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The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel that is activated by capsaicin (CAP), the main component of chili pepper. Despite studies in several neurological diseases, the role of TRPV1 in demyelinating diseases remains unknown. Herein, we reported that TRPV1 expression was increased within the corpus callosum during demyelination in a cuprizone (CPZ)-induced demyelination mouse model. TRPV1 deficiency exacerbated motor coordinative dysfunction and demyelination in CPZ-treated mice, whereas the TRPV1 agonist CAP improved the behavioral performance and facilitated remyelination. TRPV1 was predominantly expressed in Iba1 + microglia/macrophages in human brain sections of multiple sclerosis patients and mouse corpus callosum under demyelinating conditions. TRPV1 deficiency decreased microglial recruitment to the corpus callosum, with an associated increase in the accumulation of myelin debris. Conversely, the activation of TRPV1 by CAP enhanced the recruitment of microglia to the corpus callosum and potentiated myelin debris clearance. Using real-time live imaging we confirmed an increased phagocytic function of microglia following CAP treatment. In addition, the expression of the scavenger receptor CD36 was increased, and that of the glycolysis regulators Hif1a and Hk2 was decreased. We conclude that TRPV1 is an important regulator of microglial function in the context of demyelination and may serve as a promising therapeutic target for demyelinating diseases such as multiple sclerosis.

The association between type 2 diabetes （T2DM） and bone metabolism has been discussed previously but is controversial. In this study we aimed to evaluate the association of bone turnover markers with glucose metabolism in Chinese population, in which 919 males and 4171 postmenopausal females in a region of Shanghai were recruited. Anthropometric and biochemical traits related to glucose and bone metabolism were analyzed. Participants were classified according to their glucose tolerance as normal glucose tolerance （NGT）, impaired glucose regulation （IGR） or T2DM. Males and females were analyzed separately, and then associations between bone turnover markers （BTMs） and glucose metabolism were evaluated. The results showed that in females, the serum levels of N-terminal osteocalcin （N-MID）, N-terminal procollagen of type I collagen （PINP） and β-cross-linked C-telopeptide of type I collagen （β-CTX） were significantly decreased in the T2DM group compared to the NGT group （P〈0.01）. When age, body mass index, serum lipids, fat percentage, visceral fat area, subcutaneous fat area, anti-diabetic medicines, PINP, N-MID and β-CTX were included in one logistic model, N-MID （OR [95% CI]： 0.954 [0.932; 0.976]; P=0.0001） was significantly associated with T2DM in females. In females, N-MID was associated with insulin sensitivity and HOMA-β. PINP was significantly associated with HOMA-β, GUTT-ISI, Stumvo first-phase insulin secretion index （STU-1） and Stumvoll second-phase insulin secretion index （STU-2）, but β-CTX was associated only with HOMA-β （β_＋SE： 0.1331±0.0311; P=1.95×10^-5） and GUTI--ISI （β±SE： 0.0727±0.0229; P=0.0015）. In males, N-MID was significantly correlated with HOMA-β （β±SE： 0.3439±0.0633; P=7.75×10^-8）, GUTT-ISI （β±SE： 0.1601±0.0531; P=0.0027） and STU-1 （β±SE： 0.2529±0.1033; P=0.0146）. Significant associations were also detected between 13-CTX and HOMA-β （β＋SE： 0.2736±0.0812; P=0.0009）. This study reveals that BTMs are highly associated with T2DM, insulin sensitivity and beta cell function in both Chinese males and postmenopausal females.

Multiple epiphyseal dysplasia （MED; EDMI, OMIM 132400; EDM2, OMIM 600204; EDM3, OMIM 600969; EDM4, OMIM 226900; EDM5~ OMIM 607078; EDM6, OMIM 614135） is an autosomal dominant inherited disease of the skeletal system, characterized by mild short stature and early-onset degenerative joint disease, caused by heterogeneous genotypes involving more than six genes （COMP, COL9A 1, COL9A2, COL9A3, MATN3, DTDST）.However, in approximately 10-20% of all samples analyzed, a mutation cannot be identified in any of the six genes mentioned above, suggesting that the presence of other unidentified causative genes is also involved in the pathogenesis of MED.

Bug reports are essential software artifacts that describe software bugs, especially in open-source software. Lately, due to the availability of a large number of bug reports, a considerable amount of research has been carried out on bug-report analysis, such as automatically checking duplication of bug reports and localizing bugs based on bug reports. To review the work on bug-report analysis, this paper presents an exhaustive survey on the existing work on bug-report analysis. In particular, this paper first presents some background for bug reports and gives a small empirical study on the bug reports on Bugzilla to motivate the necessity for work on bug-report analysis. Then this paper summaries the existing work on bug-report analysis and points out some possible problems in working with bug-report analysis.

Background： The antibiotic meropenem is commonly administered pharmacokinetic, clinical, and bacteriological efficacies of continuous patients. n patients with severe sepsis and septic shock. We compared the infusion of meropenem versus internaittent administration in such Methods： Patients admitted to the Intensive Care Unit （ICU） with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous （n = 25） or intermittent groups 01 = 25）. The continuous group received a loading dose of 0.5 g of meropenem lbllowed by a continuous infusion of 3 g/day： the intermittent group received an initial dose of 1.5 g lbllowed by 1 g lbr every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations tbr the first and third dosing periods （steady state） were also measured. Results： Clinical success was similar in both the continuous （64%） and intermittent （56%） groups （P = 0.564）： the rates of microbiological eradication and superinfection （81.8% vs. 66.7% [P = 0.255] and 4% vs. 16% [P 0.157], respectively） showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group （7.6 vs. 9.4 days; P = 0.035）, where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first （Cmax： 19.8 mg/L vs. 51.8 mg/L, P = 0.000; Cmin： 11.2 mg/L vs. 0.5 nag/L, P = 0.000） and third dosing periods （Cmax： 12.5 mg/L vs. 46.4 rag/L, P = 0.000; Cmin： 11.4 mg/L vs. 0.6 rag/L, P = 0.000）. For medium-susceptibility pathogens, continuous inthsion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group- Conclusions： Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous inthsion may be more optimal against imermediate-susceptibility pathogens.

Mine dust is classified as one of five natural coal mining disasters because it can harm the health of miners and poses a serious threat to the safety of the coal mine. Therefore, preparation of an effective dust suppression agent is highly desired. To improve the capture efficiency of fine dust, this study examines the dust suppression effects of various combinations of wetting agents, additives, and coagulation agents by using the optimum seeking method to reduce mine dust, particularly respirable particles. The optimal formula is shown to contain 10wt% fatty alcohol polyoxyethylene ether（JFC）, 4.96wt% cationic polyacrylamide, and 4wt% calcium chloride. The dust suppression effect can be achieved at 96.1% in 5 min by using the optimal formula.

Background： Lipid storage myopathy （LSM） is a genetically heterogeneous group with variable clinical phenotypes. Late-onset multiple acyl-coenzyme A dehydrogenation deficiency （MADD） is a rather common form of LSM in China. Diagnosis and clinical management of it remain challenging, especially without robust muscle biopsy result and genetic detection. As the noninvasion and convenience, muscle magnetic resonance imaging （MRI） is a helpful assistant, diagnostic tool for neuromuscular disorders. However, the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed. Methods： We assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients, combined with detailed clinical features and gene spectrum. Fat infiltration degree of the thigh muscle was scored while that ofgluteus was described as obvious or not. Associated muscular atrophy was defined as obvious muscle bulk reduction. Results： The mean scores were significantly different among the anterior, medial, and posterior thigh muscle groups. The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group （P 〈 0.00 l）. Moreover, the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group （P 〈 0.01）. About half of the patients displayed fat infiltration and atrophy in gluteus muscles. Of 28 patients, 12 exhibited atrophy in medial and/ or posterior thigh muscle groups, especially in posterior thigh muscle group. Muscle edema pattern was not found in all the patients. Conclusions： Late-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior, posterior, and medial thigh muscle groups, with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment. Our findings also suggest that muscle MRI of lower limbs is a helpful tool in guiding clinical evaluation on late-onset MADD.

Background A later chronotype has been found to be associated with unhealthy habits and diseases, such as an unhealthy diet and metabolic syndrome in adults. Little is known about the association between chronotype, eating habits, physical activity and obesity. Thus, this study aimed to explore the relationships between chronotype, eating behaviors, physical activity, and overweight in Chinese school-aged children. Methods Data from this study was based on 952 schoolchildren (10–12 y) from six primary schools that participated in China. Anthropometric measurements of height and body weight were performed. Information about sleeping habits, dietary behaviors, and other lifestyle behaviors was gathered using a self-administered questionnaire. Multiple linear regression analysis or multivariable logistic regression model was performed to assess the associations between chronotype, eating behaviors, physical activity, and overweight. Results Nearly 70% (69.9%) of the participants had a self-reported morning chronotype. Multiple linear regression analysis revealed chronotype score was positively associated with physical activities (all P values < 0.001) and sleep duration (all P values < 0.001) and negatively associated with BMI, meal time, eating jet lag and social jet lag (all P values < 0.001). Multivariable logistic regression analysis showed that compared to morning types, non-morning types individuals were more likely to be overweight (OR = 1.593, P value < 0.05), and had more frequent consumption of fast food (OR = 1.616, P value < 0.05), but less frequent consumption of milk (OR = 0.716, P value < 0.05), less time taking part in moderate (OR = 1.356, P value < 0.05) or muscle strengthening (OR = 1.393, 1.877, P value < 0.05) physical activity. Conclusions This study indicates that early chronotype children are more active, have healthier dietary habits, get more sleep, have shorter social jet lag, and are less likely to be overweight than non-early chronotype children. Our findings suggest that later chronotype may be a potential indicator in the early detection of overweight, unhealthy eating, and physical inactivity behaviors. Plain english summary Chronotype has been found to have an important impact on individual’s health. In the present study, we conducted a cross-sectional study to investigate the association between chronotype, eating behaviors, physical activity, and overweight in school-aged children. The findings showed that children with early chronotype is associated with more active, healthier dietary behaviors, longer sleep duration, short social jet lag, and a lower risk of overweight.

Of the two cultivated species of allopolyploid cotton, Gossypium barbadense produces extra-long fibers for the production of superior textiles. We sequenced its genome (AD) 2 and performed a comparative analysis. We identified three bursts of retrotransposons from 20 million years ago (Mya) and a genome-wide uneven pseudogenization peak at 11–20 Mya, which likely contributed to genomic divergences. Among the 2,483 genes preferentially expressed in fiber, a cell elongation regulator, PRE1 , is strikingly A t biased and fiber specific, echoing the A-genome origin of spinnable fiber. The expansion of the PRE members implies a genetic factor that underlies fiber elongation. Mature cotton fiber consists of nearly pure cellulose. G. barbadense and G. hirsutum contain 29 and 30 cellulose synthase (CesA) genes, respectively; whereas most of these genes (>25) are expressed in fiber, genes for secondary cell wall biosynthesis exhibited a delayed and higher degree of up-regulation in G. barbadense compared with G. hirsutum , conferring an extended elongation stage and highly active secondary wall deposition during extra-long fiber development. The rapid diversification of sesquiterpene synthase genes in the gossypol pathway exemplifies the chemical diversity of lineage-specific secondary metabolites. The G. barbadense genome advances our understanding of allopolyploidy, which will help improve cotton fiber quality.

Matrine (MAT), a quinolizidine alkaloid component derived from the root of , suppresses experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), by inducing the production of immunomodulatory molecules, e.g., IL-10. In an effort to find the upstream pathway(s) of the mechanism underlying these effects, we have tested certain upregulated immunomodulatory molecules. Among them, we found increased levels of IL-27 and IFN-β, one of the first-line MS therapies. Indeed, while low levels of IFN-β production in sera and type I interferon receptor (IFNAR1) expression in spinal cord of saline-treated control EAE mice were detected, they were significantly increased after MAT treatment. Increased numbers of CD11b IFN-β microglia/infiltrating macrophages were observed in the CNS of MAT-treated mice. The key role of IFN-β induction in the suppressive effect of MAT on EAE was further verified by administration of anti-IFN-β neutralizing antibody, which largely reversed the therapeutic effect of MAT. Further, we found that, while MAT treatment induced production of IL-27 and IL-10 by CNS microglia/macrophages, this effect was significantly reduced by IFN-β neutralizing antibody. Finally, the role of IFN-β in MAT-induced IL-27 and IL-10 production was further confirmed in human monocytes . Together, our study demonstrates that MAT exerts its therapeutic effect in EAE through an IFN-β/IL-27/IL-10 pathway, and is likely a novel, safe, low-cost, and effective therapy as an alternative to exogenous IFN-β for MS.