AIM： To identify the protein expression differences related to the CagA-induced ERK pathway activation in AGS cells. METHODS： Human AGS cells transfected with cagA and blank vector were treated with specific mitogen...AIM： To identify the protein expression differences related to the CagA-induced ERK pathway activation in AGS cells. METHODS： Human AGS cells transfected with cagA and blank vector were treated with specific mitogenactivated protein kinase kinase （MEK） inhibitor. Total cell proteins were combined by strong anion exchange （SAX2） and weak cation exchange （CM10） ProteinChip arrays and analyzed using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry （SELDI-TOF- MS） proteomics technology. Protein expression profiles were compared with those of inhibitor-untreated cagA transfectants. SwissProt/TrEMBL database searching for differentially expressed proteins was carried out using the TagIdent tool with the pI and mass information. RESULTS： When a total of 16 proteins that showed expression differences in inhibitor-untreated cagA transfectants were compared with vector transfectants, three proteins with m/z 4229, 8162 and 9084 were found to have no expression differences after treatment with MEK inhibitor, while the other 13 maintained the same expression differences after inhibitor treatment. Seven pieces of meaningful matching information for the three proteins were obtained from database searching. CONCLUSION： Biomarkers with m/z 4229, 8162 and 9084 are ERKI/2 phosphorylation dependent, andtherefore are the downstream molecules of ERK1/2 in the ERK/MAPK signaling pathway. The three biomarkers may be important cancer-associated proteins according to SwissProt/TrEMBL database information.展开更多
A novel fluorinated polyurethane （FPU） with fluorine-containing pendent groups was prepared by using fluorinated polyether glycol （PTMG-g-HFP） as a soft segment, 1,6-hexamethylene diisocyanate （HDI） or toluene d...A novel fluorinated polyurethane （FPU） with fluorine-containing pendent groups was prepared by using fluorinated polyether glycol （PTMG-g-HFP） as a soft segment, 1,6-hexamethylene diisocyanate （HDI） or toluene diisocyanate （TD1） as a hard segment and 1,4-butanodiol （BDO） as a chain extender. FTIR, ^1H NMR, ^13C NMR and GPC were used to characterize the structure of the fluorinated polyurethane. Thermal stabilities of the fluorinated polyurethane and the corresponding hydrogenated polyurethane were studied by TGA. XPS analysis at two different sampling depths for the fluorinated polyurethane was used to investigate the surface compositions of FPU. The results showed the fluorine enrichment on the surface of FPU.展开更多
2D MXenes are highly attractive for fabricating high-precision gas sensors operated at room temperature(RT)due to their high surface-to-volume ratio.However,the limited selectivity and low sensitivity are still long-s...2D MXenes are highly attractive for fabricating high-precision gas sensors operated at room temperature(RT)due to their high surface-to-volume ratio.However,the limited selectivity and low sensitivity are still long-standing challenges for their further applications.Herein,the self-assembly of 0D-2D heterostructure for highly sensitive NO_(2) detection was achieved by integrating ZnO nanoparticles on Ti_(3)C_(2)Tx MXene-derived TiO_(2) nanosheets(designated as ZnO@MTiO_(2)).ZnO nanoparticles can not only act as spacers to prevent the restacking of MTiO_(2) nanosheets and ensure effective transfer for gas molecules,but also enhance the sensitivity of the sensor the through trapping effect on electrons.Meanwhile,MTiO_(2) nanosheets facilitate gas diffusion for rapid sensor response.Benefiting from the synergistic effect of individual components,the ZnO@MTiO_(2)0D-2D heterostructure-based sensors revealed remarkable sensitivity and excellent selectivity to low concentration NO_(2) at RT.This work may facilitate the sensing application of MXene derivative and provide a new avenue for the development of high-performance gas sensors in safety assurance and environmental monitoring.展开更多
A well-defined modification of polytetramethylene glycol （PTMG） was realized by radical grafting with hexafluoropropylene （HFP）. The structure of grafted product was confirmed by means of IR, ^1H NMR and ^13C NMR....A well-defined modification of polytetramethylene glycol （PTMG） was realized by radical grafting with hexafluoropropylene （HFP）. The structure of grafted product was confirmed by means of IR, ^1H NMR and ^13C NMR. The effects of the amount of initiator, reaction time and temperature on the grafting HFP onto PTMG were investigated.展开更多
In this article, nano-scale Al/Fe2O3 composites with different morphologies were successfully obtained by a simple electrospinning technique, which is based on a surfactant（polyvinyl pyridine, PVP） in a mixture of N...In this article, nano-scale Al/Fe2O3 composites with different morphologies were successfully obtained by a simple electrospinning technique, which is based on a surfactant（polyvinyl pyridine, PVP） in a mixture of N,N-dimethylformamide（DMF） and 2-propanol. The electrospun Al/Fe2O3 composites exhibited a crystal structure and phase composition by X-ray diffraction analysis. The different morphologies of the Al/Fe2O3 composites were also observed through scanning electron microscopy and transmission electron microscopy. It was found that the rather simple electrospinning method used to prepare the morphology-controlled Al/Fe2O3 composites may have the potential for preparation of propellants, explosives, and pyrotechnics in the future.展开更多
Anticoagulation is imperative to reduce the incidence of thrombotic complications in patients undergoing percutaneous interventional cardiovascular procedures;however,this is at the expense of increased risk of bleedi...Anticoagulation is imperative to reduce the incidence of thrombotic complications in patients undergoing percutaneous interventional cardiovascular procedures;however,this is at the expense of increased risk of bleeding.The optimal anticoagulation strategy for these procedures remains unclear.Unfractionated heparin is the most commonly used anticoagulant during interventional procedures,but has several limitations,such as relatively high incidence of bleeding events,occurrence of heparin-induced thrombocytopenia,and a paradoxical thrombotic effect.Contemporary studies have demonstrated that bivalirudin decreases the occurrence of bleeding complications,but potentially increases the risk of acute stent thrombosis.This review discusses the pharmacology of bivalirudin and its current clinical application in patients undergoing percutaneous coronary intervention and transcatheter aortic valve replacement procedures.展开更多
Design and synthesis of efficient photocatalysts for hydrogen production via water splitting are of great importance from both theoretical and practical viewpoints. Many metal-based semiconductors have been explored f...Design and synthesis of efficient photocatalysts for hydrogen production via water splitting are of great importance from both theoretical and practical viewpoints. Many metal-based semiconductors have been explored for this purpose in recent decades. Here, for the first time, an entirely carbon-based material, bulk three-dimensionally cross-linked graphene （3DG）, has been developed as a photocatalyst for hydrogen production. It exhibits a remarkable hydrogen production rate of 270 μmol-h-l.g-t under full-spectrum light via a hot/free electron emission mechanism. Furthermore, when combined with the widely used semiconductor TiO2 to form a TiO2/3DG composite, it appears to become a more efficient hydrogen production photocatalyst. The composite achieves a production rate of 1,205 bimol-h μg-t under ultraviolet-visible （UV-vis） light and a 7.2% apparent quantum efficiency at 350 nm due to the strong synergetic effects between TiO2 and 3DG.展开更多
Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in th...Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be compromised.Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.Cathepsin L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response.Here,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and CAPN1.The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1.Both showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various cells.Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance.Moreover,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in mice.In addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model.And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia.Taken together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.展开更多
The predictors and clinical outcomes of Percutaneous Coronary Intervention in patients with suspected coronary heart disease with COmorbid major DEpressive disorder(PCI CODE)study employs a prospective,multidisciplina...The predictors and clinical outcomes of Percutaneous Coronary Intervention in patients with suspected coronary heart disease with COmorbid major DEpressive disorder(PCI CODE)study employs a prospective,multidisciplinary,observational design to evaluate clinical outcomes post-percutaneous coronary intervention(PCI)between coronary heart disease(CHD)patients with or without major depressive disorder(MDD).This study is registered with ClinicalTrials.gov(NCT03852082).During enrollment,all consecutive individuals aged≥18 years who are clinically suspected of CHD and scheduled for coronary angiography at Nanjing First Hospital are our observational cohort.After completing the self-rated Patient Health Questionnaire,undergoing a clinical MDD diagnosis by a psychiatrist when indicated,and having CHD confirmed by interventional cardiologists,participants in the PCI arm are stratified into 2 groups:CHD patients with MDD and CHD patients without MDD.The primary composite endpoint is the 1-year and 5-year incidence of major adverse cardiac events including all-cause death,non-fatal myocardial infarction,and any coronary revascularization.The secondary endpoints comprise individual events,including all-cause death,cardiovascular death,non-fatal myocardial infarction,any coronary revascularization,stent thrombosis,in-stent restenosis,cardiac-related rehospitalization,non-cardiac-related rehospitalization,or stroke.The PCI CODE study,which hypothesizes that certain biomarker combinations may correlate with a higher incidence of major adverse cardiac events at 1 and 5 years post-PCI,seeks to identify the key determinants that lead to poorer prognoses following PCI in patients with CHD and comorbid MDD compared to those without MDD.展开更多
Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center...Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.展开更多
Highly sensitive broadband photodetection is of critical importance for many applications.However,it is a great challenge to realize broadband photodetection by using a single device.Here we report photodetectors(PDs)...Highly sensitive broadband photodetection is of critical importance for many applications.However,it is a great challenge to realize broadband photodetection by using a single device.Here we report photodetectors(PDs)based on three-dimensional(3 D)graphene foam(GF)photodiodes with asymmetric electrodes,which show an ultra-broadband photoresponse from ultraviolet to microwave for wavelengths ranging from 10~2 to 10~6 nm.Moreover,the devices exhibit a high photoresponsivity of 10~3 A·W^-1,short response time of 43 ms,and3 d B bandwidth of 80 Hz.The high performance of the devices can be attributed to the photothermoelectric(PTE,also known as the Seebeck)effect in 3 D GF photodiodes.The excellent optical,thermal,and electrical properties of 3 D GFs offer a superior basis for the fabrication of PTE-based PDs.This work paves the way to realize ultra-broadband and high-sensitivity PDs operated at room temperature.展开更多
Glycidyl azide polymer （GAP） with the advantages of non-volatility and excellent thermal stability is a candidate as a re- placement for nitroglycerine （NG） in a double base propellant. The GAP-NC double base prop...Glycidyl azide polymer （GAP） with the advantages of non-volatility and excellent thermal stability is a candidate as a re- placement for nitroglycerine （NG） in a double base propellant. The GAP-NC double base propellants were formulated with GAP and nitrocellulose （NC） fibers. Tensile test and SEM characterization indicated that GAP-NC propellants had a homoge- neous structure. Thermogravimetric analysis of GAP-NC propellants revealed that the onset decomposition temperature reached a high level ranging from 192.9 to 194.6 ℃, which indicated that the substitution of NG with GAP contributed to the safe storage and process operations for double base propellant. The result analysis of decomposition products of GAP-NC propellants showed that the main gas decomposition products of the propellants were NO, NO〉 CO, CO2, NH3, CH4, HCN, N2 CH20 and C2H40. The thermal decomposition process of the specimens was proposed.展开更多
Objective:Patients with untreated severe aortic regurgitation(AR)have a high risk of mortality.Transfemoral transcatheter aortic valve replacement(TF-TAVR)is a treatment option for AR;however,the safety and efficacy o...Objective:Patients with untreated severe aortic regurgitation(AR)have a high risk of mortality.Transfemoral transcatheter aortic valve replacement(TF-TAVR)is a treatment option for AR;however,the safety and efficacy of this technique have not been sufficiently established.This study aimed to evaluate the clinical and anatomical variables correlating with device success of TF-TAVR using a self-expanding valve system for pure AR.Methods:Patients with pure native severe AR who underwent TF-TAVR using a self-expanding valve system were registered at 5 Chinese centers.The primary endpoint was device success at 1 month after TAVR.The secondary endpoint was the composite of major adverse cardiovascular events(MACE)at 6 months,including all-cause death,ischemic stroke,emergency conversion to cardiac surgery,and permanent pacemaker implantation.Echocardiography was used to analyze the left ventricular function before the TAVR procedure and during follow-up.Multivariable logistic regression and Cox regression analyses were performed to find relevant independent risk factors.Results:Between September 2019 and February 2022,79 patients with AR were enrolled in the study.At 1 month,device success was achieved in 60(75.9%)patients.By 6 months,29(36.7%)patients had MACE.Echocardiography revealed improved left ventricular function after TAVR.Multivariate regression analysis demonstrated that the Society of Thoracic Surgeons risk score(odds ratio 0.760,95%confidence interval(Cl):0.584-0.989;P=0.041)and annulus perimeter(odds ratio 0.888,95%Cl:0.796-0.992;P=0.035)were 2 predictors of device success.Moreover,annulus perimeter(<80.2mm),but not Society of Thoracic Surgeons risk score,was associated with a significant reduction in MACE at 6 months(hazard ratio 2.223,95%Cl:1.060-4.659;P=0.028).Conclusions:TF-TAVR using a self-expanding valve system appears to be a safe and feasible treatment for patients with pure native severe AR,particularly those with a less enlarged annulus.展开更多
基金National High Technology 2006AA02Z341 & NSFC 30430730
文摘AIM： To identify the protein expression differences related to the CagA-induced ERK pathway activation in AGS cells. METHODS： Human AGS cells transfected with cagA and blank vector were treated with specific mitogenactivated protein kinase kinase （MEK） inhibitor. Total cell proteins were combined by strong anion exchange （SAX2） and weak cation exchange （CM10） ProteinChip arrays and analyzed using surface-enhanced laser desorption/ ionization time-of-flight mass spectrometry （SELDI-TOF- MS） proteomics technology. Protein expression profiles were compared with those of inhibitor-untreated cagA transfectants. SwissProt/TrEMBL database searching for differentially expressed proteins was carried out using the TagIdent tool with the pI and mass information. RESULTS： When a total of 16 proteins that showed expression differences in inhibitor-untreated cagA transfectants were compared with vector transfectants, three proteins with m/z 4229, 8162 and 9084 were found to have no expression differences after treatment with MEK inhibitor, while the other 13 maintained the same expression differences after inhibitor treatment. Seven pieces of meaningful matching information for the three proteins were obtained from database searching. CONCLUSION： Biomarkers with m/z 4229, 8162 and 9084 are ERKI/2 phosphorylation dependent, andtherefore are the downstream molecules of ERK1/2 in the ERK/MAPK signaling pathway. The three biomarkers may be important cancer-associated proteins according to SwissProt/TrEMBL database information.
基金Financial support from the Fundamental Research Foundation of Beijing Institute of Technology (No.20070442005)
文摘A novel fluorinated polyurethane （FPU） with fluorine-containing pendent groups was prepared by using fluorinated polyether glycol （PTMG-g-HFP） as a soft segment, 1,6-hexamethylene diisocyanate （HDI） or toluene diisocyanate （TD1） as a hard segment and 1,4-butanodiol （BDO） as a chain extender. FTIR, ^1H NMR, ^13C NMR and GPC were used to characterize the structure of the fluorinated polyurethane. Thermal stabilities of the fluorinated polyurethane and the corresponding hydrogenated polyurethane were studied by TGA. XPS analysis at two different sampling depths for the fluorinated polyurethane was used to investigate the surface compositions of FPU. The results showed the fluorine enrichment on the surface of FPU.
基金supported by the National Natural Science Foundation of China(No.52103308)the Natural Science Foundation of Jiangsu Province of China(No.BK20210826)+4 种基金Outstanding Youth Foundation of Jiangsu Province of China(No.BK20211548)National Key Research and Development Program of China(No.2017YFE0115900)Innovative Science and Technology Platform Project of Cooperation between Yangzhou City and Yangzhou University(No.YZ2020266)Lvyang Jinfeng Plan for Excellent Doctor of Yangzhou City,Special Funds for Self-Made Experimental Equipment of Yangzhou Universitythe Doctor of Suzhou University Scientific Research Foundation Project(No.2022BSK003).
文摘2D MXenes are highly attractive for fabricating high-precision gas sensors operated at room temperature(RT)due to their high surface-to-volume ratio.However,the limited selectivity and low sensitivity are still long-standing challenges for their further applications.Herein,the self-assembly of 0D-2D heterostructure for highly sensitive NO_(2) detection was achieved by integrating ZnO nanoparticles on Ti_(3)C_(2)Tx MXene-derived TiO_(2) nanosheets(designated as ZnO@MTiO_(2)).ZnO nanoparticles can not only act as spacers to prevent the restacking of MTiO_(2) nanosheets and ensure effective transfer for gas molecules,but also enhance the sensitivity of the sensor the through trapping effect on electrons.Meanwhile,MTiO_(2) nanosheets facilitate gas diffusion for rapid sensor response.Benefiting from the synergistic effect of individual components,the ZnO@MTiO_(2)0D-2D heterostructure-based sensors revealed remarkable sensitivity and excellent selectivity to low concentration NO_(2) at RT.This work may facilitate the sensing application of MXene derivative and provide a new avenue for the development of high-performance gas sensors in safety assurance and environmental monitoring.
基金Financial supports from the National Natural Science Foundation of China(No.50273035)Hangzhou Zhijiang Silicone Chemicals Co.,Ltd.are acknowledged
文摘A well-defined modification of polytetramethylene glycol （PTMG） was realized by radical grafting with hexafluoropropylene （HFP）. The structure of grafted product was confirmed by means of IR, ^1H NMR and ^13C NMR. The effects of the amount of initiator, reaction time and temperature on the grafting HFP onto PTMG were investigated.
文摘In this article, nano-scale Al/Fe2O3 composites with different morphologies were successfully obtained by a simple electrospinning technique, which is based on a surfactant（polyvinyl pyridine, PVP） in a mixture of N,N-dimethylformamide（DMF） and 2-propanol. The electrospun Al/Fe2O3 composites exhibited a crystal structure and phase composition by X-ray diffraction analysis. The different morphologies of the Al/Fe2O3 composites were also observed through scanning electron microscopy and transmission electron microscopy. It was found that the rather simple electrospinning method used to prepare the morphology-controlled Al/Fe2O3 composites may have the potential for preparation of propellants, explosives, and pyrotechnics in the future.
文摘Anticoagulation is imperative to reduce the incidence of thrombotic complications in patients undergoing percutaneous interventional cardiovascular procedures;however,this is at the expense of increased risk of bleeding.The optimal anticoagulation strategy for these procedures remains unclear.Unfractionated heparin is the most commonly used anticoagulant during interventional procedures,but has several limitations,such as relatively high incidence of bleeding events,occurrence of heparin-induced thrombocytopenia,and a paradoxical thrombotic effect.Contemporary studies have demonstrated that bivalirudin decreases the occurrence of bleeding complications,but potentially increases the risk of acute stent thrombosis.This review discusses the pharmacology of bivalirudin and its current clinical application in patients undergoing percutaneous coronary intervention and transcatheter aortic valve replacement procedures.
文摘Design and synthesis of efficient photocatalysts for hydrogen production via water splitting are of great importance from both theoretical and practical viewpoints. Many metal-based semiconductors have been explored for this purpose in recent decades. Here, for the first time, an entirely carbon-based material, bulk three-dimensionally cross-linked graphene （3DG）, has been developed as a photocatalyst for hydrogen production. It exhibits a remarkable hydrogen production rate of 270 μmol-h-l.g-t under full-spectrum light via a hot/free electron emission mechanism. Furthermore, when combined with the widely used semiconductor TiO2 to form a TiO2/3DG composite, it appears to become a more efficient hydrogen production photocatalyst. The composite achieves a production rate of 1,205 bimol-h μg-t under ultraviolet-visible （UV-vis） light and a 7.2% apparent quantum efficiency at 350 nm due to the strong synergetic effects between TiO2 and 3DG.
基金supported by the National Natural Science Foundation of China (Nos.82130105 to H.L.,82121005 to H.L.,92169112 to S.J.,82041036 to L.L.,T2225002 to M.Z.,82002142 to S.X.,82341093 to F.B.,and 32200131 to Y.Z.)the National Program on Key Research Project of China (2021YFC2300703 to L.L.)+4 种基金National Key R&D Program of China (2022YFC0868900 and 2021YFC0864900 to H.L.,2021YFC2300700 to L.Z.)Shanghai Municipal Science and Technology Major Project,Shanghai Science and Technology Development Funds (20QA1406400 to F.B.)Lingang Laboratory (LG202101-01-07 to H.Y.,LG202103-04-03 to W.D.)Youth Innovation Promotion Association CAS (2023296 to S.Z)the Science and Technology Commission of Shanghai Municipality (YDZX20213100001556 to H.Y.).
文摘Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be compromised.Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.Cathepsin L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response.Here,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and CAPN1.The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1.Both showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various cells.Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance.Moreover,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in mice.In addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model.And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia.Taken together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.
文摘The predictors and clinical outcomes of Percutaneous Coronary Intervention in patients with suspected coronary heart disease with COmorbid major DEpressive disorder(PCI CODE)study employs a prospective,multidisciplinary,observational design to evaluate clinical outcomes post-percutaneous coronary intervention(PCI)between coronary heart disease(CHD)patients with or without major depressive disorder(MDD).This study is registered with ClinicalTrials.gov(NCT03852082).During enrollment,all consecutive individuals aged≥18 years who are clinically suspected of CHD and scheduled for coronary angiography at Nanjing First Hospital are our observational cohort.After completing the self-rated Patient Health Questionnaire,undergoing a clinical MDD diagnosis by a psychiatrist when indicated,and having CHD confirmed by interventional cardiologists,participants in the PCI arm are stratified into 2 groups:CHD patients with MDD and CHD patients without MDD.The primary composite endpoint is the 1-year and 5-year incidence of major adverse cardiac events including all-cause death,non-fatal myocardial infarction,and any coronary revascularization.The secondary endpoints comprise individual events,including all-cause death,cardiovascular death,non-fatal myocardial infarction,any coronary revascularization,stent thrombosis,in-stent restenosis,cardiac-related rehospitalization,non-cardiac-related rehospitalization,or stroke.The PCI CODE study,which hypothesizes that certain biomarker combinations may correlate with a higher incidence of major adverse cardiac events at 1 and 5 years post-PCI,seeks to identify the key determinants that lead to poorer prognoses following PCI in patients with CHD and comorbid MDD compared to those without MDD.
基金The present trial was supported by grants from the National Science Foundation of China （No. NSFC 81770342）, Nanjing Health and Family Planning Commission （No. YKK16124）, and Nanjing Municipal Commission of Science and Technology （No. 201715026）.
文摘Background：The relationship between obstructive sleep apnea （OSA） and platelet reactivity in patients undergoing percutaneous coronary intervention （PCI） has not been defined.The present prospective,single-center study explored the relationship between platelet reactivity and OSA in patients with PCI.Methods：A total of 242 patients were finally included in the study.OSA was screened overnight by polysomnography.Platelet reactivity was assessed with a sequential platelet counting method,and the platelet maximum aggregation ratio （MAR） and average aggregation ratio were calculated.All patients were assigned per apnea-hypopnea index （AHI） to non-OSA （n =128） and OSA （n =l 14） groups.The receiver operating characteristic curve analysis was used to evaluate the accuracy of AHI for high platelet reactivity （HPR） on aspirin and clopidogrel,and multivariable logistic regression was used to determine the independent predictors of HPR on aspirin and clopidogrel.Results：Median AHI was significantly higher in the OSA group than in the non-OSA group （34.5 events/h vs.8.1 events/h,Z =-13.422,P 〈 0.001）.Likewise,median arachidonic acid-and adenosine diphosphate-induced maximum aggregation rate （MAR） in the OSA group was significantly higher than those in the non-OSA group （21.1% vs.17.7%,Z=-3.525,P 〈 0.001 and 45.8% vs.32.2%,Z =-5.708,P 〈 0.001,respectively）.Multivariable logistic regression showed that OSA was the only independent predictor for HPR on aspirin （odds ratio [OR]：1.055,95% confidence interval [CI]：1.033-1.077,P 〈 0.001） and clopidogrel （OR：1.036,95% CI：1.017-1.056,P 〈 0.001）.The cutoffvalue of AHI for HPR on aspirin was 45.2 events/h （sensitivity 47.1% and specificity 91.3%）,whereas cutoffvalue of AHI for HPR on clopidogrel was 21.3 events/h （sensitivity 68.3% and specificity 67.7%）.
基金National Natural Science Foundation of China(61675147,61605141,61735010,91838301)National Key Research and Development Program of China(2017YFA0700202)+2 种基金Basic Research Program of Shenzhen(JCYJ20170412154447469)Beiyang Yong Junior Faculties of Tianjin University(2019XRG-0056)Wenzhou City Governmental Public Industrial Technology Project(G20160014)。
文摘Highly sensitive broadband photodetection is of critical importance for many applications.However,it is a great challenge to realize broadband photodetection by using a single device.Here we report photodetectors(PDs)based on three-dimensional(3 D)graphene foam(GF)photodiodes with asymmetric electrodes,which show an ultra-broadband photoresponse from ultraviolet to microwave for wavelengths ranging from 10~2 to 10~6 nm.Moreover,the devices exhibit a high photoresponsivity of 10~3 A·W^-1,short response time of 43 ms,and3 d B bandwidth of 80 Hz.The high performance of the devices can be attributed to the photothermoelectric(PTE,also known as the Seebeck)effect in 3 D GF photodiodes.The excellent optical,thermal,and electrical properties of 3 D GFs offer a superior basis for the fabrication of PTE-based PDs.This work paves the way to realize ultra-broadband and high-sensitivity PDs operated at room temperature.
文摘Glycidyl azide polymer （GAP） with the advantages of non-volatility and excellent thermal stability is a candidate as a re- placement for nitroglycerine （NG） in a double base propellant. The GAP-NC double base propellants were formulated with GAP and nitrocellulose （NC） fibers. Tensile test and SEM characterization indicated that GAP-NC propellants had a homoge- neous structure. Thermogravimetric analysis of GAP-NC propellants revealed that the onset decomposition temperature reached a high level ranging from 192.9 to 194.6 ℃, which indicated that the substitution of NG with GAP contributed to the safe storage and process operations for double base propellant. The result analysis of decomposition products of GAP-NC propellants showed that the main gas decomposition products of the propellants were NO, NO〉 CO, CO2, NH3, CH4, HCN, N2 CH20 and C2H40. The thermal decomposition process of the specimens was proposed.
基金supported by the National Natural Science Foundation of China(81970307,82100357,and 82270344)jointly supported by Six Talent Peaks Project of Jiangsu Province(2019-WSN-156)+2 种基金Jiangsu Health Committee(H2019077)Nanjing Health Committee(JQX22007)National Key R&D Program of China(2020YFC2008100).
文摘Objective:Patients with untreated severe aortic regurgitation(AR)have a high risk of mortality.Transfemoral transcatheter aortic valve replacement(TF-TAVR)is a treatment option for AR;however,the safety and efficacy of this technique have not been sufficiently established.This study aimed to evaluate the clinical and anatomical variables correlating with device success of TF-TAVR using a self-expanding valve system for pure AR.Methods:Patients with pure native severe AR who underwent TF-TAVR using a self-expanding valve system were registered at 5 Chinese centers.The primary endpoint was device success at 1 month after TAVR.The secondary endpoint was the composite of major adverse cardiovascular events(MACE)at 6 months,including all-cause death,ischemic stroke,emergency conversion to cardiac surgery,and permanent pacemaker implantation.Echocardiography was used to analyze the left ventricular function before the TAVR procedure and during follow-up.Multivariable logistic regression and Cox regression analyses were performed to find relevant independent risk factors.Results:Between September 2019 and February 2022,79 patients with AR were enrolled in the study.At 1 month,device success was achieved in 60(75.9%)patients.By 6 months,29(36.7%)patients had MACE.Echocardiography revealed improved left ventricular function after TAVR.Multivariate regression analysis demonstrated that the Society of Thoracic Surgeons risk score(odds ratio 0.760,95%confidence interval(Cl):0.584-0.989;P=0.041)and annulus perimeter(odds ratio 0.888,95%Cl:0.796-0.992;P=0.035)were 2 predictors of device success.Moreover,annulus perimeter(<80.2mm),but not Society of Thoracic Surgeons risk score,was associated with a significant reduction in MACE at 6 months(hazard ratio 2.223,95%Cl:1.060-4.659;P=0.028).Conclusions:TF-TAVR using a self-expanding valve system appears to be a safe and feasible treatment for patients with pure native severe AR,particularly those with a less enlarged annulus.
