Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the...Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent tumors.How-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of tumor.Herein,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy.The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor cells.The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune activation.As a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect.Moreover,a long-term immunological memory effect to protect mice from tumor rechal-lenging is observed.Overall,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.展开更多
This paper presents a technique for low noise figure reduction of low-noise amplifier (LNA). The proposed LNA is designed in a source degeneration technique that offers lower noise figure. The resistance of the on-chi...This paper presents a technique for low noise figure reduction of low-noise amplifier (LNA). The proposed LNA is designed in a source degeneration technique that offers lower noise figure. The resistance of the on-chip inductor is reduced by using multilayer that significantly reduces the thermal noise due to spiral inductor. Also, using spiral inductor as a gate inductor reduces the effect of the input parasitic capacitance on the noise figure and provides a good matching at the input and output of the LNA. The results of the LNA using multilayer on-chip inductor compared will off-chip inductor have been illustrated. It shows that the proposed technique reduces significantly the noise figure and improves the matching. The proposed LNA is designed in 0.13 μm process with 1.3 V supply voltage and simulated using Advanced Design System (ADS) software. The simulation results show that the LNA is unconditionally stable and provides a forward gain of 11.087 dB at operating frequency of 15 GHz with 1.784 dB noise figure and input and output impedance matching of –17.93 dB, and –10.04 dB.展开更多
Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death(ICD)to provoke a robust immune response for metastasis control.Here,a self-assembled ...Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death(ICD)to provoke a robust immune response for metastasis control.Here,a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation,chemodynamic(CDT)and photothermal therapy.Ultrasmall Fe S-GOx nanodots were synthesized with glucose oxidase(GOx)as template and induced by paclitaxel(PTX)to form self-assembling Fe S-GOx@PTX(FGP)via hydrophobic interaction.After accumulated at tumor sites,FGP disassembles to smaller Fe S-GOx for enhanced deep tumor penetration.GOx maintains high enzymatic activity to catalyze glucose with assistant of oxygen to generate hydrogen peroxide(H2O2)as starvation therapy.Fenton reaction involving the regenerated H_(2)O_(2) in turn produced more hydroxyl radicals for enhanced CDT.Following near-infrared laser at 808 nm,FGPs displayed pronounced tumor inhibition in vitro and in vivo by the combination therapy.The consequent increased exposure to calreticulin amplified ICD and promoted dendritic cells maturation.In combination with anti-CTLA4 checkpoint blockade,FGP can absolutely eliminate primary tumor and avidly inhibit distant tumors due to the enhanced intratumoral infiltration of cytotoxic T lymphocytes.Our work presents a promising strategy for primary tumor and metastasis inhibition.展开更多
基金This work is supported by grants from the National Natural Science Foundation of China(Nos.22275081,and 82372117)Guangdong Basic and Applied Basic Research Foundation(2021B1515120065,China)+2 种基金Guangzhou Science and Technology Bureau(202206010068)the Natural Science Foundation of Hebei Province(E2023205004,China)China Postdoctoral Science Foundation(2022M711532 and 2022T150302).
文摘Radiotherapy(RT)is one of the most feasible and routinely used therapeutic modalities for treating malignant tumors.In particular,immune responses triggered by RT,known as radio-immunotherapy,can partially inhibit the growth of distantly spreading tumors and recurrent tumors.How-ever,the safety and efficacy of radio-immunotherapy is impeded by the radio-resistance and poor immu-nogenicity of tumor.Herein,we report oxaliplatin(IV)-iron bimetallic nanoparticles(OXA/Fe NPs)as cascade sensitizing amplifiers for low-dose and robust radio-immunotherapy.The OXA/Fe NPs exhibit tumor-specific accumulation and activation of OXA(I)and Fe^(2+)in response to the reductive and acidic microenvironment within tumor cells.The cascade reactions of the released metallic drugs can sensitize RT by inducing DNA damage,increasing ROS and O_(2) levels,and amplifying the immunogenic cell death(ICD)effect after RT to facilitate potent immune activation.As a result,OXA/Fe NPs-based low-dose RT triggered a robust immune response and inhibited the distant and metastatic tumors effectively by a strong abscopal effect.Moreover,a long-term immunological memory effect to protect mice from tumor rechal-lenging is observed.Overall,the bimetallic NPs-based cascade sensitizing amplifier system offers an effi-cient radio-immunotherapy regimen that addresses the key challenges.
文摘This paper presents a technique for low noise figure reduction of low-noise amplifier (LNA). The proposed LNA is designed in a source degeneration technique that offers lower noise figure. The resistance of the on-chip inductor is reduced by using multilayer that significantly reduces the thermal noise due to spiral inductor. Also, using spiral inductor as a gate inductor reduces the effect of the input parasitic capacitance on the noise figure and provides a good matching at the input and output of the LNA. The results of the LNA using multilayer on-chip inductor compared will off-chip inductor have been illustrated. It shows that the proposed technique reduces significantly the noise figure and improves the matching. The proposed LNA is designed in 0.13 μm process with 1.3 V supply voltage and simulated using Advanced Design System (ADS) software. The simulation results show that the LNA is unconditionally stable and provides a forward gain of 11.087 dB at operating frequency of 15 GHz with 1.784 dB noise figure and input and output impedance matching of –17.93 dB, and –10.04 dB.
基金financially supported by the Youth Foundation of Jiangsu province(No.BK20180699,China)National Natural Science Foundation of China(Nos.81803439,and 81703940)。
文摘Major challenges for cancer treatment are how to effectively eliminate primary tumor and sufficiently induce immunogenic cell death(ICD)to provoke a robust immune response for metastasis control.Here,a self-assembled cascade bioreactor was developed to improve cancer treatment with enhanced tumor penetration and synergistic therapy of starvation,chemodynamic(CDT)and photothermal therapy.Ultrasmall Fe S-GOx nanodots were synthesized with glucose oxidase(GOx)as template and induced by paclitaxel(PTX)to form self-assembling Fe S-GOx@PTX(FGP)via hydrophobic interaction.After accumulated at tumor sites,FGP disassembles to smaller Fe S-GOx for enhanced deep tumor penetration.GOx maintains high enzymatic activity to catalyze glucose with assistant of oxygen to generate hydrogen peroxide(H2O2)as starvation therapy.Fenton reaction involving the regenerated H_(2)O_(2) in turn produced more hydroxyl radicals for enhanced CDT.Following near-infrared laser at 808 nm,FGPs displayed pronounced tumor inhibition in vitro and in vivo by the combination therapy.The consequent increased exposure to calreticulin amplified ICD and promoted dendritic cells maturation.In combination with anti-CTLA4 checkpoint blockade,FGP can absolutely eliminate primary tumor and avidly inhibit distant tumors due to the enhanced intratumoral infiltration of cytotoxic T lymphocytes.Our work presents a promising strategy for primary tumor and metastasis inhibition.
