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Introduction: Trichoderma species establish symbiotic relationships with plants through both parasitic and mutualistic mechanisms. While some Trichoderma species act as plant pathogenic fungi, others utilize various strategies to protect and enhance plant growth. Methods: Phylogenetic positions of new species of Trichoderma were determined through multi-gene analysis relying on the internal transcribed spacer (ITS) regions of the ribosomal DNA, the translation elongation factor 1-α (tef1-α) gene, and the RNA polymerase II (rpb2) gene. Additionally, pathogenicity experiments were conducted, and the aggressiveness of each isolate was evaluated based on the area of the cross-section of the infected site. Results: In this study, 13 Trichoderma species, including 9 known species and 4 new species, namely, T. delicatum, T. robustum, T. perfasciculatum, and T. subulatum were isolated from the diseased tubers of Gastrodia elata in Yunnan, China. Among the known species, T. hamatum had the highest frequency. T. delicatum belonged to the Koningii clade. T. robustum and T. perfasciculatum were assigned to the Virens clade. T. subulatum emerged as a new member of the Spirale clade. Pathogenicity experiments were conducted on the new species T. robustum, T. delicatum, and T. perfasciculatum, as well as the known species T. hamatum, T. atroviride, and T. harzianum. The infective abilities of different Trichoderma species on G. elata varied, indicating that Trichoderma was a pathogenic fungus causing black rot disease in G. elata. Discussion: This study provided the morphological characteristics of new species and discussed the morphological differences with phylogenetically proximate species, laying the foundation for research aimed at preventing and managing diseases that affect G. elata.
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Covalent organic frameworks (COFs) are promising porous materials due to their high specific surface area, adjustable structure, highly ordered nanochannels, and abundant functional groups, which brings about wide applications in the field of gas adsorption, hydrogen storage, optics, and so forth. In recent years, COFs have attracted considerable attention in electrochemical energy storage and conversion. Specifically, COF-based functional separators are ideal candidates for addressing the ionic transport-related issues in high-energy batteries, such as dendritic formation and shuttle effect. Therefore, it is necessary to make a comprehensive understanding of the mechanism of COFs in functional separators. In this review, the advantages, applications as well as synthesis of COFs are firstly presented. Then, the mechanism of COFs in functional separators for high-energy batteries is summarized in detail, including pore channels regulating ionic transport, functional groups regulating ionic transport, adsorption effect, and catalytic effect. Finally, the application prospect of COFs-based separators in high-energy batteries is proposed. This review may provide new insights into the design of functional separators for advanced electrochemical energy storage and conversion systems.
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OBJECTIVE: The recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) to have a bi-specific oncolytic character in many tumor cells, but its action pathway in killing tumor cells has not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by Ad-VT and the interaction between autophagy and apoptosis. METHODS: Crystal Violet staining and CCK-8 assays were used to detect the inhibitory effect of Ad-VT on ovarian cancer cells. The antitumor effect of Ad-VT in vivo was analyzed by tumor bearing nude mouse model. Subsequently, flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by Ad-VT. RESULTS: In this study, through the in vitro cell inhibition assays, we found that Ad-VT has a significant inhibitory effect on ovarian cancer A2780 cells, but no significant inhibitory effect on normal ovarian epithelial cells. Then in vivo experiments showed that Ad-VT significantly inhibited tumor growth and extended the survival time of mice. Subsequent detection of the level of apoptosis found that Ad-VT can cause a strong apoptotic response and kill cells mainly through the endogenous apoptotic pathway. Through the staining analysis of LC3 and the analysis of autophagy-related proteins, it was found that Ad-VT could significantly increase the level of autophagy in A2780 cells, and this was a protective mechanism. CONCLUSIONS: Ad-VT, which replicates under the control of the hTERT promoter and expresses apoptin protein, have significant inhibitory effect on ovarian cancer A2780 cells and promote their apoptosis and autophagy.
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This study examined the influence of Internet use on light-intensity physical activity (LPA) and moderate-to-vigorous physical activity (MVPA) among family caregivers of older adults, utilizing data from the 2018 China Health and Retirement Longitudinal Study (N = 3,194). The Tobit model and Propensity Score Matching were first used to test the focal associations. Subsequently, mediation analyses and heterogeneity analysis were conducted to explore the pathways and urban-rural disparities. The results indicated that Internet use was negatively associated with MVPA and was not correlated with LPA. The Internet use - MVPA relationship was mediated by participation in economic activities, while participation in social activities acted as a suppressor. Further, the focal association was only found in rural family caregivers. The findings suggest that effective health promotion interventions are needed to mitigate the negative influence of Internet use on the MVPA of family caregivers of older adults, especially for those in the rural.
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The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, with clinical outcomes ranging from asymptomatic infections to severe invasive diseases. The innate immune system, particularly macrophages, is of paramount importance in resisting the invasion of host tissues and organs by the trophozoites of E. histolytica. Parasite-derived pathogenic factors, such as lectins, play a pivotal role in the promotion of macrophage polarization phenotypes that have undergone alteration. Nevertheless, the precise mechanisms by which E. histolytica modulates immune polarization remain largely unknown. The current study focused on the immunomodulatory effects of the Igl-C fragment of E. histolytica Gal/GalNAc lectin on macrophage polarization. These results demonstrated that Igl-C could induce the secretion of IL-1ß, IL-6, and other cytokines, activating a mixed M1/M2 polarization state. M1 polarization of macrophages occurs in the early stages and gradually transitions to M2 polarization in the later stages, which may contribute to the persistence of the infection. Igl-C induces the macrophage M1 phenotype and causes the release of immune effector molecules, including iNOS and cytokines, by activating the NF-κB p65 and JAK-STAT1 transcription factor signaling pathways. Furthermore, Igl-C supports the macrophage M2 phenotype via JAK-STAT3 and IL-4-STAT6 pathways, which activate arginase expression in later stages, contributing to the tissue regeneration and persistence of the parasite. The involvement of distinct signaling pathways in mediating this response highlights the complex interplay between the parasite and the host immune system. These findings enhance our understanding of the Igl-C-mediated pathogenic mechanisms during E. histolytica infection.
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Entamoeba histolytica , Entamoebiasis , Lectins , Macrophages , Entamoeba histolytica/immunology , Macrophages/immunology , Macrophages/metabolism , Macrophages/parasitology , Entamoebiasis/immunology , Entamoebiasis/parasitology , Animals , Mice , Lectins/metabolism , Lectins/immunology , Cytokines/metabolism , Macrophage Activation , Humans , Signal Transduction , Protozoan Proteins/immunology , Protozoan Proteins/metabolismABSTRACT
Energetic Metal-Organic Framework (EMOF) compounds have gained significant attention in recent years as a hot research topic in the fields of explosives and propellants. This article provides an overview of the latest research progress of EMOFs in various areas, including heat-resistant explosives, burning rate catalysts and initiating explosives. It discusses the recent development trends of high-energy EMOFs, such as high-dimensional and solvent-free structural design, simplified and scalable synthesis conditions, environmentally friendly manufacturing processes with tunable structures, high-energy, low-sensitivity and multifunctional target products. The challenges and issues faced by EMOFs in heat-resistant explosives, burning rate catalysts and initiating explosives are presented. Furthermore, the key research directions for future applications of EMOFs in the fields of explosives and propellants are discussed, including solvent-free high-dimensional EMOFs design and synthesis, precise modulation of EMOFs molecular composition and pore structure, improvement of accurate prediction methods for physicochemical properties of high-energy EMOFs, low-cost large-scale production and development of multifunctional composite EMOFs as energetic materials, exploration of influencing factors, and comprehensive study on the application of novel and high-performance multifunctional EMOFs.
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Neodymium oxide (Nd2O3) is a rare earth element that can lead to various type of tissue and organ damage with prolonged exposure. The long noncoding RNA small nucleolar ribonucleic acid host gene 5 (lncRNA SNHG5) plays a role in disease progressiong. However, its connection with Nd2O3 induced reproductive harm in males has not been thoroughly investigated. Our research discovered that exposure to Nd2O3 increases the expression of SNHG5 in the testes of mice, which in turn binds directly to and reduces in the protein levels of insulin like growth factor 2 mRNA-binding protein 1 (IGF2BP1) both in vivo and in vitro. This process disrupts the cytoskeleton of blood-testis barrier(BTB) by impacting the stability of the tight junction protein Occludin (Ocln) mRNA structure and the permeability of the BTB. In summary, our study elucidates the regulatory mechanism of SNHG5/IGF2BP1/Occludin axis in Nd2O3-induced BTB injury, providing valuable insights for the treatment of male infertility.
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Mercury (Hg), a global contaminant, can sink into cryosphere and be released into runoff through meltwater. The Tibetan Plateau (TP) has been witnessing ongoing shrinkage of alpine glaciers. However, the export of Hg from melting glacier is still sparsely reported. From October 16, 2020 to October 15, 2021, we conducted daily observations to study the variation in total Hg concentrations and its export to the Mingyong River, a glacier-fed river in southeastern TP. Results showed that the Hg concentrations were high during the monsoon season but low during the non-monsoon period. The Hg in runoff correlated with the concentrations of total suspended particulates (TSP) and dissolved inorganic carbon (DIC) during both monsoon and non-monsoon seasons (p < 0.01), and the correlation of Hg with other parameters showed seasonal variations. The input from meltwater, precipitation, and groundwater to riverine Hg were 8.3 g, 264.4 g, and 71.0 g, respectively, and the total export was 211.0 g (yield: 4.3 g/km2/year) in the hydrological year, indicating that Mingyong catchment act as a sink for Hg. For the entire TP, the annual export of Hg from glacier runoff was estimated to be 947.7 kg/year. Our study highlights the necessity for further investigations on Hg dynamics to understand the changes in the Hg cycle within glaciated aquatic ecosystems.
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BACKGROUND AND AIM: Our aim was to explore the potential relationship between SII and obesity, as well as abdominal obesity. METHODS AND RESULTS: We utilized a weighted multivariable logistic regression model to investigate the relationship between SII and obesity, as well as abdominal obesity. Generalized additive models were employed to test for non-linear associations. Subsequently, we constructed a two-piecewise linear regression model and conducted a recursive algorithm to calculate inflection points. Additionally, subgroup analyses and interaction tests were performed. A total of 7,880 U.S. adult participants from NHANES 2011-2018 were recruited for this study. In the regression model adjusted for all confounding variables, the odds ratios (95% confidence intervals) for the association between SII/100 and obesity, as well as abdominal obesity, were 1.03 (1.01, 1.06) and 1.04 (1.01, 1.08) respectively. There was a non-linear and reverse U-shaped association between SII/100 and obesity, as well as abdominal obesity, with inflection points at 7.32 and 9.98 respectively. Significant positive correlations were observed before the inflection points, while significant negative correlations were found after the inflection points. There was a statistically significant interaction in the analysis of age, hypertension, and diabetes. Moreover, a notable interaction is observed between SII/100 and abdominal obesity within non-Hispanic Asian populations. CONCLUSIONS: In adults from the United States, there is a positive correlation between SII and the high risk of obesity, as well as abdominal obesity. Further large-scale prospective studies are needed to analyze the role of SII in obesity and abdominal obesity.
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Artificial reefs (ARs) are widespread globally and play a positive role in enhancing fish communities and restoring habitat. However, the effect of ARs on phytoplankton, which are fundamental to the marine food chain, remains inconclusive. Conducting a literature review and meta-analysis, this study investigates how ARs influence phytoplankton community dynamics by comparing the biomass, density, and diversity of phytoplankton between ARs and natural water bodies across varying deployment durations, constituent materials, and climatic zones. The study findings suggest that, overall, ARs enhance the biomass, density, and diversity of phytoplankton communities, with no significant differences observed compared to natural water bodies. The enhancement effect of ARs on phytoplankton communities becomes progressively more pronounced with increasing deployment time, with the overall status of phytoplankton communities being optimal when artificial reefs are deployed for 5 years or longer. Concrete and stone ARs can significantly enhance the biomass and diversity of phytoplankton, respectively. The effect of ARs on phytoplankton diversity is unrelated to climatic zones. However, deploying ARs in temperate waters significantly enhances phytoplankton biomass, while in tropical waters, it significantly reduces phytoplankton density. The research findings provide practical implications for the formulation of artificial reef construction strategies tailored to the characteristics of different aquatic ecosystems, emphasizing the need for long-term deployment and appropriate material selection. This study offers a theoretical basis for optimizing AR design and deployment to achieve maximum ecological benefits.
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Coral Reefs , Phytoplankton , Biomass , Biodiversity , Ecosystem , Food Chain , Conservation of Natural Resources/methodsABSTRACT
OBJECTIVES: The aim of our study was to assess the association between muscle mass and strength and depression through a cross-sectional study of the National Health and Nutrition Examination Survey from 2011 to 2014. METHODS: Muscle mass was calculated by summing the lean body mass of the limbs and muscle strength was assessed by grip strength. Depression was determined by The 9-item Patient Health Questionnaire. We used weighted multivariate logistic regression models to explore the relationship between muscle mass and strength and depression. Generalized additive models were used to test for the presence of nonlinear associations. We then constructed a two-piece-wise linear regression model and performed a recursive algorithm to calculate inflection points. In addition, subgroup analyses and interaction tests were performed. RESULTS: The study recruited 4871 adults from the United States. In regression models adjusted for all confounding variables, the OR (95 % CI) for the association between grip strength and appendicular lean mass (ALM) and depression were 0.943 (0.903, 0.985), 0.945 (0.908, 0.983), respectively. There was a non-linear association between grip strength and depression with a turning point of 46.3. The OR (95 % CI) before the turning point was 0.920 (0.872, 0.972). The interaction was statistically significant only in the age analysis. There was also a nonlinear association between ALM and depression, but no significant turning point was found. The interaction was statistically significant in the gender and BMI analyses. CONCLUSION: Grip strength and ALM are negatively associated with an increased likelihood of depression in US adults. Exercises for muscle mass and strength may help prevent depression.
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BACKGROUD: New-onset atrial fibrillation (NOAF) is a common complication of sepsis and linked to higher death rates in affected patients. The lack of effective predictive tools hampers early risk assessment for the development of NOAF. This study aims to develop practical and effective predictive tools for identifying the risk of NOAF. METHODS: This case-control study retrospectively analyzed patients with sepsis admitted to the emergency department of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from September 2017 to January 2023. Based on electrocardiographic reports and electrocardiogram monitoring records, patients were categorized into NOAF and non-NOAF groups. Laboratory tests, including myeloperoxidase (MPO) and hypochlorous acid (HOCl), were collected, along with demographic data and comorbidities. Least absolute shrinkage and selection operator regression and multivariate logistic regression analyses were employed to identify predictors. The area under the curve (AUC) was used to evaluate the predictive model's performance in identifying NOAF. RESULTS: A total of 389 patients with sepsis were included in the study, of which 63 developed NOAF. MPO and HOCl levels were significantly higher in the NOAF group compared to the non-NOAF group. Multivariate logistic regression analysis identified MPO, HOCl, tumor necrosis factor-α (TNF-α), white blood cells (WBC), and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score as independent risk factors for NOAF in sepsis. Additionally, a nomogram model developed using these independent risk factors achieved an AUC of 0.897. CONCLUSION: The combination of MPO and its derivative HOCl with clinical indicators improves the prediction of NOAF in sepsis. The nomogram model can serve as a practical predictive tool for the early identification of NOAF in patients with sepsis.
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Atrial Fibrillation , Biomarkers , Hypochlorous Acid , Peroxidase , Predictive Value of Tests , Sepsis , Humans , Peroxidase/blood , Male , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/blood , Retrospective Studies , Sepsis/diagnosis , Sepsis/blood , Middle Aged , Aged , Biomarkers/blood , Risk Assessment , Risk Factors , China/epidemiology , Prognosis , Aged, 80 and over , Case-Control StudiesABSTRACT
Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.
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Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Macrophages , Obesity , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/complications , Obesity/drug therapy , Obesity/immunology , Obesity/metabolism , Obesity/complications , Humans , Macrophages/drug effects , Macrophages/immunology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Animals , Medicine, Chinese TraditionalABSTRACT
Ubiquitination plays an essential role in protein stability, subcellular localization, and interactions. Crosstalk between different types of ubiquitination results in distinct biological outcomes for proteins. However, the role of ubiquitination-related crosstalk in lymph node (LN) metastasis and the key regulatory factors controlling this process have not been determined. Using high-throughput sequencing, we found that ubiquitin-conjugating enzyme E2 C (UBE2C) was overexpressed in bladder cancer (BCa) and was strongly associated with an unfavorable prognosis. Overexpression of UBE2C increased BCa lymphangiogenesis and promoted LN metastasis both in vitro and in vivo. Mechanistically, UBE2C mediated sodium-coupled neutral amino acid transporter 2 (SNAT2) monoubiquitination at lysine 59 to inhibit K63-linked polyubiquitination at lysine 33 of SNAT2. Crosstalk between monoubiquitination and K63-linked polyubiquitination increased SNAT2 membrane protein levels by suppressing epsin 1-mediated (EPN1-mediated) endocytosis. SNAT2 facilitated glutamine uptake and metabolism to promote VEGFC secretion, ultimately leading to lymphangiogenesis and LN metastasis in patients with BCa. Importantly, inhibition of UBE2C significantly attenuated BCa lymphangiogenesis in a patient-derived xenograft model. Our results reveal the mechanism by which UBE2C mediates crosstalk between the monoubiquitination and K63-linked polyubiquitination of SNAT2 to promote BCa metastasis and identify UBE2C as a promising target for treating LN-metastatic BCa.
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Lymphatic Metastasis , Ubiquitin-Conjugating Enzymes , Ubiquitination , Urinary Bladder Neoplasms , Animals , Female , Humans , Male , Mice , Amino Acid Transport System ASC , Cell Line, Tumor , Lymphangiogenesis/genetics , Minor Histocompatibility Antigens , Neoplasm Proteins/metabolism , Neoplasm Proteins/genetics , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitin-Conjugating Enzymes/genetics , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/genetics , Vascular Endothelial Growth Factor C/metabolism , Vascular Endothelial Growth Factor C/geneticsABSTRACT
BACKGROUND: Intestinal inflammation and compromised barrier function are critical factors in the pathogenesis of gastrointestinal disorders. This study aimed to investigate the role of miR-192-5p in modulating intestinal epithelial barrier (IEB) integrity and its association with autophagy. METHODS: A DSS-induced colitis model was used to assess the effects of miR-192-5p on intestinal inflammation. In vitro experiments involved cell culture and transient transfection techniques. Various assays, including dual-luciferase reporter gene assays, quantitative real-time PCR, western blotting, and measurements of transepithelial electrical resistance, were performed to evaluate changes in miR-192-5p expression, Rictor levels, and autophagy flux. Immunofluorescence staining, H&E staining, TEER measurements, and FITC-dextran analysis were also employed. RESULTS: Our findings revealed a reduced expression of miR-192-5p in inflamed intestinal tissues, correlating with impaired IEB function. Overexpression of miR-192-5p alleviated TNF-induced IEB dysfunction by targeting Rictor, resulting in enhanced autophagy flux in enterocytes (ECs). Moreover, the therapeutic potential of miR-192-5p was substantiated in colitis mice, wherein increased miR-192-5p expression ameliorated intestinal inflammatory injury by enhancing autophagy flux in ECs through the modulation of Rictor. CONCLUSION: Our study highlights the therapeutic potential of miR-192-5p in enteritis by demonstrating its role in regulating autophagy and preserving IEB function. Targeting the miR-192-5p/Rictor axis is a promising approach for mitigating gut inflammatory injury and improving barrier integrity in enteritis patients.
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Solution-processable 2D semiconductor inks based on electrochemical molecular intercalation and exfoliation of bulk layered crystals using organic cations has offered an alternative pathway to low-cost fabrication of large-area flexible and wearable electronic devices. However, the growth of large-piece bulk crystals as starting material relies on costly and prolonged high-temperature process, representing a critical roadblock towards practical and large-scale applications. Here we report a general liquid-metal-assisted approach that enables the electrochemical molecular intercalation of low-cost and readily available crystal powders. The resulted solution-processable MoS2 nanosheets are of comparable quality to those exfoliated from bulk crystals. Furthermore, this method can create a rich library of functional 2D electronic inks ( >50 types), including 2D wide-bandgap semiconductors of low electrical conductivity. Lastly, we demonstrated the all-solution-processable integration of 2D semiconductors with 2D conductors and 2D dielectrics for the fabrication of large-area thin-film transistors and memristors at a greatly reduced cost.
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Background: Metabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM. Methods: Data encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran's Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0. Results: The IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899-0.962, p = 2.16 × 10-5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917-0.968, p = 1.64 × 10-5), Mannose (IVW: OR:1.133, 95% CI: 1.072-1.197, p = 1.02 × 10-5), X-21829 (IVW: OR:1.036, 95% CI: 1.036-1.122, p = 9.44 × 10-5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818-0.926, p = 1.29 × 10-5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism. Conclusion: This study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.
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This study aimed to investigate the roles of lysosome-related genes in BC prognosis and immunity. Transcriptome data from TCGA and MSigDB, along with lysosome-related gene sets, underwent NMF cluster analysis, resulting in two subtypes. Using lasso regression and univariate/multivariate Cox regression analysis, an 11-gene signature was successfully identified and verified. High- and low-risk populations were dominated by HR+ sample types. There were differences in pathway enrichment, immune cell infiltration, and immune scores. Sensitive drugs targeting model genes were screened using GDSC and CCLE. This study constructed a reliable prognostic model with lysosome-related genes, providing valuable insights for BC clinical immunotherapy.
Lysosome-related genes can be used to predict survival outcomes in BRCA patients.Significant differences were showed in the immune status of patient with different prognoses.Immunotherapy may show better therapeutic results in low-risk patients.The most promising targeted drugs in the low-risk group are mainly Lapatinib, Palbociclib and Ribociclib.
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Antimony ï¼Sbï¼ is a major pollutant that poses a serious threat to the environment in the mining and processing of nonferrous metals, coexisting with sulfide and oxide of arsenic ï¼Asï¼. Microorganisms play an important role in the migration, transformation, and repair of metals in soil. The ecological effects of bioavailable Sb and As on the microbial community in antimony mining areasï¼mining and smelting areasï¼are still poorly understood. The Wenzel method and high-throughput 16S rDNA amplicon were used to characterize soil pollution characteristics in different functional areas, and the relationship between the bacterial community and bioavailable concentrations have been investigated comprehensively. The results showed thatï¼ Chemical speciation of Sb and As were amorphous, and poorly crystalline hydrous oxides of Fe and Al ï¼F3ï¼ > well-crystallized hydrous oxides of Fe and Al ï¼F4ï¼ > residual phases ï¼F5ï¼ > specifically adsorbed ï¼F2ï¼ > non-specifically adsorbed ï¼F1ï¼. According to the estimation of the potential ecological risk index ï¼RIï¼ and geo-accumulation index ï¼Igeoï¼, the Sb pollution degree wasï¼ smelting area > mining area > contrast area, in which the smelting area showed serious pollution, and the mining area showed moderate to severe pollution. The As pollution degree wasï¼ mining area > smelting area > contrast area, in which the mining area and smelting area showed moderate to severe pollution. High-throughput 16S rDNA amplicon showed that Proteobacteria was the most abundant phylum in mining and smelting areasï¼ Kaistobacter, Pseudomonas, Sphingomonas, and Lysobacter were the most abundant microbial generaï¼ Geobacter and Luteolibacter had a high LDA score in mining areasï¼ and Thiobacillus had a high LDA score in antimony-contaminated areas. Spearman correlation analysis, variation partitioning analysis ï¼VPAï¼, and random forest ï¼RFï¼ analysis showed that Sb, As, bioavailable antimony [Sb ï¼Bioï¼], and bioavailable arsenic [As ï¼Bioï¼]were the main factors affecting the microbial community structure in different functional areas of antimony ore. Redundancy analysis ï¼RDAï¼ indicated that Sb and its bioavailable concentrations showed uniformly negative associations with the relative abundance of bacteria Nitrospirae and showed a significant positive correlation with Thiobacillus ï¼P<0.05ï¼. The in-depth research on the ecological effects of bioavailable Sb and As on the bacterial community provides references and new perspectives for environmental monitoring and management.