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Abstract Background Muscle satellite cells (MuSCs) exert essential roles in skeletal muscle adaptation to growth, injury and ageing, and their functions are extensively modulated by microenvironmental factors. However, the current knowledge about the interaction of MuSCs with niche cells is quite limited. Methods A 10× single‐cell RNA sequencing (scRNA‐seq) was performed on porcine longissimus dorsi and soleus (SOL) muscles to generate a single‐cell transcriptomic dataset of myogenic cells and other cell types. Sophisticated bioinformatic analyses, including unsupervised clustering analysis, marker gene, gene set variation analysis (GSVA), AUCell, pseudotime analysis and RNA velocity analysis, were performed to explore the heterogeneity of myogenic cells. CellChat analysis was used to demonstrate cell–cell communications across myogenic cell subpopulations and niche cells, especially fibro‐adipogenic progenitors (FAPs). Integrated analysis with human and mice datasets was performed to verify the expression of FGF7 across diverse species. The role of FGF7 on MuSC proliferation was evaluated through administering recombinant FGF7 to porcine MuSCs, C2C12, cardiotoxin (CTX)‐injured muscle and d‐galactose (d‐gal)‐induced ageing model. Results ScRNA‐seq totally figured out five cell types including myo‐lineage cells and FAPs, and myo‐lineage cells were further classified into six subpopulations, termed as RCN3+, S100A4+, ID3+, cycling (MKI67+), MYF6+ and MYMK+ satellite cells, respectively. There was a higher proportion of cycling and MYF6+ cells in the SOL population. CellChat analysis uncovered a particular impact of FAPs on myogenic cells mediated by FGF7, which was relatively highly expressed in SOL samples. Administration of FGF7 (10 ng/mL) significantly increased the proportion of EdU+ porcine MuSCs and C2C12 by 4.03 ± 0.81% (P

Abstract The senescence of alveolar type II (AT2) cells impedes self-repair of the lung epithelium and contributes to lung injury in the setting of idiopathic pulmonary fibrosis (IPF). Yes-associated protein 1 (YAP1) is essential for cell growth and organ development; however, the role of YAP1 in AT2 cells during pulmonary fibrosis is still unclear. YAP1 expression was found to be downregulated in the AT2 cells of PF patients. Deletion of YAP1 in AT2 cells resulted in lung injury, exacerbated extracellular matrix (ECM) deposition, and worsened lung function. In contrast, overexpression of YAP1 in AT2 cells promoted alveolar regeneration, mitigated pulmonary fibrosis, and improved lung function. In addition, overexpression of YAP1 alleviated bleomycin (BLM) -induced senescence of alveolar epithelial cells both in vivo and in vitro. Moreover, YAP1 promoted the expression of peroxiredoxin 3 (Prdx3) by directly interacting with TEAD1. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in BLM-treated MLE-12 cells, whereas depletion of Prdx3 partially abrogated the protective effect of YAP1. Furthermore, overexpression of Prdx3 facilitated self-repair of the injured lung and reduced ECM deposition, while silencing Prdx3 attenuated the antifibrotic effect of YAP1. In conclusion, this study demonstrated that YAP1 alleviates lung injury and pulmonary fibrosis by regulating Prdx3 expression to improve mitochondrial dysfunction and block senescence in AT2 cells, revealing a potential novel therapeutic strategy for pulmonary fibrosis.

Abstract Homotypic membrane fusion of the endoplasmic reticulum (ER) is mediated by dynamin-like GTPase atlastin (ATL). This fundamental process relies on GTP-dependent domain rearrangements in the N-terminal region of ATL (ATLcyto), including the GTPase domain and three-helix bundle (3HB). However, its conformational dynamics during the GTPase cycle remain elusive. Here, we combine single-molecule FRET imaging and molecular dynamics simulations to address this conundrum. Different from the prevailing model, ATLcyto can form a loose crossover dimer upon GTP binding, which is tightened by GTP hydrolysis for membrane fusion. Furthermore, the α-helical motif between the 3HB and transmembrane domain, which is embedded in the surface of the lipid bilayer and self-associates in the crossover dimer, is required for ATL function. To recycle the proteins, Pi release, which disassembles the dimer, activates frequent relative movements between the GTPase domain and 3HB, and subsequent GDP dissociation alters the conformational preference of the ATLcyto monomer for entering the next reaction cycle. Finally, we found that two disease-causing mutations affect human ATL1 activity by destabilizing GTP binding-induced loose crossover dimer formation and the membrane-embedded helix, respectively. These results provide insights into ATL-mediated homotypic membrane fusion and the pathological mechanisms of related disease.

ABSTRACT: Calf diarrhea, a common disease mainly induced by Escherichia coli infection, is one of the main reasons for nonpredator losses. Hence, an effective nonantibacterial approach to prevent calf diarrhea has become an emerging requirement. This study evaluated the microalgae Schizochytrium sp. (SZ) and lactoferrin (LF) as a nutrient intervention approach against E. coli O101:K99-induced preweaning calve diarrhea. Fifty 1-d-old male Holstein calves were randomly divided into 5 groups (n = 10): (1) control, (2) blank (no supplement or challenge), (3) 1 g/d LF, (4) 20 g/d SZ, or (5) 1 g/d LF plus 20 g/d SZ (LFSZ). The experimental period lasted 14 d. On the morning of d 7, calves were challenged with 1 × 1011 cfu of E. coli O101:K99, and rectum feces were collected on 3, 12, 24, and 168 h postchallenge for the control, LF, SZ, and LFSZ groups. The rectal feces of the blank group were collected on d 14. Data were analyzed using the mixed procedure of SAS (version 9.4; SAS Institute Inc.). The E. coli K99 challenge decreased the average daily gain (ADG) and increased feed-to-gain ratio (F:G) and diarrhea frequency (control vs. blank). Compared with the control group, the LFSZ group had a higher ADG and lower F:G, and the LFSZ and SZ groups had lower diarrhea frequency compared with the control group. In addition, the LFSZ and SZ groups have no differences in diarrhea frequency compared with the blank group. Compared with the control group, the blank group had lower serum nitric oxide (NO), endothelin-1, d-lactic acid (D-LA), and lipopolysaccharide (LPS) concentrations, as well as serum IgG, IL-1β, IL-6, IL-10, and TNF-α levels on d 7 and 14. On d 7, compared with the control group, all treatment groups had lower serum NO level, the SZ group had a lower serum D-LA concentration, and the LF and LFSZ groups had lower serum LPS concentration. On d 14, compared with the control group, the fecal microbiota of the blank group had lower Shannon, Simpson, Chao1, and ACE indexes, the LFSZ group had lower Shannon and Simpson indexes, the SZ and LFSZ groups had a higher Chao1 index, and all treatment groups had a higher ACE index. In fecal microbiota, Bifidobacterium and Actinobacteria were negatively associated with IL-10 and d-lactate, while Akkermansia was negatively associated with endothelin-1 and positively correlated with LPS, fecal scores, and d-lactate levels. Our results indicated that LF and SZ supplements could alleviate E. coli O101:K99-induced calf diarrhea individually or in combination. Supplementing 1 g/d LF and 20 g/d SZ could be a potential nutrient intervention approach to prevent bacterial diarrhea in calves.

The damage evolution process of non-penetrating cracks often causes some unexpected engineering disasters. Gypsum specimens containing non-penetrating crack(s) are used to study the damage evolution and characteristics under cyclic loading. The results show that under cyclic loading, the relationship between the number of non-penetrating crack(s) and the characteristic parameters (cyclic number, peak stress, peak strain, failure stress, and failure strain) of the pre-cracked specimens can be represented by a decreasing linear function. The damage evolution equation is fitted by calibrating the accumulative plastic strain for each cycle, and the damage constitutive equation is proposed by the concept of effective stress. Additionally, non-penetrating cracks are more likely to cause uneven stress distribution, damage accumulation, and local failure of specimen. The local failure can change the stress distribution and relieve the inhibition of non-penetrating crack extension and eventually cause a dramatic destruction of the specimen. Therefore, the evolution process caused by non-penetrating cracks can be regarded as one of the important reasons for inducing rockburst. These results are expected to improve the understanding of the process of spalling formation and rockburst and can be used to analyze the stability of rocks or rock structures.

Abstract The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway.

Abstract Background The biological behavior of low-grade glioma (LGG) is significantly affected by N6-methyladenosine (m6A) methylation, an essential epigenetic alteration. Therefore, it is crucial to create a prognostic model for LGG by utilizing genes that regulate m6A methylation. Methods Using TCGA and GTEx databases. We examined m6A modulator levels in LGG and normal tissues, and investigated PD-L1 and PD-1 expression, immune scores, immune cell infiltration, tumor immune microenvironment (TIME) and potential underlying mechanisms in different LGG clusters. We also performed immunohistochemistry and RT-qPCR to identify essential m6A adjustment factor. Results The results showed that m6A regulatory element expression was significantly increased in LGG tissues and was significantly associated with TMIE. A substantial increase in PD-L1 and PD-1 levels in LGG tissues and high-risk cohorts was observed. PD-L1 expression was positively correlated with FTO, ZCCHC4, and HNRNPD, whereas PD-1 expression was negatively correlated with FTO, ZC3H7B, and HNRNPD. The prognostic signature created using regulators of m6A RNA methylation was shown to be strongly associated with the overall survival of LGG patients, and FTO and ZCCHC4 were confirmed as independent prognostic markers by clinical samples. Furthermore, the results revealed different TIME characteristics between the two groups of patients, indicating disrupted signaling pathways associated with LGG. Conclusion Our results present that the m6A regulators play vital role in regulating PD-L1/PD-1 expression and the infiltration of immune cells, thereby exerting a sizable impact on the TIME of LGG. Therefore, m6A regulators have precise predictive value in the prognosis of LGG.

Abstract Background The prothrombotic state is a common abnormality in patients with coronavirus disease 2019 (COVID-19). However, there is controversy over the use of anticoagulants, especially oral anticoagulants (OAC) due to limited studies. We sought to evaluate the association between antithrombotic therapy on mortality and clinical outcomes in patients hospitalized for COVID-19 through propensity score matching (PSM) analysis. Methods A retrospective cohort study was performed to include adult patients with COVID-19 in a university hospital. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) admission, mechanical ventilation, and acute kidney injury (AKI) during hospitalization. PSM was used as a powerful tool for matching patients’ baseline characteristics. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated from the models. Results Of 4,881 COVID-19 patients during the study period, 690 (14.1%) patients received antithrombotic therapy and 4,191 (85.9%) patients were under no antithrombotic therapy. After adjustment with multivariate regression analysis, patients receiving OAC, compared with those who did not receive any antithrombotic therapy, had significantly lower odds for in-hospital mortality (aOR: 0.46. 95% CI: 0.24 to 0.87; P= 0.017). PSM analysis observed similar results (aOR: 0.35. 95% CI: 0.19 to 0.61; P

Currently, brain-computer interface technology still poses hidden dangers in the complete control of ideas. Additionally, there are issues with the low sampling frequency and accuracy of EEG signal acquisition equipment. To address these concerns, this study proposes a combined model for EEG signal recognition and classification analysis by combining frequency division multi-feature complex brain networks with parallel convolutional neural networks. The effectiveness of this model has been verified. In model visualization analysis, the visualization results of t-distribution random neighborhood embedding in the third separable convolutional layer indicate that the two types of imagination have already experienced separation. There is a clear boundary between the two at position 0 on both the horizontal and vertical axes. This is a significant improvement compared to the comparative model. In the model performance verification, the full band classification accuracy in the synchronous network was maintained between 60% to 84%, and the $\mu $ -rhythm was maintained between 59% to 81%. The average classification accuracy of the combined model was 77.40% with higher performance, which was higher than 68.53% and 70.87% of the single scale convolutional neural network. In comparison with deep learning algorithms, the average classification accuracy of the combined model was 85.74%, much higher than the 66.20% and 76.69% of the comparative models. The composite model constructed has good performance in recognizing and classifying electroencephalogram signals. It can be effectively applied in practical brain-computer interface technology or electroencephalogram signal analysis. The potential application area of this study in the future is the recognition and processing of complex EEG signals in medical institutions, which can improve the efficiency of signal processing in this field and reduce the manpower expenditure of medical personnel.

Abstract Background The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P

Abstract Lithium-ion batteries play a crucial role in decarbonizing transportation and power grids, but their reliance on high-cost, earth-scarce cobalt in the commonly employed high-energy layered Li(NiMnCo)O2 cathodes raises supply-chain and sustainability concerns. Despite numerous attempts to address this challenge, eliminating Co from Li(NiMnCo)O2 remains elusive, as doing so detrimentally affects its layering and cycling stability. Here, we report on the rational stoichiometry control in synthesizing Li-deficient composite-structured LiNi0.95Mn0.05O2, comprising intergrown layered and rocksalt phases, which outperforms traditional layered counterparts. Through multiscale-correlated experimental characterization and computational modeling on the calcination process, we unveil the role of Li-deficiency in suppressing the rocksalt-to-layered phase transformation and crystal growth, leading to small-sized composites with the desired low anisotropic lattice expansion/contraction during charging and discharging. As a consequence, Li-deficient LiNi0.95Mn0.05O2 delivers 90% first-cycle Coulombic efficiency, 90% capacity retention, and close-to-zero voltage fade for 100 deep cycles, showing its potential as a Co-free cathode for sustainable Li-ion batteries.

Abstract Li metal batteries using Li metal as negative electrode and LiNi1-x-yMnxCoyO2 as positive electrode represent the next generation high-energy batteries. A major challenge facing these batteries is finding electrolytes capable of forming good interphases. Conventionally, electrolyte is fluorinated to generate anion-derived LiF-rich interphases. However, their low ionic conductivities forbid fast-charging. Here, we use CsNO3 as a dual-functional additive to form stable interphases on both electrodes. Such strategy allows the use of 1,2-dimethoxyethane as the single solvent, promising superior ion transport and fast charging. LiNi1-x-yMnxCoyO2 is protected by the nitrate-derived species. On the Li metal side, large Cs+ has weak interactions with the solvent, leading to presence of anions in the solvation sheath and an anion-derived interphase. The interphase is surprisingly dominated by cesium bis(fluorosulfonyl)imide, a component not reported before. Its presence suggests that Cs+ is doing more than just electrostatic shielding as commonly believed. The interphase is free of LiF but still promises high performance as cells with high LiNi0.8Mn0.1Co0.1O2 loading (21 mg/cm2) and low N/P ratio (~2) can be cycled at 2C (~8 mA/cm2) with above 80% capacity retention after 200 cycles. These results suggest the role of LiF and Cs-containing additives need to be revisited.

BackgroundArsenic exposure can lead to liver dysfunction, liver steatosis, hepatitis, liver fibrosis, and other liver injuries, but its mechanism is still unclear and effective treatment methods are lacking.ObjectiveTo investigate the potential intervention effect and associated mechanism of Rosa roxburghii Tratt juice on arsenic-induced liver injury in rats from the perspective of S-adenosylmethionine (SAM) metabolism.MethodsThirty-six Wistar rats were randomly divided into six groups, six rats in each group, half male and half female. The low, medium, and high dose groups of sodium arsenite (NaAsO2) were given 2.5, 5.0, and 10.0 NaAsO2 mg·kg−1 (body weight, thereafter), respectively; the control group was given 10 mL·kg−1 deionized water; the Rosa roxburghii Tratt juice intervention group was given 10 mg·kg−1 NaAsO2 for 4 h and then 10 mL·kg−1 Rosa roxburghii Tratt juice; the Rosa roxburghii Tratt juice control group was given 10 mL·kg−1 Rosa roxburghii Tratt juice by gavage. All rats were gavaged once a day, 6 d per week for 4 months. Histopathological changes of rat liver were observed by hematoxylin-eosin (HE) staining. Total bile acids (TBA) and γ-glutamyl transpeptidase (γ-GT) were detected by enzyme cycle method and rate method, respectively. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS) was used to evaluate SAM and S-adenosylhomo cysteine (SAH) in rat liver. Real-time fluorescence quantitative reverse transcriptional PCR (RT-qPCR) was used to detect the mRNA expression levels of the genes of glycine-N-methyltransferase (Gnmt), nicotinamide-N-methyltransferase (Nnmt), and phosphatidylethano-lamine N-mathyltransferase (Pemt).ResultsIn the control group, the liver nuclei were stained clearly, the cytoplasm was stained uniformly, and the liver cords were arranged radially without inflammatory infiltration. In the low, medium, and high dose groups of NaAsO2, hepatic sinusoidal dilation, congestion, and inflammatory infiltration were observed to different degrees. Compared with the control group, TBA in the medium and high dose groups of NaAsO2, and γ-GT in the high dose group of NaAsO2 were significantly increased (P

Abstract Single-atom catalysts (SACs) are particularly sensitive to external conditions, complicating the identification of catalytically active species and active sites under in situ or operando conditions. We developed a methodology for tracing the structural evolution of SACs to nanoparticles, identifying the active species and their link to the catalytic activity for the reverse water gas shift (RWGS) reaction. The new method is illustrated by studying structure-activity relationships in two materials containing Pt SACs on ceria nanodomes, supported on either ceria or titania. These materials exhibited distinctly different activities for CO production. Multimodal operando characterization attributed the enhanced activity of the titania-supported catalysts at temperatures below 320 ˚C to the formation of unique Pt sites at the ceria-titania interface capable of forming Pt nanoparticles, the active species for the RWGS reaction. Migration of Pt nanoparticles to titania support was found to be responsible for the deactivation of titania-supported catalysts at elevated temperatures. Tracking the migration of Pt atoms provides a new opportunity to investigate the activation and deactivation of Pt SACs for the RWGS reaction.

IntroductionMedicinal plants, rich in phytochemicals like phenolic acids, flavonoids, and tannins, offer potential benefits in enhancing productivity, quality, and animal health. Amla fruit (Phyllanthus emblica) is one such plant with promising attributes. This study aimed to investigate the impact of fresh Amla fruit (FAF) supplementation on ruminal microbial composition and its correlation with rumen fermentation in lactating dairy cows.MethodsThe study employed a repeated crossover design involving eight ruminally cannulated mid-lactation Holstein dairy cows. Animals received varying levels of fresh Amla fruit supplementation (0, 200, 400, and 600 g/d).ResultsWhen 400 g/d of FAF was added to the diet, there was a significant increase in the relative abundance of Firmicutes (p = 0.02). However, at 200 g/d, the relative abundance of ruminal Bacteroidota was higher than the 0 and 400 g/d FAF supplementation (p

Abstract Hydrocephalus is one of the most common brain disorders and a life‐long incurable condition. An empirical “one‐size‐fits‐all” approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage‐mediated ChP inflammation and CSF hypersecretion have recently been identified as a significant discovery in the pathogenesis of hydrocephalus. In this study, a pioneering DNA nano‐drug (TSOs) is developed by modifying S2 ssDNA and S4 ssDNA with SPAK ASO and OSR1 ASO in tetrahedral framework nucleic acids (tFNAs) and synthesis via a one‐pot annealing procedure. This construct can significantly knockdown the expression of SPAK and OSR1, along with their downstream ion channel proteins in ChP epithelial cells, thereby leading to a decrease in CSF secretion. Moreover, these findings indicate that TSOs effectively inhibit the M0 to M1 phenotypic switch of ChP macrophages via the MAPK pathways, thus mitigating the cytokine storm. In in vivo post‐hemorrhagic hydrocephalus (PHH) models, TSOs significantly reduce CSF secretion rates, alleviate ChP inflammation, and prevent the onset of hydrocephalus. These compelling results highlight the potential of TSOs as a promising therapeutic option for managing hydrocephalus, with significant applications in the future.

Calotropis gigantea (Giant milkweed, GM) has the potential to be utilized as a new feed additive for ruminants, however, the presence of unpalatable or toxic compounds decreases animal feed intake. This study aimed to valorize GM as a potential new feed resource through the chemical and microbial biotransformation of toxic compounds that will henceforth, make the plant palatable for cows. After GM’s ensiling using fermentative bacteria, the plant was sampled for UHPLC-MS/MS to analyse the metabolomic changes. Illumina Miseq of the 16 S rRNA fragment genes and ITS1 were used to describe the microbial composition and structure colonizing GM silage and contributing to the biodegradation of toxic compounds. Microbial functions were predicted from metataxonomic data and KEGG pathways analysis. Eight Holstein dairy cows assigned in a cross-over design were supplemented with GM and GM silage to evaluate palatability and effects on milk yield and milk protein. Cows were fed their typical diet prior to the experiment (positive control). After ensiling, 23 flavonoids, 47 amino acids and derivatives increased, while the other 14 flavonoids, 9 amino acids and derivatives decreased, indicating active metabolism during the GM ensiling process. Lactobacillus buchneri, Bacteroides ovatus, and Megasphaera elsdenii were specific to ensiled GM and correlated to functional plant metabolites, while Sphingomonas paucimobilis and Staphylococcus saprophyticus were specific to non-ensiled GM and correlated to the toxic metabolite 5-hydroxymethylfurfural.''Xenobiotics biodegradation and metabolism'', ''cancer overview'' and ''neurodegenerative disease'' were the highly expressed microbial KEGG pathways in non-ensiled GM. Non-ensiled GM is unpalatable for cows and drastically reduces the animal’s feed intake, whereas ensiled GM does not reduce feed intake, milk yield and milk protein. This study provides essential information for sustainable animal production by valorizing GM as a new feed additive.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

Abstract Introduction There are only four sizes of implantable collamer lens (ICL) available for selection, which cannot completely fit all patients as a result of the discontinuity of ICL sizes. Sizing an optimal ICL and predicting postoperative vault are still unresolved problems. This study aimed to develop and validate innovative data-level data-balancing machine learning-based models for predicting ICL size and postoperative vault. Methods The patients were randomly assigned to training and internal validation sets in a 4:1 ratio. Feature selection was performed using analysis of variance (ANOVA) and Kruskal–Wallis feature importance methods. Traditional linear regression model and machine learning-based models were used. The accuracy of models was assessed using the area under the curve (AUC) and confusion matrix. Results A total of 564 patients (1127 eyes) were eligible for this study, consisting of 808 eyes in the training set, 202 eyes in the internal validation set, and 117 eyes in the external validation set. Compared with the traditional linear regression method, the machine learning model bagging tree showed the best performance for ICL size selection, with an accuracy of 84.5% (95% confidence interval (CI) 83.2–85.8%), and the AUC ranged from 0.88 to 0.99; the prediction accuracy of 12.1 mm and 13.7 mm ICL sizes was improved by 49% and 59%, respectively. The bagging tree model achieved the best accuracy [90.2%, (95% CI 88.9–91.5%)] for predicting the postoperative vault, and the AUC ranged from 0.90 to 0.94. The prediction accuracies of internal and external validation dataset for ICL sizing were 82.2% (95% CI 81.1–83.3%) and 82.1% (95% CI 81.1–83.1%), respectively. Conclusions The innovative data-level data balancing-based machine learning model can be used to predict ICL size and postoperative vault more accurately, which can assist surgeons in choosing optimal ICL size, thus reducing risks of postoperative complications and secondary surgery.

Objectives. Branchio-oto syndrome (BOS) primarily manifests as hearing loss, preauricular pits, and branchial defects. EYA1 is the most common pathogenic gene, and splicing mutations account for a substantial proportion of cases. However, few studies have addressed the structural changes in the protein caused by splicing mutations and potential pathogenic factors, and several studies have shown that middle-ear surgery has limited effectiveness in improving hearing in these patients. BOS has also been relatively infrequently reported in the Chinese population. This study explored the genetic etiology in the family of a proband with BOS and provided clinical treatment to improve the patient’s hearing. Methods. We collected detailed clinical features and peripheral blood samples from the patients and unaffected individuals within the family. Pathogenic mutations were identified by whole-exome sequencing and cosegregation analysis and classified according to the American College of Medical Genetics and Genomics guidelines. Alternative splicing was verified through a minigene assay. The predicted three-dimensional protein structure and biochemical experiments were used to investigate the pathogenicity of the mutation. The proband underwent middle-ear surgery and was followed up at 1 month and 6 months postoperatively to monitor auditory improvement. Results. A novel heterozygous EYA1 splicing variant (c.1050+4 A>C) was identified and classified as pathogenic (PVS1(RNA), PM2, PP1). Skipping of exon 11 of the EYA1 pre-mRNA was confirmed using a minigene assay. This mutation may impair EYA1-SIX1 interactions, as shown by an immunoprecipitation assay. The EYA1-Mut protein exhibited cellular mislocalization and decreased protein expression in cytological experiments. Middle-ear surgery significantly improved hearing loss caused by bone-conduction abnormalities in the proband. Conclusion. We reported a novel splicing variant of EYA1 in a Chinese family with BOS and revealed the potential molecular pathogenic mechanism. The significant hearing improvement observed in the proband after middle-ear surgery provides a reference for auditory rehabilitation in similar patients.

Abstract Coal mining has a significant impact on the movement of the overburden, leading to potential safety hazards in the working face. In this paper, a similarity simulation experiment was conducted to investigate the migration of overburden during the mining process of a specific working face in the Liuzhuang Coal Mine located in southern China. Sand and gravel were used to simulate the geological environment of each rock stratum. The deformation of the stratum was monitored using strain gauges, the fracture and displacement changes of the overburden stratum were recorded using cameras, and the characteristics of roof collapse was monitored using infrared thermal imager. The experimental model fully simulated the situation of the working face, and the actual working face size was obtained by enlarging the model by 100 times. The experiment found that during the initial stage of mining, there was no significant subsidence of the roof. In the course of the advancement of the working face, the primary roof intermittently fractured behind the working face, with subsequent propagation of upper cracks in an upward direction. The overburden rock layer above the goaf experienced continuous compaction, leading to the gradual closure of the separation layer. Simultaneously, new cracks constantly emerged in front of the working face, resulting in the progressive stabilization of the height of the crack zone. The stress measurements at each point exhibit a pattern of initial increased, followed by decrease, and ultimately stabilization. By considering the stress variation law of the overburden rock, the stress changes in key layers of the bedrock during mining could be categorized into four zones: the stress stable zone, stress increasing zone, stress reducing zone, and compaction stable zone. During the initial phase of coal seam mining, the presence of rock layers provided support, resulting in minimal subsidence of the overburden rock. However, as the mining operation progressed, the disturbance force and collapse of the overburden rock leaded to further downward subsidence. When the working face reached the stop line, the collapsed overburden rock gradually consolidates, resulting in a deceleration of energy release and the formation of a pressure relief zone. Consequently, the overburden rock above the working face underwent a slight additional subsidence, reaching its maximum level. A short cantilever rock beam structure was formed in the experiment. This study will provide valuable reference for future coal mining and serve as a vital theoretical basis for roof control in deep coal seam mining.

Abstract Objective The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) survivors is concerning. The goal of this study was to investigate and demonstrate the relationship between the neutrophil-to-albumin ratio (NAR) and long-term mortality of aSAH survivors. Methods A retrospective observational cohort study was conducted at Sichuan University West China Hospital between January 2009 and June 2019. The investigation of relationship between NAR and long-term mortality was conducted using univariable and multivariable Cox regression models. To demonstrate the predictive performance of different biomarkers over time, time-dependent receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were created. Results In total, 3173 aSAH patients were included in this study. There was a strong and continuous relationship between NAR levels and long-term mortality (HR 3.23 95% CI 2.75–3.79, p 0.28: adjusted HR 1.74 95% CI 1.30–2.32). Results in survivors were found to be still robust. Moreover, out of all the inflammatory markers studied, NAR demonstrated the highest correlation with long-term mortality. Conclusions A high level of NAR was associated with increased long-term mortality among patients with aSAH. NAR was a promising inflammatory marker for long-term mortality of aSAH.

The sclerotia of Wolfiporia hoelen (Fr.) Y.C. Dai & V. Papp is an important traditional Chinese medicine with diverse pharmacological properties. This study utilized a combination of PacBio Long-Read Sequencing, Illumina Short-Read Sequencing, and Hi-C Sequencing to generate a high-quality chromosome-level genome assembly of a W. hoelen strain Minling A5. There were 112 contigs in the genome, with 62.95 Mb in total length and 4.21 Mb in length for the contig N50. The average GC content was 51.89%. Based on Hi-C data, we corrected the CCS data and scaffolded them into 14 pseudo-chromosomes. The genome contained 44.37% repetitive sequences and 12,670 protein-coding genes, 86.53% (10,963) of which could be functionally annotated in at least one of the KOG, GO, Pfam, Swissprot, TrEMBL, NR, and KEGG databases. In addition, 240 transfer RNAs, 97 ribosomal RNAs, and 103 other non-coding RNAs were identified in the W. hoelen genome. A total of 755 pseudogenes were also identified, with an average length of 2665.51 bp. Further, there were 398, 100, 2837, 519, and 2068 genes annotated by CAZymes, TCDB, PHI, P450, and DFVF databases, respectively. One notable attribute of W. hoelen is its capacity to thrive in a substrate of fresh pine sawdust. Through an analysis of the growth on various pure wood sawdust culture media, we found that the growth of W. hoelen and Sparassis latifolia on pine sawdust was similar to that on broad-leaved wood sawdust, while the growth of Pleurotus ostreatus, P. eryngii, and Cyclocybe aegerita was slower than that on broad-leaved wood sawdust. By the functional annotation analysis of orthogroups in these five mushroom-forming fungi, it was determined that 645 orthogroups were specifically common in W. hoelen and S. latifolia. The genes in these specific orthogroups were significantly enriched in 12 pathways, including steroid biosynthesis, biosynthesis of antibiotics, and tyrosine metabolism. The high-quality genome and comparative genome analysis results significantly contribute to advancing our foundational knowledge of W. hoelen biology, while also offering valuable insights for the development of innovative biotechnological approaches aimed at enhancing the efficient and sustainable utilization of Pinus.

BackgroundCurrent evidence linking sedentary behavior (SB), physical activity (PA), and inflammation raises questions about their causal relationships, prompting concerns about potential residual confounding or reverse causation.MethodsA bidirectional Mendelian randomization (MR) analysis was conducted. SB data (n = 408,815) from "computer use," "television watching," and "driving" were included. The PA data encompassed nine types of PA (n = 460,376) over the last four weeks and included data on the frequency of vigorous PA (n = 440,512) and moderate PA (n = 440,266) for over 10 min. Additionally, three genome-wide association study datasets (n = 64,949) on light, moderate, and vigorous exercise were included to minimize potential bias from changes in exercise intensity. Inflammation data included levels of C-reactive protein (CRP) (n = 575,531), glycoprotein acetyl (GlycA) (n = 115,082), interleukin (IL)-8, IL-6, IL-6 receptor (IL-6R), and soluble IL-6R (sIL-6R) (n = 35,278). All datasets represented participants of European ancestry.ResultsTelevision watching as an SB showed significant positive causal effects on GlycA and CRP (inverse variance weighted (IVW), odds ratios (OR): 1.34, 95% confidence intervals (CI): 1.25-1.44, p = 3.570 × 10-17; IVW, OR: 1.21, 95% CI: 1.16-1.26, p = 1.500 × 10-19, respectively), with more robust evidence for GlycA. In the direction from inflammation to PA, a negative causal relationship between CRP and"number of days/week of moderate PA 10+ minutes"was observed (IVW, OR: 0.92, 95% CI: 0.89-0.96, p = 3.260 × 10-5). Sensitivity analyses were used to verify the robustness and reliability of the results. However, other initially observed associations ceased to be significant after controlling for obesity-related confounders.ConclusionOur MR analysis suggested a potential causal relationship between television watching and chronic low-grade inflammation, with more substantial evidence for GlycA. Additionally, different types of SB may have varying effects on inflammation. Obesity-related traits could partly or entirely influence the relationship between SB, PA, and inflammatory markers. Furthermore, Our findings indicate that SB is an independent risk factor for inflammation, separate from PA, and highlight the different mechanisms by which SB and PA affect disease.

ObjectivesThe present study analyzed the impact of the COVID-19 pandemic on the prevalence and incidence of new leprosy cases, as well as the diversity, distribution, and temporal transmission of Mycobacterium leprae strains at the county level in leprae-endemic provinces in Southwest China.MethodsA total of 219 new leprosy cases during two periods, 2018–2019 and 2020–2021, were compared. We genetically characterized 83 clinical isolates of M. leprae in Guizhou using variable number tandem repeats (VNTRs) and single nucleotide polymorphisms (SNPs). The obtained genetic profiles and cluster consequences of M. leprae were compared between the two periods.ResultsThere was an 18.97% decrease in the number of counties and districts reporting cases. Considering the initial months (January–March) of virus emergence, the number of new cases in 2021 increased by 167% compared to 2020. The number of patients with a delay of >12 months before COVID-19 (63.56%) was significantly higher than that during COVID-19 (48.51%). Eighty-one clinical isolates (97.60%) were positive for all 17 VNTR types, whereas two (2.40%) clinical isolates were positive for 16 VNTR types. The (GTA)9, (TA)18, (TTC)21 and (TA)10 loci showed higher polymorphism than the other loci. The VNTR profile of these clinical isolates generated five clusters, among which the counties where the patients were located were adjacent or relatively close to each other. SNP typing revealed that all clinical isolates possessed the single SNP3K.ConclusionCOVID-19 may have a negative/imbalanced impact on the prevention and control measures of leprosy, which could be a considerable fact for official health departments. Isolates formed clusters among counties in Guizhou, indicating that the transmission chain remained during the epidemic and was less influenced by COVID-19 preventative policies.

The domestic sewage in rural areas of South China is characterized by a relatively low concentration of organic pollutants; however, the factors causing this have not been carefully examined. This study conducted a comprehensive survey on two sewer networks in a small town of Eastern Guangdong, China, via grab water sampling at a frequency of once every 2 weeks lasting for 1 year. The sewage quality showed significant variations across the systems, while a gradual decrease in the concentrations of chemical oxygen demand (COD), total nitrogen (TN) and phosphorus (TP) from the upper to lower reaches of sewers could be observed. Storm events could have a flushing effect on TP in the upper reach of sewers, but a dilution effect on COD and TN in flat terrains. The diurnal pattern of sewage was largely impacted by the position of the manholes and water consumption difference between holidays and normal days. Both COD/TN and TN/TP ratios of the sewage showed a lognormal distribution dominating in the range of 2.0–3.0 and ~10.0, respectively. The low ratio of COD/TN in the morning discharge peak could be attributed to the wide use of septic tanks in the area, while groundwater infiltration played more important roles in the basal flow conditions. This study could serve as a basic reference for designing and managing sewage infrastructure in rural areas of South China and highlights that prevention of groundwater infiltration is crucial to improve the efficiency of sewage infrastructure in high water table areas.

Objectives Near viewing distance (VD) and longer viewing times are associated with myopia. This study aimed to identify the font size and viewing time that guarantee the appropriate VD and pixels per degree (PPD) for children’s online learning.Design This cross-sectional study comprised two experiments. In experiment A, participants read text in five font sizes on three backlit displays (a personal computer, a smartphone and a tablet), an E-ink display and paper for 5 min per font size. In experiment B, participants watched videos for 30 min on three backlit displays.Setting The Peking University People’s Hospital in Beijing (China) and the School of Ophthalmology and Optometry, Wenzhou Medical University (Zhejiang Province, China).Participants Thirty-five participants completed experiment A. Ten of them participated in experiment B.Primary and secondary outcome measures VDs were measured by Clouclip. The corresponding PPD was calculated.Results In experiment A, font size and display type significantly affected VD (F(4840)=149.44, p33 cm for all five font sizes on the PC, the tablet and paper and for 18-pt on the smartphone and 16-pt on E-ink. PPD for 16-pt on the PC, 14-pt on the tablet and all five font sizes on the phone were >60. In experiment B, VD increased over the four previous 5 min periods but decreased slightly on tablets and PCs in the fifth 5 min period. PPD was >60.Conclusion Children demonstrated different VDs and PPDs based on font size and display type. To ensure a 33 cm VD and 60 PPD, the minimum font size for online reading should be 18-pt on smartphones, 16-pt on PCs and E-ink, 10.5-pt on tablets and 9-pt on paper. More attention should be given to children’s VD with continuous video viewing of more than 25 min.Trial registration number ChiCTR2100049584.

Abstract The influence of a single water molecule on the BrO + HO2 hydrogen extraction reaction has been explored by taking advantage of CCSD(T)/aug-cc-pVTZ//B3LYP/6-311 + + G(d,p) method. The reaction in the absence of water have two distinct kinds of H-extraction channels to generate HOBr + O2 (1Δg) and HBr + O3, and the channel of generation of HOBr + O2 (1Δg) dominated the BrO + HO2 reaction. The rate coefficient of the most feasible channel for the BrO + HO2 reaction in the absence of water is estimated to be 1.44 × 10–11 cm3 molecule−1 s−1 at 298.15 K, which is consistent with the experiment. The introduction of water made the reaction more complex, but the products are unchanged. Four distinct channels, beginning with HO2 …H2O with BrO, H2O…HO2 with BrO, BrO…H2O with HO2, H2O…BrO with HO2 are researched. The most feasible channels, stemming from H2O…HO2 with BrO, and BrO…H2O with HO2, are much slower than the reaction of BrO + HO2 without water, respectively. Thus, the existence of water molecule takes a negative catalytic role for BrO + HO2 reaction.

Abstract Background The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear. Methods The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. Results In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P

Abstract Background The mining-induced stress in the surrounding rock after coal seam mining is the primary cause of damage and failure of the surrounding rock in the mining area. However, the magnitude and direction of the stress field induced by mining in the overburden strata during the excavation process of deep and adjacent coal seams are not yet clear, and it is difficult to determine how adjacent working faces interact with each other. Results In this study, a large-scale numerical model was built using FLAC3D (Fast Lagrange Analysis Continua) to simulate the sequential mining process of three adjacent working faces (No.1, No.2, and No.3) in Liuzhuang Coal Mine located in southern China. The results showed that the maximum height of plastic zone development after mining in the No.1 working face was 41 m, and the maximum height of plastic zone development was 33.8 m away from the 13 coal seam. It did not affect the top and bottom of the No.3 working face. The development height of the plastic zone on the roof of the No.2 working face after mining was 52m, and the top and bottom plates of the No.3 working face remained intact. The plastic zone of the floor of the No.3 working face after mining was not communicated with the plastic zone of the roof of the No.1 and No.2 working faces. There was a complete rock layer between the two coal seams, and there was not the mutual influence of the mining activities. During the mining process of working faces No.1 and No.2, the range of dynamic pressure influence was extended up to 100m ahead of the working face. During the mining process of the No.3 working face, the range of dynamic pressure influence was 120 m ahead of the working face. The No.1 working face goaf and the mining of No.2 working face had not disturbance to the No.3 working face. Conclusions After the mining of No.1 and No.2 working faces, the stress in the goaf significantly decreased, and the lateral support stress concentration area of No.1 and No.2 working faces had a relatively small impact on the 13 coal seam. Therefore, the No.1 goaf and mining of No.2 working faces had not disturbance to No.3 working face.

Underwater acoustic (UWA) channel prediction technology, as an important topic in UWA communication, has played an important role in UWA adaptive communication network and underwater target perception. Although many significant advancements have been achieved in underwater acoustic channel prediction over the years, a comprehensive summary and introduction is still lacking. As the first comprehensive overview of UWA channel prediction, this paper introduces past works and algorithm implementation methods of channel prediction from the perspective of linear, kernel-based, and deep learning approaches. Importantly, based on available at-sea experiment datasets, this paper compares the performance of current primary UWA channel prediction algorithms under a unified system framework, providing researchers with a comprehensive and objective understanding of UWA channel prediction. Finally, it discusses the directions and challenges for future research. The survey finds that linear prediction algorithms are the most widely applied, and deep learning, as the most advanced type of algorithm, has moved this field into a new stage. The experimental results show that the linear algorithms have the lowest computational complexity, and when the training samples are sufficient, deep learning algorithms have the best prediction performance.

Abstract Epitaxial growth is one of the most commonly used strategies to precisely tailor heterostructures with well-defined compositions, morphologies, crystal phases, and interfaces for various applications. However, as epitaxial growth requires a small interfacial lattice mismatch between the components, it remains a challenge for the epitaxial synthesis of heterostructures constructed by materials with large lattice mismatch and/or different chemical bonding, especially the noble metal-semiconductor heterostructures. Here, we develop a noble metal-seeded epitaxial growth strategy to prepare highly symmetrical noble metal-semiconductor branched heterostructures with desired spatial configurations, i.e., twenty CdS (or CdSe) nanorods epitaxially grown on twenty exposed (111) facets of Ag icosahedral nanocrystal, albeit a large lattice mismatch (more than 40%). Importantly, a high quantum yield (QY) of plasmon-induced hot-electron transferred from Ag to CdS was observed in epitaxial Ag-CdS icosapods (18.1%). This work demonstrates that epitaxial growth can be achieved in heterostructures composed of materials with large lattice mismatches. The constructed epitaxial noble metal-semiconductor interfaces could be an ideal platform for investigating the role of interfaces in various physicochemical processes.

We examined the growth tolerance, bioremoval efficacy, and metabolomic profiles of the cellular responses of Chlorella pyrenoidosa to phenol and 4-fluorophenol. We found that C. pyrenoidosa can tolerate exposure to 100 mg/L of phenol and 4-fluorophenol, and the growth of algal cells had a significant hormesis of inhibition first and then promotion. Up to 70% bioremoval of phenol and 4-fluorophenol may occur after 240 h of treatment. Superoxide dismutase (SOD) and catalase (CAT) activities, malondialdehyde (MDA) content, and reactive oxygen species (ROS) in algal cells in the phenol- and 4-fluorophenol-treated groups were similar or lower than in the control group. Furthermore, photosynthetic pigment and glycerophospholipid contents were significantly upregulated in both phenol- and 4-fluorophenol-treated groups, as indicated by the metabolomic analysis of C. pyrenoidosa, resulting in the vigorous growth of algal cells compared to the control group. Therefore, C. pyrenoidosa can be an excellent biosorbent for phenol and 4-fluorophenol. HIGHLIGHTS Chlorella pyrenoidosa can well tolerate 100 mg/L of phenol or 4-fluorophenol exposure.; 100 mg/L phenol or 4-fluorophenol can be bioremoved by >70% after 240 h of treatment.; Significant hormesis in algal growth was observed during the treatment.; Growth promotion is attributed to chlorophyll and glycerophospholipid accumulation.;

Introduction Electrocautery is used widely in surgical procedures, but making skin incision has routinely been performed with scalpel rather than electrocautery, for fear that electrocautery may cause poor incision healing, excessive scarring and increased wound complication rates. More and more studies on general surgery support the use of electrocautery for skin incision, but research comparing the two modalities for scalp incision in neurosurgery remains inadequate. This trial aims to evaluate the safety and efficacy of needle-tip monopolar for scalp incision in supratentorial neurosurgery compared with steel scalpel.Methods and analysis In this prospective, randomised, double-blind trial, 120 eligible patients who are planned to undergo supratentorial neurosurgery will be enrolled. Patients will be randomly assigned to two groups. In controlled group scalp incision will be made with a scalpel from the epidermis to the galea aponeurotica, while in intervention group scalp will be first incised with a steel scalpel from the epidermis to the dermis, and then the subcutaneous tissue and galea aponeurotica will be incised with needle-tip monopolar on cutting mode. The primary outcomes are scar score (at 90 days). The secondary outcomes include incision pain (at 1 day, on discharge, at 90 days) and alopecia around the incision (at 90 days), incision blood loss and incision-related operation time (during operation), incision infection and incision healing (on discharge, at 2 weeks, 90 days).Ethics and dissemination This trial will be performed according to the principles of Declaration of Helsinki and good clinical practice guidelines. This study has been validated by the ethics committee of West China Hospital. Informed consent will be obtained from each included patient and/or their designated representative. Final results from this trial will be promulgated through publications.Trial registration number ChiCTR2200063243.

BackgroundThe base deficit, international normalized ratio, and Glasgow Coma Scale (BIG) score was previously developed to predict the outcomes of pediatric trauma patients. We designed this study to explore and improve the prognostic value of the BIG score in adult patients with traumatic brain injury (TBI).MethodsAdult patients diagnosed with TBI in a public critical care database were included in this observational study. The BIG score was calculated based on the Glasgow Coma Scale (GCS), the international normalized ratio (INR), and the base deficit. Logistic regression analysis was performed to confirm the association between the BIG score and the outcome of included patients. Receiver operating characteristic (ROC) curves were drawn to evaluate the prognostic value of the BIG score and novel constructed models.ResultsIn total, 1,034 TBI patients were included in this study with a mortality of 22.8%. Non-survivors had higher BIG scores than survivors (p < 0.001). The results of multivariable logistic regression analysis showed that age (p < 0.001), pulse oxygen saturation (SpO2) (p = 0.032), glucose (p = 0.015), hemoglobin (p = 0.047), BIG score (p < 0.001), subarachnoid hemorrhage (p = 0.013), and intracerebral hematoma (p = 0.001) were associated with in-hospital mortality of included patients. The AUC (area under the ROC curves) of the BIG score was 0.669, which was not as high as in previous pediatric trauma cohorts. However, combining the BIG score with age increased the AUC to 0.764. The prognostic model composed of significant factors including BIG had the highest AUC of 0.786.ConclusionThe age-adjusted BIG score is superior to the original BIG score in predicting mortality of adult TBI patients. The prognostic model incorporating the BIG score is beneficial for clinicians, aiding them in making early triage and treatment decisions in adult TBI patients.

BackgroundLong-term exposure to arsenic can cause liver injury of varying degrees. Mitochondrial damage may be an early key event of arsenic-induced liver injury. Silent mating type information regulation 2 homolog 1 (SIRT1)/ recombinant peroxisome proliferators-activated receptor gamma coactivator 1 alpha (PGC-1α) is an important pathway regulating mitochondrial mass and function. However, whether arsenic-induced liver injury is related to mitochondrial dysfunction mediated by SIRT1/PGC-1α pathway remains unclear.ObjectiveTo investigate potential effects of sodium arsenite (NaAsO2) on mitochondrial function and expressions of SIRT1/PGC-1α pathway-related proteins in human normal liver cell.MethodsHuman normal liver cells (MIHA cells) were used as the research object. MIHA cells were treated with different concentrations of NaAsO2 (0, 5, 10 and 20 μmol·L−1) for 24 h, and the cells were collected for study. The ultrastructure of mitochondria was observed by transmission electron microscopy, adenosine triphosphate (ATP) concentration by fluorescence method, mitochondrial membrane potential (MMP) level by flow cytometry, and SIRT1, PGC-1α and their downstream nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) protein expression levels by Western blotting. One-way analysis of variance and trend test were used for data statistical analysis.ResultsThe viability of MIHA cells decreased gradually with the increase of NaAsO2 concentration (F=6495.47, P

Abstract Docosahexaenoic acid (DHA) can improve human and animal health, particularly including anti-inflammatory, antioxidant, anticancer, neurological, and visual functions. Schizochytrium sp. is a marine heterotrophic protist producing oil with high DHA content, which is widely used in animal and food production. However, different fermentation conditions have intensive impacts on the growth and DHA content of Schizochytrium sp. Thus, this study aimed to enhance the DHA yield and concentration of Schizochytrium sp. I-F-9 by optimizing the fermentation medium. First, a single-factor design was conducted to select a target carbon and nitrogen source from several generic sources (glucose, sucrose, glycerol, maltose, corn syrup, yeast extract, urea, peptone, and ammonium sulfate). The Plackett–Burman design and the central composite design (CCD) were utilized to optimize the fermentation mediums. Schizochytrium sp. in 50-mL fermentation broth was cultured in a 250 mL shake flask at 28 °C and 200 rpm for 120 h before collecting the cell pellet. Subsequently, the cell walls were destroyed with hydrochloric acid to extract the fatty acid using n-hexane. The DHA content was detected by gas chromatography. The single-factor test indicated that glucose and peptone, respectively, significantly improved the DHA content of Schizochytrium sp. compared to the other carbon and nitrogen sources. Glucose, sodium glutamate, and sea crystal were the key factors affecting DHA production in the Plackett–Burman test (P = 0.0247). The CCD result showed that DHA production was elevated by 34.73% compared with the initial yield (from 6.18 ± 0.063 to 8.33 ± 0.052 g/L). Therefore, the results of this study demonstrated an efficient strategy to increase the yield and content of DHA of Schizochytrium sp.

Objectives: We sought to perform a network meta-analysis to compare the safety and efficacy of the systemic administration of corticosteroids for the treatment of COVID-19. Methods: A Bayesian network meta-analysis was performed to combine the direct and indirect evidence. The surface under the cumulative ranking curve was obtained to estimate the ranking probability of the treatment agents for each outcome. The efficacy outcome was 28-day all-cause mortality. The safety outcome was serious adverse events. Results: A total of 16 trials with 2992 patients comparing four treatments (dexamethasone, hydrocortisone, methylprednisolone, and placebo) were identified. Direct analysis showed that corticosteroids were associated with a reduced risk of 28-day mortality compared with usual care (risk ratio [RR] 0.83; 95% confidence interval [CrI] 0.70-0.99). Network analysis showed that the pooled RR was 0.63 (95% CrI 0.39-0.93) for all-cause mortality at 28 days comparing methylprednisolone with usual care or placebo (surface under the cumulative ranking curve: 91%). Our analysis demonstrated that patients who received a low dose of corticosteroids (RR 0.80; 95% CrI 0.70-0.91) and a long course of treatment (RR 0.81; 95% CrI 0.71-0.91) had higher survival rates than patients in the placebo group. Conclusion: Administration of corticosteroids was associated with a reduced all-cause mortality at 28 days compared with placebo or usual care. Our analysis also confirmed the mortality benefit associated with low-dose and long-term treatment with corticosteroids.

Diet plays a crucial role in shaping the gut microbiota and overall health of animals. Traditionally, silkworms are fed fresh mulberry leaves, and artificial diets do not support good health. The aim of this study was to explore the relationship between the dietary transition from artificial diets to mulberry leaves and the effects on the gut microbiota and physiological changes in silkworms as a model organism. With the transition from artificial diets to mulberry leaves, the diversity of the silkworm gut microbiota increased, and the proportion of Enterococcus and Weissella, the dominant gut bacterial species in silkworms reared on artificial diets, decreased, whereas the abundance of Achromobacter and Rhodococcus increased. Dietary transition at different times, including the third or fifth instar larval stages, resulted in significant differences in the growth and development, immune resistance, and silk production capacity of silkworms. These changes might have been associated with the rapid adaptation of the intestinal microbiota of silkworms to dietary transition. This study preliminarily established a dietary transition–gut microbial model in silkworms based on the conversion from artificial diets to mulberry leaves, thus providing an important reference for future studies on the mechanisms through which habitual dietary changes affect host physiology through the gut microbiome.

Rice blast is one of the most devastating diseases, causing a significant reduction in global rice production. Developing and utilizing resistant varieties has proven to be the most efficient and cost-effective approach to control blasts. However, due to environmental pressure and intense pathogenic selection, resistance has rapidly broken down, and more durable resistance genes are being discovered. In this paper, a novel wall-associated kinase (WAK) gene, Pb4, which confers resistance to rice blast, was identified through a genome-wide association study (GWAS) utilizing 249 rice accessions. Pb4 comprises an N-terminal signal peptide, extracellular GUB domain, EGF domain, EGF-Ca2+ domain, and intracellular Ser/Thr protein kinase domain. The extracellular domain (GUB domain, EGF domain, and EGF-Ca2+ domain) of Pb4 can interact with the extracellular domain of CEBiP. Additionally, its expression is induced by chitin and polygalacturonic acid. Furthermore, transgenic plants overexpressing Pb4 enhance resistance to rice blast. In summary, this study identified a novel rice blast-resistant gene, Pb4, and provides a theoretical basis for understanding the role of WAKs in mediating rice resistance against rice blast disease.

Hypsizygus marmoreus is one of the main industrially cultivated varieties of edible fungi, with a delicious taste and high nutritional value. However, the long harvest period of 130–150 days greatly limits its large-scale expansion. This study aimed to investigate the effects of central carbon metabolism (CCM) on the mycelial growth performance and fruiting body formation of H. marmoreus. Nine edible fungi with different harvest periods were collected and used to evaluate their intracellular carbon metabolic differences in the CCM, which revealed that the imbalanced distribution of intracellular carbon metabolic levels in the CCM of H. marmoreus might be one of the key factors resulting in a slow mycelial growth rate and a long harvest period. Further analysis by three strategies, including metabolomics, adaptation of different carbon sources, and chemical interference, confirmed that low carbon flux into the pentose phosphate pathway (PPP) limited the supply of raw materials, reduced power, and thus influenced the mycelial growth of H. marmoreus. Furthermore, four transformants with increased expression levels of glucose-6-phosphate dehydrogenase (G6PDH), a key rate-limiting enzyme in the PPP of H. marmoreus, were developed and showed more extracellular soluble protein secretion and higher sugar assimilation rates, as well as improved mycelial growth rates in bottle substrate mixtures. Finally, cultivation experiments indicated that the maturation periods of the fruiting body with ~4–5 days in advance and the maximum fruiting body yield of 574.8 g per bag with an increase of 7.4% were achieved by improving the G6PDH expression level of the PPP in H. marmoreus. This study showed that CCM played an important role in the mycelial growth and development of H. marmoreus, which provided new insights for future advancements in cultivating and breeding edible fungi.

Steel octagon-web beam (SOWB) is a steel structure girder based on the appearance of cellular beam and assembly concept. In order to study the factors affecting deflection, parametric analysis based on finite element (FE) software ABAQUS 2017 was carried out. The factors include the opening type, expansion ratio (H/d) and height-span ratio (H/L). By analyzing the influencing factors on the structural deflection, a reasonable range of factors or the change rule between the two were obtained. In order to calculate the circumferential stress at the web opening, the web unit is divided into five parts according to the characteristics of the web unit and the Vierendeel truss theory. The calculation method of circumferential stress of each part was discussed, which was verified by comparing with the test results.

PurposeDrawing on the Job Demands-Resources (JD-R) model, this study aims to explore how telecommuting affects employee’ work engagement, and consider how perceived supervisor support moderates this effect.Design/methodology/approachA time-lagged study was conducted on 286 employees from four enterprises in southern China.FindingsThe results showed that telecommuting both decreased work engagement by triggering work–family conflict and enhanced work engagement by increasing job autonomy. In addition, perceived supervisor support enhanced the positive direct effect of telecommuting on job autonomy and the indirect effect on employee’ work engagement, while perceived supervisor support weakened the negative direct effect of telecommuting on work–family conflict and the indirect effect on employee’ work engagement.Originality/valueThis study enrich the literature on telecommuting and employee engagement, and emphasize the importance of perceived supervisor support in this context. Additionally, this study provides some practical implications for companies to adapt and manage telecommuting.

Abstract Background Comorbidities are common in aged intracerebral hemorrhage patients. The purpose of this study was to assess whether the Charlson Comorbidity Index (CCI) was associated with in-hospital death and short-term functional outcome in elderly patients (age ≥ 70) with intracerebral hemorrhage (ICH). Methods This was a retrospective cohort of aged ICH patients (≥70 years old) admitted within 24 hours of ICH onset. The CCI was derived using hospital discharge ICD-9 CM codes and patient history obtained from standardized case report forms. Multivariable logistic regression was used to determine the independent effect of the CCI score on clinical outcomes. Results In this cohort of 248 aged ICH patients, comorbid conditions were common, with CCI scores ranging from 2 to 12. Logistic regression showed that the CCI score was independently predictive of 1-month functional outcome (OR = 1.642, P

Abstract Sparassis latifolia is a valuable edible mushroom, growing on fresh pine wood sawdust substrate. However, the mechanistic bases are poorly understood. The gene expression profiles of S. latifolia were analyzed from submerged cultures with fresh pine wood sawdust substrate for different time (0 h, 1 h, 6 h, 1 day, 5 days, and 10 days, respectively). The total number of differentially expressed genes (DEGs) identified under pine sawdust inducing was 2,659 compared to 0 h (CK). And 1,073, 520, 385, 424, and 257 DEGs were identified at the five time points, respectively. There were 34 genes in common at all inoculated time points, including FAD/NAD(P)-binding domain-containing protein, glucose methanol choline (GMC) oxidoreductase, flavin-containing monooxygenase, and taurine catabolism dioxygenase. Weighted gene co-expression analysis (WGCNA) was then used to compare the molecular characteristics among the groups and identified that the blue module had the highest correlation with the time induced by pine wood sawdust. There were 102 DEGs out of 125 genes in the blue model, which were most enriched in nitronate monooxygenase activity, dioxygenase activity, and oxidation–reduction process GO terms (p

CeO2-supported Pt single atoms with different coordination environments exhibit distinct behaviors in reactant adsorption/activation and product desorption, thus showing different catalytic performance for various catalytic oxidation reactions.

Objectives: Compare the differences between the intervention and control groups in changes of primary outcomes (body mass index [BMI] and waist-to-height ratio [WHtR]) and secondary outcomes (nutrition knowledge of children and parents), from baseline to the 6- and 12-month follow-ups; examine the associations of changes in nutrition knowledge of children and their parents with children's changes in BMI and WHtR. Data sources: Data collected from four schools in two poverty-stricken counties in northern Shaanxi Province in 2020‒2021. Methods: A multifaced intervention program targeted children (promoting healthy diet and nutrition education) and their parents (promoting nutrition knowledge) was conducted in the interventional group. Four schools, with two in each group, were randomly allocated to the intervention or control group, with 814 eligible children aged 7.1 to 12.8 years. The control group conducted myopia promotion. Differences in changes of BMI and WHtR between groups were compared with t-test. Mixed-effects model was used to examine the associations between changes in nutrition knowledge of children and parents with changes in children's BMI and WHtR. Results: At the 6-month follow-up, the difference in changes in BMI between the intervention and control groups was 0.4 kg/m 2 (P < 0.001). At the 12-month follow-up, the difference in changes in BMI and WHtR between intervention and control groups was 0.1 kg/m2 (P < 0.001) and 0.01 kg/m2 (P < 0.001). In the intervention group, the nutrition knowledge awareness rate of children increased from 16.9% (69/409) at baseline to 21.3% (87/409) at 6-month, and 22.7% (93/409) at 12-month. The awareness rate of nutrition knowledge of parents also fluctuated, from 5.6% (23/409) to 6.6% (27/409) and 5.4% (22/409). However, the difference in changes in nutrition knowledge between intervention and control groups was non-significant. The 6-month follow-up changes in children's nutrition knowledge scores were negatively associated with changes in BMI in girls (β = −0.26, 95% confidence interval [CI]: −0.38 to −0.14, P < 0.001), while positively associated with changes in WHtR in boys (β = 0.003, 95% CI: −0.0002 to 0.005, P = 0.035). The 12-month follow-up changes in children's nutrition knowledge scores were positively associated with changes in children's WHtR (β = 0.003, 95% CI: 0.0004 to 0.01, P = 0.018). Conclusions: The intervention strategies did not reduce the BMI and WHtR of children, and the nutrition knowledge of children and parents increased after the intervention in intervention group. Changes in nutrition knowledge of children and their parents are associated with changes in children's BMI or WHtR. Interventions with a new focus on obesity are needed to help improve children's nutritional status in poverty-stricken areas in Shaanxi Province of China.