The piezocatalytic characteristic of bismuth oxyhalides(BiOX,X=Cl,Br,and I) has been increasingly capturing interest for its potential in hydrogen evolution reaction(HER) through water splitting process.The performanc...The piezocatalytic characteristic of bismuth oxyhalides(BiOX,X=Cl,Br,and I) has been increasingly capturing interest for its potential in hydrogen evolution reaction(HER) through water splitting process.The performance regarding these piezocatalysts is closely related to the halogen element present in BiOX;yet,the specific influence mechanisms remain unclear.In this study,we prepared BiOX catalysts via a hydrothermal process and explored their piezocatalytic HER activities.Owing to the layered bismuth s tructure,the resulting sheet-like piezocatalysts can efficiently capture the mechanic stimulus and allow the robust piezoelectric field,contributing to the piezocatalytic operation.It demonstrates that the BiOBr achieves a remarkable piezocatalytic HER efficiency of 813 μmol g^(-1)h^(-1),outperforming BiOCl and BiOI.The density functional theory(DFT)calculation results reveal that the BiOBr with moderate halogen atom size and lattice layer spacing possesses the strongest piezoelectricity,which enhances the separation and transfer of electron-hole pairs.Meanwhile,the exposed Br atom layer facilitates a large Bader charge and a low surface Gibbs free energy(ΔG_(H)),enhancing charge transfer for hydrogen reduction at the solid-liquid surface,thereby increasing the HER efficiency.This research sheds light on the halogen-dependent piezocatalytic activity of BiOX catalysts,offering valuable insights for the development of high-performance piezocatalysts.展开更多
Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of 48 New Zealand white rabbits were rand...Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of 48 New Zealand white rabbits were randomly divided into group Ⅰ(blank control group),groupⅡ(CSC injection group),group Ⅲ(CSC/bBMP injection group) and control group.White rabbit osteoporosis model was established rapidly by using castration mcthod+methylprcdnisolone candidate.After modeling,groups Ⅱ.Ⅲ were given corresponding vertebral body injection material,and 4 animals were sacrificed respectively at 24 h,6 weeks,12 weeks after vertebral plasty.Tissue pathological status,vertebral mineral density and vertebral body bone mechanical strength were observed.Results:Vertebral body structure form was normal in the groups Ⅱand Ⅲ.Trabecular bone coarsens,connection and repair were observed in micro fracture and bone defects,bone trabecular connectivity was superior to group I significantly;vertebral body compression strength in the group I was on the decline,vertebral compression strength in the groups Ⅱ and Ⅲ was on the rise,the largest vertebra.Postoperative BMC and BMD in groups Ⅱand Ⅲ were incresed,and significantly higher than group I after 6 weeks(P<0.05),BMC and BMD in group Ⅲ after 12 weeks were higher than the other three groups.Conclusion:Compound bBMP CSC has good bone induction.It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula,and can significantly improve the vertebral strength,as a vertebral packing material with good application prospect.展开更多
Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying...Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.展开更多
Background:Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease(NAFLD).Therefore,we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the a...Background:Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease(NAFLD).Therefore,we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.Methods:This 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography(ULS-NAFLD)every 3 years.A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD(MRI-NAFLD).Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants,and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)in the middle term.Results:A total of 2,522 participants finished follow-up visits.Of these participants,770,301,474,and 977 were categorized into NAFLD-free,improved,new-onset,and persistent NAFLD groups based on their ULS-NAFLD status changes,respectively,and 342/828 were MRI-verified NALFD.Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence(P-trend<0.05).Multivariable-adjusted odds ratios(ORs)/hazard ratio(HR)[95%confidence intervals(CIs)]of NAFLD for quartile 4(vs.quartile 1)of total carotenoids were 0.63(0.50,0.80)for incident ULS-NAFLD,0.20(0.15,0.27)for persistent ULS-NAFLD,1.53(1.10,2.12)for improved-NAFLD,and 0.58(0.39,0.87)for MRI-NAFLD.The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in Ruminococcaceae and Veillonellaceae family,nineteen fecal metabolites containing medium-chain fatty acids(MCFAs),bile acids,and carnitines,and sixteen serum metabolites belonging to organic acids and amino acids.The total carotenoids-related scores of significant microbial genera,fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%,12.30%,and 16.83%(all P<0.05)for persistent NAFLD and 9.46%,8.74%,and 15.7%for incident-NAFLD,respectively.Conclusions:Our study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD.The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.展开更多
Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalo...Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalovirus （CMV） is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients.This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.Methods： Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated.GraphPad Prism version 5.013 （San Diego, CA, USA） was used to conduct statistical analysis.The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test.Significance between qualitative data was analyzed using Pearson＆#39;s Chi-squared test.The cut-offthresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic （ROC） curve analysis.Results： One hundred and forty-two patients had positive CMV viral load tests.Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic.The symptomatic group received higher doses ofprednisolone （PSL） and more frequently immunosuppressants than the asymptomatic group （P 〈 0.01）.The symptomatic group had lower lymphocyte counts, especially CD4＋ T-cells, than the asymptomatic group （P 〈 0.01）.By ROC curve analysis, when CD4＋ T-cell count was 〈0.39 ＆#215; 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection.The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients （P 〈 0.01;threshold viral loads： 1.75 ＆#215; 104 copies/ml）.Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts （P 〈 0.01）, including CD4＋ and CD8＋ T-cells （P 〈 0.0 l）.Conclusions： When CD4＋ T-cell count is 〈0.39 ＆#215; 109/L, patients are at high risk for pulmonary CMV infection.Patients are prone to be symptomatic with CMV-DNA load 〉1.75 ＆#215; 104 copies/ml.Lymphopenia （especially CD4＋ T-cells）, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.展开更多
Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to...Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.Methods:We included 1430 participants from the Guangzhou Nutrition and Health Study(GNHS)with both gut microbiome and cognitive assessment data available as a discovery cohort,of whom 272 individuals provided fecal samples twice before cognitive assessment.We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit.Fecal 16S rRNA and shotgun metagenomic sequencing,tar-geted serum metabolomics,and cytokine measurements were performed in the GNHS.The validation analyses were conducted in an Alzheimer’s disease case-control study(replication study 1,n=90)and another community-based cohort(replication study 2,n=1300)with cross-sectional dataset.Results:We found protective associations of specific gut microbial genera(Odoribacter,Butyricimonas,and Bac-teroides)with cognitive impairment in both the discovery cohort and the replication study 1.Result of Bacteroides was further validated in the replication study 2.Odoribacter was positively associated with hippocampal volume(β,0.16;95%CI 0.06-0.26,P=0.002),which might be mediated by acetic acids.Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment.We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Conclusions:Our findings reveal that specific gut microbial features are closely associated with cognitive impair-ment and decreased hippocampal volume,which may play an important role in dementia development.展开更多
The use of statins as the primary therapy for reducing low-density lipoprotein cholesterol has raised concerns regarding their potential side effects in increasing the risk of type 2 diabetes(T2D).However,the underlyi...The use of statins as the primary therapy for reducing low-density lipoprotein cholesterol has raised concerns regarding their potential side effects in increasing the risk of type 2 diabetes(T2D).However,the underlying mechanism remains largely unknown.In this study,we utilized multi-omics molecular signatures to unravel the etiology of statin-induced T2D.Through systematic screening of 102 gut microbial features,40 blood metabolites,and 131 circulating proteins in East Asians and Europeans,we identified a set of blood metabolites and proteins potentially influenced by genetically proxied statin use.Notably,Mendelian randomization analyses provided evidence that elevated circulating levels of gastric inhibitory polypeptide(GIP)were associated with an increased risk of T2D.This association between genetically proxied statin use and GIP was consistently observed across East Asian and European populations,highlighting the pivotal role of GIP in modulating the risks of statin-induced T2D.Furthermore,this study established an extensive atlas of multi-omics molecular signatures associated with statin-induced T2D,offering valuable insights for prioritizing intervention targets.展开更多
基金financially supported by the Natural Science Foundation of Shandong Province(No.ZR2023MB151)the Natural Science Foundation of Shandong Province for Excellent Young Scholars(No.ZR2022YQ13)+1 种基金the Science and Technology Special Project of Qingdao(No.24-1-8-xdny-18nsh)the Taishan Scholar Project of Shandong Province(No.tsqn202211159)
文摘The piezocatalytic characteristic of bismuth oxyhalides(BiOX,X=Cl,Br,and I) has been increasingly capturing interest for its potential in hydrogen evolution reaction(HER) through water splitting process.The performance regarding these piezocatalysts is closely related to the halogen element present in BiOX;yet,the specific influence mechanisms remain unclear.In this study,we prepared BiOX catalysts via a hydrothermal process and explored their piezocatalytic HER activities.Owing to the layered bismuth s tructure,the resulting sheet-like piezocatalysts can efficiently capture the mechanic stimulus and allow the robust piezoelectric field,contributing to the piezocatalytic operation.It demonstrates that the BiOBr achieves a remarkable piezocatalytic HER efficiency of 813 μmol g^(-1)h^(-1),outperforming BiOCl and BiOI.The density functional theory(DFT)calculation results reveal that the BiOBr with moderate halogen atom size and lattice layer spacing possesses the strongest piezoelectricity,which enhances the separation and transfer of electron-hole pairs.Meanwhile,the exposed Br atom layer facilitates a large Bader charge and a low surface Gibbs free energy(ΔG_(H)),enhancing charge transfer for hydrogen reduction at the solid-liquid surface,thereby increasing the HER efficiency.This research sheds light on the halogen-dependent piezocatalytic activity of BiOX catalysts,offering valuable insights for the development of high-performance piezocatalysts.
基金Supported by Grants(in part)from the Major Projects Incubator Program of National Key Basic Research Program of China,No.2012CB526700National Natural Science Foundation of China,No.81370511+1 种基金Natural Science Foundation of Guangdong Province,No.S2011020002348Fundamental Research Funds for the Central Universities,No.13ykjc01 and No.82000-3281901
文摘AIM: To investigate the etiology and complications of liver cirrhosis (LC) in Southern China.
基金supported by Scientific Research Project of People's Hospital number IN Xinjiang Uygur Autonomous Region(20130255)
文摘Objective:To observe reinforcing effect of calcium sulfate cement(CSC) bovine bone morphogenetic protein(bBMP) on vertebral in the rabbit model of osteoporosis.Methods:A total of 48 New Zealand white rabbits were randomly divided into group Ⅰ(blank control group),groupⅡ(CSC injection group),group Ⅲ(CSC/bBMP injection group) and control group.White rabbit osteoporosis model was established rapidly by using castration mcthod+methylprcdnisolone candidate.After modeling,groups Ⅱ.Ⅲ were given corresponding vertebral body injection material,and 4 animals were sacrificed respectively at 24 h,6 weeks,12 weeks after vertebral plasty.Tissue pathological status,vertebral mineral density and vertebral body bone mechanical strength were observed.Results:Vertebral body structure form was normal in the groups Ⅱand Ⅲ.Trabecular bone coarsens,connection and repair were observed in micro fracture and bone defects,bone trabecular connectivity was superior to group I significantly;vertebral body compression strength in the group I was on the decline,vertebral compression strength in the groups Ⅱ and Ⅲ was on the rise,the largest vertebra.Postoperative BMC and BMD in groups Ⅱand Ⅲ were incresed,and significantly higher than group I after 6 weeks(P<0.05),BMC and BMD in group Ⅲ after 12 weeks were higher than the other three groups.Conclusion:Compound bBMP CSC has good bone induction.It can improve the three-dimensional construction effect for osteoporosis vertebral trabecula,and can significantly improve the vertebral strength,as a vertebral packing material with good application prospect.
基金supported by the National Natural Science Foundation of China(82073529,81903316,81773416,81972492,21904107,81672086)Zhejiang Ten-thousand Talents Program(2019R52039)+3 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(LR19C050001)the 5010 Program for Clinical Researches(2007032)the Sun Yat-sen University,Hangzhou Agriculture and Society Advancement Program(20190101A04)Tencent foundation(2020)。
文摘Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.
文摘Background:Many studies have shown that carotenoids are beneficial to non-alcoholic fatty liver disease(NAFLD).Therefore,we explored potential biomarkers of gut microbiota and fecal and serum metabolites linking the association between serum carotenoids and NAFLD in adults.Methods:This 7.8-year prospective study included 2921 participants with serum carotenoids at baseline and determined NAFLD by ultrasonography(ULS-NAFLD)every 3 years.A total of 828 subjects additionally underwent magnetic resonance imaging to identify NAFLD(MRI-NAFLD).Gut microbiota was analyzed by 16S rRNA sequencing in 1,661 participants,and targeted metabolomics profiling in 893 feces and 896 serum samples was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)in the middle term.Results:A total of 2,522 participants finished follow-up visits.Of these participants,770,301,474,and 977 were categorized into NAFLD-free,improved,new-onset,and persistent NAFLD groups based on their ULS-NAFLD status changes,respectively,and 342/828 were MRI-verified NALFD.Longitudinal analyses showed an inverse association between carotenoids and NALFD risk/presence(P-trend<0.05).Multivariable-adjusted odds ratios(ORs)/hazard ratio(HR)[95%confidence intervals(CIs)]of NAFLD for quartile 4(vs.quartile 1)of total carotenoids were 0.63(0.50,0.80)for incident ULS-NAFLD,0.20(0.15,0.27)for persistent ULS-NAFLD,1.53(1.10,2.12)for improved-NAFLD,and 0.58(0.39,0.87)for MRI-NAFLD.The biomarkers in the gut-liver axis significantly associated with both serum carotenoids and NAFLD included sixteen microbial genera mainly in Ruminococcaceae and Veillonellaceae family,nineteen fecal metabolites containing medium-chain fatty acids(MCFAs),bile acids,and carnitines,and sixteen serum metabolites belonging to organic acids and amino acids.The total carotenoids-related scores of significant microbial genera,fecal and serum metabolites mediated the carotenoids-NAFLD association by 8.72%,12.30%,and 16.83%(all P<0.05)for persistent NAFLD and 9.46%,8.74%,and 15.7%for incident-NAFLD,respectively.Conclusions:Our study reveals a beneficial association of serum carotenoids and incident and persistent NAFLD.The identified gut-liver axis biomarkers provided mechanistic linkage for the epidemiological association.
文摘Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalovirus （CMV） is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients.This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.Methods： Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated.GraphPad Prism version 5.013 （San Diego, CA, USA） was used to conduct statistical analysis.The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test.Significance between qualitative data was analyzed using Pearson＆#39;s Chi-squared test.The cut-offthresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic （ROC） curve analysis.Results： One hundred and forty-two patients had positive CMV viral load tests.Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic.The symptomatic group received higher doses ofprednisolone （PSL） and more frequently immunosuppressants than the asymptomatic group （P 〈 0.01）.The symptomatic group had lower lymphocyte counts, especially CD4＋ T-cells, than the asymptomatic group （P 〈 0.01）.By ROC curve analysis, when CD4＋ T-cell count was 〈0.39 ＆#215; 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection.The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients （P 〈 0.01;threshold viral loads： 1.75 ＆#215; 104 copies/ml）.Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts （P 〈 0.01）, including CD4＋ and CD8＋ T-cells （P 〈 0.0 l）.Conclusions： When CD4＋ T-cell count is 〈0.39 ＆#215; 109/L, patients are at high risk for pulmonary CMV infection.Patients are prone to be symptomatic with CMV-DNA load 〉1.75 ＆#215; 104 copies/ml.Lymphopenia （especially CD4＋ T-cells）, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.
基金the National Natural Science Foundation of China(82073529,81903316,81773416,and 82103826)Zhejiang Ten-thousand Talents Program(2019R52039)+3 种基金Zhejiang Provincial Natural Science Foundation of China(LQ21H260002)CHNS received funding from the National Institutes of Health(NIH)(R01HD30880,R01AG065357,P30DK056350,and R01HD38700)from 1989 to 2019was supported by the National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases(R01DK104371)the Carolina Population Center P2CHD050924,P30AG066615.The funders had no role in collecting data,study design,interpretation of data or the decision to submit the manuscript for publication.
文摘Background:Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes,but evidence from large human cohorts is lacking.This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations.Methods:We included 1430 participants from the Guangzhou Nutrition and Health Study(GNHS)with both gut microbiome and cognitive assessment data available as a discovery cohort,of whom 272 individuals provided fecal samples twice before cognitive assessment.We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit.Fecal 16S rRNA and shotgun metagenomic sequencing,tar-geted serum metabolomics,and cytokine measurements were performed in the GNHS.The validation analyses were conducted in an Alzheimer’s disease case-control study(replication study 1,n=90)and another community-based cohort(replication study 2,n=1300)with cross-sectional dataset.Results:We found protective associations of specific gut microbial genera(Odoribacter,Butyricimonas,and Bac-teroides)with cognitive impairment in both the discovery cohort and the replication study 1.Result of Bacteroides was further validated in the replication study 2.Odoribacter was positively associated with hippocampal volume(β,0.16;95%CI 0.06-0.26,P=0.002),which might be mediated by acetic acids.Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment.We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition.Conclusions:Our findings reveal that specific gut microbial features are closely associated with cognitive impair-ment and decreased hippocampal volume,which may play an important role in dementia development.
基金funded by the National Natural Science Foundation of China(Grant Nos.82073529,81903316,82073546,and 81773416)the Zhejiang Ten-thousand Talents Program(Grant No.2019R52039)+1 种基金the 5010 Program for Clinical Researches(Grant No.2007032)of the Sun Yat-sen University(Guangzhou,China)the National Key R&D Program of China(Grant Nos.2021YFA1301602,2021YFA1301601,2021YFA1301603,and 2020YFE0202200).
文摘The use of statins as the primary therapy for reducing low-density lipoprotein cholesterol has raised concerns regarding their potential side effects in increasing the risk of type 2 diabetes(T2D).However,the underlying mechanism remains largely unknown.In this study,we utilized multi-omics molecular signatures to unravel the etiology of statin-induced T2D.Through systematic screening of 102 gut microbial features,40 blood metabolites,and 131 circulating proteins in East Asians and Europeans,we identified a set of blood metabolites and proteins potentially influenced by genetically proxied statin use.Notably,Mendelian randomization analyses provided evidence that elevated circulating levels of gastric inhibitory polypeptide(GIP)were associated with an increased risk of T2D.This association between genetically proxied statin use and GIP was consistently observed across East Asian and European populations,highlighting the pivotal role of GIP in modulating the risks of statin-induced T2D.Furthermore,this study established an extensive atlas of multi-omics molecular signatures associated with statin-induced T2D,offering valuable insights for prioritizing intervention targets.
