Acetylshikonin Inhibits Colorectal Cancer Growth via PI3K/Akt/mTOR Signaling Pathway

Background: Acetylshikonin, a major constituent isolated from Arnebia euchroma, is a potential candidate for anti-colorectal cancer drugs. However, the potential activity and underlying mechanism of Acetylshikonin against colorectal cancer remain unclear. Methods: In this study, Acetylshikonin was isolated from the active CHCl3 extract of Arnebia euchroma using activity-guided screening, and elucidated by the extensive spectroscopic analysis and comparison with literature data. Human colorectal cancer cells HT29, DLD-1, HCT116 or Caco-2 were exposed to different concentrations of Acetylshikonin (6.25 - 100 μg/mL) for 24 or 48 h. Cell viability, cell apoptosis and cell cycle distribution were detected. The activity of Acetylshikonin and potential mechanism of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway were evaluated in vitro and vivo. Results: We found that Acetylshikonin exhibited remarkable anti-proliferative activity in a dose-dependent manner against HT29 cells with the IC50 values of 60.82 μg/ml and 30.78 μg/ml at 24, 48 h, respectively. Moreover, Acetylshikonin induced cell cycle arrest at G0/G1 phase and early apoptosis through inhibition of PI3K/Akt/mTOR pathway. Furthermore, the assays of cell inhibition, early apoptosis and G0/G1 phase distribution showed that suppression of the PI3K/Akt pathway using LY294002 enhanced the anti-cancer effect of Acetylshikonin. Similarly, Acetylshikonin also decreased the growth of tumour in colorectal cancer xenografts in mice through PI3K/Akt/mTOR pathway. Conclusions: To sum up, these new findings provided a framework for further exploration of Acetylshikonin which possessed the potential antitumor activity by inhibiting PI3K/Akt/mTOR pathway.

Themis suppresses the effector function of CD8^(+)T cells in acute viral infection

CD8^(+)T cells play a central role in antiviral immune responses.Upon infection,naive CD8^(+)T cells differentiate into effector cells to eliminate virus-infected cells,and some of these effector cells further differentiate into memory cells to provide long-term protection after infection is resolved.Although extensively investigated,the underlying mechanisms of CD+T-cell differentiation remain incompletely understood.Themis is a T-cell-specific protein that plays critical roles in T-cell development.Recent studies using Themis T-cell conditional knockout mice also demonstrated that Themis is required to promote mature CD8^(+)T-cell homeostasis,cytokine responsiveness,and antibacterial responses.In this study,we used LCMV Armstrong infection as a probe to explore the role of Themis in viral infection.We found that preexisting CD8^(+)T-cell homeostasis defects and cytokine hyporesponsiveness do not impair viral clearance in Themis T-cell conditional knockout mice.Further analyses showed that in the primary immune response,Themis deficiency promoted the differentiation of CD8^(+)effector cells and increased their TNF and IFNy production.Moreover,Themis deficiency impaired memory precursor cell(MPEC)differentiation but promoted short-lived effector cell(SLEC)differentiation.Themis deficiency also enhanced effector cytokine production in memory CD8^(+)T cells while impairing central memory CD8^(+)T-cell formation.Mechanistically,we found that Themis mediates PD-1 expression and its signaling in effector CD8^(+)T cells,which explains the elevated cytokine production in these cells when Themis is disrupted.

Hydriding Pd cocatalysts： An approach to giant enhancement on photocatalytic CO2 reduction into CH4

Photocatalytic reduction of CO2 into high value-added CH4 is a promising solution for energy and environmental crises. Integrating semiconductors with cocatalysts can improve the activities for photocatalytic CO2 reduction; however, most metal cocatalysts mainly produce CO and H2. Herein, we report a cocatalyst hydridation approach for significantly enhancing the photocatalytic reduction of CO2 into CH4. Hydriding Pd cocatalysts into PdH0.43 played a dual role in performance enhancement. As revealed by our isotopic labeling experiments, the PdH0.43 hydride cocatalysts reduced H2 evolution, which suppressed the H2 production and facilitated the conversion of the CO intermediate into the final product： CH4. Meanwhile, hydridation promoted the electron trapping on the cocatalysts, improving the charge separation. This approach increased the photocatalytic selectivity in CH4 production from 3.2% to 63.6% on Pd{100} and from 15.6% to 73.4% on Pd{111}. The results provide insights into photocatalytic mechanism studies and introduce new opportunities for designing materials towards photocatalytic CO2 conversion.

多模态影像技术在精准肝癌肝切除中的应用

目的探讨多模态影像技术在精准肝切除治疗原发性肝癌(肝癌)中的临床应用价值。方法回顾性分析2018年1月至2021年1月粤北人民医院行精准肝切除的69例肝癌患者临床资料。患者均签署知情同意书,符合医学伦理学规定。其中男52例,女17例;年龄21~77岁,中位年龄55岁。根据术前采用数字医学影像技术不同,将患者分为多模态影像技术指导组(多模组,32例)和三维可视化技术指导组(单模组,37例)。多模组采用三维可视化重建、3D打印、增强现实(AR)技术指导多模块进行术前评估、手术规划和手术导航。单模组术前采用三维可视化技术进行术前规划。比较两组患者围手术期情况及预后。两组手术时间、术中出血量等比较采用t检验或秩和检验,率的比较采用χ2检验。结果69例患者均成功建立三维可视化重建模型。多模组术中所见与三维可视化、3D打印及AR技术一致,手术团队对手术方案理解和手术配合高度一致。所有患者均顺利完成手术,无围手术期死亡,术后均未发生严重并发症。多模组平均手术时间、入肝血流阻断时间分别为(203±59)、(27±13)min,明显少于单模组的(235±62)、(34±13)min(t=-2.193,-2.178;P<0.05);术中出血量中位数分别为165(235)ml,亦明显少于单模组的200(100)ml(Z=-2.472,P<0.05)。单模组术后复发转移4例,多模组3例,两组无复发生存率比较差异无统计学意义(χ2=0.032,P>0.05)。结论多模态影像技术具有多信息化优势,可弥补单一模式的不足,通过精准的术前规划和手术导航,可提高精准肝癌肝切除术的精准性和安全性。