Shared genetics and causal relationships between major depressive disorder and COVID-19 related traits: a large-scale genome-wide cross-trait meta-analysis

IntroductionThe comorbidity between major depressive disorder (MDD) and coronavirus disease of 2019 (COVID-19) related traits have long been identified in clinical settings, but their shared genetic foundation and causal relationships are unknown. Here, we investigated the genetic mechanisms behind COVID-19 related traits and MDD using the cross-trait meta-analysis, and evaluated the underlying causal relationships between MDD and 3 different COVID-19 outcomes (severe COVID-19, hospitalized COVID-19, and COVID-19 infection).MethodsIn this study, we conducted a comprehensive analysis using the most up-to-date and publicly available GWAS summary statistics to explore shared genetic etiology and the causality between MDD and COVID-19 outcomes. We first used genome-wide cross-trait meta-analysis to identify the pleiotropic genomic SNPs and the genes shared by MDD and COVID-19 outcomes, and then explore the potential bidirectional causal relationships between MDD and COVID-19 outcomes by implementing a bidirectional MR study design. We further conducted functional annotations analyses to obtain biological insight for shared genes from the results of cross-trait meta-analysis.ResultsWe have identified 71 SNPs located on 25 different genes are shared between MDD and COVID-19 outcomes. We have also found that genetic liability to MDD is a causal factor for COVID-19 outcomes. In particular, we found that MDD has causal effect on severe COVID-19 (OR = 1.832, 95% CI = 1.037–3.236) and hospitalized COVID-19 (OR = 1.412, 95% CI = 1.021–1.953). Functional analysis suggested that the shared genes are enriched in Cushing syndrome, neuroactive ligand-receptor interaction.DiscussionOur findings provide convincing evidence on shared genetic etiology and causal relationships between MDD and COVID-19 outcomes, which is crucial to prevention, and therapeutic treatment of MDD and COVID-19

The reporting quality of randomized controlled trials in Chinese herbal medicine (CHM) formulas for diabetes based on the consort statement and its extension for CHM formulas

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors

RETRACTED: vB-ApyS-JF1, the First Trueperella pyogenes Phage, Shows Potential as an Alternative Treatment Strategy for Trueperella pyogenes Infections

Trueperella pyogenes (T. pyogenes) is an important opportunistic animal pathogen that causes huge economic losses to the animal husbandry industry. The emergence of bacterial resistance and the unsatisfactory effect of the vaccine have prompted investigators to explore alternative strategies for controlling T. pyogenes infection. Due to the ability of phages to kill multidrug-resistant bacteria, the use of phage therapy to combat multidrug-resistant bacterial infections has attracted attention. In this study, a T. pyogenes phage, vB-ApyS-JF1 (JF1), was isolated from sewage samples, and its whole genome and biological characteristics were elucidated. Moreover, the protective effect of phage JF1 on a mouse bacteremic model caused by T. pyogenes was studied. JF1 harbors a double-stranded DNA genome with a length of 90,130 bp (30.57% G + C). The genome of JF1 lacked bacterial virulence–, antibiotic resistance– and lysogenesis-related genes. Moreover, the genome sequence of JF1 exhibited low coverage (<6%) with all published phages in the NCBI database, and a phylogenetic analysis of the terminase large subunits and capsid indicated that JF1 was evolutionarily distinct from known phages. In addition, JF1 was stable over a wide range of pH values (3 to 11) and temperatures (4 to 50°C) and exhibited strong lytic activity against T. pyogenes in vitro. In murine experiments, a single intraperitoneal administration of JF1 30 min post-inoculation provided 100% protection for mice against T. pyogenes infection. Compared to the phosphate-buffered saline (PBS) treatment group, JF1 significantly (P < 0.01) reduced the bacterial load in the blood and tissues of infected mice. Meanwhile, treatment with phage JF1 relieved the pathological symptoms observed in each tissue. Furthermore, the levels of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-6 (IL-6) in the blood of infected mice were significantly (P < 0.01) decreased in the phage-treated group. Taken together, these results indicate that phage JF1 demonstrated great potential as an alternative therapeutic treatment against T. pyogenes infection

Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia

Dysregulation of kinase signaling pathways favors tumor cell survival and therapy resistance in cancer. Here, we reveal a posttranslational regulation of kinase signaling and nuclear receptor activity via deubiquitination in T cell acute lymphoblastic leukemia (T-ALL). We observed that the ubiquitin-specific protease 11 (USP11) is highly expressed and associates with poor prognosis in T-ALL. USP11 ablation inhibits leukemia progression in vivo, sparing normal hematopoiesis. USP11 forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK) and enhance its activity. Impairment of LCK activity leads to increased glucocorticoid receptor (GR) expression and glucocorticoids sensitivity. Genetic knockout of USP7 improved the antileukemic efficacy of glucocorticoids in vivo. The transcriptional activation of GR target genes is orchestrated by the deubiquitinase activity and mediated via an increase in enhancer-promoter interaction intensity. Our data unveil how dysregulated deubiquitination controls leukemia survival and drug resistance, suggesting previously unidentified therapeutic combinations toward targeting leukemia

Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia

Dysregulation of kinase signaling pathways favors tumor cell survival and therapy resistance in cancer. Here, we reveal a posttranslational regulation of kinase signaling and nuclear receptor activity via deubiquitination in T cell acute lymphoblastic leukemia (T-ALL).We observed that the ubiquitin-specific protease 11 (USP11) is highly expressed and associates with poor prognosis in T-ALL. USP11 ablation inhibits leukemia progression in vivo, sparing normal hematopoiesis. USP11 forms a complex with USP7 to deubiquitinate the oncogenic lymphocyte cell-specific protein-tyrosine kinase (LCK) and enhance its activity. Impairment of LCK activity leads to increased glucocorticoid receptor (GR) expression and glucocorticoids sensitivity. Genetic knockout of USP7 improved the antileukemic efficacy of glucocorticoids in vivo. The transcriptional activation of GR target genes is orchestrated by the deubiquitinase activity and mediated via an increase in enhancer-promoter interaction intensity. Our data unveil how dysregulated deubiquitination controls leukemia survival and drug resistance, suggesting previously unidentified therapeutic combinations toward targeting leukemia

Indentation of Commercial Pure Titanium Processed by Cold Rolling

In this work, the effects of plastic deformation on the indentation behaviors of commercial pure titanium alloy were investigated. Titanium experienced various kinds of deformation by cold rolling processes, and the indentation behaviors were measured using microindentation. The results showed the most deformed sample experienced the largest indentation resistance and had the highest dislocation density and the indentation size influenced the indentation behavior of the CP-Ti. The effect of strain on Vickers hardness demonstrated the dominant role of the dislocation motion in the indentation deformation of CP-Ti alloy. The dependence of the indentation hardness on both the maximum indentation load and the indentation residual depth suggested there exists size effect in the indentation. The effect of the plastic strain on the energy ratio suggested the energy ratio is related to the microstructure in materials. Additionally, the linear relationship between the energy ratio on the indentation depth ratio was obtained for hcp-structured Titanium alloys

Feeding Management and Disease Prevention and Control of Pet Guinea Pigs

Guinea pig is widely used in clinical drug experiments as a laboratory animal. Because of its small and lovely size, guinea pig is often kept as a pet by many families. However, there are few reports on the feeding management and disease prevention and control of pet guinea pigs. This article introduced the experience and technology of feeding management and disease prevention of pet guinea pigs, in order to provide a reference for the feeding management and disease prevention of pet guinea pigs

Feeding Management and Disease Prevention and Control of Pet Guinea Pigs

Guinea pig is widely used in clinical drug experiments as a laboratory animal. Because of its small and lovely size, guinea pig is often kept as a pet by many families. However, there are few reports on the feeding management and disease prevention and control of pet guinea pigs. This article introduced the experience and technology of feeding management and disease prevention of pet guinea pigs, in order to provide a reference for the feeding management and disease prevention of pet guinea pigs

Deciphering the heterogeneity dominated by tumor-associated macrophages for survival prognostication and prediction of immunotherapy response in lung adenocarcinoma

Abstract Tumor-associated macrophages (TAMs) are a specific subset of macrophages that reside inside the tumor microenvironment. The dynamic interplay between TAMs and tumor cells plays a crucial role in the treatment response and prognosis of lung adenocarcinoma (LUAD). The study aimed to examine the association between TAMs and LUAD to advance the development of targeted strategies and immunotherapeutic approaches for treating this type of lung cancer. The study employed single-cell mRNA sequencing data to characterize the immune cell composition of LUAD and delineate distinct subpopulations of TAMs. The “BayesPrism” and “Seurat” R packages were employed to examine the association between these subgroups and immunotherapy and clinical features to identify novel immunotherapy biomarkers. Furthermore, a predictive signature was generated to forecast patient prognosis by examining the gene expression profile of immunotherapy-associated TAMs subsets and using 104 machine-learning techniques. A comprehensive investigation has shown the existence of a hitherto unidentified subgroup of TAMs known as RGS1 + TAMs, which has been found to have a strong correlation with the efficacy of immunotherapy and the occurrence of tumor metastasis in LUAD patients. CD83 was identified CD83 as a distinct biomarker for the expression of RGS1 + TAMs, showcasing its potential utility as an indicator for immunotherapeutic interventions. Furthermore, the prognostic capacity of the RTMscore signature, encompassing three specific mRNA (NR4A2, MMP14, and NPC2), demonstrated enhanced robustness when contrasted against the comprehensive collection of 104 features outlined in the published study. CD83 has potential as an immunotherapeutic biomarker. Meanwhile, The RTMscore signature established in the present study might be beneficial for survival prognostication

Hollow flower-like polyhedral α-Fe₂O₃/Defective MoS₂/Ag Z-scheme heterojunctions with enhanced photocatalytic-Fenton performance via surface plasmon resonance and photothermal effects

Hollow Polyhedral superstructures can capture light effectively and have adjustable composite composition, which is useful for constructing Z-scheme systems. Here, rational design of hollow flower-like polyhedral α-Fe2O3/defective MoS2/Ag Z-Scheme heterojunctions is described, using polyhedral α-Fe2O3 as the template and via a one-pot hydrothermal and postdeposition strategy. The hollow flower-like polyhedral heterojunctions utilize multiple reflections of light in the hollow structure to achieve enhanced photocatalytic activity. Defective MoS2 acts as a link between α-Fe2O3 and Ag nanoparticles, providing a great deal of active sites and broadening the photoresponse region. Because of the enhancement of light absorption and surface plasma resonance of Ag, α-Fe2O3/defective MoS2/Ag has significant photothermal effect. The photogenerated carriers can be effectively separated by the construction of a Z-scheme system. Importantly, photocatalytic-Fenton degradation of 2,4-dichlorophenol and salicylic acid over hollow flower-like polyhedral α-Fe2O3/defective MoS2/Ag is higher than that of α-Fe2O3 and α-Fe2O3/defective MoS2