The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic...The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.展开更多
Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents...Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents a challenge.By exploiting the catalytic selectivity derived from the valence-band hybridization of noble metal nanoalloys,we introduce an alloying strategy to modulate the reaction specificity of metallic nanozymes.Ag Pd nanoalloy exhibits enhanced peroxidase-like activity and eliminated oxidase-like activity by adjusting the Ag content.The introduction of Ag changes the hybrid d band energy of the alloyed metal and inhibits the O_(2)adsorption and decomposition on Pd,while improving the peroxidase mimicry by allowing for the H_(2)O_(2)activation.By exemplifying the construction of a highly sensitive and selective colorimetric glucose detection platform with its practicality validated in serum samples,this strategy pioneers a multi-noble metal nanozyme with tailored peroxidase activity based on the chemical structure engineering and would advance the development of single-catalytic function nanozymes for building exclusively specific biosensors through reducing substrate competition.展开更多
This work develops a protein imprinted nanosphere with varied recognition specificity for bovine serum albumin(BSA)and lysozyme(Lyz)under different UV light through a gradient dual crosslinked imprinting strategy(i.e....This work develops a protein imprinted nanosphere with varied recognition specificity for bovine serum albumin(BSA)and lysozyme(Lyz)under different UV light through a gradient dual crosslinked imprinting strategy(i.e.,covalent crosslinking and dynamic reversible crosslinking).The imprinting cavities are initially constructed using irreversible covalent crosslinking to specifically recognize BSA,and then the coumarin residues in the imprinting cavities are crosslinked under 365 nm UV light to further imprint Lyz,because Lyz has smaller size than BSA.Since the photo-crosslinking of coumarin is a reversible reaction,the imprinting cavities of Lyz can be de-crosslinked under 254 nm UV light and restore the imprinting cavities of BSA.Moreover,the N-isopropyl acrylamide(NIPAM)and pyrrolidine residues copolymerized in the polymeric surface of the nanospheres are temperature-and p H-responsive respectively.Therefore,the protein rebinding and release behaviors of the nanospheres are controlled by external temperature and p H.As a result,the materials can selectively separate BSA from real bovine whole blood and Lyz from egg white under different UV light.This study may provide a new strategy for construction of protein imprinted materials with tunable specificity for different proteins.展开更多
Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environment...Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environmental factors,plays a crucial role in host adaptability and may facilitate local adaptation within species.Concurrently,the genetic background of host populations influences gut microbiome composition,highlighting the bidirectional relationship between host and microbiome.Despite this,our understanding of gut microbiome plasticity and its role in host adaptability remains limited,particularly in reptiles.To clarify this issue,we conducted a reciprocal translocation experiment with gravid females of the Qinghai toad-headed lizards(Phrynocephalus vlangalii)between high-altitude(2?600 m a.s.l.)and superhigh-altitude(3?600 m a.s.l.)environments on Dangjin Mountain of the Qinghai-Xizang Plateau,China.One year later,we assessed the phenotypes and gut microbiomes of their offspring.Results revealed significant plasticity in gut microbiome diversity and structure in response to contrasting elevations.Highaltitude conditions increased diversity,and maternal effects appeared to enable high-altitude lizards to maintain elevated diversity when exposed to superhigh-altitude environments.Additionally,superhigh-altitude lizards displayed distinct gut microbiome structures with notable host specificity,potentially linked to their lower growth rates.Overall,these findings underscore the importance of the gut microbiome in facilitating reptilian adaptation to rapid environmental changes across altitudinal gradients.Furthermore,this study provides critical insights into microbial mechanisms underpinning local adaptation and adaptative plasticity,offering a foundation for future research on host-microbiome interactions in evolutionary and ecological contexts.展开更多
Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of ...Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.展开更多
基金financial support from the National Natural Science Foundation of China (Nos.82473887 and 21927808)the Scientific and Technological Innovation Program of Shanghai (No.23DZ2202500)the CAMS Innovation Fund for Medical Sciences (No.2021-1-I2M-026)。
文摘The brain's functions are governed by molecular metabolic networks.However,due to the sophisticated spatial organization and diverse activities of the brain,characterizing both the minute and large-scale metabolic activity across the entire brain and its numerous micro-regions remains incredibly challenging.Here,we offer a high-definition spatially resolved metabolomics technique to better understand the metabolic specialization and interconnection throughout the mouse brain using improved ambient mass spectrometry imaging.This method allows for the simultaneous mapping of thousands of metabolites at a 30 μm spatial resolution across the mouse brain,ranging from structural lipids to functional neurotransmitters.This approach effectively reveals the distribution patterns of delicate microregions and their distinctive metabolic characteristics.Using an integrated database,we annotated 259 metabolites,demonstrating that the metabolome and metabolic pathways are unique to each brain microregion.The distribution of metabolites,closely linked to functionally connected brain regions and their interactions,offers profound insights into the complexity of chemical processes and their roles in brain function.An initial dataset for future metabolomics research might be obtained from the high-definition mouse brain's spatial metabolome atlas.
基金financially supported by the National Natural Science Foundation of China(No.22074038)the Luoyang Institute of Science and Technology Natural Science General Project(No.21010905)+1 种基金the Fundamental Research Funds for the Central Universitiessponsored by the Domestic Visiting Scholar Program of Shandong University of Science and Technology。
文摘Nanozymes,characterized by their stability,cost-effectiveness,and tunable catalytic activity,are promising alternatives to natural enzymes.However,specifically mimicking a single natural enzyme's activity presents a challenge.By exploiting the catalytic selectivity derived from the valence-band hybridization of noble metal nanoalloys,we introduce an alloying strategy to modulate the reaction specificity of metallic nanozymes.Ag Pd nanoalloy exhibits enhanced peroxidase-like activity and eliminated oxidase-like activity by adjusting the Ag content.The introduction of Ag changes the hybrid d band energy of the alloyed metal and inhibits the O_(2)adsorption and decomposition on Pd,while improving the peroxidase mimicry by allowing for the H_(2)O_(2)activation.By exemplifying the construction of a highly sensitive and selective colorimetric glucose detection platform with its practicality validated in serum samples,this strategy pioneers a multi-noble metal nanozyme with tailored peroxidase activity based on the chemical structure engineering and would advance the development of single-catalytic function nanozymes for building exclusively specific biosensors through reducing substrate competition.
基金financial support from the National Natural Science Foundation of China(No.22275148)National Key R&D Program of China(No.2018YFB1900201)for Qiuyu Zhang+2 种基金the National Natural Science Foundation of China(No.22271232)Fundamental Research Funds for the Central Universities(No.D5000230114)for Shixin Fathe Fundamental Research Funds for the Central Universities(No.D5000220339)for Qing Liu。
文摘This work develops a protein imprinted nanosphere with varied recognition specificity for bovine serum albumin(BSA)and lysozyme(Lyz)under different UV light through a gradient dual crosslinked imprinting strategy(i.e.,covalent crosslinking and dynamic reversible crosslinking).The imprinting cavities are initially constructed using irreversible covalent crosslinking to specifically recognize BSA,and then the coumarin residues in the imprinting cavities are crosslinked under 365 nm UV light to further imprint Lyz,because Lyz has smaller size than BSA.Since the photo-crosslinking of coumarin is a reversible reaction,the imprinting cavities of Lyz can be de-crosslinked under 254 nm UV light and restore the imprinting cavities of BSA.Moreover,the N-isopropyl acrylamide(NIPAM)and pyrrolidine residues copolymerized in the polymeric surface of the nanospheres are temperature-and p H-responsive respectively.Therefore,the protein rebinding and release behaviors of the nanospheres are controlled by external temperature and p H.As a result,the materials can selectively separate BSA from real bovine whole blood and Lyz from egg white under different UV light.This study may provide a new strategy for construction of protein imprinted materials with tunable specificity for different proteins.
基金supported by the National Natural Science Foundation of China (31861143023,31872252)Strategic Priority Research Program of the Chinese Academy of Sciences (XDA20050201)。
文摘Animal adaptation to environmental challenges is a complex process involving intricate interactions between the host genotype and gut microbiome composition.The gut microbiome,highly responsive to external environmental factors,plays a crucial role in host adaptability and may facilitate local adaptation within species.Concurrently,the genetic background of host populations influences gut microbiome composition,highlighting the bidirectional relationship between host and microbiome.Despite this,our understanding of gut microbiome plasticity and its role in host adaptability remains limited,particularly in reptiles.To clarify this issue,we conducted a reciprocal translocation experiment with gravid females of the Qinghai toad-headed lizards(Phrynocephalus vlangalii)between high-altitude(2?600 m a.s.l.)and superhigh-altitude(3?600 m a.s.l.)environments on Dangjin Mountain of the Qinghai-Xizang Plateau,China.One year later,we assessed the phenotypes and gut microbiomes of their offspring.Results revealed significant plasticity in gut microbiome diversity and structure in response to contrasting elevations.Highaltitude conditions increased diversity,and maternal effects appeared to enable high-altitude lizards to maintain elevated diversity when exposed to superhigh-altitude environments.Additionally,superhigh-altitude lizards displayed distinct gut microbiome structures with notable host specificity,potentially linked to their lower growth rates.Overall,these findings underscore the importance of the gut microbiome in facilitating reptilian adaptation to rapid environmental changes across altitudinal gradients.Furthermore,this study provides critical insights into microbial mechanisms underpinning local adaptation and adaptative plasticity,offering a foundation for future research on host-microbiome interactions in evolutionary and ecological contexts.
基金support from the National Natural Science Foundation of China(8227131503).
文摘Cytochrome P450 enzymes(P450s or CYPs)are the primary metabolic contributors to the absorption,distribution,metabolism,and excretion(ADME)properties of small-molecule drugs.These enzymes can catalyze various types of reactions,including metabolic reactions that occur at nitrogen(N)and sulfur(S)sites of small molecules.In this review,we conducted a comprehensive statistical analysis of 294 P450s-mediated small-molecule substrates,among which more than 47%substrates contained N and S.The purpose of the analysis is to elucidate the broad-spectrum cross-reactivity and specificity between these substrates and various CYP isoforms across five reaction types.Our findings reveal that substrates with molecular weights greater than 500 Da or less than 200 Da are predominantly governed by the dominant effect of the CYP isoform’s active sites.In contrast,small-to medium-sized molecules with molecular weights ranging from 200 to 400 Da exhibit a stronger dependence on the types of heteroatoms they contain,with the size of the enzyme’s catalytic site(cavity)playing a negligible role in determining substrate specificity.This review starts from the metabolic mechanisms of P450s-mediated N-and S-containing compounds,and systematically analyzes the structural characteristics of substrates involved in N-dealkylation,N-oxidation,and S-oxidation,as well as their metabolic interactions with P450s.These analyses provide a new perspective for improving the existing understanding of the relationship between the P450s substrate specificity and substrate structural characteristics,and offer a valuable perspective for enhancing drug design and predicting metabolic stability based on the P450s-catalyzed reaction framework.
