Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiven...Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.展开更多
The optical response of metal nanoparticles can be modified through near-field or far-field interaction,yet the lattice plasmon modes(LPMs)considered can only be excited from the latter.Here instead,we present a theor...The optical response of metal nanoparticles can be modified through near-field or far-field interaction,yet the lattice plasmon modes(LPMs)considered can only be excited from the latter.Here instead,we present a theoretical evaluation for LPM excitation via the near-field coupling process.The sample is an arrayed structure with specific units composed of upper metal disks,a lower metal hole and a sandwiched dielectric post.The excitation process and underlying mechanism of the LPM and the influence of the structure parameters on the optical properties have been investigated in detail by using a finite-difference time-domain(FDTD)numerical method.Our investigation presented here should advance the understanding of near-field interaction of plasmon modes for LPM excitation,and LPMs could find some potential applications,such as in near-field optical microscopes,biosensors,optical filters and plasmonic lasers.展开更多
The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory synd...The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.展开更多
Dear Editor,The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to disrupt global public health since its first report in December 2019,resulting in more than 380 billi...Dear Editor,The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to disrupt global public health since its first report in December 2019,resulting in more than 380 billion confirmed cases including nearly 5.7 billion deaths worldwide(https://covidl9.who.int).展开更多
基金support from the National Natural Science Foundation of China(Grants No.82304827,82074098,81841001)the Fundamental Research Funds for the Central public welfare research institutes(ZZ13-ZD-07),the National Key Research and Development Programof China(2020YFA0908000,2022YFC2303600)+7 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No:ZYYCXTD-C-202002)The Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation(B2302051)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Grants No.ZZ13-YQ-108)the Shenzhen Science and Technology Innovation Commission(Grants No.JCYJ20210324115800001)the Science and Technology Foundation of Shenzhen(Shenzhen Clinical Medical Research Center for Geriatric Diseases),the Distinguished Expert Project of Sichuan Province Tianfu Scholar(CW202002)Supported by Shenzhen Governmental Sustainable Development Fund(KCXFZ20201221173612034)Supported by Shenzhen key Laboratory of Kidney Diseases(ZDSYS201504301616234)Supported by Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(NO.SZGSP001).
文摘Hepatocellular carcinoma(HCC)is one of most common and deadliest malignancies.Celastrol(Cel),a natural product derived from the Tripterygium wilfordii plant,has been extensively researched for its potential effectiveness in fighting cancer.However,its clinical application has been hindered by the unclear mechanism of action.Here,we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and antitumor capacity by developing a Cel-based liposomes in HCC.We demonstrated that Cel selectively targets the voltage-dependent anion channel 2(VDAC2).Cel directly binds to the cysteine residues of VDAC2,and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore(mPTP)function.We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells.Moreover,coencapsulation of Cel into alkyl glucoside-modified liposomes(AGCL)improved its antitumor efficacy and minimized its side effects.AGCL has been shown to effectively suppress the proliferation of tumor cells.In a xenograft nude mice experiment,AGCL significantly inhibited tumor growth and promoted apoptosis.Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death,while the Cel liposomes enhance its targetability and reduces side effects.Overall,Cel shows promise as a therapeutic agent for HCC.
基金Key Laboratory of Energy Conversion and Storage Technologies(Southern University of Science and Technology),Ministry of Education,Shenzhen,China,the National Key Research and Development Program of China(Grant No.2018YFB0406702)Professorship Startup Funding(Grant No.217056)+1 种基金Innovation-Driven Project of Central South University(Grant No.2018CX001)Project of State Key Laboratory of High Performance Complex Manufacturing,Central South University(Grant No.ZZYJKT2018-01).
文摘The optical response of metal nanoparticles can be modified through near-field or far-field interaction,yet the lattice plasmon modes(LPMs)considered can only be excited from the latter.Here instead,we present a theoretical evaluation for LPM excitation via the near-field coupling process.The sample is an arrayed structure with specific units composed of upper metal disks,a lower metal hole and a sandwiched dielectric post.The excitation process and underlying mechanism of the LPM and the influence of the structure parameters on the optical properties have been investigated in detail by using a finite-difference time-domain(FDTD)numerical method.Our investigation presented here should advance the understanding of near-field interaction of plasmon modes for LPM excitation,and LPMs could find some potential applications,such as in near-field optical microscopes,biosensors,optical filters and plasmonic lasers.
基金supported by the National Key R&D Program of China(2020YFC0842000 to Z.M.Yuan and 2020YFC0842100 to C.Shan)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29010101 to Z.L.Shi)+1 种基金the China Natural Science Foundation(82041013 to P.Zhou)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(CAS)(2019328 to X.L.Yang)。
文摘The ongoing coronavirus disease 2019(COVID-19)pandemic caused more than 96 million infections and over 2 million deaths worldwide so far.However,there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the disease causative agent.Vaccine is the most effective approach to eradicate a pathogen.The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations.Here we evaluated the safety,immunogenicity,and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates.Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates,and subsequently provided partial(in low dose)or full(in high dose)protection of challenge in the tested animals.In addition,passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice.These results warranted positive outcomes in future clinical trials in humans.
基金We thank the National Key Research and Development Program of China(2018YFA0507201)for grant support.We thank the National Virus Resource center for making Omicron available.
文摘Dear Editor,The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)continues to disrupt global public health since its first report in December 2019,resulting in more than 380 billion confirmed cases including nearly 5.7 billion deaths worldwide(https://covidl9.who.int).
