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Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression

SIGNAL TRANSDUCTION AND TARGETED THERAPY 2024年第1期9卷 1-20页

作者： Peng, Hao Yang, Meng Feng, Kun lv, qingpeng Zhang, Yewei Southeast Univ Med Sch Nanjing 210009 Peoples R China Chinese Acad Med Sci & Peking Union Med Coll Peking Union Med Coll Hosp State Key Lab Complex Severe & Rare Dis Dept Ultrasound Beijing 100730 Peoples R China Nanjing Med Univ Hepatopancreatobiliary Ctr Affiliated Hosp 2 Nanjing 210009 Peoples R China

More than 90% of hepatocellular carcinoma (HCC) cases develop in the presence of fibrosis or cirrhosis, making the tumor microenvironment (TME) of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts (CAFs) and cancer stem cells (CSCs), which collectively regulate HCC progression. However, the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain elusive. Our study unveils a significant upregulation of Sema3C in fibrotic liver, HCC tissues, peripheral blood of HCC patients, as well as sorafenib-resistant tissues and cells, with its overexpression correlating with the acquisition of stemness properties in HCC. We further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C, activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor initiation. Additionally, HCC cells-derived Sema3C facilitated extracellular matrix (ECM) contraction and collagen deposition in vivo, while also promoting the proliferation and activation of hepatic stellate cells (HSCs). Mechanistically, Sema3C interacted with NRP1 and ITGB1 in HSCs, activating downstream NF-kB signaling, thereby stimulating the release of IL-6 and upregulating HMGCR expression, consequently enhancing cholesterol synthesis in HSCs. Furthermore, CAF-secreted TGF-beta 1 activates AP1 signaling to augment Sema3C expression in HCC cells, establishing a positive feedback loop that accelerates HCC progression. Notably, blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in vivo. In sum, our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CSCs and stroma during hepatocarcinogenesis, thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

关键词： CANCER-ASSOCIATED FIBROBLASTS HEPATIC STELLATE CELLS STEM-CELLS ACTIVATION POPULATIONS METASTASIS MECHANISMS PATHWAYS FIBROSIS PI3K/AKT

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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： KUN FENG HAO PENG qingpeng lv YEWEI ZHANG Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Medical School Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

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A series of naphthalimide azoles: Design, synthesis and bioactive evaluation as potential antimicrobial agents

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Science China Chemistry 2013年第7期56卷 952-969页

作者： DAMU Guri L. V. WANG qingpeng ZHANG HuiZhen ZHANG YiYi lv JingSong ZHOU ChengHe School of Chemistry and Chemical Engineering Southwest University School of Chemistry and Chemical Engineering Bijie University

A series of naphthalimide azoles as potential antibacterial and antifungal agents were conveniently and efficiently synthesized starting from commercially available 6-bromobenzo[de]isochromene-l,3-dione. All the new compounds were characterized by NMR, IR, MS and HRMS spectra. Their antimicrobial activities were evaluated against four Gram-positive bacteria, four Gram-negative bacteria and two fungi using two-fold serial dilution technique. The biological assay indicated that most of the prepared compounds exhibited inhibition to the tested strains. In particular, the triazolium derivatives not only gave higher ef- ficacy than their corresponding precursory azoles, but also demonstrated comparable or even better potency than the reference drugs Chloromycin, Orbifloxacin and Fluconazole. Some factors including structural fragments, pH and ClogP values of the target molecules were also preliminarily discussed.

关键词： naphthalimide triazole imidazole triazolium imidazolium thiol thione antibacterial antifungal antimicrobial

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冷屏件电铸设备的应用研究

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山西电子技术 2016年第3期 79-79,85页

作者：王海军师开鹏靳志强吕麒鹏中国电子科技集团公司第二研究所山西太原030024

针对镍钴合金性能的优越性,设计了制备电铸镍钴合金冷屏件的电铸设备,还设计了制备均匀镍钴合金的阴极旋转装置。

关键词：电铸冷屏件设备结构设计

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TPO防水卷材在云南科技馆新馆幕墙工程中的应用

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中国建筑防水 2021年第11期 15-19页

作者：吕敬环张青鹏北京东方雨虹防水技术股份有限公司北京100123 中国中元国际工程有限公司北京100089

云南科技馆整体造型复杂,呈不规则曲面,有防水层的幕墙从屋面到墙面一直延展到地面附近,从防水选材到施工非常有代表性。本项目非玻璃幕墙部分采用氟碳喷涂铝单板作为饰面层次,其下采用机械固定工法TPO单层屋面系统。此类带装饰板的空... 详细信息

云南科技馆整体造型复杂,呈不规则曲面,有防水层的幕墙从屋面到墙面一直延展到地面附近,从防水选材到施工非常有代表性。本项目非玻璃幕墙部分采用氟碳喷涂铝单板作为饰面层次,其下采用机械固定工法TPO单层屋面系统。此类带装饰板的空腔式公共建筑幕墙系统,也可以看做是特殊的TPO单层屋面系统。本文重点介绍了TPO系统在该幕墙工程中的应用,包括设计、安装固定、细部节点处理。

关键词：公共建筑金属板幕墙防水保温 TPO单层屋面系统

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青岛西海岸新区水文站网运行管理现状及建议

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山东水利 2022年第7期 9-11页

作者：徐保超周庆鹏吕欣青岛市水文中心山东青岛266400

通过分析青岛西海岸新区水文监测站网现状及存在的站网布设科学性、合理性不够,设备老旧,管理机制落实不到位,专业人才匮乏等问题,提出进一步优化水文站网,创新站网管理体制机制,提升现代化管理水平等建议,为水文事业“十四五”规划提... 详细信息

通过分析青岛西海岸新区水文监测站网现状及存在的站网布设科学性、合理性不够,设备老旧,管理机制落实不到位,专业人才匮乏等问题,提出进一步优化水文站网,创新站网管理体制机制,提升现代化管理水平等建议,为水文事业“十四五”规划提供思路。

关键词：青岛西海岸新区水文站网水质监测

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地质建模技术在断块油藏综合挖潜中的应用

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断块油气田 2008年第1期15卷 9-11页

作者：吕建荣赵春森王庆鹏大庆石油学院提高油气采收率教育部重点实验室黑龙江大庆163318 大庆油田有限责任公司第七采油厂黑龙江大庆163414

大庆油田葡南一断块油藏断层发育、构造复杂,应用地质建模技术可实现构造模型的三维可视化,通过分析断层在空间的延伸及相互切割关系,建立了断块区地质模型;利用三维可视化技术分析研究剩余油的分布状况,使得剩余油的分布范围和剩余量... 详细信息

大庆油田葡南一断块油藏断层发育、构造复杂,应用地质建模技术可实现构造模型的三维可视化,通过分析断层在空间的延伸及相互切割关系,建立了断块区地质模型;利用三维可视化技术分析研究剩余油的分布状况,使得剩余油的分布范围和剩余量由过去的定性描述变为定量,更精确的指导断块剩余油挖潜工作。针对葡南一断块目前剩余油分布状况的不同类型,制定了注采系统调整、复合措施等4套剩余油挖潜方案,进行对比优化,调整后已初步见到效果。该技术不仅有利于后期调整,而且为断块区提高储量动用程度打下了良好基础。

关键词：地质建模断块油藏剩余油挖潜三维可视化

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