In this paper, one class of nonlinear singular integral equation is discussed through Lagrange interpolation method. We research the connections between numerical solutions of the equations and chaos in the process of...In this paper, one class of nonlinear singular integral equation is discussed through Lagrange interpolation method. We research the connections between numerical solutions of the equations and chaos in the process of solving by iterative method.展开更多
Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,...Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.展开更多
Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technologic...Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical applications.Ginseng extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary supplements.Despite the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic instability.Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled release.This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.展开更多
Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are expl...Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.展开更多
The BAP module,comprising BRASSINAZOLE RESISTANT 1(BZR1),AUXIN RESPONSE FACTOR 6(ARF6),and PHYTOCHROME‐INTERACTING FACTOR 4(PIF4),functions as a molecular hub to orchestrate plant growth and development.In Arabidopsi...The BAP module,comprising BRASSINAZOLE RESISTANT 1(BZR1),AUXIN RESPONSE FACTOR 6(ARF6),and PHYTOCHROME‐INTERACTING FACTOR 4(PIF4),functions as a molecular hub to orchestrate plant growth and development.In Arabidopsis thaliana,components of the BAP module physically interact to form a complex system that integrates light,brassinosteroid(BR),and auxin signals.Little is known about the origin and evolution of the BAP module.Here,we conducted comparative genomic and transcriptomic analyses to investigate the evolution and functional diversification of the BAP module.Our results suggest that the BAP module originated in land plants and that theζ,ε,andγwhole‐genome duplication/triplication events contributed to the expansion of BAP module components in seed plants.Comparative transcriptomic analysis suggested that the prototype BAP module arose in Marchantia polymorpha,experienced stepwise evolution,and became established as a mature regulatory system in seed plants.We developed a formula to calculate the signal transduction productivity of the BAP module and demonstrate that more crosstalk among components enables higher signal transduction efficiency.Our results reveal the evolutionary history of the BAP module and provide insights into the evolution of plant signaling networks and the strategies employed by plants to integrate environmental and endogenous signals.展开更多
Methicillin-resistant Staphylococcus aureus(MRSA) is an increasing cause of serious infection,both in the community and hospital settings. Despite sophisticated strategies and efforts, the antibiotic options for treat...Methicillin-resistant Staphylococcus aureus(MRSA) is an increasing cause of serious infection,both in the community and hospital settings. Despite sophisticated strategies and efforts, the antibiotic options for treating MRSA infection are narrowing because of the limited number of newly developed antimicrobials. Here, four newly-isolated MRSA-virulent phages, IME-SA1, IMESA2, IME-SA118 and IME-SA119, were sequenced and analyzed. Their genome termini were identified using our previously proposed "termini analysis theory". We provide evidence that remarkable conserved terminus sequences are found in IME-SA1/2/118/119, and, moreover, are widespread throughout Twortlikevirus Staphylococcus phage G1 and K species. Results also suggested that each phage of the two species has conserved 5′ terminus while the 3′ terminus is variable. More importantly, a variable region with a specific pattern was found to be present near the conserved terminus of Twortlikevirus S. phage G1 species. The clone with the longest variable region had variable terminus lengths in successive generations, while the clones with the shortest variable region and with the average length variable region maintained the same terminal length as themselves during successive generations. IME-SA1 bacterial infection experiments showed that the variation is not derived from adaptation of the phage to different host strains. This is the first study of the conserved terminus and variable region of Twortlikevirus S. phages.展开更多
Green plants(Viridiplantae)are ancient photosynthetic organisms that thrive both in aquatic and terrestrial ecosystems,greatly contributing to the changes in global climates and ecosystems.Significant progress has bee...Green plants(Viridiplantae)are ancient photosynthetic organisms that thrive both in aquatic and terrestrial ecosystems,greatly contributing to the changes in global climates and ecosystems.Significant progress has been made toward understanding the origin and evolution of green plants,and plant biologists have arrived at the consensus that green plants first originated in marine deep-water environments and later colonized fresh water and dry land.The origin of green plants,colonization of land by plants and rapid radiation of angiosperms are three key evolutionary events during the long history of green plants.However,the comprehensive understanding of evolutionary features and molecular innovations that enabled green plants to adapt to complex and changeable environments are still limited.Here,we review current knowledge of phylogenetic relationships and divergence times of green plants,and discuss key morphological innovations and distinct drivers in the evolution of green plants.Ultimately,we highlight fundamental questions to advance our understanding of the phenotypic novelty,environmental adaptation,and domestication of green plants.展开更多
The author studies the L2 gradient flow of the Helfrich functional,which is a functional describing the shapes of human red blood cells.For any λi≥0 and c0,the author obtains a lower bound on the lifespan of the smo...The author studies the L2 gradient flow of the Helfrich functional,which is a functional describing the shapes of human red blood cells.For any λi≥0 and c0,the author obtains a lower bound on the lifespan of the smooth solution,which depends only on the concentration of curvature for the initial surface.展开更多
We use the concept of the inside-(a,η,h)domain to construct a subsolution to the Dirichlet problem for minimal graphs over convex domains in hyperbolic space.As an application,we prove that the Hölder exponent m...We use the concept of the inside-(a,η,h)domain to construct a subsolution to the Dirichlet problem for minimal graphs over convex domains in hyperbolic space.As an application,we prove that the Hölder exponent max{1/a,1/(n+1)}for the problem is optimal for any a∈[2,+∞].展开更多
Increased endogenous hydrogen sulfide(H_(2)S)level by cystathionine β-synthase(CBS)has been shown to closely relate tumorigenesis.H_(2)S promotes angiogenesis,stimulates bioenergy metabolism and inhibits selective ph...Increased endogenous hydrogen sulfide(H_(2)S)level by cystathionine β-synthase(CBS)has been shown to closely relate tumorigenesis.H_(2)S promotes angiogenesis,stimulates bioenergy metabolism and inhibits selective phosphatases.However,the role of CBS and H_(2)S in chronic myeloid leukemia(CML)remains elusive.In this study,we found that CBS and H_(2)S levels were increased in the bone marrow mononuclear cells of pediatric CML patients,as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases.Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition,apoptosis,cell cycle arrest,and migration suppression in K562 cells and tumor xenografts.The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H_(2)S levels,promoted mitochondrial-related apoptosis and inhibited the NF-xB-mediated gene expression.Our study suggests that inhibition of CBS induces cell apoptosis,as well as limits cell proliferation and migration,a potential target for the treatment of chronic myeloid leukemia.展开更多
文摘In this paper, one class of nonlinear singular integral equation is discussed through Lagrange interpolation method. We research the connections between numerical solutions of the equations and chaos in the process of solving by iterative method.
基金supported by the National Key R&D Program of China(Grant No.:2021YFC2101500)the National Natural Science Foundation of China(Grant Nos.:22078264,21978235,22108224,and 21978236)+2 种基金the Natural Science Basic Research Program of Shaanxi,China(Grant Nos.:2023-JC-JQ-17 and 2023-JCQN-0109)the Xi'an Science and Technology Project,China(Project No.:20191422315KYPT014JC016)Key Research and Development Program of Shaanxi,China(Grant No.:2022ZDLSF05-12).
文摘Hepatocellular carcinoma(HCC)is the third leading cause of cancer death worldwide.Ginsenoside Rk3,an important and rare saponin in heat-treated ginseng,is generated from Rg1 and has a smaller molecular weight.However,the anti-HCC efficacy and mechanisms of ginsenoside Rk3 have not yet been characterized.Here,we investigated the mechanism by which ginsenoside Rk3,a tetracyclic triterpenoid rare ginsenoside,inhibits the growth of HCC.We first explored the possible potential targets of Rk3 through network pharmacology.Both in vitro(HepG2 and HCC-LM3 cells)and in vivo(primary liver cancer mice and HCC-LM3 subcutaneous tumor-bearing mice)studies revealed that Rk3 significantly inhibits the proliferation of HCC.Meanwhile,Rk3 blocked the cell cycle in HCC at the G1 phase and induced autophagy and apoptosis in HCC.Further proteomics and siRNA experiments showed that Rk3 regulates the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway to inhibit HCC growth,which was validated by molecular docking and surface plasmon resonance.In conclusion,we report the discovery that ginsenoside Rk3 binds to PI3K/AKT and promotes autophagy and apoptosis in HCC.Our data strongly support the translation of ginsenoside Rk3 into novel PI3K/AKT-targeting therapeutics for HCC treatment with low toxic side effects.
基金This work was financially supported by the National Natural Science Foundation of China(Grant Nos.22078264,21978235,21776227 and 21706211)the Natural Science Basic Research Plan in Shaanxi Province of China(Grant No.2019JQ259)Northwest Northwest University Graduate Innovation Project(Grant No.YZZ17128).
文摘Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune function.Following the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical applications.Ginseng extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary supplements.Despite the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic instability.Nanoparticle formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled release.This mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.
基金This work was supported by the University Grants Committee,Hong Kong SAR Government(No.14112921,China).The support of HKPFS from the University Grants Committee to HonglanWang was greatly acknowledged.
文摘Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection.These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates.They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance,making them an invaluable asset in the era of antibiotic resistance.Numerous depolymerases have been investigated preclinically,with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models.Additionally,some formulation approaches have been developed for improved stability and activity of depolymerases.However,depolymerase formulation is limited to liquid dosage form and remains in its infancy,posing a significant hurdle to their clinical translation,compounded by challenges in their applicability and manufacturing.Future development must address these obstacles for clinical utility.Here,after unravelling the history,diversity,and therapeutic use of depolymerases,we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases.Finally,the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.
基金This study was supported by the National Natural Science FoundationofChina(32122010,31970229,and32100178)the PriorityAcademic Program Development of Jiangsu Higher Education Institutions(PAPD)the Collaborative Innovation Center for Modern Crop Production co-sponsored by Province and Ministry(CIC-MCP).
文摘The BAP module,comprising BRASSINAZOLE RESISTANT 1(BZR1),AUXIN RESPONSE FACTOR 6(ARF6),and PHYTOCHROME‐INTERACTING FACTOR 4(PIF4),functions as a molecular hub to orchestrate plant growth and development.In Arabidopsis thaliana,components of the BAP module physically interact to form a complex system that integrates light,brassinosteroid(BR),and auxin signals.Little is known about the origin and evolution of the BAP module.Here,we conducted comparative genomic and transcriptomic analyses to investigate the evolution and functional diversification of the BAP module.Our results suggest that the BAP module originated in land plants and that theζ,ε,andγwhole‐genome duplication/triplication events contributed to the expansion of BAP module components in seed plants.Comparative transcriptomic analysis suggested that the prototype BAP module arose in Marchantia polymorpha,experienced stepwise evolution,and became established as a mature regulatory system in seed plants.We developed a formula to calculate the signal transduction productivity of the BAP module and demonstrate that more crosstalk among components enables higher signal transduction efficiency.Our results reveal the evolutionary history of the BAP module and provide insights into the evolution of plant signaling networks and the strategies employed by plants to integrate environmental and endogenous signals.
基金supported by grants from the China Mega-Project on Infectious Disease Prevention (No. 2013ZX10004-605, No. 2013ZX10004-607, No. 2013ZX10004-217, and No. 2011ZX10004-001)the National Hi-Tech Research and Development (863) Program of China (No. 2014AA021402, 2012AA022-003)the National Natural Science Foundation of China (No. 81572045)
文摘Methicillin-resistant Staphylococcus aureus(MRSA) is an increasing cause of serious infection,both in the community and hospital settings. Despite sophisticated strategies and efforts, the antibiotic options for treating MRSA infection are narrowing because of the limited number of newly developed antimicrobials. Here, four newly-isolated MRSA-virulent phages, IME-SA1, IMESA2, IME-SA118 and IME-SA119, were sequenced and analyzed. Their genome termini were identified using our previously proposed "termini analysis theory". We provide evidence that remarkable conserved terminus sequences are found in IME-SA1/2/118/119, and, moreover, are widespread throughout Twortlikevirus Staphylococcus phage G1 and K species. Results also suggested that each phage of the two species has conserved 5′ terminus while the 3′ terminus is variable. More importantly, a variable region with a specific pattern was found to be present near the conserved terminus of Twortlikevirus S. phage G1 species. The clone with the longest variable region had variable terminus lengths in successive generations, while the clones with the shortest variable region and with the average length variable region maintained the same terminal length as themselves during successive generations. IME-SA1 bacterial infection experiments showed that the variation is not derived from adaptation of the phage to different host strains. This is the first study of the conserved terminus and variable region of Twortlikevirus S. phages.
基金supported by the National Natural Science Foundation of China(32122010,31970229 and 32100178)the Collaborative Innovation Center for Modern Crop Production co-sponsored by Province and Ministrythe Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Green plants(Viridiplantae)are ancient photosynthetic organisms that thrive both in aquatic and terrestrial ecosystems,greatly contributing to the changes in global climates and ecosystems.Significant progress has been made toward understanding the origin and evolution of green plants,and plant biologists have arrived at the consensus that green plants first originated in marine deep-water environments and later colonized fresh water and dry land.The origin of green plants,colonization of land by plants and rapid radiation of angiosperms are three key evolutionary events during the long history of green plants.However,the comprehensive understanding of evolutionary features and molecular innovations that enabled green plants to adapt to complex and changeable environments are still limited.Here,we review current knowledge of phylogenetic relationships and divergence times of green plants,and discuss key morphological innovations and distinct drivers in the evolution of green plants.Ultimately,we highlight fundamental questions to advance our understanding of the phenotypic novelty,environmental adaptation,and domestication of green plants.
基金Project supported by the National Natural Science Foundation of China(No.11026121)the TrainingProgramme Foundation for the Excellent Talents of Beijing(No.2012D005003000004)
文摘The author studies the L2 gradient flow of the Helfrich functional,which is a functional describing the shapes of human red blood cells.For any λi≥0 and c0,the author obtains a lower bound on the lifespan of the smooth solution,which depends only on the concentration of curvature for the initial surface.
基金This work was supported in part by the Natural Science Foundation of Beijing Municipality(No.1212002)the National Natural Science Foundation of China(Grant Nos.12071017,11871432).
文摘We use the concept of the inside-(a,η,h)domain to construct a subsolution to the Dirichlet problem for minimal graphs over convex domains in hyperbolic space.As an application,we prove that the Hölder exponent max{1/a,1/(n+1)}for the problem is optimal for any a∈[2,+∞].
文摘Increased endogenous hydrogen sulfide(H_(2)S)level by cystathionine β-synthase(CBS)has been shown to closely relate tumorigenesis.H_(2)S promotes angiogenesis,stimulates bioenergy metabolism and inhibits selective phosphatases.However,the role of CBS and H_(2)S in chronic myeloid leukemia(CML)remains elusive.In this study,we found that CBS and H_(2)S levels were increased in the bone marrow mononuclear cells of pediatric CML patients,as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases.Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition,apoptosis,cell cycle arrest,and migration suppression in K562 cells and tumor xenografts.The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H_(2)S levels,promoted mitochondrial-related apoptosis and inhibited the NF-xB-mediated gene expression.Our study suggests that inhibition of CBS induces cell apoptosis,as well as limits cell proliferation and migration,a potential target for the treatment of chronic myeloid leukemia.
