In this paper, the control of turbulent channel flow by space-dependent electromagnetic force and the mechanism of drag reduction are investigated with the direct numerical simulation(DNS) methods for different Reynol...In this paper, the control of turbulent channel flow by space-dependent electromagnetic force and the mechanism of drag reduction are investigated with the direct numerical simulation(DNS) methods for different Reynolds numbers. A formulation is derived to express the relation between the drag and the Reynolds shear stress. With the application of optimal electromagnetic force, the in-depth relations among characteristic structures in the flow field, mean Reynolds shear stress, and the effect of drag reduction for different Reynolds numbers are discussed. The results indicate that the maximum drag reductions can be obtained with an optimal combination of parameters for each case of different Reynolds numbers. The regular quasi-streamwise vortex structures, which appear in the flow field, have the same period with that of the electromagnetic force.These structures suppress the random velocity fluctuations, which leads to the absolute value of mean Reynolds shear stress decreasing and the distribution of that moving away from the wall. Moreover, the wave number of optimal electromagnetic force increases,and the scale of the regular quasi-streamwise vortex structures decreases as the Reynolds number increases. Therefore, the rate of drag reduction decreases with the increase in the Reynolds number since the scale of the regular quasi-streamwise vortex structures decreases.展开更多
Controlled and switchable adhesion is commonly observed in biological systems.In recent years,many scholars have focused on making switchable bio-inspired adhesives.However,making a bio-inspired adhesive with high adh...Controlled and switchable adhesion is commonly observed in biological systems.In recent years,many scholars have focused on making switchable bio-inspired adhesives.However,making a bio-inspired adhesive with high adhesion performance and excellent dynamic switching properties is still a challenge.A Shape Memory Polymer Bio-inspired Adhesive(SMPBA)was successfully developed,well realizing high adhesion(about 337 kPa),relatively low preload(about90 kPa),high adhesion-to-preload ratio(about 3.74),high switching ratio(about 6.74),and easy detachment,which are attributed to the controlled modulus and contact area by regulating temperature and the Shape Memory Effect(SME).Furthermore,SMPBA exhibits adhesion strength of80–337 kPa on various surfaces(silicon,iron,and aluminum)with different roughness(Ra=0.021–10.280)because of the conformal contact,reflecting outstanding surface adaptability.The finite element analysis verifies the bending ability under different temperatures,while the adhesion model analyzes the influence of preload on contact area and adhesion.Furthermore,an Unmanned Aerial Vehicle(UAV)landing device with SMPBA was designed and manufactured to achieve UAV landing on and detaching from various surfaces.This study provides a novel switchable bio-inspired adhesive and UAV landing method.展开更多
As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly...As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization.Target identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target prediction.However,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising activities.Here,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds.Then peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer.Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1.New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis.Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells.The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells.Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment.Our findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer.展开更多
Background:Polygenic risk score(PRS)derived from summary statistics of genome-wide association studies(GWAS)is a useful tool to infer an individuaPs genetic risk for health outcomes and has gained increasing popularit...Background:Polygenic risk score(PRS)derived from summary statistics of genome-wide association studies(GWAS)is a useful tool to infer an individuaPs genetic risk for health outcomes and has gained increasing popularity in human genetics research.PRS in its simplest form enjoys both computational efficiency and easy accessibility,yet the predictive performance of PRS remains moderate for diseases and traits.Results:We provide an overview of recent advances in statistical methods to improve PRS's performance by incorporating information from linkage disequilibrium,functional annotation,and pleiotropy.We also introduce model validation methods that fine-tune PRS using GWAS summary statistics.Conclusion:In this review,we showcase methodological advances and current limitations of PRS,and discuss several emerging issues in risk prediction research.展开更多
基金supported by the National Natural Science Foundation of China(No.11672135)the Foundation for the Author of National Excellent Doctoral Dissertation of China(No.201461)
文摘In this paper, the control of turbulent channel flow by space-dependent electromagnetic force and the mechanism of drag reduction are investigated with the direct numerical simulation(DNS) methods for different Reynolds numbers. A formulation is derived to express the relation between the drag and the Reynolds shear stress. With the application of optimal electromagnetic force, the in-depth relations among characteristic structures in the flow field, mean Reynolds shear stress, and the effect of drag reduction for different Reynolds numbers are discussed. The results indicate that the maximum drag reductions can be obtained with an optimal combination of parameters for each case of different Reynolds numbers. The regular quasi-streamwise vortex structures, which appear in the flow field, have the same period with that of the electromagnetic force.These structures suppress the random velocity fluctuations, which leads to the absolute value of mean Reynolds shear stress decreasing and the distribution of that moving away from the wall. Moreover, the wave number of optimal electromagnetic force increases,and the scale of the regular quasi-streamwise vortex structures decreases as the Reynolds number increases. Therefore, the rate of drag reduction decreases with the increase in the Reynolds number since the scale of the regular quasi-streamwise vortex structures decreases.
基金financial support from the National Natural Science Foundation of China(No.51605220)the Jiangsu Province Natural Science Foundation,China(No.BK20160793)+1 种基金the Postgraduate Research and Practice Innovation Program of Nanjing University of Aeronautics and Astronautics,China(No.xcxjh20210514)the Fundamental Research Funds for the Central Universities,China(No.XCA2205406)。
文摘Controlled and switchable adhesion is commonly observed in biological systems.In recent years,many scholars have focused on making switchable bio-inspired adhesives.However,making a bio-inspired adhesive with high adhesion performance and excellent dynamic switching properties is still a challenge.A Shape Memory Polymer Bio-inspired Adhesive(SMPBA)was successfully developed,well realizing high adhesion(about 337 kPa),relatively low preload(about90 kPa),high adhesion-to-preload ratio(about 3.74),high switching ratio(about 6.74),and easy detachment,which are attributed to the controlled modulus and contact area by regulating temperature and the Shape Memory Effect(SME).Furthermore,SMPBA exhibits adhesion strength of80–337 kPa on various surfaces(silicon,iron,and aluminum)with different roughness(Ra=0.021–10.280)because of the conformal contact,reflecting outstanding surface adaptability.The finite element analysis verifies the bending ability under different temperatures,while the adhesion model analyzes the influence of preload on contact area and adhesion.Furthermore,an Unmanned Aerial Vehicle(UAV)landing device with SMPBA was designed and manufactured to achieve UAV landing on and detaching from various surfaces.This study provides a novel switchable bio-inspired adhesive and UAV landing method.
基金We are grateful to National Centre for Protein Science Shanghai for their instrument support and technical assistance.We thank the staffs from BL19U1 beamline of National Facility for Protein Science Shanghai(NFPS)at Shanghai Synchrotron Radiation Facility,for assistance during data collection.We gratefully acknowledge the financial supports from the National Key Research and Development Program of China(2020YFE0202200 to H.Z.and 2021ZD0203900 to C.L.)the project of National Multidisciplinary Innovation Team of Traditional Chinese Medicine(ZYYCXTD-202004 to C.L.)+3 种基金the National Natural Science Foundation of China(81903538 to H.Z.,82104064 to H.X.,91853205 to C.L.,91853206 to G.C.,81773565 to A.Z.,81972615 to Y.X.,and 21877120,22177068 to C.D.)the Postdoctoral Research Foundation of China(2019M661673 to H.Z.)the Shanghai Sailing Plan(19YF1457200 to H.Z.)the grants from Shanghai Jiao Tong University(AF1700037,WF220217002,WH101117001,and WF540162618 to A.Z.).
文摘As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor activities.The clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural optimization.Target identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target prediction.However,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising activities.Here,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired compounds.Then peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal cancer.Our solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with PRDX1.New derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure analysis.Both Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer cells.The anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer cells.Several downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 treatment.Our findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer.
文摘Background:Polygenic risk score(PRS)derived from summary statistics of genome-wide association studies(GWAS)is a useful tool to infer an individuaPs genetic risk for health outcomes and has gained increasing popularity in human genetics research.PRS in its simplest form enjoys both computational efficiency and easy accessibility,yet the predictive performance of PRS remains moderate for diseases and traits.Results:We provide an overview of recent advances in statistical methods to improve PRS's performance by incorporating information from linkage disequilibrium,functional annotation,and pleiotropy.We also introduce model validation methods that fine-tune PRS using GWAS summary statistics.Conclusion:In this review,we showcase methodological advances and current limitations of PRS,and discuss several emerging issues in risk prediction research.