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| 1 | Extracellular ADP facilitates monocyte recruitment in bacterial infection via ERK signaling显示文摘As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5′-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4. Furthermore, the expression of P2Y13 was clearly increased in both LPS-treated macrophages and tuberculosis patients. ADP protected mice from E. coli 0111-induced peritonitis by recruiting more macrophages to the infected sites. Consistent with this, ADP and ADP-treated cell culture medium attracted more macrophages in the transwell assay by enhancing the expression of MCP-1. Nevertheless, P2Y1 is dispensable for ADP-mediated protection against bacterial infection. However, either P2Y12/P2Y13 deficiency or blocking the downstream signaling of P2Y12/P2Y13 blocked the ADP-mediated immune response and allowed more bacteria to persist in the infected mice. Furthermore, extracellular signal-regulated kinase (ERK) phosphorylation was clearly increased by ADP, and this type of activation could be blocked by either forskolin or analogs of cyclic AMP (cAMP) (for example, 8-bromo-cAMP). Accordingly, ADP-induced MCP-1 production and protection against bacterial infection could also be reduced by U0126, forskolin and 8-bromo-cAMP. Overall, our study reveals a relationship between danger signals and innate immune responses, which suggests the potential therapeutic significance of ADP-mediated purinergic signaling in infectious diseases. | Xiaoyu Zhang Juliang Qin Junyan Zou Zhangsheng Lv Binghe Tan Jueping Shi Yihan Zhao Hua Ren Mingyao Liu Min Qian Bing Du | 2018 | Cellular & Molecular Immunology2018，15，1： | 1 |
| 2 | Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in nonsmall cell lung cancer显示文摘To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma(NSCLC),we performed a two-cohort of genome-wide association studies(GWAS),including 34 for WES-based and 433 for microarray-based analyses,as well as two independent validation cohorts.After integrating the results of two studies,the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples,and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments.We found that a total of 68 variations were significant at P<1×10^(-3)in cohort 1 discovery stage,of which 3 SNPs were verified in 262 independent samples.A total of541 SNPs were significant at P<1×10^(-4)in cohort 2 discovery stage,of which 8 SNPs were verified in 347 independent samples.Comparing the validated SNPs in two GWAS,ADCY1 gene was verified in both independent studies.The results of fine-mapping showed that the G allele carriers of ADCY1rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy.In conclusion,our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients. | Chenxue Mao Juan Chen Ting Zou Yuankang Zhou Junyan Liu Xi Li Xiangping Li Min Li Pinhua Pan Wei Zhuo Yang Gao Shuo Hu Desheng Xiao Lin Wu Zhan Wang Heng Xu Wen Yang Yingjie Xu Haihua Xiao Kazuhiko Hanada Wei Zhang Honghao Zhou Jiye Yin Zhaoqian Liu | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 0 |
| 3 | A Mixed Wavelet-Learning Method of Predicting Macroscopic Effective Heat Transfer Conductivities of Braided Composite Materials显示文摘In this paper,a novel mixed wavelet-learning method is developed for predicting macroscopic effective heat transfer conductivities of braided composite materials with heterogeneous thermal conductivity.This innovative methodology integrates respective superiorities of multi-scale modeling,wavelet transform and neural networks together.By the aid of asymptotic homogenization method(AHM),off-line multi-scalemodeling is accomplished for establishing thematerial databasewith highdimensional and highly-complexmappings.Themulti-scalematerial database and the wavelet-learning strategy ease the on-line training of neural networks,and enable us to efficiently build relatively simple networks that have an essentially increasing capacity and resisting noise for approximating the high-complexity mappings.Moreover,it should be emphasized that the wavelet-learning strategy can not only extract essential data characteristics from the material database,but also achieve a tremendous reduction in input data of neural networks.The numerical experiments performed using multiple 3D braided composite models verify the excellent performance of the presentedmixed approach.The numerical results demonstrate that themixedwaveletlearningmethodology is a robustmethod for computing themacroscopic effective heat transfer conductivities with distinct heterogeneity patterns.The presentedmethod can enormously decrease the computational time,and can be further expanded into estimating macroscopic effective mechanical properties of braided composites. | Hao Dong Wenbo Kou Junyan Han Jiale Linghu Minqiang Zou Junzhi Cui | 2022 | Communications in Computational Physics2022，31，2： | 0 |
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