The Tong’an-Baishuidong mining district(TBMD),located in the eastern section of the Jiangnan Orogen,is a newly discovered granite-type lithium mining district.Thisstudy presents new monazite U-Pb chronological,whole-...The Tong’an-Baishuidong mining district(TBMD),located in the eastern section of the Jiangnan Orogen,is a newly discovered granite-type lithium mining district.Thisstudy presents new monazite U-Pb chronological,whole-rock geochemical,and Nd-Pb isotopic data to reveal the petrogenesis and geodynamic setting of the Wutang granites in the TBMD.The monazite U-Pb age of 145.8±1.0 Ma indicates that the granites were emplaced at the end of the Late Jurassic.Whole-rock geochemical results demonstrate that the Wutang granites are enriched in SiO_(2)(72.80-73.40 wt%)but depleted in CaO(0.44-0.90 wt%)and MgO+TiO_(2)+TFeO(1.79-2.05 wt%).These granites exhibit negative Eu anomalies(δEu=0.3−0.4)and high aluminum saturation indexes(A/CNK=1.2−1.6),differentiation indexes(DI=90-92),and Rb/Sr ratios(4.7-8.1).They also have moderate Ba contents(239-278 ppm)and low Sr contents(52.7-82.0 ppm)as well as low Nb/Ta(2.2-5.3)and Zr/Hf(21.3-31.5)ratios.All these indicate that they are highly fractionated granites.Additionally,these granites contain 5-10 wt%muscovite but no hornblende,with calculated corundum contents of 2.3-5.5 wt%.They have low high-field strength element(HFSE)contents(Zr+Nb+Ce+Y=182-202 ppm)and zircon saturation temperatures(700-770℃),with Th and Y negatively linked with Rb.These petrographic and geochemi-cal features further reveal that the Wutang granites belong to highly fractionated S-type granites.TheεNd(t)values of these granites range from−9.03 to−8.23,corresponding to two-stage model ages(T DM2)of 1488-1553 Ma.The initial Pb isotope ratios are:(206 Pb/^(204)Pb)i=18.38-18.55,(^(207)Pb/^(204)Pb)i=15.67-15.68,and(^(208)Pb/^(204)Pb)i=38.62-38.67.These Nd-Pb isotopic results demonstrate that the parental magma originated from the partial melting of ancient crustal materials.In the meantime,the TBMD in the eastern section of the Jiangnan Orogen was in a compression-extension transitional setting associated with the episodic subduction of the Paleo-Pacific Plate.展开更多
In response to the awareness of limited fossil resources and environmental concerns,catalytic conversion of renewable lignocellulose biomass to value-added chemicals and fuels is of great significance and attractive f...In response to the awareness of limited fossil resources and environmental concerns,catalytic conversion of renewable lignocellulose biomass to value-added chemicals and fuels is of great significance and attractive for sustainable chemistry.Division of Biomass Conversion and Bio-Energy attached to Dalian National Laboratory for Clean Energy has devoted themselves to valorization of lignocellulose biomass since launched in 2011.Our research interests focus on breeding of biomass resources(inulin and microalgae),exploration of catalytic and biological technologies,and production of energy chemicals and fuels.Although lignocellulose biomass is renewable and abundant,the way of utilization should be reasonable according to its structural characteristics in view of efficiency and economy.In this review,to celebrate the DICP's 70 th anniversary,we will highlight the major fundamental advances in DICP about the conversion of lignocellulose to value-added chemicals and liquid fuels.Particular attention will be paid to the transformation of cellulose and its derivatives to glycols,acids and nitrogen-containing chemicals,hemicellulose-derived platform molecule furfural to jet fuels and lignin to aromatics using catalytic technologies.展开更多
Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exi...Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.展开更多
Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,le...Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.展开更多
Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 ...Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.展开更多
AIM: To investigate the one-year refractive outcomes and optical quality following PRESBYOND laser-blended vision(LBV).METHODS: This retrospective study included 20 patients who underwent PRESBYOND treatment between J...AIM: To investigate the one-year refractive outcomes and optical quality following PRESBYOND laser-blended vision(LBV).METHODS: This retrospective study included 20 patients who underwent PRESBYOND treatment between Jan 2019 and Aug 2020. The patients were asked to attend a followup outpatient visit one year after surgery. Distance and near visual acuity as well as subjective refraction were examined. Optical quality was assessed using wavefront-supported custom ablation. A questionnaire evaluating optical quality and satisfaction was completed at the last visit.RESULTS: The average patient age was 48.1±7.4 y(range, 41 to 58 y). The mean preoperative spherical equivalent was-7.59±2.39D. At the one-year follow-up, two eyes(both dominant eyes) lost one line of corrected distance visual acuity(CDVA), while the remaining eyes(38/40) maintained or gained lines of CDVA. The average binocular uncorrected distance visual acuity improved from 0.15±0.03 to 0.90±0.26(decimal vision;P<0.001). The average binocular uncorrected near visual acuity increased from 0.34±0.28 to 0.97±0.07(P<0.001). The spherical aberration was 0.04±0.06 μm in the nondominant eye and 0.09±0.09 μm in the dominant eye(P=0.02). All patients were satisfied with or accepted the outcomes of the surgery. The primary complaints were related to disturbances in night vision and relatively inferior near vision.CONCLUSION: Over the one-year observation period, PRESBYOND is a safe and effective option for presbyopia correction. The optical quality and near vision deserve further investigation.展开更多
Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we dev...Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics.The results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial effects.Our work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART.展开更多
Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not be...Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.展开更多
The rapidly increasing popularity of mobile devices has changed the methods with which people access various network services and increased net-work traffic markedly.Over the past few decades,network traffic identific...The rapidly increasing popularity of mobile devices has changed the methods with which people access various network services and increased net-work traffic markedly.Over the past few decades,network traffic identification has been a research hotspot in the field of network management and security mon-itoring.However,as more network services use encryption technology,network traffic identification faces many challenges.Although classic machine learning methods can solve many problems that cannot be solved by port-and payload-based methods,manually extract features that are frequently updated is time-consuming and labor-intensive.Deep learning has good automatic feature learning capabilities and is an ideal method for network traffic identification,particularly encrypted traffic identification;Existing recognition methods based on deep learning primarily use supervised learning methods and rely on many labeled samples.However,in real scenarios,labeled samples are often difficult to obtain.This paper adjusts the structure of the auxiliary classification generation adversarial network(ACGAN)so that it can use unlabeled samples for training,and use the wasserstein distance instead of the original cross entropy as the loss function to achieve semisupervised learning.Experimental results show that the identification accuracy of ISCX and USTC data sets using the proposed method yields markedly better performance when the number of labeled samples is small compared to that of convolutional neural network(CNN)based classifier.展开更多
Many sandstone-type uranium mineralization sites have been identified along the northern margin of the Qaidam Basin in North China.Intense tectonism and multistage magmatism that occurred there have restricted the use...Many sandstone-type uranium mineralization sites have been identified along the northern margin of the Qaidam Basin in North China.Intense tectonism and multistage magmatism that occurred there have restricted the use of conventional techniques(petrogeochemistry)to deduce the sources of detritus and uranium in these sediments,and to further explore the sandstone-type uranium deposits.In this study,U-Pb geochronological and Hf isotopic analyses were conducted on detrital zircon grains collected from Jurassic to Paleogene sandstones exposed in the Yuqia area of the Qaidam Basin.The results indicate that the U-Pb ages of the analyzed zircon grains are clustered into four groups,285–229,498–401,999–806,and 2520–2305 Ma.Theε_(Hf)(t)of the analyzed zircon grains ranges from-21.9 to+10.5,with two-stage Hf model ages(T_(DM2))concentrated between 2.1 and 1.3 Ga.Based on paleocurrent studies and results of petrological,detrital zircon geochronology,and Hf isotopic analyses,the Jurassic sediments in the Yuqia area were likely derived from the tectonic belt along the northern margin of the Qaidam Basin,such as the Qilian Mountains and the Quanji Block.In contrast,the Paleogene sediments were probably sourced from the northern margin of the Qaidam Basin and the Qilian Mountains.The uranium and thorium content and Th/U value of the rock mass and sedimentary strata in the source area show that the Indosinian Early Paleozoic uranium-rich granites and the Middle Jurassic uranium-rich strata of the northern margin of the Qaidam tectonic belt in the source area provide dual uranium sources for the Yuqia sandstone-type uranium mineralization.Therefore,the study area appears to be favorable for sandstone-type uranium mineralization and may have potential for uranium prospecting.展开更多
The sandstone-hosted uranium deposits in the SW Songliao Basin differ from typical sandstone-hosted uranium deposits in terms of the geological features of the ore-deposits,including the geometry of the orebodies,mine...The sandstone-hosted uranium deposits in the SW Songliao Basin differ from typical sandstone-hosted uranium deposits in terms of the geological features of the ore-deposits,including the geometry of the orebodies,mineral assemblage and petrography.Detailed drill core and microscopic observations,scanning electron microscopy(SEM),electron microprobe analysis(EMPA),heavy mineral concentrates,and fluid inclusion studies of the Upper Cretaceous Yaojia Formation,i.e.,the uranium-bearing layer,were integrated to investigate the roles of hydrothermal fluids in the formation of these uranium deposits.We found that the kaolinite alteration is developed in the mineralized zones,but it is less common in the peripheral areas.The fluid inclusions are hydrothermal fluids with a medium-low temperature(67 to 179 ℃) and a high salinity(5.9 wt.% to 20.1 wt.%).According to the analyses,three kinds of hydrothermal fluids,i.e.,the acid fluid,the groundwater heated by the mafic magma,and the alkaline fluid rich in Ca^(2+) and CO_(3)^(2-),were identified.The fluids might have low U content,but they have participated in the formation of the uranium deposits successively.Kaolinite formed by the acid-hydrothermal fluid absorbed large amounts of uranium.Subsequently,the thermal energy from the hydrothermal fluids changed the intrastratal redox environment and increased the solubility of the uranium minerals in the fluid.The alkaline-hydrothermal fluid rich in Ca^(2+) and C0_(3)^(2-) facilitated the formation of stable Ca-U(Ⅵ)-CO_(3) complex,which led to the enrichment of soluble uranium in solution,and final precipitation as pitchblende,brannerite and Ti-bearing uranium minerals in the uranium ores.展开更多
Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an i...Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.展开更多
In this paper,experimental,theoretical and numerical approaches were employed to scrutinize the buckle propagation events occurring in pipes subjected to external pressure.Two groups of samples with different radius-t...In this paper,experimental,theoretical and numerical approaches were employed to scrutinize the buckle propagation events occurring in pipes subjected to external pressure.Two groups of samples with different radius-to-thickness ratios were fabricated using steel pipes of ultra-high strength and were subjected to compression of external pressure in a sealed pressure vessel specially designed and customized for the experiment.Experimental results were recorded through a data acquisition system.For facilitating the theoretical calculations,uniaxial tensile tests were performed on tensile pieces cut from the same pipes to obtain the material properties.It was found from the experimental results that once a buckle is initiated in a pipe,the external pressure dropped to a specific value called buckle propagation pressure and kept at this level until the whole pipe is flattened into a dog-bone shape.Based on the measured material properties and geometric parameters,theoretical solutions were computed using established ring models and shell model,and finite element predictions were also obtained from ABAQUS software.The efficiency and accuracy of the shell model and finite element model were expounded by comparing various theoretical solutions and numerical predictions with the experimental results.With the authenticated shell model and finite element model,a deep insight into the phenomenon of buckle propagation of pressurized long pipes was provided by performing a series of parametric study.展开更多
基金funded by the Program of Science and Technology Department of Jiangxi Province(2023KDG01002 and 2023KDG01003)the National Natural Science Foundation of China(42062006 and 41962007)+1 种基金the Key Research and Development Program of Jiangxi Province(20223BBG71015)the Personnel Training Project of Jiangxi Bureau of Geology(2023JXDZKJRC02,2022JXDZKJRC04,and 2024JXDZKJRC05).
文摘The Tong’an-Baishuidong mining district(TBMD),located in the eastern section of the Jiangnan Orogen,is a newly discovered granite-type lithium mining district.Thisstudy presents new monazite U-Pb chronological,whole-rock geochemical,and Nd-Pb isotopic data to reveal the petrogenesis and geodynamic setting of the Wutang granites in the TBMD.The monazite U-Pb age of 145.8±1.0 Ma indicates that the granites were emplaced at the end of the Late Jurassic.Whole-rock geochemical results demonstrate that the Wutang granites are enriched in SiO_(2)(72.80-73.40 wt%)but depleted in CaO(0.44-0.90 wt%)and MgO+TiO_(2)+TFeO(1.79-2.05 wt%).These granites exhibit negative Eu anomalies(δEu=0.3−0.4)and high aluminum saturation indexes(A/CNK=1.2−1.6),differentiation indexes(DI=90-92),and Rb/Sr ratios(4.7-8.1).They also have moderate Ba contents(239-278 ppm)and low Sr contents(52.7-82.0 ppm)as well as low Nb/Ta(2.2-5.3)and Zr/Hf(21.3-31.5)ratios.All these indicate that they are highly fractionated granites.Additionally,these granites contain 5-10 wt%muscovite but no hornblende,with calculated corundum contents of 2.3-5.5 wt%.They have low high-field strength element(HFSE)contents(Zr+Nb+Ce+Y=182-202 ppm)and zircon saturation temperatures(700-770℃),with Th and Y negatively linked with Rb.These petrographic and geochemi-cal features further reveal that the Wutang granites belong to highly fractionated S-type granites.TheεNd(t)values of these granites range from−9.03 to−8.23,corresponding to two-stage model ages(T DM2)of 1488-1553 Ma.The initial Pb isotope ratios are:(206 Pb/^(204)Pb)i=18.38-18.55,(^(207)Pb/^(204)Pb)i=15.67-15.68,and(^(208)Pb/^(204)Pb)i=38.62-38.67.These Nd-Pb isotopic results demonstrate that the parental magma originated from the partial melting of ancient crustal materials.In the meantime,the TBMD in the eastern section of the Jiangnan Orogen was in a compression-extension transitional setting associated with the episodic subduction of the Paleo-Pacific Plate.
基金supported by the National Natural Science Foundation of China(Projects 21790331,21603218,21703236 and 21872138)the Strategic Priority Research Program of the Chinese Academy of Sciences(Nos.XDB17020300 and XDA21030400)+1 种基金the Youth Innovation Promotion Association,CAS(2018219)DICP ZZBS201811
文摘In response to the awareness of limited fossil resources and environmental concerns,catalytic conversion of renewable lignocellulose biomass to value-added chemicals and fuels is of great significance and attractive for sustainable chemistry.Division of Biomass Conversion and Bio-Energy attached to Dalian National Laboratory for Clean Energy has devoted themselves to valorization of lignocellulose biomass since launched in 2011.Our research interests focus on breeding of biomass resources(inulin and microalgae),exploration of catalytic and biological technologies,and production of energy chemicals and fuels.Although lignocellulose biomass is renewable and abundant,the way of utilization should be reasonable according to its structural characteristics in view of efficiency and economy.In this review,to celebrate the DICP's 70 th anniversary,we will highlight the major fundamental advances in DICP about the conversion of lignocellulose to value-added chemicals and liquid fuels.Particular attention will be paid to the transformation of cellulose and its derivatives to glycols,acids and nitrogen-containing chemicals,hemicellulose-derived platform molecule furfural to jet fuels and lignin to aromatics using catalytic technologies.
基金the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine,China(Grant No.:ZYYCXTD-C-202002)the National Key Research and Development Program of China,China(Grant No.:2020YFA0908000)+1 种基金the National Natural Science Foundation of China,China(Grant Nos.:81803389,81903588,32101219,81702580,82074098,81903866,and 81803456)the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ14-YQ-050,ZZ14-YQ-059,ZZ15-ND-10,ZZ15-YQ-063,ZZ14-ND-010,and ZZ14-FL-002).
文摘Hepatic stellate cells(HSCs)are essential drivers of fibrogenesis.Inducing activated-HSC apoptosis is a promising strategy for treating hepatic fibrosis.18beta-glycyrrhetinic acid(18b-GA)is a natural compound that exists widely in herbal medicines,such as Glycyrrhiza uralensis Fisch,which is used for treating multiple liver diseases,especially in Asia.In the present study,we demonstrated that 18b-GA decreased hepatic fibrosis by inducing the apoptosis in activated HSCs.18b-GA inhibited the expression of a-smooth muscle actin and collagen type Ⅰ alpha-1.Using a chemoproteomic approach derived from activity-based protein profiling,together with cellular thermal shift assay and surface plasmon resonance,we found that 18b-GA covalently targeted peroxiredoxin 1(PRDX1)and peroxiredoxin 2(PRDX2)proteins via binding to active cysteine residues and thereby inhibited their enzymatic activities.18b-GA induced the elevation of reactive oxygen species(ROS),resulting in the apoptosis of activated HSCs.PRDX1 knockdown also led to ROS-mediated apoptosis in activated HSCs.Collectively,our findings revealed the target proteins and molecular mechanisms of 18b-GA in ameliorating hepatic fibrosis,highlighting the future development of 18b-GA as a novel therapeutic drug for hepatic fibrosis.
基金supported by the National Key Research and Development Program of China(Grant Nos.:2020YFA0908000,2022YFC2303600)the Establishment of Sino-Austria“Belt and Road”Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(Grant No.:2020YFE0205100)+13 种基金the National Natural Science Foundation of China(Grant Nos.:82104480,82004248,82141001,82274182,82074098,82173914)the Fundamental Research Funds for the Central public welfare research institutes(Grant Nos.:ZZ14-YQ-055,ZZ14-YQ-059,ZZ14-YQ-060,ZXKT19018,ZXKT19021,ZXKT19022,ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010,ZZ15-ND-10,ZZ16-ND-10-19)the Beijing Municipal Natural Science Foundation(Grant No.:7214287)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(Grant No.:ZYYCXTD-C-202002)the Young Elite Scientists Sponsorship Program by CACM(Grant No.:2021QNRC2B29)the CACMS Innovation Fund(Grant Nos.:CI2021A05101,CI2021A05104)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(Grant No.:CI2021B014)the Science and Technology Foundation of Shenzhen(Grant No.:JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)Shenzhen Governmental Sustainable Development Fund(Grant No.:KCXFZ20201221173612034)Shenzhen key Laboratory of Kidney Diseases(Grant No.:ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Grant No.:SZGSP001)the Distinguished Expert Project of Sichuan Province Tianfu Scholar(Grant No.:CW202002)the State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process Open Fund(Grant No.:SKL2020Z0302).
文摘Tripterygium glycosides tablet(TGT),the classical commercial drug of Tripterygium wilfordii Hook.F.has been effectively used in the treatment of rheumatoid arthritis,nephrotic syndrome,leprosy,Behcet's syndrome,leprosy reaction and autoimmune hepatitis.However,due to its narrow and limited treatment window,TGT-induced organ toxicity(among which liver injury accounts for about 40%of clinical reports)has gained increasing attention.The present study aimed to clarify the cellular and molecular events underlying TGT-induced acute liver injury using single-cell RNA sequencing(scRNA-seq)technology.The TGT-induced acute liver injury mouse model was constructed through short-term TGT exposure and further verified by hematoxylin-eosin staining and liver function-related serum indicators,including alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase and total bilirubin.Using the mouse model,we identified 15 specific subtypes of cells in the liver tissue,including endothelial cells,hepatocytes,cholangiocytes,and hepatic stellate cells.Further analysis indicated that TGT caused a significant inflammatory response in liver endothelial cells at different spatial locations;led to marked inflammatory response,apoptosis and fatty acid metabolism dysfunction in hepatocytes;activated hepatic stellate cells;brought about the activation,inflammation,and phagocytosis of liver capsular macrophages cells;resulted in immune dysfunction of liver lymphocytes;disturbed the intercellular crosstalk in liver microenvironment by regulating various signaling pathways.Thus,these findings elaborate the mechanism underlying TGT-induced acute liver injury,provide new insights into the safe and rational applications in the clinic,and complement the identification of new biomarkers and therapeutic targets for liver protection.
基金Supported by State Scientific Key Projects for New Drug Research and Development (2009ZX09102-250)High-tech Research Project for Medicine and Pharmacology of Jiangsu Province (BG20070605)
文摘Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.
基金Supported by National Natural Science Foundation of China(No.81770955)National Natural Science Foundation of China for Young Scholars(No.82000929)+6 种基金Project of Shanghai Science and Technology(No.20410710100)Clinical Research Plan of SHDC(No.SHDC2020CR1043B)Project of Shanghai Xuhui District Science and Technology(No.2020-015)Project of Shanghai Xuhui District Science and Technology(No.XHLHGG202104)Shanghai Engineering Research Center of Laser and Autostereoscopic 3D for Vision Care(No.20DZ2255000)Shanghai Sailing Program(No.20YF1405000)。
文摘AIM: To investigate the one-year refractive outcomes and optical quality following PRESBYOND laser-blended vision(LBV).METHODS: This retrospective study included 20 patients who underwent PRESBYOND treatment between Jan 2019 and Aug 2020. The patients were asked to attend a followup outpatient visit one year after surgery. Distance and near visual acuity as well as subjective refraction were examined. Optical quality was assessed using wavefront-supported custom ablation. A questionnaire evaluating optical quality and satisfaction was completed at the last visit.RESULTS: The average patient age was 48.1±7.4 y(range, 41 to 58 y). The mean preoperative spherical equivalent was-7.59±2.39D. At the one-year follow-up, two eyes(both dominant eyes) lost one line of corrected distance visual acuity(CDVA), while the remaining eyes(38/40) maintained or gained lines of CDVA. The average binocular uncorrected distance visual acuity improved from 0.15±0.03 to 0.90±0.26(decimal vision;P<0.001). The average binocular uncorrected near visual acuity increased from 0.34±0.28 to 0.97±0.07(P<0.001). The spherical aberration was 0.04±0.06 μm in the nondominant eye and 0.09±0.09 μm in the dominant eye(P=0.02). All patients were satisfied with or accepted the outcomes of the surgery. The primary complaints were related to disturbances in night vision and relatively inferior near vision.CONCLUSION: Over the one-year observation period, PRESBYOND is a safe and effective option for presbyopia correction. The optical quality and near vision deserve further investigation.
基金supported by grants from the National Key Research and Development Program of China(Nos.2020YFA0908000 and 2022YFC2303600)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202002)+10 种基金the National Natural Science Foundation of China(Nos.82141001,82274182,82074098 and 82173914)the CACMS Innovation Fund(Nos.CI2021A05101 and CI2021A05104):the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(No.CI2021B014)the Science and Technology Foundation of Shenzhen(No.JCYj20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases)Establishment of Sino-Austria"Belt and Road"Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research(No.2020YFE0205100)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Nos.ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-YQ-052,ZZ14-FL-002,ZZ14-ND-010 and ZZ15-ND-10)Introduce innovative team projects of Jinan(No.202228029)Shenzhen Governmental Sustainable Development Fund(No.KCXFZ20201221173612034)Shenzhen Key Laboratory of Kidney Diseases(No.ZDSYS201504301616234)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(No.SZGSPO01).
文摘Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics.The results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial effects.Our work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART.
基金supported by the China Postdoctoral Science Foundation(2022M723370)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA23080603)。
文摘Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.
基金This work is supported by the Science and Technology Project of State Grid Jiangsu Electric Power Co.,Ltd.under Grant No.J2020068.
文摘The rapidly increasing popularity of mobile devices has changed the methods with which people access various network services and increased net-work traffic markedly.Over the past few decades,network traffic identification has been a research hotspot in the field of network management and security mon-itoring.However,as more network services use encryption technology,network traffic identification faces many challenges.Although classic machine learning methods can solve many problems that cannot be solved by port-and payload-based methods,manually extract features that are frequently updated is time-consuming and labor-intensive.Deep learning has good automatic feature learning capabilities and is an ideal method for network traffic identification,particularly encrypted traffic identification;Existing recognition methods based on deep learning primarily use supervised learning methods and rely on many labeled samples.However,in real scenarios,labeled samples are often difficult to obtain.This paper adjusts the structure of the auxiliary classification generation adversarial network(ACGAN)so that it can use unlabeled samples for training,and use the wasserstein distance instead of the original cross entropy as the loss function to achieve semisupervised learning.Experimental results show that the identification accuracy of ISCX and USTC data sets using the proposed method yields markedly better performance when the number of labeled samples is small compared to that of convolutional neural network(CNN)based classifier.
基金supported by the National Natural Science Foundation of China (Nos. 41772066, 41902075, 41862010, 42172098, and 42002091)the Open Fund from the Key Laboratory of the Northern Qinghai-Tibet Plateau Geological Processes and Mineral Resources (No. 2019-KY-04)+1 种基金the Open Fund from the State Key Laboratory of Nuclear Resources and Environment of the East China University of Technology (No. NRE1309)the Postgraduate Innovation Fund Project of Jiangxi Province, China (No. YC2021-B161)
文摘Many sandstone-type uranium mineralization sites have been identified along the northern margin of the Qaidam Basin in North China.Intense tectonism and multistage magmatism that occurred there have restricted the use of conventional techniques(petrogeochemistry)to deduce the sources of detritus and uranium in these sediments,and to further explore the sandstone-type uranium deposits.In this study,U-Pb geochronological and Hf isotopic analyses were conducted on detrital zircon grains collected from Jurassic to Paleogene sandstones exposed in the Yuqia area of the Qaidam Basin.The results indicate that the U-Pb ages of the analyzed zircon grains are clustered into four groups,285–229,498–401,999–806,and 2520–2305 Ma.Theε_(Hf)(t)of the analyzed zircon grains ranges from-21.9 to+10.5,with two-stage Hf model ages(T_(DM2))concentrated between 2.1 and 1.3 Ga.Based on paleocurrent studies and results of petrological,detrital zircon geochronology,and Hf isotopic analyses,the Jurassic sediments in the Yuqia area were likely derived from the tectonic belt along the northern margin of the Qaidam Basin,such as the Qilian Mountains and the Quanji Block.In contrast,the Paleogene sediments were probably sourced from the northern margin of the Qaidam Basin and the Qilian Mountains.The uranium and thorium content and Th/U value of the rock mass and sedimentary strata in the source area show that the Indosinian Early Paleozoic uranium-rich granites and the Middle Jurassic uranium-rich strata of the northern margin of the Qaidam tectonic belt in the source area provide dual uranium sources for the Yuqia sandstone-type uranium mineralization.Therefore,the study area appears to be favorable for sandstone-type uranium mineralization and may have potential for uranium prospecting.
基金supported by the National Natural Science Foundation of China (Nos. U2067202, 41772068, 42172098)the Natural Science Foundation of Jiangxi Province (No. 20202BAB213017)+1 种基金the Joint Innovation Fund of China Uranium Industry Co., LTD and East China University of Technology (No. NRE2021-02)Open Foundation of State Key Laboratory of Nuclear Resources and Environment (No. JELRGBDT202007)。
文摘The sandstone-hosted uranium deposits in the SW Songliao Basin differ from typical sandstone-hosted uranium deposits in terms of the geological features of the ore-deposits,including the geometry of the orebodies,mineral assemblage and petrography.Detailed drill core and microscopic observations,scanning electron microscopy(SEM),electron microprobe analysis(EMPA),heavy mineral concentrates,and fluid inclusion studies of the Upper Cretaceous Yaojia Formation,i.e.,the uranium-bearing layer,were integrated to investigate the roles of hydrothermal fluids in the formation of these uranium deposits.We found that the kaolinite alteration is developed in the mineralized zones,but it is less common in the peripheral areas.The fluid inclusions are hydrothermal fluids with a medium-low temperature(67 to 179 ℃) and a high salinity(5.9 wt.% to 20.1 wt.%).According to the analyses,three kinds of hydrothermal fluids,i.e.,the acid fluid,the groundwater heated by the mafic magma,and the alkaline fluid rich in Ca^(2+) and CO_(3)^(2-),were identified.The fluids might have low U content,but they have participated in the formation of the uranium deposits successively.Kaolinite formed by the acid-hydrothermal fluid absorbed large amounts of uranium.Subsequently,the thermal energy from the hydrothermal fluids changed the intrastratal redox environment and increased the solubility of the uranium minerals in the fluid.The alkaline-hydrothermal fluid rich in Ca^(2+) and C0_(3)^(2-) facilitated the formation of stable Ca-U(Ⅵ)-CO_(3) complex,which led to the enrichment of soluble uranium in solution,and final precipitation as pitchblende,brannerite and Ti-bearing uranium minerals in the uranium ores.
基金suppor ted by the National Key Research and Development Program of China(2020YFA0908000)the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202002)+2 种基金the National Natural Science Foundation of China(82074098,82003814)the CACMS Innovation Fund(CI2021A05101)the Fundamental Research Funds for the Central public welfare research institutes(ZZ14-YQ-050,ZZ14-YQ-051,ZZ14-ND-010,ZZ15-ND-10 and ZZ14-FL-002)。
文摘Background: Malaria is a devastating infectious disease that disproportionally threatens hundreds of millions of people in developing countries. In the history of anti-malaria campaign, chloroquine(CQ) has played an indispensable role, however, its mechanism of action(MoA) is not fully understood.Methods: We used the principle of photo-affinity labeling and click chemistry-based functionalization in the design of a CQ probe and developed a combined deconvolution strategy of activity-based protein profiling(ABPP) and mass spectrometry-coupled cellular thermal shift assay(MS-CETSA) that identified the protein targets of CQ in an unbiased manner in this study. The interactions between CQ and these identified potential protein hits were confirmed by biophysical and enzymatic assays.Results: We developed a novel clickable, photo-affinity chloroquine analog probe(CQP) which retains the antimalarial activity in the nanomole range, and identified a total of 40 proteins that specifically interacted and photocrosslinked with CQP which was inhibited in the presence of excess CQ. Using MS-CETSA, we identified 83 candidate interacting proteins out of a total of 3375 measured parasite proteins. At the same time, we identified 8 proteins as the most potential hits which were commonly identified by both methods.Conclusions: We found that CQ could disrupt glycolysis and energy metabolism of malarial parasites through direct binding with some of the key enzymes, a new mechanism that is different from its well-known inhibitory effect of hemozoin formation. This is the first report of identifying CQ antimalarial targets by a parallel usage of labeled(ABPP)and label-free(MS-CETSA) methods.
基金The work presented herein was conducted with the financial support of Guangdong Natural Science Foundation(2017A030313013).
文摘In this paper,experimental,theoretical and numerical approaches were employed to scrutinize the buckle propagation events occurring in pipes subjected to external pressure.Two groups of samples with different radius-to-thickness ratios were fabricated using steel pipes of ultra-high strength and were subjected to compression of external pressure in a sealed pressure vessel specially designed and customized for the experiment.Experimental results were recorded through a data acquisition system.For facilitating the theoretical calculations,uniaxial tensile tests were performed on tensile pieces cut from the same pipes to obtain the material properties.It was found from the experimental results that once a buckle is initiated in a pipe,the external pressure dropped to a specific value called buckle propagation pressure and kept at this level until the whole pipe is flattened into a dog-bone shape.Based on the measured material properties and geometric parameters,theoretical solutions were computed using established ring models and shell model,and finite element predictions were also obtained from ABAQUS software.The efficiency and accuracy of the shell model and finite element model were expounded by comparing various theoretical solutions and numerical predictions with the experimental results.With the authenticated shell model and finite element model,a deep insight into the phenomenon of buckle propagation of pressurized long pipes was provided by performing a series of parametric study.
