This study utilizes radio occultation observations from the Macao Science Satellite-1 mission(MSS-1)to investigate ionospheric response to the May 2024 G5 geomagnetic storm within the South Atlantic Anomaly(SAA)region...This study utilizes radio occultation observations from the Macao Science Satellite-1 mission(MSS-1)to investigate ionospheric response to the May 2024 G5 geomagnetic storm within the South Atlantic Anomaly(SAA)region.The distinctive data from MSS-1,complemented by observations from the ground-based Global Navigation Satellite System(GNSS)and the Constellation Observing System for Meteorology,Ionosphere,and Climate follow-on satellite mission(COSMIC-2),reveal a super plasma fountain effect during the main phase of the storm.This effect was marked by peaks in the equatorial ionization anomaly that extended beyond their typical latitude range.The MSS-1 observations,particularly in the northern hemisphere of the SAA region,confirm the role of prompt penetration electric fields in driving ionospheric disturbances and amplifying scintillation at higher altitudes.The study also identifies a decrease in total electron content and a reduction in scintillation occurrence during the recovery phase of the storm.The results demonstrate the pivotal role that MSS-1 observations can play,when combined with ground-based and COSMIC-2 observations,in providing a more comprehensive understanding of ionospheric response to severe geomagnetic storms.展开更多
Impact of texture type on the magnetic properties of ultrahigh density perpendicular magnetic recording media L1_(0)-FePt thin film was investigated,so were the texture formation and evolution mechanism.Reuss,Voigt,an...Impact of texture type on the magnetic properties of ultrahigh density perpendicular magnetic recording media L1_(0)-FePt thin film was investigated,so were the texture formation and evolution mechanism.Reuss,Voigt,and Hill models were used to determine the anisotropic elastic modulus of L1_(0)-FePt thin film with fiber texture.Then,the elastic strain energies of thin films under various stress conditions were calculated.Results reveal that the stress condition has a significant influence on the fiber texture evolution.When the L1_(0)-FePt thin film is subjected to compressive in-plane strain prior to ordering phase transformation,the formation of{100}fiber texture is promoted.On the contrary,the ordering phase transformation under tensile in-plane strain promotes the{001}fiber texture formation.展开更多
Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looke...Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.展开更多
Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and e...Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.展开更多
This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square se...This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square sections)were designed and manufactured to assess the impact of casting conditions on filling length,as magnesium alloys cause severe melting and melt-mold exothermic reactions,making investment casting challenging.Combinations of traditional Mg-mold reaction mitigation techniques,such as applying a protective mold coating(Yttria)and vacuum,were examined to determine their role in the filling process.The results suggest that when induction is employed to melt reactive alloys,these methods are not always beneficial,as initially thought.Particularly at higher melt temperatures,the combination of Yttria-coated molds with low-pressure vacuum induction significantly reduce fluidity:vacuum induced melt levitation which promotes oxidation with the residual atmosphere;and Yttria-coating cracking due to thermal stress during the mold fabrication slows filling and promotes significant melt-mold reaction.This study shows that best results to investment cast thin-sections are obtained by avoiding both vacuum and protective coatings,providing a viable route for the precision manufacturing of stent biomedical devices.展开更多
Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH...Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH transcription factor 1(Sim1)gene,postulated to act as a cis-regulatory element governing flight feather morphogenesis.To investigate its functional significance,genome-edited(GE)primordial germ cell(PGC)lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing,with germline chimeric males subsequently mated with wild-type(WT)hens to obtain GE progeny.The resulting GE chickens harbored 257-260 bp deletions,excising approximately half of the Sim1-ASHCE sequence.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8(E8)compared to WT counterparts.Despite this,GE chickens developed structurally normal flight and tail feathers.In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos,but not within the buds themselves.These results suggest that partial deletion of Sim1-ASHCE,despite diminishing Sim1 expression,does not disrupt flight feather formation.The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development.Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.展开更多
This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion throug...This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.展开更多
Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and...Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and p53.While p16 is a well-established surrogate for HPV in oropharyngeal cancer,our review highlights its unreliable role in HNCSCC,where positivity is instead associated with recurrence and metastasis.Similarly,p53 illustrates a dual role-wild-type as a genomic safeguard,mutated as an oncogenic driver-complicating prognostication.Methodological considerations,including the limitations of immunohistochemistry for HPV detection,underscore the need for multi-method and molecular validation in future studies.Ultraviolet radiation is posited as a key modifier of p16 function,decoupling expression from tumor suppression.To contextualize these findings,we draw parallels to glioblastoma(GBM),where subclonal evolution,p53 dysfunction,and intratumoral heterogeneity drive relapse despite aggressive multimodal therapies.GBM exemplifies how bulk-level biomarker generalizations often obscure dynamic cellular ecosystems,reinforcing the necessity of single-cell and spatial approaches.Multi-omics integration-encompassing genome,transcriptome,proteome,and tumor microenvironment mapping-coupled with single-cell RNA sequencing and spatial transcriptomics,offers a path forward for resolving subclonal dynamics in both HNCSCC and GBM.These technologies provide the resolution needed to track tumor-immunestromal co-evolution,identify therapy-resistant clones,and anticipate recurrence.We argue for a N-of-1,patient-and cell-centric paradigm that reframes biomarkers not as static surrogates but as dynamic readouts of cancer evolution across time and tissue contexts.Conceptually,we propose kinetic and microenvironmental frameworks(e.g.,“load-and-lock”barriers;dormancy and immunesynapse stabilization)as hypothesis-generating avenues to stall clonal handoffs and improve outcome prediction.Together,these perspectives argue for revised biomarker frameworks in HNCSCC and ethically inclusive,mechanism-anchored studies that bridge discovery with individualized care.By bridging insights from HNCSCC with the lessons of GBM,this review underscores the need for ethically inclusive,mechanistically informed frameworks that integrate subclonal evolution,biomarker re-interpretation,and precision-personalized hybrid models.Such an approach will be essential for advancing from one-size-fits-all strategies to individualized lifetime cancer care.展开更多
Attempts to remove environmentally harmful materials in mass production industries are always a major issue and draw attention if the substitution guarantees a chance to lower fabrication cost and to improve device pe...Attempts to remove environmentally harmful materials in mass production industries are always a major issue and draw attention if the substitution guarantees a chance to lower fabrication cost and to improve device performance,as in a wide bandgap Zn_(1-x)Mg_(x)O(ZMO)to replace the CdS buffer in Cu(In_(1-x),Ga_(x))Se_(2)(CIGSe)thin-film solar cell structure.ZMO is one of the candidates for the buffer material in CIGSe thin-film solar cells with a wide and controllable bandgap depending on the Mg content,which can be helpful in attaining a suitable conduction band offset.Hence,compared to the fixed and limited bandgap of a CdS buffer,a ZMO buffer may provide advantages in V_(oc) and J_(sc) based on its controllable and wide bandgap,even with a relatively wider bandgap CIGSe thin-film solar cell.In addition,to solve problems with the defect sites at the ZMO/CIGSe junction interface,a few-nanometer ZnS layer is employed for heterojunction interface passivation,forming a ZMO/ZnS buffer structure by atomic layer deposition(ALD).Finally,a Cd-free all-dry-processed CIGSe solar cell with a wider bandgap(1.25 eV)and ALD-grown buffer structure exhibited the best power conversion efficiency of 19.1%,which exhibited a higher performance than the CdS counterpart.展开更多
基金support from the National Natural Science Foundation of China(No.42274027)the Fundamental Research Funds for the Central Universitiessupported also by the Macao Foundation。
文摘This study utilizes radio occultation observations from the Macao Science Satellite-1 mission(MSS-1)to investigate ionospheric response to the May 2024 G5 geomagnetic storm within the South Atlantic Anomaly(SAA)region.The distinctive data from MSS-1,complemented by observations from the ground-based Global Navigation Satellite System(GNSS)and the Constellation Observing System for Meteorology,Ionosphere,and Climate follow-on satellite mission(COSMIC-2),reveal a super plasma fountain effect during the main phase of the storm.This effect was marked by peaks in the equatorial ionization anomaly that extended beyond their typical latitude range.The MSS-1 observations,particularly in the northern hemisphere of the SAA region,confirm the role of prompt penetration electric fields in driving ionospheric disturbances and amplifying scintillation at higher altitudes.The study also identifies a decrease in total electron content and a reduction in scintillation occurrence during the recovery phase of the storm.The results demonstrate the pivotal role that MSS-1 observations can play,when combined with ground-based and COSMIC-2 observations,in providing a more comprehensive understanding of ionospheric response to severe geomagnetic storms.
基金Inner Mongolia Natural Science Foundation Project(2020LH05028)。
文摘Impact of texture type on the magnetic properties of ultrahigh density perpendicular magnetic recording media L1_(0)-FePt thin film was investigated,so were the texture formation and evolution mechanism.Reuss,Voigt,and Hill models were used to determine the anisotropic elastic modulus of L1_(0)-FePt thin film with fiber texture.Then,the elastic strain energies of thin films under various stress conditions were calculated.Results reveal that the stress condition has a significant influence on the fiber texture evolution.When the L1_(0)-FePt thin film is subjected to compressive in-plane strain prior to ordering phase transformation,the formation of{100}fiber texture is promoted.On the contrary,the ordering phase transformation under tensile in-plane strain promotes the{001}fiber texture formation.
基金supported by grants from the National Natural Science Foundation of China(grant number:82170181)Beijing Natural Science Foundation(grant number:7222027)+4 种基金Beijing Physician Scientist Train-ing Project(grant number:BJPSTP-2024-01)the National Key R&D Program of China(grant number:2022YFF1502000)to Liang Wangthe National Key R&D Program of China(grant number:2022YFF1502000)Beijing Municipal Fund for Distinguished Young Scholars(grant number:JQ22022)to Lin FengHebei province government funding for clinical medical talents training and basic research projects(grant number:361007)to Youchao Jia.
文摘Background:Previous researches mainly focused on whether cancer stem cells exist in diffuse large B-cell lym-phoma(DLBCL).However,subgroups with dismal prognosis and stem cell-like characteristics have been over-looked.Methods:Using large scale data(n=2133),we conducted machine learning algorithms to identify a high risk DLBCL subgroup with stem cell-like features,and then investigated the potential mechanisms in shaping this subgroup using transcriptome,genome and single-cell RNA-seq data,and in vitro experiments.Results:We identified a high-risk subgroup(25.6%of DLBCL)with stem cell-like characteristics and dismal prog-nosis.This high-risk group(HRG)was featured by upregulation of key enzyme(ODC1)in polyamine metabolism and cold tumor microenvironment(TME),and had a poor prognosis with lower 3-year overall survival(OS)(54.3%vs.83.6%,P<0.0001)and progression-free survival(PFS)(42.8%vs.74.7%,P<0.0001)rates com-pared to the low-risk group.HRG also exhibited malignant proliferative phenotypes similar to Burkitt lymphoma.Patients with MYC rearrangement,double-hit,double-expressors,or complete remission might have either favor-able or poor prognosis,which could be further distinguished by our risk stratification model.Genomic analysis revealed widespread copy number losses in the chemokine and interferon coding regions 8p23.1 and 9p21.3 in HRG.We identified ODC1 as a therapeutic vulnerability for HRG-DLBCL.Single-cell analysis and in vitro ex-periments demonstrated that ODC1 overexpression enhanced DLBCL cell proliferation and drove macrophage polarization towards the M2 phenotype.Conversely,ODC1 inhibition reduced DLBCL cell proliferation,induced cell cycle arrest and apoptosis,and promoted macrophage polarization towards the M1 phenotype.Finally,we developed a comprehensive database of DLBCL for clinical application.Conclusions:Our study effectively advances the precise risk stratification of DLBCL and reveals that ODC1 and immune-deserted microenvironment jointly shape a group of DLBCL patients with stem cell-like features.Target-ing ODC1 regulates immunotherapies in DLBCL,offering new insights for DLBCL treatment.
基金supported by grants from the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(PWD&RPP-MRI,JYY2023-6)the R&D Program of Beijing Municipal Education Commission(KZ20231002543).
文摘Background:Dry eye disease(DED)predominantly results from elevated tear film os-molarity,which can not only cause ocular inconvenience but may lead to visual impair-ments,severely compromising patient well-being and exerting substantial economic burdens as well.Astaxanthin(AST),a member of the xanthophylls and recognized for its robust abilities to combat inflammation and oxidation,is a common dietary sup-plement.Nonetheless,the precise molecular pathways through which AST influences DED are still poorly understood.Methods:Therapeutic targets for AST were identified using data from the GeneCards,PharmMapper,and Swiss Target Prediction databases,and STITCH datasets.Similarly,targets for dry eye disease(DED)were delineated leveraging resources such as the Therapeutic Target Database(TTD),DisGeNET,GeneCards,and OMIM databases,and DrugBank datasets.Interactions among shared targets were charted and dis-played using CytoScape 3.9.0.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to elucidate the functions of pivotal tar-gets within the protein-protein interaction network.Molecular interactions between AST and key targets were confirmed through molecular docking using AutoDock and PyMOL.Molecular dynamics simulations were performed using GROMACS 2022.3.Viability of human corneal epithelial cells(hCEC)was assessed across varying concen-trations of AST.A mouse model of experimental DED was developed using 0.1%ben-zalkonium chloride(BAC),and the animals were administered 100 mg/kg/day of AST orally for 7 days.The efficacy of the treatments was assessed through a series of di-agnostic tests to evaluate the condition of the ocular surface after the interventions.The levels of inflammation and oxidative stress were quantitatively assessed using methods such as reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunofluorescence staining.Results:Network pharmacology suggests that AST may alleviate DED by influenc-ing oxidation-reduction signaling pathways and reducing oxidative stress provoked by BAC.In vivo experiments demonstrated an improved overall condition in AST-administered mice in contrast to the control group.Immunofluorescence staining analyses indicated a decrease in Keap1 protein in the corneal tissues of AST-treated mice and a significant increase in Nrf2 and HO-1 protein.In vitro studies demon-strated that AST significantly enhanced cell viability and suppressed reactive oxy-gen species expression under hyperosmotic(HS)conditions,thereby protecting the human corneal epithelium.Conclusion:AST is capable of shielding mice from BAC-induced DED,decelerating the progression of DED,and mitigating oxidative stress damage under HS conditions in hCEC cells.The protective impact of AST on DED may operate through stimulating the Keap1-Nrf2/HO-1 signaling pathway.Our research findings indicate that AST may be a promising treatment for DED,offering new insights into DED treatment.
基金financed by National Funds through the Portuguese funding agency,FCT–Funda??o para a Ciência e a Tecnologia,within the strategic projects UIDB/04436/2020,UIDB/00481/2020 and LA/P/0063/2020(DOI 10.54499/LA/P/0063/2020)。
文摘This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square sections)were designed and manufactured to assess the impact of casting conditions on filling length,as magnesium alloys cause severe melting and melt-mold exothermic reactions,making investment casting challenging.Combinations of traditional Mg-mold reaction mitigation techniques,such as applying a protective mold coating(Yttria)and vacuum,were examined to determine their role in the filling process.The results suggest that when induction is employed to melt reactive alloys,these methods are not always beneficial,as initially thought.Particularly at higher melt temperatures,the combination of Yttria-coated molds with low-pressure vacuum induction significantly reduce fluidity:vacuum induced melt levitation which promotes oxidation with the residual atmosphere;and Yttria-coating cracking due to thermal stress during the mold fabrication slows filling and promotes significant melt-mold reaction.This study shows that best results to investment cast thin-sections are obtained by avoiding both vacuum and protective coatings,providing a viable route for the precision manufacturing of stent biomedical devices.
基金supported by the Ministry of Agriculture and Rural Affairs of the People's Republic of China(125A0607)Department of Science and Technology of Yunnan Province(XDYC-KJLJ-2022-0004)。
文摘Flight feathers represent a hallmark innovation of avian evolution.Recent comparative genomic analyses identified a 284 bp avian-specific highly conserved element(ASHCE)located within the eighth intron of the SIM bHLH transcription factor 1(Sim1)gene,postulated to act as a cis-regulatory element governing flight feather morphogenesis.To investigate its functional significance,genome-edited(GE)primordial germ cell(PGC)lines carrying targeted ASHCE deletions were generated using CRISPR/Cas9-mediated editing,with germline chimeric males subsequently mated with wild-type(WT)hens to obtain GE progeny.The resulting GE chickens harbored 257-260 bp deletions,excising approximately half of the Sim1-ASHCE sequence.Reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR)analysis showed an average 0.32-fold reduction in Sim1 expression in the forelimbs of GE embryos at day 8(E8)compared to WT counterparts.Despite this,GE chickens developed structurally normal flight and tail feathers.In situ hybridization localized Sim1 expression to the posterior mesenchyme surrounding flight feather buds in E8 WT embryos,but not within the buds themselves.These results suggest that partial deletion of Sim1-ASHCE,despite diminishing Sim1 expression,does not disrupt flight feather formation.The excised region appears to possess enhancer activity toward Sim1 but is dispensable for flight feather development.Complete ablation of the ASHCE will be necessary to fully resolve the regulatory role of Sim1 in avian feather morphogenesis.
文摘This study aimed to elucidate the role of collagen type XI alpha 1(COL11A1)-positive cancer-associated fibroblasts(CAFs)in modifying the tumor microenvironment of colon cancer(CC)and facilitating immune evasion through interactions with myeloid-derived suppressor cells(MDSCs).Using single-cell transcriptomic sequencing,we analyzed the interplay between COL11A1-positive CAFs and MDSCs in the CC microenvironment,focusing on how COL11A1 impacts MDSC differentiation and activation.The results demonstrate that COL11A1 expression in fibroblasts significantly enhances matrix metalloproteinase(MMP)3 and MMP13 expression,leading to paracrine induction of MDSC differentiation and activation,which promotes immune evasion and tumor growth.Additionally,we observed that COL11A1 knockout(COL11A1KO)suppresses tumor growth and hinders immune evasion.These findings underscore the essential role of COL11A1-positive CAFs in establishing an immunosuppressive tumor microenvironment conducive to CC progression.By elucidating the molecular pathway through which COL11A1 influences MDSC activity,this research suggests new therapeutic avenues for targeting the tumor microenvironment in CC,particularly through modulating COL11A1 expression in CAFs.
文摘Head and neck cutaneous squamous cell carcinoma(HNCSCC)remains underexplored compared to oropharyngeal squamous cell carcinoma,particularly in relation to human papillomavirus(HPV)and molecular markers such as p16 and p53.While p16 is a well-established surrogate for HPV in oropharyngeal cancer,our review highlights its unreliable role in HNCSCC,where positivity is instead associated with recurrence and metastasis.Similarly,p53 illustrates a dual role-wild-type as a genomic safeguard,mutated as an oncogenic driver-complicating prognostication.Methodological considerations,including the limitations of immunohistochemistry for HPV detection,underscore the need for multi-method and molecular validation in future studies.Ultraviolet radiation is posited as a key modifier of p16 function,decoupling expression from tumor suppression.To contextualize these findings,we draw parallels to glioblastoma(GBM),where subclonal evolution,p53 dysfunction,and intratumoral heterogeneity drive relapse despite aggressive multimodal therapies.GBM exemplifies how bulk-level biomarker generalizations often obscure dynamic cellular ecosystems,reinforcing the necessity of single-cell and spatial approaches.Multi-omics integration-encompassing genome,transcriptome,proteome,and tumor microenvironment mapping-coupled with single-cell RNA sequencing and spatial transcriptomics,offers a path forward for resolving subclonal dynamics in both HNCSCC and GBM.These technologies provide the resolution needed to track tumor-immunestromal co-evolution,identify therapy-resistant clones,and anticipate recurrence.We argue for a N-of-1,patient-and cell-centric paradigm that reframes biomarkers not as static surrogates but as dynamic readouts of cancer evolution across time and tissue contexts.Conceptually,we propose kinetic and microenvironmental frameworks(e.g.,“load-and-lock”barriers;dormancy and immunesynapse stabilization)as hypothesis-generating avenues to stall clonal handoffs and improve outcome prediction.Together,these perspectives argue for revised biomarker frameworks in HNCSCC and ethically inclusive,mechanism-anchored studies that bridge discovery with individualized care.By bridging insights from HNCSCC with the lessons of GBM,this review underscores the need for ethically inclusive,mechanistically informed frameworks that integrate subclonal evolution,biomarker re-interpretation,and precision-personalized hybrid models.Such an approach will be essential for advancing from one-size-fits-all strategies to individualized lifetime cancer care.
基金conducted under the framework of the research and development program of the Korea Institute of Energy Research(C4-2412 and C4-2413)supported by the National Research Foundation of Korea(grant number 2022M3J1A1063019)funded by the Ministry of Science and ICT.
文摘Attempts to remove environmentally harmful materials in mass production industries are always a major issue and draw attention if the substitution guarantees a chance to lower fabrication cost and to improve device performance,as in a wide bandgap Zn_(1-x)Mg_(x)O(ZMO)to replace the CdS buffer in Cu(In_(1-x),Ga_(x))Se_(2)(CIGSe)thin-film solar cell structure.ZMO is one of the candidates for the buffer material in CIGSe thin-film solar cells with a wide and controllable bandgap depending on the Mg content,which can be helpful in attaining a suitable conduction band offset.Hence,compared to the fixed and limited bandgap of a CdS buffer,a ZMO buffer may provide advantages in V_(oc) and J_(sc) based on its controllable and wide bandgap,even with a relatively wider bandgap CIGSe thin-film solar cell.In addition,to solve problems with the defect sites at the ZMO/CIGSe junction interface,a few-nanometer ZnS layer is employed for heterojunction interface passivation,forming a ZMO/ZnS buffer structure by atomic layer deposition(ALD).Finally,a Cd-free all-dry-processed CIGSe solar cell with a wider bandgap(1.25 eV)and ALD-grown buffer structure exhibited the best power conversion efficiency of 19.1%,which exhibited a higher performance than the CdS counterpart.
