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Pancancer outcome prediction via a unified weakly supervised deep learning model 认领 引用
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作者 Wei Yuan Yijiang Chen +34 位作者 Biyue Zhu Sen Yang Jiayu Zhang Ning Mao Jinxi Xiang Yuchen Li Yuanfeng Ji Xiangde Luo Kangning Zhang Xiaohan Xing Shuo Kang Dongyuan Xiao Fang Wang Jinkun Wu Haiyan Zhang Hongping Tang Himanshu Maurya German Corredor Cristian Barrera Yufei Zhou Krunal Pandav Junhan Zhao Prantesh Jain Luke Delasos Junzhou Huang Kailin Yang Theodoros N.Teknos James Lewis Jr Shlomo Koyfman Nathan A.Pennell Kun-Hsing Yu Xiao Han Jing Zhang Xiyue Wang Anant Madabhushi 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2025年第10期5454-5464,共11页
Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes.While recent studies have demonstrated the potential of histopathological images in survival analysis,existing mod... Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes.While recent studies have demonstrated the potential of histopathological images in survival analysis,existing models are typically developed in a cancerspecific manner,lack extensive external validation,and often rely on molecular data that are not routinely available in clinical practice.To address these limitations,we present PROGPATH,a unified model capable of integrating histopathological image features with routinely collected clinical variables to achieve pancancer prognosis prediction.PROGPATH employs a weakly supervised deep learning architecture built upon the foundation model for image encoding.Morphological features are aggregated through an attention-guided multiple instance learning module and fused with clinical information via a cross-attention transformer.A router-based classification strategy further refines the prediction performance.PROGPATH was trained on 7999 whole-slide images(WSIs)from 6,670 patients across 15 cancer types,and extensively validated on 17 external cohorts with a total of 7374 WSIs from 4441 patients,covering 12 cancer types from 8 consortia and institutions across three continents.PROGPATH achieved consistently superior performance compared with state-of-the-art multimodal prognosis prediction models.It demonstrated strong generalizability across cancer types and robustness in stratified subgroups,including early-and advancedstage patients,treatment cohorts(radiotherapy and pharmaceutical therapy),and biomarker-defined subsets.We further provide model interpretability by identifying pathological patterns critical to PROGPATH’s risk predictions,such as the degree of cell differentiation and extent of necrosis.Together,these results highlight the potential of PROGPATH to support pancancer outcome prediction and inform personalized cancer management strategies. 展开更多
关键词 pancancer prognosis integrating histopathological image features molecular data accurate prognosis prediction unified model histopathological images weakly supervised deep learning survival analysisexisting
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Activating lithium storage in 2D CaSi2 anode via enhancing pseudocapacitive properties with oxygen modification engineering 认领 引用
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作者 Yongzheng Zhang Lu Sun +4 位作者 Kailin Yang Youwang Ye Liang Zhan Qi Wei Jianan Gu 《Nano Research》 SCIE EI CSCD 2025年第4期199-206,共8页
Silicon(Si)has emerged as a promising anode material for lithium-ion batteries(LIBs)due to its extremely high theoretical capacity of 4200 mAh·g-1.However,its practical application is limited by several critic... Silicon(Si)has emerged as a promising anode material for lithium-ion batteries(LIBs)due to its extremely high theoretical capacity of 4200 mAh·g-1.However,its practical application is limited by several critical challenges,including severe volume expansion and poor electrical conductivity.Herein,we employ a two-dimensional(2D)oxygen modification engineering approach to fabricate 2D oxygen-functionalized CaSi2(CaSi2Ox)layers.During the preparation of 2D CaSi2 layers,O atoms are gradually incorporated onto their surface.The resulting 2D CaSi2Ox layers have a thickness of 3-5 nm,closely matching the theoretical thickness of 6-10 layers.When used as lithium anodes,the 2D CaSi2Ox layers exhibit exceptional electrochemical performance,maintaining stability over 3000 cycles at an ultrahigh current density of 30 A·g-1.By tailoring the surface properties,their pseudocapacitive charge storage mechanism is significantly enhanced,effectively overcoming the intrinsic limitations of traditional Si anodes.This study highlights the promise of 2D surface engineering in the development of advanced materials for next-generation LIBs. 展开更多
关键词 two-dimensional(2D)CaSi2Ox Si anode volume change pseudocapacitive surface modification lithium storage
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High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors 认领 引用 被引量：18
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作者 Yao Zhao Xiaoyu Du +23 位作者 Yinkai Duan Xiaoyan Pan Yifang Sun Tian You Lin Han Zhenming Jin Weijuan Shang Jing Yu Hangtian Guo Qianying Liu Yan Wu Chao Peng Jun Wang Chenghao Zhu Xiuna Yang Kailin Yang Ying Lei Luke W.Guddat Wenqing Xu Gengfu Xiao Lei Sun Leike Zhang Zihe Rao Haitao Yang 《Protein & Cell》 SCIE CSCD 2021年第11期877-888,共12页
A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identif... A new coronavirus(SARS-CoV-2)has been identified as the etiologic agent for the COVID-19 outbreak.Currently,effective treatment options remain very limited for this disease;therefore,there is an urgent need to identify new anti-COVID-19 agents.In this study,we screened over 6,000 compounds that included approved drugs,drug candidates in clinical trials,and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease(PLpro).Together with main protease(Mpro),PLpro is responsible for processing the viral replicase polyprotein into functional units.There-fore,it is an attractive target for antiviral drug develop-ment.Here we discovered four compounds,YM155,cryptotanshinone,tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 pmol/L.These compounds also exhibit strong antiviral activities in cell-based assays.YM155,an anti-cancer drug candidate in clinical trials,has the most potent antiviral activity with an EC50 value of 170 nmol/L.In addition,we have determined the crystal structures of this enzyme and its complex with YM155,revealing a unique binding mode.YM155 simultaneously targets three"hot"spots on PLpro,including the substrate-binding pocket,the interferon stimulating gene product 15(ISG15)binding site and zinc finger motif.Our results demonstrate the efficacy of this screening and repur-posing strategy,which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments. 展开更多
关键词 SARS-CoV-2 papain-like protease YM155 interferon stimulating gene product 15 drug repurposing
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Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332 认领 引用 被引量：29
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作者 Yao Zhao Chao Fang +15 位作者 Qi Zhang Ruxue Zhang Xiangbo Zhao Yinkai Duan Haofeng Wang Yan Zhu Lu Feng Jinyi Zhao Maolin Shao Xiuna Yang Leike Zhang Chao Peng Kailin Yang Dawei Ma Zihe Rao Haitao Yang 《Protein & Cell》 SCIE CSCD 2022年第9期689-693,共5页
Dear Editor,Since December 2019,the pandemic of coronavirus disease 2019(COVID-19)has taken a heavy toll on global health,creating an urgent need to develop effective strategies for prevention and treatment.The etiolo... Dear Editor,Since December 2019,the pandemic of coronavirus disease 2019(COVID-19)has taken a heavy toll on global health,creating an urgent need to develop effective strategies for prevention and treatment.The etiological agent,known as severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected nearly 229.2 million people worldwide with more than 4.7 million deaths as of September 15,2021.Older age and preexisting health conditions are associated with worse clinical prognosis including higher mortality rates(Zhou et al.,2020).The global race to combat this pandemic has led to rapid deployment of numerous effective vaccines against SARS-CoV-2(Tregoning et al.,2021).However,the emergence of viral variants,including the Delta variant(B.1.617.2),compromised vaccine effectiveness with resurgence of SARS-CoV-2 infection among highly vaccinated population(Keehner et al.,2021).Therefore,development of therapeutics against the more conserved viral targets would be essential to contain the spread of COVID-19 and reduce mortality. 展开更多
关键词 mortality prevention Crystal
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Rhizosphere microbial markers (micro-markers): A new physical examination indicator for traditional Chinese medicines 认领 引用 被引量：6
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作者 Kailin Yang Yaping Zheng +4 位作者 Kangmeng Sun Xinyan Wu Zheng Zhang Chunnian He Peigen Xiao 《Chinese Herbal Medicines》 CAS 2024年第2期180-189,共10页
Rhizosphere microorganisms,as one of the most important components of the soil microbiota and plant holobiont,play a key role in the medicinal plant-soil ecosystem,which are closely related to the growth,adaptability,... Rhizosphere microorganisms,as one of the most important components of the soil microbiota and plant holobiont,play a key role in the medicinal plant-soil ecosystem,which are closely related to the growth,adaptability,nutrient absorption,stress tolerance and pathogen resistance of host plants.In recent years,with the wide application of molecular biology and omics technologies,the outcomes of rhizosphere microorganisms on the health,biomass production and secondary metabolite biosynthesis of medicinal plants have received extensive attention.However,whether or to what extent rhizosphere microorganisms can contribute to the construction of the quality evaluation system of Chinese medicinal materials is still elusive.Based on the significant role of rhizosphere microbes in the survival and quality formation of medicinal plants,this paper proposed a new concept of rhizosphere microbial markers(micro-markers),expounded the relevant research methods and ideas of applying the new concept,highlighted the importance of micro-markers in the quality evaluation and control system of traditional Chinese medicines(TCMs),and introduced the potential value in soil environmental assessment,plant pest control and quality assessment of TCMs.It provides reference for developing ecological planting of TCMs and ensuring the production of high quality TCMs by regulating rhizosphere microbial communities. 展开更多
关键词 physical examination indicator quality evaluation quality formation of medicinal plants rhizosphere microorganisms rhizosphere microbial markers
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The genomic and immunogenomic landscape of mechanics pathway informs clinical prognosis and response to mechanotherapy 认领 引用 被引量：2
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作者 Peidong Zhang Peiwei Li +11 位作者 Muya Tang Ryan CGimple Liang Huang Jing Yue Qiuhong Shen Yiwei Du Qian Zhang Zhengnan Yang Haihuai He Kailin Yang Linjie Zhao Shengtao Zhou 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第8期1549-1562,共14页
Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogr... Mechanics shape cell and tissue plasticity and maintain their homeostasis.In cancers,mechanical signals regulate cancer hallmarks via mechanotransduction pathways,such as proliferation,metastasis and metabolic reprogramming.However,comprehensive characterization of mechanotransduction pathway genes and their clinical relevance across different cancer types remains untouched.Herein,we systematically portrayed the alterations of mechanotransduction pathway genes across 31 cancer types using The Cancer Genome Atlas(TCGA)databases.All the cancer types could be categorized into 6 subtypes based upon the transcriptional pattern of mechanics pathway genes.Each subtype has its own unique molecular expression pattern,mutation landscapes,immune infiltrates,and patient clinical outcome.We further found that the responses of two subtypes of cancers,one with the optimal outcome and the other with the worst prognosis,to a classical mechanotherapeutic agent(Fasudil,RhoA/ROCK inhibitor)were totally different,indicating that our cancer stratification system based upon mechanotransduction pathway genes could inform clinical responses of patients to mechanotherapeutic agents.Collectively,our study provides a novel pan-cancer landscape of the mechanotransduction pathways and underscores its potential clinical significance in the prediction of clinical prognosis and therapeutic responses to mechanotherapy among cancer patients. 展开更多
关键词 pan-cancer cancer mechanics multi-omics immunology
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Structural basis of Zika virus helicase in recognizing its substrates 认领 引用 被引量：3
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作者 Hongliang Tian Xiaoyun Ji +12 位作者 Xiaoyun Yang Zhongxin Zhang zuoku Lu Kailin Yang Cheng Chen Qi Zhao Heng Chi Zhongyu Mu Wei Xie Zefang Wang Huiqiang Lou Haitao Yang Zihe Rao 《Protein & Cell》 SCIE CSCD 2016年第8期562-570,共9页
The recent explosive outbreak of Zika virus （ZlKV） infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health ... The recent explosive outbreak of Zika virus （ZlKV） infection has been reported in South and Central America and the Caribbean. Neonatal microcephaly associated with ZIKV infection has already caused a public health emergency of international concern. No specific vaccines or drugs are currently available to treat ZIKV infection. The ZIKV helicase, which plays a pivotal role in viral RNA replication, is an attractive tar- get for therapy. We determined the crystal structures of ZIKV helicase-ATP-Mnz＋ and ZlKV helicase-RNA. This is the first structure of any flavivirus helicase bound to ATP. Comparisons with related flavivirus helicases have shown that although the critical P-loop in the active site has variable conformations among different species, it adopts an identical mode to recognize ATPIMn2＋. The structure of ZlKV helicase-RNA has revealed that upon RNA binding, rotations of the motor domains can cause significant conformational changes. Strikingly, although ZlKV and dengue virus （DENV） apo-helicases share conserved residues for RNA binding, their different manners of motor domain rotations result in distinct individual modes for RNA recognition. It suggests that flavivirus helicases could have evolved a conserved engine to convert chemical energy from nucleoside triphosphate to mechanical energy for RNA unwinding, but different motor domain rotations result in variable RNA recognition modes to adapt to individual viral replication. 展开更多
关键词 Zika virus helicase ATP crystal structure,flavivirus
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The crystal structure of Zika virus helicase:basis for antiviral drug design 认领 引用 被引量：5
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作者 Hongliang Tian Xiaoyun Ji +8 位作者 Xiaoyun Yang Wei Xie Kailin Yang Cheng Chen Chen Wu Heng Chi ZhongyuMu Zefang Wang Haitao Yang 《Protein & Cell》 SCIE CSCD 2016年第6期450-454,共5页
Dear Editor The genus of Flavivirus contains important human patho- gens, including dengue (DENV), yellow fever (YFV), West Nile (WNV), Japanese encephalitis (JEV), and tick-borne encephalitis (TBEV) viruses, which ca... Dear Editor The genus of Flavivirus contains important human patho- gens, including dengue (DENV), yellow fever (YFV), West Nile (WNV), Japanese encephalitis (JEV), and tick-borne encephalitis (TBEV) viruses, which cause a number of seri- ous human diseases throughout the world (Pierson TC, 2013). Zika virus (ZIKV) is also an arthropod-borne flavivirus, which was initially isolated in 1947 from a febdle sentinel rhesus monkey in the Zika forest in Entebbe, Uganda. 展开更多
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