Clinical and Translational Medicine最新文献

{"title":"Stereo-cell: Advancing spatial single-cell biology towards clinical translation","authors":"Christian Baumgartner","doi":"10.1002/ctm2.70480","DOIUrl":"10.1002/ctm2.70480","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Stereo-cell is a newly developed platform for spatial single-cell sequencing that integrates morphology, transcriptomics, and proteomics in high resolution. By preserving spatial context while enabling multimodal profiling, it bridges the gap between advanced omics and traditional pathology, supporting the detection of rare cells and clinically interpretable diagnoses. This letter highlights the technical innovations of Stereo-cell, its positioning within the spatial omics landscape, and its potential for precision medicine. Important challenges in data integration, regulatory compliance, and digital modelling are discussed as essential steps on the path to clinical implementation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124331","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":"Extrachromosomal circular DNA expressing miRNA promotes ovarian cancer progression","authors":"Ning Wu,&nbsp;Ling Wei,&nbsp;Qiyu Liu,&nbsp;Tianhui He,&nbsp;Cuiyu Huang,&nbsp;Yunpeng Jiang,&nbsp;Kailong Li,&nbsp;Hongyan Guo,&nbsp;Fengbiao Mao,&nbsp;Xiaolu Zhao","doi":"10.1002/ctm2.70445","DOIUrl":"10.1002/ctm2.70445","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;Extrachromosomal circular DNA (eccDNA) has emerged as a critical driver of oncogenesis, yet its functional roles in high-grade serous ovarian cancer (HGSOC) remain poorly characterized. This highlights the need for comprehensive investigations into the abundance, biogenesis, and functional implications of eccDNA in HGSOC.&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;To characterize eccDNA in HGSOC, we performed comprehensive Circle-seq analysis to assess eccDNA abundance and genomic annotation in HGSOC tissues compared to normal ovarian tissue. For mechanistic validation of eccDNA biogenesis pathways, targeted knockdown experiments of microhomology-mediated end-joining (MMEJ) dependent on LIG3 and POLQ were conducted. Functional characterization of HGSOC-specific eccDNA-harboring precursor microRNAs (eccMIRs) included in vitro assays using HGSOC cells and in vivo tumor growth experiments.&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;Circle-seq analysis revealed a 13-fold increase in eccDNA abundance in HGSOC compared to normal ovarian tissue, with significant enrichment in promoter and coding regions. The MMEJ pathway was identified as the predominant pathway for eccDNA biogenesis in HGSOC, supported by characteristic microhomologies at junction sites and validation via LIG3 and POLQ knockdown experiments. Notably, HGSOC-specific eccDNA frequently contained functional eccMIRs (eccMIR3661, eccMIR618, and eccMIR2277), which generate oncogenic miRNAs. These miRNAs promote tumor progression by downregulating tumor suppressor genes and activating key oncogenic pathways. Functional assays confirmed that these eccMIRs significantly enhanced HGSOC cell proliferation, migration, and invasion in vitro and promoted tumor growth in vivo.&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;These results underscore eccDNA as an oncogenic driver in HGSOC through non-coding RNA-mediated regulatory mechanisms, revealing novel therapeutic opportunities for targeting eccDNA biogenesis in this aggressive malignancy.&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;This study revealed a 13-fold increase of eccDNA in HGSOC compared to normal tissues, with significant enrichment in promoter and coding regions.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;eccDNA-derived miRNAs (eccMIRs) were shown to enhance cancer cell proliferation, invasion, and tumor","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124306","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":"Gene expression differences in differentially methylated sites associated with HIV status and cocaine use","authors":"Eric J. Earley,&nbsp;Bryan C. Quach,&nbsp;Fang Fang,&nbsp;Laura J. Bierut,&nbsp;M-J S. Milloy,&nbsp;Kanna Hayashi,&nbsp;Kora DeBeck,&nbsp;Dana B. Hancock,&nbsp;Bradley E. Aouizerat,&nbsp;Ke Xu,&nbsp;Eric Otto Johnson","doi":"10.1002/ctm2.70466","DOIUrl":"10.1002/ctm2.70466","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Advances in antiretroviral therapy (ART) have made HIV a chronic, manageable disease for people living with HIV (PLWH) with consistent ART access. However, HIV still increases risk of non-AIDS defining conditions such as cancer and impaired cognitive function.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; DNA methylation and gene expression dynamics appear to play a role in these comorbid disease-related processes.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Furthering a mechanistic understanding of the risk of non-AIDS defining conditions, this study is the first to demonstrate that many immune response genes, previously identified via epigenome-wide association studies (EWAS) of DNA methylation, also show consistently upregulated gene expression in PLWH, especially among those with detectable viral load despite ART and those who recently used cocaine.&lt;/p&gt;&lt;p&gt;HIV-1 infection is characterised by persistent immune activation and chronic inflammation.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; DNA methylation – particularly at CpG sites near immune-regulatory genes – has been linked to HIV acquisition, viral control, and comorbidities such as cancer and impaired cognitive function.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Recent EWAS have identified hypomethylation in key antiviral response genes such as &lt;i&gt;MX1&lt;/i&gt; and &lt;i&gt;NLRC5&lt;/i&gt;, and hypermethylation in genes linked to HIV progression including &lt;i&gt;CX3CR1&lt;/i&gt; and &lt;i&gt;TNF&lt;/i&gt;.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; However, it remains unclear whether such methylation changes translate into changes in gene expression. Moreover, cocaine use, common among PLWH and associated with faster disease progression, may further influence gene expression via epigenetic mechanisms.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;To investigate this, we analysed gene expression via RNAseq in whole blood from 588 individuals enrolled in the Vancouver People Who Inject Drugs Study (VPWIDS), including 227 PLWH (38.6%) with a mean age of 49.6 years (± 9.6 SD; Table 1).&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; All PLWH were on ART at the time of blood draw, 194 had undetectable viral load (&lt; 200 viral copies/mL), and 33 had detectable viral load (mean 18 850 viral copies/mL). The cohort had high prevalence of cocaine, opioid, and methamphetamine use. Focusing on cocaine use (crack and powder), 121 PLWH (47%) and 180 HIV-negative (50%) participants reported recent use.&lt;/p&gt;&lt;p&gt;A PubMed search using ‘HIV’ and ‘epigenome’ identified five in vivo human whole blood–based EWAS relevant to HIV acquisition or severity (Table S1). From these, we selected 18 genes for expression analyses based on stringent criteria: (1) harbouring CpG sites differentially methylated in association with HIV acquisition or severity that were independently replicated in at least one other study, or (2) containing CpG sites identified as significant mediators of cocaine's impact on HIV severity in prior mediation analyses. Expression differences by HIV status were assessed using negative binomial regression, adjusting for sex, age, RNA Integrity","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70466","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085294","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":"Neural mechanism of conscious perception for potential clinical applications","authors":"Yong Wang,&nbsp;Shouyang Yu,&nbsp;Yueqing Dong,&nbsp;Yuanyuan Dang,&nbsp;Hulin Zhao,&nbsp;Mingsha Zhang,&nbsp;Xiaoli Li","doi":"10.1002/ctm2.70387","DOIUrl":"10.1002/ctm2.70387","url":null,"abstract":"<p>The generation of consciousness has remained one of the most enduring scientific quests in human history. When a visual stimulus enters the eye, how does the brain transform it into the subjective experience of “I see”? Traditional theories posited the cerebral cortex as the epicenter of conscious perception, relegating the thalamus to a mere relay station for sensory signals. However, a groundbreaking study recently published in Science has overturned this paradigm, identifying the mediodorsal thalamic nuclei (MDm) and intralaminar nuclei (ILN) as the true “gatekeepers” of conscious perception.<span>¹</span> Through dynamic connectivity with the prefrontal cortex, these nuclei determine which sensory information gains access to the conscious perception. What groundbreaking clinical implications might this discovery yield?</p><p>Conscious perception, is one of the most complex issues in the field of cognitive science, meaning subjects convert external stimuli into subjective experiences through neural activity. Conscious perception involves the awareness and understanding of one's environment, internal stimuli, and cognitive processes. As a key capability for human cognition, it enables individuals to be aware of events, emotions, thoughts, and bodily states. From the perspective of neuroscience, conscious perception is a process that involves several brain regions, particularly the thalamus and the prefrontal cortex.<span>^{2, 3}</span> These regions synthesize information from sensory systems, such as vision, hearing, and touch, to construct a clear conscious experience.</p><p>Conscious perception is impaired in various medical conditions (see Figure 1). Neurodegenerative diseases, including Alzheimer's and Parkinson's, are linked to progressive deterioration in awareness and perception. Individuals with Alzheimer's disease often exhibit a decline in consciousness and self-awareness,<span>⁴</span> whereas those with Parkinson's may endure visual perception problems due to the loss of dopamine-producing cells in the retina.<span>⁵</span> Other conditions that affect conscious perception include epilepsy, which can cause sensory disturbances; and sleep disorders, which can lead to perceptual changes due to sleep deprivation or disrupted circadian rhythms (Figure 1).</p><p>This paradigm shift, from cortical-centric to thalamocortical network models of consciousness, calls for multidisciplinary collaboration. By integrating sEEG-guided neuromodulation, computational modeling of mesocircuit dynamics, and machine learning-based biomarker discovery, clinicians can develop precision therapies that bridge molecular mechanisms with systems-level network reorganization. These advances not only redefine our approach to DoC but also offer novel pathways for treating perceptual-cognitive deficits across neurological and psychiatric disorders.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085328","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":"Significance of stereologically spatiotemporal cells in molecular medicine","authors":"Xuanqi Liu,&nbsp;Wanxin Duan,&nbsp;Yuyang Qiu,&nbsp;Ruyi Li,&nbsp;Yuanlin Song,&nbsp;Xiangdong Wang","doi":"10.1002/ctm2.70470","DOIUrl":"10.1002/ctm2.70470","url":null,"abstract":"<p>Spatiotemporal distributions of intracellular elements (e.g., small molecules, proteins and organelles) dynamically altered in response to extracellular stimuli and pathogens, regulating those element movements, remodelling, and functions independently of mere changes in element abundance. To distinguish from conventional one- or two-dimensional spatialization, we define the precise three-dimensional localisation and interactions of intra- and extracellular elements at the single cell level as the “stereologically spatiotemporal cell” (SST-cell). For example, the three-dimensional construction of chromosomes ensures their proper formation and spatial positioning, facilitates the recruitment of regulatory factors, and underlies the mechanisms by which these factors maintain chromatin architecture. A large number of intracellular organelles and sub-organelles, along with their intercommunications, decide cellular biological types, subtype specification and type-specific functions. With the development of Stereo-Cell and Stereo-seq, the measurement of spatial SST-cell omics probably enables the detailed dissection of spatial heterogeneity among different cell subtypes and states, as well as their intercellular communications. Furthermore, the new approach of single SST-cell drug screening will be innovated for developing the new generation of clinical precision therapies.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069140","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":"Plasma metabolites in patients of the REDINSCOR III registry hospitalised for de novo heart failure with preserved ejection fraction: Prognostic implications of linoleamide and 2-trans,4-cisdecadienoylcarnitine levels","authors":"Marta Delgado-Arija,&nbsp;M Dolores García-Cosío Carmena,&nbsp;Manuel Martínez-Sellés,&nbsp;José M Guerra,&nbsp;Sandra Valdivielso,&nbsp;José R González-Juanatey,&nbsp;Mercedes Rivas-Lasarte,&nbsp;Esther Roselló-Lletí,&nbsp;Julián Pérez-Villacastín,&nbsp;Anna Carrasquer,&nbsp;Lucía Matute-Blanco,&nbsp;Antonio Grande-Trillo,&nbsp;Maria Generosa Crespo-Leiro,&nbsp;Juan F Delgado,&nbsp;Luis Martínez-Dolz,&nbsp;REDINSCOR III registry","doi":"10.1002/ctm2.70398","DOIUrl":"https://doi.org/10.1002/ctm2.70398","url":null,"abstract":"&lt;p&gt;Dear Editor&lt;/p&gt;&lt;p&gt;Heart failure with preserved ejection fraction (HFpEF) constitutes approximately 50% of all heart failure (HF) diagnoses. Despite its prevalence, effective therapies are limited given the incomplete understanding of its pathogenesis and pathophysiology.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Taking into account these considerations, in this multicentre cohort of new-onset HFpEF hospitalised patients, we described a comprehensive untargeted metabolomic study to determine endogenous metabolites that were associated with the risk of suffering an event of death or readmission for cardiovascular causes.&lt;/p&gt;&lt;p&gt;A total of 126 plasma samples were analysed (Figure S1), including those from 105 patients with new-onset HFpEF. At enrolment, the median age of these patients was 75 ± 10 years, 51% were male, and in the previous year mostly were pauci-symptomatic (81% NYHA class I-II). At the last evaluation, 18 patients suffered an event (all-cause mortality or cardiovascular readmission), while 82 patients did not. Table 1 summarises the demographic and clinical characteristics of HFpEF patients by event status at the end of the follow-up. Both groups were similar regarding variables except for haemoglobin, creatinine and NT-proBNP values prior to discharge. Additionally, the 20 healthy controls (CNT) individuals had a mean age of 66 ± 5 years, and 60% were male.&lt;/p&gt;&lt;p&gt;Metabolic differences between CNT and HFpEF patients groups were assessed after data preprocessing in both positive and negative ESI modes (Figure S2). As shown in Table S1, we identified 24 metabolites that showed statistically significant differences between HFpEF patients and the CNT group, with a fold change threshold of |FC| ≥ 2. Regarding this finding, we performed an analysis between the HFpEF patients who experienced an event with those who did not to discover if there were metabolomic changes. As a result, seven metabolites exhibited significant differences, being linoleamide levels the ones that were most altered in this comparison (Table S1). Then, we focused on linoleamide, an endogenous lipid which is structurally related to sphingosine and sphiganine and closely related with sarco/endoplasmic reticulum Ca&lt;sup&gt;2+&lt;/sup&gt;-ATPase (SERCA) activity,&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; whose levels were higher in patients who were rehospitalised for an event (&lt;i&gt;p&lt;/i&gt; &lt; .0001) (Figure S3A). Previously, Tarazón et al.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; determined through untargeted metabolomics that circulating sphingosine-1-phosphate (S1P), a metabolite also closely related with SERCA, could be a novel approach to detect cardiac rejection. In addition, significant alterations in the main components of the sphingolipid metabolism pathways and an accumulation of SP1 was observed in HF patients.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; Collectively, these findings highlight the potential role of linoleamide in HFpEF patients who experienced an event. Furthermore, it is widely known that the heart is a mitochondrion","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062637","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":"Metabolic signatures and a diagnostic model for citrin deficiency based on urinary organic acids","authors":"Peiyao Wang,&nbsp;Peichun Chen,&nbsp;Xinjie Yang,&nbsp;Ziyan Cen,&nbsp;Yu Zhang,&nbsp;Qimin He,&nbsp;Benqing Wu,&nbsp;Xinwen Huang","doi":"10.1002/ctm2.70467","DOIUrl":"https://doi.org/10.1002/ctm2.70467","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>This study aimed to characterise urinary organic acid profiles in Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD) and develop a diagnosis model to distinguish NICCD patients from those in the non-specific metabolic abnormalities group (NAG), both of which exhibit elevated urinary 4-hydroxyphenyllactic acid (4-HPLA) and 4-hydroxyphenylpyruvic acid (4-HPPA), potentially leading to misdiagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective study was conducted from February 2021 to February 2025, enrolling 105 NICCD patients, 144 healthy controls (HC), and 298 individuals from NAG. Urine organic acids were measured using gas chromatography-mass spectrometry. Data from NICCD and NAG collected before October 2024 were used for model training and internal testing, with later data serving as an external validation. A three-step feature selection strategy identified biomarkers. Five machine learning (ML) methods were used to construct the model. Performance was compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, <i>F</i>1 score, etc.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to HC, NICCD patients exhibited 39 differential metabolites, enriched in tyrosine, aspartate, pyruvate, lipoic acid, and TCA cycle pathways. 4-HPLA, 4-HPPA, galactitol, 4-hydroxyphenylacetic acid, pyruvic acid, quinolinic acid, homovanillic acid, 4-hydroxybenzoic acid, and malic acid showed high diagnostic performance (AUC &gt; .8). Nine robust markers were identified between NICCD and NAG. The random forest model demonstrated superior classification performance, with high AUC, accuracy, <i>F</i>1 score, and low Brier score. An online calculator was developed for clinical use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings highlight NICCD metabolic enrichment in energy and amino acid pathways and present an interpretable ML model for distinguishing NICCD from those of NAG.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 9","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062590","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":"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":"<p>A recent groundbreaking study by Xing et al. published in <i>Cell</i> 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.<span>¹</span> 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.<span>^{1, 2}</span></p><p>While elucidation of the SARS-CoV-2 E-FIC has addressed a significant knowledge gap,<span>³</span> the fusion intermediate states for most coronaviruses remain uncharacterized. Recent evidence indicates that several MERS-related coronaviruses (MERSr-CoVs), such as NeoCoV,<span>⁴</span> MOW15-22<span>⁵</span> and HKU5,<span>⁶</span> 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.<span>⁷</span> Furthermore, NeoCoV S protein containing a T510F mutation has acquired the capacity to bind the hACE2 receptor, representing a potential threat of zoonotic spillover.<span>⁴</span> 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.</p><p>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.<span>⁸</span> 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.<span>⁹</span> 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}