Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
An intrinsic magnetic topological insulator(TI) is a stoichiometric magnetic compound possessing both inherent magnetic order and topological electronic states. Such a material can provide a shortcut to various novel ...An intrinsic magnetic topological insulator(TI) is a stoichiometric magnetic compound possessing both inherent magnetic order and topological electronic states. Such a material can provide a shortcut to various novel topological quantum effects but remained elusive experimentally for a long time. Here we report the experimental realization of thin films of an intrinsic magnetic TI, MnBi2Te4, by alternate growth of a Bi2Te3 quintuple layer and a MnTe bilayer with molecular beam epitaxy. The material shows the archetypical Dirac surface states in angle-resolved photoemission spectroscopy and is demonstrated to be an antiferromagnetic topological insulator with ferromagnetic surfaces by magnetic and transport measurements as well as first-principles calculations. The unique magnetic and topological electronic structures and their interplays enable the material to embody rich quantum phases such as quantum anomalous Hall insulators and axion insulators at higher temperature and in a well-controlled way.展开更多
To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly...To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.展开更多
[Objectives]To study the quality standard of Chinese drug in compound Qianglinaogingsu Tablets(Fructus Schisandrae Chinensis and Coru Cervi Pantotrichum).[Methods]The thin layer chromatography(TLC)differentiation meth...[Objectives]To study the quality standard of Chinese drug in compound Qianglinaogingsu Tablets(Fructus Schisandrae Chinensis and Coru Cervi Pantotrichum).[Methods]The thin layer chromatography(TLC)differentiation method was established for Fructus Schisandrae Chinensis and Cornu Cervi Pantotrichum.[Results]TLC spots developed were fairly clear,and the blank test showed no interference.[Conclusions]The method is fast,simple and can be used for quality control of Qianglinaoqingsu Tablets.展开更多
Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear...Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.展开更多
This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in t...This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in the 17-19 GHz frequency band of satellite communication.Through systematic simulation analysis,it is found that flexible RF MEMS switch can achieve certain bending radius by miniaturizing the electronic dimension,without degrading the RF performance.It is demonstrated that the RF characteristics of flexible RF MEMS switch with special anchor structural design,fabricated by modified surface MEMS processing,are not sensitive to bending deformation under the curvature of 0 mm^(-1),0.05 mm^(-1),0.10 mm^(-1).Furthermore,the range of bending curvature which will affect the RF characteristics is given through systematic simulation.The flexible RF MEMS switch with high process compatibility and stable RF performance is believed to be promising candidates for future microwave communications and other consumer electronics.展开更多
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.
基金Supported by the Ministry of Science and Technology of Chinathe National Science Foundation of Chinathe Beijing Advanced Innovation Center for Future Chip(ICFC)
文摘An intrinsic magnetic topological insulator(TI) is a stoichiometric magnetic compound possessing both inherent magnetic order and topological electronic states. Such a material can provide a shortcut to various novel topological quantum effects but remained elusive experimentally for a long time. Here we report the experimental realization of thin films of an intrinsic magnetic TI, MnBi2Te4, by alternate growth of a Bi2Te3 quintuple layer and a MnTe bilayer with molecular beam epitaxy. The material shows the archetypical Dirac surface states in angle-resolved photoemission spectroscopy and is demonstrated to be an antiferromagnetic topological insulator with ferromagnetic surfaces by magnetic and transport measurements as well as first-principles calculations. The unique magnetic and topological electronic structures and their interplays enable the material to embody rich quantum phases such as quantum anomalous Hall insulators and axion insulators at higher temperature and in a well-controlled way.
基金National Basic Research Program of China(973 Program)(No.2015CB932100)National Natural Science Foundation of China(No.81473165)+1 种基金Liaoning Provincial Key Laboratory of Drug Preparation Design&Evaluation of Liaoning Provincial Education Department(LZ2014045)Liaoning Provincial Key Laboratory of Studying the Modern Drug preparations.
文摘To achieve GSH-responsive 5-Fluorouridine(5-FU) delivery, a novel family of nanogel drug carriers has been successfully prepared. The new class of PAHy-based nanogels was prepared by the crossing-link reaction of poly-α, β-polyasparthydrazide(PAHy) chains and 3,3′-dithiodipropionic acid(DTDPA) consisting of a redox-responsive chain network. This particle highlights recent efforts in introducing a disulfide bond to drug delivery nanogel by DTDPA,and the increased release properties of complex nanogels produced excellent glutathione(GSH)-sensitivity and significant anti-tumor therapeutic efficacy. The PAHy-based nanogels were characterized by Fourier transform infrared spectroscopy(FT-IR), dynamic light scattering(DLS)(nano-particle size ~200 nm), UV–vis spectrometry, X-ray diffraction(XRD) and differential scanning calorimetric(DSC). PAHy-based nanogels are promising controlledrelease carriers for the tumor-targeting delivery of the anticancer agent 5-Fluorouridine.
基金Chinese Pharmacopoeia Commission Drug Standardization Research Project(2019Z061).
文摘[Objectives]To study the quality standard of Chinese drug in compound Qianglinaogingsu Tablets(Fructus Schisandrae Chinensis and Coru Cervi Pantotrichum).[Methods]The thin layer chromatography(TLC)differentiation method was established for Fructus Schisandrae Chinensis and Cornu Cervi Pantotrichum.[Results]TLC spots developed were fairly clear,and the blank test showed no interference.[Conclusions]The method is fast,simple and can be used for quality control of Qianglinaoqingsu Tablets.
基金supported by grants to Chunyu Zeng from the Program of Innovative Research Team by National Natural Science Foundation(81721001,China)National Natural Science Foundation of China(31430043,31730043)+5 种基金Program for Changjiang Scholars,and Innovative Research Team in University(IRT1216,China)the National Key R&D Program of China(2018YFC1312700)by grant to Jingwen Guo from the National Natural Science Foundation of China(82000476)by grant to Yijie Hu from the Excellent Talents Project of Third Military Medical University(B-3232,China)by grant to Hongyong Wang from the Clinical Technology Innovation and Cultivation Program of AMU(CX2019JS220,China)by grant to Xinyue Li from Chongqing Natural Science Foundation(CSTB2022NSCQ-BHX0025,China)。
文摘Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.
基金supported by the National Natural Science Foundation of China(51872204,52072261 and 22011540379)the National Key Research and Development Program of China(2017YFA0204600)+1 种基金Shanghai Social Development Science and Technology Project(20dz1201800)Shanghai Sailing Program(21YF1430900).
文摘具有四面体钴和八面体钴的Co_(2)VO_(4)在电催化和电池领域已取得重要进展.然而,金属-金属之间强的相互作用会降低活性物质的电导率,又会影响表面反应活性,因此同时提升超级电容器活性、电导率和稳定性具有挑战性.本工作利用锌-钴金属有机骨架(ZnCo-MOF)的离子交换合成了具有高比表面的尖晶石结构CoZn_(0.5)V_(1.5)O_(4).密度泛函理论计算表明,用锌取代过渡金属可以减少过渡金属之间的相互作用,使π^(*)轨道(V-O)和半满的a 1 g轨道下移至费米能级附近,从而提高CoZn_(0.5)V_(1.5)O_(4)的电导率和稳定性.作为超级电容器电极,CoZn_(0.5)V_(1.5)O_(4)具有较高的循环稳定性(18,000次循环后电容保持率为99.4%)和比容量(1 mA cm^(-2)时为1100 mF cm^(-2)).这项工作为设计过渡金属八面体和四面体的位置以提高材料的电化学性能提供了可能性.
基金supported by BOE Technology Group Co.,Ltd.Y.L.acknowledges support from the National Natural Science Foundation of China under grant numbers 61825102 and U21A20460.
文摘This paper presents a flexible radio-frequency microelectromechanical system(RF MEMS)switch integrated on cyclo-olefin polymer(COP)substrate using a modified surface MEMS processing technology,which could be used in the 17-19 GHz frequency band of satellite communication.Through systematic simulation analysis,it is found that flexible RF MEMS switch can achieve certain bending radius by miniaturizing the electronic dimension,without degrading the RF performance.It is demonstrated that the RF characteristics of flexible RF MEMS switch with special anchor structural design,fabricated by modified surface MEMS processing,are not sensitive to bending deformation under the curvature of 0 mm^(-1),0.05 mm^(-1),0.10 mm^(-1).Furthermore,the range of bending curvature which will affect the RF characteristics is given through systematic simulation.The flexible RF MEMS switch with high process compatibility and stable RF performance is believed to be promising candidates for future microwave communications and other consumer electronics.