The paper deals with the g2-stability analysis of multi-input-multi-output(MIMO)systems,governed by integral equations,with a matrix of periodic/aperiodic time-varying gains and a vector of monotone,non-monotone and q...The paper deals with the g2-stability analysis of multi-input-multi-output(MIMO)systems,governed by integral equations,with a matrix of periodic/aperiodic time-varying gains and a vector of monotone,non-monotone and quasi-monotone nonlin-earities.For nonlinear MIMO systems that are described by differential equations,most of the literature on stability is based on an application of quadratic forms as Lyapunov-function candidates.In contrast,a non-Lyapunov framework is employed here to derive new and more general g2-stability conditions in the frequency domain.These conditions have the following features:i)They are expressed in terms of the positive definiteness of the real part of matrices involving the transfer function of the linear time-invariant block and a matrix multiplier function that incorporates the minimax properties of the time-varying linear/nonlinear block,ii)For certain cases of the periodic time-varying gain,they contain,depending on the multiplier function chosen,no restrictions on the normalized rate of variation of the time-varying gain,but,for other periodic/aperiodic time-varying gains,they do.Overall,even when specialized to periodic-coefficient linear and nonlinear MIMO systems,the stability conditions are distinct from and less restrictive than recent results in the literature.No comparable results exist in the literature for aperiodic time-varying gains.Furthermore,some new stability results concerning the dwell-time problem and time-varying gain switching in linear and nonlinear MIMO systems with periodic/aperiodic matrix gains are also presented.Examples are given to illustrate a few of the stability theorems.展开更多
New conditions are derived for the l2-stability of time-varying linear and nonlinear discrete-time multiple-input multipleoutput （MIMO） systems, having a linear time time-invariant block with the transfer function F...New conditions are derived for the l2-stability of time-varying linear and nonlinear discrete-time multiple-input multipleoutput （MIMO） systems, having a linear time time-invariant block with the transfer function F（z）, in negative feedback with a matrix of periodic/aperiodic gains A（k）, k = 0,1, 2,... and a vector of certain classes of non-monotone/monotone nonlinearities φp（-）, without restrictions on their slopes and also not requiring path-independence of their line integrals. The stability conditions, which are derived in the frequency domain, have the following features： i） They involve the positive definiteness of the real part （as evaluated on ｜z｜ = 1） of the product of Г （z） and a matrix multiplier function of z. ii） For periodic A（k）, one class of multiplier functions can be chosen so as to impose no constraint on the rate of variations A（k）, but for aperiodic A（k）, which allows a more general multiplier function, constraints are imposed on certain global averages of the generalized eigenvalues of （A（k ＋ 1）,A（k））, k = 1, 2 iii） They are distinct from and less restrictive than recent results in the literature.展开更多
Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to i...Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.展开更多
As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and ant...As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and antiphotoaging effects comparable to those of AA,and it plays a key role in maintaining organismal health.Owing to its superior stability and bioavailability,AA-2βG is considered as a promising,longer-lasting natural alternative to conventional vitamin C.It was first identified and is particularly abundant in Lycii Fructus(Gouqizi in Chinese)but has been detected in several crop plants.This review offers a comprehensive overview of recent advances in AA-2βG research,covering key aspects including discovery,structure,natural sources,extraction and detection methods,chemical and in vitro enzymatic synthesis,biosynthetic pathways,as well as applications in health care,skin care,and functional foods.Additionally,we highlight strategies for leveraging plant resources and enhancing AA-2βG biosynthesis,which are expected to accelerate future research and support the sustainable development and utilization of AA-2βG and other high-value natural products.展开更多
Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and trans...Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.展开更多
文摘The paper deals with the g2-stability analysis of multi-input-multi-output(MIMO)systems,governed by integral equations,with a matrix of periodic/aperiodic time-varying gains and a vector of monotone,non-monotone and quasi-monotone nonlin-earities.For nonlinear MIMO systems that are described by differential equations,most of the literature on stability is based on an application of quadratic forms as Lyapunov-function candidates.In contrast,a non-Lyapunov framework is employed here to derive new and more general g2-stability conditions in the frequency domain.These conditions have the following features:i)They are expressed in terms of the positive definiteness of the real part of matrices involving the transfer function of the linear time-invariant block and a matrix multiplier function that incorporates the minimax properties of the time-varying linear/nonlinear block,ii)For certain cases of the periodic time-varying gain,they contain,depending on the multiplier function chosen,no restrictions on the normalized rate of variation of the time-varying gain,but,for other periodic/aperiodic time-varying gains,they do.Overall,even when specialized to periodic-coefficient linear and nonlinear MIMO systems,the stability conditions are distinct from and less restrictive than recent results in the literature.No comparable results exist in the literature for aperiodic time-varying gains.Furthermore,some new stability results concerning the dwell-time problem and time-varying gain switching in linear and nonlinear MIMO systems with periodic/aperiodic matrix gains are also presented.Examples are given to illustrate a few of the stability theorems.
文摘New conditions are derived for the l2-stability of time-varying linear and nonlinear discrete-time multiple-input multipleoutput （MIMO） systems, having a linear time time-invariant block with the transfer function F（z）, in negative feedback with a matrix of periodic/aperiodic gains A（k）, k = 0,1, 2,... and a vector of certain classes of non-monotone/monotone nonlinearities φp（-）, without restrictions on their slopes and also not requiring path-independence of their line integrals. The stability conditions, which are derived in the frequency domain, have the following features： i） They involve the positive definiteness of the real part （as evaluated on ｜z｜ = 1） of the product of Г （z） and a matrix multiplier function of z. ii） For periodic A（k）, one class of multiplier functions can be chosen so as to impose no constraint on the rate of variations A（k）, but for aperiodic A（k）, which allows a more general multiplier function, constraints are imposed on certain global averages of the generalized eigenvalues of （A（k ＋ 1）,A（k））, k = 1, 2 iii） They are distinct from and less restrictive than recent results in the literature.
文摘Background:Epidemiological studies have confirmed that longer exposure to insecticides like cypermethrin(CYP)significantly increases the risk of male reproductive toxicity.Crocus sativus L.has been recognized due to its therapeutic properties,but its exact role and molecular mechanisms in treatment of reproductive dysfunction remain unclear.Methods:During this study,36 rats were randomly divided into six groups(n=6):control,CYP-induced(60 mg/kg),standard(leuprolide 3 mg/kg)and three treatment groups receiving aqueous,ethanolic,and oil extracts(50 mg/kg or 20 mL/kg)for post-toxicity induction.Results:The finding represented that exposure of CYP significantly increased oxidative stress,disrupted testicular architecture,and markedly reduced testosterone levels(P<0.05).Importantly,Crocus sativus L.treatment alleviated these changes by increasing the expression of Nrf2(nuclear factor erythroid 2-related factor 2),restoring the activity of antioxidant enzymes,and enhancing testicular histomorphology.Surprisingly,molecular docking established a high binding affinity of Crocus sativus L.phytoconstituents such as gallic acid,cinnamic acid and quercetin to the Nrf2-Keap1 complex.It is worth noting that,Crocus sativus L.exhibited a high level of protection against reproductive toxicity caused by CYP in male rats,which was mediated by the activation of Nrf2 pathway,reduction of oxidative damage,and favorable ADMET characteristics.Conclusion:Notably,this research provides a more valid,safe,and effective method of developing new drugs for reproductive disorders,however,further investigation is needed to support the research findings and implement it in clinical practice.
基金funded by the National Key Research and Development Program(Nos.2023YFC3504104 and 2024YFD2100700)the Fundamental Research Funds for the Central public welfare research institutes(No.ZZ13-YQ-101)Scientific and technological innovation project of China Academy of Chinese Medical Sciences(No.CI2023E002-Y-28).
文摘As the only naturally occurring stable derivative of L-ascorbic acid(AA;vitamin C),2-O-β-D-glucopyranosyl-L-ascorbic acid(AA-2βG)is hydrolyzed in vivo to release active AA.AA-2βG exhibits strong antioxidant and antiphotoaging effects comparable to those of AA,and it plays a key role in maintaining organismal health.Owing to its superior stability and bioavailability,AA-2βG is considered as a promising,longer-lasting natural alternative to conventional vitamin C.It was first identified and is particularly abundant in Lycii Fructus(Gouqizi in Chinese)but has been detected in several crop plants.This review offers a comprehensive overview of recent advances in AA-2βG research,covering key aspects including discovery,structure,natural sources,extraction and detection methods,chemical and in vitro enzymatic synthesis,biosynthetic pathways,as well as applications in health care,skin care,and functional foods.Additionally,we highlight strategies for leveraging plant resources and enhancing AA-2βG biosynthesis,which are expected to accelerate future research and support the sustainable development and utilization of AA-2βG and other high-value natural products.
文摘Objectives:The current treatment options and therapeutic targets for triple-negative breast cancer(TNBC),an aggressive subtype of breast cancer(BrCA),are limited.This study aimed to identify novel biomarkers and transcriptional regulatory networks(TRN)inherent in TNBC samples.Methods:We analyzed pan-cancer BrCA datasets from The Cancer Genome Atlas(TCGA)to compare triple-positive breast cancer(TPBC)with TNBC.TRN algorithms and virtual inference of protein-enriched regulon(VIPER)were used to identify master regulators and their target genes.Utilizing TNBC cells(MDA-MB-231 and MDA-MB-468),we validated the relationship of nuclear factor erythroid 2-like 3(NFE2L3)and basic helix-loop-helix family member E 40(BHLHE40)by performing a luciferase assay.The expression levels of these targets were measured after transfections with plasmid and siRNA via qRT-PCR and western blots.The effect of these genes on cell proliferation and migration was studied using phenotypic assays.Results:Using computational approaches,we identified NFE2L3 as a master regulator with BHLHE40 as its target gene.NFE2L3 protein binds to the promoter region of BHLHE40 and regulates its transcriptional activity.Additionally,silencing and overexpressing NFE2L3 and BHLHE40 in TNBC cell lines MDA-MB-231 and MDA-MB-468 showed that NFE2L3 directly regulates BHLHE40 at both transcriptional and translational levels.We found that BHLHE40 requires NFE2L3 for cell proliferation and migration in TNBC.Conclusion:These findings underscore the significance of NFE2L3 and BHLHE40 in TNBC,highlighting NFE2L3’s role in regulating the oncogenic activity of BHLHE40 in TNBC cells.
