OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and...OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and in vivo validation.METHODS:A mouse model of MGD was induced using the stearoyl-coenzyme a desaturase 1 inhibitor,followed by PGYYQR treatment for 2 weeks.MGD sign scoring,hematoxylin and eosin(HE)staining,oil red o(ORO)staining,and serum inflammatory cytokine analysis were conducted to assess the effects of PGYYQR on meibomian gland(MG)function,histopathology,and associated inflammation.Network pharmacology was employed to identify the active compounds and potential targets of PGYYQR.Molecular mechanisms were further investigated using Western blotting,reverse transcription quantitative real-time polymerase chain reaction,and reactive oxygen species(ROS)assays.RESULTS:PGYYQR treatment significantly reduced the scores of MG orifice obstruction and meibum quality in MGD mice.HE and ORO staining further demonstrated that PGYYQR ameliorated glandular damage and lipid dysfunction.Enzyme-linked immunosorbent assay results revealed that PGYYQR markedly decreased the serum levels of key inflammatory cytokines,including interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.Network pharmacology identified 162 active compounds and 598 target genes in PGYYQR.Among these,IL-6,IL-1β,matrix metalloproteinase-9,and C-X-C motif chemokine ligand 8 were recognized as core targets related to MGD and were mainly enriched in the IL-17/nuclear factor kappa B(NF-κB)signaling pathway.Further molecular analyses confirmed that PGYYQR significantly inhibited the IL-17/NF-κB axis by downregulating IL-17 expression and reducing phosphorylated NF-κB p65 levels at both the protein and m RNA levels in MG tissues.PGYYQR also effectively reduced ROS levels in the conjunctival tissues of MGD mice.CONCLUSION:PGYYQR effectively improves MG function and preserves local tissue morphology in MGD model mice,primarily by suppressing the inflammatory response through coordinated modulation of the IL-17/NF-κB signaling pathway and oxidative stress.展开更多
Diabetes mellitus(DM)is a chronic disease influenced by gut microbiome disturbances.Honokiol(HON),a low oral bioavailability compound from Magnolia officinalis bark,has demonstrated potential as a treatment for DM.Thi...Diabetes mellitus(DM)is a chronic disease influenced by gut microbiome disturbances.Honokiol(HON),a low oral bioavailability compound from Magnolia officinalis bark,has demonstrated potential as a treatment for DM.This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM.After 8 weeks of intervention through fecal microbiota transplantation(FMT)or antibiotic treatment,HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner.Specifically,HON administration significantly increased Akkermansia muciniphila(AKK)abundance and modulated tryptophan(TRP)metabolism,as evidenced by 16S ribosomal ribonucleic acid(rRNA)gene sequencing and untargeted/targeted metabolomics analysis.Notably,research revealed that AKK metabolized TRP into tryptamine(TA)and other metabolites in vitro.Both AKK and TA activated the aryl hydrocarbon receptor(AHR)pathway,increasing circulating glucagon-like peptide-1(GLP-1)levels and ameliorating diabetes-related symptoms in DM mice.These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA,potentially enhancing HON’s clinical applications.展开更多
Background:Soil structure is a key indicator of the functioning of soil processes in grasslands,which is influenced by site conditions and management.Methods:In this study,we investigated soil structure and its relati...Background:Soil structure is a key indicator of the functioning of soil processes in grasslands,which is influenced by site conditions and management.Methods:In this study,we investigated soil structure and its relationship with root growth in 31 Leptosols under different grassland management intensities using X-ray microcomputed tomography.A close relationship between land use intensity,soil structure,and root growth was observed.Results:Our results show that land use type affects root development and soil structure.Pastures had more developed roots and more structured soils than meadows and mown pastures.However,all pastures were unfertilized,while meadows and mown pastures had both fertilized and unfertilized plots.Although no significant differences were found in the unfertilized plots,sample size was limited.In particular,fertilization negatively affected root growth and soil structure,resulting in significant differences between fertilized and unfertilized grasslands.Mowing frequency also had an effect on soil physics,but to a much lesser extent than fertilization.Conclusions:Increased land use intensity,characterized by increased fertilization and more frequent mowing,reduces root growth and adversely affects soil structure.Therefore,X-ray microcomputed tomography is a suitable method to investigate the relationship between soil structure and roots in the soil.展开更多
The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of du...The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalystfree conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights(up to 34,100) and welldefined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells.Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers.展开更多
基金Supported by National Famous and Senior Chinese Medicine Expert Heritage Studio Construction Project:Zhi Nan Heritage Studio(No.75[2022])Beijing Municipal Key Traditional Chinese Medicine Specialty Development Project during the 14th Five-Year Plan Period(No.BJZKBC0029)。
文摘OBJECTIVE:To investigate the pharmacological effects and underlying mechanisms of Pinggan Yuyin Qingre formula(平肝育阴清热方,PGYYQR)in the treatment of meibomian gland dysfunction(MGD)through network pharmacology and in vivo validation.METHODS:A mouse model of MGD was induced using the stearoyl-coenzyme a desaturase 1 inhibitor,followed by PGYYQR treatment for 2 weeks.MGD sign scoring,hematoxylin and eosin(HE)staining,oil red o(ORO)staining,and serum inflammatory cytokine analysis were conducted to assess the effects of PGYYQR on meibomian gland(MG)function,histopathology,and associated inflammation.Network pharmacology was employed to identify the active compounds and potential targets of PGYYQR.Molecular mechanisms were further investigated using Western blotting,reverse transcription quantitative real-time polymerase chain reaction,and reactive oxygen species(ROS)assays.RESULTS:PGYYQR treatment significantly reduced the scores of MG orifice obstruction and meibum quality in MGD mice.HE and ORO staining further demonstrated that PGYYQR ameliorated glandular damage and lipid dysfunction.Enzyme-linked immunosorbent assay results revealed that PGYYQR markedly decreased the serum levels of key inflammatory cytokines,including interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.Network pharmacology identified 162 active compounds and 598 target genes in PGYYQR.Among these,IL-6,IL-1β,matrix metalloproteinase-9,and C-X-C motif chemokine ligand 8 were recognized as core targets related to MGD and were mainly enriched in the IL-17/nuclear factor kappa B(NF-κB)signaling pathway.Further molecular analyses confirmed that PGYYQR significantly inhibited the IL-17/NF-κB axis by downregulating IL-17 expression and reducing phosphorylated NF-κB p65 levels at both the protein and m RNA levels in MG tissues.PGYYQR also effectively reduced ROS levels in the conjunctival tissues of MGD mice.CONCLUSION:PGYYQR effectively improves MG function and preserves local tissue morphology in MGD model mice,primarily by suppressing the inflammatory response through coordinated modulation of the IL-17/NF-κB signaling pathway and oxidative stress.
基金supported by the National Key Research and Development Program of China (No. 2023YFC3502605)the National Natural Science Foundation of China (Nos. 82104360,82274074, and 82204598)+1 种基金Jiangsu Funding Program for Excellent Postdoctoral TalentChina Postdoctoral Science Foundation (No. 2022M713483)
文摘Diabetes mellitus(DM)is a chronic disease influenced by gut microbiome disturbances.Honokiol(HON),a low oral bioavailability compound from Magnolia officinalis bark,has demonstrated potential as a treatment for DM.This research investigates the effects of HON on gut microbiota and host metabolism to elucidate its mechanism of action in DM.After 8 weeks of intervention through fecal microbiota transplantation(FMT)or antibiotic treatment,HON improved glucose tolerance and lipid metabolism in a gut microbiota-dependent manner.Specifically,HON administration significantly increased Akkermansia muciniphila(AKK)abundance and modulated tryptophan(TRP)metabolism,as evidenced by 16S ribosomal ribonucleic acid(rRNA)gene sequencing and untargeted/targeted metabolomics analysis.Notably,research revealed that AKK metabolized TRP into tryptamine(TA)and other metabolites in vitro.Both AKK and TA activated the aryl hydrocarbon receptor(AHR)pathway,increasing circulating glucagon-like peptide-1(GLP-1)levels and ameliorating diabetes-related symptoms in DM mice.These findings indicate that HON’s hypoglycemic effect primarily stems from AHR-GLP-1 pathway activation through targeted modulation of AKK and microbial TRP metabolite TA,potentially enhancing HON’s clinical applications.
文摘Background:Soil structure is a key indicator of the functioning of soil processes in grasslands,which is influenced by site conditions and management.Methods:In this study,we investigated soil structure and its relationship with root growth in 31 Leptosols under different grassland management intensities using X-ray microcomputed tomography.A close relationship between land use intensity,soil structure,and root growth was observed.Results:Our results show that land use type affects root development and soil structure.Pastures had more developed roots and more structured soils than meadows and mown pastures.However,all pastures were unfertilized,while meadows and mown pastures had both fertilized and unfertilized plots.Although no significant differences were found in the unfertilized plots,sample size was limited.In particular,fertilization negatively affected root growth and soil structure,resulting in significant differences between fertilized and unfertilized grasslands.Mowing frequency also had an effect on soil physics,but to a much lesser extent than fertilization.Conclusions:Increased land use intensity,characterized by increased fertilization and more frequent mowing,reduces root growth and adversely affects soil structure.Therefore,X-ray microcomputed tomography is a suitable method to investigate the relationship between soil structure and roots in the soil.
基金supported by the National Natural Science Foundation of China(22101028,21788102)the start-up funding from Beijing Normal University(310432102,310432103)+3 种基金the Innovation and Technology Commission(ITC-CNERC14SC01)the Science and Technology Plan of Shenzhen(JCYJ20160229205601482,JCYJ20180507183832744,JCYJ20170818113602462)the Natural Science Foundation of Guangdong Province(2019B121205002)the Research Grants Council of Hong Kong(16305618,16304819,16305320,NHKUST609/19,C6009-17G,C6014-20W/16)。
文摘The development of new polymerization routes to afford N-heterocyclic polymers is of vital importance and highly desired for various practical applications. Herein, a facile and efficient polyannulation reaction of dual-activated alkyne and pyridines was developed to construct novel N-heterocyclic poly(quinolizine)s. This polymerization can proceed smoothly under catalystfree conditions with 100% atom utilization to furnish poly(quinolizine)s with high molecular weights(up to 34,100) and welldefined structures in acceptable yields. The resulting polymers show good solubility, high thermal stability and strong red emission. Moreover, the prepared poly(quinolizine)s exhibit low cytotoxicity and can selectively label lysosomes in live cells.Considering the remarkable advantages of readily available raw materials, mild polymerization conditions, atom economy, and excellent product performance, this new and efficient polymerization tool will open up enormous opportunities for preparing functional N-heterocyclic polymers.
