Search

Abstract Human brucellosis is a re-emerging disease in Sichuan Province, China. In this study, bacteriology, conventional bio-typing, multi-locus sequence typing (MLST), and multiple locus variable-number tandem repeat analysis (MLVA) were applied to preliminarily characterize the strains in terms of genetic diversity and epidemiological links. A total of 101 Brucella strains were isolated from 16 cities (autonomous prefectures) from 2014 to 2021, and all of the strains were identified as Brucella melitensis bv. 3, suggesting that surveillance should focus on ruminants. MLST analysis identified four STs, namely, ST8 (n = 93), ST39 (n = 6), ST101 (n = 1), and ST118 (n = 1). The latter were new STs, indicating that strains displayed high population diversity. Six MLVA-8, namely, 42, 43, 45, 63, 83, and 114, and eight MLVA-11, namely, 111, 115, 116, 125, 180, 291, 298, and 342, genotypes were identified, demonstrating that all of the strains were from the Eastern Mediterranean lineage, and these strains exhibited a high genotype diversity. MLVA-16 analysis revealed that there was a co-existing transmission pattern, where sporadic cases and multiple outbreak events had a common origin. The dominant STs and MLVA genotypes of strains were epidemic in Northern, China, and 36 MLVA-16 genotypes were shared among strains (n = 51, 50.4%, 51/101) from Sichuan and strains from 22 other provinces. The findings imply that infected animals were introduced from outside the province. The surveillance and control of the disease have become public health challenges. Animal quarantines should be strengthened to prevent the spread of B. melitensis species among adjacent regions.

The comprehensive process of laser peening (LP) for forming and fatigue strengthening of 6005A-T6 integral stiffened structure (ISS) was investigated. The formation characteristics of ISS under the accumulation of multiple pulse lasers were emphasized. The stress distribution, microstructure response, and phase evolution of the LPed region and deformation region were analyzed. The fatigue crack propagation mode and the mechanism for extending fatigue life were revealed. The results demonstrate that a scanning method perpendicular to the target forming direction achieves better forming effects. For specimens scanned in unfold direction scanning, chord direction scanning, and unfold-chord directions, compressive stresses at the bottom of stiffeners are −87 MPa, −134 MPa, and −169 MPa, respectively. The overall bending elongation forming combined with local impact plastic deformation induced by LP refines surface grains, while slightly elongating those in the deformation region through compression. LP enhances the solid solubility of alloy elements, while residual compressive stress (RCS) does not significantly influence the dissolution of the second phase. The fatigue extension percentages for three specimens are 33.9%, 17.3%, and 43.5%, respectively. The increase in grain boundary density of refined grains impedes crack propagation, while RCS that brings materials on both sides of the crack tip closer together induces deviation from the original crack path. Under RCS, micropores and microcracks are closed to prevent further propagation. Fatigue striations propagate simultaneously parallel and perpendicular to the surface, and the multi-level dimple structure consisting of “large dimples containing small dimples” suppresses crack propagation.

Abstract Background Gastrointestinal (GI) cancers have heavily burdened public health. Few studies reported GI cancer burden among adolescents and young adults (AYA). To address this gap, we explored the burden of GI cancer among people aged 15–39. Methods We retrieved data from the Global Burden of Disease Study 2019 Data Resources. The average annual percent change (AAPC) of rates was calculated by linear regression analysis of the natural logarithm. Bayesian age-period-cohort model was applied to predict the future burden. Results In 2019, there were 171,857 (95% uncertain interval [95% UI]: 157,092–187,974) new GI cancer cases with a rate of 5.79/100,000 (95% UI: 5.29–6.33) and 91,033 (95% UI: 83,156–99,399) deaths at a rate of 3.07/100,000 (95% UI: 2.80–3.35) among AYA. The number of prevalent cases and disability-adjusted life years (DALYs) were 722,573 (95% UI: 660,806–789,476) and 5,151,294 (95% UI: 4,706,065–56,188,77), with rates of 24.35/100,000 (95% UI: 22.27–26.60) and 173.57/100,000 (95% UI: 158.57–189.32) respectively. The overall rates of mortality (AAPC = -1.281, p

Abstract The study aims to develop and validate a predictive model for effectively predicting in-hospital mortality in patients admitted to the intensive care unit due to Gastrointestinal bleeding (GIB). A retrospective cohort study was conducted, including data from patients in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD) and Medical Information Mart for Intensive Care-IV Database (MIMIC-IV) with a diagnosis of GIB. Patients from the eICU-CRD were randomly allocated into both development and validation sets, and those from MIMIC-IV were assigned as an external validation group. Multivariate logistic regression was employed to create a predictive model, which was depicted as a nomogram. This study included a total of 2929 patients with GIB from the eICU-CRD and 718 patients from the MIMIC-IV. To access the dynamic nomogram, please use the following link: https://kangzou.shinyapps.io/DynNomapp_GIB/ . The area under the receiver operating characteristic curve for the nomogram was 0.893 in the development set, 0.860 in the internal validation set, and 0.781 in the external validation set. The mortality rate was 25.7% in the high-risk group (nomogram scores > 101.974) and 2.8% in the low-risk group (nomogram scores ≤ 101.974). The nomogram exhibited excellent discrimination, calibration, and clinical utility in predicting in-hospital mortality among patients admitted to the intensive care unit with GIB.

Abstract. Background:. China is one of the countries with the largest burden of gastrointestinal and liver diseases (GILD) in the world. The GILD constitutes various causes of mortality and disability. The study aimed to investigate the trend of GILD in China using the Global Burden of Diseases Study 2019 (GBD 2019) data resources from 1990 to 2019. Methods:. The data on the age-standardized mortality rates (ASMR) and disability-adjusted life years (DALYs) for GILD in China from 1990 to 2019 were collected from the GBD 2019 data resources. Furthermore, the ranking of the main causes of deaths and DALYs, as well as the trends of ASMR, DALYs, years of life lost (YLLs), and years of life lost due to disability (YLDs) per 1,000,000 in GILD were reported. Results:. The ASMR and DALYs for stomach cancer, liver cancer, and esophageal cancer, which ranked top three among the GILDs from 1990 to 2019, were gradually decreasing. Significant decreases in the ASMR and DALYs were found in diarrheal diseases and acute hepatitis (A, E, and C). However, noteworthy increases were found in those of colon and rectum cancer (CRC) and pancreatic cancer. Trend of DALYs, mortality, and YLLs rates for most of GILD were decreasing from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trend. The DALYs, mortality and YLLs of most GILD diseases showed decreasing trends from 1990 to 2019, except the burden of CRC and pancreatic cancer with an increasing trends. Conclusions:. The result of the GBD 2019 showed that the rates of most GILDs decreased in China; however, gastrointestinal and liver cancer, such as stomach cancer still held the top ranking. Furthermore, the shift from infectious diseases to non-communicable causes among GILD burden is occurring.

Abstract Background The pathogenesis of osteoarthritis (OA) involves the progressive degradation of articular cartilage. Exosomes derived from mesenchymal stem cells (MSC-EXOs) have been shown to mitigate joint pathological injury by attenuating cartilage destruction. Optimization the yield and therapeutic efficacy of exosomes derived from MSCs is crucial for promoting their clinical translation. The preconditioning of MSCs enhances the therapeutic potential of engineered exosomes, offering promising prospects for application by enabling controlled and quantifiable external stimulation. This study aims to address these issues by employing pro-inflammatory preconditioning of MSCs to enhance exosome production and augment their therapeutic efficacy for OA. Methods The exosomes were isolated from the supernatant of infrapatellar fat pad (IPFP)-MSCs preconditioned with a pro-inflammatory factor, TNF-α, and their production was subsequently quantified. The exosome secretion-related pathways in IPFP-MSCs were evaluated through high-throughput transcriptome sequencing analysis, q-PCR and western blot analysis before and after TNF-α preconditioning. Furthermore, exosomes derived from TNF-α preconditioned IPFP-MSCs (IPFP-MSC-EXOsTNF−α) were administered intra-articularly in an OA mouse model, and subsequent evaluations were conducted to assess joint pathology and gait alterations. The expression of proteins involved in the maintenance of cartilage homeostasis within the exosomes was determined through proteomic analysis. Results The preconditioning with TNF-α significantly enhanced the exosome secretion of IPFP-MSCs compared to unpreconditioned MSCs. The potential mechanism involved the activation of the PI3K/AKT signaling pathway in IPFP-MSCs by TNF-α precondition, leading to an up-regulation of autophagy-related protein 16 like 1(ATG16L1) levels, which subsequently facilitated exosome secretion. The intra-articular administration of IPFP-MSC-EXOsTNF−α demonstrated superior efficacy in ameliorating pathological changes in the joints of OA mice. The preconditioning of TNF-α enhanced the up-regulation of low-density lipoprotein receptor-related protein 1 (LRP1) levels in IPFP-MSC-EXOsTNF−α, thereby exerting chondroprotective effects. Conclusion TNF-α preconditioning constitutes an effective and promising method for optimizing the therapeutic effects of IPFP-MSCs derived exosomes in the treatment of OA. Graphical Abstract

Joint diseases greatly impact the daily lives and occupational functioning of patients globally. However, conventional treatments for joint diseases have several limitations, such as unsatisfatory efficacy and side effects, necessitating the exploration of more efficacious therapeutic strategies. Mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have demonstrated high therapeutic efficacyin tissue repair and regeneration, with low immunogenicity and tumorigenicity. Recent studies have reported that EVs-based therapy has considerable therapeutic effects against joint diseases, including osteoarthritis, tendon and ligament injuries, femoral head osteonecrosis, and rheumatoid arthritis. Herein, we review the therapeutic potential of various types of MSC-EVs in the aforementioned joint diseases, summarise the mechanisms underlying specific biological effects of MSC-EVs, and discuss future prospects for basic research on MSC-EV-based therapeutic modalities and their clinical translation. In general, this review provides an in-depth understanding of the therapeutic effects of MSC-EVs in joint diseases, as well as the underlying mechanisms, which may be beneficial to the clinical translation of MSC-EV-based treatment.The translational potential of this article: MSC-EV-based cell-free therapy can effectively promote regeneration and tissue repair. When used to treat joint diseases, MSC-EVs have demonstrated desirable therapeutic effects in preclinical research. This review may supplement further research on MSC-EV-based treatment of joint diseases and its clinical translation.

BackgroundStatins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.MethodsIn this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.ResultsIn this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.ConclusionThis study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.

Abstract Background Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. Methods We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. Conclusions Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.

Abstract Background Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO2 to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO2 capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications. Results In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity. Conclusions Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli.

Laser powder bed fusion (LPBF) Al–Li alloy technology demonstrates adaptability to the development requirements of structural complexity and functional integration, making it a promising area of research in additive manufacturing for the aerospace, defense industry, and other fields. However, challenges such as microstructure anisotropy and metallurgical defects inevitably arise during the LPBF process of lightweight alloys, significantly impeding further enhancements in their formability properties. Some improvement measures offer a viable solution to enhance the microstructure, mitigate metallurgical defects, and optimize residual stress distribution in additive structures, thereby enabling high–performance Al–Li alloy production by LPBF. This paper first introduces the fundamental principle of LPBF and discusses the process of parameter optimization for LPBF Al–Li alloys. It then describes the typical microstructures and common metallurgical defects of LPBF Al–Li alloys, along with examining the evolution process of microstructures and formation mechanism of metallurgical defects. Specifically, it focuses on discussing the influence of Li element on solidification structure. On this basis, it presents the mechanical properties and anisotropy of mechanical properties for LPBF Al–Li alloys. Afterward, a comprehensive review is provided of the current research status regarding LPBF improvement measures, including powder alloying, heat treatment, and other technologies. Emphasis is placed on improvements in microstructure anisotropy and reductions in metallurgical defects through these improvement measures. Finally, this article summarizes the research progress made in LPBF Al–Li alloys and its improvement measures while also prospecting future research work.

BackgroundIFN-γ+CD4+ cells (type 1 helper T cells, Th1) represent a critical component of the inflammatory environment in the lungs of chronic obstructive pulmonary disease (COPD). Identifying influencing factors related to COPD-associated Th1 cells will enhance our understanding of the inflammatory mechanisms involved and facilitate the development of targeted interventions.MethodWe describe T-cell immunoglobulin and mucin-domain containing-3 (Tim3) as a key gene regulating COPD-associated Th1 cells through single-cell sequencing, flow cytometry and knockout mice.ResultsOur findings indicate that Havcr2 expression gradually increases during CD4+ T cell activation in COPD mice, with Tim3 being highly expressed on both CD4+ T cells and Th1 cells. Notably, the knockout of HAVCR2 further promotes the infiltration of CD4+ T cells and the expression of IFN-γ in the lungs, resulting in a more severe emphysema phenotype, although it does not significantly affect TNF-α expression. Additionally, NFIL3, an upstream regulator of Tim3, is also highly expressed in the CD4+ T cells of COPD mice. Mice with NFIL3 knockout exhibit phenotypes similar to those of HAVCR2 knockout mice, along with a significant downregulation of Tim3 expression. In vitro, we simulated the activation process by polarizing primary CD4+ Tn cells from COPD mice and observed that NFIL3/Tim3 expression was significantly upregulated following Th1 polarization.ConclusionOur study demonstrates that the NFIL3/Tim3 axis plays a role in Th1 imbalance in the lungs of COPD by inhibiting Th1 differentiation.

Abstract Mental disorders are the leading contributors to the globally nonfatal burden of disease. This study was aimed to estimate the burden of mental disorders in Asian countries. Based on GBD 2019, the prevalence and disability-adjusted life of years (DALYs) rates with 95% uncertainty intervals (UI) were estimated in Asian countries. Predictions for the future burden of 8 selected countries, ranks of the burden of mental disorders and correlations with Sociodemographic Index (SDI) were also estimated. During the past 3 decades, while the number of DALYs of mental disorders increased from 43.9 million (95% UI: 32.5–57.2) to 69.0 million (95% UI: 51.0–89.7), the age-standardized rates of DALYs of mental disorders remained largely consistent from 1452.2 (95% UI: 1080.16–1888.53) per 100,000 population in 1990 to 1434.82 (95% UI: 1065.02–1867.27) per 100,000 population in 2019, ranked as the eighth most significant disease burden in Asia in 2019. Depressive disorders (37.2%) were the leading contributors to the age-standardized DALY rates of mental disorders in Asia, followed by anxiety disorders (21.5%). The age-standardized DALY rates in females were higher than their male counterparts, both peaked at 30-34 years. The age-standardized DALY rates were predicted to remain stable, with the number of DALYs presented an upward trend in the future. There was no significant correlation between the burden of mental disorders and SDI. All mental disorders ranked higher in 2019, compared in 1990. To reduce this burden, urgent measures for prevention, treatment, and rehabilitation for mental disorders need to be taken by Asian governments.

Abstract Background Cancer burden from the elderly has been rising largely due to the aging population. However, research on the long‐term epidemiological trends in cancer of the elderly is lacking. Methods Registry data of this population‐based cross‐sectional study were from the Surveillance, Epidemiology, and End Results (SEER) database. The study population aged 65 years or more, from geographically distinct regions. Joinpoint regression and JP Surv method were used to analyze cancer trends and survival. Results Mortality rate during 1975–2020 decreased from 995.20 to 824.99 per 100,000 elderly persons, with an average annual decrease of 0.421% (95% CI, 0.378–0.464). While overall incidence increased with no significance. Prostate (29%) and breast (26%) cancer were the most common malignancies, respectively, in elderly males and females, and the mortality for both of the two (prostate 15%, breast 14%) ranked just behind lung and bronchus cancer, which had the highest mortality rates in males (29%) and females (23%). Many cancers showed adverse trends in the latest follow‐up periods (the last period calculated by the Joinpoint method). For intrahepatic cholangiocarcinoma, incidence (male Annual Percentage Change [APC] = 7.4*; female APC = 6.7*) and mortality (male APC = 3.0*; female APC = 3.3*) increased relatively fast, and its survival was also terrible (3‐year survival only 10%). Other cancers with recent increasing mortality included cancer of anus, anal canal and anorectum, retroperitoneum, pleura, peritoneum, etc. Most cancers had favorable trends of survival during the nearest follow‐up period. Conclusion Against the background of overall improvement, many cancers showed adverse trends. Further research for the underlying mechanisms and targeted implements towards adverse trends is also urgent.

BackgroundChildhood and adolescent cancer represent a significant health burden in the United States. Current and precise epidemiological data are crucial to develop effective cancer control plans and ultimately reduce the burden of childhood and adolescent cancer.MethodsWe analyzed data obtained from cancer registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Age-standardized incidence and death rates, assessed using joinpoint analysis, were quantified as annual percentage changes (APC) and average percentage changes (AAPC).ResultsThe overall cancer incidence rate in 2008–2018 was 187.9 per 1,000,000 persons. Cancer incidence rates demonstrated a sustained upward trend, with an APC of 0.8 from 1975 to 2018. Incidence rates during 2008–2018 remained stable among non-Hispanic Black children but increased among other racial and ethnic groups. Leukemias, central nervous system tumors, and lymphomas were the most common cancer groups for patients aged 0–19 years. Cancer death rates decreased among children [AAPC, −1.3 (95% CI, −1.5 to −1.1)] during 2009–2019, while were stable among adolescents during that period.ConclusionsIn this study, we analyzed cancer incidence and mortality rates and trends in children aged 0–19 years in the United States. Our findings revealed an overall increase in cancer incidence rates among children and adolescents, accompanied by a decline in cancer mortality rates over time. These rates and trends varied by age, sex, and particularly race and ethnicity, highlighting the significance of comprehending and addressing disparities and ultimately reducing the disease burden of childhood and adolescent cancer.

Abstract Background Acyl-CoA-binding domain-containing 3 (ACBD3) is a multifunctional protein, that plays essential roles in cellular signaling and membrane domain organization. Although the precise roles of ACBD3 in various cancers remain unclear. Thus, we aimed to determine the diverse roles of ACBD3 in pan-cancers. Methods Relevant clinical and RNA-sequencing data for normal tissues and 33 tumors from The Cancer Genome Atlas (TCGA) database, the Human Protein Atlas, and other databases were applied to investigate ACBD3 expression in various cancers. ACBD3-binding and ACBD3-related target genes were obtained from the STRING and GEPIA2 databases. The possible functions of ACBD3-binding genes were explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We also applied the diagnostic value and survival prognosis analysis of ACBD3 in pan-cancers using R language. The mutational features of ACBD3 in various TCGA cancers were obtained from the cBioPortal database. Results When compared with normal tissues, ACBD3 expression was statistically upregulated in eleven cancers and downregulated in three cancers. ACBD3 expression was remarkably different among various pathological stages of tumors, immune and molecular subtypes of cancers, cancer phosphorylation levels, and immune cell infiltration. The survival of four tumors was correlated with the expression level of ACBD3, including pancreatic adenocarcinoma, adrenocortical carcinoma, sarcoma, and glioma. The high accuracy in diagnosing multiple tumors and its correlation with prognosis indicated that ACBD3 may be a potential biomarker of pan-cancers. Conclusion According to our pan-cancer analysis, ACBD3 may serve as a remarkable prognostic and diagnostic biomarker of pan-cancers as well as contribute to tumor development. ACBD3 may also provide new directions for cancer treatment targets in the future.

Abstract Inflammasome activity is important for the immune response and is instrumental in numerous clinical conditions. Here we identify a mechanism that modulates the central Caspase-1 and NLR (Nod-like receptor) adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). We show that the function of ASC in assembling the inflammasome is controlled by its modification with SUMO (small ubiquitin-like modifier) and identify that the nuclear ZBTB16 (zinc-finger and BTB domain-containing protein 16) promotes this SUMOylation. The physiological significance of this activity is demonstrated through the reduction of acute inflammatory pathogenesis caused by a constitutive hyperactive inflammasome by ablating ZBTB16 in a mouse model of Muckle-Wells syndrome. Together our findings identify an further mechanism by which ZBTB16-dependent control of ASC SUMOylation assembles the inflammasome to promote this pro-inflammatory response.

Abstract Background Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC. Methods The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan–Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein–protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed. Results Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia. Conclusion Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.

IntroductionChina has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China.MethodsWe extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group.ResultsIn 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of −0.219 and −0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates.ConclusionChina bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.

Objectives This study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time.Design We used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect.Setting and data Case data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University.Outcome measures The number of monthly hospitalised patients with EGVB in our hospital.Results A total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40–60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12 with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively.Conclusions The number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.

Background: Mitochondria are dynamic organelles, and mitochondrial dynamics are important for the maintenance of mitochondrial inheritance and function. Recently, an increasing number of studies have shown that mitochondrial dynamics play an important role in the occurrence and development of hepatocellular carcinoma (HCC). However, bibliometric analyses of mitochondrial dynamics in HCC are scarce. Therefore, we conducted a bibliometric analysis to explore the current global research status and trends in mitochondrial dynamics and HCC. Methods: Global publications on mitochondrial dynamics and HCC published between 2007 and May 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was performed using Bibliometrix, VOSviewer, and CiteSpace to analyze the numbers, citations, countries, institutions, authors, journals, references, and keywords. Results: A total of 518 publications were retrieved fromthe WoSCC database. China and The Fourth Military Medical University were the most productive countries and institutions. Zorzano, A published the most literature whereas Chen, HC was the author with the highest number of co-citations. Plos One was the most popular journal, whereas the Journal of Biological Chemistry had the highest number of co-citations. The most frequently used keyword was “mitochondria”. Further analysis of the references and keywords showed that the molecular mechanisms linking them to drug therapy targets should be the focus of future studies. Conclusions: Research on mitochondrial dynamics in HCC has received much attention, and many studies have been published. However, research on mitochondrial dynamics and HCC has been limited by insufficient regional development imbalances and global cooperation. Nevertheless, future research on mitochondrial dynamics and HCC is promising, especially regarding the molecular mechanisms of mitochondrial fission and fusion and how to link the currently known molecular mechanisms with drug therapy targets for HCC.

BackgroundGender disparity is pervasive in academic medicine. This study aimed to assess the disparity between men and women with regard to first and senior author positions in primary studies on liver cancer over the last two decades.MethodsWe conducted a review of articles published in high-impact factor journals of the field of Gastroenterology and Hepatology in 2005, 2010, 2015 and 2020. First and senior authors of all ages were considered as the study population. The authors' genders were determined using the online artificial intelligence tool genderize.io (https://genderize.io/). The disparity between men and women authors was assessed using the linear-by-linear association test.Results665 original articles from 10 journals were reviewed. The point prevalence of first women authors was 25.0% compared with 75.0% for men. The point prevalence of senior women authors was 16.3% compared with 83.7% for men. From 2000 to 2020, the proportion of first women authors increased 14.4% to 26.8% compared with 85.6%-73.2% for men (P = 0.009), and the proportion of senior women authors increased from 7.4% to 19.5%, compared with 92.6%-80.5% for men (P = 0.035). The factor independently associated with a reduced representation of women among first authors was the region of author. The factor independently associated with a reduced representation of women among senior authors was the impact factor of journals.ConclusionThe findings indicated a remarkable increase in the proportion of women, both first and senior authors, over the past two decades in the field of liver cancers. However, the representation of women authors in this area is far less than that of men.

Abstract Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while the efficacy is still unsatisfactory and limited by the unique immunosuppressive microenvironment in metastatic bone site. Here, we developed a bone-targeted nano-delivery system as a nano-regulator to enhance the immunotherapy of bone metastatic PCa. The nanosystem was assembled via coordination between phytic acid (PA) and Fe3+ to form nano-sized metal–organic framework (MOF), through which mitoxantrone (MTO) was encapsulated. At cellular level, the nanosystem showed selective cytotoxicity towards RM-1 PCa cells over immune cells, and could induce tumor cells immunogenic cell death (ICD) to improve the immunogenicity of the tumor. Moreover, the nanosystem was able to induce ubiquitination of TGFβ receptor (TβR) on immune cells to promote its degradation, thus serving as a nano-regulator to block the functions of TGF-β, an abundant cytokine that has a systematically immunosuppressive effect in the tumor microenvironment. Upon intravenous injection, the nanoparticle showed pro-longed blood circulation and targeting accumulation into bone metastatic site, and imposed robust anti-tumor effect in combination with αCTLA-4. In addition, bone destruction was significantly alleviated after treatment to reduce the skeletal-related events. Overall, this work provides a biocompatible nanomedicine to restore immune sensitivity of bone metastatic tumor for enhanced immunotherapy by blocking TGF-β signaling pathway.

A large-span steel–concrete composite beam with precast hollow core slabs (CBHCSs) is a relatively new floor structure that can be applied to various long-span structures. However, human-induced vibrations may present serviceability issues in such structures. To alleviate vibrations, both the walking forces excited by humans and the associated floor responses must be elucidated. In this study, 150 load–time histories of walking, excited by 25 test participants, are obtained using a force measuring plate. The dynamic loading factors and phase angles in the Fourier series functions for one-step walking are determined. Subsequently, walking tests are performed on seven CBHCS specimens to capture the essential dynamic properties of mode shapes, natural frequencies, damping ratios, and acceleration time histories. The CBHCS floor system generally exhibits a high frequency (> 10 Hz) and low damping (damping ratio

In order to investigate the hydrogen permeation behavior of 316L stainless steel during the microstructural evolution induced by laser peening (LP), an electrochemical hydrogen charging system for initial hydrogen charging of LPed and non-LPed specimen was developed. Afterward, the microhardness, residual stress, and microstructures of the samples were determined and analyzed. Finally, electrochemical hydrogen permeation experiments were undertaken to verify LP's influence on hydrogen permeation parameters of 316L. The results showed that LP reduced the hydrogen-induced hardening rate of the alloy and additionally invoked high magnitude compressive residual stress on its surface. At the layer close to the face of the specimen, the grain refinement rate was as high as 56.18%, which was accompanied by the appearance of high-density dislocations. Compared with the non-LPed sample, the hydrogen permeation time increased significantly, and the saturation current density in steady state hydrogen permeation also decreased gradually.

Osteoarthritis (OA) is associated with ferroptosis, a newly discovered form of programmed cell death associated with lipid peroxidation. Curcumin, the main monomer component in turmeric rhizomes, possesses antioxidant and anti-ferroptosis properties, but its effect on ferroptosis in chondrocytes of OA is unknown. This study aimed to investigate the protective effect and potential mechanism of curcumin on chondrocytes induced by erastin, a ferroptosis inducer. CCK-8 assays were used to assess cell viability in mouse primary chondrocytes treated with 3.33 μM erastin alone or in combination with different doses of curcumin. Various parameters were detected, including LDH, SOD, GSH-PX, MDA, ROS and Fe2+ contents. The ferroptosis-related proteins, such as SLC7A11, GPX4, TFR1, ACSL4, and FTH1, were examined using immunofluorescence and western blotting. Nrf2 was knocked down using siRNA to explore the molecular mechanism through which curcumin protects chondrocytes from erastin-induced ferroptosis. In a mouse model of knee ferroptosis induced by intracavity injection of 10 μL erastin (5 mg/mL), HE staining, Safranin O-Fast Green staining, and immunohistochemistry were employed to evaluate articular cartilage injury. The results demonstrated that erastin significantly suppressed the expression of SOD, GSH-PX, SLC7A11, GPX4, and FTH1 while upregulating the levels of LDH, MDA, ROS, ACSL4, and TFR1 in chondrocytes. Moreover, erastin-induced chondrocyte ferroptosis, lipid ROS, and Fe2+ production were reversed by curcumin. Additionally, curcumin significantly upregulated the expression level of the Nrf2 gene and protein. Silencing Nrf2 reversed the protective effect of curcumin on erastin-induced chondrocyte ferroptosis. In animal experiments, silencing Nrf2 counteracted the impact and damage of curcumin on erastin-induced ferroptosis of cartilage tissue in vivo, leading to significant inhibition of OA progression. Taken together, these findings suggest that curcumin can inhibit chondrocyte ferroptosis by activating the Nrf2 signaling pathway, providing further insight into the regulatory mechanism of curcumin in OA and supporting its potential therapeutic use in OA treatment.

IntroductionAlthough carbohydrates and lipids are important energy substances for Chinese mitten crab (Eriocheir sinensis), little is known about their synergistic effect on the growth, energy utilization characteristics and mechanisms involved in this process.MethodsA 58-d feeding experiment was conducted to investigate the effects of dietary carbohydrate to lipid ratio (C/L) on the growth performance, biochemical indices, and metabolism-related differential gene expression of juvenile E. sinensis in both intermolt (InM) and premolt (PrM) stages. Five experimental diets were formulated with increasing dietary C/L (1.34, 2.39, 3.59, 5.52 and 9.42).ResultsThe results showed that the weight growth rate of juvenile E. sinensis was highest in dietary C/L3.59 group, which was significantly higher than that in the other groups. As dietary C/L increased, the hepatic glycogen contents increased, but triglyceride contents decreased in the hepatopancreas of E. sinensis in the InM. In both two molting stages, the activities of glycogen synthase and fatty acid synthase paralleled with their contents, respectively. Crabs in the InM showed higher contents of triglyceride and the activities of glycolytic rate-limiting enzymes but lower contents of hepatic glycogen than those in the PrM, especially in the C/L 1.34 and C/L 3.59 groups. In all dietary groups, the activities and transcription of gluconeogenesis and fatty acid synthesis related enzymes were significantly higher in the InM than those in the PrM. KEGG analysis showed that differential genes were enriched in fatty acid biosynthesis, fatty acid metabolism, oxidative phosphorylation pathway, pentose phosphate pathway, pyruvate metabolism and steroid biosynthesis between different dietary groups and molting stages.DiscussionTo conclude, the optimal dietary C/L was estimated to be 3.59 for juvenile E. sinensis based on the survival and growth performance. Compared to PrM, E. sinensis in the InM was more active in the carbohydrate metabolism (glycolysis and gluconeogenesis) and fatty acid synthesis, with more triglyceride and less glycogen accumulated in the hepatopancreas.This study could contribute to better understanding the carbohydrate and lipid metabolism between different molting stages, and optimizing the precise feed formulation for juvenile E. sinensis.

Abstract Objective Individuals with mental illnesses are exposed to an increased risk of suicide. In this study, we aimed to investigate the clinical characteristics and outcome of psychiatric patients who attempted suicide by drug overdose and required emergency care. Methods A retrospective study was carried out in the Department of Emergency, the First Affiliated Hospital, Zhejiang University School of Medicine. Electronic medical records of psychiatric patients who were hospitalized due to suicide attempts from March 2019 to February 2022, with a discharge diagnosis of drug overdose were reviewed. Suicide‐related data of patients were collected, including suicide month, time from suicide to admission, type of drugs, the number of tablets taken, as well as demographic and clinical profiles (e.g., gender, age, marital status, profession, physical comorbidities, and diagnosis of mental illness). Results In the results, half of the patients were young people, female patients accounted for a higher proportion (72.5%), and the incidence of suicide was higher in winter than other seasons. Among the 109 psychiatric patients, 60 patients (55.0%) had a history of major depressive disorder, and 86 patients (78.9%) committed suicide with various psychotropic drugs, among which anxiolytics were the most commonly used drugs. Thirty‐seven patients (33.9%) experienced severe physical complications caused by drug overdose, with lung infections being the most common. The clinical outcome of most patients was favorable following emergent treatment, while 2 patients (1.8%) older than 80 failed to survive. Conclusion A better understanding of psychiatric patients referred to emergency care due to suicide by drug overdose helps to improve the clinical management and prognosis of patients.

The aim of this study was to investigate the function and regulatory mechanism of long non-coding RNA (lncRNA) X-inactive-specific transcript (XIST) in cerebral ischemic stroke (CIS). The impact of lncRNA XIST on CIS was evaluated in acute CIS patients, middle cerebral artery occlusion (MCAO) mice, and oxygen-glucose deprivation and restoration brain endothelial cells. Our results demonstrated that the expression of lncRNA XIST decreased during the early stages of CIS but then increased in the later stages in CIS patients and ischemic models in vivo and in vitro. In addition, the serum levels of lncRNA XIST negatively correlated with severity of neurological impairment of CIS patients. Further studies exhibited that lncRNA XIST regulated the expression of proangiogenic factor-integrin α5 (Itgα5) and anti-inflammation factor-Kruppel-like transcription factor 4 (KLF4) by targeting microRNA-92a (miR-92a). Silencing of lncRNA XIST impaired angiogenesis and exacerbated cerebral vascular injury following CIS, leading to larger infarcts and worse neurological deficits in transient MCAO mice. Mechanistic analysis revealed that lncRNA XIST modulated angiogenesis and alleviated cerebral vascular injury following CIS through mediating the miR-92a/Itgα5 or KLF4 axis, respectively. These data indicate that lncRNA XIST confers protection against CIS, providing a valuable target for future prevention and treatment of CIS.

ObjectiveThis study aimed to develop and validate predictive models using electronic health records (EHR) data to determine whether hospitalized COVID-19-positive patients would be admitted to alternative medical care or discharged home.MethodsWe conducted a retrospective cohort study using deidentified data from the University of Florida Health Integrated Data Repository. The study included 1,578 adult patients (≥18 years) who tested positive for COVID-19 while hospitalized, comprising 960 (60.8%) female patients with a mean (SD) age of 51.86 (18.49) years and 618 (39.2%) male patients with a mean (SD) age of 54.35 (18.48) years. Machine learning (ML) model training involved cross-validation to assess their performance in predicting patient disposition.ResultsWe developed and validated six supervised ML-based prediction models (logistic regression, Gaussian Naïve Bayes, k-nearest neighbors, decision trees, random forest, and support vector machine classifier) to predict patient discharge status. The models were evaluated based on the area under the receiver operating characteristic curve (ROC-AUC), precision, accuracy, F1 score, and Brier score. The random forest classifier exhibited the highest performance, achieving an accuracy of 0.84 and an AUC of 0.72. Logistic regression (accuracy: 0.85, AUC: 0.71), k-nearest neighbor (accuracy: 0.84, AUC: 0.63), decision tree (accuracy: 0.84, AUC: 0.61), Gaussian Naïve Bayes (accuracy: 0.84, AUC: 0.66), and support vector machine classifier (accuracy: 0.84, AUC: 0.67) also demonstrated valuable predictive capabilities.SignificanceThis study's findings are crucial for efficiently allocating healthcare resources during pandemics like COVID-19. By harnessing ML techniques and EHR data, we can create predictive tools to identify patients at greater risk of severe symptoms based on their medical histories. The models developed here serve as a foundation for expanding the toolkit available to healthcare professionals and organizations. Additionally, explainable ML methods, such as Shapley Additive Explanations, aid in uncovering underlying data features that inform healthcare decision-making processes.

Vaccination is considered the most effective way to reduce the impact of coronavirus disease 2019 (COVID-19). Several new vaccines have been manufactured. This study aimed to assess the current status and prospects of COVID-19 vaccine research using a bibliometric analysis. We analyzed 3,954 scientific articles on COVID-19 vaccines in the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were used for bibliometric visualization. Original articles and reviews were used for the analysis. A total of 2,783 (70.38%) studies were published in 2021. The USA contributed the highest, publishing 1,390 articles with 41,788 citations, followed by China and the UK. The USA’s primary collaborators were the UK (n = 133), China (n = 87), and Canada (n = 65). The most active institutions were the University of Oxford and Harvard Medical School, while Emory University was the most influential. The Vaccines journal had the most number of publications (402). The most cited journal was the New England Journal of Medicine. In 2021, the focus was on RNA vaccines, attitudes toward vaccination, and hesitancy. In contrast, studies in 2022 focused on vaccine double-blind trials, viral mutations, and antibodies. In the context of rapid virus transmission, vaccine studies on immunogenicity, spike proteins, efficacy, safety, and antibody response have been prioritized. Additional phased clinical trials are needed to determine the effectiveness, acceptance, and side effects of vaccines against mutated strains of the virus.

This study investigated the effects of replacing commercial feeds with fresh black soldier fly larvae (BSFL) on the immune enzyme activities, water quality in the culturing environment, and intestinal microbiota of Pacific white shrimp (Litopenaeus vannamei). Five different feeding regimes were designed, in which 0% (control group), 25%, 50%, 75%, and 100% commercial feeds were replaced with equal wet weight of fresh BSFL, respectively. The experiment lasted for 45 days, and the results showed that the serum T-NOS (total nitric oxide synthase), AKP (alkaline phosphatase), and ACP (acid phosphatase) activity were significantly increased in the BSFL25% group. However, the immune enzymes of the hepatopancreas decreased significantly in all the BSFL-containing groups compared to the control group. Total ammonia nitrogen concentrations throughout the experimental phase and nitrate concentrations in the middle and later phases of the experiment were negatively correlated with the replacement rate of fresh BSFL in the diet, whereas pH was positively correlated with the replacement rate of fresh BSFL in the diet. Proteobacteria and Bacteroidetes were dominant phyla in the intestines of shrimps, but the relative abundances of Proteobacteria and Firmicutes decreased, with those of Bacteroidetes and Planctomycetes increased in the BSFL-containing groups. Among them, higher relative abundances of potential probiotics such as Motilimonas, Shimia, Pseudoalteromonas, and Shewanella and lower relative abundance of genus Vibrio were observed in the fresh BSFL-containing groups. Furthermore, shrimps fed with BSFL-containing diets had higher bacterial richness and diversity in the intestines. In conclusion, a proper replacement of commercial feed with fresh BSFL had a positive effects on the immune-related enzyme activities, water quality, and intestinal health in the L. vannamei.

With the rapid development of fingerprint recognition systems, fingerprint liveness detection is gradually becoming regarded as the main countermeasure to protect the fingerprint identification system from spoofing attacks. Convolutional neural networks have shown great potential in fingerprint liveness detection. However, the generalization ability of the deep network model for unknown materials, and the computational complexity of the network, need to be further improved. A new lightweight fingerprint liveness detection network is here proposed to distinguish fake fingerprints from real ones. The method includes mainly foreground extraction, fingerprint image blocking, style transfer based on CycleGan and an improved ResNet with multi-head self-attention mechanism. The proposed method can effectively extract ROI and obtain the end-to-end data structure, which increases the amount of data. For false fingerprints generated from unknown materials, the use of CycleGan network improves the model generalization ability. The introduction of Transformer with MHSA in the improved ResNet improves detection performance and reduces computing overhead. Experiments on the LivDet2011, LivDet2013 and LivDet2015 datasets showed that the proposed method achieves good results. For example, on the LivDet2015 dataset, our methods achieved an average classification error of 1.72 across all sensors, while significantly reducing network parameters, and the overall parameter number was only 0.83 M. At the same time, the experiment on small-area fingerprints yielded an accuracy of 95.27%.

The Forkhead Box O (FOXO) gene plays a key role in various biological processes, such as growth, metabolism, development, immunity and longevity. Molting is an essential process for crustacean growth, which is mainly regulated by 20-hydroxyecdysone (20E) and molt-inhibiting hormone (MIH). Although the role of FOXO in regulating the immune response of crustaceans is well documented, its involvement in controlling crustacean molting remains unclear. In this study, a FOXO-like gene (designed as EsFOXO-like) was identified in Eriocheir sinensis, and the regulation of the 20E pathway by EsFOXO-like was also investigated. The coding sequence of EsFOXO-like was 852 bp, which consisted of 283 amino acids including a conserved Forkhead (FH) domain. EsFOXO-like shared high similarity with FOXO genes from other crustaceans, and the mRNA expression levels of the EsFOXO-like gene were highest in the hepatopancreas and lowest in the hemocytes. However, transcription and protein expression of the EsFOXO-like gene were found to be up-regulated only during the pre-molt stage in the hepatopancreas, with lower expression levels observed at the post-molt stage. To explore the role of EsFOXO-like in the 20E pathway, EsFOXO-like was firstly inhibited by a specific FOXO inhibitor (AS1842856) and then through an EsFOXO-like dsRNA injection, respectively, and the results showed that the relative expression levels of EsFOXO-like were notably decreased in the hepatopancreas after both the inhibitor and dsRNA treatments. The 20E concentration, the mRNA expression levels of the 20E receptors including the ecdysone receptor (EcR) and the retinoid-X receptor (RXR) and EsmTOR transcription in the AS1842856 group or the EsFOXO-RNAi group were all significantly higher than that in the control group, while the mRNA expression level of EsMIH was significantly decreased after EsFOXO-like inhibition. To further investigate whether the EsFOXO-like acts through mTOR or not, Rapamycin was administered to inhibit mTOR activity in EsFOXO-like inhibited crabs. The results revealed a significant reduction in the concentration of 20E and the expression level of EsMIH in the AS1842856 + Rapamycin group compared to the AS1842856 + DMSO group, accompanied by an increase in EsEcR and EsRXR expression. These findings collectively suggest that EsFOXO-like regulates the 20E pathway through mTOR, which offered valuable insights into the understanding of the molting process in crustaceans.

Inflammatory bowel disease (IBD) has been reported to be associated with NLRP3 inflammasome activation. Therefore inhibiting inflammasome activation could be a new approach to treat IBD. Inflammasome inhibitors NLRP3-IN-2, JC124, and 3,4-methylenedioxy-β-nitrostyrene (MNS) were previously reported to exert anti-inflammatory effects in various disease models but not in the dextran sulfate sodium (DSS)–induced colitis model. Here, we showed that MNS was more efficient in inhibiting the secretion of interleukin-1β (IL-1β) by blocking oligomerization of apoptosis-associated speck-like protein (ASC) than NLRP3-IN-2 and JC124. To investigate the protective effects of MNS on enteritis, we administered intragastric MNS to DSS-induced colitis mice. The results demonstrated that MNS attenuated DSS-induced body weight loss, colon length shortening, and pathological damage. In addition, MNS inhibited the infiltration of macrophages and inflammatory cells and reduced IL-1β and IL-12p40 pro-inflammatory cytokines but had no significant effect on tumor necrosis factor α (TNF-α) and IL-6. Furthermore, we also found that the differentiation of IL-17A+interferon-γ (IFN-γ)+CD4+ T cell was decreased in the colon after MNS treatment, which might be mediated by IL-1β, etc. cytokine release. Taken together, MNS alleviated DSS-induced intestinal inflammation by inhibiting NLRP3 inflammasome activation, which may function as an effective therapeutic for IBD.

Abstract Background At present, coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, is spreading all over the world, with disastrous consequences for people of all countries. The traditional Chinese medicine prescription Dayuanyin (DYY), a classic prescription for the treatment of plague, has shown significant effects in the treatment of COVID-19. However, its specific mechanism of action has not yet been clarified. This study aims to explore the mechanism of action of DYY in the treatment of COVID-19 with the hope of providing a theoretical basis for its clinical application. Methods First, the TCMSP database was searched to screen the active ingredients and corresponding target genes of the DYY prescription and to further identify the core compounds in the active ingredient. Simultaneously, the Genecards database was searched to identify targets related to COVID-19. Then, the STRING database was applied to analyse protein–protein interaction, and Cytoscape software was used to draw a network diagram. The R language and DAVID database were used to analyse GO biological processes and KEGG pathway enrichment. Second, AutoDock Vina and other software were used for molecular docking of core targets and core compounds. Finally, before and after application of DYY, the core target gene IL6 of COVID-19 patients was detected by ELISA to validate the clinical effects. Results First, 174 compounds, 7053 target genes of DYY and 251 genes related to COVID-19 were selected, among which there were 45 target genes of DYY associated with treatment of COVID-19. This study demonstrated that the use of DYY in the treatment of COVID-19 involved a variety of biological processes, and DYY acted on key targets such as IL6, ILIB, and CCL2 through signaling pathways such as the IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and cytokine–cytokine receptor interaction. DYY might play a vital role in treating COVID-19 by suppressing the inflammatory storm and regulating immune function. Second, the molecular docking results showed that there was a certain affinity between the core compounds (kaempferol, quercetin, 7-Methoxy-2-methyl isoflavone, naringenin, formononetin) and core target genes (IL6, IL1B, CCL2). Finally, clinical studies showed that the level of IL6 was elevated in COVID-19 patients, and DYY can reduce its levels. Conclusions DYY may treat COVID-19 through multiple targets, multiple channels, and multiple pathways and is worthy of clinical application and promotion.

ObjectiveIn order to better understand the relative surgical process, this work used a model-based computational analysis on the effectiveness of enhanced recovery after surgery (ERAS) in the operating room with nursing.MethodsA total of 360 surgical patients in the First Affiliated Hospital, Sun Yat-sen University, from the period June 2020 to March 2021, were randomly divided into two groups, namely, observation group and control group, with 180 cases in each group. Routine nursing was used in the control group, while ERAS was implemented in the observation group from the point of view of four aspects, namely, preoperative visit, intraoperative cooperation, postoperative return visit, and psychological intervention.ResultsPostoperative complications, average hospital stay, nursing satisfaction, and postoperative quality of life in the observation group were significantly better than those in the control group (all p

Background and ObjectivesThe study aims to test the hypotheses that a higher burden of cerebral small vascular disease (CSVD) predicts major adverse cardiac and cerebrovascular events (MACCE) in patients with hypertension (HTN) and that abnormal blood pressure variability (BPV) pattern aggravates total CSVD burden.MethodsWe retrospectively reviewed patients with HTN prospectively selected between February 2015 and February 2019 from three participating centers. Patients were included if they had HTN for over 1 year and had at least one MRI feature of CSVD. Independent predictors were found using multivariate logistic regression.ResultsAmong the 908 patients who finally enrolled in the study, the number of CSVD markers (OR = 1.940; 95% CI = 1.393–2.703; P < 0.001) independently predicted MACCE with acceptable predictive value (C-statistic = 0.730; 95% CI = 0.669–0.791; P < 0.001). An abnormal BPV pattern was identified as an independent risk factor for increased CSVD burden. Among them, reverse-dipper subtype demonstrated the most significant relationship (OR = 1.725; 95% CI = 1.129–2.633; P = 0.012).ConclusionTotal CSVD burden predicts an increased risk of composite MACCE independently. An abnormal BPV pattern is associated with a higher burden of CSVD.

The clinical severity of Staphylococcus aureus (S. aureus) respiratory infection correlates with antibacterial gene signature. S. aureus infection induces the expression of an antibacterial gene, as well as a central stress response gene, thus activating transcription factor 3 (ATF3). ATF3-deficient mice have attenuated protection against lethal S. aureus pneumonia and have a higher bacterial load. We tested the hypothesis that ATF3-related protection is based on the increased function of macrophages. Primary marrow-derived macrophages (BMDM) were used in vitro to determine the mechanism through which ATF3 alters the bacterial-killing ability. The expression of ATF3 correlated with the expression of antibacterial genes. Mechanistic studies showed that ATF3 upregulated antibacterial genes, while ATF3-deficient cells and lung tissues had a reduced level of antibacterial genes, which was accompanied by changes in the antibacterial process. We identified multiple ATF3 regulatory elements in the antibacterial gene promoters by chromatin immunoprecipitation analysis. In addition, Wild type (WT) mice had higher F4/80 macrophage migration in the lungs compared to ATF3-null mice, which may correlate with actin filament severing through ATF3-targeted actin-modifying protein gelsolin (GSN) for the macrophage cellular motility. Furthermore, ATF3 positively regulated inflammatory cytokines IL-6 and IL-12p40 might be able to contribute to the infection resolution. These data demonstrate a mechanism utilized by S. aureus to induce ATF3 to regulate antibacterial genes for antimicrobial processes within the cell, and to specifically regulate the actin cytoskeleton of F4/80 macrophages for their migration.

The miniature serpentine robot can be applied to NOTES (Natural Orifice Transluminal Endoscopic Surgery). In this paper, a bronchoscopy application is addressed. This paper describes the basic mechanical design and control scheme of this miniature serpentine robotic bronchoscopy. In addition, off-line backward path planning and real-time and in situ forward navigation in this miniature serpentine robot are discussed. The proposed backward-path-planning algorithm utilizes the 3D model of a bronchial tree constructed from the synthetization of medical images such as images from CT (Computed Tomography), MRI (Magnetic Resonance Imaging), or X-ray, to define a series of nodes/events backward from the destination, for example, the lesion, to the original starting point, for example, the oral cavity. Accordingly, forward navigation is designed to make sure this series of nodes/events shall be passed/occur from the origin to the destination. This combination of backward-path planning and forward navigation does not require accurate positioning information of the tip of the miniature serpentine robot, which is where the CMOS bronchoscope is located. Collaboratively, a virtual force is introduced to maintain the tip of the miniature serpentine robot at the center of the bronchi. Results show that this method of path planning and navigation of the miniature serpentine robot for bronchoscopy applications works.

Background and aimsAt present, it is difficult and risky to diagnose splenic lesions by conventional needle biopsy using computed tomography (CT) or ultrasound (US). Endoscopic ultrasound (EUS)-guided tissue acquisition is increasingly being used as a new technique to determine the tissue diagnosis of splenic lesions. Therefore, our goal was to determine the efficacy and safety of EUS-guided tissue acquisition for splenic lesions.MethodsWe performed a systematic review and meta-analysis to evaluate the pooled sensitivity and specificity of EUS-guided tissue acquisition for the diagnosis of splenic lesions using Metadisc. The Quality Assessment of Diagnostic Accuracy Studies Questionnaire, a quality assessment tool, was used to scrutinize the quality of the studies.ResultsSix eligible studies between January 2000 and June 2022 were identified, and a total number of 62 patients (aged range from 19 to 84) were enrolled. One patient was excluded because of insufficient specimens. The pooled sensitivity and specificity of included studies were 0.85 [95% confidence interval (CI), 0.73-0.93] and 0.77 (95% CI, 0.46-0.95), respectively. The pooled positive likelihood ratio (LR) was 2.38 (95% CI, 1.24-4.57), the pooled negative LR was 0.31 (95% CI, 0.17-0.55), the pooled diagnostic odds ratio (DOR) was 8.67 (95% CI, 2.80-26.82), the area under the summary receiver operating characteristic (SROC) curve was 0.8100 (Standard Error 0.0813).ConclusionEUS-guided tissue acquisition is a safe technique with high sensitivity in the diagnosis of splenic lesions. However, because of the small sample sizes, more studies with more cases are needed to further validate these results.

Numerous studies have been conducted to demonstrate that miRNA is strongly related to colon cancer progression. Nevertheless, there are few studies regarding the function for miR-1266-3p in colon cancer, and the molecular mechanism remains poorly know. Our study was designed to examine the level of miR-1266-3p expression among the colon cancer tissue and cell and to study the role and regulatory mechanism for miR-1266-3p among colon cancer’s malignant biologic behavior. First, we found that miR-1266-3p expression was distinctly lower in colonic carcinoma tissues and cells than in nontumor ones, and the prognosis of low miR-1266-3p patients was distinctly worse than that of high miR-1266-3p patients. Second, we predicted that the target gene of miR-1266-3p was prolyl 4-hydroxylase subunit alpha 3 (P4HA3) through bioinformatics, and the targeting relationship between the two was verified by a dual luciferase assay report. Furthermore, miR-1266-3p inhibited the growth and metastasis of colon cancer in vitro as well as in vivo, and this effect could be alleviated by overexpressing P4HA3. Even more importantly, our study demonstrated that miR-1266-3p inhibited epithelial-mesenchymal transition (EMT) by targeting P4HA3. In conclusion, miR-1266-3p could inhibit growth, metastasis, and EMT in colon cancer by targeting P4HA3. Our discoveries might offer a novel target for colon cancer diagnosis and treatment.

Background and Aims. The adequate myotomy length during peroral endoscopic myotomy (POEM) is still controversial. We performed this systematic review and meta-analysis to determine the efficacy and safety of the modified POEM with shorter myotomy (SM) and compare the outcomes between SM and longer myotomy (LM) in achalasia patients. Methods. A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception to May 28, 2021. The primary outcome was clinical success rate and incidence of reflux-relative adverse events (AEs). Fixed- or random-effect models were adopted for the analysis according to the heterogeneity. Results. Five studies involving 225 patients in SM group and 222 patients in LM group were included. The overall clinical success of SM was 96.6% (95% confidence interval (CI) 92.7 to 98.4%). SM showed noninferior response as compared to LM (risk ratio (RR) 1.02, 95% CI 0.98 to 1.06, P=0.41, I2=0%). Based on the abnormal acid reflux by pH monitoring, its incidence was significantly lower in the SM group than that in the LM group (RR 0.58, 95% CI 0.36 to 0.94, P=0.03, I2=0%). With respect to procedure-related parameters, the total procedure time of SM was significantly shorter than that of LM (mean difference (MD) -16.30, 95% CI -23.10 to -9.49, P

Objective To study the sedative efficacy and safety of nitrous oxide (N2O ) inhalation combined with oral midazolam in children with impacted supernumerary teeth for extraction under sedation and to provide a reference for the selection of anesthetic methods for children undergoing impacted teeth extraction. Methods Sixty patients aged 5 ⁃ 10 years with maxillary impacted supernumerary teeth were randomly divided into three groups, with 20 in each group, as follows: the N2O group: N2O inhalation sedation before the operation; the midazolam group: oral midazolam se⁃ dation before the operation; the combination group: N2O inhalation combined with oral midazolam sedation before the operation. Sedation was performed before extraction under local anesthesia. The Ramsay sedation effect, Houpt behavior⁃ al score and incidence of adverse reactions were evaluated after the operation. Results The Ramsay sedation scale score was significantly higher in the combination group (2.75 ± 0.55) than in the N2O group (2.30 ± 0.47) and the mid⁃ azolam group (2.40 ± 0.50) (P < 0.05). Similarly, the Houpt behavioral rating scale score was significantly higher in the combination group (5.25 ± 0.64) than in the N2O group (4.70 ± 0.73) and the midazolam group (4.80 ± 0.69) (P < 0.05). The adverse reaction rate was lower in the combination group (5%) than in the N2O group (10%) and the midazolam group (10% ), but the difference was not significant (χ2＝0.436, P＝0.804). Conclusion N2O inhalation combined with oral midazolam sedation in the extraction of impacted supernumerary teeth in children can significantly improve the sedative and therapeutic efficacy and is a safe and effective sedation method.

Background: The efficacy and safety of peroral endoscopic myotomy (POEM) in the treatment of sigmoid-type achalasia is unknown. This meta-analysis aims to explore the clinical outcomes of POEM for sigmoid-type achalasia.Method: We searched all relevant studies published up to September 2020 in PubMed, Embase, and Cochrane library databases. Meta-analyses for clinical success, Eckardt score, angle of esophageal tortuosity, diameter of esophagus, lower esophageal sphincter (LES) pressure, integrated relaxation pressure (IRP), adverse events, and gastroesophageal reflux diseases were performed based on random or fixed-effects models as needed.Results: We found a total of eight studies that provided data on 248 patients. Overall, the pooled clinical success was achieved in 211 sigmoid-type achalasia patients [90.4%; 95% confidence interval (CI), 85.5%−93.8%]. The pre- and post-POEM Eckardt scores, angle of esophageal tortuosity, diameter of esophageal, LES pressure, and IRP were significantly improved (All p < 0.05). The pooled adverse events rate was 13.0% (95% CI, 3.6%−37.4%). The pooled objective confirmation of reflux rate was 41.5% (95% CI, 26.5%−58.3%), and symptomatic reflux rate was 12.5% (95% CI, 8.3%−18.4%).Conclusions: Our current evidence indicated that POEM is an effective and safe therapeutic modality for the treatment of sigmoid-type achalasia.

Laser shock peening (LSP) induces an irregular topography on the treated metal surface, thereby reducing the gain effect of the metal fatigue property caused by compressive residual stress. A technique named laser shock imprinting (LSI) is proposed in this paper to guide plastic deformation on a titanium surface. An FEM simulation and experiment were conducted to explore the embossment forming process and residual stress distribution of TA2 pure titanium. The simulated results show that the embossment on the sample surface went through five stages, namely, static, growth, rebound, fluctuation and stabilization, under a single LSI. With an increase in loading pressure, the contact pressure between the sample and contact foil increased along with increasing embossment height. Sufficient loading pressure could induce a difference in residual stress between the zones with and without embossment. The experimental results show that the height and clarity of embossment increased with increasing laser energy, a result similar to that of the simulation. In addition, compared with LSP, the sample treated by LSI had a lower surface roughness and flatter surface profile.

Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression in vitro. Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.

Biological particles in the Earth’s atmosphere are a distinctive category of ice nucleating particles (INPs) due to their capability of facilitating ice crystal formation in clouds at relatively warm temperatures. Field observations and model simulations have shown that biological INPs affect cloud and precipitation formation and regulate regional or even global climate, although there are considerable uncertainties in modeling and large gaps between observed and model simulated contribution of biological particles to atmospheric INPs. This paper overviews the latest researches about biological INPs in the atmosphere. Firstly, we describe the primary ice nucleation mechanisms, and measurements and model simulations of atmospheric biological INPs. Secondly, we summarize the ice nucleating properties of biological INPs from diverse sources such as soils or dust, vegetation (e.g., leaves and pollen grains), sea spray, and fresh waters, and controlling factors of biological INPs in the atmosphere. Then we review the abundance and distribution of atmospheric biological INPs in diverse ecosystems. Finally, we discuss the open questions in further studies on atmospheric biological INPs, including the requirements for developing novel detection techniques and simulation models, as well as the comprehensive investigation of characteristics and influencing factors of atmospheric biological INPs.

In this study, we performed a retrospective and prospective study of preoperative predictors of the length of stay (LOS) in three groups of surgical patients and conducted a clinical retrospective study of the current research status of preoperative predictors of LOS prolongation in three groups of patients under ERAS (enhanced recovery after surgery) mode, such as patient characteristics and comorbidities. Information such as patients’ exercise preferences, exercise time, frequency and duration, footwear, location of knee osteoarthritis, whether there is a past history of knee injury, and smoking and drinking history was collected, and the research data of 312 patients undergoing the three operations were analyzed by SPSS. Meniscal injury-knee arthroscopy sample included a total of 104 people. Surgical sample for anterior cruciate ligament reconstruction included a total of 100 subjects. Knee osteoarthritis-knee replacement surgery sample included 148 people who were divided into two groups in a ratio of 1 : 1: one group used Mailuo Shutong pills during hospitalization (intervention group) and the other group did not (control group). The research conclusions are as follows. Meniscal Knee Arthroscopy. (1) Samples from different causes of injury showed significant differences for all injured sites. (2) Samples with different smoking and drinking histories all showed significant differences for the causes of injury. (3) Exercise hobby, exercise frequency, duration of each exercise and duration of exercise, and warm-up time before exercise all showed positive correlation. Anterior Cruciate Ligament Reconstruction Surgery. (4) Samples from different causes of injury showed significant differences for all the injured sites. (5) Age has a significant negative influence on the wearing of shoes at ordinary times. (6) Exercise hobby: the warm-up time before exercise had a significant negative influence on the injured area. (7) Two groups of analysis items of exercise frequency, exercise duration and exercise duration, preexercise warm-up time, and exercise hobby were typically positively correlated. Total Knee Arthroplasty. (8) There was a significant difference of 0.01 between the hospitalization days of the intervention group and the control group (p