As novel alternative indicators of insulin resistance (IR), the triglyceride-glucose (TyG) and atherogenic index of plasma (AIP) are closely associated with the occurrence and progression of circulatory system diseases (CSD). However, it remains unclear whether TyG-derived indices (TyG, TyG-BMI, TyG-WC, TyG-WHtR) and AIP-derived indices (AIP, AIP-BMI, AIP-WC, AIP-WHtR) are associated with the terminal survival time of older patients with CSD. A dynamic cohort study was conducted involving older adults aged ≥ 60 years with the underlying cause of death attributed to CSD and who had completed at least three follow-ups. Cumulative TyG- and AIP-derived indices were calculated from longitudinal data. Logistic regression (LR), generalized linear models (GLM), generalized estimating equations (GEE), and restricted cubic splines (RCS) were used to analyze the association between each cumulative index and terminal survival time. Subgroup analyses, receiver operating characteristic (ROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were conducted to assess the robustness and predictive performance of each index. A total of 2302 participants were included, with a median follow-up time of 34.10 months and a median terminal survival time of 12 months. After adjusting for covariates, both LR, GLM, GEE, and RCS showed that higher cumulative TyG- and AIP-derived indices were associated with shorter terminal survival time, with nonlinear relationships observed. Subgroup analysis revealed that the cumulative TyG- and AIP-derived indices were generally significantly associated with terminal survival time across age and gender strata (except for the cumulative AIP index in females), and significant age interaction was observed for cumulative TyG-BMI, TyG-WC, and TyG-WHtR. The results of ROC, NRI, and IDI indicated that the cumulative indices of TyG-BMI and TyG-WC significantly outperform other indicators in predictive efficacy. Reducing TyG- and AIP-derived indices may help prolong terminal survival time in older patients with CSD. Furthermore, monitoring TyG-BMI and TyG-WC holds potential value for terminal survival time and may be considered for future integration into comprehensive assessment systems.

Background:Cervical cancer (CC) ranks as the fourth most prevalent cancer in women worldwide. While biomarkers exist, previous studies are often limited by public dataset heterogeneity, incomplete spectrum coverage, or lack of clinical validation. To address these limitations, this study aims to profile fresh tissues spanning the full continuum to systematically identify hub genes with dysregulated expression during malignant progression. Methods:This study collected cervical epithelial tissue from 10 patients each with low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL), and squamous cell carcinoma (SCC) for transcriptome sequencing. The differentially expressed genes (DEGs) analysis and Mfuzz clustering were employed to identify candidate genes showing monotonic expression trends. Candidate genes were prioritized using a protein-protein interaction (PPI) network with three centrality algorithms and validated in Gene Expression Omnibus to define hub genes. Subsequently, Gene Set Enrichment Analysis (GSEA), immune infiltration analysis, and regulatory network analyses were performed. Finally, hub gene expression was validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR) in an independent clinical cohort. Results:A total of 1,654 DEGs (HSIL vs. LSIL) and 6,635 DEGs (SCC vs. HSIL) were identified. Mfuzz clustering and PPI analysis yielded nine candidates, with BUB1B, KIF14, and MELK finalized as hub genes via GEO validation. GSEA showed the three hub genes were significantly enriched in multiple shared pathways and exhibited stage-specific differences. Immune infiltration analysis showed no significant association between hub-gene expression and immune cell fractions. Regulatory network prediction implicated miRNAs (e.g., hsa-miR-192-5p, hsa-miR-215-5p, hsa-miR-193b-3p) and TFs (e.g., AF4, E2F1, FOXA1, KDM5B) as potential upstream regulators. The lncRNAs (e.g., KCNQ1OT1, LINC01089, XIST3) were linked to these miRNAs. Finally, RT-qPCR in independent clinical samples confirmed hub-gene expression changes consistent with the bioinformatics findings. Conclusion:This study found the progressive upregulation of BUB1B, KIF14, and MELK across the LSIL-HSIL-SCC continuum, strengthening existing evidence of their association with cervical oncogenesis and highlighting their potential as candidate biomarkers for CC progression. However, the single-center design, limited sample size, and exploratory nature of the immune infiltration, regulatory network, and drug prediction analyses warrant cautious interpretation and underscore the need for further experimental validation.

Zinc pyrithione (ZPT), a broad-spectrum antimicrobial agent widely used in anti-dandruff shampoos and antifouling coatings, has an unclear toxic effect on embryonic trophoblast cells. To systematically evaluate the toxicological impact of ZPT on human trophoblast cell line JEG-3 and its underlying mechanisms, cells were treated with 90 nM ZPT for 72 h. A series of assays, including Cell Counting Kit-8(CCK-8), flow cytometry, wound healing, and Transwell, were performed to assess cell proliferation, apoptosis, migration, and invasion. Intracellular reactive oxygen species (ROS) levels and DNA damage were assessed using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) probe and γ-H2AX immunofluorescence, respectively. Transcriptome sequencing and Gene Ontology(GO) enrichment analysis were also performed. The results indicated that ZPT significantly inhibited cell proliferation, migration, and invasion, induced late-stage apoptosis, and increased ROS levels and DNA damage. RNA sequencing (RNA-seq) identified 1020 differentially expressed genes, suggesting an upregulation in autophagy and mitochondrial apoptosis pathways, and a significant downregulation in glycolysis, NAD⁺ regeneration, and hypoxia response pathways. Quantitative real-time polymerase chain reaction (qPCR) validation further confirmed the upregulation of key stress- and autophagy-related genes (NUPR1, SQSTM1) and the downregulation of genes involved in trophoblast function and mitochondrial quality control (BMP4, BNIP3, BNIP3L). These in vitro findings suggest that ZPT may impair trophoblast function through mechanisms involving oxidative stress, DNA damage, and perturbations in mitochondrial apoptosis/autophagy and energy metabolism.

Low-molecular-weight polycyclic aromatic hydrocarbons (LMW-PAHs), such as the 400 μM mixture of phenanthrene and fluorene used in this study, are prevalent environmental pollutants. Induction of epithelial–mesenchymal transition (EMT) by LMW-PAHs promote cell invasion and migration and contribute to disease pathogenesis. Long non-coding RNAs (lncRNAs) regulate gene expression by acting as competing endogenous RNAs (ceRNAs) that sequester microRNAs (miRNAs), a mechanism important for modulating EMT. Previously, regulation of the PI3K/AKT pathway and EMT in A549 cells are shown to occur through the hsa_circ_0039929/miR-15b-3p_R-1/FGF2 axis. Here, the functional role of the related LINC01376/miR-15b-3p_R-1/FGF2 axis in LMW-PAH-induced EMT was examined in A549 and H1299 cells. The miR-15b-3p_R-1 was downregulated, whereas LINC01376 and FGF2 were upregulated following LMW-PAH exposure. LINC01376 overexpression enhanced EMT, migration, and invasion. Interactions between miR-15b-3p_R-1 and FGF2, as well as direct binding of LINC01376 to miR-15b-3p_R-1, were confirmed experimentally. The results indicate that, in LMW-PAH-treated cells, LINC01376 functions as a ceRNA to sponge miR-15b-3p_R-1, thereby elevating FGF2 expression and promoting EMT, migration, and invasion. Identification of the LINC01376/miR-15b-3p_R-1/FGF2 regulatory axis highlighted as a key mechanism in LMW-PAH-driven EMT and suggests its potential as a therapeutic target in PAH-related pathologies.

Objective The objective of this study is to elucidate the breast cancer (BC)-associated ceRNA regulatory network by examining the expression profiles of lncRNAs, miRNAs, and mRNAs. Methods Using RNA sequencing data from The Cancer Genome Atlas (TCGA), we compared the expression profiles of lncRNAs, miRNAs, and mRNAs between 976 breast cancer (BC) tissues and 104 matched non-cancerous samples. Then, we constructed a BRCA-specific ceRNA network and evaluated the lncRNA-miRNA-mRNA regulatory relationships. The DAVID tool was used to investigate the functional enrichment of the key, significantly dysregulated mRNAs within the ceRNA network. Moreover, we analyzed the associations between the expression levels of key genes in the ceRNA network and the clinicopathological features as well as the overall survival of the BC patients from the TCGA database. Finally, to validate our bioinformatics findings, we utilized datasets from the Gene Expression Omnibus (GEO) database (GSE42568 and GSE65194) and additionally collected 20 tissue samples from BC patients for experimental assessment. Results A total of 231 dysregulated lncRNAs, 50 miRNAs, and 1136 mRNAs were identified in BC samples from the TCGA database. Among these, 52 lncRNAs, 24 miRNAs, and 126 mRNAs were found to potentially interact through ceRNA regulatory mechanisms. Based on these key genes, we analyzed the associations between their expression levels and the clinicopathological characteristics as well as the overall survival of BC patients from TCGA. The expression of 40 lncRNAs and 20 miRNAs was significantly associated with the patients’ clinical features (P < 0.05). Notably, 12 genes (including 4 lncRNAs, 2 miRNAs, and 6 mRNAs) in the ceRNA network were statistically significantly associated with overall survival time (log-rank test, P < 0.05). Comparative analysis of the GSE42568 and GSE65194 datasets and experimental validation by RT-qPCR revealed that the expression levels and changing trends of the key genes in the ceRNA network were highly consistent with the TCGA results, confirming the reliability of our bioinformatics analysis. Conclusion This study identified key BC-related ceRNA network 52 lncRNAs, 24 miRNAs and 126 mRNAs. These key genes are worthy to further explore as potential novel biomarkers for diagnosis, classification, and prognosis of BC.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants recognized for their toxicological significance. Increasing evidence suggests that chronic exposure to low-molecular-weight PAHs (LMW-PAHs) contributes to heightened disease vulnerability and immune dysregulation, particularly among rural female populations. Recent studies have further linked a significant association between PAH exposure and gut microbiome (GM) modifications. Considering the common embryonic origin of the intestinal and respiratory systems, cross-organ communication under conditions of PAH exposure warrants deeper exploration. Although current gut–lung axis research largely emphasizes microbial metabolites such as short-chain fatty acids and bile acids, the contribution of arachidonic acid (AA) metabolites in LMW-PAH-induced pulmonary inflammation via this axis remains poorly defined. To address this knowledge gap, we developed an animal model employing integrated 16S rRNA sequencing and metabolomics approaches to systematically examine phenanthrene (Phe) and fluorene (Flu) induced GM compositional shifts and associated metabolic reprogramming. Through comprehensive profiling, we identified candidate microorganisms and metabolites potentially involved in dysbiosis-mediated pulmonary inflammation, thereby elucidating the mechanistic basis of Phe and Flu-associated health risks.

Cadmium (Cd) is a major environmental pollutant associated with male reproductive health. Lycium barbarum polysaccharides (LBP) and selenium (Se) have been shown to protect against testicular damage. Male rats (180–200 g) were selected to construct a Cd-exposed model by intraperitoneal injection with concentrations of 0.0, 0.5, 1.0, 1.5, and 2.0 mg/kg. Then, LBP and sodium selenite (Na2SeO3) were given by gavage for treatment. The results showed that Cd accumulates in the testis in a dose-dependent manner, and compared with the control group, after Cd-exposed, the testis suffered significant toxic damage. The differences in mRNA enrichment analysis between the Cd-exposed and the control groups showed that the differential genes were mainly involved in peroxidase activity, iron regulation, and cellular energy metabolism. Compared with the Cd-exposed group, LBP and Na2SeO3 intervention could antagonize the toxic damaging effects caused by Cd, and the combined intervention of LBP and Na2SeO3 could better antagonize the toxic damaging effects caused by Cd compared with the intervention alone. In general, Cd exposure caused testicular damage, increased testicular hormonal disorders, oxidative stress damage, energy metabolism disorders, and iron atrophy in the testis, while treatment with LBP and selenium alleviated the effects of Cd-induced testicular toxicity damage.

Ventilator-associated pneumonia (VAP) is a common and life-threatening complication in ICU patients, with its occurrence closely related to ICU nurses' knowledge, attitudes, and practices. This study aimed to investigate the current status and influencing factors of ICU nurses' knowledge, attitudes, and practices regarding VAP prevention in Gansu Province, and to provide a basis for improving the effectiveness of VAP prevention. A stratified random sampling method was used to select 600 ICU nurses from 24 hospitals in Gansu Province as study participants. Data related to VAP prevention among the nurses were collected through a questionnaire survey and statistically analyzed using SPSS 26.0. The overall score of nurses on VAP prevention was 113.92 ± 8.472, with the lowest score in the knowledge dimension (7.66 ± 1.200) and higher scores in the attitude (28.67 ± 3.528) and practice (77.59 ± 5.839) dimensions. Factors such as region, ICU type, number of training sessions, and years of work experience significantly affected VAP prevention knowledge, attitudes, and practices. The knowledge scores of nurses in the Lanzhou and Zhangye regions were significantly higher than those in other regions, and nurses in comprehensive ICUs had higher VAP knowledge scores. Additionally, nurses who participated in four or more VAP prevention training sessions had significantly higher scores in all dimensions compared to those with fewer training sessions. A significant positive correlation was found between knowledge, attitudes, and practices related to VAP prevention. ICU nurses in Gansu Province performed better in the attitudes and practices of VAP prevention, but there is still room for improvement in their knowledge. Regional differences, ICU type, and the number of training sessions are important factors influencing VAP prevention and control abilities. The study suggests that enhanced training in VAP prevention and control knowledge can help improve nurses' attitudes and practical skills. To improve the effectiveness of VAP prevention, hospitals should focus on strengthening training in areas with weaker knowledge and increasing the frequency of training sessions.

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Zinc finger MYND-type containing 15 (ZMYND15) has been documented to play important roles in spermatogenesis, and mutants contribute to recessive azoospermia, severe oligozoospermia, non-obstructive azoospermia, teratozoospermia, even male infertility. ZMYND10 is involved in sperm motility. Whether environmental pollutants impair male fertility via regulating the expression of ZMYND15 and ZMYND10 has not been studied. Arsenic exposure results in poor sperm quality and male infertility. In order to investigate whether arsenic-induced male reproductive toxicity is related to the expression of ZMYND15, ZMYND10 and their target genes, we established a male rat model of sodium arsenite exposure-induced reproductive injury, measured sperm quality, serum hormone levels, mRNA and protein expressions of intratesticular ZMYND15 and ZMYND10 as well as their target genes. The results showed that, in addition to the increased mRNA expression of Tnp1, sodium arsenite exposure reduced sperm quality, serum hormone levels, and mRNA and protein expression of intratesticular ZMYND15 and ZMYND10 and their target genes in male rats compared with the control group (p < .05). Therefore, our study first showed that the environmental pollutant arsenic impairs sperm quality in male rats by reducing the expression of ZMYND10 and ZMYND15 and their regulatory genes, which provides a possible diagnostic marker for environmental pollutants-induced male infertility.

Arsenic exposure has been known to be associated with the male reproduction injury. Exploring the antidote of arsenic and ascertaining proper dose of antidote are important for detoxifying the male reproductive toxicity of arsenic. Selenium, which is essential for the male reproduction and spermatogenesis, can alleviate the toxicity of many environmental toxins, such as metals, and F. Selenium relives arsenic-induced reductions in spermatogenesis index and testicular function marker enzymes via promoting the antioxidative ability of rats. Our previous study has found that arsenic can induce reproductive toxicity by affecting the level of H3K14ac in the testis, so we further investigate whether selenium can antagonize arsenic-induced male reproductive toxicity through the H3K14ac pathway, and ascertain the appropriate dose of selenium. The results show that selenium intervention reduce the accumulation of arsenic in rat testis probably attributing to promote the excretion of arsenic from rat, then improve the testis injury induced by arsenic. Selenium intervention enhances sperm quality, testosterone level and expression of steroidogenic genes by regulating H3K14ac level and expression of its associated enzymes (KAT2A, P300, BAZ2A, HDAC3 and HDAC6), thus alleviates the male reproductive toxicity of arsenic and the proper dose of Se for mitigating arsenic male reproductive toxicity is 1mg/kg.

大气细颗粒物(fine particulate matter,PM2.5)是重要的环境健康危险因素.PM2.5暴露对包括肺部感染,异常肺功能和肺癌在内的呼吸系统疾病产生重要影响.目前已经提出了参与PM2.5不良作用的几种机制,包括氧化应激、DNA损伤、炎症反应和上皮-间充质转化(epithelial-mesenchymal transition,EMT)等[1-2].其中,EMT在多种细胞命运决定和转移过程中发挥重要作用,引起广泛关注.有机物是PM2.5的重要化学组分,其在健康相关研究最多的是多环芳烃(Polycyclic aromatic hydrocarbon,PAHs)及其衍生物.

目的 观察N-亚硝基化合物-甲基硝基亚硝基胍(MNNG)亚慢性暴露对大鼠胃黏膜组织炎性损伤的影响.方法 75只SPF级雄性Wistar大鼠(体重80～100 g)随机分为生理盐水对照组、MNNG染毒组(0.08、0.12、0.16和0.20 mg/kg),每组15只.对照组大鼠采用等量生理盐水灌胃,实验组大鼠以0.08、0.12、0.16和0.20 mg/kg MNNG灌胃染毒,同时自由饮用含30 μg/ml MNNG的水,持续染毒13周.苏木素-伊红(HE)染色观察大鼠胃组织结构改变,Western blot技术及免疫组化实验检测大鼠胃组织凋亡、炎性相关蛋白及胃癌肿瘤相关Wnt信号通路关键蛋白的表达变化.结果 大鼠胃组织切片结果显示,MNNG亚慢性暴露可引起大鼠胃黏膜糜烂、脱落、坏死,胃黏膜下出血,部分胃组织切片中可见大量炎性细胞浸润.与对照组大鼠相比,MNNG亚慢性暴露大鼠胃组织中凋亡相关蛋白Bcl-2呈明显降低趋势,而Bax,半胱氨酸天冬氨酸蛋白酶3(Caspase-3)蛋白表达量呈上升,差异有统计学意义(P＜0.05).与对照组相比,实验组大鼠Wnt信号通路关键蛋白β-catenin,p-GSK-3β,CK1,Axin1和TCF7的表达水均升高,差异具有统计学意义(P＜0.05);免疫组化结果显示,与对照组相比,MNNG亚慢性暴露大鼠胃组织Wnt信号通路关键蛋白β-catenin,p-GSK-3β表达水平升高,数据差异具有统计学意义(P＜0.05).结论 MNNG亚慢性暴露可引起大鼠胃黏膜组织结构发生炎性损伤,并引诱发胃组织凋亡、炎性相关蛋白及胃癌肿瘤相关Wnt信号通路关键蛋白的表达变化,本研究可为MNNG亚慢性暴露致大鼠胃损伤及炎性反应机制探索提供参考.

EDITORIAL article Front. Microbiol., 15 July 2022Sec. Microbiotechnology https://doi.org/10.3389/fmicb.2022.971696

目的:探讨miR-101基因簇与食管癌发病风险的关系.方法:收集3例食管癌进展期患者的新鲜组织标本进行组织芯片高通量microRNA检测,采用肿瘤基因组图谱(TCGA)数据库食管癌RNA测序数据验证的方式对miR-101基因簇表达水平进行分析;另收集33例食管癌患者癌组织和癌旁组织标本,分别提取样本总RNA,采用实时荧光定量PCR法(qPCR)检测miR-101基因簇相关基因的表达,logistic回归分析miRNA异常表达对食管癌发病风险的影响,受试者特征曲线(ROC)评价miR-101基因簇对食管癌的诊断效力,Fisher检验分析基因簇各miRNA的表达和食管癌患者临床病理指标之间的相关性.结果:miRNA芯片高通量检测及TCGA数据库生物信息学分析结果显示,与食管正常组织相比,miR-101-3p、miR-125a-5p和miR-145-5p在食管癌组织中表达下调(P<0.05).qPCR结果显示miR-101基因簇在33例食管癌组织中均呈低表达,多因素logistic回归分析显示,miR-101基因簇miR-101-3p、miR-127-5p与miR-145-5p表达水平与食管癌的发病风险呈负相关[OR(95％CI)值分别为:0.717(0.563,0.912)、0.717(0.534,0.962)和0.597(0.426,0.838),均为P<0.05];ROC分析显示miR-101基因簇曲线下面积(AUC)分别为0.753、0.792、0.763和0.800(P<0.05).此外,miR-101-3p、miR-145-5p的表达水平与食管癌患者肿瘤大小相关(P<0.05),miR-125a-5p的表达水平与患者淋巴结转移相关(P<0.05).结论:miR-101基因簇在食管癌患者癌组织中呈低表达,可作为食管癌诊断的潜在生物标志物,其在食管癌进程中的功能和调控机制有待进一步研究.

目的 探究枸杞多糖(LBP)、亚硒酸钠(Na2SeO3)对氯化镉(CdCl2)诱导的大鼠肾脏毒性的拮抗作用.方法 将40只雄性SD大鼠随机分为对照组、CdCl2组、CdCl2+LBP组、CdCl2+Na2SeO3组及CdCl2+LBP+Na2SeO3组,CdCl2腹腔注射染毒,LBP和Na2SeO3经口灌胃方式干预.染毒+干预35d后测定大鼠肾脏组织中镉质量分数,观察病理学变化,检测血清肌酐(CRE)、尿素、尿酸(UA)含量,组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)活性.结果 相比CdCl2组,各干预组可降低镉在大鼠肾脏的蓄积(P＜0.05);CdCl2+LBP+Na2SeO3组较CdCl2+LBP、CdCl2+Na2SeO3组肾脏组织结构完整,炎性渗出少.CdCl2+LBP+Na2SeO3组与CdCl2组相比,CRE、尿素、UA含量降低,与 CdCl2+Na2SeO3组相比,尿素降低(P＜0.05);CdCl2+LBP+Na2SeO3组与 CdCl2、CdCl2+LBP、CdCl2+Na2SeO3组相比,大鼠肾脏中SOD、GSH-Px活性升高,MDA活性降低(P＜0.05).结论 LBP和Na2SeO3联合干预可以增强大鼠肾脏的抗氧化能力,拮抗CdCl2对大鼠的肾脏毒性.

Recalcitrancy in microplastics (MPs) contributes to white pollution. Bioremediation can remove MPs and facilitate environmental sustainability. Although recent studies have been conducted on the interaction of algae and MPs, the role of algae in MP removal with the simultaneous implementation of 'omics studies has not yet been discussed. Here, we review the adverse effects of MPs on the environment and possible approaches to remove them from the aquatic environment by using algae. We highlight the mechanism of MP biodegradation, the algal species that have been used, and how these are affected by MPs. We propose that algomics, characterization of biodegrading enzymes, and genetic engineering could be effective strategies for optimizing MP degradation.