Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of ...Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.展开更多
Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as bioch...Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.展开更多
Hematite(α-Fe_(2)O_(3))constitutes one of the most promising photoanode materials for oxygen evolution reaction(OER).Recent research on Fe_(2)O_(3) have found a fast OER rate dependence on surface hole density,sugges...Hematite(α-Fe_(2)O_(3))constitutes one of the most promising photoanode materials for oxygen evolution reaction(OER).Recent research on Fe_(2)O_(3) have found a fast OER rate dependence on surface hole density,suggesting a multisite reaction pathway.However,the effect of heteroatom in Fe_(2)O_(3) on the multisite mechanism is still poorly understood.Herein we synthesized Fe_(2)O_(3) on Ti substrates(Fe_(2)O_(3)/Ti)to study the oxygen intermediates of OER by light-dark electrochemical scans.We identified the Fe-OH species disappeared and Ti-OH intermediates appeared on Fe_(2)O_(3)/Ti when pH=11‒14,which significantly improved the OER performance of Fe_(2)O_(3)/Ti.Combined with the density functional theory calculations,we propose that Ti atom acts as cocatalyst site and captures proton from neighboring Fe-OH species under highly alkaline condition,thereby promoting the coupling of Fe=O and reducing the energy barrier of the non-electrochemical step.Our work provides a new insight into the role of heteroatom in OER multisite mechanism based on clarifying the reaction intermediates.展开更多
Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, ...Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, more and more EDCs were released into the environment. EDCs go into water body via atmosphere sedi-mentation, surface runoff, soil eluviation, etc., so water body becomes the main place for existing. In order to attract scientific and public attention worldwide and to prevent EDCs pol ution, in this study we reviewed the classification of EDCs and their concentrations in natural water bodies, drinking water sources and water plants, and the reproductive toxicity of EDCs to fish were reviewed. EDCs could disturb the endocrine system and make reproductive organs and reproduction abnor-mal, resulting in fertility descending, reproduction function damage, community quan-tity decrease and even species extinction. In addition, EDCs could disrupt the homeostasis maintained by hormones, which would result in defects of neural de-velopment and abnormalities of the endocrine and reproductive systems. The exact molecular mechanisms have not been completely reported, but researches have suggested that multiple mechanisms were involved in the action of EDCs. Although there have been researches on the biohazard of EDCs, there stil exist problems of weakness in fundamental researches, difficulties in recognizing and identifying EDCs and high cost, which restraint the knowledge on them.展开更多
Objective: To investigate the role of collagen IV and PAS positive substancesecreted by tumor cells in vasculogenic mimicry (VM) and the effects of VM on tumor cells expressingVEGF. Methods: 158 cases of bi-direction ...Objective: To investigate the role of collagen IV and PAS positive substancesecreted by tumor cells in vasculogenic mimicry (VM) and the effects of VM on tumor cells expressingVEGF. Methods: 158 cases of bi-direction differential malignant tumor specimens withparaffin-embedded were enrolled into our study and made tissue microarray which were dual-stainedwith CD31-PAS and stained with collagen IV. The difference of the areas and distribution withpattern surrounded by between CD31 and PAS positive respectively were identified via grid-counting,as well as the difference of VEGF expression with VE absent and present. Results: The basementmembrane of VM was both PAS and collagen IV positive. VEGF expression in the bi-directiondifferential malignant tumor was higher VM-absent than VM-present and the difference wasstatistically significance in malignant melanoma and alveolar rhabdomyosarcoma (P 【 0.05).Conclusion: PAS positive substance and collagen IV compose the wall of VE and VE could provide theoxygen and nutrition for tumor growth and progression.展开更多
Planarian is among the simplest animals that possess a centralized nervous system （CNS）, and its neural regenera- tion involves the replacement of cells lost to normal ＇wear and tear＇ （cell turnover）, and/or inj...Planarian is among the simplest animals that possess a centralized nervous system （CNS）, and its neural regenera- tion involves the replacement of cells lost to normal ＇wear and tear＇ （cell turnover）, and/or injury. In this review, we state and discuss the recent studies on molecular control of neural regeneration in planarians. The spatial and temporal expression patterns of genes in intact and regenerating planarian CNS have already been described relatively clearly. The bone morphogenetic protein （BMP） and Wnt signaling pathways are identified to regulate neural regeneration. During neural regeneration, conserved axon guidance mechanisms are necessary for proper wiring of the nervous system. In addition, apoptosis may play an important role in controlling cell numbers, eliminating unnecessary tissues or cells and remodeling the old tissues for regenerating CNS. The bilateral symmetry is established by determination of anterior-posterior （A-P） and dorsal-ventral （D-V） patterns. Moreover, neurons positive to dopamine, serotonin （5-HT）, and gamma-aminobutyric acid （GABA） have been detected in planarians. Therefore, planarians present us with new, experimentally accessible contexts to study the molecular actions guiding neural regeneration.展开更多
基金National Natural Science Foundation of China(81960877).
文摘Objective To explore the differential expression and mechanisms of bone formation-related genes in osteoporosis(OP)leveraging bioinformatics and machine learning methodologies;and to predict the active ingredients of targeted traditional Chinese medicine(TCM)herbs.Methods The Gene Expression Omnibus(GEO)and GeneCards databases were employed to conduct a comprehensive screening of genes and disease-associated loci pertinent to the pathogenesis of OP.The R package was utilized as the analytical tool for the identification of differentially expressed genes.Least absolute shrinkage and selection operator(LASSO)logis-tic regression analysis and support vector machine-recursive feature elimination(SVM-RFE)algorithm were employed in defining the genetic signature specific to OP.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses for the selected pivotal genes were conducted.The cell-type identification by estimating rela-tive subsets of RNA transcripts(CIBERSORT)algorithm was leveraged to examine the infiltra-tion patterns of immune cells;with Spearman’s rank correlation analysis utilized to assess the relationship between the expression levels of the genes and the presence of immune cells.Coremine Medical Database was used to screen out potential TCM herbs for the treatment of OP.Comparative Toxicogenomics Database(CTD)was employed for forecasting the TCM ac-tive ingredients targeting the key genes.AutoDock Vina 1.2.2 and GROMACS 2020 softwares were employed to conclude analysis results;facilitating the exploration of binding affinity and conformational dynamics between the TCM active ingredients and their biological targets.Results Ten genes were identified by intersecting the results from the GEO and GeneCards databases.Through the application of LASSO regression and SVM-RFE algorithm;four piv-otal genes were selected:coat protein(CP);kallikrein 3(KLK3);polymeraseγ(POLG);and transient receptor potential vanilloid 4(TRPV4).GO and KEGG pathway enrichment analy-ses revealed that these trait genes were predominantly engaged in the regulation of defense response activation;maintenance of cellular metal ion balance;and the production of chemokine ligand 5.These genes were notably associated with signaling pathways such as ferroptosis;porphyrin metabolism;and base excision repair.Immune infiltration analysis showed that key genes were highly correlated with immune cells.Macrophage M0;M1;M2;and resting dendritic cell were significantly different between groups;and there were signifi-cant differences between different groups(P<0.05).The interaction counts of resveratrol;curcumin;and quercetin with KLK3 were 7;3;and 2;respectively.It shows that the interac-tions of resveratrol;curcumin;and quercetin with KLK3 were substantial.Molecular docking and molecular dynamics simulations further confirmed the robust binding affinity of these bioactive compounds to the target genes.Conclusion Pivotal genes including CP;KLK3;POLG;and TRPV4;exhibited commendable significant prognostic value;and played a crucial role in the diagnostic assessment of OP.Resveratrol;curcumin;and quercetin;natural compounds found in TCM;showed promise in their potential to effectively modulate the bone-forming gene KLK3.This study provides a sci-entific basis for the interpretation of the pathogenesis of OP and the development of clinical drugs.
文摘Aptamers are a type of single-chain oligonucleotide that can combine with a specific target.Due to their simple preparation,easy modification,stable structure and reusability,aptamers have been widely applied as biochemical sensors for medicine,food safety and environmental monitoring.However,there is little research on aptamer-target binding mechanisms,which limits their application and development.Computational simulation has gained much attention for revealing aptamer-target binding mechanisms at the atomic level.This work summarizes the main simulation methods used in the mechanistic analysis of aptamer-target complexes,the characteristics of binding between aptamers and different targets(metal ions,small organic molecules,biomacromolecules,cells,bacteria and viruses),the types of aptamer-target interactions and the factors influencing their strength.It provides a reference for further use of simulations in understanding aptamer-target binding mechanisms.
文摘Hematite(α-Fe_(2)O_(3))constitutes one of the most promising photoanode materials for oxygen evolution reaction(OER).Recent research on Fe_(2)O_(3) have found a fast OER rate dependence on surface hole density,suggesting a multisite reaction pathway.However,the effect of heteroatom in Fe_(2)O_(3) on the multisite mechanism is still poorly understood.Herein we synthesized Fe_(2)O_(3) on Ti substrates(Fe_(2)O_(3)/Ti)to study the oxygen intermediates of OER by light-dark electrochemical scans.We identified the Fe-OH species disappeared and Ti-OH intermediates appeared on Fe_(2)O_(3)/Ti when pH=11‒14,which significantly improved the OER performance of Fe_(2)O_(3)/Ti.Combined with the density functional theory calculations,we propose that Ti atom acts as cocatalyst site and captures proton from neighboring Fe-OH species under highly alkaline condition,thereby promoting the coupling of Fe=O and reducing the energy barrier of the non-electrochemical step.Our work provides a new insight into the role of heteroatom in OER multisite mechanism based on clarifying the reaction intermediates.
基金Supported by the China Agriculture Research System(CARS49)~~
文摘Environmental endocrine disrupting chemicals （EDCs）, commonly found in the environment, come from industry and agriculture, including pesticides, fungicides, insecticides, herbicides, and other chemicals. Nowadays, more and more EDCs were released into the environment. EDCs go into water body via atmosphere sedi-mentation, surface runoff, soil eluviation, etc., so water body becomes the main place for existing. In order to attract scientific and public attention worldwide and to prevent EDCs pol ution, in this study we reviewed the classification of EDCs and their concentrations in natural water bodies, drinking water sources and water plants, and the reproductive toxicity of EDCs to fish were reviewed. EDCs could disturb the endocrine system and make reproductive organs and reproduction abnor-mal, resulting in fertility descending, reproduction function damage, community quan-tity decrease and even species extinction. In addition, EDCs could disrupt the homeostasis maintained by hormones, which would result in defects of neural de-velopment and abnormalities of the endocrine and reproductive systems. The exact molecular mechanisms have not been completely reported, but researches have suggested that multiple mechanisms were involved in the action of EDCs. Although there have been researches on the biohazard of EDCs, there stil exist problems of weakness in fundamental researches, difficulties in recognizing and identifying EDCs and high cost, which restraint the knowledge on them.
基金This work was partially supported by a grant from the National Natural Science Foundation of China (No. 30370378)
文摘Objective: To investigate the role of collagen IV and PAS positive substancesecreted by tumor cells in vasculogenic mimicry (VM) and the effects of VM on tumor cells expressingVEGF. Methods: 158 cases of bi-direction differential malignant tumor specimens withparaffin-embedded were enrolled into our study and made tissue microarray which were dual-stainedwith CD31-PAS and stained with collagen IV. The difference of the areas and distribution withpattern surrounded by between CD31 and PAS positive respectively were identified via grid-counting,as well as the difference of VEGF expression with VE absent and present. Results: The basementmembrane of VM was both PAS and collagen IV positive. VEGF expression in the bi-directiondifferential malignant tumor was higher VM-absent than VM-present and the difference wasstatistically significance in malignant melanoma and alveolar rhabdomyosarcoma (P 【 0.05).Conclusion: PAS positive substance and collagen IV compose the wall of VE and VE could provide theoxygen and nutrition for tumor growth and progression.
基金the Southeast University Foundation for Excellent Young Scholars (No. 4023001013)the Program for New Century Excellent Talents in University.
文摘Planarian is among the simplest animals that possess a centralized nervous system （CNS）, and its neural regenera- tion involves the replacement of cells lost to normal ＇wear and tear＇ （cell turnover）, and/or injury. In this review, we state and discuss the recent studies on molecular control of neural regeneration in planarians. The spatial and temporal expression patterns of genes in intact and regenerating planarian CNS have already been described relatively clearly. The bone morphogenetic protein （BMP） and Wnt signaling pathways are identified to regulate neural regeneration. During neural regeneration, conserved axon guidance mechanisms are necessary for proper wiring of the nervous system. In addition, apoptosis may play an important role in controlling cell numbers, eliminating unnecessary tissues or cells and remodeling the old tissues for regenerating CNS. The bilateral symmetry is established by determination of anterior-posterior （A-P） and dorsal-ventral （D-V） patterns. Moreover, neurons positive to dopamine, serotonin （5-HT）, and gamma-aminobutyric acid （GABA） have been detected in planarians. Therefore, planarians present us with new, experimentally accessible contexts to study the molecular actions guiding neural regeneration.
