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Neural Regeneration Research 2025年第1期20卷 139-158页

作者： Fengjuan jiao Lingyan meng Kang Du Xuezhi Li School of Mental Health Jining Medical UniversityJiningShandong ProvinceChina Shandong Collaborative Innovation Center for Diagnosis Treatment and Behavioral Interventions of Mental DisordersInstitute of Mental HealthJining Medical UniversityJiningShandong ProvinceChina

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

关键词： autophagy chemical therapy gene therapy Parkinson’s disease α-synuclein

Physiological,transcriptome and gene functional analysis provide novel sights into cadmium accumulation and tolerance mechanisms in kenaf

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Journal of Environmental Sciences 2024年第3期137卷 500-514页

作者： Shan Cao meng Wang jiao Pan Dengjie Luo Samavia Mubeen Caijin Wang jiao Yue Xia Wu Qijing Wu Hui Zhang Canni Chen Muzammal Rehman Sichen Xie Ru Li Peng Chen Guangxi Key Laboratory of Agro-environment and Agric-products safety Key Laboratory of Plant Genetics and BreedingCollege of AgricultureGuangxi UniversityNanning 530004China State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources College of Life Science and TechnologyGuangxi UniversityNanning 530004China

Kenaf is considered to have great potential for remediation of heavy metals in ecosystems.However,studies on molecular mechanisms of root Cd accumulation and tolerance are still inadequate.In this study,two differently tolerant kenaf cultivars were selected as materials and the physiological and transcriptomic effects were evaluated under Cd stress.This study showed that 200μmol/L CdCl_(2) treatment triggered the reactive oxygen species(ROS)explosion and membrane lipid peroxidation.Compared with the Cd-sensitive cultivar‘Z',the Cd-tolerant cultivar‘F'was able to resist oxidative stress in cells by producing higher antioxidant enzyme activities and increasing the contents of ascorbic acid(AsA)and glutathione(GSH).The root cell wall of‘F'exhibited higher polysaccharide contents under Cd treatment,providing more Cd-binding sites.There were 3,439 differentially expressed genes(DEGs)that were co-regulated by Cd treatment in two cultivars.Phenylpropanoid biosynthesis and plant hormone signal transduction pathways were significantly enriched by functional annotation analysis.DEGs associated with pectin,cellulose,and hemi-cellulose metabolism were involved in Cd chelation of root cell wall;V-ATPases,ABCC3 and Narmp3 could participated in vacuolar compartmentalization of Cd;PDR1 was responsible for Cd effux;the organic acid transporters contributed to the absorption of Cd in soil.These genes might have played key roles in kenaf Cd tolerance and Cd accumulation.Moreover,HcZIP2 was identified to be involved in Cd uptake and transport in kenaf.Our findings provide a deeper understanding of the molecular pathways underlying Cd accumulation and detoxification mechanisms in kenaf.

关键词： Kenaf Cd stress Physiological Transcriptome HcZIP2

Vitamin D-binding protein in plasma microglia-derived extracellular vesicles as a potential biomarker for major depressive disorder

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Genes & Diseases 2024年第2期11卷 1009-1021页

作者： Gaojia Zhang Ling Li Yan Kong Dandan Xu Yu Bao Zhiting Zhang Zhixiang Liao jiao jiao Dandan Fan Xiaojing Long Ji Dai Chunming Xie Zhiqiang meng Zhijun Zhang Department of Neurology Affiliated Zhongda HospitalResearch Institution of NeuropsychiatrySchool of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Shenzhen Key Laboratory of Drug Addiction Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)ShenzhenGuangdong 518000China CAS Key Laboratory of Brain Connectome and Manipulation The Brain Cognition and Brain Disease Institute (BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Lauterbur Research Center for Biomedical Imaging Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Shenzhen-Hong Kong Institute of Brain Sciences-Shenzhen Fundamental Research Institutions ShenzhenGuangdong 518000China Brain Cognition and Brain Disease Institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

No well-established biomarkers are available for the clinical diagnosis of major depressive disorder(MDD).Vitamin D-binding protein(VDBP)is altered in plasma and postmortem dorsolateral prefrontal cortex(DLPFC)tissues of MDD patients.Thereby,the role of VDBP as a potential biomarker of MDD diagnosis was further assessed.Total extracellular vesicles(EVs)and brain cell-derived EVs(BCDEVs)were isolated from the plasma of first-episode drug-naïve or drug-free MDD patients and well-matched healthy controls(HCs)in discovery(20 MDD patients and 20 HCs)and validation cohorts(88 MDD patients and 38 HCs).VDBP level in the cerebrospinal fluid(CSF)from chronic glucocorticoid-induced depressed rhesus macaques or prelimbic cortex from lipopolysaccharide(LPS)-induced depressed mice and wild control groups was measured to evaluate its relationship with VDBP in plasma microglia-derived extracellular vesicles(MDEVs).VDBP was significantly decreased in MDD plasma MDEVs compared to HCs,and negatively correlated with HAMD-24 score with the highest diagnostic accuracy among BCDEVs.VDBP in plasma MDEVs was decreased both in depressed rhesus macaques and mice.A positive correlation of VDBP in MDEVs with that in CSF was detected in depressed rhesus macaques.VDBP levels in prelimbic cortex microglia were negatively correlated with those in plasma MDEVs in depressed mice.The main results suggested that VDBP in plasma MDEVs might serve as a prospective candidate biomarker for MDD diagnosis.

关键词： Biomarker Cerebrospinal fluid Major depressive disorder Microglia derived extracellular vesicles Vitamin-D binding protein

Multiple mixed state variable incremental integration for reconstructing extreme multistability in a novel memristive hyperchaotic jerk system with multiple cubic nonlinearity

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Chinese Physics B 2024年第2期33卷 238-246页

作者：王梦蛟辜玲芳 School of Automation and Electronic Information Xiangtan UniversityXiangtan 411105China

Memristor-based chaotic systems with infinite equilibria are interesting because they generate extreme multistability.Their initial state-dependent dynamics can be explained in a reduced-dimension model by converting the incremental integration of the state variables into system parameters.However,this approach cannot solve memristive systems in the presence of nonlinear terms other than the memristor term.In addition,the converted state variables may suffer from a degree of divergence.To allow simpler mechanistic analysis and physical implementation of extreme multistability phenomena,this paper uses a multiple mixed state variable incremental integration(MMSVII)method,which successfully reconstructs a four-dimensional hyperchaotic jerk system with multiple cubic nonlinearities except for the memristor term in a three-dimensional model using a clever linear state variable mapping that eliminates the divergence of the state variables.Finally,the simulation circuit of the reduced-dimension system is constructed using Multisim simulation software and the simulation results are consistent with the MATLAB numerical simulation results.The results show that the method of MMSVII proposed in this paper is useful for analyzing extreme multistable systems with multiple higher-order nonlinear terms.

关键词： extreme multistability hyperchaotic jerk system nonlinearity

Naringin ameliorates H_(2)O_(2)-induced oxidative damage in cells and prolongs the lifespan of female Drosophila melanogaster via the insulin signaling pathway

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Food Science and Human Wellness 2024年第3期13卷 1231-1245页

作者： Xiaomei Du Kexin Wang Xiaoyan Sang Xiangxing meng jiao Xie Tianxin Wang Xiaozhi Liu Qun Huang Nan Zhang Hao Wang State Key Laboratory of Food Nutrition and Safety Tianjin University of Science and TechnologyTianjin 300457China The key Laboratory of Environmental Pollution Monitoring and Disease Control Ministry of EducationGuizhou Medical UniversityGuizhou 550025China Department of neurosurgery the Fifth Central Hospital of TianjinTianjin 300450China Tianjin Key Laboratory of Epigenetics for Organ Department in Preterm Infants the Fifth Central Hospital of TianjinTianjin 300450China

Naringin exists in a wide range of Chinese herbal medicine and has proven to possess several pharmacological properties.In this study,PC12,HepG2 cells,and female Drosophila melanogaster were used to investigate the antioxidative and anti-aging effects of naringin and explore the underlying mechanisms.The results showed that naringin inhibited H_(2)O_(2)-induced decline in cell viability and decreased,the content of reactive oxygen species in cells.Meanwhile,naringin prolonged the lifespan of flies,enhanced the abilities of climbing and the resistance to stress,improved the activities of antioxidant enzymes,and decreased malondialdehyde content.Naringin also improved intestinal barrier dysfunction and reduced abnormal proliferation of intestinal stem cells.Moreover,naringin down-regulated the mRNA expressions of inr,chico,pi 3k,and akt-1,and up-regulated the mRNA expressions of dilp2,dilp3,dilp5,and foxo,thereby activating autophagy-related genes and increasing the number of lysosomes.Furthermore,the mutant stocks assays and computer molecular simulation results further indicated that naringin delayed aging by inhibiting the insulin signaling(IIS)pathway and activating the autophagy pathway,which was consistent with the result of network pharmacological predictions.

关键词： Drosophila melanogaster Insulin signaling(IIS)pathway Naringin PC12 cell HepG2 cell

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 382-395页

作者： Jing-Yao Ren meng Xu Xiang-Dong Niu Shi-Xun Ma Ya-Jun jiao Da Wang Miao Yu Hui Cai School of Clinical Medicine Ningxia Medical UniversityYinchuan 750000Ningxia Hui autonomous regionChina Gansu Provincial Hospital Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina General Surgery Clinical Medical Center Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina Medical College of Jiangsu University Jiangsu UniversityZhenjiang 212013Jiangsu ProvinceChina Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province Gansu Provincial HospitalLanzhou 730000Gansu ProvinceChina

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

关键词： Systemic inflammatory response index Prognosis Gastric cancer Complications Meta-analysis

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan jiao XU meng jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia

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World Journal of Clinical Cases 2024年第18期12卷 3468-3475页

作者： meng-jiao Lin Shu-Bin Zou Bai-Xiang Zhu Three departments of cardiovascular medicine Harbin 242 HospitalHarbin 150066Heilongjiang ProvinceChina

BACKGROUND Patients with chronic heart failure(CHF)frequently develop hyperuricemia,an elevated serum uric acid level,associated with adverse outcomes.Dapagliflozin,a sodium-glucose cotransporter-2 inhibitor,demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction(HFrEF),irrespective of diabetes.However,dapagliflozin’s effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear.AIM To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia.METHODS We conducted a randomized,double-blind,placebo-controlled trial in 200 patients with CHF and hyperuricemia,with HFrEF and serum uric acid levels≥7 mg/dL(≥416μmol/L).The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months.The primary endpoint was the change in serum uric acid level from baseline to 24 months.Secondary endpoints included changes in left ventricular ejection fraction(LVEF),Nterminal pro-B-type natriuretic peptide(NT-proBNP),and quality of life(QoL)scores,as well as the incidence of cardiovascular death and hospitalization for heart failure.RESULTS At 24 months,dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL(71μmol/L)compared with placebo(95%CI:-1.5 to-0.9;P<0.001).Dapagliflozin also significantly improved LVEF by 3.5%(95%CI:2.1-4.9;P<0.001),NT-proBNP by 25%(95%CI:18-32;P<0.001),and QoL scores by 10 points(95%CI:7-13;P<0.001)and reduced the risk of cardiovascular death and hospitalization for heart failure by 35%(95%CI:15–50;P=0.002)compared with the placebo.Adverse events were similar between the two groups,except for a higher rate of genital infections in the dapagliflozin group(10%vs 2%,P=0.01).CONCLUSION Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia.Therefore,dapagliflozin may be a useful therapeutic option for this high-risk population.

关键词： Dapagliflozin Hyperuricemia Chronic heart failure Sodium-glucose cotransporter-2 inhibitor Uric acid levels Cardiovascular mortality

Experimental observation of the significant difference between surface and bulk Kondo processes in Kondo lattice YbCu_(2)Si_(2)

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Science China(Physics,Mechanics & Astronomy) 2024年第4期67卷 154-160页

作者： Yin-Zou Zhao jiao-jiao Song Qi-Yi Wu Hao Liu Chen Zhang Bo Chen Hong-Yi Zhang Zhen-Hua Chen Yao-Bo Huang Xue-Qing Ye Ya-Hua Yuan Yu-Xia Duan Jun He Jian-Qiao meng School of Physics Central South UniversityChangsha 410083China Shanghai Institute of Applied Physics Chinese Academy of SciencesShanghai 201204China

Synchrotron-based angle-resolved photoemission spectroscopy was employed to investigate the temperature evolution of the Yb 4 f spectral for surface and bulk in the Kondo lattice YbCu_(2)Si_(2).Our study quantitatively distinguishes between the surface and bulk hybridization processes,revealing that the onset temperatures for both surface and bulk hybridization processes are significantly higher than the Kondo temperature.Additionally,we found that the effective surface Kondo temperature is much lower than that of the bulk.These findings offer valuable insights into the understanding of heavy fermion physics.

关键词： Kondo lattice angle-resolved photoemission spectroscopy electronic structure hybridization surface state

Redox-stress response resistance(RRR)mediated by hyperoxidation of peroxiredoxin 2 in senescent cells

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Science China(Life Sciences) 2023年第10期66卷 2280-2294页

作者： jiao meng Yuanyuan Wang Zhenyu Lv Xinhua Qiao Aojun Ye Qiaoli Zhu Chang Chen National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Beijing Institute for Brain Disorders Capital Medical UniversityBeijing 100069China

Aging is closely related to redox regulation.In our previous work,we proposed a new concept,“redox-stress response capacity(RRC),”and found that the decline in RRC was a dynamic characteristic of aging.However,the mechanism of RRC decline during aging remains unknown.In this study,using the senescent human fibroblast cell model and Caenorhabditis elegans model,we identified that peroxiredoxin 2(PRDX2),as a hydrogen peroxide(H_(2)O_(2))sensor,was involved in mediating RRC.PRDX2 knockdown led to a decline of RRC and accelerated senescence in fibroblasts and prdx-2 mutant C.elegans also showed decreased RRC.The mechanism study showed that the decreased sensor activity of PRDX2 was related to the increase in hyperoxidation of PRDX2 in senescent cells.Moreover,the level of PRDX2 hyperoxidation also increased in old C.elegans.Simultaneous overexpression of both PRDX2 and sulfiredoxin(SRX)rescued the reduced RRC and delayed senescence.The increase in PRDX2 hyperoxidation in senescent cells led to a decrease in its sensor activity,resulting in the decreased cellular response to H_(2)O_(2),which is similar to the mechanism of insulin resistance due to the lower insulin receptor sensitivity.Treatment of young cells with a high level of H_(2)O_(2)to induce a higher level of PRDX2-SO_(3) resulted in mimicking the RRC decline in senescent cells,which is also similar to a model of insulin resistance induced by high levels of insulin.All these results thrillingly indicate that there is an insulin-resistance-like phenomenon in senescent cells,we named it redox-stress response resistance,RRR.RRR in senescent cells is an important new discovery that explains RRC decline during aging and reveals the internal relationship between redox regulation and aging from a new perspective.

关键词： peroxiredoxin 2(PRDX2) redox-stress response capacity(RRC) redox-stress response resistance(RRR) H_(2)O_(2)sensor redox relay aging oxidative stress