AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional...AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional survey of ocular symptoms and clinical eye examinations were performed in a sample of 35 rural primary schools in the semi-arid region of Kajiado West sub-county in S.W.Kenya,amongst a seminomadic tribe(Maasai).Students in Grades 1-8 were included.Visual acuity was measured using the Snellen“tumbling E”chart at 6 m.Children with symptoms of refractive error underwent non-cycloplegic refraction.RESULTS:A total of 2036 children(1084 males)between the ages of 4-20y were examined.Conjunctival actinic changes were present in 22%(442/2036).Nine cases were seen with a potential squamous carcinoma.No overt classical ocular signs of vitamin A deficiency were noted,although 181(8.9%)children complained of nyctalopia.Three hundred thirty-six(16.5%)children had a visual acuity worse than 6/12 in either eye,were unable to read N10 near text at 40 cm or had symptoms suggestive of refractive error.Refractive data led to an estimate of hyperopia of+1.00 D or more in 3.9%and of myopia of-0.50 D or more in either eye in 3.0%of the study population.CONCLUSION:Solar exposure-and dust-related conjunctival pathology is common.As this may develop into potentially sight-or even life-threatening conditions,it warrants further study,and preventive strategies may be needed.Complaints of nyctalopia were common and could suggest vitamin A deficiency.The prevalence of refractive errors is low in this rural African population.展开更多
Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at th...Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.展开更多
BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METH...BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METHODS:Blood-brain barrier(BBB) permeability was assessed by measuring the concentration of sodium fl uorescein(NaF) in the brain tissues of rats and fl uorescein isothiocyanate-dextran(FITC-dextran)in a single-cell layer model.Neutrophil infiltration in the brain tissue,inflammatory cytokine levels in the serum,neurological function,and 7-day survival rates were used to evaluate therapeutic eff ects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and fi lamentous actin(F-actin) levels were measured,and the relationship between F-actin and the endothelial glycocalyx layer(EGL) was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide.RESULTS:Following mannitol administration,the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min,indicating that mannitol increased BBB permeability for 30 min.In vitro,mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls.In the MRSA intracranial infection model,rats treated with mannitol and vancomycin simultaneously presented less infl ammation,improved neurological function,and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues,which was confi rmed by in vitro experiments showing that mannitol signifi cantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION:Mannitol may enhance the therapeutic effi cacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.展开更多
Alkaline stress in saline soil limits cotton production that may be improved by using emerging nanobiotechnology approaches.Here,we applied poly acrylic acid coated Mn3O4 nanoparticles(PMO)on cotton leaves which showe...Alkaline stress in saline soil limits cotton production that may be improved by using emerging nanobiotechnology approaches.Here,we applied poly acrylic acid coated Mn3O4 nanoparticles(PMO)on cotton leaves which showed higher chlorophyll content(up to 100.0%)and fresh weight(46.9%)and lower electrolyte leakage rate(up to 6.8%)and cell death rate(up to 84.8%)than controls.Further investigation showed that PMO can maintain reactive oxygen species(ROS)homeostasis,increase the stability of actin filament(AF),and reduce Na^(+)content.Confocal imaging and ROS content measurement showed that PMO foliar application effectively alleviated ROS over-accumulation(up to 16.4%decrease for H_(2)O_(2)and 45.3%decrease for O_(2)^(•-))in cotton leaves.Moreover,under alkaline stress,genes for AF depolymerization such as GhADF1/8 and GhADF6 and for AF polymerization such as GhADF5 were significantly down-regulated in PMO treated cotton lines relative to those in the control,consistent with the fluorescence intensities of AFs.Furthermore,our results showed that PMO mitigated Na^(+)toxicity under alkaline stress,as indicated by the reduced Na^(+)fluorescence intensity and Na^(+)content.Furthermore,relative to those of the control,PMO treatment increased seed yield and lint yield by 65.0%and 66.3%respectively.Together,our work demonstrates that ROS scavenging PMO alleviated alkaline stress by stabilizing actin filaments and reducing Na^(+)toxicity.展开更多
Cell division is a fundamental biological process in which a parent cell divides into two daughter cells.The cell cortex,a thin layer primarily composed of actin filaments and myosin motors beneath the plasma membrane...Cell division is a fundamental biological process in which a parent cell divides into two daughter cells.The cell cortex,a thin layer primarily composed of actin filaments and myosin motors beneath the plasma membrane,plays a critical role in ensuring proper cell division.In this study,we apply a hydrodynamic model to describe the actin cortex as an active nematic surface,incorporating orientational order arising from actin filament alignment and anisotropic active stress produced by myosin motors.By analyzing the linearized dynamics,we investigate how shape,flow,and stress regulators evolve over time when the surface deviates slightly from a sphere.Our findings reveal that the active alignment of actin filaments,often overlooked in previous studies,is crucial for successful division.Furthermore,we demonstrate that a cortical chiral flow naturally emerges as a consequence of this active alignment.Overall,our results provide a mechanistic explanation for key phenomena observed during cell division,offering new insights into the role of active stress and filament alignment in cortical dynamics.展开更多
Cell fusion is a basic biological process that plays critical roles in both physiological and pathological processes.However,how mechanical factors influence the fusion process is not fully understood.In this study,we...Cell fusion is a basic biological process that plays critical roles in both physiological and pathological processes.However,how mechanical factors influence the fusion process is not fully understood.In this study,we reported filopodia-mediated fusion among MCF-7 cells.We showed that the filopodia protrusion force induced significant bending of the cell membrane,which was essential for membrane fusion between neighboring cells,and then eventually induced the formation of multinucleated syncytia.The inhibition of actin polymerization significantly reduced the fusion ratio,whereas increased actin polymerization promoted fusion.We found that several factors influence the fusion process,e.g.,the cell density,substrate pattern,and stiffness.For example,cell density has a significant effect on cell fusion.There was an optimal cell density for cell fusion.The fusion probability increased with increasing cell density within a moderate cell density range but decreased within a high cell density range.Substrate properties also influence the fusion behavior.For example,the fusion ratio was reduced on nanogrooved surfaces and soft substrates because the surface pattern restricted cell alignment and motility,and soft substrates reduced the activity of the actin dynamics of filopodia for cell fusion.This study not only contributes to our under-standing of the basic biology of cell fusion but also has important implications for understanding the mechanisms of cancer progression and potential therapeutic intervention methods.展开更多
A mutation in oxysterol-binding protein-like 2(OSBPL2)has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss(DFNA67,Online Mendelian Inheritance in Man No.616340).However,the pathogen...A mutation in oxysterol-binding protein-like 2(OSBPL2)has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss(DFNA67,Online Mendelian Inheritance in Man No.616340).However,the pathogenesis of the OSBPL2 mutation in DFNA remains unclear.Our previous work showed that Osbpl2 deficiency impaired cell adhesion in auditory HEI-OC1 cells.In addition,loss of hair cells(HCs)and morphological abnormalities of HC stereocilia were detected in OSBPL2-knockout pigs,suggesting that OSBPL2 plays an important role in regulating the actin cytoskeleton in auditory cells.In the present study,we found that Osbpl2 deficiency inhibited the Rho/ROCK2 signaling pathway and downregulated phosphorylated ezrin-radixinmoesin(p-ERM),resulting in abnormal F-actin morphology in HEI-OC1 cells and stereociliary defects in mouse HCs.The present study demonstrates the underlying mechanism of OSBPL2 in regulating the actin cytoskeleton in HCs,contributing to a deeper understanding of the pathogenesis of OSBPL2 mutations in DFNA.展开更多
利用SMART(switching mechanismat5’end of RNA transcript)技术,提取果实少量总RNA,经15-25轮LD-PCR扩增获得全长ds-cDNA,构建了海南主栽的食用香蕉巴西蕉(Musa AAA Group Cavendish)果实的cDNA文库。所构建的文库容量为5×106Pfu...利用SMART(switching mechanismat5’end of RNA transcript)技术,提取果实少量总RNA,经15-25轮LD-PCR扩增获得全长ds-cDNA,构建了海南主栽的食用香蕉巴西蕉(Musa AAA Group Cavendish)果实的cDNA文库。所构建的文库容量为5×106Pfuml-1,重组率93%。利用此cDNA文库,采用96孔板PCR法筛选香蕉Actin2基因,测序结果显示,序列全长1723bp,编码区长1134bp,编码378个氨基酸,与蝴蝶兰Actin2基因序列同源率达83%,已递交GenBank,接受号692696。展开更多
基金Supported by Vision International Eye Missions-USA,“One Drop for All”,Italy,and Private Donors in the Netherlands.
文摘AIM:To ascertain the pattern of ocular morbidity in a population of primary school children in rural Kenya as it is a prerequisite for planning effective preventive and therapeutic strategies.METHODS:A cross-sectional survey of ocular symptoms and clinical eye examinations were performed in a sample of 35 rural primary schools in the semi-arid region of Kajiado West sub-county in S.W.Kenya,amongst a seminomadic tribe(Maasai).Students in Grades 1-8 were included.Visual acuity was measured using the Snellen“tumbling E”chart at 6 m.Children with symptoms of refractive error underwent non-cycloplegic refraction.RESULTS:A total of 2036 children(1084 males)between the ages of 4-20y were examined.Conjunctival actinic changes were present in 22%(442/2036).Nine cases were seen with a potential squamous carcinoma.No overt classical ocular signs of vitamin A deficiency were noted,although 181(8.9%)children complained of nyctalopia.Three hundred thirty-six(16.5%)children had a visual acuity worse than 6/12 in either eye,were unable to read N10 near text at 40 cm or had symptoms suggestive of refractive error.Refractive data led to an estimate of hyperopia of+1.00 D or more in 3.9%and of myopia of-0.50 D or more in either eye in 3.0%of the study population.CONCLUSION:Solar exposure-and dust-related conjunctival pathology is common.As this may develop into potentially sight-or even life-threatening conditions,it warrants further study,and preventive strategies may be needed.Complaints of nyctalopia were common and could suggest vitamin A deficiency.The prevalence of refractive errors is low in this rural African population.
基金supported by the National Key Research and Development Program of China,No.2021ZD0202503(to AHT)the National Natural Science Foundation of China,Nos.31872759(to AHT)and 32070707(to CF)+1 种基金Shenzhen Science and Technology Program,No.RCJC20210609104333007(to ZW)Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Fundamental Research Institutions,No.2021SHIBS0002(to ZW).
文摘Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.
基金supported by the National Natural Science Foundation for Young Scientists of China (grant no.2002074)the Natural Science Foundation of Guangdong Province(2023A1515010267, 2023A1515012665, 2024A1515010073)+1 种基金the China International Medical Foundation Cerebrovascular Disease Youth Innovation Fund (Z-2016-20-2201)the Medical Leading Talents Fund of Guangdong Province (KJ012019430)。
文摘BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METHODS:Blood-brain barrier(BBB) permeability was assessed by measuring the concentration of sodium fl uorescein(NaF) in the brain tissues of rats and fl uorescein isothiocyanate-dextran(FITC-dextran)in a single-cell layer model.Neutrophil infiltration in the brain tissue,inflammatory cytokine levels in the serum,neurological function,and 7-day survival rates were used to evaluate therapeutic eff ects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and fi lamentous actin(F-actin) levels were measured,and the relationship between F-actin and the endothelial glycocalyx layer(EGL) was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide.RESULTS:Following mannitol administration,the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min,indicating that mannitol increased BBB permeability for 30 min.In vitro,mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls.In the MRSA intracranial infection model,rats treated with mannitol and vancomycin simultaneously presented less infl ammation,improved neurological function,and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues,which was confi rmed by in vitro experiments showing that mannitol signifi cantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION:Mannitol may enhance the therapeutic effi cacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.
基金supported by the National Natural Science Foundation of China(32120103008)the National Key Research and Development Program of China(2023YFD1901700-3)+3 种基金Fundamental Research Funds for the Central Universities(2662024JC011,2662025HXPY005)the HZAU-AGIS Fund(SZYJY2021008)the Key Research and Development Projects of Henan province(231111113000)the Hubei Agricultural Science and Technology Innovation Center Program(2021-620-000-001-032).
文摘Alkaline stress in saline soil limits cotton production that may be improved by using emerging nanobiotechnology approaches.Here,we applied poly acrylic acid coated Mn3O4 nanoparticles(PMO)on cotton leaves which showed higher chlorophyll content(up to 100.0%)and fresh weight(46.9%)and lower electrolyte leakage rate(up to 6.8%)and cell death rate(up to 84.8%)than controls.Further investigation showed that PMO can maintain reactive oxygen species(ROS)homeostasis,increase the stability of actin filament(AF),and reduce Na^(+)content.Confocal imaging and ROS content measurement showed that PMO foliar application effectively alleviated ROS over-accumulation(up to 16.4%decrease for H_(2)O_(2)and 45.3%decrease for O_(2)^(•-))in cotton leaves.Moreover,under alkaline stress,genes for AF depolymerization such as GhADF1/8 and GhADF6 and for AF polymerization such as GhADF5 were significantly down-regulated in PMO treated cotton lines relative to those in the control,consistent with the fluorescence intensities of AFs.Furthermore,our results showed that PMO mitigated Na^(+)toxicity under alkaline stress,as indicated by the reduced Na^(+)fluorescence intensity and Na^(+)content.Furthermore,relative to those of the control,PMO treatment increased seed yield and lint yield by 65.0%and 66.3%respectively.Together,our work demonstrates that ROS scavenging PMO alleviated alkaline stress by stabilizing actin filaments and reducing Na^(+)toxicity.
基金support from the National Nat-ural Science Foundation of China(Grant No.12474199)the Fundamental Research Funds for Central Universities of China(Grant No.20720240144),and 111 Project(B16029).
文摘Cell division is a fundamental biological process in which a parent cell divides into two daughter cells.The cell cortex,a thin layer primarily composed of actin filaments and myosin motors beneath the plasma membrane,plays a critical role in ensuring proper cell division.In this study,we apply a hydrodynamic model to describe the actin cortex as an active nematic surface,incorporating orientational order arising from actin filament alignment and anisotropic active stress produced by myosin motors.By analyzing the linearized dynamics,we investigate how shape,flow,and stress regulators evolve over time when the surface deviates slightly from a sphere.Our findings reveal that the active alignment of actin filaments,often overlooked in previous studies,is crucial for successful division.Furthermore,we demonstrate that a cortical chiral flow naturally emerges as a consequence of this active alignment.Overall,our results provide a mechanistic explanation for key phenomena observed during cell division,offering new insights into the role of active stress and filament alignment in cortical dynamics.
基金supported by the National Natural Science Foundation of China(Grant Nos.11932017 and 12122212).
文摘Cell fusion is a basic biological process that plays critical roles in both physiological and pathological processes.However,how mechanical factors influence the fusion process is not fully understood.In this study,we reported filopodia-mediated fusion among MCF-7 cells.We showed that the filopodia protrusion force induced significant bending of the cell membrane,which was essential for membrane fusion between neighboring cells,and then eventually induced the formation of multinucleated syncytia.The inhibition of actin polymerization significantly reduced the fusion ratio,whereas increased actin polymerization promoted fusion.We found that several factors influence the fusion process,e.g.,the cell density,substrate pattern,and stiffness.For example,cell density has a significant effect on cell fusion.There was an optimal cell density for cell fusion.The fusion probability increased with increasing cell density within a moderate cell density range but decreased within a high cell density range.Substrate properties also influence the fusion behavior.For example,the fusion ratio was reduced on nanogrooved surfaces and soft substrates because the surface pattern restricted cell alignment and motility,and soft substrates reduced the activity of the actin dynamics of filopodia for cell fusion.This study not only contributes to our under-standing of the basic biology of cell fusion but also has important implications for understanding the mechanisms of cancer progression and potential therapeutic intervention methods.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.82071052 to J.Y.and 81771000 to X.C.)。
文摘A mutation in oxysterol-binding protein-like 2(OSBPL2)has been identified as the genetic cause of autosomal dominant nonsyndromic hearing loss(DFNA67,Online Mendelian Inheritance in Man No.616340).However,the pathogenesis of the OSBPL2 mutation in DFNA remains unclear.Our previous work showed that Osbpl2 deficiency impaired cell adhesion in auditory HEI-OC1 cells.In addition,loss of hair cells(HCs)and morphological abnormalities of HC stereocilia were detected in OSBPL2-knockout pigs,suggesting that OSBPL2 plays an important role in regulating the actin cytoskeleton in auditory cells.In the present study,we found that Osbpl2 deficiency inhibited the Rho/ROCK2 signaling pathway and downregulated phosphorylated ezrin-radixinmoesin(p-ERM),resulting in abnormal F-actin morphology in HEI-OC1 cells and stereociliary defects in mouse HCs.The present study demonstrates the underlying mechanism of OSBPL2 in regulating the actin cytoskeleton in HCs,contributing to a deeper understanding of the pathogenesis of OSBPL2 mutations in DFNA.
文摘利用SMART(switching mechanismat5’end of RNA transcript)技术,提取果实少量总RNA,经15-25轮LD-PCR扩增获得全长ds-cDNA,构建了海南主栽的食用香蕉巴西蕉(Musa AAA Group Cavendish)果实的cDNA文库。所构建的文库容量为5×106Pfuml-1,重组率93%。利用此cDNA文库,采用96孔板PCR法筛选香蕉Actin2基因,测序结果显示,序列全长1723bp,编码区长1134bp,编码378个氨基酸,与蝴蝶兰Actin2基因序列同源率达83%,已递交GenBank,接受号692696。
