Clinical and Translational Medicine最新文献

{"title":"ATF3-mediated transactivation of CXCL14 in HSCs during liver fibrosis","authors":"Xinmiao Li,&nbsp;Lifan Lin,&nbsp;Yifei Li,&nbsp;Weizhi Zhang,&nbsp;Zhichao Lang,&nbsp;Jianjian Zheng","doi":"10.1002/ctm2.70040","DOIUrl":"10.1002/ctm2.70040","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and aims</h3>\u0000 \u0000 <p>Myofibroblasts, the primary producers of extracellular matrix, primarily originate from hepatic stellate cells (HSCs), and their activation plays a pivotal role in liver fibrosis. This study aimed to investigate the function of CXC motif ligand 14 (CXCL14) in the progression of liver fibrosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Approach and results</h3>\u0000 \u0000 <p>CXCL14 knockdown significantly reduced the extent of liver fibrosis. Using Ingenuity pathway analysis and qRT-PCR, activating transcription factor 3 (ATF3) was identified as a key upstream regulator of CXCL14 expression. Mechanistically, ATF3 was shown to bind to the CXCL14 promoter, promoting its transactivation by TGF-β in HSCs. Notably, both global CXCL14 deletion (<i>CXCL14^−/−</i>) and HSC/myofibroblast-specific CXCL14 knockdown significantly attenuated liver fibrosis in mice. RNA-seq comparisons between <i>CXCL14^−/−</i> and WT mice highlighted Jak2 as the most significantly downregulated gene, implicating its role in the antifibrotic effects of CXCL14 suppression on HSC inactivation. Moreover, Jak2 overexpression reversed the inhibition of liver fibrosis caused by CXCL14 knockdown in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings unveil a novel ATF3/CXCL14/Jak2 signalling axis in liver fibrosis, presenting potential therapeutic targets for the disease.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364598","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":"Single-cell and spatial omics unravel the spatiotemporal biology of tumour border invasion and haematogenous metastasis","authors":"Xifu Cheng,&nbsp;Yuke Cao,&nbsp;Xiangyi Liu,&nbsp;Yuanheng Li,&nbsp;Qing Li,&nbsp;Dian Gao,&nbsp;Qiongfang Yu","doi":"10.1002/ctm2.70036","DOIUrl":"10.1002/ctm2.70036","url":null,"abstract":"<p>Solid tumours exhibit a well-defined architecture, comprising a differentiated core and a dynamic border that interfaces with the surrounding tissue. This border, characterised by distinct cellular morphology and molecular composition, serves as a critical determinant of the tumour's invasive behaviour. Notably, the invasive border of the primary tumour represents the principal site for intravasation of metastatic cells. These cells, known as circulating tumour cells (CTCs), function as ‘seeds’ for distant dissemination and display remarkable heterogeneity. Advancements in spatial sequencing technology are progressively unveiling the spatial biological features of tumours. However, systematic investigations specifically targeting the characteristics of the tumour border remain scarce. In this comprehensive review, we illuminate key biological insights along the tumour body-border-haematogenous metastasis axis over the past five years. We delineate the distinctive landscape of tumour invasion boundaries and delve into the intricate heterogeneity and phenotype of CTCs, which orchestrate haematogenous metastasis. These insights have the potential to explain the basis of tumour invasion and distant metastasis, offering new perspectives for the development of more complex and precise clinical interventions and treatments.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342703","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":"Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity","authors":"Baochao Li,&nbsp;Yuqin Jin,&nbsp;Bingqing Zhang,&nbsp;Tong Lu,&nbsp;Jialing Li,&nbsp;Jingzi Zhang,&nbsp;Yiwen Zhou,&nbsp;Yanyi Wang,&nbsp;Caixia Zhang,&nbsp;Yue Zhao,&nbsp;Huang Li","doi":"10.1002/ctm2.70029","DOIUrl":"10.1002/ctm2.70029","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Objectives&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA.&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;The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo.&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;Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (&lt;i&gt;Ggpps&lt;/i&gt;) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process .&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;Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA.&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;High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.&lt;/li&gt;\u0000 &lt;/ul&gt;\u0000 &lt;/div&gt;\u0000 &lt;/sect","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342702","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":"Trem2 acts as a non-classical receptor of interleukin-4 to promote diabetic wound healing","authors":"Xinlin Zhu,&nbsp;Chao Zhang,&nbsp;Weiwei Jiang,&nbsp;Zhaoxiang Zeng,&nbsp;Keming Zhang,&nbsp;Mingwei Du,&nbsp;Juan Chen,&nbsp;Qian Wu,&nbsp;Wanqing Liao,&nbsp;Youming Chen,&nbsp;Wenjie Fang,&nbsp;Weihua Pan","doi":"10.1002/ctm2.70026","DOIUrl":"10.1002/ctm2.70026","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The immunoglobulin superfamily protein Trem2 (triggering receptor expressed on myeloid cells 2) is primarily expressed on myeloid cells where it functions to regulate macrophage-related immune response induction. While macrophages are essential mediators of diabetic wound healing, the specific regulatory role that Trem2 plays in this setting remains to be established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study was developed to explore the potential importance of Trem2 signalling in diabetic wound healing and to clarify the underlying mechanisms through which it functions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Following wound induction, diabetic model mice exhibited pronounced upregulation of Trem2 expression, which was primarily evident in macrophages. No cutaneous defects were evident in mice bearing a macrophage-specific knockout of Trem2 (T2-cKO), but they induced more pronounced inflammatory responses and failed to effectively repair cutaneous wounds, with lower levels of neovascularization, slower rates of wound closure, decreased collagen deposition following wounding. Mechanistically, we showed that interleukin (IL)-4 binds directly to Trem2, inactivating MAPK/AP-1 signalling to suppress the expression of inflammatory and chemoattractant factors. Co-culture of fibroblasts and macrophages showed that macrophages from T2-cKO mice suppressed the in vitro activation and proliferation of dermal fibroblasts through upregulation of leukaemia inhibitory factor (Lif). Injecting soluble Trem2 in vivo was also sufficient to significantly curtail inflammatory responses and to promote diabetic wound healing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These analyses offer novel insight into the role of IL-4/Trem2 signalling as a mediator of myeloid cell-fibroblast crosstalk that may represent a viable therapeutic target for efforts to enhance diabetic wound healing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 10","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342704","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":"Corrigendum to ‘Adipocyte-specific FAK deletion promotes pancreatic β-cell apoptosis via adipose inflammatory response to exacerbate diabetes mellitus’","authors":"","doi":"10.1002/ctm2.70033","DOIUrl":"10.1002/ctm2.70033","url":null,"abstract":"<p>In this article, we have just realized the wrong usage of flow cytometry chart in the FAK siRNA group in Figure S7B of Supplementary Material.</p><p>The wrong Figure S7 is as follows.</p><p></p><p>The corrected Figure S7 is as follows.</p><p></p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307231","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":"RETRACTION: The Novel Role of Circular RNA ST3GAL6 on Blocking Gastric Cancer Malignant Behaviours Through Autophagy Regulated by the FOXP2/MET/Mtor Axis","authors":"","doi":"10.1002/ctm2.70025","DOIUrl":"10.1002/ctm2.70025","url":null,"abstract":"<p><b>RETRACTION</b>: P. Xu, X. Zhang, J. Cao, J. Yang, Z. Chen, W. Wang, S. Wang, L. Zhang, L. Xie, L. Fang, Y. Xia, Z. Xuan, J. Lv, H. Xu, and Z. Xu, “The Novel Role of Circular RNA ST3GAL6 on Blocking Gastric Cancer Malignant Behaviours Through Autophagy Regulated by the FOXP2/MET/Mtor Axis,” <i>Clinical and Translational Medicine</i> 12, no.1 (2022): e707, https://doi.org/10.1002/ctm2.707.</p><p>The above article, published online on 21 January 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Xiangdong Wang; the Shanghai Institute of Clinical Bioinformatics; and John Wiley &amp; Sons Australia, Ltd. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate duplications of image panels within the article (Figures 6H and 7J) and between this article (Figures 2D, 7B, 7K, 8E and 8J) and another article previously published elsewhere by an overlapping group of authors in a different scientific context. The authors were unable to provide a satisfactory explanation and the raw data they supplied could not explain the identified issues. In addition, the cell line SGC-7901 used in this study has been reported as contaminated with HeLa cells, making it a problematic model for gastric cancer [1,2]. Given the extent of the identified issues, the editors have lost confidence in the data presented and the article's conclusions can no longer be considered reliable.</p><p><b>References</b></p><p>[1] F. Ye, C. Chen, J. Qin, J. Liu, and C. Zheng, “Genetic Profiling Reveals an Alarming Rate of Cross-Contamination Among Human Cell Lines Used in China,” <i>The FASEB Journal</i> 29, no. 10 (2015):4268–4272, https://doi.org/10.1096/fj.14-266718.</p><p>[2] X. Bian, Z. Yang, H. Feng, H. Sun, and Y. Liu, “A Combination of Species Identification and STR Profiling Identifies Cross-contaminated Cells from 482 Human Tumor Cell Lines,” <i>Scientific Reports</i> 7, no. 1 (2017):9774, https://doi.org/10.1038/s41598-017-09660-w.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307234","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":"Rapid, portable Epstein‒Barr virus DNA detection using enzymatic recombinase amplification combined with the CRISPR–Cas12a system","authors":"Jia Li,&nbsp;Hao Cheng,&nbsp;Xiaojun Wang,&nbsp;Ning Chen,&nbsp;Liujie Chen,&nbsp;Lili Duan,&nbsp;Fenghua Tan,&nbsp;Kai Li,&nbsp;Duanfang Liao,&nbsp;Zheng Hu","doi":"10.1002/ctm2.70028","DOIUrl":"10.1002/ctm2.70028","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Nasopharyngeal carcinoma (NPC), a malignancy affecting the head and neck region, is prevalent in the southern and southeastern coastal regions of China. The primary cause of NPC is the Epstein−Barr virus (EBV).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; EBV DNA detection is crucial for the screening and monitoring of NPC and other EBV infection-related diseases. Plasma EBV DNA is considered an important indicator for early NPC screening,&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; as well as monitoring NPC prognosis and treatment efficacy.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; However, the clinical diagnostic method involves quantitative polymerase chain reaction (qPCR), the application of which is limited by its time, cost and convenience.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Recently, rapid detection techniques that combine the CRISPR-Cas system with isothermal amplification technique (for instance recombinase polymerase amplification [RPA], rolling circle amplification [RCA] and loop-mediated isothermal amplification [LAMP]) have been increasingly developed and used for identifying various pathogens, (e.g. SARS-CoV-2,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; HPV16/18,&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; HIV&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;). Enzymatic recombination amplification (ERA) is an advanced version of isothermal amplification technology,&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; building on RPA technology. Given its efficiency, adaptability and robustness, ERA is a promising method for enhancing the sensitivity of CRISPR-based pathogen detection.&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; In this study, we developed a rapid, portable method for detecting EBV nucleic acids by ERA combined with CRISPR–Cas12a (ERA–Cas12a).&lt;/p&gt;&lt;p&gt;Firstly, we tested the enhanced effect of ERA amplification to CRISPR–Cas12a detection of EB DNA by CRISPR–Cas12a-mediated fluorescence cleavage assay. EBV DNA samples that were not pre-amplified by ERA showed no notable alteration of fluorescence intensity contrast to the negative control (Figure S1). On the other hand, employing ERA amplification significantly improved the sensitivity of EBV DNA detection using the CRISPR‒Cas12a system (Figure S1).&lt;/p&gt;&lt;p&gt;Secondly, the reaction conditions of ERA (such as primer, volume) were optimized to improve the system of ERA–Cas12a sensitivity and specificity.&lt;/p&gt;&lt;p&gt;Primer design is crucial for ERA. LMP2A transcripts are relatively stable and can be detected persistently in NPC and other EBV-related malignant tumours. In total, we designed and tested 18 ERA primer pairs targeting the LMP-2A gene of EBV. Of them, 12 primer pairs were tested for LMP1 fragments, with the most efficient amplification achieved using LMP1-F2+R3 and LMP1-F3+R3 (Figure S2A). Moreover, six primer pairs were tested for LMP2 fragments, with the most efficient amplification achieved using LMP2-F3+R1 and LMP2-F3+R2 (Figure S2B). The real-time fluorescence curve demonstrated that LMP1-F3+R3 and LMP2-F3+R1 reached a plateau phase rapidly. Consequently, the primer pairs LMP1-F3+R3 and LMP2-F3+R1 were identified as","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307233","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":"IBR1, a novel endogenous IFIH1-binding dsRNA, governs IFIH1 activation and M1 macrophage polarisation in ARDS","authors":"Shi Zhang,&nbsp;Wei Huang,&nbsp;Xueling Wu,&nbsp;Hanbing Chen,&nbsp;Lu Wang,&nbsp;Jie Chao,&nbsp;Jianfeng Xie,&nbsp;Haibo Qiu","doi":"10.1002/ctm2.70027","DOIUrl":"10.1002/ctm2.70027","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;Uncontrolled inflammation caused by macrophages and monocytes plays a crucial role in worsening acute respiratory distress syndrome (ARDS). Previous studies have highlighted the importance of IFIH1 in regulating macrophage polarisation in ARDS triggered by pneumonia. However, the mechanisms by which IFIH1 is activated in ARDS remain 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;In this study, we utilised multiomics sequencing and molecular interaction experiments to explore the molecular mechanisms underlying IFIH1 activation in ARDS. Through the use of conditional gene knockout mice and primary cells, we demonstrated the significant role of these mechanisms in the development of ARDS. Additionally, we validated the associations between these mechanisms and ARDS by quantitative PCR analysis of CD14&lt;sup&gt;+&lt;/sup&gt; cells obtained from the peripheral blood of 140 ARDS patients.&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;Our investigation revealed that lipopolysaccharide, a critical component derived from Gram-negative bacteria, activated IFIH1 by upregulating a novel transcript known as IFIH1-binding RNA1 (IBR1) in monocytes and macrophages. Specifically, as an endogenous double-stranded RNA, IBR1 bind to the helicase domain of IFIH1 because of its unique double-stranded structure. Deletion of IBR1 significantly reduced the activation of IFIH1, M1 polarisation of macrophages, and inflammatory lung injury in ARDS. Moreover, IBR1 directly induced M1 polarisation of macrophages and ARDS, whereas deletion of IFIH1 inhibited IBR1-induced macrophage M1 polarisation and inflammatory lung injury. Importantly, we observed a notable increase in IBR1 expression in ARDS patients with pneumonia caused by Gram-negative bacteria. Furthermore, we demonstrated that the delivery of IFIH1 mutants through exosomes effectively counteracted IBR1, thereby reducing pulmonary inflammation and alleviating lung injury.&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;This study revealed a novel mechanism involving IBR1, an endogenous double-stranded RNA (dsRNA) that binds to IFIH1, shedding light on the complex process of macrophage polarisation in ARDS. The administration of IFIH1 variants has the potential to eliminate pulmonary dsRNA and alleviate inflammatory lung injury in ARDS.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ol&gt;\u0000 \u0000 &lt;li&gt;\u0000 ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142307232","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 mode of single-cell measurements: An artificial intelligent single-cell","authors":"Xiangdong Wang,&nbsp;Charles A. Powell,&nbsp;Qin Ma,&nbsp;Jia Fan","doi":"10.1002/ctm2.1818","DOIUrl":"10.1002/ctm2.1818","url":null,"abstract":"<p>With rapid development and mature of single-cell measurements, single-cell biology and pathology become an emerging discipline to understand the disease. However, it is important to address concerns raised by clinicians as to how to apply single-cell measurements for clinical practice, translate the signals of single-cell systems biology into determination of clinical phenotype, and predict patient response to therapies. The present Perspective proposes a new system coined as the clinical artificial intelligent single-cell (caiSC) with the dynamic generator of clinical single-cell informatics, artificial intelligent analyzers, molecular multimodal reference boxes, clinical inputs and outs, and AI-based computerization. This system provides reliable and rapid information for impacting clinical diagnoses, monitoring, and prediction of the disease at the single-cell level. The caiSC represents an important step and milestone to translate the single-cell measurement into clinical application, assist clinicians’ decision-making, and improve the quality of medical services. There is increasing evidence to support the possibility of the caiSC proposal, since the corresponding biotechnologies associated with caiSCs are rapidly developed. Therefore, we call the special attention and efforts from various scientists and clinicians on the caiSCs and believe that the appearance of the caiSCs can shed light on the future of clinical molecular medicine.</p>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.1818","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281189","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":"Distinct discrepancy in breast cancer organoids recapitulation among molecular subtypes revealed by single-cell transcriptomes analysis","authors":"Ziqi Jia,&nbsp;Hengyi Xu,&nbsp;Yaru Zhang,&nbsp;Heng Cao,&nbsp;Chunyu Deng,&nbsp;Longchen Xu,&nbsp;Yuning Sun,&nbsp;Jiayi Li,&nbsp;Yansong Huang,&nbsp;Pengming Pu,&nbsp;Tongxuan Shang,&nbsp;Xiang Wang,&nbsp;Jianzhong Su,&nbsp;Jiaqi Liu","doi":"10.1002/ctm2.70023","DOIUrl":"https://doi.org/10.1002/ctm2.70023","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Breast cancer organoids (BCOs) are increasingly recognised as crucial tools in personalised medicine,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; yet a significant gap remains between the need for precise drug sensitivity assessments and the biological disparities observed between BCOs and primary breast cancer (PBC) tissues.&lt;span&gt;&lt;sup&gt;2, 3&lt;/sup&gt;&lt;/span&gt; Our extensive analysis of paired single-cell RNA sequencing data has revealed a substantial preservation of molecular characteristics in hormone receptor-positive (HR-positive) and HER2-positive breast cancers. However, in triple-negative breast cancer (TNBC), we observed marked variability in cell subpopulations, likely influenced by oxygen-enriched culture conditions.&lt;/p&gt;&lt;p&gt;To investigate the preservation of characteristics across different molecular subtypes of breast cancer, we cultured six BCOs representing three subtypes: two HR-positive, two HER2-positive, and two TNBCs derived from surgical samples without prior adjuvant treatments (for study design, see Figure S1; for images of successfully established organoids, see Figure S2; patient clinical characteristics are detailed in the Supplementary Table). Following establishment, single-cell RNA sequencing was performed on matched PBCs and BCOs, yielding 66,920 quality-controlled cells (Figure 1A; for contributions of samples, molecular subtypes, and sample sources, see Figure S3). Our analysis of cell type composition revealed a significant reduction in immune and stromal cells in BCOs compared to PBCs (adjusted &lt;i&gt;p&lt;/i&gt; &lt; 0.001; Figure 1B), while epithelial cells proportions nearly doubled (&lt;i&gt;p&lt;/i&gt; = 0.031, median fold change = 0.96, IQR = 0.94-1.78, Figure 1C). This suggests that organoid culture better preserves epithelial cells, and co-culture systems are required for the preservation of the tumour microenvironment (TME).&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Further analyses demonstrated reductions in both the proportions and functionality of all immune and stromal cell subpopulations (Figure 1D-F). Notably, both malignant and non-malignant epithelial cells were amplified in BCOs while maintaining key functional characteristics (Figure 1G-I; see Methods section in Supplementary Materials for malignancy determination). Thus, despite the observed differences in cell type distribution, these findings did not diminish the value of organoids as robust in vitro models for studying epithelial components of tumours.&lt;/p&gt;&lt;p&gt;To assess genomic concordance in PDOs,&lt;sup&gt;5&lt;/sup&gt; we analysed copy number variation (CNV) as a genomic marker between BCOs and PBCs using both paired and unpaired comparisons. Our findings revealed that BCOs effectively preserved cellular-level CNVs from PBCs in five out of six cases (Figure 2A), with an average retention rate of 71.6%. This preservation was particularly robust in HR-positive breast cancer at 88.2%, though it was less pronounced in TNBC at 62.4% (Figure 2B and C). Moreover, BCOs demonstrated the ability to amplify ","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"14 9","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ctm2.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276619","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}