As a fundamental operation in ad hoc networks,broadcast could achieve efficient message propagations.Particularl y in the cognitive radio ad hoc network where unlicensed users have different sets of available channels...As a fundamental operation in ad hoc networks,broadcast could achieve efficient message propagations.Particularl y in the cognitive radio ad hoc network where unlicensed users have different sets of available channels,broadcasts are carried out on multiple channels.Accordingly,channel selection and collision avoidance are challenging issues to balance the efficiency against the reliability of broadcasting.In this paper,an anticollision selective broadcast protocol,called acSB,is proposed.A channel selection algorithm based on limited neighbor information is considered to maximize success rates of transmissions once the sender and receiver have the same channel.Moreover,an anticollision scheme is adopted to avoid simultaneous rebroadcasts.Consequently,the proposed broadcast acSB outperforms other approaches in terms of smaller transmission delay,higher message reach rate and fewer broadcast collisions evaluated by simulations under different scenarios.展开更多
Gross primary production(GPP) plays a crucial part in the carbon cycle of terrestrial ecosystems.A set of validated monthly GPP data from 1957 to 2010 in 0.5°× 0.5° grids of China was weighted from the ...Gross primary production(GPP) plays a crucial part in the carbon cycle of terrestrial ecosystems.A set of validated monthly GPP data from 1957 to 2010 in 0.5°× 0.5° grids of China was weighted from the Multi-scale Terrestrial Model Intercomparison Project using Bayesian model averaging(BMA).The spatial anomalies of detrended BMA GPP during the growing seasons of typical El Nino years indicated that GPP response to El Nino varies with Pacific Decadal Oscillation(PDO) phases: when the PDO was in the cool phase,it was likely that GPP was greater in northern China(32°–38°N,111°–122°E) and less in the Yangtze River valley(28°–32°N,111°–122°E);in contrast,when PDO was in the warm phase,the GPP anomalies were usually reversed in these two regions.The consistent spatiotemporal pattern and high partial correlation revealed that rainfall dominated this phenomenon.The previously published findings on how El Nino during different phases of PDO affecting rainfall in eastern China make the statistical relationship between GPP and El Nino in this study theoretically credible.This paper not only introduces an effective way to use BMA in grids that have mixed plant function types,but also makes it possible to evaluate the carbon cycle in eastern China based on the prediction of El Nino and PDO.展开更多
The land surface processes of the Noah-MP and Noah models are evaluated over four typical landscapes in the Haihe River Basin(HRB) using in-situ observations. The simulated soil temperature and moisture in the two lan...The land surface processes of the Noah-MP and Noah models are evaluated over four typical landscapes in the Haihe River Basin(HRB) using in-situ observations. The simulated soil temperature and moisture in the two land surface models(LSMs) is consistent with the observation, especially in the rainy season. The models reproduce the mean values and seasonality of the energy fluxes of the croplands, despite the obvious underestimated total evaporation. Noah shows the lower deep soil temperature. The net radiation is well simulated for the diurnal time scale. The daytime latent heat fluxes are always underestimated, while the sensible heat fluxes are overestimated to some degree. Compared with Noah, Noah-MP has improved daily average soil heat flux with diurnal variations. Generally, Noah-MP performs fairly well for different landscapes of the HRB. The simulated cold bias in soil temperature is possibly linked with the parameterized partition of the energy into surface fluxes. Thus, further improvement of these LSMs remains a major challenge.展开更多
Purpose: To describe the magnetic resonance imaging(MRI)features of orbital rhabdomyosarcoma(RMS).Methods: Thirty-nine patients with histopathologically confirmed orbital RMS were retrospectively reviewed. All patient...Purpose: To describe the magnetic resonance imaging(MRI)features of orbital rhabdomyosarcoma(RMS).Methods: Thirty-nine patients with histopathologically confirmed orbital RMS were retrospectively reviewed. All patients underwent orbital conventional MRI, including axial, sagittal,and coronal T1-weighted, T2-weighted, and postcontrast T1-weighted sequences. The location, shape, margin, and MRI signal of the 39 lesions were reviewed. DWI in 15 patients and susceptibility weighted imaging(SWI) in 2 patients were also analyzed.Results: Orbital MRI was available in 39 patients and revealed a soft tissue mass in the orbital region in all cases. Of the 39 patients, the primary tumor sites were limited to the orbital proper in 31 cases, while 28 cases had extraocular muscle invasion and 8 cases had extraorbital invasion. All lesions were unilateral. Thirty-three cases were well-defined soft tissue masses and 6 cases appeared as less well-defined softtissue masses. Thirty-four cases showed homogeneous isointense or slightly hypointense signals on T1-weighted imaging(T1WI) and hyperintense signal on T2-weighted imaging(T2WI) compared with extraocular muscles. Five cases had heterogeneous signals with focal areas of increased signal on T1WI or decreased signal on T2WI, including 1 case with hypointense signal on SWI. The mean apparent diffusion coefficient(ADC) value of the viable part of tumors was(0.925±0.09)×10-3mm2/ s. All cases showed moderate to marked enhancement after contrast administration.Conclusion: Several MRI features-including homogeneous isointense or slightly hypointense signal on T1WI and slightly hyperintense signal on T2WI, relative low ADC values, and moderate to marked enhancement, extraocular muscles invasion, and extraorbital extensionare helpful in the diagnosis of orbital RMS.展开更多
The recruitment of key cells to regeneration sites is a promising strategy to promote functional wound healing.Dermal fibroblasts exhibit a heterogeneous population of cells during homeostasis and in response to injur...The recruitment of key cells to regeneration sites is a promising strategy to promote functional wound healing.Dermal fibroblasts exhibit a heterogeneous population of cells during homeostasis and in response to injury.Papillary fibroblasts play central regulatory roles in the regeneration of skin appendages during wound healing.Inspired by the phenomenon where bait for grass carp can attract grouped grass carps to a fishing spot soon,“Grass Carp Fishing”multifunctional hydrogels,that is,codelivery of an antibody of leucine-rich repeats and immunoglobulin-like domains 1(Lrig1)on the surface of papillary fibroblasts and insulinlike growth factor 1(IGF1)with recruitment function,can recruit papillary fibroblasts.In the experiments,carboxymethyl chitosan showed positive effects in promoting cell proliferation and neovascularization,while dopamine-grafted gelatin was effective in stabilizing the structure and prolonging the degradation time.The sustained release of Lrig1 antibodies and IGF1 from injectable self-healing multifunctional hydrogels persistently accelerated the migration and proliferation of Lrig1+fibroblasts.The in vivo results from a full-thickness cutaneous wound model showed that injectable self-healing multifunctional hydrogel accelerated wound healing and skin regeneration through the recruitment of Lrig1+papillary fibroblasts in wound tissue.Our findings reveal an injectable self-healing multifunctional hydrogel for regeneration,a promising approach to promoting skin wound healing.展开更多
The spatial and temporal variations of the vegetation carbon flux in China from 1901 to 2005 were studied using the vegetation net primary production(NPP)values from seven Earth-system models.In addition,the temporal ...The spatial and temporal variations of the vegetation carbon flux in China from 1901 to 2005 were studied using the vegetation net primary production(NPP)values from seven Earth-system models.In addition,the temporal and spatial changes in the nitrogen deposition flux in China were studied using the NHx and NOy fluxes from 1901 to 2005.The relationship between changes in the carbon flux,nitrogen flux and climate was analyzed.The results show that(1)over the past 100 years,NPP in China has shown an upward trend.The average trend coefficient is 0.88 and the NPP distribution trend is generally low in the north and high in the south,with a gradual increase from the northwest to the southeast.Temperature,precipitation and radiation are all conducive to plant growth in the direction of the gradient.The correlation coefficients between the ensemble model mean NPP and temperature,precipitation,longwave radiation and shortwave radiation are 0.88,0.73,0.91 and 0.67,respectively.(2)In the past 100 years,the NHx and NOy fluxes in China have shown an upward trend,with trend coefficients of 0.98 and 0.98,respectively,which pass the 99.9%confidence level of the t-test.NHx and NOy fluxes are also generally low in the north and high in the south,with a gradual increase from the northwest to the southeast in a step-like pattern.(3)The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and air temperature is similar,with only slight differences in values.The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and precipitation is similar in overall pattern,but the pattern is relatively complicated,with a positive-negative-positive-negative-positive pattern occurring across the monsoon region from north to south,and a negative-positive-negative-positive pattern occurring beyond the monsoon region from east to west.(4)The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and NPP shows a generally consistent pattern,but the pattern is relatively uneven.The average distribution of the ensemble model mean is positive correlation in northeast China and southwest China,and alternating positive and negative correlation in other regions.展开更多
Nonalcoholic fatty liver disease(NAFLD)is reported to affect 20-30%of adults and is accompanied by various metabolic comorbidities,where the economic and clinical burden of NAFLD is attributed to the progression of li...Nonalcoholic fatty liver disease(NAFLD)is reported to affect 20-30%of adults and is accompanied by various metabolic comorbidities,where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases.Chronic kidney disease(CKD),which has a high incidence rate,high morbidity and mortality rates,and high medical costs,has been linked to NAFLD.CKD is associated with some metabolismrelated risk factors that overlap with metabolic comorbidities of NAFLD.Therefore,to investigate the potential factors that influence CKD occurrence,the association between NAFLD and CKD should be clarified.Some studies have confirmed that NAFLD influences the occurrence and severity of CKD,whereas some studies have indicated that there is no correlation.In this review,the results of a few studies have been discussed,the potential risk factors for CKD in NAFLD are explored,and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.展开更多
Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health.Small molecule antivirals are an effective treatment strategy to fight against the viru...Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health.Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals eithershow limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of thesedrugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a newgeneration antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). Thiscompound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, butalso other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology.Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstandingsafety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigationprovides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.展开更多
Aims:Proton pump inhibitors(PPI)are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy,although the effect of PPI on these patients remains controversial.This study aimed to e...Aims:Proton pump inhibitors(PPI)are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy,although the effect of PPI on these patients remains controversial.This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy,including variceal bleeding and adverse events.Methods:Cirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019.Eligible patients were randomized into two groups:one group received PPI for 14 days and the other group did not receive PPI treatment(n=53 in each group).All patients were followed for 8 weeks.Results:During the follow‐up period,three patients(5.66%)in the PPI group experienced variceal bleeding on days 9,16,and 25 after endoscopic therapy,including two patients with acute bleeding and one with primary prophylaxis.In the non‐PPI group,three patients(5.66%)experienced variceal bleeding on days 7,42,and 56 after endoscopic therapy,including one patient with acute bleeding and two with secondary prophylaxis(p=0.990).The incidence of adverse events was similar between the two groups(37.74%vs.28.30%,p=0.30).Conclusions:PPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.展开更多
High yield production of phenol from hydroxylation of benzene with low energy consumption is of paramount importance,but still challenging.Herein,a new strategy,consisting of using diatomic synergistic modulation(DSM)...High yield production of phenol from hydroxylation of benzene with low energy consumption is of paramount importance,but still challenging.Herein,a new strategy,consisting of using diatomic synergistic modulation(DSM)to effectively control the separation of photo-generated carriers for an enhanced production of phenol is reported.The atomic level dispersion of Fe and Cr respectively decorated on Al based MIL-53-NH_(2)photocatalyst(Fe1/Cr:MIL-53-NH_(2))is designed,in which Cr single atoms are substituted for Al3+while Fe single atoms are coordinated by N.Notably,the Fe1/Cr:MIL-53-NH_(2)significantly boosts the photooxidation of benzene to phenol under visible light irradiation,which is much higher than those of MIL-53-NH_(2),Cr:MIL-53-NH_(2),Fe1/MIL-53-NH_(2),and Fe nanoparticles/Cr:MIL-53-NH_(2)catalysts.Theoretical and experimental results reveal that the Cr single atoms and Fe single atoms can act as electron acceptor and electron donor,respectively,during photocatalytic reaction,exhibiting a synergistic effect on the separation of the photo-generated carriers and thereby causing great enhancement on the benzene oxidation.This strategy provides new insights for rational design of advanced photocatalysts at the atomic level.展开更多
A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabrica...A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.展开更多
文摘As a fundamental operation in ad hoc networks,broadcast could achieve efficient message propagations.Particularl y in the cognitive radio ad hoc network where unlicensed users have different sets of available channels,broadcasts are carried out on multiple channels.Accordingly,channel selection and collision avoidance are challenging issues to balance the efficiency against the reliability of broadcasting.In this paper,an anticollision selective broadcast protocol,called acSB,is proposed.A channel selection algorithm based on limited neighbor information is considered to maximize success rates of transmissions once the sender and receiver have the same channel.Moreover,an anticollision scheme is adopted to avoid simultaneous rebroadcasts.Consequently,the proposed broadcast acSB outperforms other approaches in terms of smaller transmission delay,higher message reach rate and fewer broadcast collisions evaluated by simulations under different scenarios.
基金supported by the National Key Research and Development Program of China (Grant Nos.2016YFA0602501 and 2018YFA0606004)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant Nos.XDA20040301 and XDA20020201)。
文摘Gross primary production(GPP) plays a crucial part in the carbon cycle of terrestrial ecosystems.A set of validated monthly GPP data from 1957 to 2010 in 0.5°× 0.5° grids of China was weighted from the Multi-scale Terrestrial Model Intercomparison Project using Bayesian model averaging(BMA).The spatial anomalies of detrended BMA GPP during the growing seasons of typical El Nino years indicated that GPP response to El Nino varies with Pacific Decadal Oscillation(PDO) phases: when the PDO was in the cool phase,it was likely that GPP was greater in northern China(32°–38°N,111°–122°E) and less in the Yangtze River valley(28°–32°N,111°–122°E);in contrast,when PDO was in the warm phase,the GPP anomalies were usually reversed in these two regions.The consistent spatiotemporal pattern and high partial correlation revealed that rainfall dominated this phenomenon.The previously published findings on how El Nino during different phases of PDO affecting rainfall in eastern China make the statistical relationship between GPP and El Nino in this study theoretically credible.This paper not only introduces an effective way to use BMA in grids that have mixed plant function types,but also makes it possible to evaluate the carbon cycle in eastern China based on the prediction of El Nino and PDO.
基金supported by a project of the National Key Research and Development Program of China (Grant No.2016YFA0602501)a project of the National Natural Science Foundation of China (Grant Nos.41630532 and 41575093)
文摘The land surface processes of the Noah-MP and Noah models are evaluated over four typical landscapes in the Haihe River Basin(HRB) using in-situ observations. The simulated soil temperature and moisture in the two land surface models(LSMs) is consistent with the observation, especially in the rainy season. The models reproduce the mean values and seasonality of the energy fluxes of the croplands, despite the obvious underestimated total evaporation. Noah shows the lower deep soil temperature. The net radiation is well simulated for the diurnal time scale. The daytime latent heat fluxes are always underestimated, while the sensible heat fluxes are overestimated to some degree. Compared with Noah, Noah-MP has improved daily average soil heat flux with diurnal variations. Generally, Noah-MP performs fairly well for different landscapes of the HRB. The simulated cold bias in soil temperature is possibly linked with the parameterized partition of the energy into surface fluxes. Thus, further improvement of these LSMs remains a major challenge.
文摘Purpose: To describe the magnetic resonance imaging(MRI)features of orbital rhabdomyosarcoma(RMS).Methods: Thirty-nine patients with histopathologically confirmed orbital RMS were retrospectively reviewed. All patients underwent orbital conventional MRI, including axial, sagittal,and coronal T1-weighted, T2-weighted, and postcontrast T1-weighted sequences. The location, shape, margin, and MRI signal of the 39 lesions were reviewed. DWI in 15 patients and susceptibility weighted imaging(SWI) in 2 patients were also analyzed.Results: Orbital MRI was available in 39 patients and revealed a soft tissue mass in the orbital region in all cases. Of the 39 patients, the primary tumor sites were limited to the orbital proper in 31 cases, while 28 cases had extraocular muscle invasion and 8 cases had extraorbital invasion. All lesions were unilateral. Thirty-three cases were well-defined soft tissue masses and 6 cases appeared as less well-defined softtissue masses. Thirty-four cases showed homogeneous isointense or slightly hypointense signals on T1-weighted imaging(T1WI) and hyperintense signal on T2-weighted imaging(T2WI) compared with extraocular muscles. Five cases had heterogeneous signals with focal areas of increased signal on T1WI or decreased signal on T2WI, including 1 case with hypointense signal on SWI. The mean apparent diffusion coefficient(ADC) value of the viable part of tumors was(0.925±0.09)×10-3mm2/ s. All cases showed moderate to marked enhancement after contrast administration.Conclusion: Several MRI features-including homogeneous isointense or slightly hypointense signal on T1WI and slightly hyperintense signal on T2WI, relative low ADC values, and moderate to marked enhancement, extraocular muscles invasion, and extraorbital extensionare helpful in the diagnosis of orbital RMS.
基金Funding for this study was provided by the Natural Science Foundation of Jiangsu Province(No.BK20191141)Top Talent Support Program for Young and Middle-aged People of Wuxi Health Committee(Nos.BJ2020044,BJ2020057,and HB2020043)+2 种基金Fundamental Research Funds of Health and Family Planning Commission of Wuxi(No.M202024)the Special Program for Translational Medicine Research of Wuxi Translational Medicine Center(Nos.2020DHYB07 and 2020DHYB03)Key Special Project of Precision Medicine of Wuxi Health Commission(No.J202101).
文摘The recruitment of key cells to regeneration sites is a promising strategy to promote functional wound healing.Dermal fibroblasts exhibit a heterogeneous population of cells during homeostasis and in response to injury.Papillary fibroblasts play central regulatory roles in the regeneration of skin appendages during wound healing.Inspired by the phenomenon where bait for grass carp can attract grouped grass carps to a fishing spot soon,“Grass Carp Fishing”multifunctional hydrogels,that is,codelivery of an antibody of leucine-rich repeats and immunoglobulin-like domains 1(Lrig1)on the surface of papillary fibroblasts and insulinlike growth factor 1(IGF1)with recruitment function,can recruit papillary fibroblasts.In the experiments,carboxymethyl chitosan showed positive effects in promoting cell proliferation and neovascularization,while dopamine-grafted gelatin was effective in stabilizing the structure and prolonging the degradation time.The sustained release of Lrig1 antibodies and IGF1 from injectable self-healing multifunctional hydrogels persistently accelerated the migration and proliferation of Lrig1+fibroblasts.The in vivo results from a full-thickness cutaneous wound model showed that injectable self-healing multifunctional hydrogel accelerated wound healing and skin regeneration through the recruitment of Lrig1+papillary fibroblasts in wound tissue.Our findings reveal an injectable self-healing multifunctional hydrogel for regeneration,a promising approach to promoting skin wound healing.
基金supported by the National Natural Science Foundation of China(Grant Nos.41630532&41575093)the National Key Research and Development Program of China(Grant Nos.2016YFA0602501&2018YFA0606004).
文摘The spatial and temporal variations of the vegetation carbon flux in China from 1901 to 2005 were studied using the vegetation net primary production(NPP)values from seven Earth-system models.In addition,the temporal and spatial changes in the nitrogen deposition flux in China were studied using the NHx and NOy fluxes from 1901 to 2005.The relationship between changes in the carbon flux,nitrogen flux and climate was analyzed.The results show that(1)over the past 100 years,NPP in China has shown an upward trend.The average trend coefficient is 0.88 and the NPP distribution trend is generally low in the north and high in the south,with a gradual increase from the northwest to the southeast.Temperature,precipitation and radiation are all conducive to plant growth in the direction of the gradient.The correlation coefficients between the ensemble model mean NPP and temperature,precipitation,longwave radiation and shortwave radiation are 0.88,0.73,0.91 and 0.67,respectively.(2)In the past 100 years,the NHx and NOy fluxes in China have shown an upward trend,with trend coefficients of 0.98 and 0.98,respectively,which pass the 99.9%confidence level of the t-test.NHx and NOy fluxes are also generally low in the north and high in the south,with a gradual increase from the northwest to the southeast in a step-like pattern.(3)The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and air temperature is similar,with only slight differences in values.The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and precipitation is similar in overall pattern,but the pattern is relatively complicated,with a positive-negative-positive-negative-positive pattern occurring across the monsoon region from north to south,and a negative-positive-negative-positive pattern occurring beyond the monsoon region from east to west.(4)The spatial distribution of the correlation coefficients between the NHx and NOy fluxes and NPP shows a generally consistent pattern,but the pattern is relatively uneven.The average distribution of the ensemble model mean is positive correlation in northeast China and southwest China,and alternating positive and negative correlation in other regions.
文摘Nonalcoholic fatty liver disease(NAFLD)is reported to affect 20-30%of adults and is accompanied by various metabolic comorbidities,where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases.Chronic kidney disease(CKD),which has a high incidence rate,high morbidity and mortality rates,and high medical costs,has been linked to NAFLD.CKD is associated with some metabolismrelated risk factors that overlap with metabolic comorbidities of NAFLD.Therefore,to investigate the potential factors that influence CKD occurrence,the association between NAFLD and CKD should be clarified.Some studies have confirmed that NAFLD influences the occurrence and severity of CKD,whereas some studies have indicated that there is no correlation.In this review,the results of a few studies have been discussed,the potential risk factors for CKD in NAFLD are explored,and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.
基金National Natural Science Foundation of China[82130104,81930125,T2221004(S.Y.)22107081(B.Q.)],National Key R&D Program of China[2022YFC2303701 and 2021YFF0702004(J.L.)],1.3.5 project for disciplines of excellence+7 种基金West China Hospital,Sichuan University[ZYXY21001(S.Y.)ZYYC21008(J.L.)],the fast-track grants of SARS-CoV-2 research,West China Hospital,Sichuan University[HX-2019-nCoV-053(S.Y.)]National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University[Z2021JC008(J.L.)]National Natural Science Foundation of China Excellent Young Scientists Fund(Hong Kong and Macao)[32122001(H.C.)]the Health and Medical Research Fund[CID-HKU1-5,COVID1903010-14,and 20190652(H.C.)]the Food and Health Bureau,The Government of the Hong Kong Special Administrative Regionthe General Research Fund[17118621,17123920 and 17119122(H.C.)]of Research Grants Council,the Government of the Hong Kong Special Administrative Regionthe National Program on Key Research Project of China[2020YFA0707500 and 2020YFA0707504(H.C.)].
文摘Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health.Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals eithershow limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of thesedrugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a newgeneration antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). Thiscompound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, butalso other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology.Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstandingsafety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigationprovides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.
基金supported by the Key Research and Development Program of Shandong Province(NO.2019GSF108254,China).
文摘Aims:Proton pump inhibitors(PPI)are widely used for gastroesophageal varices in patients with cirrhosis after endoscopic therapy,although the effect of PPI on these patients remains controversial.This study aimed to evaluate the effect of PPI on gastroesophageal varices in patients with cirrhosis after endoscopic therapy,including variceal bleeding and adverse events.Methods:Cirrhotic patients with endoscopically confirmed gastroesophageal varices were enrolled in this study between May 2017 and June 2019.Eligible patients were randomized into two groups:one group received PPI for 14 days and the other group did not receive PPI treatment(n=53 in each group).All patients were followed for 8 weeks.Results:During the follow‐up period,three patients(5.66%)in the PPI group experienced variceal bleeding on days 9,16,and 25 after endoscopic therapy,including two patients with acute bleeding and one with primary prophylaxis.In the non‐PPI group,three patients(5.66%)experienced variceal bleeding on days 7,42,and 56 after endoscopic therapy,including one patient with acute bleeding and two with secondary prophylaxis(p=0.990).The incidence of adverse events was similar between the two groups(37.74%vs.28.30%,p=0.30).Conclusions:PPI did not appear to reduce variceal bleeding and adverse events in patients with cirrhosis after endoscopic therapy.
基金the National Natural Science Foundation of China(No.21971002)the Natural Science Foundation of Anhui Province(Nos.1908085QB45 and 2008085QB81)。
文摘High yield production of phenol from hydroxylation of benzene with low energy consumption is of paramount importance,but still challenging.Herein,a new strategy,consisting of using diatomic synergistic modulation(DSM)to effectively control the separation of photo-generated carriers for an enhanced production of phenol is reported.The atomic level dispersion of Fe and Cr respectively decorated on Al based MIL-53-NH_(2)photocatalyst(Fe1/Cr:MIL-53-NH_(2))is designed,in which Cr single atoms are substituted for Al3+while Fe single atoms are coordinated by N.Notably,the Fe1/Cr:MIL-53-NH_(2)significantly boosts the photooxidation of benzene to phenol under visible light irradiation,which is much higher than those of MIL-53-NH_(2),Cr:MIL-53-NH_(2),Fe1/MIL-53-NH_(2),and Fe nanoparticles/Cr:MIL-53-NH_(2)catalysts.Theoretical and experimental results reveal that the Cr single atoms and Fe single atoms can act as electron acceptor and electron donor,respectively,during photocatalytic reaction,exhibiting a synergistic effect on the separation of the photo-generated carriers and thereby causing great enhancement on the benzene oxidation.This strategy provides new insights for rational design of advanced photocatalysts at the atomic level.
基金National Natural Science Foundation of China(Nos.U1704161,U1504203,21601158)Zhengzhou University(No.32210431)for the financial supports。
文摘A ratiometric fluorescent hybrid nanoprobe CDs-1 for arginine(Arg),exhibiting high sensitivity(the limit of detection,LOD,being 6.5×10^-8 mol/L) and excellent selectivity and anti-interference ability,was fabricated through fluorescence resonance energy transfer(FRET) and the electrostatic attraction between positively-charged hemicyanine molecules and negatively-charged carbon dots(CDs).Arg can be quantitatively detected in the concentration range from 6.0×10^-5 mol/L to 2.7×10^-4 mol/L.Further,due to its ability to target mitochondrion and low cytotoxicity,intracellular Arg was succes s fully tracked through ratiometric fluorescence imaging.