Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic ski...Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.展开更多
BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte pheno...BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.展开更多
Lithium-sulfur batteries(LSBs)have already developed into one of the most promising new-generation high-energy density electrochemical energy storage systems with outstanding features including high-energy density,low...Lithium-sulfur batteries(LSBs)have already developed into one of the most promising new-generation high-energy density electrochemical energy storage systems with outstanding features including high-energy density,low cost,and environmental friendliness.However,the development and commercialization path of LSBs still presents significant limitations and challenges,particularly the notorious shuttle effect triggered by soluble longchain lithium polysulfides(LiPSs),which inevitably leads to low utilization of cathode active sulfur and high battery capacity degradation,short cycle life,etc.Substantial research efforts have been conducted to develop various sulfur host materials capable of effectively restricting the shuttle effect.This review firstly introduces the fundamental electrochemical aspects of LSBs,followed by a comprehensive analysis of the mechanism underlying the shuttle effect in Li–S batteries and its profound influence on various battery components as well as the overall battery performance.Subsequently,recent advances and strategies are systematically reviewed,including physical confinement,chemisorption,and catalytic conversion of sulfur hosts for restricting LiPSs shuttle effects.The interplay mechanisms of sulfur hosts and LiPSs are discussed in detail and the structural advantages of different host materials are highlighted.Furthermore,key insights for the rational design of advanced host materials for LSBs are provided,and the upcoming challenges and the prospects for sulfur host materials in lithium-sulfur batteries are also explored.展开更多
Selenium(Se)is a promising cathode material for lithium batteries due to its high volumetric energy density(2528 Wh·L^(-1)).However,its practical application is restricted by rapid capacity fading resulting from ...Selenium(Se)is a promising cathode material for lithium batteries due to its high volumetric energy density(2528 Wh·L^(-1)).However,its practical application is restricted by rapid capacity fading resulting from the shuttle effect and slow reaction kinetics.Herein,a N/Co co-doped three-dimensional porous carbon(Co-NC)is prepared and used as Se host for lithium-selenium batteries(LSeBs).Co-NC displays a high specific surface area of1201 m^(2)·g^(-1)which benefits from N and Co doping.The N and Co not only enhance the electrical conductivity of porous carbon but also possess an adsorption effect on polyselenide.Thus,Se/Co-NC electrode exhibits excellent cycling performance(a stable specific capacity of 480 mAh·g^(-1)after 200 cycles at 1.0C with a much lowcapacity decay of 0.028%per cycle)and outstanding rate performance(a high specific capacity of 414 mAh·g^(-1)at5.0C).This work inspires highly stable Se cathode design for LSeBs.展开更多
Since Co_(2)VO_(4) possesses a solid spinel structure and a high degree of stability,it has gained interest as a possible anode material for sodium-ion batteries.However,the application of this electrode material is s...Since Co_(2)VO_(4) possesses a solid spinel structure and a high degree of stability,it has gained interest as a possible anode material for sodium-ion batteries.However,the application of this electrode material is still hampered by its poor electrical conductivity and severe volume expansion.Uniform Co_(2)VO_(4) nanoparticles(CVO)were grown on carbon nanotubes(CNTs)by a simple solvothermal method to form string-like conductive networks(CVO/CNTs).The flexible and highly conductive three-dimensional(3D)carbon nano tubes and small-sized CVO NPs can enhance the rapid transport of electrons,thereby enhancing the conductivity of the composite.String-like conductive network structures have a larger specific surface area,enhancing electron/ion transmission by fully contacting the electrolyte.The findings demonstrate the superior Na^(+)storing capability of the CVO/CNTs composite.The battery has a great rate performance(148.2 mAh·g^(-1)at 5 A·g^(-1))and outstanding long-term cycling performance(147.3 mAh·g^(-1)after 1000 cycles at 1A·g^(-1)).In high-rate,long-cycle sodium-ion batteries,CVO/CNTs composites offer a wide range of possible applications.展开更多
Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FA...Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FAM46C)is closely related with the occurrence and progression of MM.Recently,FAM46C has been identified as a non-canonical poly(A)polymerase(PAP)that functions as a tumor suppressor in MM.This study aimed to elucidate the structural features of this novel non-canonical PAP and how MM-related mutations affect the structural and biochemical properties of FAM46C,eventually advancing our understandings towards FAM46C mutation-related MM occurrence.Methods:We purified and crystallized a mammalian FAM46C construct,and solved its structure.Next,we characterized the property of FAM46C as a PAP through a combination of structural analysis,site-directed mutagenesis and biochemical assays,and by comparison with its homolog FAM46B.Finally,we structurally analyzed MM-related FAM46C mutations and tested the enzymatic activity of corresponding mutants.Results:We determined the crystal structure of a mammalian FAM46C protein at 2.35 A,and confirmed that FAM46C preferentially consumed adenosine triphosphate(ATP)and extended A-rich RNA substrates.FAM46C showed a weaker PAP activity than its homolog FAM46B,and this difference was largely dependent on the residue variance at particular sites.Of them,residues at positions 77,290,and 298 of mouse FAM46C weremost important for the divergence in enzymatic activity.Among the MM-associated FAM46C mutants,those residing at the catalytic site(D90G and D90H)or putative RNA-binding site(I155L,S156F,D182Y,F184L,Y247V,andM270V)showed abolished or compromised PAP activity of FAM46C,while N72A and S248A did not severely affect the PAP activity.FAM46C mutants D90G,D90H,I155L,S156F,F184L,Y247V,and M270V had significantly lower inhibitory effect on apoptosis of RPMI-8226 cells as compared to wild-type FAM46C.Conclusions:FAM46C is a prokaryotic-like PAP with preference forA-richRNA substrates,and showed distinct enzymatic efficiency with its homolog FAM46B.The MM-related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.展开更多
基金supported by the Key Program of Yunnan Applied Basic Research Project(202301AS070036)Outstanding Youth Program of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202301AY070001-301)+2 种基金First-Class Discipline Team of Skin&Mucosal Regenerative Medicine of Kunming Medical University(2024XKTDTS10)National Natural Science Foundation of China(32360138,32301054,32060212,82371567)Program of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202301AY070001-012,202101AY070001-006,202301AY070001-198,202101AY070001-035,202101AY070001-036,202401AY070001-028,202401AY070001-068)。
文摘Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.
基金the National Natural Science Foundation of China,No.82270649.
文摘BACKGROUND Liver cirrhosis is a progressive hepatic disease whose immunological basis has attracted increasing attention.However,it remains unclear whether a concrete causal association exists between immunocyte phenotypes and liver cirrhosis.AIM To explore the concrete causal relationships between immunocyte phenotypes and liver cirrhosis through a mendelian randomization(MR)study.METHODS Data on 731 immunocyte phenotypes were obtained from genome-wide assoc-iation studies.Liver cirrhosis data were derived from the Finn Gen dataset,which included 214403 individuals of European ancestry.We used inverse variable weighting as the primary analysis method to assess the causal relationship.Sensitivity analyses were conducted to evaluate heterogeneity and horizontal pleiotropy.RESULTS The MR analysis demonstrated that 11 immune cell phenotypes have a positive association with liver cirrhosis[P<0.05,odds ratio(OR)>1]and that 9 immu-nocyte phenotypes were negatively correlated with liver cirrhosis(P<0.05,OR<1).Liver cirrhosis was positively linked to 9 immune cell phenotypes(P<0.05,OR>1)and negatively linked to 10 immune cell phenotypes(P<0.05;OR<1).None of these associations showed heterogeneity or horizontally pleiotropy(P>0.05).CONCLUSION This bidirectional two-sample MR study demonstrated a concrete causal association between immunocyte phenotypes and liver cirrhosis.These findings offer new directions for the treatment of liver cirrhosis.
基金supported by the National Natural Science Foundation of China(Nos.52105575&52205593)the Fundamental Research Funds for the Central Universities(No.QTZX23063)+1 种基金the Proof of Concept Foundation of Xidian University Hangzhou Institute of Technology(Nos.GNYZ2023YL0302&GNYZ2023QC0401)the Aeronautical Science Foundation of China(No.2022Z073081001)。
文摘Lithium-sulfur batteries(LSBs)have already developed into one of the most promising new-generation high-energy density electrochemical energy storage systems with outstanding features including high-energy density,low cost,and environmental friendliness.However,the development and commercialization path of LSBs still presents significant limitations and challenges,particularly the notorious shuttle effect triggered by soluble longchain lithium polysulfides(LiPSs),which inevitably leads to low utilization of cathode active sulfur and high battery capacity degradation,short cycle life,etc.Substantial research efforts have been conducted to develop various sulfur host materials capable of effectively restricting the shuttle effect.This review firstly introduces the fundamental electrochemical aspects of LSBs,followed by a comprehensive analysis of the mechanism underlying the shuttle effect in Li–S batteries and its profound influence on various battery components as well as the overall battery performance.Subsequently,recent advances and strategies are systematically reviewed,including physical confinement,chemisorption,and catalytic conversion of sulfur hosts for restricting LiPSs shuttle effects.The interplay mechanisms of sulfur hosts and LiPSs are discussed in detail and the structural advantages of different host materials are highlighted.Furthermore,key insights for the rational design of advanced host materials for LSBs are provided,and the upcoming challenges and the prospects for sulfur host materials in lithium-sulfur batteries are also explored.
基金financially supported by the National Key Research and Development Project(No.2018YFE0124800)the Research Project of Education Department of Jiangxi Province(No.GJJ190310)Natural Science Foundation of Jiangxi Province(No.20212BAB204006)。
文摘Selenium(Se)is a promising cathode material for lithium batteries due to its high volumetric energy density(2528 Wh·L^(-1)).However,its practical application is restricted by rapid capacity fading resulting from the shuttle effect and slow reaction kinetics.Herein,a N/Co co-doped three-dimensional porous carbon(Co-NC)is prepared and used as Se host for lithium-selenium batteries(LSeBs).Co-NC displays a high specific surface area of1201 m^(2)·g^(-1)which benefits from N and Co doping.The N and Co not only enhance the electrical conductivity of porous carbon but also possess an adsorption effect on polyselenide.Thus,Se/Co-NC electrode exhibits excellent cycling performance(a stable specific capacity of 480 mAh·g^(-1)after 200 cycles at 1.0C with a much lowcapacity decay of 0.028%per cycle)and outstanding rate performance(a high specific capacity of 414 mAh·g^(-1)at5.0C).This work inspires highly stable Se cathode design for LSeBs.
基金financially supported by the National Key Research and Development Project (No.2018YFE0124800)the National Nature Science Foundation of China (No.51702157)。
文摘Since Co_(2)VO_(4) possesses a solid spinel structure and a high degree of stability,it has gained interest as a possible anode material for sodium-ion batteries.However,the application of this electrode material is still hampered by its poor electrical conductivity and severe volume expansion.Uniform Co_(2)VO_(4) nanoparticles(CVO)were grown on carbon nanotubes(CNTs)by a simple solvothermal method to form string-like conductive networks(CVO/CNTs).The flexible and highly conductive three-dimensional(3D)carbon nano tubes and small-sized CVO NPs can enhance the rapid transport of electrons,thereby enhancing the conductivity of the composite.String-like conductive network structures have a larger specific surface area,enhancing electron/ion transmission by fully contacting the electrolyte.The findings demonstrate the superior Na^(+)storing capability of the CVO/CNTs composite.The battery has a great rate performance(148.2 mAh·g^(-1)at 5 A·g^(-1))and outstanding long-term cycling performance(147.3 mAh·g^(-1)after 1000 cycles at 1A·g^(-1)).In high-rate,long-cycle sodium-ion batteries,CVO/CNTs composites offer a wide range of possible applications.
基金National Key R&D Program of China,Grant/Award Number:2018YFA0508300National Natural Science Foundation of China,Grant/Award Numbers:81772977,31722016,31470729+1 种基金Natural Science Foundation of Guangdong Province,Grant/Award Numbers:2019TX05Y598,2014TQ01R584,2014A030312015Innovative Team Program of Guangzhou Regenerative Medicine and Health Guangdong Laboratory,Grant/Award Number:2018GZR110103002。
文摘Background:Multiple myeloma(MM)is a hematologic malignancy characterized by the accumulation of aberrant plasma cells within the bone marrow.The high frequent mutation of family with sequence similarity 46,member C(FAM46C)is closely related with the occurrence and progression of MM.Recently,FAM46C has been identified as a non-canonical poly(A)polymerase(PAP)that functions as a tumor suppressor in MM.This study aimed to elucidate the structural features of this novel non-canonical PAP and how MM-related mutations affect the structural and biochemical properties of FAM46C,eventually advancing our understandings towards FAM46C mutation-related MM occurrence.Methods:We purified and crystallized a mammalian FAM46C construct,and solved its structure.Next,we characterized the property of FAM46C as a PAP through a combination of structural analysis,site-directed mutagenesis and biochemical assays,and by comparison with its homolog FAM46B.Finally,we structurally analyzed MM-related FAM46C mutations and tested the enzymatic activity of corresponding mutants.Results:We determined the crystal structure of a mammalian FAM46C protein at 2.35 A,and confirmed that FAM46C preferentially consumed adenosine triphosphate(ATP)and extended A-rich RNA substrates.FAM46C showed a weaker PAP activity than its homolog FAM46B,and this difference was largely dependent on the residue variance at particular sites.Of them,residues at positions 77,290,and 298 of mouse FAM46C weremost important for the divergence in enzymatic activity.Among the MM-associated FAM46C mutants,those residing at the catalytic site(D90G and D90H)or putative RNA-binding site(I155L,S156F,D182Y,F184L,Y247V,andM270V)showed abolished or compromised PAP activity of FAM46C,while N72A and S248A did not severely affect the PAP activity.FAM46C mutants D90G,D90H,I155L,S156F,F184L,Y247V,and M270V had significantly lower inhibitory effect on apoptosis of RPMI-8226 cells as compared to wild-type FAM46C.Conclusions:FAM46C is a prokaryotic-like PAP with preference forA-richRNA substrates,and showed distinct enzymatic efficiency with its homolog FAM46B.The MM-related missense mutations of FAM46C lead to various structural and biochemical outcomes to the protein.
