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Novel ACADVL variants resulting in mitochondrial defects in long-chain acyl-CoA dehydrogenase deficiency

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2020年第11期21卷 885-896页

作者： Ting CHEN Fan TONG xiao-yu WU Ling ZHU Qiu-zi YI Jing ZHENG Ru-lai YANG Zheng-yan ZHAO xiao-hui cang Qiang SHU Ping-ping JlANG Division of Medical Genetics and Genomics The Children's HospitalZhejiang University School of Medicine/National Clinical Research Center for Child HealthHangzhou 310052China Institute of Genetics and Department of Human Genetics Zhejiang University School of MedicineHangzhou 310058China

The pathogenesis of very-long-chain acyl-CoA dehydrogenase(VLCAD)deficiency is highly heterogeneous and still *** novel variants have been recently detected in the *** molecular and cellular effects of these previously unreported variants are still poorly understood and require further *** address this problem,we have evaluated the various functions and biochemical consequences of six novel missense variants that lead to mild VLCAD *** deficiencies in fatty acid oxidation(FAO)and other mitochondrial defects were observed in cells carrying one of these six variants(c.541 C>T,c.863 T>G,c.895 A>G,c.1238 T>C,c.1276 G>A,and c.1505 T>A),including reductions in mitochondrial respiratory-chain function and adenosine teriphosphate(ATP)production,and increased levels of mitochondrial reactive oxygen species(ROS).Intriguingly,higher apoptosis levels were found in cells carrying the mutant VLCAD under glucose-limited ***,the stability of the mutant homodimer was disturbed,and major conformational changes in each mutant VLCAD structure were predicted by molecular dynamics(MD)*** data presented here may provide valuable information for improving management of diagnosis and treatment of VLCAD deficiency and for a better understanding of the general molecular bases of disease variability.

关键词： Mitochondrial dysfunction Very-long-chain acyl-CoA dehydrogenase(VLCAD) β-Oxidation Molecular dynamics(MD)simulation

Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration Research 2025年第11期20卷 3193-3206页

作者： Ling-xiao Yi hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature Research Program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

Zwitterionic hyaluronic acid derivatives for co-delivery of both chemotherapeutic and nucleic acid drugs in breast cancer treatment

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Nano Research 2025年第1期18卷 607-617页

作者： Ruo-Lin Jiang hui-Na Liu Yu-Fan Yang Zhi-Cheng Zhang Qi Dai xiao-Yan Bao Lin-Jie Wu Ya-Xin Qin Xin Tan xiao-Yan Sun Xu-Fang Ying Zhi-Qing Ben Min Han Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Radiation Oncology Key Laboratory of Cancer Prevention and InterventionThe Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310058China Hangzhou Institute of Innovative Medicine Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang UniversityHangzhou 310058China Polytechnic institute Zhejiang UniversityHangzhou 310015China

Traditionally,hyaluronic acid has been widely used for drug delivery,but the current application bottleneck is that hyaluronic acid is hydrophilic and electronegative,which makes it difficult to carry hydrophobic drugs and small interfering RNA(siRNA)with the same *** on previous studies,we designed and synthesized hyaluronic acid nanocarriers HA-spermine/N,N,N-trimethylcystamine/DOX-TPP(HSTD)for loading siRNA to overcome the problem of siRNA release caused by strong electrostatic ***,N,N,Ntrimethylcystamine in the carrier can be degraded by intracellular glutathione to completely and rapidly release siRNA,thus promoting ***,when codelivered with the chemotherapy drug doxorubicin(DOX),this novel nanocarrier showed promising synergy in inhibiting tumor growth.

关键词： zwitterionic hyaluronic acid N N N-trimethylcystamine small interfering RNA(siRNA) doxorubicin

Analysis of the anti-T2DM components in dichloromethane fraction of Schisandra sphenanthera and its mechanism

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Traditional Medicine Research 2025年第1期10卷 27-43页

作者： Shi-Bo Feng Hai-hui Jiang hui-Li Kang Yi Jiang Hua-Wei Zhang xiao-Mei Song Yu-Ze Li Wen-Li Huang Dong-Dong Zhang Chong Deng School of Pharmacy Shaanxi University of Chinese MedicineXianyang 712046China School of Pharmacy and Shaanxi Qinling Application Development and Engineering Center of Chinese Herbal Medicine Shaanxi University of Chinese MedicineXianyang 712046China Key Laboratory for Research and Development of“Qin Medicine”of Shaanxi Administration of Traditional Chinese Medicine Xianyang 712046China Shaanxi Key Laboratory of Research and Application of“Taibai Qi Yao” Xianyang 712046China

Background:The type 2 diabetes mellitus(T2DM)pharmacodynamic study of various parts of Schisandra sphenanthera was conducted in the previous stage,and it was found that dichloromethane extracted part(SDP)had a significant hypoglycemic ***,the components of SDP were analyzed,and the specific mechanism of its anti-T2DM was ***:We used a high-fat,high-sugar diet in combination with streptozotocin to induce a T2DM rat model,and the model rats were divided into two groups according to body weight and blood ***,oral glucose tolerance test,fasting blood glucose,low density lipoprotein cholesterol,superoxide dismutase,insulin,glycated hemoglobin,total cholesterol,nonesterified free fatty acids,alanine aminotransferase,high-density lipoprotein cholesterol,aspartate aminotransferase,malondialdehyde,and glutathione peroxidase were measured,organ indices were calculated,and pathological sections of pancreas and liver were *** 16S rRNA V3–V4 region of intestinal flora was sequenced to explore the effect of SDP on biochemical indicators and intestinal *** on the above indicators,the anti-T2DM mechanism of SDP in Schisandra sphenanthera was ***:After six weeks of administration,the biochemical indices of diabetic rats were diminished compared to the control *** SDP could significantly increase the gut microbialα-diversity index,resulting in significant changes in the flora of T2DM rats,with increased richness and diversity,reduced harmful flora,and significantly back-regulated the levels of acetic acid,propionic acid,and butyric ***:SDP can improve the symptoms associated with elevated blood glucose,dyslipidemia,elevated fasting insulin levels,and damaged glucose tolerance in *** against T2DM may be through the control of intestinal flora to normalize and exert anti-diabetic effect;its main active components may be lignans and terpenoids.

关键词： Schisandra sphenanthera T2DM intestinal flora HPLC

Burden of mental disorders and risk factors in the Western Pacific region from 1990 to 2021

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World Journal of Psychiatry 2025年第1期15卷 93-105页

作者： Ya-Xin Xu xiao-Xuan Niu Wen-Chang Jia Jing Wen Xue-Lin Cheng Yan Han Ming-hui Peng Jing Zhou Yao Liu Sun-Fang Jiang xiao-Pan Li Department of Health Management Centre Zhongshan HospitalFudan UniversityShanghai 200030China Department of General Practice Zhongshan HospitalFudan UniversityShanghai 200030China Department of Nutrition Zhongshan HospitalFudan UniversityShanghai 200032China School of Public Health Fudan UniversityShanghai 200032China

BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and *** To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging *** We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to *** methods included age-standardisation and uncertainty analysis to address variations in population structure and data *** Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age *** and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum ***,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the ***,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk *** This study highlights the significant burden of MD in the WPR,with variations by age,gender,and *** coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.

关键词： Mental disorders Western pacific region Global Burden of Disease Risk factors Disability-adjusted life years

Joint modelling of location and scale parameters of the skew-normal distribution

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Applied Mathematics(A Journal of Chinese Universities) 2014年第3期29卷 265-272页

作者： LI hui-qiong WU Liu-cang Department of statistics Yunnan Unversity Faculty of Science Kunming University of Science and Technology

Joint location and scale models of the skew-normal distribution provide useful ex- tension for joint mean and variance models of the normal distribution when the data set under consideration involves asymmetric outcomes. This paper focuses on the maximum likelihood estimation of joint location and scale models of the skew-normal distribution. The proposed procedure can simultaneously estimate parameters in the location model and the scale model. Simulation studies and a real example are used to illustrate the proposed methodologies.

关键词： joint mean and variance models of the normal distribution joint location and scale models ofthe skew-normal distribution maximum likelihood estimators skew-normal distribution.

Quantifying multiple-site compositional turnover in an Afrotemperate forest, using zeta diversity

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Forest Ecosystems 2018年第2期5卷 189-197页

作者： cang hui Wessel Vermeulen Graham Durrheim Centre for Invasion Biology Department of Mathematical SciencesStellenbosch University Mathematical and Physical Biosciences African Institute for Mathematical Sciences Garden Route Scientific Services South African National Parks

Background： Species turnover is typically measured by partitioning diversity components into alpha and pairwise beta diversity. However, alpha and beta components cannot express the full spectrum of multiple-site compositional turnover. To this end, zeta diversity has been proposed as an extended framework to allow complete biodiversity partitioning and to measure multiple-site species turnover. We use a zeta-diversity framework to explore the turnover and potential community assembly processes of an African Montane Forest. Methods： Using a 20 m grid, we explore the species turnover in a 4.55 ha forest plot located in the Garden Route National Park of South Africa, with 47 and 27 canopy and sub-canopy tree species in the regional poo We first calculate how zeta diversity declines and how the probability of retention of species with particular occupancies changes with increasing zeta orders （i.e. the number of sites [grid cells] involved in the calculation）. Using null models with row sums and column sums constrained respectively, we explore whether species turnover is driven by mechanisms of ecological differences （species-specific occupancies） or habitat heterogeneity （site-specific alpha diversity and thus environmental filters）. Results： The decline of zeta diversity with zeta order followed a power law; that is, the probability of retention increased with species occupancies, suggesting common species being more likely to be discovered in extra sites. The null model retaining row sums （species＇ occupancy） of the species-by-site matrix recreated perfectly the decline of zeta diversity, while the null model of habitat heterogeneity （retaining column sums） was rejected. This suggests that mechanisms driving species-specific occupancies （i.e. ecological differences between species） dictate the multi-site species turnover in the community. The spatial patterns of zeta diversity revealed little spatial structuring forces, supporting a fine-grain structure in these sou

关键词： Species turnover Diversity partitioning Zeta diversity Community assembly Southern cape forest Afromontane forest

Design of Networked Control Systems with Bounded Arbitrary Time Delays

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International Journal of Automation and computing 2012年第2期9卷 182-190页

作者： xiao-Ming Tang Bao-cang Ding College of Automation Chongqing UniversityChongqing 400044PRC

This paper is mainly concerned with the model predictive control （MPC） of networked control systems （NCSs） with uncertain time delay and data packets disorder. The network-induced time delay is described as bounded and arbitrary process. For the usual state feedback controller, by considering all the possibilities of delays, an augmented state space model of the closed-loop system, which characterizes all the delay cases, is obtained. The stability conditions are given according to the Lyapunov method based on this augmented model. The stability property is inherited in MPC which explicitly considers the physical constraints. A numerical example is given to demonstrate the effectiveness of the proposed MPC.

关键词： Model predictive control (MPC) state feedback networked control systems (NCSs) robust control network-induceddelay.

Synthesis and Structures of Two New Molybdophosphates

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Chemical Research in Chinese Universities 2003年第3期19卷 257-262页

作者： LINZheng-zhong ZHANGHan-hui HUANGChang-cang SUNRui-qing YANGQi-yu ChemistryDepartment FuzhouUniversityFuzhou350002P.R.China；StateKeyLaboratoryofStructuralChemistryFujianInstituteofResearchontheStructureofMatterFuzhou350002P.R.China ChemistryDepartment FuzhouUniversityFuzhou350002P.R.China

A one dimension solid and a two dimension solid consisting of polyoxoanions bridged by {CoO 3N 2} and {CoO 4} groups respectively have been synthesized by the hydrothermal method and structurally characterized by X Ray crystallography. Each structure has the [(PO 4) 4Mo 6O 15 ] 12- cluster that is commonly observed in many molybdophosphates. In compound 1, [(PO 4) 4Mo 6O 15 ] 12- clusters are linked by {CoO 3N 2} groups to form a chain like structure, and the chains are hydrogen bonded into a network. Compound 2 is a layer structure with channnels constructed from [(PO 4) 4Mo 6O 15 ] 12- clusters and {CoO 4} groups, the organic molecules and the lattice water molecules are distributed disorderly in the interlamellar region and form strong hydrogen bonds with inorganic framework. The IR and the fluorescent spectra were investigated and discussed.

关键词： Hydrothermal Molybdophosphates Crystal structure