The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped w...The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped with a 2.5-meter diameter primary mirror, an active optics system, and a mosaic CCD camera with 0.73 gigapixels on the primary focal plane for highquality image capture over a 6.5-square-degree field of view. The installation of WFST near the summit of Saishiteng mountain in the Lenghu region is scheduled in summer of 2023, and the operation is planned to start three months later. WFST will scan the northern sky in four optical bands(u, g, r and i) at cadences from hourly/daily in the deep high-cadence survey(DHS) program, to semi-weekly in the wide field survey(WFS) program. During a photometric night, a nominal 30 s exposure in the WFS program will reach a depth of 22.27, 23.32, 22.84, and 22.31(AB magnitudes) in these four bands, respectively, allowing for the detection of a tremendous amount of transients in the low-z universe and a systematic investigation of the variability of Galactic and extragalactic objects. In the DHS program, intranight 90 s exposures as deep as 23(u) and 24 mag(g), in combination with target of opportunity follow-ups, will provide a unique opportunity to explore energetic transients in demand for high sensitivities, including the electromagnetic counterparts of gravitational wave events, supernovae within a few hours of their explosions,tidal disruption events and fast, luminous optical transients even beyond redshift of unity. In addition, the final 6-year co-added images, anticipated to reach g■25.8 mag in WFS or 1.5 mags deeper in DHS, will be of fundamental importance to general Galactic and extragalactic science. The highly uniform legacy surveys of WFST will serve as an indispensable complement to those of the Vera C. Rubin Observatory's Legacy Survey of Space and Time(LSST) that monitors the southern sky.展开更多
The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their produc...The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.展开更多
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemis...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.展开更多
BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a no...BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.展开更多
Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated gluc...Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated glucose uptake(IMGU)is critical in skeletal muscle and cardiac myocytes,but non-insulin-mediated glucose uptake(NIMGU)should not be neglected.Methods:CAV3 siRNAs were designed and transfected in C2C12 cells and H9c2 cells in skeletal muscle and cardiac muscle,respectively,and C2C12 and H9c2 cells were cultured in DMEM medium with and without insulin,respectively.Glucose transporter 4(GLUT4)protein expression was detected by Western blot,and the glucose uptake rate of cells was measured by biochemical kit.Results:Transfection with CAV3 siRNA successfully down-regulated CAV3 protein expression in C2C12 and H9c2 cells.In the absence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.05)after 48 h of transfection in C2C12 cells,and GLUT4 expression was decreased(P<0.05)and glucose uptake was reduced(P<0.01)after 48 h of transfection in H9c2 cells.In the presence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.01)after 48 h of transfection in C2C12 cells,and the downregulation of GLUT4 was not statistically significant and glucose uptake was reduced(P<0.01)after 48 hours of transfection in H9c2 cells.Conclusion:Two different states,IMGU and NIMGU,exist in C2C12 cells and H9c2 cells.Both in the quiet state stimulated by insulin as well as in the absence of insulin stimulation,the cellular uptake of glucose is affected by GLUT4 changes regulated by CAV3.展开更多
Cu-Cr-W composite coatings were prepared by mechanical alloying(MA)method using different powder ratios,rotational speeds and milling time.The micro structures and chemical compositions of as-synthesized coatings were...Cu-Cr-W composite coatings were prepared by mechanical alloying(MA)method using different powder ratios,rotational speeds and milling time.The micro structures and chemical compositions of as-synthesized coatings were analyzed by scanning electron microscopy(SEM)and energy-dispersive spectroscopy(EDS).Phases of ball-milled powders were identified by X-ray diffraction(XRD).The results indicate that the coating fabricated with powder ratio of 40 wt%Cu-Cr-W has better surface and cross-sectional microstructures and higher microhardness.The comparisons of cross-sectional micro structures of the coatings fabricated at different rotational speeds suggest that rotational speed of 300 r·min-1is the optimal for fabrication the coating,and the optimal milling time for the formation of coating is 7 h.The results of microhardness test show that the hardness of the substrate is largely improved because of the as-fabricated coatings.The results of the friction and wear tests indicate that the wear resistance of the copper substrate is improved after the deposition of Cu-Cr-W coating on it.The coating fabricated for 7 h exhibits the lowest friction coefficient,indicating its favorable friction and wear resistance.The formation mechanism of the coating was elucidated.According to the investigations in this work,the Cu-Cr-W coating fabricated by MA method is considered to be effective to reinforce the copper substrate.展开更多
基金supported by the Cyrus Chun Ying Tang Foundationsthe Major Science and Technology Project of Qinghai Province(Grant No.2019ZJ-A10)+4 种基金the 111 Project for“Observational and Theoretical Research on Dark Matter and Dark Energy”(Grant No.B23042)the National Natural Science Foundation of China(Grant Nos.11833007,12073078,12173088,12192221,12192224,12233008,12273036,and 12273113)the Frontier Scientific Research Program of Deep Space Exploration Laboratory(Grant No.2022-QYKYJH-HXYF-012)the support from the USTC Research Funds of the Double First-Class Initiative(Grant No.YD2030002009)Project for Young Scientists in Basic Research of the Chinese Academy of Sciences(Grant No.YSBR-061),respectively。
文摘The Wide Field Survey Telescope(WFST) is a dedicated photometric surveying facility being built jointly by University of Science and Technology of China(USTC) and the Purple Mountain Observatory(PMO). It is equipped with a 2.5-meter diameter primary mirror, an active optics system, and a mosaic CCD camera with 0.73 gigapixels on the primary focal plane for highquality image capture over a 6.5-square-degree field of view. The installation of WFST near the summit of Saishiteng mountain in the Lenghu region is scheduled in summer of 2023, and the operation is planned to start three months later. WFST will scan the northern sky in four optical bands(u, g, r and i) at cadences from hourly/daily in the deep high-cadence survey(DHS) program, to semi-weekly in the wide field survey(WFS) program. During a photometric night, a nominal 30 s exposure in the WFS program will reach a depth of 22.27, 23.32, 22.84, and 22.31(AB magnitudes) in these four bands, respectively, allowing for the detection of a tremendous amount of transients in the low-z universe and a systematic investigation of the variability of Galactic and extragalactic objects. In the DHS program, intranight 90 s exposures as deep as 23(u) and 24 mag(g), in combination with target of opportunity follow-ups, will provide a unique opportunity to explore energetic transients in demand for high sensitivities, including the electromagnetic counterparts of gravitational wave events, supernovae within a few hours of their explosions,tidal disruption events and fast, luminous optical transients even beyond redshift of unity. In addition, the final 6-year co-added images, anticipated to reach g■25.8 mag in WFS or 1.5 mags deeper in DHS, will be of fundamental importance to general Galactic and extragalactic science. The highly uniform legacy surveys of WFST will serve as an indispensable complement to those of the Vera C. Rubin Observatory's Legacy Survey of Space and Time(LSST) that monitors the southern sky.
基金supported by the Key Research and Development Program of Guangxi(2021AB13014)Major Project of Guangxi Innovation Driven(AA18118016)+7 种基金National Key Research and Development Program of China(2017YFC0908000)Natural Key Research and Development Project(2020YFA0113200)National Natural Science Foundation of China(81770759,82060145,31970814)Natural Science Foundation of Guangxi Zhuang Autonomous Region(2021JJA140912)Advanced Innovation Teams and Xinghu Scholars Program of Guangxi Medical University,Guangxi Key Laboratory for Genomic and Personalized Medicine(19-050-22,19-185-33,20-065-33,22-35-17)Major Project of Scientific Research and Technology Development Plan of Nanning(20221023)Guangxi Natural Science Foundation(2022GXNSFAA035641)Self-funded Project of Health Commission of Guangxi Zhuang Autonomous Region(Z-A20230620)。
文摘The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.
基金the Suzhou Medical Center,No.Szlcyxzx202103the National Natural Science Foundation of China,No.82171828+9 种基金the Key R&D Plan of Jiangsu Province(Social Development),No.BE2021652the Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011Wu Jieping Medical Foundation,No.320.6750.2021-01-12the Special Project of“Technological Innovation”Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113Beijing Bethune Charitable Foundation,No.STLKY0016Research Projects of China Baoyuan Investment Co.,No.270004Suzhou Gusu Health Talent Program,No.GSWS2022028Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
基金Supported by Shanghai Natural Science Foundation,No.22ZR1455900Shanghai Putuo District Health System Science and Technology Innovation Project Key Project,No.ptkwws202201Shanghai Putuo District Xinglin Excellent Youth Talent Training Program,No.ptxlyq2201.
文摘BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious charac-teristics.Approximately 50%of the patients have a normal weight or are not obese.They are said to have lean-type MAFLD,and few studies of such patients are available.Because MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.MAFLD and analyze metabolic pathways.UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD patients.RESULTS Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P<0.05).Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy indi-viduals(P<0.01).The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals(P<0.05)and the expression of triglycerides and fasting blood glucose were increased(P<0.01).A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with P<0.05 and variable importance in projection>1.The levels of PA,OA,LA,and AA were significantly increased compared with healthy individuals.CONCLUSION The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified biomarkers.PA,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.
基金the financial supports from the National Natural Science Foundation of China(Nos.72088101,51739004,72004060,21776066)the Natural Science Foundation of Hunan Province,China(No.2021JJ40157)the Scientific Research Project of Hunan Education Department,China(No.20C0545)。
基金This study was supported by the National Natural Science Foundation of China(No.81660360)The Natural Science Foundation of Guangxi(No.2019JJA140605)。
文摘Objective:To observe whether CAV3 is involved in the physiological process of IMGU and NIMGU.Down-regulation of caveolin-3(CAV3)protein expression by small interference RNAs(iRNA)has been studied.Insulin-mediated glucose uptake(IMGU)is critical in skeletal muscle and cardiac myocytes,but non-insulin-mediated glucose uptake(NIMGU)should not be neglected.Methods:CAV3 siRNAs were designed and transfected in C2C12 cells and H9c2 cells in skeletal muscle and cardiac muscle,respectively,and C2C12 and H9c2 cells were cultured in DMEM medium with and without insulin,respectively.Glucose transporter 4(GLUT4)protein expression was detected by Western blot,and the glucose uptake rate of cells was measured by biochemical kit.Results:Transfection with CAV3 siRNA successfully down-regulated CAV3 protein expression in C2C12 and H9c2 cells.In the absence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.05)after 48 h of transfection in C2C12 cells,and GLUT4 expression was decreased(P<0.05)and glucose uptake was reduced(P<0.01)after 48 h of transfection in H9c2 cells.In the presence of insulin stimulation,GLUT4 expression was decreased(P<0.01)and glucose uptake was reduced(P<0.01)after 48 h of transfection in C2C12 cells,and the downregulation of GLUT4 was not statistically significant and glucose uptake was reduced(P<0.01)after 48 hours of transfection in H9c2 cells.Conclusion:Two different states,IMGU and NIMGU,exist in C2C12 cells and H9c2 cells.Both in the quiet state stimulated by insulin as well as in the absence of insulin stimulation,the cellular uptake of glucose is affected by GLUT4 changes regulated by CAV3.
基金financially supported by the National Nature Science Foundation of China (No.51475232)the Jiangsu Province Natural Science Foundation (No.BK20141411)a Project Founded by the Priority Academic Program Development of Jiangsu Higher Education Institution
文摘Cu-Cr-W composite coatings were prepared by mechanical alloying(MA)method using different powder ratios,rotational speeds and milling time.The micro structures and chemical compositions of as-synthesized coatings were analyzed by scanning electron microscopy(SEM)and energy-dispersive spectroscopy(EDS).Phases of ball-milled powders were identified by X-ray diffraction(XRD).The results indicate that the coating fabricated with powder ratio of 40 wt%Cu-Cr-W has better surface and cross-sectional microstructures and higher microhardness.The comparisons of cross-sectional micro structures of the coatings fabricated at different rotational speeds suggest that rotational speed of 300 r·min-1is the optimal for fabrication the coating,and the optimal milling time for the formation of coating is 7 h.The results of microhardness test show that the hardness of the substrate is largely improved because of the as-fabricated coatings.The results of the friction and wear tests indicate that the wear resistance of the copper substrate is improved after the deposition of Cu-Cr-W coating on it.The coating fabricated for 7 h exhibits the lowest friction coefficient,indicating its favorable friction and wear resistance.The formation mechanism of the coating was elucidated.According to the investigations in this work,the Cu-Cr-W coating fabricated by MA method is considered to be effective to reinforce the copper substrate.
基金supported in part by the National Key R&D Program of China(2021YFC2203100)CAS Young Interdisciplinary Innovation Team(JCTD-2022–20)+8 种基金the National Natural Science Foundation of China(11875113,11961131007,12261131497,12003029,11833005,and 12192224)the 111 Project for“Observational and Theoretical Research on Dark Matter and Dark Energy”(B23042)Fundamental Research Funds for Central Universitiesthe Disposizione del Presidente INFN n.24433 in INFN Sezione di MilanoChina Postdoctoral Science Foundation(2023TQ0355)CSC Innovation Talent FundsUSTC Fellowship for International CooperationUSTC Research Funds of the Double First-Class InitiativeCAS project for young scientists in basic research(YSBR-006)。
