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Paternal mixed exposure to nicotine/ethanol/caffeine damaged cartilage quality in paternal/offspring rats and its differential glucocorticoid regulation mechanisms

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Food Science and Human Wellness 2024年

作者： Yi Liu Hao Xiao Yi Liu Bin Li Hui Wang Liaobin Chen Division of joint Surgery and Sports Medicine， department of Orthopedic Surgery， Zhongnan Hospital of Wuhan University Hubei Provincial Key Laboratory of Developmentally Originated disease joint disease research Center of Wuhan University department of Pharmacology， Wuhan University School of Basic Medical Sciences

Nicotine， ethanol， and caffeine are the most common exogenous substances in the men’s living environment， but their effects on the cartilage quality in the father and offspring have not been reported. According to the average daily intake of adult men， we constructed a male rat model of paternal mixed exposure (PME) to low-dose nicotine (0.1 mg/kg.d)， ethanol (0.5 g/kg.d)， and caffeine (7.5 mg/kg.d) for 8 weeks. Then， the male rats mated with normal female rats to obtain offspring. The results showed that PME reduced the cartilage quality of paternal and offspring rats. Among them， the paternal cartilage was damaged by enhancing matrix degradation， while the offspring cartilage was damaged by reducing matrix synthesis. The cartilage damage in male offspring rats was more evident than in female offspring. It was further confirmed that differential GC regulation mechanisms were the main reasons for the intergenerational differential damage of paternal/offspring cartilage quality caused by PME. In addition， the sex hormone receptor AR and ERβ mediated the sex difference of PME-induced fetal cartilage dysplasia by affecting the binding degree of GR/P300. This study provided a theoretical and experimental basis for guiding male healthy lifestyle and exploring early prevention and treatment strategies for paternal diseases.

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Magnitude and direction of temperature variability affect hospitalization for myocardial infarction and stroke:population-based evidence from Guangzhou,China

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 1-11页

作者： Zhou Yang Murui Zheng Ze-Lin Yan Hui Liu Xiangyi Liu Jie-Qi Jin Jiagang Wu Chun-Quan Ou State Key Laboratory of Organ Failure research Department of BiostatisticsGuangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public HealthSouthern Medical UniversityGuangzhou 510515China Guangzhou Center for disease Control and Prevention Guangzhou 510440China

Relationships between nonoptimal temperatures and cardiovascular disease(CVD)mortality have been well ***,evidence of the association between temperature variability(TV)and CVD morbidity is *** study aimed to quantify the risk and burden of CVD-related hospitalization associated with the magnitude and direction of *** on meteorology and population-based hospitalizations for myocardial infarction(MI)and stroke were collected in Guangzhou,China,from 2013 to *** temperature variability(HTV)was measured as the standard deviation of hourly temperature records over specific exposure *** direction(upward or downward)of HTV was defined as the average daily mean temperature change relative to that of the previous day during the exposure ***-Poisson regression was applied to assess the impact of HTV after adjusting for the daily mean temperature,and the hospitalization fractions attributable to HTV were calculated.A 1℃-increase in HTV was significantly associated with a 2.24%and 1.72%increase in hospitalizations for MI and hemorrhagic stroke(HS)at lag 0–1 d,respectively,and a 1.55%increase in hospitalizations for ischemic stroke(IS)at lag 0–3 *** the study period,5.99%,4.64%,and 4.53%of MI,HS,and IS hospitalizations,respectively,were attributable to *** upward TV exerts acute effects on CVD hospital admissions,whereas the impact of downward TV generally *** findings highlight the importance of the magnitude and direction of temperature fluctuations,in addition to the mean level,in assessing the adverse health impacts of temperature variations.

关键词： Hourly temperature variability Cardiovascular Hospitalization Direction China

LncRNA CCRR maintains Ca^(2+)homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China(Life Sciences) 2024年第8期67卷 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun department of Pharmacology Harbin Medical University(State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical UniversityHarbin 150081China

Cardiac conduction regulatory RNA(CCRR)has been documented as an antiarrhythmic lncRNA in our earlier *** study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca^(2+)homeostasis in myocardial infarction(MI).Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca^(2+)homeostasis and reduced the heightened methylation level of SERCA2a following *** effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full ***,silencing CCRR in healthy mice led to intracellular Ca^(2+)overloading of *** increased SERCA2a protein stability by upregulating FTO *** direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP)analysis and RNA pulldown *** of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in *** study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO,thereby reducing the m^(6)A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in ***,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

关键词： CCRR calcium homeostasis FTO myocardial infarction SERCA2a

Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun Guangxi Key Laboratory of Brain and Cognitive Neuroscience Guilin Medical University department of Genetic disease research Osaka Metropolitan University Graduate School of Medicine department of Scientific research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,*** works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s *** intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent ***,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical ***,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in *** the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent *** findings indicate strong cross-talk between the two proteins in physiology and *** this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of Digestive disease and department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong Clinical research Center of Neurological disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric DiseasesSoochow UniversitySuzhouJiangsu ProvinceChina department of Neurology and Clinical research Center of Neurological disease The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural *** brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and *** the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular *** crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier *** this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain *** review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

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World Journal of Gastroenterology 2024年第11期30卷 1556-1571页

作者： Yan-Chao Hu Xiang-Chun Ding Hui-Juan Liu Wan-Long Ma Xue-Yan Feng Li-Na Ma department of Infectious disease General Hospital of Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina Infectious disease Clinical research Center of Ningxia Yinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic *** the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been *** To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC *** This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December *** were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment *** samples were collected at the onset and conclusion of the 12-wk intervention *** structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were *** Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful ***,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

关键词： Hepatitis B cirrhosis N1115 ready-to-eat lactobacillus Inflammation Liver function Lachnospiraceae incertae sedis Probiotic

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu Translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China department of Infectious disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical Key Laboratory of Emergency and Trauma research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(CAP),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included CAP patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and CAP.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match

Eliciting CD4-mimicking broadly neutralizing antibodies:new avenues towards the rational design of an HIV vaccine

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Signal Transduction and Targeted Therapy 2024年第3期9卷 836-838页

作者： Frauke Muecksch Oliver T.Fackler department of Infectious diseases Heidelberg UniversityMedical Faculty HeidelbergVirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany Chica and Heinz Schaller(CHS)research Group Department of Infectious DiseasesVirologyUniversity Hospital HeidelbergHeidelbergGermany department of Infectious diseases Heidelberg UniversityMedical Faculty HeidelbergIntegrative VirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany German Centre for Infection research(DZIF) Partner Site HeidelbergHeidelbergGermany

In a study recently published in Cell,Saunders et *** that a new anti-HIV vaccine triggers antibody responses resembling CD4-binding site broadly neutralizing antibody precursors in rhesus macaques.1 This study provid... 详细信息

关键词： al. vaccine rational