One-Pot Hydrothermal-Derived rGO/MXene/Sulfur Composite Aerogels as Free-Standing Cathodes in Lithium-Sulfur Batteries.

The confinement and high utilization of sulfur in the cathodes is critical for improved cycling performance of lithium-sulfur batteries. In this case one-pot hydrothermal strategy is developed to produce rGO/MXene/sulfur composite aerogels where sulfur is in situ trapped in the 3D rGO/MXene conductive skeleton. The optimized composite aerogels as free-standing cathodes delivery a specific capacity of 951 mAhg-1 after 100 cycles at 0.2 C with a low fading rate of 0.062% per cycle. The excellent cycling performance is correlated with highly oxidized MXene and in situ formed sulfate/thiosulfate complex layer in the long-term cycles.

Discovery and characterization of novel jeilongviruses in wild rodents from Hubei, China.

The genus Jeilongvirus comprises non-segmented negative-stranded RNA viruses that are classified within the Paramyxoviridae family by phylogeny. Jeilongviruses are found in various reservoirs, including rodents and bats. Rodents are typical viral reservoirs with diverse spectra and zoonotic potential. Little is currently known about jeilongviruses in rodents from central China. The study utilized high-throughput and Sanger sequencing to obtain jeilongvirus genomes, including those of two novel strains (HBJZ120/CHN/2021 (17,468 nt) and HBJZ157/CHN/2021 (19,143 nt)) and three known viruses (HBXN18/CHN/2021 (19,212 nt), HBJZ10/CHN/2021 (19,700 nt), HBJM106/CHN/2021 (18,871 nt)), which were characterized by genome structure, identity matrix, and phylogenetic analysis. Jeilongviruses were classified into three subclades based on their topology, phylogeny, and hosts. Based on the amino acid sequence identities and phylogenetic analysis of the L protein, HBJZ120/CHN/2021 and HBJZ157/CHN/2021 were found to be strains rather than novel species. Additionally, according to specific polymerase chain reaction screening, the positive percentage of Beilong virus in Hubei was 6.38%, suggesting that Beilong virus, belonging to the Jeilongvirus genus, is likely to be widespread in wild rodents. The identification of novel strains further elucidated the genomic diversity of jeilongviruses. Additionally, the prevalence of jeilongviruses in Hubei, China, was profiled, establishing a foundation for the surveillance and early warning of emerging paramyxoviruses.

Generation of a genetically modified pig model with CREBRFR457Q variant.

Obesity is among the strongest risk factors for type 2 diabetes (T2D). The CREBRF missense allele rs373863828 (p. Arg457Gln, p. R457Q) is associated with increased body mass index but reduced risk of T2D in people of Pacific ancestry. To investigate the functional consequences of the CREBRF variant, we introduced the corresponding human mutation R457Q into the porcine genome. The CREBRFR457Q pigs displayed dramatically increased fat deposition, which was mainly distributed in subcutaneous adipose tissue other than visceral adipose tissue. The CREBRFR457Q variant promoted preadipocyte differentiation. The increased differentiation capacity of precursor adipocytes conferred pigs the unique histological phenotype that adipocytes had a smaller size but a greater number in subcutaneous adipose tissue (SAT) of CREBRFR457Q variant pigs. In addition, in SAT of CREBRFR457Q pigs, the contents of the peroxidative metabolites 4-hydroxy-nonenal and malondialdehyde were significantly decreased, while the activity of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase, and catalase, was increased, which was in accordance with the declined level of the reactive oxygen species (ROS) in CREBRFR457Q pigs. Together, these data supported a causal role of the CREBRFR457Q variant in the pathogenesis of obesity, partly via adipocyte hyperplasia, and further suggested that reduced oxidative stress in adipose tissue may mediate the relative metabolic protection afforded by this variant despite the related obesity.

Development and validation of a deep learning model using convolutional neural networks to identify femoral internal fixation device in radiographs.

OBJECTIVE: The purpose of this study is to develop and validate a deep convolutional neural network (DCNN) model to automatically identify the manufacturer and model of hip internal fixation devices from anteroposterior (AP) radiographs. MATERIALS AND METHODS: In this retrospective study, 1721 hip AP radiographs, including six internal fixation devices from 1012 patients, were collected from an orthopedic center between June 2014 and June 2022 to establish a classification network. The images were divided into training set (1106 images), validation set (272 images), and test set (343 images). The model efficacy is evaluated by using the data on the test set. The overall TOP-1 accuracy, and the precision, sensitivity, specificity, and F1 score of each model are calculated, and receiver operating characteristic (ROC) curves are plotted to evaluate the model performance. Gradient-weighted class activation mapping (Grad-CAM) images are used to determine the image features that are most important for DCNN decisions. RESULTS: A total of 1378 (80%) images were used for model development, and model efficacy was validated on a test set with 343 (20%) images. The overall TOP-1 accuracy was 98.5%. The area under the receiver operating characteristic curve (AUC) values for each internal fixation model were 1.000, 1.000, 0.980, 1.000, 0.999, and 1.000, respectively. Gradient-weighted class activation mapping showed the unique design of the internal fixation device. CONCLUSION: We developed a deep convolutional neural network model that can identify the manufacturer and model of hip internal fixation devices from the hip AP radiographs.

KIRA8 attenuates non-alcoholic steatohepatitis through inhibition of the IRE1α/XBP1 signalling pathway.

Endoplasmic reticulum (ER) stress is enhanced in non-alcoholic steatohepatitis (NASH). Among three signalling pathways, the IRE1α/XBP1 signalling pathway is strongly implicated in the pathogenesis of NASH but its significance is still largely uncharacterised. In this report, we constructed a hepatocyte-specific XBP1-Luciferase knock-in mouse model that allows in vivo monitoring of the IRE1α/XBP1 activity in hepatocytes. Using this mouse model, we found that IRE1α/XBP1 was activated within hepatocytes during the pathogenesis of NASH. Significantly, a specific IRE1α kinase-inhibiting RNase attenuator, KIRA8, attenuated NASH in mice. In conclusion, our hepatocyte-specific XBP1 splicing reporter mouse represents a valid model for research and drug development of NASH, which showed that the IRE1α-induced XBP splicing is potentiated in hepatocytes during pathogenesis of NASH. Furthermore, we carried out the proof-of-concept study to demonstrate that the allosteric IRE1α RNase inhibitor serves as a promising therapeutic agent for the treatment of NASH.

The natural compound rutaecarpine promotes white adipocyte browning through activation of the AMPK-PRDM16 axis.

The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.

Comparison between minimally invasive plate osteosynthesis and open reduction-internal fixation for proximal humeral fractures: a meta-analysis based on 1050 individuals.

BACKGROUND: This meta-analysis aimed to compare the clinical outcomes and complications of minimally invasive plate osteosynthesis (MIPO) and open reduction-internal fixation (ORIF) in patients with proximal humeral fractures. METHODS: We searched PubMed, EMBASE, Ovid, and the Cochrane Library to identify all relevant studies from inception to April 2019. Cochrane Collaboration's Review Manage 5.3 was used for meta-analysis. RESULTS: Sixteen studies involving 1050 patients (464 patients in the MIPO group and 586 patients in the ORIF group) were finally included. According to the meta-analysis, MIPO was superior to ORIF in operation time, blood loss, postoperative pain, fracture union time, and constant score. However, MIPO was associated with more exposure to radiation and axillary nerve injury. No significant differences were found in length of hospital stays and complication except for axillary nerve injury. CONCLUSION: The present evidence indicates that compared to ORIF, MIPO had advantages in functional outcomes, operation time, blood loss, postoperative pain, and fracture union time for the treatment of PHFs. However, the MIPO technique had a higher rate of axillary nerve injury and longer radiation time compared to ORIF.

Correlation between the sagittal spinopelvic alignment and degenerative lumbar spondylolisthesis: a retrospective study.

BACKGROUND: Pain and disability associated with degenerative lumbar spondylolisthesis (DLS) results in significant burden on both the patients' quality of life and healthcare costs. Currently, there is controversy regarding the specificity of spinopelvic measures of sagittal plane alignment with respect to DLS. Moreover, the correlation among spinopelvic parameters of sagittal plane alignment remains to be clarified. Our aim in this study was to compare these measurements between patients with single-segment DLS at L5 and a control group with no history of DLS. METHODS: Our study group was formed of 132 patients who underwent full length lateral view radiographs of the spine in a relaxed standing posture. Among these, DLS at L5 was identified in 72 patients, forming the DLS group, with no radiographic evidence of lumbar spine disease in the remaining 60 patients, forming the control group. The patient and control groups were balanced with regard to age and sex distribution. The following spinopelvic parameters of sagittal plane alignment were measured: angle of incidence (PI) and tilt (PT) of the pelvis; sacral slope (SS); thoracic kyphosis (TK); lumbar lordosis (LL); and the spinal sagittal vertical axis (SVA). The Meyerding grade of L5 slippage was quantified for each patient in the DLS group. RESULTS: Measures of TK, PI, SS, and LL were significantly greater in the DLS than control group (P <  0.05), with no between-group difference in SVA and PT. In the DLS group, the grade of L5 slippage correlated with SS (r = 0.873, P <  0.0001), PI (r = 0.791, P <  0.0001) and LL (r = 0.790, P <  0.0001). Moreover, the measurement for SS correlated more strongly with the PI (r = 0.94, P <  0.01) than the LL (r = 0.69, P <  0.01). CONCLUSION: Measurements of SS, PI, and LL were specifically associated with DLS, with measurements correlating positively with the grade of slippage.

[Discussion on the Key Aspects of Quality Control for Custom Ocular Prosthesis].

Custom ocular prosthesis as a kind of product to make up the eye defects. It can not only improve patient's comfort adaptation and restore the normal structures but also let the patient regain confidence. However, it is in infant stage in our country for custom ocular prosthesis that the professional engineer is not enough, standards for the products are shortage. These factors together result in poor understanding of product management control and impede the development of ocular prostheses. This article gives the suggestions for quality management mainly focus on human resources, raw material, production and so on.

The discovery of novel and selective fatty acid binding protein 4 inhibitors by virtual screening and biological evaluation.

Adipocyte fatty acid binding protein (AFABP, FABP4) has been proven to be a potential therapeutic target for diabetes, atherosclerosis and inflammation-related diseases. In this study, a series of new scaffolds of small molecule inhibitors of FABP4 were identified by virtual screening and were validated by a bioassay. Fifty selected compounds were tested, which led to the discovery of seven hits. Structural similarity-based searches were then performed based on the hits and led to the identification of one high affinity compound 33b (Ki=0.29±0.07µM, ΔTm=8.5°C). This compound's effective blockade of inflammatory response was further validated by its ability to suppress pro-inflammatory cytokines induced by lipopolysaccharide (LPS) stimulation. Molecular dynamics simulation (MD) and mutagenesis studies validated key residues for its inhibitory potency and thus provide an important clue for the further development of drugs.

Conversion of non-adipogenic fibroblasts into adipocytes by a defined hormone mixture.

Obesity is accompanied by an increase in the size and the number of adipocytes. As adipocytes are thought to differentiate from pre-adipocytes, we postulate that non-adipogenic fibroblasts contribute to adipocyte formation under certain conditions such as obesity. We report for the first time that NIH-3T3 fibroblasts, which are generally considered to be non-adipogenic, can be converted into mature adipocytes by treatment with a defined hormone mixture comprising EGF (epidermal growth factor), HGF (hepatocyte growth factor), Dex (dexamethasone) and insulin. Furthermore, NIH-3T3 cells transplanted into obese immunodeficient NOD/SCID (non-obese diabetic/severe combined immunodeficient) mice formed adipocytes in vivo. Interestingly, the mixture elicited conversion of NIH-3T3 cells directly into adipocytes without a preceding pre-adipocyte stage. Functional analysis revealed that each component of the mixture was necessary for the induction of adipogenesis, including Dex which inhibited the cell proliferation stimulated by EGF. Upon profiling the signalling pathways employed by EGF and HGF, we found STAT5 (signal transducer and activator of transcription 5) signalling to be activated, predominantly at the levels of both transcription and post-translational modification. Inhibition of the STAT5 pathway, either by genetic knockdown or a specific pharmacological agent, blocked adipogenesis in NIH-3T3 cells. Taken together, these data not only establish a newly recognized grouping of factors that can induce trans-differentiation of non-adipogenic fibroblasts into adipocytes, but also give us a greater understanding of obesity.

1-Benzyl-4-phenyl-1H-1,2,3-triazoles improve the transcriptional functions of estrogen-related receptor γ and promote the browning of white adipose.

The estrogen-related receptor γ (ERRγ) is a potential molecular target for the development of small molecules to stimulate the adipose browning process, which may represent a novel attractive strategy to treat obesity related disorders. The receptor possesses a very small ligand binding cavity and therefore identification of small molecule ERRγ modulators is a considerable challenge. We have successfully designed and synthesized a series of 1-benzyl-4-phenyl-1H-1,2,3-triazoles and demonstrated that they improve the transcriptional functions of ERRγ, potently elevating both the mRNA levels and the protein levels of ERRγ downstream targets. One of the most promising compounds, 4-(1-(4-iso-propylbenzyl)-1H-1,2,3-triazol-4-yl)benzene-1,2-diol (2e) was further shown to directly bind with the ERRγ ligand binding domain (ERRγ-LBD) in an isothermal calorimetric (ITC) assay and to thermally stabilize ERRγ-LBD protein by increasing its melting temperature (Tm) as demonstrated by circular dichroism (CD) spectroscopy. Furthermore, 2e potently stimulates the adipocyte browning process and induces mitochondrial biogenesis both in vitro and in vivo, suggesting the considerable therapeutic potential of this compound for the treatment of obesity and related disorders.

Combining PLGA microspheres loaded with Liver X receptor agonist GW3965 with a chitosan nerve conduit can promote the healing and regeneration of the wounded sciatic nerve.

Globally, peripheral nerve injury (PNI) is a common clinical issue. Successfully repairing severe PNIs has posed a major challenge for clinicians. GW3965 is a highly selective LXR agonist, and previous studies have demonstrated its positive protective effects in both central and peripheral nerve diseases. In this work, we examined the potential reparative effects of GW3965-loaded polylactic acid co-glycolic acid microspheres in conjunction with a chitosan nerve conduit for peripheral nerve damage. The experiment revealed that GW3965 promoted Schwann cell proliferation and neurotrophic factor release in vitro. In vivo experiments conducted on rats showed that GW3965 facilitated the restoration of motor function, promoted axon and myelin regeneration in the sciatic nerve, and enhanced the microenvironment of nerve regeneration. These results offer a novel therapeutic approach for the healing of nerve damage. Overall, this work provides valuable insights and presents a promising therapeutic strategy for addressing PNI.

Latest advances in the regulatory genes of adipocyte thermogenesis.

An energy imbalance cause obesity: more energy intake or less energy expenditure, or both. Obesity could be the origin of many metabolic disorders, such as type 2 diabetes and cardiovascular disease. UCP1 (uncoupling protein1), which is highly and exclusively expressed in the thermogenic adipocytes, including beige and brown adipocytes, can dissipate proton motive force into heat without producing ATP to increase energy expenditure. It is an attractive strategy to combat obesity and its related metabolic disorders by increasing non-shivering adipocyte thermogenesis. Adipocyte thermogenesis has recently been reported to be regulated by several new genes. This work provided novel and potential targets to activate adipocyte thermogenesis and resist obesity, such as secreted proteins ADISSP and EMC10, enzyme SSU72, etc. In this review, we have summarized the latest research on adipocyte thermogenesis regulation to shed more light on this topic.

Androgen Receptor is a Negative Regulator of PRDM16 in Beige Adipocyte.

PRDM16 (PR domain containing protein 16) serves as a dominant activator of brown and beige adipocyte. However, mechanisms underlying the regulation of PRDM16 expression are incompletely understood. A Prdm16 luciferase knockin reporter mouse model is generated, enabling high throughput monitoring of Prdm16 transcription. Single clonal analysis reveals high heterogeneity of Prdm16 expression in the inguinal white adipose tissue (iWAT) cells. Amongst all transcription factors, androgen receptor (Ar) shows the strongest negative correlation with Prdm16. A sex dimorphism for PRDM16 mRNA expression is present in human WAT, with female individuals exhibiting increased expression than males. Androgen-AR signaling mobilization suppresses Prdm16 expression, accompanied by attenuated beiging in beige adipocytes, but not in brown adipose tissue. The suppressive effect of androgens on beiging is abolished upon overexpression of Prdm16. Cleavage under targets and tagmentation mapping reveals direct binding of AR within the intronic region of Prdm16 locus, whereas no direct binding is detected on Ucp1 and other browning-related genes. Adipocyte-selective deletion of Ar potentiates beige cell biogenesis whereas adipocyte-specific overexpression of AR attenuates white adipose beiging. This study highlights an essential role of AR in negative regulation of PRDM16 in WAT and provides an explanation for the observed sex difference in adipose beiging.

Correction: Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity.

Correction for 'Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity' by Liufeng Mao et al., Food Funct., 2018, 9, 2362-2373, https://doi.org/10.1039/C7FO01835E.

[Codon optimization and eukaryotic expression analysis of the analgesic peptide gene BmK AngM1 from Buthus martensii Karsch].

Codon bias is an important factor which influences heterologous gene expression. Optimizing codon sequence could improve expression level of heterologous gene. In order to improve the expression level of BmK AngM1 gene encoding the analgesic peptide from Buthus martensii Karsch in Pichia pastoris, the codon-optimized BmK AngM1 gene according to its cDNA sequence and the preference codon usage of P. pastoris were cloned into expression vector pPIC9K and then transformed into P. pastoris. The expersion of recombinant BmK AngM1 (rBmK AngM1) was inducced by methanol in the medium, and the expression level of the optimized BmK AngM1 gene was 3.7 times of the native one. These results suggested that the expression of BmK AngM1 in P. pastoris could be successfully improved by codon optimization.

Is There a Missing Link? Exploring the Effects of Institutional Pressures on Environmental Performance in the Chinese Construction Industry.

Although institutional pressures have huge strategic implications for organizational activities, this certainly does not mean that organizations under institutional pressures can improve environmental performance automatically. Institutional pressures are critical but not sufficient to affect environmental performance directly. Therefore, additional research is needed to explore the missing link between institutional pressures and environmental performance. Based on the "pressure-response-performance" framework, this study integrates perspectives of institutional theory and organizational learning to argue the mediating role of organizational learning in the relationship between institutional pressures and environmental performance. Data were collected via 268 valid questionnaires from construction firms located in Shanxi Province in central China. Hypotheses in the conceptual model were tested with structural equation modeling. Empirical results reveal that both coercive and mimetic pressures have significantly positive effects on organizational learning, whereas normative pressures have a non-significant effect on organizational learning. Besides that, organizational learning has a significantly positive effect on environmental performance. In addition, organizational learning partially mediates the relationship between coercive pressures and environmental performance and completely mediates the relationship between mimetic pressures and environmental performance. By exploring the mediating role of organizational learning, the article uncovers the missing link in the relationship between institutional pressures and environmental performance.

Discovery of JND003 as a New Selective Estrogen-Related Receptor α Agonist Alleviating Nonalcoholic Fatty Liver Disease and Insulin Resistance.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent forms of chronic liver diseases and is causally linked to hepatic insulin resistance and reduced fatty acid oxidation. Therapeutic treatments targeting both hepatic insulin resistance and lipid oxidative metabolism are considered as feasible strategies to alleviate this disease. Emerging evidence suggests Estrogen-Related Receptor alpha (ERRα), the first orphan nuclear receptor identified, as a master regulator in energy homeostasis by controlling glucose and lipid metabolism. Small molecules improving the functions of ERRα may provide a new option for management of NAFLD. In the present study, by using liver-specific Errα knockout mouse (Errα-LKO), we showed that liver-specific deletion of ERRα exacerbated diet-evoked fatty liver, hepatic and systemic insulin resistance in mice. A potent and selective ERRα agonist JND003 (7) was also discovered. In vitro and in vivo investigation demonstrated that the compound enhanced the transactivation of ERRα downstream target genes, which was accompanied by improved insulin sensitivity and fatty liver symptoms. Furthermore, the therapeutic effects were completely abolished in Errα-LKO mice, indicative of its on-target efficacy. Our study thus suggests that hepatic ERRα is a viable target for NAFLD and that ERRα agonist may serve as an intriguing pharmacological option for management of metabolic diseases.

Comparative transcriptomic analysis of rabbit interscapular brown adipose tissue whitening under physiological conditions.

Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, a detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis of morphological, histological and molecular features. Principal component analysis (PCA) of differentially expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signalling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.