Proper treatment of acidleaching tailings(ALTs)of vanadiumbearing stone coal minerals is of great urgency.One approach is adding it into the raw materials during the preparation of lightweight aggregate(LWA).But clay ...Proper treatment of acidleaching tailings(ALTs)of vanadiumbearing stone coal minerals is of great urgency.One approach is adding it into the raw materials during the preparation of lightweight aggregate(LWA).But clay is always needed.In this paper,another solid waste,red mud,was mixed with ALTs as a source of flux components instead of clay.Evaluation of the physical characteristics,morphological structures,as well as crystal phases during the sintering process were investigated.When their mixtures with a proper ratio were sintered at 1080℃,a glassy phase with certain viscosity was formed,and the gases generated simultaneously were encapsulated by the melt.Finally,LWA with a onehour water absorption as low as 1.46%,a bulk density as low as 728.76 kgm 3 and a compressive strength as high as 10.77 MPa was fabricated.展开更多
Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water ...Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.展开更多
Hierarchical mesoporous MoO_2/Mo_2C/C microspheres,which are composed of primary nanoparticles with a size of about 30 nm,have been designed and synthesized through polymer regulation and subsequent carbonization proc...Hierarchical mesoporous MoO_2/Mo_2C/C microspheres,which are composed of primary nanoparticles with a size of about 30 nm,have been designed and synthesized through polymer regulation and subsequent carbonization processes.The as-synthesized microspheres were characterized by XRD,Raman,SEM,TEM,XPS measurements and so on.It was found that polyethylene glycol acted as a structure-directing agent,mild reducing agent and carbon source in the formation of these hierarchical mesoporous Mo O_2/Mo_2C/C microspheres.Moreover,the electrochemical property of the microspheres was also investigated in this work.Evaluated as an anode material for lithium ion batteries,the hierarchical mesoporous Mo O_2/Mo_2C/C electrode delivered the discharge specific capacities of 665 and 588 m Ah/g after 100 cycles at current densities of 100 and 200 m A/g,respectively.The satisfactory cycling performance and controllable process facilitate the practical applications of the hierarchical mesoporous Mo O_2/Mo_2C/C as a potential anode material in high-energy density lithium-ion batteries.展开更多
Sepsis and septic shock remain the leading causes of death in intensive care units.Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,...Sepsis and septic shock remain the leading causes of death in intensive care units.Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,necessitating extracorporeal membrane oxygenation(ECMO).However,the role of ECMO in adult patients with sepsis has not been fully established.According to existing studies,ECMO may be a viable salvage therapy in carefully selected adult patients with sepsis.The choice of venovenous,venoarterial,or hybrid ECMO modes is primarily determined by the patient’s oxygenation and hemodynamics(distributive shock with preserved cardiac output,septic cardiomyopathy(left,right,or biventricular heart failure),or right ventricular failure caused by acute respiratory distress syndrome).Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails,and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of survival.When ECMO is indicated,the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical,particularly in an experienced ECMO center.Furthermore,some special issues,such as ECMO flow,anticoagulation,and antibiotic therapy,should be noted during the management of ECMO support.展开更多
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementati...Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer treatment.Herein,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility.Notably,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent biosafety.Once accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment.This profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor cells.Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of DSF.This system provided a promising strategy for the application of DSF in tumor therapy.展开更多
The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,...The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,a system enabling long-term maintenance of imprints in ESCs has proven challenging.Here,we report that the use of a two-step a2i(alternative two inhibitors of Src and Gsk3β,TSa2i)derivation/culture protocol results in the establishment of androgenetic haploid ESCs(AG-haESCs)with stable DNA methylation at paternal DMRs(differentially DNA methylated regions)up to passage 60 that can efficiently support generating mice upon oocyte injection.We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations.Furthermore,we demonstrate that TSa2itreated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation.Strikingly,AGhaESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells,in part through the enhanced proliferation of H19-DMR hypermethylated cells.Together,we establish AG-haESCs that can longterm maintain paternal imprints.展开更多
文摘Proper treatment of acidleaching tailings(ALTs)of vanadiumbearing stone coal minerals is of great urgency.One approach is adding it into the raw materials during the preparation of lightweight aggregate(LWA).But clay is always needed.In this paper,another solid waste,red mud,was mixed with ALTs as a source of flux components instead of clay.Evaluation of the physical characteristics,morphological structures,as well as crystal phases during the sintering process were investigated.When their mixtures with a proper ratio were sintered at 1080℃,a glassy phase with certain viscosity was formed,and the gases generated simultaneously were encapsulated by the melt.Finally,LWA with a onehour water absorption as low as 1.46%,a bulk density as low as 728.76 kgm 3 and a compressive strength as high as 10.77 MPa was fabricated.
基金supported by grants from the National Natural Science Foundation of China(Nos.81273451,81302717 and81101684)
文摘Nanomaterials with multiple functions have become more and more popular in the domain of cancer research. MoS2 has a great potential in photothermal therapy, X-ray/CT imaging and drug delivery. In this study, a water soluble MoS2 nanosystem(MoS2-PEG) was synthesized and explored in drug delivery, photothermal therapy(PTT) and X-ray imaging.Doxorubicin(DOX) was loaded onto MoS2-PEG with a high drug loading efficiency(~69%)and obtained a multifunctional drug delivery system(MoS2-PEG/DOX). As the drug delivery, MoS2-PEG/DOX could efficiently cross the cell membranes, and escape from the endosome via NIR light irradiation, lead to more apoptosis in MCF-7 cells, and afford higher antitumor efficacy without obvious toxic effects to normal organs owing to its prolonged blood circulation and 11.6-fold higher DTX uptake of tumor than DOX. Besides, MoS2-PEG/DOX not only served as a drug delivery system, but also as a powerful PTT agent for thermal ablation of tumor and a strong X-ray contrast agent for tumor diagnosis. In the in vitro and in vivo studies, MoS2-PEG/DOX exhibited excellent tumor-targeting efficacy, outstanding synergistic anti-cancer effect of photothermal and chemotherapy and X-ray imaging property,demonstrating that MoS2-PEG/DOX had a great potential for simultaneous diagnosis and photothermal-chemotherapy in cancer treatment.
基金supported by the National Natural Science Foundation of China(No.21376251 and 21406233)the National Basic Research Development Program of China(2013CB632600)
文摘Hierarchical mesoporous MoO_2/Mo_2C/C microspheres,which are composed of primary nanoparticles with a size of about 30 nm,have been designed and synthesized through polymer regulation and subsequent carbonization processes.The as-synthesized microspheres were characterized by XRD,Raman,SEM,TEM,XPS measurements and so on.It was found that polyethylene glycol acted as a structure-directing agent,mild reducing agent and carbon source in the formation of these hierarchical mesoporous Mo O_2/Mo_2C/C microspheres.Moreover,the electrochemical property of the microspheres was also investigated in this work.Evaluated as an anode material for lithium ion batteries,the hierarchical mesoporous Mo O_2/Mo_2C/C electrode delivered the discharge specific capacities of 665 and 588 m Ah/g after 100 cycles at current densities of 100 and 200 m A/g,respectively.The satisfactory cycling performance and controllable process facilitate the practical applications of the hierarchical mesoporous Mo O_2/Mo_2C/C as a potential anode material in high-energy density lithium-ion batteries.
文摘Sepsis and septic shock remain the leading causes of death in intensive care units.Some patients with sepsis fail to respond to routine treatment and rapidly progress to refractory respiratory and circulatory failure,necessitating extracorporeal membrane oxygenation(ECMO).However,the role of ECMO in adult patients with sepsis has not been fully established.According to existing studies,ECMO may be a viable salvage therapy in carefully selected adult patients with sepsis.The choice of venovenous,venoarterial,or hybrid ECMO modes is primarily determined by the patient’s oxygenation and hemodynamics(distributive shock with preserved cardiac output,septic cardiomyopathy(left,right,or biventricular heart failure),or right ventricular failure caused by acute respiratory distress syndrome).Veno-venous ECMO can be used in patients with sepsis and severe acute respiratory distress syndrome when conventional mechanical ventilation fails,and early application of veno-arterial ECMO in patients with sepsis-induced refractory cardiogenic shock may be critical in improving their chances of survival.When ECMO is indicated,the choice of an appropriate mode and determination of the optimal timing of initiation and weaning are critical,particularly in an experienced ECMO center.Furthermore,some special issues,such as ECMO flow,anticoagulation,and antibiotic therapy,should be noted during the management of ECMO support.
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
基金supported by National Natural Science Foundation of China(81972893)Key Program for Basic Research of Universities in Henan province(19zx005,China)+2 种基金Chinese Postdoctoral Funding Association(2018M640686 and 2019T120651,China)Youth talent promotion project in Henan province(2019HYTP017,China)Training program for young key teachers in Henan Province(2020GGJS019,China)
文摘Although approved as an alcohol-abuse drug,disulfiram(DSF)exhibited potential anticancer activity when chelated with copper(Cu).However,the low level of intrinsic Cu,toxicity originated from exogenous Cu supplementation,and poor stability of DSF in vivo severely limited its application in cancer treatment.Herein,we proposed an in situ DSF antitumor efficacy triggered system,taking advantages of Cu-based metal-organic framework(MOF).In detail,DSF was encapsulated into Cu-MOF nanoparticles(NPs)during its formation,and the obtained NPs were coated with hyaluronic acid to enhance the tumor targetability and biocompatibility.Notably,DSF loaded Cu-MOF NPs maintained stability and integrity without Cu;leakage in blood circulation,thus showing excellent biosafety.Once accumulating at tumor site,NPs were internalized into tumor cells via receptor-mediated endocytosis and released DSF and Cu;simultaneously in the hyaluronidase-enriched and acidic intracellular tumor microenvironment.This profile lead to in situ chelation reaction between DSF and Cu;,generating toxic DSF/Cu complex against tumor cells.Both in vitro and in vivo results demonstrated the programmed degradation and recombination property of Cu-based MOF NPs,which facilitated the tumor-specific chemotherapeutic effects of DSF.This system provided a promising strategy for the application of DSF in tumor therapy.
基金This study was supported by Genome Tagging Project and grants from the Chinese Academy of Sciences,the National Key Research and Development Program of Chinathe National Natural Science Foundation of China(2019YFA0109900,2020YFA0509000,XDB19010204,QYZDJ-SSW-SMC023,Facility-based Open Research Program,31821004,32030029,and 31730062).
文摘The use of two inhibitors of Mek1/2 and Gsk3β(2i)promotes the generation of mouse diploid and haploid embryonic stem cells(ESCs)from the inner cell mass of biparental and uniparental blastocysts,respectively.However,a system enabling long-term maintenance of imprints in ESCs has proven challenging.Here,we report that the use of a two-step a2i(alternative two inhibitors of Src and Gsk3β,TSa2i)derivation/culture protocol results in the establishment of androgenetic haploid ESCs(AG-haESCs)with stable DNA methylation at paternal DMRs(differentially DNA methylated regions)up to passage 60 that can efficiently support generating mice upon oocyte injection.We also show coexistence of H3K9me3 marks and ZFP57 bindings with intact DMR methylations.Furthermore,we demonstrate that TSa2itreated AG-haESCs are a heterogeneous cell population regarding paternal DMR methylation.Strikingly,AGhaESCs with late passages display increased paternal-DMR methylations and improved developmental potential compared to early-passage cells,in part through the enhanced proliferation of H19-DMR hypermethylated cells.Together,we establish AG-haESCs that can longterm maintain paternal imprints.