Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not...Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro. Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.展开更多
To address the challenges associated with existing separated zone oil production technologies,such as incompatibility with pump inspection operations,short effective working life,and poor communication reliability,an ...To address the challenges associated with existing separated zone oil production technologies,such as incompatibility with pump inspection operations,short effective working life,and poor communication reliability,an innovative electromagnetic coupling intelligent zonal oil production technology has been proposed.The core and accessory tools have been developed and applied in field tests.This technology employs a pipe string structure incorporation a release sub,which separates the production and allocation pipe strings.When the two strings are docked downhole,electromagnetic coupling enables close-range wireless transmission of electrical power and signals between the strings,powering multiple downhole intelligent production allocators(IPAs)and enabling two-way communication.Core tools adapted to the complex working conditions downhole were developed,including downhole electricity&signal transmission equipment based on electromagnetic coupling(EST),IPAs,and ground communication controllers(GCCs).Accessory tools,including large-diameter release sub anchor and cable-crossing packers,have also been technically finalized.Field tests conducted on ten wells in Daqing Oilfield demonstrated that the downhole docking of the two strings was convenient and reliable,and the EST worked stably.Real-time monitoring of flow rate,pressure and temperature in separate layers and regulation of zonal fluid production were also achieved.This technology has enhanced reservoir understanding and achieved practical production results of increased oil output with reduced water cut.展开更多
基金the National Natural Science Foundation of China(Nos.51932002,52072127,51903087,52003085,21975079)the Science and Technology Program of Guangzhou(No.202002030308).
文摘Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating tumor progression. However, traditional vascular normalization strategies are not fully effective and limited by the development of resistance. Herein, inspired by the intervention of endogenous bioelectricity in vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable of breaking bioelectric homeostasis within cells, to achieve tumor vascular normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity pulsed ultrasound. We demonstrated that wireless electrical stimulation significantly inhibited endothelial cell migration and differentiation in vitro. Interestingly, we found that the angiogenesis-related eNOS/NO pathway was inhibited, which could be attributed to the destruction of the intracellular calcium ion gradient by wireless electrical stimulation. In vivo tumor-bearing mouse model indicated that wireless electrical stimulation normalized tumor vasculature by optimizing vascular structure, enhancing blood perfusion, reducing vascular leakage, and restoring local oxygenation. Ultimately, the anti-tumor efficacy of combination treatment was 1.8 times that of the single chemotherapeutic drug doxorubicin group. This work provides a wireless electrical stimulation strategy based on the mechano-electrical conversion performance of piezoelectric nanoparticles, which is expected to achieve safe and effective clinical adjuvant treatment of malignant tumors.
基金Supported by the National Natural Science Foundation of China(52374067)PetroChina Scientific Research and Technology Development Project(2021ZG12)PetroChina Technology Project(2023ZZ09).
文摘To address the challenges associated with existing separated zone oil production technologies,such as incompatibility with pump inspection operations,short effective working life,and poor communication reliability,an innovative electromagnetic coupling intelligent zonal oil production technology has been proposed.The core and accessory tools have been developed and applied in field tests.This technology employs a pipe string structure incorporation a release sub,which separates the production and allocation pipe strings.When the two strings are docked downhole,electromagnetic coupling enables close-range wireless transmission of electrical power and signals between the strings,powering multiple downhole intelligent production allocators(IPAs)and enabling two-way communication.Core tools adapted to the complex working conditions downhole were developed,including downhole electricity&signal transmission equipment based on electromagnetic coupling(EST),IPAs,and ground communication controllers(GCCs).Accessory tools,including large-diameter release sub anchor and cable-crossing packers,have also been technically finalized.Field tests conducted on ten wells in Daqing Oilfield demonstrated that the downhole docking of the two strings was convenient and reliable,and the EST worked stably.Real-time monitoring of flow rate,pressure and temperature in separate layers and regulation of zonal fluid production were also achieved.This technology has enhanced reservoir understanding and achieved practical production results of increased oil output with reduced water cut.
