Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation...Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes： the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.展开更多
Extracellular aggregation of amyloid-beta(Aβ)and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer’s disease.A linear interaction between Aβand tau protein has been char...Extracellular aggregation of amyloid-beta(Aβ)and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer’s disease.A linear interaction between Aβand tau protein has been characterized in several models.Aβinduces tau hyperphosphorylation through a complex mechanism;however,the master regulators involved in this linear process are still unclear.In our study with Drosophila melanogaster,we found that Aβregulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase.Importantly,Aβtoxicity was dependent on tau hyperphosphorylation,and flies with hypophosphorylated tau were insulated against Aβ-induced toxicity.Strikingly,tau accumulation reciprocally interfered with Aβdegradation and correlated with the reduction in mRNA expression of genes encoding Aβ-degrading enzymes,including dNep1,dNep3,dMmp2,dNep4,and dIDE.Our results indicate that Aβand tau protein work synergistically to further accelerate Alzheimer’s disease progression and may be considered as a combined target for future development of Alzheimer’s disease therapeutics.展开更多
Synthetic macrocycles have served as principal tools for supramolecular chemistry since their establishment,and the investigation of macrocycles-aided organicinorganic hybrid nanomaterials has also attracted broad int...Synthetic macrocycles have served as principal tools for supramolecular chemistry since their establishment,and the investigation of macrocycles-aided organicinorganic hybrid nanomaterials has also attracted broad interest in chemistry and material communities during the past decade owing to their widespread applications in optical sensing,catalytic degradation,biomedicine,and other related fields.Herein,a new class of silver nanoparticles(AgNPs)modified by anionic watersoluble[2]biphenyl-extended pillar[6]arene(WBpP6),namely WBpP6-AgNPs,is designed and synthesized through a facile one-pot method.WBpP6-AgNPs with good dispersion and stability exhibit efficient catalytic properties toward the hydrogenation of a series of aromatic nitro compounds and also show good performance in label-free detection toward diquat.展开更多
Photothermal conversion—the process of transforming light into thermal energy—is pivotal for next-generation technologies such as solar energy harvesting,water purification,seawater desalination,and biomedical appli...Photothermal conversion—the process of transforming light into thermal energy—is pivotal for next-generation technologies such as solar energy harvesting,water purification,seawater desalination,and biomedical applications.Achieving high photothermal efficiency depends on materials with broad-spectrum light absorption,excellent heat conversion capabilities,and outstanding chemical stability[1–3].展开更多
Objective: Huazhi Rougan granules(HRGs) are a promising drug to improve alcoholic liver disease(ALD), but its mechanism remains unclear. Materials and Methods: Network pharmacology, molecular docking, and animal exper...Objective: Huazhi Rougan granules(HRGs) are a promising drug to improve alcoholic liver disease(ALD), but its mechanism remains unclear. Materials and Methods: Network pharmacology, molecular docking, and animal experiments were used to reveal the potential mechanism of HRG against ALD. Results: A total of 245 potential targets of HRG against ALD were obtained. Functional enrichment analysis suggests that HRG could synergistically regulate various biological pathways to exert therapeutic effects on ALD. Molecular docking showed that the key targets exhibited the good binding ability with the key compounds. The in vivo experiments showed that HRG can effectively alleviate pathological changes in liver tissue, improve blood lipid levels, antioxidant stress ability, and liver function, and reduce the release of inflammatory cytokines in the liver. Conclusions: This study reflects that HRG is an effective strategy for treating ALD, providing a basis for revealing the prevention and treatment mechanisms of ALD.展开更多
Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order a...Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order as(or a close sister to)primates,and thus may be an ideal model in which to study human disease.In this study,the proteome of liver and muscle tissue in tree the shrew was identified by combining peptide fractionation and LC-MS/MS identification.In total,2146 proteins were detected,including 1759 proteins in liver samples and 885 proteins in skeletal muscle samples from the tree shrew.Further sub-source analysis revealed that nearly half of the identified proteins(846 proteins and 418 proteins)were derived from human database.In this study,we are the first to describe the characteristics of the proteome from the liver and skeletal muscle of the tree shrew.Phylogenetic tree analysis based on these proteomic data showed that the tree shrew is closer to primates(human)than to glires(the mouse and rat).展开更多
The detection of single amino-acid variants （SAVs） usually depends on single-nucleotide polymorphisms （SNPs） database. Here, we describe a novel method that discovers SAVs at proteome level independent of SNPs dat...The detection of single amino-acid variants （SAVs） usually depends on single-nucleotide polymorphisms （SNPs） database. Here, we describe a novel method that discovers SAVs at proteome level independent of SNPs data. Using mass spectrometry-based de novo sequencing algorithm, peptide-candidates are identified and compared with theoretical protein database to generate SAVs under pairing strategy, which is followed by database re-searching to control false discovery rate. in human brain tissues, we can confidently identify known and novel protein variants with diverse origins. Combined with DNA/RNA sequencing, we verify SAVs derived from DNA mutations, RNA alternative splicing, and unknown post-transcriptional mechanisms. Furthermore, quantitative analysis in human brain tissues reveals several tissue-specific differential expressions of SAVs. This approach provides a novel access to high-throughput detection of protein variants, which may offer the potential for clinical biomarker discovery and mechanistic research.展开更多
For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interac...For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interaction are based on cell level,there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection.Based on collected proteomic datasets from human lung,colon,kidney,liver,and heart,we constructed a virus-receptor network,a virus-interaction network,and a virus-perturbation network.In the tissue-specific networks associated with virus-host crosstalk,both common and different key hubs are revealed in diverse tissues.Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation.Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction.The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues,and the treatment of COVID-19 would be a complex task.展开更多
The production of high-purity n-hexane under mild conditions is of great significance in both the petrochemical industry and synthetic chemistry.Here,we report an easy-to-operate and energy-efficient n-hexane purifica...The production of high-purity n-hexane under mild conditions is of great significance in both the petrochemical industry and synthetic chemistry.Here,we report an easy-to-operate and energy-efficient n-hexane purification strategy using nonporous adaptive crystals of perethylated leaning pillar[6]arene(EtLP6).Adaptive EtLP6 crystals preferentially absorb n-hexane over other branched or cyclic C6 alkanes with similar boiling points.This selectivity arises from the different thermodynamic stabilities and variabilities of EtLP6 crystalloids loaded with n-hexane and other C6 alkanes.Moreover,the reversible transformations between the nonporous vip-free and n-hexane-containing structures make the EtLP6 crystals highly recyclable.展开更多
A bacterial cell has many different two component systems(TCSs)that allow it to sense and adapt to various environmental stimulations,such as temperature,oxygen concentration,degree of acidity and alkalinity[1].Each T...A bacterial cell has many different two component systems(TCSs)that allow it to sense and adapt to various environmental stimulations,such as temperature,oxygen concentration,degree of acidity and alkalinity[1].Each TCS is composed of a sensor histidine kinase(HK)and a response regulator(RR)[2,3].To investigate TCSs in a systematical way,we built light-sensing TCSs in E.coli by reengineering wild-type HKs.A modified HK展开更多
Single-nucleotide polymorphisms(SNPs)are recognized as one kind of major genetic variants in population scale.However,polymorphisms at the proteome level in population scale remain elusive.In the present study,we nam...Single-nucleotide polymorphisms(SNPs)are recognized as one kind of major genetic variants in population scale.However,polymorphisms at the proteome level in population scale remain elusive.In the present study,we named amino acid variances derived from SNPs within coding regions as single amino acid polymorphisms(SAPs)at the proteome level,and developed a pipeline of nontargeted and targeted proteomics to identify and quantify SAP peptides in human plasma.The absolute concentrations of three selected SAP-peptide pairs among 290 Asian individuals were measured by selected reaction monitoring(SRM)approach,and their associations with both obesity and diabetes were further analyzed.This work revealed that heterozygotes and homozygotes with various SAPs in a population could have different associations with particular traits.In addition,the SRM approach allows us for the first time to separately measure the absolute concentration of each SAP peptide in the heterozygotes,which also shows different associations with particular traits.展开更多
Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of...Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB.Results:A total of 112 active compounds of RSGB were found,and 501 targets were predicted.Furthermore,2974 immune targets were obtained from UniProt and NCBI Gene databases,and 111 common targets of RSGB and immunity were obtained.Among them,interleukin(IL)6,tumor necrosis factor,AKT1,VEGFA,STAT3,MAPK1,SRC,EGFR,IL1B,and PTGS2 might be the key targets for RSGB to improve immunity.ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway.Furthermore,this study preliminarily explored the mechanism of RSGB improving menopausal syndrome,polycystic ovary syndrome,and cancer-related fatigue by enhancing immunity.Conclusions:RSGB can improve the body's immunity through multicomponent,multitarget,and multipathway.In addition,RSGB can also improve the immune capacity of the body to assist in the treatment of diseases,which has great potential as an immunomodulator.展开更多
文摘Coordination of cell differentiation and proliferation is a key issue in the development process of multi-cellular organisms and stem cells. Here we provide evidence that the establishment of adipocyte differentiation of 3T3-L1 cells requires two processes： the licensing of an adipogenesis gene-expression program within a particular growth-arrest stage, i.e., the contact-inhibition stage, and then the execution of this program in a cell-cycle-independent manner, by which the licensed progenitors are differentiated into adipocytes in the presence of inducing factors. Our results showed that differentiation licensing of 3T3-L1 cells during the contact-inhibition stage involved epigenetic modifications such as DNA methylation and histone modifications, whereas disturbing these epigenetic modifications by DNA methylation inhibitors or RNAi during the contact-inhibition stage significantly reduced adipogenesis efficiency. More importantly, when these licensed 3T3-L1 cells were re-cultured under non-differentiating conditions or treated only with insulin, this adipogenesis commitment could be maintained from one cell generation to the next, whereby the licensed program could be activated in a cell-cycle-independent manner once these cells were subjected to adipo- genesis-inducing conditions. This result suggests that differentiation licensing and differentiation execution can be uncoupled and disparately linked to cell proliferation. Our findings deliver a new concept that cell-fate decision can be subdivided into at least two stages, licensing and execution, which might have different regulatory relationships with cell proliferation. In addition, this new concept may provide a clue for developing new strategies against obesity.
基金supported by the National Basic Research Program of China,Nos.31700883(to YPH)and 91649118(to BZ)China Postdoctoral Science Foundation,No.2015M581072(to YPH)the Strategic Priority Research Program of the Chinese Academy of Sciences,No.XDB38000000(to JRW).
文摘Extracellular aggregation of amyloid-beta(Aβ)and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer’s disease.A linear interaction between Aβand tau protein has been characterized in several models.Aβinduces tau hyperphosphorylation through a complex mechanism;however,the master regulators involved in this linear process are still unclear.In our study with Drosophila melanogaster,we found that Aβregulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase.Importantly,Aβtoxicity was dependent on tau hyperphosphorylation,and flies with hypophosphorylated tau were insulated against Aβ-induced toxicity.Strikingly,tau accumulation reciprocally interfered with Aβdegradation and correlated with the reduction in mRNA expression of genes encoding Aβ-degrading enzymes,including dNep1,dNep3,dMmp2,dNep4,and dIDE.Our results indicate that Aβand tau protein work synergistically to further accelerate Alzheimer’s disease progression and may be considered as a combined target for future development of Alzheimer’s disease therapeutics.
基金the National Natural Science Foundation of China(Nos.52173200 and 22201096)the Natural Science Foundation of Jilin Province(No.20230101052JC)the Fundamental Research Funds for the Central Universities(No.2022-JCXK-13)for financial support.
文摘Synthetic macrocycles have served as principal tools for supramolecular chemistry since their establishment,and the investigation of macrocycles-aided organicinorganic hybrid nanomaterials has also attracted broad interest in chemistry and material communities during the past decade owing to their widespread applications in optical sensing,catalytic degradation,biomedicine,and other related fields.Herein,a new class of silver nanoparticles(AgNPs)modified by anionic watersoluble[2]biphenyl-extended pillar[6]arene(WBpP6),namely WBpP6-AgNPs,is designed and synthesized through a facile one-pot method.WBpP6-AgNPs with good dispersion and stability exhibit efficient catalytic properties toward the hydrogenation of a series of aromatic nitro compounds and also show good performance in label-free detection toward diquat.
文摘Photothermal conversion—the process of transforming light into thermal energy—is pivotal for next-generation technologies such as solar energy harvesting,water purification,seawater desalination,and biomedical applications.Achieving high photothermal efficiency depends on materials with broad-spectrum light absorption,excellent heat conversion capabilities,and outstanding chemical stability[1–3].
文摘Objective: Huazhi Rougan granules(HRGs) are a promising drug to improve alcoholic liver disease(ALD), but its mechanism remains unclear. Materials and Methods: Network pharmacology, molecular docking, and animal experiments were used to reveal the potential mechanism of HRG against ALD. Results: A total of 245 potential targets of HRG against ALD were obtained. Functional enrichment analysis suggests that HRG could synergistically regulate various biological pathways to exert therapeutic effects on ALD. Molecular docking showed that the key targets exhibited the good binding ability with the key compounds. The in vivo experiments showed that HRG can effectively alleviate pathological changes in liver tissue, improve blood lipid levels, antioxidant stress ability, and liver function, and reduce the release of inflammatory cytokines in the liver. Conclusions: This study reflects that HRG is an effective strategy for treating ALD, providing a basis for revealing the prevention and treatment mechanisms of ALD.
基金supported by the grants from the Knowledge Innovation Program of the Chinese Academy of Sciences(No.KSCX2-EW-R-12)grants from National Natural Science Foundation Youth Fund of China(Grant No.30900261)the Support of SA-SIBS Scholarship Program.
文摘Valid animal models are useful for studying the pathophysiology of specific disorders,such as neural disease,diabetes and cancer.Previous molecular phylogeny studies indicate that the tree shrew is in the same order as(or a close sister to)primates,and thus may be an ideal model in which to study human disease.In this study,the proteome of liver and muscle tissue in tree the shrew was identified by combining peptide fractionation and LC-MS/MS identification.In total,2146 proteins were detected,including 1759 proteins in liver samples and 885 proteins in skeletal muscle samples from the tree shrew.Further sub-source analysis revealed that nearly half of the identified proteins(846 proteins and 418 proteins)were derived from human database.In this study,we are the first to describe the characteristics of the proteome from the liver and skeletal muscle of the tree shrew.Phylogenetic tree analysis based on these proteomic data showed that the tree shrew is closer to primates(human)than to glires(the mouse and rat).
文摘The detection of single amino-acid variants （SAVs） usually depends on single-nucleotide polymorphisms （SNPs） database. Here, we describe a novel method that discovers SAVs at proteome level independent of SNPs data. Using mass spectrometry-based de novo sequencing algorithm, peptide-candidates are identified and compared with theoretical protein database to generate SAVs under pairing strategy, which is followed by database re-searching to control false discovery rate. in human brain tissues, we can confidently identify known and novel protein variants with diverse origins. Combined with DNA/RNA sequencing, we verify SAVs derived from DNA mutations, RNA alternative splicing, and unknown post-transcriptional mechanisms. Furthermore, quantitative analysis in human brain tissues reveals several tissue-specific differential expressions of SAVs. This approach provides a novel access to high-throughput detection of protein variants, which may offer the potential for clinical biomarker discovery and mechanistic research.
基金This work was supported by grants from the Ministry of Science and Technology(2017YFA0505500)the Strategic CAS Project(XDA12010000 and XDB3000000).
文摘For patients with COVID-19 caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the damages to multiple organs have been clinically observed.Since most of current investigations for virus-host interaction are based on cell level,there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection.Based on collected proteomic datasets from human lung,colon,kidney,liver,and heart,we constructed a virus-receptor network,a virus-interaction network,and a virus-perturbation network.In the tissue-specific networks associated with virus-host crosstalk,both common and different key hubs are revealed in diverse tissues.Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation.Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction.The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues,and the treatment of COVID-19 would be a complex task.
基金the National Natural Science Foundation of China(21871108)Jilin Province-University Cooperative Construction Project-Special Funds for New Materials(SXGJSF2017-3)Jilin University Talents Cultivation Program for financial support.
文摘The production of high-purity n-hexane under mild conditions is of great significance in both the petrochemical industry and synthetic chemistry.Here,we report an easy-to-operate and energy-efficient n-hexane purification strategy using nonporous adaptive crystals of perethylated leaning pillar[6]arene(EtLP6).Adaptive EtLP6 crystals preferentially absorb n-hexane over other branched or cyclic C6 alkanes with similar boiling points.This selectivity arises from the different thermodynamic stabilities and variabilities of EtLP6 crystalloids loaded with n-hexane and other C6 alkanes.Moreover,the reversible transformations between the nonporous vip-free and n-hexane-containing structures make the EtLP6 crystals highly recyclable.
基金supported by grants to W.J.R.from the National Natural Science Foundation of China(31130034 and 31470808)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12000000)grants to Z.L.from the Ministry of Science and Technology(2014CB910600)
文摘A bacterial cell has many different two component systems(TCSs)that allow it to sense and adapt to various environmental stimulations,such as temperature,oxygen concentration,degree of acidity and alkalinity[1].Each TCS is composed of a sensor histidine kinase(HK)and a response regulator(RR)[2,3].To investigate TCSs in a systematical way,we built light-sensing TCSs in E.coli by reengineering wild-type HKs.A modified HK
基金supported by the grants from the Ministry of Science and Technology(2011CB910200,2011CB910601)a grant from the National Natural Science Foundation of China(30821065)the grants from the Knowledge Innovation Program of the Chinese Academy of Sciences(KSCX1-YW-02,KJCX2-YW-M15).
文摘Single-nucleotide polymorphisms(SNPs)are recognized as one kind of major genetic variants in population scale.However,polymorphisms at the proteome level in population scale remain elusive.In the present study,we named amino acid variances derived from SNPs within coding regions as single amino acid polymorphisms(SAPs)at the proteome level,and developed a pipeline of nontargeted and targeted proteomics to identify and quantify SAP peptides in human plasma.The absolute concentrations of three selected SAP-peptide pairs among 290 Asian individuals were measured by selected reaction monitoring(SRM)approach,and their associations with both obesity and diabetes were further analyzed.This work revealed that heterozygotes and homozygotes with various SAPs in a population could have different associations with particular traits.In addition,the SRM approach allows us for the first time to separately measure the absolute concentration of each SAP peptide in the heterozygotes,which also shows different associations with particular traits.
基金the National Nature Science Foundation of China(No.81673829)。
文摘Objective:To investigate the mechanism of Renshen Guben oral liquid(RSGB)enhancing immune function.Materials and Methods:Network pharmacology and molecular docking were used to intuitively demonstrate the mechanism of immune regulation of RSGB.Results:A total of 112 active compounds of RSGB were found,and 501 targets were predicted.Furthermore,2974 immune targets were obtained from UniProt and NCBI Gene databases,and 111 common targets of RSGB and immunity were obtained.Among them,interleukin(IL)6,tumor necrosis factor,AKT1,VEGFA,STAT3,MAPK1,SRC,EGFR,IL1B,and PTGS2 might be the key targets for RSGB to improve immunity.ClueGO and Kyoto Encyclopedia of Genes and Genomes analysis showed that the immunoregulatory mechanism of RSGB may find a relation with the B cell receptor signaling pathway and T cell receptor signaling pathway.Furthermore,this study preliminarily explored the mechanism of RSGB improving menopausal syndrome,polycystic ovary syndrome,and cancer-related fatigue by enhancing immunity.Conclusions:RSGB can improve the body's immunity through multicomponent,multitarget,and multipathway.In addition,RSGB can also improve the immune capacity of the body to assist in the treatment of diseases,which has great potential as an immunomodulator.
