Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role i...Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.展开更多
Three-dimensional(3D)printing technology has been widely used to create artificial rock samples in rock mechanics.While 3D printing can create complex fractures,the material still lacks sufficient similarity to natura...Three-dimensional(3D)printing technology has been widely used to create artificial rock samples in rock mechanics.While 3D printing can create complex fractures,the material still lacks sufficient similarity to natural rock.Extrusion free forming(EFF)is a 3D printing technique that uses clay as the printing material and cures the specimens through high-temperature sintering.In this study,we attempted to use the EFF technology to fabricate artificial rock specimens.The results show the physico-mechanical properties of the specimens are significantly affected by the sintering temperature,while the nozzle diameter and layer thickness also have a certain impact.The specimens are primarily composed of SiO_(2),with mineral compositions similar to that of natural rocks.The density,uniaxial compressive strength(UCS),elastic modulus,and tensile strength of the printed specimens fall in the range of 1.65–2.54 g/cm3,16.46–50.49 MPa,2.17–13.35 GPa,and 0.82–17.18 MPa,respectively.It is capable of simulating different types of rocks,especially mudstone,sandstone,limestone,and gneiss.However,the simulation of hard rocks with UCS exceeding 50 MPa still requires validation.展开更多
Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the com...Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.展开更多
Low temperature is one of the adversities threatening the growth and development and reduces the yield of rubber trees.However,molecular mechanisms toward rubber trees in response to low temperature are largely unclea...Low temperature is one of the adversities threatening the growth and development and reduces the yield of rubber trees.However,molecular mechanisms toward rubber trees in response to low temperature are largely unclear.In this study,7,159 and 7,600 differentially expressed genes(DEGs)were identified in‘Reyan 73397’rubber trees.Through GO analysis,the catalytic activity was the representative of the GO term in the only DEGs at the two studied temperatures(room temperature and 4°C,respectively),while KEGG analysis showed that carbon metabolism was the most important grouping under the comparison of these two temperatures.In addition,expression of 9 members of transcription factor MYB family genes were further verified by qRT-PCR,and MYB family genes may play important roles in the regulation of rubber trees under low temperature stress.This study provided a theoretical foundation for(1)revealing the molecular mechanisms of rubber trees in response to low temperature and(2)breeding of tolerant varieties of rubber trees.展开更多
The geographical condition of Qingdao, China is relatively special;the transport of various inland pollutants, the emissions of marine aerosol and local pollutants will have an impact on the changes of atmospheric aer...The geographical condition of Qingdao, China is relatively special;the transport of various inland pollutants, the emissions of marine aerosol and local pollutants will have an impact on the changes of atmospheric aerosol concentration. By using the stability classification method, trajectory clustering analysis and the NOAA HYSPLIT model, the seasonal distribution characteristics of atmospheric inhalable particulate matter concentration in Qingdao, China and its relationship with meteorological conditions, mixed layer height, and the seasonal characteristics of Qingdao pollutant transport were analyzed. The results show that the variation trends of PM2.5 and PM10 were about the same, and there are obvious seasonal differences, which are high in winter and spring, and low in summer and autumn. The concentration of inhalable particulate matter has a negative correlation with temperature, wind speed and relative humidity. The concentration of inhalable particulate matter is distinct in different relative humidity ranges. When the wind speed is less than 3 - 4 m/s, there are more inhalable particles, while the mass concentration shows obvious reduction with the wind speed more than 4 m/s. There is a significant negative correlation between the mass concentration of pollutants and the daily maximum mixed layer height. The larger the concentration of pollutants, the smaller the thickness of the daily largest mixed layer. Conversely, the smaller the mass concentration of pollutants, the larger the thickness of the daily largest mixed layer. The pollutant transport in Qingdao has obvious seasonal characteristics. The air mass in spring, autumn and winter is mainly medium-long distance transport from Mongolia and southern Russia, and medium-short distance transport from Inner Mongolia and northeast of China. The source of air masses in summer is mainly transported from the eastern and sea areas.展开更多
The visibility characteristics and meteorological conditions of a sea fog process on 27</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-fa...The visibility characteristics and meteorological conditions of a sea fog process on 27</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> February, 2016 are analyzed and the heavy fog process is simulated by the Weather Research and Forecasting (WRF) model in this paper. The forecast results show that the visibility in Qingdao coastal area is light fog on the night of the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">. In the WRF simulation, it can be observed from the sea-level pressure that the wind direction of Qingdao and the coastal area turned southerly with the eastward movement of the low pressure system on surface from 1200 UTC to 1800 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">. A large amount of water vapor brought by easterly and southerly wind provides sufficient water vapor conditions for the formation and development of the sea fog. At 975 hPa, there is a strong warm tongue over Shandong Peninsula at 0600 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">, w</span><span><span style="font-family:Verdana;">hile the offshore is affected by the cold tongue, where the horizontal temperature gradient is large and there is a strong baroclinicity. At 850 hPa, there is a weak warm ridge over Qingdao at 1200 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">, which means that it is an inversion layer, which is conducive to the maintenance of fog.展开更多
NCEP/NCAR reanalysis data, the Arctic Oscillation (AO) index and the atmospheric visibility (Vis) data at 134 sites in eastern China (ECN) are used to investigate the possible influence of AO on the wintertime weather...NCEP/NCAR reanalysis data, the Arctic Oscillation (AO) index and the atmospheric visibility (Vis) data at 134 sites in eastern China (ECN) are used to investigate the possible influence of AO on the wintertime weather and Vis over ECN. A higher relative humidity (RH, compared with the normal year) is identified over ECN in the winters with a positive phase of AO, and the wind anomaly is generally inshore in the coast areas of China. All these processes are consistent with Vis degradation over ECN. On the contrary, in the winters with a negative phase of AO, a lower RH can be identified over ECN, and the wind anomaly is generally offshore, which is favorable for Vis improvement.展开更多
The relationship between time-space variation characteristics and the variation of the general atmospheric circulation of rainfall occurred in Asia, Africa through North Africa-Middle East-Western Middle Asia-Eastern ...The relationship between time-space variation characteristics and the variation of the general atmospheric circulation of rainfall occurred in Asia, Africa through North Africa-Middle East-Western Middle Asia-Eastern Middle Asia, Northwest China-Eastern Northwest China-North China and Northeast China is studied based on the analysis of GPCC rainfall data from 1901 to 2010 and annual precipitation in relevant cities of China from 1901 to 2010, and the data of NCEP of surface pressure as well as 500 Hpa potential high from 1950 to 2010. The result shows that the total precipitation presents a decreasing trend in north Africa to the northeast of China in recent 100 years. It has a mutation in 1950s. The precipitation presented a decreasing trend in North Africa and Middle East, in recent 100 years;it presented a further decreasing trend after 1950s. It presented a decreasing trend before 1950s and an increasing trend after 1950s in Middle Asia and Northwest china. It also presented a decreasing trend before 1950s and an increasing trend between 1950s to 1990s, and decreased later in Eastern Northwest China, North China and Northeast China which also presented in a more or less period in different areas from North Africa to Northeast China. The beginning of less precipitation years and less period occurred after it presented less period in north Africa in time and space. After it moved to the east areas as the year past, at last, the SLPA fields which presented more or less precipitations of years from North Africa to Northeast China were analyzed. It also shows that the SLPA fields which presented more were beneficial to the precipitations and presented negative effects of precipitations in the polar, high and mid- and lower latitudes.展开更多
We studied effects of sea surface temperature anomaly (SSTA) in the Barents Sea in autumn on the atmospheric circulation in northeast China in winter, using the NCEP reanalysis data and sea surface temperature (SST) d...We studied effects of sea surface temperature anomaly (SSTA) in the Barents Sea in autumn on the atmospheric circulation in northeast China in winter, using the NCEP reanalysis data and sea surface temperature (SST) data of the Hadley Center. The results show that the ocean thermal conditions in the Barents Sea in autumn can be used as an important reference factor for predicting the cold air activity in China. When the sea surface temperature anomaly of the Barents Sea elevated in the autumn, the sea-level pressure anomaly elevated in eastern China on December, northeast China and southeastern Russia on January and February. In the years when the SSTA of the Barents Sea elevated in the autumn, the abnormal high-pressure ridge developed over Europe, and the geopotential height in western China appeared negative anomaly at 500 hPa. At 1000 hPa, the Mongolia high-pressure increased and the northerly airflow strengthened the cold high-latitude air broke out to the south, which was easy to affect northeast and north of China. In negative SSTA years, the high-pressure ridge was west to the north Atlantic, and the geopotential height in central and northern Siberia appeared negative anomaly at 500 hPa;the Mongolia high-pressure was weakened at 1000 hPa.展开更多
Rare-earth(RE)halide solid electrolytes(HSEs)have been an emerging research area due to their good electrochemical and mechanical properties for all-solid-state lithium batteries(ASSBs).However,only very limited types...Rare-earth(RE)halide solid electrolytes(HSEs)have been an emerging research area due to their good electrochemical and mechanical properties for all-solid-state lithium batteries(ASSBs).However,only very limited types of HSEs have been reported with high performance.In this work,tens of grams of RE-HSE Li_(3)TbBr_(6)(LTbB)was synthesized by a vacuum evaporationassisted method.The as-prepared LTbB displays a high ionic conductivity of 1.7 mS·cm^(-1),a wide electrochemical window,and good formability.Accordingly,the assembled solid lithium-tellurium(Li-Te)battery based on the LTbB HSE exhibits excellent cycling stability up to 600 cycles,which is superior to most previous reports.The processes and the chemicals during the discharge/charge of Li-Te batteries have been studied by various in situ and ex situ characterizations.Theoretical calculations have demonstrated the dominant conductivity contributions of the direct[octahedral]-[octahedral]([Oct]-[Oct])pathway for Li ion migrations in the electrolyte.The Tb sites guarantee efficient electron transfer while the Li 2s orbitals are not affected during migration,leading to a low activation barrier.Therefore,this successful fabrication and application of LTbB have offered a highly competitive solution for solid electrolytes in ASSBs,indicating the great potential of RE-based HSEs in energy devices.展开更多
Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applic...Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.展开更多
Solid lithium-ion-conducting material is the key component in the fabrication of next-gene ration all solid state lithium ion batteries(LIBs)which would exhibit superior safety and performance compared with the curren...Solid lithium-ion-conducting material is the key component in the fabrication of next-gene ration all solid state lithium ion batteries(LIBs)which would exhibit superior safety and performance compared with the currently widely used ones that resort to essentially inflammable and volatile organic solvents.To date,great efforts have been made in developing solid conductors with high lithium ion conductivity,such as polymers and inorganic materials.Rare earths play a very important role in this area and have attracted extensive interest since the recent decades for their unique properties in the realm of solidstate inorganic lithium-ion-conducting electrolyte materials.In this introduction,we focus on the role of rare earths in solid conductors for lithium ion,especially in a few most studied systems such as perovskites,garnets,silicates,borohydride and the recently reported halides in which rare earths act as a key framing component.Besides,the effect of rare earths as dopants is also discussed in some recently studied systems.Valence,coordination,and size are the most important factors that influence the crystal structure and property of these lithium ion conductors.The aim of this review is to highlight the great potentials of these unique elements of rare earths,and to help improve the performance of existing materials and explore new applications in the development of new LIBs with high performances.展开更多
It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and ...It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.展开更多
Na-O_(2) and K-O_(2) batteries have attracted extensive attention in recent years.However,the parasitic reactions involving the discharge product of NaO_(2) or K anode with electrolytes and the severe Na or K dendrite...Na-O_(2) and K-O_(2) batteries have attracted extensive attention in recent years.However,the parasitic reactions involving the discharge product of NaO_(2) or K anode with electrolytes and the severe Na or K dendrites plague their rechargeability and cycle stability.Herein,we report a hybrid Na//K^(+)-containing electrolyte//O_(2) battery consisting of a Na anode,1.0 M of potassium trifate in diglyme,and a porous carbon cathode.Upon discharging,KO_(2) is preferentially produced via oxygen reduction in the cathode with Na+stripped from the Na anode,and reversely,the KO_(2) is electrochemically decomposed with Na+plated back onto the anode.Te new reaction pathway can circumvent the parasitic reactions involving instable NaO_(2) and active K anode,and alternatively,the good stability and conductivity of KO_(2) and stable Na stripping/plating in the presence of K^(+) enable the hybrid battery to exhibit an average discharge/charge voltage gap of 0.15 V,high Coulombic efciency of>96%,and superior cycling stability of 120 cycles.Tis will pave a new pathway to promote metal-air batteries.展开更多
This paper introduces a kind of open cycle absorption heat wet flue gas heat recovery system,which use CaCl_(2) as the working medium.The system will use the wet heat recovery method and combined with an efficient hea...This paper introduces a kind of open cycle absorption heat wet flue gas heat recovery system,which use CaCl_(2) as the working medium.The system will use the wet heat recovery method and combined with an efficient heat pump system for flue gas as a heat source generator.Through direct contact with the solution in the absorber,the flue gas is going to carry out gas,liquid heat transfer between heat exchanger,realization of sensible heat and latent heat step by step.As the key part of the system,absorber is established by one-dimensional steady-state heat transfer and mass transfer model.This paper uses the finite difference method to model the discrete numerical methods,and an-alyzes the characteristics of heat and mass transfer in the absorber.We obtain the concentration curves of the three kinds of working medium’s temperature and flow along the height direction.We also analyze the influence of CaCl_(2) solution parameters changes on the absorption process,parsing the reason of the temperature change by analyzing the three working medium’s energy flow trend.We found that the temperature change of flue gas is non-monotonic,which decreases gradually in the range of absorption tower height 0-0.9 m,and then increases gradually.The reason for this change is that sensible heat exchange and latent heat exchange exist between flue gas and solution.Although such a change has an impact on the efficiency of the system,it prevents the"white smoke"from condensing in the air,which effectively protects the environment.Compared with conventional LiBr absorption heat pump,the system constructed in this paper has certain advantages in latent heat recovery,flue gas heat energy utilization,energy conservation and emission reduction and economy.展开更多
As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for ca...As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for cancer treatment.Errors in cytokinesis increase CIN,so cytokinesis components are valuable targets for treating cancer.However,due to the short time span and confined space of cytokinesis bridges,profiling cytokinesis fac-tors is challenging.Taking advantage of engineered ascorbate peroxidase(APEX2),we established a cytokinesis bridge-APEX reaction in living cells.A total of 218 cytokinesis bridge proteins were identified with high relia-bility.Knockdown of cytokinesis bridge genes generated micronuclei that activate the cGAS-pathway and cause apoptosis in cancer cells bearing high CIN rather than low CIN.Thus,our study proposes a strategy for killing high-CIN tumors regardless of tumor type,and provides a proteome resource of cytokinetic bridges for future research.展开更多
基金supported by National Natural Science Foundation of China(Grant Nos.:81891010/81891011,81725023,82003614,82173950,31770192,32070187,32161133003 and 82003681)China Postdoctoral Science Foundation(Grant No:2022T150029).
文摘Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.
基金financially supported by the Beijing Natural Science Foundation for Young Scientists(Grant No.8214052)the Talent Fund of Beijing Jiaotong University(Grant No.2021RC226)the State Key Laboratory for GeoMechanics and Deep Underground Engineering,China University of Mining and Technology(Grant No.SKLGDUEK2115).
文摘Three-dimensional(3D)printing technology has been widely used to create artificial rock samples in rock mechanics.While 3D printing can create complex fractures,the material still lacks sufficient similarity to natural rock.Extrusion free forming(EFF)is a 3D printing technique that uses clay as the printing material and cures the specimens through high-temperature sintering.In this study,we attempted to use the EFF technology to fabricate artificial rock specimens.The results show the physico-mechanical properties of the specimens are significantly affected by the sintering temperature,while the nozzle diameter and layer thickness also have a certain impact.The specimens are primarily composed of SiO_(2),with mineral compositions similar to that of natural rocks.The density,uniaxial compressive strength(UCS),elastic modulus,and tensile strength of the printed specimens fall in the range of 1.65–2.54 g/cm3,16.46–50.49 MPa,2.17–13.35 GPa,and 0.82–17.18 MPa,respectively.It is capable of simulating different types of rocks,especially mudstone,sandstone,limestone,and gneiss.However,the simulation of hard rocks with UCS exceeding 50 MPa still requires validation.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) (XDB29010102)National Natural Science Foundation of China (NSFC) (91957124,82161148010,32041010)+4 种基金Self-supporting Program of Guangzhou Laboratory (SRPG22-001)National Science and Technology Infrastructure of China (National Pathogen Resource Center-NPRC-32)Management Strategy of the Tertiary Prevention and Treatment of Diabetes Based on DIP system (supported by China Health Promotion Foundation)supported by the Youth Innovation Promotion Association of CAS (Y2021034)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202208)。
文摘Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.
基金supported by the following grants:the National Key R&D Program of China(2019YFD1000500)the National Natural Science Foundations of Shandong Province(ZR2020MC138)the Agricultural Variety Improvement Project of Shandong Province(2020LZGC007).
文摘Low temperature is one of the adversities threatening the growth and development and reduces the yield of rubber trees.However,molecular mechanisms toward rubber trees in response to low temperature are largely unclear.In this study,7,159 and 7,600 differentially expressed genes(DEGs)were identified in‘Reyan 73397’rubber trees.Through GO analysis,the catalytic activity was the representative of the GO term in the only DEGs at the two studied temperatures(room temperature and 4°C,respectively),while KEGG analysis showed that carbon metabolism was the most important grouping under the comparison of these two temperatures.In addition,expression of 9 members of transcription factor MYB family genes were further verified by qRT-PCR,and MYB family genes may play important roles in the regulation of rubber trees under low temperature stress.This study provided a theoretical foundation for(1)revealing the molecular mechanisms of rubber trees in response to low temperature and(2)breeding of tolerant varieties of rubber trees.
文摘The geographical condition of Qingdao, China is relatively special;the transport of various inland pollutants, the emissions of marine aerosol and local pollutants will have an impact on the changes of atmospheric aerosol concentration. By using the stability classification method, trajectory clustering analysis and the NOAA HYSPLIT model, the seasonal distribution characteristics of atmospheric inhalable particulate matter concentration in Qingdao, China and its relationship with meteorological conditions, mixed layer height, and the seasonal characteristics of Qingdao pollutant transport were analyzed. The results show that the variation trends of PM2.5 and PM10 were about the same, and there are obvious seasonal differences, which are high in winter and spring, and low in summer and autumn. The concentration of inhalable particulate matter has a negative correlation with temperature, wind speed and relative humidity. The concentration of inhalable particulate matter is distinct in different relative humidity ranges. When the wind speed is less than 3 - 4 m/s, there are more inhalable particles, while the mass concentration shows obvious reduction with the wind speed more than 4 m/s. There is a significant negative correlation between the mass concentration of pollutants and the daily maximum mixed layer height. The larger the concentration of pollutants, the smaller the thickness of the daily largest mixed layer. Conversely, the smaller the mass concentration of pollutants, the larger the thickness of the daily largest mixed layer. The pollutant transport in Qingdao has obvious seasonal characteristics. The air mass in spring, autumn and winter is mainly medium-long distance transport from Mongolia and southern Russia, and medium-short distance transport from Inner Mongolia and northeast of China. The source of air masses in summer is mainly transported from the eastern and sea areas.
文摘The visibility characteristics and meteorological conditions of a sea fog process on 27</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;"> February, 2016 are analyzed and the heavy fog process is simulated by the Weather Research and Forecasting (WRF) model in this paper. The forecast results show that the visibility in Qingdao coastal area is light fog on the night of the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">. In the WRF simulation, it can be observed from the sea-level pressure that the wind direction of Qingdao and the coastal area turned southerly with the eastward movement of the low pressure system on surface from 1200 UTC to 1800 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">. A large amount of water vapor brought by easterly and southerly wind provides sufficient water vapor conditions for the formation and development of the sea fog. At 975 hPa, there is a strong warm tongue over Shandong Peninsula at 0600 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">, w</span><span><span style="font-family:Verdana;">hile the offshore is affected by the cold tongue, where the horizontal temperature gradient is large and there is a strong baroclinicity. At 850 hPa, there is a weak warm ridge over Qingdao at 1200 UTC on the 26</span><sup><span style="font-family:Verdana;">th</span></sup><span style="font-family:Verdana;">, which means that it is an inversion layer, which is conducive to the maintenance of fog.
文摘NCEP/NCAR reanalysis data, the Arctic Oscillation (AO) index and the atmospheric visibility (Vis) data at 134 sites in eastern China (ECN) are used to investigate the possible influence of AO on the wintertime weather and Vis over ECN. A higher relative humidity (RH, compared with the normal year) is identified over ECN in the winters with a positive phase of AO, and the wind anomaly is generally inshore in the coast areas of China. All these processes are consistent with Vis degradation over ECN. On the contrary, in the winters with a negative phase of AO, a lower RH can be identified over ECN, and the wind anomaly is generally offshore, which is favorable for Vis improvement.
文摘The relationship between time-space variation characteristics and the variation of the general atmospheric circulation of rainfall occurred in Asia, Africa through North Africa-Middle East-Western Middle Asia-Eastern Middle Asia, Northwest China-Eastern Northwest China-North China and Northeast China is studied based on the analysis of GPCC rainfall data from 1901 to 2010 and annual precipitation in relevant cities of China from 1901 to 2010, and the data of NCEP of surface pressure as well as 500 Hpa potential high from 1950 to 2010. The result shows that the total precipitation presents a decreasing trend in north Africa to the northeast of China in recent 100 years. It has a mutation in 1950s. The precipitation presented a decreasing trend in North Africa and Middle East, in recent 100 years;it presented a further decreasing trend after 1950s. It presented a decreasing trend before 1950s and an increasing trend after 1950s in Middle Asia and Northwest china. It also presented a decreasing trend before 1950s and an increasing trend between 1950s to 1990s, and decreased later in Eastern Northwest China, North China and Northeast China which also presented in a more or less period in different areas from North Africa to Northeast China. The beginning of less precipitation years and less period occurred after it presented less period in north Africa in time and space. After it moved to the east areas as the year past, at last, the SLPA fields which presented more or less precipitations of years from North Africa to Northeast China were analyzed. It also shows that the SLPA fields which presented more were beneficial to the precipitations and presented negative effects of precipitations in the polar, high and mid- and lower latitudes.
文摘We studied effects of sea surface temperature anomaly (SSTA) in the Barents Sea in autumn on the atmospheric circulation in northeast China in winter, using the NCEP reanalysis data and sea surface temperature (SST) data of the Hadley Center. The results show that the ocean thermal conditions in the Barents Sea in autumn can be used as an important reference factor for predicting the cold air activity in China. When the sea surface temperature anomaly of the Barents Sea elevated in the autumn, the sea-level pressure anomaly elevated in eastern China on December, northeast China and southeastern Russia on January and February. In the years when the SSTA of the Barents Sea elevated in the autumn, the abnormal high-pressure ridge developed over Europe, and the geopotential height in western China appeared negative anomaly at 500 hPa. At 1000 hPa, the Mongolia high-pressure increased and the northerly airflow strengthened the cold high-latitude air broke out to the south, which was easy to affect northeast and north of China. In negative SSTA years, the high-pressure ridge was west to the north Atlantic, and the geopotential height in central and northern Siberia appeared negative anomaly at 500 hPa;the Mongolia high-pressure was weakened at 1000 hPa.
基金This work was supported by the National Key R&D Program of China(No.2021YFA1501101)the Natural Science Foundation of China(No.21971117)+11 种基金Functional Research Funds for the Central Universities,Nankai University(No.63186005)Tianjin Key Lab for Rare Earth Materials and Applications(No.ZB19500202)the National Natural Science Foundation of China/Research Grant Council Joint Research Scheme(No.N_PolyU502/21)111 Project(No.B18030)from ChinaOutstanding Youth Project of Tianjin Natural Science Foundation(No.20JCJQJC00130)Key Project of Tianjin Natural Science Foundation(No.20JCZDJC00650)the Projects of Strategic Importance of The Hong Kong Polytechnic University(No.1-ZE2V)Shenzhen Fundamental Research Scheme-General Program(No.JCYJ20220531090807017)National Postdoctoral Program for Innovative Talents(No.BX20220157)Open Foundation of State Key Laboratory of Featured Metal Materials and Life-cycle Safety for Composite Structures(No.2022GXYSOF07)Haihe Laboratory of Sustainable Chemical Transformations.B.L.H.also thanks the support from Research Centre for Carbon-Strategic Catalysis(RCCSC),Research Institute for Smart Energy(RISE)Research Institute for Intelligent Wearable Systems(RI-IWEAR)of the Hong Kong Polytechnic University.
文摘Rare-earth(RE)halide solid electrolytes(HSEs)have been an emerging research area due to their good electrochemical and mechanical properties for all-solid-state lithium batteries(ASSBs).However,only very limited types of HSEs have been reported with high performance.In this work,tens of grams of RE-HSE Li_(3)TbBr_(6)(LTbB)was synthesized by a vacuum evaporationassisted method.The as-prepared LTbB displays a high ionic conductivity of 1.7 mS·cm^(-1),a wide electrochemical window,and good formability.Accordingly,the assembled solid lithium-tellurium(Li-Te)battery based on the LTbB HSE exhibits excellent cycling stability up to 600 cycles,which is superior to most previous reports.The processes and the chemicals during the discharge/charge of Li-Te batteries have been studied by various in situ and ex situ characterizations.Theoretical calculations have demonstrated the dominant conductivity contributions of the direct[octahedral]-[octahedral]([Oct]-[Oct])pathway for Li ion migrations in the electrolyte.The Tb sites guarantee efficient electron transfer while the Li 2s orbitals are not affected during migration,leading to a low activation barrier.Therefore,this successful fabrication and application of LTbB have offered a highly competitive solution for solid electrolytes in ASSBs,indicating the great potential of RE-based HSEs in energy devices.
基金This research was made possible as a result of a generous grant from the Beijing National Science Foundation(grant no.JQ18024)the National Key R&D Program of China(grant no.2018YFA0507602)the National Natural Science Foundation of China(grant nos.91953111 and 91853113).
文摘Peptides can be potentmolecules with high efficacy and selectivity in the development of biotherapeutics.However,the poor pharmacokinetic properties of peptides pose major challenges for their broader medicinal applications.Inspired by the proteinstabilizing role of natural N-glycosylation,we design and synthesize a series of parathyroid hormone(PTH)peptides(1-34),bearing either N-GlcNAc or biantennary complex-type N-glycan modification,and evaluate their serum stability and biological activities.The results indicate that an N-Asn-linked complex-type sialylundecasaccharide can increase the serum half-life and in vivo bioactivity of PTH peptides with a broad tolerance of modification sites.Further,hydrogen/deuterium exchange mass spectroscopy indicates that the larger-sized Nglycan can induce enhanced hydration dynamics in its surroundings,which may facilitate an improved resistance for the peptide against enzymatic proteolysis.This sialylundecasaccharide-based peptideengineering strategy has also been applied to glucagon-like peptide-1(7-37),leading to glycopeptides with enhanced hypoglycemic activity and acting time in vivo.Together,these results demonstrate the potential of using sialylated complextype N-glycan as a general engineering strategy for developing long-acting peptide therapeutics.
基金Project supported by the National Key R&D Program of China(2017YFA0208000)the National Natural Science Foundation of China(21971117,21522106)111 Project(B18030)from China。
文摘Solid lithium-ion-conducting material is the key component in the fabrication of next-gene ration all solid state lithium ion batteries(LIBs)which would exhibit superior safety and performance compared with the currently widely used ones that resort to essentially inflammable and volatile organic solvents.To date,great efforts have been made in developing solid conductors with high lithium ion conductivity,such as polymers and inorganic materials.Rare earths play a very important role in this area and have attracted extensive interest since the recent decades for their unique properties in the realm of solidstate inorganic lithium-ion-conducting electrolyte materials.In this introduction,we focus on the role of rare earths in solid conductors for lithium ion,especially in a few most studied systems such as perovskites,garnets,silicates,borohydride and the recently reported halides in which rare earths act as a key framing component.Besides,the effect of rare earths as dopants is also discussed in some recently studied systems.Valence,coordination,and size are the most important factors that influence the crystal structure and property of these lithium ion conductors.The aim of this review is to highlight the great potentials of these unique elements of rare earths,and to help improve the performance of existing materials and explore new applications in the development of new LIBs with high performances.
基金supported by National Natural Science Foundation of China(Nos.81891010/81891011,81725023,82003614,82173950,31770192,32070187 and 82003681)China Postdoctoral Science Foundation(2022T150029,China)+1 种基金the National Key Research and Development Program of China(No.2017-YFC1700405)the Science&Technology Department of Xinjiang Uygur Autonomous Region(2018AB012,China)。
文摘It is an urgent demand worldwide to control the coronavirus disease 2019(COVID-19)pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The 3-chymotrypsin-like protease(3CL^(pro))and papain-like protease(PL^(pro))are key targets to discover SARS-CoV-2 inhibitors.After screening 12 Chinese herbal medicines and 125 compounds from licorice,we found that a popular natural product schaftoside inhibited 3CL^(pro)and PL^(pro)with IC_(50)values of 1.73±0.22 and 3.91±0.19μmol/L,respectively,and inhibited SARS CoV-2 virus in Vero E6 cells with EC_(50)of 11.83±3. 23μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of3CLpro, and K157, E167 and A246 of PLpro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The antiinflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.
基金Financial support from National Key R&D Program of China(2017YFA0206700)NSFC(grant No.21603108&51671107)+1 种基金National Natural Science Foundation of ChinaResearch Grants Council of Hong Kong joint project(NSFCRGC project of 51761165025)the 111 project of B12015 is acknowledged.
文摘Na-O_(2) and K-O_(2) batteries have attracted extensive attention in recent years.However,the parasitic reactions involving the discharge product of NaO_(2) or K anode with electrolytes and the severe Na or K dendrites plague their rechargeability and cycle stability.Herein,we report a hybrid Na//K^(+)-containing electrolyte//O_(2) battery consisting of a Na anode,1.0 M of potassium trifate in diglyme,and a porous carbon cathode.Upon discharging,KO_(2) is preferentially produced via oxygen reduction in the cathode with Na+stripped from the Na anode,and reversely,the KO_(2) is electrochemically decomposed with Na+plated back onto the anode.Te new reaction pathway can circumvent the parasitic reactions involving instable NaO_(2) and active K anode,and alternatively,the good stability and conductivity of KO_(2) and stable Na stripping/plating in the presence of K^(+) enable the hybrid battery to exhibit an average discharge/charge voltage gap of 0.15 V,high Coulombic efciency of>96%,and superior cycling stability of 120 cycles.Tis will pave a new pathway to promote metal-air batteries.
基金This paper is supported by The National Natural Science Foundation of China.The project approval number is 52076050.In addition,we would like to thank Jiyou Lin and Jianfeng Wu for their support to this paper.
文摘This paper introduces a kind of open cycle absorption heat wet flue gas heat recovery system,which use CaCl_(2) as the working medium.The system will use the wet heat recovery method and combined with an efficient heat pump system for flue gas as a heat source generator.Through direct contact with the solution in the absorber,the flue gas is going to carry out gas,liquid heat transfer between heat exchanger,realization of sensible heat and latent heat step by step.As the key part of the system,absorber is established by one-dimensional steady-state heat transfer and mass transfer model.This paper uses the finite difference method to model the discrete numerical methods,and an-alyzes the characteristics of heat and mass transfer in the absorber.We obtain the concentration curves of the three kinds of working medium’s temperature and flow along the height direction.We also analyze the influence of CaCl_(2) solution parameters changes on the absorption process,parsing the reason of the temperature change by analyzing the three working medium’s energy flow trend.We found that the temperature change of flue gas is non-monotonic,which decreases gradually in the range of absorption tower height 0-0.9 m,and then increases gradually.The reason for this change is that sensible heat exchange and latent heat exchange exist between flue gas and solution.Although such a change has an impact on the efficiency of the system,it prevents the"white smoke"from condensing in the air,which effectively protects the environment.Compared with conventional LiBr absorption heat pump,the system constructed in this paper has certain advantages in latent heat recovery,flue gas heat energy utilization,energy conservation and emission reduction and economy.
基金supported by the National Natural Science Foundation of China(NSFC)(Grants No.81672610,81521002,81871160)to ML,and by the“Clinic+X”program(to ML)of Peking University.
文摘As a common feature of tumors,chromosomal instability(CIN)not only forces carcinomatous evolution,but also loads cancer cells with extra pressure through a robust imbalance of genome patterning that may be used for cancer treatment.Errors in cytokinesis increase CIN,so cytokinesis components are valuable targets for treating cancer.However,due to the short time span and confined space of cytokinesis bridges,profiling cytokinesis fac-tors is challenging.Taking advantage of engineered ascorbate peroxidase(APEX2),we established a cytokinesis bridge-APEX reaction in living cells.A total of 218 cytokinesis bridge proteins were identified with high relia-bility.Knockdown of cytokinesis bridge genes generated micronuclei that activate the cGAS-pathway and cause apoptosis in cancer cells bearing high CIN rather than low CIN.Thus,our study proposes a strategy for killing high-CIN tumors regardless of tumor type,and provides a proteome resource of cytokinetic bridges for future research.
