BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent...BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.展开更多
Field-effect transistors （FETs） for logic applications, graphene and MoS2, are discussed. These materials have based on two representative two-dimensional （2D） materials, drastically different properties and requi...Field-effect transistors （FETs） for logic applications, graphene and MoS2, are discussed. These materials have based on two representative two-dimensional （2D） materials, drastically different properties and require different consider- ations. The unique band structure of graphene necessitates engineering of the Dirac point, including the opening of the bandgap, the doping and the interface, before the graphene can be used in logic applications. On the other hand, MoS2 is a semiconductor, and its electron transport depends heavily on the surface properties, the number of layers, and the carrier density. Finally, we discuss the prospects for the future developments in 2D material transistors.展开更多
A fast multipole method(FMM)is applied for BEM to reduce both the operation and memory requirement in dealing with very large scale problems.In this paper,a new version of fast multipole BEM for 2D elastostatics is pr...A fast multipole method(FMM)is applied for BEM to reduce both the operation and memory requirement in dealing with very large scale problems.In this paper,a new version of fast multipole BEM for 2D elastostatics is presented and used for simulation of 2D elastic solid with a large number of randomly distributed inclusions combined with a similar subregion approach.Generalized minimum residual method(GMRES)is used as an iterative solver to solve the equation system formed by BEM iteratively.The numerical results show that the scheme presented is applicable to certain large scale problems.展开更多
Lithium-sulfur batteries(LSBs)have emerged as promising power sources for high-performance devices such as electric vehicles.However,the poor energy density of LSBs owing to polysulfide shuttling and passivation has l...Lithium-sulfur batteries(LSBs)have emerged as promising power sources for high-performance devices such as electric vehicles.However,the poor energy density of LSBs owing to polysulfide shuttling and passivation has limited their further market penetration.To mitigate this challenge,two-dimensional(2D)siloxene(2DSi),a Si-based analog of graphene,is utilized as an additive for sulfur cathodes.The 2DSi is fabricated on a large scale by simple solvent extraction of calcium disilicide to form a thin-layered structure of Si planes functionalized with vertically aligned hydroxyl groups in the 2DSi.The stoichiometric reaction of 2DSi with polysulfides generates a thiosulfate redox mediator,secures the intercalation pathway,and reveals Lewis acidic sites within the siloxene galleries.The 2DSi utilizes the corresponding in-situ-formed electrocatalyst,the 2D confinement effect of the layered structure,and the surface affinity based on Lewis acid-base interaction to improve the energy density of 2DSi-based LSB cells.Combined with the commercial carbon-based current collector,2DSi-based LSB cells achieve a volumetric energy density of 612 Wh Lcell^(−1) at 1 mA cm^(−2) with minor degradation of 0.17%per cycle,which rivals those of state-of-the-art LSBs.This study presents a method for the industrial production of high-energy-dense LSBs.展开更多
Two-dimensional(2D) materials have attracted extensive interest due to their excellent electrical, thermal,mechanical, and optical properties. Graphene has been one of the most explored 2D materials. However, its zero...Two-dimensional(2D) materials have attracted extensive interest due to their excellent electrical, thermal,mechanical, and optical properties. Graphene has been one of the most explored 2D materials. However, its zero band gap has limited its applications in electronic devices. Transition metal dichalcogenide(TMDC), another kind of 2D material,has a nonzero direct band gap(same charge carrier momentum in valence and conduction band) at monolayer state,promising for the efficient switching devices(e.g., field-effect transistors). This review mainly focuses on the recent advances in charge carrier mobility and the challenges to achieve high mobility in the electronic devices based on 2DTMDC materials and also includes an introduction of 2D materials along with the synthesis techniques. Finally, this review describes the possible methodology and future prospective to enhance the charge carrier mobility for electronic devices.展开更多
文摘BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of survival.Recent studies have shown potent anti-neoplastic effects of curcumin and its analogues.In addition,the role of histone methyltransferases on cancer therapeutics has also been elucidated.However,the relationship between these two factors in the treatment of pancreatic cancer remains unknown.Our working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic efficacy.METHODS The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation assay.Apoptosis,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric acquisition.In vitro migration was assessed by the wound healing assay.The protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative PCR.The in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by immunohistochemistry.In vivo tumor xenografts were established by injecting nude mice with PDAC cells.Bioinformatics analyses were also conducted using gene expression databases and TCGA.RESULTS L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4(ATF4)/CHOP signaling pathway.Knocking down ATF4 significantly upregulated KMT2D in PDAC cells,and also decreased L48H37-induced apoptosis.Furthermore,silencing KMT2D in L48H37-treated cells significantly augmented apoptosis and the ER stress pathway,indicating that KMT2D depletion is essential for the anti-neoplastic effects of L48H37.Administering L48H37 to mice bearing tumors derived from control or KMT2Dknockdown PDAC cells significantly decreased the tumor burden.We also identified several differentially expressed genes in PDAC cell lines expressing very low levels of KMT2D that were functionally categorized into the extrinsic apoptotic signaling pathway.The KMT2D high-and low-expressing PDAC patients from the TCGA database showed similar survival rates,but higher KMT2D expression was associated with poor tumor grade in clinical and pathological analyses.CONCLUSION L48H37 exerts a potent anti-cancer effect in PDAC,which is augmented by KMT2D deficiency.
基金supported by the National Basic Research Program of China (Grant No. 2013CBA01600)the National Natural Science Foundation of China (Grant Nos. 61261160499 and 11274154)+2 种基金the National Science and Technology Major Project of the Ministry of Science and Technology of China (Grant No. 2011ZX02707)the Natural Science Foundation of Jiangsu Province, China (Grant No. BK2012302)the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120091110028)
文摘Field-effect transistors （FETs） for logic applications, graphene and MoS2, are discussed. These materials have based on two representative two-dimensional （2D） materials, drastically different properties and require different consider- ations. The unique band structure of graphene necessitates engineering of the Dirac point, including the opening of the bandgap, the doping and the interface, before the graphene can be used in logic applications. On the other hand, MoS2 is a semiconductor, and its electron transport depends heavily on the surface properties, the number of layers, and the carrier density. Finally, we discuss the prospects for the future developments in 2D material transistors.
基金The project supported by the National Nature Science Foundation of China(10172053)the Ministry of Education
文摘A fast multipole method(FMM)is applied for BEM to reduce both the operation and memory requirement in dealing with very large scale problems.In this paper,a new version of fast multipole BEM for 2D elastostatics is presented and used for simulation of 2D elastic solid with a large number of randomly distributed inclusions combined with a similar subregion approach.Generalized minimum residual method(GMRES)is used as an iterative solver to solve the equation system formed by BEM iteratively.The numerical results show that the scheme presented is applicable to certain large scale problems.
基金supported by the R&D Convergence Program of NST(National Research Council of Science&Technology)of the Republic of Korea(CAP-15-02-KBSI)a National Research Foundation of Korea(NRF)grant funded by the Korean Government(MSIT)(no.2019R1C1C1007745)a National Research Foundation of Korea(NRF)grant funded by the Korean Government(Ministry of Science,ICT&Future Planning)(no.2019R1A4A2001527).
文摘Lithium-sulfur batteries(LSBs)have emerged as promising power sources for high-performance devices such as electric vehicles.However,the poor energy density of LSBs owing to polysulfide shuttling and passivation has limited their further market penetration.To mitigate this challenge,two-dimensional(2D)siloxene(2DSi),a Si-based analog of graphene,is utilized as an additive for sulfur cathodes.The 2DSi is fabricated on a large scale by simple solvent extraction of calcium disilicide to form a thin-layered structure of Si planes functionalized with vertically aligned hydroxyl groups in the 2DSi.The stoichiometric reaction of 2DSi with polysulfides generates a thiosulfate redox mediator,secures the intercalation pathway,and reveals Lewis acidic sites within the siloxene galleries.The 2DSi utilizes the corresponding in-situ-formed electrocatalyst,the 2D confinement effect of the layered structure,and the surface affinity based on Lewis acid-base interaction to improve the energy density of 2DSi-based LSB cells.Combined with the commercial carbon-based current collector,2DSi-based LSB cells achieve a volumetric energy density of 612 Wh Lcell^(−1) at 1 mA cm^(−2) with minor degradation of 0.17%per cycle,which rivals those of state-of-the-art LSBs.This study presents a method for the industrial production of high-energy-dense LSBs.
基金funded by Australian Research Council discovery project DP140103041Future Fellowship FT160100205
文摘Two-dimensional(2D) materials have attracted extensive interest due to their excellent electrical, thermal,mechanical, and optical properties. Graphene has been one of the most explored 2D materials. However, its zero band gap has limited its applications in electronic devices. Transition metal dichalcogenide(TMDC), another kind of 2D material,has a nonzero direct band gap(same charge carrier momentum in valence and conduction band) at monolayer state,promising for the efficient switching devices(e.g., field-effect transistors). This review mainly focuses on the recent advances in charge carrier mobility and the challenges to achieve high mobility in the electronic devices based on 2DTMDC materials and also includes an introduction of 2D materials along with the synthesis techniques. Finally, this review describes the possible methodology and future prospective to enhance the charge carrier mobility for electronic devices.
