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
Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is co...Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China. Methods The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell （CRBC） agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers. Results Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains： A/Guangdong/1/06 （A/GD/1/06） and A/Guangxi/1/08 （A/GX/1/08）. Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses. Conclusion The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.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
The genus Actinidia is primarily functionally dioecious,and early sex identification plays a crucial role in improving breeding efficiency and reducing production costs.In this study,the accuracy of three sex-linked m...The genus Actinidia is primarily functionally dioecious,and early sex identification plays a crucial role in improving breeding efficiency and reducing production costs.In this study,the accuracy of three sex-linked molecular markers(SyGI[Shy Girl],FrBy[Friendly Boy],and SmY1)in sex identification was evaluated in various Actinidia species.The selected marker products were subsequently cloned and sequenced in six wild Actinidia species.Ninety-six wild A.chinensis chinensis accessions and 74 A.chinensis deliciosa accessions,most of which were wild,with only one cultivated,were used for comprehensive primer validation.Thirty-three juvenile A.chinensis chinensis hybrid seedlings were used for practical application tests.The results showed that the marker SyGI accurately identified the sex of 20 samples from six Actinidia species and 96 A.chinensis chinensis accessions with 100%reliability.For Actinidia chinensis deliciosa,the identification accuracy reached 98.65%.Sequence analysis revealed that SyGI shared the highest similarity with the male-specific genomic region.Furthermore,SyGI achieved 100%accuracy in identifying the sex of 33 juvenile A.chinensis chinensis individuals.The findings confirm that the SyGI marker possesses high accuracy,strong specificity,and broad applicability,making it a valuable tool for kiwifruit breeding programs.The cloned sequences from wild Actinidia species also provide important references for future research on the mechanisms of sexual evolution and determination.展开更多
With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raisin...With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raising increasing concerns about their security.Existing fuzz testing methods include random or dictionary-based input generation,which often fail to ensure both syntactic and semantic correctness,and OpenAPIbased approaches,which offer better accuracy but typically lack detailed descriptions of endpoints,parameters,or data formats.To address these issues,this paper proposes the APIDocX fuzz testing framework.It introduces a crawler tailored for dynamic web pages that automatically simulates user interactions to trigger APIs,capturing and extracting parameter information from communication packets.A multi-endpoint parameter adaptation method based on improved Jaccard similarity is then used to generalize these parameters to other potential API endpoints,filling in gaps in OpenAPI specifications.Experimental results demonstrate that the extracted parameters can be generalized with 79.61%accuracy.Fuzz testing using the enriched OpenAPI documents leads to improvements in test coverage,the number of valid test cases generated,and fault detection capabilities.This approach offers an effective enhancement to automated REST API security testing.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challengin...Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challenging due to its large genome size and high proportion of repetitive sequences.Allele-specific expression(ASE)plays a key role in regulating plant development and evolution,yet research on ASE in coconut is limited(Shao et al.,2019;Li et al.,2021;Zhang et al.,2021;Hu et al.,2022).Among phenotypic traits,fruit color is especially important as an indicator of maturity,guiding harvest timing and post-harvest processes(Kapoor et al.,2022).While prior studies have explored various coconut traits such as salt tolerance,fiber content,and plant height(Wang et al.,2021;Yang et al.,2021),investigations into ASE and fruit color remain scarce.展开更多
This study was to investigate the efficiency and specificity of RNAi silencing on the expression of endogenous fad2 gene in transgenic line W-4. [Method] The relative expression of fad2 gene in seeds at different deve...This study was to investigate the efficiency and specificity of RNAi silencing on the expression of endogenous fad2 gene in transgenic line W-4. [Method] The relative expression of fad2 gene in seeds at different developmental stages of 7th, 14th, 21st and 28th day after flowering （DAF） as wel as the root, stem, leaf at winter seedling stages of both the transgenic line W-4 and non-transgenic control Westar by real-time fluorescence quantitative PCR. [Results] The results showed the relative expression of fad2 gene was gradual y increasing with the days after flowering in the seeds of the control Westar, while it was found decreasing significantly since the 21st DAF in the seeds of the line W-4. The decline was up to 60% in comparison with the control Westar. However, no significant difference in the relative expression of fad2 gene in other organs like root, stem and leaf was observed between transgenic line W-4 and non-transgenic control Westar. Fatty acid composition analysis showed the oleic acid desaturation parameter（ODP） in seeds of the line W-4 was 0.07 in average, decreased by nearly 75% than control Westar which was 0.24 in average, while no significant difference in the seedling root, stem and leaf was measured between transgenic rapeseed and control. [Conclusion] The results above validated that RNA interference in transgenic rapeseed W-4 is at a seed-specific manner, not interfering with fad2 gene expression in organs such as the root, stem and leaf. The study also found that the period of fad2 gene expres-sion decline was wel coincided with the expression of napin gene, both appeared at the 21st DAF, indicating that the expression of dsRNA of fad2 gene is precisely control ed by the napin promoter.展开更多
Objective To explore the specificity of acupoint effect and its fundamental laws. Methods We use evidence-based medicine method and data mining technology for ancient and modern acupuncture literature of migraine and ...Objective To explore the specificity of acupoint effect and its fundamental laws. Methods We use evidence-based medicine method and data mining technology for ancient and modern acupuncture literature of migraine and functional dyspepsia to uncover the specificity and its laws. We apply multicenter,randomized controlled trials of acupuncture for migraine to identify the specificity from clini-cal aspects; to explain the biological base of the specificity,we analyze the PET/CT and NMR result on migraine and functional dyspepsia cases treated by acupuncture. Results The viewpoint of specificity of acupoint effect and its two fundamental laws (meridian course specificity and meridian qi convergence specificity)were found both in ancient and modern literature; compared to non-acupoints,the acupoints effect was specific on 180 migraine patients in the randomized controlled trials; the results of PET/CT scan showed that brain response to acupoint needling is more obvious than that of non-acupoint needling; NMR detected the influence on metabolic product of acupoint needling is more apparent than non-acupoint needling. Conclusions Our research confirmed that acupoint effect not only has its specificity but also has two fundamental laws:meridian course specificity and meridian qi convergence specificity,of which the biological base is supported by imaging and metabonomic studies.展开更多
The status quo of study on specificity of meridian acupoints is summarized in this article through retrieval of relative literatures published in the recent 10 years in databases such as CNKI and SCI. The result indic...The status quo of study on specificity of meridian acupoints is summarized in this article through retrieval of relative literatures published in the recent 10 years in databases such as CNKI and SCI. The result indicates that specificity, which is brought into play through the inner biological mechanism, can be found in meridian acupoint efficacy. However, problems still remain since studies at present are still not systematic, comprehensive and scientific. In the future, relative studies should be carried out on extensive diseases and disease models with modern scientific technologies and equipments, strict as well as scientific experimental designation and evaluation methods.展开更多
[Objective] This study aimed to establish molecular identification methods for Bacillus licheniformis. [Method] Based on clone sequencing and difference analysis for 16S and ITS sequences of B. licheniformis TS-01, sp...[Objective] This study aimed to establish molecular identification methods for Bacillus licheniformis. [Method] Based on clone sequencing and difference analysis for 16S and ITS sequences of B. licheniformis TS-01, specific primers were designed using region sequences as the targets used for amplifying all test strains. [Result] The specific primers of B. licheniformis were designed from the ITS and 16S rDNA regions. The optimal annealing temperature of the specific primers for PCR was 67.2 ℃ with 24 cycles. A 905 bp marker fragment was amplified for B. licheniformis TS-01, while all other test strains showed negative results. This indicated that a specific 16S-ITS marker was obtained, which accurately identified the strain at the species level. [Conclusion] This molecular identification method for B. licheniformis TS-01 has laid the foundation for molecular diagnosis of B. licheniformis.展开更多
A simple and rapid new method is presented to determine the CO 2/O 2 specificity factor for ribulose_1,5_bisphosphate(RuBP) carboxylase/oxygenase (Rubisco). In principle, the quantitative formula, which intrinsicall...A simple and rapid new method is presented to determine the CO 2/O 2 specificity factor for ribulose_1,5_bisphosphate(RuBP) carboxylase/oxygenase (Rubisco). In principle, the quantitative formula, which intrinsically resulted in error or enormous error in all reported methods, was improved to circumvent the problem. In practice, the complicated procedure with radiolabelling and chromatographic separation of 3_phosphoglycerate and 2_phosphoglycolate was substituted by one_step procedure without radiolabelling and chromatographic separation to decrease the random error. The effects of pH, temperature and ionic strength on accuracy of the data and the reliability of the calculation of the CO 2/O 2 specificity factor are also discussed.展开更多
Interactions between bacteria and cyanobacteria have been suggested to have a potential to influence harmful algal bloom dynamics; however, little information on these interactions has been reported. In this study, th...Interactions between bacteria and cyanobacteria have been suggested to have a potential to influence harmful algal bloom dynamics; however, little information on these interactions has been reported. In this study, the bacterial communities associated with five strains of Microcystis aeruginosa, three species of other Microcystis spp., and four representative species of non-Microcystis cyanobacteria were compared. Bacterial 16S rDNA fragments were amplified and separated by denaturing gradient gel electrophoresis （DGGE） followed by DNA sequence analysis. The similarities among bacterial communities associated with these cyanobacteria were compared to the digitized DGGE profiles using the cluster analyses. The bacterial community structure of all cyanobacterial cultures differed. Cluster analysis showed that the similarity values among M. aeruginosa cultures were higher than those of other cyanobacterial cultures. Sequence analysis of DGGE fragments indicated the presence of bacteria including, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Bacteroidetes and Actinobacteria in the cyanobacterial cultures. Members of the Sphingomonadales were the prevalent group among the Microcystis-associated bacteria. The results provided further evidence for species-specific associations between cyanoabcteria and heterotrophic bacteria, which are useful for understanding interactions between Microcystis and their associated bacteria.展开更多
The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the th...The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.展开更多
AIM：To study the expression of collagen I and transcription factor specificity protein 1（Sp1）,a transforming growth factor-β1（TGF-β1） downstream target,and reveal the impact of the TGF-β1-Sp1 signaling pathway...AIM：To study the expression of collagen I and transcription factor specificity protein 1（Sp1）,a transforming growth factor-β1（TGF-β1） downstream target,and reveal the impact of the TGF-β1-Sp1 signaling pathway on collagen remodeling in myopic sclera.METHODS：Seventy-five 1-week-old guinea pigs were randomly divided into normal control,form deprivation myopia（FDM）,and self-control groups.FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment;then,changes in refractive power and axial length were measured.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia,and the relationship between collagen I and Sp1 levels was analyzed.RESULTS：In the FDM group,the refractive power was gradually changed（from 2.09±0.30 D at week 0 to-1.23±0.69 D,-4.17±0.59 D,-7.07±0.56 D,and-4.30±0.58 D at weeks 2,4,6,and 1wk after 4wk,respectively;P〈0.05）,indicating deepening of myopia.The axial length was increased（from 5.92±0.39 mm at week 0 to 6.62±0.36 mm,7.30±0.34 mm,7.99±0.32 mm,and 7.41±0.36 mm at weeks 2,4,6,and 1wk after 4wk;P〈0.05）.The m RNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups（P〈0.05）,and the reduction was eye-coverage time-dependent.Furthermore,correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed.CONCLUSION：Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagensynthesis/degradation during myopic sclera remodeling,suggesting that TGF-β1 signaling plays a role in the development and progression of myopia.展开更多
Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at rece...Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral " Xiaguan" (ST 7 on face ) or "Zusanli" (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at "Xiaguan" butnot "Zusanlil", showing the specificity of acupoints. High intensity EA at either "Xiaguan" or "Zusan-li" also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that "the gate of control" mechanism plays a main role in low intensity EA and "diffuse noxiousinhibitory controls" (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints,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supported by the Ministry of Science and Technology (project No.2007AA02Z417)
文摘Objective Both the 2, 6 linkage and its topology on target cells are critical for the recognition by human influenza virus. The binding preference of avian flu virus H5N1 HA to the 2, 3-1inked sialylated glycans is considered the major factor limiting its efficient infection and transmission in humans. To monitor potential adaptation of H5N1 virus in human population, the surveillance of receptor-binding specificity was undertaken in China. Methods The binding specificity of 32 human H5N1 virus strains isolated from 2003 to 2009 was tested by 2, 3-specific sialidase-treated chicken red blood cell （CRBC） agglutination assay and a solid-phase direct binding assay with synthetic sialylglycopolymers. Results Dual binding preference to 2, 3 and 2, 6-glycans were found in two strains： A/Guangdong/1/06 （A/GD/1/06） and A/Guangxi/1/08 （A/GX/1/08）. Though minor effect of short-2, 6-binding was detected in A/GX/1/08 at a low virus titer, both showed high affinity to the oligosaccharide at a high load. Notably both are of the long-2, 6-recognition, with the same topology as that of human H1N1 and H3N2 viruses. Conclusion The findings suggest that human H5N1 virus in China likely acquired the potential human-adaptation ability. Further research and surveillance on receptor-binding specificity of H5N1 viruses are required.
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.
基金funded by Sichuan Science and Technology Program,grant numbers 2021YFYZ0010,2023YFH0006,2025YFHZ0295The Basic Research Program of Sichuan Provincial Research Institutes,grant numbers 2024JDKY0001 and 2023JDKY0001.
文摘The genus Actinidia is primarily functionally dioecious,and early sex identification plays a crucial role in improving breeding efficiency and reducing production costs.In this study,the accuracy of three sex-linked molecular markers(SyGI[Shy Girl],FrBy[Friendly Boy],and SmY1)in sex identification was evaluated in various Actinidia species.The selected marker products were subsequently cloned and sequenced in six wild Actinidia species.Ninety-six wild A.chinensis chinensis accessions and 74 A.chinensis deliciosa accessions,most of which were wild,with only one cultivated,were used for comprehensive primer validation.Thirty-three juvenile A.chinensis chinensis hybrid seedlings were used for practical application tests.The results showed that the marker SyGI accurately identified the sex of 20 samples from six Actinidia species and 96 A.chinensis chinensis accessions with 100%reliability.For Actinidia chinensis deliciosa,the identification accuracy reached 98.65%.Sequence analysis revealed that SyGI shared the highest similarity with the male-specific genomic region.Furthermore,SyGI achieved 100%accuracy in identifying the sex of 33 juvenile A.chinensis chinensis individuals.The findings confirm that the SyGI marker possesses high accuracy,strong specificity,and broad applicability,making it a valuable tool for kiwifruit breeding programs.The cloned sequences from wild Actinidia species also provide important references for future research on the mechanisms of sexual evolution and determination.
基金supported by the Open Foundation of Key Laboratory of Cyberspace Security,Ministry of Education of China(KLCS20240211)。
文摘With the rapid development of Internet technology,REST APIs(Representational State Transfer Application Programming Interfaces)have become the primary communication standard in modern microservice architectures,raising increasing concerns about their security.Existing fuzz testing methods include random or dictionary-based input generation,which often fail to ensure both syntactic and semantic correctness,and OpenAPIbased approaches,which offer better accuracy but typically lack detailed descriptions of endpoints,parameters,or data formats.To address these issues,this paper proposes the APIDocX fuzz testing framework.It introduces a crawler tailored for dynamic web pages that automatically simulates user interactions to trigger APIs,capturing and extracting parameter information from communication packets.A multi-endpoint parameter adaptation method based on improved Jaccard similarity is then used to generalize these parameters to other potential API endpoints,filling in gaps in OpenAPI specifications.Experimental results demonstrate that the extracted parameters can be generalized with 79.61%accuracy.Fuzz testing using the enriched OpenAPI documents leads to improvements in test coverage,the number of valid test cases generated,and fault detection capabilities.This approach offers an effective enhancement to automated REST API security testing.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by Central Public-interest Scientific Institution Basal Research Fund(CATAS-Nos.1630152023007,1630152023011,1630152023012,1630152023013)the National Natural Science Foundation of China(Grant No.32071805).
文摘Coconut(Cocos nucifera L.),a major oil and fruit crop of the Arecaceae family,is extensively cultivated across the Asia—Pacific region.Despite its agricultural importance,genome assembly in coconut remains challenging due to its large genome size and high proportion of repetitive sequences.Allele-specific expression(ASE)plays a key role in regulating plant development and evolution,yet research on ASE in coconut is limited(Shao et al.,2019;Li et al.,2021;Zhang et al.,2021;Hu et al.,2022).Among phenotypic traits,fruit color is especially important as an indicator of maturity,guiding harvest timing and post-harvest processes(Kapoor et al.,2022).While prior studies have explored various coconut traits such as salt tolerance,fiber content,and plant height(Wang et al.,2021;Yang et al.,2021),investigations into ASE and fruit color remain scarce.
基金Supported by Fund for National Rapeseed Research System(CARS-13)~~
文摘This study was to investigate the efficiency and specificity of RNAi silencing on the expression of endogenous fad2 gene in transgenic line W-4. [Method] The relative expression of fad2 gene in seeds at different developmental stages of 7th, 14th, 21st and 28th day after flowering （DAF） as wel as the root, stem, leaf at winter seedling stages of both the transgenic line W-4 and non-transgenic control Westar by real-time fluorescence quantitative PCR. [Results] The results showed the relative expression of fad2 gene was gradual y increasing with the days after flowering in the seeds of the control Westar, while it was found decreasing significantly since the 21st DAF in the seeds of the line W-4. The decline was up to 60% in comparison with the control Westar. However, no significant difference in the relative expression of fad2 gene in other organs like root, stem and leaf was observed between transgenic line W-4 and non-transgenic control Westar. Fatty acid composition analysis showed the oleic acid desaturation parameter（ODP） in seeds of the line W-4 was 0.07 in average, decreased by nearly 75% than control Westar which was 0.24 in average, while no significant difference in the seedling root, stem and leaf was measured between transgenic rapeseed and control. [Conclusion] The results above validated that RNA interference in transgenic rapeseed W-4 is at a seed-specific manner, not interfering with fad2 gene expression in organs such as the root, stem and leaf. The study also found that the period of fad2 gene expres-sion decline was wel coincided with the expression of napin gene, both appeared at the 21st DAF, indicating that the expression of dsRNA of fad2 gene is precisely control ed by the napin promoter.
文摘Objective To explore the specificity of acupoint effect and its fundamental laws. Methods We use evidence-based medicine method and data mining technology for ancient and modern acupuncture literature of migraine and functional dyspepsia to uncover the specificity and its laws. We apply multicenter,randomized controlled trials of acupuncture for migraine to identify the specificity from clini-cal aspects; to explain the biological base of the specificity,we analyze the PET/CT and NMR result on migraine and functional dyspepsia cases treated by acupuncture. Results The viewpoint of specificity of acupoint effect and its two fundamental laws (meridian course specificity and meridian qi convergence specificity)were found both in ancient and modern literature; compared to non-acupoints,the acupoints effect was specific on 180 migraine patients in the randomized controlled trials; the results of PET/CT scan showed that brain response to acupoint needling is more obvious than that of non-acupoint needling; NMR detected the influence on metabolic product of acupoint needling is more apparent than non-acupoint needling. Conclusions Our research confirmed that acupoint effect not only has its specificity but also has two fundamental laws:meridian course specificity and meridian qi convergence specificity,of which the biological base is supported by imaging and metabonomic studies.
基金Supported by National Program on Key Basic Research Project (973 Program): 2010 CB 530506
文摘The status quo of study on specificity of meridian acupoints is summarized in this article through retrieval of relative literatures published in the recent 10 years in databases such as CNKI and SCI. The result indicates that specificity, which is brought into play through the inner biological mechanism, can be found in meridian acupoint efficacy. However, problems still remain since studies at present are still not systematic, comprehensive and scientific. In the future, relative studies should be carried out on extensive diseases and disease models with modern scientific technologies and equipments, strict as well as scientific experimental designation and evaluation methods.
文摘[Objective] This study aimed to establish molecular identification methods for Bacillus licheniformis. [Method] Based on clone sequencing and difference analysis for 16S and ITS sequences of B. licheniformis TS-01, specific primers were designed using region sequences as the targets used for amplifying all test strains. [Result] The specific primers of B. licheniformis were designed from the ITS and 16S rDNA regions. The optimal annealing temperature of the specific primers for PCR was 67.2 ℃ with 24 cycles. A 905 bp marker fragment was amplified for B. licheniformis TS-01, while all other test strains showed negative results. This indicated that a specific 16S-ITS marker was obtained, which accurately identified the strain at the species level. [Conclusion] This molecular identification method for B. licheniformis TS-01 has laid the foundation for molecular diagnosis of B. licheniformis.
文摘A simple and rapid new method is presented to determine the CO 2/O 2 specificity factor for ribulose_1,5_bisphosphate(RuBP) carboxylase/oxygenase (Rubisco). In principle, the quantitative formula, which intrinsically resulted in error or enormous error in all reported methods, was improved to circumvent the problem. In practice, the complicated procedure with radiolabelling and chromatographic separation of 3_phosphoglycerate and 2_phosphoglycolate was substituted by one_step procedure without radiolabelling and chromatographic separation to decrease the random error. The effects of pH, temperature and ionic strength on accuracy of the data and the reliability of the calculation of the CO 2/O 2 specificity factor are also discussed.
基金supported by the National Basic Research Program (973) of China (No. 2008CB418004)the Natural Science Foundation of Jiangsu Province (No.BK2007150)the China Postdoctoral Science Foundation (No. 20070410345)
文摘Interactions between bacteria and cyanobacteria have been suggested to have a potential to influence harmful algal bloom dynamics; however, little information on these interactions has been reported. In this study, the bacterial communities associated with five strains of Microcystis aeruginosa, three species of other Microcystis spp., and four representative species of non-Microcystis cyanobacteria were compared. Bacterial 16S rDNA fragments were amplified and separated by denaturing gradient gel electrophoresis （DGGE） followed by DNA sequence analysis. The similarities among bacterial communities associated with these cyanobacteria were compared to the digitized DGGE profiles using the cluster analyses. The bacterial community structure of all cyanobacterial cultures differed. Cluster analysis showed that the similarity values among M. aeruginosa cultures were higher than those of other cyanobacterial cultures. Sequence analysis of DGGE fragments indicated the presence of bacteria including, Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Bacteroidetes and Actinobacteria in the cyanobacterial cultures. Members of the Sphingomonadales were the prevalent group among the Microcystis-associated bacteria. The results provided further evidence for species-specific associations between cyanoabcteria and heterotrophic bacteria, which are useful for understanding interactions between Microcystis and their associated bacteria.
基金supported by the National Natural Science Foundation of China (Grant No.81622035, 81672610, and 81521002)
文摘The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents.These damages could potentially lead to genomic instability and thus to tumorigenesis.To cope with the threats, cells have evolved an intricate network, namely DNA damage response(DDR) system that senses and deals with the lesions of DNA.Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues.In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis.We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.
基金Supported by the Natural Science Foundation of Anhui Province(No.1508085MH188)Science Foundation of Anhui Provincial Health Bureau(No.13zc040No.13zc046)
文摘AIM：To study the expression of collagen I and transcription factor specificity protein 1（Sp1）,a transforming growth factor-β1（TGF-β1） downstream target,and reveal the impact of the TGF-β1-Sp1 signaling pathway on collagen remodeling in myopic sclera.METHODS：Seventy-five 1-week-old guinea pigs were randomly divided into normal control,form deprivation myopia（FDM）,and self-control groups.FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment;then,changes in refractive power and axial length were measured.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia,and the relationship between collagen I and Sp1 levels was analyzed.RESULTS：In the FDM group,the refractive power was gradually changed（from 2.09±0.30 D at week 0 to-1.23±0.69 D,-4.17±0.59 D,-7.07±0.56 D,and-4.30±0.58 D at weeks 2,4,6,and 1wk after 4wk,respectively;P〈0.05）,indicating deepening of myopia.The axial length was increased（from 5.92±0.39 mm at week 0 to 6.62±0.36 mm,7.30±0.34 mm,7.99±0.32 mm,and 7.41±0.36 mm at weeks 2,4,6,and 1wk after 4wk;P〈0.05）.The m RNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups（P〈0.05）,and the reduction was eye-coverage time-dependent.Furthermore,correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed.CONCLUSION：Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagensynthesis/degradation during myopic sclera remodeling,suggesting that TGF-β1 signaling plays a role in the development and progression of myopia.
文摘Experiments were carried out on rats anaesthetized with uraethane. The sponta-neous discharges and nociceptive responses of convergent neurons in the right trigerninal nucleus cau-dalis(TNC) to noxious stimuli at receptive field (cheek) were recorded extracellularly with glass mi-cro-electrode. Electroacupuncture (EA ) was applied at bilateral " Xiaguan" (ST 7 on face ) or "Zusanli" (ST 36 on shank) acupoint with Iow (2V) and high (18V) intensity. The noclceptive re-sponse of convergent neurons in TNC could be inhihited by low intensity EA applied at "Xiaguan" butnot "Zusanlil", showing the specificity of acupoints. High intensity EA at either "Xiaguan" or "Zusan-li" also reduced the nociceptive responses, showing the analgesic extensiveness of acupoints. We sug-gest that "the gate of control" mechanism plays a main role in low intensity EA and "diffuse noxiousinhibitory controls" (DNIC) rnechanism does so in high intensity EA.The results suggest that we should pay attention to the location of acupoints,
