Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.Subject terms: Liver cancer, Mitophagy, Apoptosis     

Robust Laminated Anode with an Ultrathin Titanium Nitride Layer for High-Efficiency Top-Emitting Organic Light-Emitting Diodes

The effective reflective anode remains a highly desirable component for the fabrication of reliable top-emitting organic light-emitting diodes (TE-OLEDs) which have the potential to be integrated with complementary metal-oxide-semiconductor (CMOS) circuits for microdisplays. This work demonstrates a novel laminated anode consisting of a Cr/Al/Cr multilayer stack. Furthermore, we implement an ultra-thin titanium nitride (TiN) layer as a protective layer on the top of the Cr/Al/Cr composite anode, which creates a considerably reflective surface in the visible range, and meanwhile improves the chemical stability of the electrode against the atmosphere or alkali environment. Based on [2-(2-pyridinyl-N)phenyl-C](acetylacetonate)iridium(III) as green emitter and Mg/Ag as transparent cathode, our TE-OLED using the TiN-coated anode achieves the maximum current efficiency of 71.2 cd/A and the maximum power efficiency of 66.7 lm/W, which are 81% and 90% higher than those of the reference device without TiN, respectively. The good device performance shows that the Cr/Al/Cr/TiN could function as a promising reflective anode for the high-resolution microdisplays on CMOS circuits.     

Cold Sintering of Li6.4La3Zr1.4Ta0.6O12/PEO Composite Solid Electrolytes

Ceramic/polymer composite solid electrolytes integrate the high ionic conductivity of in ceramics and the flexibility of organic polymers. In practice, ceramic/polymer composite solid electrolytes are generally made into thin films rather than sintered into bulk due to processing temperature limitations. In this work, Li_6.4La₃Zr_1.4Ta_0.6O₁₂ (LLZTO)/polyethylene-oxide (PEO) electrolyte containing bis(trifluoromethanesulfonyl)imide (LiTFSI) as the lithium salt was successfully fabricated into bulk pellets via the cold sintering process (CSP). Using CSP, above 80% dense composite electrolyte pellets were obtained, and a high Li-ion conductivity of 2.4 × 10⁻⁴ S cm^–1 was achieved at room temperature. This work focuses on the conductivity contributions and microstructural development within the CSP process of composite solid electrolytes. Cold sintering provides an approach for bridging the gap in processing temperatures of ceramics and polymers, thereby enabling high-performance composites for electrochemical systems.     

RuH2和RuN2电子组态与光谱性质的从头计算

用量子化学从头算方法在B3LYP/6 311G 的水平上 ,研究了RuH2 和RuN2 可能的电子组态和光谱性质 .结果表明 ,RuH2 的3 B2 和5Σ-态对应于静电作用的物理吸附态 .RuN2 的一重态和三重态的计算结果跟钌单晶面上的实验值相接近 .而RuN2 在C∞v对称性时 ,五重态5Σ-的计算频率比实验值稍低 .在C2v对称性时 ,五重态的计算频率值则更低 ,3 B2 和5A1态不能稳定存在     

一种实现光子晶体波导定向耦合型多路光均分的新方法

将多光子晶体单模波导平行、邻近放置构成定向耦合器. 依据自映像原理,数值分析了输入光场对称入射时,该系统中光的传播行为. 基于此结构,以三、四通道为例,设计了超微多路光分束器,并仅通过对称地改变耦合区中两个介质柱的有效折射率,使光场在横向发生重新分布,实现了输出能量的均分或自由分配. 和已报道结果相比,此调制方法更为简单易行而且效率更高,并可以推广到具有更多输出通道的光分束器中,在未来的集成光回路中具有广泛的应用价值. 关键词： 光子晶体波导 定向耦合器 分束器 能量均分     

Magnetic transition and large reversible magnetocaloric effect in EuCu1.75P2 compound

The magnetocaloric effect(MCE) in EuCu1.75P2 compound is studied by the magnetization and heat capacity measurements.Magnetization and modified Arrott plots indicate that the compound undergoes a second-order phase transition at TC ～ 51 K.A large reversible MCE is observed around TC.The values of maximum magnetic entropy change(-△SxMma) reach 5.6 J·kg-1·K-1 and 13.3 J·kg-1·K-1 for the field change of 2 T and 7 T,respectively,with no obvious hysteresis loss in the vicinity of Curie temperature.The corresponding maximum adiabatic temperature changes(△Tadmax) are evaluated to be 2.1 K and 5.0 K.The magnetic transition and the origin of large MCE in EuCu1.75P2 are also discussed.     

汉语句法的分段循环分析策略

定义了汉语的分段语法，并根据自然语言的分段循环结构，提出了汉语的分段循环分析策略．它的基本思想是确定语言的一组基本范畴，其相应的句法规则段及其之间的优先关系，对于每一个句法规则段，分别依次采用改进的Ｋｉｌｂｕｒｙ算法、它的优点在于分析过程中的项目集比较小，而且避免了无用分析树的产生，从而大大提高了分析效率．     

亚半正定阵左右逆特征值问题的进一步研究

１　引　言文［１］研究了亚半正定阵的左右逆特征值问题,它的更一般提法是问题Ｉ给定Ｘ、Ｚ使得其中Ｒｎ×ｍ表示全体ｎ×ｍ实阵的集合;即表示全体亚半正定阵集合［２］．文［１］得到了问题１有解的充要条件及解的通式,但从文［１］中主要定理给出的通式来看,子矩阵Ａ１３、Ａ１４及Ａ４３的表达式还没有得到,因此有必要对问题Ⅰ的通解作进一步的研究．本文将通过建立一个亚半正定阵的判定准则,圆满地解决以上问题． 为方便起见,本文用 及Ⅰ分别表示Ｒｎ×ｍ中秩为ｒ的矩阵集合、ｎ×正交矩阵集合及单位矩阵;而用　分别表示ｎ ×…     

激光诱导熔石英表面损伤修复中的气泡形成和控制研究

基于熔石英材料在CO_2激光作用下的温度分布和结构参数变化的计算结果,对熔石英损伤修复中的气泡形成和控制进行了研究.针对损伤尺寸介于150—250μm之间的损伤点,提出了一种能够有效控制气泡形成的长时间低温预热修复方法.基于低温下熔石英材料结构弛豫时间常数较长的特点,该方法在不引起熔石英材料结构发生显著变化的同时,能够解吸附表面和裂纹处所附着的气体和杂质,可有效降低裂纹闭合过程中气泡形成的概率.实验结果表明,长时间低温预热修复方法的成功修复概率可达到98%.