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.
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.
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.
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.
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.
作者机构：
[Li, Gang; Han, Yang; Bai, Chenjun; Zhao, Hongling; Guan, Hua; Gao, Shanshan; Jia, Jin; Luo, Jinhua; Zhou, Ping-Kun; Liu, Xiaochang; Xie, Dafei; Guo, Hejiang; Xuan, Lihui; Gu, Yongqing; Tan, Jinpeng; Huang, Xin; Hu, Weixiang; Guan, H; Liu, Yuhao] Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiobiol, Beijing, Peoples R China.;[Huang, Ruixue; Luo, Jinhua; Xuan, Lihui] Cent South Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha, Hunan, Peoples R China.;[Li, Zhongjun; Ran, Qian] Army Mil Med Univ, Affiliated Hosp 2, Lab Med Ctr, Dept Blood Transfus,Lab Radiat Biol, Chongqing, Peoples R China.;[Li, Gang; Jia, Jin; Zhou, Ping-Kun; Tan, Jinpeng] Univ South China, Hengyang Med Coll, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[Ma, Teng] Capital Med Univ, Beijing Chest Hosp, Beijing TB & Thorac Tumor Res Inst, Canc Res Ctr, Beijing, Peoples R China.
通讯机构：
[Guan, H; Zhou, PK ] B;[Huang, RX ] C;Beijing Inst Radiat Med, Dept Radiat Biol, Beijing Key Lab Radiobiol, Beijing, Peoples R China.;Cent South Univ, Xiangya Sch Publ Hlth, Dept Occupat & Environm Hlth, Changsha, Hunan, Peoples R China.;Univ South China, Hengyang Med Coll, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.
摘要：
Chemo-/radioresistance of malignant tumors hampers cancer control and increases patient mortality. Efficient repair of damaged DNA is critical for the maintenance of genomic integrity and fidelity of genetic information. In reverse, increased DNA repair capability in cancer cells contributes to chemo-/radioresistance of malignant tumors. DNA double-strand break (DSB) is the most serious DNA damage and is also the principal molecular basis of radiotherapy. Upon DNA damage, the Ku80 is recruited and forms a critical DNA-PK complex at the DSB sites with Ku70 and the catalytic subunit (DNA-PKcs) to initiate DNA repair. How DNA-PK is assembled and activated is not fully understood. Based on the identification of radiation-reduced Ku80 K568 crotonylation through quantitative global lysine crotonylome analysis, we reveal that Ku80 K568 is crotonylated by p300-CBP-associated factor (PCAF). Upon DNA damage, the K568cr is decrotonylated by HDAC8 (Histone deacetylase 8). Decrotonylation of K568cr empties this site for the subsequent SUMOylation of Ku80 by CBX4. The conversion of Ku80 from K568 crotonylation to SUMOylation facilitates the assembly of DNA-PK complex and autophosphorylation of DNA-PKcs S2056, consequently activating the DSB repair. Moreover, mutation disrupting the post-translational modification (PTM) of Ku80 K568 site sensitizes cancer cells to radiotherapy in tumor-bearing nude mice models. This study elucidates the conversion model between two different forms of PTMs in the regulation of DNA-PK complex assembly and DSB repair, highlighting this model's potential in controlling chemo-/radioresistance of malignant tumors, as well as expands the atlas of therapeutic targets.
摘要：
BACKGROUND: Antibiotics, as the most commonly prescribed class of drugs in neonatal intensive care units, have an important impact on the developing neonatal gut microbiota. Therefore, comprehending the effects of commonly used antibiotic therapy on the gut microbiota and butyrate-producers in early infants could provide information for therapeutic decision-making in the NICU. OBJECTIVES: To explore the effects of antibiotic therapy on the early development of gut microbiota and butyrate-producers in early infants. METHODS: A total of 72 infants were included in the study. We performed 16S rRNA sequencing on stool swab samples collected from neonatal intensive care unit patients who received amoxicillin-clavulanic acid (AC, n = 10), moxalactam (ML, n = 28) and non-antibiotics (NA, n = 34). We then compared the taxonomic composition between treatment regimens, focusing on differences in butyrate-producers. RESULTS: Our study showed that there were significant differences in Shannon index (p = 0.033) and Beta diversity (p = 0.014) among the three groups. At the family level, compared with the other two groups, the relative abundance of Clostridiaceae (p < 0.001) and Veillonellaceae (p = 0.004) were significantly higher, while the relative abundance of Enterococcidae (p < 0.001) was significantly lower in the NA group. The relative abundance of Enterobacteriaceae (p = 0.022) in the AC group was greater than that in the other two groups. Additionally, butyrate-producers (p < 0.001), especially Clostridiaceae (p < 0.001), were noticeably more abundant in the NA group. The relative abundance of Clostridiaceae and butyrate-producers were the lowest in the ML group (p < 0.001). CONCLUSION: We found that antibiotic therapy had an adverse impact on the initial development of gut microbiota and leaded to a reduction in the abundance of butyrate-producers, particularly Clostridiaceae. Furthermore, moxalactam had a more pronounced effect on the gut microbiota compared to amoxicillin-clavulanic acid.
摘要：
Occupational exposure to N-hexane/2,5-hexanedione (2,5-HD) was found to adversely affect reproductive functions in females. However, there are few studies regarding the mechanisms underlying reproductive system damage initiated by 2,5-HD. Several studies demonstrated that 2,5-HD exerts hormonal dysfunctions in females by promoting apoptosis using rat ovarian granulosa cells (GCs) as a model. The endoplasmic reticulum (ER) plays a key role in cellular processes such as protein folding and modification, Ca(2+) storage, and lipid synthesis, which are known to involve the activation of stress (ERS)-dependent m-TOR signaling pathway. Thus, the aim of this study was to examine the effects of 2,5-HD on ER and the associated activation of stress (ERS)-dependent m-TOR signaling pathway resulting in consequent apoptosis of ovarian GCs. Data demonstrated that after intraperitoneal treatment with 100, 200, or 400 mg/kg 2,5-HD for 6 consecutive weeks, 5 times per week, a decrease in body weight, ovarian weight, and relative ovary weight was found. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay showed that 2,5-HD promoted apoptosis of ovarian GCs, which involved enhanced relative protein expression levels of m-TOR/p-mTOR. Our findings demonstrated that 2,5-HD (1) elevated expression levels of pro-apoptosis-related genes Bax and Caspase 3, (2) decreased expression levels of the anti-apoptosis gene Bcl-2, and (3) activated the protein expression of glucose-regulatory protein 78 (GRP78), inositol-requiring enzyme-1 (IRE1), and c-Jun terminal kinase (JNK) associated with increased apoptosis. Evidence indicates that chronic exposure to 2,5-HD induced apoptosis of ovarian GCs, and the possible mechanism underlying this effect involves the ERS-dependent m-TOR signaling pathway.
作者机构：
[Zhao, Kunyan; Song, Fengmei; Yang, Fei; Tang, Yan] Univ South China, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Wu, Mingyang] Cent South Univ, Xiangya Sch Publ Hlth, Dept Maternal & Child Hlth, Changsha 410007, Peoples R China.;[Qiu, Jun; Qiu, J; Pan, Xiongfeng; Liu, Caixia; Xiang, Shiting] Cent South Univ, Affiliated Childrens Hosp, Hunan Childrens Hosp, Pediat Res Inst Hunan Prov,Xiangya Sch Med, Changsha 410007, Peoples R China.;[Peng, Yunlong] Soochow Univ, Dept Epidemiol & Hlth Stat, Med Coll, Suzhou 215123, Peoples R China.;[Cao, Yunhui; Wu, Sha] Univ South China, Hengyang Med Sch, Dept Pediat, Hengyang 421001, Peoples R China.
通讯机构：
[Qiu, J ] C;Cent South Univ, Affiliated Childrens Hosp, Hunan Childrens Hosp, Pediat Res Inst Hunan Prov,Xiangya Sch Med, Changsha 410007, Peoples R China.
关键词：
Early life;Gut microbiota;Neonate;Thallium
摘要：
Previous research has found a correlation between heavy metals and gut microbiota in humans. However, there are few population-based studies examining the impact of early life thallium (Tl) exposure on neonatal microbiome. 342 newborns were recruited from Hunan Children's Hospital and subsequently divided into three groups (low, medium, and high) based on the 25th and 75th percentiles of serum Tl concentration. Additionally, the relationship between Tl and gut microbiota was analyzed in subgroups (preterm or full-term neonates). The association between Tl and gut microbiota in neonates was analyzed by Redundancy analysis, Spearman correlation analysis and MaAsLin2. The detection rate of Tl in neonates was 100%, with the median concentration of 0.021 μg/L. In all neonates, we found significant differences in the Chao1 and ACE indices of α-diversity in gut microbiota, and the relative abundances of Bacteroidota and Bacteroidetes were significantly different among groups ( p < 0.05). Following the covariate adjustment, Tl was negatively correlated with Gemmatimonadota (Coef = 0.265, p < 0.05) in preterm neonates. In full-term neonates, Tl exhibited a positive correlation with the relative abundance of Robinsoniella (Coef = 0.563, p = 0.009) and a negative correlation with that of Pseudomonas (Coef = - 0.592, p = 0.012). Tryptophan and renin-angiotensin system pathways might exert important roles in Tl exposure. This study indicated that Tl exposure was associated with changes in α-diversity and the composition of gut microbiota in neonates, with Gemmatimonadota being predominantly affected in preterm neonates and Robinsoniella and Pseudomonas in full-term neonates.
Previous research has found a correlation between heavy metals and gut microbiota in humans. However, there are few population-based studies examining the impact of early life thallium (Tl) exposure on neonatal microbiome. 342 newborns were recruited from Hunan Children's Hospital and subsequently divided into three groups (low, medium, and high) based on the 25th and 75th percentiles of serum Tl concentration. Additionally, the relationship between Tl and gut microbiota was analyzed in subgroups (preterm or full-term neonates). The association between Tl and gut microbiota in neonates was analyzed by Redundancy analysis, Spearman correlation analysis and MaAsLin2. The detection rate of Tl in neonates was 100%, with the median concentration of 0.021 μg/L. In all neonates, we found significant differences in the Chao1 and ACE indices of α-diversity in gut microbiota, and the relative abundances of Bacteroidota and Bacteroidetes were significantly different among groups ( p < 0.05). Following the covariate adjustment, Tl was negatively correlated with Gemmatimonadota (Coef = 0.265, p < 0.05) in preterm neonates. In full-term neonates, Tl exhibited a positive correlation with the relative abundance of Robinsoniella (Coef = 0.563, p = 0.009) and a negative correlation with that of Pseudomonas (Coef = - 0.592, p = 0.012). Tryptophan and renin-angiotensin system pathways might exert important roles in Tl exposure. This study indicated that Tl exposure was associated with changes in α-diversity and the composition of gut microbiota in neonates, with Gemmatimonadota being predominantly affected in preterm neonates and Robinsoniella and Pseudomonas in full-term neonates.
作者机构：
[Liu, Yu; Long, Dingxin; Ning, Yujun; Zhang, Zhibo; Wang, Ru; Zhong, Chiting; Zhao, Weichao; Zhao, WC; Wang, Kongfan; Chen, Xiaobing; Ou, Yiquan] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.;[Ou, Yiquan] Chenzhou Peoples Hosp 1, Dept Nutr, Chenzhou 423000, Peoples R China.;[Jiang, Yi] Sichuan Univ, West China Sch Publ Hlth, Chengdu 610041, Peoples R China.;[Jiang, Yi] Sichuan Univ, West China Hosp 4, Chengdu 610041, Peoples R China.;[Zhang, Zhibo] Univ South China, Hengyang Med Sch, Clin Fac 1, Hengyang 421001, Peoples R China.
通讯机构：
[Long, DX; Zhao, WC ] 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：
Growth and development;Neurobehavior;Oxygenated polycyclic aromatic hydrocarbons (OPAHs);Polyethylene
摘要：
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of anthropogenic, persistent, and highly toxic PAH contaminants associated with developmental toxicity, 9-fluorenone (9-FLO) is a typical member of the OPAH family. Due to its ketone group, it has higher polarity, which results in increased solubility in water and greater potential for transport via atmospheric particles or water bodies. Polyethylene (PE), an amorphous polymer, is characterized by high diffusivity, high permeability, and a large internal molecular free volume, which confers a strong absorption capacity for organic pollutants. The effects of individual and combined exposures to these two common environmental pollutants on aquatic life remain unclear. In this study, we evaluated the effects of PE and 9-FLO exposure on growth, development, metabolism, and behavior using zebrafish as a model organism. We employed methods and techniques such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking, automated behavior analysis, microscopy imaging, and real-time fluorescence quantification. Zebrafish embryos at 2 hours post-fertilization (hpf) were exposed to PE and 9-FLO, both individually and in combination. Our studies showed that exposure to PE or 9-FLO alone increases embryonic mortality and decreases hatchability compared to the control group. The 9-FLO group exhibited delayed hatching and inhibited larval length growth. The exposed groups showed a loose arrangement of telencephalic neurons, partial apoptosis, decreased dopamine (DA) content, increased serotonin (5-HT) content, decreased exercise capacity, reduced rhythmic amplitude, and increased rest time. The combined exposure group showed a slight alleviation of these effects compared to the single exposure groups but still exhibited significant differences from the control group. In summary, early exposure to PE and 9-FLO in zebrafish embryos, whether alone or in combination, affects growth, development, apoptosis, neurotransmitter release, and motor behavior of zebrafish neurons.
Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are a class of anthropogenic, persistent, and highly toxic PAH contaminants associated with developmental toxicity, 9-fluorenone (9-FLO) is a typical member of the OPAH family. Due to its ketone group, it has higher polarity, which results in increased solubility in water and greater potential for transport via atmospheric particles or water bodies. Polyethylene (PE), an amorphous polymer, is characterized by high diffusivity, high permeability, and a large internal molecular free volume, which confers a strong absorption capacity for organic pollutants. The effects of individual and combined exposures to these two common environmental pollutants on aquatic life remain unclear. In this study, we evaluated the effects of PE and 9-FLO exposure on growth, development, metabolism, and behavior using zebrafish as a model organism. We employed methods and techniques such as acridine orange staining, enzyme-linked immunosorbent assay (ELISA), video tracking, automated behavior analysis, microscopy imaging, and real-time fluorescence quantification. Zebrafish embryos at 2 hours post-fertilization (hpf) were exposed to PE and 9-FLO, both individually and in combination. Our studies showed that exposure to PE or 9-FLO alone increases embryonic mortality and decreases hatchability compared to the control group. The 9-FLO group exhibited delayed hatching and inhibited larval length growth. The exposed groups showed a loose arrangement of telencephalic neurons, partial apoptosis, decreased dopamine (DA) content, increased serotonin (5-HT) content, decreased exercise capacity, reduced rhythmic amplitude, and increased rest time. The combined exposure group showed a slight alleviation of these effects compared to the single exposure groups but still exhibited significant differences from the control group. In summary, early exposure to PE and 9-FLO in zebrafish embryos, whether alone or in combination, affects growth, development, apoptosis, neurotransmitter release, and motor behavior of zebrafish neurons.
摘要：
Lactic acid has aroused increasing attention due to its close association with serious diseases. A real-time, dynamic, and intelligent detection method is vital for sensitive detection of lactic acid. Here, a machine learning (ML)-assisted perspiration-driven self-powered sensor (PDS sensor) is fabricated using Ni-ZIF-8@lactate oxidase and pyruvate oxidase (Ni-ZIF-8@LOx&POx)/laser-induced graphene (LIG), bilirubin oxidase (BOD)/LIG, and a microchannel for highly sensitive and real-time monitoring of lactic acid in sweat. Driven by the oxidation reaction of lactic acid, PDS sensors exhibit excellent sensitivity, a wide detection range, good reproducibility, and excellent selectivity for lactic acid detection in sweat. When subjects with different body mass index (BMI) undergo aerobic or anaerobic exercise or maintain a sedentary state, PDS sensors can monitor lactic acid in sweat wirelessly and in real-time. Moreover, a ML algorithm was employed to assist PDS sensors to detect lactic acid in the subjects' sweat with a high prediction accuracy of 96.0%.
摘要：
Beryllium (Be) is a recognised environmental toxicant associated with pulmonary fibrosis. Epithelial-mesenchymal transition (EMT), a critical process in cell phenotype conversion, plays a key role in its pathophysiology. Methyltransferase-like 3 (METTL3), a major N6-methyladenosine methyltransferase, regulates gene expression and cellular functions. However, its role in Be-induced EMT remains unclear. In this study, human bronchial epithelial cell line (16HBE cells) were exposed to varying concentrations of beryllium sulphate (BeSO(4)) to assess changes in METTL3 expression. METTL3 overexpression vectors were constructed, and quantitative reverse transcription-polymerase chain reaction, western blotting and immunofluorescence were used to detect METTL3, EMT markers and Wingless/Integrated (Wnt)/β-catenin pathway proteins. The Wnt/β-catenin pathway inhibitor ICG-001 was also employed to explore the role of the Wnt/β-catenin pathway in BeSO(4)-induced EMT. The study demonstrated that BeSO(4) suppressed METTL3 expression, induced EMT and activated the Wnt/β-catenin pathway in 16HBE cells. Both METTL3 overexpression and ICG-001 pretreatment mitigated BeSO(4)-induced EMT and Wnt/β-catenin pathway activation. These findings suggest that METTL3 inhibits BeSO(4)-induced EMT by suppressing the Wnt/β-catenin pathway, offering novel mechanistic insights into beryllium toxicity and a potential therapeutic target for Be-related pulmonary fibrosis.
关键词：
Aptasensor;Dose assessment;Electrochemical impedance aptasensor;Radiation biodosimeters;p21 protein
摘要：
Radiation dose assessment is the main basis for the diagnosis of acute radiation sickness. At present, there is a lack of rapid and portable dose assessment methods, which has an important impact on the rapid diagnosis and precise treatment of radiation accident patients and nuclear practitioners. We selected and obtained specific aptamers for radiation-sensitive protein p21 protein by the magnetic cross-linking precipitation (MCP)-SELEX procedure. The aptamer has a high affinity for binding to the p21 protein and its K d value is 2.21×10 -7 mol/L. We subsequently established a new method for radiation dose assessment of an electrochemical impedance (EIS) aptasensor with screen-printed electrode chips. There was a good dose-effect relationship between the p21 protein expression level in PBMCs in human peripheral blood detected by this method within the dose range of 0-10 Gy, and detection limit of radiation dose is 0.38 Gy (LOD, S/N = 3). This dose range covers the diagnostic range of acute radiation sickness in the bone marrow. This method is not only portable but also fast, saving hours to days compared with the previous dose assessment method based on radiation sensitive protein. It can be applied to the rapid and portable diagnosis of acute radiation sickness.
Radiation dose assessment is the main basis for the diagnosis of acute radiation sickness. At present, there is a lack of rapid and portable dose assessment methods, which has an important impact on the rapid diagnosis and precise treatment of radiation accident patients and nuclear practitioners. We selected and obtained specific aptamers for radiation-sensitive protein p21 protein by the magnetic cross-linking precipitation (MCP)-SELEX procedure. The aptamer has a high affinity for binding to the p21 protein and its K d value is 2.21×10 -7 mol/L. We subsequently established a new method for radiation dose assessment of an electrochemical impedance (EIS) aptasensor with screen-printed electrode chips. There was a good dose-effect relationship between the p21 protein expression level in PBMCs in human peripheral blood detected by this method within the dose range of 0-10 Gy, and detection limit of radiation dose is 0.38 Gy (LOD, S/N = 3). This dose range covers the diagnostic range of acute radiation sickness in the bone marrow. This method is not only portable but also fast, saving hours to days compared with the previous dose assessment method based on radiation sensitive protein. It can be applied to the rapid and portable diagnosis of acute radiation sickness.
期刊：
Journal of Nanobiotechnology,2025年23(1):1-15 ISSN：1477-3155
通讯作者：
Du, Meng;Chen, ZY
作者机构：
[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M; Xu, Haonan] Univ South China, Affiliated Changsha Cent Hosp, Coll Hunan Prov, Hengyang Med Sch,Key Lab Med Imaging Precis Theran, Changsha, Peoples R China.;[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M] Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Med Imaging, Changsha, Peoples R China.;[Lei, Lingling; Du, Meng; Chen, Zhiyi; Li, Mingjie; Du, M; Xu, Haonan] Univ South China, Inst Med Imaging, Hengyang Med Sch, Hengyang, Peoples R China.;[Xu, Haonan] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.
通讯机构：
[Chen, ZY ; Du, M] U;Univ South China, Affiliated Changsha Cent Hosp, Coll Hunan Prov, Hengyang Med Sch,Key Lab Med Imaging Precis Theran, Changsha, Peoples R China.;Univ South China, Affiliated Changsha Cent Hosp, Hengyang Med Sch, Dept Med Imaging, Changsha, Peoples R China.;Univ South China, Inst Med Imaging, Hengyang Med Sch, Hengyang, Peoples R China.
摘要：
BACKGROUND: Radiotherapy efficacy remains constrained by two key challenges: dose-dependent toxicity to healthy tissues at high radiation doses and hypoxia-mediated tumor radioresistance. While radiosensitizers like gold nanoparticles can enhance tumor-specific radiation deposition, their targeted delivery to tumors presents a significant hurdle. Bacteria have emerged as promising bio-carriers that not only actively target tumors and penetrate complex microenvironments, but can also be genetically engineered as multifunctional platforms for radiosensitizer delivery and hypoxia alleviation. RESULTS: An integrated nanosystem (PCM@AuNPs), composed of engineered bacteria (PCM) and gold nanoparticles (AuNPs), is used to increase the effectiveness of radiotherapy. PCM can target and colonize tumor sites more effectively, thus improving the delivery efficiency of radiosensitizers. Furthermore, PCM overexpresses catalase (CAT), which decomposes excess H(2)O(2) into O(2), helping to mitigate hypoxia in the TME. Under X-ray irradiation, PCM@AuNPs significantly enhance radiosensitization, leading to improved tumor growth inhibition while maintaining good biocompatibility. CONCLUSIONS: An effective strategy based on an integrated nanosystem (PCM@AuNPs) for radiosensitization through multiple pathways is developed. This novel engineered bacterial strategy holds great promise for enhancing radiosensitization in cancer therapy.
摘要：
Uranium is the core material for the development of the nuclear industry, but its irreversible radiation damage poses a significant threat to human health. In this context, an innovative dual-mode colorimetric and electrochemical sensor was developed for the detection of uranyl ions (UO(2)(2+)), utilizing a covalent organic framework@gold nanoclusters (AuNCs@COF) composite. The synthesis of AuNCs@COF was simple, and the incorporation of AuNCs imparted the composite with exceptional peroxidase-like catalytic activity and enhanced electrochemical properties. By regulating the adsorption and desorption of aptamers on the AuNCs@COF surface, both peroxidase-like activity and conductivity were modulated, enabling the detection of UO(2)(2+) utilizing colorimetric and electrochemical dual signals. Under optimal conditions, the sensor revealed a broad linear detection range and a low detection limit, with ranges of 1.36 × 10(-10)-1.36 × 10(-5)mol/L for colorimetric detection and 5.0 × 10(-10)-2.5 × 10(-5)mol/L for electrochemical detection, achieving detection limitsfor these two methodsof 107 pmol/L and 347 pmol/L, respectively. Unlike other single-mode sensorsfor UO(2)(2+) detection, this dual-mode sensor demonstrated superior sensitivity, specificity, and repeatability. Furthermore, the results of spiked recovery experiments in real water samples highlight the promising potential of this dual-mode sensor for environmental water monitoring applications.
