The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of for...The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of foreign manned launch abort systems are also presented.The development trends of the solid rocket motor for future Chinese manned launch vehicle escape systems are proposed,which can provide a reference for the future development of manned launch vehicle escape systems.展开更多
The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escap...The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x±of bistable.However,the asymmetric parameter r enhances the particle escape from stable state x_+,and holds back the particle escape from stable state x_-.展开更多
Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the s...Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the study,a novel HIF-1αASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA.The physicochemical properties of nanocomposite were characterized using TEM,FTIR,DLS and zeta potentials.The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170–192 nm,and according to the agarose gel retardation assay,the loading amount of ASODN accounted for 166.7 mg/g.The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells.The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL.The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite.In vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit m RNA expression and HIF-1αprotein translation at different levels.In vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor tissue.In vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%.These results manifested that the GEL-DGL-FA-ASODNDCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.展开更多
The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise...The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise coefficient with the RER of the piecewise constant multiplicative noise coefficient in the bistable sawtooth system,finally compare the RER of the bistable sawtooth potential with the RER of the quartic potential in the case of linear multiplicative noise coefficient.It can be seen that the form of the multiplicative noise coefficient and the nonlinearity of potential have an important influence on the resonant activation and the suppression of the RER.The resonant activation of the RER vanishes in the negative correlation when the multiplicative noise coefficient was shifted from piecewise constant to linear function in the bistable sawtooth potential.The suppression of the RER disappears in the negative correlation when thelinear potential is converted into nonlinear one.展开更多
A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is sh...A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is shown that,in some circumstances,this noise can make the particles escape over the potential barrier;but in other circumstances,it cannot. Resonant activation phenomenon appears for the system considered by us.展开更多
Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the a...Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the attention of schools,all levels of government,and other organizations.Many types of organi-zations carry out fire drills throughout the year.Because this kind of drill cannot anticipate the specific circumstances of each fire,which are generally far more complicated than drills,most people cannot correctly choose the optimal escape route from real fires.Thus,a fire-scene virtual simulation system based on the Dijkstra algorithm is here proposed to address such problems as casualties caused by frequent fires and the inability of most people to correctly choose a fire escape route.This virtual fire escape simulation system uses Maya to carry out 3D recon-struction of the fire scene,the Unity engine to conduct interactive function design,and the Dijkstra algorithm to calculate the best escape route.The results of the example indicate that the simulation system solves the problems of the traditional simulation system,such as stiffness,lack of intelligence,and poor simulation.展开更多
Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limite...Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.展开更多
Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors...Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors.This study focuses on Eurasian Tree Sparrows(Passer montanus)from five cities across different latitudes in China,comparing their flight initiation distance(FID)in urban and rural areas to assess the impact of urbanization on their escape behavior and the trend of ecological homogenization.The results confirm the established pattern at the geographic level:a reduction of FID in urban habitats and a decrease in FID with increasing latitude.That is,northern populations of the Eurasian Tree Sparrow in China are bolder than the southern populations.In addition,FID is positively correlated with flock size,with rural flocks exhibiting more pronounced group behavior(observed flocking frequency for urban and rural is 28.74%vs.40.7%,flock size variance is 26.90 vs.55.63).Despite the differences between northern and southern latitudes,the variability of FID in urban individuals consistently remains lower than that in rural areas,supporting the trend of reduced variability in escape behavior among birds in urban environments.Driven by urbanization,the escape behavior of Eurasian Tree Sparrows tends toward ecological homogenization,meaning that behavioral differences between urban areas in different cities are diminishing.This trend may obscure the behavioral variability brought about by latitude gradients,indicating that urbanization not only shapes the behavioral adaptations of birds but also potentially weakens their behavioral diversity.展开更多
Atmospheric escape plays a critical role in shaping the long-term climate evolution of Mars.Among the various escape mechanisms,energetic neutral atoms(ENAs)generated through charge exchange between solar wind ions an...Atmospheric escape plays a critical role in shaping the long-term climate evolution of Mars.Among the various escape mechanisms,energetic neutral atoms(ENAs)generated through charge exchange between solar wind ions and exospheric neutrals serve as an important diagnostic for ion-neutral interactions and upper atmospheric loss.This study presents direct observations of hydrogen ENAs(H-ENAs)on the dayside of Mars by using the Mars Ion and Neutral Particle Analyzer(MINPA)onboard China’s Tianwen-1 orbiter.By analyzing H-ENA data during a coronal mass ejection and a stream interaction region from December 29,2021,to January 1,2022,and comparing these data with MAVEN/SWIA(Mars Atmosphere and Volatile EvolutioN/Solar Wind Ion Analyzer)solar wind measurements,we examine the temporal evolution of H-ENA flux and the associated sputtered escape of atmospheric constituents.The observed H-ENA velocity is consistent with upstream solar wind ions,and the H-ENA-to-ion intensity ratio is used to infer variations in exospheric density,revealing a delayed response to enhanced solar wind activity.Penetrating H-ENA intensities reach up to 5.3×10^(6)s^(−1) cm^(−2),with energy fluxes on the order of(0.5-8.1)×10^(−3) mW/m^(2).The estimated oxygen sputtered escape rate driven by penetrating H-ENAs ranges from 5.5×10^(23)s^(−1) to 5.2×10^(24)s^(−1),comparable to or exceeding previous estimates based on penetrating ions.The findings highlight the need for low-altitude H-ENA observations to better quantify their atmospheric interactions and refine our understanding of nonthermal escape processes at Mars.展开更多
Zebrafish larvae are useful for identifying chemicals against lateral line(LL)hair cell(HC)damage and this type of chemical screen mainly focuses on searching for protectors against cell death.To expand the candidate ...Zebrafish larvae are useful for identifying chemicals against lateral line(LL)hair cell(HC)damage and this type of chemical screen mainly focuses on searching for protectors against cell death.To expand the candidate pool of HC protectors,a self-built acoustic escape response(AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules.The device quickly confirmed the changed LL HC functions caused by most known ototoxins,protectors,and neural transmission modifiers,or knockdown of LL HC-expressing genes.With ten devices wired in tandem,five‘hit’chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day.AS2863619,ribociclib,and SU9516 among the hits,protected the HCs in the mouse cochlea.Therefore,using free-swimming larval zebrafish,the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage,including cell death and loss-of-function.展开更多
Background:Motif interacting with ubiquitin-containing novelDUB family-1(MINDY1)could enhance the stability of programmed death-ligand 1(PD-L1).The study aimed to investigate whether MINDY1 regulates the immune escape...Background:Motif interacting with ubiquitin-containing novelDUB family-1(MINDY1)could enhance the stability of programmed death-ligand 1(PD-L1).The study aimed to investigate whether MINDY1 regulates the immune escape of hepatocellular carcinoma(HCC)mediated by PD-L1.Methods:MINDY1 and PD-L1 levels were detected throughWestern blot.The link between MINDY1 and PD-L1 was validated using the co-immunoprecipitation assay.The malignant biology of HCC cells was assessed through Cell Counting Kit-8,Carboxyfluorescein Succinimidyl Ester staining,transwell,and wound healing assay.CD8^(+)T cells were isolated and then co-cultured with HCC cells.Enzyme-linked immunosorbent Assay kits detected CD8^(+)T cytokine content.CD8^(+)T cell activation markers,PD-L1 ubiquitination levels,andWnt/β-catenin pathway-associated protein levels were detected throughWestern blot.AHCC nude mouse model was developed,Ki-67 positivity and CD8^(+)T-cell infiltration were assessed through pathological staining and flow cytometry.Results:MINDY1 and PD-L1 levels were elevated in HCC.Overexpression of MINDY1 increased migrating and invading cells,elevated cell viability,and decreased apoptosis in HCC cells,leading to PD-L1 deubiquitination.Knockdown of MINDY1 reversed all of these indicators.Co-culturing withHCC cells overexpressing MINDY1 resulted in decreased proliferative capacity and cytotoxicity of CD8^(+)T cells,increased apoptosis,and decreased levels of cytokines and activation markers in CD8^(+)T cells.MINDY1 triggeredWnt/β-catenin pathway,Wnt activators further promoted PD-L1 deubiquitination and suppressed CD8^(+)T cell activation.MINDY1 overexpression increased PD-L1 and Ki67 positivity level in HCC tumors,suppressed CD8^(+)T-cell infiltration.Conclusion:MINDY1 promotes PD-L1 deubiquitination and inhibits CD8^(+)T cell activation by stimulating the Wnt/β-catenin pathway,consequently promoting HCC tumor immune escape.展开更多
Emerging therapies rely on the efficient and specific delivery of targeted agents into the cytosol,such as DNA,siRNA and proteins.Nanoparticles showed great potentials in safe delivery and transportation of the target...Emerging therapies rely on the efficient and specific delivery of targeted agents into the cytosol,such as DNA,siRNA and proteins.Nanoparticles showed great potentials in safe delivery and transportation of the targeted cargoes;however,the entrapment in endosomes and degradation by specific enzymes in the lysosome hindered the bioavailability,cytosolic delivery and subsequent therapeutic efficacy.In this case,the development of methods for efficient and specific delivery of targeted therapeutic agents focuses on overcoming the major challenge of endo/lysosomal escape,which relies on the development of safe and efficient nanodelivery systems.A deeper mechanistic understanding in the endo/lysosomal escape will guide the development of more efficient nano-delivery systems.In this review,we summarize various mechanisms by which nanoparticles escape from the endo/lysosome,and showcase the recent progress in dissecting the endo/lysosomal approaches based on nano-delivery systems.Emphasis will lie on the properties of nanoparticles that govern the endo/lysosomal escape pathway as well as the latest promising applications in vaccine delivery and genetic engineering field.展开更多
Objective： To investigate the expression of Fas, Fas ligand （FasL） and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods： The expression of Fas, Fas...Objective： To investigate the expression of Fas, Fas ligand （FasL） and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods： The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine （^3H-TdR） Incorporation. Results： The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% （n=5） respectively, and the expression of FasL was up to 63.73%±5.23% （n=5）. The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% （n=5） respectively when WEHI-3 （effector cell, E） and Fas^＋ YAC-1 cells （target cell, T） were cultured in the ratio of 3：1, 10：1 and 30：1. Conclusion： WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^＋ YAC-1 cells.展开更多
Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumo...Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.展开更多
文摘The solid rocket motors for the escape system of China’s LM-2 F manned launch vehicle are described,the key technologies and technical innovations utilized are summarized.The technical features and development of foreign manned launch abort systems are also presented.The development trends of the solid rocket motor for future Chinese manned launch vehicle escape systems are proposed,which can provide a reference for the future development of manned launch vehicle escape systems.
基金Supported by the Natural Science Foundation of China under Grant No.10865006the Natural Science Foundation of Shaanxi Province under Grant No.2010JQ1014the Science Foundation of Baoji University of Science and Arts of China under Grant No.ZK0954
文摘The asymmetric effects on the escape rates from the stable states x±in the bistable system are analyzed. The results indicate that the multiplicative noise and the additive noise always enhance the particle escape from stable states x±of bistable.However,the asymmetric parameter r enhances the particle escape from stable state x_+,and holds back the particle escape from stable state x_-.
基金supported by the National Natural Science Foundation of China Fund(No 81541060)Science and Technology Projects from the Science Technology and Innovation Committee of Shenzhen Municipality(grant no.JCJY20170818110340383 and JCJY20170307163529489)。
文摘Antisense oligodeoxynucleotide(ASODN)can directly interfere a series of biological events of the target RNA derived from tumor cells through Watson-Crick base pairing,in turn,plays antitumor therapeutic roles.In the study,a novel HIF-1αASODN-loaded nanocomposite was formulated to efficiently deliver gene to the target RNA.The physicochemical properties of nanocomposite were characterized using TEM,FTIR,DLS and zeta potentials.The mean diameter of resulting GEL-DGL-FA-ASODN-DCA nanocomposite was about 170–192 nm,and according to the agarose gel retardation assay,the loading amount of ASODN accounted for 166.7 mg/g.The results of cellular uptake showed that the nanocomposite could specifically target to HepG2 and Hela cells.The cytotoxicity assay demonstrated that the toxicity of vectors was greatly reduced by using DCA to reversibly block the cationic DGL.The subcellular distribution images clearly displayed the lysosomal escape ability of the DCA-modified nanocomposite.In vitro exploration of molecular mechanism indicated that the nanocomposite could inhibit m RNA expression and HIF-1αprotein translation at different levels.In vivo optical images and quantitative assay testified that the formulation accumulated preferentially in the tumor tissue.In vivo antitumor efficacy research confirmed that this nanocomposite had significant antitumor activity and the tumor inhibitory rate was 77.99%.These results manifested that the GEL-DGL-FA-ASODNDCA nanocomposite was promising in gene therapeutics for antitumor by interacting directly with target RNA.
文摘The relative escape rate (RER) in the bistable sawtooth system driven by correlated white noises was studied in the case of linear multiplicative noise coefficient.And we compare the RER of linear multiplicative noise coefficient with the RER of the piecewise constant multiplicative noise coefficient in the bistable sawtooth system,finally compare the RER of the bistable sawtooth potential with the RER of the quartic potential in the case of linear multiplicative noise coefficient.It can be seen that the form of the multiplicative noise coefficient and the nonlinearity of potential have an important influence on the resonant activation and the suppression of the RER.The resonant activation of the RER vanishes in the negative correlation when the multiplicative noise coefficient was shifted from piecewise constant to linear function in the bistable sawtooth potential.The suppression of the RER disappears in the negative correlation when thelinear potential is converted into nonlinear one.
基金supported by National Natural Science Foundation of China,SRF for ROCS,SEM,and K.C.Wong Magna Fund in Ningbo University
文摘A three-state Markovian noise is investigated.Its probability density and statistical properties are obtained. Escape of particles for a system with potential barrier only driven by this noise is investigated.It is shown that,in some circumstances,this noise can make the particles escape over the potential barrier;but in other circumstances,it cannot. Resonant activation phenomenon appears for the system considered by us.
文摘Despite the support of all kinds of fire prevention measures and high-tech fire prevention equipment,fires still occur frequently because of both anthro-pogenic factors and natural disasters.This issue has drawn the attention of schools,all levels of government,and other organizations.Many types of organi-zations carry out fire drills throughout the year.Because this kind of drill cannot anticipate the specific circumstances of each fire,which are generally far more complicated than drills,most people cannot correctly choose the optimal escape route from real fires.Thus,a fire-scene virtual simulation system based on the Dijkstra algorithm is here proposed to address such problems as casualties caused by frequent fires and the inability of most people to correctly choose a fire escape route.This virtual fire escape simulation system uses Maya to carry out 3D recon-struction of the fire scene,the Unity engine to conduct interactive function design,and the Dijkstra algorithm to calculate the best escape route.The results of the example indicate that the simulation system solves the problems of the traditional simulation system,such as stiffness,lack of intelligence,and poor simulation.
基金supported by grants from the Dongguan Science and Technology of Social Development Program(No.20231800940192)the Talent Development Foundation of the First Dongguan Affiliated Hospital of Guangdong Medical University(No.PU2023002).
文摘Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer type.Despite substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with SCLC.In the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were elucidated.Methods:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in SCLC.The functional role of the key gene identified in SCLC was determined both in vitro and in vivo.Results:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell proportion.Furthermore,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in SCLC.Bioinformatics analysis revealed that USP1 is upregulated in SCLC.In addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune responses.By co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological inhibition.Furthermore,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated markers.Conclusions:Our study findings highlight the importance of NK cells in regulating SCLC.USP1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.
基金supported by the National Key R&D Program of China(2023YFF1304600)。
文摘Urbanization has significantly altered the habitat structure and behavioral patterns of animals.In urban environments with frequent human disturbances,animals may undergo adaptive adjustments in their escape behaviors.This study focuses on Eurasian Tree Sparrows(Passer montanus)from five cities across different latitudes in China,comparing their flight initiation distance(FID)in urban and rural areas to assess the impact of urbanization on their escape behavior and the trend of ecological homogenization.The results confirm the established pattern at the geographic level:a reduction of FID in urban habitats and a decrease in FID with increasing latitude.That is,northern populations of the Eurasian Tree Sparrow in China are bolder than the southern populations.In addition,FID is positively correlated with flock size,with rural flocks exhibiting more pronounced group behavior(observed flocking frequency for urban and rural is 28.74%vs.40.7%,flock size variance is 26.90 vs.55.63).Despite the differences between northern and southern latitudes,the variability of FID in urban individuals consistently remains lower than that in rural areas,supporting the trend of reduced variability in escape behavior among birds in urban environments.Driven by urbanization,the escape behavior of Eurasian Tree Sparrows tends toward ecological homogenization,meaning that behavioral differences between urban areas in different cities are diminishing.This trend may obscure the behavioral variability brought about by latitude gradients,indicating that urbanization not only shapes the behavioral adaptations of birds but also potentially weakens their behavioral diversity.
基金supported by the National Natural Science Foundation of China (Grant Nos. 42188101, 42274211, 41974170, 42374184, 42122032, and 41974196)the Chinese Academy of Sciences (Grant Nos. QYZDJSSW-JSC028, XDA15052500, XDA17010301, and XDB41000000)+3 种基金the CNSA (Grant No. D050103)the Specialized Research Fund for State Key Laboratories of Chinathe Specialized Research Fund for Laboratory of Geospace Environment of the University of Science and Technology of Chinasupported by the International Space Science Institute (ISSI) in Bern and Beijing through the ISSI/ISSI-BJ International Team Project titled “Understanding the Mars Space Environment Through Multi-Spacecraft Measurements” (ISSI Team Project No. 23-582 and ISSI-BJ Team Project No. 58)
文摘Atmospheric escape plays a critical role in shaping the long-term climate evolution of Mars.Among the various escape mechanisms,energetic neutral atoms(ENAs)generated through charge exchange between solar wind ions and exospheric neutrals serve as an important diagnostic for ion-neutral interactions and upper atmospheric loss.This study presents direct observations of hydrogen ENAs(H-ENAs)on the dayside of Mars by using the Mars Ion and Neutral Particle Analyzer(MINPA)onboard China’s Tianwen-1 orbiter.By analyzing H-ENA data during a coronal mass ejection and a stream interaction region from December 29,2021,to January 1,2022,and comparing these data with MAVEN/SWIA(Mars Atmosphere and Volatile EvolutioN/Solar Wind Ion Analyzer)solar wind measurements,we examine the temporal evolution of H-ENA flux and the associated sputtered escape of atmospheric constituents.The observed H-ENA velocity is consistent with upstream solar wind ions,and the H-ENA-to-ion intensity ratio is used to infer variations in exospheric density,revealing a delayed response to enhanced solar wind activity.Penetrating H-ENA intensities reach up to 5.3×10^(6)s^(−1) cm^(−2),with energy fluxes on the order of(0.5-8.1)×10^(−3) mW/m^(2).The estimated oxygen sputtered escape rate driven by penetrating H-ENAs ranges from 5.5×10^(23)s^(−1) to 5.2×10^(24)s^(−1),comparable to or exceeding previous estimates based on penetrating ions.The findings highlight the need for low-altitude H-ENA observations to better quantify their atmospheric interactions and refine our understanding of nonthermal escape processes at Mars.
基金supported by grants from Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2023SHIBS0002)the National Key Research and Development Program of China(2023YFF1203505)+5 种基金the National Key R&D Program of China(2024YFC2417900)Shenzhen Municipal Science and Technology Innovation Council(202110293000007)Shenzhen Science and Technology Program(KJZD20230923114909019)the National Key R&D Program of China(2018YFA0801006)the National Natural Science Foundation of China(31771618)Guangdong Natural Science Foundation(2022A1515011878).
文摘Zebrafish larvae are useful for identifying chemicals against lateral line(LL)hair cell(HC)damage and this type of chemical screen mainly focuses on searching for protectors against cell death.To expand the candidate pool of HC protectors,a self-built acoustic escape response(AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules.The device quickly confirmed the changed LL HC functions caused by most known ototoxins,protectors,and neural transmission modifiers,or knockdown of LL HC-expressing genes.With ten devices wired in tandem,five‘hit’chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day.AS2863619,ribociclib,and SU9516 among the hits,protected the HCs in the mouse cochlea.Therefore,using free-swimming larval zebrafish,the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage,including cell death and loss-of-function.
基金Xuzhou City’s Project for introducing Clinical Medical Expert Teams(No.2018TD001)Innovation Team Project of Xuzhou Medical University Affiliated Hospital Development Fund,Project Number:XYFC202202.
文摘Background:Motif interacting with ubiquitin-containing novelDUB family-1(MINDY1)could enhance the stability of programmed death-ligand 1(PD-L1).The study aimed to investigate whether MINDY1 regulates the immune escape of hepatocellular carcinoma(HCC)mediated by PD-L1.Methods:MINDY1 and PD-L1 levels were detected throughWestern blot.The link between MINDY1 and PD-L1 was validated using the co-immunoprecipitation assay.The malignant biology of HCC cells was assessed through Cell Counting Kit-8,Carboxyfluorescein Succinimidyl Ester staining,transwell,and wound healing assay.CD8^(+)T cells were isolated and then co-cultured with HCC cells.Enzyme-linked immunosorbent Assay kits detected CD8^(+)T cytokine content.CD8^(+)T cell activation markers,PD-L1 ubiquitination levels,andWnt/β-catenin pathway-associated protein levels were detected throughWestern blot.AHCC nude mouse model was developed,Ki-67 positivity and CD8^(+)T-cell infiltration were assessed through pathological staining and flow cytometry.Results:MINDY1 and PD-L1 levels were elevated in HCC.Overexpression of MINDY1 increased migrating and invading cells,elevated cell viability,and decreased apoptosis in HCC cells,leading to PD-L1 deubiquitination.Knockdown of MINDY1 reversed all of these indicators.Co-culturing withHCC cells overexpressing MINDY1 resulted in decreased proliferative capacity and cytotoxicity of CD8^(+)T cells,increased apoptosis,and decreased levels of cytokines and activation markers in CD8^(+)T cells.MINDY1 triggeredWnt/β-catenin pathway,Wnt activators further promoted PD-L1 deubiquitination and suppressed CD8^(+)T cell activation.MINDY1 overexpression increased PD-L1 and Ki67 positivity level in HCC tumors,suppressed CD8^(+)T-cell infiltration.Conclusion:MINDY1 promotes PD-L1 deubiquitination and inhibits CD8^(+)T cell activation by stimulating the Wnt/β-catenin pathway,consequently promoting HCC tumor immune escape.
基金support from the Postdoctoral Fellowship Scheme of The Chinese University of Hong Kong,the Postdoctoral Fellowship Program of CPSF(GZC20241828)The China Postdoctoral Science Foundation(2024M763416).
文摘Emerging therapies rely on the efficient and specific delivery of targeted agents into the cytosol,such as DNA,siRNA and proteins.Nanoparticles showed great potentials in safe delivery and transportation of the targeted cargoes;however,the entrapment in endosomes and degradation by specific enzymes in the lysosome hindered the bioavailability,cytosolic delivery and subsequent therapeutic efficacy.In this case,the development of methods for efficient and specific delivery of targeted therapeutic agents focuses on overcoming the major challenge of endo/lysosomal escape,which relies on the development of safe and efficient nanodelivery systems.A deeper mechanistic understanding in the endo/lysosomal escape will guide the development of more efficient nano-delivery systems.In this review,we summarize various mechanisms by which nanoparticles escape from the endo/lysosome,and showcase the recent progress in dissecting the endo/lysosomal approaches based on nano-delivery systems.Emphasis will lie on the properties of nanoparticles that govern the endo/lysosomal escape pathway as well as the latest promising applications in vaccine delivery and genetic engineering field.
基金Supported by a grant from National Natural Sciences Foundation of China (30240022).
文摘Objective： To investigate the expression of Fas, Fas ligand （FasL） and CD80 on the cell surface of mouse acute myelomonocytic leukemia cell line WEHI-3 and the function of FasL. Methods： The expression of Fas, FasL and CD80 was detected on WEHI-3 cell surface by flow cytometry. Simultaneously the function of FasL was determined by Thymidine （^3H-TdR） Incorporation. Results： The expression of CD80 and Fas on WEHI-3 cell surface was 5.06%±0.41% and 6.75%±2.31% （n=5） respectively, and the expression of FasL was up to 63.73%±5.23% （n=5）. The apoptotic rate of YAC-1 cells was 26%±4.5%, 35%±3.2% and 43%±2.7% （n=5） respectively when WEHI-3 （effector cell, E） and Fas^＋ YAC-1 cells （target cell, T） were cultured in the ratio of 3：1, 10：1 and 30：1. Conclusion： WEHI-3 cells express high FasL, low Fas and CD80, and can induce apoptosis of Fas^＋ YAC-1 cells.
文摘Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.
