Advanced biologyPub Date : 2025-03-31DOI: 10.1002/adbi.202400671
Noga Sharf-Pauker, Ido Galil, Omer Kfir, Gal Chen, Rotem Menachem, Jeny Shklover, Avi Schroeder, Shanny Ackerman
{"title":"Scaling Up Synthetic Cell Production Using Robotics and Machine Learning Toward Therapeutic Applications.","authors":"Noga Sharf-Pauker, Ido Galil, Omer Kfir, Gal Chen, Rotem Menachem, Jeny Shklover, Avi Schroeder, Shanny Ackerman","doi":"10.1002/adbi.202400671","DOIUrl":"https://doi.org/10.1002/adbi.202400671","url":null,"abstract":"<p><p>Synthetic cells (SCs), developed through bottom-up synthetic biology, hold great potential for biomedical applications, with the promise of replacing malfunctioning natural cells and treating diseases with spatiotemporal control. Currently, most SC synthesis and characterization processes are manual, limiting scalability and efficiency. In this study, an automated method is developed for large-scale production of protein-producing SCs for therapeutic applications. The optimized process, compatible with a robotic liquid handling system (LiHa), reduces production time by half. Additionally, incorporation of an automated tissue dissociator-based emulsification increases batch size 30-fold while preserving SC characteristics. To assess SC quality and protein synthesis, artificial intelligence (AI)-based image analysis is employed, allowing for automated, accurate and high-throughput SC characterization. Large-scale luciferase-expressing SCs from a single homogeneous batch are administered to mice, allowing for real-time monitoring of protein expression and reducing experimental variability. By troubleshooting several central steps in SC synthesis, it is demonstrated that automation and computerized quality control can significantly improve the process of SC synthesis for preclinical and clinical applications.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400671"},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-24DOI: 10.1002/adbi.202400597
Amrita Nepalia, Deepak Kumar Saini
{"title":"Ameliorating TIMM50 Loss Slows Senescence by Improving Mitochondrial Structure and Function.","authors":"Amrita Nepalia, Deepak Kumar Saini","doi":"10.1002/adbi.202400597","DOIUrl":"https://doi.org/10.1002/adbi.202400597","url":null,"abstract":"<p><p>Mitochondrial dysfunction is an irrefutable hallmark of cellular senescence and aging. The dysfunction is marked by increased mitochondrial volume and reduced function, typified by low Adenosine Triphosphate (ATP) production and higher Reactive Oxygen Species (ROS) generation. Over the years, this dysfunction has been linked to Electron Transport Chain (ETC) malfunction and low NAD levels, augmented by poor mitophagy. However, the genetic regulation of mitochondrial dysfunction is still not clear. Here, using several senescence models, the first report on the role of the downregulation of a mitochondrial protein, Translocase of Inner Mitochondrial Membrane 50 (TIMM50), in senescence is presented. The downregulation of TIMM50 is also sufficient for triggering senescence through impaired mitochondrial function, characterized using a variety of mitochondrial function assessment assays. Reduced levels of TIMM50 initiated all the hallmarks of senescence, and overexpression significantly slowed senescence onset in response to an external trigger. The pathway analysis revealed that TIMM50 loss is mediated by the sirtuin1-dependent downregulation of CCAAT enhancer binding protein alpha (CEBPα), a transcription activator for TIMM50 expression. To establish the translational value of the observation, screening several potential anti-aging compounds revealed TIMM50 stabilizing and senescence-delaying effects only for verapamil and mitochondrial ROS quencher, Mito (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO), both known anti-aging entities. Overall, TIMM50 is identified as the key mitochondrial protein whose downregulation is a critical step in initiating cellular senescence.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400597"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-24DOI: 10.1002/adbi.202400564
Changwei Yin, Yi Miao, Wei Lu, Zhenxing Liu
{"title":"IER3 Facilitates Tumor Progression and Aberrant Glycolysis via Activating wnt/β-Catenin Pathway in Oral Squamous Cell Carcinoma.","authors":"Changwei Yin, Yi Miao, Wei Lu, Zhenxing Liu","doi":"10.1002/adbi.202400564","DOIUrl":"https://doi.org/10.1002/adbi.202400564","url":null,"abstract":"<p><p>The function and molecular biological mechanism of immediate early response 3 (IER3) on the tumorigenesis of oral squamous cell carcinoma (OSCC) are aimed to be explored. The effects of IER3 on the proliferation, apoptosis, and mobility of OSCC cells are first assessed utilizing colony formation, EdU assay, flow cytometry, and transwell assay. The effect of IER3 on the glycolytic ability of OSCC cells is validated by detecting the extracellular acidification rate and oxygen consumption rate. Additionally, glycolysis- and wnt/β-catenin signaling-associated protein expressions are examined by western blot. Besides, a mouse tumor xenograft model is established to evaluate the effect of IER3 on tumor progression. IER3 expression is upregulated in OSCC cells and tissues. IER3 enhanced tumor cells' malignant behaviors and also promoted the glycolysis of OSCC cells. Moreover, IER3 is verified to promote the activation of wnt/β-catenin signaling in OSCC. Besides, rescue experiments further proved that IER3 knockdown can inhibit the malignant biological behavior of OSCC cells through inactivating wnt/β-catenin signaling. In vivo, the downregulation of IER3 is also demonstrated to suppress OSCC progression by inactivating wnt/β-catenin signaling. IER3 facilitated tumor progression and aberrant glycolysis via activating wnt/β-catenin pathway in OSCC.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400564"},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mitigating Oxidative Stress Enhances Cartilage Regeneration by Ameliorating Apoptosis of Cartilage Progenitor Cells in Adult Mice.","authors":"Xuewei Zhang, Zhihao Fang, Boon Chin Heng, Xiaoyu Hu, Zigang Ge","doi":"10.1002/adbi.202400739","DOIUrl":"https://doi.org/10.1002/adbi.202400739","url":null,"abstract":"<p><p>Cartilage regeneration in juvenile mice was better than in adult mice. This study evaluated the roles of cytokines and reactive oxygen species (ROS) after cartilage injury in both juvenile and adult mice and attempted to correlate these with cartilage progenitor cells and age-related differences in cartilage regeneration. Full-thickness cartilage defects were created in the femoral trochlea of knee joints in both 4-week-old (juvenile) and 8-week-old (adult) mice. Adult mice showed higher ROS peaks than juveniles at day 7 post-injury. Protein expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) significantly decreased after surgery, while interleukin-1β (IL-1β) levels displayed no significant change. There were more cartilage progenitor cells together with more cell proliferation in juvenile versus adult mice, while there was much less apoptosis of cartilage progenitor cells in juvenile mice compared to adult mice. ROS inhibition enhanced cartilage regeneration in adult mice by promoting progenitor cell proliferation and reducing apoptosis, mimicking the regenerative pattern seen in juveniles. This study demonstrated that inhibiting ROS in adult mice promoted cartilage regeneration, possibly by enhancing proliferation and decreasing apoptosis of cartilage progenitor cells.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400739"},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-19DOI: 10.1002/adbi.202400458
Sungryeal Kim, Jeong-Mi Kim, Eun-Jeong Jeon, Seo-Young Park, Jin-Mi Park, Jeong-Seok Choi
{"title":"Preventive Effect of Metformin in Radiation-Induced Xerostomia.","authors":"Sungryeal Kim, Jeong-Mi Kim, Eun-Jeong Jeon, Seo-Young Park, Jin-Mi Park, Jeong-Seok Choi","doi":"10.1002/adbi.202400458","DOIUrl":"https://doi.org/10.1002/adbi.202400458","url":null,"abstract":"<p><p>Radiation induced structural damage of salivary gland including reducing acinar cell and fibrosis. These changes result in hypofunction of salivary gland which has a significant impact on the quality of life of head and neck cancer patients who treated with radiotherapy. Nevertheless, no preventive method has been found. Metformin, a diabetes drug, has recently attracted considerable attention because it can cause tissue regeneration by anti-inflammatory action and influencing stem cells. This study examined the effects of metformin on salivary gland tissue damage caused by radiation therapy. Cultured human parotid epithelial cells are irradiated with 15 Gy of 4MV X-rays. The analysis including DNA damage, inflammatory markers and proliferation, is conducted to confirm the effect of metformin. Similarly, an in vivo mouse model is established. Histologic and functional analyses, such as salivary flow rate and lag time, are performed. The in vitro experiment revealed irradiation increased DNA damage, NF-кB, IL-6, and apoptosis with reduced proliferation. The treatment with metformin decreased the radiation-induced DNA damage and inflammation, and increased proliferation. The in vivo model also shows the same results. The group taking metformin after irradiation has preserved salivary gland parenchyma compared to irradiation only group, and the functional analysis results are comparable to the normal group. Histologic and functional analysis shows that metformin reduced radiation-induced hypofunction of salivary gland. Hence, metformin can be used to prevent radiation-induced salivary gland dysfunction.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400458"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Application of Immune Repertoire Analysis in Differentiating Thyroid Cancer and Large Benign Thyroid Nodules.","authors":"Jun Zhu, Xu Zhang, Xiangqing Zhu, Ziran Gao, Zhong Ni, Tiancheng Zhang, Meijin Huang","doi":"10.1002/adbi.202400760","DOIUrl":"https://doi.org/10.1002/adbi.202400760","url":null,"abstract":"<p><p>This study compares the peripheral T-cell receptor (TCR) and B-cell receptor (BCR) immune repertoires among early-stage papillary thyroid carcinoma (PTC) patients, patients with benign thyroid nodules larger than 4 cm, and healthy controls. Adaptive immune repertoire sequencing is used to analyze peripheral immune profile differences among these groups. Results indicates that early PTC and large benign nodules show significantly higher proportions of expanded clones than healthy controls, reflecting antigen-driven clonal expansion. By introducing the concept of \"publicness,\" disease-specific high-publicness clonotypes is identified. These clonotypes exhibits distinct V-J rearrangement characteristics and strong immune heterogeneity. This study further reveals that this immune heterogeneity may be associated with patients' thyroid hormone levels and autoimmune antibody levels. These findings provides new insights into the immunopathological mechanisms of thyroid disorders.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400760"},"PeriodicalIF":3.2,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-17DOI: 10.1002/adbi.202570095
Yi Yang, Yining Meng, Daijie Chen, Ping Hou, Zhipeng Zhang, Wenqiang Cao, Ye Meng, Qianwen Zhang, Runyan Tu, Xiaoli Hao, Aijian Qin, Shaobin Shang, Zhangping Yang
{"title":"Lysozyme/Tracheal Antimicrobial Peptide-Based Tissue-Specific Expression Antimicrobial Plasmids Show Broad-Spectrum Antibacterial Activities in the Treatment of Mastitis in Mice (Adv. Biology 3/2025)","authors":"Yi Yang, Yining Meng, Daijie Chen, Ping Hou, Zhipeng Zhang, Wenqiang Cao, Ye Meng, Qianwen Zhang, Runyan Tu, Xiaoli Hao, Aijian Qin, Shaobin Shang, Zhangping Yang","doi":"10.1002/adbi.202570095","DOIUrl":"https://doi.org/10.1002/adbi.202570095","url":null,"abstract":"<p><b>Non-Antibiotic Therapies for Bacterial Infections</b></p><p>The treatment of bacterial diseases is becoming more and more challenging due to the concern of increasing antibiotic resistance. Yi Yang, Yining Meng, and co-workers have developed lysozyme/tracheal antimicrobial peptide-based tissue-specific expression antimicrobial plasmids, alleviating mastitis in mice with a favorable safety profile. Their work offers promising antibiotic alternatives. More details can be found in article number 2400132.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202570095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143632838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological AIE Molecules: Innovations in Synthetic Design and AI-Driven Discovery.","authors":"Raj Dave, Kshipra Pandey, Viral Khatri, Ritu Patel, Nidhi Gour, Dhiraj Bhatia","doi":"10.1002/adbi.202400792","DOIUrl":"https://doi.org/10.1002/adbi.202400792","url":null,"abstract":"<p><p>Biological aggregation -induced emission (AIE) molecules offer significant advantages over synthetic organic fluorophores, particularly in biocompatibility, environmental sustainability, and emission properties in biological systems. Derived from biomolecules such as peptides, proteins, and nucleic acids, biological AIE molecules hold great promise for applications in biosensing, bioimaging, and target drug delivery. This review explores the design principles, mechanistic insights, and functional properties of biological AIE molecules whiles highlighting the role of artificial intelligence (AI) in accelerating their discovery and optimization. AI-driven approaches, including machine learning and computational modeling, are transforming the identification and synthesis of AIE molecules by enabling precise structural modifications and enhanced fluorescence efficiency. These advancements are paving the way for the integration of AIE molecules in next-generation smart biomedical devices, personalized medicine and sustainable technological applications. Emerging trends, including hybrid biomaterials, Ai-guided molecular engineering, and advanced imaging techniques, are expanding the scope of biological AIE molecules in healthcare and environmental monitoring. The synergy between AI and biological AIE molecules is unlocking new frontiers in biomedical technology, enabling transformative advancements in material science and healthcare applications, and shaping the future of fluorescence- based diagnostics and therapeutics.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400792"},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-12DOI: 10.1002/adbi.202400601
Paula De Dios Andres, Mousumi Akter, Cecilie Ryberg, Brigitte Städler, Allen P Liu
{"title":"Distinct Network Morphologies from In Situ Polymerization of Microtubules in Giant Polymer-Lipid Hybrid Vesicles.","authors":"Paula De Dios Andres, Mousumi Akter, Cecilie Ryberg, Brigitte Städler, Allen P Liu","doi":"10.1002/adbi.202400601","DOIUrl":"https://doi.org/10.1002/adbi.202400601","url":null,"abstract":"<p><p>Creating artificial cells with a dynamic cytoskeleton, akin to those in living cells, is a major goal in bottom-up synthetic biology. In this study, we demonstrate the in situ polymerization of microtubules encapsulated in giant polymer-lipid hybrid vesicles (GHVs) composed of 1,2-dioleoyl-sn-glycero-3-phosphocholine and an amphiphilic block copolymer. The block copolymer is comprised of poly(cholesteryl methacrylate-co-butyl methacrylate) as the hydrophobic block and either poly(6-O-methacryloyl-D-galactopyranose) or poly(carboxyethyl acrylate) as the hydrophilic extension. Depending on the concentrations of guanosine triphosphate (GTP) or its slowly hydrolyzable analog, guanosine-5'-[(α,β)-methyleno]triphosphate (GMPCPP), different microtubule morphologies are observed, including encapsulated microtubule networks, spike protrusions, as well as membrane-associated or aggregated microtubules. Overall, this work represents a step forward in mimicking the cellular cytoskeletons and uncovering the influence of membrane composition on microtubule morphologies.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400601"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced biologyPub Date : 2025-03-12DOI: 10.1002/adbi.202400814
Britta Eggers, Simone Steinbach, Isabel Gil Aldea, Sharon Keers, Mariana Molina, Lea T Grinberg, Helmut Heinsen, Renata E Paraizo Leite, Johannes Attems, Caroline May, Katrin Marcus
{"title":"The Aging Substantia Nigra is Characterized by ROS Accumulation Potentially Resulting in Increased Neuroinflammation and Cytoskeletal Remodeling.","authors":"Britta Eggers, Simone Steinbach, Isabel Gil Aldea, Sharon Keers, Mariana Molina, Lea T Grinberg, Helmut Heinsen, Renata E Paraizo Leite, Johannes Attems, Caroline May, Katrin Marcus","doi":"10.1002/adbi.202400814","DOIUrl":"https://doi.org/10.1002/adbi.202400814","url":null,"abstract":"<p><p>Aging is a progressive and irreversible process, serving as the primary risk factor for neurodegenerative disorders. This study aims to identify the molecular mechanisms underlying physiological aging within the substantia nigra, which is primarily affected by Parkinson's disease, and to draw potential conclusions on the earliest events leading to neurodegeneration in this specific brain region. The characterization of essential stages in aging progress can enhance knowledge of the mechanisms that promote the development of Parkinson's disease. To gain a comprehensive overview three study groups are utilized: young individuals (mean age: 28.7 years), middle-aged (mean age: 62.3 years), and elderly individuals (mean age: 83.9 years). Using the proteomic approach, crucial features of physiological aging are able to be identified. These include heightened oxidative stress, enhanced lysosomal degradation, autophagy, remodeling of the cytoskeleton, changes in the structure of the mitochondria, alterations in vesicle transportation, and synaptic plasticity.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400814"},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}