Advanced SciencePub Date : 2025-01-28DOI: 10.1002/advs.202410990
Shu Li, Xing Zhou, Liangliang Liu, Zhe Su, Jun Zhao, Jinbo Zhang, Zucong Cai, Josep Peñuelas, Xinqi Huang
{"title":"Plant Diversity Reduces the Risk of Antibiotic Resistance Genes in Agroecosystems.","authors":"Shu Li, Xing Zhou, Liangliang Liu, Zhe Su, Jun Zhao, Jinbo Zhang, Zucong Cai, Josep Peñuelas, Xinqi Huang","doi":"10.1002/advs.202410990","DOIUrl":"https://doi.org/10.1002/advs.202410990","url":null,"abstract":"<p><p>Despite advances in dispersal mechanisms and risk assessment of antibiotic resistance genes (ARGs), how plants influence ARG contamination in agricultural soils remains underexplored. Here, the impacts of plant species and diversity on ARGs and mobile genetic elements (MGEs) in three agricultural soils are comprehensively investigated in a pot experiment. The results indicate that increased plant diversity reduces ARGs and MGEs abundance by 19.2%-51.2%, whereas plant species exhibit inconsistent and soil-dependent effects. Potential bacterial hosts harboring abundant ARGs have greater relative abundance than nonhosts, and both their richness and cumulative relative abundance are reduced by plant diversity. Notably, hosts inhibited by plant diversity present a greater relative abundance than the other hosts. The enriched compounds in root exudates due to plant diversity play a more important role in the metabolic network and contribute to rebalancing of the abundance of potential hosts and nonhosts. An independent test using pure organics reveals that higher resource diversity, resulting from increased plant diversity, reduces the relative abundance and mobility of abundant and high-risk ARGs. This study highlights the resource-mediated mitigation of the risks posed by ARG contamination and indicates that ensuring plant and resource diversity is a promising strategy for controlling ARGs in agroecosystems.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410990"},"PeriodicalIF":14.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-28DOI: 10.1002/advs.202414396
Yanpeng Guo, Xinqi Wei, Cheng Zeng, Xinyu Ji, Yao Liu, Shuhao Wang, Xizheng Liu, Tianyou Zhai, Huiqiao Li
{"title":"In Situ Analysis of Li Plating and Stripping Behaviors Under Dynamic Current Conditions for Realistic Application Scenarios.","authors":"Yanpeng Guo, Xinqi Wei, Cheng Zeng, Xinyu Ji, Yao Liu, Shuhao Wang, Xizheng Liu, Tianyou Zhai, Huiqiao Li","doi":"10.1002/advs.202414396","DOIUrl":"https://doi.org/10.1002/advs.202414396","url":null,"abstract":"<p><p>Lithium metal batteries are considered the holy grail for next-generation high-energy systems. However, lithium anode faces poor reversibility, unsatisfying cyclability and rate capability due to its uncontrollable plating/stripping behavior. While galvanostatic conditions are extensively studied, the behavior under more realistic application scenarios with variable inputs are less explored. Here, an in situ imaging platform using in-plane microdevice configurations is developed to effectively investigate Li plating/stripping behavior under dynamic conditions. This platform offers high detectivity for analyzing the nuclei size, density, distribution, and growth location, rate, and mode. It is for the first time revealed that nuclei density and growth locations remain constant and are solely determined by the initial nucleation overpotentials during dynamic plating. A transition in growth modes from uniform granular growth to tip-induced dendrite growth, and finally to directional growth among the dendrites is also observed. Guided by these findings, a dynamic plating protocol is proposed, which can greatly improve the Li reversibility and cycling stability. This work not only provides a novel approach to visualize the evolution of key nucleation and growth parameters, especially under variable inputs, but also offers valuable guidance for the future industrialization of metal batteries and the rational design of charging facilities.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2414396"},"PeriodicalIF":14.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evenly Distributed Microporous Structure and E7 Peptide Functionalization Synergistically Accelerate Osteogenesis and Angiogenesis in Engineered Periosteum.","authors":"Qihong Li, Chen Li, Jun Yan, Chunli Zhang, Yu Jiang, Xiantong Hu, Liwei Han, Li Li, Peng Wang, Lingzhou Zhao, Yantao Zhao","doi":"10.1002/advs.202406084","DOIUrl":"https://doi.org/10.1002/advs.202406084","url":null,"abstract":"<p><p>Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2406084"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-27DOI: 10.1002/advs.202410063
Weinan Du, Jun Huang, Aizhen Zhang, Fangfang Zhao, Tianwen Chen, Quinn M McDermott, Tony Zheng, Haibo Wang, Rongli Zhang, Xiaolin Zhang, Jerome Allison, Hong Zhu, Wu Zhou, Qing Yin Zheng
{"title":"Long-Lasting Auditory and Vestibular Recovery Following Gene Replacement Therapy in a Novel Usher Syndrome Type 1c Mouse Model.","authors":"Weinan Du, Jun Huang, Aizhen Zhang, Fangfang Zhao, Tianwen Chen, Quinn M McDermott, Tony Zheng, Haibo Wang, Rongli Zhang, Xiaolin Zhang, Jerome Allison, Hong Zhu, Wu Zhou, Qing Yin Zheng","doi":"10.1002/advs.202410063","DOIUrl":"https://doi.org/10.1002/advs.202410063","url":null,"abstract":"<p><p>Usher syndrome type 1C (USH1C) is a genetic disorder caused by mutations in the USH1C gene, which encodes harmonin, a key component of the mechanoelectrical transduction complex in auditory and vestibular hair cells. USH1C leads to deafness and vestibular dysfunction in humans. An Ush1c knockout (KO) mouse model displaying these characteristic deficits is generated in our laboratory. To examine gene replacement therapy (GT) in this model, a synthetic adeno-associated viral vector, Anc80L65, driving harmonin expression is administered, to the inner ears of Ush1c KO mice at postnatal day 2 (P2). Remarkably, this single treatment significantly improved auditory brainstem response (ABR) thresholds and balance motor function at 1 month post-injection, with these effects persisting for up to 10 months. At 12 months post-treatment, the vestibular function is assessed using the vestibular-ocular reflexes (VOR) and single vestibular afferent recordings. The GT treatment significantly restored both the canal and otolith VORs and increased vestibular afferent spontaneous firing rates and responses to head rotation and translation. These findings provide the first evidence of long-lasting restoration of both the auditory and vestibular functions by GT in a novel mouse model of Usher syndrome, highlighting the potential of GT for treating deficits associated with USH1C.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2410063"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"METTL3 Potentiates M2 Macrophage-Driven MMT to Aggravate Renal Allograft Fibrosis via the TGF-β1/Smad3 Pathway.","authors":"Qinfan Yao, Xiaoxiao Zheng, Xinyi Zhang, Yucheng Wang, Qin Zhou, Junhao Lv, Li Zheng, Jiahua Lan, Wei Chen, Jianghua Chen, Dajin Chen","doi":"10.1002/advs.202412123","DOIUrl":"https://doi.org/10.1002/advs.202412123","url":null,"abstract":"<p><p>METTL3, a key enzyme in N6-methyladenosine (m6A) modification, plays a crucial role in the progression of renal fibrosis, particularly in chronic active renal allograft rejection (CAR). This study explored the mechanisms by which METTL3 promotes renal allograft fibrosis, focusing on its role in the macrophage-to-myofibroblast transition (MMT). Using a comprehensive experimental approach, including TGF-β1-induced MMT cell models, METTL3 conditional knockout (METTL3 KO) mice, and renal biopsy samples from patients with CAR, the study investigates the involvement of METTL3/Smad3 axis in driving MMT and renal fibrosis during the episodes of CAR. We found that elevated m6A modification and METTL3 levels strongly correlated with enhanced MMT and increased fibrotic severity. METTL3 knockout (METTL3 KO) significantly increased the m6A modification of Smad3, decreased Smad3 expression, and inhibited M2-driven MMT. Smad3 knockdown with siRNA (siSmad3) further inhibited M2-driven MMT, while Smad3 overexpression rescued the inhibitory effects of METTL3 silencing, restoring M2-driven MMT and fibrotic tissue damage. Additionally, the METTL3 inhibitor STM2457 effectively reversed M2-driven MMT and alleviated fibrotic tissue damage in CAR. These findings highlight that METTL3 enhances M2-driven MMT in renal fibrosis during CAR by promoting the TGF-β1/Smad3 axis, suggesting that METTL3 is a promising therapeutic target for mitigating renal fibrosis in CAR.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2412123"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pressure-Induced Emission Enhancement of Multi-Resonance o-Carborane Derivatives via Exciton‒Vibration Coupling Suppression.","authors":"Zening Li, Qing Zhang, Fangxiang Sun, Chunyan Lv, Xinmiao Meng, Yu Hu, Dongqian Xu, Chengjian Li, Lei Li, Kai Wang, Yujian Zhang","doi":"10.1002/advs.202411765","DOIUrl":"https://doi.org/10.1002/advs.202411765","url":null,"abstract":"<p><p>Polycyclic multiple resonance (MR) molecules reveal narrowband emission, making them very promising emitters for high color purity display. Nevertheless, they still have challenges such as aggregation-induced emission quenching and spectral broadening. Overcoming these obstacles requires an in-depth understanding of the correlations among the alterations in their geometries, packing structures, and molecular vibrations and their corresponding changes in their photoluminescence (PL) properties. Herein, it is demonstrated that high-pressure infrared, UV-visible absorption, and fluorescence spectroscopies can be combined with computational results to elucidate the influence of the subtle structural variations on the exciton‒vibration couplings and their PL properties. An ortho-carborane-decorated MR emitter (BNC) is a piezochromic molecule and exhibits emission enhancement under high pressure. A thorough analysis of the in situ experimental measurements and calculated results reveals that the pressure-induced changes in the exciton binding energy and exciton‒vibration couplings are responsible for the unusual piezochromism. This research provides insights into the structure‒fluorescence relationship and potential for high-pressure techniques to optimize MR materials for advanced organic light-emitting diodes (OLEDs) applications.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2411765"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-27DOI: 10.1002/advs.202414195
Qingmei Xu, Yuntong Wang, Songtao Dou, Yang Xu, Zhenhe Xu, Han Xu, Yi Zhang, Yanming Xia, Ying Xue, Hang Li, Xiao Ma, Kunlong Zhang, Huan Wang, Fengzhou Ma, Qi Wang, Bei Li, Wei Wang
{"title":"High-Viability Circulating Tumor Cells Sorting From Whole Blood at Single Cell Level Using Laser-Induced Forward Transfer-Assisted Microfiltration.","authors":"Qingmei Xu, Yuntong Wang, Songtao Dou, Yang Xu, Zhenhe Xu, Han Xu, Yi Zhang, Yanming Xia, Ying Xue, Hang Li, Xiao Ma, Kunlong Zhang, Huan Wang, Fengzhou Ma, Qi Wang, Bei Li, Wei Wang","doi":"10.1002/advs.202414195","DOIUrl":"https://doi.org/10.1002/advs.202414195","url":null,"abstract":"<p><p>The efficient isolation and molecular analysis of circulating tumor cells (CTCs) from whole blood at single-cell level are crucial for understanding tumor metastasis and developing personalized treatments. The viability of isolated cells is the key prerequisite for the downstream molecular analysis, especially for RNA sequencing. This study develops a laser-induced forward transfer -assisted microfiltration system (LIFT-AMFS) for high-viability CTC enrichment and retrieval from whole blood. The LIFT-compatible double-stepped microfilter (DSMF), central to this system, comprises two micropore layers: the lower layer's smaller micropores facilitate size-based cell separation, and the upper layer's larger micropores enable liquid encapsulating captured cells. By optimizing the design of the DSMFs, the system has a capture efficiency of 88% at the processing throughput of up to 15.0 mL min<sup>-1</sup> during the microfilter-based size screening stage, with a single-cell yield of over 95% during the retrieval stage. The retrieved single cells, with high viability, are qualified for ex vivo culture and direct RNA sequencing. The cDNA yield from isolated CTCs surpassed 4.5 ng, sufficient for library construction. All single-cell sequencing data exhibited Q30 scores above 95.92%. The LIFT-AMFS shows promise in cellular and biomedical research.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2414195"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-27DOI: 10.1002/advs.202415772
Yao Xiao, Jinjin Ma, Xiaonan Yuan, Huan Wang, Fengyu Ma, Jun Wu, Qianglong Chen, Jie Hu, Lijie Wang, Zhendong Zhang, Chao Wang, Jiaying Li, Weishan Wang, Bin Li
{"title":"Acid-Triggered Dual-Functional Hydrogel Platform for Enhanced Bone Regeneration.","authors":"Yao Xiao, Jinjin Ma, Xiaonan Yuan, Huan Wang, Fengyu Ma, Jun Wu, Qianglong Chen, Jie Hu, Lijie Wang, Zhendong Zhang, Chao Wang, Jiaying Li, Weishan Wang, Bin Li","doi":"10.1002/advs.202415772","DOIUrl":"https://doi.org/10.1002/advs.202415772","url":null,"abstract":"<p><p>Stem cell implantation holds promise for enhancing bone repair, but risks of pathogen transmission and malignant cell transformation should not be ignored. Compared to stem cell implantation, recruitment of endogenous stem cells to injured sites is more critical for in situ bone regeneration. In this study, based on the acidic microenvironment of bone injury, an HG-AA<sub>1:1</sub>-SDF-1α composite hydrogel with a dual-control intelligent switch function is developed by incorporating stromal cell-derived factor (SDF-1α), arginine carbon dots (Arg-CDs), and calcium ions (Ca<sup>2+</sup>) into the oxidized hyaluronic acid/gelatin methacryloyl (HG) hydrogel. The acidic microenvironment triggers the first switch (Schiff base bond is broken between HG-AA<sub>1:1</sub> and SDF-1α) of HG-AA<sub>1:1</sub>-SDF-1α composite hydrogel to continuously release SDF-1α. Compared to the neutral (pH 7.4) media, the cumulative release of SDF-1α in acidic (pH 5.5) media is ≈2.5 times higher, which enhances the migration and recruitment of endogenous mesenchymal stem cells (MSCs). The recruited MSCs immediately initiate the second switch and metabolize Arg-CDs into the bioactive nitric oxide (NO) in the presence of Ca<sup>2+</sup>, activating NO/cyclic guanosine monophosphate (cGMP) signaling pathway to promote angiogenesis. Therefore, the engineered HG-AA<sub>1:1</sub>-SDF-1α composite hydrogel shows promising potential to achieve \"coupling osteogenesis and angiogenesis\" for bone regeneration.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2415772"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-27DOI: 10.1002/advs.202407494
Xin Cui, Yueming Zhu, Lidan Zeng, Mengyuan Zhang, Amad Uddin, Theresa W Gillespie, Lauren E McCullough, Shaying Zhao, Mylin A Torres, Yong Wan
{"title":"Pharmacological Dissection Identifies Retatrutide Overcomes the Therapeutic Barrier of Obese TNBC Treatments through Suppressing the Interplay between Glycosylation and Ubiquitylation of YAP.","authors":"Xin Cui, Yueming Zhu, Lidan Zeng, Mengyuan Zhang, Amad Uddin, Theresa W Gillespie, Lauren E McCullough, Shaying Zhao, Mylin A Torres, Yong Wan","doi":"10.1002/advs.202407494","DOIUrl":"10.1002/advs.202407494","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) in obese patients remains challenging. Recent studies have linked obesity to an increased risk of TNBC and malignancies. Through multiomic analysis and experimental validation, a dysfunctional Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3H)/Yes-associated protein (YAP) proteolytic axis is identified as a pivotal junction mediating the interplay between cancer-associated adipocytes and the response to anti-cancer drugs in TNBC. Mechanistically, cancer-associated adipocytes drive metabolic reprogramming resulting in an upregulated hexosamine biosynthetic pathway (HBP). This aberrant upregulation of HBP promotes YAP O-GlcNAcylation and the subsequent recruitment of EIF3H deubiquitinase, which stabilizes YAP, thus promoting tumor growth and chemotherapy resistance. It is found that Retatrutide, an anti-obesity agent, inhibits HBP and YAP O-GlcNAcylation leading to increased YAP degradation through the deprivation of EIF3H-mediated deubiquitylation of YAP. In preclinical models of obese TNBC, Retatrutide downregulates HBP, decreases YAP protein levels, and consequently decreases tumor size and enhances chemotherapy efficacy. This effect is particularly pronounced in obese mice bearing TNBC tumors. Overall, these findings reveal a critical interplay between adipocyte-mediated metabolic reprogramming and EIF3H-mediated YAP proteolytic control, offering promising therapeutic strategies to mitigate the adverse effects of obesity on TNBC progression.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2407494"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced SciencePub Date : 2025-01-27DOI: 10.1002/advs.202409641
Yiming Leng, Wei Wang, Jun Lu, Jingyuan Chen, Xuliang Chen, Yalan Li, Jie Wang, Yuanyuan Liu, Qian Tan, Wenjing Yang, Youxiang Jiang, Peiyuan Huang, Jingjing Cai, Hong Yuan, Liang Weng, Qingbo Xu, Yao Lu
{"title":"Endothelial TRIM35-Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts.","authors":"Yiming Leng, Wei Wang, Jun Lu, Jingyuan Chen, Xuliang Chen, Yalan Li, Jie Wang, Yuanyuan Liu, Qian Tan, Wenjing Yang, Youxiang Jiang, Peiyuan Huang, Jingjing Cai, Hong Yuan, Liang Weng, Qingbo Xu, Yao Lu","doi":"10.1002/advs.202409641","DOIUrl":"https://doi.org/10.1002/advs.202409641","url":null,"abstract":"<p><p>Vascular calcification is a highly regulated process in cardiovascular disease (CVD) and is strongly correlated with morbidity and mortality, especially in the adverse stage of vascular remodeling after coronary artery bypass graft surgery (CABG). However, the pathogenesis of vascular graft calcification, particularly the role of endothelial-smooth muscle cell interaction, is still unclear. To test how ECs interact with SMCs in artery grafts, single-cell analysis of wild-type mice is first performed using an arterial isograft mouse model and found robust cytokine-mediated signaling pathway activation and SMC proliferation, together with upregulated endothelial tripartite motif 35 (TRIM35) expression. Unexpectedly, severe SMC calcification in artery grafts is found in TRIM35 conditional endothelial knockout (cKO) mice. Calcified medium (comprising calcium chloride and beta-glycerophosphate)-induced calcium deposition in vitro is also found in SMCs cocultured with TRIM35 knockout endothelium. This extraordinary phenomenon is further confirmed to be induced by increased MMP10 secretion. Mechanistically, endothelial TRIM35 inhibits MMP10 expression and secretion by promoting K63-linked ubiquitination of RelB and maintaining its nuclear localization, consequently inhibiting nuclear transcription of MMP10 through the noncanonical NF-κB signaling pathway. Targeting MMP10 in situ in arterial isografts can effectively alleviate vascular calcification caused by conditional endothelial TRIM35 knockout. These findings demonstrated that TRIM35 inhibited vascular calcification during arterial isograft remodeling, a process that is driven by the aberrant secretion of endothelial MMP10. Targeting MMP10 pathway may be a potential therapeutic strategy for vascular calcification in vessel grafts.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2409641"},"PeriodicalIF":14.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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