The lunar surface is a typical vacuum environment,and its harsh heat rejection conditions bring great challenges to the thermal control technology of the exploration mission.In addition to the radiator,the sublimator ...The lunar surface is a typical vacuum environment,and its harsh heat rejection conditions bring great challenges to the thermal control technology of the exploration mission.In addition to the radiator,the sublimator is recommended as one of the promising options for heat rejection.The sublimator makes use of water to freeze and sublimate in a porous medium,rejecting heat to the vacuum environment.The complex heat and mass transfer process involves many physical phenomena such as the freezing and sublimation phase change of water in the porous medium and the movement of the phase-change interface.In this paper,the visualized ground-based experimental approaches of space sublimation cooling were presented to reveal the moving law of threephase point and the growth phenomenon of ice-peak and icicle in microchannels under vacuum conditions.The visualized experiments and results prove that the freezing ice is divided into the porous ice-peak and the transparent icicle.As the sublimation progresses,the phase-change interface moves downward steadily,the length of the ice-peak increases,but the icicle decreases.The visualized experiments of space sublimation cooling in the capillary have guiding significance to reveal the sublimation cooling mechanism of water in the sublimator for lunar exploration missions.展开更多
Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhiz...Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhizoma,has shown anti-tumor potential.This study investigated the efficacy of curcumol in overcoming cisplatin resistance and elucidated its underlying molecular mechanisms in bladder cancer progression.Methods:Clinical correlation was assessed in patients receiving neoadjuvant chemotherapy with or without Curcumae Rhizoma.The anti-tumor effects of curcumol were evaluated in both cisplatin-sensitive and cisplatinresistant bladder cancer cells.Multi-omics approaches,including RNA sequencing,proteomics and metabolomics,were employed.Key mechanisms involving H3K9 lactylation(H3K9la)were explored via Western blotting,immunohistochemistry,and cleavage under targets and tagmentation(CUT&Tag)assays.The role of the identified target ORC6 was validated through genetic knockout and overexpression.Finally,ferroptosis was confirmed by measuring lipid peroxidation[malondialdehyde(MDA)],total iron levels,and ferroptosis-related protein markers in vitro.Results:Clinical data indicated that patients administered Curcumae Rhizoma exhibited enhanced responses to neoadjuvant chemotherapy.In addition,curcumol suppressed the proliferation,migration,and invasion of both bladder cancer cells and cisplatin-resistant cells.Mechanistically,proteomic analysis and non-targeted metabolomics revealed that curcumol suppresses glycolysis and lactate production.Subsequently,Western blotting analysis demonstrated a marked reduction in H3K9la levels in both T24 and 5637 cells following curcumol treatment.This decrease in H3K9la was also observed in patient tumor tissues via immunohistochemistry staining.CUT&Tag analysis identified that H3K9la is enriched with the highest number of reads at the ORC6 promoter region.Combined in vitro and in vivo experiments indicated that OCR6 exerted a tumor-promoting effect on bladder cancer.Its knockout induced G0/G1 phase arrest and enhanced apoptosis,while its expression contributed to cancer progression by enhancing invasive and migratory capabilities.Furthermore,ORC6 overexpression correlated with ferroptosis scores and ferroptosis-related genes.In vitro,OCR6 knockout promoted ferroptosis via DNA damage,characterized by elevated MDA content,decreased expression of core ferroptosis-related proteins(GPX4 and SLC7A11),increased percentage ofγH2AX-positive cells and longer DNA tails.Finally,we performed rescue experiments using a ferroptosis inhibitor in ORC6 knockout cells,which indicated that ferroptosis inhibitor could weaken the effect of ORC6 knockout on the invasive,migratory,and proliferative capacities.Conclusions:Our findings demonstrated that curcumol effectively counteracted cisplatin resistance and inhibited bladder cancer progression by targeting the glycolysis-H3K9la-ORC6 axis to induce ferroptosis.This study established a critical link between metabolic reprogramming,histone lactylation,and ferroptosis,providing a novel therapeutic avenue for treating chemoresistant bladder cancer.展开更多
脆性X综合征(Fragile X syndrome)是一种最常见的遗传性智力低下疾病,并且伴有语言和行为障碍等。该疾病是由脆性X智力低下基因(Fragile X mental retardation 1,FMR1)突变而导致脆性X智力低下蛋白(Fragile X mental retardation protei...脆性X综合征(Fragile X syndrome)是一种最常见的遗传性智力低下疾病,并且伴有语言和行为障碍等。该疾病是由脆性X智力低下基因(Fragile X mental retardation 1,FMR1)突变而导致脆性X智力低下蛋白(Fragile X mental retardation protein,FMRP)表达异常造成的。近年来,研究发现FMRP参与非编码RNA通路,并发挥多种重要生物学功能,这对理解脆性X综合征发病机理具有重要的推动作用。首先发现FMRP与siRNA和miRNA通路中Dicer酶、Ago1和Ago2蛋白相互作用,参与神经活动及生殖干细胞命运决定等重要过程。随后又发现FMRP与piRNA通路中Aub、Ago1和Piwi蛋白相互作用,维持了染色体正常结构和基因组稳定性。最新研究结果发现FMRP与lncRNA相互作用,其功能和价值正引起关注。本文从FMRP与非编码RNA通路的关系展开,着重介绍了FMRP与piRNA之间的相互作用,以期为深入理解非编码RNA通路在脆性X综合征的发病过程中作用提供参考,同时期望与临床医学领域尽快形成交叉研究,早日促进理论成果转化为临床应用。展开更多
基金primarily funded by the cooperative project offered by Beijing Key Laboratory of Space Thermal Control Technologyfunded by China Postdoctoral Science Foundation(No.2020 M671618)。
文摘The lunar surface is a typical vacuum environment,and its harsh heat rejection conditions bring great challenges to the thermal control technology of the exploration mission.In addition to the radiator,the sublimator is recommended as one of the promising options for heat rejection.The sublimator makes use of water to freeze and sublimate in a porous medium,rejecting heat to the vacuum environment.The complex heat and mass transfer process involves many physical phenomena such as the freezing and sublimation phase change of water in the porous medium and the movement of the phase-change interface.In this paper,the visualized ground-based experimental approaches of space sublimation cooling were presented to reveal the moving law of threephase point and the growth phenomenon of ice-peak and icicle in microchannels under vacuum conditions.The visualized experiments and results prove that the freezing ice is divided into the porous ice-peak and the transparent icicle.As the sublimation progresses,the phase-change interface moves downward steadily,the length of the ice-peak increases,but the icicle decreases.The visualized experiments of space sublimation cooling in the capillary have guiding significance to reveal the sublimation cooling mechanism of water in the sublimator for lunar exploration missions.
基金supports of Science and Technology Plan Basic Project of Guizhou Province(No.ZK[2022]General 446)the Natural Science Fundation of Zhejiang Province(No.Q24H160134)+4 种基金Science and Technology Project of Zhejiang Health Commission(No.2024660542)Clinical Research Plan for TCM of Administration of Traditional Chinese Medicine of Zhejiang Province(No.2025075369)Bijie City Science and Technology Plan Project(No.[2025]No.60)National Health Commission of the People’s Republic of China-Zhejiang Province Jointly Constructed ProjectZhejiang Province Medical and Health Science and Technology Plan(No.WKJ-ZJ-2517)。
文摘Objective:Cisplatin-based chemotherapy is a cornerstone for bladder cancer treatment,but the development of resistance remains a major clinical challenge.Curcumol,a bioactive sesquiterpenoid derived from Curcumae Rhizoma,has shown anti-tumor potential.This study investigated the efficacy of curcumol in overcoming cisplatin resistance and elucidated its underlying molecular mechanisms in bladder cancer progression.Methods:Clinical correlation was assessed in patients receiving neoadjuvant chemotherapy with or without Curcumae Rhizoma.The anti-tumor effects of curcumol were evaluated in both cisplatin-sensitive and cisplatinresistant bladder cancer cells.Multi-omics approaches,including RNA sequencing,proteomics and metabolomics,were employed.Key mechanisms involving H3K9 lactylation(H3K9la)were explored via Western blotting,immunohistochemistry,and cleavage under targets and tagmentation(CUT&Tag)assays.The role of the identified target ORC6 was validated through genetic knockout and overexpression.Finally,ferroptosis was confirmed by measuring lipid peroxidation[malondialdehyde(MDA)],total iron levels,and ferroptosis-related protein markers in vitro.Results:Clinical data indicated that patients administered Curcumae Rhizoma exhibited enhanced responses to neoadjuvant chemotherapy.In addition,curcumol suppressed the proliferation,migration,and invasion of both bladder cancer cells and cisplatin-resistant cells.Mechanistically,proteomic analysis and non-targeted metabolomics revealed that curcumol suppresses glycolysis and lactate production.Subsequently,Western blotting analysis demonstrated a marked reduction in H3K9la levels in both T24 and 5637 cells following curcumol treatment.This decrease in H3K9la was also observed in patient tumor tissues via immunohistochemistry staining.CUT&Tag analysis identified that H3K9la is enriched with the highest number of reads at the ORC6 promoter region.Combined in vitro and in vivo experiments indicated that OCR6 exerted a tumor-promoting effect on bladder cancer.Its knockout induced G0/G1 phase arrest and enhanced apoptosis,while its expression contributed to cancer progression by enhancing invasive and migratory capabilities.Furthermore,ORC6 overexpression correlated with ferroptosis scores and ferroptosis-related genes.In vitro,OCR6 knockout promoted ferroptosis via DNA damage,characterized by elevated MDA content,decreased expression of core ferroptosis-related proteins(GPX4 and SLC7A11),increased percentage ofγH2AX-positive cells and longer DNA tails.Finally,we performed rescue experiments using a ferroptosis inhibitor in ORC6 knockout cells,which indicated that ferroptosis inhibitor could weaken the effect of ORC6 knockout on the invasive,migratory,and proliferative capacities.Conclusions:Our findings demonstrated that curcumol effectively counteracted cisplatin resistance and inhibited bladder cancer progression by targeting the glycolysis-H3K9la-ORC6 axis to induce ferroptosis.This study established a critical link between metabolic reprogramming,histone lactylation,and ferroptosis,providing a novel therapeutic avenue for treating chemoresistant bladder cancer.
文摘脆性X综合征(Fragile X syndrome)是一种最常见的遗传性智力低下疾病,并且伴有语言和行为障碍等。该疾病是由脆性X智力低下基因(Fragile X mental retardation 1,FMR1)突变而导致脆性X智力低下蛋白(Fragile X mental retardation protein,FMRP)表达异常造成的。近年来,研究发现FMRP参与非编码RNA通路,并发挥多种重要生物学功能,这对理解脆性X综合征发病机理具有重要的推动作用。首先发现FMRP与siRNA和miRNA通路中Dicer酶、Ago1和Ago2蛋白相互作用,参与神经活动及生殖干细胞命运决定等重要过程。随后又发现FMRP与piRNA通路中Aub、Ago1和Piwi蛋白相互作用,维持了染色体正常结构和基因组稳定性。最新研究结果发现FMRP与lncRNA相互作用,其功能和价值正引起关注。本文从FMRP与非编码RNA通路的关系展开,着重介绍了FMRP与piRNA之间的相互作用,以期为深入理解非编码RNA通路在脆性X综合征的发病过程中作用提供参考,同时期望与临床医学领域尽快形成交叉研究,早日促进理论成果转化为临床应用。
