目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgt...目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgtC转录的影响。最后,通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果:所有27个候选中药成分均显示出与MgtC结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgtC的转录活性降低了15%以上。这四个成分对mgtC转录的最低抑制浓度分别为:阿魏酸16μM;对羟基肉桂酸40μM;牛蒡子苷80μM;掌叶防己碱160μM。此外,我们证实这四种成分均未抑制细菌生长。结论:在本研究中,我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标,筛选了27种中药成分,发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。展开更多
A neuroprosthesis is a type of precision medical device that is intended to manipulate the neuronal signals of the brain in a closed-loop fashion,while simultaneously receiving stimuli from the environment and control...A neuroprosthesis is a type of precision medical device that is intended to manipulate the neuronal signals of the brain in a closed-loop fashion,while simultaneously receiving stimuli from the environment and controlling some part of a human brain or body.Incoming visual information can be processed by the brain in millisecond intervals.The retina computes visual scenes and sends its output to the cortex in the form of neuronal spikes for further computation.Thus,the neuronal signal of interest for a retinal neuroprosthesis is the neuronal spike.Closed-loop computation in a neuroprosthesis includes two stages:encoding a stimulus as a neuronal signal,and decoding it back into a stimulus.In this paper,we review some of the recent progress that has been achieved in visual computation models that use spikes to analyze natural scenes that include static images and dynamic videos.We hypothesize that in order to obtain a better understanding of the computational principles in the retina,a hypercircuit view of the retina is necessary,in which the different functional network motifs that have been revealed in the cortex neuronal network are taken into consideration when interacting with the retina.The different building blocks of the retina,which include a diversity of cell types and synaptic connections-both chemical synapses and electrical synapses(gap junctions)-make the retina an ideal neuronal network for adapting the computational techniques that have been developed in artificial intelligence to model the encoding and decoding of visual scenes.An overall systems approach to visual computation with neuronal spikes is necessary in order to advance the next generation of retinal neuroprosthesis as an artificial visual system.展开更多
Salmonellosis poses a serious challenge to public health and poultry industries worldwide.With the emergence of multi-drug resistant Salmonella,the burden caused by Salmonella infections has increased steadily.Enhanci...Salmonellosis poses a serious challenge to public health and poultry industries worldwide.With the emergence of multi-drug resistant Salmonella,the burden caused by Salmonella infections has increased steadily.Enhancing the understanding of the Salmonella infection process may aid the development of new treatments and effective preventive strategies against the disease.This review outlined the Salmonella infection process and introduced the pathogenesis of Salmonella and its virulence factors,such as Type III Secretion Systems effectors.The author summarized the recent advances in the application of Chinese herbal medicine(CHM)in the inhibition of drug-resistant Salmonella and its virulence and discussed the possible mechanisms of CHM inhibiting Salmonella growth and affecting its virulence.CHM has been shown to be effective in inhibiting bacterial growth and alter the virulence properties of pathogens.It is shown that CHM is much less likely to produce drug resistance to bacteria comparing to conventional antibiotics.One reason for this is that CHM may enhance host immunity to control the bacterial infection indirectly whereas conventional antibiotics directly kill the bacteria or inhibit their growth.At present,the percentage of antibiotic-resistant Salmonella isolates is increasing globally.CHM shows great potential for the development of new medicines.It may be an alternative solution to preventing and treating Salmonellosis caused by antibiotic-resistant strains.Further studies on the molecular mechanisms of the active ingredients of CHM may help the future development of novel antibacterial drug designs to contain bacterial infections.展开更多
Chinese herbal medicines(CHMs)play an increasingly important role in the field of medicine and affects public health in the world.Although more and more strict has been employed to ensure the quality and safety of CHM...Chinese herbal medicines(CHMs)play an increasingly important role in the field of medicine and affects public health in the world.Although more and more strict has been employed to ensure the quality and safety of CHMs,pesticide residues in CHMs remain a serious issue and are the bottleneck for the global development of CHMs.In this work,we applied molecularly imprinted membrane electrospray mass spectrometry(MIM-ESI MS)for rapid detecting 4 classes of pesticide residues in CHMs,including organophosphorus(OPP),carbamates,pyrethroids and neonicotinoids in CHMs.Compared with our previous ambient ionization method MESI,MIM-ESI is capable of achieving a~50-fold increase in the detection limit of conventional analytical methods owing to the specificity recognition and unique enrichment of MIM.The optimal experimental conditions were determined,and the method was further validated for its sensitivity and specificity.Our data showed that MIM-ESI MS is applicable for the direct quantitation of pesticide residues in CHMs.This detection technology may help to ensure the quality of CHMs in the future.展开更多
Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined...Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined to a single functional region of the brain.Here,we demonstrate a novel technique,termed the multiarea two-photon real-time in vivo explorer(MATRIEX),that allows the user to target multiple functional brain regions distributed within a zone of up to 12mm in diameter,each with a field of view(FOV)of ~200μm in diameter,thus performing two-photon Ca2+imaging with single-cell resolution in all of the regions simultaneously.For example,we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex,primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states.A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances(>1 mm)both laterally and axially but that are imaged by a single conventional laser scanning device.In particular,the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself.Thus,the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.展开更多
Simple saccharides have a variety of biological functions,but their structural diversity and inherent structural features pose a major challenge for rapid analysis.In this work,we developed a derivative-free and ion m...Simple saccharides have a variety of biological functions,but their structural diversity and inherent structural features pose a major challenge for rapid analysis.In this work,we developed a derivative-free and ion mobility-free method for the rapid analysis of monosaccharides and disaccharides using paper spray tandem mass spectrometry.Trimeric cluster ions consisting of saccharide analytes,ligands and transition metal ions are used as precursor ions.We defined the R-value as the ratio of the intensity of the product ion that loses one molecule of ligand over the intensity of the product ion that loses one molecule of saccharide via collision induced dissociation(CID).The species and conformation of simple saccharides can be easily differentiated by calculating this R-value.With the capability of directly analyzing clinical samples using paper spray ionization,our method can be used to rapidly quantify the molar ratio of galactose to glucose in dried plasma samples to aid in the diagnosis of galactosemia.The analytical strategy provided herein has good potential to be applied to a wide range of saccharide analysis applications in the future.展开更多
Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy admini...Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.Methods:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019.The efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were evaluated.Results:Fifty-five children aged from 2.2 months to 169.7 months were included,with a median age at KD initiation of 14.1 months,and 32 cases(58.2%)responded to the diet therapy at the last contact.The responder rates were 16.4%(9/55);36.4%(20/55),30.9%(17/55),27.3%(15/55)at 1,3,6 and 12 months,respectively.Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness.Poor compliance and lack of response were main reasons for discontinuation of KD.There are a few side effects of KD,most of which were minor.Conclusions:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest China.Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.展开更多
Summary What is already known about this topic?The prevalence of underweight malnutrition largely decreased in Chinese adults in recent thirty years while obesity became increasingly concerning.However,underweight mal...Summary What is already known about this topic?The prevalence of underweight malnutrition largely decreased in Chinese adults in recent thirty years while obesity became increasingly concerning.However,underweight malnutrition still affected elderly populations and increased risk of anemia,infection diseases,some non-communicable chronic diseases and disability.展开更多
基金supported by the National Natural Science Foundation of China(82072247 and 82374154)National Key Research and Development Project of China(2022YFC3502300)+2 种基金Natural Science Foundation of Beijing Municipality(L222150)Tianjin Chasesun Pharmaceutical(BUCM-2022-JS-FW-076)Zhuhai Yourun Co.,Ltd.(BUCM-2023-JS-KF-018)
文摘目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgtC转录的影响。最后,通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果:所有27个候选中药成分均显示出与MgtC结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgtC的转录活性降低了15%以上。这四个成分对mgtC转录的最低抑制浓度分别为:阿魏酸16μM;对羟基肉桂酸40μM;牛蒡子苷80μM;掌叶防己碱160μM。此外,我们证实这四种成分均未抑制细菌生长。结论:在本研究中,我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标,筛选了27种中药成分,发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。
基金supported by projects of the National Natural Science Foundation of China(61425025)the Beijing Municipal Science and Technology Project(Z151100000915070 and Z171100000117008)。
基金supported by the National Basic Research Program of China(2015CB351806)the National Natural Science Foundation of China(61806011,61825101,61425025,and U1611461)+4 种基金the National Postdoctoral Program for Innovative Talents(BX20180005)the China Postdoctoral Science Foundation(2018M630036)the International Talent Exchange Program of Beijing Municipal Commission of Science and Technology(Z181100001018026)the Zhejiang Lab(2019KC0AB03 and 2019KC0AD02)the Royal Society Newton Advanced Fellowship(NAF-R1-191082).
文摘A neuroprosthesis is a type of precision medical device that is intended to manipulate the neuronal signals of the brain in a closed-loop fashion,while simultaneously receiving stimuli from the environment and controlling some part of a human brain or body.Incoming visual information can be processed by the brain in millisecond intervals.The retina computes visual scenes and sends its output to the cortex in the form of neuronal spikes for further computation.Thus,the neuronal signal of interest for a retinal neuroprosthesis is the neuronal spike.Closed-loop computation in a neuroprosthesis includes two stages:encoding a stimulus as a neuronal signal,and decoding it back into a stimulus.In this paper,we review some of the recent progress that has been achieved in visual computation models that use spikes to analyze natural scenes that include static images and dynamic videos.We hypothesize that in order to obtain a better understanding of the computational principles in the retina,a hypercircuit view of the retina is necessary,in which the different functional network motifs that have been revealed in the cortex neuronal network are taken into consideration when interacting with the retina.The different building blocks of the retina,which include a diversity of cell types and synaptic connections-both chemical synapses and electrical synapses(gap junctions)-make the retina an ideal neuronal network for adapting the computational techniques that have been developed in artificial intelligence to model the encoding and decoding of visual scenes.An overall systems approach to visual computation with neuronal spikes is necessary in order to advance the next generation of retinal neuroprosthesis as an artificial visual system.
文摘Salmonellosis poses a serious challenge to public health and poultry industries worldwide.With the emergence of multi-drug resistant Salmonella,the burden caused by Salmonella infections has increased steadily.Enhancing the understanding of the Salmonella infection process may aid the development of new treatments and effective preventive strategies against the disease.This review outlined the Salmonella infection process and introduced the pathogenesis of Salmonella and its virulence factors,such as Type III Secretion Systems effectors.The author summarized the recent advances in the application of Chinese herbal medicine(CHM)in the inhibition of drug-resistant Salmonella and its virulence and discussed the possible mechanisms of CHM inhibiting Salmonella growth and affecting its virulence.CHM has been shown to be effective in inhibiting bacterial growth and alter the virulence properties of pathogens.It is shown that CHM is much less likely to produce drug resistance to bacteria comparing to conventional antibiotics.One reason for this is that CHM may enhance host immunity to control the bacterial infection indirectly whereas conventional antibiotics directly kill the bacteria or inhibit their growth.At present,the percentage of antibiotic-resistant Salmonella isolates is increasing globally.CHM shows great potential for the development of new medicines.It may be an alternative solution to preventing and treating Salmonellosis caused by antibiotic-resistant strains.Further studies on the molecular mechanisms of the active ingredients of CHM may help the future development of novel antibacterial drug designs to contain bacterial infections.
基金supported by the National Natural Science Foundation of China(No.82072247)to MZthe Young Scholar Project of Beijing University of Chinese Medicine(Nos.2019-JYBJS-017 and 2021-JYB-XJSJJ001)to SJ and MZ。
文摘Chinese herbal medicines(CHMs)play an increasingly important role in the field of medicine and affects public health in the world.Although more and more strict has been employed to ensure the quality and safety of CHMs,pesticide residues in CHMs remain a serious issue and are the bottleneck for the global development of CHMs.In this work,we applied molecularly imprinted membrane electrospray mass spectrometry(MIM-ESI MS)for rapid detecting 4 classes of pesticide residues in CHMs,including organophosphorus(OPP),carbamates,pyrethroids and neonicotinoids in CHMs.Compared with our previous ambient ionization method MESI,MIM-ESI is capable of achieving a~50-fold increase in the detection limit of conventional analytical methods owing to the specificity recognition and unique enrichment of MIM.The optimal experimental conditions were determined,and the method was further validated for its sensitivity and specificity.Our data showed that MIM-ESI MS is applicable for the direct quantitation of pesticide residues in CHMs.This detection technology may help to ensure the quality of CHMs in the future.
基金supported by the“100-Talents Program for Elite Engineers”of the CAS(H.J.)the Key Scientific Research Equipment Development Project of the CAS(Super-resolution Microscopy Systems and Key Components,ZDYZ2013-1)+3 种基金the“1000-Talents Program for Young Scholars”of China(X.C.)grants from the Ministry of Science and Technology of China(“973 Program”:2015CB759500,2018YFA0109600)the National Natural Science Foundation of China(61705251,81671106,81771175,31700933,81721001)the China Postdoctoral Science Foundation(2018M632374).
文摘Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains.However,the extent of such studies is typically confined to a single functional region of the brain.Here,we demonstrate a novel technique,termed the multiarea two-photon real-time in vivo explorer(MATRIEX),that allows the user to target multiple functional brain regions distributed within a zone of up to 12mm in diameter,each with a field of view(FOV)of ~200μm in diameter,thus performing two-photon Ca2+imaging with single-cell resolution in all of the regions simultaneously.For example,we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex,primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states.A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances(>1 mm)both laterally and axially but that are imaged by a single conventional laser scanning device.In particular,the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself.Thus,the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.
基金supported by NNSF China(No.82072247)Research Projects of Beijing University of Chinese Medicine(Nos.2021-JYB-XJSJJ-001,XJYS21005 and 2021-SYJS-007)。
文摘Simple saccharides have a variety of biological functions,but their structural diversity and inherent structural features pose a major challenge for rapid analysis.In this work,we developed a derivative-free and ion mobility-free method for the rapid analysis of monosaccharides and disaccharides using paper spray tandem mass spectrometry.Trimeric cluster ions consisting of saccharide analytes,ligands and transition metal ions are used as precursor ions.We defined the R-value as the ratio of the intensity of the product ion that loses one molecule of ligand over the intensity of the product ion that loses one molecule of saccharide via collision induced dissociation(CID).The species and conformation of simple saccharides can be easily differentiated by calculating this R-value.With the capability of directly analyzing clinical samples using paper spray ionization,our method can be used to rapidly quantify the molar ratio of galactose to glucose in dried plasma samples to aid in the diagnosis of galactosemia.The analytical strategy provided herein has good potential to be applied to a wide range of saccharide analysis applications in the future.
基金This work was supported by the Shanxi Science and Technology Support Program(Grant number 2017SF-292).
文摘Background:Due to the tradition of carbohydrate-rich diet,challenges exist for ketogenic diet(KD)implementation in Northwest China.This study was aimed to investigate the efficacy and tolerability of KD therapy administered with gradual initiation protocols in Chinese children with pharmacoresistant epilepsy in Northwest China.Methods:In this single-center study,55 children with drug-resistant epilepsy were enrolled from June 2013 to June 2019.The efficacy of KD,reasons for discontinuation,duration of retention and rate of adverse events were evaluated.Results:Fifty-five children aged from 2.2 months to 169.7 months were included,with a median age at KD initiation of 14.1 months,and 32 cases(58.2%)responded to the diet therapy at the last contact.The responder rates were 16.4%(9/55);36.4%(20/55),30.9%(17/55),27.3%(15/55)at 1,3,6 and 12 months,respectively.Univariate analysis indicated that the duration of epilepsy and the duration of KD therapy were predictors for KD effectiveness.Poor compliance and lack of response were main reasons for discontinuation of KD.There are a few side effects of KD,most of which were minor.Conclusions:The KD therapy with a gradual-initiation protocol is effective and tolerable for children with drug-resist-ant epilepsy in Northwest China.Early start of KD and KD duration of more than 6 months may be predictive factors for KD efficacy.
文摘Summary What is already known about this topic?The prevalence of underweight malnutrition largely decreased in Chinese adults in recent thirty years while obesity became increasingly concerning.However,underweight malnutrition still affected elderly populations and increased risk of anemia,infection diseases,some non-communicable chronic diseases and disability.
