Because China is becoming an aging society,the incidence of diabetes and diabetic foot have been increasing.Diabetic foot has become one of the main health-related killers due to its high disability and mortality rate...Because China is becoming an aging society,the incidence of diabetes and diabetic foot have been increasing.Diabetic foot has become one of the main health-related killers due to its high disability and mortality rates.Negative pressure wound therapy(NPWT)is one of the most effective techniques for the treatment of diabetic foot wounds and great progress,both in terms of research and its clinical application,has been made in the last 20 years of its development.However,due to the complex pathogenesis and management of diabetic foot,irregular application of NPWT often leads to complications,such as infection,bleeding and necrosis,that seriously affect its treatment outcomes.In 2020,under the leadership of Burns,Trauma and Tissue Repair Committee of the Cross-Straits Medicine Exchange Association,the writing group for‘Consensus on the application of negative pressure wound therapy of diabetic foot wounds’was established with the participation of scholars from the specialized areas of burns,endocrinology,vascular surgery,orthopedics and wound repair.Drawing on evidence-based practice suggested by the latest clinical research,this consensus proposes the best clinical practice guidelines for the application and prognostic evaluation of NPWT for diabetic foot.The consensus aims to support the formation of standardized treatment schemes that clinicians can refer to when treating cases of diabetic foot.展开更多
Three new sesquiterpene glycosides,named codonopsesquilosides A C(1 3),were isolated from an aqueous extract of the dried roots of Codonopsis pilosula.Their structures including absolute configurations were determined...Three new sesquiterpene glycosides,named codonopsesquilosides A C(1 3),were isolated from an aqueous extract of the dried roots of Codonopsis pilosula.Their structures including absolute configurations were determined by spectroscopic and chemical methods.These glycosides are categorized as C_(15) carotenoid(1),gymnomitrane(2),and eudesmane(3)types of sesquiterpenoids,respectively.Compound 1 is the first diglycoside of C_(15) carotenoids to be reported.Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants.The absolute configurations were supported by comparison of the experimental circular dichroism(CD)spectra with the calculated electronic CD(ECD)spectra of 13,their aglycones,and model compounds based on quantummechanical time-dependent density functional theory.The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids,as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed.展开更多
Four new acetylenes (1-4) and one new unsaturated to-hydroxy fatty acid (5), together with known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spect...Four new acetylenes (1-4) and one new unsaturated to-hydroxy fatty acid (5), together with known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradocenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of I. was assigned by comparison of the experimental circular dichroism (Cl)) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher's method based on the MPA determination rule of AoRs values for diols. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier By.展开更多
Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their struct...Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.展开更多
Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A-F(1–6), were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute configurations wer...Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A-F(1–6), were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis and enzyme hydrolysis. The validity of Δδ_(C8-C7) values to distinguish threo and erythro aryl glycerol units and Cotton effects at 235±5 nm to determine absolute configurations at C-8 in 1–6 and their aglycones(1a–6a) are discussed.展开更多
Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(—)-1 and(+)-1], phaitanthrin A and epiphaitanthrin A [(—)-2 and(+)-2], a...Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(—)-1 and(+)-1], phaitanthrin A and epiphaitanthrin A [(—)-2 and(+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(—)-3and(+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column.Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism(ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A[(—)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.展开更多
The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 3...The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.展开更多
Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in c...Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.展开更多
SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis ...SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a"spike protein-CD147-CyPA signaling axis":Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.展开更多
基金Research on in situ skin repair and regeneration based on micro-tissue engineering technology and 3D printing.(The National Key R&D Program of China,Grant Number 2019YFA0110503).The study on natural living micro-amniotic scaffolds to dynamic regulate immune inflammation and reconstruct wound repairing.(National Natural Science Foundation of China,Grant Number 81971836).The systemic study of miR-23b_24-1 cluster in the prevention and treatment of MODS caused by sepsis after burns.(National Natural Science Foundation of China,Grant Number 81930057).The experimental study on regulating the immune inflammatory microenvironment of burn wounds and promoting repair and regeneration based on micro-tissue engineering technology.(National Natural Science Foundation of China,Grant Number 81871559).
文摘Because China is becoming an aging society,the incidence of diabetes and diabetic foot have been increasing.Diabetic foot has become one of the main health-related killers due to its high disability and mortality rates.Negative pressure wound therapy(NPWT)is one of the most effective techniques for the treatment of diabetic foot wounds and great progress,both in terms of research and its clinical application,has been made in the last 20 years of its development.However,due to the complex pathogenesis and management of diabetic foot,irregular application of NPWT often leads to complications,such as infection,bleeding and necrosis,that seriously affect its treatment outcomes.In 2020,under the leadership of Burns,Trauma and Tissue Repair Committee of the Cross-Straits Medicine Exchange Association,the writing group for‘Consensus on the application of negative pressure wound therapy of diabetic foot wounds’was established with the participation of scholars from the specialized areas of burns,endocrinology,vascular surgery,orthopedics and wound repair.Drawing on evidence-based practice suggested by the latest clinical research,this consensus proposes the best clinical practice guidelines for the application and prognostic evaluation of NPWT for diabetic foot.The consensus aims to support the formation of standardized treatment schemes that clinicians can refer to when treating cases of diabetic foot.
基金Financial support from the National Natural Sciences Foundation of China(NNSFC,Grant Nos.30825044 and 20932007)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,Grant No.IRT1007)the National Science and Technology Project of China(Nos.2012ZX09301002-002 and 2011ZX09307-002-01)
文摘Three new sesquiterpene glycosides,named codonopsesquilosides A C(1 3),were isolated from an aqueous extract of the dried roots of Codonopsis pilosula.Their structures including absolute configurations were determined by spectroscopic and chemical methods.These glycosides are categorized as C_(15) carotenoid(1),gymnomitrane(2),and eudesmane(3)types of sesquiterpenoids,respectively.Compound 1 is the first diglycoside of C_(15) carotenoids to be reported.Compound 2 represents the second reported example of gymnomitrane-type sesquiterpenoids from higher plants.The absolute configurations were supported by comparison of the experimental circular dichroism(CD)spectra with the calculated electronic CD(ECD)spectra of 13,their aglycones,and model compounds based on quantummechanical time-dependent density functional theory.The influences of the glycosyls on the calculated ECD spectra of the glycosidic sesquiterpenoids,as well as some nomenclature and descriptive problems with gymnomitrane-type sesquiterpenoids are discussed.
基金Financial support from the National Natural Sciences Foundation of China,China (NSFCNos.30825044 and 20932007)+1 种基金the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT,No.IRT1007)the National Science and Technology Project of China (Nos.2012ZX09301002-002 and 2011ZX09307-002-01)
文摘Four new acetylenes (1-4) and one new unsaturated to-hydroxy fatty acid (5), together with known analogues, were isolated from an aqueous extract of Codonopsis pilosula roots. Their structures were determined by spectroscopic and chemical methods. The new acetylenes are categorized as an unusual cyclotetradecatrienynone (1), tetradocenynetriol (2), and rare octenynoic acids (3 and 4), respectively, and 3 and 4 are possibly derived from oxidative metabolic degradation of 1 and/or 2. The absolute configuration of I. was assigned by comparison of the experimental circular dichroism (Cl)) spectrum with the calculated electronic circular dichroism (ECD) spectra of stereoisomers based on the quantum-mechanical time-dependent density functional theory, while the configuration of 2 was assigned by using modified Mosher's method based on the MPA determination rule of AoRs values for diols. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier By.
基金Financial support from the National Natural Sciences Foundation of China(NNSFCgrant Nos.81373287,81630094 and 30825044)is acknowledged
文摘Six new indole alkaloid sulfonic acids(1–6), together with two analogues(7 and 8) that were previously reported as synthetic products, were isolated from an aqueous extract of the Isatis indigotica root. Their structures including the absolute configurations were determined by spectroscopic data analysis, combined with enzyme hydrolysis and comparison of experimental circular dichroism and calculated electronic circular dichroism spectra. In the preliminary assay, compounds 2 and 4 showed antiviral activity against Coxsackie virus B3 and influenza virus A/Hanfang/359/95(H3N2), respectively.
基金Financial support from the National Natural Sciences Foundation of China(NNSFCGrant Nos.81373287,81630094,and 30825044)
文摘Three pairs of glycosidic 8,4′-oxyneolignane diastereoisomers, named isatioxyneolignosides A-F(1–6), were isolated from an aqueous extract of Isatis indigotica roots. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis and enzyme hydrolysis. The validity of Δδ_(C8-C7) values to distinguish threo and erythro aryl glycerol units and Cotton effects at 235±5 nm to determine absolute configurations at C-8 in 1–6 and their aglycones(1a–6a) are discussed.
基金Financial support from the National Natural Sciences Foundation of China (NNSFC Grant Nos. 81373287 and 30825044)+1 种基金the Beijing Excellent Talent Training Project (Grant No. 2013D009008000002)the National Science and Technology Project of China (Nos. 2012ZX09301002-002 and 2011ZX0 9307002-01)
文摘Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(—)-1 and(+)-1], phaitanthrin A and epiphaitanthrin A [(—)-2 and(+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(—)-3and(+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column.Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism(ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A[(—)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products.
基金support from diverse funding sources,including the National Key Program for S&T Research and Development of the Ministry of Science and Technology(MOST),Yifang Wang's Science Studio of the Ten Thousand Talents Project,the CAS Key Foreign Cooperation Grant,the National Natural Science Foundation of China(NSFC)Beijing Municipal Science&Technology Commission,the CAS Focused Science Grant,the IHEP Innovation Grant,the CAS Lead Special Training Programthe CAS Center for Excellence in Particle Physics,the CAS International Partnership Program,and the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by China,fostered through extensive collaboration with international partners.The complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs factory.In its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2)s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs bosons.Increasing the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of magnitude.This Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2015)and the Conceptual Design Report(CDR,2018),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering aspects.Additionally,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection procedures.Construction is anticipated to begin around 2027-2028,pending government approval,with an estimated duration of 8 years.The commencement of experiments and data collection could potentially be initiated in the mid-2030s.
基金the National Natural Science Foundation of China(Nos.31830053,31920103007,8207112072,82122056)the National Key Research and Development Program of China(2020YFA0803201)the Science Technology Commission of Shanghai Municipality(No.20S11900700).
文摘Cancer immunotherapy,mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells,has revolutionized the oncology landscape as it utilizes patients’own immune systems in combating the cancer cells.Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes.Phagocytosis checkpoints,such as CD47,CD24,MHC-I,PD-L1,STC-1 and GD2,have emerged as essential checkpoints for cancer immunotherapy by functioning as“don’t eat me”signals or interacting with“eat me”signals to suppress immune responses.Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy.Genetic ablation of these phagocytosis checkpoints,as well as blockade of their signaling pathways,robustly augments phagocytosis and reduces tumor size.Among all phagocytosis checkpoints,CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment.CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials.However,anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes.Here,we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy,highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.
基金supported by the National Science and Technology Major Project of China(2019ZX09732-001)the Key R&D Plan Projects in Shaanxi Province(2020ZDXM2-SF-01)the Young Talent Fund of the University Association for Science and Technology in Shaanxi,China(20200304).
文摘SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape,compromising the effectiveness of existing vaccines and neutralizing antibodies.An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants.Here,we identified CD147 as a universal receptor for SARS-CoV-2 and its variants.Meanwhile,Meplazeumab,a humanized anti-CD147 antibody,could block cellular entry of SARS-CoV-2 and its variants-alpha,beta,gamma,and delta,with inhibition rates of 68.7,75.7,52.1,52.1,and 62.3%at 60μg/ml,respectively.Furthermore,humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants,alpha and beta.When infected,these mice developed exudative alveolar pneumonia,featured by immune responses involving alveoli-infiltrated macrophages,neutrophils,and lymphocytes and activation of IL-17 signaling pathway.Mechanistically,we proposed that severe COVID-19-related cytokine storm is induced by a"spike protein-CD147-CyPA signaling axis":Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway,which further induced expression of cyclophilin A(CyPA);CyPA reciprocally bound to CD147 and triggered MAPK pathway.Consequently,the MAPK pathway regulated the expression of cytokines and chemokines,which promoted the development of cytokine storm.Importantly,Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants.Therefore,our findings provided a new perspective for severe COVID-19-related pathogenesis.Furthermore,the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.
