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Objective: To investigate the prevalence and reopen the drive procedure of early complications of electrode dislodgement in patients with an indication for permanent pacemaker implantation at the Vietnam National Heart Institute. Methods: This is a study on patients who received permanent pacemaker implantation at the Vietnam National Heart Institute during the period from August 1, 2019 to March 30, 2020. Results: In all cases with complications of electrode dislodgement after implantation indicated to reopen the machine to handle complications, the results of handling complications are safe and stable. Conclusion: There is a positive relationship between the events of electrode dislodgement on the pacemaker and the degree of tricuspid valve regurgitation with a statistically significant difference (P < 0.01, OR = 8.2; 95% CI: 1.6–42.9).

Yingli Liu,1 Dan Si,2 Pingping Bai,3 Li Zhu,4 Lili Zhang,1 Qi Chen,5 Yong Qi6 1Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan, 451464, People’s Republic of China; 3Department of Health Management, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450003, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Yong Qi, Department of Pulmonary and Critical Care Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan University People’s Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, People’s Republic of China, Tel +8615890110258, Email qiyong@zzu.edu.cnBackground: Although the potential of coronavirus disease 2019 (COVID-19) patients to develop pulmonary embolism (PE) is widely recognized, the underlying mechanism has not been completely elucidated. This study aimed to identify genes common to COVID-19 and PE to reveal the underlying pathogenesis of susceptibility to PE in COVID-19 patients.Methods: COVID-19 genes were obtained from the GEO database and the OMIM, CTD, GeneCards, and DisGeNET databases; PE genes were obtained from the OMIM, CTD, GeneCards, and DisGeNET databases. We overlapped the genes of COVID-19 and PE to obtain common genes for additional analysis, including functional enrichment, protein–protein interaction, and immune infiltration analysis. Hub genes were identified using cytoHubba, a plugin of Cytoscape, and validated using the independent datasets GSE167000 and GSE13535. The genes validated by the above datasets were further validated in clinical samples.Results: We obtained 36 genes shared by PE and COVID-19. Functional enrichment and immune infiltration analyses revealed the involvement of cytokines and immune activation. Five genes (CCL2, CXCL10, ALB, EGF, and MKI67) were identified as hub genes common to COVID-19 and PE. CXCL10 was validated in both independent datasets (GSE167000 and GSE13535). Serum levels of CXCL10 in the COVID-19 group and the COVID-19 combined with PE group were significantly higher than those in the healthy control group (P< 0.001). In addition, there were significant differences between the COVID-19 group and the COVID-19 combined with PE group (P< 0.01).Conclusion: Our study reveals common genes shared by PE and COVID-19 and identifies CXCL10 as a possible cause of susceptibility to PE in COVID-19 patients.Graphical Abstract: Keywords: pulmonary embolism, coronavirus disease 2019, bioinformatics, CXCL10

Qian Zhang,1 Zhongfan Zhang,1 Lina Jin,2 Chengbing Wang,3 Haikuo Zheng,1 Shouping Li,1 Miao Yu,1 Daoyuan Si,1 Wenqi Zhang1 1Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin Provincial Molecular Biology Research Center for Precision Medicine of Major Cardiovascular Disease, Changchun, People’s Republic of China; 2Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Daoyuan Si;Wenqi ZhangDepartment of Cardiology, China-Japan Union Hospital of Jilin University, Xiantai Street No. 126, Changchun, Jilin, People’s Republic of ChinaTel +86 135 78949866; +86 136 44407485Fax +86 431 84995233; +86 431 84995259Email sidaoyuan@jlu.edu.cn; wenqi@jlu.edu.cnObjective: In the current era of primary percutaneous coronary intervention (PPCI), the prognosis of the left ventricular thrombus (LVT) is not well assessed.Methods: We performed a retrospective, single-center study of 1305 consecutive ST-segment-elevation myocardial infarction (STEMI) patients treated with PPCI. During a mean period of 27 months of follow-up, the major adverse cardiovascular and cerebrovascular events (MACCE) were recorded.Results: The incidence of LVT (n = 47) was 3.60%. The independent risk factors of LVT included anterior STEMI, left ventricular (LV) aneurysm, reduced LV ejection fraction (LVEF), dilated LV end-diastolic dimension (LVEDD), and delayed door-to-balloon time (DTBT). During follow-up, LVT was an independent risk factor for MACCE [hazard ratio (HR)=3.46; 95% confidence interval (CI) = 2.23– 3.38; P < 0.01]. Patients with LVT were more likely to have the following complications: heart failure (P < 0.001), embolic events (P = 0.034), and all-cause mortality (P = 0.020). Notably, the regression of LVT was not independently associated with those three adverse events (P > 0.05).Conclusion: In the era of PPCI, the presence of early LVT following STEMI was associated with adverse events. Furthermore, the prognosis of patients with LVT did not improve even if the LVT regressed. LVT was likely a generalized indicator of impaired cardiac performance, rather than the cause. This indicated that prophylactic therapy and identifying individuals with a high risk of developing LVT were of substantial importance.Keywords: left ventricular thrombus, ST-segment elevation myocardial infarction, prognosis, risk factors

Di Si,1 Guochao Nie,2– 4 Tamiika K Hurst,1 Carol A Fierke,1 Raoul Kopelman1 1Department of Chemistry, University of Michigan, Ann Arbor, MI, USA; 2School of Physics and Telecommunication Engineering, Yulin Normal University, Yulin, People’s Republic of China; 3China-Ukraine Joint Research Center for Nano Carbon Black, Yulin, People’s Republic of China; 4Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin, People’s Republic of ChinaCorrespondence: Guochao NieSchool of Physics and Telecommunication Engineering, Yulin Normal University, Yulin, People’s Republic of ChinaEmail bccu518@ylu.edu.cnRaoul KopelmanDepartment of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, MI, USAEmail kopelman@umich.eduBackground: Due to its excellent biocompatibility, the polyacrylamide (PAAm) hydrogel has shown great potential for the immobilization of enzymes used in biomedical applications. The major challenge involved is to preserve, during the immobilization process, both the biological activity and the structural integrity of the enzymes. Here we report, for the first time, a proof-of-concept study for embedding active carbonic anhydrase (CA) into polyacrylamide (PAAm) nanogels. By immobilizing CA in these nanogels, we hope to provide important advantages, such as matrix protection of the CA as well as its targeted delivery, and also for potentially using these nanogels as zinc nano-biosensors, both in-vitro and in-vivo.Methods and Results: Two methods are reported here for CA immobilization: encapsulation and surface conjugation. In the encapsulation method, the common process was improved, so as to best preserve the CA, by 1) using a novel biofriendly nonionic surfactant system (Span 80/Tween 80/Brij 30) and 2) using an Al2O3 adsorptive filtration purification procedure. In the surface conjugation method, blank PAAm nanogels were activated by N-hydroxysuccinimide and the CA was cross-linked to the nanogels. The amount of active CA immobilized in the nanoparticles was quantified for both methods. Per 1 g nanogels, the CA encapsulated nanogels contain 11.3 mg active CA, while the CA conjugated nanogels contain 22.5 mg active CA. Also, the CA conjugated nanoparticles successfully measured free Zn2+ levels in solution, with the Zn2+ dissociation constant determined to be 9 pM.Conclusion: This work demonstrates universal methods for immobilizing highly fragile bio-macromolecules inside nanoparticle carriers, while preserving their structural integrity and biological activity. The advantages and limitations are discussed, as well as the potential biomedical applications.Keywords: PAAm hydrogel, nanogels, nanoparticles, carbonic anhydrase, encapsulation, conjugation, Zn2+

Daolin Si,1 Fei Yin,1 Jing Peng,1 Guangying Zhang2 1Department of Pediatric Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, People’s Republic of China; 2Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, People’s Republic of ChinaCorrespondence: Guangying ZhangDepartment of Oncology, Xiangya Hospital, Central South University, 87 Xiangya Road, Kaifu District, Changsha, Hunan Province 410008, People’s Republic of ChinaTel +86-731- 89753043Fax +86-731- 89753332Email 437783777@qq.comPurpose: Glioblastoma multiforme (GBM) is the most common of the malignant and invasive gliomas. High grade glioma is prone to relapse and has a poor prognosis. However, there is a big difference in terms of survival time with the same grade glioma. Cluster of differentiation 44 (CD44) is an indicator of cancer stem cells with abnormal expression in many malignant tumors, however the expression in GBM is unknown.Methods: Tissue specimens were collected from 62 GBM patients to investigate CD44 expression and their prognosis was followed-up. Chi-square test was used to identify the association between CD44 staining and clinical characteristics of the patients. Kaplan-Meier analysis was performed to draw survival curves and Cox regression analysis to confirm the independent prognostic factors of GBM patients.Results: In total, 38.7% (24/62) of the patients had high CD44 staining. The median survival times were 3.5 months and 18.5 months for high and low expressions of CD44, respectively. Kaplan-Meier analysis revealed that tumor location, the extent of tumor resection, adjuvant chemotherapy, and CD44 expression were related to overall survival time of GBM patients (P

Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c, il-8, tir4 and inf-γ, but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC.

The extracellular matrix (ECM) and cells are crucial components of natural tissue microenvironments, and they both demonstrate dynamic mechanical properties, particularly viscoelastic behaviors, when exposed to external stress or strain over time. The capacity to modify the mechanical properties of cells and ECM is crucial for gaining insight into the development, physiology, and pathophysiology of living organisms. As an illustration, researchers have developed hydrogels with diverse compositions to mimic the properties of the native ECM and use them as substrates for cell culture. The behavior of cultured cells can be regulated by modifying the viscoelasticity of hydrogels. Moreover, there is widespread interest across disciplines in accurately measuring the mechanical properties of cells and the surrounding ECM, as well as exploring the interactive relationship between these components. Nevertheless, the lack of standardized experimental methods, conditions, and other variables has hindered systematic comparisons and summaries of research findings on ECM and cell viscoelasticity. In this review, we delve into the origins of ECM and cell viscoelasticity, examine recently developed methods for measuring ECM and cell viscoelasticity, and summarize the potential interactions between cell and ECM viscoelasticity. Recent research has shown that both ECM and cell viscoelasticity experience alterations during in vivo pathogenesis, indicating the potential use of tailored viscoelastic ECM and cells in regenerative medicine.

Introduction: The permanent pacemaker implantation has a history of more than 60 years with improved mortality and quality of life but also recorded many complications. Objectives: The objective is to evaluate the rate of early complications at the National Heart Institute of Vietnam and the factors associated with the early complication of the permanent pacemaker implantation procedure. Methods: A cross-sectional descriptive is about 294 patients who received permanent pacemaker implantation at the National Heart Institute of Vietnam from 01/08/2020 to 30/30/2020. Results: The rate of complications is statistically higher in the diabetic group (OR = 2.5; 95% CI: 1.1–5.6), chronic kidney failure (OR = 2.7; 95% CI: 1.1–6.6), preheart surgery (OR = 3.8; 95% CI: 1.3–11.8), taking oral anticoagulants (OR = 4.3; 95% CI: 1.9–9.9), dual antiplatelets (OR = 2.95; 95% CI: 1.1–8.1), continuation to maintain anticoagulants, or dual antiplatelets (OR = 2.7; 95% CI: 1.2–6.4). Conclusion: Early onset of complications (onset of early complications) has been associated with some factors such as diabetes disease, chronic kidney failure, preheart surgery, oral anticoagulants, dual antiplatelets, continuation to maintain anticoagulation, and antiplatelets with statistical significance.

The available information regarding the impact of antimony (Sb), a novel environmental pollutant, on the intestinal microbiota and host health is limited. In this study, we conducted physiological characterizations to investigate the response of adult zebrafish to different environmental concentrations (0, 30, 300, and 3000 µg/L) of Sb over a period of 14 days. Biochemical and pathological changes demonstrated that Sb effectively compromised the integrity of the intestinal physical barrier and induced inflammatory responses as well as oxidative stress. Analysis of both intestinal microbial community and metabolome revealed that exposure to 0 and 30 µg/L of Sb resulted in similar microbiota structures; however, exposure to 300 µg/L altered microbial communities’ composition (e.g., a decline in genus Cetobacterium and an increase in Vibrio). Furthermore, exposure to 300 µg/L significantly decreased levels of bile acids and glycerophospholipids while triggering intestinal inflammation but activating self-protective mechanisms such as antibiotic presence. Notably, even exposure to 30 µg/L of Sb can trigger dysbiosis of intestinal microbiota and metabolites, potentially impacting fish health through the ''microbiota-intestine-brain axis'' and contributing to disease initiation. This study provides valuable insights into toxicity-related information concerning environmental impacts of Sb on aquatic organisms with significant implications for developing management strategies.

Abstract Background and aims To study the role of gene mutations in the development of severe hypertriglyceridemia (HTG) in patients with hyperlipidemic acute pancreatitis (HLAP), especially different apolipoprotein A5 (APOA5) mutations. Methods Whole-exome sequencing was performed on 163 patients with HLAP and 30 patients with biliary acute pancreatitis (BAP). The pathogenicity of mutations was then assessed by combining clinical information, predictions of bioinformatics programs, information from multiple gene databases, and residue location and conservation. The pathogenic mutations of APOA5 were visualized using the software. Results 1. Compared with BAP patients, pathogenic mutations of APOA5 were frequent in HLAP patients; among them, the heterozygous mutation of p.G185C was the most common. 2. All six pathogenic mutations of APOA5 identified in this study (p.S35N, p.D167V, p.G185C, p.K188I, p.R223C, and p.H182fs) were positively correlated with severe HTG; they were all in the important domains of apolipoprotein A-V (apoA-V). Residue 223 is strictly conserved in multiple mammals and is located in the lipoprotein lipase (LPL)-binding domain (Pro215–Phe261). When Arg 223 is mutated to Cys 223, the positive charge of this residue is reduced, which is potentially destructive to the binding function of apoA-V to LPL. 3. Four new APOA5 mutations were identified, namely c.563A > T, c.667C > T, c.788G > A, and c.544_545 insGGTGC. Conclusions The pathogenic mutations of APOA5 were specific to the patients with HLAP and severe HTG in China, and identifying such mutations had clinical significance in elucidating the etiology and subsequent treatment. Graphical Abstract

In daily practice, there are several instances of diverse object handover between humans. For example, in an automobile production line, workers need to pick up parts and deliver them to colleagues or acquire parts from them and put the parts in the appropriate position. Similarly, in households, children assist bedridden elderly people by passing them a cup of water, and in medical surgeries, assistants take over surgical tools used by doctors. These tasks require a considerable amount of time and manpower. In these scenarios, it is necessary to deliver the target object efficiently and quickly while prioritizing the safety of the object. Collaborative robots can serve as human colleagues to perform these simple, time-consuming, and laborious tasks. We expect humans and robots to hand over objects seamlessly in a natural and efficient way, just as humans naturally hand over objects to each other. This paper proposes a 6-dimensional (6D) pose recognition-based human–robot collaborative handover system to address the problem of inaccurate object grasping caused by imprecise recognition of object poses during the human–robot collaborative handover process. The main contents are as follows: To solve the 6D pose recognition problem, a residual network (ResNet) is introduced to conduct semantic segmentation and key-point vector field prediction on the image, and the random sample consensus (RANSAC) voting is used to predict key-point coordinates. Further, an improved efficient perspective-n-point (EPnP) algorithm is used to predict the object pose, which can improve the accuracy. An improved dataset production method is proposed by analyzing the advantages and disadvantages of the LineMod dataset and based on the latest 3-dimensional (3D) reconstruction technology. To realize the accurate identification of daily objects, which can reduce the time required for dataset production. The transformation relationship (from the object to the camera and then to the robot base coordinate systems) is obtained through internal parameter calibration and hand–eye calibration methods of the camera. Thus, the pose of the target object in the robot base coordinate system is determined. Further, a grasping method for effective position and orientation calculation is proposed to realize precise object pose localization and accurate grasping. A handover experiment platform was set up to validate the effectiveness of the proposed human–robot collaborative handover system, with four volunteers conducting 80 handover experiments. The results showed that the average deviation distance of the proposed human–robot handover system is 1.97 cm, the average handover success rate is 76%, and the average handover time is 30 s, while the average handover success rate can reach 89% without considering the grasping posture. These results demonstrate that the proposed human–robot collaborative handover system is robust and can be applied to different scenarios and interactive objects with promising application prospects.

Abstract The biosynthesis of neurotoxin aetokthonotoxin (AETX) that features a unique structure of pentabrominated biindole nitrile involves a first-of-its-kind nitrile synthase termed AetD, an enzyme that shares very low sequence identity to known structures and catalyzes an unprecedented mechanism. In this study, we resolve the crystal structure of AetD in complex with the substrate 5,7-di-Br-L-Trp. AetD adopts the heme oxygenase like fold and forms a hydrophobic cavity within a helical bundle to accommodate the indole moiety. A diiron cluster comprising two irons that serves as a catalytic center binds to the carboxyl O and the amino N of the substrate. Notably, we demonstrate that the AetD-catalyzed reaction is independent of the bromination of the substrate and also solved crystal structures of AetD in complex with 5-Br-L-Trp and L-Trp. Altogether, the present study reveals the substrate-binding pattern and validates the diiron cluster-comprising active center of AetD, which should provide important basis to support the mechanistic investigations into this class of nitrile synthase.

Abstract Background cblC defect is the most common type of methylmalonic acidemia in China. Patients with late-onset form (>1 year) are often misdiagnosed due to heterogeneous symptoms. This study aimed to describe clinical characteristics and evaluate long-term outcomes of Chinese patients with late-onset cblC defect. Methods A total of 85 patients with late-onset cblC defect were enrolled. Clinical data, including manifestations, metabolites, molecular diagnosis, treatment and outcome, were summarized and analyzed. Results The age of onset ranged from 2 to 32.8 years old (median age 8.6 years, mean age 9.4 years). The time between first symptoms and diagnosis ranged from a few days to 20 years (median time 2 months, mean time 20.7 months). Neuropsychiatric symptoms were presented as first symptoms in 68.2% of cases, which were observed frequently in schoolchildren or adolescents. Renal involvement and cardiovascular disease were observed in 20% and 8.2% of cases, respectively, which occurred with the highest prevalence in preschool children. Besides the initial symptoms, the disease progressed in most patients and cognitive decline became the most frequent symptom overall. The levels of propionylcarnitine, propionylcarnitine / acetylcarnitine ratio, methylmalonic acid, methylcitric acid and homocysteine, were decreased remarkably after treatment (PA variant was the most frequent mutated allele in this cohort (25%). Except for 16 patients who recovered completely, the remaining patients were still left with varying degrees of sequelae in a long-term follow-up. The available data from 76 cases were analyzed by univariate analysis and multivariate logistic regression analysis, and the results showed that the time from onset to diagnosis (OR = 1.025, P = 0. 024) was independent risk factors for poor outcomes. Conclusions The diagnosis of late-onset cblC defect is often delayed due to poor awareness of its various and nonspecific symptoms, thus having an adverse effect on the prognosis. It should be considered in patients with unexplained neuropsychiatric and other conditions such as renal involvement, cardiovascular diseases or even multiple organ damage. The c.482G>A variant shows the highest frequency in these patients. Prompt treatment appears to be beneficial.

BackgroundThe use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism.MethodsA stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort.ResultsFive factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism.ConclusionThis risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.

IntroductionSulforaphane (SFN) has been found to alleviate complications linked with several diseases by regulating gut microbiota (GM), while the effect of GM on SFN for autism spectrum disorders (ASD) has not been studied. Therefore, this study aimed to investigate the relationship between the effects of SFN on childhood ASD and GM through animal model and human studies.MethodsWe evaluated the therapeutic effects of SFN on maternal immune activation (MIA) induced ASD-like rat model and pediatric autism patients using three-chamber social test and OSU Autism Rating Scale-DSM-IV (OARS-4), respectively, with parallel GM analysis using 16SrRNA sequencing.ResultsSFN significantly improved the sniffing times of ASD-like rats in the three-chamber test. For human participants, the average verbal or non-verbal communication (OSU-CO) scores of SFN group had changed significantly at the 12-wk endpoint. SFN was safe and no serious side effects after taking. GM changes were similar for both ASD-like rats and ASD patients, such as consistent changes in order Bacillales, family Staphylococcaceae and genus Staphylococcus. Although the gut microbiota composition was significantly altered in SFN-treated ASD-like rats, the alteration of GM was not evident in ASD patients after 12 weeks of SFN treatment. However, in the network analysis, we found 25 taxa correlated with rats' social behavior, 8 of which were associated with SFN treatment in ASD-like rats, For ASD patients, we found 35 GM abundance alterations correlated with improvements in ASD symptoms after SFN treatment. Moreover, family Pasteurellaceae and genus Haemophilus were found to be associated with SFN administration in the network analyses in both ASD-like rats and ASD patients.DiscussionThese findings suggest that SFN could provide a novel avenue for preventing and treating ASD, and its therapeutic effects might be related to gut microbiota.

Largemouth bass virus (LMBV) poses a significant threat to largemouth bass farming, leading to substantial economic losses. In December 2022, massive largemouth bass juveniles died at a fish farm in the city of Xinxiang, China. Through a series of experiments, we conclusively identified LMBV as the causative pathogen. The affected fish displayed anorexia, lethargy, and hemorrhage at the pectoral and caudal fin base. No parasites or pathogenic bacteria were detected on the body surface or gills, or isolated from the diseased fish. Severe hemorrhage, lymphocyte infiltration, and extensive necrosis were observed in the liver, spleen, intestine, and stomach of the moribund fish. The tissue homogenate from the diseased fish induced epithelioma papulosum cyprini cells (EPC) cell death, while no such effects were observed in grouper spleen (GS) cells. Sequence similarity analysis of the major capsid protein (MCP) indicated the virus shared 100% similarity with the LMBV-FS2021 strain, placing it within the Ranavirus genus. Transmission electron microscopy (TEM) observations revealed plenty of hexagonal virions accumulated in the cytoplasm of infected EPC cells. Artificial infection demonstrated that LMBV-XX01 was highly fatal to Micropterus salmoides juveniles, with an LD50 of 103.081 TCID50/fish. RT-qPCR detection confirmed that LMBV appeared in all sampled tissues of the challenged largemouth bass, with significantly higher viral loads detected in the liver and heart compared to other tissues. Additionally, we successfully obtained a highly purified recombinant MCP of LMBV and developed two strains of monoclonal antibodies targeting MCP of LMBV-XX01. Overall, our findings provide valuable materials and insights for the design of prevention strategies and the development of detection methods for LMBV.

ABSTRACT Newborn screening (NBS) is a public health service aimed at identifying infants with severe genetic disorders, thus providing effective treatment early enough to prevent or ameliorate the onset of symptoms. Current NBS uses biochemical analysis of dried blood spots, predominately with time‐resolved fluorescence immunoassay and tandem mass spectrometry, which produces some false positives and false negatives. The application of enzymatic activity‐based testing technology provides a reliable screening method for some disorders. Genetic testing is now commonly used for secondary or confirmatory testing after a positive result in some NBS programs. Recently, next‐generation sequencing (NGS) has emerged as a robust tool that enables large panels of genes to be scanned together rapidly. Rapid advances in NGS emphasize the potential for genomic sequencing to improve NBS programs. However, some challenges still remain and require solution before this is applied for population screening.

OBJECTIVE: The aim of this study was to investigate the effects of microRNA-5195-3p (miR-5195-3p) on the proliferation of glioma cells and to explore its related mechanisms. PATIENTS AND METHODS: The expression level of miR-5195-3p in glioma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Online prediction websites (TargetScan and mi-Randa) were used to screen the potential targets of miR-5195-3p. Luciferase reporter gene assay and Western blot were performed to confirm the targets of miR-5195-3p. Furthermore, the effects of miR-5195-3p on cell proliferation were detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), colony formation assay, and flow cytometry, respectively. RESULTS: MiR-5195-3p was lowly expressed in both glioma tissues and cells. Baculoviral IAP repeat-containing 2 (BIRC2) was identified as a direct target of miR-5195-3p. Over-expression of miR-5195-3p in glioma cells significantly decreased the protein expression of BIRC2. Besides, the proliferative capacity and colony formation ability were significantly inhibited after transfection of miR-5195-3p in vitro. In addition, flow cytometry indicated that an evident G1 phase arrest occurred in miR-5195-3p over-expressed group. CONCLUSIONS: In this work, we emphasized the suppressor function of miR-5195-3p in the proliferation of glioma cells. Furthermore, our findings provided an experimental basis for the research and treatment of glioma. [ABSTRACT FROM AUTHOR]