Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen...多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。展开更多
为了评估API RP 5C5 CALⅣ循环交变复合载荷对螺纹接头密封性能的影响,基于Abaqus软件按照API RP 5C5 CALⅣ的B系、C系、A系试验载荷对特殊螺纹接头进行了有限元仿真分析。结果表明,运用有限元法可实现API RP 5C5 CALⅣ级试验加载全过...为了评估API RP 5C5 CALⅣ循环交变复合载荷对螺纹接头密封性能的影响,基于Abaqus软件按照API RP 5C5 CALⅣ的B系、C系、A系试验载荷对特殊螺纹接头进行了有限元仿真分析。结果表明,运用有限元法可实现API RP 5C5 CALⅣ级试验加载全过程的仿真模拟,循环复合载荷试验对接头密封性能有一定影响,其中C系载荷循环对接头的密封能下降量影响最小,密封能倍数最高;A系载荷下的接头的密封能倍数达到最低,其中在“24和25”载荷点下密封能倍数最低,是该类型接头的潜在泄漏危险点,需要重点关注。建议油田客户对于已通过API RP 5C5 CALⅣ试验验证的特殊螺纹接头系列,针对其新增准入规格可以进行简化的API RP 5C5气密封试验,此举既能在一定程度上有效表征其气密封性能,同时节约油田和厂家双方的时间和经济成本。展开更多
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
文摘多发性骨髓瘤(multiple myeloma,MM)是一种不可治愈的血液系统恶性肿瘤,尽管新型蛋白酶体抑制剂、免疫调节剂及CD38单抗等药物的应用显著延长了患者的生存时间,但复发耐药仍难以避免。细胞免疫治疗,特别是嵌合抗原受体(chimeric antigen receptor,CAR)T细胞疗法的快速发展,极大程度的改变了复发/难治性(relapsed/refractory,R/R)MM患者的治疗现状。FDA目前已批准了2款靶向B细胞成熟抗原(B cell maturation antigen,BCMA)的CAR-T细胞产品,使其用于既往接受过4线及以上治疗的R/R MM患者。随着临床研究的不断深入,靶向GPRC5D(G protein-coupled receptor C class Group 5 member D,G蛋白偶联受体C类第5组成员D)的CAR-T细胞治疗也显示出其独特的优势。除了应用于难治复发的患者,多项临床试验支持CAR-T在MM中治疗线数的前移。本文就CAR-T细胞治疗在MM中开展的关键性临床研究展开综述,旨在为临床应用提供参考。
文摘为了评估API RP 5C5 CALⅣ循环交变复合载荷对螺纹接头密封性能的影响,基于Abaqus软件按照API RP 5C5 CALⅣ的B系、C系、A系试验载荷对特殊螺纹接头进行了有限元仿真分析。结果表明,运用有限元法可实现API RP 5C5 CALⅣ级试验加载全过程的仿真模拟,循环复合载荷试验对接头密封性能有一定影响,其中C系载荷循环对接头的密封能下降量影响最小,密封能倍数最高;A系载荷下的接头的密封能倍数达到最低,其中在“24和25”载荷点下密封能倍数最低,是该类型接头的潜在泄漏危险点,需要重点关注。建议油田客户对于已通过API RP 5C5 CALⅣ试验验证的特殊螺纹接头系列,针对其新增准入规格可以进行简化的API RP 5C5气密封试验,此举既能在一定程度上有效表征其气密封性能,同时节约油田和厂家双方的时间和经济成本。
