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.
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.
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.
期刊：
Science of The Total Environment,2025年958:178088 ISSN：0048-9697
通讯作者：
Fei Yang<&wdkj&>Hongli Tan
作者机构：
[Li, Jing] School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China;[Li, Jing] Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education, Xi'an 710061, China;[Yang, Liu] School of Geography, Earth & Environmental Sciences, University of Birmingham, Birmingham B15 2TT, UK;[Ding, Yuying] Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China;[Ding, Yuying] School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China
通讯机构：
[Fei Yang] H;[Hongli Tan] G;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, China
关键词：
Health risk;Indoor dust;Organophosphate esters;Spatial variations;Temporal trends
摘要：
This study investigated the presence of 20 organophosphate esters (OPEs) in indoor dust samples collected from the Chinese cities of Lanzhou, Xining, and Lhasa. The results demonstrate the ubiquitous presence of most OPEs in these three cities, with the highest concentrations of ΣOPEs found in Xining. We also summarized the occurrence of OPEs in indoor environments from 38 studies with 1875 samples collected across various regions of mainland China from 2012 to 2023. The weighted-median concentration of ΣOPEs in indoor dust exhibited region-specific variations, range from 381.9 to 6622.5 ng/g. Chloroalkyl-OPEs (Cl-OPEs) (e.g., tris(2-chloroethyl) phosphate (TCEP), tri(1-chloro-2-propyl) phosphate (TCIPP), and tri (1,3-dichloro-2-propyl) phosphate (TDCIPP)) predominated in all seven regions (range: 38.9 %–71.4 %). TCIPP was predominant in the Central China, North China, Northeast China, Northwest China, Southwest China, and Southwest China regions, while TCEP dominated in the Eastern China region. A significant downward trend in OPE concentrations in indoor environments was observed during the investigated period. Dust ingestion was identified as the predominant pathway of human exposure to OPEs indoors. The hazard quotients for Cl-OPEs were below the non-carcinogenic threshold, suggesting significant health risks are unlikely. This study underscores the widespread occurrence of OPEs in indoor dust across mainland China, emphasizing the necessity for ongoing monitoring and regulation of these chemicals.
This study investigated the presence of 20 organophosphate esters (OPEs) in indoor dust samples collected from the Chinese cities of Lanzhou, Xining, and Lhasa. The results demonstrate the ubiquitous presence of most OPEs in these three cities, with the highest concentrations of ΣOPEs found in Xining. We also summarized the occurrence of OPEs in indoor environments from 38 studies with 1875 samples collected across various regions of mainland China from 2012 to 2023. The weighted-median concentration of ΣOPEs in indoor dust exhibited region-specific variations, range from 381.9 to 6622.5 ng/g. Chloroalkyl-OPEs (Cl-OPEs) (e.g., tris(2-chloroethyl) phosphate (TCEP), tri(1-chloro-2-propyl) phosphate (TCIPP), and tri (1,3-dichloro-2-propyl) phosphate (TDCIPP)) predominated in all seven regions (range: 38.9 %–71.4 %). TCIPP was predominant in the Central China, North China, Northeast China, Northwest China, Southwest China, and Southwest China regions, while TCEP dominated in the Eastern China region. A significant downward trend in OPE concentrations in indoor environments was observed during the investigated period. Dust ingestion was identified as the predominant pathway of human exposure to OPEs indoors. The hazard quotients for Cl-OPEs were below the non-carcinogenic threshold, suggesting significant health risks are unlikely. This study underscores the widespread occurrence of OPEs in indoor dust across mainland China, emphasizing the necessity for ongoing monitoring and regulation of these chemicals.
作者机构：
[Yao, Xiang-Rong; He, Jun-Yan] Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China;[Yao, Xiang-Rong; Xiao, Fang-Zhu] School of Public Health, University of South China, Hengyang, China;[Xiao, Wen-Tao] Department of Radiation Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong University, Nantong, China;[Huang, Cui-Qin] Department of Pathology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 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.
期刊：
Biosensors and Bioelectronics,2025年267:116756 ISSN：0956-5663
通讯作者：
Xiangheng Niu
作者机构：
[Niu, Xiangheng; Zhu, Hengjia] School of Agricultural Engineering, Jiangsu University, Zhenjiang, 212013, PR China;[Niu, Xiangheng; Zhu, Hengjia] School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China;[Liu, Bangxiang; Hu, Panwang] School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China;[Pan, Jianming] School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: pjm@ujs.edu.cn;[Xu, Lizhang] School of Agricultural Engineering, Jiangsu University, Zhenjiang, 212013, PR China. Electronic address: justxlz@ujs.edu.cn
通讯机构：
[Xiangheng Niu] S;School of Agricultural Engineering, Jiangsu University, Zhenjiang, 212013, PR China<&wdkj&>School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China<&wdkj&>School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, PR China<&wdkj&>School of Mechanical and Materials Engineering, Washington State University, Pullman, WA, 99164, USA
摘要：
In view of the current serious situation of organophosphorus pesticides (OPs) residue contamination, developing rapid and accurate OPs sensors is a matter of urgency. Redox-nanozyme based colorimetric sensors have been widely researched and utilized in OPs residue determination, but overcoming the interference of external redox substances and the effect of single-signal modes on detection performance is still a challenge. Here we fabricated a Zr-based metal-organic framework (MOF) featuring specific phosphatase-like activity and strong aggregation-induced emission (AIE) fluorescence for redox interference-free bimodal pesticide sensing. In the MOF, the activity-tunable Zr(4+) node offered high hydrolytic activity and affinity toward P-O containing substrates, and the rigid framework structure effectively enhanced the fluorescence emission of the ligand 1,1,2,2-tetra(4-carboxylphenyl)ethylene. The developed AIEzyme could efficiently catalyze the hydrolysis of paraoxon to yellow p-nitrophenol, which further reduced the intrinsic AIE fluorescence of AIEzyme through internal filtration effect. Thereby, a natural enzyme-free dual-mode colorimetric/fluorescence approach was established for paraoxon detection with no interference from redox substances, and a smartphone-assisted portable platform was further developed to enable the facile, rapid, and high-performance sensing of the pesticide in complex practical matrices.
作者机构：
[Li, Gang; Han, Yang; Bai, Chenjun; Zhao, Hongling; Guan, Hua; Gao, Shanshan; Jia, Jin; Luo, Jinhua; Zhou, Ping-Kun; Liu, Xiaochang; Xie, Dafei; Guo, Hejiang; Xuan, Lihui; Gu, Yongqing; Tan, Jinpeng; Huang, Xin; Hu, Weixiang; Guan, H; Liu, Yuhao] Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiobiol, Beijing, Peoples R China.;[Huang, Ruixue; Luo, Jinhua; Xuan, Lihui] Cent South Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha, Hunan, Peoples R China.;[Li, Zhongjun; Ran, Qian] Army Mil Med Univ, Affiliated Hosp 2, Lab Med Ctr, Dept Blood Transfus,Lab Radiat Biol, Chongqing, Peoples R China.;[Li, Gang; Jia, Jin; Zhou, Ping-Kun; Tan, Jinpeng] Univ South China, Hengyang Med Coll, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[Ma, Teng] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Res Inst, Canc Res Ctr, Beijing, Peoples R China.
通讯机构：
[Guan, H; Zhou, PK ] B;[Huang, RX ] C;Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiobiol, Beijing, Peoples R China.;Cent South Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.
摘要：
Chemo-/radioresistance of malignant tumors hampers cancer control and increases patient mortality. Efficient repair of damaged DNA is critical for the maintenance of genomic integrity and fidelity of genetic information. In reverse, increased DNA repair capability in cancer cells contributes to chemo-/radioresistance of malignant tumors. DNA double-strand break (DSB) is the most serious DNA damage and is also the principal molecular basis of radiotherapy. Upon DNA damage, the Ku80 is recruited and forms a critical DNA-PK complex at the DSB sites with Ku70 and the catalytic subunit (DNA-PKcs) to initiate DNA repair. How DNA-PK is assembled and activated is not fully understood. Based on the identification of radiation-reduced Ku80 K568 crotonylation through quantitative global lysine crotonylome analysis, we reveal that Ku80 K568 is crotonylated by p300-CBP-associated factor (PCAF). Upon DNA damage, the K568cr is decrotonylated by HDAC8 (Histone deacetylase 8). Decrotonylation of K568cr empties this site for the subsequent SUMOylation of Ku80 by CBX4. The conversion of Ku80 from K568 crotonylation to SUMOylation facilitates the assembly of DNA-PK complex and autophosphorylation of DNA-PKcs S2056, consequently activating the DSB repair. Moreover, mutation disrupting the post-translational modification (PTM) of Ku80 K568 site sensitizes cancer cells to radiotherapy in tumor-bearing nude mice models. This study elucidates the conversion model between two different forms of PTMs in the regulation of DNA-PK complex assembly and DSB repair, highlighting this model's potential in controlling chemo-/radioresistance of malignant tumors, as well as expands the atlas of therapeutic targets.
摘要：
Occupational exposure to N-hexane/2,5-hexanedione (2,5-HD) was found to adversely affect reproductive functions in females. However, there are few studies regarding the mechanisms underlying reproductive system damage initiated by 2,5-HD. Several studies demonstrated that 2,5-HD exerts hormonal dysfunctions in females by promoting apoptosis using rat ovarian granulosa cells (GCs) as a model. The endoplasmic reticulum (ER) plays a key role in cellular processes such as protein folding and modification, Ca(2+) storage, and lipid synthesis, which are known to involve the activation of stress (ERS)-dependent m-TOR signaling pathway. Thus, the aim of this study was to examine the effects of 2,5-HD on ER and the associated activation of stress (ERS)-dependent m-TOR signaling pathway resulting in consequent apoptosis of ovarian GCs. Data demonstrated that after intraperitoneal treatment with 100, 200, or 400 mg/kg 2,5-HD for 6 consecutive weeks, 5 times per week, a decrease in body weight, ovarian weight, and relative ovary weight was found. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that 2,5-HD promoted apoptosis of ovarian GCs, which involved enhanced relative protein expression levels of m-TOR/p-mTOR. Our findings demonstrated that 2,5-HD (1) elevated expression levels of pro-apoptosis-related genes Bax and Caspase 3, (2) decreased expression levels of the anti-apoptosis gene Bcl-2, and (3) activated the protein expression of glucose-regulatory protein 78 (GRP78), inositol-requiring enzyme-1 (IRE1), and c-Jun terminal kinase (JNK) associated with increased apoptosis. Evidence indicates that chronic exposure to 2,5-HD induced apoptosis of ovarian GCs, and the possible mechanism underlying this effect involves the ERS-dependent m-TOR signaling pathway.
作者机构：
[Zhao, Kunyan; Song, Fengmei; Yang, Fei; Tang, Yan] Univ South China, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Wu, Mingyang] Cent South Univ, Xiangya Sch Publ Hlth, Dept Maternal & Child Hlth, Changsha 410007, Peoples R China.;[Qiu, Jun; Qiu, J; Pan, Xiongfeng; Liu, Caixia; Xiang, Shiting] Cent South Univ, Affiliated Childrens Hosp, Hunan Childrens Hosp, Pediat Res Inst Hunan Prov,Xiangya Sch Med, Changsha 410007, Peoples R China.;[Peng, Yunlong] Soochow Univ, Dept Epidemiol & Hlth Stat, Med Coll, Suzhou 215123, Peoples R China.;[Cao, Yunhui; Wu, Sha] Univ South China, Hengyang Med Sch, Dept Pediat, Hengyang 421001, Peoples R China.
通讯机构：
[Qiu, J ] C;Cent South Univ, Affiliated Childrens Hosp, Hunan Childrens Hosp, Pediat Res Inst Hunan Prov,Xiangya Sch Med, Changsha 410007, Peoples R China.
关键词：
Early life;Gut microbiota;Neonate;Thallium
摘要：
Previous research has found a correlation between heavy metals and gut microbiota in humans. However, there are few population-based studies examining the impact of early life thallium (Tl) exposure on neonatal microbiome. 342 newborns were recruited from Hunan Children's Hospital and subsequently divided into three groups (low, medium, and high) based on the 25th and 75th percentiles of serum Tl concentration. Additionally, the relationship between Tl and gut microbiota was analyzed in subgroups (preterm or full-term neonates). The association between Tl and gut microbiota in neonates was analyzed by Redundancy analysis, Spearman correlation analysis and MaAsLin2. The detection rate of Tl in neonates was 100%, with the median concentration of 0.021 μg/L. In all neonates, we found significant differences in the Chao1 and ACE indices of α-diversity in gut microbiota, and the relative abundances of Bacteroidota and Bacteroidetes were significantly different among groups ( p < 0.05). Following the covariate adjustment, Tl was negatively correlated with Gemmatimonadota (Coef = 0.265, p < 0.05) in preterm neonates. In full-term neonates, Tl exhibited a positive correlation with the relative abundance of Robinsoniella (Coef = 0.563, p = 0.009) and a negative correlation with that of Pseudomonas (Coef = - 0.592, p = 0.012). Tryptophan and renin-angiotensin system pathways might exert important roles in Tl exposure. This study indicated that Tl exposure was associated with changes in α-diversity and the composition of gut microbiota in neonates, with Gemmatimonadota being predominantly affected in preterm neonates and Robinsoniella and Pseudomonas in full-term neonates.
Previous research has found a correlation between heavy metals and gut microbiota in humans. However, there are few population-based studies examining the impact of early life thallium (Tl) exposure on neonatal microbiome. 342 newborns were recruited from Hunan Children's Hospital and subsequently divided into three groups (low, medium, and high) based on the 25th and 75th percentiles of serum Tl concentration. Additionally, the relationship between Tl and gut microbiota was analyzed in subgroups (preterm or full-term neonates). The association between Tl and gut microbiota in neonates was analyzed by Redundancy analysis, Spearman correlation analysis and MaAsLin2. The detection rate of Tl in neonates was 100%, with the median concentration of 0.021 μg/L. In all neonates, we found significant differences in the Chao1 and ACE indices of α-diversity in gut microbiota, and the relative abundances of Bacteroidota and Bacteroidetes were significantly different among groups ( p < 0.05). Following the covariate adjustment, Tl was negatively correlated with Gemmatimonadota (Coef = 0.265, p < 0.05) in preterm neonates. In full-term neonates, Tl exhibited a positive correlation with the relative abundance of Robinsoniella (Coef = 0.563, p = 0.009) and a negative correlation with that of Pseudomonas (Coef = - 0.592, p = 0.012). Tryptophan and renin-angiotensin system pathways might exert important roles in Tl exposure. This study indicated that Tl exposure was associated with changes in α-diversity and the composition of gut microbiota in neonates, with Gemmatimonadota being predominantly affected in preterm neonates and Robinsoniella and Pseudomonas in full-term neonates.
摘要：
Lactic acid has aroused increasing attention due to its close association with serious diseases. A real-time, dynamic, and intelligent detection method is vital for sensitive detection of lactic acid. Here, a machine learning (ML)-assisted perspiration-driven self-powered sensor (PDS sensor) is fabricated using Ni-ZIF-8@lactate oxidase and pyruvate oxidase (Ni-ZIF-8@LOx&POx)/laser-induced graphene (LIG), bilirubin oxidase (BOD)/LIG, and a microchannel for highly sensitive and real-time monitoring of lactic acid in sweat. Driven by the oxidation reaction of lactic acid, PDS sensors exhibit excellent sensitivity, a wide detection range, good reproducibility, and excellent selectivity for lactic acid detection in sweat. When subjects with different body mass index (BMI) undergo aerobic or anaerobic exercise or maintain a sedentary state, PDS sensors can monitor lactic acid in sweat wirelessly and in real-time. Moreover, a ML algorithm was employed to assist PDS sensors to detect lactic acid in the subjects' sweat with a high prediction accuracy of 96.0%.
期刊：
Journal of Nanobiotechnology,2025年23(1):1-15 ISSN：1477-3155
通讯作者：
Du, Meng;Chen, ZY
作者机构：
[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M; Xu, Haonan] Univ South China, Affiliated Changsha Cent Hosp, Coll Hunan Prov, Hengyang Med Sch,Key Lab Med Imaging Precis Theran, Changsha, Peoples R China.;[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Med Imaging, Changsha, Peoples R China.;[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M; Xu, Haonan] Univ South China, Inst Med Imaging, Hengyang Med Sch, Hengyang, Peoples R China.;[Xu, Haonan] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.
通讯机构：
[Chen, ZY ; Du, M] U;Univ South China, Affiliated Changsha Cent Hosp, Coll Hunan Prov, Hengyang Med Sch,Key Lab Med Imaging Precis Theran, Changsha, Peoples R China.;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Med Imaging, Changsha, Peoples R China.;Univ South China, Inst Med Imaging, Hengyang Med Sch, Hengyang, Peoples R China.
摘要：
BACKGROUND: Radiotherapy efficacy remains constrained by two key challenges: dose-dependent toxicity to healthy tissues at high radiation doses and hypoxia-mediated tumor radioresistance. While radiosensitizers like gold nanoparticles can enhance tumor-specific radiation deposition, their targeted delivery to tumors presents a significant hurdle. Bacteria have emerged as promising bio-carriers that not only actively target tumors and penetrate complex microenvironments, but can also be genetically engineered as multifunctional platforms for radiosensitizer delivery and hypoxia alleviation. RESULTS: An integrated nanosystem (PCM@AuNPs), composed of engineered bacteria (PCM) and gold nanoparticles (AuNPs), is used to increase the effectiveness of radiotherapy. PCM can target and colonize tumor sites more effectively, thus improving the delivery efficiency of radiosensitizers. Furthermore, PCM overexpresses catalase (CAT), which decomposes excess H(2)O(2) into O(2), helping to mitigate hypoxia in the TME. Under X-ray irradiation, PCM@AuNPs significantly enhance radiosensitization, leading to improved tumor growth inhibition while maintaining good biocompatibility. CONCLUSIONS: An effective strategy based on an integrated nanosystem (PCM@AuNPs) for radiosensitization through multiple pathways is developed. This novel engineered bacterial strategy holds great promise for enhancing radiosensitization in cancer therapy.
摘要：
Uranium is the core material for the development of the nuclear industry, but its irreversible radiation damage poses a significant threat to human health. In this context, an innovative dual-mode colorimetric and electrochemical sensor was developed for the detection of uranyl ions (UO(2)(2+)), utilizing a covalent organic framework@gold nanoclusters (AuNCs@COF) composite. The synthesis of AuNCs@COF was simple, and the incorporation of AuNCs imparted the composite with exceptional peroxidase-like catalytic activity and enhanced electrochemical properties. By regulating the adsorption and desorption of aptamers on the AuNCs@COF surface, both peroxidase-like activity and conductivity were modulated, enabling the detection of UO(2)(2+) utilizing colorimetric and electrochemical dual signals. Under optimal conditions, the sensor revealed a broad linear detection range and a low detection limit, with ranges of 1.36 × 10(-10)-1.36 × 10(-5)mol/L for colorimetric detection and 5.0 × 10(-10)-2.5 × 10(-5)mol/L for electrochemical detection, achieving detection limitsfor these two methodsof 107 pmol/L and 347 pmol/L, respectively. Unlike other single-mode sensorsfor UO(2)(2+) detection, this dual-mode sensor demonstrated superior sensitivity, specificity, and repeatability. Furthermore, the results of spiked recovery experiments in real water samples highlight the promising potential of this dual-mode sensor for environmental water monitoring applications.
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES,2025年88(8):339-348 ISSN：1528-7394
通讯作者：
Liu, Jun;Zhan, CH
作者机构：
[Liu, Jun; Zhan, Chunhua; Yang, Yue; Yang, Fei; Wang, Yaqi] Univ South China, Sch Basic Med Sci, Sch Publ Hlth, Hunan Key Lab Typ Environm Pollut & Hlth Hazards,H, Hengyang 421001, Hunan, Peoples R China.;[Zeng, Wen; Zhan, Chunhua] Cent Hosp Shaoyang, Dept Publ Hlth, Shaoyang, Peoples R China.;[Yuan, Mei] Univ South China, Affiliated Hosp 2, Hengyang Med Sch, Dept Neurol, Hengyang, Hunan, Peoples R China.;[Zhan, Chunhua] Univ South China, Key Lab Rare Pediat Dis, Minist Educ, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Liu, J; Zhan, CH ] U;Univ South China, Sch Basic Med Sci, Sch Publ Hlth, Hunan Key Lab Typ Environm Pollut & Hlth Hazards,H, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Key Lab Rare Pediat Dis, Minist Educ, Hengyang 421001, Hunan, Peoples R China.
关键词：
MC-LR;Apoptosis;TNF-R1;RIPK1;HEK293
摘要：
In recent years, the outbreak of cyanobacterial blooms has become increasingly frequent. Microcystin-LR (MC-LR), a metabolite of cyanobacteria, poses a significant threat to the ecosystem and human health. Several studies have demonstrated that MC-LR might induce renal cell apoptosis, as a consequence of tissue damage. However, the molecular mechanisms underlying MC-LR-initiated renal injury remain to be determined. This investigation aimed to determine the role of apoptosis in MC-LR-induced kidney damage and its potential underlying mechanisms using the human embryonic kidney (HEK293) cell line. The results of TUNEL and immunofluorescence assays indicated that MC-LR induced increased apoptosis in HEK293 cells. Compared to control, the mRNA expression levels of RIPK1, caspase-8, and TNF-α were elevated following incubation with MC-LR, while the mRNA expression level of Bcl-2/Bax was decreased. The protein levels of RIPK1, TNF-R1, and caspase-8 were elevated in the MC-LR-treated HEK293 cells. Data demonstrated that MC-LR induced renal cell apoptosis through activation of the TNF-R1/RIPK1 pathway, providing new insights into understanding the toxic mechanisms attributed to MC-LR.
期刊：
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH,2025年51(1):e16120- ISSN：1341-8076
通讯作者：
Wu, CQ
作者机构：
[Wu, CQ; Xie, Yinghao; Wu, Chengqiu; Zhu, Qiong] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Liu, Jun] Hengyang Cent Dis Control & Prevent, Hengyang, Peoples R China.
通讯机构：
[Wu, CQ ] U;Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.
关键词：
CD1a;ovarian cancer;prognosis;recurrence;recurrent ovarian cancer
摘要：
OBJECTIVE: Explored the correlation between CD1a expression in recurrence and prognosis of ovarian cancer (OV). METHODS: The CD1a expression profile in OV, recurrent OV, and normal tissues, as well as corresponding clinical data, were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), and Genotype Tissue Expression (GTEx) databases. Meanwhile, immunohistochemical detection of CD1a expression in normal and OV tissues. Kaplan-Meier curves were plotted to estimate the hazard ratio (HR) of survival in OV. In addition, the correlation between CD1a and immune cells in OV, as well as the CD1a expression profile and corresponding survival time in pan-cancer were obtained from TCGA database. RESULTS: CD1a was overexpressed in OV and was significantly under-expressed in recurrent OV (TCGA-OV, p < 0.0001 and ICGC-OV, p < 0.0001). CD1a immunohistochemistry is significantly overexpressed in OV compared to normal tissue (p < 0.05). Recurrent OV (ICGC, p < 0.001; GSE17260, p < 0.001; GSE32062, p < 0.05). The prognosis in OV was significantly better when CD1a is overexpressed compared to under-expressed (HR [low], 1.426: 95% confidence interval [CI], 0.912-2.128; p = 0.050). Meanwhile, the overexpression of CD1a has a better prognosis than low expression in OV and recurrent OV (p = 0.004, HR [low] = 2.462, 95%CI [1.346-4.504] and p = 0.011, HR [low] = 2.199, 95%CI [1.202-4.024]). In addition, CD1a expression was closely correlated with immune cells, the CD8+ T cells, macrophages, and NK cells, while uncharacterized cells were significantly different (p = 2.65e-6, p = 7.52e-13, p = 8.28e-12, and p = 5.89e-8, respectively). Moreover, CD1a expression affected the prognosis in various other cancers. CONCLUSIONS: CD1a expression affected the recurrence and prognosis of OV and is closely related to various immune cell levels.
期刊：
Chemical Communications,2025年61(18):3756-3759 ISSN：1359-7345
通讯作者：
Pan, Jiafeng;Yang, F
作者机构：
[Wang, Yuyan; Yang, F; Pan, Jiafeng; Zeng, Ying; Ren, Xiaoya; Yang, Fei] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Qiu, Jun] Hunan Childrens Hosp, Changsha 410000, Hunan, Peoples R China.
通讯机构：
[Yang, F ; Pan, JF] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
摘要：
Based on a Y-shaped wheel-mediated triple walker, an enzyme-free biosensor was reported for UO22+ detection. Due to the DNAzyme-driven mechanism, our walker was activated and produced a fluorescence signal for UO22+ assay. The sensor demonstrated ultra-sensitivity, good specificity and excellent accuracy, holding great promise for UO22+ sensing in complex water samples.
通讯机构：
[Yang, F ] U;[Chen, JH ] G;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;Guangdong Acad Sci, Inst Ecoenvironm & Soil Sci, Guangzhou 510650, Peoples R China.
摘要：
A sensitive fluorescence biosensor was developed for microcystin-LR (MC-LR) detection using H1, H2, and H3 DNA probes as sensing elements. The aptamer in H1 can recognize the target. H2 was labeled with FAM and BHQ. The MC-LR and H1 binding will activate the H2 and H3 self-assemblies through toehold-mediated strand displacement. In the formed products (MC-LR/H1/nH2/nH3), FAM and BHQ will be separated and a high FAM fluorescence signal can be observed for the MC-LR assay. The biosensor is sensitive with a detection limit of 53 fM. We further constructed several logic circuits (AND-AND cascaded circuit, feedforward circuit, and resource allocation circuit) using MC-LR, MC-LA, and MC-YR as the three inputs. The numbers 0 and 1 are used to code the input and output signals. The AND-AND cascade circuit can produce a high output signal only in the (111) input combination. In the feedforward circuit, MC-LR and MC-LA can activate the logic circuit to produce high signals, and MC-YR will inhibit the self-assembly and execute the negative feedforward operation. Through the rational design of the DNA probe hybridizations on four different magnetic beads (MBs), the resource allocation circuit can achieve an intelligent allocation of input information. Our proposed fluorescence biosensor can not only provide a sensitive platform for microcystin detection but also serve as a smart and intelligent logic system for microcystin sensing.
作者机构：
[Yuting Li; Xiayu Zhao; Yichun Hu; Siran Li; Huidi Zhang; Yang Cao; Rui Wang; Lichen Yang] Key Laboratory of Public Nutrition and Health, National Health Commission of the People's Republic of China, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China;Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 241001, Hunan, China;[Xiaoyun Shan] Key Laboratory of Public Nutrition and Health, National Health Commission of the People's Republic of China, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China<&wdkj&>Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 241001, Hunan, China
关键词：
25-hydroxyvitamin D;Gene polymorphism;Osteocalcin;Procollagen type 1 N-terminal propeptide;β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide
摘要：
Objective This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age.
This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age.
Methods In total, 1,505 non-pregnant or non-lactating women (18–45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.
In total, 1,505 non-pregnant or non-lactating women (18–45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds.
Results The median serum 25(OH)D was 16.63 (11.96–22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84–15.23) ng/mL], β-CTX [13.94 (12.49–15.39) ng/mL], and P1NP [13.87 (12.37–15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68–13.91) ng/mL], β-CTX [12.23 (10.22–14.23) ng/mL], and P1NP [11.85 (10.40–13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81–13.68) ng/mL], β-CTX [13.05 (11.78–14.32) ng/mL], and P1NP [12.81 (11.57–14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued.
The median serum 25(OH)D was 16.63 (11.96–22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84–15.23) ng/mL], β-CTX [13.94 (12.49–15.39) ng/mL], and P1NP [13.87 (12.37–15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68–13.91) ng/mL], β-CTX [12.23 (10.22–14.23) ng/mL], and P1NP [11.85 (10.40–13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81–13.68) ng/mL], β-CTX [13.05 (11.78–14.32) ng/mL], and P1NP [12.81 (11.57–14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued.
Conclusion In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
作者机构：
[Tian, Qingzhen; Liu, Jinjin; Tang, Zheng; Niu, Xiangheng; Li, Shu; Chen, Xinyu] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Niu, XH ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要：
Organophosphorus pesticides (OPs) are widely used in agricultural production, posing a great threat to human health and the environment. Given that different OPs present different toxicology and toxicities, identifying individual pesticide residues becomes important for assessing food safety and environmental implications. In this work, a kinetics difference-driven analyte hydrolysis strategy is proposed for the first time and validated to identify p-nitrophenyl pesticides by developing an organophosphorus hydrolase-like nanozyme-coded sensor array. Ultrasmall bare CeO(2) nanoparticles were synthesized and employed as the only sensing unit to catalyze the hydrolysis of multiple analytes. With catalytic preferences and kinetics differences under identical reaction conditions, five common OPs analogues (methyl-paraoxon, paraoxon, methyl-parathion, parathion, and fenitrothion) offered discriminable colors. By coupling the color fingerprints with pattern recognition, the accurate identification of individual p-nitrophenyl pesticides and their mixtures at a variety of concentrations and ratios was verified in laboratory and practical scenarios. Attractively, apart from excellent performance and convenient operation, the proposed hydrolytic nanozyme-coded pattern presents strong resistance against redox substances that often cause interference in previous oxidoreductase-based sensor arrays. Our study provides a new paradigm of discriminating specific OPs precisely, showing promising applications in multitarget analysis in complex matrices.
作者机构：
[Peng, Jiayi; Liu, Jinjin; Tang, Zheng; Liu, JJ; Liang, Hao; Niu, Xiangheng; Chen, Xinyu] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Liu, Shuangquan; Tang, Zheng; Niu, Xiangheng] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Peoples R China.
通讯机构：
[Liu, JJ; Niu, XH ] U;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要：
With their important role in regulating intracellular redox balance and maintaining cell homeostasis, endogenous mercaptans are recognized as biomarkers of many diseases in clinical practice, and thus establishing efficient yet simple methods to distinguish and quantify endogenous mercaptans is of great significance for health management. Here, we propose a machine learning-enabled time-resolved nanozyme-encoded strategy to identify endogenous mercaptans in the presence of potential interferents for disease diagnosis. Diethylenetriaminepenta(methylenephosphonic) acid was first employed to coordinate with Mn(3+) to prepare a new amorphous nanozyme, which exhibited excellent oxidase-like activity in catalyzing the oxidation of colorless 3,3',5,5'-tetramethylbenzidine to its blue oxide. The addition of endogenous mercaptans (cysteine, homocysteine, and glutathione) could competitively suppress the chromogenic process to different extents due to their discrepant antioxidant abilities, providing specific fingerprints over time for each species. With this mechanism, a time-resolved sensor array with the nanozyme as a sole sensing unit was constructed to accurately identify different types and levels of mercaptans and their various mixtures with the help of pattern recognition. Furthermore, machine learning was combined with the sensor array to construct a stepwise prediction model consisting of concentration-independent classification and concentration-associated regression, which could not only differentiate cancer cells from normal ones based on intracellular glutathione but also evaluate the severity of cardiovascular diseases according to serum homocysteine, showing great application potential in disease diagnosis.
摘要：
BACKGROUND: Coinfections involving multiple diarrheal viruses have gained increasing recognition as a significant cause of acute gastroenteritis in recent years. Understanding the genetic diversity and evolutionary relationships of these viruses is crucial for effective outbreak identification and tracking. OBJECTIVE: To report two cases of HAdV and SaV coinfections and elucidate the genetic diversity and evolutionary patterns of these viruses through whole-genome sequencing (WGS) and phylogenetic analysis. METHODS: A total of 873 diarrheal stool samples were collected from sentinel hospitals in Shenzhen, China, in 2021. The collected stool samples were identified using RT-PCR and positive samples were subjected to WGS on the NovaSeq platform. phylogenetic trees were constructed using MEGA to analyze genetic relationships. RESULTS: The sequencing results showed that both samples were human adenovirus type 41, which clustered in two distinct evolutionary clades. Additionally, we also retrieved the complete genome of sapovirus (GI.1 genotype) from the same sample. Phylogenetic analysis revealed that they were similar to previously reported strains, belonging to the clade predominating in China. CONCLUSIONS: This study reveals the genetic diversity of epidemic strains involved in coinfections of human adenovirus and sapovirus. The findings establish a groundwork for the identification and traces of acute gastroenteritis outbreaks.
