As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,t...As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.展开更多
Deciphering the context-specific relationship between sequence and function is a major challenge in genomics.Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limi...Deciphering the context-specific relationship between sequence and function is a major challenge in genomics.Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited.Here we present a programmable platform for long-range,locus-specific hypermutation called helicase-assisted continuous editing(HACE).HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large(>1000-base pair)genomic intervals.We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1(MEK1)that confer kinase inhibitor resistance,to dissect the impact of individual variants in splicing factor 3B subunit 1(SF3B1)-dependent missplicing,and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69.HACE provides a powerful tool for investigating coding and noncoding variants,uncovering combinatorial sequence-to-function relationships,and evolving new biological functions.展开更多
The endogenous GAs, ABA and IAA in the shoot apices of 8-year-old Chinese pines, flowered, non-flowered and non-flowered but treated with GA4/7 were analyzed by GC-MS-SIM.The results demonstrated that GA3 and GA9 leve...The endogenous GAs, ABA and IAA in the shoot apices of 8-year-old Chinese pines, flowered, non-flowered and non-flowered but treated with GA4/7 were analyzed by GC-MS-SIM.The results demonstrated that GA3 and GA9 levels were obviously higher in flowered plants than in non-flowered. A peak value of GA3 in flowered plants occurred after appearance of the earliest auxiliary bud primorda which had the possibility of transforming into male cone bud primordia and before the morphological initiation of male cone bud primordia. Exogenously applied GA4/7 could enhance the endogenous GA3 and GA9, this may benefit the promotion of male cone buds in Chinese pine. The relations among ex-ogenously applied GA4/7 endogenous GAs, ABA and IAA in the shoot apices, and the initiation of male cone bud are discussed.展开更多
Following the bone marrow or cardiac derived progenitor cells transplantation,improved left ventricular(LV) function,decreased LV remodeling, and decreased fibrosis of non-infarcted LV regions,and in some cases,the re...Following the bone marrow or cardiac derived progenitor cells transplantation,improved left ventricular(LV) function,decreased LV remodeling, and decreased fibrosis of non-infarcted LV regions,and in some cases,the reduction of infarct scar size have been reported to occur in animal mycardial infarction(MI) models.In clinical trials, stem cell transplantation has also been associated with significant,but modest improvements of LV functional parameters.These beneficial effects do occur although in many animal studies there is often very low long term engraftment or transdifferentiation of transplanted cells into myocytes and vascular cells.Importantly,paracrine signals generated by the implanted progenitor cells seem to play an important role in limiting or reversing myocardial damage as- sociated with acute MI.Paracrine signaling effects include increased myocardial vascularization and reduced apoptosis of native cardiomyocytes;these responses are most prominent in peri-myocardial infarction (MI) boarder zone(BZ) of the heart.Although much data supports the possibility that engrafted progenitor cells can mobilize endogenous cardiac progenitor cells(CPC) to the cardiac injury site and also stimulate them to propagate and transd-ifferentiate into cardiomyocytes and vascular cells, this concept remains controversial.We and others have reported evidences supporting the view that endogenous CPC can be stimulated to differentiate and partially replace cardiomyocytes destroyed during an MI.Data from our laboratory will be reviewed.展开更多
The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptom...The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.展开更多
Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to p...Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.展开更多
基金the Natural Science Foundation of Hubei Province,China(2021CFB468)Sci-tech Innovation Foundation of Huazhong Agriculture University(2662020LXPY007)National Key Research and Development Program of China(2021YFD1400800).
文摘As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.
文摘Deciphering the context-specific relationship between sequence and function is a major challenge in genomics.Existing tools for inducing locus-specific hypermutation and evolution in the native genome context are limited.Here we present a programmable platform for long-range,locus-specific hypermutation called helicase-assisted continuous editing(HACE).HACE leverages CRISPR-Cas9 to target a processive helicase-deaminase fusion that incurs mutations across large(>1000-base pair)genomic intervals.We applied HACE to identify mutations in mitogen-activated protein kinase kinase 1(MEK1)that confer kinase inhibitor resistance,to dissect the impact of individual variants in splicing factor 3B subunit 1(SF3B1)-dependent missplicing,and to evaluate noncoding variants in a stimulation-dependent immune enhancer of CD69.HACE provides a powerful tool for investigating coding and noncoding variants,uncovering combinatorial sequence-to-function relationships,and evolving new biological functions.
基金The research was funded by the National Natural Science Foundation of China
文摘The endogenous GAs, ABA and IAA in the shoot apices of 8-year-old Chinese pines, flowered, non-flowered and non-flowered but treated with GA4/7 were analyzed by GC-MS-SIM.The results demonstrated that GA3 and GA9 levels were obviously higher in flowered plants than in non-flowered. A peak value of GA3 in flowered plants occurred after appearance of the earliest auxiliary bud primorda which had the possibility of transforming into male cone bud primordia and before the morphological initiation of male cone bud primordia. Exogenously applied GA4/7 could enhance the endogenous GA3 and GA9, this may benefit the promotion of male cone buds in Chinese pine. The relations among ex-ogenously applied GA4/7 endogenous GAs, ABA and IAA in the shoot apices, and the initiation of male cone bud are discussed.
文摘Following the bone marrow or cardiac derived progenitor cells transplantation,improved left ventricular(LV) function,decreased LV remodeling, and decreased fibrosis of non-infarcted LV regions,and in some cases,the reduction of infarct scar size have been reported to occur in animal mycardial infarction(MI) models.In clinical trials, stem cell transplantation has also been associated with significant,but modest improvements of LV functional parameters.These beneficial effects do occur although in many animal studies there is often very low long term engraftment or transdifferentiation of transplanted cells into myocytes and vascular cells.Importantly,paracrine signals generated by the implanted progenitor cells seem to play an important role in limiting or reversing myocardial damage as- sociated with acute MI.Paracrine signaling effects include increased myocardial vascularization and reduced apoptosis of native cardiomyocytes;these responses are most prominent in peri-myocardial infarction (MI) boarder zone(BZ) of the heart.Although much data supports the possibility that engrafted progenitor cells can mobilize endogenous cardiac progenitor cells(CPC) to the cardiac injury site and also stimulate them to propagate and transd-ifferentiate into cardiomyocytes and vascular cells, this concept remains controversial.We and others have reported evidences supporting the view that endogenous CPC can be stimulated to differentiate and partially replace cardiomyocytes destroyed during an MI.Data from our laboratory will be reviewed.
基金the financial support of Isfahan University of Medical Sciences by grant No.#199180.
文摘The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.
基金supported by the Key-Area Research and Development Program of Guangdong Province[grant numbers 21202107201900005,21202107201900003].
文摘Sensitive skin is a clinical syndrome characterized by a hyper-reactive state of the skin,primarily on the face.It is accompanied by subjective symptoms such as burning,stinging,itching,and tightness when exposed to physical,chemical,or psychological stimuli.Objective signs,such as erythema,scales,and dilated blood vessels,may or may not be present.The discomfort associated with sensitive skin can be triggered by various endogenous and exogenous factors,which usually have no significant effect on the individual and do not induce irritant reactions.Sensitive skin often presents as a subjective state without clinical signs and exhibits diversity,posing challenges in sensitive skin research and care.This review summarizes the prevalence,key factors,pathophysiological mechanisms,diagnosis,and progress in daily care for sensitive skin.The aim is to provide a clearer and more systematic understanding of sensitive skin and offer guidance for sensitive skin care.
