Mclaughlinhines1953
Granger causality analyses showed that the PAG Granger caused vmPFC time series in men and the reverse was true in women, substantiating sex differences in the directional interactions of the PAG and vmPFC.
The findings provide the first evidence in humans implicating the PAG circuit in cocaine withdrawal and cocaine craving and advance our understanding of the role of the pain circuit and negative reinforcement in sustaining habitual drug use in cocaine addiction.
The findings provide the first evidence in humans implicating the PAG circuit in cocaine withdrawal and cocaine craving and advance our understanding of the role of the pain circuit and negative reinforcement in sustaining habitual drug use in cocaine addiction.In this study, the double-layered nHA and PCL/nHA coatings were prepared on the substrate of Mg66Zn28Ca6 amorphous alloy. The phase composition and morphological were analyzed by Scanning electron microscopy, Energy dispersive spectrometry and X-ray diffraction. The electrochemical properties of these samples were measured on electrochemical workstation. The degradation rate was evaluated by measuring the pH value and weight loss. Experiment results show that the outer composite PCL/nHA coating is a porous structure, where the porosity and pore size could be easily controlled by adding nHA. The combined properties of double-layered nHA and PCL/nHA coating can control the degradation of the Mg66Zn28Ca6 amorphous alloy in the scheduled time. Moreover,the cell co-culture and cell adhesion tests show that the double-layered nHA and PCL/2%nHA coating possesses the best cytocompatibility with cell organization. The above experiments have demonstrated that the Mg66Zn28Ca6 amorphous alloy which was coated with PCL/nHA composite coating have good mechanical properties, good corrosion resistance and perfect cytocompatibility. It can be used as a potential novel biomaterial for bone tissue engineering.
This study aims to estimate the mental distress prevalence of Chinese postgraduate students and the association with the social changes based on the data between 2000 and 2019.
This is a cross-temporal meta-analysis study.
The literature was retrieved with both English and Chinese electronic databases, including articles published from 2002 to 2019. Statistical analyses were performed with R 3.6.1 and SPSS 22.
Eighty-nine primary studies with 99 reports were included in our meta-analysis, totaling 54,722 Chinese postgraduate students. The result showed that (a) the prevalence of mental distress was 28% (95% confidence interval [CI] 25%-31%), and the prevalence of moderately positive symptoms was 9% (95% CI 7%-11%); (b) the prevalence of positive symptoms was negatively correlated with the years of data collection and the prevalence of mental distress decreased by at least 16% from 2000 to 2019; and (c) social changes, particularly the policies of mental health and the educational environment had a significant contribution to these changes.
More than a quarter of postgraduate students have mental illness in China, whereas the prevalence of their mental distress has been decreasing. Social changes are shown to play an important role in contributing to this change.
More than a quarter of postgraduate students have mental illness in China, whereas the prevalence of their mental distress has been decreasing. Social changes are shown to play an important role in contributing to this change.Latent factor modeling applied to single-cell RNA sequencing (scRNA-seq) data is a useful approach to discover gene signatures. However, it is often unclear what methods are best suited for specific tasks and how latent factors should be interpreted. Here, we compare four state-of-the-art methods and propose an approach to assign derived latent factors to pathway activities and specific cell subsets. By applying this framework to scRNA-seq datasets from biopsies of patients with rheumatoid arthritis and systemic lupus erythematosus, we discover disease-relevant gene signatures in specific cellular subsets. In rheumatoid arthritis, we identify an inflammatory OSMR signaling signature active in a subset of synovial fibroblasts and an efferocytic signature in a subset of synovial monocytes. Overall, we provide insights into latent factors models for the analysis of scRNA-seq data, develop a framework to identify cell subtypes in a phenotype-driven way, and use it to identify novel pathways dysregulated in rheumatoid arthritis.The ability of propionate, a short-chain fatty acid produced from the fermentation of non-digestible carbohydrates in the colon, to stimulate the release of anorectic gut hormones, such as glucagon like peptide-1 (GLP-1), is an attractive approach to enhance appetite regulation, weight management, and glycemic control. Propionate induces GLP-1 release via its G protein-coupled receptor (GPCR), free fatty acid receptor 2 (FFA2), a GPCR that activates Gαi and Gαq/11. However, how pleiotropic GPCR signaling mechanisms in the gut regulates appetite is poorly understood. Here, we identify propionate-mediated G protein signaling is spatially directed within the cell whereby FFA2 is targeted to very early endosomes. Furthermore, propionate activates a Gαi/p38 signaling pathway, which requires receptor internalization and is essential for propionate-induced GLP-1 release in enteroendocrine cells and colonic crypts. Our study reveals that intestinal metabolites engage membrane trafficking pathways and that receptor internalization could orchestrate complex GPCR pathways within the gut.Loss of midbrain dopaminergic (mDA) neurons and their axons is central to Parkinson's disease (PD). Growth differentiation factor (GDF)5 is a potential neurotrophic factor for PD therapy. However, the molecular mediators of its neurotrophic action are unknown. Our proteomics analysis shows that GDF5 increases the expression of serine threonine receptor-associated protein kinase (STRAP) and nucleoside diphosphate kinase (NME)1 in the SH-SY5Y neuronal cell line. GDF5 overexpression increased NME1 expression in adult rat brain in vivo. NME and STRAP mRNAs are expressed in developing and adult rodent midbrain. Expression of both STRAP and NME1 is necessary and sufficient for the promotion of neurite growth in SH-SY5Y cells by GDF5. NME1 treatment increased neurite growth in both SH-SY5Y cells and cultured mDA neurons. Expression patterns of NME and STRAP are altered in PD midbrain. NME1 and STRAP are thus key mediators of GDF5's neurotrophic effects, rationalizing their future study as therapeutic targets for PD.The novel semi-autonomous vehicles are becoming a reality in our roads, being a very important technological advance with promising operational and safety improvements. However, road infrastructure must be ready to host them. The technologies of these driving automation systems require certain road conditions that are not always fulfilled, causing the systems to fail. These failures generally transfer negotiation control to drivers, which may induce a crash if they were not aware of road and traffic conditions. This research analyses how ready the road horizontal alignment is for existing semi-autonomous systems. A Level 2 vehicle has been tested on many different horizontal curves, finding a strong relationship between the maximum speed that the autonomous system can attain and the curve geometry. This maximum speed is proposed as a new concept (automated speed) and has been found to be lower than the design, operating and posted speeds in many cases. Staurosporine order Another new concept - automated driving consistency - arises, as the difference between automated and operating speeds. The related inconsistencies can be addressed with the new concept of Level of Service for Automated Driving (LOSAD), which summarizes how ready a corridor is for a certain driving automation system. This parameter should be determined - further certified - for any homogeneous road segment, and later informed to drivers.
Impaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Calcitonin gene-related peptide (CGRP), a neuropeptide targeted by emerging anti-migraine drugs, is also expressed in sensory nerve fibres innervating bone tissue.
Bone healing following a femoral osteotomy stabilized with an external fixator was analysed over 21 days in αCGRP-deficient and WT mice. Bone regeneration was evaluated by serum analysis, µCT analysis, histomorphometry and genome-wide expression analysis. Bone-marrow-derived osteoblasts and osteoclasts, as well as the CGRP antagonist olcegepant were employed for mechanistic studies.
WT mice with a femoral fracture display increased CGRP serum levels. αCGRP mRNA expression after skeletal injury is exclusively induced in callus tissue, but not in other organs. On protein level, CGRP and its receptor, calcitonin receptor-like receptor (CRLR) complexing with RAMP1, are differentially expressed in the callus during bone regeneration. On the othf Health (BIH).
This work was funded by grants from the Else-Kröner-Fresenius-Stiftung (EKFS), the Deutsche Forschungsgemeinschaft (DFG), and the Berlin Institute of Health (BIH).Coronavirus disease-2019 (COVID-19) is associated with severe inflammation in mainly the lung, and kidney. Reports suggest a beneficial effect of the use of heparin/low molecular weight heparin (LMWH) on mortality in COVID-19. In part, this beneficial effect could be explained by the anticoagulant properties of heparin/LMWH. Here, we summarise potential beneficial, non-anticoagulant mechanisms underlying treatment of COVID-19 patients with heparin/LMWH, which include (i) Inhibition of heparanase activity, responsible for endothelial leakage; (ii) Neutralisation of chemokines, and cytokines; (iii) Interference with leukocyte trafficking; (iv) Reducing viral cellular entry, and (v) Neutralisation of extracellular cytotoxic histones. Considering the multiple inflammatory and pathogenic mechanisms targeted by heparin/LMWH, it is warranted to conduct clinical studies that evaluate therapeutic doses of heparin/LMWH in COVID-19 patients. In addition, identification of specific heparin-derived sequences that are functional in targeting non-anticoagulant mechanisms may have even higher therapeutic potential for COVID-19 patients, and patients suffering from other inflammatory diseases.
Some COVID-19 cases test positive again for SARS-CoV-2 RNA following negative test results and discharge, raising questions about the meaning of virus detection. Better characterization of re-positive cases is urgently needed.
Clinical data were obtained through Guangdong's COVID-19 surveillance network. Neutralization antibody titre was determined using microneutralization assays. Potential infectivity of clinical samples was evaluated by cell inoculation. SARS-CoV-2 RNA was detected using three different RT-PCR kits and multiplex PCR with nanopore sequencing.
Among 619 discharged COVID-19 cases, 87 re-tested as SARS-CoV-2 positive in circumstances of social isolation. All re-positive cases had mild or moderate symptoms at initial diagnosis and were younger on average (median, 28). Re-positive cases (n=59) exhibited similar neutralization antibodies (NAbs) titre distributions to other COVID-19 cases (n=218) tested here. No infectious strain could be obtained by culture and no full-length viral genomes could be sequenced from re-positive cases.