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ObjectiveThis study aimed to explore the impact of the COVID-19 pandemic on non-suicidal self-injury (NSSI) among youth students, and the mediating role of psychological factors in the relationship between the COVID-19 pandemic and NSSI.MethodAn online survey was conducted at junior and senior high schools, as well as universities located in Jingzhou, Hubei Province, China between June 2021 and January 2022. The COVID-19 Impact Index was constructed using multiple correspondence analysis (MCA) method. The bootstrapping method was used for mediation analysis.ResultsA total of 16025 youth participated in the study and 12507 youth (78.1%) finished the questionnaires. The COVID-19 Impact Index had a significantly positive effect on NSSI (r=0.16, p

Abstract In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the “Precision Pro”, “Dynamic Precision”, and “Intelligent Precision”. This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.

The available sea surface temperature (SST) products are too coarse to assess the fine-scale ( lagoon > reef slope/offshore sea. The reef flat was usually approximately 0.05°C–0.2°C hotter than the lagoon in the hot season. The SST in the lagoon also increased from south to north and the shallow lagoon was usually warmer than the deep lagoon in the hot season. Our results suggested that scleractinian corals in the reef flat and the lagoon were more susceptible to bleaching-level thermal stress than other geomorphic zones. During the cool season, the SST fluctuated markedly among coral reefs and geomorphic zones.

ObjectiveInfectious diseases including COVID-19 and mental disorders are two of the most common health conditions associated with stigma. However, the comparative stigma of these two conditions has received less attention in research. This study aimed to compare the prevalence of stigmatizing views toward people with COVID-19 and mental disorders and the factors associated with these views, among a large sample of adolescent and young adult students in China.MethodsA total of 9,749 adolescents and young adults aged 15–24 years completed a survey on stigmatizing attitudes toward COVID-19 and mental disorders, as well as mental health-related factors, including general mental health status and symptoms of depression, anxiety, insomnia, and post-traumatic stress disorder (PTSD). Multivariable linear regression analyses were conducted to identify factors associated with stigmatizing views.FindingsThe prevalence of COVID-19 and mental disorders-related stigma was 17.2% and 40.7%, respectively. COVID-19-related stigma scores were significantly higher among male students (β = 0.025, p < 0.05), those without quarantine experience (β = 0.035, p < 0.001), those with lower educational level (p < 0.001), those with lower family income (p < 0.01), and those with higher PTSD symptoms (β = 0.045, p < 0.05). Mental disorder-related stigma scores were significantly higher among individuals with average and lower-than-average levels of family income (p < 0.01), depression symptoms (β = 0.056, p < 0.001), anxiety symptoms (β = 0.051, p < 0.001), and mental health problems (β = 0.027, p < 0.05).ConclusionThe stigma of mental disorders is higher in the youth population than the stigma of COVID-19. Factors associated with stigmatizing attitudes toward people with COVID-19 and mental disorders varied across the youth. Stigma-reduction interventions among the youth should be targeted specifically to COVID-19 or mental disorders conditions.

Abstract To obtain a comprehensive scenario of T cell profiles and synergistic immune responses, we performed single-cell RNA sequencing (scRNA-seq) on the peripheral T cells of 14 individuals with chronic human immunodeficiency virus 1 (HIV-1) infection, including nine treatment-naive (TP) and eight antiretroviral therapy (ART) participants (of whom three were paired with TP cases), and compared the results with four healthy donors (HD). Through analyzing the transcriptional profiles of CD4+ and CD8+ T cells, coupled with assembled T cell receptor sequences, we observed the significant loss of naive T cells, prolonged inflammation, and increased response to interferon-α in TP individuals, which could be partially restored by ART. Interestingly, we revealed that CD4+ and CD8+ Effector-GNLY clusters were expanded in TP cases, and persistently increased in ART individuals where they were typically correlated with poor immune restoration. This transcriptional dataset enables a deeper understanding of the pathogenesis of HIV-1 infection and is also a rich resource for developing novel immune targeted therapeutic strategies.

BackgroundTumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism.MethodsWe enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database.ResultsAmong the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients.ConclusionsTMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.

Immunophenotyping of patients with COVID-19 is ongoing, but much remains to be learned. Here the authors analyze 41 hospitalized patients with COVID-19 and show a higher degree of lymphopenia in various immune cell subsets as well as cytotoxicity and T cell inhibitory marker expression in severe cases compared with mild.

Chronic HIV-1 infection is associated with persistent inflammation, which contributes to disease progression. Platelet-T cell aggregates play a critical role in maintaining inflammation. However, the phenotypic characteristics and clinical significance of platelet-CD4+ T cell aggregates remain unclear in different HIV-infected populations. In this study, we quantified and characterized platelet-CD4+ T cell aggregates in the peripheral blood of treatment-naïve HIV-1-infected individuals (TNs), immunological responders to antiretroviral therapy (IRs), immunological non-responders to antiretroviral therapy (INRs), and healthy controls (HCs). Flow cytometry analysis and immunofluorescence microscopy showed increased platelet-CD4+ T cell aggregate formation in TNs compared to HCs during HIV-1 infection. However, the frequencies of platelet-CD4+ T cell aggregates decreased in IRs compared to TNs, but not in INRs, which have shown severe immunological dysfunction. Platelet-CD4+ T cell aggregate frequencies were positively correlated with HIV-1 viral load but negatively correlated with CD4+ T cell counts and CD4/CD8 ratios. Furthermore, we observed a higher expression of CD45RO, HIV co-receptors, HIV activation/exhaustion markers in platelet-CD4+ T cell aggregates, which was associated with HIV-1 permissiveness. High levels of caspase-1 and caspase-3, and low levels of Bcl-2 in platelet-CD4+ T cell aggregates imply the potential role in CD4+ T cell loss during HIV-1 infection. Furthermore, platelet-CD4+ T cell aggregates contained more HIV-1 gag viral protein and HIV-1 DNA than their platelet-free CD4+ T cell counterparts. The platelet-CD4+ T cell aggregate levels were positively correlated with plasma sCD163 and sCD14 levels. Our findings demonstrate that platelet-CD4+ T cell aggregate formation has typical characteristics of HIV-1 permissiveness and is related to immune activation during HIV-1 infection.

The gut microbiota plays a key role in host health, and disruptions to gut bacterial homeostasis can cause disease. However, the effect of disease on gut microbiota assembly remains unclear and gut microbiota-based predictions of health status is a promising yet poorly established field. Using Illumina high-throughput sequencing technology, we compared the gut microbiota between healthy (HA and HB) and diarrhoeic (DS) Rana dybowskii groups and analyzed the functional profiles through a phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis. In addition, we estimated the correlation between gut microbiota structures and predicted the functional compositions. The results showed significant differences in the phylogenetic diversity (Pd), Shannon, and observed richness (Sobs) indices between the DS and HB groups, with significant differences observed in the gut microbiota composition between the DS group and the HA and HB groups. Linear discriminant analysis (LDA) effect size (LEfSe) results revealed that Proteobacteria were significantly enriched in the DS group; Bacteroidetes were significantly enriched in the HA and HB groups; and Aeromonas, Citrobacter, Enterococcus, Hafnia-Obesumbacterium, Morganella, Lactococcus, Providencia, Vagococcus, and Staphylococcus were significantly enriched in the DS group. Venn diagrams revealed that there were many more unique genera in the DS group than the HA and HB groups. Among 102 sensitive species selected using the indicator method, 33 indicated a healthy status and 69 (e.g., Acinetobacter, Aeromonas, Legionella, Morganella, Proteus, Providencia, Staphylococcus, and Vagococcus) indicated a diseased status. There was a significant and positive association between the composition and functional composition of the gut microbiota, thus indicating low functional redundancy of the frog gut bacterial community. Rana dybowskii disease was associated with changes in the gut microbiota, which subsequently disrupted bacterial-mediated functions. The results of this study can aid in revealing the effect of the R. dybowskii gut microbiota on host health and provide a basis for elucidating the mechanism of the occurrence of R. dybowskii disease.

We describe the isolation of Bacillus subtilis strain JA and demonstrate that this bacterium exhibited strong algicidal effects on the algae Alexandrium minutum with an inhibition rate exceeding 80 % within 48 h. B. subtilis JA significantly reduced the photosynthetic efficiency of A. minutum and caused extensive morphological damage to the algae. Genomic analysis of B. subtilis JA demonstrated that a putative AI-2 type quorum sensing (QS) gene (LuxS) is present in its genome cluster, which is regulate pheromone biosynthesis. Interestingly, the exogenous addition of a QS-oligopeptide (ComX-pheromone) improved the algicidal efficiency of B. subtilis JA, thus indicating that the algicidal activity of this bacterium is potentially regulated by QS. Collectively, our data describe a potential antialgal bacterium and speculated that its behavior can be modulated by QS signal. B. subtilis JA may therefore represent a valuable tool for the development of novel chemical-ecological methods with which to control harmful algae. Keywords: B. subtilis JA, Quorum sensing, Whole-genome sequencing, Antialgal agent, Harmful algal blooms

Well-controlled development leads to uniform body size and a better growth rate; therefore, the ability to determine the growth rate of frogs and their period of sexual maturity is essential for producing healthy, high-quality descendant frogs. To establish a working model that can best predict the growth performance of frogs, the present study examined the growth of one-year-old and two-year-old brown frogs (Rana dybowskii) from metamorphosis to hibernation (18 weeks) and out-hibernation to hibernation (20 weeks) under the same environmental conditions. Brown frog growth was studied and mathematically modelled using various nonlinear, linear, and polynomial functions. The model input values were statistically evaluated using parameters such as the Akaike’s information criterion. The body weight/size ratio (Kwl) and Fulton’s condition factor (K) were used to compare the weight and size of groups of frogs during the growth period. The results showed that the third- and fourth-order polynomial models provided the most consistent predictions of body weight for age 1 and age 2 brown frogs, respectively. Both the Gompertz and third-order polynomial models yielded similarly adequate results for the body size of age 1 brown frogs, while the Janoschek model produced a similarly adequate result for the body size of age 2 brown frogs. The Brody and Janoschek models yielded the highest and lowest estimates of asymptotic weight, respectively, for the body weights of all frogs. The Kwl value of all frogs increased from 0.40 to 3.18. The K value of age 1 frogs decreased from 23.81 to 9.45 in the first four weeks. The K value of age 2 frogs remained close to 10. Graphically, a sigmoidal trend was observed for body weight and body size with increasing age. The results of this study will be useful not only for amphibian research but also for frog farming management strategies and decisions.

Viruses are key biogeochemical engines in the regulation of the dynamics of phytoplankton. However, there has been little research on viral communities in relation to algal blooms. Using the virMine tool, we analyzed viral information from metagenomic data of field dinoflagellate (Gymnodinium catenatum) blooms at different stages. Species identification indicated that phages were the main species. Unifrac analysis showed clear temporal patterns in virioplankton dynamics. The viral community was dominated by Siphoviridae, Podoviridae, and Myoviridae throughout the whole bloom cycle. However, some changes were observed at different phases of the bloom; the relatively abundant Siphoviridae and Myoviridae dominated at pre-bloom and peak bloom stages, while at the post-bloom stage, the members of Phycodnaviridae and Microviridae were more abundant. Temperature and nutrients were the main contributors to the dynamic structure of the viral community. Some obvious correlations were found between dominant viral species and host biomass. Functional analysis indicated some functional genes had dramatic response in algal-associated viral assemblages, especially the CAZyme encoding genes. This work expands the existing knowledge of algal-associated viruses by characterizing viral composition and function across a complete algal bloom cycle. Our data provide supporting evidence that viruses participate in dinoflagellate bloom dynamics under natural conditions.

ABSTRACT Hepatic injuries in hepatitis B virus (HBV) patients are caused by immune responses of the host. In our previous study, microRNA-146a (miR-146a), an innate immunity-related miRNA, and complement factor H (CFH), an important negative regulator of the alternative pathway of complement activation, were differentially expressed in HBV-expressing and HBV-free hepatocytes. Here, the roles of these factors in HBV-related liver inflammation were analyzed in detail. The expression levels of miR-146a and CFH in HBV-expressing hepatocytes were assessed via analyses of hepatocyte cell lines, transgenic mice, adenovirus-infected mice, and HBV-positive human liver samples. The expression level of miR-146a was upregulated in HBV-expressing Huh-7 hepatocytes, HBV-expressing mice, and patients with HBV infection. Further results demonstrated that the HBV X protein (HBx) was responsible for its effects on miR-146a expression through NF-κB-mediated enhancement of miR-146a promoter activity. HBV/HBx also downregulated the expression of CFH mRNA in hepatocyte cell lines and the livers of humans and transgenic mice. Furthermore, overexpression and inhibition of miR-146a in Huh-7 cells downregulated and upregulated CFH mRNA levels, respectively. Luciferase reporter assays demonstrated that miR-146a downregulated CFH mRNA expression in hepatocytes via 3′-untranslated-region (UTR) pairing. The overall effect of this process in vivo is to promote liver inflammation. These results demonstrate that the HBx–miR-146a–CFH–complement activation regulation pathway might play an important role in the immunopathogenesis of chronic HBV infection. These findings have important implications for understanding the immunopathogenesis of chronic hepatitis B and developing effective therapeutic interventions. IMPORTANCE Hepatitis B virus (HBV) remains an important pathogen and can cause severe liver diseases, including hepatitis, liver cirrhosis, and hepatocellular carcinoma. Although HBV was found in 1966, the molecular mechanisms of pathogenesis are still poorly understood. In the present study, we found that the HBV X protein (HBx) promoted the expression of miR-146a, an innate immunity-related miRNA, through the NF-κB signal pathway and that increasingly expressed miR-146a downregulated its target complement factor H (CFH), an important negative regulator of the complement alternative pathway, leading to the promotion of liver inflammation. We demonstrated that the HBx–miR-146a–CFH–complement activation regulation pathway is potentially an important mechanism of immunopathogenesis caused by chronic HBV infection. Our data provide a novel molecular mechanism of HBV pathogenesis and thus help to understand the correlations between the complement system, an important part of innate immunity, and HBV-associated disease. These findings will also be important to identify potential therapeutic targets for HBV infection.

The biological network database presents exponential growth, how to find the target network accurately from the network database becomes the difficult problem. This paper proposes a new network similarity search algorithm, the similar network of Top k is calculated by two methods, the similar networks returned by the two algorithms are then filtered by overlap fractions, the weighted reordering algorithm is used to reorder the two sets of data, a precise set of similar network data sets is returned finally.In this paper, the accuracy of the query is judged by the comparison of the edge correctness (EC) value and the maximum public connection subgraph (LCCS) value of the returned sorted similar network data set, and compare query time with other algorithms.From the results, this algorithm is superior to other algorithms in query accuracy and query speed.

Objective: To investigate the value of spatiotemporal image correlation (STIC) technique in the ventricular septal defect diagnosis., Methods: A total of 1,163 fetuses were enrolled in this study, diagnosed by fetal echocardiography and analyzed by STIC technique. We obtained effective STIC volumes from the fetus according to the Goncalves' report, and judged fetal cardiac structure from STIC volume information again with a double-blind method. Another echocardiography was obtained during neonatal or infant period as follow-up., Results: (1) As much as 1,062 cases were diagnosed to have normal fetal heart by fetal echocardiography, 43 cases had congenital heart disease without VSD, and 58 cases had VSD [21 cases (36.2%) were simple VSD and 37 cases (63.8%)were VSD with other heart malformation]. (2) Three fetal VSD cases (0.26%) were missed and one normal case was diagnosed as VSD after two-dimensional (2D) echocardiography. STIC technique corrected the diagnosis for two cases: one case of VSD after fetal 2D echocardiography was confirmed to be normal with STIC and neonatal heart examination; one case that was diagnosed as normal by fetal 2D echocardiography was confirmed to have VSD with STIC and neonatal heart examination., Conclusions: The special value of STIC technique in the diagnosis of VSD had been confirmed by this study, and it had been proved as the best additional method to fetal echocardiography.