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Relative exchangeable copper, a high-quality biomarker for differentiation of Traditional Chinese Medicine syndrome in Wilson's disease

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Journal of Traditional Chinese Medicine 2024年第5期44卷 1017-1023页

作者： DING Yufeng YANG Wenming CHENG Yuan YANG Yulong ZHU Jun LU Yachun FANG Xiang ZHANG Jing department of Neurology the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine department of clinical laboratory the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine

OBJECTIVE: To investigate the value of relative exchangeable copper(REC) in diagnosing Wilson's disease(WD) and to determine its significance in the differentiation of Traditional Chinese Medicine(TCM) ***: A total of 78 patients with WD were recruited on the same day of the medical visit, and among them,32 were suffering from non-WD(N-WD) and 37 were heterozygous ATP7B carriers(HC) enrolled as *** genetic testing was performed for diagnosing WD and HC. Additionally, REC levels in different TCM syndromes were investigated. The correlation between REC and serum ceruloplasmin(Cp), serum copper oxidase(CO), and 24-h urinary copper was analyzed using the Global Assessment Scale and Unified Wilson's Disease Rating Scale and the significance of REC in WD diagnosis was investigated. Resting-state functional magnetic resonance imaging was used to assess the clinical symptoms of WD and analyze its severity in different TCM ***: REC determination helped in significantly distinguishing patients with N-WD or HC from those with WD with a cut-off of 21.15%. Furthermore, the comparative analysis of REC ratios among different TCM syndromes showed markedly high REC levels in the dampness-heat internal accumulation syndrome ***, the seed-based functional connectivity value from the putamen to the cerebellum was significantly correlated with TCM ***: REC level is a high-quality biomarker for diagnosing WD that effectively reflects disease severity and plays an essential role in deciding on treatment strategies and prognosis. Furthermore, REC levels are closely related to TCM syndromes in WD; thus, it is a potential objective quantitative indicator for distinguishing TCM syndromes in WD.

关键词： Global Assessment Scale Traditional Chinese Medicine syndrome Wilson’s disease relative exchangeable copper the Unified Wilson’s Disease Rating Scale

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BTG2 interference ameliorates high glucose-caused oxidative stress, cell apoptosis, and lipid deposition in HK-2 cells

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BIOCELL 2024年第9期48卷 1379-1388页

作者： WENJUAN ZHU ZHENGZHENG JU FAN CUI department of Blood Transfusion The First People’s Hospital of WuhuWuhu241000China department of clinical laboratory The First People’s Hospital of WuhuWuhu241000China

Objective:Diabetic nephropathy(DN)is a deleterious microangiopathy of diabetes,constituting a critical determinant of fatality in diabetic *** work is purposed to disclose the effects and modulatory mechanism of BTG anti-proliferation factor 2(BTG2)during the pathological process of ***:BTG2 expression in kidney tissues of diabetic mice and high glucose(HG)-exposed human proximal tubular cell line HK-2 was assessed with Western blot and *** diabetic mice model was constructed by streptozotocin injection and confirmed by the blood glucose level beyond 16.7 mmol/*** and eosin(H&E)staining and measurement of kidney function hallmarks were conducted to assess kidney *** counting kit(CCK)-8 method and TUNEL assay appraised cell activity and *** red O staining assayed lipid *** commercial kits were used to estimate oxidative stress-related ***-immunoprecipitation(Co-IP)assay testified the binding relationship of BTG2 with protein arginine methyltransferase 1(PRMT1).Results:BTG2 expression was significantly raised in renal tissues of diabetic mice and HK-2 cells exposed to ***2 deficiency improved viability and extenuated the apoptosis,lipid deposition as well as oxidative stress in HK-2 cells following HG *** addition,PRMT1 was also overexpressed in HK-2 cells exposed to ***2 interacted with PRMT1 and positively modulated PRMT1 *** effects of BTG2 interference on viability,apoptosis,lipid deposition,and oxidative stress in HG-challenged HK-2 cells were partially abrogated by PRMT1 ***:Altogether,BTG2 might aggravate HK-2 cell injury in response to HG by binding with PRMT1,providing a novel target for the therapeutic strategy of DN.

关键词： BTG2 Diabetic nephropathy Lipid deposition Oxidative stress PRMT1

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A novel mechanism of PHB2-mediated mitophagy participating in the development of Parkinson's disease

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Neural Regeneration Research 2024年第8期19卷 1828-1834页

作者： Yongjiang Zhang Shiyi Yin Run Song Xiaoyi Lai Mengmeng Shen Jiannan Wu Junqiang Yan Key laboratory of Neuromolecular Biology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina department of Neurology The First Affiliated HospitalCollege of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan ProvinceChina

Endoplasmic reticulum stress and mitochondrial dysfunction play important roles in Parkinson s disease,but the regulato ry mechanism remains ***-2(PHB2)is a newly discove red autophagy receptor in the mitochondrial inner membrane,and its role in Parkinson’s disease remains *** kinase R(PKR)-like endoplasmic reticulum kinase(PERK)is a factor that regulates cell fate during endoplasmic reticulum *** is regulated by PERK and is a target of the unfolded protein *** is unclear whether PERK regulates PHB2-mediated mitophagy thro ugh *** this study,we established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced mouse model of Parkinson’s *** used adeno-associated virus to knockdown PHB2 *** res ults showed that loss of dopaminergic neurons and motor deficits were aggravated in the MPTP-induced mouse model of Parkinson’s *** rexpression of PHB2 inhibited these *** also established a 1-methyl-4-phenylpyridine(MPP+)-induced SH-SY5Y cell model of Parkinson’s *** found that ove rexpression of Parkin increased co-localization of PHB2 and microtubule-associated protein 1 light chain 3,and promoted *** addition,MPP+regulated Parkin involvement in PHB2-mediated mitophagy through phosphorylation of *** findings suggest that PHB2 participates in the development of Parkinson’s disease by intera cting with endoplasmic reticulum stress and Parkin.

关键词： endoplasmic reticulum dopaminergic neuron microtubule-associated protein 1 light chain 3 mitophagy oxidative stress Parkin Parkinson’s disease PKR-like endoplasmic reticulum kinase reactive oxygen species prohibitin-2

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Effects of Bisphenol A and Its Substitute, Bisphenol F, on the Gut Microbiota in Mice

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Biomedical and Environmental Sciences 2024年第1期37卷 19-30页

作者： MENG Li Ying TAO Wen Fu LI Jing ZHU Min ZHONG De Bin ZHOU Jing QIN Xue WEI Rong Guo department of clinical laboratory The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina department of clinical laboratory The Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021GuangxiChina Jiangsu Key laboratory of Environmental Engineering Jiangsu Academy of Environmental SciencesNanjing 210000JiangsuChina

Objective The aim of this study was to assess the impact of bisphenol A(BPA)and its substitute,bisphenol F(BPF),on the colonic fecal community structure and function of *** We exposed 6–8-week-old male C57BL/6 mice to 5 mg/(kg∙day)and 50μg/(kg∙day)of BPA or BPF for 14 *** samples from the colon were analyzed using 16S rRNA *** Gut microbiome community richness and diversity,species composition,and function were significantly altered in mice exposed to BPA or *** change was characterized by elevated levels of Ruminococcaceae UCG-010 and Oscillibacter and decreased levels of Prevotella 9 and ***,pathways related to carbohydrate and amino acid metabolism showed substantial *** Mice exposed to different BP analogs exhibited distinct gut bacterial community richness,composition,and related metabolic *** the essential role of gut bacteria in maintaining intestinal homeostasis,our study highlights the intestinal toxicity of BPs in vertebrates.

关键词： Bisphenol A(BPA) Bisphenol F(BPF) 16S rRNA Microbiota

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang department of laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical Medicine Shandong UniversityJinanChina Core Unit of National clinical Research Center for laboratory Medicine HefeiChina Neurosurgical department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina department of clinical laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of *** studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of *** a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular *** be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological *** this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied *** regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial *** we highlight the regulation of RNA modifications on immunometabolism,further influencing immune *** all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted ***,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen department of laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key laboratory of clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of laboratory Medicine Zhejiang UniversityHangzhou 310000China department of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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Voluntary wheel running ameliorated the deleterious effects of high-fat diet on glucose metabolism,gut microbiota and microbial-associated metabolites

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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng department of Endocrinology Peking University First HospitalBeijing 100034China laboratory Animal Facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： High-fat diet Voluntary wheel running Gut microbiota Metabolomics Glucose metabolism

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Interaction between systemic iron parameters and left ventricular structure and function in the preserved ejection fraction population:a two-sample bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第1期21卷 64-80页

作者： Xiong-Bin MA Yong-Ming LIU Yan-Lin LV Lin QIAN The first clinical Medical College of Lanzhou University LanzhouGansuChina Geriatric Cardiovascular department and Gansu clinical Research Center for Geriatric Diseases First Hospital of Lanzhou UniversityGansuChina

BACKGROUND Left ventricular(LV)remodeling and diastolic function in people with heart failure(HF)are correlated with iron status;however,the causality is *** Mendelian randomization(MR)study investigated the bidirectional causal relationship between systemic iron parameters and LV structure and function in a preserved ejection fraction *** Transferrin saturation(TSAT),total iron binding capacity(TIBC),and serum iron and ferritin levels were extracted as instrumental variables for iron parameters from meta-analyses of public genome-wide association *** without myocardial infarction history,HF,or LV ejection fraction(LVEF)<50%(n=16,923)in the UK Biobank Cardiovascular Magnetic Resonance Imaging Study constituted the outcome *** dataset included LV end-diastolic volume,LV endsystolic volume,LV mass(LVM),and LVM-to-end-diastolic volume ratio(LVMVR).We used a two-sample bidirectional MR study with inverse variance weighting(IVW)as the primary analysis method and estimation methods using different algorithms to improve the robustness of the *** In the IVW analysis,one standard deviation(SD)increased in TSAT significantly correlated with decreased LVMVR(β=-0.1365;95%confidence interval[CI]:-0.2092 to-0.0638;P=0.0002)after Bonferroni ***,no significant relationships were observed between other iron and LV *** Bonferroni correction,reverse MR analysis showed that one SD increase in LVEF significantly correlated with decreased TSAT(β=-0.0699;95%CI:-0.1087 to-0.0311;P=0.0004).No heterogeneity or pleiotropic effects evidence was observed in the *** We demonstrated a causal relationship between TSAT and LV remodeling and function in a preserved ejection fraction population.

关键词： fraction function parameters

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Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 557-567页

作者： Sheng ZENG Shaoqiang XING Yifei ZHANG Haifeng WANG Qian LIU department of Urology Tianjin First Central HospitalTianjin 300192China department of Urology First Central Clinical CollegeTianjin Medical UniversityTianjin 300192China

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery,radiotherapy,and chemotherapy,with some promising *** aims to kill tumor cells by mobilizing or stimulating cytotoxic immune ***,the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high ***,nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens,activating targeted T cells,modulating the immunosuppressive tumor microenvironment,and improving the treatment *** Calmette-Gué;rin(BCG)is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis,which was first reported to have antitumor activity in *** therapy can activate the immune system by inducing various cytokines and chemokines,and its specific immune and inflammatory responses exert antitumor *** was first used during the 1970s as an intravesical treatment agent for bladder cancer,which effectively improved immune antitumor activity and prevented tumor *** recently,nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune *** this study,we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

关键词： Bladder cancer Bacillus Calmette-Gué rin vaccine Nanocarrier Genetic engineering Immunotherapy

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Ginsenoside Rb1 induces hepatic stellate cell ferroptosis to alleviate liver fibrosis via the BECN1/SLC7A11 axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 744-757页

作者： Lifan Lin Xinmiao Li Yifei Li Zhichao Lang Yeping Li Jianjian Zheng Key laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China department of Urology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China Key laboratory of clinical laboratory Diagnosis and Translational Research of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang325000China

Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with *** Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC ***,the potential role of GRb1 in mediating HSC ferroptosis remains *** study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 *** findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)***,GRb1 significantly alleviated CCl4-induced liver fibrosis in *** a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of ***,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit *** experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by ***,BECN1 could directly interact with SLC7A11,initiating HSC *** conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in ***,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.

关键词： Ginsenoside Rb1 Ferroptosis Liver fibrosis Hepatic stellate cells

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