Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data...Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.展开更多
The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial pepti...The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.展开更多
Microstructural evolution features have been systematically investigated for the weld metal of EH36 shipbuilding steel under an in situ confocal scanning laser microscope.The influence of cooling rate on microstructur...Microstructural evolution features have been systematically investigated for the weld metal of EH36 shipbuilding steel under an in situ confocal scanning laser microscope.The influence of cooling rate on microstructural changes during the transformation from austenite to ferrite has been clarified.It is found that ferrite side plates form preceding to acicular ferrites,although the starting temperature of respective component decreases as the cooling rate is raised.In particular,the growth rate of acicular ferrite is measured to increase significantly,rising from 30.4μm/s at a cooling rate of 3 K/s to 109.0μm/s at 15 K/s,driven primarily by an ever-increasing degree of undercooling.These findings highlight the critical role of cooling rate in dictating the sequence and growth rate of microstructural transformations,which is crucial for optimizing welding processes to obtain desired microstructures while avoiding the formation of deleterious components.展开更多
Robotic autonomous operating systems in global n40avigation satellite system(GNSS)-denied agricultural environments(green houses,feeding farms,and under canopy)have recently become a research hotspot.3D light detectio...Robotic autonomous operating systems in global n40avigation satellite system(GNSS)-denied agricultural environments(green houses,feeding farms,and under canopy)have recently become a research hotspot.3D light detection and ranging(LiDAR)locates the robot depending on environment and has become a popular perception sensor to navigate agricultural robots.A rapid development methodology of a 3D LiDAR-based navigation system for agricultural robots is proposed in this study,which includes:(i)individual plant clustering and its location estimation method(improved Euclidean clustering algorithm);(ii)robot path planning and tracking control method(Lyapunov direct method);(iii)construction of a robot-LiDAR-plant unified virtual simulation environment(combination use of Gazebo and SolidWorks);and(vi)evaluating the accuracy of the navigation system(triple evaluation:virtual simulation test,physical simulation test,and field test).Applying the proposed methodology,a navigation system for a grape field operation robot has been developed.The virtual simulation test,physical simulation test with GNSS as ground truth,and field test with path tracer showed that the robot could travel along the planned path quickly and smoothly.The maximum and mean absolute errors of path tracking are 2.72 cm,1.02 cm;3.12 cm,1.31 cm,respectively,which meet the accuracy requirements of field operations,establishing the effectiveness of the proposed methodology.The proposed methodology has good scalability and can be implemented in a wide variety of field robot,which is promising to shorten the development cycle of agricultural robot navigation system working in GNSS-denied environment.展开更多
Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities agains...Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.展开更多
基金supported by the National Innovation and Enterpreneurship Training Program for College Students(202210367002)the Key Laboratory Open Project of An-hui Province(AHCM2022Z004).
文摘Objective To identify nivolumab resistance-related genes in patients with head and neck squamous cell carcinoma(HNSCC)using single-cell and bulk RNA-sequencing data.Methods The single-cell and bulk RNA-sequencing data downloaded from the Gene Expression Omnibus database were analyzed to screen out differentially expressed genes(DEGs)between nivolumab resistant and nivolumab sensitive patients using R software.The Least Absolute Shrinkage Selection Operator(LASSO)regression and Recursive Feature Elimination(RFE)algorithm were performed to identify key genes associated with nivolumab resistance.Functional enrichment of DEGs was analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses.The relationships of key genes with immune cell infiltration,differentation trajectory,dynamic gene expression profiles,and ligand-receptor interaction were explored.Results We found 83 DEGs.They were mainly enriched in T-cell differentiation,PD-1 and PD-L1 checkpoint,and T-cell receptor pathways.Among six key genes identified using machine learning algorithms,only PPP1R14A gene was differentially expressed between the nivolumab resistant and nivolumab sensitive groups both before and after immunotherapy(P<0.05).The high PPP1R14A gene expression group had lower immune score(P<0.01),higher expression of immunosuppressive factors(such as PDCD1,CTLA4,and PDCD1LG2)(r>0,P<0.05),lower differentiation of infiltrated immune cells(P<0.05),and a higher degree of interaction between HLA and CD4(P<0.05).Conclusions PPP1R14A gene is closely associated with resistance to nivolumab in HNSCC patients.Therefore,PPP1R14A may be a target to ameliorate nivolumab resistance of HNSCC patients.
基金supported by grants from the National Natural Science Foundation of China (81770176)the special support plan for Zhejiang Province High-Level Talents (2019R52011)。
文摘The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
基金support from the National Natural Science Foundation of China(Grant Nos.U20A20277 and 52350610226)National Key Research and Development Plan of China(Grant No.2022YFE0123300).
文摘Microstructural evolution features have been systematically investigated for the weld metal of EH36 shipbuilding steel under an in situ confocal scanning laser microscope.The influence of cooling rate on microstructural changes during the transformation from austenite to ferrite has been clarified.It is found that ferrite side plates form preceding to acicular ferrites,although the starting temperature of respective component decreases as the cooling rate is raised.In particular,the growth rate of acicular ferrite is measured to increase significantly,rising from 30.4μm/s at a cooling rate of 3 K/s to 109.0μm/s at 15 K/s,driven primarily by an ever-increasing degree of undercooling.These findings highlight the critical role of cooling rate in dictating the sequence and growth rate of microstructural transformations,which is crucial for optimizing welding processes to obtain desired microstructures while avoiding the formation of deleterious components.
基金research is funded by the Agricultural Equipment Department of Jiangsu University(Grant No.NZXB20210106)the National Natural Science Foundation of China(Grant No.52105284)+1 种基金the Leading Goose Program of Zhejiang Province(Grant No.2022C02052)the China Agriculture Research System of MOF and MARA and Basic,and the Applied Basic Research Project of Guangzhou Basic Research Program in 2022(Grant No.202201011691).
文摘Robotic autonomous operating systems in global n40avigation satellite system(GNSS)-denied agricultural environments(green houses,feeding farms,and under canopy)have recently become a research hotspot.3D light detection and ranging(LiDAR)locates the robot depending on environment and has become a popular perception sensor to navigate agricultural robots.A rapid development methodology of a 3D LiDAR-based navigation system for agricultural robots is proposed in this study,which includes:(i)individual plant clustering and its location estimation method(improved Euclidean clustering algorithm);(ii)robot path planning and tracking control method(Lyapunov direct method);(iii)construction of a robot-LiDAR-plant unified virtual simulation environment(combination use of Gazebo and SolidWorks);and(vi)evaluating the accuracy of the navigation system(triple evaluation:virtual simulation test,physical simulation test,and field test).Applying the proposed methodology,a navigation system for a grape field operation robot has been developed.The virtual simulation test,physical simulation test with GNSS as ground truth,and field test with path tracer showed that the robot could travel along the planned path quickly and smoothly.The maximum and mean absolute errors of path tracking are 2.72 cm,1.02 cm;3.12 cm,1.31 cm,respectively,which meet the accuracy requirements of field operations,establishing the effectiveness of the proposed methodology.The proposed methodology has good scalability and can be implemented in a wide variety of field robot,which is promising to shorten the development cycle of agricultural robot navigation system working in GNSS-denied environment.
基金supported by grants from Science Foundation of Shenyang Pharmaceutical University(No.QNJJ2014502)
文摘Based on our previous work,a series of hydrazone moiety-bearing aminopyrimidines were synthesized.The compounds were evaluated for inhibitory activities against EGFRT790M/L858 R and antiproliferative activities against H1975 and A549 NSCLC cell lines harboring different forms of EGFR.Compounds 7f and7 k exhibited potent and selective activity in inhibition of gefitinib-resistant H1975 cancer cells（IC50;0.45,0.2μmol/L） while were much less active on A549 cancer cells（IC50;52.83,〉100μmol/L）.Both compounds could be served as promising lead compounds for further investigation.
