A set of closed-loop normative standards of PDCA(planning-implementing-checking-improvement) of the quality management system is applied to promote the standardization, normalization and institutionalization of grass-...A set of closed-loop normative standards of PDCA(planning-implementing-checking-improvement) of the quality management system is applied to promote the standardization, normalization and institutionalization of grass-roots meteorological observations, further improve the service availability and timely rate of data, and improve the quality and efficiency of meteorological observations.展开更多
Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Here...Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Herein,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical responses.The multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in PCa.Through the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary cells.We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations.Surprisingly,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model.Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.展开更多
A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and el...A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and eliminated out of the body in proper manner.The processes of drug getting into and out of the body involve Absorption,Distribution,Metabolism,and Excretion（ADME）,展开更多
The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reve...The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.展开更多
Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direct...Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future.展开更多
We present a discovery of an unusual unidirectionally rotating windmill scattering of electromagnetic waves by a magnetized gyromagnetic cylinder via an analytical theory for rigorous solution to fields and charges an...We present a discovery of an unusual unidirectionally rotating windmill scattering of electromagnetic waves by a magnetized gyromagnetic cylinder via an analytical theory for rigorous solution to fields and charges and an understanding of the underlying mathematical and physical mechanisms. Mathematically, the generation of nonzero off-diagonal components can break the symmetry of forward and backward scattering coefficients, producing unidirectional windmill scattering. Physically, this windmill scattering originates from the nonreciprocal unidirectional rotation of polarized magnetic charges on the surface of a magnetized gyromagnetic cylinder, which drives the scattering field to radiate outward in the radial direction and unidirectionally emit in the tangential direction. Interestingly, the unidirectional electromagnetic windmill scattering is insensitive to the excitation direction. Moreover, we also discuss the size dependence of unidirectional windmill scattering by calculating the scattering spectra of the gyromagnetic cylinder. These results are helpful for exploring and understanding novel interactions between electromagnetic waves and gyromagnetic materials or structures and offer deep insights for comprehending topological photonic states in gyromagnetic systems from the aspect of fundamental classical electrodynamics and electromagnetics.展开更多
文摘A set of closed-loop normative standards of PDCA(planning-implementing-checking-improvement) of the quality management system is applied to promote the standardization, normalization and institutionalization of grass-roots meteorological observations, further improve the service availability and timely rate of data, and improve the quality and efficiency of meteorological observations.
基金supported by National Natural Science Foundation of China(22137002[Y.D.],32071432[M.T.],81872102[H.J.])University Innovation Research Group Project of Chongqing(CXQT21016[Y.D.])+3 种基金High-Level Innovation Platform Project of Chongqing[Y.D.]Talent Program of Chongqing(CQYC202003053[Y.D.])The collaborative project of Chinese Academy of Sciences institutions and universities in Chongqing(HZ2021006[Y.D.])Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZDCX20181202[M.T.]).
文摘Prostate cancer(PCa)is the second most prevalent malignancy in males across the world.A greater knowledge of the relationship between protein abundance and drug responses would benefit precision treatment for PCa.Herein,we establish 35 Chinese PCa primary cell models to capture specific characteristics among PCa patients,including gene mutations,mRNA/protein/surface protein distributions,and pharmaceutical responses.The multi-omics analyses identify Anterior Gradient 2(AGR2)as a pre-operative prognostic biomarker in PCa.Through the drug library screening,we describe crizotinib as a selective compound for malignant PCa primary cells.We further perform the pharmacoproteome analysis and identify 14,372 significant protein-drug correlations.Surprisingly,the diminished AGR2 enhances the inhibition activity of crizotinib via ALK/c-MET-AKT axis activation which is validated by PC3 and xenograft model.Our integrated multi-omics approach yields a comprehensive understanding of PCa biomarkers and pharmacological responses,allowing for more precise diagnosis and therapies.
基金supported by the Natural Science Foundation ofChina(Nos.30873159 and 31271405)
文摘A good drug or drug candidate should not only interact with its target molecule effectively and specifically,but also be absorbed into the body,distributed to the right location,metabolized into right compounds,and eliminated out of the body in proper manner.The processes of drug getting into and out of the body involve Absorption,Distribution,Metabolism,and Excretion（ADME）,
基金supported by the National Institutes of Health(NIH),USA(Grant Nos.U19AI131130,R01GM111514,R21AI131706,R35NS097370,and R37NS047344)the Intramural Research Program of the NCATS/NIH,USA
文摘The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.
基金supported by the National Natural Science Foundation of China(No.82073413 to S.J.)the Clinical and Research Fund of Wu Jieping Medical Foundation(No.320.6750.2020-01-12 to S.J.)+1 种基金the National Natural Science Foundation of China(No.22137002 to Y.D.)the China Postdoctoral Science Foundation(No.2020TQ0068 to J.W.).
文摘Bladder cancer(BLCA)remains a difficult malignancy to manage because of its high recurrence,intense follow-up,and invasive diagnostic and treatment techniques.Immune checkpoint inhibitors(ICIs)have forged a new direction for the treatment of BLCA,but it is currently challenging to predict whether an individual patient will be sensitive to ICIs.We collected 43 urine/tumor samples from BLCA patients for primary bladder cancer cells(BCCs)culturing using our previously reported BCC culture platform.We used flow cytometry(FCM)to measure the expression levels of Programmed Death-Ligand 1(PD-L1)on BCCs before and after interferon-gamma(IFN-γ)treatment and found that PD-L1 expression and the sensitivities to IFN-γvaried among patients.RNA-sequencing,western blotting,and programmed death-1(PD-1)binding assays confirmed that the BCC FCM-based PD-L1 detection platform(BC-PD-L1)was reliable and was not hindered by the glycosylation of PD-L1.In the subsequent retrospective study,we found that IFN-γ-stimulated PD-L1(sPD-L1)expression on BCCs detected by BC-PD-L1 could predict the prognosis of BLCA patients.Importantly,the prognostic value was similar or even better in urine-derived BC-PD-L1(UBC-PD-L1).Transcriptome analysis showed that BCCs with high sPD-L1 tended to enrich genes associated with the collagen-containing extracellular matrix,cell–cell adhesion,and positive regulation of the immune system.In addition,the UBC-PD-L1 also exhibited predictive value for ICI response in BLCA patients.In conclusion,as a novel personalized urine-detection method,UBC-PD-L1 may provide a rapid,accurate,and non-invasive tool for monitoring tumor progression,predicting therapeutic responses,and helping improve BLCA clinical treatment in future.
基金This work was supported by the National Natural Science Foundation of China(Nos.11974119 and 12074127)Science and Technology Project of Guangdong(No.2020B010190001)+2 种基金Science and Technology Program of Guangzhou(No.201904010105)Guangdong Innovative and Entrepreneurial Research Team Program(No.2016ZT06C594)National Key R&D Program of China(No.2018YFA0306200).
文摘We present a discovery of an unusual unidirectionally rotating windmill scattering of electromagnetic waves by a magnetized gyromagnetic cylinder via an analytical theory for rigorous solution to fields and charges and an understanding of the underlying mathematical and physical mechanisms. Mathematically, the generation of nonzero off-diagonal components can break the symmetry of forward and backward scattering coefficients, producing unidirectional windmill scattering. Physically, this windmill scattering originates from the nonreciprocal unidirectional rotation of polarized magnetic charges on the surface of a magnetized gyromagnetic cylinder, which drives the scattering field to radiate outward in the radial direction and unidirectionally emit in the tangential direction. Interestingly, the unidirectional electromagnetic windmill scattering is insensitive to the excitation direction. Moreover, we also discuss the size dependence of unidirectional windmill scattering by calculating the scattering spectra of the gyromagnetic cylinder. These results are helpful for exploring and understanding novel interactions between electromagnetic waves and gyromagnetic materials or structures and offer deep insights for comprehending topological photonic states in gyromagnetic systems from the aspect of fundamental classical electrodynamics and electromagnetics.
