate the evidence for the efficacy of ICS in reducing the severity of cough in children with subacute cough (defined as cough duration of two to four weeks) systematically. To evaluate the efficacy of ICS in reducing the severity of cough in children with subacute cough. The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of relevant articles were searched. The latest searches were performed in November 2011. All randomised controlled trials (RCTs) comparing ICS with a control group in children with subacute cough were considered for inclusion. Search results were reviewed against pre-determined criteria for inclusion. Two sets of review authors independently selected, extracted and assessed the data for inclusion. Study authors were contacted for further information where required. Data were analysed as 'intention to treat'. The search identified 1178 potentially relevant titles; however, there were no published studies that were specifically designed to answer this question. Two studies met criteria for inclusion in the review and 98 children were included in the meta-analysis. There was no significant difference between groups in the proportion of children 'not cured' at follow-up (primary outcome measure), with a pooled odds ratio (OR) of 0.61 (95% confidence interval (CI) 0.24 to 1.55). However, the included studies were limited in their ability to answer the review question by the fact that all participants were infants, post acute bronchiolitis illness, and cough duration at the start of study medication was ill-defined. There is currently no evidence to support the use of ICS for treatment of subacute cough in children. However, this systematic review is limited by the small number of studies available for analysis and the size, quality and design of these studies. Further well-designed RCTs are required to support or refute the efficacy of treatment with ICS in children with subacute cough.


[Assisted procreation for male indication].
Strategy for male infertility looks like a compromise between diagnosis methods with their efficacy and complexity and treatment with their own risks, cost, efficacy. Infertility duration as well as woman's fertility play a key role for such a strategy. Definitive infertility without any correction (secretory azoospermia) will be proposed for alternate projects. Some situations may benefit from specific therapy (hypogonadotropic hypogonadism, anejaculations or retrograde ejaculation). More frequently male hypofertility is suspected with non specific sperm alterations, then assisted reproductive technologies will be discussed. Intra-cervical way artificial insemination with husband semen may be proposed in case of hypospadias, anejaculation, retrograde ejaculation, small volume ejaculate or self-cryostored semen, however negative post-coital test, positive crossed penetration test and positive post-insemination test need to be confirmed. Intrauterine way enhance fertilizing probability by discarding cervical step. It will be justified in case of negative post-coital test as well as crossed penetration test except that sperm preparation allowed to inseminate 500,000 to 1 million motile spermatozoa. Both rigorous monitoring and synchronism between insemination and ovulation enhance the efficacy of IU AIH which allowed a two to four fold increase in the pregnancy rate on a total of six cycles. In vitro fertilization for male factor represent around 15% of all IVF attempts. Both decrease in the fertilization rate and the increase in the pregnancy rate by transfer as compared with tubal factor are well accepted. The fertilization failure remain difficult to explain and need to be cautiously confirmed. Thus IVF represent an actual fertilization test but remain limited by the heterogeneity of parameters under "male factor".(ABSTRACT TRUNCATED AT 250 WORDS)


Water and peptide backbone structure in the active center of bovine rhodopsin.
Difference FTIR spectra in the conversion of rhodopsin or isorhodopsin to bathorhodopsin were recorded for recombinant wild-type and E113Q bovine rhodopsins. Differences in various vibrational modes between E113Q and the wild-type proteins whose Schiff bases interact with chloride and Glu113, respectively, were analyzed. Water molecules in rhodopsin that change upon formation of bathorhodopsin are detected by a change in frequency of the O-H stretching vibration from 3538 to 3525 cm(-1). This change in the wild-type protein is absent in E113Q. One or a few water molecules are therefore suggested to be located in the proximity of Glu113, the counterion of the Schiff base. Another water vibration at 3564 cm(-1), which is shifted to 3542 cm(-1) in bathorhodopsin in the wild type, persists in E113Q but with approximately 5-cm(-1) shift toward higher frequency. This is due to water molecules that may be located at a site somewhat more remote from Glu113. Structural changes of some peptide carbonyls and amides are also absent in E113Q. On the other hand, the E113Q protein shows shifts of the N-H+ stretching vibrational band, that is probably due to the protonated Schiff base, upon conversion of rhodopsin to bathorhodopsin. No corresponding changes were observed in the wild type. We propose a model in which a water molecule interacts with Glu113, the protonated Schiff base, and peptide carbonyls, and amides. These residues undergo structural changes upon formation of bathorhodopsin.


Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells.
Notch signaling can promote tumorigenesis in the nervous system and plays important roles in stem-like cancer cells. However, little is known about how Notch inhibition might alter tumor metabolism, particularly in lesions arising in the brain. The gamma-secretase inhibitor MRK003 was used to treat glioblastoma neurospheres, and they were subdivided into sensitive and insensitive groups in terms of canonical Notch target response. Global metabolomes were then examined using proton magnetic resonance spectroscopy, and changes in intracellular concentration of various metabolites identified which correlate with Notch inhibition. Reductions in glutamate were verified by oxidation-based colorimetric assays. Interestingly, the alkylating chemotherapeutic agent temozolomide, the mTOR-inhibitor MLN0128, and the WNT inhibitor LGK974 did not reduce glutamate levels, suggesting that changes to this metabolite might reflect specific downstream effects of Notch blockade in gliomas rather than general sequelae of tumor growth inhibition. Global and targeted expression analyses revealed that multiple genes important in glutamate homeostasis, including glutaminase, are dysregulated after Notch inhibition. Treatment with an allosteric inhibitor of glutaminase, compound 968, could slow glioblastoma growth, and Notch inhibition may act at least in part by regulating glutaminase and glutamate.


Molecular analysis in diagnostic procedure of hearing impairment in newborns.
To determine the proportion of newborns diagnosed with hearing impairment through the hearing impairment screening program in newborns, and the frequency of 35delG/GJB2 mutation as a cause of hearing impairment. The results of the study imply the integration of the mutation analysis in the neonatal screening program. Evoked otoacustic emission (E-OAE) screening program was performed among 6019 newborns at the Department of Obstetrics and Gynaecology, Rijeka University Hospital Center, between October 2002 and December 2004. Newborns diagnosed with hearing impairment were re-examined after three weeks and if abnormal responses persisted, the diagnosis was evaluated by auditory brainstem evoked response (ABER) testing. Children with confirmed diagnosis were examined by allele-specific polymerase chain reaction to identify the presence of 35delG/GJB2 mutation. After the first and second stage of screening, 86 newborns were suspect of having hearing impairment. ABER confirmed the diagnosis of hearing impairment in 14 children. Molecular analysis revealed 35delG/GJB2 mutation in 2 of 8 children analyzed. The mutation was homozygous in one, and heterozygous in the other child. Neonatal hearing impairment screening is useful for early diagnosis of hearing impairment. It should be complemented with the 35delG/GJB2 mutation analysis, because the identification of the mutation and the etiologic diagnosis might improve the medical treatment and genetic counselling of patients and families with hearing impairment.


Prevention of hyponatraemia and cerebral oedema by the vasopressin antagonist d/CH2/5Tyr/Et/VAVP in rats treated with pitressin tannate.
A rat model of the Schwartz-Bartter syndrome was created by the administration of a high dose of a long-acting vasopressin preparation (pitressin tannate ) together with a forced water intake. The treatment led to water retention, hypernatriuria , marked hyponatraemia (in 4-5 days) and severe cerebral oedema. These changes could be prevented by the simultaneous administration of [1-(beta-mercapto-beta, beta- cyclopentamethylene -propionic acid),2-0- ethyltyrosine ,4-valine]arginine vasopressin. The observations indicate that this vasopressin antagonist analogue might be of use in the future as an effective drug against the Schwartz-Bartter syndrome.


AML-derived Extracellular Vesicles Confer De Novo Chemoresistance to Leukemic Myeloblast Cells by Promoting Drug Export Genes Expression and ROS Inhibition.
In spite of successful initial remission, chemo-resistance and relapse are still concerning points in acute myeloid leukemia (AML) treatment strategies. Multidrug resistance (MDR) appears to be the major contributor of chemo-resistance, arising in some sub-clones of cancers and could be developed in others. The aim of this study was to investigate the role of extracellular vesicles (EVs) derived from AML patients on the transmission of chemo-resistance phenotype. Ultracentrifugation was employed to isolate EVs from healthy controls, new cases, and relapsed AML patients. The EVs size, morphology, and immunophenotype were determined by dynamic light scattering, TEM, and flow cytometry respectively. Bradford assay was performed to measure the protein content of EVs. MTT assay and flow cytometry analysis were also used to determine the viability index, induction of apoptosis, and ROS generation in U937 cells. The expression level of two efflux pumps was assessed using qRT-PCR analysis. Findings of TEM, DLS, and flow cytometry confirmed that EVs had a desirable shape, size, and surface markers. EVs derived from both new cases and relapsed AML patients significantly reduced idarubicin-induced apoptosis in the U937 cells. The analysis of drug efflux pumps gens revealed that EVs over-express MRD1 and MRP1 in the target cells. These findings suggested a novel role of EVs in mediating the acquired chemo-resistance in AML patients by inducing the expression of the drug efflux pumps; however, further investigations will be required to elucidate other underlying mechanisms of resistance that are mediated by EVs.


Cross talk between signaling and vitamin A transport by the retinol-binding protein receptor STRA6.
The plasma membrane protein STRA6 transports vitamin A from its blood carrier retinol binding protein (RBP) into cells, and it also functions as a cytokine receptor which activates JAK/STAT signaling. We show here that, unlike other cytokine receptors, phosphorylation of STRA6 is not simply induced upon binding of its extracellular ligand. Instead, activation of the receptor is triggered by STRA6-mediated translocation of retinol from serum RBP to an intracellular acceptor, the retinol-binding protein CRBP-I. The observations also demonstrate that the movement of retinol from RBP to CRBP-I, and thus activation of STRA6, is critically linked to the intracellular metabolism of the vitamin. Furthermore, the data show that STRA6 phosphorylation is required for retinol uptake to proceed. Hence, the observations demonstrate that STRA6 orchestrates a multicomponent "machinery" that couples vitamin A homeostasis and metabolism to activation of a signaling cascade and that, in turn, STRA6 signaling regulates the cellular uptake of the vitamin. STRA6 appears to be a founding member of a new class of proteins that may be termed "cytokine signaling transporters."


Salvage of intraoperative deep inferior epigastric perforator flap venous congestion with augmentation of venous outflow: flap morbidity and review of the literature.
Breast reconstruction with deep inferior epigastric perforator (DIEP) flaps has gained considerable popularity due to reduced donor-site morbidity. Previous studies have identified the superficial venous system as the dominant outflow to DIEP flaps. DIEP flap venous congestion occurs if superficial venous outflow via the deep venous system is insufficient for effective flap drainage. Although augmentation of venous outflow through a second venous anastomosis may relieve venous congestion, effects on flap morbidity remain ill defined. A retrospective analysis of 1616 patients who underwent 2618 DIEP flap breast reconstructions between March 2005 and January 2012 was performed. Patients with intraoperative venous congestion underwent a second venous anastomosis. Preoperative demographic data and methods used to relieve venous congestion were recorded. Incidence of flap morbidity was calculated and compared with a group of 418 controls having 639 DIEP flap breast reconstructions with no venous congestion. Venous augmentation was required to relieve venous congestion in 87 (3.3%) DIEP flaps on 81 patients. The superficial inferior epigastric vein or accompanying deep inferior epigastric venae comitantes was used to augment venous outflow. Preoperative comorbidities were similar between both groups. Patients requiring a second venous anastomosis had a longer operative time and length of hospital stay. Overall, flap morbidity, delayed wound healing, fat necrosis, and flap loss were similar to controls. Arterial and venous anatomies play unique roles in flap reliability. DIEP flap venous congestion must be treated expeditiously with venous augmentation to relieve venous congestion and mitigate flap morbidity.


Glucolipotoxicity Suppressed Autophagy and Insulin Contents in Human Islets, and Attenuation of PERK Activity Enhanced Them in an ATG7-Dependent Manner.
Administration of pancreatic endoplasmic reticulum kinase inhibitor (PERKi) improved insulin secretion and hyperglycemia in obese diabetic mice. In this study, autophagic balance was studied whether to mediate it. Human islets were isolated from living patients without diabetes. PERKi GSK2606414 effects were evaluated in the islets under glucolipotoxicity by palmitate. Islet insulin contents and secretion were measured. Autophagic flux was assessed by microtubule associated protein 1 light chain 3 (LC3) conversion, a red fluorescent protein (RFP)-green fluorescent protein (GFP)- LC3 tandem assay, and P62 levels. For mechanical analyses, autophagy was suppressed using 3-methyladenine in mouse islets. Small interfering RNA for an autophagy-related gene autophagy related 7 (Atg7) was transfected to interfere autophagy. PERKi administration to mice decreased diabetes-induced P62 levels in the islets. Glucolipotoxicity significantly increased PERK phosphorylation by 70% and decreased insulin contents by 50% in human islets, and addition of PERKi (40 to 80 nM) recovered both. PERKi also enhanced glucose-stimulated insulin secretion (6-fold). PERKi up-regulated LC3 conversion suppressed by glucolipotoxicity, and down-regulated P62 contents without changes in P62 transcription, indicating enhanced autophagic flux. Increased autophagosome-lysosome fusion by PERKi was visualized in mouse islets, where PERKi enhanced ATG7 bound to LC3. Suppression of Atg7 eliminated PERKi-induced insulin contents and secretion. Conclusion: This study provided functional changes of human islets with regard to autophagy under glucolipotoxicity, and suggested modulation of autophagy as an anti-diabetic mechanism of PERKi.


The production and physicochemical properties of a biosurfactant mixture obtained from Sphingobacterium detergens.
The commercial application of a new biosurfactant such as the one produced by Sphingobacteriumdetergens needs a cost-effective process and knowledge of its properties. In the present study, a specific medium and a downstream process have been developed to enhance biosurfactant production. Optimal concentrations of nutrients in MCA medium were (g/L) the following: KH(2)PO(4), 1; K(2)HPO(4), 2; CO(NH(2))(2) 0.88; CaCl(2) 0.01; FeSO(4)·7H(2)O, 0.01; MgSO(4)·7H(2)O 0.5; KCl, 1.0; trace elements 0.05 mL. Biosurfactant production in the MCA medium required a bacterial co-metabolism of glucose and an n-alkane. A fed-batch culture with supernatant lyophilization prior to organic extraction produced 466 mg/L of organic extract, which represents a 6.9-fold increase in production. The newly obtained biosurfactant was a complex mixture of molecules. The three characterized fractions consisted of the complete fraction and two second-level purification fractions with apolar and polar characteristics. The complete and apolar fractions have been shown to self-aggregate in the form of lamellar liquid crystals at a high concentration and bilayers at lower concentrations. Negatively charged particles were identified, which were neutralized at a low pH with a concomitant increase in size. The pH affected the surface tension of the solutions congruently with phosphate headgroups.


Aberrant Cholesterol Metabolic Genes Regulation in a Negative Feedback Loop Induced by an Alphacoronavirus.
Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that causes acute inflammation and severe diarrhea in newborn piglets with a high mortality rate. Given that cholesterol is required for coronavirus infection in vitro, the role of endogenous cholesterol metabolism in regulating coronavirus infection and the mechanism behind it ought to be elucidated. In this study, we found that the levels of cholesterol and bile acids were both elevated in the livers of PEDV-infected piglets compared to those of the control group. Consistently, in the livers of PEDV-infected piglets, the expression of key genes involved in cholesterol metabolism was significantly increased. Transcriptomic analysis indicated that the cholesterol homeostasis pathway was among the most enriched pathways in the livers of PEDV-infected piglets. Unexpectedly, the expression of key genes in the cholesterol metabolic pathway was downregulated at the messenger RNA (mRNA) level, but upregulated at the protein level. While the primary transcriptional factors (TFs) of cholesterol metabolism, including SREBP2 and FXR, were upregulated at both mRNA and protein levels in response to PEDV infection. Further Chromatin Immunoprecipitation Quantitative Real-time PCR (ChIP-qPCR) analysis demonstrated that the binding of these TFs to the locus of key genes in the cholesterol metabolic pathway was remarkably inhibited by PEDV infection. It was also observed that the occupancies of histone H3K27ac and H3K4me1, at the locus of the cholesterol metabolic genes HMGCR and HMGCS1, in the livers of PEDV-infected piglets, were suppressed. Together, the PEDV triggers an aberrant regulation of cholesterol metabolic genes via epigenetic inhibition of SREBP2/FXR-mediated transcription, which provides a novel antiviral target against PEDV and other coronaviruses.


Controlled Growth of Ultrathin Film of Organic Semiconductors by Balancing the Competitive Processes in Dip-Coating for Organic Transistors.
Ultrathin film with thickness below 15 nm of organic semiconductors provides excellent platform for some fundamental research and practical applications in the field of organic electronics. However, it is quite challenging to develop a general principle for the growth of uniform and continuous ultrathin film over large area. Dip-coating is a useful technique to prepare diverse structures of organic semiconductors, but the assembly of organic semiconductors in dip-coating is quite complicated, and there are no reports about the core rules for the growth of ultrathin film via dip-coating until now. In this work, we develop a general strategy for the growth of ultrathin film of organic semiconductor via dip-coating, which provides a relatively facile model to analyze the growth behavior. The balance between the three direct factors (nucleation rate, assembly rate, and recession rate) is the key to determine the growth of ultrathin film. Under the direction of this rule, ultrathin films of four organic semiconductors are obtained. The field-effect transistors constructed on the ultrathin film show good field-effect property. This work provides a general principle and systematic guideline to prepare ultrathin film of organic semiconductors via dip-coating, which would be highly meaningful for organic electronics as well as for the assembly of other materials via solution processes.


[Correlation analysis of surnames and Y-chromosome genetic heritage in 3 provinces of southwestern Colombia].
In Colombia, surnames are characters usually passed to the children by the father, and they have been compared to neutral alleles associated with the Y-chromosome. Population frequencies were determined for 17 short tandem repeats (STR) DNA markers on the Y-chromosome to compare the two identity codes and define the correlation between haplotypes and surnames in each individual. DNA was extracted from blood samples from 308 male individuals in provinces of Valle del Cauca, Cauca and Nariño, all in southwestern Colombia. Sample DNA was analyzed with the commercial kit AmpFLSTR Yfiler (Applied Biosystems) and examined for the following 17 Y-chromosome STR markers: DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385a/b, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and Y-GATA-H4. The frequencies of molecular haplotypes were associated with the surname reported by each individual, and a correlation table was constructed. Amerindian and European surnames were associated with the presence of allele DYS19/13, a characteristic of Amerindian populations. Allele frequencies were reported for each of the 17 STR markers in the southwestern region of Colombia-high genetic and haplotypic diversities were obtained. Approximately 40% of lineage inconsistencies were found when the molecular genotype was compared with the European or Amerindian surnames. Surnames must be used as population markers with reservation. The genetic evidence indicates that traditional genealogies based on surnames with or without documental support, may be inconsistant with their biological provenance.


The impact of stimulus attributes on engagement of nursing home residents with dementia.
We examined the influence of stimulus attributes on the engagement of 69 nursing home residents with dementia. Specifically, we looked at work-related stimuli versus manipulative block stimuli, and whether the color, size, and material of a stimulus affect the duration and quality of engagement. Engagement was assessed using the Observational Measurement of Engagement (OME). Results revealed a clear preference for the work-related rather than manipulative block stimuli. In addition, the study participants showed a significant preference for small rather than large blocks, regardless of color or material. The effect of material and color was not statistically significant. These findings may assist nursing home caregivers who wish to provide appropriate stimuli for engaging nursing home residents with dementia.


Quantum dot-based nanocomposites for biomedical applications.
Quantum dot (QD) has been extensively investigated as a nanoprobe to replace conventional organic dyes due to its unique optical properties. However, nanotoxicity of QD greatly hampers its biomedical applications, particularly in in vivo imaging. It is critical to functionalize QD and/or composite QD with other functional materials for biocompatibility, multifunction and expanded applications. In this review, advances of QD-based nanocomposites are addressed with emphasis of their synthesis, fundamental understanding and applications in biosensor, multimodal imaging, drug delivery, diagnostics and cancer therapy. Some specific QD-based bionanosystems and future development directions are also discussed.


Effects of age and anxiety on learning and memory.
This study aims to investigate the effects of age and anxiety on behavior, learning and memory in rats. Before and after the anxiety and learning tests, locomotor activity, exploratory activity and autonomic functions of the rats were tested in open field area. At the beginning and at the end of behavior tests, urines were collected so as to determine 5-hydroxyindolaceticacid (5-HIAA) levels. Following these tests, rats were anesthetized and their serum corticosteron (CORT) levels were analyzed. After anxiety, except for defecation, all parameters in open field such as line crossing, rearing, sitting and number of grooming were decreased in both young and aged animals. 5-Hydroxyindolaceticacid levels were decreased and serum CORT levels were increased, it is supported that especially the aged rats were much more affected from anxiety compared to the young ones. Elevated T-maze results show that emotional learning did not change while conditioned performance was tested in the closed arm and unconditioned performance was tested in the open arm. Nevertheless, it is observed that aging leaded to extensions in avoidance responses and thus caused difficulty in learning. In water maze test, rats showed higher performance in reaching the platform in repetitive trials; this demonstrates that they have learned by environmental cues. Experimental group had not better performance in reaching the platform according to control group, so this supports that anxiety affects spatial learning. As a conclusion, it could be stated that especially in aged rats, anxiety that is created by elevated T-maze and cat odor and supported with 5-hydroxyindoleacetic acid and serum corticosterone, causes difficulty in emotional and spatial learning.


[Effects of three different etching methods on surface morphology and element of pure titanium].
The pure titanium disks were divided into three groups and etched for 30 minutes with HNO3, hot H2SO4/H2O2 or hot H2SO4/HCl respectively. The treated disks were studied and analyzed with scanning electron microscope (SEM) and X-ray photoelectron spectroscopy (XPS). The disks etched with HNO3 had a smooth surface, while those etched with hot H2SO4/H2O2 or hot H2SO4/HCl had rough surfaces, and the surface etched with hot H2SO4/HCl had larger micropores. The XPS analysis demonstrated that the main elements of the surface in three groups were titanium, oxygen and carbon. The carbon concentration was the lowest on the surface etched with hot H2SO4/H2O2 and the highest on that etched with hot H2SO4/HCl. The substances were TiO2, Ti2O3, TiO and metal Ti on the surface etched with HNO3 or hot H2SO4/H2O2. Only TiO2 was detected on the surface etched with hot H2SO4/HCl.


Metabolomics Study of Different Germplasm Resources for Three Polygonatum Species Using UPLC-Q-TOF-MS/MS.
Rhizomes of the Polygonatum species are well-known in traditional Chinese medicine. The 2020 edition of Chinese Pharmacopoeia includes three different species that possess different pharmacological effects. Due to the lack of standardized discriminant compounds there has often been inadvertently incorrect prescriptions given for these medicines, resulting in serious consequences. Therefore, it is critical to accurately distinguish these herbal Polygonatum species. For this study, UPLC-Q-TOF-MS/MS based metabolomics was employed for the first time to discriminate between three Polygonatum species. Partial least squares discriminant analysis (PLS-DA) models were utilized to select the potential candidate discriminant compounds, after which MS/MS fragmentation patterns were used to identify them. Meanwhile, metabolic correlations were identified using the R language package corrplot, and the distribution of various metabolites was analyzed by box plot and the Z-score graph. As a result, we found that adenosine, sucrose, and pyroglutamic acid were suitable for the identification of different Polygonatum species. In conclusion, this study articulates how various herbal Polygonatum species might be more accurately and efficiently distinguished.


Unconventional, Gram-Scale Synthesis of a Molecular Dimer Organic Luminogen with Aggregation-Induced Emission.
Organic luminogens have been widely used in optoelectronic devices, bioimaging, and sensing. Conventionally, the synthesis of organic luminogens requires sophisticated, multistep design, reaction, and isolation procedures. Herein, the products of the melt-phase condensation of benzoguanamine (BG; 2,4-diamino-6-phenyl-1,3,5-triazine) at 370-410 °C display interesting reaction-condition-dependent luminescence properties, including photoluminescence (PL) at a variety of wavelengths in the visible spectrum and quantum efficiencies (PLQE) of up to 58% in the powder form. With a simple and straightforward solvent washing procedure, the prominent blue luminescent component BG dimer was obtained in gram scale with >93% purity (96.5% purity after fractional sublimation). The BG dimer exhibited distinct aggregation-induced emission (AIE) properties. PL measurements indicate that the electronically excited state of the BG dimer undergoes efficient intramolecular nonradiative deactivation in room-temperature solution, leading to a significantly reduced PLQE (<0.1%) in solution. These nonradiative processes are substantially inhibited when the dimer existed in the form of crystals, solid aggregates in solution or being fixed in a rigid polymer film, resulting in a significant increase in the PLQE and lifetime. This work not only provided a new understanding for PL properties of self-condensation luminescent products but also represented an unconventional strategy for large-scale preparation of organic luminogens with high purity.


Comparison of dry ice baited light traps with human bait collections for surveillance of mosquitoes in northern Queensland, Australia.
Adult mosquitoes were collected from April 1984 to September 1985, at 3 sites at or adjacent to the Ross River Dam, north Queensland. The numbers attracted to dry ice baited encephalitis virus surveillance (EVS) light traps and to human bait were similar. Both methods sampled 18 taxa and ranked the abundances of Culex annulirostris, Anopheles annulipes s.l., Aedes vigilax, Mansonia uniformis and Ma. septempunctata similarly at each locality. Significant correlations between the 2 methods were found for all 5 of the dominant species, but were stronger for Ae. vigilax, Ma. uniformis and Ma. septempunctata than for Cx. annulirostris or An. annulipes. Human bait attracted more Cx. annulirostris, Ae. vigilax and Ma. uniformis than the EVS traps. The relative effectiveness of the 2 methods varied significantly with time for Cx. annulirostris and An. annulipes, but both methods revealed similar long term population trends. These data suggest that EVS surveillance may be better suited for sampling Ae. vigilax, and human bait (or alternatively animal bait) or a combination of both methods would be more appropriate for sampling Cx. annulirostris at the dam.


Nucleotype and cell size in vertebrates: a review.
The relationships between genome size and various cell morphometric parameters have been assayed in 357 species of Vertebrates, in order to verify the existence and significance of the so-called "nucleotypic effect" in this subphylum. The results obtained clearly manifest a significant relationship between the increase in genome size and that in nuclear volume, nuclear surface, cell volume and cell surface. A precise correlation is also observed between the increase in DNA content and the decrease in the surface/volume ratios of the nucleus and the cell. Other parameters, such as the nucleoplasmic index and DNA concentration, though showing a slight increase with increasing genome size, have values rather homogeneous in each Vertebrate group. These results have allowed some interesting speculations on various problems; for example, the mechanisms through which genome size can influence the cell size; the influence of the DNA content and cell morphometric parameters on functional level of the cell and the organism; the importance of the nucleotypic effect in the adaptation to the environment of the various Vertebrate groups. From this study it seems possible to make the following conclusions: 1) in Vertebrates, genome size would exert a real nucleotypic influence on cell size; 2) genome sizes and cell morphometric parameters seem to be involved in the regulation of cell metabolism; 3) the regulation of some morphometric parameters depends strictly and automatically on the DNA amount or on other morphometric parameters. The regulation of others, instead, depends on the interaction of different factors, which do not always act synergically; 4) the nucleotypic effect seems to have different distribution and importance in Anamniotes and Amniotes.


VvWRKY5 enhances white rot resistance in grape by promoting the jasmonic acid pathway.
Grape white rot is a disease caused by Coniella diplodiella (Speg.) Sacc. (Cd) can drastically reduce the production and quality of grape (Vitis vinifera). WRKY transcription factors play a vital role in the regulation of plant resistance to pathogens, but their functions in grape white rot need to be further explored. Here, we found that the expression of the WRKY IIe subfamily member VvWRKY5 was highly induced by Cd infection and jasmonic acid (JA) treatment. Transient injection and stable overexpression (in grape calli and Arabidopsis) demonstrated that VvWRKY5 positively regulated grape resistance to white rot. We also determined that VvWRKY5 regulated the JA response by directly binding to the promoters of VvJAZ2 (a JA signaling suppressor) and VvMYC2 (a JA signaling activator), thereby inhibiting and activating the transcription of VvJAZ2 and VvMYC2, respectively. Furthermore, the interaction between VvJAZ2 and VvWRKY5 enhanced the suppression and promotion of VvJAZ2 and VvMYC2 activities by VvWRKY5, respectively. When VvWRKY5 was overexpressed in grape, JA content was also increased. Overall, our results suggested that VvWRKY5 played a key role in regulating JA biosynthesis and signal transduction as well as enhancing white rot resistance in grape. Our results also provide theoretical guidance for the development of elite grape cultivars with enhanced pathogen resistance.


P-N Conversion in a Water-Ionic Liquid Binary System for Nonredox Thermocapacitive Converters.
An intriguing p-n conversion of thermoelectric property was observed in a water-ionic liquid ([EMIm][Ac]) binary system with precise control over water content. The highest p-type and n-type Seebeck coefficient were optimized at water-[EMIm][Ac] molar ratio of 2:1 and 4:1, respectively. DFT calculation illustrates that a configuration of solvent separation ion pairs is preferred at the water-[EMIm][Ac] molar ratio of 4:1, leading to the p-n conversion through weakening interaction between anion clusters and gold electrodes. Furthermore, p-n thermocapacitive converters were integrated to enhance the output Seebeck voltages. This work opens up new perspectives for harvesting low grade heat with the use of fluidic materials.


Melanocytic lesions excised from the skin: what percentage are malignant?
We estimated the diagnostic skill of clinicians managing melanocytic skin naevi by measuring the percentage of malignant melanomas, premalignant and potentially malignant naevi, in 1896 excised melanocytic lesions submitted to a pathology service over 11 weeks. They comprised 8 per cent. The percentage increased with age: 4 per cent in the under-40s, 17 per cent in those aged 40-59, and 30 per cent in those over 60, (P < 0.001, sex-adjusted). Although the percentage was twice as high in males (11 per cent) as females (6 per cent), after adjustment for age the difference was not significant. Invasive melanomas, 3 per cent of the total, were similar: 1 per cent were from under-40s; 7 per cent from those aged 40-59 years; and 14 per cent from those over 60. They comprised 4 per cent of lesions from males and 2 per cent from females. These trends may indicate poor specificity of clinical diagnosis, notwithstanding other reasons for removal of naevi (cosmetic), particularly among patients under 40, and females.


Eculizumab in low-middle income countries: how much does a life cost?
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease and eculizumab was approved as first line therapy in 2011 by the Food and Drug Administration. Access to eculizumab in low-middle income countries is challenging. We discuss access to eculizumab in Brazil that was made possible by judicialization or compassionate use. We showed a nationwide cohort of unplanned eculizumab interruptions resulted in higher rates of aHUS relapse. Similar to the French cohort, the use of eculizumab after transplantation showed superior graft survival compared to conventional treatment. We speculate a possible solution to the higher cost of eculizumab in which the government negotiates with the manufacturers. In this process, the government should compromise to ensure validated protocols of drug use, and the pharmaceutical companies, on the other hand, should reduce prices, especially in low-income countries. We also suggest a price adjustment based on gross domestic product.


The new regulatory state: the social powers of the European Union.
The understanding of the European Union poses a challenge for Sociology and its traditional conceptions of the state. In particular, the impact of the social dimension has been underestimated and undervalued. This paper explores the implications of the developing social dimension of the European Union for European social relations in the context of globalization which allegedly reduces the power of states to act effectively in the social realm. It argues for a broader conceptualization of the social dimension and for a new conception of the regulatory state. It argues that the significance of a politico-legal project social justice. It concludes with a re-consideration of the powers of the state in an era of globalization


The intricate role of CXCR4 in cancer.
Chemokines mediate numerous physiological and pathological processes related primarily to cell homing and migration. The chemokine CXCL12, also known as stromal cell-derived factor-1, binds the G-protein-coupled receptor CXCR4, which, through multiple divergent pathways, leads to chemotaxis, enhanced intracellular calcium, cell adhesion, survival, proliferation, and gene transcription. CXCR4, initially discovered for its involvement in HIV entry and leukocytes trafficking, is overexpressed in more than 23 human cancers. Cancer cell CXCR4 overexpression contributes to tumor growth, invasion, angiogenesis, metastasis, relapse, and therapeutic resistance. CXCR4 antagonism has been shown to disrupt tumor-stromal interactions, sensitize cancer cells to cytotoxic drugs, and reduce tumor growth and metastatic burden. As such, CXCR4 is a target not only for therapeutic intervention but also for noninvasive monitoring of disease progression and therapeutic guidance. This review provides a comprehensive overview of the biological involvement of CXCR4 in human cancers, the current status of CXCR4-based therapeutic approaches, as well as recent advances in noninvasive imaging of CXCR4 expression.


Metformin reverses impaired osteogenesis due to hyperglycemia-induced neutrophil extracellular traps formation.
Diabetic patients suffer from delayed fracture healing and impaired osteogenic function, but the underlying pathophysiological mechanisms are not fully understood. Neutrophil extracellular traps (NETs) formed by neutrophils in high glucose microenvironments affect the healing of wounds and other tissues. Some evidence supports that NETs may inhibit osteogenic processes in the microenvironment through sustained inflammatory activation. In this study, we observed that high glucose-induced NETs led to sustained inflammatory activation of macrophages. Pro-inflammatory NETs inhibited the osteogenic function of osteoblasts in vitro. A bone defect healing model based on diabetic rat animal models confirmed that bone healing was impaired in a high glucose environment, but this process could be reversed by DNase I, a NETs clearance agent. More importantly, the classic hypoglycemic drug metformin had a similar antagonistic effect as DNase I and could reverse the inhibitory effect of NETs on osteogenesis in a high-glucose environment. In summary, we found that NETs formation induced by high glucose microenvironment is a potential cause of osteogenic dysfunction in diabetic patients, and metformin can reverse this osteogenic disadvantage.


Comparison of targeted metagenomics and IS-Pro methods for analysing the lung microbiome.
Targeted metagenomics and IS-Pro method are two of the many methods that have been used to study the microbiome. The two methods target different regions of the 16 S rRNA gene. The aim of this study was to compare targeted metagenomics and IS-Pro methods for the ability to discern the microbial composition of the lung microbiome of COPD patients. Spontaneously expectorated sputum specimens were collected from COPD patients. Bacterial DNA was extracted and used for targeted metagenomics and IS-Pro method. The analysis was performed using QIIME2 (targeted metagenomics) and IS-Pro software (IS-Pro method). Additionally, a laboratory cost per isolate and time analysis was performed for each method. Statistically significant differences were observed in alpha diversity when targeted metagenomics and IS-Pro methods' data were compared using the Shannon diversity measure (p-value = 0.0006) but not with the Simpson diversity measure (p-value = 0.84). Distinct clusters with no overlap between the two technologies were observed for beta diversity. Targeted metagenomics had a lower relative abundance of phyla, such as the Proteobacteria, and higher relative abundance of phyla, such as Firmicutes when compared to the IS-Pro method. Haemophilus, Prevotella and Streptococcus were most prevalent genera across both methods. Targeted metagenomics classified 23 % (144/631) of OTUs to a species level, whereas IS-Pro method classified 86 % (55/64) of OTUs to a species level. However, unclassified OTUs accounted for a higher relative abundance when using the IS-Pro method (35 %) compared to targeted metagenomics (5 %). The two methods performed comparably in terms of cost and time; however, the IS-Pro method was more user-friendly. It is essential to understand the value of different methods for characterisation of the microbiome. Targeted metagenomics and IS-Pro methods showed differences in ability in identifying and characterising OTUs, diversity and microbial composition of the lung microbiome. The IS-Pro method might miss relevant species and could inflate the abundance of Proteobacteria. However, the IS-Pro kit identified most of the important lung pathogens, such as Burkholderia and Pseudomonas and may work in a more diagnostics-orientated setting. Both methods were comparable in terms of cost and time; however, the IS-Pro method was easier to use.


Separation of flavonoids from Millettia griffithii with high-performance counter-current chromatography guided by anti-inflammatory activity.
Millettia griffithii is a unique Chinese plant located in the southern part of Yunnan Province. Up to now, there is no report about its phytochemical or related bioactivity research. In our previous study, the n-hexane crude extract of Millettia griffithii revealed significant anti-inflammatory activity at 100 μg/mL, inspiring us to explore the anti-inflammatory constituents. Four fractions (I, II, III, and A) were fractionated from n-hexane crude extract by high-performance counter-current chromatography with solvent system composed of n-hexane/ethyl acetate/methanol/water (8:9:8:9, v/v) and then were investigated for the potent anti-inflammatory activity. Fraction A, with the most potent inhibitory activity was further separated to give another four fractions (IV, V, VI, and B) with solvent system composed of n-hexane/ethyl acetate/methanol/water (8:4:8:4, v/v). Compound V and fraction B exhibited remarkable anti-inflammatory activity with nitric oxide inhibitory rate of 80 and 65%, which was worth further fractionation. Then, three fractions (VII, VIII, and IX) were separated from fraction B with a solvent system composed of n-hexane/ethyl acetate/methanol/water (8:1:8:1, v/v), with compound VIII demonstrating the most potent inhibitory activity (80%). Finally, the IC50 values of compound V and VIII were tested as 38.2 and 14.9 μM. The structures were identified by electrospray ionization mass spectrometry and(1)H and (13)C NMR spectroscopy.


From collectivism to individualism? The acculturation of greek immigrants in australia.
The present study examined whether Greek immigrants in Australia have retained traditional Greek values and behaviours or moved to an integration of these with Anglo-Australian values and behaviours. The sample consisted of Anglo- and Greek-Australian parents and young adolescents and a comparison group of Greeks, resident in Greece. Measures were obtained of values and behaviows considered to be appropriate for family members in the culture. Results showed that Greek-Australians retained the collectivistic values of their Greek culture while Anglo-Australians demonstrated a more individualistic orientation. There was evidence for convergence of Anglo- and Greek-Australian perceptions of appropriate behaviours and thus support for a view that acculturation is more likely to be manifested in behaviours than in core values. Although there were some differences in expressed values and behaviours, overall there was little evidence for a cultural gap between Greek-Australian parents and their adolescents.


Toward Precision Medicine in Brain Metastases.
Brain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs. However, this genetic divergence also results in genetic alterations associated with resistance to targeted therapies. A deeper insight on the genetic alterations of BMs and the interaction with the brain microenvironment will likely reveal new treatment targets, moving toward more precision therapies for patients with BMs.


Identification of odor biomarkers in irradiation injury urine based on headspace SPME-GC-MS.
The threat of population exposure to ionizing radiation is increasing rapidly worldwide. Such exposure, especially at high-dose, is known to cause acute radiation syndrome (ARS). Hence, it is necessary to develop specific and sensitive biomarkers to accurately diagnose radiation injury and evaluate medical countermeasures. Caenorhabditis elegans (C. elegans), a model organism with a fine and sound olfactory system, was used to examine the odor of urine samples collected from irradiation-injured rats, and compared with those from un-irradiated control rats to investigate the 'special odor' of radiation injury. Subsequently, headspace SPME-GC-MS was applied for non-targeted metabolomic analysis of volatile organic compounds (VOCs) in urine, with the aim to discover changes of small molecule metabolites and identify odor biomarkers of irradiation injury. C. elegans showed significant attraction to the urine of total body irradiation (TBI) rats compared with control rats, indicating that irradiation injury can emit 'special odor' and the metabolites in urine VOCs were changed. Using metabolomics based on headspace SPME-GC-MS for metabolic profiles analysis, we screened 63 differentially expressed metabolites. Among them, 10 metabolites including p-Cresol with excellent diagnostic ability were identified as odor biomarkers according to receiver operating characteristic (ROC) curve analysis. This study confirmed the 'special odor' induced by irradiation injury, and identified biomarkers through urine VOCs analysis for the first time, which can provide a novel approach and insight to evaluate irradiation injury noninvasively, accurately and conveniently.[Figure: see text].


Survey of Hox-like genes in the teleost Morone saxatilis: implications for evolution of the Hox gene family.
We used a PCR-based method to survey a defined subset of Hox-like genes in the genome of Morone saxatilis (striped bass) to determine their relationship to similar Hox genes in other vertebrates, to estimate Hox cluster number, and to gain additional information about vertebrate Hox gene evolution. We identified eight distinct striped bass Hox-like genes representing Hox clusters A, B, and C. Comparison of Hox gene evolutionary trees from striped bass, zebrafish, and mouse provided evidence consistent with current views of early evolutionary divergence of genes from the Hox 3' and central classes. However, estimates of Hox gene divergence based on nucleotide substitution frequencies among four fish species and the mouse were contrary to established vertebrate phylogenies according to either traditional or molecular taxonomic analyses.


[Physicochemical properties of the hoof horn in healthy highly productive cows and in those with hoof diseases].
Comparative investigations were carried out to determine the water content, total protein, the macroelements Ca, P, Na, and K and the trace elements Zn, Mn, and S in the wall and sole horn of the front and hind hooves of high-producing cows of the Bulgarian Brown breed and the Black Pied cattle. The hoof water content in both breeds did not show any substantial differences in normal and diseased cows, and varied within the limits of 19 to 34 per cent. In affected hooves the water content was higher than that in normal hooves. The contents of total protein, Ca, P, K, Na, Zn, and Mn did not show, essential differences of either. The low level of total sulfur in diseased hooves was an indication of the lowered resistance of hoof horn.


Confluence-induced cell cycle exit involves pre-mitotic CDK inhibition by p27(Kip1) and cyclin D1 downregulation.
Tissue homeostasis requires precise control of cell proliferation and arrest in response to environmental cues. In situation such as wound healing, injured cells are stimulated to divide, but as soon as confluence is reached proliferation must be blocked. Such reversible cell cycle exit occurs in G(1), requires pRb family members, and is driven by p27(Kip1)-dependent Cdk inactivation. This implies that, while dividing, cells should simultaneously prepare the exit once mitosis is accomplished. For a long time, the decision to cycle or not was presumed to occur in G(1), prior to the restriction point, beyond which the cells were bound to divide even in the absence of mitogens, before finally arresting after mitosis. However, more recent reports suggested that the commitment to cycle in response to serum occurs already in G(2) phase and requires the Ras-dependent induction of cyclin D1, which promotes following G(1)/S transition. To test whether this hypothesis applies to arrest induced by contact inhibition, we used an in vitro wounding model where quiescent human dermal fibroblasts, stimulated to proliferate by mechanical injury, synchronously exit cell cycle after mitosis due to renewed confluence. We show that this exit is preceded by p27-dependent inhibition of cyclin A-Cdk1/2, cyclin D1 downregulation and reduced pre-mitotic pRb pocket protein phosphorylation. Overexpression of cyclin D1 but not p27 depletion reversed this phenotype and compromised confluence-driven cell cycle exit. Thus, a balance between cyclin D1 and p27 may provide sensitive responses to variations in proliferative cues operating throughout the cell cycle.


[What does the visceral surgeon need to know about computed tomography in the diagnostic work-up of the acute abdomen?].
The acute abdomen is a very serious yet common condition of patients presenting in the emergency department. The clinical symptoms of patients with acute abdomen are often unspecific. The responsibility of the surgeon in charge is to differentiate acute life-threatening from less serious conditions with a high level of diagnostic accuracy in a minimal period of time. Imaging represents a cornerstone in the diagnostic work-up of patients with acute abdomen. Computed tomography (CT) is increasingly utilised to detect emergency conditions in patients with acute abdomen. In this review article we aim to elaborate the role of CT in the imaging strategy for acute abdomen in comparison to conventional radiography, ultrasonography and magnetic resonance imaging. In addition, relevant factors pertaining for the indication of CT such as exposure to ionising radiation and safety of iodinated contrast media are discussed.


Rojiroti microfinance and child nutrition: a cluster randomised trial.
To determine whether Rojiroti microfinance, for poor Indian women, improves child nutrition. Cluster randomised trial. Tolas (village communities) in Bihar State. Women and children under 5 years. With Rojiroti microfinance, women form self-help groups and save their money to provide loans to group members. After 6 months, they receive larger external loans. Tolas were randomised to receive Rojiroti immediately or after 18 months. The primary analysis compared the mean weight for height Z score (WHZ) of children under 5 years in the intervention versus control tolas who attended for weight and height measurement 18 months after randomisation. Secondary outcomes were weight for age Z score (WAZ), height for age Z score, mid-upper arm circumference (MUAC), wasting, underweight and stunting. We randomised 28 tolas to each arm and collected data from 2469 children (1560 mothers) at baseline and 2064 children (1326 mothers) at follow-up. WHZ was calculated for 1718 children at baseline and 1377 (674 intervention and 703 control) at follow-up. At 18 months, mean WHZ was significantly higher for intervention (-1.02) versus controls (-1.37; regression coefficient adjusted for clustering β=0.38, 95% CI 0.16 to 0.61, p=0.001). Significantly fewer children were wasted in the intervention group (122, 18%) versus control (200, 29%; OR=0.46, 95% CI 0.28 to 0.74, p=0.002). Mean WAZ was better in the intervention group (-2.13 vs -2.37; β=0.27, 95% CI 0.11 to 0.43, p=0.001) as was MUAC (13.6 cm vs 13.4 cm; β=0.22, 95% CI 0.03 to 0.40, p=0.02). In an analysis adjusting for baseline nutritional measures (259 intervention children and 300 control), only WAZ and % underweight showed significant differences in favour of the intervention. In marginalised communities in rural India, child nutrition was better in those who received Rojiroti microfinance, compared with controls. NCT01845545.


Confirmation of the trials and tribulations of vaping.
Responses to our article indicate consensus on the need for expedited scientific and regulatory action related to vaping of cannabis and other substances to curtail untoward public health impact and identify potential benefits. How to speed up science, increase knowledge and enact responsible regulatory policy poses a formidable challenge.


Premature discontinuation of curative radiation therapy: Insights from head and neck irradiation.
Factors related to premature discontinuation of curative radiation therapy (PDCRT) are understudied. This study aimed to examine causes and clinical outcomes of PDCRT at our institution by investigating the most common anatomical site associated with PDCRT. Among the 161 patients with PDCRT of various anatomic sites at our institution between 2010 and 2017, 36% received radiation to the head and neck region. Pertinent demographic, clinical, and treatment-related data on these 58 patients were collected. Survival was examined using the life-table method and log-rank test. The majority of patients were male (81%), white (67%), ≥60 years old (59%), living ≥10 miles away from the hospital (60%), single (57%), with Eastern Cooperative Oncology Group score ≥1 (86%), experiencing significant pain issues (67%), and had treatment interruptions in radiation therapy (RT; 66%). The most common reasons for PDCRT were discontinuation against medical advice (33%), medical comorbidity (24%), and RT toxicity (17%). Of the comorbidities leading to PDCRT, 50% was acute cardiopulmonary issues and 43% was infection. The mean follow-up time was 15.9 months, and the 2-year overall survival and disease-specific survival rates were 61% and 78%, respectively. Patients with illicit substance abuse, cardiovascular disease, and Eastern Cooperative Oncology Group score ≥2 had worse survival. A trend toward improved survival with total completed dose ≥50 Gy versus <50 Gy existed (74% versus 44%, respectively; P = .07). In this largest-to-date, modern analysis of PDCRT, the most common cause of discontinuation was discontinuation against medical advice, which underscores the importance of patient education, optimization of RT symptoms, involvement of social work, and integration of other supportive services early in treatment. Survival remains suboptimal after PDCRT for H&N tumors, with a 2-year overall survival rate of 61%. Completing >50 Gy appears to confer a relative therapeutic benefit.


Phytoremediative urban design: transforming a derelict and polluted harbour area into a green and productive neighbourhood.
Many urban areas are polluted by industrial activities and waste disposal in landfills. Since conventional soil remediation techniques are costly and unsustainable, phytoremediation might offer an alternative. In this article, we explore how phytoremediation can be integrated into the transformation of urban post-industrial areas, while improving public space. Buiksloterham, a polluted and deprived industrial area in Amsterdam, serves as case study. Buiksloterham is polluted with heavy metals, with Zinc (Zn) concentrations being the highest. A regression-model for Alpine Pennycress (Thlaspi caerulescens) is used to estimate the time needed to remediate the site. This reveals a conflict in time between remediation and urban development. A research by design experiment shows how to overcome this conflict by dealing with polluted soil innovatively while emphasizing spatial and aesthetic qualities of the phytoremediation plant species. The resulting landscape framework integrates phytoremediation with biomass production and gives new ecological, economic and social value to Buiksloterham.


Investigation of antifungal response of NiO and copper-doped NiO thin films against Aspergillus niger and Macrophomina phaseolina fungi.
Pure NiO and NiO thin films doped with 0.1 to 25% Cu were grown on pre-heated soda-lime glass substrates via spray pyrolysis technique. The surface roughness of the NiO:Cu thin films decreased as Cu/Ni ratio was increased. Antifungal activity of these thin films against Aspergillus niger (A. niger) which affects some of the fruits, and Macrophomina phaseolina (M. phaseolina) which is a soil borne fungus responsible for the infection of root and lower stem of several plants, was then investigated by bioassay and broth dilution methods. The antifungal response of pure NiO thin film was weak but it improved considerably on doping with copper. The higher the copper content in NiO:Cu thin film, the better was its antifungal response. Moreover, for the given Cu/Ni ratio range of 0-25%, the optical density (OD) of Potato Dextrose (PD) broth inoculated with A. niger and containing NiO:Cu material was reduced or antifungal ability was enhanced by 8.3, 9.9, 11.7, and 13.4 times for the exposure time of 6, 8, 10, and 12 days, respectively. Similarly, the OD of PD broth inoculated with M. phaseolina and containing NiO:Cu material was reduced or antifungal ability was enhanced by 16-37 times in the exposure temperature range of 20-40 °C. A linear relationship of OD with crystallite size and lattice strain of the thin films showed that NiO:Cu material possessed memory of the structural modifications induced by the dopant atoms though its phase changed from crystalline to non-crystalline state. These results can be utilized in agricultural sector. Graphical abstract.


Liposomal prednisolone phosphate potentiates the antitumor activity of liposomal 5-fluorouracil in C26 murine colon carcinoma in vivo.
The antitumor efficacy of 5-fluorouracil (5-FU) in advanced colorectal cancer (CRC) is hindered not only by the low therapeutic index, but also by tumor cell resistance to this cytotoxic drug. Therefore, to enhance the 5-FU antitumor activity, the present research used a novel tumor-targeted therapy based on the co-administration of 5-FU encapsulated in long-circulating liposomes (LCL-5-FU) together with liposomal prednisolone phosphate (LCL-PLP), a formulation with known anti-angiogenic actions on C26 murine colon carcinoma cells. Thus, we assessed the in vivo effects of the combined liposomal drug therapy on C26 carcinoma growth as well as on the production of molecular markers with key roles in tumor development such as angiogenic, inflammatory, and oxidative stress molecules. To get further insight into the polarization state of tumor microenvironment after the treatment, we determined the IL-10/IL-12p70 ratio in tumors. Our results showed that combined liposomal drug therapy inhibited almost totally tumor growth and was superior as antitumor activity to both single liposomal drug therapies tested. The antitumor efficacy of the combined therapy was mainly related to the anti-angiogenic and anti-inflammatory actions on C26 carcinoma milieu, being favored by its controlling effect on intratumor oxidative stress and the skewing of polarization of tumor microenvironmental cells toward their antineoplastic phenotypes. Thus, our study unveils a promising treatment strategy for CRC that should be furthermore considered.


Measurement of the differential cross-sections of prompt and non-prompt production of [Formula: see text] and [Formula: see text] in pp collisions at [Formula: see text] and 8 TeV with the ATLAS detector.
The production rates of prompt and non-prompt [Formula: see text] and [Formula: see text] mesons in their dimuon decay modes are measured using 2.1 and 11.4 fb[Formula: see text] of data collected with the ATLAS experiment at the Large Hadron Collider, in proton-proton collisions at [Formula: see text] and 8 respectively. Production cross-sections for prompt as well as non-prompt sources, ratios of [Formula: see text] to [Formula: see text] production, and the fractions of non-prompt production for [Formula: see text] and [Formula: see text] are measured as a function of meson transverse momentum and rapidity. The measurements are compared to theoretical predictions.


Evaluating asthma control: a comparison of measures using an item response theory approach.
Self-reported symptoms, FEV(1), and clinician judgment are all used to evaluate asthma control. The relative utility of each measure of control cannot be easily assessed. Item response theory (IRT) approaches allow for the direct comparison of the utility of different types of measures used to assess control. The objective of this study was to evaluate the validity and reliability of evaluating asthma control using symptom, clinical, and physiologic measures by applying an IRT approach. Subjects receiving care at an asthma clinic were evaluated on measures of asthma control. Based on 114 evaluations, IRT parameters were estimated to evaluate whether measures assessed a single underlying construct, the hierarchical relationship between the measures and the level of control each measure assessed, whether measures targeted all levels of asthma control, and whether the scoring categories distinguished between different levels of control. Infit statistics (0.74-1.5) for individual items showed that all items fit the underlying concept of asthma control. The reproducibility of the hierarchal scale was high (0.9). The results also demonstrated that items differentiated two strata (high, low) of control. The gaps in the hierarchal scale showed that for many subjects (37%) there were no items at their level of asthma control. The IRT approach identified gaps in current measurement that need to be addressed to provide more precise evaluations of control required to accurately monitor changes in patient status.


[Limitations of the diagnosis of bipolar disorder].
It has been studied the possible confusion in the diagnosis of bipolar disorder when there are no clear mania symptoms and other psychiatric disorders, due to his clinic similarity. The diagnosis received from a group of patients admitted in a Psychiatric Unit of a General Hospital by manic episode were studied. 84 admitted patients have been followed up along an average of 32 months. By means logistic regression, there were found the factors that explained the change in the diagnosis along the evolution. 87% of the patients after the follow up kept the diagnosis of bipolar disorder. However, 63.1% had received other diagnosis. Two factors predicted to receive other diagnosis: depressive clinic and not having stable couple. Bipolar disorder presents a proper stability once diagnosis have been made. It may be confused with psychotic sight, unipolar depression and B cluster personality disorders. It is checked that patients which start with manic psychosis phases are the ones that present biggest diagnosis stability.


Facile synthesis of highly substituted 3-aminofurans from thiazolium salts, aldehydes, and dimethyl acetylenedicarboxylate.
[reaction: see text] A facile preparation of 3-aminofuran derivatives via multicomponent reactions of thiazole carbenes, aldehydes, and dimethyl acetylenedicarboxylate (DMAD) is reported. In this process, the thiazole carbenes, generated in situ from thiazolium salts, reacted with aldehydes and DMAD at -78 to 0 degree C in CH(2)Cl(2) to afford the substituted furans in moderate to good yields. Eight substituted thiazolium salts were employed as carbene precursors in the reaction. Besides aryl aldehydes, alpha,beta-unsaturated aldehydes, aliphatic aldehydes, and arenedial were also investigated and found to be applicable to this reaction.


The impact of genetic variation in IL28B, IFNL4 and HLA genes on treatment responses against chronic hepatitis C virus infection.
Single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B), interferon lambda 4 (IFNL4) and the human leukocyte antigen (HLA) gene are associated with treatment responses in patients with chronic hepatitis C (CHC) virus infection treated with pegylated interferon-α and ribavirin (pegIFN-α/RBV). We compared the role of IL28B SNPs (rs12979860, rs12980275, and rs8099917), IFNL4 ss469415590 and HLA rs4273729 with treatment outcomes in patients with CHC virus. A total of 520 Iranian patients with CHC infection were enrolled. SNPs in IL28B, IFNL4 ss469415590 and HLA rs4273729 were genotyped by PCR-restriction fragment length polymorphism, TaqMan® Real-Time PCR and direct sequence. Out of 520 CHC treatment-naive patients, 42.9% were infected with HCV-1a, 15.4% with HCV-1b, 9.8% with HCV-2, and 31.9% with HCV-3a. Rapid virologic response (RVR), complete early virologic response (cEVR), and sustained virologic response (SVR) were 53.3%, 73.8%, and 66.7%, respectively. Multivariate logistic regression analysis showed that IL28B rs12980275 and IFNL4 ss469415590 in all HCV genotypes were associated with RVR. In addition, IL28B rs12979860 and RVR in all HCV genotypes and IL28B rs12980275, IFNL4 ss469415590, and HLA rs4273729 in HCV subtypes 1a, 1b, and 3a correlated with cEVR. In patient's achieving-SVR, IL28B rs12980275, and RVR in all HCV genotypes and IL28B rs12979860, IFNL4 ss469415590, and HLA rs4273729 in HCV subtypes 1a, 1b, and 3a were the powerful predictor factors. As the first report of its kind published in Iran, we indicated that beside IL28B SNPs and HLA rs4273729, IFNL4 ss469415590 was a powerful predictor factor for RVR, cEVR and SVR. Genotyping these SNPs may be a helpful priority in the treatment of patients with HCV infection, especially in countries where access to triple or double therapy with a viral protease inhibitor is limited.


Differences between Belgian and Brazilian group A Streptococcus epidemiologic landscape.
Group A Streptococcus (GAS) clinical and molecular epidemiology varies with location and time. These differences are not or are poorly understood. We prospectively studied the epidemiology of GAS infections among children in outpatient hospital clinics in Brussels (Belgium) and Brasília (Brazil). Clinical questionnaires were filled out and microbiological sampling was performed. GAS isolates were emm-typed according to the Center for Disease Control protocol. emm pattern was predicted for each isolate. 334 GAS isolates were recovered from 706 children. Skin infections were frequent in Brasília (48% of the GAS infections), whereas pharyngitis were predominant (88%) in Brussels. The mean age of children with GAS pharyngitis in Brussels was lower than in Brasília (65/92 months, p<0.001). emm-typing revealed striking differences between Brazilian and Belgian GAS isolates. While 20 distinct emm-types were identified among 200 Belgian isolates, 48 were found among 128 Brazilian isolates. Belgian isolates belong mainly to emm pattern A-C (55%) and E (42.5%) while emm pattern E (51.5%) and D (36%) were predominant in Brasília. In Brasília, emm pattern D isolates were recovered from 18.5% of the pharyngitis, although this emm pattern is supposed to have a skin tropism. By contrast, A-C pattern isolates were infrequently recovered in a region where rheumatic fever is still highly prevalent. Epidemiologic features of GAS from a pediatric population were very different in an industrialised country and a low incomes region, not only in term of clinical presentation, but also in terms of genetic diversity and distribution of emm patterns. These differences should be taken into account for designing treatment guidelines and vaccine strategies.


Orbital-selective mott transitions in the degenerate Hubbard model.
We investigate the Mott transitions in two-band Hubbard models with different bandwidths. Applying dynamical mean field theory, we discuss the stability of itinerant quasiparticle states in each band. We demonstrate that separate Mott transitions occur at different Coulomb interaction strengths in general, which merge to a single transition only under special conditions. This kind of behavior may be relevant for the physics of the single-layer ruthenates, Ca2-xSrxRuO4.


Preoperative delay of more than 1 hour increases the risk of surgical site infection.
Retrospective institutional database review. To determine whether preoperative in-room time is a risk factor for surgical site infection (SSI). Prior to spine surgery, while the patient is in the operating room, several procedures may be performed that may delay surgery. During this time, the sterile field may be exposed and may become contaminated. The hypothesis of this study was that the length of time in the operative room prior to surgical incision (anesthesia ready time [ART]) was related to the risk of SSI. From 2005 to 2009, we identified 276 patients who developed SSI out of 7991 cases that underwent spine surgery from 2005 to 2009. Patient demographic factors, American Society of Anesthesiologists score, wound classification, number of levels, anatomic region, type of surgical approach, and length of surgery were extrapolated. ART was calculated as the time after the patient was brought into the operating room prior to surgical incision. Multivariate analysis was performed to identify risk factors for SSI. Mean ART was significantly (P = 0.001) higher in patients with infection (68 min) compared with those without infection (60 min). The infection rate was higher in cases with ART more than 1 hour compared with those with less than 1 hour (4.9% vs. 2.3%, P = 0.001). In multivariate analysis, ART more than 1 hour was an independent risk factor for SSI, along with number of levels, American Society of Anesthesiologists score and posterior approach. The highest percentage of cases with ART more than 1 hour occurred in August and September. Preoperative in-room time prior to the start of surgical incision is an independent risk factor for SSI. All possible steps should be taken prior to entry into the operating theater to reduce in-room time and opening of surgical sterile instrumentation be delayed until the surgery is ready to proceed.


Totipotency, cell differentiation and reprogramming in humans.
Understanding the molecular mechanisms defining totipotency and cell differentiation in humans is a promising strategy in order to expand knowledge about reprogramming. Totipotency and the very first steps of cell differentiation can be studied well in early human embryos. Based on analysis of marker genes such as Oct-4 and -HCG, blastomeres seem to differ in their potency and can be regarded as lineage-specific stem cells as early as the 4-cell stage. The allocation of these stem cells to specific fates might hereby follow a pattern reminiscent of animal and vegetal poles. On the opposite end of the developmental spectrum, differentiated human cells can be used as a means of studying nuclear reprogramming. Intact human 293T kidney cells and primary leukocytes were reprogrammed towards a more undifferentiated state by Xenopus laevis egg extract. Molecular screens identified the chromatin-remodelling ATPase BRG1 as a factor required for this process. Based on these results, more efficient reprogramming protocols allowing for the generation of fully differentiated or undifferentiated human cells for clinical application may be developed.


Mycobiota and mycotoxins in bee pollen collected from different areas of Slovakia.
Contamination by microscopic fungi and mycotoxins in different bee pollen samples, which were stored under three different ways of storing as freezing, drying and UV radiation, was investigated. During spring 2009, 45 samples of bee-collected pollen were gathered from beekeepers who placed their bee colonies on monocultures of sunflower, rape and poppy fields within their flying distance. Bee pollen was collected from bees' legs by special devices placed at the entrance to hives. Samples were examined for the concentration and identification of microscopic fungi able to grow on Malt and Czapek-Dox agar and mycotoxins content [deoxynivalenol (DON), T-2 toxin (T-2), zearalenone (ZON) and total aflatoxins (AFL), fumonisins (FUM), ochratoxins (OTA)] by direct competitive enzyme-linked immunosorbent assays (ELISA). The total number of microscopic fungi in this study ranged from 2.98 ± 0.02 in frozen sunflower bee pollen to 4.06 ± 0.10 log cfu.g(-1) in sunflower bee pollen after UV radiation. In this study, 449 isolates belonging to 21 fungal species representing 9 genera were found in 45 samples of bee pollen. The total isolates were detected in frozen poppy pollen 29, rape pollen 40, sunflower pollen 80, in dried poppy pollen 12, rape pollen 36, sunflower 78, in poppy pollen after UV radiation treatment 54, rape 59 and sunflower 58. The most frequent isolates of microscopic fungi found in bee pollen samples of all prevalent species were Mucor mucedo (49 isolates), Alternaria alternata (40 isolates), Mucor hiemalis (40 isolates), Aspergillus fumigatus (33 isolates) and Cladosporium cladosporioides (31 isolates). The most frequently found isolates were detected in sunflower bee pollen frozen (80 isolates) and the lowest number of isolates was observed in poppy bee pollen dried (12 isolates). The most prevalent mycotoxin of poppy bee pollen was ZON (361.55 ± 0.26 μg.kg(-1)), in rape bee pollen T-2 toxin (265.40 ± 0.18 μg.kg(-1)) and in sunflower bee pollen T-2 toxin (364.72 ± 0.13 μg.kg(-1)) in all cases in frozen samples.


A Novel Method to Adjust Saphenous Vein Graft Lengths Using 3D Printing Models.
The optimal length of saphenous vein grafts can be challenging in surgical coronary revascularization. It is the cornerstone for graft patency. In this study, we tried to demonstrate the value of 3D printing in determining optimal saphenous graft length. Sixteen patients who underwent bypass surgery with only vein grafts were examined. Patients' measurements of graft lengths were obtained from postoperative CT images and from both 3D print models manually with plastic tubes and via 3D print digital images of Mimics software during segmentation. Another measurement was done using the Fit Centerline tool in the analysis module of Mimics software after segmentation. These 3 measurements were compared. There was a statistically significant difference between 3 measurement methods for each graft length (P < .001). Measurements of actual grafts were longer than measurements of 3D printed models manually and segmentation images from software were similar (P > .05). 3D printing models and their software may be used to determine optimal saphenous graft length and the anastomosis site to decrease operation time. It can be deducted from these results that 3D printing is a promising method for reducing operator dependent variables in adjusting graft size and finding optimal anastomosis sites.


Prevalence of traumatic injuries and knowledge regarding emergency care among 11-14 years government school children in rural area, Dehra, Kangra district, Himachal Pradesh.
To assess the prevalence of traumatic injuries and the knowledge regarding the emergency care among school children in rural area Dehra, Kangra district, Himachal Pradesh. A cross-sectional survey was carried out in 13 government schools among 1041 subjects aged 11- 14 years. The demographic details and knowledge regarding emergency care was recorded on a structured questionnaire. The data regarding the traumatic injuries was recorded using modified Ellis' classification. Prevalence of Traumatic Dental Injuries (TDI) was found to be 5.12 %. Maxillary central incisor was the most common tooth to be affected (58.1%). The main cause for TDI was found to be due to falls (51.2%). Enamel with dentin fracture with pulp exposure was the main type of TDI (46.7%). The awareness regarding emergency care revealed that 63.4% of subjects were aware of emergency care. The knowledge regarding TDI increased with increase in age. The prevalence of dental trauma was found to be low and the awareness level regarding emergency care was found to be fair. Hence it is highly recommended to plan a community wide trauma prevention campaign targeting parents, children and dental care providers.


A novel MitoNEET ligand, TT01001, improves diabetes and ameliorates mitochondrial function in db/db mice.
The mitochondrial outer membrane protein mitoNEET is a binding protein of the insulin sensitizer pioglitazone (5-[[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione) and is considered a novel target for the treatment of type II diabetes. Several small-molecule compounds have been identified as mitoNEET ligands using structure-based design or virtual docking studies. However, there are no reports about their therapeutic potential in animal models. Recently, we synthesized a novel small molecule, TT01001 [ethyl-4-(3-(3,5-dichlorophenyl)thioureido)piperidine-1-carboxylate], designed on the basis of pioglitazone structure. In this study, we assessed the pharmacological properties of TT01001 in both in vitro and in vivo studies. We found that TT01001 bound to mitoNEET without peroxisome proliferator-activated receptor-γ activation effect. In type II diabetes model db/db mice, TT01001 improved hyperglycemia, hyperlipidemia, and glucose intolerance, and its efficacy was equivalent to that of pioglitazone, without the pioglitazone-associated weight gain. Mitochondrial complex II + III activity of the skeletal muscle was significantly increased in db/db mice. We found that TT01001 significantly suppressed the elevated activity of the complex II + III. These results suggest that TT01001 improved type II diabetes without causing weight gain and ameliorated mitochondrial function of db/db mice. This is the first study that demonstrates the effects of a mitoNEET ligand on glucose metabolism and mitochondrial function in an animal disease model. These findings support targeting mitoNEET as a potential therapeutic approach for the treatment of type II diabetes.


Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.
Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells.IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41 infection on human enterochromaffin cells and found it stimulates serotonin secretion in the cells, which is involved in regulation of intestinal secretion and gut motility and can also activate enteric glia cells, which are found in close proximity to enterochromaffin cells in vivo This disruption of gut barrier homeostasis as maintained by these cells following human adenovirus 41 infection might be a mechanism in enteric adenovirus pathogenesis in humans and could indicate a possible serotonin-dependent cross talk between human adenovirus 41, enterochromaffin cells, and enteric glia cells.


Protein patterns of the Brassica rapa ovules and seeds under altered gravity.
Electrophoretic investigation of protein patterns of Brassica rapa L. ovules and seeds from plants grown under clinorotation and in the laboratory control was carried out. Ovules at different stages (7 and 18 days after pollination) and mature seeds were analyzed. Polymorphism of seed storage proteins of B. rapa was taken into consideration in analysis of changes in ovule protein patterns under clinorotation. The appearance of a protein component in the region of about 43 kDa was detected in protein patterns of 7-day-old and 18-day-old ovules in the clinostat variants. Under altered gravity, in 18-day-old ovules, the appearance of a protein in the region of about 70 kDa was also revealed. The appearance of the protein component with the similar mobility (about 43 kDa) in ovules of different age from plants grown at clinorotation suggests that synthesis of this protein may be associated with the plant response to altered gravity. However, the investigation of the nature of this protein and its role requires further research to rule out its appearance because of genotypic differences between ovules of the control and experimental variants.


Flexible Piezoelectricity of Two-Dimensional Materials Governed by Effective Berry Curvature.
Two-dimensional piezoelectric materials have been regarded as ideal candidates for flexible and versatile nanoelectromechanical systems, yet their fundamental piezoelectric mechanisms remain to be fully understood. Employing joint theoretical-statistical analyses, we develop universal models for quantifying the piezoelectricity of three-coordinated honeycomb-like monolayers at the atomistic level. The theoretical model within the framework of modern polarization theory suggests that the distribution of effective Berry curvature is essential for interpreting the relation between microscopic/electronic structures and piezoelectric properties. The statistical model based on DFT high-throughput calculation reveals that 2D piezoelectricity crucially depends on the effective mass, bandgap, and atomic distance along the rotation axis. Implementing stress and doping is demonstrated to be effective for optimizing piezoelectricity. Such findings provide valuable guidelines for designing 2D piezoelectric materials.


Microscopic anterior clinoidectomy with micro-rongeurs for a superior projecting paraclinoid internal carotid artery aneurysm: a technical note.
Anterior clinoidectomy is an essential manoeuvre for clipping paraclinoid internal carotid artery (ICA) aneurysms. However, the use of a drill or an ultrasonic bone curette in an anterior clinoidectomy involves a high risk for heat or mechanical injury of the superior projecting paraclinoid aneurysm. We report our technique for microscopic anterior clinoidectomy performed only using a micro-rongeur. The case of a superior projecting paraclinoid ICA aneurysm is presented. The anterior clinoid process was removed with our specially crafted micro-rongeurs, while we observed the extradural and intradural routes under a microscope. The aneurysm was completely clipped without any resulting neurological deficits. This technique can be safely used for paraclinoid ICA aneurysms, especially for superiorly projecting aneurysms.


Identification and Validation of Invasion-Related Molecular Subtypes and Prognostic Features for Cervical Cancer.
As one of the main causes leading to female cancer deaths, cervical cancer shows malignant features of local infiltration and invasion into adjacent organs and tissues. This study was designed to categorize novel molecular subtypes according to cervical cancer invasion and screen reliable prognostic markers. Invasion-related gene sets and expression profiles of invasion-related genes were collected from the CancerSEA database and The Cancer Genome Atlas (TCGA), respectively. Samples were clustered by nonnegative matrix factorization (NMF) to obtain different molecular subgroups, immune microenvironment characteristics of which were further systematically compared. Limma was employed to screen differentially expressed gene sets in different subtypes, followed by Lasso analysis for dimension reduction. Multivariate and univariate Cox regression analysis was performed to determine prognostic characteristics. The Kaplan-Meier test showed the prognostic differences of patients with different risks. Additionally, receiver operating characteristic (ROC) curves were applied to validate the prognostic model performance. A nomogram model was developed using clinical and prognostic characteristics of cervical cancer, and its prediction accuracy was reflected by calibration curve. This study filtered 19 invasion-related genes with prognosis significance in cervical cancer and 2 molecular subtypes (C1, C2). Specifically, the C1 subtype had an unfavorable prognosis, which was associated with the activation of the TGF-beta signaling pathway, focal adhesion, and PI3K-Akt signaling pathway. 875 differentially expressed genes were screened, and 8 key genes were finally retained by the dimension reduction analysis. An 8-gene signature was established as an independent factor predictive of the prognosis of cervical cancer. The signature performance was even stronger when combined with N stage. Based on invasion-related genes, the present study categorized two cervical cancer subtypes with distinct TME characteristics and established an 8-gene marker that can accurately and independently predict the prognosis of cervical cancer.