Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations th...Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.展开更多
The cubic or third-power(TP)nonlinear energy sink(NES)has been proven to be an effective method for vibration suppression,owing to the occurrence of targeted energy transfer(TET).However,TET is unable to be triggered ...The cubic or third-power(TP)nonlinear energy sink(NES)has been proven to be an effective method for vibration suppression,owing to the occurrence of targeted energy transfer(TET).However,TET is unable to be triggered by the low initial energy input,and thus the TP NES would get failed under low-amplitude vibration.To resolve this issue,a new type of NES with fractional nonlinearity,e.g.,one-third-power(OTP)nonlinearity,is proposed.The dynamic behaviors of a linear oscillator(LO)with an OTP NES are investigated numerically,and then both the TET feature and the vibration attenuation performance are evaluated.Moreover,an analogy circuit is established,and the circuit simulations are carried out to verify the design concept of the OTP NES.It is found that the threshold for TET of the OTP NES is two orders of magnitude smaller than that of the TP NES.The parametric analysis shows that a heavier mass or a lower stiffness coefficient of the NES is beneficial to the occurrence of TET in the OTP NES system.Additionally,significant energy transfer is usually accompanied with efficient energy dissipation.Consequently,the OTP NES can realize TET under low initial input energy,which should be a promising approach for micro-vibration suppression.展开更多
A substantial reduction in groundwater level,exacerbated by coal mining activities,is intensifying water scarcity in western China’s ecologically fragile coal mining areas.China’s national strategic goal of achievin...A substantial reduction in groundwater level,exacerbated by coal mining activities,is intensifying water scarcity in western China’s ecologically fragile coal mining areas.China’s national strategic goal of achieving a carbon peak and carbon neutrality has made eco-friendly mining that prioritizes the protection and efficient use of water resources essential.Based on the resource characteristics of mine water and heat hazards,an intensive coal-water-thermal collaborative co-mining paradigm for the duration of the mining process is proposed.An integrated system for the production,supply,and storage of mining companion resources is achieved through technologies such as roof water inrush prevention and control,hydrothermal quality improvement,and deep-injection geological storage.An active preventive and control system achieved by adjusting the mining technology and a passive system centered on multiobjective drainage and grouting treatment are suggested,in accordance with the original geological characteristics and dynamic process of water inrush.By implementing advanced multi-objective drainage,specifically designed to address the“skylight-type”water inrush mode in the Yulin mining area of Shaanxi Province,a substantial reduction of 50%in water drillings and inflow was achieved,leading to stabilized water conditions that effectively ensure subsequent safe coal mining.An integrated-energy complementary model that incorporates the clean production concept of heat utilization is also proposed.The findings indicate a potential saving of 8419 t of standard coal by using water and air heat as an alternative heating source for the Xiaojihan coalmine,resulting in an impressive energy conservation of 50.2%and a notable 24.2%reduction in carbon emissions.The ultra-deep sustained water injection of 100 m^(3)·h^(-1)in a single well would not rupture the formation or cause water leakage,and 7.87×10^(5)t of mine water could be effectively stored in the Liujiagou Formation,presenting a viable method for mine-water management in the Ordos Basin and providing insights for green and low-carbon mining.展开更多
基金supported by the National Natural Science Foundation of China(52073145 and 82004081)the Jiangsu Talent Professor Program,Jiangsu Innovation Project of Graduate Student(KYCX23-2192)+1 种基金the National Natural Science Foundation of Nanjing University of Chinese Medicine(NZY82004081)the Special Grants of China Postdoctoral Science Foundation(2021T140792).
文摘Multiple myeloma(MM)is the second most prevalent hematological malignancy.Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy.This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy,which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes,termed T-PB@M.The results from our investigations highlight the considerable bone affinity of T-PB@M,both in vitro and in vivo.Additionally,this material demonstrated a capability for drug release triggered by low pH conditions.Moreover,T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose)polymerase 1(PARP1)-Caspase-3-B-cell lymphoma-2(Bcl-2)pathway in MM cells.Notably,T-PB@M preferentially targeted bone-involved sites,thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice.Therefore,this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.
基金Project supported by the National Natural Science Foundation of China(Nos.12122206,11972152,12002122)the Natural Science Foundation of Hunan Province of China(No.2021JJ40092)the Natural Science Foundation of Chongqing of China(No.cstc2021jcyj-msxmX0461)。
文摘The cubic or third-power(TP)nonlinear energy sink(NES)has been proven to be an effective method for vibration suppression,owing to the occurrence of targeted energy transfer(TET).However,TET is unable to be triggered by the low initial energy input,and thus the TP NES would get failed under low-amplitude vibration.To resolve this issue,a new type of NES with fractional nonlinearity,e.g.,one-third-power(OTP)nonlinearity,is proposed.The dynamic behaviors of a linear oscillator(LO)with an OTP NES are investigated numerically,and then both the TET feature and the vibration attenuation performance are evaluated.Moreover,an analogy circuit is established,and the circuit simulations are carried out to verify the design concept of the OTP NES.It is found that the threshold for TET of the OTP NES is two orders of magnitude smaller than that of the TP NES.The parametric analysis shows that a heavier mass or a lower stiffness coefficient of the NES is beneficial to the occurrence of TET in the OTP NES system.Additionally,significant energy transfer is usually accompanied with efficient energy dissipation.Consequently,the OTP NES can realize TET under low initial input energy,which should be a promising approach for micro-vibration suppression.
基金supported by the National Key Research and Development Program of China(2021YFC2902004)the National Natural Science Foundation of China(42072284,42027801,and 41877186).
文摘A substantial reduction in groundwater level,exacerbated by coal mining activities,is intensifying water scarcity in western China’s ecologically fragile coal mining areas.China’s national strategic goal of achieving a carbon peak and carbon neutrality has made eco-friendly mining that prioritizes the protection and efficient use of water resources essential.Based on the resource characteristics of mine water and heat hazards,an intensive coal-water-thermal collaborative co-mining paradigm for the duration of the mining process is proposed.An integrated system for the production,supply,and storage of mining companion resources is achieved through technologies such as roof water inrush prevention and control,hydrothermal quality improvement,and deep-injection geological storage.An active preventive and control system achieved by adjusting the mining technology and a passive system centered on multiobjective drainage and grouting treatment are suggested,in accordance with the original geological characteristics and dynamic process of water inrush.By implementing advanced multi-objective drainage,specifically designed to address the“skylight-type”water inrush mode in the Yulin mining area of Shaanxi Province,a substantial reduction of 50%in water drillings and inflow was achieved,leading to stabilized water conditions that effectively ensure subsequent safe coal mining.An integrated-energy complementary model that incorporates the clean production concept of heat utilization is also proposed.The findings indicate a potential saving of 8419 t of standard coal by using water and air heat as an alternative heating source for the Xiaojihan coalmine,resulting in an impressive energy conservation of 50.2%and a notable 24.2%reduction in carbon emissions.The ultra-deep sustained water injection of 100 m^(3)·h^(-1)in a single well would not rupture the formation or cause water leakage,and 7.87×10^(5)t of mine water could be effectively stored in the Liujiagou Formation,presenting a viable method for mine-water management in the Ordos Basin and providing insights for green and low-carbon mining.
