Dopaminergic neurons in the ventral tegmental area(VTA)play an important role in cognition,emergence from anesthesia,reward,and aversion,and their projection to the cortex is a crucial part of the"bottom-up"...Dopaminergic neurons in the ventral tegmental area(VTA)play an important role in cognition,emergence from anesthesia,reward,and aversion,and their projection to the cortex is a crucial part of the"bottom-up"ascending activating system.The prelimbic cortex(PrL)is one of the important projection regions of the VTA.However,the roles of dopaminergic neurons in the VTA and the VTADA–PrL pathway under sevoflurane anesthesia in rats remain unclear.In this study,we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist(Chloro-APB)into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats,while injection of a dopamine D1 receptor antagonist(SCH23390)deepened anesthesia.The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA–PrL pathway prolonged the induction time and shortened the emergence time of anesthesia.These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA–PrL pathway facilitates emergence from sevoflurane anesthesia.展开更多
Acute myocardial infarction(AMI)is associated with a challenging prognosis.Notably,the Tongxinluo capsule(TXL),a proprietary Chinese medicine,has garnered attention for its potential therapeutic effects.This study aim...Acute myocardial infarction(AMI)is associated with a challenging prognosis.Notably,the Tongxinluo capsule(TXL),a proprietary Chinese medicine,has garnered attention for its potential therapeutic effects.This study aimed to elucidate the concealed pharmacological benefits of TXL in AMI patients and identify pertinent immunological targets.In the GSE66360 dataset,172 upregulated genes and 16 downregulated genes were discerned.Subsequently,803 key targets of TXL were meticulously sifted through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Herbal Ingredients’Targets(HERB)databases.The intersection of these datasets was determined using Venn diagrams.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses unveiled that these genes were predominantly associated with the NF-kappa B signaling pathway,TNF signaling pathway,IL-17 signaling pathway,and other signaling cascades.The extent of immune infiltration between AMI and control samples was assessed using Cibersort,and Spearman’s rank correlation was employed to explore the relationship between immune cells and the amalgamated genes.This investigation revealed that the amelioration of AMI with TXL might be linked to an augmentation in mast cell-activated cells and neutrophil invasion.The Weighted Gene Co-expression Network Analysis(WGCNA)identified gene modules strongly correlated with 22 immune cells.These modules were further scrutinized using the Cibersort algorithm,leading to the recognition of eight genes deemed pivotal as potential novel molecular markers for TXL treatment of AMI.The infiltration of defense cells was also found to exert a significant impact.This study contributed to our understanding of the pharmacological mechanisms of TXL and provided valuable insights for future investigations into potential targets for AMI immunotherapy.展开更多
Comprehensive Summary Polyether materials,derived from the ring-opening polymerization(ROP)of epoxides,are widely used in biomedicine and functional materials.However,due to the steric hindrance of the high-freedom su...Comprehensive Summary Polyether materials,derived from the ring-opening polymerization(ROP)of epoxides,are widely used in biomedicine and functional materials.However,due to the steric hindrance of the high-freedom substituents,monosubstituted epoxides are difficult to activate and exhibit the characteristics of being difficult to polymerize.In addition,traditional anionic ring-opening polymerization(AROP)usually has functional group tolerance problems.展开更多
Currently,factor Ⅸ replacement is the mainstay treatment for hemophilia B in clinical practice.However,since the disease cannot be cured,lifelong treatment and frequent infusion is required.In recent years,hemophilia...Currently,factor Ⅸ replacement is the mainstay treatment for hemophilia B in clinical practice.However,since the disease cannot be cured,lifelong treatment and frequent infusion is required.In recent years,hemophilia B gene therapy has achieved significant advancements,with 3 adeno-associated virus(AAV)vector-based gene therapy products receiving market authorization.Among these,BBM-H901(Dalnacogene Ponparvovec Injection)has just been approved in China.AAV vector-based gene therapy is characterized by irreversible treatment effects and potential long-term efficacy.However,cases of suboptimal efficacy have been observed in early clinical trials.Eligibility for AAV vector gene therapy primarily depends on factors including patient diagnosis subtype,age,inhibitor status,AAV capsid antibody titer,and patient/family preferences.Given that AAV vector-based gene therapy for hemophilia has become an accessible frontier treatment,Thrombosis and Hemostasis Group and Hemophilia Treatment Center Collaborative Network of China jointly formulated this guidance.It aims to standardize operational procedures and follow-up recommendations to ensure patients receive standardized management when adopting this novel therapeutic approach.展开更多
Comprehensive Summary Four heterometallic rare earth(Ⅲ)-cobalt(Ⅱ)complexes(rare earth=Y(1),Sm(2),Nd(3),La(4))stabilized by an o-phenylenediamine-bridged tris(phenolato)ligand(L)have been synthesized and characterize...Comprehensive Summary Four heterometallic rare earth(Ⅲ)-cobalt(Ⅱ)complexes(rare earth=Y(1),Sm(2),Nd(3),La(4))stabilized by an o-phenylenediamine-bridged tris(phenolato)ligand(L)have been synthesized and characterized.In these tetranuclear complexes,one polydentate L coordinates to one rare earth(Ⅲ)ion,and one cobalt(Ⅱ)ion,respectively,while two rare earth ions are bridged by four acetate groups.These complexes were applied in the copolymerization of cyclohexene oxide and CO_(2),which showed good activity(TON up to 440)and high poly(cyclohexene carbonate)selectivity(>99%).Kinetic studies determined the equation as rate=k[CHO]1[CO_(2)]0[initiator]1,which proves a first-order dependence on initiator concentrations and implies a synergistic mechanism with rare earth and cobalt ions cooperating in epoxide ring-opening and chain propagation.展开更多
The publisher regrets the omission of the below footnote for the author Dr.Nu Zhang.The publisher would like to apologise for any inconvenience caused.
Physical signals provided by the extracellular matrix(ECM)are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells(HSPC)in bone marrow.Insights into cell-ECM interactions ...Physical signals provided by the extracellular matrix(ECM)are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells(HSPC)in bone marrow.Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering.Herein,we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells(HPCs).Three-dimensional(3D)collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors.Using single-cell RNA sequencing(scRNA-seq),we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional(2D)and 3D hydrogels.A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results.3D-derived macrophages expressed high levels of various cytokines and chemokines,such as Saa3,Cxcl2,Socs3 and Tnf.Furthermore,enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses.Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.展开更多
基金supported by the National Natural Science Foundation of China(81801366 and 82001453)and the National Key R&D Program of China(2018YFC2001901).
文摘Dopaminergic neurons in the ventral tegmental area(VTA)play an important role in cognition,emergence from anesthesia,reward,and aversion,and their projection to the cortex is a crucial part of the"bottom-up"ascending activating system.The prelimbic cortex(PrL)is one of the important projection regions of the VTA.However,the roles of dopaminergic neurons in the VTA and the VTADA–PrL pathway under sevoflurane anesthesia in rats remain unclear.In this study,we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist(Chloro-APB)into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats,while injection of a dopamine D1 receptor antagonist(SCH23390)deepened anesthesia.The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA–PrL pathway prolonged the induction time and shortened the emergence time of anesthesia.These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA–PrL pathway facilitates emergence from sevoflurane anesthesia.
文摘Acute myocardial infarction(AMI)is associated with a challenging prognosis.Notably,the Tongxinluo capsule(TXL),a proprietary Chinese medicine,has garnered attention for its potential therapeutic effects.This study aimed to elucidate the concealed pharmacological benefits of TXL in AMI patients and identify pertinent immunological targets.In the GSE66360 dataset,172 upregulated genes and 16 downregulated genes were discerned.Subsequently,803 key targets of TXL were meticulously sifted through the Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Herbal Ingredients’Targets(HERB)databases.The intersection of these datasets was determined using Venn diagrams.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses unveiled that these genes were predominantly associated with the NF-kappa B signaling pathway,TNF signaling pathway,IL-17 signaling pathway,and other signaling cascades.The extent of immune infiltration between AMI and control samples was assessed using Cibersort,and Spearman’s rank correlation was employed to explore the relationship between immune cells and the amalgamated genes.This investigation revealed that the amelioration of AMI with TXL might be linked to an augmentation in mast cell-activated cells and neutrophil invasion.The Weighted Gene Co-expression Network Analysis(WGCNA)identified gene modules strongly correlated with 22 immune cells.These modules were further scrutinized using the Cibersort algorithm,leading to the recognition of eight genes deemed pivotal as potential novel molecular markers for TXL treatment of AMI.The infiltration of defense cells was also found to exert a significant impact.This study contributed to our understanding of the pharmacological mechanisms of TXL and provided valuable insights for future investigations into potential targets for AMI immunotherapy.
基金support from the National Natural Science Foundation of China(22271205)PAPD is gratefully acknowledged.
文摘Comprehensive Summary Polyether materials,derived from the ring-opening polymerization(ROP)of epoxides,are widely used in biomedicine and functional materials.However,due to the steric hindrance of the high-freedom substituents,monosubstituted epoxides are difficult to activate and exhibit the characteristics of being difficult to polymerize.In addition,traditional anionic ring-opening polymerization(AROP)usually has functional group tolerance problems.
基金supported by grants from the National Natural Science Foundation of China(82430010 ZL,82470138 XF)National Key Research and Development Program of China(2023YFC2507802 XF)CAMS Innovation Fund for Medical Sciences(CIFMS)(2024-I2M-ZH-016 ZL).
文摘Currently,factor Ⅸ replacement is the mainstay treatment for hemophilia B in clinical practice.However,since the disease cannot be cured,lifelong treatment and frequent infusion is required.In recent years,hemophilia B gene therapy has achieved significant advancements,with 3 adeno-associated virus(AAV)vector-based gene therapy products receiving market authorization.Among these,BBM-H901(Dalnacogene Ponparvovec Injection)has just been approved in China.AAV vector-based gene therapy is characterized by irreversible treatment effects and potential long-term efficacy.However,cases of suboptimal efficacy have been observed in early clinical trials.Eligibility for AAV vector gene therapy primarily depends on factors including patient diagnosis subtype,age,inhibitor status,AAV capsid antibody titer,and patient/family preferences.Given that AAV vector-based gene therapy for hemophilia has become an accessible frontier treatment,Thrombosis and Hemostasis Group and Hemophilia Treatment Center Collaborative Network of China jointly formulated this guidance.It aims to standardize operational procedures and follow-up recommendations to ensure patients receive standardized management when adopting this novel therapeutic approach.
基金financial support from the National Natural Science Foundation of China(21871198)the Major Research Project of the Natural Science of the Jiangsu Higher Education Institutions(19KJA360005 and 19KJA320007),and PAPD.
文摘Comprehensive Summary Four heterometallic rare earth(Ⅲ)-cobalt(Ⅱ)complexes(rare earth=Y(1),Sm(2),Nd(3),La(4))stabilized by an o-phenylenediamine-bridged tris(phenolato)ligand(L)have been synthesized and characterized.In these tetranuclear complexes,one polydentate L coordinates to one rare earth(Ⅲ)ion,and one cobalt(Ⅱ)ion,respectively,while two rare earth ions are bridged by four acetate groups.These complexes were applied in the copolymerization of cyclohexene oxide and CO_(2),which showed good activity(TON up to 440)and high poly(cyclohexene carbonate)selectivity(>99%).Kinetic studies determined the equation as rate=k[CHO]1[CO_(2)]0[initiator]1,which proves a first-order dependence on initiator concentrations and implies a synergistic mechanism with rare earth and cobalt ions cooperating in epoxide ring-opening and chain propagation.
文摘The publisher regrets the omission of the below footnote for the author Dr.Nu Zhang.The publisher would like to apologise for any inconvenience caused.
基金supported by grants from National Natural Science Foundation of China(Nos.12002285,11672227,61927810)Natural Science Basic Research Plan in Shaanxi Province of China(Nos.2018JQ1033,2020JZ-11)Innovation Foundation for Doctor Dissertation of Northwestern Polytechnical University(No.CX202058).
文摘Physical signals provided by the extracellular matrix(ECM)are key microenvironmental parameters for the fate decision of hematopoietic stem and progenitor cells(HSPC)in bone marrow.Insights into cell-ECM interactions are critical for advancing HSC-based tissue engineering.Herein,we employed collagen hydrogels and collagen-alginate hydrogels of defined stiffness to study the behaviors of hematopoietic progenitor cells(HPCs).Three-dimensional(3D)collagen hydrogels with a stiffness of 45 Pa were found to promote HPC maintenance and colony formation of monocyte/macrophage progenitors.Using single-cell RNA sequencing(scRNA-seq),we also characterized the comprehensive transcriptional profiles of cells randomly selected from two-dimensional(2D)and 3D hydrogels.A distinct maturation trajectory from HPCs into macrophages within the 3D microenvironment was revealed by these results.3D-derived macrophages expressed high levels of various cytokines and chemokines,such as Saa3,Cxcl2,Socs3 and Tnf.Furthermore,enhanced communication between 3D-macrophages and other hematopoietic clusters based on ligand-repair interactions was demonstrated through bioinformatic analyses.Our research underlines the regulatory role of matrix-dimensionality in HPC differentiation and therefore probably be applied to the generation of specialized macrophages.
