Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic repro...Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.展开更多
Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer trea...Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.展开更多
The deterioration of aqueous zinc-ion batteries(AZIBs)is confronted with challenges such as unregulated Zn^(2+)diffusion,dendrite growth and severe decay in battery performance under harsh environments.Here,a design c...The deterioration of aqueous zinc-ion batteries(AZIBs)is confronted with challenges such as unregulated Zn^(2+)diffusion,dendrite growth and severe decay in battery performance under harsh environments.Here,a design concept of eutectic electrolyte is presented by mixing long chain polymer molecules,polyethylene glycol dimethyl ether(PEGDME),with H_(2)O based on zinc trifluoromethyl sulfonate(Zn(OTf)2),to reconstruct the Zn^(2+)solvated structure and in situ modified the adsorption layer on Zn electrode surface.Molecular dynamics simulations(MD),density functional theory(DFT)calculations were combined with experiment to prove that the long-chain polymer-PEGDME could effectively reduce side reactions,change the solvation structure of the electrolyte and priority absorbed on Zn(002),achieving a stable dendrite-free Zn anode.Due to the comprehensive regulation of solvation structure and zinc deposition by PEGDME,it can stably cycle for over 3200 h at room temperature at 0.5 mA/cm^(2)and 0.5 mAh/cm^(2).Even at high-temperature environments of 60℃,it can steadily work for more than 800 cycles(1600 h).Improved cyclic stability and rate performance of aqueous Zn‖VO_(2)batteries in modified electrolyte were also achieved at both room and high temperatures.Beyond that,the demonstration of stable and high-capacity Zn‖VO_(2)pouch cells also implies its practical application.展开更多
Shaped charge has been widely used for penetrating concrete.However,due to the obvious difference between the propagation of shock waves and explosion products in water and air,the theory governing the formation of sh...Shaped charge has been widely used for penetrating concrete.However,due to the obvious difference between the propagation of shock waves and explosion products in water and air,the theory governing the formation of shaped charge jets in water as well as the underwater penetration effect of concrete need to be studied.In this paper,we introduced a modified forming theory of an underwater hemispherical shaped charge,and investigated the behavior of jet formation and concrete penetration in both air and water experimentally and numerically.The results show that the modified jet forming theory predicts the jet velocity of the hemispherical liner with an error of less than 10%.The underwater jets exhibit at least 3%faster and 11%longer than those in air.Concrete shows different failure modes after penetration in air and water.The depth of penetration deepens at least 18.75%after underwater penetration,accompanied by deeper crater with 65%smaller radius.Moreover,cracks throughout the entire target are formed,whereas cracks exist only near the penetration hole in air.This comprehensive study provides guidance for optimizing the structure of shaped charge and improves the understanding of the permeability effect of concrete in water.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
基金supported in part by grants from the following sources:the National Natural Science Foundation of China(No.82090051,32371477,92168207)the National Key Research and Development Program of China(No.2022YFA1103400,2022YFC2406704)+1 种基金the Chief Scientist Research Project of Hubei Shizhen Laboratory(HSL2024SX0001)the Beijing Tsinghua Changgung Hospital Foundation(No.12025C01011).
文摘Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality,and resistance to systemic therapies remains a significant clinical challenge.This study investigated the mechanisms by which metabolic reprogramming contributes to systemic treatment resistance in HCC.We established HCC cell lines with multidrug resistance characteristics and observed enhanced metabolic activity in these cells.Integrated multiomics analyses revealed hyperactive glucose‒lipid and glutathione metabolic pathways that play critical roles in supporting tumor cell proliferation and survival.We constructed a metabolic reprogramming atlas for HCC-resistant cells and identified aldo-keto reductase(Aldo-keto reductase family 1 Member B1,AKR1B1)as a key regulator of this reprogramming,which sustains drug resistance by regulating energy metabolism and enhancing stress tolerance.Importantly,AKR1B1 expression levels are closely associated with drug resistance and poor prognosis in HCC patients.The secretory nature of AKR1B1 not only underscores its predictive value but also facilitates the intercellular transmission of drug resistance.In terms of overcoming resistance,the AKR1B1 inhibitor epalrestat significantly mitigated drug resistance when it was used in combination with standard therapies.These findings underscore the importance of metabolic reprogramming in the development of HCC resistance.AKR1B1,a key enzyme that regulates metabolic reprogramming,has been identified as a potential biomarker and therapeutic target,providing new insights into overcoming resistance in HCC treatment.
基金the National Natural Science Foundation of China(82260695,82360781)the Jiangxi Provincial Natural Science Foundation(20232ACB206062)+4 种基金Jiangxi Provincial Department of Education(GJJ2400823)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207)Young Jinggang Scholar of Jiangxi Province(Jing Zhang)and New Century Talents Project of Jiangxi Province(2017082,Xiang Li and 2020028,Jing Zhang)the Science and Technology Innovation Team of Jiangxi University of Chinese Medicine(CXTD22001 and CXTD22006)Jiangxi University of Traditional Chinese Medicine Special Zone Construction Project of Traditional Chinese Medicine(New Drug Creation Direction)(TQ-20).
文摘Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.
基金supported by the National Natural Science Foundation of China(Nos.22208221,22178221)the Natural Science Foundation of Guangdong Province(Nos.2024A1515011078,2024A1515011507)+1 种基金the Shenzhen Science and Technology Program(Nos.JCYJ20220818095805012,JCYJ20230808105109019)the Start-up Research Funding of Shenzhen University(No.868-000001032522).
文摘The deterioration of aqueous zinc-ion batteries(AZIBs)is confronted with challenges such as unregulated Zn^(2+)diffusion,dendrite growth and severe decay in battery performance under harsh environments.Here,a design concept of eutectic electrolyte is presented by mixing long chain polymer molecules,polyethylene glycol dimethyl ether(PEGDME),with H_(2)O based on zinc trifluoromethyl sulfonate(Zn(OTf)2),to reconstruct the Zn^(2+)solvated structure and in situ modified the adsorption layer on Zn electrode surface.Molecular dynamics simulations(MD),density functional theory(DFT)calculations were combined with experiment to prove that the long-chain polymer-PEGDME could effectively reduce side reactions,change the solvation structure of the electrolyte and priority absorbed on Zn(002),achieving a stable dendrite-free Zn anode.Due to the comprehensive regulation of solvation structure and zinc deposition by PEGDME,it can stably cycle for over 3200 h at room temperature at 0.5 mA/cm^(2)and 0.5 mAh/cm^(2).Even at high-temperature environments of 60℃,it can steadily work for more than 800 cycles(1600 h).Improved cyclic stability and rate performance of aqueous Zn‖VO_(2)batteries in modified electrolyte were also achieved at both room and high temperatures.Beyond that,the demonstration of stable and high-capacity Zn‖VO_(2)pouch cells also implies its practical application.
基金supported by the National Science Foundation of China(Grant Nos.12372361,12102427,12372335 and 12102202)the Fundamental Research Funds for the Central Universities(Grant No.30923010908)Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX23_0520).
文摘Shaped charge has been widely used for penetrating concrete.However,due to the obvious difference between the propagation of shock waves and explosion products in water and air,the theory governing the formation of shaped charge jets in water as well as the underwater penetration effect of concrete need to be studied.In this paper,we introduced a modified forming theory of an underwater hemispherical shaped charge,and investigated the behavior of jet formation and concrete penetration in both air and water experimentally and numerically.The results show that the modified jet forming theory predicts the jet velocity of the hemispherical liner with an error of less than 10%.The underwater jets exhibit at least 3%faster and 11%longer than those in air.Concrete shows different failure modes after penetration in air and water.The depth of penetration deepens at least 18.75%after underwater penetration,accompanied by deeper crater with 65%smaller radius.Moreover,cracks throughout the entire target are formed,whereas cracks exist only near the penetration hole in air.This comprehensive study provides guidance for optimizing the structure of shaped charge and improves the understanding of the permeability effect of concrete in water.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
