Suppression of mTOR signaling pathway promotes bone marrow mesenchymal stem cells differentiation into osteoblast in degenerative scoliosis: in vivo and in vitro

To investigate the role of mTOR signaling pathway in bone marrow mesenchymal stem cells (BMSCs) differentiation into osteoblast in degenerative scoliosis (DS). The rat model of DS was established. Thirty-two Sprague–Dawley (SD) rats were selected and divided into the normal control group, the positive control group (normal rats injected with rapamycin), the negative control group (DS rats injected with PBS) and the experiment group (DS rats injected with rapamycin). H&E staining was performed to observe the osteogenesis of scoliosis. The BMSCs were obtained and assigned into seven groups: the normal control group, the positive control group, the negative control group and 1.0/10.0/100.0/1000.0 nmol/L experiment groups. Flow cytometry was conducted to testify cell cycle. The mRNA and protein expressions of mTOR and osteoblastic differentiation markers were measured by qRT-PCR and western blotting. In vivo, compared with the negative control group, bone trabecular area and the number of differentiated bone cells were significantly increased in the experiment groups. In vitro, at 24 and 48 h after rapamycin treatment, compared with the negative control group, BMSCs at G0/G1 stage increased, but BMSCs at S stage decreased in the 1.0/10.0/100.0/1000.0 nmol/L experiment groups; the expressions of mTOR and p70-S6K1 proteins were reduced in the 1.0/10.0/100.0/1000.0 nmol/L experiment groups, while ALP activity, OC levels, calcium deposition, Co1-I protein expression and the mRNA expressions of OC and Co1-I were significantly increased. Suppression of mTOR signaling pathway by rapamycin could promote BMSCs differentiation into osteoblast in DS.     

Amphiphilic Blockers Punch through a Mutant CLC-0 Pore

Intracellularly applied amphiphilic molecules, such as p-chlorophenoxy acetate (CPA) and octanoate, block various pore-open mutants of CLC-0. The voltage-dependent block of a particular pore-open mutant, E166G, was found to be multiphasic. In symmetrical 140 mM Cl⁻, the apparent affinity of the blocker in this mutant increased with a negative membrane potential but, paradoxically, decreased when the negative membrane potential was greater than −80 mV, a phenomenon similar to the blocker “punch-through” shown in many blocker studies of cation channels. To provide further evidence of the punch-through of CPA and octanoate, we studied the dissociation rate of the blocker from the pore by measuring the time constant of relief from the block under various voltage and ionic conditions. Consistent with the voltage dependence of the effect on the steady-state current, the rate of CPA dissociation from the E166G pore reached a minimum at −80 mV in symmetrical 140 mM Cl⁻, and the direction of current recovery suggested that the bound CPA in the pore can dissociate into both intracellular and extracellular solutions. Moreover, the CPA dissociation depends upon the Cl⁻ reversal potential with a minimal dissociation rate at a voltage 80 mV more negative than the Cl⁻ reversal potential. That the shift of the CPA-dissociation rate follows the Cl⁻ gradient across the membrane argues that these blockers can indeed punch through the channel pore. Furthermore, a minimal CPA-dissociation rate at a voltage 80 mV more negative than the Cl⁻ reversal potential suggests that the outward blocker movement through the CLC-0 pore is more difficult than the inward movement.     

碳离子辐射诱导的远隔效应

放射治疗诱导的远隔效应能够抑制非辐射区域内肿瘤的生长，目前已有临床和临床前研究表明，常规放疗射线（X射线、γ射线）能够诱导远隔效应的发生，但是对于其发生的机理以及碳离子诱导的远隔效应研究较少。与常规放疗射线相比，碳离子束具有高传能线密度、高相对生物效应、低氧增强比以及复杂DNA损伤等优势，并且具有激活肿瘤细胞更强免疫原性的潜力。本文综述了常规放疗以及碳离子放射治疗诱导的远隔效应及其机理，为寻找更有效的癌症放疗方法提供参考。     

The polymorphism of CLOCK gene rs4864548 A>G is associated with susceptibility of Alzheimer’s disease in Chinese population

The aim of this study was to investigate the correlation between polymorphism of circadian locomotor output cycle kaput (CLOCK) gene rs4864548 A/G and susceptibility of Alzheimer’s disease (AD). A total of 296 unrelated AD patients and 423 control subjects were enrolled in the case-control study. Genotypes of apolipoprotein E (APOE) and CLOCK gene rs4864548 A/G were determined by a Polymerase Chain Reaction (PCR) restriction fragment length polymorphism detection method. Our results showed that in the whole sample or APOE ε 4 non-carriers, prevalence of A carriers in CLOCK gene rs4864548 A/G in AD patients was remarkably higher than that in control subjects (in the whole sample: χ² = 47.614, p < 0.0001; in APOE ε 4 non-carriers: χ² = 22.493, p < 0.0001). However, among APOE ε 4 carriers, the difference in the prevalence of A carriers in CLOCK gene rs4864548 A/G between AD patients and controls was no statistically significant (χ² = 0.669, p = 0.379). These findings demonstrate that A carriers in CLOCK gene rs 4864548 A/G were closely related to a high susceptibility of AD among APOE ε 4 non-carriers while the functional polymorphism of CLOCK gene rs4864548 A/G was not associated with the susceptibility of AD among APOE ε 4 carriers.     

高负载Cu单原子纳米酶的制备和类酶活性研究

目的 单原子纳米酶（single-atom nanozyme，SAN）因其高原子利用率及丰富的类酶活性被广泛研究。但是目前大多数SAN活性位点负载量较低，限制了其进一步应用和发展。本研究旨在制备一种高原子负载量的SAN，并对其类酶活性进行系统研究，希望为高负载SAN的制备提供思路，并为SAN在更广泛领域的应用提供理论支持。方法 本研究通过原位锚定策略将金属盐前驱体锚定在氨基化石墨烯量子点框架中，在惰性气体保护下进行高温热解稳定Cu原子和载体之间的化学键，制备出负载量高达7.66%（质量百分比）的高负载Cu单原子纳米酶（high-loading Cu SAN）。此外，以3,3",5,5"-四甲基联苯胺（TMB）和氮蓝四唑（NBT）为显色剂，评估了high-loading Cu SAN的类过氧化物酶（POD）、类氧化物酶（OXD）及类超氧化物歧化酶（SOD）活性，并与传统金属有机框架锚定法制备的低负载Cu单原子纳米酶（low-loading Cu SAN）作比较。以过氧化氢（H₂O₂）为催化底物，对比研究了高/低负载Cu SAN的类过氧化氢酶（CAT）活性。结果 研究表明，本文制备的高负载Cu SAN的类POD和SOD活性分别是低负载Cu SAN的3.4倍和8.88倍，且表现出类酶催化选择性。结论 本研究为高负载SAN的制备和活性研究提供了思路，为SAN在检测传感、疾病治疗以及环境保护等方面的应用奠定了基础。     

我国大陆红火蚁入侵扩张趋势长期预测

红火蚁Solenopsis invicta Buren是一种严重危害农林业生产、生命健康、公共安全和生态环境的国际性重大外来入侵害虫。2004年9月中国大陆首次发现红火蚁,2021年12月该蚁已入侵了12个省区近500个县区。本研究根据中国大陆红火蚁入侵发生县区数量变化,结合潜在适生区域评价信息,建立了红火蚁入侵县区数量与入侵时间长度间关系模型,并对入侵县区数量变化趋势作出长期预测。当中国大陆红火蚁潜在入侵县区数量上限分别为1 400、1 500和1 600个时,入侵县区数量与入侵时间长度关系模型分别为N=1400/(1+e^{5.4048-0.1784T})、N=1500/(1+e^{5.4335-0.1757T})和N=1600/(1+e^{5.464-0.1734T})。基于以上模型的分析结果显示,我国红火蚁快速扩散传播从2009-2010年开始,快速扩张期可能持续26～28年,年平均新增县区41～52个/年,预测2035-2037年入侵县区数量增长速率将开始减缓,2...