作者机构：
[Liu, Xing; Xiao, Xilin; Xiao, XL; Liu, Zhen; Sun, Jie] Univ South China, Sch Publ Hlth, Hengyang Sch Med, Hengyang 421001, Peoples R China.;[Xiao, Xilin; Xiao, XL] Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.;[Xiao, Xilin; Xiao, XL] Univ South China, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
通讯机构：
[Xiao, XL ] U;Univ South China, Sch Publ Hlth, Hengyang Sch Med, Hengyang 421001, Peoples R China.;Hunan Univ, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Peoples R China.;Univ South China, Dept Publ Hlth Lab Sci, Hengyang 421001, Peoples R China.
关键词：
fluorescent sensor;mercury ion detection;silver ion detection;cascade isothermal signal amplification;catalytic hairpin assembly
摘要：
In this study, novel fluorescent DNA biosensors for mercury (Hg2+) and silver (Ag+) ions were developed based on thymine (T)- and cytosine (C)-rich recognition elements in combination with exonuclease III and a mismatch-catalyzed hairpin assembly (MCHA)-based cascade isothermal signal-amplification strategy. In the presence of the respective target analytes, the recognition element terminals form so-called T-Hg2+-T or C-Ag+-C structures, resulting in cleavage by Exo III and the release of the trigger strand for MCHA. This binds to the H1 hairpin, which is fluorescently labeled with carboxyfluorescein (FAM) and tetramethylrhodamine (TAMRA), disrupting fluorescence resonance energy transfer between them and, thus, restoring FAM fluorescence, generating a strong signal at 520 nm. The linear range of the Hg2+ sensor is 0.5 to 3 pM, with a detection limit of 0.07 pM. The recovery range in actual spiked water samples is between 98.5% and 105.2%, with a relative standard deviation (RSD) ranging from 2.0% to 4.2%. The linear range of the Ag+ sensor is 10 to 90 pM, with a detection limit of 7.6 pM. The recovery range in actual spiked water samples is between 96.2% and 104.1%, with an RSD ranging from 3.2% to 6.3%. The cascade isothermal signal amplification strategy effectively enhances sensor sensitivity, while MCHA decreases the false-positive rate. The aptamer sensor exhibits high specificity, is resistant to interference, and can be used for the detection of Hg2+ and Ag+ in environmental water samples.
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：
[Tang, Jingjing; Tang, Wei; Li, Yanlin] Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China;[Liu, Cong] Department of Health Inspection and Quarantine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China;[Li, Zhenkui] Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address: lizhenkui@usc.edu.cn
通讯机构：
[Li, Zhenkui] I;Institute of Pathogenic Biology and Key Laboratory of Special Pathogen Prevention and Control of Hunan Province, School of Basic Medical Sciences, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China. Electronic address:
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：
This work delves into the mechanism enabling pH interference resistance in iron-based bimetallic oxides within the peroxymonosulfate (PMS) system. We employed MnFe₂O₄ spinel oxides as a catalyst for an in-depth comparison with monometallic analogs. We discovered that Fe(III) sites within the bimetallic oxide serve as sacrificial sites for hydroxyl ions as pH rises, stabilizing the cycling of active Mn sites. Elevated pH promotes the formation of surface hydroxyl groups, which enhance PMS and phenol adsorption via hydrogen bonding, thereby facilitating PMS activation by adjacent Mn sites and accelerating phenol degradation on the catalyst's surface. The cooperative effects of Fe(III) sacrifice and enhanced hydrogen bonding contribute significantly to the expanded pH tolerance of the iron-based bimetallic system, achieving nearly a 4.9-fold increase in kinetic efficiency at pH 6.2 relative to pH 3.2. This study deepens our understanding of sustainable Fenton-like systems and highlights their promising role in the degradation of pollutants.
This work delves into the mechanism enabling pH interference resistance in iron-based bimetallic oxides within the peroxymonosulfate (PMS) system. We employed MnFe₂O₄ spinel oxides as a catalyst for an in-depth comparison with monometallic analogs. We discovered that Fe(III) sites within the bimetallic oxide serve as sacrificial sites for hydroxyl ions as pH rises, stabilizing the cycling of active Mn sites. Elevated pH promotes the formation of surface hydroxyl groups, which enhance PMS and phenol adsorption via hydrogen bonding, thereby facilitating PMS activation by adjacent Mn sites and accelerating phenol degradation on the catalyst's surface. The cooperative effects of Fe(III) sacrifice and enhanced hydrogen bonding contribute significantly to the expanded pH tolerance of the iron-based bimetallic system, achieving nearly a 4.9-fold increase in kinetic efficiency at pH 6.2 relative to pH 3.2. This study deepens our understanding of sustainable Fenton-like systems and highlights their promising role in the degradation of pollutants.
作者机构：
[Zi-An Wang] The School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China;[Fangfang Huang; Yashi Feng] The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health, Guilin Medical University, Guilin, China;[Yunchang Cao] The Department of Molecular Biology, School of Intelligent Medicine and Biotechnology, Guilin Medical University, Guilin, China;[Wuxiang Wang] The School of Public Health, University of South China, Hengyang, China;The State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China
通讯机构：
[Shaolong Feng] T;The Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Heath, School of Public Health, Guilin Medical University, Guilin, China<&wdkj&>The School of Public Health, University of South China, Hengyang, China<&wdkj&>The State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, China
摘要：
Titanium dioxide nanoparticles (TiO(2)-NPs) have been ever increasingly exposed to people through all possible routes, while studies focusing on their potential cardiovascular risks are relatively lacking, especially the underlying biological mechanisms that are not yet elucidated. In this study, the ferroptotic effect of TiO(2)-NPs (30 nm) at environmentally relevant concentrations (0, 3, 12, and 48 μg/mL) on human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism were studied with the corresponding biochemical and molecular biology assays. The results showed that TiO(2)-NPs at the tested concentrations could reduce HUVEC viability, but ferrostatin-1 might rescue this reduction in cell viability. Also, TiO(2)-NPs exposure increased Fe(2+), reactive oxygen species, and malondialdehyde, but decreased glutathione, mitochondrial membrane potential, and activities of anti-oxidative enzymes (catalase, superoxide dismutase, and glutathione peroxidase) in HUVECs through an integrated signaling pathway. Meanwhile, enhanced p38 protein phosphorylation and keap1 protein and decreased Nrf2 protein phosphorylation with reductions in mRNA expressions of downstream anti-oxidative enzyme genes (catalase, superoxide dismutase, glutathione peroxidase, and phospholipid hydroperoxidase) were identified in the TiO(2)-NPs-exposed HUVECs. These indicated that TiO(2)-NPs exposure induced ferroptosis in HUVECs via the p38/keap1 inhibiting Nrf2 pathway. EC ferroptosis will be a promising biomarker for assessing the cardiovascular health risks of environmental contaminants.
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.
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; Cao, Yi; Wang, Yijin; Luo, Sihuan] 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：
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：
[Tong, Wei; Liu, Shunchang; Liu, Jinquan; Huang, Ziyi; Xiao, Fubing; Huang, Zhenwei; Chen, Danrong] College of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China;[Yang, Shengyuan] College of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China. Electronic address: yangshyhy@126.com
通讯机构：
[Yang, Shengyuan] C;College of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China. Electronic address:
摘要：
Accidental leakage of uranium causes a huge threat to human health and environmental security. Herein, a novel fluorescent MOF-on-MOF hydrogel complex, namely Tb-MOF@ZIF-8@PAM, is constructed using a “three-in-one” synthetic strategy for the simultaneous adsorption enrichment and sensitive detection of uranyl ions (UO 2 2+ ) in water. Combining ZIF-8 with Tb-MOF enables the composite to exhibit remarkable fluorescence enhancement, large fluorescence quantum yield, and exceptional stability. When used to detect of UO 2 2+ in water, the method demonstrates excellent sensitivity (LOD=0.551 nmol/L). Experimental characterizations suggest that the static quenching effect (SQE) and photoinduced electron transfer (PET) may be possible sensing mechanisms. Furthermore, Tb-MOF@ZIF-8@PAM is rich in amino and carboxyl groups and exhibits superior hydrophilicity, an abundant pore structure, and numerous active adsorption sites, which leads to a remarkable absorption capability of 603 mg/g specifically for UO 2 2+ . Tb-MOF@ZIF-8@PAM has a straightforward recycling strategy, and its adsorption efficiency remains above 80 % after 4 cycles of use. Thus, this research introduces an innovative approach for synthesis of a low-cost and multifunctional adsorbent MOF-on-MOF hydrogel composite, which can be employed for the simultaneous adsorption and detection of UO 2 2+ .
Accidental leakage of uranium causes a huge threat to human health and environmental security. Herein, a novel fluorescent MOF-on-MOF hydrogel complex, namely Tb-MOF@ZIF-8@PAM, is constructed using a “three-in-one” synthetic strategy for the simultaneous adsorption enrichment and sensitive detection of uranyl ions (UO 2 2+ ) in water. Combining ZIF-8 with Tb-MOF enables the composite to exhibit remarkable fluorescence enhancement, large fluorescence quantum yield, and exceptional stability. When used to detect of UO 2 2+ in water, the method demonstrates excellent sensitivity (LOD=0.551 nmol/L). Experimental characterizations suggest that the static quenching effect (SQE) and photoinduced electron transfer (PET) may be possible sensing mechanisms. Furthermore, Tb-MOF@ZIF-8@PAM is rich in amino and carboxyl groups and exhibits superior hydrophilicity, an abundant pore structure, and numerous active adsorption sites, which leads to a remarkable absorption capability of 603 mg/g specifically for UO 2 2+ . Tb-MOF@ZIF-8@PAM has a straightforward recycling strategy, and its adsorption efficiency remains above 80 % after 4 cycles of use. Thus, this research introduces an innovative approach for synthesis of a low-cost and multifunctional adsorbent MOF-on-MOF hydrogel composite, which can be employed for the simultaneous adsorption and detection of UO 2 2+ .
作者：
Rong Zhang;Lili Yang;Sihong Long;Shengyu Zhang;Jia Wei;...
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES,2025年88(8):329-338 ISSN：1528-7394
通讯作者：
Jia Wei<&wdkj&>Fei Yang
作者机构：
[Rong Zhang; Lili Yang; Sihong Long; Shengyu Zhang] Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China;Xiangya School of Public Health, Central South University, Changsha, China;The Department of Public Health, The Central Hospital of Shaoyang, Shaoyang, China;Nuclear Medicine Department, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China;[Jia Wei] Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>The Department of Public Health, The Central Hospital of Shaoyang, Shaoyang, China
通讯机构：
[Jia Wei] X;[Fei Yang] H;Xiangya School of Public Health, Central South University, Changsha, China<&wdkj&>The Department of Public Health, The Central Hospital of Shaoyang, Shaoyang, China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China<&wdkj&>Nuclear Medicine Department, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China
摘要：
Microcystins (MCs) are one of the most widespread cyanotoxins produced by harmful cyanobacterial blooms (Ren et al. 2024). To date, more than 300 isomers of MCs have been identified (Baliu-Rodrigue...
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.
摘要：
OBJECTIVE: To analyze the expression of the SOX gene family in lung adenocarcinoma and its impact on the prognosis of lung adenocarcinoma patients using tumor databases. METHODS: The cBioPortal database was used to retrieve and analyze the mutation frequencies and variants of 10 genes in the SOX gene family in lung adenocarcinoma tissues. Using clinical information from the Kaplan-Meier plotter database, the potential prognostic values of 10 genes in the SOX gene family in lung adenocarcinoma patients were further explored. The UALCAN database and TCGA database were used to obtain the expression of methylation of SOX gene family members and compare the mRNA expression of 10 genes in lung adenocarcinoma tissues and paracancerous tissues, respectively. The miRCancer database was intersected with miRTarBase, ENCORI, and miRWalk databases to find the lung adenocarcinoma-related miRNAs that regulate the SOX gene family. RESULTS: Most members in the SOX gene family had expansion mutation, but SOX15 had a deletion mutation. Upregulation of SOX8 and SOX17 is associated with improved outcomes in LUAD patients (HR < 1, log-rank P < 0.05), whereas high expression of SOX3, SOX5, SOX6, SOX12, SOX14, SOX15, SOX18, and SRY correlates with poor prognosis in LUAD patients (HR > 1, log-rank P < 0.05). The mRNA expression of SOX3 and SOX15 was significantly higher in LUAD tissues compared to adjacent normal tissues, while SOX5, SOX6, SOX12, SOX17, SOX18, and SRY were lower in LUAD tissues than in adjacent normal tissues (P < 0.05). Moreover, SOX3, SOX5, SOX8, SOX14, SOX17 and SOX18 showed hypermethylation, while SOX15 showed hypomethylation in LUAD tissues (P < 0.05). Furthermore, hsa-miR-1-3p and miR-499a-5p were positively correlated with SOX5 (r = 0.272, P = 3.87 × 10(-10)) and SOX6 (r = 0.109, P = 1.34 × 10(-2)), respectively. CONCLUSION: The SOX gene family is closely implicated in the onset and progression of lung adenocarcinoma, of which most members may be used as prognostic marker genes for patients.
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.
期刊：
Frontiers in Microbiology,2025年16:1496514 ISSN：1664-302X
作者机构：
[Liu, Hongwei; Zhou, Peng; Ma, Peng; Liu, Yaqin; Xu, Lingqing; Yin, Weiguo; Li, Linhai; Lu, Yang] The Affiliated Qingyuan Hospital (Qingyuan People's Hospital),Guangzhou Medical University, Qingyuan, China;[Zhang, Yingfeng] Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical College, University of South China, Hengyang, Hunan Province, China;[Li, Qiwei] Department of Laboratory Medicine, The Second Affiliated Hospital, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China;[Yuan, Wenchang] KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, Guangdong Province, China
摘要：
ABSTRACTCarbapenem-resistant (CR) Gram-negative pathogens, prioritized by the WHO as critical threats, face limited therapeutic options, with cefiderocol (CFD) emerging as a promising siderophore cephalosporin. This study investigated the prevalence, clinical impact, and genetic mechanisms of cefiderocol heteroresistance (CFD-HR) in 407 CR and ESBL-producing clinical isolates from China, where CFD remains unapproved. Population analysis profiles (PAPs) revealed CFD-HR rates of 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 P. aeruginosa extended-spectrum β-lactamase (ESBL), 8/177 in E. coli ESBL). 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 a murine peritonitis model, CFD achieved 100% (3/3) survival in non-HR infections but only 16.7% (1/6) in HR-infected mice, directly linking HR to in vivo treatment failure. Whole-genome sequencing identified transient genetic alterations in HR subpopulations, including sitABCD duplications (CRE), oprD mutations (CRAB), and vgrG SNPs (CRPA), which reverted post-antibiotic withdrawal. Fitness cost assays revealed unstable growth deficits in 33.3% (2/6) of HR subpopulations, correlating with genetic instability. 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 use.
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.
摘要：
Fine particulate matter (PM(2.5)) exposure is significantly linked to lung epithelial cell senescence, and autophagy dysfunction being a key contributor to the aging process. Although the anti-aging properties of ellagic acid (EA) are well-documented, its specific protective effect on PM(2.5)-induced lung epithelial cell senescence still needs to be studied in depth. To investigate the impacts of PM(2.5) on autophagy and senescence in lung epithelial cells, 16HBE and A549 cells were exposed to PM(2.5) suspension. Additionally, to explore the potential intervention effect of EA, cells were pretreated with EA before exposure to PM(2.5) suspension. Cell morphology, proliferation, senescence-related markers, senescence-associated secretory phenotype (SASP), and autophagy-related markers were then assessed. Our results showed that the proliferation of 16HBE and A549 cells were inhibited and autophagy dysfunction and senescence were induced under PM(2.5) exposure. However, pretreatment with EA can significantly improve the obstruction of autophagy flux caused by PM(2.5), thereby effectively alleviating cell senescence. This study reveals the mechanism by which PM(2.5) induces senescence in lung epithelial cells and confirms the protective role of ellagic acid in this process.
作者机构：
[Xiao, Fubing; Wang, Yuxiao; Deng, Chenyi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards,D, Hengyang 421001, Peoples R China.;[Du, Wenfang; Du, WF] Hunan Inst Technol, Sch Chem & Environm Engn, Hengyang 421002, Peoples R China.;[Song, Yan; Chen, Shusen; Wu, Haotian] Beijing Res Inst Chem Engn & Met, CNNC Key Lab Uranium Extract Seawater, Beijing 101121, Peoples R China.
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,D, Hengyang 421001, Peoples R China.;Hunan Inst Technol, Sch Chem & Environm Engn, Hengyang 421002, Peoples R China.
摘要：
Uranium, in terms of both its radioactivity and chemical toxicity, poses significant environmental and health risks when released through nuclear industry activities and its mining. The sensitive detection of uranyl ions (UO(2)(2+)) in wastewater is crucial for mitigating these risks and safeguarding public health. Herein, we present an innovative approach by synthesizing the functional monomer 6-(3-(2-(methacryloyloxy)ethyl)ureido)picolinate (K6MUPA) to create a novel europium ion (Eu(3+))-K6MUPA-AAm hydrogel sensor. Through simple ionic coordination, europium ions (Eu(3+)) were incorporated into the hydrogel, which initially exhibited weak fluorescence. Remarkably, the fluorescence intensity was significantly enhanced by the cationic interactions between UO(2)(2+) and Eu(3+), enabling highly sensitive and selective detection of UO(2)(2+). The sensor demonstrated a linear response in the range of 1-100 nmol L(-1) (F - F(0) = 10.52C(uranyl) + 97.38) with a detection limit of 1 nmol L(-1). Practical applicability was confirmed through real sample analysis, achieving excellent recoveries of 100.18-107.36%. This work not only advances UO(2)(2+) detection but also highlights the potential of innovative hydrogel-based sensors for environmental monitoring.
期刊：
Separation and Purification Technology,2025年354:129241 ISSN：1383-5866
通讯作者：
Zhongran Dai
作者机构：
[Dai, Zhongran; Liang, Beichao; Chen, Lijie] Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang 421001, China;[Zhang, Weilin] College of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;[Gao, Yuan] School of Chemical Engineering and Technology, China University of Mining & Technology, Xuzhou, Jiangsu 221116, China;[Li, Le] Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang 421001, China<&wdkj&>College of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
通讯机构：
[Zhongran Dai] K;Key Discipline Laboratory for National Defense for Biotechnology in Uranium Mining and Hydrometallurgy, University of South China, Hengyang 421001, China
摘要：
Photocatalysis holds promise for extracting uranium from aqueous solution. Nevertheless, conventional approaches generally rely on sacrificial agents and anaerobic conditions to maintain photocatalytic efficiency, which increases costs and causes secondary pollution. Herein, we introduce the design and synthesis of an S-scheme ZnIn2S4/g-C3N4 (ZISCN) heterojunction photocatalyst for the efficient removal of uranium via in-situ generating ZnIn2S4 on g-C3N4. Photoelectric characterization and theoretical calculation indicate that ZISCN boosts the absorption of visible light and promotes the effective separation and migration of charge carriers by forming an internal electric field (IEF) at the S-scheme heterojunction interface. This configuration integrates the strong reducing electrons of g-C3N4 and the potent oxidation holes of ZnIn2S4. Consequently, the as-synthesized ZISCN can efficiently remove uranium under an air atmosphere without the need for sacrificial agents and anaerobic conditions. The achieved U(VI) removal rate of 94.8 % surpasses that of ZnIn2S4 and g-C3N4 individually. Moreover, the photocatalytic extraction of U(VI) by ZISCN photocatalyst demonstrated excellent stability and anti-interference performance. After five cycles, the U(VI) removal rate remained above 85 %. Mechanism studies reveal that when electrons are generated by light in the ZISCN systems, they can reduce O2, leading to the formation of reactive species ·O2/H2O2. These species subsequently interact with U(VI), resulting in the precipitation of (UO2)O2·2H2O on the surface of ZISCN. This research provides valuable insights for the design of heterojunction photocatalysts for efficient, sacrificial agent-free uranium removal in ambient air environments.
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.
