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reprogramming naturally evolved switches for Streptomyces chassis development

TRENDS IN BIOTECHNOLOGY 2025年第1期43卷 12-15页

作者： Yan, Hao Li, Shanshan Wang, Weishan Chinese Acad Sci Inst Microbiol State Key Lab Microbial Resources Beijing 100101 Peoples R China Chinese Acad Agr Sci Inst Plant Protect State Key Lab Biol Plant Dis & Insect Pests Beijing 100193 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China

The Streptomyces chassis serves as an important platform for efficient biomanufacture of diverse secondary metabolite (SM) compounds, but the current chassis lacks compatibility for integration of these SM biosynthetic pathways reliably and consistently. This forum discusses harnessing naturally evolved multifaceted switches to reprogram the Streptomyces chassis for biomanufacturing applications.

关键词： Streptomyces chassis development secondary metabolite naturally evolved switch reprogramming

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reprogramming of updated neurostimulators in chronically implanted patients with Parkinson's disease: A double-blind randomized controlled trial

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BRAIN STIMULATION 2025年第1期18卷 138-140页

作者： Boogers, Alexandra Justich, Maria Belen Montiel, Marcela Alhashyan, Ibrahim Naghdlou, Sara Sumarac, Srdjan Milosevic, Luka Lozano, Andres M. Kalia, Suneil K. Munhoz, Renato P. Fasano, Alfonso Univ Toronto Edmond J Safra Program Parkinsons Dis Toronto ON Canada Univ Toronto Toronto Western Hosp Morton & Gloria Shulman Movement Disorders Ctr UHN Toronto ON Canada Univ Toronto Div Neurol Toronto ON Canada Krembil Brain Inst Toronto ON Canada Ctr Adv Neurotechnol Innovat Applicat CRANIA Toronto ON Canada Toronto Western Hosp Dept Neurosurg Toronto ON Canada Humanitas Univ Dept Biomed Sci Via Rita Levi Montalcini 4 I-20090 Pieve Emanuele Milan Italy IRCCS Humanitas Res Hosp Via Manzoni 56 I-20089 Rozzano Milan Italy

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reprogramming

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2017年

reprogramming by Central Intelligence Agency; published by

关键词： central intelligence agency cia crest general cia records memo reprogramming rippub

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Investigating Müller glia reprogramming in mice: a retrospective of the last decade, and a look to the future

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Neural Regeneration Research 2025年第4期20卷 946-959页

作者： Zhiyuan Yin Jiahui Kang Xuan Cheng Hui Gao Shujia Huo Haiwei Xu Key Lab of Visual Damage and Regeneration&Restoration of Chongqing Southwest Eye HospitalSouthwest HospitalThird Military Medical University(Army Medical University)ChongqingChina

Müller glia,as prominent glial cells within the retina,plays a significant role in maintaining retinal homeostasis in both healthy and diseased *** lower vertebrates like zebrafish,these cells assume responsibility for spontaneous retinal regeneration,wherein endogenous Müller glia undergo proliferation,transform into Müller glia-derived progenitor cells,and subsequently regenerate the entire retina with restored ***,Müller glia in the mouse and human retina exhibit limited neural reprogramming.Müller glia reprogramming is thus a promising strategy for treating neurodegenerative ocular disorders.Müller glia reprogramming in mice has been accomplished with remarkable success,through various *** in molecular,genetic,epigenetic,morphological,and physiological evaluations have made it easier to document and investigate the Müller glia programming process in ***,there remain issues that hinder improving reprogramming efficiency and ***,understanding the reprogramming mechanism is crucial toward exploring factors that will improve Müller glia reprogramming efficiency,and for developing novel Müller glia reprogramming *** review describes recent progress in relatively successful Müller glia reprogramming *** also provides a basis for developing new Müller glia reprogramming strategies in mice,including epigenetic remodeling,metabolic modulation,immune regulation,chemical small-molecules regulation,extracellular matrix remodeling,and cell-cell fusion,to achieve Müller glia reprogramming in mice.

关键词： cell fusion chemical small-molecules epigenetic extracellular matrix immune metabolic mice Müller glia neurodegenerative diseases reprogramming retina regeneration

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Spontaneously Immortalised Nonhuman Primate Müller Glia Cell Lines as Source to Explore Retinal reprogramming Mechanisms for Cell Therapies

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JOURNAL OF CELLULAR PHYSIOLOGY 2025年第1期240卷 e31482页

作者： Salman, Ahmed Amoros, Arantxa Bolinches Storm, Tina Moralli, Daniela Bryika, Paulina Russell, Angela J. Davies, Stephen G. Barnard, Alun R. Maclaren, Robert E. Univ Oxford Nuffield Dept Clin Neurosci Oxford Oxon England Univ Oxford Welcome Ctr Human Genet Oxford Oxon England Univ Oxford Dept Chem Oxford Oxon England Univ Oxford Dept Pharmacol Oxford Oxon England Oxford Eye Hosp Oxford Oxon England

Cell replacement therapies for ocular diseases characterised by photoreceptors degeneration are challenging due to poor primary cell survival in culture. A stable retinal cell source to replace lost photoreceptors holds promise. M & uuml;ller glia cells play a pivotal role in retinal homoeostasis by providing metabolic and structural support to retinal neurons, preventing aberrant photoreceptors migration, and facilitating safe glutamate uptake. In fish and amphibians, injured retinas regenerate due to M & uuml;ller-like glial stem cells, a phenomenon absent in the mammalian retina for unknown reasons. Research on M & uuml;ller cells has been complex due to difficulties in obtaining pure cell population and their rapid de-differentiation in culture. While various M & uuml;ller glia cell lines from human and rats are described, no nonhuman primate M & uuml;ller glia cell line is currently available. Here, we report spontaneously immortalised M & uuml;ller glia cell lines derived from macaque neural retinas that respond to growth factors and expand indefinitely in culture. They exhibit M & uuml;ller cells morphology, such as an elongated shape and cytoplasmic projections, express M & uuml;ller glia markers (VIMENTIN, GLUTAMINE SYNTHASE, glutamate-aspartate transporter, and CD44), and express stem cell markers such as PAX6 and SOX2. In the presence of factors that induce photoreceptor differentiation, these cells show a shift in gene expression patterns suggesting a state of de-differentiation, a phenomenon known in reprogrammed mammalian M & uuml;ller cells. The concept of self-renewing retina might seem unfeasible, but not unprecedented. While vertebrate M & uuml;ller glia have a regeneration potential absent in mammals, understanding the mechanisms behind reprogramming of M & uuml;ller glia in mammals could unlock their potential for treating retinal degenerative diseases.

关键词： cellular therapy differentiation glia nonhuman primate model reprogramming retina self-renewal

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Targeted nanoparticle delivery system for tumor-associated macrophage reprogramming to enhance TNBC therapy

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CELL BIOLOGY AND TOXICOLOGY 2025年第1期41卷 1-32页

作者： Dong, Xiaoshen Wang, Xiaoou Zheng, Xinyu Jiang, Haiyang Liu, Lu Ma, Ningye Wang, Shuo China Med Univ Hosp 1 Dept Surg Oncol Breast Surg Gen Surg 155 North Nanjing St Shenyang 110001 Peoples R China China Med Univ Hosp 1 Dept Geriatr Cardiovasc 155 North Nanjing St Shenyang 110001 Peoples R China China Med Univ Hosp 1 Canc Inst Lab 1 Shenyang Liaoning Peoples R China China Med Univ Shengjing Hosp Dept Obstet & Gynecol 36 Sanhao St Shenyang Liaoning Peoples R China

Triple-negative breast cancer (TNBC) poses as a daunting and intricate manifestation of breast cancer, highlighted by few treatment options and a poor outlook. The crucial element in fostering tumor growth and immune resistance is the polarization of tumor-associated macrophages (TAMs) into the M2 state within the tumor microenvironment (TME). To address this, we developed M2 targeting peptide-chitosan-curcumin nanoparticles (M2pep-Cs-Cur NPs), a targeted delivery system utilizing chitosan (Cs) as a carrier, curcumin (Cur) as a therapeutic agent, and targeting peptides for specificity. These NPs effectively inhibited TNBC cell proliferation (similar to 70%) and invasion (similar to 70%), while increasing the responsiveness of tumors to anti-PD-L1 treatment (similar to 50% survival enhancement) in vitro and in vivo. Bioinformatics analysis suggested that Cur modulates TAM polarization by influencing key genes such as COX-2, offering insights into its underlying mechanisms. This study highlights the potential of M2pep-Cs-Cur NPs to reverse M2 polarization in TAMs, providing a promising targeted therapeutic strategy to overcome immunotherapy resistance and improve TNBC outcomes.

关键词： Triple-negative breast cancer Tumor-associated macrophages Curcumin Nanoparticles COX-2 reprogramming Immunotherapy resistance

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Interplay between pioneer transcription factors and epigenetic modifiers in cell reprogramming

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REGENERATIVE THERAPY 2025年 28卷 246-252页

作者： Mirizio, Gerardo Sampson, Samuel Iwafuchi, Makiko Cincinnati Childrens Hosp Med Ctr Ctr Stem Cell & Organoid Med Div Dev Biol Cincinnati OH 45229 USA Univ Cincinnati Coll Med Dept Pediat Cincinnati OH 45229 USA

The generation of induced pluripotent stem cells (iPSCs) from differentiated somatic cells by Yamanaka factors, including pioneer transcription factors (TFs), has greatly reshaped our traditional understanding of cell plasticity and demonstrated the remarkable potential of pioneer TFs. In addition to iPSC reprogramming, pioneer TFs are pivotal in direct reprogramming or transdifferentiation where somatic cells are converted into different cell types without passing through a pluripotent state. Pioneer TFs initiate a reprogramming process through chromatin opening, thereby establishing competence for new gene regulatory programs. The action of pioneer TFs is both influenced by and exerts influence on epigenetic regulation. Despite significant advances, many direct reprogramming processes remain inefficient, which limits their reliability for clinical applications. In this review, we discuss the molecular mechanisms underlying pioneer TF-driven reprogramming, with a focus on their interactions with epigenetic modifiers, including Polycomb repressive complexes (PRCs), nucleosome remodeling and deacetylase (NuRD) complexes, and the DNA methylation machinery. A deeper understanding of the dynamic interplay between pioneer TFs and epigenetic modifiers will be essential for advancing reprogramming technologies and unlocking their full clinical potential. (c) 2024 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine. This is an open access article under the CC BY-NC-ND license (http://***/ licenses/by-nc-nd/4.0/).

关键词： reprogramming Differentiation Pioneer transcription factor PRC NuRD DNA methylation

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Novel reprogramming of Polyketide Synthase for Valerolactam Production

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ACS SYNTHETIC BIOLOGY 2025年第3期14卷 833-841页

作者： Zong, Jikai Xiao, Kaixing Wang, Dan Kang, Yaqi Peng, Zhiyao Yu, Bo Chongqing Univ Sch Chem & Chem Engn Dept Chem Engn Chongqing 401331 Peoples R China Chinese Acad Sci Inst Microbiol CAS Key Lab Microbial Physiol & Metab Engn State Key Lab Mycol Beijing 100101 Peoples R China

delta-Valerolactam (VL), as an organic compound, is an important precursor chemical for nylon and has a wide range of applications in organic synthesis, pharmaceutical synthesis, polymer materials, and other fields. This study introduces a novel biosynthetic method for producing VL in the engineered strain Escherichia coli BL21 through the reprogramming of polyketide synthases (PKS). Initially, an in vitro multienzyme system was constructed to verify the reliability of the VL synthesis pathway. Subsequently, an optimized biosynthetic pathway was established in E. coli, converting l-aspartate to VL with a yield of 3.66 mg/L in a 250 mL shake flask. Various engineering strategies were then implemented to enhance VL production, including substrate-enzyme affinity modification and multidimensional substrate optimization. These methods resulted in a 3.7-fold increase in VL yield, reaching 13.5 mg/L in shake flask cultures. Further scale-up in a 5 L fed-batch fermenter achieved a VL concentration of 76.2 mg/L. This research provides innovative insights into the optimization of VL production pathways and industrial-scale production.

关键词： delta-valerolactam polyketidesynthases metabolic engineering reprogramming moleculardocking de novo biosynthesis

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Effect of in vivo reprogramming of astrocytes combined with exercise training on neurorepair in rats with spinal cord injury

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Animal Models and Experimental Medicine 2025年第4期8卷 595-605页

作者： Zuliyaer Talifu Xin Xu Huayong Du Zehui Li Xiaoxin Wang Chunjia Zhang Yunzhu Pan Han Ke Wubo Liu Feng Gao Degang Yang Yingli Jing Yan Yu Liangjie Du Jianjun Li School of Rehabilitation Capital Medical UniversityBeijingChina Department of Spinal and Neural Functional Reconstruction China Rehabilitation Research CenterBeijingChina Chinese Institute of Rehabilitation Science BeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Beijing Key Laboratory of Neural Injury and Rehabilitation BeijingChina School of Population Medicine and Public Health Chinese Academy of Medical Sciences/Peking Union Medical CollegeBeijingChina Department of Neurology Cheeloo College of MedicineShandong UniversityQilu Hospital of Shandong UniversityJinanChina School of Health and Life Sciences University of Health and Rehabilitation SciencesQingdaoChina

Background:The inability of damaged neurons to regenerate and of axons to estab-lish new functional connections leads to permanent functional deficits after spinal cord injury(SCI).Although astrocyte reprogramming holds promise for neurorepair in various disease models,it is not sufficient on its own to achieve significant functional ***:A rat SCI model was established using a spinal cord *** days postsurgery,adeno-associated virus were injected to overexpress the transcription factors NeuroD1 and Neurogenin-2(Ngn2)in the spinal *** rats were then trained to walk on a weight-supported treadmill for 4 weeks,starting 14 days after *** effects of these interventions on motor and sensory functions,as well as spinal cord tissue repair,were subsequently ***:The combination of NeuroD1 and Ngn2 overexpression with weight-supported exercise training significantly improved gait compared to either inter-vention *** group receiving the combined intervention exhibited enhanced sensitivity in sensory *** analysis revealed increased colocalization of astrocytes and microtubule-associated protein 2-positive neurons in the injury *** effects were more pronounced than those observed with spinal cord tissue repair ***,the combined intervention significantly reduced glial scarring and the size of the injury ***:Exercise intervention enhances the reprogramming effects of astrocytes and restores motor function,yielding better results than either intervention alone.

关键词： astrocyte exercise training functional recovery reprogramming spinal cord injury

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Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration

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DEVELOPMENTAL CELL 2025年第8期60卷 1153-1167.e6页

作者： Lee, Laura R. Guillotin, Bruno Rahni, Ramin Hutchison, Chanel Desvoyes, Benedicte Gutierrez, Crisanto Birnbaum, Kenneth D. NYU Ctr Genom & Syst Biol Dept Biol New York NY 10003 USA Ctr Biol Mol Severo Ochoa Madrid 28049 Spain

The plasticity of plant cells underlies their wide capacity to regenerate, with increasing evidence in plants and animals implicating cell-cycle dynamics in cellular reprogramming. To investigate the cell cycle during cellular reprogramming, we developed a comprehensive set of cell-cycle-phase markers in the Arabidopsis root. Using single-cell RNA sequencing profiles and live imaging during regeneration, we found that a subset of cells near an ablation injury dramatically increases division rate by truncating G1 phase. Cells in G1 undergo a transient nuclear peak of glutathione (GSH) prior to coordinated entry into S phase, followed by rapid divisions and cellular reprogramming. A symplastic block of the ground tissue impairs regeneration, which is rescued by exogenous GSH. We propose a model in which GSH from the outer tissues is released upon injury, licensing an exit from G1 near the wound to induce rapid cell division and reprogramming.

关键词： cell cycle scRNA-seq regeneration plant regeneration glutathione rapid divisions reprogramming time-lapse microscopy

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