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targeting trkB–PSD-95 coupling to mitigate neurological disorders

Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-wen Alvin Huang John Marshall Department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA Department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

tropomyosin receptor kinase B(trkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic trkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with trkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss trkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of trkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with trkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated trkB.t1 *** trkB agonists and antibodies that activate trkB are being intensively investigated,they cannot distinguish the multiple human trkB splicing isoforms or cell type-specific *** trkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost trkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity trkB

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Engineered Cancer Nanovaccines:A New Frontier in Cancer therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu Chao Fang Qiuxia Peng wen Qin Xuebing Yan Kun Zhang Central Laboratory and Department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China Department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice Base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of t cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic t lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

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Drosophila models used to simulate human AtP1A1 gene mutations that cause Charcot-Marie-tooth type 2 disease and refractory seizures

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Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of the First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-AtPase pump,AtPase Na^(+)/K^(+)transporting subunit alpha 1(AtP1A1),cause Charcot-Marie-tooth disease type 2(CMt2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-AtPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human AtP1A1 gene mutations that cause *** located within the helical linker region of human AtP1A1(I592t,A597t,P600t,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(tttF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571t),Atpα^(A576t),Atpα^(P579t),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571t)and Atpα^(P579t)).three alleles(Atpα^(A576t),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMt2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(tttF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： AtP1A1 Atpα bang-sensitive paralysis Charcot-Marie-tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-AtPase point mutation seizures sodium pump

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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying tan Li Zhang wen-tao Jiang School of Medicine Nankai UniversityTianjin 300192China tianjin Key Laboratory of Molecular Diagnosis and treatment of Liver Cancer Tianjin First Center HospitalTianjin 300192China Department of Liver transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** to investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion tumor immune microenvironment Apoptosis

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Light tuning CO/H_(2)composition on Ag:Unraveling CO_(2)mass transfer and electron-phonon coupling in plasmon-enhanced electrocatalysis

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Nano Research 2025年第1期18卷 173-185页

作者： Rui Lin Dong Fan Luca MBerger thomas Possmayer Yu Zhou Jiexin Zhu Xingbao Chen wen Luo Lars Allmendinger Andreas tittl Leonardo de Souza Menezes Guillaume Maurin Shihe Yang and Stefan AMaier Nanoinstitute Munich Faculty of PhysicsLudwig-Maximilians-Universität München80539 MunichGermany Institut Charles Gerhardt Montpellier UMR 5253 CNRS ENSCM UniversitéMontpellierPlace E.Bataillon34090 MontpellierFrance Guangdong Provincial Key Lab of Nano-Micro Material Research School of Advanced MaterialsPeking University Shenzhen Graduate SchoolShenzhen 518055China State Key Laboratory of Advanced technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China Faculty of Chemistry and Pharmacy Ludwig-Maximilians-Universität München81377 MunichGermany Departamento de Física Universidade Federal de Pernambuco50670-901 Recife-PEBrazil School of Physics and Astronomy Monash University Clayton CampusMelbourneVictoria 3800Australia Department of Physics Imperial College LondonSW72AZ LondonUK

Plasmon-enhanced electrocatalysis(PEEC)is an emerging approach to mitigate CO_(2)*** mechanisms behind CO_(2)adsorption and reduction at the catalyst-electrolyte interface in PEEC still need to be further ***,we employ a well-defined Ag nanostructure to elucidate these pivotal *** shining light with wavelengths of 625,525,405 nm on Ag,an adjustable CO/H_(2)ratio from 35 to 1 can be *** reaction pathway changing under plasmonic excitation does not originate from the lowered CO_(2)mass transfer in the vicinity of Ag,as the electrochemical quartz crystal microbalance results unravel that a slightly elevated temperature in bulk electrolyte caused by light irradiation cannot weaken the CO_(2)adsorption at the Ag catalyst-electrolyte *** calculations reveal that optical excitation towards shorter wavelengths leads to a progressive lowered energy barrier for H_(2)formation together with an enhanced energy barrier for^(*)COOH *** thermodynamically suppressed,CO_(2)reduction can still be improved kinetically by optimizing the excitation wavelength and intensity,being accompanied with the enhanced *** absorption spectroscopy results further correlate the higher photocurrent with a prolonged electron-phonon coupling time,verifying that the improvement of CO_(2)reduction kinetics in PEEC can be realized by hot electron harnessing.

关键词： plasmonic catalysis photoelectrochemical CO_(2)reduction CO/H_(2)ratio hot electron generation electronphonon coupling thermal effect

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Decoding the evolution and transmissions of the novel pneumonia coronavirus(SARS-CoV-2/HCoV-19)using whole genomic data

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Zoological Research 2020年第3期41卷 247-257页

作者： wen-Bin Yu Guang-Da tang Li Zhang Richard t.Corlett Center for Integrative Conservation Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaYunnan 666303China Center of Conservation Biology Core Botanical GardensChinese Academy of SciencesMenglaYunnan 666303China Henry Fok College of Biology and Agriculture Shaoguan UniversityShaoguanGuangdong 512005China College of Forestry and Landscape Architecture South China Agricultural UniversityGuangzhouGuangdong 510642China Chinese Institute for Brain Research Beijing 102206China

the outbreak of COVID-19 started in mid-December2019 in Wuhan, China. Up to 29 February 2020,SARS-CoV-2(HCoV-19/2019-nCoV) had infected more than 85 000 people in the world. In this study,we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu tM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the *** constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. the date of population expansion was calculated based on the expansion parameter tau(τ)using the formula t=τ/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 *** non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. the 58 haplotypes(31 found in samples from China and 31 from outside China)were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome(bat-RatG13-CoV)as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes,and later H1 was derived from the intermediate haplotype H3. the population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore,phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.

关键词： COVID-19 HCoV-19 SARS-CoV-2 Novel pneumonia outbreak Human-to-human transmission Phyloepidemiology

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Extended Impact of Cold Air Invasions in East Asia in Response to a Warm South China Sea and Philippine Sea

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Advances in Atmospheric Sciences 2023年第3期40卷 531-540页

作者： Marco Y.-t.LEUNG Dongxiao WANG wen ZHOU Yuntao JIAN School of Marine Sciences Sun Yat-Sen UniversityZhuhai 519082China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) Zhuhai 519000China Department of Atmospheric and Oceanic Sciences&Institute of Atmospheric Sciences Fudan UniversityShanghai 200438China Guy Carpenter Asia-Pacific Climate Impact Centre Center for Ocean Research in Hong Kong and Macao(CORE)School of Energy and EnvironmentCity University of Hong KongHong KongChina

During boreal winter,the invasion of cold air can lead to remarkable temperature drops in East Asia which can result in serious socioeconomic ***,we find that the intensity of strong synoptic cold days in the East China Sea and Indochina Peninsula are *** enhanced synoptic cold days in these two regions are attributed to surface warming over the South China Sea and Philippine Sea(SCSPS).the oceanic forcing of the SCSPS on the synoptic cold days in the two regions is verified by numerical *** warming of the SCSPS enhances the baroclinicity,which intensifies meridional wind and cold advection on synoptic *** leads to a more extended region that is subject to the influence of cold invasion.

关键词： ocean warming extra-tropical cyclones baroclinicity temperature whiplash

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Comparative analyses of mitogenomes in the social bees with insights into evolution of long inverted repeats in the Meliponini

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Zoological Research 2024年第1期45卷 160-175页

作者： Yu-Ran Li Zheng-Wei Wang Richard t.Corlett.wen-Bin Yu Yunnan Key Laboratory for the Conservation of tropical Rainforests and Asian Elephants&Center for Integrative Conservation Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaYunnan 666303China CAS Key Laboratory of tropical Forest Ecology Xishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglaYunnan 666303China Southeast Asia Biodiversity Research Institute Chinese Academy of SciencesMenglaYunnan 666303China University of Chinese Academy of Sciences Shijingshan DistrictBeijing 100049China

the insect mitogenome is typically a compact circular molecule with highly conserved gene ***,mitogenome structural variations have been reported in specific taxa,and gene rearrangements,usually the tRNAs,occur in different *** synapomorphies of mitogenome organizations can provide information for phylogenetic inferences,comparative analyses of mitogenomes have been given increasing ***,most studies use a very few species to represent the whole genus,tribe,family,or even order,overlooking potential variations at lower taxonomic levels,which might lead to some incorrect *** provide new insights into mitogenome organizations and their implications for phylogenetic inference,this study conducted comparative analyses for mitogenomes of three social bee tribes(Meliponini,Bombini,and Apini)based on the phylogenetic framework with denser taxonomic sampling at the species and population *** analyses revealed that mitogenomes of Apini and Bombini are the typical type,while those of Meliponini show diverse variations in mitogenome sizes and *** inverted repeats(IRs)cause significant gene rearrangements of protein coding genes(PCGs)and rRNAs in Indo-Malay/Australian stingless bee *** evolution analyses showed that the lineage with IRs have lower dN/dS ratios for PCGs than lineages without IRs,indicating potential effects of IRs on the evolution of mitochondrial *** finding of IRs and different patterns of gene rearrangements suggested that Meliponini is a hotspot in mitogenome *** conserved PCGs and rRNAs whose rearrangements were found only in the mentioned lineages within Meliponini,tRNA rearrangements are common across all three tribes of social bees,and are significant even at the species level,indicating that comprehensive sampling is needed to fully understand the patterns of tRNA rearrangements,and their implications for phylogenetic inference.

关键词： Social bees Phylogeny Mitogenome structure Gene rearrangement Inverted repeats

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国际学校高中生抑郁情绪与人际关系能力和跨文化敏觉力的关系

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中国心理卫生杂志 2025年第1期39卷 57-62页

作者：何嘉殷文汉宜张瑞彬南方医科大学公共卫生学院心理学系认知控制与脑健康实验室广州510515 广东省中医院心理睡眠科广州510120 南方医科大学珠江医院精神心理科广州510282

目的:探讨国际学校高中生在微观跨文化环境中的抑郁情绪,并检验抑郁情绪与人际关系能力和跨文化敏觉力的关系。方法:选取某国际学校10年级学生94人,在其高中阶段共3年6个学期(标记为t1~t6)使用抑郁自评量表(SDS) 6次(t1~t6)测量其抑郁程... 详细信息

目的:探讨国际学校高中生在微观跨文化环境中的抑郁情绪,并检验抑郁情绪与人际关系能力和跨文化敏觉力的关系。方法:选取某国际学校10年级学生94人,在其高中阶段共3年6个学期(标记为t1~t6)使用抑郁自评量表(SDS) 6次(t1~t6)测量其抑郁程度,使用人际关系能力问卷(ICQ)、跨文化敏觉力量表(ISS) 2次(t1、t5)测量其人际关系能力、跨文化敏觉力水平。结果:t1~t6阶段SDS得分呈现先增长后降低的模式(Pt1和t5的SDS与ICQ得分(r=-0.48、-0.47,均P t1的ICQ得分(β=-0.20,P=0.057)、ISS得分(β=-0.02,P=0.897)不能预测t5的SDS得分。ISS得分在ICQ与SDS得分间分别起横向(t1 95%CI:-0.41~-0.12;t5 95%CI:-0.53~-0.13)、纵向中介效应(95%CI:-0.42~-0.15)。结论:国际学校高中生人际关系能力和跨文化敏觉力对缓解其微观跨文化环境适应过程中的抑郁情绪有积极意义。

关键词：国际高中微观跨文化环境抑郁情绪人际关系能力跨文化敏觉力

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Second Chern crystals with inherently non-trivial topology

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National Science Review 2023年第8期10卷 148-155页

作者： Xiao-Dong Chen Fu-Long Shi Jian-Wei Liu Ke Shen Xin-tao He C.t. Chan wen-Jie Chen Jian-wen Dong School of Physics and State Key Laboratory of Optoelectronic Materials and technologies Sun Yat-sen University Department of Physics The Hong Kong University of Science and Technology

Chern insulators have been generalized to many classical wave systems and thereby lead to many potential applications such as robust waveguides, quantum computation and high-performance lasers. However, the band structure of a material can be either topologically trivial or non-trivial, depending on how the crystal structure is designed. Here, we propose a second Chern crystal in a four-dimensional parameter space by introducing two extra synthetic translation dimensions. Since the topology of the bulk bands in the synthetic translation space is intrinsically non-trivial, our proposed four-dimensional crystal is guaranteed to be topologically non-trivial regardless of the crystal’s detailed configuration. We derive the topologically protected modes on the lower dimensional boundaries of such a crystal via dimension ***, we observe the one-dimensional gapless dislocation modes and confirm their robustness in experiments. Our findings provide novel perspectives on topologically non-trivial crystals and may inspire designs of classical wave devices.

关键词： topological photonics synthetic dimension photonic crystals dislocation mode

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