Background
The aim of this study was to explore the association between tumor necrosis factor superfamily number 4 (TNFSF4) rs1234315, rs2205960 polymorphisms and systemic lupus erythematosus (SLE) ...susceptibility.
Methods
A meta-analysis was performed on the association between rs1234315 and rs2205960 polymorphisms and SLE by allelic contrast, additive model, recessive model and dominant model.
Results
Regarding rs1234315 polymorphism, a total of five studies were included (6575 cases, 14,798 controls). Meta-analysis showed significant associations between the T allele and SLE in overall subjects and Asians (OR = 1.310, 95%CI: 1.104–1.553, p = 0.002; OR = 1.458, 95%CI: 1.328–1.602, p < 0.001). With respect to the rs2205960 polymorphism, significant associations between the T allele and SLE were found in all subjects (OR = 1.333, 95%CI: 1.254–1.418, p < 0.001), Asians (OR = 1.407, 95%CI: 1.345–1.471, p < 0.001) and Europeans (OR = 1.254, 95%CI: 1.185–1.328, p < 0.001). Results also showed significant associations between the additive model and SLE in all subjects and Asians (OR = 1.934, 95%CI: 1.500–2.494, p < 0.001; OR = 1.882, 95%CI: 1.318–2.689, p = 0.001). Furthermore, we detected significant associations between the dominant model and SLE in all subjects and Asians (OR = 1.421, 95%CI: 1.239–1.629, p < 0.001; OR = 1.297, 95%CI: 1.083–1.555, p = 0.005). Significant associations were found between the recessive model and SLE in overall subjects and Asians (OR = 1.677, 95%CI: 1.312–2.144, p < 0.001; OR = 1.751, 95%CI: 1.235–2.483, p = 0.002).
Conclusion
The present study suggested that TNFSF4 rs1234315 and rs2205960 polymorphisms were associated with SLE susceptibility.
The probability of suffering the mood disorder depression is up to 30% in women and 15% in men during their life span. Pharmacological options for depression are limited: conventional antidepressants ...have low efficacy and a delayed onset of action (several weeks). Here we investigate the antidepressant actions of inhibitors of monoacylglycerol lipase (MAGL), the major degradative enzyme of the endocannabinoid 2-arachidonoylglycerol. A low-dose of MAGL inhibitors produces antidepressant effects on acute stress-exposed mice, through glutamatergic synaptic long-term depression (LTD), without significant effects on chronic corticosterone-exposed mice. In contrast, a high-dose of MAGL inhibitors produces pro- or antidepressant effects on acute stress- or chronic corticosterone-exposed mice, respectively, through GABAergic synaptic disinhibition. In the hippocampus, in vivo inhibition of MAGL induces a CB
cannabinoid receptor (CB
R)-dependent suppression of inhibitory GABAergic synapses and an in vivo LTD of excitatory glutamatergic synapses. LTD induction requires CB
R in astroglial cells (but not in GABAergic or glutamatergic neurons) and postsynaptic glutamate receptors. The conventional antidepressant fluoxetine produces rapid or delayed antidepressant effects in acute stress- or chronic corticosterone-exposed mice, respectively. We propose that depression-like behavior of animals in response to acute stress is the normal behavioral response, and thus, MAGL inhibitors, which produce antidepressant effects in chronic corticosterone-exposed animals through GABAergic synaptic disinhibition, represent a new class of rapidly-acting and long-lasting antidepressants.
Summary
Fat‐tailed sheep have commercial value because consumers prefer high‐protein and low‐fat food and producers care about feed conversion rate. However, fat‐tailed sheep still have some ...scientific significance, as the fat tail is commonly regarded as a characteristic of environmental adaptability. Finding the candidate genes associated with fat tail formation is essential for breeding and conservation. To identify these candidate genes, we applied FST and hapFLK approaches in fat‐ and thin‐tailed sheep with available 50K SNP genotype data. These two methods found 6.24 Mb of overlapped regions and 43 genes that may associated with fat tail development. Gene annotation showed that HOXA11, BMP2, PPP1CC, SP3, SP9, WDR92, PROKR1 and ETAA1 may play important roles in fat tail formation. These findings provide insight into tail fat development and a guide for molecular breeding and conservation.
In order to better match the multi-level structural characteristics and multi-scale fracture process of cementitious composite, multi-scale hybrid fiber-reinforced strain hardening cementitious ...composite (MsHySHCC) was designed by adding hooked steel fiber and calcium carbonate (CaCO3) whisker into conventional polyvinyl alcohol (PVA) fiber-reinforced SHCC. Compressive properties of PVA-SHCC and MsHySHCC were evaluated experimentally. The results indicate that the designed MsHySHCC had a better compressive performance than that of PVA-SHCC. Moderately partially substituted PVA fibers by steela fiber and CaCO3 whisker enhanced the compressive parameters, however, further substitution of PVA fibers by increasing the content of CaCO3 whisker didn’t bring a higher promotion. Two kinds of semi-theoretical compression constitutive models were developed from the perspective of damage mechanics theory and geometrical mathematical description, respectively. It was found that both of the proposed models can be applied to predict the uniaxial compressive stress-strain relationships of PVA-SHCC and MsHySHCCs.
We present the achievements of the last years of the experimental and theoretical groups working on hadronic cross section measurements at the low-energy
e
+
e
−
colliders in Beijing, Frascati, ...Ithaca, Novosibirsk, Stanford and Tsukuba and on
τ
decays. We sketch the prospects in these fields for the years to come. We emphasise the status and the precision of the Monte Carlo generators used to analyse the hadronic cross section measurements obtained as well with energy scans as with radiative return, to determine luminosities and
τ
decays. The radiative corrections fully or approximately implemented in the various codes and the contribution of the vacuum polarisation are discussed.
Primary analysis of the phase III trial BG01-1323L demonstrated that utidelone plus capecitabine significantly improved progression-free survival (PFS) and overall response rate (ORR) versus ...capecitabine alone in heavily-pretreated patients with metastatic breast cancer (MBC). Here, we report the final overall survival (OS) analysis and updates of other endpoints.
In total, 405 patients were randomised 2:1 to receive utidelone (30 mg/m2 IV daily, days 1-5, over 90 min) plus capecitabine (1000 mg/m2 orally b.i.d., days 1-14) or capecitabine alone (1250 mg/m2 orally b.i.d., days 1-14) every 21 days. The secondary endpoint, OS, was estimated using the Kaplan–Meier product-limit approach at a two-sided alpha level of 0.05 after the prespecified 310 death events had been reached. Exploratory analyses of the primary endpoint, PFS, and the secondary endpoint, ORR, were also done. Safety was analysed in patients who had at least one dose of study drug.
At the final OS analysis, the median duration of follow-up was 19.6 months in the utidelone plus capecitabine group and 15.4 months in the capecitabine alone group. In the intention-to-treat population, 313 deaths had occurred at data cut-off, 203 of 270 patients in the combination group and 110 of 135 in the monotherapy group. Median OS in the combination group was 19.8 months compared with 16.0 months in the monotherapy group hazard ratio (HR) = 0.75, 95% confidence intervals (CI) 0.59-0.94, P = 0.0142. The updated analysis of PFS and ORR showed that the combination therapy remained superior to monotherapy. Safety results were similar to those previously reported with respect to incidence, severity and specificity. No late-emerging toxicities or new safety concerns occurred.
For heavily-pretreated, anthracycline- and taxane-resistant MBC patients, utidelone plus capecitabine significantly improved OS versus capecitabine alone. These results support the use of utidelone plus capecitabine as a novel therapeutic regimen for patients with MBC.
•The phase III study evaluated utidelone plus CAP versus CAP alone in patients with anthracycline- and taxane-refractory MBC.•In this final analysis of OS, utidelone plus CAP significantly improved OS compared with CAP alone.•No significant differences were observed in the safety profiles of the treatment groups.•Of note, utidelone caused only mild myelosuppression and no significant hepatic toxicity.•Although peripheral neuropathy was common, it was generally manageable and reversible with dose modifications.
Among renewable energy resources, bioenergy is one of the fastest growth energy alternatives with tremendous potential in China. The thermal, physical, and biological processes of conversion of ...biomass yield a number of products and can be obtained as gases, liquids, solid fuels, and electricity as well as a variety of chemicals. Various bioenergy technologies that have been developed are at the fundamental research, demonstration, and commercialization stages. This review concentrates on the processes that are attracting the most attention in China.
This paper presents the important roles bioenergy plays in China. Firstly, the application status of bioenergy technologies are introduced, including biogas, fuel ethanol, biodiesel, and power generation at the commercialization stage. Then, the current research progresses are analyzed of ethanol derived from
lignocellulose, sweet sorghum and
cassava, biodiesel from
jatropha, biomass briquetting, synthesized fuels and pyrolysis technologies at the fundamental research and demonstration stages. Finally, it is concluded that the key areas for developing bioenergy for the future are the exploitation of new biomass resources and R&D in biofuels from non-food biomass resources, as well as the development of commercialization methods suitable for developing countries.
Skeletal muscle plays an important role in glycaemic control and metabolic homeostasis, making it a tissue of interest with respect to type 2 diabetes mellitus. The aim of the present study was to ...determine if ligands of Toll-like receptors (TLRs) could have an impact on energy metabolism and myokine expression and secretion in cultured human skeletal muscle cells. The myotubes expressed mRNA for TLRs 1-6. TLR3, TLR4, TLR5 and TLR6 ligands (TLRLs) increased glucose metabolism. Furthermore, TLR4L and TLR5L increased oleic acid metabolism. The metabolic effects of TLRLs were not evident until after at least 24 h pre-incubation of the cells and here the metabolic effects were more evident for the metabolism of glucose than oleic acid, with a shift towards effects on oleic acid metabolism after chronic exposure (168 h). However, the stimulatory effect of TLRLs on myokine expression and secretion was detected after only 6 h, where TLR3-6L stimulated secretion of interleukin-6 (IL-6). TLR5L also increased secretion of interleukin-8 (IL-8), while TLR6L also increased secretion of granulocyte-macrophage colony stimulating factor (GM-CSF). Pre-incubation of the myotubes with IL-6 for 24 h increased oleic acid oxidation but had no effect on glucose metabolism. Thus IL-6 did not mimic all the metabolic effects of the TLRLs, implying metabolic effects beyond the actions of this myokine.
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