Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly l...Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.展开更多
Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under ...Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under laser irradiation. Differently, ferroptosis therapy exerts its antitumor effect by inducing excessive accumulation of lipid peroxides on tumor cell membranes. Based on that, ROS produced by PDT may promote ferroptosis in tumor cells, and ferroptosis therapy is expected eliminate apoptosis-resistant tumor cells. Therefore, a synergistic ferroptosis-photodynamic therapy will be more effective and more potential in breast cancer treatment. Considering PDT has the characteristic of producing ROS, and neutrophil has a natural tendency to ROS, a neutrophil-mimetic hybrid liposome (CR-NML) was designed for co-delivery of the photosensitizer Ce6 and the ferroptosis inducer RSL3. CR-NML targeted tumor through the ROS tendency of neutrophil and the enhanced permeability and retention (EPR) effect of liposome, then induced both apoptosis and ferroptosis in tumor cells, which increased ROS level and finally realized ROS cascade amplification. The synergistic ferroptosis-photodynamic therapy demonstrated significant therapeutic efficacy in 4T1 tumor bearing mice, which provided a promising strategy for breast cancer treatment.展开更多
We present an experimental study on low-threshold broadband spectrum generation mainly due to the amplirfication of the cascaded stimulated Raman scattering （SRS） effect in a four-stage fiber master oscillator power...We present an experimental study on low-threshold broadband spectrum generation mainly due to the amplirfication of the cascaded stimulated Raman scattering （SRS） effect in a four-stage fiber master oscillator power amplifier system. The cascaded SRS is achieved by using a long passive fiber pumped by a pulsed fiber laser cen： tered at wavelength 1064 nm. The amplified spontaneous emission during the amplification process is efficiently suppressed by cutting the length of the passive fiber and by using a double-clad ytterbium-doped fiber amplifier. The generated broadband spectrum spans from 960nm to 1700nm with maximum average output 13.6 W and average spectral power density approximately 17. 7 mW/nm.展开更多
Human T-cell lymphophilic virus type 1(HTLV-1),the known retrovirus causing cancer in humans,is closely associated with adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis.Due ...Human T-cell lymphophilic virus type 1(HTLV-1),the known retrovirus causing cancer in humans,is closely associated with adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis.Due to its ability to evade the host's defense mechanisms,early tracking of HTLV-1 becomes crucial.In this study,we integrateλ-Exonuclease(λ-Exo)-assisted target recycling with a terminal deoxynucleotidyl transferase(TdT)-mediated template-free DNA extension process to develop an electrochemical analysis platform for the specific and sensitive detection of HTLV-1 DNA.During theλ-Exo-assisted target recycling,HTLV-1 DNA is recognized by hairpin DNA(Hp-DNA),forming double-stranded DNA(dsDNA)through DNA hybridization.The dsDNA,featuring blunt 5'terminal phosphorylation,is cleaved byλ-Exo,generating abundant short output sequence(sDNA).HTLV-1 DNA is released,initiating a cyclic hybridization-cleavage process.Subsequently,thiol-labelled capture DNA(CP-DNA)assembled on gold electrode surface captures a substantial amount of the generated sDNA,forming CP-DNA-sDNA nanostructures.When TdT and dNTPs are present on the electrode surface,the 3'-OH terminal of sDNA extends to generate long single-stranded DNA(ssDNA)structure.Methylene blue(MB)is selected as the electrochemical signal molecule.MB not only binds with ssDNA but also interacts specifically with dsDNA,resulting in a significantly enhanced electrochemical signal on modified electrode surface.The detection limit of HTLV-1 DNA is as low as 19 amol/L(S/N=3)when the two signal amplification strategies are combined.The analysis platform exhibits excellent analytical performance and holds promise as a novel tool for the early tracing and diagnosis of HTLV-1 DNA.展开更多
We presented a broadband optical parametric chirped pulse amplification(OPCPA)system based on dual-crystal spectra cascading amplification in the short-wave infrared(SWIR)region.By cascading two crystals with differen...We presented a broadband optical parametric chirped pulse amplification(OPCPA)system based on dual-crystal spectra cascading amplification in the short-wave infrared(SWIR)region.By cascading two crystals with different phase-matching angles,the impact of gain bandwidth narrowing in OPCPA is reduced.In addition,due to the different phase-matching wavelengths,the energy backflow of the idler pulses is also mitigated,thereby enhancing the overall energy conversion efficiency of the system.Ultimately,SWIR pulses with a full-width at half-maximum(FWHM)exceeding 110 nm,a near Fourier-transform limit(FTL)pulse duration of 42.15 fs,and a pulse energy of 30 mJ are obtained(25.9%pump energy conversion efficiency),corresponding to a peak power of 0.75 TW.Compared to single-crystal amplification,this configuration achieves an 80 nm expansion in FWHM,the output pulse duration is reduced by more than 40%,the pump efficiency is increased by 17.22%,and a 2.3-time enhancement in peak power is achieved.This high-energy,terawatt-class SWIR source has significant applications in strong-field physics,including high-intensity THz and water-window X-ray generation,among other areas.展开更多
A new concept for a hybrid structure gaseous detector module with ion backflow suppression for the time projection chamber in a future circular collider is presented.It is a hybrid structure cascaded Gas Electron Mult...A new concept for a hybrid structure gaseous detector module with ion backflow suppression for the time projection chamber in a future circular collider is presented.It is a hybrid structure cascaded Gas Electron Multiplier（GEM） with a Micromegas detector.Both Micromegas and GEM have the capability to naturally reduce most of the ions produced in the amplification region.The GEM also acts as the preamplifer device and increases gas gain together with the Micromegas.Feasibility tests of the hybrid detector are performed using an ^（55）Fe X-ray source.The energy resolution is better than 27% for 5.9 keV X-rays.It is demonstrated that a backflow ratio better than 0.2% can be reached in the hybrid readout structure at a gain of 5000.展开更多
基金supported by the National Natural Science Foundation of China(Nos.T2293753,52203194)the National Key R&D Program of China(No.2021YFA1201200)+1 种基金the Natural Science Foundation of Zhejiang Province(No.LR18E030002)2023 Hangzhou West Lake Pearl Project Leading Innovative Youth Team Project.
文摘Chemodynamic therapy(CDT),using Fenton agents to generate highly cytotoxic•OH from H_(2)O_(2)has been demonstrated as a powerful anticancer method.However,the insufficient endogenous H_(2)O_(2)in tumor cells greatly limited its therapeutic effect.Herein,we prepared a pH-responsiveβ-lapachone-loaded ironpolyphenol nanocomplex(LIPN)through a one-pot method.β-Lapachone in LIPN selectively enhanced H_(2)O_(2)concentration in tumor cells,and ferrous ions cascadely generated abundant cytotoxic•OH.Therefore,LIPN with cascade amplification of reactive oxygen species(ROS)showed high chemodynamic cytotoxicity in tumor cells,efficiently improving the expression of damage-associated molecular patterns(DAMPs),and exerting strong immunogenic cell death(ICD).As a result,LIPN exhibited efficient tumor inhibition ability in 4T1 subcutaneous tumor model in vivo with great biocompatibility.Additionally,the infiltration of cytotoxic CD8^(+)T lymphocytes and inhibition of regulatory CD4^(+)FoxP3^(+)T lymphocytes in tumors demonstrated the activation of immunosuppressive tumor microenvironment by LIPN-induced ICD.Therefore,this work provided a new approach to enhance ICD of chemodynamic therapy through selective cascade amplification of ROS in cancer cells.
基金supported by Sichuan Science and Technology program(No.2022NSFSC0045)Sichuan University Postdoctoral Research Foundation(No.2024SCU12130)National Postdoctoral Program(No.GZC20231780).
文摘Photodynamic therapy (PDT) and ferroptosis therapy have received extensive attention in breast cancer treatment. PDT induced apoptosis of tumor cells by producing a large amount of reactive oxygen species (ROS) under laser irradiation. Differently, ferroptosis therapy exerts its antitumor effect by inducing excessive accumulation of lipid peroxides on tumor cell membranes. Based on that, ROS produced by PDT may promote ferroptosis in tumor cells, and ferroptosis therapy is expected eliminate apoptosis-resistant tumor cells. Therefore, a synergistic ferroptosis-photodynamic therapy will be more effective and more potential in breast cancer treatment. Considering PDT has the characteristic of producing ROS, and neutrophil has a natural tendency to ROS, a neutrophil-mimetic hybrid liposome (CR-NML) was designed for co-delivery of the photosensitizer Ce6 and the ferroptosis inducer RSL3. CR-NML targeted tumor through the ROS tendency of neutrophil and the enhanced permeability and retention (EPR) effect of liposome, then induced both apoptosis and ferroptosis in tumor cells, which increased ROS level and finally realized ROS cascade amplification. The synergistic ferroptosis-photodynamic therapy demonstrated significant therapeutic efficacy in 4T1 tumor bearing mice, which provided a promising strategy for breast cancer treatment.
基金Supported by the National Natural Science Foundation of China under Grant No 11404404the Outstanding Youth Fund Project of Hunan Provincethe Fund of Innovation of National University of Defense Technology under Grant No B120701
文摘We present an experimental study on low-threshold broadband spectrum generation mainly due to the amplirfication of the cascaded stimulated Raman scattering （SRS） effect in a four-stage fiber master oscillator power amplifier system. The cascaded SRS is achieved by using a long passive fiber pumped by a pulsed fiber laser cen： tered at wavelength 1064 nm. The amplified spontaneous emission during the amplification process is efficiently suppressed by cutting the length of the passive fiber and by using a double-clad ytterbium-doped fiber amplifier. The generated broadband spectrum spans from 960nm to 1700nm with maximum average output 13.6 W and average spectral power density approximately 17. 7 mW/nm.
基金financially supported by Central Leading Local Science and Technology Development Fund Project(guikeZY22096017)Natural Science Foundation of Guangxi Province(2024GXNSFDA010036)National Natural Science Foundation of China(22164014,U23A2089).
文摘Human T-cell lymphophilic virus type 1(HTLV-1),the known retrovirus causing cancer in humans,is closely associated with adult T-cell leukemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis.Due to its ability to evade the host's defense mechanisms,early tracking of HTLV-1 becomes crucial.In this study,we integrateλ-Exonuclease(λ-Exo)-assisted target recycling with a terminal deoxynucleotidyl transferase(TdT)-mediated template-free DNA extension process to develop an electrochemical analysis platform for the specific and sensitive detection of HTLV-1 DNA.During theλ-Exo-assisted target recycling,HTLV-1 DNA is recognized by hairpin DNA(Hp-DNA),forming double-stranded DNA(dsDNA)through DNA hybridization.The dsDNA,featuring blunt 5'terminal phosphorylation,is cleaved byλ-Exo,generating abundant short output sequence(sDNA).HTLV-1 DNA is released,initiating a cyclic hybridization-cleavage process.Subsequently,thiol-labelled capture DNA(CP-DNA)assembled on gold electrode surface captures a substantial amount of the generated sDNA,forming CP-DNA-sDNA nanostructures.When TdT and dNTPs are present on the electrode surface,the 3'-OH terminal of sDNA extends to generate long single-stranded DNA(ssDNA)structure.Methylene blue(MB)is selected as the electrochemical signal molecule.MB not only binds with ssDNA but also interacts specifically with dsDNA,resulting in a significantly enhanced electrochemical signal on modified electrode surface.The detection limit of HTLV-1 DNA is as low as 19 amol/L(S/N=3)when the two signal amplification strategies are combined.The analysis platform exhibits excellent analytical performance and holds promise as a novel tool for the early tracing and diagnosis of HTLV-1 DNA.
基金National Key Research and Development Program of China(2023YFA1608504,2022YFA1604401)National Natural Science Foundation of China(12388102,22227901,62305353,U22A2090)+2 种基金Shanghai Science and Technology Committee Program(22DZ1100300,22560780100,23560750200)Talent Plan of Shanghai Branch,Chinese Academy of SciencesCAS Project for Young Scientists in Basic Research(YSBR-115).
文摘We presented a broadband optical parametric chirped pulse amplification(OPCPA)system based on dual-crystal spectra cascading amplification in the short-wave infrared(SWIR)region.By cascading two crystals with different phase-matching angles,the impact of gain bandwidth narrowing in OPCPA is reduced.In addition,due to the different phase-matching wavelengths,the energy backflow of the idler pulses is also mitigated,thereby enhancing the overall energy conversion efficiency of the system.Ultimately,SWIR pulses with a full-width at half-maximum(FWHM)exceeding 110 nm,a near Fourier-transform limit(FTL)pulse duration of 42.15 fs,and a pulse energy of 30 mJ are obtained(25.9%pump energy conversion efficiency),corresponding to a peak power of 0.75 TW.Compared to single-crystal amplification,this configuration achieves an 80 nm expansion in FWHM,the output pulse duration is reduced by more than 40%,the pump efficiency is increased by 17.22%,and a 2.3-time enhancement in peak power is achieved.This high-energy,terawatt-class SWIR source has significant applications in strong-field physics,including high-intensity THz and water-window X-ray generation,among other areas.
基金Supported by National Key Programme for S&T Research and Development(2016YFA0400400)National Natural Science Foundation of China(11275224)
文摘A new concept for a hybrid structure gaseous detector module with ion backflow suppression for the time projection chamber in a future circular collider is presented.It is a hybrid structure cascaded Gas Electron Multiplier（GEM） with a Micromegas detector.Both Micromegas and GEM have the capability to naturally reduce most of the ions produced in the amplification region.The GEM also acts as the preamplifer device and increases gas gain together with the Micromegas.Feasibility tests of the hybrid detector are performed using an ^（55）Fe X-ray source.The energy resolution is better than 27% for 5.9 keV X-rays.It is demonstrated that a backflow ratio better than 0.2% can be reached in the hybrid readout structure at a gain of 5000.
