摘要：
Ferroptosis has been linked to the pathogenesis of hepatic injury induced by ischemia/reperfusion (I/R). However, the mechanistic basis remains unclear. In this study, by using a mouse model of hepatic I/R injury, it is observed that glutathione (GSH) and cysteine depletion are associated with deficiency of the reducing power of nicotinamide adenine dinucleotide phosphate (NADPH). Genes involved in maintaining NADPH homeostasis are screened, and it is identified that I/R-induced hepatic ferroptosis is significantly associated with reduced expression and activity of NADP(+)-dependent malic enzyme 1 (Me1). Mice with hepatocyte-specific Me1 gene deletion exhibit aggravated ferroptosis and liver injury under I/R treatment; while supplementation with L-malate, the substrate of ME1, restores NADPH and GSH levels and eventually inhibits I/R-induced hepatic ferroptosis and injury. A mechanistic study further reveals that downregulation of hepatic Me1 expression is largely mediated by the phosphatase and tensin homologue (PTEN)-dependent suppression of the mechanistic target of rapamycin/sterol regulatory element-binding protein 1 (mTOR/SREBP1) signaling pathway in hepatic I/R model. Finally, PTEN inhibitor, mTOR activator, or SREBP1 over-expression all increase hepatic NADPH, block ferroptosis, and protect liver against I/R injury. Taken together, the findings suggest that targeting ME1 may provide new therapeutic opportunities for I/R injury and other ferroptosis-related hepatic conditions.
摘要：
Nanomaterials with enzyme-like catalytic features (nanozymes) find wide use in analytical sensing. Apart from catalytic characteristics, some other interesting functions coexist in the materials. How to combine these properties to design multifunctional nanozymes for new sensing strategy development is challenging. Besides, in nanozymes it is still a challenge to conveniently control the catalytic process, which also hinders their further applications in advanced biochemical analysis. To remove the above barriers, here we design a light-controllable multifunctional nanozyme, namely manganese-inserted cadmium telluride (Mn-CdTe) particles, that integrates oxidase-like activity with luminescence together, to achieve the fluorometric/colorimetric dual-mode detection of toxic mercury ions (Hg(2+)) at ambient pH. The Mn-CdTe exhibits a light-triggered oxidase-mimicking catalytic behavior to induce chromogenic reactions, thus enabling one to start or stop the catalytic progress easily via applying or withdrawing light irradiation. Meanwhile, the quantum dot material can exhibit bright photoluminescence, which provides the fluorometric channel to sense targets. When Hg(2+) is introduced, it rapidly leans toward Mn-CdTe through electrostatic interaction and Te-Hg bonding and induces the aggregation of the latter. As a result, the luminescence of Mn-CdTe is dynamically quenched, and the masking of active sites in aggregated Mn-CdTe leads to the decrease of light-initiated oxidase-mimetic activity. According to this principle, a new fluorometric/colorimetric bimodal method was established for Hg(2+) determination with excellent performance. A 3D-printed portable platform combining paper-based test strips and an App-equipped smartphone was further fabricated, making it possible to achieve in-field sensing of the analyte in various matrices.
摘要：
Type 2 diabetes mellitus (T2DM) is frequently associated with diabetic cognitive impairment (DCI), and recent studies have shown a strong association between DCI and hippocampal ferroptosis. In this study, we administered dihydromyricetin (DHM) or JNK inhibitor SP600125, to T2DM rats and monitored changes in blood glucose levels, conducted behavioral tests, and detected changes in JNK, inflammatory factors and ferroptosis-related indicators. Our findings demonstrated that T2DM rats displayed signs of cognitive impairment (CI), with ferrozine assays indicating elevated iron content in the hippocampus. Concurrently, there was an increase in p-JNK activity and inflammatory factors IL-6 and TNF-α in the hippocampal region of these rats. Furthermore, we observed elevated levels of Fe(2+), MDA, ROS, LPO, and ACSL4, along with a decrease in GPX4 and GSH, suggesting the occurrence of hippocampal ferroptosis. SP600125 application reversed these changes in the T2DM rats, although it exhibited no significant effects in the control group. Treatment with high and low doses of DHM led to a reduction in p-JNK expression, inflammatory factor-related proteins, and iron accumulation in the hippocampal region, effectively alleviating hippocampal ferroptosis in T2DM rats. No notable effects of DHM were observed in the control group. To conclude, our study suggests that DHM can potentially alleviate hippocampal ferroptosis of T2DM cognitive impairment rats, primarily by suppressing the JNK-inflammatory factor pathway in the hippocampus.
通讯机构：
[Yang, HF ] U;[Cai, R ] H;Hunan Univ, Coll Mat Sci & Engn, Coll Chem & Chem Engn, Coll Biol,State Key Lab ChemoBio Sensing & Chemome, 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 self-powered biosensing system with multivariate signal amplification is designed for the ultrasensitive, highly efficient, rapid-response, and real-time detection of platelet-derived growth factor-BB (PDGF-BB). The biosensing system is composed of enzymatic biofuel cells (EBFCs), a capacitor, a digital multimeter (DMM), and a computer. Using the hybridization chain reaction (HCR), a few single DNA chains are transformed into abundant double-helix chains, which stimulates the reduction of [Ru(NH3)(6)](3+) to [Ru(NH3)(6)](2+) by electrostatic interaction, corresponding to the "on" state for HCR. As a result, the open-circuit voltage (E-OCV) is significantly increased in this self-powered biosensing system. When PDGF-BB is present, a binding interaction between the target and the aptamer, i.e., PDGF-BB/Apt, corresponding to the "off" state for HCR, results in a decrease of E-OCV. The PDGF-BB concentration is inversely proportional to E-OCV, allowing readable, effective, and precise real-time detection of PDGF-BB. The detection limit of the biosensing system is 0.031 pg/mL (S/N = 3). This strategy provides a promising and powerful tool for the early clinical diagnosis of related colorectal cancer markers.
作者机构：
[Hu, Fan; Li, Mei; Wang, Wei; Xu, Chongsi; Xiao, You] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 5, Changsha, Peoples R China.;[He, Yuanyuan] Hunan Univ, Hunan Univ Chinese Med, Grad Sch, Changsha, Peoples R China.;[Wang, Zhenquan] Hunan Univ Tradit Chinese Med, Affiliated Hosp 2, Dept Anorectal 3, Changsha 410005, Peoples R China.;[Cao, Yi] Univ South China, Hengyang Med Sch, Sch Publ Hlth, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.
通讯机构：
[Zhenquan Wang] T;Third Department of Anorectal, The Second Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, China
关键词：
3D Caco-2 spheroids;Kruppel-like factor 4 (KLF4);MoS2 nanosheets (NSs);Oral exposure;RNA-sequencing
摘要：
MoS(2) nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS(2) NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS(2) NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS(2) NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS(2) materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
通讯机构：
[Liang, GY ] S;Southeast Univ, Minist Educ, Sch Publ Hlth, Key Lab Environm Med Engn, Nanjing, Peoples R China.
关键词：
AOP;Hepatotoxicity;MNPLs;New toxicological methodologies;Organoids and organ-on-chips;“Trojan horse” effect
摘要：
Plastic pollution has become a significant global problem over the years, leading to the continuous decomposition and accumulation of micro/nanoplastics (MNPLs) in the environment. As a result, human exposure to these MNPLs is inevitable. The liver, in particular, is highly susceptible to potential MNPL toxicity. In this study, we systematically reviewed the current literature on MNPLs-induced hepatotoxicity and collected data on toxic events occurring at different biological levels. Then, to better understand the cause-mechanism causality, we developed an Adverse Outcome Pathway (AOP) framework for MNPLs-induced hepatotoxicity. The AOP framework provided insights into the mechanism of MNPL-induced hepatotoxicity and highlighted potential health risks such as liver dysfunction and inflammation, metabolism disorders and liver fibrosis. Moreover, we discussed the potential application of emerging toxicological models in the hepatotoxicity study. Liver organoids and liver-on-chips, which can simulate the structure and function of the liver in vitro, offer a promising alternative platform for toxicity testing and risk assessment. We proposed combining the AOP framework with these emerging toxicological models to improve our understanding of the hepatotoxic effects of MNPLs. Overall, this study performed a preliminary exploration of novel toxicological methodologies to assess the hepatotoxicity of MNPLs, providing a deeper understanding of environmental toxicology.
作者机构：
[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru; Liu, Xiaocheng; Li, Guojuan; Tang, Yonghong; Rang, Ouyan; Wang, Mu; Cao, Lin] Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;[Qin, Xinru] Univ South China, Sch Publ Hlth, Hengyang 421001, Hunan, Peoples R China.;[Zhong, Jing; Zhong, J] Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
通讯机构：
[Zhong, J ; Wang, M ] U;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Clin Mass Spectrometry Lab,Clin Res Inst, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Nanhua Hosp, Hengyang Med Sch, Dept Basic Med,Nucl Ind Hyg Sch, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Affiliated Hosp 1, Hengyang Med Sch, Canc Res Inst,Inst Clin Med, Hengyang 421001, Hunan, Peoples R China.
摘要：
The consumption of fructose has increased dramaticly during the last few decades, inducing a great increase in the risk of intrahepatic lipid accumulation, hypertriglyceridemia, hyperuricemia and cancer. However, the underlying mechanism has not yet been fully elucidated. Amino acid metabolism may play an important role in the process of the diseases caused by fructose, but there is still a lack of corresponding evidence. In present study, we provide an evidence of how fructose affects amino acids metabolism in 1895 ordinary residents in Chinese community using UPLC-QqQMS based amino acid targeted metabolomics and the underlying mechanism of fructose exposure how interferes with amino acid metabolism related genes and acetylated modification of proteome in the liver of rats model. We found people with high fructose exposure had higher levels of Asa, EtN, Asp, and Glu, and lower levels of 1MHis, PEtN, Arg, Gln, GABA, Aad, Hyl and Cys. The further mechanism study displayed amino acid metabolic genes of Aspa, Cndp1, Dbt, Dmgdh, and toxic metabolites such as N-acetylethanolamines accumulation, interference of urea cycle, as well as acetylated modification of key enzymes in glutamine metabolic network and glutamine derived NEAAs synthesis pathway in liver may play important roles in fructose caused reprogramming in amino acid metabolism. This research provides novel insights of the mechanism of amino acid metabolic disorder caused by fructose and supplies new targets for clinical therapy.
作者机构：
[Peng, Yousong; You, Ruina; Ma, Huan; Tuo, Chaohao; Li, Huiru; Zhu, Zhaozhong; Meng, Xiangxian] Hunan Univ, Coll Biol, Changsha, Peoples R China.;[Zhu, Zhaozhong; Feng, Shuidong] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Feng, Shuidong; Feng, Song] Cent South Univ, Xiangya Hosp, Changsha, Peoples R China.
通讯机构：
[Peng, YS ] H;[Feng, S ] C;Hunan Univ, Coll Biol, Changsha, Peoples R China.;Cent South Univ, Xiangya Hosp, Changsha, Peoples R China.
关键词：
Bioinformatics;Influenza virus;Multi-omics data
摘要：
Influenza viruses pose a significant and ongoing threat to human health. Many host factors have been identified to be associated with influenza virus infection. However, there is currently a lack of an integrated resource for these host factors. This study integrated human genes and proteins associated with influenza virus infections for 14 subtypes of influenza A viruses, as well as influenza B and C viruses, and built a database named H2Flu to store and organize these genes or proteins. The database includes 28,639 differentially expressed genes (DEGs), 1,850 differentially expressed proteins, and 442 proteins with differential posttranslational modifications after influenza virus infection, as well as 3,040 human proteins that interact with influenza virus proteins and 57 human susceptibility genes. Further analysis showed that the dynamic response of human cells to virus infection, cell type and strain specificity contribute significantly to the diversity of DEGs. Additionally, large heterogeneity was also observed in protein-protein interactions between humans and different types or subtypes of influenza viruses. Overall, the study deepens our understanding of the diversity and complexity of interactions between influenza viruses and humans, and provides a valuable resource for further studies on such interactions.
通讯机构：
[Tao, L.; Luo, C.] D;[Wang, F.] T;Department of Forensic Medicine, School of Basic Medicine and Biological Sciences, Soochow University, Suzhou, 215123, China
摘要：
Although traumatic brain injury (TBI) is a common cause of death and disability worldwide, there is currently a lack of effective therapeutic drugs and targets. To reveal the complex pathophysiologic mechanisms of TBI, we performed transcriptome analysis of the mouse cerebral cortex and immunohistochemical analysis of human cerebral tissues. The genes Mt1, Mt2, Il33, and Fth1 were upregulated post-TBI and enriched in pathways associated with the inflammatory response, oxidative phosphorylation, and ferroptosis. As an agonist of MT1/2, melatonin (MLT) confers anti-oxidant, anti-inflammatory, and anti-ferroptosis effects after TBI. However, whether these upregulated genes and their corresponding pathways are involved in the neuroprotective effect of MLT remains unclear. In this study, interventions to inhibit MT1/2, IL-33, and ferroptosis (i.e., ferritin H (Fth)-KO) were applied post-TBI. The results showed that MLT attenuated TBI-induced cerebral edema and neurological outcomes by inhibiting inflammation and ferroptosis. Mechanistically, MLT mainly suppressed inflammatory responses and ferroptosis via the activation of MT2 and IL-33 pathways. Building on the previous finding that Fth deletion increases susceptibility to ferroptosis post-TBI, we demonstrated that Fth depletion remarkably exacerbated the post-TBI inflammatory response, and abolished the anti-inflammatory effects of MLT both in vivo and in vitro. Furthermore, the post-TBI anti-inflammatory effect of MLT, which occurs by promoting the polarization of CD206(+) macrophages, was dependent on Fth. Taken together, these results clarified that MLT alleviates inflammation- and ferroptosis-mediated brain edema and neurological deficits by activating the MT2/IL-33/Fth pathway, which provides a novel target and theoretical basis for MLT to treat TBI patients.
作者：
Cao, Wandi;Liu, Mingkang;Wang, Canyang;Jing, Guoxing;Cao, Yi
期刊：
Journal of Applied Toxicology,2023年43(5):706-718 ISSN：0260-437X
通讯作者：
Guoxing Jing<&wdkj&>Yi Cao
作者机构：
[Liu, Mingkang; Jing, Guoxing; Cao, Wandi] Xiangtan Univ, Sch Chem Engn, Xiangtan, Peoples R China.;[Wang, Canyang; Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang, Peoples R China.;[Jing, Guoxing] Xiangtan Univ, Sch Chem Engn, Xiangtan 511105, Peoples R China.;[Cao, Yi] Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hunan Prov Key Lab Typ Environm Pollut & Hlth Haza, Hengyang 421001, Peoples R China.
通讯机构：
[Guoxing Jing] S;[Yi Cao] H;School of Chemical Engineering, Xiangtan University, Xiangtan, China<&wdkj&>Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
关键词：
3D Caco-2 spheroids;Kruppel-like factors (KLFs);mouse intestines;RNA-sequencing;TiO2 nanoparticles (NPs)
摘要：
Kruppel-like factors (KLFs) are a set of transcription factors (TFs) involved in the regulation of many basic biological processes, and recent studies suggested that nanoparticles (NPs) were capable to change KLFs in different models even at non-cytotoxic concentrations. In this study, we repeatedly exposed 3D Caco-2 spheroids and mice to TiO(2) NPs, one of the most frequently used metal oxide NPs, and investigated the changes of KLF-signaling pathways based on RNA-sequencing. Although the internalization of TiO(2) NPs did not induce cytotoxicity in vitro, repeated exposure (three times within 7 days) to 15.7 ng/ml TiO(2) NPs increased KLF4 but decreased KLF6. Consistently, KLF4/KLF6-regulated gene ontology terms were altered, including those involved in the regulation of gene expression. We further verified that repeated exposure to 15.7 ng/ml TiO(2) NPs increased the expression of KLF4 and proto-oncogene, bHLH transcription factor (MYC), but decreased the expression of KLF6 and activating transcription factor 3 (ATF3). But with the increase of NP concentrations, the expression of these genes was decreased. In mice following intragastrical exposure to 4.39 and 43.9 mg/kg TiO(2) NPs (once a day for 5 continuous days), we observed increased expression of klf4, klf6, myc, and atf3, along with morphological changes of intestines. We concluded that repeated exposure to low levels of TiO(2) NPs altered KLF-signaling pathways in intestinal cells both in vitro and in vivo.
作者机构：
[Long, Xizi] Univ South China, Sch Key Lab Typ Environm Pollut & Hlth Hazards Hun, Sch Basic Med, Sch Publ Hlth,Hengyang Med Sch, Hengyang 421001, Peoples R China.;[Tokunou, Yoshihide; Long, Xizi; Okamoto, Akihiro] Int Ctr Mat Nanoarchitecton WPI MANA, Natl Inst Mat Sci, Tsukuba, Ibaraki 3050044, Japan.;[Tokunou, Yoshihide] Univ Tsukuba, Fac Life & Environm Sci, Tsukuba, Ibaraki 3058577, Japan.;[Okamoto, Akihiro] Hokkaido Univ, Grad Sch Chem Sci & Engn, Sapporo, Hokkaido 0608628, Japan.
通讯机构：
[Akihiro Okamoto] I;International Center for Materials Nanoarchitectonics (WPI-MANA), National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan<&wdkj&>Graduate School of Chemical Sciences and Engineering, Hokkaido University, North 13 West 8, Kitaku, Sapporo, Hokkaido 060-8628, Japan
关键词：
circular dichroism;electron transport;exciton coupling;mechanobiology;multi-heme cytochrome C
摘要：
Pulmonary fibrosis represents the advanced phase of diverse pulmonary ailments, and at present, a definitive cure for these ailments is lacking. Furthermore, underlying mechanisms causative of these ailments remain elusive. Macrophages are immune cells that resist external stimuli in the early stages after birth. These cells can polarize into the classically (M1) and alternatively (M2) activated macrophages. When stimulated owing to the presence of toxic factors, M1 macrophages produce several pro-inflammatory factors, which mediate the inflammatory injury response of the alveolar tissue. The secretion of diverse growth factors by M2 macrophages contributes to the pathogenesis of aberrant alveolar structural fibrosis and remodeling. The abnormal activity of M2 macrophages is considered a critical factor in the formation of pulmonary fibrosis. In this mini-review, to highlight the clinical implications of research studies, we summarize the role and therapeutic targets of polarized subtypes of macrophages in pulmonary fibrosis and the role of targeting macrophages for the treatment of pulmonary fibrosis. M1-type macrophages and M2-type macrophages can transform into each other.M1-type macrophages participate in the early stage of pulmonary fibrosis by producing inflammatory cytokines, ROS and MMP.M2-type macrophages mediate abnormal alveolar tissue repair and tissue remodeling through the production of TGF-& beta;, FGF, and exosomes.Three therapeutic ideas were summarized in this paper: inhibition of the number and activity of lung macrophages, inhibition of M2-type macrophage polarization, inhibition of TGF-& beta; expression and its signalling pathway.
通讯机构：
[Feng, RL ] F;[Niu, XH ; Pan, JM] J;Jiangsu Univ, Inst Green Chem & Chem Technol, Sch Chem & Chem Engn, Zhenjiang 212013, Peoples R China.;Univ South China, Sch Publ Hlth, Hengyang Med Sch, Hengyang 421001, Peoples R China.;Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China.
关键词：
Prussian blue analogue;oxidase-like nanozyme;molecular imprinting;tetracycline detection;etching induced activity enhancement
摘要：
As a typical antibiotic pollutant, tetracycline (TC) is producing increasing threats to the ecosystem and human health, and exploring convenient means for monitoring of TC is needed. Here, we proposed alkali-etched imprinted Mn-based Prussian blue analogues featuring superior oxidase-mimetic activity and precise recognition for the colorimetric sensing of TC. Simply etching Mn-based Prussian blue analogues (Mn-PBAs) with NaOH could expose the sites and surfaces to significantly improve their catalytic activity. Density functional theory calculations were employed to screen the molecularly imprinted polymer (MIP) layer for target identification. Consequently, the designed Mn-PBA(NaOH)@MIP possessed the rich channels for substrates to get in touch with the active Mn-PBA(NaOH) core, showing an excellent catalytic capacity to trigger the chromogenic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) without the use of H(2)O(2). If TC was introduced, it would be recognized selectively by the MIP shell and masked the channels for TMB access, resulting in the obstruction of the chromogenic reaction. According to this mechanism, selective optical detection of TC was achieved, and performance stability, reusability, and reliability as well as practicability were also verified, promising potential for TC monitoring in complex matrices. Our work not only presents an effective way to enhance the enzyme-like activity of Prussian blue analogues but also provides a facile approach for TC sensing. Additionally, the work will inspire the exploration of molecularly imprinted nanozymes for various applications.
通讯机构：
[Jianming Pan] I;[Lizhang Xu; Xiangheng Niu] S;School of Agricultural Engineering, Jiangsu University, Zhenjiang 212013, China<&wdkj&>School of Agricultural Engineering, Jiangsu University, Zhenjiang 212013, China<&wdkj&>Institute of Green Chemistry and Chemical Technology, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China<&wdkj&>School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China<&wdkj&>Institute of Green Chemistry and Chemical Technology, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, China
期刊：
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY,2023年78(2):546-549 ISSN：0305-7453
通讯作者：
Jin Zhao
作者机构：
[Zhao, Jin; Zhu, Yue] Shantou Univ, Sch Publ Hlth, Shantou, Peoples R China.;[Jiang, Lijuan; Zheng, Chenli; Liu, Shaochu; Tan, Jingguang; Huang, Yuanmei; Zhao, Jin; Tan, Wei; Xie, Wei; Yang, Zhengrong; Zeng, Guang; Zhu, Yue; Zhang, Yan; Tang, Jie] Shenzhen Ctr Dis Control & Prevent, Dept HIV AIDS Control & Prevent, Shenzhen, Peoples R China.;[Huang, Yuanmei; Zhao, Jin] Shanxi Med Univ, Sch Publ Hlth, Taiyuan, Peoples R China.;[Zeng, Guang; Tang, Jie] Univ South China, Sch Publ Hlth, Hengyang, Peoples R China.;[Wang, Hui; Xu, Liumei; He, Yun; Zhang, Lukun] Third Peoples Hosp Shenzhen, Dept Infect Dis, Shenzhen, Peoples R China.
通讯机构：
[Jin Zhao] S;School of Public Health, Shantou University , Shantou , China<&wdkj&>Department of HIV/AIDS Control and Prevention, Shenzhen Center for Disease Control and Prevention , Shenzhen , China<&wdkj&>School of Public Health, Shanxi Medical University , Taiyuan , China
摘要：
OBJECTIVES: In recent years, integrase strand transfer inhibitor (INSTI)-containing regimens have been increasingly adopted in treatment for HIV/AIDS and promoted as non-occupational post-exposure prophylaxis in China. This study aims to describe the prevalence of resistance to integrase and drug resistance mutations (DRMs) among ART-naive patients in Shenzhen, China. METHODS: Serum samples and demographic information were collected from newly reported ART-naive patients in Shenzhen in 2020. The study sequenced the coding sequence of the HIV-1 integrase gene and determined the DRMs.. RESULTS: In this study, 1682 newly reported cases were included and 1071 of them were successfully sequenced finally. The prevalence of primary drug resistance was 1.77%, with 19 samples showing varying degrees of resistance to INSTIs. The study detected six major DRMs in 16 individuals and eight accessory DRMs in 24 individuals. The prevalence of transmitted drug resistance (TDR) mutations was 1.21%, with five transmitted mutations detected in 13 individuals. The prevalence of drug resistance to raltegravir and elvitegravir was statistically higher than to bictegravir, cabotegravir and dolutegravir. CONCLUSIONS: The prevalence of INSTI resistance in Shenzhen in 2020 was relatively high. Continued surveillance for resistance to INSTIs is recommended and treatment regimens should be adopted based on the pattern of resistance to INSTIs. Dolutegravir or bictegravir is first recommended when considering INSTIs as treatment regimens.
摘要：
Annexin A2 is a Ca(2+) regulated protein belonging to the Annexin family and is found in the cytoplasm and cell membrane. It can exist in a monomeric form or in a heterotetrameric form with the S100A10 dimer. The research on Annexin A2 in tumours is currently active, and studies on its role in pathogen infection are increasing. Annexin A2 plays a crucial role in the life cycle of viruses by mediating adhesion, internalization, uncoating, transport, and release. In the case of parasites, bacteria, mycoplasma, fungi, and other pathogens, Annexin A2 binds to the ligand on the pathogen, which mediates the pathogen's adhesion to the host cell, ultimately leading to infection and damage to the host. Furthermore, some studies have developed biological or chemical drugs that target Annexin A2, which have demonstrated promising anti-infective effects. Thus, targeting Annexin A2 may present a promising therapeutic approach for the treatment of diverse infectious diseases. In summary, this paper provides an overview of Annexin A2 and its role in various pathogens. It highlights its regulation of pathogen infection and its potential as a therapeutic target for the treatment of infectious diseases.
通讯机构：
[Fei Yang] H;Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang, Hunan 421001, China
摘要：
Microcystins (MCs) are harmful to the ecology and public health. Some bacteria can degrade MCs into Adda, but few can destroy Adda. Adda is the key bioactive moiety of MCs and mainly contributes to hepatotoxicity. We had previously isolated an indigenous novel bacterial strain named Sphingopyxis sp. YF1 that can efficiently degrade MCs and its key bioactive moiety Adda, but the mechanisms remained unknown. Here, the biodegradation mechanisms and pathways of Adda were systematically investigated using multi-omics analysis, mass spectrometry and heterologous expression. The transcriptomic and metabolomic profiles of strain YF1 during Adda degradation were revealed for the first time. Multi-omics analyses suggested that the fatty acid degradation pathway was enriched. Specifically, the expression of genes encoding aminotransferase, beta oxidation (β-oxidation) enzymes and phenylacetic acid (PAA) degradation enzymes were significantly up-regulated during Adda degradation. These enzymes were further proven to play important roles in the biodegradation of Adda. Simultaneously, some novel potential degradation products of Adda were identified successfully, including 7‑methoxy-4,6-dimethyl-8-phenyloca-2,4-dienoic acid (C(17)H(22)O(3)), 2-methyl-3‑methoxy-4-phenylbutyric acid (C(12)H(16)O(3)) and phenylacetic acid (PAA, C(8)H(8)O(2)). In summary, the Adda was converted into PAA through aminotransferase and β-oxidation enzymes, then the PAA was further degraded by PAA degradation enzymes, and finally to CO(2) via the tricarboxylic acid cycle. This study comprehensively elucidated the novel MC-LR biodegradation mechanisms, especially the new enzymatic pathway of Adda degradation. These findings provide a new perspective on the applications of microbes in the MCs polluted environment.
