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Improved CaP Nanoparticles for Nucleic Acid and Protein Delivery to Neural Primary Cultures and Stem Cells

ACS Nano 2024年第6期18卷 4822-4839页

作者： Chao, Yu-Wen Lee, Yen-Lurk Tseng, Ching-San Wang, Lily Ueh-Hsi Hsia, Kuo-Chiang Chen, Huatao Fustin, Jean-Michel Azeem, Sayma Chang, Tzu-Tung Chen, Chiung-Ya Kung, Fan-Che Hsueh, Yi-Ping Huang, Yi-Shuian Chao, Hsu-Wen Department of Physiology School of Medicine College of Medicine Taipei Medical University Taipei110301 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei110301 Taiwan Department of Anatomy School of Medicine China Medical University Taichung40402 Taiwan Institute of Molecular Biology Academia Sinica Taipei115201 Taiwan Institute of Biomedical Sciences Academia Sinica Taipei115201 Taiwan Department of Clinical Veterinary Medicine College of Veterinary Medicine Northwest A&F University Shaanxi Yangling712100 China Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs Northwest A&F University Shaanxi Yangling712100 China The University of Manchester Faculty of Biology Medicine and Health Oxford Road ManchesterM13 9PL United Kingdom Taiwan International Graduate Program in Interdisciplinary Neuroscience National Yang-Ming Chao-Tung University and Academia Sinica Taipei115201 Taiwan Institute of Molecular Medicine College of Medicine National Taiwan University Taipei10002 Taiwan Department of Biomedical Science and Environmental Biology Kaohsiung Medical University Kaohsiung80708 Taiwan

Efficiently delivering exogenous materials into primary neurons and neural stem cells (NSCs) has long been a challenge in neurobiology. Existing methods have struggled with complex protocols, unreliable reproducibility, high immunogenicity, and cytotoxicity, causing a huge conundrum and hindering in-depth analyses. Here, we establish a cutting-edge method for transfecting primary neurons and NSCs, named teleofection, by a two-step process to enhance the formation of biocompatible calcium phosphate (CaP) nanoparticles. Teleofection enables both nucleic acid and protein transfection into primary neurons and NSCs, eliminating the need for specialized skills and equipment. It can easily fine-tune transfection efficiency by adjusting the incubation time and nanoparticle quantity, catering to various experimental requirements. Teleofection’s versatility allows for the delivery of different cargos into the same cell culture, whether simultaneously or sequentially. This flexibility proves invaluable for long-term studies, enabling the monitoring of neural development and synapse plasticity. Moreover, teleofection ensures the consistent and robust expression of delivered genes, facilitating molecular and biochemical investigations. Teleofection represents a significant advancement in neurobiology, which has promise to transcend the limitations of current gene delivery methods. It offers a user-friendly, cost-effective, and reproducible approach for researchers, potentially revolutionizing our understanding of brain function and development. © 2024 The Authors. Published by American Chemical Society.

关键词： Calcium phosphate

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Microenvironmental regulation of stem cells injected in the area at risk of neurodegenerative diseases

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BIOCELL 2022年第10期46卷 2231-2234页

作者： JU HYUNG LEE IL-KWON KIM SANG WOO KIM SOYEON LIM SEAHYOUNG LEE KI-CHUL HWANG BYEONG-WOOK SONG Graduate Program of Biomedical Engineering Yonsei UniversitySeoul03722Korea Institute for Bio-Medical Convergence College of MedicineCatholic Kwandong UniversityGangwon-do25601Korea Department for Medical Science College of MedicineCatholic Kwandong UniversityGangwon-do25601Korea

The complex mechanism of degenerative diseases and the non-specific modulation of regenerative targets aretopics that need to be elucidated in order to advance the use of stem cells in improvement of neurodegenerative *** pre-transplantation through post-transplantation, there are many changes in the conditions, both inside andoutside of the stem cells that have not been carefully considered. This has hindered development in the field of celltherapy and regeneration. This viewpoint highlights the potential implications of intracellular and extracellularalterations of stem cells in transplanted areas at risk of neurodegenerative disease.

关键词： Cell therapy Microenvironment Neurodegenerative disease Stem cells

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Macrophages as determinants and regulators of systemic sclerosis-related interstitial lung disease

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Journal of Translational medicine 2024年第1期22卷 600页

作者： Lee, Shih-Ching Huang, Chen-Hao Oyang, Yen-Jen Huang, Hsuan-Cheng Juan, Hsueh-Fen Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei 10617 Taiwan Division of Rheumatology Allergy and Immunology Department of Internal Medicine Chang Gung Memorial Hospital Taoyuan 333 Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei 11221 Taiwan Department of Life Science National Taiwan University Taipei 106 Taiwan Center for Computational and Systems Biology National Taiwan University Taipei 106 Taiwan

Background: Interstitial lung disease (ILD) is the primary cause of mortality in systemic sclerosis (SSc), an autoimmune disease characterized by tissue fibrosis. SSc-related ILD (SSc-ILD) occurs more frequently in females aged 30–55 years, whereas idiopathic pulmonary fibrosis (IPF) is more prevalent in males aged 60–75 years. SSc-ILD occurs earlier than IPF and progresses rapidly. FCN1, FABP4, and SPP1 macrophages are involved in the pathogenesis of lung fibrosis;SPP1 macrophages demonstrate upregulated expression in both SSc-ILD and IPF. To identify the differences between SSc-ILD and IPF using single-cell analysis, clarify their distinct pathogeneses, and propose directions for prevention and treatment. Methods: We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE159354 and GSE212109, and analyzed lung tissue samples across healthy controls, IPF, and SSc-ILD. The primary measures were the filtered genes integrated with batch correction and annotated cell types for distinguishing patients with SSc-ILD from healthy controls. We proposed an SSc-ILD pathogenesis using cell–cell interaction inferences, and predicted transcription factors regulating target genes using SCENIC. Drug target prediction of the TF gene was performed using Drug Bank Online. Results: A subset of macrophages activates the MAPK signaling pathway under oxidative stress. Owing to the lack of inhibitory feedback from ANNEXIN and the autoimmune characteristics, this leads to an earlier onset of lung fibrosis compared to IPF. During initial lung injury, fibroblasts begin to activate the IL6 pathway under the influence of SPP1 alveolar macrophages, but IL6 appears unrelated to other inflammatory and immune cells. This may explain why tocilizumab (an anti-IL6-receptor antibody) only preserves lung function in patients with early SSc-ILD. Finally, we identified BCLAF1 and NFE2L2 as influencers of MAPK activation in macrophages. Metformin downregulates NFE2L2 and c

关键词： IL6 Lung fibrosis Macrophage MAPK SSc-ILD Systemic sclerosis

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Enhanced diabetic wound healing using platelet-derived extracellular vesicles and reduced graphene oxide in polymer-coordinated hydrogels

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Journal of Nanobiotechnology 2023年第1期21卷 1-17页

作者： Hao, Ping-Chien Burnouf, Thierry Chiang, Chih-Wei Jheng, Pei-Ru Szunerits, Sabine Yang, Jen-Chang Chuang, Er-Yuan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei10617 Taiwan Department of Orthopedics Taipei Medical University Hospital Taipei11031 Taiwan Univ. Lille CNRS Centrale Lille Univ. Polytechnique Hauts-de-France UMR 8520 IEMN LilleF- 59000 France Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University Taipei110-52 Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei11696 Taiwan Precision Medicine and Translational Cancer Research Center Taipei Medical University Hospital Taipei11031 Taiwan

Impaired wound healing is a significant complication of diabetes. Platelet-derived extracellular vesicles (pEVs), rich in growth factors and cytokines, show promise as a powerful biotherapy to modulate cellular proliferation, angiogenesis, immunomodulation, and inflammation. For practical home-based wound therapy, however, pEVs should be incorporated into wound bandages with careful attention to delivery strategies. In this work, a gelatin-alginate hydrogel (GelAlg) loaded with reduced graphene oxide (rGO) was fabricated, and its potential as a diabetic wound dressing was investigated. The GelAlg@rGO-pEV gel exhibited excellent mechanical stability and biocompatibility in vitro, with promising macrophage polarization and reactive oxygen species (ROS)-scavenging capability. In vitro cell migration experiments were complemented by in vivo investigations using a streptozotocin-induced diabetic rat wound model. When exposed to near-infrared light at 2 W cm− 2, the GelAlg@rGO-pEV hydrogel effectively decreased the expression of inflammatory biomarkers, regulated immune response, promoted angiogenesis, and enhanced diabetic wound healing. Interestingly, the GelAlg@rGO-pEV hydrogel also increased the expression of heat shock proteins involved in cellular protective pathways. These findings suggest that the engineered GelAlg@rGO-pEV hydrogel has the potential to serve as a wound dressing that can modulate immune responses, inflammation, angiogenesis, and follicle regeneration in diabetic wounds, potentially leading to accelerated healing of chronic wounds. © 2023, BioMed Central Ltd., part of Springer Nature.

关键词： Platelets

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3D-printed porous titanium suture anchor: a rabbit lateral femoral condyle model

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BMC Musculoskeletal Disorders 2024年第1期25卷 1页

作者： Wu, Lien-Chen Hsieh, Yueh-Ying Hsu, Ting-Shuo Liu, Po-Yi Tsuang, Fon-Yih Kuo, Yi-Jie Chen, Chia-Hsien Van Huynh, T.I.N. Chiang, Chang-Jung Department of Orthopaedics Shuang Ho Hospital Taipei Medical University Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Division of Neurosurgery Department of Surgery National Taiwan University Hospital Spine Tumor Center National Taiwan University Hospital Department of Orthopedic Surgery Wan Fang Hospital Taipei Medical University School of Biomedical Engineering College of Biomedical Engineering Taipei Medical University Department of Interventional Cardiology Thong Nhat Hospital International Ph.D program in medicine college of medicine Taipei medical university

Background: The inclusion of a connecting path in a porous implant can promote nutrient diffusion to cells and enhance bone ingrowth. Consequently, this study aimed to evaluate the biomechanical, radiographic, and histopathological performance of a novel 3D-printed porous suture anchor in a rabbit femur model. Methods: Three test groups were formed based on the type of suture anchor (SA): Commercial SA (CSA, Group A, n = 20), custom solid SA (CSSA, Group B, n = 20), and custom porous SA (CPSA, Group C, n = 20). The SAs were implanted in the lateral femoral condyle of the right leg in each rabbit. The rabbits (New Zealand white rabbits, male, mean body weight of 2.8 ± 0.5 kg, age 8 months) underwent identical treatment and were randomized into experimental and control groups via computer-generated randomization. Five rabbits (10 femoral condyles) were euthanized at 0, 4, 8, and 12 weeks post-implantation for micro-CT, histological analysis, and biomechanical testing. Results: At 12 weeks, the CPSA showed a higher BV/TV (median 0.7301, IQR 0.7276–0.7315) than the CSSA and CSA. The histological analysis showed mineralized osteocytes near the SA. At 4 weeks, new bone was observed around the CPSA and had penetrated its porous structure. By 12 weeks, there was no significant difference in ultimate failure load between the CSA and CPSA. Conclusions: We demonstrated that the innovative 3D-printed porous suture anchor exhibited comparable pullout strength to conventional threaded suture anchors at the 12-week postoperative time-point period. Furthermore, our porous anchor design enhanced new bone formation and facilitated bone growth into the implant structure, resulting in improved biomechanical stability. © The Author(s) 2024.

关键词： 3D-printed porous anchor Bone formation Bone ingrowth Suture anchor

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A deep learning approach to Lung Nodule Growth Prediction using CT image combined with Demographic and image features 23

A deep learning approach to Lung Nodule Growth Prediction us...

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7th International Conference on Medical and Health informatics, ICMHI 2023

作者： Li, Ai-Hsien Adams Nguyen, Duc-Khanh Lai, Yen-Jun Chien, Ting-Ying Chiu, Yen-Ling Chan, Chien-Lung Yang, Pan-Chyr Division of Cardiology Far Eastern Memorial Hospital Taipei220 Taiwan Graduate Program in Biomedical Informatics Yuan Ze University Taoyuan City Taiwan Department of Information Management Yuan Ze University Taoyuan320 Taiwan Department of Radiology Far Eastern Memorial Hospital Taipei220 Taiwan Department of Computer Science and Engineering Yuan Ze University Taoyuan City Taiwan Innovation Center for Big Data and Digital Convergence Yuan Ze University Taoyuan City Taiwan Graduate Institute of Medicine and Graduate Program in Biomedical Informatics Yuan Ze University Taoyuan Taiwan Department of Medical Research Far Eastern Memorial Hospital Taipei Taiwan Innovation Center for Big Data and Digital Convergence Yuan Ze University Taoyuan320 Taiwan Institute of Biomedical Sciences Academia Sinica Taipei106 Taiwan Department of Internal Medicine College of Medicine National Taiwan University Taipei100 Taiwan Center of Genomic Medicine National Taiwan University Taipei100 Taiwan

ISBN: (纸本)9798400700712

Lung cancer remains a significant global public health concern, being the leading cause of cancer-related deaths worldwide. Despite recent medical advancements, the disease still has a high mortality rate, making early detection and treatment critical for improving patient outcomes. Accurate prediction of nodule growth is key to early lung cancer treatment, but current assessments offer unclear indications of future growth, leading physicians to recommend costly and anxiety-provoking follow-up appointments every 3 to 12 months. To address this need, this study develops an ensemble deep learning approach that combines demographic data with existing CT images to predict whether lung nodules will grow, potentially reducing unnecessary examinations and easing the burden on patients. Our study, conducted on 862 patients with 1004 nodules, produced promising preliminary results with Accuracy, Sensitivity, Precision, F1 Score, and AUC of 0.66, 0.66, 0.67, 0.66, and 0.71, respectively. The proposed method provides a promising support system to empower patients to make informed decisions about seeking medical attention and helps physicians facilitate early treatment regimens, leading to improved patient outcomes and potentially saving lives. © 2023 ACM.

关键词： Forecasting

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Rapid plasma membrane isolation via intracellular polymerization-mediated biomolecular confinement

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Acta Biomaterialia 2024年 173卷 325-335页

作者： Lin, Chi-Long Fang, Zih-Syun Hsu, Chung-Yao Liu, Yu-Han Lin, Jung-Chen Yao, Bing-Yu Li, Fu-An Yen, Shin-Chwen Bruce Chang, Yuan-Chih Hu, Che-Ming J. Institute of Biomedical Sciences Academia Sinica. 128 Academia Road Sec. 2 Taipei11529 Taiwan Institute of Cellular and Organismic Biology Academia Sinica No. 128 Sec. 2 Taipei11529 Taiwan Research Center for Nanotechnology and Infectious Diseases Taipei Taiwan Taiwan International Graduate Program in Molecular Medicine National Yang Ming Chiao Tung University and Academia Sinica Taipei Taiwan

Plasma membrane isolation is a foundational process in membrane proteomic research, cellular vesicle studies, and biomimetic nanocarrier development, yet separation processes for this outermost layer are cumbersome and susceptible to impurities and low yield. Herein, we demonstrate that cellular cytosol can be chemically polymerized for decoupling and isolation of plasma membrane within minutes. A rapid, non-disruptive in situ polymerization technique is developed with cell membrane-permeable polyethyleneglycol-diacrylate (PEG-DA) and a blue-light-sensitive photoinitiator, lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). The photopolymerization chemistry allows for precise control of intracellular polymerization and tunable confinement of cytosolic molecules. Upon cytosol solidification, plasma membrane proteins and vesicles are rapidly derived and purified as nucleic acids and intracellular proteins as small as 15 kDa are stably entrapped for removal. The polymerization chemistry and membrane derivation technique are broadly applicable to primary and fragile cell types, enabling facile membrane vesicle extraction from shorted-lived neutrophils and human primary CD8 T cells. The study demonstrates tunable intracellular polymerization via optimized live cell chemistry, offers a robust membrane isolation methodology with broad biomedical utility, and reveals insights on molecular crowding and confinement in polymerized cells. Statement of significance: Isolating the minute fraction of plasma membrane proteins and vesicles requires extended density gradient ultracentrifugation processes, which are susceptible to low yield and impurities. The present work demonstrates that the membrane isolation process can be vastly accelerated via a rapid, non-disruptive intracellular polymerization approach that decouples cellular cytosols from the plasma membrane. Following intracellular polymerization, high-yield plasma membrane proteins and vesicles can be derived from lysi

关键词： Cell membranes

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SwiftMedSAM: An Ultra-lightweight Prompt-Based Universal Medical Image Segmentation Model for Highly Constrained Environments 1

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International Challenge on Segment Anything in Medical Images on Laptop held in conjunction with the IEEE/CVF Conference on Computer Vision and Pattern Recognition, CVPR 2024

作者： Kong, Youngbin Kim, Kwangtai Jeong, Seoi Lee, Kyu Eun Kong, Hyoun-Joong Interdisciplinary Program in Bioengineering Graduate School Seoul National University Seoul Korea Republic of Department of Transdisciplinary Medicine Seoul National University Hospital Seoul Korea Republic of Department of Surgery Seoul National University Hospital and College of Medicine Seoul Korea Republic of Department of Medicine Seoul National University College of Medicine Seoul Korea Republic of Innovative Medical Technology Research Institute Seoul National University Hospital Seoul Korea Republic of Interdisciplinary Program of Medical Informatics Seoul National University College of Medicine Seoul Korea Republic of

ISBN: (数字)9783031818547

ISBN: (纸本)9783031818530

Medical image segmentation is a crucial step for accurate diagnosis and treatment planning, as it provides quantitative information about anatomical structures and pathological lesions in various clinical scenarios. However, the existing methodologies have limitations in terms of their generalizability and computational efficiency. In this study, we propose SwiftMedSAM, an ultra-lightweight prompt-based general model, to enable efficient medical image segmentation even in resource-constrained environments. Based on LiteMedSAM, we significantly reduced the model size and computational complexity through the hyperparameter optimization of the image encoder and mask decoder components. SwiftMedSAM showed remarkable performance across various imaging modalities enabling real-time inference in resource-limited computing environments. It achieved a validation score of 0.75 demonstrating that SwiftMedSAM outperformed the existing methodologies in terms of the trade-off between accuracy and efficiency. Owing to its unprecedented generalizability and low computational cost, SwiftMedSAM is expected to enable high-quality medical image analysis in resource-constrained settings, thereby contributing to advancements in precision medicine and telemedicine. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.

关键词： Medical imaging

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Investigating the impact of probiotic on neurological outcomes in Rett syndrome: A randomized, double-blind, and placebo-controlled pilot study

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Autism 2024年第9期28卷 2267-2281页

作者： Wong, Lee Chin Hsu, Chia-Jui Wu, Yen-Tzu Chu, Hsu-Feng Lin, Jui-Hsiang Wang, Hsin-Pei Hu, Su-Ching Tsai, Ying-Chieh Tsai, Wen-Che Lee, Wang-Tso Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan Department of Pediatrics National Taiwan University Hospital and National Taiwan University College of Medicine Taipei Taiwan Department of Pediatrics National Taiwan University Hospital Hsin-Chu Branch Hsin-Chu Taiwan School and Graduate Institute of Physical Therapy National Taiwan University College of Medicine Taiwan Department of Physical Medicine and Rehabilitation National Taiwan University Taipei Taiwan Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei Taiwan Institute of Statistical Science Academia Sinica Taipei Taiwan Department of Pediatrics National Taiwan University Hospital YunLin Branch YunLin Taiwan Department of Pediatrics Cathay General Hospital Taipei Taiwan Institute of Biochemistry and Molecular Biology National Yang Ming Chiao Tung University Taipei Taiwan Department of Psychiatry National Taiwan University Hospital Taipei Taiwan Graduate Institute of Brain and Mind Sciences National Taiwan University College of Medicine Taipei Taiwan

This pilot study investigates the feasibility and assesses the impact of Lactobacillus plantarum PS128 probiotics on the neurological function in Rett syndrome. We conducted a randomized, double-blind, and placebo-controlled trial on Rett syndrome with MECP2 mutation aged between 1 and 50 years in Taiwan. In this pilot study, twice-daily L. plantarum PS128 or placebo was administered for 16 weeks. In addition to feasibility, we also assessed the changes utilizing the Mullen Scales of Early Learning. In total, 36 participants were finally randomized into L. plantarum PS128 (n = 18) or placebo (n = 18) groups. At the end of intervention, the retention rates were 100% for L. plantarum PS128 and 94.44% for placebo, with withdrawal rates of 5.56% for the placebo group. Both groups tolerated well, except for one L. plantarum PS128 participant who reported loose stool. The probiotic group showed a change of 2.19 ± 3.76, while the placebo group had −0.85 ± 5.09 (p = 0.051) in the total age-equivalent scores of Mullen Scales of Early Learning. There was a significant difference in the change of the total score on the Burke–Fahn–Marsden Movement Scale between probiotc group and placebo group (−12.19 ± 12.12 vs −4.59 ± 4.20, p = 0.020). In leg dystonia, the probiotic group exhibited a change of −4.11 ± 5.11 compared with −0.38 ± 1.50 in the placebo group (p = 0.008). Our findings affirm the feasibility of L. plantarum PS128 in Rett syndrome. Future clinical trials are mandatory to further explore its long-term impact on Rett syndrome. Lay abstract: Rett syndrome often involves gastrointestinal symptoms and gut microbiota imbalances. We conducted a study to explore the feasibility of probiotic Lactobacillus plantarum PS128 and the impact on neurological functions in Rett syndrome. The results of our investigation demonstrated that the supplementation of probiotic L. plantarum PS128 was feasible and well tolerated, with 100% retention rate and 0% withdrawal rate. In addition, th

关键词： dystonia microbiota–gut–brain axis probiotics Rett syndrome

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Multiomics Reveals Induction of Neuroblastoma SK-N-BE(2)C Cell Death by Mitochondrial Division Inhibitor 1 through Multiple Effects

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Journal of Proteome Research 2024年第1期23卷 301-315页

作者： Wang, Wei-Hsuan Kao, Yi-Chun Hsieh, Chiao-Hui Tsai, Shin-Yu Cheung, Chantal Hoi Yin Huang, Hsuan-Cheng Juan, Hsueh-Fen Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taipei 106 Taiwan Department of Life Science National Taiwan University Taipei 106 Taiwan Center for Computational and Systems Biology National Taiwan University Taipei 106 Taiwan Institute of Biomedical Informatics National Yang Ming Chiao Tung University Taipei 112 Taiwan Graduate Institute of Biomedical Electronics and Bioinformatics National Taiwan University Taipei 106 Taiwan Center for Advanced Computing and Imaging in Biomedicine National Taiwan University Taipei 106 Taiwan

Mitochondrial division inhibitor 1 (Mdivi-1) is a well-known synthetic compound aimed at inhibiting dynamin-related protein 1 (Drp1) to suppress mitochondrial fission, making it a valuable tool for studying mitochondrial dynamics. However, its specific effects beyond Drp1 inhibition remain to be confirmed. In this study, we employed integrative proteomics and phosphoproteomics to delve into the molecular responses induced by Mdivi-1 in SK-N-BE(2)C cells. A total of 3070 proteins and 1945 phosphorylation sites were identified, with 880 of them represented as phosphoproteins. Among these, 266 proteins and 97 phosphorylation sites were found to be sensitive to the Mdivi-1 treatment. Functional enrichment analysis unveiled their involvement in serine biosynthesis and extrinsic apoptotic signaling pathways. Through targeted metabolomics, we observed that Mdivi-1 enhanced intracellular serine biosynthesis while reducing the production of C24:1-ceramide. Within these regulated phosphoproteins, dynamic dephosphorylation of proteasome subunit alpha type 3 serine 250 (PSMA3-S250) occurred after Mdivi-1 treatment. Further site-directed mutagenesis experiments revealed that the dephosphorylation-deficient mutant PSMA3-S250A exhibited a decreased cell survival. This research confirms that Mdivi-1’s inhibition of mitochondrial division leads to various side effects, ultimately influencing cell survival, rather than solely targeting Drp1 inhibition. © 2023 American Chemical Society.

关键词： Mdivi-1 multiomics neuroblastoma phosphoproteome proteome targeted metabolome

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