Clinical and Translational Medicine最新文献

{"title":"Single-cell transcriptomic analysis reveals subtle fluctuations of oocyte cryopreservation on mouse early embryo development.","authors":"Yixin Ren, Qingyang Zhang, Fanqing Xu, Yao Li, Tianyi Liao, Mengyuan Zhao, Zhiqiang Yan, Xiaohui Zhu, Nan Wang, Peng Yuan, Gary D Smith, Jie Qiao, Jie Yan, Liying Yan, Qilong He","doi":"10.1002/ctm2.70801","DOIUrl":"10.1002/ctm2.70801","url":null,"abstract":"<p><strong>Background: </strong>Oocyte cryopreservation is widely used in assisted reproductive technology, but its effects on embryonic development remain a concern. This study aimed to determine whether oocyte cryopreservation induces transcriptional alterations at the early cleavage and blastocyst stages.</p><p><strong>Methods: </strong>We performed single-cell RNA sequencing on mouse Metaphase II oocyte and embryos at early/late 1 cell, early/late 2 cell, morula and blastocyst stages derived from cryopreserved (cryo) and fresh (fresh) oocytes. Transcriptomic profiles were compared between the two groups.</p><p><strong>Results: </strong>Global transcriptomes were highly similar between cryo and fresh blastocysts. Oocyte cryopreservation did not alter the sex ratio or the developmental progression through preimplantation development. In blastocysts, cryopreservation affected only a few individual genes. In both male and female blastocysts, although oocyte cryopreservation increased the proportion of low Xist-expressing cells, it did not disrupt X-linked gene dosage. In the inner cell mass (ICM) of blastocysts, a negative correlation between X-linked gene expression and cell cycle progression was identified, and this negative correlation was more pronounced in trophectoderm (TE) cells. Overall, this stage-dependent coordination remained unperturbed by cryopreservation. CellChat analysis revealed that the signalling interaction strength between ICM and TE also showed no significant changes in the cryo group.</p><p><strong>Conclusions: </strong>Oocyte cryopreservation does not severely disrupt overall transcriptional integrity, developmental potency and X-chromosome dosage compensation of embryos, but it may cause subtle molecular changes. These findings highlight the need for continued refinement of cryopreservation methods and further investigation into the sub-acute safety of assisted reproductive technology procedures.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70801"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of cell-free RNA in seminal plasma reveals functional links to spermatogenic impairment","authors":"Qing Zhou,&nbsp;Yuting Jiang,&nbsp;Fagui Yue,&nbsp;Chaoxing Wang,&nbsp;Tingyu Yang,&nbsp;Yulong Qin,&nbsp;Chengbin Hu,&nbsp;Zhongzhen Liu,&nbsp;Yuwei Liu,&nbsp;Jinghua Sun,&nbsp;Fang Chen,&nbsp;Ya Gao,&nbsp;Xin Jin,&nbsp;Ruizhi Liu,&nbsp;Wen-Jing Wang,&nbsp;Hongguo Zhang","doi":"10.1002/ctm2.70788","DOIUrl":"10.1002/ctm2.70788","url":null,"abstract":"&lt;p&gt;To the Editor,&lt;/p&gt;&lt;p&gt;We provide a systematic multi-class cell-free RNA (cfRNA) atlas of seminal plasma, establishing it as a powerful, non-invasive strategy that both elucidates molecular mechanisms underlying spermatogenic impairment and offers candidate biomarkers to optimize the outcome of assisted reproductive technology (ART) before treatment for infertile men.&lt;/p&gt;&lt;p&gt;Seminal plasma is a promising, non-invasive source of biomarkers for diagnosing and treating male infertility. However, the absence of systematic characterization of seminal cfRNA hinders our understanding of the full molecular diversity in seminal plasma and limits the development of clinical strategies for male infertility.&lt;/p&gt;&lt;p&gt;We established a comprehensive multi-class cfRNA atlas of human seminal plasma from 419 men, including 101 healthy individuals, 128 with reduced sperm motility (defined as AZS), 93 with reduced sperm number and motility (defined as OAS), and 97 with azoospermia (AZO) (Figure 1A; Figure S1; Tables S1 and S2; Materials and Methods). After quality control (Figure S2), we robustly detected diverse small and long RNA in human seminal plasma (Table S3). Long RNA (mRNA and lncRNA) constituted the largest proportion, followed by transfer RNA (tRNA) and piwi-RNA (piRNA) (Figure 1B). For microRNA (miRNA), we also captured biologically relevant species (Figure S3). The fragments of 17–33 nucleotides with a strong bias for a 5′-terminal uridine (1U bias) provided evidence for the existence of mature piRNA in seminal plasma (Figure 1C), and the most abundant tRNA and their fragmentation patterns were consistent with those in mouse and human sperm (Figure 1D,E; Figure S4).&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; Thus, seminal cfRNA offers a unique window into the dynamic RNA payload switch, whereby epididymosomes deliver tRNA fragments that largely replace piRNA during epididymal transit.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; By deconvoluting the testicular cellular origins of seminal cfRNA, macrophages showed the highest contribution score (Figure 1F; Table S4), aligning with the known presence of immune modulators in seminal plasma.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; We also detected significant signals from germ cells across multiple stages, indicating the release of RNA from the entire spermatogenic lineage. Our findings suggest seminal plasma as a rich source of molecular information reflecting testicular microenvironment dynamics.&lt;/p&gt;&lt;p&gt;Next, we observed distinct cfRNA composition shifts across infertility subtypes, most notably in AZO patients across all RNA classes (Figure 2A). Differential abundance analysis identified hundreds of altered cfRNA (Figure 2B; Table S5, adjusted &lt;i&gt;p&lt;/i&gt;-value &lt; .05 and |log&lt;sub&gt;2&lt;/sub&gt;(fold change)| ≥ 1), with declined mRNA involving core spermatogenic functions, including piRNA metabolic pathways (Figure 2C,D). Strikingly, pachytene piRNA was preferentially decreased in patients with AZS and a substantial fraction became undetectable in patients with AZ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why is nanomedicine needed to treat disorders of the endometrium?","authors":"Saed Abbasi, Laura M Ensign","doi":"10.1002/ctm2.70811","DOIUrl":"10.1002/ctm2.70811","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70811"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan metabolism in colorectal cancer: From mechanistic insights to novel therapeutic strategies.","authors":"Ran Wang, Wenke Shen, Ping Yang, Dongxue Yang, Yuepeng Cao, Yuping Zhou","doi":"10.1002/ctm2.70831","DOIUrl":"10.1002/ctm2.70831","url":null,"abstract":"<p><strong>Background: </strong>Tryptophan metabolism drives colorectal cancer (CRC) pathogenesis through three interconnected cascades: the kynurenine pathway, the serotonin pathway, and the gut-microbiota-dominated indole pathway. These pathways exert context-dependent dual activities determined by disease stage, metabolite concentration, cell type and tumor microenvironment. Substrate competition and metabolic flux redistribution occur across the three branches, while extra-intestinal tryptophan metabolites mediate multi-organ crosstalk. Despite substantial preclinical findings, clinical translation is hindered by imperfect predictive biomarkers, therapeutic bypass resistance and insufficient causal evidence for the microbiota-metabolite-host axis.</p><p><strong>Main body: </strong>This review summarizes biotransformation features and substrate-competing networks of tryptophan metabolism. The kynurenine pathway, responsible for approximately 95% of systemic tryptophan catabolism, exerts stage-dependent dual roles. Its plasma- and feces-derived metabolites and rate-limiting enzyme indoleamine 2,3-dioxygenase 1 show diagnostic and prognostic potential, yet monotherapies targeting this enzyme yield poor outcomes due to interleukin-4-induced gene 1-mediated bypass resistance. The serotonin pathway accounts for only 1%-2% of tryptophan flux; it is predominantly tumor-promoting and protective solely in early-phase colitis-associated tumorigenesis. Selective serotonin reuptake inhibitors hold promise for chemoprevention and immunotherapy sensitization. The microbiota-governed indole pathway generates diverse compounds: indole-3-lactic acid, indole-3-acetic acid and indole-3-propionic acid boost programmed cell death protein 1 (PD-1)-based therapeutic efficacy; indole-3-acrylic acid and 3-methylindole facilitate tumor progression; indole-3-acetaldehyde displays concentration-dependent bidirectional effects. We also discuss natural-product-based and microbiota-targeted interventions, as well as key experimental bottlenecks.</p><p><strong>Conclusion: </strong>Preclinical metabolite-guided personalized therapy for CRC requires multi-omics, stable-isotope tracing and organoid-based large-scale prospective cohorts. Standardized patient stratification and clarification of causal metabolic networks are urgently needed.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70831"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13574542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148966754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence-based ranking of diabetes prevention in prediabetes: A comprehensive network meta-analysis of 378 randomised controlled trials.","authors":"Bucur Maria, Eperjesi Orsolya, Panait Robert Iulian, Topala Mihaela, Babakhani Avin Aphrodite, Rancz Anett, Kói Tamás, Fazekas Karen, Obeidat Mahmoud, Papp Renáta, Ferdinándy Péter, Szentesi Andrea, Gheorghe Cristian, Hegyi Peter, Bunduc Stefania","doi":"10.1002/ctm2.70829","DOIUrl":"10.1002/ctm2.70829","url":null,"abstract":"<p><strong>Background: </strong>Ten percent of the global population presents impaired glucose tolerance. Although numerous interventions have been investigated to prevent type 2 diabetes (T2D), their comparative effectiveness remains uncertain. In this study, we assessed and ranked current pharmacological and non-pharmacological interventions for preventing diabetes in individuals with prediabetes.</p><p><strong>Methods: </strong>The study protocol was registered on PROSPERO (CRD42023473875). Randomised controlled trials (RCTs) reporting on adult patients with prediabetes undergoing any intervention addressing dysglycaemia were eligible. Our systematic search was conducted from database inception to 19 December 2025 in three databases (MEDLINE, Embase and Cochrane Library [CENTRAL]). Network meta-analysis was performed using the random-effect frequentist method. Our primary outcomes were the incidence of T2D, haemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and 2-h glucose after the glucose oral tolerance test (2hPG) expressed as relative risk (RR) and mean difference (MD), respectively, with the corresponding 95% confidence intervals (CIs).</p><p><strong>Results: </strong>We included 378 RCTs comprising 113 122 patients. The highest risk reduction for T2D when compared with control was obtained with dual incretin-based therapy (glucagon-like peptide 1 [GLP-1] and gastric inhibitory polypeptide (GIP) receptor agonists [GLP-1 + GIP RAs]) (RR = .1, CI [.05;  .21]), with GLP-1 receptor agonists (GLP-1 RAs) ranking second (RR = .26, CI [.19;  .4]) followed closely by metformin plus intensive lifestyle intervention (ILI) (RR = .27, CI [.12;  .64]). Only curcumin (MD = -.49, CI [-.70; -.28]), dual GLP-1 + GIP RA (MD = -.46, CI [-.63; -.29]), single GLP-1 RA (MD = -.41, CI [-.50; -.31]) and physical activity (MD = -.35, CI [-.48; -.23]) achieved >.3% HbA1c reductions after 1 year. Sulphonylureas and physical activity were most effective for the 1-year FPG decrease, while the greatest 2hPG reduction was obtained with zinc supplementation and sulphonylureas.</p><p><strong>Conclusion: </strong>Incretin-based therapies, particularly dual GLP-1 + GIP RA and single GLP-1 RA, followed by metformin together with ILI, are the most effective interventions to prevent T2D in patients with prediabetes.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70829"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bevacizumab plus nab-paclitaxel and platinum as second-line therapy for driver-gene-negative non-squamous non-small cell lung cancer after immunochemotherapy: A prospective single-arm single-centre study.","authors":"Ying Lin, Yunbo Yu, Zhihuang Hu, Chenchen Wei, Zezhou Wang, Yao Zhang, Zhenhua Wu, Bo Yu, Xinmin Zhao, Hui Yu, Xianghua Wu, Huijie Wang, Jialei Wang","doi":"10.1002/ctm2.70814","DOIUrl":"10.1002/ctm2.70814","url":null,"abstract":"<p><strong>Background: </strong>Effective second-line therapy is urgently needed for patients with driver-gene-negative non-squamous non-small cell lung cancer (nsqNSCLC) who progress after first-line immunochemotherapy. This study aims to evaluate the efficacy and safety of bevacizumab combined with nab-paclitaxel and platinum (the BAP regimen) in this setting.</p><p><strong>Methods: </strong>This prospective, single-arm, single-centre study enrolled 56 patients with advanced driver-gene-negative nsqNSCLC failing first-line immunochemotherapy. Patients received bevacizumab, nab-paclitaxel, and platinum (carboplatin or cisplatin) for 4-6 cycles, followed by bevacizumab maintenance. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety.</p><p><strong>Results: </strong>All patients had failed first-line platinum-based immunochemotherapy. The confirmed ORR was 46.4% (26/56, 95% confidence interval [CI]: 34.0%-59.3%, p < 0.001), and DCR was 75%. The median PFS and OS were 5.6 (95% CI: 4.35-6.79) and 18.8 (95% CI: 10.31-27.24) months. Patients with ≤ 2 metastatic organs had a significantly longer median PFS than those with >2 metastatic organs (p = 0.014). Multivariable Cox analysis showed that a platinum-free interval <6 months was an independent biomarker of worse PFS. The safety profile was manageable. Plasma proteomics identified baseline high TWEAK level as a potential biomarker for response to both the second-line BAP regimen and first-line immunochemotherapy. Patients with high baseline TWEAK levels before first-line immunochemotherapy showed a median OS of 39.8 months under this sequential treatment modality.</p><p><strong>Conclusions: </strong>The BAP regimen demonstrated preliminary efficacy with manageable safety as a second-line therapy for patients with advanced driver-gene-negative nsqNSCLC after immunochemotherapy. Plasma TWEAK levels may serve as a potential biomarker to help identify patients who might benefit most from this sequential treatment modality, pending further independent validation. Further studies are needed.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70814"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyrroline-5-carboxylate reductase 1 interacts with Nudix hydrolase 5 to drive bladder cancer malignant progression via activation of the APOE/JAK2/STAT3 signalling axis.","authors":"Haotian Chen, Shuya Ji, Pengfei Wu, Ji Liu, Wentao Zhang, Yadong Guo, Jingcheng Zhang, Zhijing Zhang, YanLing Liu, Yongqiang Liu, Chengqi Jin, Sichen Di, Yang Wu, Junfeng Zhang, Xiaojun Zhu, Shiyu Mao, Bing Shen, Xudong Yao","doi":"10.1002/ctm2.70840","DOIUrl":"10.1002/ctm2.70840","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BCa) is one of the most common urological malignancies, with a steadily increasing global incidence. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a metabolic regulator with noncanonical oncogenic functions; however, its protein interaction network and downstream mechanisms in BCa remain incompletely understood.</p><p><strong>Methods: </strong>PYCR1 expression and its clinical significance were evaluated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and tissue microarrays. Cell counting kit-8, colony formation, EdU, 3D Transwell experiments and xenograft models were used to investigate the biological functions of PYCR1. RNA sequencing, Western blot and quantitative polymerase chain reaction (qPCR) were performed to identify its downstream targets. Mass spectrometry combined with co-immunoprecipitation identified Nudix hydrolase 5 (NUDT5) as a PYCR1-interacting protein. Nuclear-cytoplasmic fractionation and adenosine triphosphate (ATP) quantification were used to measure nuclear ATP levels.</p><p><strong>Results: </strong>PYCR1 was upregulated in BCa and promoted tumour proliferation and migration in vitro and in vivo. Mechanistically, PYCR1 interacted with NUDT5 and promoted NUDT5-dependent nuclear ATP generation. Wild-type NUDT5 restored Apolipoprotein E (APOE) expression in PYCR1-knockdown cells, whereas a catalytically inactive NUDT5 mutant failed to do so. RNA sequencing, gene set enrichment analysis, Western blot, and qPCR demonstrated that PYCR1 activated the APOE/JAK2/STAT3 signalling axis. Transcription factor prediction and dual-luciferase reporter assays identified SP1 as a transcriptional regulator of APOE. Moreover, pharmacological inhibition of NUDT5 with TH5427 suppressed BCa progression and JAK2/STAT3 activation in vitro and inhibited xenograft growth in vivo.</p><p><strong>Conclusions: </strong>PYCR1 interacts with NUDT5 to increase nuclear ATP levels, thereby sustaining SP1-dependent APOE transcription and activating JAK2/STAT3 signalling, ultimately promoting BCa progression. TH5427 may represent a promising therapeutic candidate for BCa.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70840"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13588273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer-related pain: A bidirectional modulator of cancer progression.","authors":"Junzhe He, Yu Zhang, Qian Liu, Biao Yan, Peiwei Chai, Renbing Jia","doi":"10.1002/ctm2.70817","DOIUrl":"10.1002/ctm2.70817","url":null,"abstract":"<p><strong>Background: </strong>Cancer-related pain (CRP), with a high prevalence and prognostic value in malignancies, is not only a passive phenomenon but rather engages in a bidirectional crosstalk with cancer progression.</p><p><strong>Main topics: </strong>This review focuses on the intricate reciprocal relationship between CRP and cancer progression, delineating how advanced cancers promote CRP directly through tissue destruction, invasion and inflammation, or indirectly via inflammatory, neural, stromal and metabolic components within the tumour microenvironment. However, controversies remain in the field, such as the ambiguous role of sensory neurons in cancer progression and the potential pro-tumorigenic risk of opioids. Notably, CRP regulates cancer progression through local pain-associated mediators (e.g., CGRP, SP), the pain-stress axis, central nuclei-mediated peripheral immune modulation, sensory-sympathetic/vagal circuits and direct effects on tumour biology.</p><p><strong>Conclusion: </strong>Future research should further elucidate the mechanistic interplay between pain and cancer, as targeting CRP may offer novel therapeutic opportunities for anti-cancer treatment.</p><p><strong>Highlights: </strong>CRP and tumour progression engage in a dynamic, bidirectional circuit mediated by multiple mechanisms in neuroimmunology and cancer neuroscience. Analgesic interventions may affect tumour progression, while anticancer therapies can influence pain. Targeting pain in cancer may have promising therapeutic value in cancer progression.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":"e70817"},"PeriodicalIF":7.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM25 facilitates mitochondrial dysfunction and extracellular matrix degradation by enhancing USP7-driven ENO1 deubiquitination during intervertebral disc degeneration","authors":"Xiaoming Liu,&nbsp;Wenyu Zhang,&nbsp;Hang Feng,&nbsp;Linying Lai,&nbsp;Chen Cao,&nbsp;Guang Yang,&nbsp;Yanzheng Gao,&nbsp;Bijun Wang,&nbsp;Hui Wang,&nbsp;Bin Yu,&nbsp;Zhenghong Yu","doi":"10.1002/ctm2.70785","DOIUrl":"10.1002/ctm2.70785","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The pathology of intervertebral disc degeneration (IDD) is characterized by metabolic dysregulation within nucleus pulposus (NP) cells. TRIM25 has been implicated in diverse tumors and pathological processes, yet its precise role in mediating mitochondrial function and metabolic alterations during IDD progression remains unclear.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Transcriptome sequencing was performed to analyze gene expression changes during IDD progression. Molecular biology techniques including co-immunoprecipitation and ubiquitination assays were used to investigate the interaction between TRIM25 and the glycolytic enzyme ENO1 and its regulatory mechanism. Cellular and in vivo animal models were employed to validate the effects of the TRIM25-USP7-ENO1 axis on glycolysis, mitochondrial function, ATP levels, and extracellular matrix degradation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Transcriptome sequencing revealed that glycolysis-related pathways and TRIM25 were significantly upregulated during IDD progression. Mechanistically, TRIM25 interacted with ENO1. Contrary to its typical E3 ligase function, TRIM25 overexpression stabilized ENO1 by reducing its K48-linked polyubiquitination. Furthermore, TRIM25 enhanced the interaction between USP7 and ENO1, leading to USP7-mediated deubiquitination and stabilization of ENO1. Disruption of the TRIM25-USP7-ENO1 axis suppressed glycolysis, improved mitochondrial function, elevated ATP levels, and inhibited extracellular matrix degradation. In vivo, modulation of this axis correspondingly accelerated or ameliorated IDD progression.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We identified a novel TRIM25-USP7-ENO1 axis, through which TRIM25 stabilizes ENO1 by promoting USP7-ENO1 interaction and subsequent USP7-dependent deubiquitination. This non-canonical function expands the known role of TRIM25 and highlights a promising therapeutic target for restoring mitochondrial dysfunction and metabolic homeostasis in IDD.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;TRIM25 recruits the deubiquitinating enzyme USP7 to collaboratively enhance the deubiquitination and stability of the key glycolytic enzyme ENO1, establishing a new regulatory pathway linking inflammation and metabolism.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;This regulatory axis exacerbates glycolys","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Borrowing sunlight: Photosynthetic bioengineering as an emerging therapeutic paradigm","authors":"Fangyu Zhou,&nbsp;Nengyi Ni,&nbsp;Kuoran Xing,&nbsp;Xiao Sun","doi":"10.1002/ctm2.70816","DOIUrl":"10.1002/ctm2.70816","url":null,"abstract":"&lt;p&gt;Light is one of the most abundant and continuously available energy sources on Earth, but unlike plant cells, mammalian cells lack the ability to directly convert the abundant light energy into biochemical energy. In recent years, a series of studies have begun to attempt to cross this bioenergy boundary, introducing plant-derived thylakoids and their light-response functions into inflamed joints, damaged kidneys, infarcted myocardium and, most recently, corneal tissue (Figure 1A),&lt;span&gt;&lt;sup&gt;1-7&lt;/sup&gt;&lt;/span&gt; to explore a common question: Can the mechanism of photosynthesis be used to provide controllable local energy and reducing power to mammalian tissues? Individually, these works are proof-of-concept for different organs; collectively, they are outlining a new therapeutic paradigm—photosynthetic medicine. This emerging concept of ‘photosynthetic medicine’ encompasses therapeutic strategies that convert exogenous light energy into locally usable chemical energy by transplanting or reconstructing photosynthetic machinery in mammalian systems.&lt;/p&gt;&lt;p&gt;These studies share a common thread: the use of thylakoids derived from chloroplasts and, more importantly, the validation of a shared scientific hypothesis. The light-dependent reactions of photosynthesis can be decoupled to some extent from other chloroplast functions, temporarily maintaining their energy conversion capabilities in mammalian systems. Its potential application value lies in the fact that light may serve as a continuous external energy input, converted into locally available reducing power and chemical energy. For example, NADPH (reduced nicotinamide adenine dinucleotide phosphate) is a key coenzyme for maintaining cellular redox homeostasis and antioxidant defence;&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; its depletion is widely involved in inflammation and ischemic injury. Continuous light-driven NADPH replenishment may therefore offer a distinct alternative to stoichiometric antioxidant or anti-inflammatory therapies.&lt;/p&gt;&lt;p&gt;However, this strategy still faces key engineering and translational hurdles. The separated thylakoid structure is relatively fragile, and its photoreaction products may be consumed by residual chloroplast components, thus limiting the net output to the host cell.&lt;/p&gt;&lt;p&gt;The recently developed LEAF (light-reaction enriched thylakoid NADPH-foundry) has further promoted this strategy from proof of concept to engineering and translational application.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; By selectively removing components in chloroplasts that consume NADPH while retaining thylakoid grana and their photoreaction function, LEAF improves the net output of NADPH, compared to untreated thylakoids. After topical administration, LEAF can be taken up by corneal cells and maintain photosynthetic electron transport activity, providing photogenerated NADPH and ATP (adenosine triphosphate) in the cell; at the same time, NADPH released into the local environment can enhance antioxidant defence and reduc","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"16 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}