The combination of silicon carbide(SiC)ceramics and stereolithography technology shows promise for manufacturing complex-shaped SiC components,expanding application possibilities.However,high sintering temperature and...The combination of silicon carbide(SiC)ceramics and stereolithography technology shows promise for manufacturing complex-shaped SiC components,expanding application possibilities.However,high sintering temperature and structural-performance anisotropy limit the practical use of 3D-printed SiC components.Herein,a novel method is introduced to produce high-specific-strength SiC-based ceramics at a relatively low temperature of 1100℃.A mixed SiC/SiO_(2) slurry(30%SiO_(2) and 70%SiC by volume)with a solid loading of up to 40%was prepared to improve UV light penetration and printability.Additionally,incorporating a high content of methyl-phenyl-polysiloxane(PSO)solution(75%by weight)enabled low-temperature pyrolysis of SiC/SiO_(2)/PSO ceramics.The SiC/SiO_(2)/PSO ceramic lattices after pyrolysis achieved a specific strength as high as(1.03×10^(5))N·m·kg^(-1) and a density of 1.75 g·cm^(-3),outperforming similar SiC-based lattices structures of similar porosities.The bending strength of(95.49±8.79)MPa was comparable to that of ceramics sintered at 1400℃ or higher.Notably,the addition of the silicon carbide oxide(SiOC)phase reduced anisotropy,lowering the transverse and longitudinal compression strength ratios from 1.87 to 1.08,and improving mechanical properties by 79%.This improvement is attributed to SiOC shrinkage,promoting a uniform distribution of sintered components,resulting in a more robust and balanced material structure.This method offers valuable insight into the additive manufacturing(AM)of SiC-based ceramics at lower temperatures and provides new guidance for controlling anisotropy in 3D-printed ceramic parts.展开更多
Cuproptosis,a recently identified form of regulated cell death triggered by excess intracellular copper,has emerged as a promising cytotoxic strategy for cancer therapy.However,the therapeutic efficacy of copper ionop...Cuproptosis,a recently identified form of regulated cell death triggered by excess intracellular copper,has emerged as a promising cytotoxic strategy for cancer therapy.However,the therapeutic efficacy of copper ionophores such as elesclomol(ES)is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction.To address this challenge,we developed a nanoagent utilizing outer membrane vesicle(OMV)derived from Akkermansia muciniphila(Akk)for co-delivery of antioxidant 1 copper chaperone(Atox1)-targeting siRNA and ES(siAtox1/ES@OMV)to tumors.In vitro,we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms,resulting in elevated intracellular copper levels.Simultaneously,ES facilitated efficient copper influx and mitochondrial transport,leading to Fe–S cluster depletion,increased proteotoxic stress,and robust cuproptosis.In vivo,siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis.Furthermore,leveraging the immunomodulatory properties of OMVs,siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells,enhancing tumor immune responses.The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models.This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector,offering a promising combinatorial strategy for cancer therapy.展开更多
Objectives:Racial disparities persist despite attempts to establish an egalitarian framework for surgical care.This study aimed to investigate racioethnic disparities in comorbidities and outcomes following surgery fo...Objectives:Racial disparities persist despite attempts to establish an egalitarian framework for surgical care.This study aimed to investigate racioethnic disparities in comorbidities and outcomes following surgery for head and neck tumors.Methods:This retrospective study included adult patients who underwent head and neck oncologic surgery between 2008 and 2020 from the National Surgical Quality Improvement Program.Multivariable regression analyses were conducted to explore the association of the following racioethnic categories with postoperative outcomes:White,Black,Hispanic,and Asian.Results:A total of 113,234 patients were included in the study,comprising 78.3%White,8.7%Black,6.9%Hispanic,and 6.0%Asian patients.Black patients had higher rates of pre-existing comorbidities compared to White patients.Specifically,the rates of comorbidities such as diabetes mellitus(19.8%vs.12.4%),hypertension(57.5%vs.41.5%),smoking history(18.8%vs.15.0%),dyspnea(7.4%vs.5.7%),and preoperative anemia(43.6%vs.36.5%)were higher among Black patients.On regression analyses,Black race was not associated with major morbidity following head and neck oncologic surgeries(odds ratio,1.098,95%confidence interval,0.935–1.289)when compared to White patients.However,there were significant associations between the comorbidities associated with the Black race and an increased risk of major morbidity.Conclusions:Black patients undergoing head and neck oncologic surgery face a significant challenge due to a higher burden of comorbidities.These comorbidities,in turn,have been found to be associated with postoperative major morbidity.展开更多
LoRa technology contributes to green energy by enabling efficient,long-range communication for the Internet of Things(IoT).This paper addresses the challenges related to coverage range in outdoor monitoring systems ut...LoRa technology contributes to green energy by enabling efficient,long-range communication for the Internet of Things(IoT).This paper addresses the challenges related to coverage range in outdoor monitoring systems utilizing LoRa,where the network performance is affected by the density of gateways(GWs)and end devices(EDs),as well as environmental conditions.To mitigate interference,data throughput losses,and high-power consumption,the proposed spreading factor(SF)and hybrid(data rate|SF)models dynamically adjust the transmission parameters.The orchestration of concurrent data modifications within the network server(NS)is crucial for uninterrupted communication between GWs and EDs,especially in monitoring electric vehicle(EV)stations to reduce traffic congestion and pollution.Employing K-means and density-based spatial clustering of applications with noise(DBSCAN)algorithms optimizes ED allocation,averts data congestion,and improves the signal-tointerference noise ratio(SINR).These methods ensure seamless information reception by meticulously allocated EDs across various GW combinations.To estimate the free-space losses(FSL),a log-distance path loss model(log-PL)is used.Exploring various bandwidths(BWs),bidirectional communications,and duty cycles(DCs)helps to prevent saturation,thus prolonging the operational lifespan of EDs.Empirical findings reveal a notable packet rejection rate(PRR)of 0%for the DBSCAN(hybrid model).In contrast,the K-means exhibits a PRR ranging from 5%(hybrid model)to 35.29%(SF model)for the ten GWs combination.Notably,the network saturation is reduced to 10.185%and 9.503%,respectively,highlighting an improvement in the average efficiency of slotted ALOHA(91.1%)and pure ALOHA(90.7%).These enhancements increase the lifespan of EDs to 15,465.27 days.展开更多
Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).M...Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.展开更多
基金financially supported by the Key Project of Department of Education of Guangdong Province(Grant No.2022ZDZX3017)Special Support Plan of Guangdong Province(Grant No.2021TQ05Z151)+2 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.2024A1515010049)SZU Research Fund(Grant No.GFPY-YB-2024-03)Shenzhen Science and Technology Programs(Grant Nos.GJHZ20210705141803011 and 20200731211324001).
文摘The combination of silicon carbide(SiC)ceramics and stereolithography technology shows promise for manufacturing complex-shaped SiC components,expanding application possibilities.However,high sintering temperature and structural-performance anisotropy limit the practical use of 3D-printed SiC components.Herein,a novel method is introduced to produce high-specific-strength SiC-based ceramics at a relatively low temperature of 1100℃.A mixed SiC/SiO_(2) slurry(30%SiO_(2) and 70%SiC by volume)with a solid loading of up to 40%was prepared to improve UV light penetration and printability.Additionally,incorporating a high content of methyl-phenyl-polysiloxane(PSO)solution(75%by weight)enabled low-temperature pyrolysis of SiC/SiO_(2)/PSO ceramics.The SiC/SiO_(2)/PSO ceramic lattices after pyrolysis achieved a specific strength as high as(1.03×10^(5))N·m·kg^(-1) and a density of 1.75 g·cm^(-3),outperforming similar SiC-based lattices structures of similar porosities.The bending strength of(95.49±8.79)MPa was comparable to that of ceramics sintered at 1400℃ or higher.Notably,the addition of the silicon carbide oxide(SiOC)phase reduced anisotropy,lowering the transverse and longitudinal compression strength ratios from 1.87 to 1.08,and improving mechanical properties by 79%.This improvement is attributed to SiOC shrinkage,promoting a uniform distribution of sintered components,resulting in a more robust and balanced material structure.This method offers valuable insight into the additive manufacturing(AM)of SiC-based ceramics at lower temperatures and provides new guidance for controlling anisotropy in 3D-printed ceramic parts.
基金supported by grants from the National Key R&D program of China(2021YFA1201100,2022YFA1206100,2022YFA1207300)Beijing Natural Science Foundation(Z230008,L232125,7242132,China)the National Natural Science Foundation of China(No.32201158,No.32271449,No.82170087).
文摘Cuproptosis,a recently identified form of regulated cell death triggered by excess intracellular copper,has emerged as a promising cytotoxic strategy for cancer therapy.However,the therapeutic efficacy of copper ionophores such as elesclomol(ES)is often hindered by cellular copper homeostasis mechanisms that limit copper influx and cuproptosis induction.To address this challenge,we developed a nanoagent utilizing outer membrane vesicle(OMV)derived from Akkermansia muciniphila(Akk)for co-delivery of antioxidant 1 copper chaperone(Atox1)-targeting siRNA and ES(siAtox1/ES@OMV)to tumors.In vitro,we demonstrated that Atox1 knockdown via siRNA significantly disrupted copper export mechanisms,resulting in elevated intracellular copper levels.Simultaneously,ES facilitated efficient copper influx and mitochondrial transport,leading to Fe–S cluster depletion,increased proteotoxic stress,and robust cuproptosis.In vivo,siAtox1/ES@OMV achieved targeted tumor delivery and induced pronounced cuproptosis.Furthermore,leveraging the immunomodulatory properties of OMVs,siAtox1/ES@OMV promoted T-cell infiltration and the activation of tumor-reactive cytotoxic T cells,enhancing tumor immune responses.The combination of siAtox1/ES-induced cuproptosis and immunogenic cell death synergistically suppressed tumor growth in both subcutaneous breast cancer and orthotopic rectal cancer mouse models.This study highlights the potential of integrating copper homeostasis disruption with a copper ionophore using an immunomodulatory OMV-based vector,offering a promising combinatorial strategy for cancer therapy.
文摘Objectives:Racial disparities persist despite attempts to establish an egalitarian framework for surgical care.This study aimed to investigate racioethnic disparities in comorbidities and outcomes following surgery for head and neck tumors.Methods:This retrospective study included adult patients who underwent head and neck oncologic surgery between 2008 and 2020 from the National Surgical Quality Improvement Program.Multivariable regression analyses were conducted to explore the association of the following racioethnic categories with postoperative outcomes:White,Black,Hispanic,and Asian.Results:A total of 113,234 patients were included in the study,comprising 78.3%White,8.7%Black,6.9%Hispanic,and 6.0%Asian patients.Black patients had higher rates of pre-existing comorbidities compared to White patients.Specifically,the rates of comorbidities such as diabetes mellitus(19.8%vs.12.4%),hypertension(57.5%vs.41.5%),smoking history(18.8%vs.15.0%),dyspnea(7.4%vs.5.7%),and preoperative anemia(43.6%vs.36.5%)were higher among Black patients.On regression analyses,Black race was not associated with major morbidity following head and neck oncologic surgeries(odds ratio,1.098,95%confidence interval,0.935–1.289)when compared to White patients.However,there were significant associations between the comorbidities associated with the Black race and an increased risk of major morbidity.Conclusions:Black patients undergoing head and neck oncologic surgery face a significant challenge due to a higher burden of comorbidities.These comorbidities,in turn,have been found to be associated with postoperative major morbidity.
基金funded by the National Key Research and Development Plan of China(2018AAA0101000)the National Natural Science Foundation of China(62076028).
文摘LoRa technology contributes to green energy by enabling efficient,long-range communication for the Internet of Things(IoT).This paper addresses the challenges related to coverage range in outdoor monitoring systems utilizing LoRa,where the network performance is affected by the density of gateways(GWs)and end devices(EDs),as well as environmental conditions.To mitigate interference,data throughput losses,and high-power consumption,the proposed spreading factor(SF)and hybrid(data rate|SF)models dynamically adjust the transmission parameters.The orchestration of concurrent data modifications within the network server(NS)is crucial for uninterrupted communication between GWs and EDs,especially in monitoring electric vehicle(EV)stations to reduce traffic congestion and pollution.Employing K-means and density-based spatial clustering of applications with noise(DBSCAN)algorithms optimizes ED allocation,averts data congestion,and improves the signal-tointerference noise ratio(SINR).These methods ensure seamless information reception by meticulously allocated EDs across various GW combinations.To estimate the free-space losses(FSL),a log-distance path loss model(log-PL)is used.Exploring various bandwidths(BWs),bidirectional communications,and duty cycles(DCs)helps to prevent saturation,thus prolonging the operational lifespan of EDs.Empirical findings reveal a notable packet rejection rate(PRR)of 0%for the DBSCAN(hybrid model).In contrast,the K-means exhibits a PRR ranging from 5%(hybrid model)to 35.29%(SF model)for the ten GWs combination.Notably,the network saturation is reduced to 10.185%and 9.503%,respectively,highlighting an improvement in the average efficiency of slotted ALOHA(91.1%)and pure ALOHA(90.7%).These enhancements increase the lifespan of EDs to 15,465.27 days.
基金supported by grants from the National Key R&D Program of China(Nos.2021YFA1201100,and 2022YFA1206100)the National Natural Science Foundation of China(Nos.32271449,32201158,and 51773188)+2 种基金CAS Project for Young Scientists in Basic Research(No.YSBR-036)Key Project of Natural Science Foundation of Shandong Province(No.ZR2020KE016)Shandong Provincial Key Research and Development Program(Major Scientific and Technological Innovation Project,No.2022CXGC010505).
文摘Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by metals.Therefore,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating cancer.However,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting specificity.This review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of cancer.Essential trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune interplay.The latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be discussed.These concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.
