Yuan Liu, Kai Huang, Sheng-Liang Zhou, Shuai Li, Hai-Bo Si, Yi Zeng, Hui-Qi Xie, Bin Shen
{"title":"Engineered exosomal miR140 modulates mitophagy of chondrocytes through targeting CAPN1 to alleviate osteoarthritis.","authors":"Yuan Liu, Kai Huang, Sheng-Liang Zhou, Shuai Li, Hai-Bo Si, Yi Zeng, Hui-Qi Xie, Bin Shen","doi":"10.1007/s11427-024-2843-7","DOIUrl":"10.1007/s11427-024-2843-7","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a prevalent degenerative disease involving mitophagy dysfunction of chondrocytes. As OA progresses, miR140 expression in chondrocytes decreases, and its therapeutic potential has shown protective effects. However, the variation in mitophagy across different stages of OA in human chondrocytes, as well as the role of miR140 in modulating mitophagy, have remained insufficiently elucidated. In this study, we observed that mitochondrial morphology deteriorates with OA progression, from mild swelling in the early stage of OA (E-OA) to disrupted cristae in the mid-to-late stage of OA (ML-OA). Mitophagy levels were mildly elevated in E-OA chondrocytes compared with normal controls, whilst ML-OA chondrocytes exhibited significantly reduced and impaired mitophagy. Notably, miR140 was found to down-regulate CAPN1, an intracellular cysteine protease affecting mitochondrial and lysosomal membranes. Targeting the miR140/CAPN1 axis was revealed to improve mitochondrial morphology, decrease reactive oxygen species (ROS) accumulation, and promote mitophagy in chondrocytes. To further overcome the inherent instability and limited bioavailability of miR140 when administered directly, engineered exosomes overexpressing miR140 derived from human urine-derived stem cells (hUSCs-140-Exos) were constructed. In vitro, hUSCs-140-Exos were demonstrated to promote mitophagy and preserve mitochondrial function. Moreover, intra-articular injection of hUSCs-140-Exos in vivo effectively delivered miR140 to OA chondrocytes, resulting in improved gait, restoration of subchondral bone structure, and mitigation of OA progression. Overall, this study provides a novel and promising strategy for OA treatment, demonstrating significant therapeutic potential.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2617-2634"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conservation epigenomics: integrating epigenetic mechanisms into species conservation.","authors":"Yisi Hu, Wenliang Zhou, Fuwen Wei","doi":"10.1007/s11427-025-2945-4","DOIUrl":"10.1007/s11427-025-2945-4","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2800-2803"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuanqing Xu, Bentao Wu, Mario Vallejo-Marín, Peter Bernhardt, Mark Jankauski, De-Zhu Li, Stephen Buchmann, Jianing Wu, Hong Wang
{"title":"Vibration mechanics involved in buzz pollination lead to size-dependent associations between bumblebees and Pedicularis flowers.","authors":"Yuanqing Xu, Bentao Wu, Mario Vallejo-Marín, Peter Bernhardt, Mark Jankauski, De-Zhu Li, Stephen Buchmann, Jianing Wu, Hong Wang","doi":"10.1007/s11427-024-2858-5","DOIUrl":"10.1007/s11427-024-2858-5","url":null,"abstract":"<p><p>Floral traits modify pollinator behavior and shape the plant-pollinator interaction pattern at ecological and evolutionary levels. Biomechanical traits are important in mediating interactions between flowers and their pollinators in some cases, such as in buzz pollination. During buzz pollination, a bee produces vibrations using its thoracic muscles and transfers these vibrations primarily through its mandibles as it bites the flower. The interaction between buzz-pollinated flowers and their pollinators is influenced by their physical size relative to each other, but the drivers of these size-dependent associations remain unclear. Using eight beaked louseworts (Pedicularis) as a model system, we combined behavioral observations, biomechanical analyses, and pollinator network analyses to test the hypothesis that the location of where a bee bites should constrain the interaction between Pedicularis and bumblebees during buzz pollination. We found that bumblebees always chose to bite the same site at the base of the floral beak when buzzing Pedicularis, and this site is optimal for transferring vibrations from the bee to release pollen from the anthers. Bee bodies must be long enough for the mandibles to clamp onto the same optimal site on the floral beak, while its pollen-collecting abdomen is positioned at the opening of the floral beak where pollen grains are ejected. Our pollination networks showed size matching between the floral beak length of each Pedicularis species and the body length of individual bumblebees regardless of bee species. These results suggest that the optimal excitation point on the Pedicularis flower links a suite of floral traits to its pollinators' dimensions, potentially contributing to prezygotic isolation among co-flowering, sympatric Pedicularis species.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2503-2514"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alpha-ketoglutarate restores oral epithelial homeostasis via FOXM1-mediated cell cycle regulation.","authors":"Yuan Wang, Yimeng Cai, Qi Yin, Shuqin Cao, Yuyu Li, Yuhan Li, Qiwen Li, Qian Wang, Pochun Lin, Li Mei, Malcolm Xing, Leixiao Yu, Zhipeng Fan, Quan Yuan","doi":"10.1007/s11427-024-2984-1","DOIUrl":"https://doi.org/10.1007/s11427-024-2984-1","url":null,"abstract":"<p><p>The rapid repair of intraoral mucosal injuries is crucial for restoring oral epithelial homeostasis. Alpha-ketoglutarate (αKG), a multi-potential metabolite involved in protein synthesis, epigenetic regulation, and immune response, holds the potential in tissue homeostasis and wound repair. Here, we report that administration of αKG accelerates palatal wound healing, with enhanced re-epithelialization and increased collagen deposition. αKG increases the number of Ki67<sup>+</sup> cells in the palatal epithelium and elevates the percentage of EdU<sup>+</sup> cells in cultured human gingival epithelial cells (HGEs). Importantly, αKG treatment upregulates cell cycle-related pathways, primarily modulating the activity of CDK1-cyclin A and CDK1-cyclin B complexes. Mechanistically, αKG promotes the expression of FOXM1 and mediates the downstream cell cycle regulation. To further optimize local delivery of αKG, we develop the polyethyleneimine (PEI)/polyacrylic acid (PAA)/αKG supramolecular network to promote oral wound healing. Taken together, our findings demonstrate that αKG restores oral epithelial homeostasis via FOXM1-mediated cell cycle regulation, highlighting its therapeutic potential for oral wound repair.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":""},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Flooding followed by drought in urban and forest soils: unraveling microbial dynamics and ecological functions.","authors":"Yilong Hao, Yifang Zhang, Changyi Lu, Anqi Sun, Qing-Lin Chen","doi":"10.1007/s11427-024-2893-1","DOIUrl":"10.1007/s11427-024-2893-1","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2813-2816"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuekai Wang, Hu Li, Jianrui Li, Lei Lei, Jingchen Xu, Han Sun, Jiayu Li, Jing Jiang, Hongying Li, Mei Tang, Biao Dong, Yue Gong, Jiandong Jiang, Zonggen Peng
{"title":"Berberine dissociates mitochondrial complex I by SIRT3-dependent deacetylation of NDUFS1 to improve hepatocellular glucose and lipid metabolism.","authors":"Xuekai Wang, Hu Li, Jianrui Li, Lei Lei, Jingchen Xu, Han Sun, Jiayu Li, Jing Jiang, Hongying Li, Mei Tang, Biao Dong, Yue Gong, Jiandong Jiang, Zonggen Peng","doi":"10.1007/s11427-024-2834-8","DOIUrl":"10.1007/s11427-024-2834-8","url":null,"abstract":"<p><p>Many metabolic diseases show mitochondrial abnormalities because of dysfunction of complex I (CI). Therefore, the discovery of drugs that target the CI is of great interest. Berberine (BBR) is a botanic agent and has been included in the latest ESC/EAS Guidelines for the management of dyslipidemias. Here, we showed that BBR enters hepatocyte mitochondria after oral administration and improves glucose and lipid metabolism by reducing oxidative phosphorylation in hepatocytes. BBR inhibits CI function rapidly, selectively, and reversibly, not by directly inhibiting CI enzyme activity but by reducing the abundance of CI in the mitochondria through dissociation of CI. BBR directly binds to and activates Sirtuin 3 (SIRT3), thereby reducing acetylation of the catalytic subunit NDUFS1 in the N-module of CI, leading to dissociation of mitochondrial CI. Conclusively, BBR, as a mitochondria-homing agent, selectively and reversibly dissociates mitochondrial CI through SIRT3-dependent NDUFS1 deacetylation to improve hepatocellular glucose and lipid metabolism, highlighting that CI may be a promising target for innovative natural products to treat metabolic diseases.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2676-2696"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in the chemical synthesis of human proteoforms.","authors":"Ziyi Yang, Yudi Xiao, Yang Shi, Lei Liu","doi":"10.1007/s11427-024-2860-5","DOIUrl":"10.1007/s11427-024-2860-5","url":null,"abstract":"<p><p>Access to structurally-defined human proteoforms is essential to the biochemical studies on human health and medicine. Chemical protein synthesis provides a bottom-up and atomic-resolution approach for the preparation of homogeneous proteoforms bearing any number of post-translational modifications of any structure, at any position, and in any combination. In this review, we summarize the development of chemical protein synthesis, focusing on the recent advances in synthetic methods, product characterizations, and biomedical applications. By analyzing the chemical protein synthesis studies on human proteoforms reported to date, this review demonstrates the significant methodological improvements that have taken place in the field of human proteoform synthesis, especially in the last decade. Our analysis shows that although further method development is needed, all the human proteoforms could be within reach in a cost-effective manner through a divide-and-conquer chemical protein synthesis strategy. The synthetic proteoforms have been increasingly used to support biomedical research, including spatial-temporal studies and interaction network analysis, activity quantification and mechanism elucidation, and the development and evaluation of diagnostics and therapeutics.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2515-2549"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unique structures and functions of ATP-binding cassette type H transporters.","authors":"Qing X Li","doi":"10.1007/s11427-025-2956-6","DOIUrl":"10.1007/s11427-025-2956-6","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2820-2822"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KIAA1522 isoform switching regulates LTR-RTs activity in distinct pluripotency states of hESCs.","authors":"Ning Yang, Wen Sun, Shiwei Cao, Chen Zhao, Nannan Wang, Pengcheng Li, Yu Zou, Siqi Wang, Tongtong Cui, Shuyu Guo, Wei Li, Haoyi Wang, Guihai Feng","doi":"10.1007/s11427-025-2972-1","DOIUrl":"10.1007/s11427-025-2972-1","url":null,"abstract":"<p><p>Human embryonic stem cells (hESCs) can be classified as having naïve and primed pluripotency states. While several studies have reported different gene expression networks between these two pluripotency states, the role of alternative splicing (AS) in regulating these differences has not been well characterized. In this study, we performed RNA sequencing and identified differential AS events in 784 genes between naïve and primed hESCs. Among these, KIAA1522, whose function has not been well studied, has state-specific isoforms regulated by alternative first exon (AFE). This splicing event resulted in isoforms with distinct N-terminal domains and subcellular localization. Notably, the sequences and alternative isoform patterns of KIAA1522 were conserved between humans and mice. Further investigation using cleavage under targets and tagmentation (CUT&Tag) experiments in cells with specific-isoform overexpression or knockdown revealed the opposite activity of long terminal repeat retrotransposons (LTR-RTs) and motif enrichment profiles. The naïve-specific (N-P) isoform upregulated naïve marker gene expression and preferentially activated LTR-RTs by binding to the motifs enriched for POU and FOX family transcription factor binding sites. Conversely, the primed-specific (P-P) isoform promoted primed marker gene expression and suppressed LTR-RTs activity by binding to the motifs enriched for zinc finger protein binding sites. Collectively, KIAA1522 regulates the balance between naïve and primed pluripotency states through isoform-specific regulation of LTR-RTs activity and collaboration with distinct transcriptional regulators. In summary, our results characterize the splicing atlas of hESCs in naïve and primed states and reveal the regulatory function and mechanism of AFE usage by KIAA1522.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2635-2647"},"PeriodicalIF":9.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}