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Synergistic innovation in organ-on-a-chip and organoid technologies: Reshaping the future of disease modeling, drug development and precision medicine. 芯片上器官和类器官技术的协同创新:重塑疾病建模、药物开发和精准医学的未来。
IF 21.1 1区 生物学
Protein & Cell Pub Date : 2025-07-13 DOI: 10.1093/procel/pwaf058
Bing Li,Yuanjun Tang,Zhanya Huang,Lijun Ma,Jiagui Song,Lixiang Xue
{"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}
引用次数: 0
Insights of mammalian hibernator-derived cholangiocyte organoids in improving liver cold preservation. 哺乳动物冬眠源性胆管细胞类器官改善肝脏低温保存的研究进展。
IF 21.1 1区 生物学
Protein & Cell Pub Date : 2025-07-01 DOI: 10.1093/procel/pwaf052
Chuman Wu,Changliang Wang,Meifeng Gu,Weiya He,Wenjun Deng,Wenjie Huang,Jiayu Liao,Changhui Li,Weilue Chen,Ruiping Chen,Ji Dong,Meiling Liu
{"title":"Insights of mammalian hibernator-derived cholangiocyte organoids in improving liver cold preservation.","authors":"Chuman Wu,Changliang Wang,Meifeng Gu,Weiya He,Wenjun Deng,Wenjie Huang,Jiayu Liao,Changhui Li,Weilue Chen,Ruiping Chen,Ji Dong,Meiling Liu","doi":"10.1093/procel/pwaf052","DOIUrl":"https://doi.org/10.1093/procel/pwaf052","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"36 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533292","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}
引用次数: 0
Discovery and structural investigation of Varicella-Zoster virus gE-neutralizing antibodies isolated from a convalescent patient. 水痘-带状疱疹病毒ge中和抗体的发现及结构研究。
IF 21.1 1区 生物学
Protein & Cell Pub Date : 2025-06-30 DOI: 10.1093/procel/pwaf051
Lulu Wang,Zihan Jia,Xiaohan Ye,Chunxiao Chen,Baofa Sun,Xiangshuai Zhao,Ruiqi Zhang,Ying Li,Wenya Wang,Zixian Sun,Lushuai Zhou,Zhiyu Ni,Nan Zhang,Yu Guo
{"title":"Discovery and structural investigation of Varicella-Zoster virus gE-neutralizing antibodies isolated from a convalescent patient.","authors":"Lulu Wang,Zihan Jia,Xiaohan Ye,Chunxiao Chen,Baofa Sun,Xiangshuai Zhao,Ruiqi Zhang,Ying Li,Wenya Wang,Zixian Sun,Lushuai Zhou,Zhiyu Ni,Nan Zhang,Yu Guo","doi":"10.1093/procel/pwaf051","DOIUrl":"https://doi.org/10.1093/procel/pwaf051","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":"19 1","pages":""},"PeriodicalIF":21.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520833","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}
引用次数: 0
BAFF-based trifunctional T-cell engagers trigger robust tumor immunity against B-cell malignancies. 基于baff的三功能t细胞接合物触发对b细胞恶性肿瘤的强大肿瘤免疫。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-27 DOI: 10.1093/procel/pwaf054
Shuhong Li, Licai Shi, Qiaoru Guo, Lijun Zhao, Xuexiu Qi, Zelin Liu, Zhi Guo, Yu J Cao
{"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}
引用次数: 0
Structural studies promote vaccine development - Lessons from African Swine Fever Virus. 结构研究促进疫苗开发——非洲猪瘟病毒的经验教训。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-27 DOI: 10.1093/procel/pwaf055
Yuxia Zhang, Ling Zhu
{"title":"Structural studies promote vaccine development - Lessons from African Swine Fever Virus.","authors":"Yuxia Zhang, Ling Zhu","doi":"10.1093/procel/pwaf055","DOIUrl":"https://doi.org/10.1093/procel/pwaf055","url":null,"abstract":"","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":"144512419","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}
引用次数: 0
Targeting IRG1 in tumor-associated macrophages for cancer therapy. 靶向肿瘤相关巨噬细胞中的IRG1用于癌症治疗。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-20 DOI: 10.1093/procel/pwaf012
Shuang Liu, Lin-Xing Wei, Qian Yu, Zhi-Wei Guo, Chang-You Zhan, Lei-Lei Chen, Yan Li, Dan Ye
{"title":"Targeting IRG1 in tumor-associated macrophages for cancer therapy.","authors":"Shuang Liu, Lin-Xing Wei, Qian Yu, Zhi-Wei Guo, Chang-You Zhan, Lei-Lei Chen, Yan Li, Dan Ye","doi":"10.1093/procel/pwaf012","DOIUrl":"10.1093/procel/pwaf012","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"478-483"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449645","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}
引用次数: 0
Emerging roles of RNA N4-acetylcytidine modification in reproductive health. RNA n4 -乙酰胞苷修饰在生殖健康中的新作用。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-20 DOI: 10.1093/procel/pwaf013
Zibaguli Wubulikasimu, Hongyu Zhao, Fengbiao Mao, Xiaolu Zhao
{"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}
引用次数: 0
Setd2 overexpression rescues bivalent gene expression during SCNT-mediated ZGA. 在scnt介导的ZGA中,Setd2过表达挽救了二价基因的表达。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-20 DOI: 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}
引用次数: 0
Endothelial-to-Osteoblast Conversion maintains bone homeostasis through Kindlin-2/Piezo1/TGFβ/Runx2 axis. 内皮细胞到成骨细胞的转化通过Kindlin-2/Piezo1/TGFβ/Runx2轴维持骨稳态。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-20 DOI: 10.1093/procel/pwae066
Guixing Ma, Yingying Han, Wanze Tang, Bo Zhou, Litong Chen, Zhen Ding, Siyuan Cheng, Di Chen, Huiling Cao
{"title":"Endothelial-to-Osteoblast Conversion maintains bone homeostasis through Kindlin-2/Piezo1/TGFβ/Runx2 axis.","authors":"Guixing Ma, Yingying Han, Wanze Tang, Bo Zhou, Litong Chen, Zhen Ding, Siyuan Cheng, Di Chen, Huiling Cao","doi":"10.1093/procel/pwae066","DOIUrl":"10.1093/procel/pwae066","url":null,"abstract":"","PeriodicalId":20790,"journal":{"name":"Protein & Cell","volume":" ","pages":"497-502"},"PeriodicalIF":13.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823946","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}
引用次数: 0
Microbiome, metabolome, and transcriptome analyses in esophageal squamous cell carcinoma: insights into immune modulation by F. nucleatum. 食管鳞状细胞癌的微生物组、代谢组和转录组分析:洞察核酸酵母菌的免疫调节作用。
IF 13.6 1区 生物学
Protein & Cell Pub Date : 2025-06-20 DOI: 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}
引用次数: 0
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