Study on Antidepressant Effect and Mechanism of Crocin Mediated by the mTOR Signaling Pathway

Neurochemical Research - Crocin is a monomer of Chinese traditional herbs extracted from saffron, relieving depression-like behavior. However, its underlying mechanism of action remains unclear....     

Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice. Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength.     

A Versatile Sn‐Substituted Argyrodite Sulfide Electrolyte for All‐Solid‐State Li Metal Batteries

Sulfide‐based solid‐state electrolytes (SSEs) for all‐solid‐state Li metal batteries (ASSLMBs) are attracting significant attention due to their high ionic conductivity, inherently soft properties, and decent mechanical strength. However, the poor incompatibility with Li metal and air sensitivity have hindered their application. Herein, the Sn (IV) substitution for P (V) in argyrodite sulfide Li₆PS₅I (LPSI) SSEs is reported, in the preparation of novel LPSI‐xSn SSEs (where x is the Sn substitution percentage). Appropriate aliovalent element substitutions with larger atomic radius (R_<Sn> > R_<P>) provides the optimized LPSI‐20Sn electrolyte with a 125 times higher ionic conductivity compared to that of the LPSI electrolyte. The high ionic conductivity of LPSI‐20Sn enables the rich I‐containing electrolyte to serve as a stabilized interlayer against Li metal in sulfide‐based ASSLMBs with outstanding cycling stability and rate capability. Most importantly, benefiting from the strong Sn–S bonding in Sn‐substituted electrolytes, the LPSI‐20Sn electrolyte shows excellent structural stability and improved air stability after exposure to O₂ and moisture. The versatile Sn substitution in argyrodite LPSI electrolytes is believed to provide a new and effective strategy to achieve Li metal‐compatible and air‐stable sulfide‐based SSEs for large‐scale applications.     

中华猕猴桃蛋白酶在盐酸胍中分子折叠与活力的关系

中华猕猴桃蛋白酶(Actinidin)在盐酸胍溶液中活力变化结果提示:酶在0.1mol/L胍中活力略有升高,随胍浓度增大,活力先经历一个陡降区,在1—2mol/L胍中有个稳定区域,随胍浓度增大,活力继续下降。同时以荧光光谱,圆二色光谱研究该酶分子的构象变化。结果表明引起酶构象发生明显变化所需胍浓度(3mol/L)远比酶明显失活所需胍浓度(0.5mol/L)大。相同胍浓度下酶活力丧失速度快于构象变化速度。经5mol/L胍变性的酶直接稀释至胍浓度为0.05mol/L时,酶活力不能恢复,而构象迅速恢复。失活酶先稀释至胍浓度为1—2mol/L、再进一步稀释至胍浓度为0.05mol/L,活力能恢复50％左右。以上结果表明,相对于整个酶分子来说,活性中心的构象变化对变性剂更敏感。Actinidin的失活及复活过程是多相的复杂过程。     

Host E3 ligase HUWE1 attenuates the proapoptotic activity of the MERS-CoV accessory protein ORF3 by promoting its ubiquitin-dependent degradation

With the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), coronaviruses have begun to attract great attention across the world. Of the known human coronaviruses, however, Middle East respiratory syndrome coronavirus (MERS-CoV) is the most lethal. Coronavirus proteins can be divided into three groups: nonstructural proteins, structural proteins, and accessory proteins. While the number of each of these proteins varies greatly among different coronaviruses, accessory proteins are most closely related to the pathogenicity of the virus. We found for the first time that the ORF3 accessory protein of MERS-CoV, which closely resembles the ORF3a proteins of severe acute respiratory syndrome coronavirus and SARS-CoV-2, has the ability to induce apoptosis in cells in a dose-dependent manner. Through bioinformatics analysis and validation, we revealed that ORF3 is an unstable protein and has a shorter half-life in cells compared to that of severe acute respiratory syndrome coronavirus and SARS-CoV-2 ORF3a proteins. After screening, we identified a host E3 ligase, HUWE1, that specifically induces MERS-CoV ORF3 protein ubiquitination and degradation through the ubiquitin–proteasome system. This results in the diminished ability of ORF3 to induce apoptosis, which might partially explain the lower spread of MERS-CoV compared to other coronaviruses. In summary, this study reveals a pathological function of MERS-CoV ORF3 protein and identifies a potential host antiviral protein, HUWE1, with an ability to antagonize MERS-CoV pathogenesis by inducing ORF3 degradation, thus enriching our knowledge of the pathogenesis of MERS-CoV and suggesting new targets and strategies for clinical development of drugs for MERS-CoV treatment.     

Preactivation of β-catenin in osteoblasts improves the osteoanabolic effect of PTH in type 1 diabetic mice

Type 1 diabetes (T1D) is correlated with osteopenia primarily due to low bone formation. Parathyroid hormone (PTH) is a known anabolic agent for bone, the anabolic effects of which are partially mediated through the Wnt/β-catenin signaling pathway. In the present study, we first determined the utility of intermittent PTH treatment in a streptozotocin-induced T1D mouse model. It was shown that the PTH-induced anabolic effects on bone mass and bone formation were attenuated in T1D mice compared with nondiabetic mice. Further, PTH treatment failed to activate β-catenin signaling in osteoblasts of T1D mice and was unable to improve osteoblast proliferation and differentiation. Next, the Col1–3.2 kb-CreERTM; β-cateninfx(ex3) mice were used to conditionally activate β-catenin in osteoblasts by injecting tamoxifen, and we addressed whether or not preactivation of β-catenin boosted the anabolic action of PTH on T1D-related bone loss. The results demonstrated that pretreatment with activation of osteoblastic β-catenin followed by PTH treatment outperformed PTH or β-catenin activation monotherapy and led to greatly improved bone structure, bone mass, and bone strength in this preclinical model of T1DM. Further analysis demonstrated that osteoblast proliferation and differentiation, as well as osteoprogenitors in the marrow, were all improved in the combination treatment group. These findings indicated a clear advantage of developing β-catenin as a target to improve the efficacy of PTH in the treatment of T1D-related osteopenia.     

青钱柳功能性多糖的研究现状及展望

青钱柳叶是一种古老茶饮,也是国家卫健委认定的新食品原料。青钱柳多糖是其主要活性成分之一,具有降血糖、降血脂、抗氧化、免疫调节等多种功能,在食品、医药和生物医学等领域应用市场潜力巨大。通过综述国内外相关研究文献报道,对青钱柳叶所含功能性多糖的提取工艺、结构特征、药理活性及开发应用的研究现状进行较系统的归纳和分析,并对青钱柳多糖未来研究方向作了展望,拟为开发高活性青钱柳多糖保健食品或药物提供理论依据及研究支撑。