Japanese encephalitis(JE)is a viral encephalitis disease caused by Japanese encephalitis virus(JEV)infection.Uncontrolled inflammatory responses in the central nervous system(CNS)are a hallmark of severe JE.Although t...Japanese encephalitis(JE)is a viral encephalitis disease caused by Japanese encephalitis virus(JEV)infection.Uncontrolled inflammatory responses in the central nervous system(CNS)are a hallmark of severe JE.Although the CCR2-CCL2 axis is important for monocytes trafficking during JEV infection,little is known about its role in CNS trafficking of CD8^+T cells.Here,we characterized a mouse model of JEV infection,induced via intravenous injection(i.v.)and delineated the chemokines and infiltrating peripheral immune cells in the brains of infected mice.The CNS expression of chemokines,Ccl2,Ccl3,and Ccl5,and their receptors,Ccr2 or Ccr5.was significantly up-regulated after JEV infection and was associated with the degree of JE pathogenesis.Moreover,JEV infection resulted in the migration of a large number of CD8^+T cells into the CNS.In the brains of JEV-infected mice,infiltrating CD8^+T cells expressed CCR2 and CCR5 and were found to comprise mainly effector T cells(CD44^+CD62L_).JEV infection dramatically enhanced the expression of programmed death 1(PD-1)on infiltrating CD8^+T cells in the brain,as compared to that on peripheral CD8^+T cells in the spleen.This effect was more pronounced on infiltrating CCR2^+CD8^+T cells than on CCR2-CD8^+T cells.In conclusion,we identified a new subset of CD8^+T cells(PD1^+CCR2^+CD8^+T cells)present in the CNS of mice during acute JEV infection.These CD8^+T cells might play a role in JE pathogenesis.展开更多
This study examines the impact of atmospheric and oceanic conditions during May–August of 2004 and 2010 on the frequency and genesis location of tropical cyclones over the western North Pacific. Using the WRF model, ...This study examines the impact of atmospheric and oceanic conditions during May–August of 2004 and 2010 on the frequency and genesis location of tropical cyclones over the western North Pacific. Using the WRF model, four numerical experiments were carried out based on different atmospheric conditions and SST forcing. The numerical experiments indicated that changes in atmospheric and oceanic conditions greatly affect tropical cyclone activity, and the roles of atmospheric conditions are slightly greater than oceanic conditions. Specifically, the total number of tropical cyclones was found to be mostly affected by atmospheric conditions, while the distribution of tropical cyclone genesis locations was mainly related to oceanic conditions, especially the distribution of SST. In 2010, a warmer SST occurred west of 140°E, with a colder SST east of 140°E. On the one hand, the easterly flow was enhanced through the effect of the increase in the zonal SST gradient.The strengthened easterly flow led to an anomalous boundary layer divergence over the region to the east of 140°E, which suppressed the formation of tropical cyclones over this region. On the other hand, the colder SST over the region to the east of 140°E led to a colder low-level air temperature, which resulted in decreased CAPE and static instability energy. The decrease in thermodynamic energy restricted the generation of tropical cyclones over the same region.展开更多
Introduction:Accurate prediction of protocadherin 8(PCDH8)gene expression status from whole-slide images(WSIs)is critical for thyroid cancer diagnosis and prognosis,as PCDH8 overexpression is associated with tumor agg...Introduction:Accurate prediction of protocadherin 8(PCDH8)gene expression status from whole-slide images(WSIs)is critical for thyroid cancer diagnosis and prognosis,as PCDH8 overexpression is associated with tumor aggressiveness and poor outcomes.Existing methods for PCDH8 detection are often costly,time-consuming,or require specialized expertise.To address these limitations,we developed a novel depth-wise separable residual neural network(DSRNet)for noninvasive PCDH8 status prediction directly from WSIs.Materials and methods:We collected 403 thyroid cancer WSIs from The Cancer Genome Atlas(TCGA),with PCDH8 expression status classified as high or low based on median expression values.Each WSI was divided into 512×512 pixel tiles,with the top 100 non-white tiles selected per slide.DSRNet integrates depth-wise separable convolutions,residual connections,and a deformable convolutional pyramid pooling module to efficiently capture multiscale and long-range features in gigapixel WSIs.The model was trained using tenfold cross-validation.Results:DSRNet achieved state-of-the-art performance with 92.76%accuracy,91.92%precision,92.69%recall,and 0.93 area under the curve on the thyroid cancer dataset(TCGA-THCA),significantly outperforming leading convolutional neural networks and Transformer models.Ablation studies confirmed the contributions of each component,and attention visualization showed that DSRNet focuses on biologically relevant regions.The model also generalized well to a breast cancer dataset(TCGA-BRCA),achieving 89.13%accuracy.Conclusions:We developed DSRNet,a deep learning-based model for predicting PCDH8 status directly from routine hematoxylin and eosin-stained pathological images.DSRNet combines the efficiency of convolutional operations with enhanced long-range dependency modeling,providing a noninvasive,accurate,and interpretable tool for auxiliary thyroid cancer diagnosis and prognosis.The results demonstrate its strong potential for clinical translation,though further multicenter validation is warranted.展开更多
Dear Editor,Auxin is the major plant hormone regulating growth and development(Friml,2022).Forward genetic approaches have identified major components of auxin signaling and established the canonical mechanism mediati...Dear Editor,Auxin is the major plant hormone regulating growth and development(Friml,2022).Forward genetic approaches have identified major components of auxin signaling and established the canonical mechanism mediating transcriptional and thus developmental reprogramming in Arabidopsis thaliana.In this textbook view,TRANSPORT INHIBITOR RESPONSE 1(TIR1)/AUXIN-SIGNALING F-BOX(AFB)proteins are auxin receptors,which act as F-box subunits determining the substrate specificity of the Skp1-Cullin1-F box protein(SCF)type E3 ubiquitin ligase complex.Auxin acts as a"molecular glue,"increasing the affinity between TIR1/AFBs and the Auxin/lndole-3-Acetic Acid(Aux/IAA)repressors.Subsequently,Aux/IAAs are ubiquitinated and degraded,thus releasing auxin transcription factors from their repression and making them free to mediate transcription of auxin response genes(Yu et al.,2022).展开更多
基金supported by grants from the Key Research and Development Program of the Ministry of Science and Technology of China (2016YFD500407)Precision Medicine program of Ministry of Science and Technology of China (2016YFC0905902)the National Natural Science Foundation of China (81630043, 81571552)
文摘Japanese encephalitis(JE)is a viral encephalitis disease caused by Japanese encephalitis virus(JEV)infection.Uncontrolled inflammatory responses in the central nervous system(CNS)are a hallmark of severe JE.Although the CCR2-CCL2 axis is important for monocytes trafficking during JEV infection,little is known about its role in CNS trafficking of CD8^+T cells.Here,we characterized a mouse model of JEV infection,induced via intravenous injection(i.v.)and delineated the chemokines and infiltrating peripheral immune cells in the brains of infected mice.The CNS expression of chemokines,Ccl2,Ccl3,and Ccl5,and their receptors,Ccr2 or Ccr5.was significantly up-regulated after JEV infection and was associated with the degree of JE pathogenesis.Moreover,JEV infection resulted in the migration of a large number of CD8^+T cells into the CNS.In the brains of JEV-infected mice,infiltrating CD8^+T cells expressed CCR2 and CCR5 and were found to comprise mainly effector T cells(CD44^+CD62L_).JEV infection dramatically enhanced the expression of programmed death 1(PD-1)on infiltrating CD8^+T cells in the brain,as compared to that on peripheral CD8^+T cells in the spleen.This effect was more pronounced on infiltrating CCR2^+CD8^+T cells than on CCR2-CD8^+T cells.In conclusion,we identified a new subset of CD8^+T cells(PD1^+CCR2^+CD8^+T cells)present in the CNS of mice during acute JEV infection.These CD8^+T cells might play a role in JE pathogenesis.
基金supported by the Chinese Academy of Sciences’Project“Western Pacific Ocean System:Structure,Dynamics and Consequences”(Grant No.XDA10010405)the National High Technology Research and Development Program of China(863 program)(Grant No.2012AA091801)+1 种基金the National Natural Science Foundation of China(Grant Nos.41205044 and 41205075)the Natural Science Foundation of Jiangsu Province(Grant No.BK2012062)
文摘This study examines the impact of atmospheric and oceanic conditions during May–August of 2004 and 2010 on the frequency and genesis location of tropical cyclones over the western North Pacific. Using the WRF model, four numerical experiments were carried out based on different atmospheric conditions and SST forcing. The numerical experiments indicated that changes in atmospheric and oceanic conditions greatly affect tropical cyclone activity, and the roles of atmospheric conditions are slightly greater than oceanic conditions. Specifically, the total number of tropical cyclones was found to be mostly affected by atmospheric conditions, while the distribution of tropical cyclone genesis locations was mainly related to oceanic conditions, especially the distribution of SST. In 2010, a warmer SST occurred west of 140°E, with a colder SST east of 140°E. On the one hand, the easterly flow was enhanced through the effect of the increase in the zonal SST gradient.The strengthened easterly flow led to an anomalous boundary layer divergence over the region to the east of 140°E, which suppressed the formation of tropical cyclones over this region. On the other hand, the colder SST over the region to the east of 140°E led to a colder low-level air temperature, which resulted in decreased CAPE and static instability energy. The decrease in thermodynamic energy restricted the generation of tropical cyclones over the same region.
基金partially supported by the Henan Provincial Key Research and Promotion Projects(Grant No.:242102211012)the Ministry of Education in China Project of Humanities and Social Sciences(Grant No.:24YJCZH261).
文摘Introduction:Accurate prediction of protocadherin 8(PCDH8)gene expression status from whole-slide images(WSIs)is critical for thyroid cancer diagnosis and prognosis,as PCDH8 overexpression is associated with tumor aggressiveness and poor outcomes.Existing methods for PCDH8 detection are often costly,time-consuming,or require specialized expertise.To address these limitations,we developed a novel depth-wise separable residual neural network(DSRNet)for noninvasive PCDH8 status prediction directly from WSIs.Materials and methods:We collected 403 thyroid cancer WSIs from The Cancer Genome Atlas(TCGA),with PCDH8 expression status classified as high or low based on median expression values.Each WSI was divided into 512×512 pixel tiles,with the top 100 non-white tiles selected per slide.DSRNet integrates depth-wise separable convolutions,residual connections,and a deformable convolutional pyramid pooling module to efficiently capture multiscale and long-range features in gigapixel WSIs.The model was trained using tenfold cross-validation.Results:DSRNet achieved state-of-the-art performance with 92.76%accuracy,91.92%precision,92.69%recall,and 0.93 area under the curve on the thyroid cancer dataset(TCGA-THCA),significantly outperforming leading convolutional neural networks and Transformer models.Ablation studies confirmed the contributions of each component,and attention visualization showed that DSRNet focuses on biologically relevant regions.The model also generalized well to a breast cancer dataset(TCGA-BRCA),achieving 89.13%accuracy.Conclusions:We developed DSRNet,a deep learning-based model for predicting PCDH8 status directly from routine hematoxylin and eosin-stained pathological images.DSRNet combines the efficiency of convolutional operations with enhanced long-range dependency modeling,providing a noninvasive,accurate,and interpretable tool for auxiliary thyroid cancer diagnosis and prognosis.The results demonstrate its strong potential for clinical translation,though further multicenter validation is warranted.
基金the European Research Council Advanced Grant(ETAP-742985).
文摘Dear Editor,Auxin is the major plant hormone regulating growth and development(Friml,2022).Forward genetic approaches have identified major components of auxin signaling and established the canonical mechanism mediating transcriptional and thus developmental reprogramming in Arabidopsis thaliana.In this textbook view,TRANSPORT INHIBITOR RESPONSE 1(TIR1)/AUXIN-SIGNALING F-BOX(AFB)proteins are auxin receptors,which act as F-box subunits determining the substrate specificity of the Skp1-Cullin1-F box protein(SCF)type E3 ubiquitin ligase complex.Auxin acts as a"molecular glue,"increasing the affinity between TIR1/AFBs and the Auxin/lndole-3-Acetic Acid(Aux/IAA)repressors.Subsequently,Aux/IAAs are ubiquitinated and degraded,thus releasing auxin transcription factors from their repression and making them free to mediate transcription of auxin response genes(Yu et al.,2022).
