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Carbon fibre-reinforced polymer (CFRP) plates can efficiently repair or enhance the mechanical properties of the square hollow section. However, the loading end of such a CFRP-strengthened member is prone to local bearing failure under compressive load. Given this limitation, an innovative CFRP-plate-strengthened square hollow section composite member (CFRP-SHSCM) was raised, and the thick-walled section was welded on both ends of the thin-walled steel column. The mechanical properties of CFRP-SHSCMs were investigated through parameter finite element (FE) analysis, focusing on the influence of the amount of CFRP layers (nc), the slenderness ratio (λ), the initial geometric imperfections (v0), the CFRP layouts (2S and 4S) and the length of the exposed steel column (Le). The load–displacement curves, the bearing force, and typical failure modes were also acquired. Results indicated that with increasing nc and v0, and decreasing λ, the conventional CFRP-SHSCMs were prone to local bearing failure with poor ductility, leading to the insufficient use of the CFRP plate, in contrast, the improved CFRP-SHSCMs primarily underwent overall buckling failure and exhibited better bearing force and ductility. Finally, the modified Perry-Robertson formula was put forward to predict the ultimate load of the CFRP-SHSCMs. The coefficients of variation between the FE simulation and the theoretical results were 0.00436 and 0.0292, respectively. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that SNARE fusion machinery play critical roles in postsynaptic neurotransmitter receptor trafficking, which is essential for synaptic plasticity. However, the key SNAREs involved remain highly controversial; syntaxin-3 and syntaxin-4 are leading candidates for the syntaxin isoform underlying postsynaptic plasticity. In a previous study, we showed that pyramidal-neuron specific conditional knockout (cKO) of syntaxin-4 significantly reduces basal transmission, synaptic plasticity and impairs postsynaptic receptor trafficking. However, this does not exclude a role for syntaxin-3 in such processes. Here, we generated and analyzed syntaxin-3 cKO mice. Extracellular field recordings in hippocampal slices showed that syntaxin-3 cKO did not exhibit significant changes in CA1 basal neurotransmission or in paired-pulse ratios. Importantly, there were no observed differences during LTP in comparison to control mice. Syntaxin-3 cKO mice performed similarly as the controls in spatial and contextual learning tasks. Consistent with the minimal effects of syntaxin-3 cKO, syntaxin-3 mRNA level was very low in hippocampal and cortex pyramidal neurons, but strongly expressed in the corpus callosum and caudate axon fibers. Together, our data suggest that syntaxin-3 is dispensable for hippocampal basal neurotransmission and synaptic plasticity, and further supports the notion that syntaxin-4 is the major isoform mediating these processes. [ABSTRACT FROM AUTHOR]

Impairment of renal phosphate elimination in chronic kidney disease (CKD) leads to enhanced plasma and tissue phosphate concentration, which in turn up-regulates transcription factor NFAT5 and serum & glucocorticoid-inducible kinase SGK1. The kinase upregulates ORAI1, a Ca2+-channel accomplishing store-operated Ca2+-entry (SOCE). ORAI1 is stimulated following intracellular store depletion by Ca2+-sensors STIM1 and/or STIM2. In megakaryocytes and blood platelets SOCE and thus ORAI1 are powerful regulators of activity. The present study explored whether the phosphate-donor ß-glycerophosphate augments NFAT5, ORAI1,2,3 and/or STIM1,2 expressions and thus SOCE in megakaryocytes. Human megakaryocytic Meg01cells were exposed to 2 mM of phosphate-donor ß-glycerophosphate for 24 hours. Platelets were isolated from blood samples of patients with impaired kidney function or control volunteers. Transcript levels were estimated utilizing q-RT-PCR, cytosolic Ca2+-concentration ([Ca2+]i) by Fura-2-fluorescence, and SOCE from increase of [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 µM). NFAT5 and ORAI1 protein abundance was estimated with Western blots. As a result, ß-glycerophosphate increased NFAT5, ORAI1/2/3, STIM1/2 transcript levels, as well as SOCE. Transcript levels of NFAT5, SGK1, ORAI1/2/3, and STIM1/2 as well as NFAT5 and ORAI1 protein abundance were significantly higher in platelets isolated from patients with impaired kidney function than in platelets from control volunteers. In conclusion, phosphate-donor ß-glycerophosphate triggers a signaling cascade of NFAT5/SGK1/ORAI/STIM, thus up-regulating store-operated Ca2+-entry. [ABSTRACT FROM AUTHOR]

The number of mice used for these analysis are: day 0 (WT n = 6, Rev-/- n = 6), day 3 (WT n = 6, Rev-/- n = 5), day 5 (WT n = 7, Rev-/- n = 6), day 8 (WT n = 5, Rev-/- n = 6), day 14 (WT n = 6, Rev-/- n = 5), day 30 (WT n = 6, Rev-/- n = 8). Author Correction: The Nuclear Receptor and Clock Repressor Rev-erb Suppresses Myogenesis (B) Quantitative analysis of regenerated myofiber diameter distribution at 30 days after cardiotoxin injury in WT (n = 6) and Rev-/- mice (n = 8). [Extracted from the article]

Novel coronavirus 2019 (COVID-19) infection is a global public health issue, that has now affected more than 200 countries worldwide and caused a second wave of pandemic. Severe adult respiratory syndrome-CoV-2 (SARS-CoV-2) pneumonia is associated with a high risk of mortality. However, prognostic factors predicting poor clinical outcomes of individual patients with SARS-CoV-2 pneumonia remain under intensive investigation. We conducted a retrospective, multicenter study of patients with SARS-CoV-2 who were admitted to four hospitals in Wuhan, China from December 2019 to February 2020. Mortality at the end of the follow up period was the primary outcome. Factors predicting mortality were also assessed and a prognostic model was developed, calibrated and validated. The study included 492 patients with SARS-CoV-2 who were divided into three cohorts: the training cohort (n = 237), the validation cohort 1 (n = 120), and the validation cohort 2 (n = 135). Multivariate analysis showed that five clinical parameters were predictive of mortality at the end of follow up period, including advanced age [odds ratio (OR), 1.1/years increase (p < 0.001)], increased neutrophil-to-lymphocyte ratio [(NLR) OR, 1.14/increase (p < 0.001)], elevated body temperature on admission [OR, 1.53/°C increase (p = 0.005)], increased aspartate transaminase [OR, 2.47 (p = 0.019)], and decreased total protein [OR, 1.69 (p = 0.018)]. Furthermore, the prognostic model drawn from the training cohort was validated with validation cohorts 1 and 2 with comparable area under curves (AUC) at 0.912, 0.928, and 0.883, respectively. While individual survival probabilities were assessed, the model yielded a Harrell's C index of 0.758 for the training cohort, 0.762 for the validation cohort 1, and 0.711 for the validation cohort 2, which were comparable among each other. A validated prognostic model was developed to assist in determining the clinical prognosis for SARS-CoV-2 pneumonia. Using this established model, individual patients categorized in the high risk group were associated with an increased risk of mortality, whereas patients predicted to be in the low risk group had a higher probability of survival. [ABSTRACT FROM AUTHOR]

We found an unusual Escherichia coli strain with resistance to colistin, carbapenem and amikacin from sewage. We therefore characterized the strain and determined the co-transfer of the resistance determinants. Whole genome sequencing was performed using both Illumina HiSeq X10 and MinION sequencers. Short and long reads were subjected to de novo hybrid assembly. Sequence type, antimicrobial resistance genes and plasmid replicons were identified from the genome sequences. Phylogenetic analysis of all IncHI2 plasmids carrying mcr-1 available in GenBank was performed based on core genes. Conjugation experiments were performed. mcr-3.5 was cloned into E. coli DH5α. The strain belonged to ST410, a type with a global distribution. Two colistin-resistant genes, mcr-1.1 and mcr-3.5, a carbapenemase gene blaNDM-5, and a 16S methylase gene rmtB were identified on different plasmids of IncHI2(ST3)/IncN, IncP, IncX3 and IncFII, respectively. All of the four plasmids were self-transmissible and mcr-1.1, mcr-3.5, blaNDM-5 and rmtB were transferred together. mcr-1-carrying IncHI2 plasmids belonged to several sequence types with ST3 and ST4 being predominant. MIC of colistin (4 μg/ml) for DH5α containing mcr-3.5 was identical to that containing the original mcr-3 variant. In conclusion, carbapenem resistance, colistin resistance and high-level aminoglycoside resistance can be transferred together even when their encoding genes are not located on the same plasmid. The co-transfer of multiple clinically-important antimicrobial resistance represents a particular challenge for clinical treatment and infection control in healthcare settings. Isolates with resistance to both carbapenem and colistin are not restricted to a given sequence type but rather are diverse in clonal background, which warrants further surveillance. The amino acid substitutions of MCR-3.5 have not altered its activity against colistin. [ABSTRACT FROM AUTHOR]

The real-time monitoring and evaluation of the severity and progression of cerebral hemorrhage is essential to its intensive care and its successful emergency treatment. Based on magnetic induction phase shift technology combined with a PCI data acquisition system and LabVIEW software, this study established a real-time monitoring system for cerebral hemorrhage. To test and evaluate the performance of the system, the authors performed resolution conductivity experiments, salted water simulation experiments and cerebral hemorrhage experiments in rabbits and found that when the conductivity difference was 0.73 S/m, the phase difference was 13.196°. The phase difference change value was positively proportional to the volume of saline water, and the conductivity value was positively related to the phase difference of liquid under the same volume conditions. After injecting 3 mL blood into six rabbits, the average change in the blood phase difference was −2.03783 ± 0.22505°, and it was positively proportional to the volume of blood, which was consistent with the theoretical results. The results show that the system can monitor the progressive development of cerebral hemorrhage in real-time and has the advantages of low cost, small size, high phase accuracy, and good clinical application potentiality. [ABSTRACT FROM AUTHOR]

Rev-erbα is a ligand-dependent nuclear receptor and a key repressor of the molecular clock transcription network. Accumulating evidence indicate that the circadian clock machinery governs diverse biological processes in skeletal muscle, including muscle growth, repair and mass maintenance. The physiological function of Rev-erbα in myogenic regulation remains largely unknown. Here we show that Rev-erbα exerts cell-autonomous inhibitory effects on proliferation and differentiation of myogenic precursor cells, and these actions concertedly inhibit muscle regeneration in vivo. Mechanistic studies reveal Rev-erbα direct transcriptional control of two major myogenic mechanisms, proliferative pathway and the Wnt signaling cascade. Consistent with this finding, primary myoblasts lacking Rev-erbα display significantly enhanced proliferative growth and myogenic progression. Furthermore, pharmacological activation of Rev-erbα activity attenuates, whereas its inhibition by an antagonist promotes these processes. Notably, upon muscle injury, the loss-of-function of Rev-erbα in vivo augmented satellite cell proliferative expansion and regenerative progression during regeneration. Collectively, our study identifies Rev-erbα as a novel inhibitory regulator of myogenic progenitor cell properties that suppresses postnatal myogenesis. Pharmacological interventions to dampen Rev-erbα activity may have potential utilities to enhance regenerative capacity in muscle diseases. [ABSTRACT FROM AUTHOR]

As post-transcriptional regulators, microRNAs (miRNAs) play an important role in growth and reproductive processes. So far, there is limited information regarding crustacean miRNAs. To explore the potential role of miRNAs in the gonadal development of the prawn Macrobrachium rosenbergii, we constructed seven small RNA libraries from ovarian and testicular tissues at various stages using somatic tissue as the control. A total of 1,954 known and 129 novel miRNAs were retrieved. By comparing differentially expressed miRNAs (DEMs) between testes and ovaries, forty-one miRNAs were identified with sex-biased expression patterns, including 17 ovary-biased and 24 testis-biased patterns. Furthermore, the putative target genes of the sex-biased miRNAs, such as cyclin L1, mitogen-activated protein kinase 7 (MAPK 7), heat shock protein (HSP), and zinc finger protein, were significantly enriched in many reproduction-related pathways including the Gonadotropin-releasing hormone (GnRH) pathway, glycolysis, gluconeogenesis pathway, ovarian steroidogenesis, estrogen signaling pathway, MAPK pathway, Wnt pathway, and insulin signaling pathway, implicating potential regulatory roles of miRNAs in reproduction. These data aid in the further investigation of the mechanism of gonadal development and reproductive regulation mediated by miRNA in M. rosenbergii. [ABSTRACT FROM AUTHOR]

Brown adipose tissue is a major thermogenic organ that plays a key role in maintenance of body temperature and whole-body energy homeostasis. Rev-erbα, a ligand-dependent nuclear receptor and transcription repressor of the molecular clock, has been implicated in the regulation of adipogenesis. However, whether Rev-erbα participates in brown fat formation is not known. Here we show that Rev-erbα is a key regulator of brown adipose tissue development by promoting brown adipogenesis. Genetic ablation of Rev-erbα in mice severely impairs embryonic and neonatal brown fat formation accompanied by loss of brown identity. This defect is due to a cell-autonomous function of Rev-erbα in brown adipocyte lineage commitment and terminal differentiation, as demonstrated by genetic loss- and gain-of-function studies in mesenchymal precursors and brown preadipocytes. Moreover, pharmacological activation of Rev-erbα activity promotes, whereas its inhibition suppresses brown adipocyte differentiation. Mechanistic investigations reveal that Rev-erbα represses key components of the TGF-β cascade, an inhibitory pathway of brown fat development. Collectively, our findings delineate a novel role of Rev-erbα in driving brown adipocyte development, and provide experimental evidence that pharmacological interventions of Rev-erbα may offer new avenues for the treatment of obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Four new ambuic acid derivatives (1-4), and four known derivatives (5-8), were isolated from the solid culture of a plant pathogenic fungus Pestalotiopsis neglecta. Their structures were elucidated by extensive NMR experiments. The absolute configuration of the C-16 secondary alcohol in 1 was deduced via the CD data of the in situ formed [Rh2(OCOCF3)4] complex with the acetonide derivative of 1. The absolute configuration in 3 was assigned by comparison of the experimental and simulated electronic circular dichroism (ECD) spectrum. The NMR data of compound 5 was reported for the first time. In the nitric oxide (NO) inhibition assay, compounds 4, 6 and 7 showed inhibitory activity against the NO production in the lipopolysaccharide (LPS)-induced macrophage with IC50 values of 88.66, 11.20, and 20.80 µM, respectively. [ABSTRACT FROM AUTHOR]