作者：
Luo, Sihuan;Zhao, Xiaomei;Wang, Yijin;Jiang, Miao;Cao, Yi
期刊：
Food and Chemical Toxicology,2025年197:115304 ISSN：0278-6915
通讯作者：
Cao, Y
作者机构：
[Zhao, Xiaomei; Wang, Yijin; Luo, Sihuan; Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Jiang, Miao] Univ South China, Inst Cardiovasc Dis, Hengyang Med Coll, Key Lab Arteriosclerol Hunan Prov,Hunan Int Sci &, Hengyang 421001, Peoples R China.
通讯机构：
[Cao, Y ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
关键词：
Autophagy;In vivo toxicity;Lipid profiles;Nanoplastics;Oral exposure
摘要：
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
The wide uses of plastics lead to nanoplastic exposure in reality. Previous studies reported that micro- and nano-plastics (MNPs) disrupted metabolism, but few studies investigated lipid profile changes. Hereby, we exposed mice to vehicles (control), 0.05 or 0.5 mg/kg 20 or 100 nm nanoplastics via gavage, once a day, for 14 days. Albeit no obvious tissue damage, lipidomics data revealed 76 up-regulated and 29 down-regulated lipid molecules in mouse intestines. Further analysis revealed that a number of up-regulated lipid molecules belong to glycerophospholipid (GP). Among GP, we noticed an up-regulation of 9 phosphatidylserine (PS) molecules, and we further verified the presence of autophagosomes and co-localization of typical autophagic lipolysis proteins in intestinal sections, as well as decreased lysosomal associated protein 2 (LAMP2) and increased adipose triglyceride lipase (ATGL) in intestinal homogenates, indicating perturbed autophagic pathway. The exposure also up-regulated 9 phosphatidylinositol (PI) molecules, and we verified a significant decrease of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), indicating altered PI3K-signaling pathway. Besides GP, nanoplastics also significantly up-regulated some sphingolipids (SP), such as ceramide (Cer), and some sterol lipids, such as cholesterol derivatives. Combined, these results suggested that oral exposure to nanoplastics altered lipid profiles and related signaling pathway in mouse intestines.
期刊：
International Journal of Molecular Sciences,2025年26(14) ISSN：1661-6596
通讯作者：
Zhou, Ping-Kun;Gu, YQ
作者机构：
[Wang, Yilong; Zhu, Jiaojiao; Zhou, Lin; Yan, Ziyan; Gu, Yongqing; Liu, Yuhao; Zhou, Ping-Kun] Beijing Inst Radiat Med, Beijing 100850, Peoples R China.;[Chen, Huixi; Gu, Yongqing] Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Hou, Yifan; Gu, Yongqing] Hebei Univ, Coll Life Sci, Baoding 071001, Peoples R China.;[Zhang, Xinyu; Gu, Yongqing] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;[Chen, Zhongmin] PLA Rocket Force Characterist Med Ctr, Beijing 100850, Peoples R China.
通讯机构：
[Zhou, PK; Gu, YQ ] B;Beijing Inst Radiat Med, Beijing 100850, Peoples R China.;Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;Hebei Univ, Coll Life Sci, Baoding 071001, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
关键词：
DNA methylation;MassArray;RRBS;episignatures;lung cancer;radon
摘要：
Radon (Rn) exposure has a strong association with lung cancer risk and is influenced by epigenetic modifications. To investigate the characterization of DNA methylation (DNAm) episignatures for radon-induced lung cancer, we detected the specific changes in DNAm in blood and lung tissues using reduced representation bisulfite sequencing (RRBS). We identified the differentially methylated regions (DMRs) induced by radon exposure. The bioinformatics analysis of the DMR-mapped genes revealed that pathways in cancer were affected by radon exposure. Among them, the DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 were repeated between lung tissue and blood, and validated by the MassArray. In addition, radon exposure promoted lung cancer development in the genetic engineering mouse model (GEMM), accompanied by decreased MAPK10 and increased PLCG1, PLCβ3, and PIK3R2 with mRNA and protein levels. Conclusively, radon exposure significantly changes the genomic DNAm patterns in lung tissue and blood. The DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 have a significant influence on radon-induced lung cancer. This brings a new perspective to understanding the pathways involved in radon-induced lung cancer and offers potential targets for developing blood-based biomarkers and epigenetic therapeutics.
摘要：
BACKGROUND: Studies have documented associations among workplace violence (WPV), psychological capital (PsyCap), and professional commitment (PC). But limited research has investigated how PsyCap mediates the relationship between WPV and PC, particularly among nursing interns. OBJECTIVE: This study assessed the current status of WPV, PsyCap, and PC among Chinese nursing students, analyzed thier interrelationships and further determined whether PsyCap mediated the association between WPV and PC. METHODS: A cross-sectional survey of 520 nursing interns used validated instruments: a demographic questionnaire, the WPV Scale, the PC Scale, and the PsyCap Questionnaire (Chinese version of PCQ). Pearson correlation analyzed the relationships among PsyCap, WPV, and PC, while hierarchical regression tested the mediation model. RESULTS: The total scores for PC and PsyCap among nursing students were (77.04 ± 17.04) and (91.90 ± 16.16), respectively. Approximately 31.54% of the participants reported experiencing WPV. PsyCap was inversely associated with WPV (r = -0.619, p = 0.024) and positively associated with PC (r = 0.620, p < 0.001), in contrast WPV showed a negative correlation with PC (r = -0.807, p = 0.005). Mediation analysis revealed that PsyCap mediated the WPV-PC relationship, accounting for 47.5% of the total effect. CONCLUSION: Nursing students exhibited moderate levels of PsyCap and PC, with the prevalence of WPV being slightly lower than reported in comparable studies. And PsyCap fully mediated the relationship between WPV and PC. These findings revealed that nursing administrators and educators should enhance and develop nursing students' PsyCap to lower the adverse effects of WPV and promote higher levels of PC.
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES,2025年88(10):385-394 ISSN：1528-7394
通讯作者：
Yang, Yue;Yang, F;Yang, Y
作者机构：
[Zhang, Yin; Yang, F; Dai, Manni; Yang, Yue; Yang, Fei; Guan, Ying] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Yang, Yue] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Yang, Yue] Cent Hosp Shaoyang, Dept Publ Hlth, Shaoyang, Peoples R China.;[Yang, F; Yang, Fei] Hunan Prov Maternal & Child Hlth Care Hosp, Changsha, Hunan, Peoples R China.
通讯机构：
[Yang, F ; Yang, Y] U;[Yang, Y ] C;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;Cent Hosp Shaoyang, Dept Publ Hlth, Shaoyang, Peoples R China.;Hunan Prov Maternal & Child Hlth Care Hosp, Changsha, Hunan, Peoples R China.
摘要：
Microcystin-LR (MC-LR) a cyclic toxin produced by cyanobacterial species is known to exert detrimental effects on various organs, including lung. Several investigators demonstrated that MC-LR exerts pulmonary toxicity, but the underlying mechanisms remain unclear. This study aimed to investigate whether exposure to MC-LR-induced lung inflammation and examine the underlying mechanisms. Thirty specific pathogen-free (SPF) male mice were allocated into control and MC-LR treatment groups. Mice were intraperitoneally injected with physiological saline or MC-LR (20 mu g/kg) daily for a total of 21 days. Our findings indicated that exposure to MC-LR-produced histopathological changes in lung tissue, including thickening of alveolar walls and inflammatory infiltration. MC-LR was found to upregulate mRNA expression levels of pro-inflammatory cytokines TNF alpha, IL-6, IL-1 beta, and IL-18. Further, MC-LR significantly elevated the expression levels of proteins associated with the NF-kappa B/NLRP3 pathway p-NF-kappa B, NLRP3, Caspase-1, ASC. The activation of NF-kappa B/NLRP3 pathway further promoted the release of inflammatory cytokine IL-1 beta and cleavage of pyroptosis-associated GSDMD protein. These findings indicate that MC-LR may induce lung inflammation by promoting cell pyroptosis via the activation of the NF-kappa B/NLRP3 pathway.
作者机构：
[Tian, Qingzhen; Tang, Zheng; Zhang, Ziyu; Niu, Xiangheng; Li, Shu] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Lin, YH; Du, Dan; Niu, Xiangheng; Lin, Yuehe] Washington State Univ, Sch Mech & Mat Engn, Pullman, WA 99164 USA.;[Zhang, Xiao] Washington State Univ, Sch Chem Engn & Bioengn, Pullman, WA 99164 USA.
通讯机构：
[Lin, YH ; Niu, XH] W;[Niu, XH ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Washington State Univ, Sch Mech & Mat Engn, Pullman, WA 99164 USA.
关键词：
biomarkers;biomedical applications;catalytic signal amplifications;disease diagnosis;nanozymes
摘要：
An overview of nanozyme‐enabled biomedical sensing and diagnosis is presented. The preparation of nanozymes is first summarized, followed by a discussion of typical strategies that are applied to promote the catalytic specificity and activity of nanozymes; whereafter, the main use of nanozymes in biomarker detection and disease diagnosis is discussed; finally, development trends are forecasted, and corresponding challenges are also pointed out. Abstract As nanoscale materials with the function of catalyzing substrates through enzymatic kinetics, nanozymes are regarded as potential alternatives to natural enzymes. Compared to protein‐based enzymes, nanozymes exhibit attractive characteristics of low preparation cost, robust activity, flexible performance adjustment, and versatile functionalization. These advantages endow them with wide use from biochemical sensing and environmental remediation to medical theranostics. Especially in biomedical diagnosis, the feature of catalytic signal amplification provided by nanozymes makes them function as emerging labels for the detection of biomarkers and diseases, with rapid developments observed in recent years. To provide a comprehensive overview of recent progress made in this dynamic field, here an overview of biomedical diagnosis enabled by nanozymes is provided. This review first summarizes the synthesis of nanozyme materials and then discusses the main strategies applied to enhance their catalytic activity and specificity. Subsequently, representative utilization of nanozymes combined with biological elements in disease diagnosis is reviewed, including the detection of biomarkers related to metabolic, cardiovascular, nervous, and digestive diseases as well as cancers. Finally, some development trends in nanozyme‐enabled biomedical diagnosis are highlighted, and corresponding challenges are also pointed out, aiming to inspire future efforts to further advance this promising field.
摘要：
Endothelial cells (ECs) are interior surface cells covering blood vessels, which play a crucial role in maintaining vascular homeostasis. In vascular pharmacology and toxicology, ECs directly contact drugs or toxicants entering circulation. Therefore, the bio-effects of pharmacological/toxicological substances on ECs have gained extensive research interest, which needs to be evaluated by reliable models. Human umbilical vein endothelial cells (HUVECs) have been served as versatile platforms to mimic diverse pathophysiological processes in vitro, stemming from their unique fetal arterial-like exposure microenvironment, expression of key EC markers, and comparable EC responses to various pathophysiological stimuli. This review provides an overview of the application of HUVECs in pharmacology and toxicology, with a focus on their utility and limitations. HUVECs have been widely used to model the effects of pharmacological or toxicological substances on material exchange, barrier functions, cell death, endothelial nitric oxide synthase (eNOS) uncoupling, and EC dysfunction, angiogenesis, and thrombosis. However, their applicability is constrained primarily due to vascular-type and organ-specific heterogeneity. The review highlights key mechanisms investigated using HUVECs, including oxidative stress, inflammation, organelle damage, and autophagy, metabolic reprogramming (endometabolism), and epigenetic regulation. Strategies to overcome HUVECs' limitations, such as microfluidic techniques, co-culture, and organoid models, are discussed. Finally, future directions are outlined, emphasizing the integration of HUVECs into multi-scale models, dynamic microenvironment simulations, artificial intelligence (AI)-assisted big data analysis, and patient-derived ECs for precision toxicology and personalized medicine. This review aims to guide researchers in optimizing the use of HUVECs in pharmacological and toxicological studies.
摘要：
Microcystin-LR (MC-LR) is a toxin that causes hepatic steatosis. Our previous study found that exposure to 60 μg/L MC-LR for 9 months resulted in liver lipid accumulation, but the underlying mechanisms remain elusive. Herein, for the first time, fatty acid-targeted metabolome and RNA-seq were combined to probe the effect and mechanism of chronic (12-month) MC-LR treatment on mice lipid metabolism at environmental-related levels (1, 60, and 120 μg/L). It was found that MC-LR dose-dependently raised serum and liver lipid levels. The total cholesterol (TC) levels in the liver were significantly increased following treatment with 1 μg/L MC-LR (equivalent to 0.004 μ/L in human). Treatment with 60 and 120 μg/L MC-LR significantly elevated TC and triglyceride (TG) levels in both serum and liver. Serum fatty acid-targeted metabolome analysis demonstrated that exposure to 1, 60, and 120 μg/L MC-LR caused significant alterations in the fatty acid profile. Chronic 1, 60, and 120 μg/L MC-LR treatment significantly increased serum polyunsaturated fatty acids (PUFAs), including conjugated linoleic acid and eicosapentaenoic acid, which positively correlated with serum or liver TG levels. Chronic exposure to 120 μg/L MC-LR led to a significant decrease in the accumulation of saturated fatty acids, including citramalic acid, pentadecanoic acid, and docosanoic acid, which were negatively correlated with serum or liver lipid levels. These findings suggested that 1 μg/L MC-LR exposure caused mild lipid metabolism disruption, while 60 and 120 μg/L MC-LR treatment resulted in pronounced hepatic steatosis in mice. Transcriptome analysis revealed that chronic environmental MC-LR treatment regulated the expression of genes involved in the phosphatidylinositol 3-kinase (PI3K) complex and fatty acid metabolism. Western blotting and RT-qPCR confirmed that chronic environmental MC-LR exposure activated the PI3K/AKT/mTOR signaling pathway, the downstream of fads3 gene that participates in fatty acid desaturation was upregulated, fatty acid degradation-related genes, including acsl1, acsl4, and ehhadh were inhibited, and lipid transport-related genes, including slc27a4 and apol7a, were promoted. Thus, chronic environmental MC-LR exposure boosts hepatic steatosis. Our work indicated that the limit concentration of 1 μg/L MC-LR in human drinking water for safety needs to be discussed. The study provides the first evidence of the fatty acid profile and gene changes and gains new insights into the mechanisms of chronic environmental MC-LR treatment-induced hepatic steatosis.
作者机构：
[Yao, Xiang-Rong; He, Jun-Yan] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;[Yao, Xiang-Rong; Xiao, Fang-Zhu] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Xiao, Wen-Tao] Nantong Univ, Affiliated Hosp, Med Sch, Dept Radiat Oncol, Nantong, Peoples R China.;[Huang, Cui-Qin] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
通讯机构：
[He, JY ; Huang, CQ ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
摘要：
Head and neck squamous cell carcinoma (HNSC) is a prevalent and aggressive malignancy with poor prognosis, underscoring the need for novel biomarkers and therapeutic strategies. This study investigates the role of C16orf74 as a potential diagnostic and prognostic biomarker in HNSC. Bioinformatics analyses revealed that C16orf74 is significantly overexpressed in HNSC and is associated with advanced disease stages, therapy resistance, and shorter overall and progression-free survival. A prognostic nomogram integrating C16orf74 expression with clinicopathological features demonstrated robust predictive performance. Functional enrichment and immune infiltration analyses suggest that high C16orf74 expression might contribute to an immunosuppressive tumor microenvironment by reducing key immune cell populations, such as B cells, T cells, and natural killer cells, which are critical for anti-tumor immunity. Moreover, C16orf74 expression was inversely associated with immune checkpoint expression and immunotherapy response, highlighting its potential as a predictive biomarker for immune checkpoint blockade (ICB) efficacy. Drug sensitivity analyses identified potential therapeutic agents, including arsenic trioxide, carmustine, vincristine, quercetin, and carboplatin for patients with high C16orf74 expression. These findings highlight the potential of C16orf74 as a biomarker and therapeutic target to improve HNSC management.
摘要：
The combined effect of environmental exposure and dietary behavior plays a vital role in the occurrence of diseases. Bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used substitutes for bisphenol A (BPA). Previous studies have shown that the combined exposure to BPA and fructose caused significant disturbances in glycolipid metabolism in adipose tissue, however, the interference caused by the combined exposure to BPS and fructose or BPF and fructose on adipose tissue is still unclear. In the present study, we performed a integrated analysis of targeted energy metabolomics and widely targeted quantitative lipidomics on the adipose tissue of Sprague Dawley rats after combined exposure to 2 levels of BPS or BPF (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months. Based on the results, lower dose BPS combined with fructose increased succinate significantly, while higher dose BPS or lower dose BPF combined with fructose decreased succinate significantly. Additionally, lower dose BPS combined with fructose might lead to polyunsaturated lipid depletion, while higher dose BPS combined with fructose exposure might lead to choline and carnitine depletion; lower dose BPF combined with fructose might inhibit lipolysis, while higher dose BPF combined with fructose might cause accumulation of free fatty acids. These results indicated the response patterns of adipose tissue to different dose of BPS or BPF combined with fructose were significantly different, and the adipocyte succinate signaling pathway might be the important target for metabolic remodeling in adipose tissue.
期刊：
CURRENT ANALYTICAL CHEMISTRY,2025年20(9):1199-1212 ISSN：1573-4110
通讯作者：
Tan, Yan;Xiao, XL
作者机构：
[Chen, Zijie; Tan, Yan; Tan, Y; Xiao, Xilin; Huang, Shaorong; Wu, Qian; Xiao, XL; Liu, Zhen] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.;[Liu, Jingjing] Univ South China, Sch Chem & Chem Engn, Hengyang, Hunan, Peoples R China.;[Xiao, Xilin] Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Changsha, Hunan, Peoples R China.
通讯机构：
[Tan, Y; Xiao, XL ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Hunan, Peoples R China.
关键词：
Magnetic nanoparticles;MnFe2O4;graphene oxide;treatment;adsorption;uranium ions.
摘要：
Background: The problem of nuclear water pollution is becoming serious worldwide. Uranium, as a metal substance with long half-life radioactivity, is commonly treated by various methods. Adsorption is considered to be one of the most promising methods for treating uraniumcontaining wastewater.<&wdkj&>Method: Magnetic nanoparticles MnFe2O4 were prepared via the coprecipitation method, followed by modification of silica using the improved Stöber method. Subsequently, amino was functionalized and grafted onto graphene oxide to prepare a novel magnetic graphene oxide composite MnFe2O4@SiO2-NH2@GO.<&wdkj&>Results: The highest adsorption rate of MnFe2O4@SiO2-NH2@GO for uranium can reach 97.27% in 1 mg·L-1 uranium solution, and the adsorption process conformed to the quasi-second-order kinetic model and Langmuir adsorption isotherm model, indicating that it was a monolayer adsorption dominated by chemisorption. The adsorption thermodynamic parameters demonstrated that the adsorption process was a spontaneous endothermic reaction.<&wdkj&>Conclusion: MnFe2O4@SiO2-NH2@GO had excellent adsorption properties for uranium, which has great application potential in the treatment of low-concentration uranium-containing wastewater.
通讯机构：
[Xiao, FB ] U;[Du, WF ] H;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;Hunan Inst Technol, Sch Chem & Environm Engn, Hengyang 421002, Peoples R China.
关键词：
Glutathione;Structural color hydrogel;Competitive coordination reaction;Colorimetric detection;Smartphone-assisted detection
摘要：
AnAg(+)-functionalized structural color hydrogel (Ag(+)-SCH) sensor is constructed for colorimetric detection of glutathione (GSH). The hydrogel is prepared by using the coordination of Ag(+) and 1-vinylimidazole (1-VI) as cross-linking network. GSH acts as a competitive ligand to break the coordination between Ag(+) and 1-VI, leading to the expansion and structural color change of the hydrogel. Quantification was achieved by measuring particle spacing changes, yielding a dynamic range of 0.1-200μM with a limit of detection (LOD) of 0.04μM. Alternatively, smartphone-based hue analysis enables sensitive GSH detection with a LOD of 0.79μM. The sensor has proven to show high selectivity, excellent reusability, and long-term stability. In human serum tests, the Ag(+)-SCH performed comparably to commercial kits, while offering significantly lower cost. This portable, low-cost platform meets practical needs for GSH monitoring in diverse settings.
关键词：
Drug reposition;Enrichment score;Immunoregulation;LINCS;Lenalidomide;Radioprotection
摘要：
Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.
摘要：
Although the adverse effects induced by acute high-dose radiation from nuclear accidents have been intensively explored, the biological effects of low-dose radiation remain unclear. This study aimed to identify the role of low-dose radiation in three-dimensional (3D) lung organoids using transcriptomic and metabolomic analyses. An irradiation dose of 0 01 Gy was utilized to simulate environmental radiation exposure. Lung organoids were included in the study. Through metabolomic analysis, compared to the control, 290, 284, and 492 metabolites were significantly up-regulated, while 150, 605, and 310 metabolites were significantly down-regulated in the 0.01 Gy, 0.05 Gy, and 2 Gy groups, respectively. However, only the metabolites in the glycerophospholipid metabolism pathway increased significantly in the group treated with 0. 01 Gy radiation, with the lipid substances Carnitine C18:0(Car (18: 0)), palmitoylcarnitine, and PE (18: 3 (9 Z, 12 Z, 15 Z)/P- 16: 0) showing the most significant increase. Significantly, compared to the control, lipid metabolism can be affected by 0.01 Gy radiation. Furthermore, these altered lipid metabolites, such as triglycerides and sterols, were enriched in pathways related to cell signaling and affected cell proliferation, differentiation, and death after bioinformatics analysis. Through transcriptomic analysis, compared with the 0 Gy group, the expression of 19 genes in the 0.01 Gy group was up-regulated, while the expression of 6 genes was down-regulated. The 0.01 Gy irradiation affects the cardiac muscle contraction pathway and glycerolipid metabolism pathway. Moreover, using lung epithelial cells, we further identified that compared with the control group, there was no significant change in cystine uptake capacity, lipid peroxide levels, or mitochondrial membrane potential under irradiation conditions of 0.01 Gy and 0.05 Gy. In summary, our combined transcriptomic and metabolomic analysis of lung organoids provides an effective approach to understanding the biological effects of low-dose radiation exposure.
Although the adverse effects induced by acute high-dose radiation from nuclear accidents have been intensively explored, the biological effects of low-dose radiation remain unclear. This study aimed to identify the role of low-dose radiation in three-dimensional (3D) lung organoids using transcriptomic and metabolomic analyses. An irradiation dose of 0 01 Gy was utilized to simulate environmental radiation exposure. Lung organoids were included in the study. Through metabolomic analysis, compared to the control, 290, 284, and 492 metabolites were significantly up-regulated, while 150, 605, and 310 metabolites were significantly down-regulated in the 0.01 Gy, 0.05 Gy, and 2 Gy groups, respectively. However, only the metabolites in the glycerophospholipid metabolism pathway increased significantly in the group treated with 0. 01 Gy radiation, with the lipid substances Carnitine C18:0(Car (18: 0)), palmitoylcarnitine, and PE (18: 3 (9 Z, 12 Z, 15 Z)/P- 16: 0) showing the most significant increase. Significantly, compared to the control, lipid metabolism can be affected by 0.01 Gy radiation. Furthermore, these altered lipid metabolites, such as triglycerides and sterols, were enriched in pathways related to cell signaling and affected cell proliferation, differentiation, and death after bioinformatics analysis. Through transcriptomic analysis, compared with the 0 Gy group, the expression of 19 genes in the 0.01 Gy group was up-regulated, while the expression of 6 genes was down-regulated. The 0.01 Gy irradiation affects the cardiac muscle contraction pathway and glycerolipid metabolism pathway. Moreover, using lung epithelial cells, we further identified that compared with the control group, there was no significant change in cystine uptake capacity, lipid peroxide levels, or mitochondrial membrane potential under irradiation conditions of 0.01 Gy and 0.05 Gy. In summary, our combined transcriptomic and metabolomic analysis of lung organoids provides an effective approach to understanding the biological effects of low-dose radiation exposure.
摘要：
Microcystin-LR (MC-LR), a potent cyclic heptapeptide hepatotoxin released by Microcystis aeruginosa , poses significant threats to aquatic ecosystems and human health. Although microbial degradation provides an eco-friendly remediation strategy, approaches to actively modulate microbial physiology for improved detoxification remain poorly defined. Here, we hypothesize that bioelectrochemical stimulation via microbial fuel cells (MFCs) can enhance the metabolic activity and MC-LR degradation capacity of the facultative anaerobe Alcaligenes faecalis D04 ( A. faecalis D04) through extracellular electron transfer (EET). Upon anodic colonization of A. faecalis D04, MC-LR degradation efficiency increased from 11.2 % (open-circuit control) to 70 % within 48 h (500 Ω external resistor). Acetate supplementation elevated the relative abundance of A. faecalis D04 to 7 % in the anodic community, suggesting improved colonization and activity under electroactive conditions. Moreover, optimizing the external resistance to 50 Ω led to increased current generation and further boosted degradation efficiency to 80 %. Electrochemical cultivation in a three-electrode system confirmed that the anodic potentials (−0.3 V vs. Ag/AgCl) significantly enhanced the electroactivity of A. faecalis D04, producing current responses of −85 μA and achieving 52 % MC-LR removal ratio lifting with substantial detoxification, as confirmed via Ames assays. Mechanistic insights from RT-qPCR analyses showed that bioelectrochemical stimulation upregulated genes associated with MC-LR biodegradation and key metabolic pathways. Our findings establish a mechanistic link between EET activity and enhanced anaerobic toxin degradation, offering a scalable framework for the electrochemical control of pollutant-degrading microbial systems.
Microcystin-LR (MC-LR), a potent cyclic heptapeptide hepatotoxin released by Microcystis aeruginosa , poses significant threats to aquatic ecosystems and human health. Although microbial degradation provides an eco-friendly remediation strategy, approaches to actively modulate microbial physiology for improved detoxification remain poorly defined. Here, we hypothesize that bioelectrochemical stimulation via microbial fuel cells (MFCs) can enhance the metabolic activity and MC-LR degradation capacity of the facultative anaerobe Alcaligenes faecalis D04 ( A. faecalis D04) through extracellular electron transfer (EET). Upon anodic colonization of A. faecalis D04, MC-LR degradation efficiency increased from 11.2 % (open-circuit control) to 70 % within 48 h (500 Ω external resistor). Acetate supplementation elevated the relative abundance of A. faecalis D04 to 7 % in the anodic community, suggesting improved colonization and activity under electroactive conditions. Moreover, optimizing the external resistance to 50 Ω led to increased current generation and further boosted degradation efficiency to 80 %. Electrochemical cultivation in a three-electrode system confirmed that the anodic potentials (−0.3 V vs. Ag/AgCl) significantly enhanced the electroactivity of A. faecalis D04, producing current responses of −85 μA and achieving 52 % MC-LR removal ratio lifting with substantial detoxification, as confirmed via Ames assays. Mechanistic insights from RT-qPCR analyses showed that bioelectrochemical stimulation upregulated genes associated with MC-LR biodegradation and key metabolic pathways. Our findings establish a mechanistic link between EET activity and enhanced anaerobic toxin degradation, offering a scalable framework for the electrochemical control of pollutant-degrading microbial systems.
摘要：
African swine fever virus (ASFV) predominantly infects Argasidae and suids, resulting in high morbidity and mortality in pigs. Despite the crucial role that viral sequences resembling those of the host play in the virus's survival, there are limited comprehensive studies on the genomic similarities between ASFV and its hosts. Consequently, this study employs homology analysis to construct a similarity network between ASFV and its hosts (Argasidae and suids), investigating the distribution, function, evolution, and origins of these similar sequences in ASFV. Our findings indicate that the host-similar fragments are mainly distributed between positions 70000 and 180000 of the ASFV genome, primarily within non-coding regions. Notably, these non-coding fragments are often associated with promoter functions. Furthermore, the analysis of suid proteins that share similarities with ASFV proteins reveals that they predominantly exhibit RNA polymerase activity and are involved in metabolic processes. Evolutionary analysis indicates that pan-similar sequences of ASFV exist in an open state, highlighting the diversity of these analogous sequences. Additionally, a positive correlation was identified between the occurrence of recombination breakpoints and similar sequences, indicating that homologous recombination may serve as a crucial mechanism driving the formation of these analogous sequences.
作者机构：
[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Liu, Cong] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Hlth Inspect & Quarantine, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, ZK ] U;Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.
摘要：
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle , which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process . This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development , influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle , which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process . This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development , influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
摘要：
INTRODUCTION: Carbapenem-resistant (CR) Gram-negative pathogens are classified by the WHO as critical threats due to limited therapeutic options. Cefiderocol (CFD), a novel siderophore cephalosporin, shows promise but remains unapproved in China. This study investigated the prevalence, clinical impact, and genetic mechanisms of cefiderocol heteroresistance (CFD-HR) in CR and ESBL-producing clinical isolates from China, where CFD remains unapproved. METHODS: A total of 407 CR and ESBL-producing isolates were analyzed. CFD-HR was identified by population analysis profiles (PAPs). Clinical relevance was assessed through disk diffusion susceptibility testing, time-kill assays, and a murine peritonitis model. Genetic mechanisms and stability were elucidated by whole-genome sequencing (WGS) and fitness cost assays. RESULTS: CFD-HR prevalence was 17.4% (16/92) in carbapenem-resistant A. baumannii (CRAB), 27.9% (24/86) in carbapenem-resistant P. aeruginosa (CRPA), 23.8% (10/42) in carbapenem-resistant E. coli (CRE), and ≤10% (1/10 in ESBL-producing P. aeruginosa and 8/177 in ESBL-producing E. coli). Although 72.9% (43/59) of HR isolates were classified as CFD-susceptible by disk diffusion, time-kill assays showed that 66.7% (4/6) of HR strains required ≥8 mg/L CFD (vs. 4 mg/L for non-HR) to prevent regrowth. In vivo, CFD achieved 100% (3/3) survival in non-HR infections but only 16.7% (4/6) in HR-infected mice. WGS identified transient genetic alterations in HR subpopulations, including sitABCD duplications (CRE), oprD mutations (CRAB), and vgrG SNPs (CRPA), which reverted after antibiotic withdrawal. Fitness cost assays revealed unstable growth deficits in 33.3% (2/6) of HR subpopulations, correlating with genetic instability. DISCUSSION: These findings highlight the clinical significance of CFD-HR, even in susceptible isolates, and underscore the need for improved diagnostic methods to detect HR and monitor cross-resistance, offering critical insights for regions transitioning to CFD implementation.
摘要：
A multifunctional electrochemiluminescence (ECL) coreaction accelerator, AuAgPt nanoframes (NFs), is described for use in an ECL aptasensor for highly sensitive aflatoxin B1 (AFB1) detection. As a signal quencher, the broad UV-vis absorption spectrum of AuAgPt nanosheets (NSs) overlaps the ECL emission spectrum of g-C(3)N(4)@Au, triggering an ECL resonance energy transfer (ECL-RET). By the adjustment of the dosage of hydrogen peroxide (H(2)O(2)), the AuAgPt NSs are transformed into AuAgPt NFs because H(2)O(2) etches Ag in AuAgPt NSs into Ag(+), which disrupts the RET process. The as-formed AuAgPt NFs act as a coreaction accelerator to enhance the ECL response of the g-C(3)N(4)@Au/K(2)S(2)O(8) system. Without AFB1, the Ag-dependent DNAzyme is inactive, and a strong ECL signal is observed. After AFB1 is added, the AFB1 aptamer targets AFB1 and the DNAzyme active site is exposed. As-generated Ag(+) further activates DNAzyme to cut the substrate strand (S-DNA), which causes AuAgPt NFs to detach from the electrode surface and the ECL signal to significantly decrease. Under optimal conditions, the proposed ECL aptasensor exhibits high sensitivity with a limit of detection (LOD) of 0.11 fg/mL in the range of 1 fg/mL to 1 μg/mL for AFB1 detection.
摘要：
While numerous genetic risk loci are linked to kidney disease, a unifying therapeutic target for diverse renal pathologies remains elusive. Here, through large-cohort polymorphic locus screening, we identify the SLC39A8 A391T variant (rs13107325) as a shared modifier of multiple kidney diseases. Functional characterization using Slc39a8 A391T knock-in mice and kidney-specific Slc39a8 knockout mice reveals that loss of SLC39A8 function reduces renal zinc accumulation, thereby mitigating susceptibility to kidney injury and disease progression. Mechanistically, we demonstrate that perturbed zinc homeostasis drives renal damage, and limiting zinc levels-whether via impaired SLC39A8 activity or direct chelation-activates the zinc-AKT-FOXO1-G6PC axis to confer protection. Critically, zinc chelation with EDTA recapitulates this benefit, significantly preventing and ameliorating experimental acute and chronic kidney disease. These findings establish renal zinc homeostasis as a key therapeutic node, with SLC39A8 and zinc-modulating strategies representing promising avenues for treating a broad range of kidney diseases.
