Blood doping remains a significant problem that threatensthe integrity ofsport.The currentindirect method for detecting blood doping involves the longitudinal measurement of an athlete’s haematological variables and i...Blood doping remains a significant problem that threatensthe integrity ofsport.The currentindirect method for detecting blood doping involves the longitudinal measurement of an athlete’s haematological variables and identification of suspicious results that are indicative of doping(i.e.,the athlete biological passport).While this has played a significant role in the protection of clean sport,improvements are needed.The development of a transcriptomic test,that can be used to detect the use of blood doping has been discussed and researched for decades and yet,an anti-doping test that can be adopted by the World Anti-Doping Agency(WADA)is yet to be established.With recent advancements in our understanding,as well as in methods of sample collection,the possibility of a transcriptomic test that can be used by WADA,is imminent.There are,however,several practical considerations that mustfirst be made,that will be highlighted in this perspective article.展开更多
Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics t...Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3(CVB3)-induced FM in A/J mice,spanning seven distinct time points pre-and post-treatment.Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection.This triggers the activation of macrophages,initiating a cascade of inflammation.Subsequently,pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium,driving tissue damage.We also identified Cd8+effector T cells as key mediators of cardiomyocyte injury.These cells release cytotoxic molecules,particularly IFN-γ,which modulates the expression of Spi1,a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression.Therapeutic interventions targeting the IFN-γ/Spi1 axis demonstrated significant efficacy in FM models.Notably,intravenous immunoglobulin(IVIG)treatment reduced mortality,suppressed viral proliferation,and mitigated the hyperinflammatory state of FM.IVIG therapy also downregulated IFN-γ and Spi1 expression,underscoring its immunomodulatory and therapeutic potential.This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets,paving the way for more effective management strategies for this life-threatening condition.展开更多
Chikungunya virus(CHIKV)infection,responsible for chikungunya fever and occasionally severe symptoms,has emerged as an increasing global health concern following several large-scale outbreaks from Africa,Asia,Europe,a...Chikungunya virus(CHIKV)infection,responsible for chikungunya fever and occasionally severe symptoms,has emerged as an increasing global health concern following several large-scale outbreaks from Africa,Asia,Europe,and America.Over the past two decades,South and Southeast Asia regions have gradually become hot spots for outbreaks involving multiple CHIKV lineages.In China,most CHIKV infections are imported,making it crucial to trace the origins and transmission routes for effective prevention and control.In January 2024,a case of imported chikungunya fever was confirmed in Guangzhou City,Guangdong Province,China.However,the serum CHIKV viral concentration was too low for cultivation[reverse transcription-polymerase chain reaction(RT-PCR)detection,cycle threshold=32.62].Despite this,we suc-cessfully obtained the viral genome sequence directly from the whole blood sample using an optimized meta-transcriptomic sequencing strategy,achieving a full-length viral genome with an average depth of 54.3x.Further analysis confirmed that the CHIKV virus belonged to the Asian lineage,traced to Timor-Leste,where an endemic CHIKV outbreak had been reported in January 2024,consistent with the patient's travel history.Finally,we analyzed genetic evolutionary trends and amino acid site variations.This study highlights the iden-tification of a CHIKV infection origin using direct whole-blood metatranscriptomic sequencing,a valuable method for rapidly sequencing low viral-load samples.展开更多
文摘Blood doping remains a significant problem that threatensthe integrity ofsport.The currentindirect method for detecting blood doping involves the longitudinal measurement of an athlete’s haematological variables and identification of suspicious results that are indicative of doping(i.e.,the athlete biological passport).While this has played a significant role in the protection of clean sport,improvements are needed.The development of a transcriptomic test,that can be used to detect the use of blood doping has been discussed and researched for decades and yet,an anti-doping test that can be adopted by the World Anti-Doping Agency(WADA)is yet to be established.With recent advancements in our understanding,as well as in methods of sample collection,the possibility of a transcriptomic test that can be used by WADA,is imminent.There are,however,several practical considerations that mustfirst be made,that will be highlighted in this perspective article.
基金supported by the High-performance Computing Platform of YaZhou Bay Science and Technology City Advanced Computing Center(YZBSTCACC)the National Natural Science Foundation of China(Nos.82330010 and 82241034 to DWW).
文摘Fulminant myocarditis(FM)is a severe inflammatory condition of the myocardium that often results in sudden death,particularly in young individuals.In this study,we employed single-nucleus and spatial transcriptomics to perform a comprehensive analysis of coxsackievirus B3(CVB3)-induced FM in A/J mice,spanning seven distinct time points pre-and post-treatment.Our findings reveal that mesothelial cells play a critical role in the early stage of myocarditis by acting as primary targets for CVB3 infection.This triggers the activation of macrophages,initiating a cascade of inflammation.Subsequently,pro-inflammatory Inflammatory_Mac and T cells infiltrate the myocardium,driving tissue damage.We also identified Cd8+effector T cells as key mediators of cardiomyocyte injury.These cells release cytotoxic molecules,particularly IFN-γ,which modulates the expression of Spi1,a factor implicated in exacerbating cardiomyocyte death and amplifying disease progression.Therapeutic interventions targeting the IFN-γ/Spi1 axis demonstrated significant efficacy in FM models.Notably,intravenous immunoglobulin(IVIG)treatment reduced mortality,suppressed viral proliferation,and mitigated the hyperinflammatory state of FM.IVIG therapy also downregulated IFN-γ and Spi1 expression,underscoring its immunomodulatory and therapeutic potential.This comprehensive spatiotemporal transcriptomic analysis provides profound insights into the pathogenesis of FM and highlights actionable therapeutic targets,paving the way for more effective management strategies for this life-threatening condition.
基金approved by the institutional review board of the Guangzhou Eighth People's Hospital(No.202312249)the patient provided written informed consent。
文摘Chikungunya virus(CHIKV)infection,responsible for chikungunya fever and occasionally severe symptoms,has emerged as an increasing global health concern following several large-scale outbreaks from Africa,Asia,Europe,and America.Over the past two decades,South and Southeast Asia regions have gradually become hot spots for outbreaks involving multiple CHIKV lineages.In China,most CHIKV infections are imported,making it crucial to trace the origins and transmission routes for effective prevention and control.In January 2024,a case of imported chikungunya fever was confirmed in Guangzhou City,Guangdong Province,China.However,the serum CHIKV viral concentration was too low for cultivation[reverse transcription-polymerase chain reaction(RT-PCR)detection,cycle threshold=32.62].Despite this,we suc-cessfully obtained the viral genome sequence directly from the whole blood sample using an optimized meta-transcriptomic sequencing strategy,achieving a full-length viral genome with an average depth of 54.3x.Further analysis confirmed that the CHIKV virus belonged to the Asian lineage,traced to Timor-Leste,where an endemic CHIKV outbreak had been reported in January 2024,consistent with the patient's travel history.Finally,we analyzed genetic evolutionary trends and amino acid site variations.This study highlights the iden-tification of a CHIKV infection origin using direct whole-blood metatranscriptomic sequencing,a valuable method for rapidly sequencing low viral-load samples.
