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Cell reprogramming therapy for Parkinson’s disease

Neural Regeneration Research 2024年第11期19卷 2444-2455页

作者： Wenjing Dong Shuyi Liu Shangang Li Zhengbo Wang State Key laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan ProvinceChina yunnan Key laboratory of Primate Biomedical Research KunmingYunnan ProvinceChina

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

关键词： animal models astrocytes autologous cell reprogramming cell therapy direct lineage reprogramming dopaminergic neurons induced pluripotent stem cells non-human primates Parkinson’s disease

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Loss of SHROOM3 affects neuroepithelial cell shape through regulating cytoskeleton proteins in cynomolgus monkey organoids

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Zoological Research 2024年第2期45卷 233-241页

作者： Peng Li Ting Zhang Ruo Wu Jun-Yu Zhang Yan Zhuo Shan-Gang Li Jiao-Jian Wang Wen-Ting Guo Zheng-Bo Wang Yong-Chang Chen State Key laboratory of Primate Biomedical Research Institute of Primate Translational MedicineKunming University of Science and TechnologyKunmingYunnan 650500China yunnan Key laboratory of Primate Biomedical Research KunmingYunnan 650500China

Neural tube defects(NTDs)are severe congenital neurodevelopmental disorders arising from incomplete neural tube closure.Although folate supplementation has been shown to mitigate the incidence of NTDs,some cases,often attributable to genetic factors,remain unpreventable.The SHROOM3 gene has been implicated in NTD cases that are unresponsive to folate supplementation;at present,however,the underlying mechanism remains unclear.Neural tube morphogenesis is a complex process involving the folding of the planar epithelium of the neural plate.To determine the role of SHROOM3 in early developmental morphogenesis,we established a neuroepithelial organoid culture system derived from cynomolgus monkeys to closely mimic the in vivo neural plate phase.Loss of SHROOM3 resulted in shorter neuroepithelial cells and smaller nuclei.These morphological changes were attributed to the insufficient recruitment of cytoskeletal proteins,namely fibrous actin(F-actin),myosin II,and phospho-myosin light chain(PMLC),to the apical side of the neuroepithelial cells.Notably,these defects were not rescued by folate supplementation.RNA sequencing revealed that differentially expressed genes were enriched in biological processes associated with cellular and organ morphogenesis.In summary,we established an authentic in vitro system to study NTDs and identified a novel mechanism for NTDs that are unresponsive to folate supplementation.

关键词： Neural tube defects SHROOM3 Neuroepithelial Organoids Cynomolgus monkey

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Feedback of Efficient Shock Acceleration on Magnetic-field Structure Inside Young Type Ia Supernova Remnants

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Research in Astronomy and Astrophysics 2024年第6期24卷 236-246页

作者： Jun-Yu Shen Bi-Wen Bao Li Zhang Department of Astronomy Key Laboratory of Astroparticle Physics of Yunnan Province Yunnan University Key laboratory of Statistical Modeling and Data Analysis of yunnan Province Yunnan University

Using an effective adiabatic index γeffto mimic the feedback of efficient shock acceleration, we simulate the temporal evolution of a young type Ia supernova remnant （SNR） with two different background magnetic field（BMF） topologies:a uniform and a turbulent BMF. The density distribution and magnetic-field characteristics of our benchmark SNR are studied with two-dimensional cylindrical magnetohydrodynamic simulations. When γeffis considered, we find that:（1） the two-shock structure shrinks and the downstream magnetic-field orientation is dominated by the Rayleigh–Taylor instability structures;（2） there exists more quasi-radial magnetic fields inside the shocked region; and （3） inside the intershock region, both the quasi-radial magnetic energy density and the total magnetic energy density are enhanced:in the radial direction, with γeff=1.1, they are amplified about 10–26 times more than those with γeff=5/3. While in the angular direction, the total magnetic energy densities could be amplified about 350 times more than those with γeff=5/3, and there are more grid cells within the intershock region where the magnetic energy density is amplified by a factor greater than 100.

关键词： ISM: magnetic fields ISM: supernova remnants magnetohydrodynamics (MHD) methods: numerical

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Evolution and conservation genetics of pangolins

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Integrative Zoology 2024年第3期19卷 426-441页

作者： Tongtong GU Jingyang HU Li YU State Key laboratory for Conservation and Utilization of Bio-Resource in yunnan School of Life SciencesYunnan UniversityKunmingChina

Pangolins(Pholidota,Manidae)are classified as an evolutionarily distinct and globally endangered mammal due to their unique morphology(nail-like scales and a myrmecophagous diet)and being the victim of heavy poaching and worldwide trafficking.As such,pangolins serve as a textbook example for studying the special phenotypic evolutionary adaptations and conservation genetics of an endangered species.Recent years have demonstrated significant advancements in the fields of molecular genetics and genomics,which have translated to a series of important research achievements and breakthroughs concerning the evolution and conservation genetics of pangolins.This review comprehensively presents the hitherto advances in phylogeny,adaptive evolution,conservation genetics,and conservation genomics that are related to pangolins,which will provide an ample understanding of their diversity,molecular adaptation mechanisms,and evolutionary potentials.In addition,we highlight the priority of investigating species/population diversity among pangolins and suggest several avenues of research that are highly relevant for future pangolin conservation.

关键词： adaptive evolution conservation genetics conservation genomics pangolins phylogeny

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Sex-specific facilitation and reproduction of the gynodioecious cushion plant Arenaria polytrichoides on the Himalaya-Hengduan mountains,SW China

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Plant Diversity 2024年第2期46卷 247-255页

作者： Xufang Chen Yazhou Zhang Lishen Qian Renyu Zhou Hang Sun Jianguo Chen State Key laboratory of Plant Diversity and Specialty Crops Kunming Institute of BotanyChinese Academy of SciencesKunmingYunnanChina yunnan Key laboratory of Plateau Wetland Conservation Restoration and Ecological ServicesSouthwest Forestry UniversityKunmingYunnanChina

When benefiting other beneficiaries,cushion plants may reciprocally receive feedback effects.The feedback effects on different sex morphs,however,remains unclear.In this study,taking the gynodioecious Arenaria polytrichiodes as a model species,we aimed to assess the sex-specific facilitation intensity of cushion plant by measuring the beneficiary cover ratio,and to assess the potential costs in cushion reproductive functions by measuring the flower and fruit cover ratios.The total beneficiary cover ratio was similar between females and hermaphrodites.Females produced much less flowers but more fruits than hermaphrodites.These results suggested that females and hermaphrodites possess similar facilitation intensity,and female cushion A.polytrichoides may allocate more resources saved from pollen production to seed production,while hermaphrodites possibly allocate more resources to pollen production hence reducing seed production.The surface areas covered by beneficiaries produced less flowers and fruits than areas without beneficiaries.In addition,strong negative correlations between beneficiary cover and flower cover were detected for both females and hermaphrodites,but the correlation strength were similar for these two sex morphs.However,the correlation between beneficiary cover and fruit cover was only significantly negative for females,suggesting that beneficiary plants negatively affect fruit reproduction of females while have neutral effects on hermaphrodites.All the results suggest that to facilitate other beneficiaries can induce reproductive costs on cushion A.polytrichoides,with females possibly suffering greater cost than hermaphrodites.Such differentiation in reproductive costs between sex morphs,in long-term perspective,may imply sex imbalance in population dynamics.

关键词： Facilitation intensity Feedback effect Sex-specific facilitation Nurse plant Population dynamics Reproductive function

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Opportunities and challenges in studies of mammalian hybrid speciation

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Science China(Life Sciences) 2024年第3期67卷 614-617页

作者： Hong Wu Yuxing Zhang Li Yu State Key laboratory for Conservation and Utilization of Bio-Resource in yunnan School of Life SciencesYunnan UniversityKunming 650091China

Revealing the mechanisms of speciation remains one of the most attractive and challenging issues in the field of evolutionary biology, and is also key to understanding the biodiversity present in nature.

关键词： biodiversity attractive evolutionary

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Aryl hydrocarbon receptor:Linking environment to aging process in elderly patients with asthma

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Chinese Medical Journal 2024年第4期137卷 382-393页

作者： Tianrui Yang Rongjun Wan Wei Tu Sai Nithin Avvaru Peisong Gao Division of Allergy and Clinical Immunology Department of MedicineJohns Hopkins University School of MedicineBaltimoreMD 21224USA Department of Geriatric medicine The First People’s Hospital of Yunnan ProvinceKunmingYunnan 650032China Department of Respiratory medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China The State Key laboratory of Respiratory Disease for Allergy Shenzhen Key Laboratory of Allergy and ImmunologyShenzhen University School of MedicineShenzhenGuangdong 518055China

Aging is a significant risk factor for various diseases,including asthma,and it often leads to poorer clinical outcomes,particularly in elderly individuals.It is recognized that age-related diseases are due to a time-dependent accumulation of cellular damage,resulting in a progressive decline in cellular and physiological functions and an increased susceptibility to chronic diseases.The effects of aging affect not only the elderly but also those of younger ages,posing significant challenges to global healthcare.Thus,understanding the molecular mechanisms associated with aging in different diseases is essential.One intriguing factor is the aryl hydrocarbon receptor(AhR),which serves as a cytoplasmic receptor and ligand-activated transcription factor and has been linked to the aging process.Here,we review the literature on several major hallmarks of aging,including mitochondrial dysfunction,cellular senescence,autophagy,mitophagy,epigenetic alterations,and microbiome disturbances.Moreover,we provide an overview of the impact of AhR on these hallmarks by mediating responses to environmental exposures,particularly in relation to the immune system.Furthermore,we explore how aging hallmarks affect clinical characteristics,inflammatory features,exacerbations,and the treatment of asthma.It is suggested that AhR signaling may potentially play a role in regulating asthma phenotypes in elderly populations as part of the aging process.

关键词： Aging Environment Reactive oxygen species Senescence Aryl hydrocarbon receptor Asthma

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Patterns and drivers of plant sexual systems in the dry-hot valley region of southwestern China

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Plant Diversity 2024年第2期46卷 158-168页

作者： Rong Ma Qi Xu Yongqian Gao Deli Peng Hang Sun Bo Song State Key laboratory of Plant Diversity and Specialty Crops/yunnan Key laboratory for Integrative Conservation of Plant Species with Extremely Small Populations Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China College of Life Sciences Shaanxi Normal UniversityXi'an 710119China yunnan Forestry Technological College Kunming 650224China School of Life Science/Key laboratory of yunnan for Biomass Energy and Biotechnology of Environment Yunnan Normal UniversityKunming 650500YunnanChina

Sexual systems play important roles in angiosperm evolution and exhibit substantial variations among different floras. Thus, studying their evolution in a whole flora is crucial for understanding the formation and maintenance of plant biodiversity and predicting its responses to environmental change. In this study, we determined the patterns of plant sexual systems and their associations with geographic elements and various life-history traits in dry-hot valley region of southwestern China, an extremely vulnerable ecosystem. Of the 3166 angiosperm species recorded in this area, 74.5% were hermaphroditic,13.5% were monoecious and 12% were dioecious, showing a high incidence of diclinous species. Diclinous species were strongly associated with tropical elements, whereas hermaphroditic species were strongly associated with temperate and cosmopolitan elements. We also found that hermaphroditism was strongly associated with showy floral displays, specialist entomophily, dry fruits and herbaceous plants.Dioecy was strongly associated with inconspicuous, pale-colored flowers, generalist entomophily, fleshy fruits, and woody plants, whereas monoecy was strongly associated with inconspicuous, pale-colored flowers, anemophily, dry fruits, and herbaceous plants. In addition, hermaphroditic species with generalist entomophily tended to flower in the dry season, whereas diclinous species with specialist entomophily tended to flower in the rainy season. However, independent of sexual systems, plants that produce dry fruits tended to flower in the rainy season and set fruits in the dry season, but the opposite pattern was found for fleshy fruit-producing plants. Our results suggest that in the dry-hot valleys, plant sexual systems are associated with geographic elements as well as various life-history traits that are sensitive to environmental change.

关键词： Floral traits Fruit type Growth form Pollination system Reproductive phenology

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Single-center retrospective study of the diagnostic value of doubleballoon enteroscopy in Meckel’s diverticulum with bleeding

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1043-1054页

作者： Tian He Chao Yang Jing Wang Ji-Sheng Zhong Ai-Hua Li Ya-Jing Yin Li-Ling Luo Chun-Mei Rao Nian-Fen Mao Qiang Guo Zan Zuo Wen Zhang Ping Wan yunnan Digestive Endoscopy Clinical Medical Center Department of GastroenterologyThe First People’s Hospital of Yunnan ProvinceThe Affiliated Hospital of Kunming University of Science and TechnologyKunming 650032Yunnan ProvinceChina Department of medicine Kunming University of Science and TechnologyKunming 650093Yunnan ProvinceChina School of medicine Yunnan University of Traditional Chinese MedicineKunming 650011Yunnan ProvinceChina Department of Gastroenterology Qujing Hospital of Traditional Chinese MedicineQujing 655000Yunnan ProvinceChina Department of Gastroenterology Yunnan University of Traditional Chinese MedicineKunming 650011Yunnan ProvinceChina

BACKGROUND The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel’s diverticulum(MD)complicated by digestive tract hemorrhage.Moreover,we aimed to evaluate the value of double-balloon enteroscopy(DBE)in MD diagnosis and the prognosis after laparoscopic diverticula resection.AIM To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding.METHODS The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations,auxiliary examination,and follow-up after laparoscopic resection of diverticula.RESULTS(1)Among 84 MD patients complicated with hemorrhage,77 were male,and 7 were female with an average age of 31.31±10.75 years.The incidence was higher in men than in women of different ages;(2)Among the 84 MD patients,65(78.40%)had defecated dark red stools,and 50(58.80%)had no accompanying symptoms during bleeding,indicating that most MD bleeding appeared a dark red stool without accompanying symptoms;(3)The shock index of 71 patients(85.20%)was30%;(4)The DBE-positive rate was 100%(54/54),99mTcpertechnetate-positive scanning rate was 78%(35/45)compared with capsule endoscopy(36%)and small intestine computed tomography(19%).These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding,especially DBE was a highly precise examination method in MD diagnosis;(5)A total of 54 MD patients with hemorrhage underwent DBE examination before surgery.DBE endoscopy revealed many mucosal manifestations including normal appearance,inflammatory changes,ulcerative changes,diverticulum inversion,and nodular hyperplasia,with ulcerative changes being the most common(53.70%).This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding;and(6

关键词： Meckel’s diverticulum with bleeding Double-balloon colonoscopy 99mTc-pertechnetate scanning Capsule endoscopy Ectopic gastric mucosa

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Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

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Traditional medicine Research 2024年第9期9卷 14-20页

作者： Cheng Qin Xiang-Yi Kong Fang Wang Jin Xu Zhuo Zhang Xue-Song Yang Jian-Zhou Ye College of First Clinical medicine Yunnan University of Traditional Chinese MedicineKunming 650500China yunnan Key laboratory of Dai and Yi medicines Yunnan University of Chinese MedicineKunming 650500China yunnan Provincial Key laboratory of Molecular Biology for Sinomedicine Yunnan University of Chinese MedicineKunming 650500China Department of Dermatology The First Affiliated Hospital of Yunnan University of Traditional Chinese MedicineKunming 650021China

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

关键词： atopic dermatitis acupoint catgut-embedding therapy Th2 type immune response

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