All-solid-state lithium batteries(ASSLBs),utilizing sulfide solid electrolyte,are considered as the promising design on account of their superior safety and high energy density,whereas the time-consuming preparation p...All-solid-state lithium batteries(ASSLBs),utilizing sulfide solid electrolyte,are considered as the promising design on account of their superior safety and high energy density,whereas the time-consuming preparation process of sulfide electrolyte powders and the thickness of electrolyte layer hinder their practical application.Herein,an innovative ultimate-energy mechanical alloying plus rapid thermal processing approach is employed to rapidly synthesize the crystalline Argyrodite-type conductor Li_(5.3)PS_(4.3)ClBr_(0.7)(LPSCIBr)with superior ionic conductivity(11.7 mS cm^(-1)).Furthermore,to realize the higher energy density of the battery,an ultrathin LPSCIBr sulfide electrolyte membrane with superior ionic conductivity of 6.5 mS cm^(-1)is fabricated with the aid of polytetrafluoroethylene(PTFE)binder and the reinforced cellulose mesh.Moreover,a simple solid electrolyte interphase(SEI)is constructed on the surface of lithium metal to enhance anodic stability.Benefiting from the joint efforts of these merits,the modified ASSLBs with a high cell-level energy density of 311 Wh kg^(-1) show an excellent cyclic stability.The assembled all-solid-state Li_(2) S/Li pouch cell can operate even under the severe conditions of bending and cutting,demonstrating the enormous potential of the sulfide electrolyte membrane for ASSLBs application.展开更多
Leukemia is a malignant disease characterized by progressive accumulation with high morbidity and mortality rates,and investigating its disease genes is crucial for understanding its etiology and pathogenesis.Network ...Leukemia is a malignant disease characterized by progressive accumulation with high morbidity and mortality rates,and investigating its disease genes is crucial for understanding its etiology and pathogenesis.Network propagation methods have emerged and been widely employed in disease gene prediction,but most of them focus on static biological networks,which hinders their applicability and effectiveness in the study of progressive diseases.Moreover,there is currently a lack of special algorithms for the identification of leukemia disease genes.Here,we proposed a novel Dynamic Network-based model integrating Differentially expressed Genes(DyNDG)to identify leukemia-related genes.Initially,we constructed a time-series dynamic network to model the development trajectory of leukemia.Then,we built a background-temporal multilayer network by integrating both the dynamic network and the static background network,which was initialized with differentially expressed genes at each stage.To quantify the associations between genes and leukemia,we extended a random walk process to the background-temporal multilayer network.The results demonstrate that DyNDG achieves superior accuracy compared to several state-of-the-art methods.Moreover,after excluding housekeeping genes,DyNDG yields a set of promising candidate genes associated with leukemia progression or potential biomarkers,indicating the value of dynamic network information in identifying leukemia-related genes.The implementation of DyNDG is available at both https://ngdc.cncb.ac.cn/biocode/tool/BT7617 and https://github.com/CSUBioGroup/DyNDG.展开更多
The hypoxic microenvironment is an essential characteristic of most malignant tu-mors.Notably,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical path...The hypoxic microenvironment is an essential characteristic of most malignant tu-mors.Notably,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via HIF-1a.In the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in patients.Recently,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,etc.Apart from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple myeloma.Targeted inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic agents.In the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various malignancies.It is expected that they will have future potential fortargeted therapy.展开更多
Background:T-cell acute lymphoblastic leukemia(T-ALL)is an uncommon and aggressive subtype of acute lymphoblastic leukemia(ALL).In the serum of T-ALL patients,the activity of lactate dehydrogenase A(LDHA)is increased....Background:T-cell acute lymphoblastic leukemia(T-ALL)is an uncommon and aggressive subtype of acute lymphoblastic leukemia(ALL).In the serum of T-ALL patients,the activity of lactate dehydrogenase A(LDHA)is increased.We proposed that targeting LDHA may be a potential strategy to improve T-ALL outcomes.The current study was conducted to investigate the antileukemic effect of LDHA gene-targeting treatment on T-ALL and the underlying molecular mechanism.Methods:Primary T-ALL cell lines Jurkat and DU528 were treated with the LDH inhibitor oxamate.MTT,colony formation,apoptosis,and cell cycle assays were performed to investigate the effects of oxamate on T-ALL cells.Quantitative real-time PCR(qPCR)and Western blotting analyses were applied to determine the related signaling pathways.A mitochondrial reactive oxygen species(ROS)assay was performed to evaluate ROS production after T-ALL cells were treated with oxamate.A T-ALL transgenic zebrafish model with LDHA gene knockdown was established using CRISPR/Cas9 gene-editing technology,and then TUNEL,Western blotting,and T-ALL tumor progression analyses were conducted to investigate the effects of LDHA gene knockdown on T-ALL transgenic zebrafish.Results:Oxamate significantly inhibited proliferation and induced apoptosis of Jurkat and DU528 cells.It also arrested Jurkat and DU528 cells in G0/G1 phase and stimulated ROS production(all P<0.001).Blocking LDHA significantly decreased the gene and protein expression of c-Myc,as well as the levels of phosphorylated serine/threonine kinase(AKT)and glycogen synthase kinase 3 beta(GSK-3β)in the phosphatidylinositol 3′-kinase(PI3K)signaling pathway.LDHA gene knockdown delayed disease progression and down-regulated c-Myc mRNA and protein expression in T-ALL transgenic zebrafish.Conclusion:Targeting LDHA exerted an antileukemic effect on T-ALL,representing a potential strategy for T-ALL treatment.展开更多
Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment.The developments of the molecular mechanisms on cancer progression provide insight into novel targeted th...Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment.The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies,which are emerging as groundbreaking and promising cancer treatment strategies.In gynecologic malignancies,potential therapeutic targeted agents include antiangiogenic agents,poly(ADP-ribose)polymerase(PARP)inhibitors,tumor-intrinsic signaling pathway inhibitors,selective estrogen receptor downregulators,and immune checkpoint inhibitors.In this article,we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.展开更多
Hematopoiesis requires finely tuned regulation of gene expression at each stage of development.The regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complex...Hematopoiesis requires finely tuned regulation of gene expression at each stage of development.The regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complexes(TCs)composed of transcription factor(s)and multisubunit cofactors.In their normal compositions,TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis.The integration of posttranslational and conformational modifcations in the chromatin landscape,nucleosomes,histones and interacting components via the cofactor-TF interplay is critical to optimal TF activity.Mutations or translocations of cofactor genes are expected to alter cofactor-TF interactions,which may be causative for the pathogenesis of various hematologic disorders.Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy.In this review,we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies.This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.展开更多
In this paper,we demonstrate nBn InAs/InAsSb type II superlattice(T2SL)photodetectors with AlAsSb as the barrier that targets mid-wavelength infrared(MWIR)detection.To improve operating temperature and suppress dark c...In this paper,we demonstrate nBn InAs/InAsSb type II superlattice(T2SL)photodetectors with AlAsSb as the barrier that targets mid-wavelength infrared(MWIR)detection.To improve operating temperature and suppress dark current,a specific Sb soaking technique was employed to improve the interface abruptness of the superlattice with device passivation using a SiO_(2) layer.These result in ultralow dark current density of 6.28×10^(-6)A/cm^(2)and 0.31 A/cm^(2)under-600 mV at 97 K and297 K,respectively,which is lower than most reported InAs/InAsSb-based MWIR photodetectors.Corresponding resistance area product values of 3.20×10^(4)Ω·cm^(2)and 1.32Ω·cm^(2)were obtained at 97 K and 297 K.A peak responsivity of 0.39 A/W with a cutoff wavelength around 5.5μm and a peak detectivity of 2.1×10^(9)cm·Hz^(1/2)/W were obtained at a high operating temperature up to 237 K.展开更多
In this paper,high-uniformity 2×64 silicon avalanche photodiode[APD]arrays are reported.Silicon multiple epitaxy technology was used,and the high performance APD arrays based on double-layer epiwafers are achieve...In this paper,high-uniformity 2×64 silicon avalanche photodiode[APD]arrays are reported.Silicon multiple epitaxy technology was used,and the high performance APD arrays based on double-layer epiwafers are achieved for the first time,to the best of our knowledge.A high-uniformity breakdown voltage with a fluctuation of smaller than 3.5 V is obtained for the fabricated APD arrays.The dark currents are below 90 pA for all 128 pixels at unity gain voltage.The pixels in the APD arrays show a gain factor of larger than 300 and a peak responsivity of 0.53 A/W@M=1 at 850 nm[corresponding to maximum external quantum efficiency of 81%]at room temperature.Quick optical pulse response time was measured,and a corresponding cutoff frequency up to 100 MHz was obtained.展开更多
In this paper, we present a detector-integrated vertical-cavity surface-emitting laser(VCSEL) with a movable high-contrast grating(HCG) mirror in an n-i-p-i-n manner. The detector-integrated VCSEL with a movable HCG c...In this paper, we present a detector-integrated vertical-cavity surface-emitting laser(VCSEL) with a movable high-contrast grating(HCG) mirror in an n-i-p-i-n manner. The detector-integrated VCSEL with a movable HCG can achieve three functions, including wavelength tuning, power monitoring, and resonant-cavity-enhanced(RCE)photon detection. Currently, the device can achieve a wavelength tuning range of 27 nm at room temperature when the suspended HCG is driven by the reverse-bias voltage. The n-i-p structure located at the upper part of the device can serve as an intra-cavity photodiode to monitor the output power due to the defect absorption. The RCE photon detection function of the detector-integrated VCSEL with a movable HCG is measured, and it has a peak responsivity at about 926 nm. This detector-integrated VCSEL with a movable HCG will be useful for sensing and imaging.展开更多
基金supported by the National Natural Science Foundation of China(U20A20126,51971201)the Key Research and Development Program of Zhejiang Province(2021C01175)。
文摘All-solid-state lithium batteries(ASSLBs),utilizing sulfide solid electrolyte,are considered as the promising design on account of their superior safety and high energy density,whereas the time-consuming preparation process of sulfide electrolyte powders and the thickness of electrolyte layer hinder their practical application.Herein,an innovative ultimate-energy mechanical alloying plus rapid thermal processing approach is employed to rapidly synthesize the crystalline Argyrodite-type conductor Li_(5.3)PS_(4.3)ClBr_(0.7)(LPSCIBr)with superior ionic conductivity(11.7 mS cm^(-1)).Furthermore,to realize the higher energy density of the battery,an ultrathin LPSCIBr sulfide electrolyte membrane with superior ionic conductivity of 6.5 mS cm^(-1)is fabricated with the aid of polytetrafluoroethylene(PTFE)binder and the reinforced cellulose mesh.Moreover,a simple solid electrolyte interphase(SEI)is constructed on the surface of lithium metal to enhance anodic stability.Benefiting from the joint efforts of these merits,the modified ASSLBs with a high cell-level energy density of 311 Wh kg^(-1) show an excellent cyclic stability.The assembled all-solid-state Li_(2) S/Li pouch cell can operate even under the severe conditions of bending and cutting,demonstrating the enormous potential of the sulfide electrolyte membrane for ASSLBs application.
基金supported by grants from the National Natural Science Foundation of China(Grant No.62225209)to Min Lithe National Natural Science Foundation of China(Grant No.62472051)to Ju Xiangthe High Performance Computing Center of Central South University,China.
文摘Leukemia is a malignant disease characterized by progressive accumulation with high morbidity and mortality rates,and investigating its disease genes is crucial for understanding its etiology and pathogenesis.Network propagation methods have emerged and been widely employed in disease gene prediction,but most of them focus on static biological networks,which hinders their applicability and effectiveness in the study of progressive diseases.Moreover,there is currently a lack of special algorithms for the identification of leukemia disease genes.Here,we proposed a novel Dynamic Network-based model integrating Differentially expressed Genes(DyNDG)to identify leukemia-related genes.Initially,we constructed a time-series dynamic network to model the development trajectory of leukemia.Then,we built a background-temporal multilayer network by integrating both the dynamic network and the static background network,which was initialized with differentially expressed genes at each stage.To quantify the associations between genes and leukemia,we extended a random walk process to the background-temporal multilayer network.The results demonstrate that DyNDG achieves superior accuracy compared to several state-of-the-art methods.Moreover,after excluding housekeeping genes,DyNDG yields a set of promising candidate genes associated with leukemia progression or potential biomarkers,indicating the value of dynamic network information in identifying leukemia-related genes.The implementation of DyNDG is available at both https://ngdc.cncb.ac.cn/biocode/tool/BT7617 and https://github.com/CSUBioGroup/DyNDG.
基金supported by the National Natural Science Foundation of China(No.82070175)the Natural Science Foundation of Hunan Province(No.2022JJ30830)the Scientific Program of the Health Commission of Hunan Province(China)(No.20201179).
文摘The hypoxic microenvironment is an essential characteristic of most malignant tu-mors.Notably,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via HIF-1a.In the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in patients.Recently,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,etc.Apart from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple myeloma.Targeted inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic agents.In the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various malignancies.It is expected that they will have future potential fortargeted therapy.
基金This work was supported by the National Natural Science Foundation of China(81200368,81670160)the Hunan Natural Science Foundation(2017JJ2355).
文摘Background:T-cell acute lymphoblastic leukemia(T-ALL)is an uncommon and aggressive subtype of acute lymphoblastic leukemia(ALL).In the serum of T-ALL patients,the activity of lactate dehydrogenase A(LDHA)is increased.We proposed that targeting LDHA may be a potential strategy to improve T-ALL outcomes.The current study was conducted to investigate the antileukemic effect of LDHA gene-targeting treatment on T-ALL and the underlying molecular mechanism.Methods:Primary T-ALL cell lines Jurkat and DU528 were treated with the LDH inhibitor oxamate.MTT,colony formation,apoptosis,and cell cycle assays were performed to investigate the effects of oxamate on T-ALL cells.Quantitative real-time PCR(qPCR)and Western blotting analyses were applied to determine the related signaling pathways.A mitochondrial reactive oxygen species(ROS)assay was performed to evaluate ROS production after T-ALL cells were treated with oxamate.A T-ALL transgenic zebrafish model with LDHA gene knockdown was established using CRISPR/Cas9 gene-editing technology,and then TUNEL,Western blotting,and T-ALL tumor progression analyses were conducted to investigate the effects of LDHA gene knockdown on T-ALL transgenic zebrafish.Results:Oxamate significantly inhibited proliferation and induced apoptosis of Jurkat and DU528 cells.It also arrested Jurkat and DU528 cells in G0/G1 phase and stimulated ROS production(all P<0.001).Blocking LDHA significantly decreased the gene and protein expression of c-Myc,as well as the levels of phosphorylated serine/threonine kinase(AKT)and glycogen synthase kinase 3 beta(GSK-3β)in the phosphatidylinositol 3′-kinase(PI3K)signaling pathway.LDHA gene knockdown delayed disease progression and down-regulated c-Myc mRNA and protein expression in T-ALL transgenic zebrafish.Conclusion:Targeting LDHA exerted an antileukemic effect on T-ALL,representing a potential strategy for T-ALL treatment.
基金supported by National Major Scientific and Technological Project for“Significant New Drugs Development”in China(2018ZX09733001).
文摘Advanced and recurrent gynecological cancers are associated with poor prognosis and lack of effective treatment.The developments of the molecular mechanisms on cancer progression provide insight into novel targeted therapies,which are emerging as groundbreaking and promising cancer treatment strategies.In gynecologic malignancies,potential therapeutic targeted agents include antiangiogenic agents,poly(ADP-ribose)polymerase(PARP)inhibitors,tumor-intrinsic signaling pathway inhibitors,selective estrogen receptor downregulators,and immune checkpoint inhibitors.In this article,we provide a comprehensive review of the clinical evidence of targeted agents in gynecological cancers and discuss the future implication.
基金This work was supported by the grants from National Key Research and Development Program of China(Grant number 2108YFA0107800)National Natural Science Foundation of China(Grant numbers 81920108004,81770107,81702722,81470362 and 81700168)+3 种基金National Postdoctoral Program for Innovative Talents(Grant number BX201700292)Natural Science Foundation of Hunan Province(Grant num ber 2018JJ3703)Science and Technology Key Project of Hunan Province(Grant number 2018SK21212)Fundamental Research Funds for the Central Universities of Central South University(Grant number 2018zzts386).
文摘Hematopoiesis requires finely tuned regulation of gene expression at each stage of development.The regulation of gene transcription involves not only individual transcription factors(TFs)but also transcription complexes(TCs)composed of transcription factor(s)and multisubunit cofactors.In their normal compositions,TCs orchestrate lineage-specific patterns of gene expression and ensure the production of the correct proportions of individual cell lineages during hematopoiesis.The integration of posttranslational and conformational modifcations in the chromatin landscape,nucleosomes,histones and interacting components via the cofactor-TF interplay is critical to optimal TF activity.Mutations or translocations of cofactor genes are expected to alter cofactor-TF interactions,which may be causative for the pathogenesis of various hematologic disorders.Blocking TF oncogenic activity in hematologic disorders through targeting cofactors in aberrant complexes has been an exciting therapeutic strategy.In this review,we summarize the current knowledge regarding the models and functions of cofactor-TF interplay in physiological hematopoiesis and highlight their implications in the etiology of hematological malignancies.This review presents a deep insight into the physiological and pathological implications of transcription machinery in the blood system.
基金supported by the National Science and Technology Major Project(No.2018YFE0200900)。
文摘In this paper,we demonstrate nBn InAs/InAsSb type II superlattice(T2SL)photodetectors with AlAsSb as the barrier that targets mid-wavelength infrared(MWIR)detection.To improve operating temperature and suppress dark current,a specific Sb soaking technique was employed to improve the interface abruptness of the superlattice with device passivation using a SiO_(2) layer.These result in ultralow dark current density of 6.28×10^(-6)A/cm^(2)and 0.31 A/cm^(2)under-600 mV at 97 K and297 K,respectively,which is lower than most reported InAs/InAsSb-based MWIR photodetectors.Corresponding resistance area product values of 3.20×10^(4)Ω·cm^(2)and 1.32Ω·cm^(2)were obtained at 97 K and 297 K.A peak responsivity of 0.39 A/W with a cutoff wavelength around 5.5μm and a peak detectivity of 2.1×10^(9)cm·Hz^(1/2)/W were obtained at a high operating temperature up to 237 K.
基金supported by the National Science and Technology Major Project(No.2018YFE0200900)。
文摘In this paper,high-uniformity 2×64 silicon avalanche photodiode[APD]arrays are reported.Silicon multiple epitaxy technology was used,and the high performance APD arrays based on double-layer epiwafers are achieved for the first time,to the best of our knowledge.A high-uniformity breakdown voltage with a fluctuation of smaller than 3.5 V is obtained for the fabricated APD arrays.The dark currents are below 90 pA for all 128 pixels at unity gain voltage.The pixels in the APD arrays show a gain factor of larger than 300 and a peak responsivity of 0.53 A/W@M=1 at 850 nm[corresponding to maximum external quantum efficiency of 81%]at room temperature.Quick optical pulse response time was measured,and a corresponding cutoff frequency up to 100 MHz was obtained.
基金National Natural Science Foundation of China(62075209, 62275243, 61675193)Beijing Municipal Natural Science Foundation (Z200006)。
文摘In this paper, we present a detector-integrated vertical-cavity surface-emitting laser(VCSEL) with a movable high-contrast grating(HCG) mirror in an n-i-p-i-n manner. The detector-integrated VCSEL with a movable HCG can achieve three functions, including wavelength tuning, power monitoring, and resonant-cavity-enhanced(RCE)photon detection. Currently, the device can achieve a wavelength tuning range of 27 nm at room temperature when the suspended HCG is driven by the reverse-bias voltage. The n-i-p structure located at the upper part of the device can serve as an intra-cavity photodiode to monitor the output power due to the defect absorption. The RCE photon detection function of the detector-integrated VCSEL with a movable HCG is measured, and it has a peak responsivity at about 926 nm. This detector-integrated VCSEL with a movable HCG will be useful for sensing and imaging.
