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Transcriptomic analyses of localized prostate cancers of East Asian and North American men reveal race-specific luminal-basal and microenvironmental differences

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cancer communications 2023年第10期43卷 1164-1168页

作者： Melvin L.K.chua Alexander K.Hakansson Enya H.W.Ong Boon Hao Hong Jing Jing Miao Adelene Y.L.sim Janice s.H.tan Kah Min tan Gabrielle c.J.Lee Kar Perng Low Jeffrey K.L.Tuan Terence W.K.tan michael L.c.Wang Joe P.s.Yeong michael c.s.tan Lui shiong Lee Ravindran Kanesvaran Xin Zhao Julian Ho Daniel E.spratt Edward M.schaeffer Kae-Jack Tay Yang Liu Elai Davicioni Li Yan Khor Division of Radiation Oncology National Cancer Centre SingaporeSingaporeSingapore Duke-NUs Medical school SingaporeSingapore Division of Medical sciences National Cancer Centre SingaporeSingaporeSingapore Veracyte IncSan DiegoCAUSA Department of Nasopharyngeal carcinoma State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China Faculty of Medicine Nursing and Health SciencesMonash UniversityVictoriaAustralia Department of Anatomical Pathology Singapore General HospitalSingaporeSingapore Department of Pathology Changi General HospitalSingaporeSingapore Department of Urology Sengkang General HospitalSingaporeSingapore Division of Medical Oncology National Cancer Centre SingaporeSingaporeSingapore Department of Radiation Oncology University Hospitals Seidman Cancer CenterCase Comprehensive Cancer CenterClevelandOHUSA Department of Urology Northwestern University Feinberg School of MedicineChicagoILUSA Department of Urology Singapore General HospitalSingaporeSingapore

Dear editor,Prostate cancer(Pca)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the National comprehensive cancer Network(NccN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].several studies have since characterized the molecular landscape of localized Pca in White[4,5]and Black/African-American men[6],but data is lacking in Asian *** chinese Prostate cancer Genome and Epigenome Atlas(cPGEA)reported on the genomic and epigenomic landscape of 208 Pca of men from china[7].comparative analyses between the cPGEA cohort and data from The cancer Genome Atlas(TcGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(cHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRss2-ERG)fusion in chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of Pca.

关键词： landscape Atlas editor

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Emerging structures and dynamic mechanisms ofγ-secretase for Alzheimer’s disease

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Neural Regeneration Research 2025年第1期20卷 174-180页

作者： Yinglong Miao michael s.Wolfe computational Medicine Program and Department of Pharmacology University of North Carolina–Chapel HillChapel HillNCUSA Department of Medicinal chemistry University of KansasLawrenceKSUSA

γ-secretase,called“the proteasome of the membrane,”is a membrane-embedded protease complex that cleaves 150+peptide substrates with central roles in biology and medicine,including amyloid precursor protein and the Notch family of cell-surface *** inγ-secretase and amyloid precursor protein lead to early-onset familial Alzheimer’s disease.γ-secretase has thus served as a critical drug target for treating familial Alzheimer’s disease and the more common late-onset Alzheimer’s disease as ***,critical gaps remain in understanding the mechanisms of processive proteolysis of substrates,the effects of familial Alzheimer’s disease mutations,and allosteric modulation of substrate cleavage byγ-*** this review,we focus on recent studies of structural dynamic mechanisms ofγ-*** mechanisms,including the“Fit-stay-Trim,”“sliding-Unwinding,”and“Tilting-Unwinding,”have been proposed for substrate proteolysis of amyloid precursor protein byγ-secretase based on all-atom molecular dynamics *** an incorrect registry of the Notch1 substrate was identified in the cryo-electron microscopy structure of Notch1-boundγ-secretase,molecular dynamics simulations on a resolved model of Notch1-boundγ-secretase that was reconstructed using the amyloid precursor protein-boundγ-secretase as a template successfully capturedγ-secretase activation for proper cleavages of both wildtype and mutant Notch,being consistent with biochemical experimental *** approach could be potentially applied to decipher the processing mechanisms of various substrates byγ-*** addition,controversy over the effects of familial Alzheimer’s disease mutations,particularly the issue of whether they stabilize or destabilizeγ-secretase-substrate complexes,is ***,an outlook is provided for future studies ofγ-secretase,including pathways of substrate binding and product release,effects of modulators on familial Alzheimer’s disease mutations

关键词： Alzheimer’s disease amyloid precursor protein cryo-EM structures drug design intramembrane proteolysis molecular dynamics Notch

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NEcAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.schafer sudena Wang michael J.schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NEcAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized c-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NEcAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NEcAB2 interacts with predominantly striatal G-protein-coupled receptors, while NEcAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NEcAB proteins exhibit distinct subcellular localizations: NEcAB1 is found in the nucleus and cytosol, NEcAB2 resides in endosomes and the plasma membrane, and NEcAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NEcAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NEcAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： shan Ping Yu Emily choi michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the ca^(2+)hypothesis of Alzheimer's disease and recent advances,this ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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scalable Ir‑Doped NiFe_(2)O_(4)/TiO_(2)Heterojunction Anode for Decentralized saline Wastewater Treatment and H_(2)Production

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Nano-Micro Letters 2025年第3期17卷 1-18页

作者： sukhwa Hong Jiseon Kim Jaebeom Park sunmi Im michael R.Hoffmann Kangwoo cho Division of Environmental science and Engineering Pohang University of Science and Technology(POSTECH)Pohang 790−784Korea Linde Laboratory California Institute of TechnologyPasadenaCA 91125USA Institute for convergence Research and Education in Advanced Technology(I‑cREATE) Yonsei University International CampusIncheon 21983Republic of Korea

Wastewater electrolysis cells(WEcs)for decentralized wastewater treatment/reuse coupled with H_(2)production can reduce the carbon footprint associated with transportation of water,waste,and energy *** study reports Ir-doped NiFe_(2)O_(4)(NFI,~5 at%Ir)spinel layer with TiO_(2)overlayer(NFI/TiO_(2)),as a scalable heterojunction anode for direct electrolysis of wastewater with circumneutral pH in a single-compartment *** dilute(0.1 M)Nacl solutions,the NFI/TiO_(2)marks superior activity and selectivity for chlorine evolution reaction,outperforming the benchmark IrO_(2).Robust operation in near-neutral pH was *** including operando X-ray absorption spectroscopy unveiled crucial roles of TiO_(2) which serves both as the primary site for cl−chemisorption and a protective layer for NFI as an ohmic *** electrolysis of NH4+-laden synthetic wastewater demonstrated that NFI/TiO_(2)not only achieves quasi-stoichiometric NH_(4)^(+)-to-N_(2)conversion,but also enhances H_(2)generation efficiency with minimal competing reactions such as reduction of dissolved oxygen and reactive *** scaled-up WEc with NFI/TiO_(2)was demonstrated for electrolysis of toilet wastewater.

关键词： Wastewater electrolysis cell Ir-doped NiFe_(2)O_(4) Reactive chlorine species Decentralized H_(2)production On-site wastewater treatment

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A systematic review of progenitor survival and maturation in Parkinsonian models

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Neural Regeneration Research 2025年第11期20卷 3172-3178页

作者： Giulia comini Eilís Dowd Pharmacology&Therapeutics and Galway Neuroscience center University of GalwayGalwayIreland

stem cell-based brain repair is a promising emergent therapy for Parkinson's disease based on years of foundational research using human fetal donors as a cell *** current therapeutic options for patients,this approach has the potential to provide longterm stem cell–derived reconstruction and restoration of the dopaminergic input to denervated regions of the brain allowing for restoration of certain functions to *** ultimate clinical success of stem cell–derived brain repair will depend on both the safety and efficacy of the approach and the latter is dependent on the ability of the transplanted cells to survive and differentiate into functional dopaminergic neurons in the Parkinsonian *** the pre-clinical literature suggests that there is considerable variability in survival and differentiation between studies,the aim of this systematic review was to assess these parameters in human stem cell-derived dopaminergic progenitor transplant studies in animal models of Parkinson's disease.A defined systematic search of the PubMed database was completed to identify relevant studies published up to March *** screening,76 articles were included in the analysis from which 178 separate transplant studies were *** these,graft survival could be assessed in 52 studies and differentiation in 129 ***,we found that graft survival ranged fromcells transplanted,with a median of 51%of transplanted cells surviving in the brain;while dopaminergic differentiation of the cells ranged from 0% to 46% of cells transplanted with a median of 3%.This systematic review suggests that there is considerable scope for improvement in the differentiation of stem cell-derived dopaminergic progenitors to maximize the therapeutic potential of this approach for patients.

关键词： cell replacement therapy differentiation embryonic stem cells graft induced pluripotent stem cells Parkinson's disease survival transplant

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New Generations: sequencing Machines and Their computational challenges

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Journal of computer science & Technology 2010年第1期25卷 3-9页

作者： David c. schwartz michael s. Waterman Laboratory for Molecular and computational Genomics Departme4nt of Chemistry and Laboratory of Genetics University of Wisconsin-Madison Department of Biological sciences University of Southern California Department of Automation Tsinghua University

New generation sequencing systems are changing how molecular biology is practiced. The widely promoted $1000 genome will be a reality with attendant changes for healthcare, including personalized medicine. More broadly the genomes of many new organisms with large samplings from populations will be commonplace. What is less appreciated is the explosive demands on computation, both for cPU cycles and storage as well as the need for new computational methods. In this article we will survey some of these developments and demands.

关键词： genome sequencing new generation sequencing read mapping optical mapping sequence assembly Eulerian graphs

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Deepening collaboration china and Africa need to further align development strategies to realise the immense potential of economic cooperation

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chinAfrica 2025年第1期17卷 24-26页

作者： EHIZUELEN michael MITcHELL OMORUYI centre for Nigerian studies Institute of African StudiesZhejiang Normal University

Humming factories,bustling ports,and shuttling merchants highlight the vibrancy of china-Africa economic and trade *** the years,this partnership has grown significantly,optimising trade structures and fostering mutual *** deepening collaboration is evident in china’s role as Africa’s largest bilateral trading partner for 15 consecutive *** the first seven months of 2024,trade between china and African countries reached$167 billion,reflecting a 5.5-percent increase compared to the same period in *** to the International Monetary Fund,approximately 20 percent of Africa’s exports now go to china,while 16 percent of its imports originate there.

关键词： trading deepening Africa

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Unveiling an ancient whole-genome duplication event in stentor,the model unicellular eukaryotes

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science china Life sciences 2025年

作者： Weibo Zheng chao Li Zhaorui Zhou Xiao chen michael Lynch Ying Yan school of Life sciences Ludong University Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity Ocean University of China Biodesign center for Mechanisms of Evolution Arizona State University Marine college Shandong University

Whole-genome duplication(WGD) events are widespread across eukaryotes and have played a significant role in moulding the genetic architectures of diverse organisms. In the present study, the newly sequenced genome of a giant ciliated protist, stentor roeselii, provides an opportunity for the analysis of the collinearity and retention of reciprocal best-hit genes between two stentor species. As a main result, we have unveiled a previously undetected ancient WGD event shaping the genome of its congener, stentor coeruleus, a model protist used in cytological and evolutionary studies. Genomes of two congeners, s. coeruleus and s. roeselii, are compared and analyzed, revealing that:(i)the former exhibits a much higher retention rate of colinear-gene pairs(28%) than does s. roeselii, and in s. coeruleus, 75% of genes that have a RBH hit in s. roeselii, have paralogs with high amino-acid identity, consistent with a WGD event in the lineage leading to s. coeruleus;(ii) the s. roeselii genome possesses extremely short intergenic regions, implying that the lengths of intergenic regions are under strong selection;(iii) the unique characteristics of introns may have been shaped in the common ancestor of heterotrichs;(iv) gene families that play a role in activities of multiple protein kinases and voltage-gated ion channels expanded rapidly in the ancestor of both taxa, possibly relating to the remarkable regenerative ability in stentor. This study offers new insights into the evolutionary dynamics of ciliate genomes,with implications for understanding of the processes underlying the evolution of genomic complexity.

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skeletal muscle-specific Bambi deletion induces hypertrophy and oxidative switching coupling with adipocyte thermogenesis against metabolic disorders

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science china Life sciences 2025年

作者： Xiangping Yao Xudong Mai Ye Tian Yifan Liu Guanghui Jin Ze Li shujie chen Xiaoshuang Dai Liujing Huang Zijing Fan Guihua Pan Xiaohan Pan Xiangmin Li michael c Yu Jia sun Jingxing Ou Hong chen Liwei Xie college of Life and Health sciences Guangdong Industry Polytechnic Department of Endocrinology and Metabolism Zhujiang Hospital Southern Medical University state Key Laboratory of Applied Microbiology southern china Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application Guangdong Open Laboratory of Applied MicrobiologyInstitute of Microbiology Guangdong Academy of Sciences Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics School of Medical Technology Guangdong Medical University Department of Hepatic surgery and Liver transplantation center of the Third Affiliated Hospital Organ Transplantation Institute Sun Yat-sen University Organ Transplantation Research Center of Guangdong ProvinceGuangdong province engineering laboratory for transplantation medicine Guangdong Provincial Key Laboratory of Liver Disease Research school of Public Health Xinxiang Medical University BGI Institute of Applied Agriculture BGI-Shenzhen Department of Applied Biology and chemical Technology The Hong Kong Polytechnic University Department of Biological sciences State University of New York at Buffalo Department of Internal Medicine Shunde Women and Children's Hospital (Maternity and Child Healthcare Hospital of Shunde Foshan) Guangdong Medical University

skeletal muscle plays a significant role in both local and systemic energy metabolism. The current investigation aims to explore the role of the Bambi gene in skeletal muscle, focusing on its implications for muscle hypertrophy and systemic metabolism. We hypothesize that skeletal muscle-specific deletion of Bambi induces muscle hypertrophy, improves metabolic performance, and activates thermogenic adipocytes via the reprogramming of progenitor of i WAT, offering potential therapeutic strategies for metabolic syndromes. Leveraging the chromatin immunoprecipitation(chIP)-seq and bioinformatics analysis, Bambi gene is shown to be a direct target of HIF2α, which is further confirmed by chIP-qPcR and promoter luciferase assay. skeletal muscle-specific Bambi deletion led to significant muscle hypertrophy and improved metabolic parameters, even under high-fat diet conditions. This deletion induced metabolic reprogramming of stromal vascular fractions(sVFs) into thermogenic adipocytes, contributing to systemic metabolic improvements, potentially through the secretory ***, mice with skeletal muscle-specific Bambi deletion demonstrate resistance to high-fat diet-induced metabolic disorders, highlighting a potential therapeutic pathway for metabolic syndrome management. Thus, skeletal muscle-specific deletion of Bambi triggers muscle growth, enhances metabolic performance, and activates thermogenic adipocytes. These findings suggest Bambi as a novel therapeutic target for metabolic syndromes, providing new insights into the interaction between muscle hypertrophy and systemic metabolic improvement. The study underscores the potential of manipulating muscle physiology to regulate whole-body metabolism, offering a novel perspective on treating metabolic disorders.

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