作者机构：
[童学智; 杨胜园] Department of Public Health Laboratory Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China;[陈东洋; 范翔; 张昊; 冯家力] Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China
通讯机构：
[Dongyang, C.] H;Hunan Provincial Center for Disease Control and PreventionChina
期刊：
Journal of Pharmacy and Pharmacology,2023年75(8):1086-1099 ISSN：0022-3573
通讯作者：
Xifei Yang
作者机构：
[Yang, Xifei; Gao, Chuanyue; Wang, Xingxing] Shanxi Med Univ, Sch Publ Hlth, Taiyuan, Peoples R China.;[Deng, Huiping; Liu, Jianjun; Yang, Xifei; Huang, Xinfeng; Gao, Chuanyue; Nie, Lulin; He, Kaiwu; Wang, Xingxing; Zhang, Huan] Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 2024, Shenzhen, Peoples R China.;[Zhang, Huan] Univ South China, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[Nie, Lulin] Jinan Univ Coll Pharm, Inst New Drug Res & Guangzhou, Key Lab Innovat Chem Drug Res Cardiocerebrovasc Di, Guangzhou 510632, Peoples R China.;[Li, Peimao] Shenzhen Prevent & Treatment Ctr Occupat Dis, Med Lab, Shenzhen, Peoples R China.
通讯机构：
[Xifei Yang] S;School of Public Health, Shanxi Medical University , Taiyuan , China<&wdkj&>Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology (2020–2024), Shenzhen Center for Disease Control and Prevention , Shenzhen , China
关键词：
NAFLD;chrysin;inflammation;inflammasome;AMPK
摘要：
OBJECTIVES: We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism. METHODS: To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin's therapeutic effects further. KEY FINDINGS: CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression. CONCLUSIONS: In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.
作者机构：
[Liu, Yan; Wen, Haoyu; Sun, Jinyi; Bai, Jianjun; Chen, Jiahao] Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China;[Liu, Yan] Hunan Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, China;[Yu, Chuanhua] Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan, China. Electronic address: yuchua@whu.edu.cn
通讯机构：
[Chuanhua Yu] D;Department of Epidemiology and Biostatistics, School of Public Health, Wuhan University, Wuhan
摘要：
BACKGROUND: This study investigated the impact of epidemiologic and sociodemographic changes in tracheal, bronchus, and lung cancer associated with residential radon, solid fuels, and particulate matter. RESEARCH QUESTION: What are the influencing factors of tracheal, bronchus, and lung cancer disease burden attributable to the three pollutants? STUDY DESIGN AND METHODS: Data were obtained from the Global Burden of Disease 2019. Age-standardized mortality rate (ASMR) and sociodemographic index (SDI) values were collected from 21 regions, and restricted cubic splines and quantile regression were used to investigate the relationship between ASMR or age-standardized disability-adjusted life years rate (ASDR), and SDI. Additionally, five countries with different SDIs were selected, and the Bayesian age-period-cohort model was used to predict the ASMR trends from 2020 to2030. RESULTS: High SDI quintiles were associated with increased residential radon pollution. The disease burden attributed to these three pollutants was particularly severe in the middle SDI quintiles. Older adults aged 80 to 89 years had the highest age-specific mortality, and the disease burden was greater in male patients than in female patients with these cancers attributed to the pollutants. The highest ASMR attributable to particulate matter when the SDI was 0.7. As the SDI increased, the disease burden caused by radon increased, whereas the burden caused by solid fuels decreased. Projections have indicated a rise in the death burden in patients with this cancer from particulate pollution in China, India, and Uganda over the next decade. INTERPRETATION: The disease burden of tracheal, bronchus, and lung cancer attributed to the three pollutants was influenced by SDI, sex, and age. Older men are more susceptible to be affected. More preventive interventions may be required for men at younger ages to reduce the high death burden of older men. However, it is necessary to give due attention to women in specific countries in the future.
期刊：
Journal of Medical Virology,2023年95(5):e28797- ISSN：0146-6615
通讯作者：
Yang, ZR;Feng, SD
作者机构：
[Zheng, Chenli; Wang, Xiaohui; Gan, Yongxia; Zhao, Jin; Yang, Zhengrong; Zeng, Guang; Li, Guilian] Shenzhen Ctr Dis Control & Prevent, Dept HIV AIDS Prevent & Control, Shenzhen, Peoples R China.;[Zeng, Guang; Feng, Shuidong; Tang, Jie] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Peoples R China.;[He, Fei] Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Stomatol, Shenzhen, Peoples R China.;[Zhang, Xiaomin] Shenzhen Ctr Dis Control & Prevent, Inst Pathogen Biol, Shenzhen, Peoples R China.;[Xu, Liumei] Southern Univ Sci & Technol, Peoples Hosp Shenzhen 3, Affiliated Hosp 2, Natl Clin Res Ctr Infect Dis, Shenzhen, Peoples R China.
通讯机构：
[Yang, ZR ] S;[Feng, SD ] U;Shenzhen Ctr Dis Control & Prevent, Dept HIV AIDS Prevent & Control, Shenzhen, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang, Peoples R China.
摘要：
The immunogenicity induced by the third dose of inactivated coronavirus disease 2019 (COVID-19) vaccines in people living with HIV (PLWH) is unclear, and relevant literature is extremely scarce. It is important to add evidence on the humoral immune response induced by the third dose of inactivated COVID-19 vaccine in PLWH. We collected peripheral venous blood for spike receptor binding domain-protein specific immunoglobulin G (S-RBD-IgG) antibody tests at 28 days after the second dose (T(1) ), 180 days after the second dose (T(2) ) and 35 days after the third dose (T(3) ) of inactivated COVID-19 vaccines in PLWH. The differences in S-RBD-IgG antibody levels and specific seroprevalence among T(1) , T(2) , and T(3) time periods were analyzed, and the effects of age, vaccine brand, and CD4(+) T cell count on the levels and specific seroprevalence of S-RBD-IgG antibody induced by the third dose in PLWH were examined. The third dose of inactivated COVID-19 vaccines induced strong S-RBD-IgG antibody responses in PLWH. The levels and specific seroprevalence of S-RBD-IgG antibody were significantly higher than those at 28 and 180 days after the second dose and were not affected by vaccine brand or CD4(+) T cell count. Younger PLWH produced higher levels of S-RBD-IgG antibody. The third dose of inactivated COVID-19 vaccine showed good immunogenicity in PLWH. It is necessary to popularize the third dose in the PLWH population, especially PLWH who do not respond to two doses of inactivated COVID-19 vaccines. Meanwhile, the durability of the protection provided by the third dose in PLWH must be continuously monitored.
摘要：
Cadmium (Cd) contamination of rice is an urgent ecological and agricultural problem. Strontium (Sr) has been shown to promote plant growth. However, the effect of Sr on rice seedlings under Cd stress is currently unclear. In this work hydroponic experiments were used to assess the impact of Sr on rice seedling growth under Cd stress. The findings demonstrated that foliar application of 0.5mgL(-1) Sr had no discernible impact on the development of rice seedlings. However, Sr significantly alleviated growth inhibition and toxicity in rice seedlings when threatened by Cd. Compared with the Cd treatment (Cd, 2.5mgL(-1)), the root length, shoot height, and whole plant length of rice seedlings in the Cd+Sr treatment (Cd, 2.5mgL(-1); Sr, 0.5mgL(-1)) increased by 4.96%, 12.47% and 9.60%, respectively. The content of Cd in rice decreased by 23.34% (roots) and 5.79% (shoots). Sr lessened the degree of membrane lipid peroxidation damage (lower MDA concentration) among the seedlings of rice under Cd stress by controlling the activities of antioxidant enzymes and GSH content. By changing the expression of antioxidant enzyme-encoding genes and downregulating the heavy metal transporter gene (OsNramp5), Sr reduced accumulation and the detrimental effects of Cd on rice seedlings. Our study provides a new solution to the problem of Cd contamination in rice, which may promote the safe production of rice and benefit human health.
摘要：
Previous studies have primarily concentrated on the hepatotoxicity of MC-LR, whereas its gastric toxicity effects and mechanisms of long-term exposure under low dosage remain unknown. Herein, the gastric tissue from C57BL/6 mice fed with drinking water contaminated by low-dose MC-LR (including 1, 60, and 120 μg/L) was investigated. The results obtained showed that exposure to different concentrations of MC-LR resulted in significant shedding and necrosis of gastric epithelial cells in mice, and a down-regulation of tight junction markers, including ZO-1, Claudin1, and Occludin in the stomach, which might lead to increased permeability of the gastric mucosa. Moreover, the protein expression levels of p-RAF/RAF, p-ERK1/2/ERK1/2, Pink1, Parkin, and LC3-II/LC-3-I were increased in the gastric tissue of mice exposed to 120 μg/L of MC-LR, while the protein expression level of P62 was significantly decreased. Furthermore, we found that pro-inflammatory factors, including IL-6 and TNF-ɑ, were dramatically increased, while the anti-inflammatory factor IL-10 was significantly decreased in the gastric tissue of MC-LR-exposed mice. The activation of the MAPK signaling pathway and mitophagy might contribute to the development of gastric damage by promoting inflammation. We first reported that long-term exposure to MC-LR induced gastric toxicity by activating the MAPK signaling pathway, providing a new insight into the gastric toxic mechanisms caused by MC-LR.
作者机构：
[Tang, Peng; Wang, Yue; Yao, Xueqiong; Wang, Yangcan; Song, Fengmei; Deng, Shuxiang; Yang, Fei; Tang, Yan] Department of Epidemiology and Health Statistics, The Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Basic Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China;[Tang, Peng] Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China;[Tang, Peng] Department of Maternal and Child Health, School of Public Health, Peking University, Beijing, 100191, China;[Liao, Qian] Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China;[Du, Can] Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, 410078, China
通讯机构：
[Xiaoqiang Qiu; Fei Yang] D;Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China<&wdkj&>Department of Epidemiology and Health Statistics, The Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, School of Basic Medicine, School of Public Health, Hengyang Medical School, University of South China, Hengyang, 421001, China<&wdkj&>Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha, 410078, China
摘要：
BACKGROUND: Heavy metals entering the human body could cause damage to a variety of organs. However, the combined harmful effects of exposure to various metals on liver function are not well understood. The purpose of the study was to investigate the independent and joint relationships between heavy metal exposure and liver function in adults. METHODS: The study involved 3589 adults from the National Health and Nutrition Examination Survey. Concentrations of urinary metals, including arsenic (As), cadmium (Cd), lead (Pb), antimony (Sb), barium (Ba), thallium (Tl), tungsten (W), uranium (U), were determined in urine using inductively coupled plasma mass spectrometry. Data for liver function biomarkers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transaminase (GGT), and alkaline phosphatase (ALP). Survey-weighted linear regression and quantile g-computation (qgcomp) were employed to evaluate the relationship of urinary metals with the markers of liver injury. RESULTS: Cd, U and Ba were found to have positive correlations with ALT, AST, GGT, and ALP in the survey-weighted linear regression analyses. According to the qgcomp analyses, the total metal mixture was positively correlated with ALT (percent change: 8.15; 95% CI: 3.84, 12.64), AST (percent change: 5.55; 95% CI: 2.39, 8.82), GGT (percent change: 14.30; 95% CI: 7.81, 21.18), and ALP (percent change: 5.59; 95% CI: 2.65, 8.62), and Cd, U, and Ba were the main contributors to the combined effects. Positive joint effects were observed between Cd and U on ALT, AST, GGT and ALP, and U and Ba had positive joint effects on ALT, AST and GGT. CONCLUSION: Exposures to Cd, U, and Ba were individually associated with multiple markers of liver injury. Mixed metal exposure might be adversely correlated with markers of liver function. The findings indicated the potential harmful effect of metal exposure on liver function.
摘要：
Polysaccharide chitosan and L-histidine were applied to synthesize chitosan-based carbon dots (CA-CDs) by a simple laser ablation method. After characterization of the CA-CDs by FT-IR, UV-vis, Raman, XRD, TEM, and XPS, the CA-CDs were introduced as an eco-friendly and high-performance corrosion inhibitor for mild steel (MS) in 1.0M HCl solution. The inhibition action and mechanism of CA-CDs were determined by weight loss and electrochemical measurements, in combination with SEM, AFM, and XPS. The results show that CA-CDs as mixed-type inhibitors could effectively weaken the corrosion of MS in 1.0M HCl solution, and their maximum inhibition efficiency reaches 97.4% at 40mgL(-1). The adsorption behavior of CA-CDs well obeys the Langmuir adsorption isotherm containing both chemisorption and physisorption. The chemisorption mainly results from the multiple adsorption sites in the CA-CDs, and the physical adsorption is due to the blocking and barrier effect of CA-CD nanoparticles. Both adsorption behaviors were proposed to elucidate the corrosion inhibition mechanism of CA-CDs.
摘要：
Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F− + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.
关键词：
DNA damage response;PARP1;chromatin accessibility;m(6)A methylation;radiosensitivity
摘要：
Chromatin remodeling and N(6)-methyladenosine (m(6)A) modification are two critical layers in controlling gene expressionand DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m(6)A methylation of poly(A)(+) RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m(6)A methylation. Lysophosphatidic Acid Receptor 5(LPAR5) mRNA was identified as a target of METTL3, and m(6)A methylation was located at A1881. The level of m(6)A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m(6)A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy invivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.
通讯机构：
[Xu, LZ; Niu, XH ; Pan, JM] J;Jiangsu Univ, Sch Agr Engn, Zhenjiang 212013, Peoples R China.;Jiangsu Univ, Sch Chem & Chem Engn, Zhenjiang 212013, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.
摘要：
Nanozyme-based multimode detection is a useful means to improve the accuracy and stability of analytical methods. However, both multifunctional nanozymes and related multimodal sensing strategies are still very scarce. Besides, they require complex processes to fabricate and operate. To fill this gap, here we propose a spontaneous interfacial in situ growth strategy to prepare a new bifunctional material (CePO(4):Tb@MnO(x)) featuring good oxidase-like activity and green photoluminescence for the dual-mode colorimetric/luminescence determination of ascorbic acid (AA)-related biomarkers specifically. CePO(4):Tb@MnO(x) was gained through the controllable redox reaction between KMnO(4) and CePO(4):Tb nanorods. It was interestingly found that MnO(x) in situ growth not only significantly enhanced the enzyme-like activity but also could reversibly regulate the luminescence of CePO(4):Tb via a dual quenching mechanism. More interestingly, CePO(4):Tb@MnO(x) exhibited a distinctive response toward AA against other reducing species. A double-coordination regulation mechanism was further verified to clarify the catalytic activity and luminescence switching behaviors in CePO(4):Tb@MnO(x). Based on these findings, a dual-mode colorimetric/luminescence approach was established for AA sensing in a "one-stone-two-birds" manner, providing excellent selectivity, sensitivity, and practicability. Furthermore, the determination of AA-related biomarkers, including acid phosphatase activity and organophosphorus residue, was also validated by the sensing principle. Our work not only deepens the understanding of the coordinated regulation of the luminescence and enzyme-like features in lanthanide-based materials but also offers a novel way to design and develop multifunctional nanozymes for advanced bioanalytical applications.
期刊：
International Journal of Biological Macromolecules,2023年252:126500 ISSN：0141-8130
通讯作者：
Chen, LL;Bai, YL
作者机构：
[Pu, Chunmin; Chen, Lili; Liao, Xiaoyan] Univ South China, Coll Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;[Pu, Chunmin; Bai, Yalong; Liao, Xiaoyan] Shanghai Acad Agr Sci, Inst Agrifood Stand & Testing Technol, 1000 Jinqi Rd, Shanghai 201403, Peoples R China.;[Shi, Xianming; Cui, Yan] Shanghai Jiao Tong Univ, MOST USDA Joint Res Ctr Food Safety, Sch Agr & Biol, State Key Lab Microbial Metab, Shanghai 200240, Peoples R China.
通讯机构：
[Chen, LL ] U;[Bai, YL ] S;Univ South China, Coll Publ Hlth, Hengyang Med Sch, Dept Publ Hlth Lab Sci, 28 Changsheng West Rd, Hengyang 421001, Hunan, Peoples R China.;Shanghai Acad Agr Sci, Inst Agrifood Stand & Testing Technol, 1000 Jinqi Rd, Shanghai 201403, Peoples R China.
关键词：
Agarose gel;Amino-modified magnetic particles;Aptamer;DNA extraction;Short single-stranded DNA
摘要：
With the rapid advancements in aptamer screening, the efficient extraction of short single-stranded DNA (ssDNA) from agarose gel has become a new requirement. However, the currently available products are primarily designed for double-stranded DNA (dsDNA) and exhibit limited efficacy when applied to the extraction of short ssDNA. In this study, we successfully developed a novel method based on amino-modified silica-coated magnetic particles (ASMPs) for the extraction of short ssDNA from agarose gel. The gel slices containing short ssDNA were subjected to centrifugation in a spin column/centrifugation tube assembly with silica wool, followed by the adsorption using ASMPs. Subsequently, reagents containing phosphate groups were employed to desorb ssDNA from the surface of ASMPs. Through optimization of each step, we realized remarkable efficiency in the extraction of short ssDNA. To assess the efficacy of our method, we utilized it in aptamer screening. The results demonstrated that our method outperformed three commercially available DNA gel extraction products (Q-kit, S-kit, and V-kit). The relative recovery rates of all methods were as follows: M-dNTP (100.00%)>M-BB (63.38%)>Q-kit (46.64%)>S-kit (15.98%)>V-kit (0.38%). The results strongly suggest that the developed method holds promise for short ssDNA extraction from agarose gel.
通讯机构：
[Wang, FD ; Wang, YZ ] Z;Zhejiang Univ, Coll Anim Sci, Key Lab Mol Anim Nutr, Minist Educ, Hangzhou, Peoples R China.;Minist Agr, Key Lab Anim Nutr & Feed Sci Eastern China, Hangzhou, Zhejiang, Peoples R China.;Zhejiang Univ, Affiliated Hosp 2, Sch Publ Hlth, State Key Lab Expt Hematol,Sch Med, Hangzhou, Peoples R China.;Univ South China, Affiliated Hosp 1, Sch Publ Hlth, Hengyang Med Sch,Basic Med Sci, Hengyang, Peoples R China.
摘要：
As a family of cationic host defense peptides, defensins are mainly synthesized by Paneth cells, neutrophils, and epithelial cells, contributing to host defense. Their biological functions in innate immunity, as well as their structure and activity relationships, along with their mechanisms of action and therapeutic potential, have been of great interest in recent years. To highlight the key research into the role of defensins in human and animal health, we first describe their research history, structural features, evolution, and antimicrobial mechanisms. Next, we cover the role of defensins in immune homeostasis, chemotaxis, mucosal barrier function, gut microbiota regulation, intestinal development and regulation of cell death. Further, we discuss their clinical relevance and therapeutic potential in various diseases, including infectious disease, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis and cancer. Finally, we summarize the current knowledge regarding the nutrient-dependent regulation of defensins, including fatty acids, amino acids, microelements, plant extracts, and probiotics, while considering the clinical application of such regulation. Together, the review summarizes the various biological functions, mechanism of actions and potential clinical significance of defensins, along with the challenges in developing defensins-based therapy, thus providing crucial insights into their biology and potential clinical utility.
通讯机构：
[Yang, HF ] U;[Cai, R ] H;Hunan Univ, Coll Mat Sci & Engn, Coll Chem & Chem Engn, Coll Biol,Mol Sci & Biomed Lab,State Key Labr Chem, 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：
Novel and effective coreaction accelerators are of great importance in electrochemiluminescence (ECL) systems. In this work, novel AuPt nanodonuts, i.e., SnS2 quantum dots (QDs)/Cys-AuPt heterogeneous nanorings (NRs), serve as both a highly effective coreaction accelerator and the luminophore in a label-free ECL aptasensor. The novel AuPt nanodonuts were formed by decorating SnS2 QDs onto AuPt NR surfaces, which would promote the production of more coreactant intermediate in the SnS2 QDs/K2S2O8 system. As a result, the ECL performance was greatly improved. Meanwhile, l-cysteine (l-Cys) played an important role in the combination between AuPt NRs and SnS2 QDs, and the nanodonuts served as the matrix to load numerous lincomycin (Lin) aptamers. Under optimal conditions, the ECL aptasensor exhibited ultrasensitive detection of Lin from 1 fg/mL to 0.1 pg/mL with a limit of detection (LOD) of 0.7 fg/mL (1.72 fM).
作者机构：
[Liu, Ying; Yao, Xueqiong; Yang, F; Hu, Na; Song, Fengmei; Li, Yafang; Yang, Fei] Univ South China, Hengyang Med Sch, Sch Basic Med, Sch Publ Hlth,Dept Epidemiol & Hlth Stat,Key Lab T, Hengyang 421001, Peoples R China.;[Yang, F; Yang, Fei; Yang, Yue] Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Hunan Prov Key Lab Clin Epidemiol, Changsha 410017, Peoples R China.;[Yang, F; Yang, Fei] Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn, Minist Educ, Nanjing 210000, Peoples R China.
通讯机构：
[Yang, F ] U;Univ South China, Hengyang Med Sch, Sch Basic Med, Sch Publ Hlth,Dept Epidemiol & Hlth Stat,Key Lab T, Hengyang 421001, Peoples R China.;Cent South Univ, Xiangya Sch Publ Hlth, Dept Social Med & Hlth Management, Hunan Prov Key Lab Clin Epidemiol, Changsha 410017, Peoples R China.;Southeast Univ, Sch Publ Hlth, Key Lab Environm Med Engn, Minist Educ, Nanjing 210000, Peoples R China.
关键词：
microcystin-LR;kidney damage;MKK6;mitophagy
摘要：
Previous studies have reported that microcystin-LR (MC-LR) levels are highly correlated with abnormal renal function indicators, suggesting that MC-LR is an independent risk factor for kidney damage. However, the evidence for the exact regulation mechanism of MC-LR on kidney damage is still limited, and further in-depth exploration is needed. In addition, the mitochondria-related mechanism of MC-LR leading to kidney damage has not been elucidated. To this end, the present study aimed to further explore the mechanism of mitophagy related to kidney damage induced by MC-LR through in vitro and in vivo experiments. Male C57BL/6 mice were fed with a standard rodent pellet and exposed daily to MC-LR (20 μg/kg·bw) via intraperitoneal injections for 7 days. Moreover, HEK 293 cells were treated with MC-LR (20 μM) for 24 h. The histopathological results exhibited kidney damage after MC-LR exposure, characterized by structurally damaged nephrotomies, with inflammatory cell infiltration. Similarly, a significant increase in renal interstitial fibrosis was observed in the kidneys of MC-LR-treated mice compared with those of the control group (CT) mice. MC-LR exposure caused impaired kidney function, with markedly increased blood urea nitrogen (BUN), creatinine (Cr), and uric acid (UA) levels in mice. Ultrastructural analysis exhibited obviously swollen, broken, and disappearing mitochondrial crests, and partial mitochondrial vacuoles in the MC-LR-treated HEK 293 cells. The Western blotting results demonstrated that exposure to MC-LR significantly increased the protein expressions of MKK6, p-p38, and p62, while the expression of mitophagy-related proteins was significantly inhibited in the kidneys of mice and HEK293 cells, including parkin, TOM20, and LC3-II, indicating the inhibition of mitophagy. Therefore, our data suggest that the inhibition of MKK6-mediated mitophagy might be the toxicological mechanism of kidney toxicity in mice with acute exposure to MC-LR.
摘要：
Mitochondrial dysfunction and lung cellular senescence are significant features involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) stands as the primary contributing factor to COPD. This study examined mitochondrial dynamics, mitophagy and lung cellular senescence in COPD patients and investigated the effects of modulation of mitochondrial fusion [mitofusin2 (MFN2) and Optic atrophy 1 (OPA1)] on CS extract (CSE)-induced lung cellular senescence. Senescence-associated secretory phenotype (SASP) component mRNAs (IL-1β, IL-6, CXCL1 and CXCL8), mitochondrial morphology, mitophagy and mitochondria-related proteins (including phosphorylated-DRP1(p-DRP1), DRP1, MFF, MNF2, OPA1, PINK1, PARK2, SQSTM1/p62 and LC3b) and senescence-related proteins (including P16, H2A.X and Klotho) were measured in lung tissues or primary alveolar type II (ATII) cells of non-smokers, smokers and COPD patients. Alveolar epithelial (A549) cells were exposed to CSE with either pharmacologic inducer (leflunomide and BGP15) or genetic induction of MFN2 and OPA1 respectively. There were increases in mitochondrial number, and decreases in mitochondrial size and activity in lung tissues from COPD patients. SASP-related mRNAs, DRP1 phosphorylation, DRP1, MFF, PARK2, SQSTM1/p62, LC3B II/LC3B I, P16 and H2A.X protein levels were increased, while MFN2, OPA1, PINK1 and Klotho protein levels were decreased in lung tissues from COPD patients. Some similar results were identified in primary ATII cells of COPD patients. CSE induced increases in oxidative stress, SASP-related mRNAs, mitochondrial damage and dysfunction, mitophagy and cellular senescence in A549 cells, which were ameliorated by both pharmacological inducers and genetic overexpression of MFN2 and OPA1. Impaired mitochondrial fusion, enhanced mitophagy and lung cellular senescence are observed in the lung of COPD patients. Up-regulation of MFN2 and OPA1 attenuates oxidative stress, mitophagy and lung cellular senescence, offering potential innovative therapeutic targets for COPD therapy.
作者机构：
[曹滨; 于晋杰] School of Public Health, University of South China, Hengyang 421001, China National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory of Infectious Disease Prevention and Control, Beijing 102206, China;[李桂莲; 赵秀芹; 王瑞欢; 刘海灿; 范雪亭; 万康林; 栾秀丽; 李马超] National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory of Infectious Disease Prevention and Control, Beijing 102206, China;[钱程宇] National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention/State Key Laboratory of Infectious Disease Prevention and Control, Beijing 102206, China School of Life Sciences, College of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325035, China;[袁秀琴] School of Public Health, University of South China, Hengyang 421001, China
