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Modeling tuberous sclerosis complex with human induced pluripotent stem cells

World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing Wen Department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in Molecular and Systems Pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA Department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA Department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and ***,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum *** in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling *** models have been widely used to study the effect of TSCl/2 genes on the development and function of the *** considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human *** sources Literature reviews and research articles were published in PubMed-indexed *** Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human *** In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

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Preclinical Assessment of Enhanced Chemodynamic Therapy by an FeMnOx-Based Nanocarrier: Tumor-Microenvironment-Mediated Fenton Reaction and ROS-Induced Chemotherapeutic for Boosted Antitumor Activity

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ACS Applied Materials and Interfaces 2023年第48期15卷 55258-55275页

作者： Dirersa, Worku Batu Kan, Tzu-Chun Getachew, Girum Wibrianto, Aswandi Ochirbat, Sonjid Rasal, Akash Chang, Jungshan Chang, Jia-Yaw Department of Chemical Engineering National Taiwan University of Science and Technology Taiwan Taipei106335 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan

In recent studies, iron-containing Fenton nanocatalysts have demonstrated significant promise for clinical use due to their effective antitumor activity and low cytotoxicity. A new approach was reported in this work utilizing cation exchange synthesis to fabricate FeMnOx nanoparticles (NPs) that boost Fenton reactions and responses to the tumor microenvironment (TME) for chemodynamic therapy (CDT) and chemotherapy (CT). Within the TME, the redox metal pair of Fe2+/Mn2+ helps break down endogenous hydrogen peroxide (H2O2) into very harmful hydroxyl radicals (•OH) while simultaneously deactivating glutathione (GSH) to boost CDT performance. To further enhance the therapeutic potential, FeMnOx NPs were encapsulated with thioketal-linked camptothecin (CPT-TK-COOH), a reactive oxygen species (ROS)-responsive prodrug, achieving a high CPT-loading capacity of up to 51.1%. Upon ROS generation through the Fenton reaction, the prodrug TK linkage was disrupted, releasing 80% of the CPT payload within 48 h. Notably, FeMnOx@CPT exhibited excellent dual-modal imaging capabilities, enabling magnetic resonance and fluorescence imaging for image-guided therapy. In vitro studies showed the cytocompatibility of FeMnOx NPs using MDA-Mb-231 and 4T1 cells, but in the presence of H2O2, they induced significant cytotoxicity, resulting in 80% cell death through CDT and CT effects. Upon intravenous administration, FeMnOx@CPT displayed remarkable tumor accumulation, which enhanced tumor suppression in xenografts through improved CDT and CT effects. Moreover, no significant adverse effects were observed in the FeMnOx NP-treated animals. In the current study, the FeMnOx@CPT anticancer platform, with its boosted •OH-producing capability and ROS-cleavable drug release, has been validated utilizing in vitro and animal studies, suggesting its capacity as a viable strategy for clinical trials. © 2023 American Chemical Society.

关键词： Chemotherapy

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MUC1 and MUC4 expression are inversely correlated and trigger immunological response and transport pathways in adult-type diffuse gliomas

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Computers in Biology and Medicine 2025年 187卷 109730-109730页

作者： Machado, Gabriel Cardoso Ferrer, Valéria Pereira Graduate Program in Pathological Anatomy Faculty of Medicine Rio de Janeiro Federal University Rio de Janeiro Brazil Laboratory of Cell and Molecular Biology of Tumors Department of Cell and Molecular Biology Biology Institute Fluminense Federal University Niterói Rio de Janeiro Brazil

Adult-type diffuse gliomas arise from glial or progenitor cells. These tumors are currently classified as astrocytoma isocitrate dehydrogenase (IDH)-mutant or IDH-mutant oligodendroglioma with co-deletion of chromosomal arms 1p and 19q, both of which could be either slow-growing tumors, or glioblastoma (GBM), which is a more aggressive tumor. Despite advances in diagnosis and treatment, the median survival time after GBM diagnosis remains low at approximately 15 months, with a 5-year overall survival (OS) rate of 6.8 %. Therefore, new biomarker and therapeutic target discoveries are required to improve prognosis. Mucin 1 (MUC1) and MUC4 are membrane-bound mucins and potential biomarkers of several tumors. However, the role of these mucins in adult gliomas has not been well explored. In this retrospective study, in silico analysis of data from patients with adult-type diffuse glioma revealed differential methylation and expression patterns of MUC1 and MUC4 between GBM and non-GBM groups. In the GBM group, decreased methylation and elevated expression of MUC1 were observed (r = −0.25, p © 2025 Elsevier Ltd

关键词： Methylation

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Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis (vol 14, 3750, 2023)

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NATURE COMMUNICATIONS 2023年第1期14卷 1-16页

作者： Takada, Hitomi Sasagawa, Yohei Yoshimura, Mika Tanaka, Kaori Iwayama, Yoshimi Hayashi, Tetsutaro Isomura-Matoba, Ayako Nikaido, Itoshi Kurisaki, Akira Laboratory of Stem Cell Technologies Graduate School of Science and Technology Nara Institute of Science and Technology Takayama-cho Ikoma Nara Japan Laboratory for Bioinformatics Research RIKEN Center for Biosystems Dynamics Research Wako Saitama Japan Department of Functional Genome Informatics Biological Data Science Medical Research Institute Tokyo Medical and Dental University Bunkyo Tokyo Japan Master’s/Doctoral Program in Life Science Innovation (Bioinformatics) Degree Programs in Systems and Information Engineering Graduate School of Science and Technology University of Tsukuba Tsukuba Ibaraki Japan

Defects in gastric progenitor cell differentiation are associated with various gastric disorders, including atrophic gastritis, intestinal metaplasia, and gastric cancer. However, the mechanisms underlying the multilineage differentiation of gastric progenitor cells during healthy homeostasis remain poorly understood. Here, using a single-cell RNA sequencing method, Quartz-Seq2, we analyzed the gene expression dynamics of progenitor cell differentiation toward pit cell, neck cell, and parietal cell lineages in healthy adult mouse corpus tissues. Enrichment analysis of pseudotime-dependent genes and a gastric organoid assay revealed that EGFR-ERK signaling promotes pit cell differentiation, whereas NF-κB signaling maintains gastric progenitor cells in an undifferentiated state. In addition, pharmacological inhibition of EGFR in vivo resulted in a decreased number of pit cells. Although activation of EGFR signaling in gastric progenitor cells has been suggested as one of the major inducers of gastric cancers, our findings unexpectedly identified that EGFR signaling exerts a differentiation-promoting function, not a mitogenic function, in normal gastric homeostasis.

关键词： Adult stem cells Stem-cell differentiation Stem-cell niche

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A BAND GROUPING BASED APPROACH FOR PHENOTYPE-CLASS MAPPING OF TREE GENOTYPES USING SPECTRO-TEMPORAL INFORMATION IN HYPERSPECTRAL TIME-SERIES UAV DATA

A BAND GROUPING BASED APPROACH FOR PHENOTYPE-CLASS MAPPING O...

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2021 IEEE International Geoscience and Remote Sensing Symposium, IGARSS 2021

作者： Harikumar, Aravind Wang, Siyu Ensminger, Ingo Department of Biology University of Toronto Canada Graduate Program in Ecology and Evolutionary Biology University of Toronto Canada Graduate Programs in Cell and Systems Biology University of Toronto Canada

Modern genomic tree breeding studies and forest health monitoring programs demand accurate mapping of tree phenotype. However, conventional field-based approaches to map phenotype are costly in terms of time and money. The recent phenomenal advances in the low-flying Unmanned Airborne Vehicle (UAV) remote sensing platforms together with the availability of high-resolution hyperspectral cameras allow to periodically capture a huge amount of crown spectral details of individual trees. These details can be exploited to map phenotypic class of tree genotypes. State-of-the-art methods that maps tree phenotype often underexploit the information in hyperspectral time-series data by using only a few specific band-based remote sensing (RS) indices to model phenological tree parameters that define the phenotypic response. Thus, we propose a wavelet-based approach to map tree phenotype of trees that a) maximally exploits the spectral and temporal information in band-groups by addressing data redundancy problem, and b) uses spectro-temporal/phenological information in the hyperspectral time-series data to map phenotype class of tree genotype. The improved performance of the proposed method over a RS index-based state-of-the-art one to map trees to a phenotypic class, on a set of 100 trees from 10 genotypes, proves the method to be performing. © 2021 IEEE.

关键词： Remote sensing

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Online Multi-spectral Neuron Tracing

arXiv

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arXiv 2024年

作者： Duan, Bin Shang, Yuzhang Cai, Dawen Yan, Yan Department of Computer Science Illinois Institute of Technology United States Neuroscience Graduate Program University of Michigan United States Cell and Developmental Biology Michigan Medicine United States

In this paper, we propose an online multi-spectral neuron tracing method with uniquely designed modules, where no offline training are required. Our method is trained online to update our enhanced discriminative correlation filter to conglutinate the tracing process. This distinctive offline-training-free schema differentiates us from other training-dependent tracing approaches like deep learning methods since no annotation is needed for our method. Besides, compared to other tracing methods requiring complicated set-up such as for clustering and graph multi-cut, our approach is much easier to be applied to new images. In fact, it only needs a starting bounding box of the tracing neuron, significantly reducing users’ configuration effort. Our extensive experiments show that our training-free and easy-configured methodology allows fast and accurate neuron reconstructions in multi-spectral images. © 2024, CC BY-NC-ND.

关键词： Neurons

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The association between urinary tract infections and diet: a literature review

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Discover Medicine 2025年第1期2卷 1-17页

作者： Çelik, Haluk Kozan, Esra Caf, Balım Bengisu Çebi, Gizem Koç, Murat Vivosens Inc. San Francisco USA Program of Stem Cell and Tissue Engineering Institute of Graduate Education Istinye University Istanbul Türkiye Department of Health Informatics University of Health Science Hamidiye Institute of Health Sciences Istanbul Türkiye

Urinary tract infections (UTIs) are a significant global health concern, affecting millions worldwide, with particular prevalence among specific vulnerable populations. Women of sexually active age, post-menopausal women, pregnant women, individuals with diabetes, catheterized patients, childs and older indivisuals face heightened risk due to various physiological, hormonal, and anatomical factors. While anatomical abnormalities and behavioral factors contribute to UTI susceptibility, the growing challenge of antibiotic resistance has necessitated exploration of alternative treatment approaches. Non-antibiotic interventions, including probiotics, cranberry products, and natural remedies, are gaining attention for their potential role in UTI prevention and management. Recent studies suggest the efficacy of probiotics and plant extracts in promoting urinary tract health and preventing bacterial colonization. Additionally, research highlights the importance of dietary factors, such as vitamin D and probiotic intake, in reducing UTI susceptibility. This review examines the emerging shift toward non-drug strategies, offering a more comprehensive approach to UTI management while addressing the pressing concern of antibiotic resistance.

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Original article – Effect of different resistance training intensities on endothelial function in people with type 2 diabetes mellitus: A systematic review

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Diabetes Research and Clinical Practice 2023年第1期200卷 110676-110676页

作者： Borges Madureira Sabino, Thiago Maria Martins Vancea, Denise da Cunha Costa, Manoel José Perrier de Melo, Raphael Vilela Dantas, Iago Nicolas dos Santos Ribeiro, Jonathan Federal University of Pernambuco Graduate Program in Physical Education Recife Brazil University of Pernambuco High School Physical Education Recife Brazil University of Pernambuco Graduate Program in Applied Cell and Molecular Biology Recife Brazil

Aims: The objective of this systematic review was to analyze the effects of different resistance training (RT) intensities compared with group control (GC) or control conditions (CON) on endothelial function (EF) in people with type 2 diabetes mellitus (T2DM). Methods: Seven electronic databases were searched Pubmed, Embase, Cochrane, Web of Science, Scopus, PEDro and CINAHL) until February 2021. Results: This systematic review retrieved a total of 2,991 studies of which 29 articles fulfilled the eligibility criteria. Four studies were included in the systematic review compared RT intervention with GC or CON. One study demonstrated an increase in blood flow-mediated dilation (FMD) of the brachial artery immediately after (95% CI: 3.0% to 5.9%;p < 0.05), 60 min after (95% CI: 0.8 % to 4.2%;p < 0.05) and 120 min after (95%CI: 0.7% to 3.1%;p < 0.05) a single high-intensity resistance training session (RPE ∼ 5 “hard”), compared to the control condition. Nevertheless, this increase was not significantly demonstrated in three longitudinal studies (more than 8 weeks). Conclusions: This systematic review suggest that a single session of high-intensity resistance training improves the EF of people with T2DM. More studies are needed to establish the ideal intensity and effectiveness for this training method. © 2023 Elsevier B.V.

关键词： Cardiovascular diseases Diabetes mellitus Endothelium Resistance training

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U1 snRNP regulates alternative promoter activity by inhibiting premature polyadenylation

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Molecular cell 2025年第10期85卷 1968-1981.e7页

作者： Kim, GyeungYun Carroll, Christine L. Wakefield, Zachary Peters Tuncay, Mustafa Fiszbein, Ana Biology Department Boston University Boston 02215 United States Graduate Program in Molecular Biology Cell Biology & Biochemistry Boston University Boston 02215 United States Graduate Program in Cell and Molecular Biology Boston University Boston 02215 United States Bioinformatics Program Faculty of Computing and Data Science Boston University Boston 02215 United States Center for Computing & Data Sciences Boston University Boston 02215 United States

Emerging evidence indicates that splicing factors mediate the close link between transcription and splicing. However, the mechanisms underlying this coupling remain unclear. U1 small nuclear ribonucleoprotein particle (U1 snRNP) not only initiates splicing but also plays a crucial role in preventing premature cleavage and polyadenylation, facilitating long-distance transcriptional elongation. Here, we show that U1 snRNP regulates alternative promoter activity in human cells by inhibiting premature polyadenylation. In genes carrying premature polyadenylation sites between two promoters, U1 snRNP inhibition with antisense oligonucleotides leads to a significant decrease in downstream promoter activity. Conversely, restoring U1 snRNP activity or inhibiting premature polyadenylation rescues downstream promoter activity. Mechanistically, U1 snRNP inhibition correlates with reduced chromatin accessibility, decreased RNA polymerase II serine 5 phosphorylation, and increased promoter-proximal pause at downstream promoters. Our findings support a model in which U1 snRNP favors productive elongation from upstream promoters, triggering downstream promoter activation by destabilizing nucleosomes and promoting promoter escape. © 2025 The Author(s)

关键词： alternative promoters dowsntream promoters promoter-proximal pause splicing factors splicing transcription transcription cooperativity transcription initiation transcription interfierence transcription start sites U1 snRNP

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Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state

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细胞研究（英文版） 2023年第9期33卷 712-726页

作者： Peng Wang Xupeng Liu Ziyue Yao Yu Chen Lanfang Luo Kun Liang Jun-Hao Elwin Tan Min-Wen Jason Chua Yan-Jiang Benjamin Chua Shilin Ma Liping Zhang Wenwu Ma Shuqing Liu Wenhua Cao Luyao Guo Lu Guang Yuefan Wang He Zhao Na Ai Yun Li Chunwei Li Ruiqi Rachel Wang Bin Tean Teh Lan Jiang Kang Yu Ng Shyh Chang Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina NUS Graduate School for Integrative Sciences and Engineering National University of SingaporeSingaporeSIngapore institute of Molecular and Cell Biology Genome Institute of SingaporeAgency for Science Technology and ResearchSingaporeSingapore Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore University of Chinese Academy of Sciences BeijingChina CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina Department of Clinical Nutrition Peking Union Medical College HospitalChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina Institute of Zoology Chinese Academy of SciencesBeijingChina Beijing.Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationChinese Academy of SciencesBeijingChina Laboratory of Cancer Therapeutics Program in Cancer and Stem Cell BiologyDuke-National University of Singapore Medical SchoolSingaporeSingapore Laboratory of Cancer Epigenome Division of Medical ScienceNational Cancer Centre SingaporeSingaporeSingapore CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina

During homeostasis and after injury,adult muscle stem cells(MuSCs)activate to mediate muscle ***,much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and ***,we show that Lin28a is expressed in embryonic limb bud muscle progenitors,and that a rare reserve subset of Lin28a+Pax7-skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+MuSC pool to drive muscle *** with adult Pax7+MuSCs,Lin28a+MuSCs displayed enhanced myogenic potency in vitro and in vivo upon *** epigenome of adult Lin28a+MuSCs showed resemblance to embryonic muscle *** addition,RNA-sequencing revealed that Lin28a+MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors,telomerase components and the p53 inhibitor Mdm4,and lower levels of myogenic differentiation markers compared to adult Pax7+MuSCs,resulting in enhanced self-renewal and stress-response ***,conditional ablation and induction of Lin28a+MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle ***,our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

关键词： Muscle stem cells Regeneration

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