Clinical and Translational Medicine最新文献

{"title":"Correction to “Comparative impact of proton versus photon irradiation on triple-negative breast cancer: Role of VEGFC in tumour aggressiveness”","authors":"","doi":"10.1002/ctm2.70468","DOIUrl":"https://doi.org/10.1002/ctm2.70468","url":null,"abstract":"<p>Citation to article being corrected: Comparative impact of proton versus photon irradiation on triple-negative breast cancer: Role of VEGFC in tumour aggressiveness.</p><p>Sarlak S, Marotte D, Karaulic A, Sirera J, Pierantoni A, Tsai MC, Sylvestre R, Molina C, Gouraud A, Bancaud A, Kousteridou P, Vidal M, Hérault J, Doyen J, Dufies M, Morfoisse F, Garmy-Susini B, Luciano F, <b>Pagès G</b>. Clin Transl Med. 2025 May;15(5):e70330. https://doi.org/10.1002/ctm2.70330. PMID: 40400121</p><p>Description of error: (1) Jessy SIRERA is now the third author and Arthur KARAULIC is the fourth author. We made a mistake that did not consider the fair participation of two co-authors for this manuscript. (2) Béatrice CAMBIEN was added in the manuscript because we forgot her strong collaborative participation.</p><p>Therefore, the correct list of authors is the following:</p><p>Sarlak S, Marotte D, <span>Sirera J</span>, <span>Karaulic A</span>, Pierantoni A, Tsai MC, Sylvestre R, Molina C, Gouraud A, Bancaud A, <span>Cambien, B</span>, Kousteridou P, Vidal M, Hérault J, Doyen J, Dufies M, Morfoisse F, Garmy-Susini B, Luciano F#, <b>Pagès G</b>#.</p><p>The authors corresponding to these modifications are underlined.</p><p>Moreover, Dr Luciano and Dr Pagès equally participated to the work. Therefore, # was inserted after LUCIANO and PAGES authors which means that Frédéric LUCIANO and Gilles PAGES are the co-last authors.</p><p>We apologize for this error.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037593","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":"Predicted early fusion intermediates in the spike of ACE2-utilising bat coronavirus unveil broad-spectrum antiviral mechanisms","authors":"Lujia Sun,&nbsp;Zhimin Liu,&nbsp;Lixiao Xing,&nbsp;Xiaoxing Liang,&nbsp;Lu Lu,&nbsp;Shibo Jiang,&nbsp;Lei Sun,&nbsp;Xinling Wang","doi":"10.1002/ctm2.70459","DOIUrl":"https://doi.org/10.1002/ctm2.70459","url":null,"abstract":"&lt;p&gt;A recent groundbreaking study by Xing et al. published in &lt;i&gt;Cell&lt;/i&gt; has successfully captured the early fusion intermediate conformation (E-FIC) of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) spike (S) protein induced by ACE2.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; In this conformation, the heptad repeat 1 (HR1) domain of the S2 subunit has ejected, while the S1 subunit carrying the receptor binding domain (RBD) still binds to S2. This intermediate conformation establishes a distinctive therapeutic window wherein the spatial separation between the RBD and HR1 domain enables concurrent engagement by a dual-target inhibitor, AL5E (targeting both RBD and HR1), which sterically blocks conformational transitions essential for fusion pore expansion, thereby inhibiting viral fusion and entry and potentially inducing viral inactivation.&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;While elucidation of the SARS-CoV-2 E-FIC has addressed a significant knowledge gap,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; the fusion intermediate states for most coronaviruses remain uncharacterized. Recent evidence indicates that several MERS-related coronaviruses (MERSr-CoVs), such as NeoCoV,&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; MOW15-22&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; and HKU5,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; utilise bat or non-bat ACE2 as a functional receptor. Notably, among these, BtHKU5-CoV-2-441(BtHKU5-CoV-2) can utilise human ACE2 (hACE2) to mediate host cell infection.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; Furthermore, NeoCoV S protein containing a T510F mutation has acquired the capacity to bind the hACE2 receptor, representing a potential threat of zoonotic spillover.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Consequently, investigating the fusion mechanisms of these MERSr-CoVs and developing broad-spectrum membrane fusion inhibitors that exploit such mechanisms should be considered an imperative for mitigating the potential risks of cross-species transmission.&lt;/p&gt;&lt;p&gt;Structural analysis of the SARS-CoV-2 E-FIC revealed that an amino acid sequence, designated as one intermediate loop (IL)—IL770, engages the HR1 domain within the E-FIC S2 subunit (Figure 1A). Notably, the S2' protease cleavage site also resides within IL770. Consequently, elucidating variations in IL770 across coronaviruses holds essential implications for understanding both protease accessibility and the regulation of membrane fusion efficiency in the E-FIC S2 context. To explore the fusion mechanisms of such hACE2-using MERSr-CoVs, we first predicted the three-dimensional structures of BtHKU5-CoV-2 and NeoCoV S2 in E-FIC using SWISS-MODEL homology modelling.&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; The overall structures of the S2 in E-FIC from BtHKU5-CoV-2 and NeoCoV resemble that of SARS-CoV-2, in which HR1, CH and part of the FP form a long central three-stranded coiled coil (Figure 1B). This coiled-coil is stabilised by a three-helix segment (3H) and an IL replaced by HR2 in the post-fusion structure.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; Consequently, the characteristics of IL, especially at ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012389","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":"Computational modeling and simulation in oncology","authors":"Christian Baumgartner","doi":"10.1002/ctm2.70456","DOIUrl":"https://doi.org/10.1002/ctm2.70456","url":null,"abstract":"<p>Computational modeling and simulation are playing an increasingly important role in oncology, bridging biological research, data science and clinical practice to better understand cancer complexity and inform therapeutic development. This special issue presents recent advances in multiscale modeling, artificial intelligence-driven systems, digital twins, and in silico trials, illustrating the evolving potential of computational tools to support innovation from bench to bedside. Together, these contributions outline a future in which precision medicine, adaptive therapies and personalized diagnostics are guided by integrative and predictive modeling approaches.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990654","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":"Immunometabolism: The role of gut-derived microbial metabolites in optimising immune response during checkpoint inhibitor therapy","authors":"Agnieszka Beata Malczewski,&nbsp;Jermaine Ig Coward,&nbsp;Natkunam Ketheesan,&nbsp;Severine Navarro","doi":"10.1002/ctm2.70472","DOIUrl":"https://doi.org/10.1002/ctm2.70472","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Checkpoint inhibitor therapy is the most common type of immunotherapy used in the clinical setting, however, there are significant obstacles with treatment resistance and cancer progression. Since its introduction, there have been relatively few advances in the development of prognostic or predictive biomarkers. The field of metabolomics studies small molecules and can provide us with an understanding of the dynamic events evolving during the tumour-drug-immune-system interaction. Several key pathways have emerged as important in understanding resistance mechanisms thereby providing a rationale for targeting immunometabolism in order to enhance the immune response during checkpoint inhibitor therapy. In the first part of this review, we explore the role of gut microbiome-derived short-chain fatty acids, which are recognized as important immunoregulatory molecules shaping T-cell activation, effector and memory function. We then discuss tryptophan catabolism as a key predictor of primary checkpoint inhibitor failure. Lastly, we focus on immunometabolism as an important future target in immunotherapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> One sentence summary</h3>\u0000 \u0000 <p>This review focusses on microbiome-derived metabolites and their role in immunometabolism and the enhancement of checkpoint inhibitor responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990655","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":"Pathogen sharing in the digital age: The unfinished agenda of the WHO pandemic agreement","authors":"WooJung Jon","doi":"10.1002/ctm2.70473","DOIUrl":"https://doi.org/10.1002/ctm2.70473","url":null,"abstract":"&lt;p&gt;The world cheered on May 20, 2025, when the World Health Assembly adopted the World Health Organization (WHO) Pandemic Agreement – a landmark global treaty forged after three years of intense negotiations – hailed as a triumph of multilateralism.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This accord, the first-ever treaty focused on pandemic prevention, preparedness, and response, embodies a collective resolve to avert a repeat of the devastation caused by COVID-19. However, this celebratory moment is not the end of the story; rather, it is the beginning of a far more challenging chapter.&lt;/p&gt;&lt;p&gt;At the heart of the Pandemic Agreement is its most innovative and contentious element: a Pathogen Access and Benefit-Sharing (PABS) system (Article 12). PABS was envisioned as the Agreement's grand bargain to correct the inequities observed during COVID-19, when pathogens were often detected in the Global South but vaccines and therapeutics were hoarded by the Global North.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Under the PABS framework, countries are required to promptly share pathogen samples and genetic sequence data; in return, pharmaceutical manufacturers using that data must share the benefits. The key commitment is for companies to provide 20% of their real-time pandemic production to the WHO for distribution based on public health need (Article 12.6(a) ). At least half of this (10% of total production) would be donated outright, and the rest would be offered at affordable prices. This mechanism aims to replace the chaotic, market-driven scramble for life-saving tools with a predictable, needs-based system that ensures more equitable access.&lt;/p&gt;&lt;p&gt;Yet the technical and political complexities of PABS proved too difficult to resolve during the main treaty negotiations. To avoid a collapse of the talks, member states took a high-stakes step: they adopted the core agreement text but deferred all operational details of PABS to a separate, legally binding annex.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Pursuant to Article 31.2, the Pandemic Agreement cannot be opened for signature or ratification until this PABS annex is successfully negotiated and adopted.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This task now falls to a new Intergovernmental Working Group (IGWG), which convened in July 2025 with a mandate to complete the annex by the 2026 World Health Assembly.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;A major complication for PABS is the role of digital sequence information (DSI) – essentially the genetic code of pathogens stored as data. DSI allows researchers and companies to work with a pathogen's genome without needing the physical virus or bacteria in hand. For example, the first COVID-19 vaccines (like the mRNA vaccines) were designed using the digitally shared SARS-CoV-2 genome sequence, without any laboratory exchanging live virus samples.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; This ability to ‘dematerialize’ pathogens into data means that a company can obtain the genetic sequence of a dangerous pathogen from a public database ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990656","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":"Peripheral blood mesenchymal stem cell-derived exosomes improve renal sympathetic denervation efficacy through β-catenin-mediated cardiac reprogramming","authors":"Lan Zhao,&nbsp;Chen Li,&nbsp;Zhichuan Huang,&nbsp;Jianshuo Wang,&nbsp;Zhanyu Deng,&nbsp;Yanwen Deng,&nbsp;Pengzhen Wang,&nbsp;Shaoheng Zhang","doi":"10.1002/ctm2.70475","DOIUrl":"https://doi.org/10.1002/ctm2.70475","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;To investigate the role of self-peripheral blood mesenchymal stem cell (PBMSC)-derived exosomes (Exos) in enhancing renal sympathetic denervation (RD)-mediated heart regeneration following myocardial infarction (MI) in a porcine model.&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;Pigs (ejection fraction [EF] &lt; 40% post-MI) were randomised to early sham RD or RD. At 2 weeks post-MI, autologous PBMSC-Exos were collected. At 30 days post-MI, pigs received either PBMSC-Exos (2 × 10&lt;sup&gt;13&lt;/sup&gt; particles) or phosphate-buffered saline and were followed until 90 days. Another cohort underwent myocardial biopsy at 14 days post-MI to assess PBMSC-Exos effects on ischaemic cardiomyocyte (CM) reprogramming, followed by adeno-associated viral therapy with miR-141-200-429 sponges or negative control sponges to explore the role of miR-141-200-429 clusters in reprogramming.&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;Two weeks post-MI, RD hearts showed increased Exos uptake and inhibited the sympathetic nervous system. By 90 days, the RD+Exos group had 11%–26% higher EF than single-treatment groups (all &lt;i&gt;p&lt;/i&gt; &lt; .001), with improved survival and reduced fibrosis. Exos therapy enhanced RD effects by suppressing the renin‒angiotensin‒aldosterone system and transferring the miR-141-200-429 cluster into ischaemic CMs. CMs from RD-treated hearts cocultured with PBMSC-Exos&lt;sup&gt;RD&lt;/sup&gt; exhibited a more immature state, promoting reprogramming. β-Catenin overexpression further enhanced PBMSC-Exos&lt;sup&gt;RD&lt;/sup&gt; effects, while miR-141-200-429 inhibition blocked RD-induced CM reprogramming and survival. Ultimately, PBMSC-Exos&lt;sup&gt;RD&lt;/sup&gt; reduced dickkopf-1 (Dkk1) expression and activated GSK3β phosphorylation, thereby stimulating the Wnt/β-catenin pathway.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;PBMSC-Exos&lt;sup&gt;RD&lt;/sup&gt; enhances RD-mediated cardiac repair through miR-141-200-429 cluster-dependent activation of the Wnt/β-catenin pathway, offering a novel therapeutic strategy for MI-induced heart failure. Our findings unveil a novel therapeutic strategy, highlighting that RD maintains its efficacy and safety when integrated with complementary approaches over extended periods.&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;\u0000 &lt;p&gt;Myocardial infarction triggers cardiomyocyte depletion and sympathetic overactivation, culmina","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70475","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990768","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":"PCDHGB7 inhibits the progression of triple-negative breast cancer by suppressing XRCC5/MYC-mediated ribosome biogenesis","authors":"Ming Shan,&nbsp;Hongjie Bi,&nbsp;Hua Sun,&nbsp;Yixin Li,&nbsp;Zhiqi Li,&nbsp;Ziyuan Wang,&nbsp;Jianguo Dong,&nbsp;Shengbo Sang,&nbsp;Lili Ren,&nbsp;Yuguang Ye,&nbsp;Tianzhen Wang,&nbsp;Siniša Volarević,&nbsp;Rui Su,&nbsp;Lei Zhang,&nbsp;Minghui Zhang,&nbsp;Yan He,&nbsp;Guoqiang Zhang,&nbsp;Jing Li,&nbsp;Xiaobo Li","doi":"10.1002/ctm2.70437","DOIUrl":"https://doi.org/10.1002/ctm2.70437","url":null,"abstract":"&lt;p&gt;To the Editor:&lt;/p&gt;&lt;p&gt;Hyperactivation of ribosome biogenesis plays a crucial role in driving cancer initiation and progression,&lt;span&gt;&lt;sup&gt;1-5&lt;/sup&gt;&lt;/span&gt; but the underlying molecular mechanisms are unclear. In this study, we demonstrated that PCDHGB7 negatively regulates ribosome biogenesis in triple-negative breast cancer (TNBC) by suppressing the XRCC5-enhanced MYC activity.&lt;/p&gt;&lt;p&gt;By investigating the expression and clinical correlation of three clustered PCDH genes (including 15 &lt;i&gt;PCDHA&lt;/i&gt; genes, 16 &lt;i&gt;PCDHB&lt;/i&gt; genes and 22 &lt;i&gt;PCDHG&lt;/i&gt; genes) in breast cancer, we demonstrated that PCDHGB7 was significantly decreased in TNBC tissues than in normal tissues and other subtypes of breast cancer (Figure 1A,C,D; Figure S1A,B,D) due to its high DNA methylation level (Figure S1E–M). We also showed that lower expression of PCDHGB7 was associated with poor survival outcomes in TNBC patients (Figure 1B,E–H; Figure S1C). Functionally, we demonstrated that PCDHGB7 overexpression significantly decreased proliferation and metastasis, whereas PCDHGB7 knockdown enhanced the proliferation and metastasis of TNBC cells both in vivo and in vitro (Figure 1I–P; Figure S2A–K).&lt;/p&gt;&lt;p&gt;To elucidate the mechanisms by which PCDHGB7 inhibits TNBC progression, we employed mass spectrometry (MS) to identify 219 proteins that were upregulated and 231 proteins that were downregulated following &lt;i&gt;PCDHGB7&lt;/i&gt; knockdown in TNBC cells (Figure S3A; Table S2). Gene Ontology analysis revealed that a subset of proteins upregulated upon &lt;i&gt;PCDHGB7&lt;/i&gt; knockdown were enriched in pathways related to ribosome biogenesis and rRNA processing (Figure 2A; Table S3), indicating that PCDHGB7 may negatively regulate ribosome biogenesis in TNBC cells. Polysome profiling revealed that PCDHGB7 overexpression decreased, whereas PCDHGB7 knockdown increased the number of ribosomes in TNBC cells (Figure 2B,C; Figure S3B,C). RT-qPCR results showed that the levels of 47S pre-rRNA, 28S, 18S and 5.8S rRNA were significantly decreased upon PCDHGB7 overexpression, but increased upon PCDHGB7 knockdown in both TNBC cell lines (Figure S3D,E,G,H). ChIP experiment showed PCDHGB7 overexpression decreased Pol I occupancy in TNBC cells (Figure 2D; Figure S3F). Moreover, the AHA and SUnSET assays consistently demonstrated that PCDHGB7 depletion significantly increased, whereas PCDHGB7 overexpression decreased protein synthesis in both TNBC cells (Figure 2E–G; Figure S3I,J). Consistent with these findings, we demonstrated that the translation efficacy and number of ribosomes in TNBC cells were significantly greater than those in immortal human breast cells (Figure 2H,I). Additionally, the area of AgNOR staining in TNBC tissues was larger and darker than that in normal breast tissues (Figure 2J,K), and a high staining index predicts a poor prognosis in TNBC patients (Figure 2L). Our findings highlight that increased ribosome biogenesis and increased protein synthesis are characteristic features of TNBC, and that","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70437","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930038","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":"CLINICAL AND TRANSLATIONAL MEDICINE","authors":"","doi":"10.1002/ctm2.70476","DOIUrl":"https://doi.org/10.1002/ctm2.70476","url":null,"abstract":"","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927630","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":"Advancing standards in biomedical image analysis validation: A perspective on Metrics Reloaded","authors":"Annika Reinke,&nbsp;Minu D Tizabi,&nbsp;Lena Maier-Hein","doi":"10.1002/ctm2.70237","DOIUrl":"https://doi.org/10.1002/ctm2.70237","url":null,"abstract":"&lt;p&gt;Over the past years, medical artificial intelligence (AI) research has seen tremendous progress and found entrance into various disciplines of clinical medicine, such as medical imaging. However, a—frequently unspoken—part of the truth is that the majority of newly developed AI methods do not see the light of translation into clinical practice.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; This lack can, to a large extent, be attributed to flaws in the robust and clinically useful validation of AI methods: in the absence of meaningful performance validation that takes into account the specific properties of the underlying clinical task, progress cannot be measured and clinical usability of a new method cannot be gauged. In other words, we spend vast resources to develop new algorithms, yet cannot trust them to perform well under real-world clinical conditions, for example, marked by the presence of data shifts (see, e.g., Castro et al.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;), poor data quality (see, e.g., Jogan et al.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;), or different scanners (see, e.g., Kilim et al.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;). Despite its tremendous importance, validation is often still treated as algorithm development's poor cousin: neither as glamorous nor as financially attractive as the latter, it is plagued by poor scientific practices and, to date, a lack of standards.&lt;/p&gt;&lt;p&gt;This becomes particularly evident in the case of validation metrics: In our recent sister publications,&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt; we showed that choosing inadequate performance metrics (for example, by popularity) that do not reflect the clinical needs is both a prevalent common practice and a dangerous one: In the segmentation of brain magnetic resonance imaging (MRI) images for tumour detection, for instance, an AI algorithm considered as the state of the art could achieve impressive scores of a popular validation metric, yet consistently fail to detect small, clinically significant tumour lesions—with potentially fatal consequences for patients.&lt;/p&gt;&lt;p&gt;The choice of metrics in medical imaging is seemingly endless—and so are the pitfalls into which we can stumble when selecting and applying them. How, then, to identify metrics that we can trust to properly reflect an algorithm's real-world clinical usability? This is where &lt;i&gt;Metrics Reloaded&lt;/i&gt; comes in: &lt;i&gt;Metrics Reloaded&lt;/i&gt; is the first comprehensive recommendation framework that guides researchers in the problem-aware selection of clinically meaningful performance metrics in medical imaging (see Figure 1). It supports recommendations for any image-based task related to the classification of the image (e.g., based on a computed tomography (CT) image, decide if a tumour is malignant or benign), object detection (e.g., tumour detection and localization in a CT image), or pixel and/or object segmentation level (e.g., outlining a tumour in a CT image). It thus follows a task-agnostic approach, which could be achieved by abstracting from the actual underlyi","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923412","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":"Atg7 in CD4+ T cells improves intestinal mucosal inflammation by regulating Ets1-mediated T cell differentiation","authors":"Yue-Tao Zhou,&nbsp;Quan-Gui Zhang,&nbsp;Si-Yuan Du,&nbsp;Hong Chen,&nbsp;Mei-Zhen Zhu,&nbsp;Min Ai,&nbsp;Shuang-Shuang Li,&nbsp;Meng-Nan Dai,&nbsp;Xi-Ting Wang,&nbsp;Yan Jin,&nbsp;Ying-Wei Zhu,&nbsp;Jian Lu,&nbsp;Fei Xu,&nbsp;Xue-Xue Zhu,&nbsp;Li-Ying Qiu,&nbsp;Hai-Jian Sun","doi":"10.1002/ctm2.70462","DOIUrl":"https://doi.org/10.1002/ctm2.70462","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;Atg7-autophagy–related gene 7 contributes as an immune cell function regulator, particularly involved in CD4⁺ T cell response. Nevertheless, the specific contribution of Atg7 in CD4⁺ T cells sensitive immune responses in inflammatory bowel disease (IBD) remains largely unclear. This study explores the functional significance and regulatory mechanisms of CD4⁺ T cell-specific Atg7 in IBD.&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;Real-Time Quantitative Reverse Transcription PCR (qRT-PCR), western blotting analysis, flow cytometry and immunohistochemistry were employed to evaluate ATG7 expression in peripheral blood and colonic mucosal biopsies from IBD patients. Peripheral CD4⁺ T cells were transfected with lentivirus vectors encoding either &lt;i&gt;ATG7&lt;/i&gt; (LV-&lt;i&gt;ATG7&lt;/i&gt;) or &lt;i&gt;ATG7&lt;/i&gt; short hairpin RNA (LV-sh&lt;i&gt;ATG7&lt;/i&gt;). Furthermore, mice with a CD4⁺ T cell conditional knockout of &lt;i&gt;Atg7&lt;/i&gt; (&lt;i&gt;Atg7&lt;sup&gt;ΔCD4&lt;/sup&gt;&lt;/i&gt;) were generated, and CD4&lt;sup&gt;+&lt;/sup&gt; T cells of splenic origin were subjected to RNA-seq.&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;&lt;i&gt;ATG7&lt;/i&gt; level was markedly elevated in inflamed mucosa tissues and peripheral blood CD4&lt;sup&gt;+&lt;/sup&gt; T cells of patients with active Crohn's disease compared to healthy individuals. Overexpression of &lt;i&gt;ATG7&lt;/i&gt; suppressed Th1 differentiation while enhancing the induction of iTreg cells. &lt;i&gt;Atg7&lt;sup&gt;ΔCD4&lt;/sup&gt;&lt;/i&gt; mice exhibited exacerbated result of 2,4,6-trinitrobenzenesulphonic acid-induced experimental colitis, as did &lt;i&gt;Rag1&lt;sup&gt;−/−&lt;/sup&gt;&lt;/i&gt; mice adoptively transferred with CD45&lt;sup&gt;RBhigh&lt;/sup&gt; CD4&lt;sup&gt;+&lt;/sup&gt; T cells from &lt;i&gt;Atg7&lt;sup&gt;ΔCD4&lt;/sup&gt;&lt;/i&gt; donors. RNA-seq analysis revealed that E26 transformation-specific sequence-1 (&lt;i&gt;Ets1&lt;/i&gt;) acts downstream of &lt;i&gt;Atg7&lt;/i&gt; and mediates its regulatory effects on Th1 and Treg cell differentiation.&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;Our data indicate that Atg7 alleviates mucosal inflammation by modulating Th1/Treg differentiation through the regulation of Ets1 expression. Thus, CD4⁺ T cell-expressed Atg7 may serve as a promising therapeutic approach for IBD.&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;Atg7 expression was significantly elevated in the inflamed mucosa and blood CD4&lt;sup&gt;+&lt;/sup&gt; T cells of patients with active Crohn's disease.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Specific-knockout of A","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144923500","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}