Loss of Spike N370 glycosylation as an important evolutionary event for the enhanced infectivity of SARS-CoV-2

Dear Editor, SARS-CoV-2 belongs to the Sarbecovirus subgenus of betacor-onaviruses and other members in this subgenus include SARS-CoV and coronaviruses mainly ...     

水体浊度对菹草(Potamogeton cripus)幼苗生长发育的影响

用粒径小于100 μm的泥沙配置浊度为30、60、90、120、150 NTU和180 NTU的混浊水体,将菹草（Potamogeton cripus）幼苗分别移栽于上述水体中,观测菹草幼苗在各浊度水体中的生长发育状况,并用水下饱和脉冲叶绿素荧光仪（DIVING-PAM）测定菹草幼苗光合作用PSII最大量子产量 （Fv/Fm）、有效荧光产量（Yield）、光化学荧光淬灭系数（qP）、非光化学荧光淬灭系数（qN）等指标。结果表明,菹草幼苗对混浊水体有较强的耐受能力,在30、60NTU和90NTU的混浊水体中,水体浊度对菹草幼苗的存活、生长发育及光合结构PSII影响不显著（p>0.05）。当水体浊度≥120NTU时,在短期（<10d）胁迫下,水体浊度对于菹草幼苗的存活、生长发育无显著影响（p>0.05）,但是,随着胁迫时间的延长(>10d),菹草幼苗虽能成活但生长发育明显受到抑制,幼苗叶片受光胁迫时,能通过增加热耗散（qN）保护其光合结构PSII免受伤害;而更长时间的胁迫（80d）,在高浊度（120、150 NTU和180 NTU）水体中的菹草幼苗开始大量死亡,其Fv/Fm、Yield、qP值均显著低于对照（p<0.05）, qN值的急剧下降,说明光合结构PSII开始受到破坏。     

MiR133b-mediated inhibition of EGFR-PTK pathway promotes rAAV2 transduction by facilitating intracellular trafficking and augmenting second-strand synthesis

Recombinant adeno-associated virus (rAAV) is an extremely attractive vector in the in vivo delivery of gene therapy as it is safe and its genome is simple. However, challenges including low permissiveness to specific cells and restricted tissue specificity have hindered its clinical application. Based on the previous studies, epidermal growth factor receptor-protein tyrosine kinase (EGFR-PTK) negatively regulated rAAV transduction, and EGFR-positive cells were hardly permissive to rAAV transduction. We constructed a novel rAAV-miRNA133b vector, which co-expressed miRNA133b and transgene, and investigated its in vivo and in vitro transduction efficiency. Confocal microscopy, live-cell imaging, pharmacological reagents and labelled virion tracking were used to analyse the effect of miRNA133b on rAAV2 transduction and the underlying mechanisms. The results demonstrated that miRNA133b could promote rAAV2 transduction and the effects were limited to EGFR-positive cells. The increased transduction was found to be a direct result of decreased rAAV particles degradation in the cytoplasm and enhanced second-strand synthesis. ss-rAAV2-miRNA133b vector specifically increased rAAV2 transduction in EGFR-positive cells or tissues, while ss-rAAV2-Fluc-miRNA133b exerted an antitumor effect. rAAV-miRNA133b vector might emerge as a promising platform for delivering various transgene to treat EGFR-positive cell-related diseases, such as non-small-cell lung cancer.     

Psychomotor Dysfunction in Rett Syndrome: Insights into the Neurochemical and Circuit Roots

Rett syndrome (RTT) is a monogenic neurodevelopmental disorder caused by mutations in the methyl‐CpG binding protein 2 (MECP2) gene. Patients with RTT develop symptoms after 6–18 months of age, exhibiting characteristic movement deficits, such as ambulatory difficulties and loss of hand skills, in addition to breathing abnormalities and intellectual disability. Given the striking psychomotor dysfunction, numerous studies have investigated the underlying neurochemical and circuit mechanisms from different aspects. Here, I review the evidence linking MeCP2 deficiency to alterations in neurotransmission and neural circuits that govern the psychomotor function and discuss a recently identified pathological origin underlying the psychomotor deficits in RTT.     

Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease.

Microglial activation is a key feature in Alzheimer's disease and is considered to contribute to progressive neuronal injury by release of neurotoxic products. The innate immune receptor Toll-like-receptor 4 (TLR4), localized on the surface of microglia, is a first-line host defense receptor against invading microorganisms. Here, we show that a spontaneous loss-of-function mutation in the Tlr4 gene strongly inhibits microglial and monocytic activation by aggregated Alzheimer amyloid peptide resulting in a significantly lower release of the inflammatory products IL-6, TNFalpha and nitric oxide. Treatment of primary murine neuronal cells with supernatant of amyloid peptide-stimulated microglia demonstrates that Tlr4 contributes to amyloid peptide-induced microglial neurotoxicity. In addition, stimulation experiments in transfected HEK293 cells allowed to define a tri-molecular receptor complex consisting of TLR4, MD-2 and CD14 necessary for full cellular activation by aggregated amyloid peptide. A clinical relevance of these findings is supported by a marked upregulation of Tlr4 mRNA in APP transgenic mice and by an increased expression of TLR4 in Alzheimer's disease brain tissue associated with amyloid plaque deposition. Together, these observations provide the first evidence for a role of the key innate immune receptor, TLR4, in neuroinflammation in Alzheimer's disease.     

中国鹿类动物遗传相关试验分析研究简述

介绍了国内学者对中国鹿类动物与遗传相关的试验研究的基本情况,涉及血液蛋白等分析、性状相关分析、染色体和线粒体相关分析等方面,对各项内容的总体及各项所采用的技术和方法、部分研究成果进行概述,并对其发展趋势进行展望。     

Tetrandrine Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer BGC-823 Cells

Tetrandrine, a bis-benzylisoquinoline alkaloid isolated from the dried root of Hang-Fang-Chi ( Stephania tetrandra S. Moore), has been reported to possess anti-cancer effects on many tumors. In this study, we investigated tetrandrine-induced apoptosis on human gastric cancer BGC-823 cells in vitro and in vivo. The results showed that tetrandrine significantly inhibited cell viability in a dose- and time-dependent manner and induced apoptosis. It increased the apoptosis; upregulation of Bax, Bak, and Bad; and downregulation of Bcl-2 and Bcl-xl in BGC-823 cells. Moreover, tetrandrine increased the activation of caspase-3 and -9, release of cytochrome c, and upregulation of apaf-1, suggesting that tetrandrine-induced apoptosis was related to the mitochondrial pathway. Meanwhile, pretreatment with the pan-caspase inhibitor z-VAD-fmk in BGC-823 cells reduced tetrandrine-induced apoptosis by blocking activation of caspases. Furthermore, tetrandrine effectively inhibited tumor growth via apoptosis induction, which was verified by immunohistochemical analysis in a nude mouse xenograft model. Taken together, we concluded that tetrandrine significantly inhibited the proliferation of gastric cancer BGC-823 cells through mitochondria-dependent apoptosis, which may play a promising role in gastric cancer therapy.