{"title":"Synergistic innovation in organ-on-a-chip and organoid technologies: Reshaping the future of disease modeling, drug development and precision medicine.","authors":"Bing Li,Yuanjun Tang,Zhanya Huang,Lijun Ma,Jiagui Song,Lixiang Xue","doi":"10.1093/procel/pwaf058","DOIUrl":"https://doi.org/10.1093/procel/pwaf058","url":null,"abstract":"FDA issued guidance on April 10th, 2025 to phase out animal trials in favor of organoids and organ-on-a-chip systems. This pivotal move was swiftly followed by National Institutes of Health (NIH) on April 29th, when it inaugurated the Office of Research Innovation, Validation, and Application (ORIVA). The establishment of ORIVA aims to spearhead the advancement of human-centric organ-on-a-chip technologies, marking a major stride toward more accurate, ethical, and efficient research methods in the biomedical field. Compared to traditional 2D cell cultures and animal models, organ-on-a-chip systems enable precise control of hydrodynamic parameters and biomechanical microenvironments. This review systematically elaborates on applications of single-organ, multi-organ, and organoid-on-a-chip technologies in modeling complex diseases, host-microbiome interactions, inter-organ physiological networks, and quantitative prediction of pharmacokinetics, toxicity responses, and personalized therapies. Furthermore, the core challenges in translating these technologies to pharmaceutical development and clinical practice are critically analyzed. With interdisciplinary integration of materials engineering, biosensing, and artificial intelligence, organ-on-a-chip technologies are transcending the limitations of conventional preclinical research. Their strategic value as 'patient surrogates' is poised to accelerate breakthroughs in precision medicine and rare disease treatments.","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"14 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies.","authors":"Shuhong Li, Licai Shi, Qiaoru Guo, Lijun Zhao, Xuexiu Qi, Zelin Liu, Zhi Guo, Yu J Cao","doi":"10.1093/procel/pwaf054","DOIUrl":"https://doi.org/10.1093/procel/pwaf054","url":null,"abstract":"<p><p>Advancements in protein engineering have driven the continuous optimization of T-cell engagers (TCEs), resulting in remarkable clinical outcomes in the treatment of B-cell malignancies. Moreover, developing tri- or multispecific TCEs has emerged as a promising strategy to address the challenges of tumor heterogeneity and antigen escape. However, considerable obstacles remain, primarily in format design. In this study, we engineered BAFF-based TCEs with various formats that incorporate anti-CD3 Fab or IgG domains fused with BAFF ligands to target BAFF receptors (BAFFR, BCMA and TACI). These constructs varied in valency and the presence or absence of long-acting elements such as Fc domains or the albumin binding domain consensus sequence (ABDCon). Although the inclusion of an Fc domain did not enhance sustained tumor eradication, variations in valency and spatial configuration profoundly influenced cytotoxicity. We identified TriBAFF/CD3/ABDCon as the optimal trifunctional construct, featuring an anti-CD3 Fab backbone with BAFF and ABDCon fused to the C-termini of the heavy and light chains. This design facilitates optimal immune synapses formation between the target cells and T cells and effectively controls tumor burdens in various B-cell malignancy models with good tolerability. Notably, TriBAFF/CD3/ABDCon outperformed conventional therapies, including blinatumomab and BAFF-based CAR-T cells, in models of heterogeneous leukemia and aggressive lymphoma. These findings underscore the potential of using natural ligands as antibody-targeting modules and provide valuable insights into the design of the next generation of multispecific TCEs, which hold promise for improving treatment outcomes in a wide range of malignancies and beyond.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":""},"PeriodicalIF":13.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Emerging roles of RNA N4-acetylcytidine modification in reproductive health.","authors":"Zibaguli Wubulikasimu, Hongyu Zhao, Fengbiao Mao, Xiaolu Zhao","doi":"10.1093/procel/pwaf013","DOIUrl":"10.1093/procel/pwaf013","url":null,"abstract":"<p><p>N4-acetylcytidine (ac4C), an emerging posttranscriptional RNA modification, plays a pivotal role in epigenetic regulation. Ac4C is detected not only in tRNA, rRNA, and mRNA, but also in miRNA, lncRNA, viral RNA, and even DNA. Functionally, ac4C stabilizes mRNA, enhances protein translation fidelity, and impacts various biological processes and diseases such as cancer, inflammation, immune regulation, neural diseases, osteogenic differentiation, cardiovascular diseases, viral infections, and replication. Current research primarily focuses on ac4C's roles in cancer progression and immunity, with emerging findings in gynecological diseases and reproduction. However, a comprehensive understanding of ac4C's implications in reproductive health is lacking. This review provides a historical perspective on ac4C's discovery and detection methods, elucidates its functions in reproductive development and gynecological disorders, and offers insights for further research in reproductive health. This review aims to pave the way for innovative therapeutic approaches and precise diagnostic tools tailored to this field.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"458-477"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protein & CellPub Date : 2025-06-20DOI: 10.1093/procel/pwaf010
Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li
{"title":"Setd2 overexpression rescues bivalent gene expression during SCNT-mediated ZGA.","authors":"Xiaolei Zhang, Ruimin Xu, Yuyan Zhao, Yijia Yang, Qi Shi, Hong Wang, Xiaoyu Liu, Shaorong Gao, Chong Li","doi":"10.1093/procel/pwaf010","DOIUrl":"10.1093/procel/pwaf010","url":null,"abstract":"<p><p>Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.</p>","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"439-457"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protein & CellPub Date : 2025-06-20DOI: 10.1093/procel/pwae063
Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni
{"title":"Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum.","authors":"Xue Zhang, Jing Han, Yudong Wang, Li Feng, Zhisong Fan, Yu Su, Wenya Song, Lan Wang, Long Wang, Hui Jin, Jiayin Liu, Dan Li, Guiying Li, Yan Liu, Jing Zuo, Zhiyu Ni","doi":"10.1093/procel/pwae063","DOIUrl":"10.1093/procel/pwae063","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"491-496"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}