Alumina ceramics are crucial for high-performance applications,such as turbine blades,due to their excellent thermal stability and mechanical properties.However,existing fabrication methods often fail to balance stren...Alumina ceramics are crucial for high-performance applications,such as turbine blades,due to their excellent thermal stability and mechanical properties.However,existing fabrication methods often fail to balance strength,porosity,and dimensional precision.This study partially fills this research gap through a systematic investigation of calcium oxide(CaO)doping effects on alumina ceramic cores fabricated via ceramic stereolithography,with controlled doping ratios and sintering parameters.A ceramic paste was prepared using coarse and fine Al_(2)O_(3) particles mixed with CaO as a sintering aid,followed by debinding and sintering to achieve optimal mechanical properties.The results show that CaO doping significantly enhances the fiexural strength of alumina cores while maintaining porosity levels between 20%and 30%and controlling the sintering shrinkage rate to about 5%.Additionally,CaO doping alters the microstructure by inhibiting the transformation of spherical fine particles into fiaky grains,improving sintering activity.However,as the CaO doping content increases,the bending strength increases,while the shrinkage rate of the material also tends to increase,resulting in a reduction in the overall porosity.This has a negative impact on the control of the manufacturing precision of turbine blades.Thus,although CaO doping improves strength and microstructure,achieving necessary dimensional control requires further optimization of doping content and sintering conditions.展开更多
AIM To assess the insulating effect of a poloxamer 407(P407)-based gel during microwave ablation of liver adjacent to the diaphragm.METHODS We prepared serial dilutions of P407, and 22.5%(w/w) concentration was identi...AIM To assess the insulating effect of a poloxamer 407(P407)-based gel during microwave ablation of liver adjacent to the diaphragm.METHODS We prepared serial dilutions of P407, and 22.5%(w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits(gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN) and creatinine(Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups(P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups(P > 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum(all P > 0.05).CONCLUSION Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted.展开更多
As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,w...As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,we design a kind of near-infrared(NIR)light-and acidity-activated micellar i PUTDN nanoparticle for mitochondria-targeting doxorubicin(DOX)delivery to combat DOX resistance in small-cell lung cancer.While the PEGylated i PUTDN nanoparticles can keep stealth in blood circulation,NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles,and the exposed i RGD can facilitate deep tumor penetration of the nanoparticles.After being internalized by DOX-resistant H69AR cells,the poly(β-aminoester)s(PAE)-based nanoparticles can release the triphenylphosphonium(TPP)-conjugated DOX(TDOX)into the cytosol,which can further accumulate in mitochondria with the aid of TPP.Consequently,the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells.The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.展开更多
Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampe...Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery.Herein,we developed a metal-drug self-delivery nanomedicine(FDAH)to improve the chemo/chemodynamic therapeutic efficacy of HCC.The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs,Doxorubicin(DOX)and Plerixafor(AMD3100).Additionally,the nanomedicine is externally modified with a hyaluronic acid(HA)shell,which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration.After entering the bloodstream,the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction.Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS,causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX.In addition,AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells.This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy.展开更多
Let C be a conjugation on a separable complex Hilbert space H.An operator T on H is said to be C-symmetric if CTC=-T^(*),and T is said to be Cskew symmetric if CTC=-T^(*).It is proved in this paper that each C-skew sy...Let C be a conjugation on a separable complex Hilbert space H.An operator T on H is said to be C-symmetric if CTC=-T^(*),and T is said to be Cskew symmetric if CTC=-T^(*).It is proved in this paper that each C-skew symmetric operator can be written as the sum of two commutators of C-symmetric operators.展开更多
Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in con...Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in conventional mitochondrial targeting strategies,we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin(DOX)resistance in lung cancer.Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors.As a consequence,thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice.This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.展开更多
基金financially supported by the National Key R&D Program of China(No.2023YFB4606101)the National Key R&D Program of China(No.2022YFB4601404)+3 种基金the Innovative and Entrepreneurial PhD Program of Jiangsu Province(No.JSSCBS20210836)the youth program of Jiangnan University(No.JUSRP121038)the Taihu Talent Program of Wuxi Citythe Innovative and Entrepreneurial Talent Program of Jiangsu Province(No.JSSCRC2021531)。
文摘Alumina ceramics are crucial for high-performance applications,such as turbine blades,due to their excellent thermal stability and mechanical properties.However,existing fabrication methods often fail to balance strength,porosity,and dimensional precision.This study partially fills this research gap through a systematic investigation of calcium oxide(CaO)doping effects on alumina ceramic cores fabricated via ceramic stereolithography,with controlled doping ratios and sintering parameters.A ceramic paste was prepared using coarse and fine Al_(2)O_(3) particles mixed with CaO as a sintering aid,followed by debinding and sintering to achieve optimal mechanical properties.The results show that CaO doping significantly enhances the fiexural strength of alumina cores while maintaining porosity levels between 20%and 30%and controlling the sintering shrinkage rate to about 5%.Additionally,CaO doping alters the microstructure by inhibiting the transformation of spherical fine particles into fiaky grains,improving sintering activity.However,as the CaO doping content increases,the bending strength increases,while the shrinkage rate of the material also tends to increase,resulting in a reduction in the overall porosity.This has a negative impact on the control of the manufacturing precision of turbine blades.Thus,although CaO doping improves strength and microstructure,achieving necessary dimensional control requires further optimization of doping content and sintering conditions.
基金Supported by the Clinical-Basic Cooperation Program from Capital Medical University,No.15JL10the National Key Research and Development Program,No.2016YFA0201504the Beijing Training Project For The Leading Talents in S&T,No.Z14110700154002
文摘AIM To assess the insulating effect of a poloxamer 407(P407)-based gel during microwave ablation of liver adjacent to the diaphragm.METHODS We prepared serial dilutions of P407, and 22.5%(w/w) concentration was identified as suitable for ablation procedures. Subsequently, microwave ablations were performed on the livers of 24 rabbits(gel, saline, control groups, n = 8 in each). The P407 solution and 0.9% normal saline were injected into the potential space between the diaphragm and liver in experimental groups. No barriers were applied to the controls. After microwave ablations, the frequency, size and degree of thermal injury were compared histologically among the three groups. Subsequently, another 8 rabbits were injected with the P407 solution and microwave ablation was performed. The levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), blood urea nitrogen(BUN) and creatinine(Cr) in serum were tested at 1 d before microwave ablation and 3 and 7 d after operation. RESULTS In vivo ablation thermal injury to the adjacent diaphragm was evaluated in the control, saline and 22.5% P407 gel groups(P = 0.001-0.040). However, there was no significant difference in the volume of ablation zone among the three groups(P > 0.05). Moreover, there were no statistical differences among the preoperative and postoperative gel groups according to the levels of ALT, AST, BUN and Cr in serum(all P > 0.05).CONCLUSION Twenty-two point five percent P407 gel could be a more effective choice during microwave ablation of hepatic tumors adjacent to the diaphragm. Further studies for clinical translation are warranted.
基金the National Natural Science Foundation of China(Nos.11875269 and 21574136)the Beijing Natural Science Foundation(No.7212212).
文摘As one of the major challenges in tumor chemotherapy,multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells.Herein,we design a kind of near-infrared(NIR)light-and acidity-activated micellar i PUTDN nanoparticle for mitochondria-targeting doxorubicin(DOX)delivery to combat DOX resistance in small-cell lung cancer.While the PEGylated i PUTDN nanoparticles can keep stealth in blood circulation,NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles,and the exposed i RGD can facilitate deep tumor penetration of the nanoparticles.After being internalized by DOX-resistant H69AR cells,the poly(β-aminoester)s(PAE)-based nanoparticles can release the triphenylphosphonium(TPP)-conjugated DOX(TDOX)into the cytosol,which can further accumulate in mitochondria with the aid of TPP.Consequently,the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells.The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.
基金supported by the Beijing Natural Science Foundation(L248075)the National Natural Science Foundation of China(32171370)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022A1515140073 and 2022A1515010415)the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2023C012YL)the Science and Technology Program of Guangzhou(2023A03J0493).
文摘Hepatocellular carcinoma(HCC)is the most common primary liver cancer with a poor prognosis.Chemotherapy is one of the first-line clinical therapeutic strategies for HCC.Still,the effectiveness of chemotherapy is hampered by the tumor immunosuppressive microenvironment and drug resistance caused by insufficient delivery.Herein,we developed a metal-drug self-delivery nanomedicine(FDAH)to improve the chemo/chemodynamic therapeutic efficacy of HCC.The core of FDAH is an iron-based nanoparticle chelated with two clinical drugs,Doxorubicin(DOX)and Plerixafor(AMD3100).Additionally,the nanomedicine is externally modified with a hyaluronic acid(HA)shell,which can prolong the circulation time of the nanoparticles in the bloodstream after intravenous administration.After entering the bloodstream,the nanomedicine reaches the tumor tissue through the EPR effect and is phagocytosed by the tumor cells via HA/CD44-specific interaction.Iron ion-mediated chemodynamic therapy is mediated by the Fenton reaction to generate ROS,causing an imbalance of redox homeostasis within the tumor cells and enhancing the sensitivity of tumor cells to DOX.In addition,AMD3100 intervenes in the CXCL12/CXCR4 axis to influence the infiltration level of immune cells and promote DOX chemotherapy in tumor cells.This work suggests that alleviating immunosuppression via a metal-drug self-delivery system of the CXCR4 inhibitor can effectively improve the DOX chemotherapy and iron ions-mediated chemodynamic therapy.
基金partly supported by the National Natural Science Foundation of China(Grant No.12i7195)by the National Key R&D Program(Grant No.2020YFA0714101).
文摘Let C be a conjugation on a separable complex Hilbert space H.An operator T on H is said to be C-symmetric if CTC=-T^(*),and T is said to be Cskew symmetric if CTC=-T^(*).It is proved in this paper that each C-skew symmetric operator can be written as the sum of two commutators of C-symmetric operators.
基金We are grateful to Beijing Natural Science Foundation(7212212)National Natural Science Foundation of China(11875269 and 21574136)Hundred Talents Program of CAS for financial support。
文摘Reversal of cancer drug resistance remains a critical challenge in chemotherapy.Mitochondria-targeted drug delivery has been suggested to mitigate drug resistance in cancer.To overcome the intrinsic limitations in conventional mitochondrial targeting strategies,we develop mitochondrial temperature-responsive drug delivery to reverse doxorubicin(DOX)resistance in lung cancer.Results demonstrate that the thermoresponsive nanocarrier can prevent DOX efflux and facilitate DOX accumulation and mitochondrial targeting in DOX-resistant tumors.As a consequence,thermoresponsive nanocarrier enhances the cytotoxicity of DOX and reverses the drug resistance in tumor-bearing mice.This work represents the first example of mitochondrial temperature-responsive drug delivery for reversing cancer drug resistance.
