摘要：
A multifunctional electrochemiluminescence (ECL) coreaction accelerator, AuAgPt nanoframes (NFs), is described for use in an ECL aptasensor for highly sensitive aflatoxin B1 (AFB1) detection. As a signal quencher, the broad UV-vis absorption spectrum of AuAgPt nanosheets (NSs) overlaps the ECL emission spectrum of g-C(3)N(4)@Au, triggering an ECL resonance energy transfer (ECL-RET). By the adjustment of the dosage of hydrogen peroxide (H(2)O(2)), the AuAgPt NSs are transformed into AuAgPt NFs because H(2)O(2) etches Ag in AuAgPt NSs into Ag(+), which disrupts the RET process. The as-formed AuAgPt NFs act as a coreaction accelerator to enhance the ECL response of the g-C(3)N(4)@Au/K(2)S(2)O(8) system. Without AFB1, the Ag-dependent DNAzyme is inactive, and a strong ECL signal is observed. After AFB1 is added, the AFB1 aptamer targets AFB1 and the DNAzyme active site is exposed. As-generated Ag(+) further activates DNAzyme to cut the substrate strand (S-DNA), which causes AuAgPt NFs to detach from the electrode surface and the ECL signal to significantly decrease. Under optimal conditions, the proposed ECL aptasensor exhibits high sensitivity with a limit of detection (LOD) of 0.11 fg/mL in the range of 1 fg/mL to 1 μg/mL for AFB1 detection.
摘要：
Endothelial cells (ECs) are interior surface cells covering blood vessels, which play a crucial role in maintaining vascular homeostasis. In vascular pharmacology and toxicology, ECs directly contact drugs or toxicants entering circulation. Therefore, the bio-effects of pharmacological/toxicological substances on ECs have gained extensive research interest, which needs to be evaluated by reliable models. Human umbilical vein endothelial cells (HUVECs) have been served as versatile platforms to mimic diverse pathophysiological processes in vitro, stemming from their unique fetal arterial-like exposure microenvironment, expression of key EC markers, and comparable EC responses to various pathophysiological stimuli. This review provides an overview of the application of HUVECs in pharmacology and toxicology, with a focus on their utility and limitations. HUVECs have been widely used to model the effects of pharmacological or toxicological substances on material exchange, barrier functions, cell death, endothelial nitric oxide synthase (eNOS) uncoupling, and EC dysfunction, angiogenesis, and thrombosis. However, their applicability is constrained primarily due to vascular-type and organ-specific heterogeneity. The review highlights key mechanisms investigated using HUVECs, including oxidative stress, inflammation, organelle damage, and autophagy, metabolic reprogramming (endometabolism), and epigenetic regulation. Strategies to overcome HUVECs' limitations, such as microfluidic techniques, co-culture, and organoid models, are discussed. Finally, future directions are outlined, emphasizing the integration of HUVECs into multi-scale models, dynamic microenvironment simulations, artificial intelligence (AI)-assisted big data analysis, and patient-derived ECs for precision toxicology and personalized medicine. This review aims to guide researchers in optimizing the use of HUVECs in pharmacological and toxicological studies.
This review summarizes the pathophysiological roles of ECs, the applicable and non-applicable scopes of HUVECs in modeling ECs, and the uses of HUVECs in studying the pharmacological or toxicological effects and mechanisms. This review also discusses the strategies to overcome HUVECs' limitations and outlines future directions.
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：
[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：
The combined effect of environmental exposure and dietary behavior plays a vital role in the occurrence of diseases. Bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used substitutes for bisphenol A (BPA). Previous studies have shown that the combined exposure to BPA and fructose caused significant disturbances in glycolipid metabolism in adipose tissue, however, the interference caused by the combined exposure to BPS and fructose or BPF and fructose on adipose tissue is still unclear. In the present study, we performed a integrated analysis of targeted energy metabolomics and widely targeted quantitative lipidomics on the adipose tissue of Sprague Dawley rats after combined exposure to 2 levels of BPS or BPF (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months. Based on the results, lower dose BPS combined with fructose increased succinate significantly, while higher dose BPS or lower dose BPF combined with fructose decreased succinate significantly. Additionally, lower dose BPS combined with fructose might lead to polyunsaturated lipid depletion, while higher dose BPS combined with fructose exposure might lead to choline and carnitine depletion; lower dose BPF combined with fructose might inhibit lipolysis, while higher dose BPF combined with fructose might cause accumulation of free fatty acids. These results indicated the response patterns of adipose tissue to different dose of BPS or BPF combined with fructose were significantly different, and the adipocyte succinate signaling pathway might be the important target for metabolic remodeling in adipose tissue.
关键词：
Drug reposition;Enrichment score;Immunoregulation;LINCS;Lenalidomide;Radioprotection
摘要：
Ionizing radiation induces DNA damage and impairs genomic integrity, leading to cell death and tissue injuries or carcinogenesis. Medical radiation protectors are essential and necessary. However, there are limited radioprotectors in clinics, which can't meet the growing demand for countering radiation emergencies. Traditional drug discovery approach has been proven expensive and risky. Computational drug repositioning provides an attractive strategy for radioprotector discovery. Here we constructed a systematic workflow to identify repositioning radioprotectors by comparison of biosimilarity between γ-ray and known medicines characterized by gene expression signatures from GEO and LINCS. Using enrichment scoring, medicines with negative scores were considered as candidates of revising or mitigating radiation injuries. Seven approved medicines were identified, and their targets enriched in steroid and estrogen metabolic, chemical carcinogenesis associated pathways. Lenalidomide, an approved medicine for multiple myeloma and anemia, was further verified as a promising potential radioprotector. It increases survival of mice after lethal doses of irradiation by alleviating bone marrow and intestinal injury in vivo, and inhibits apoptosis of cultured irradiated AHH- 1 and IEC- 6 cells in vitro. This study introduces rational drug repositioning to radiation medicine and provides viable candidates for radioprotective therapeutic regimens.
摘要：
Microcystin-LR (MC-LR), a potent cyclic heptapeptide hepatotoxin released by Microcystis aeruginosa , poses significant threats to aquatic ecosystems and human health. Although microbial degradation provides an eco-friendly remediation strategy, approaches to actively modulate microbial physiology for improved detoxification remain poorly defined. Here, we hypothesize that bioelectrochemical stimulation via microbial fuel cells (MFCs) can enhance the metabolic activity and MC-LR degradation capacity of the facultative anaerobe Alcaligenes faecalis D04 through extracellular electron transfer (EET). Upon anodic colonization of A. faecalis D04, MC-LR degradation efficiency increased from 11.2 % (open-circuit control) to 70 % within 48 h. Acetate supplementation further elevated the relative abundance of A. faecalis D04 to 7 % in the anodic community, suggesting improved colonization and activity under electroactive conditions. Optimizing the external resistance to 50 Ω led to increased current generation and further boosted degradation efficiency to 80 %. Electrochemical cultivation in a three-electrode system confirmed that anodic potentials (−0.3 V vs. Ag/AgCl) significantly enhanced the electroactivity of A. faecalis D04, producing current responses of −85 μA and achieving 90 % MC-LR removal with substantial detoxification, as confirmed via AMES assays. Mechanistic insights from RT-PCR analyses showed that bioelectrochemical stimulation upregulated genes associated with MC-LR biodegradation and key metabolic pathways. Our findings establish a mechanistic link between EET activity and enhanced anaerobic toxin degradation, offering a scalable framework for the electrochemical control of pollutant-degrading microbial systems.
Microcystin-LR (MC-LR), a potent cyclic heptapeptide hepatotoxin released by Microcystis aeruginosa , poses significant threats to aquatic ecosystems and human health. Although microbial degradation provides an eco-friendly remediation strategy, approaches to actively modulate microbial physiology for improved detoxification remain poorly defined. Here, we hypothesize that bioelectrochemical stimulation via microbial fuel cells (MFCs) can enhance the metabolic activity and MC-LR degradation capacity of the facultative anaerobe Alcaligenes faecalis D04 through extracellular electron transfer (EET). Upon anodic colonization of A. faecalis D04, MC-LR degradation efficiency increased from 11.2 % (open-circuit control) to 70 % within 48 h. Acetate supplementation further elevated the relative abundance of A. faecalis D04 to 7 % in the anodic community, suggesting improved colonization and activity under electroactive conditions. Optimizing the external resistance to 50 Ω led to increased current generation and further boosted degradation efficiency to 80 %. Electrochemical cultivation in a three-electrode system confirmed that anodic potentials (−0.3 V vs. Ag/AgCl) significantly enhanced the electroactivity of A. faecalis D04, producing current responses of −85 μA and achieving 90 % MC-LR removal with substantial detoxification, as confirmed via AMES assays. Mechanistic insights from RT-PCR analyses showed that bioelectrochemical stimulation upregulated genes associated with MC-LR biodegradation and key metabolic pathways. Our findings establish a mechanistic link between EET activity and enhanced anaerobic toxin degradation, offering a scalable framework for the electrochemical control of pollutant-degrading microbial systems.
作者机构：
[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;[Tang, Jingjing; Tang, Wei; Li, Yanlin; Li, Zhenkui] Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.;[Liu, Cong] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Dept Hlth Inspect & Quarantine, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Li, ZK ] U;Univ South China, Inst Pathogen Biol, Sch Basic Med Sci, Hengyang Med Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Sch Basic Med Sci, Hengyang Med Sch, Key Lab Special Pathogen Prevent & Control Hunan P, Hengyang 421001, Hunan, Peoples R China.
摘要：
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle, which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process. This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development, influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
Malaria, a severe parasitic disease caused by Plasmodium infections, remains a major global health challenge. Efforts to eradicate malaria are complicated by the parasite’s intricate life cycle, which alternates between vertebrate hosts and mosquito vectors. Host-derived factors and parasite-sourced components exert crucial roles in regulating this biological process. This review explores the critical role of host-derived factors in shaping Plasmodium sexual differentiation and transmission. We examine how vertebrate and mosquito host-specific factors either promote or restrict parasite development, influencing the transition from vertebrates to mosquitoes. Understanding these host-mediated mechanisms is crucial for developing novel transmission-blocking strategies to reduce malaria prevalence. By highlighting key interactions between hosts and parasites, this review provides insights into potential interventions that could disrupt Plasmodium transmission and contribute to malaria control efforts.
摘要：
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.
摘要：
To overcome the drawbacks of poor stability and analytical accuracy with exogenous co-reactants in electrochemiluminescence (ECL), a self-enhanced nanoemitter, i.e., polyethylenimine-coupled pyrene derivative doped silica nanoparticles (H 4 -PEI@SiO 2 NPs), is proposed in this work. Here, H 4 -PEI@SiO 2 NPs not only serves as an emitter, but also plays the role of endogenous coreactant. Based on H 4 -PEI@SiO 2 NPs, a self-enhanced ECL aptasensor is fabricated for ultra-sensitive detection of di-2-ethylhexyl phthalate (DEHP). Notably, as the endogenous coreactant, polyethyleneimine (PEI) covalently connects with 1, 3, 6, 8-tetra(4-carboxyphenyl)pyrene (H 4 TBAPy) to form H 4 -PEI@SiO 2 NPs, which exhibit robust ECL emission. When DEHP is present, its aptamer would target DEHP and release trigger DNA (tDNA) to initiate catalytic hairpin assembly (CHA) cycles. Then, ferrocene (Fc)-modified hairpin chain DNA2 (H2-Fc) is captured by the as-opened hairpin chain DNA1 (H1). As a result, the ECL signal of H 4 -PEI@SiO 2 NPs is significantly quenched by H2-Fc. The ECL aptasensor exhibits ultra-sensitive and highly selective detection of DEHP in a wide concentration range of 1 fg/mL to 0.1 μg/mL with a low detection limit (LOD) of 0.04 fg/mL. What’s more, the ECL aptasensor exhibits outstanding practicality for DEHP assay in real food and water samples. This work provides a promising ECL platform for monitoring pollutants and food safety.
To overcome the drawbacks of poor stability and analytical accuracy with exogenous co-reactants in electrochemiluminescence (ECL), a self-enhanced nanoemitter, i.e., polyethylenimine-coupled pyrene derivative doped silica nanoparticles (H 4 -PEI@SiO 2 NPs), is proposed in this work. Here, H 4 -PEI@SiO 2 NPs not only serves as an emitter, but also plays the role of endogenous coreactant. Based on H 4 -PEI@SiO 2 NPs, a self-enhanced ECL aptasensor is fabricated for ultra-sensitive detection of di-2-ethylhexyl phthalate (DEHP). Notably, as the endogenous coreactant, polyethyleneimine (PEI) covalently connects with 1, 3, 6, 8-tetra(4-carboxyphenyl)pyrene (H 4 TBAPy) to form H 4 -PEI@SiO 2 NPs, which exhibit robust ECL emission. When DEHP is present, its aptamer would target DEHP and release trigger DNA (tDNA) to initiate catalytic hairpin assembly (CHA) cycles. Then, ferrocene (Fc)-modified hairpin chain DNA2 (H2-Fc) is captured by the as-opened hairpin chain DNA1 (H1). As a result, the ECL signal of H 4 -PEI@SiO 2 NPs is significantly quenched by H2-Fc. The ECL aptasensor exhibits ultra-sensitive and highly selective detection of DEHP in a wide concentration range of 1 fg/mL to 0.1 μg/mL with a low detection limit (LOD) of 0.04 fg/mL. What’s more, the ECL aptasensor exhibits outstanding practicality for DEHP assay in real food and water samples. This work provides a promising ECL platform for monitoring pollutants and food safety.
期刊：
International Journal of Molecular Sciences,2025年26(14) ISSN：1661-6596
通讯作者：
Zhou, Ping-Kun;Gu, YQ
作者机构：
[Wang, Yilong; Zhu, Jiaojiao; Zhou, Lin; Yan, Ziyan; Gu, Yongqing; Liu, Yuhao; Zhou, Ping-Kun] Beijing Inst Radiat Med, Beijing 100850, Peoples R China.;[Chen, Huixi; Gu, Yongqing] Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;[Hou, Yifan; Gu, Yongqing] Hebei Univ, Coll Life Sci, Baoding 071001, Peoples R China.;[Zhang, Xinyu; Gu, Yongqing] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;[Chen, Zhongmin] PLA Rocket Force Characterist Med Ctr, Beijing 100850, Peoples R China.
通讯机构：
[Zhou, PK; Gu, YQ ] B;Beijing Inst Radiat Med, Beijing 100850, Peoples R China.;Univ South China, Hengyang Med Coll, Hengyang 421001, Peoples R China.;Hebei Univ, Coll Life Sci, Baoding 071001, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.
关键词：
DNA methylation;MassArray;RRBS;episignatures;lung cancer;radon
摘要：
Radon (Rn) exposure has a strong association with lung cancer risk and is influenced by epigenetic modifications. To investigate the characterization of DNA methylation (DNAm) episignatures for radon-induced lung cancer, we detected the specific changes in DNAm in blood and lung tissues using reduced representation bisulfite sequencing (RRBS). We identified the differentially methylated regions (DMRs) induced by radon exposure. The bioinformatics analysis of the DMR-mapped genes revealed that pathways in cancer were affected by radon exposure. Among them, the DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 were repeated between lung tissue and blood, and validated by the MassArray. In addition, radon exposure promoted lung cancer development in the genetic engineering mouse model (GEMM), accompanied by decreased MAPK10 and increased PLCG1, PLCβ3, and PIK3R2 with mRNA and protein levels. Conclusively, radon exposure significantly changes the genomic DNAm patterns in lung tissue and blood. The DNAm episignatures of MAPK10, PLCG1, PLCβ3 and PIK3R2 have a significant influence on radon-induced lung cancer. This brings a new perspective to understanding the pathways involved in radon-induced lung cancer and offers potential targets for developing blood-based biomarkers and epigenetic therapeutics.
摘要：
INTRODUCTION: Carbapenem-resistant (CR) Gram-negative pathogens are classified by the WHO as critical threats due to limited therapeutic options. Cefiderocol (CFD), a novel siderophore cephalosporin, shows promise but remains unapproved in China. This study investigated the prevalence, clinical impact, and genetic mechanisms of cefiderocol heteroresistance (CFD-HR) in CR and ESBL-producing clinical isolates from China, where CFD remains unapproved. METHODS: A total of 407 CR and ESBL-producing isolates were analyzed. CFD-HR was identified by population analysis profiles (PAPs). Clinical relevance was assessed through disk diffusion susceptibility testing, time-kill assays, and a murine peritonitis model. Genetic mechanisms and stability were elucidated by whole-genome sequencing (WGS) and fitness cost assays. RESULTS: CFD-HR prevalence was 17.4% (16/92) in carbapenem-resistant A. baumannii (CRAB), 27.9% (24/86) in carbapenem-resistant P. aeruginosa (CRPA), 23.8% (10/42) in carbapenem-resistant E. coli (CRE), and ≤10% (1/10 in ESBL-producing P. aeruginosa and 8/177 in ESBL-producing E. coli). Although 72.9% (43/59) of HR isolates were classified as CFD-susceptible by disk diffusion, time-kill assays showed that 66.7% (4/6) of HR strains required ≥8 mg/L CFD (vs. 4 mg/L for non-HR) to prevent regrowth. In vivo, CFD achieved 100% (3/3) survival in non-HR infections but only 16.7% (4/6) in HR-infected mice. WGS identified transient genetic alterations in HR subpopulations, including sitABCD duplications (CRE), oprD mutations (CRAB), and vgrG SNPs (CRPA), which reverted after antibiotic withdrawal. Fitness cost assays revealed unstable growth deficits in 33.3% (2/6) of HR subpopulations, correlating with genetic instability. DISCUSSION: These findings highlight the clinical significance of CFD-HR, even in susceptible isolates, and underscore the need for improved diagnostic methods to detect HR and monitor cross-resistance, offering critical insights for regions transitioning to CFD implementation.
期刊：
Biosensors and Bioelectronics,2025年:117950 ISSN：0956-5663
通讯作者：
Yu Liu
作者机构：
[Yao Yu; Sihan Chen; Le Li] Hunan Key Laboratory of Typical Environment Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, PR China;Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China;[Qingyun Cai] State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China;[Deshuai Zhen; Qiuhui Deng] Hunan Key Laboratory of Typical Environment Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China;[Yu Liu] Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
通讯机构：
[Yu Liu] C;Cancer Research Institute, The First Affiliated Hospital, University of South China, Hengyang 421001, PR China<&wdkj&>State Key Laboratory of Chemo/Biosensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, PR China
摘要：
A highly sensitive, selective, and simple method for detecting uranyl ions (UO 2 2+ ) is crucial for human health and environmental safety. Amidoxime-based nanomaterials have been widely employed for UO 2 2+ detection, but their higher affinity for vanadium than UO 2 2+ limits their practical applications. Herein, a novel covalent organic polymer fluorescent probe (TT-COP) for UO 2 2+ detection was innovatively developed by a one-step Schiff-base condensation reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and 2,4,6-triformylphloroglucinol (Tp). TT-COP not only possesses excellent thermodynamic stability, hydrophilicity, synthetic reproducibility, and fluorescence stability but also achieves outstanding sensing performance, with its interaction with UO 2 2+ reaching equilibrium within 5 min and a detection limit of 35.75 nM. Further investigations reveal that UO 2 2+ coordinates with the imine and hydroxyl groups of TT-COP, thereby inhibiting the intramolecular charge transfer (ICT) process and leading to fluorescence quenching. Moreover, TT-COP exhibits extraordinary selectivity and biocompatibility, enabling reliable UO 2 2+ quantification in complex matrices including environmental waters, food, and biological samples, with recovery rates ranging from 94.54% to 106.43%. The detection results closely align with those obtained from high-precision ICP-MS measurements. These findings underscore the promising practical applications of TT-COP in food safety, environmental monitoring, and human health assessment.
A highly sensitive, selective, and simple method for detecting uranyl ions (UO 2 2+ ) is crucial for human health and environmental safety. Amidoxime-based nanomaterials have been widely employed for UO 2 2+ detection, but their higher affinity for vanadium than UO 2 2+ limits their practical applications. Herein, a novel covalent organic polymer fluorescent probe (TT-COP) for UO 2 2+ detection was innovatively developed by a one-step Schiff-base condensation reaction between 3,3',5,5'-tetramethylbenzidine (TMB) and 2,4,6-triformylphloroglucinol (Tp). TT-COP not only possesses excellent thermodynamic stability, hydrophilicity, synthetic reproducibility, and fluorescence stability but also achieves outstanding sensing performance, with its interaction with UO 2 2+ reaching equilibrium within 5 min and a detection limit of 35.75 nM. Further investigations reveal that UO 2 2+ coordinates with the imine and hydroxyl groups of TT-COP, thereby inhibiting the intramolecular charge transfer (ICT) process and leading to fluorescence quenching. Moreover, TT-COP exhibits extraordinary selectivity and biocompatibility, enabling reliable UO 2 2+ quantification in complex matrices including environmental waters, food, and biological samples, with recovery rates ranging from 94.54% to 106.43%. The detection results closely align with those obtained from high-precision ICP-MS measurements. These findings underscore the promising practical applications of TT-COP in food safety, environmental monitoring, and human health assessment.
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+ .
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] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;[Yao, Xiang-Rong; Xiao, Fang-Zhu] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Xiao, Wen-Tao] Nantong Univ, Affiliated Hosp, Med Sch, Dept Radiat Oncol, Nantong, Peoples R China.;[Huang, Cui-Qin] Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
通讯机构：
[He, JY ; Huang, CQ ] U;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Dept Oncol, Hengyang, Peoples R China.;Univ South China, Hengyang Med Sch, Affiliated Hosp 1, Dept Pathol, Hengyang, Peoples R China.
摘要：
Head and neck squamous cell carcinoma (HNSC) is a prevalent and aggressive malignancy with poor prognosis, underscoring the need for novel biomarkers and therapeutic strategies. This study investigates the role of C16orf74 as a potential diagnostic and prognostic biomarker in HNSC. Bioinformatics analyses revealed that C16orf74 is significantly overexpressed in HNSC and is associated with advanced disease stages, therapy resistance, and shorter overall and progression-free survival. A prognostic nomogram integrating C16orf74 expression with clinicopathological features demonstrated robust predictive performance. Functional enrichment and immune infiltration analyses suggest that high C16orf74 expression might contribute to an immunosuppressive tumor microenvironment by reducing key immune cell populations, such as B cells, T cells, and natural killer cells, which are critical for anti-tumor immunity. Moreover, C16orf74 expression was inversely associated with immune checkpoint expression and immunotherapy response, highlighting its potential as a predictive biomarker for immune checkpoint blockade (ICB) efficacy. Drug sensitivity analyses identified potential therapeutic agents, including arsenic trioxide, carmustine, vincristine, quercetin, and carboplatin for patients with high C16orf74 expression. These findings highlight the potential of C16orf74 as a biomarker and therapeutic target to improve HNSC management.
摘要：
African swine fever virus (ASFV) predominantly infects Argasidae and suids, resulting in high morbidity and mortality in pigs. Despite the crucial role that viral sequences resembling those of the host play in the virus's survival, there are limited comprehensive studies on the genomic similarities between ASFV and its hosts. Consequently, this study employs homology analysis to construct a similarity network between ASFV and its hosts (Argasidae and suids), investigating the distribution, function, evolution, and origins of these similar sequences in ASFV. Our findings indicate that the host-similar fragments are mainly distributed between positions 70000 and 180000 of the ASFV genome, primarily within non-coding regions. Notably, these non-coding fragments are often associated with promoter functions. Furthermore, the analysis of suid proteins that share similarities with ASFV proteins reveals that they predominantly exhibit RNA polymerase activity and are involved in metabolic processes. Evolutionary analysis indicates that pan-similar sequences of ASFV exist in an open state, highlighting the diversity of these analogous sequences. Additionally, a positive correlation was identified between the occurrence of recombination breakpoints and similar sequences, indicating that homologous recombination may serve as a crucial mechanism driving the formation of these analogous sequences.
作者机构：
[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.
作者机构：
[Li, Jingxian; Lyu, Yifan; Shen, Yan; Li, Yujin; Wang, Futing; Cai, Ren; Tan, Weihong] Hunan Univ, Mol Sci & Biomed Lab, State Key Lab Chemo Biosensing & Chemometr, Coll Mat Sci & Engn,Coll Chem & Chem Engn,Coll Bio, Changsha 410082, Peoples R China.;[Li, Yujin] Xinyang Normal Univ, Coll Chem & Chem Engn, Xinyang 464000, Peoples R China.;[Yang, Dan] RMIT Univ, Sch Engn, Melbourne, Vic 3000, Australia.;[Yang, Hongfen] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.;[Tan, Weihong] Chinese Acad Sci, Univ Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM,Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China.
通讯机构：
[Yang, HF ] U;[Cai, R ] H;Hunan Univ, Mol Sci & Biomed Lab, State Key Lab Chemo Biosensing & Chemometr, Coll Mat Sci & Engn,Coll Chem & Chem Engn,Coll Bio, Changsha 410082, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Key Lab Typ Environm Pollut & Hlth Hazards, Hengyang 421001, Peoples R China.
摘要：
A highly sensitive self-powered biosensor is designed based on gold-platinum nanorods (AuPt NRs) and the cascade reaction of catalytic hairpin assembly (CHA) and hybrid chain reaction (HCR) toward the miRNA-141 assay. As a cosignal accelerator, AuPt NRs enhance electrical conductivity between glucose oxidase (GOD) and a carbon paper (CP) electrode, thereby assisting in output signal enhancement. The cascade reaction of CHA-HCR is employed to efficiently amplify the detection signal and improve the sensitivity of the self-powered biosensor. Consequently, the self-powered biosensor provides highly sensitive detection of miRNA-141 with a wide linear response in the range of 0.1-10(4) fM and exhibits a low limit of detection (LOD) of 0.034 fM (S/N = 3). In addition, the self-powered biosensor exhibits high applicability in a real sample for the miRNA-141 assay.
期刊：
Chemical Engineering Journal,2025年:167389 ISSN：1385-8947
通讯作者：
Xizi Long
作者机构：
[Xizi Long; Piao Yi; Weiqi Yang; Zhaozhong Zhu; Tangjian Peng; Xiaoya Ren; Pengji Zhou; Fei Yang] Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China;[Bin Bian] School of Sustainable Energy and Resources, Nanjing University, Suzhou 215163, China
通讯机构：
[Xizi Long] K;Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China
