Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was...Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.展开更多
Targeted protein degrader has emerged as a transformative therapeutic technology,offering a novel modality to address previously intractable drug targets and enabling innovative approaches to disease treatment1.Unlike...Targeted protein degrader has emerged as a transformative therapeutic technology,offering a novel modality to address previously intractable drug targets and enabling innovative approaches to disease treatment1.Unlike conventional small-molecule drugs that function through occupancy-driven mechanisms,targeted protein degradation(TPD)employs an event-driven pharmacological strategy by harnessing the ubiquitin–proteasome system(UPS)and lysosomal degradation pathways2.展开更多
A Riemannian gradient descent algorithm and a truncated variant are presented to solve systems of phaseless equations|Ax|^(2)=y.The algorithms are developed by exploiting the inherent low rank structure of the problem...A Riemannian gradient descent algorithm and a truncated variant are presented to solve systems of phaseless equations|Ax|^(2)=y.The algorithms are developed by exploiting the inherent low rank structure of the problem based on the embedded manifold of rank-1 positive semidefinite matrices.Theoretical recovery guarantee has been established for the truncated variant,showing that the algorithm is able to achieve successful recovery when the number of equations is proportional to the number of unknowns.Two key ingredients in the analysis are the restricted well conditioned property and the restricted weak correlation property of the associated truncated linear operator.Empirical evaluations show that our algorithms are competitive with other state-of-the-art first order nonconvex approaches with provable guarantees.展开更多
Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue...Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue,enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment.This approach has shown significant improvements in bioavailability and patient compliance.Moreover,the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix,along with controllable drug release,exceptional swelling ability,hydrophilicity,and biocompatibility.These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts.In addition,the incorporation of nanoparticles(NPs)has been shown to improve the solubility of hydrophobic drugs,enhance mechanical properties,enable intelligent drug release,and facilitate precise targeting of HMN.The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings,as well as offer valuable insights for biomaterial development.This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications.We also analyze the mechanisms,advantages,challenges,and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.展开更多
Poly(α-L-lysine)(PLL)is a class of water-soluble,cationic biopolymer composed ofα-L-lysine structural units.The previous decade witnessed tremendous progress in the synthesis and biomedical applications of PLL and i...Poly(α-L-lysine)(PLL)is a class of water-soluble,cationic biopolymer composed ofα-L-lysine structural units.The previous decade witnessed tremendous progress in the synthesis and biomedical applications of PLL and its composites.PLL-based polymers and copolymers,till date,have been extensively explored in the contexts such as antibacterial agents,gene/drug/protein delivery systems,bio-sensing,bio-imaging,and tissue engineering.This review aims to summarize the recent advances in PLL-based nanomaterials in these biomedical fields over the last decade.The review first describes the synthesis of PLL and its derivatives,followed by the main text of their recent biomedical applications and translational studies.Finally,the challenges and perspectives of PLL-based nanomaterials in biomedical fields are addressed.展开更多
Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity.Since simultaneously enhancing the activ...Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity.Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches,we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects.Herein,a surface-nanoengineered antimicrobial liposome(SNAL)is developed with the morphological features of enveloped viruses,including a moderate size range,lipid-based membrane structure,and highly lipopeptide-enriched bilayer surface.The SNAL possesses virus-like infection to bacterial cells,which can mediate high-efficiency and high-selectivity bacteria binding,rapidly attack and invade bacteria via plasma membrane fusion pathway,and induce a local“burst”release of lipopeptide to produce irreversible damage of cell membrane.Remarkably,viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations(1.6-6.3μg mL1),high bactericidal efficiency of>99%within 2 h,>10-fold enhanced selectivity over free lipopeptide,99.8%reduction in skin MRSA load after a single treatment,and negligible toxicity.This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.展开更多
Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers.Although monoclonal antibodies are currently used as marketed drugs...Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers.Although monoclonal antibodies are currently used as marketed drugs,their large molecular weight,high cost of production and susceptibility to proteolysis could be a hurdle for long-term application.In this study,we reported a strategy for the development of artificial antibody based on y-AApeptides to target HER2 extracellular domain(ECD).To achieve this,we synthesized a one-bead-two-compound(OBTC)library containing 320,000 cyclic y-AApeptides,from which we identified a y-AApeptide,M-3-6,that tightly binds to HER2 selectively.Subsequently,we designed an antibody-like dimer of M-3-6,named M-3-6-D,which showed excellent binding affinity toward HER2 comparable to monoclonal antibodies.Intriguingly,M-3-6-D was completely resistant toward enzymatic degradation.In addition,it could effectively inhibit the phosphorylation of HER2,as well as the downstream signaling pathways of AKT and ERK.Furthermore,M-3-6-D also efficiently inhibited cell proliferation in vitro,and suppressed tumor growth in SKBR3 xenograft model in vivo,implying its therapeutic potential for the treatment of cancers.Its small molecular weight,antibody-like property,resistance to proteolysis,may enable it a new generation of artificial antibody surrogate.Furthermore,our strategy of artificial antibody surrogate based on dimers of cyclicγ-AApeptides could be applied to a myriad of disease-related receptor targets in future.展开更多
Since insulin,a natural peptide composed of 51 amino acids,was first isolated and commercialized in the 1920s,peptide drugs have greatly reshaped our modern drug discovery area^(1).To date,the total number of approved...Since insulin,a natural peptide composed of 51 amino acids,was first isolated and commercialized in the 1920s,peptide drugs have greatly reshaped our modern drug discovery area^(1).To date,the total number of approved peptide drugs for human use worldwide has exceeded 60^(2).Popular peptide drugs such as liraglutide(Victoza)^(2) and glucagon-like peptide 1(GLP-1)^(3) are the topselling drugs for type 2 diabetes.However,significant hurdles associated with natural peptide sequences as therapeutics,such as metabolic instability and,consequently,have low oral bioavailability and shorter half-life^(4),are still remaining.To overcome the limitations of natural peptides and further optimize their advantages,peptidomimetics emerged as an alternative strategy.展开更多
Peptides are increasingly important resources for biological and therapeutic development,however,their intrinsic susceptibility to proteolytic degradation represents a big hurdle.As a natural agonist for GLP-1R,glucag...Peptides are increasingly important resources for biological and therapeutic development,however,their intrinsic susceptibility to proteolytic degradation represents a big hurdle.As a natural agonist for GLP-1R,glucagon-like peptide 1(GLP-1)is of significant clinical interest for the treatment of type-2 diabetes mellitus,but its in vivo instability and short half-life have largely prevented its therapeutic application.Here,we describe the rational design of a series of a/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists.Certain GLP-1 hybrid analogues exhibited enhanced stability(t_(1/2)>14 days)compared to t_(1/2)(<1 day)of GLP-1 in the blood plasma and in vivo.These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment.Additionally,our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.展开更多
In quantitative susceptibility mapping(QSM),the background field removal is an essential data acquisition step because it has a significant effect on the restoration quality by generating a harmonic incompatibility in...In quantitative susceptibility mapping(QSM),the background field removal is an essential data acquisition step because it has a significant effect on the restoration quality by generating a harmonic incompatibility in the measured local field data.Even though the sparsity based first generation harmonic incompatibility removal(1GHIRE)model has achieved the performance gain over the traditional approaches,the 1GHIRE model has to be further improved as there is a basis mismatch underlying in numerically solving Poisson’s equation for the background removal.In this paper,we propose the second generation harmonic incompatibility removal(2GHIRE)model to reduce a basis mismatch,inspired by the balanced approach in the tight frame based image restoration.Experimental results shows the superiority of the proposed 2GHIRE model both in the restoration qualities and the computational efficiency.展开更多
Angiogenesis is a vital process in the event of various healthy and diseased conditions especially in the tumor metastatic pathway,and it is one of the key hallmarks of cancer cells^(1,2),therefore,angiogenesis inhibi...Angiogenesis is a vital process in the event of various healthy and diseased conditions especially in the tumor metastatic pathway,and it is one of the key hallmarks of cancer cells^(1,2),therefore,angiogenesis inhibitors are potential anti-cancer agents.However,silenced angiogenesis on the other hand could result in stroke,heart attack,and other cardiovascular diseases^(3).Yet,the precise manipulation of contradictory pro-angiogenic and anti-angiogenic signaling remains extremely challenging in both molecular biology and therapeutics.In the recent issue of J Am Chem Soc.展开更多
Cobalt oxide,as one of the most fascinating examples of correlated electronic system,exhibits several exotic transport characteristics,such as superconductivity,charge ordering,and topological frustration.In this stud...Cobalt oxide,as one of the most fascinating examples of correlated electronic system,exhibits several exotic transport characteristics,such as superconductivity,charge ordering,and topological frustration.In this study,we are reporting the observation of another intriguing transport phenomenon in calcium cobaltates.Specifically,under a large magnetic field of 7 T,we observed an anomalously enhanced thermal conductivity that was accompanied with a largely suppressed thermopower.This observation reveals a hitherto undiscovered correlation between the two transport factors.Within the premise of Heisenberg model,we have shown that the observed experimental results can be explained consistently only if the magnon excitation is taken into account.Our study offers an insight into the puzzling origin of large thermopower observed in layered cobaltates and provides a specific strategy for further optimization of thermopower.展开更多
NaxCoO_(2)was known 20 years ago as a unique example in which spin entropy dominates the thermoelectric behavior.Hitherto,however,little has been learned about how to manipulate the spin degree of freedom in thermoele...NaxCoO_(2)was known 20 years ago as a unique example in which spin entropy dominates the thermoelectric behavior.Hitherto,however,little has been learned about how to manipulate the spin degree of freedom in thermoelectrics.Here,we report the enhanced thermoelectric performance of GeMnTe_(2)by controlling the spin’s thermodynamic entropy.The anomalously large thermopower of GeMnTe_(2)is demonstrated to originate from the disordering of spin orientation under finite temperature.Based on the careful analysis of Heisenberg model,it is indicated that the spin-system entropy can be tuned by modifying the hybridization between Te-p and Mn-d orbitals.As a consequent strategy,Se doping enlarges the thermopower effectively,while neither carrier concentration nor band gap is affected.The measurement of magnetic susceptibility provides a solid evidence for the inherent relationship between the spin’s thermodynamic entropy and thermopower.By further introducing Bi doing,the maximum ZT in Ge_(0.94)Bi_(0.06)MnTe_(1.94)Se_(0.06)reaches 1.4 at 840 K,which is 45%higher than the previous report of Bi-doped GeMnTe_(2).This work reveals the high thermoelectric performance of GeMnTe_(2)and also provides an insightful understanding of the spin degree of freedom in thermoelectrics.展开更多
基金supported by the 2022 Natural Science Foundation of Fujian Province(No.2022J011486).
文摘Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain unclear.Methods:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was assessed.LUAD cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor growth.The downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)database.Additionally,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD cells.Results:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell lines.The silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of LUAD.Additionally,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its expression.Further assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 overexpression.Conclusions:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.
文摘Targeted protein degrader has emerged as a transformative therapeutic technology,offering a novel modality to address previously intractable drug targets and enabling innovative approaches to disease treatment1.Unlike conventional small-molecule drugs that function through occupancy-driven mechanisms,targeted protein degradation(TPD)employs an event-driven pharmacological strategy by harnessing the ubiquitin–proteasome system(UPS)and lysosomal degradation pathways2.
文摘A Riemannian gradient descent algorithm and a truncated variant are presented to solve systems of phaseless equations|Ax|^(2)=y.The algorithms are developed by exploiting the inherent low rank structure of the problem based on the embedded manifold of rank-1 positive semidefinite matrices.Theoretical recovery guarantee has been established for the truncated variant,showing that the algorithm is able to achieve successful recovery when the number of equations is proportional to the number of unknowns.Two key ingredients in the analysis are the restricted well conditioned property and the restricted weak correlation property of the associated truncated linear operator.Empirical evaluations show that our algorithms are competitive with other state-of-the-art first order nonconvex approaches with provable guarantees.
基金supported by China Postdoctoral Science Foundation(2023M740789)Guangdong Basic and Applied Basic Research Foundation(2023A1515110441,2024A1515011248,2024A1515030104)+1 种基金Guangzhou S&T Programme Foundation(202206010051,202205110009)Young Talent Support Project of Guangzhou Association for S&T(QT20220101041).
文摘Nanoparticles-incorporated hydrogel microneedles(NPs-HMN)have attracted significant attention due to their exceptional biomedical applications.The arrayed needle tips of NPsHMN effectively penetrate the skin or tissue,enabling minimally invasive and painless delivery of therapeutic molecules into the tissue microenvironment.This approach has shown significant improvements in bioavailability and patient compliance.Moreover,the functionalized hydrogel materials of NPs-HMN exhibit a three-dimensional network structure resembling the extracellular matrix,along with controllable drug release,exceptional swelling ability,hydrophilicity,and biocompatibility.These characteristics broaden the potential applications of HMN in therapeutic and biosensing contexts.In addition,the incorporation of nanoparticles(NPs)has been shown to improve the solubility of hydrophobic drugs,enhance mechanical properties,enable intelligent drug release,and facilitate precise targeting of HMN.The versatility and diversity of treatment options afforded by NPs-HMN contribute to significant advancements in animal models and clinical settings,as well as offer valuable insights for biomaterial development.This review provides a comprehensive examination of the fabrication strategies of NPs-HMN and their recent advancements in biomedical applications.We also analyze the mechanisms,advantages,challenges,and future prospects of this system in enhancing drug delivery efficiency to provide theoretical references for further breakthroughs in novel delivery platforms.
基金This work was financially supported by the National Natural Science Foundation of China,China(No.81803467)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant,Hong Kong(2020LKSFG18B,2020LKSFG02E)the grant for Key Disciplinary Project of Clinical Medicine under the Guangdong High-Level University Development Program,Guangdong,China(002-18120314,002-18120311).
文摘Poly(α-L-lysine)(PLL)is a class of water-soluble,cationic biopolymer composed ofα-L-lysine structural units.The previous decade witnessed tremendous progress in the synthesis and biomedical applications of PLL and its composites.PLL-based polymers and copolymers,till date,have been extensively explored in the contexts such as antibacterial agents,gene/drug/protein delivery systems,bio-sensing,bio-imaging,and tissue engineering.This review aims to summarize the recent advances in PLL-based nanomaterials in these biomedical fields over the last decade.The review first describes the synthesis of PLL and its derivatives,followed by the main text of their recent biomedical applications and translational studies.Finally,the challenges and perspectives of PLL-based nanomaterials in biomedical fields are addressed.
基金This work was financially supported by the National Natural Science Foundation of China(No.81803467,81773660)the Research and Development Plan for Key Areas in Guangdong Province(No.2019B020204002).
文摘Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity.Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches,we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects.Herein,a surface-nanoengineered antimicrobial liposome(SNAL)is developed with the morphological features of enveloped viruses,including a moderate size range,lipid-based membrane structure,and highly lipopeptide-enriched bilayer surface.The SNAL possesses virus-like infection to bacterial cells,which can mediate high-efficiency and high-selectivity bacteria binding,rapidly attack and invade bacteria via plasma membrane fusion pathway,and induce a local“burst”release of lipopeptide to produce irreversible damage of cell membrane.Remarkably,viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations(1.6-6.3μg mL1),high bactericidal efficiency of>99%within 2 h,>10-fold enhanced selectivity over free lipopeptide,99.8%reduction in skin MRSA load after a single treatment,and negligible toxicity.This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
基金supported by USF start-up fund(Jianfeng Cai)supported by the National Natural Science Foundation of China(Qi Li,81520108031,81573764,81774095)+1 种基金a Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai(Qi Li,2017BR031,China)Three-years Plan for the Development of T.C.M(ZY(2018e2020)-CCCX-2003-03,China)
文摘Inhibition of human epidermal growth factor receptor 2 mediated cell signaling pathway is an important therapeutic strategy for HER2-positive cancers.Although monoclonal antibodies are currently used as marketed drugs,their large molecular weight,high cost of production and susceptibility to proteolysis could be a hurdle for long-term application.In this study,we reported a strategy for the development of artificial antibody based on y-AApeptides to target HER2 extracellular domain(ECD).To achieve this,we synthesized a one-bead-two-compound(OBTC)library containing 320,000 cyclic y-AApeptides,from which we identified a y-AApeptide,M-3-6,that tightly binds to HER2 selectively.Subsequently,we designed an antibody-like dimer of M-3-6,named M-3-6-D,which showed excellent binding affinity toward HER2 comparable to monoclonal antibodies.Intriguingly,M-3-6-D was completely resistant toward enzymatic degradation.In addition,it could effectively inhibit the phosphorylation of HER2,as well as the downstream signaling pathways of AKT and ERK.Furthermore,M-3-6-D also efficiently inhibited cell proliferation in vitro,and suppressed tumor growth in SKBR3 xenograft model in vivo,implying its therapeutic potential for the treatment of cancers.Its small molecular weight,antibody-like property,resistance to proteolysis,may enable it a new generation of artificial antibody surrogate.Furthermore,our strategy of artificial antibody surrogate based on dimers of cyclicγ-AApeptides could be applied to a myriad of disease-related receptor targets in future.
文摘Since insulin,a natural peptide composed of 51 amino acids,was first isolated and commercialized in the 1920s,peptide drugs have greatly reshaped our modern drug discovery area^(1).To date,the total number of approved peptide drugs for human use worldwide has exceeded 60^(2).Popular peptide drugs such as liraglutide(Victoza)^(2) and glucagon-like peptide 1(GLP-1)^(3) are the topselling drugs for type 2 diabetes.However,significant hurdles associated with natural peptide sequences as therapeutics,such as metabolic instability and,consequently,have low oral bioavailability and shorter half-life^(4),are still remaining.To overcome the limitations of natural peptides and further optimize their advantages,peptidomimetics emerged as an alternative strategy.
基金supported by NIH R01AI152416(to Jianfeng Cai,USA)NIH R01 AG056569(to Jianfeng Cai,USA)。
文摘Peptides are increasingly important resources for biological and therapeutic development,however,their intrinsic susceptibility to proteolytic degradation represents a big hurdle.As a natural agonist for GLP-1R,glucagon-like peptide 1(GLP-1)is of significant clinical interest for the treatment of type-2 diabetes mellitus,but its in vivo instability and short half-life have largely prevented its therapeutic application.Here,we describe the rational design of a series of a/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists.Certain GLP-1 hybrid analogues exhibited enhanced stability(t_(1/2)>14 days)compared to t_(1/2)(<1 day)of GLP-1 in the blood plasma and in vivo.These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment.Additionally,our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.
基金The research of the first author is supported in part by the NSFC Youth Program 11901338The research of the second author is supported by the Hong Kong Research Grant Council(HKRGC)GRF 16306317 and 16309219+2 种基金The research of the third author is supported by the NSFC Youth Program 11901436 and the Fundamental Research Program of Science and Technology Commission of Shanghai Municipality(20JC1413500)The research of the fourth author is supported by the NSFC grant 11831002The research of the fifth author is supported by the National Natural Science Foundation of China Youth Program grant 11801088 and the Shanghai Sailing Program(18YF1401600).
文摘In quantitative susceptibility mapping(QSM),the background field removal is an essential data acquisition step because it has a significant effect on the restoration quality by generating a harmonic incompatibility in the measured local field data.Even though the sparsity based first generation harmonic incompatibility removal(1GHIRE)model has achieved the performance gain over the traditional approaches,the 1GHIRE model has to be further improved as there is a basis mismatch underlying in numerically solving Poisson’s equation for the background removal.In this paper,we propose the second generation harmonic incompatibility removal(2GHIRE)model to reduce a basis mismatch,inspired by the balanced approach in the tight frame based image restoration.Experimental results shows the superiority of the proposed 2GHIRE model both in the restoration qualities and the computational efficiency.
文摘Angiogenesis is a vital process in the event of various healthy and diseased conditions especially in the tumor metastatic pathway,and it is one of the key hallmarks of cancer cells^(1,2),therefore,angiogenesis inhibitors are potential anti-cancer agents.However,silenced angiogenesis on the other hand could result in stroke,heart attack,and other cardiovascular diseases^(3).Yet,the precise manipulation of contradictory pro-angiogenic and anti-angiogenic signaling remains extremely challenging in both molecular biology and therapeutics.In the recent issue of J Am Chem Soc.
基金the supports from National Natural Science Foundation of China through grant#52002383Ningbo Municipal Bureau of Science and Technology through grant#202003N4365+1 种基金supported by National Natural Science Foundation of China(Grant No.52001012)Beijing Natural Science Foundation(Grant No.2214070).
文摘Cobalt oxide,as one of the most fascinating examples of correlated electronic system,exhibits several exotic transport characteristics,such as superconductivity,charge ordering,and topological frustration.In this study,we are reporting the observation of another intriguing transport phenomenon in calcium cobaltates.Specifically,under a large magnetic field of 7 T,we observed an anomalously enhanced thermal conductivity that was accompanied with a largely suppressed thermopower.This observation reveals a hitherto undiscovered correlation between the two transport factors.Within the premise of Heisenberg model,we have shown that the observed experimental results can be explained consistently only if the magnon excitation is taken into account.Our study offers an insight into the puzzling origin of large thermopower observed in layered cobaltates and provides a specific strategy for further optimization of thermopower.
基金supported by the National Natural Science Foun-dation of China(21875273 and 51872301)Natural Science Foundation of Zhejiang Province(LY18A040008)Youth Innovation Promotion Association of CAS(2019298).
文摘NaxCoO_(2)was known 20 years ago as a unique example in which spin entropy dominates the thermoelectric behavior.Hitherto,however,little has been learned about how to manipulate the spin degree of freedom in thermoelectrics.Here,we report the enhanced thermoelectric performance of GeMnTe_(2)by controlling the spin’s thermodynamic entropy.The anomalously large thermopower of GeMnTe_(2)is demonstrated to originate from the disordering of spin orientation under finite temperature.Based on the careful analysis of Heisenberg model,it is indicated that the spin-system entropy can be tuned by modifying the hybridization between Te-p and Mn-d orbitals.As a consequent strategy,Se doping enlarges the thermopower effectively,while neither carrier concentration nor band gap is affected.The measurement of magnetic susceptibility provides a solid evidence for the inherent relationship between the spin’s thermodynamic entropy and thermopower.By further introducing Bi doing,the maximum ZT in Ge_(0.94)Bi_(0.06)MnTe_(1.94)Se_(0.06)reaches 1.4 at 840 K,which is 45%higher than the previous report of Bi-doped GeMnTe_(2).This work reveals the high thermoelectric performance of GeMnTe_(2)and also provides an insightful understanding of the spin degree of freedom in thermoelectrics.
