Pterostilbene protects against UVB-induced photo-damage through a phosphatidylinositol-3-kinase-dependent Nrf2/ARE pathway in human keratinocytes

Objective: Ultraviolet B (UVB) irradiation is the initial etiological factor for various skin disorders, including erythema, sunburn, photoaging, and photocarcinogenesis. Pterostilbene (Pter) displayed remarkable antioxidant, anti-inflammatory, and anticarcinogenic activities. This study aimed to investigate the effective mechanism of Pter against UVB-induced photodamage in immortalized human keratinocytes.

Methods: Human keratinocytes were pretreated with Pter (5 and 10?μM) for 24?h prior to UVB irradiation (300?mJ/cm²). Harvested cells were analyzed by MTT, DCFH-DA, comet, western blotting, luciferase promoter, small interference RNA transfection, and quantitative real-time polymerase chain reaction assay.

Results: Pter significantly attenuated UVB-induced cell death and reactive oxygen species (ROS) generation, and effectively increased nuclear translocation of NF-E2-related factor-2 (Nrf2), expression of Nrf2-dependent antioxidant enzymes, and DNA repair activity. Moreover, the protective effects of Pter were abolished by small interference RNA-mediated Nrf2 silencing. Furthermore, Pter was also found to induce the phosphorylation of Nrf2 and the known phosphatidylinositol-3-kinase (PI3K) phosphorylated kinase, Akt. The specific inhibitor of PI3K, LY294002, successfully abrogated Pter-induced Nrf2 phosphorylation, activation of Nrf2-antioxidant response element pathway, ROS scavenging ability, and DNA repair activity.

Conclusion: The present study indicated that Pter effectively protected against UVB-induced photodamage by increasing endogenous defense mechanisms, scavenging UVB-induced ROS, and aiding in damaged DNA repair through a PI3K-dependent activation of Nrf2/ARE pathway.     

Three‐Stage Inter‐Orthorhombic Evolution and High Thermoelectric Performance in Ag‐Doped Nanolaminar SnSe Polycrystals

The ultrahigh thermoelectric performance of SnSe‐based single crystals has attracted considerable interest in their polycrystalline counterparts. However, the temperature‐dependent structural transition in SnSe‐based thermoelectric materials and its relationship with their thermoelectric performance are not fully investigated and understood. In this work, nanolaminar SnSe polycrystals are prepared and characterized in situ using neutron and synchrotron powder diffraction measurements at various temperatures. Rietveld refinement results indicate that there is a complete inter‐orthorhombic evolution from Pnma to Cmcm by a series of layer slips and stretches along the a‐ and b‐axes over a 200 K temperature range. This phase transition leads to drastic enhancement of the carrier concentration and phonon scattering above 600 K. Moreover, the unique nanolaminar structure effectively enhances the carrier mobility of SnSe. Their grain and layer boundaries further improve the phonon scattering. These favorable factors result in a high ZT of 1.0 at 773 K for pristine SnSe polycrystals. The thermoelectric performances of polycrystalline SnSe are further improved by p‐type and n‐type dopants (i.e., doped with Ag and SnCl₂, respectively), and new records of ZT are achieved in Ag_0.015Sn_0.985Se (ZT of 1.3 at 773 K) and SnSe_0.985Cl_0.015 (ZT of 1.1 at 773 K) polycrystals.     

Dissociation of PTPase levels from their modulation of insulin receptor signal transduction

Protein tyrosine phosphatases have been implicated in the regulation of receptor tyrosine kinase signalling pathways, including that of the insulin receptor. Here, cell density-dependent changes in PTPase expression have been exploited to investigate the relationship between cellular PTPase levels and the insulin receptor signal transduction pathway. Increasing cell density (20%, 50%, and >90%) in the rat McA-RH7777 hepatoma cell line resulted in increased protein expression of the receptor-like PTPase LAR (14-fold), and the nonreceptor PTPases PTP1B (11-fold) and SHP2 (10-fold). Each of these PTPases has previously been implicated in regulating insulin receptor signal transduction. Despite these marked increases, maximum insulin receptor autophosphorylation as well as receptor expression actually increased 2-fold. MAP kinase also increased approximately 2-fold as a function of cell density and paralleled increases in expression levels. Neither sensitivity nor maximum responsiveness to insulin were decreased at increasing cell densities as assessed by activation of PI 3-kinase. Duration of response was also unimpaired. These results suggest that expression levels of relevant PTPases are not the primary determinant in their modulation of insulin receptor kinase activity. Restricted accessibility at the molecular level or involvement of accessory proteins may be more critical parameters.     

Varicella-Zoster Virus Fc Receptor Component gI Is Phosphorylated on Its Endodomain by a Cyclin-Dependent Kinase

Varicella-zoster virus (VZV) glycoprotein gI is a type 1 transmembrane glycoprotein which is one component of the heterodimeric gE:gI Fc receptor complex. Like VZV gE, VZV gI was phosphorylated in both VZV-infected cells and gI-transfected cells. Preliminary studies demonstrated that a serine 343-proline 344 sequence located within the gI cytoplasmic tail was the most likely phosphorylation site. To determine which protein kinase catalyzed the gI phosphorylation event, we constructed a fusion protein, consisting of glutathione-S-transferase (GST) and the gI cytoplasmic tail, called GST-gI-wt. When this fusion protein was used as a substrate for gI phosphorylation in vitro, the results demonstrated that GST-gI-wt fusion protein was phosphorylated by a representative cyclin-dependent kinase (CDK) called P-TEFb, a homologue of CDK1 (cdc2). When serine 343 within the serine-proline phosphorylation site was replaced with an alanine residue, the level of phosphorylation of the gI fusion protein was greatly reduced. Subsequent experiments with individually immunoprecipitated mammalian CDKs revealed that the VZV gI fusion protein was phosphorylated best by CDK1, to a lesser degree by CDK2, and not at all by CDK6. Transient-transfection assays carried out in the presence of the specific CDK inhibitor roscovitine strongly supported the prior results by demonstrating a marked decrease in gI phosphorylation while gI protein expression was unaffected. Finally, the possibility that VZV gI contained a CDK phosphorylation site in its endodomain was of further interest because its partner, gE, contains a casein kinase II phosphorylation site in its endodomain; prior studies have established that CDK1 can phosphorylate casein kinase II.     

ISOLATION OF RICKETTSIA TSUTSUGAMUSHI FROM TROMBICULID MITES (ACARI:TROMBICULIDAE) IN FEIXIAN COUNTY, SHANDONG PROVINCE, CHINA

Abstract  Investigations on trombiculid mites and isolation of Rickettsia tsutsugamushi therefrom were carried out in Feixian County, Shandong Province. A total of 11 762 trombiculid mites, consisting of 5 species from two genera, were collected from 352 rodents (including 247 Apodemus agrarius , 80 Cricetulus triton , 23 Rattus noruegicus , 2 Crocidura suaveolens ), and Walchia pacifica was the most predominant (36.73%), followed by Leptotrombididium linhuaikonense (24.04%), L. scutellare (21.65%), L. palpale (13. 57%), and L. taishanium (3. 96%). L. scutellare was found from September to December with a remarkable peak in November, whereas L. palpale occurred from October to April (the second year) with peak in December. L. linhuaikonense was found from May to November, with peak in August. W. pacifica appeared from April to December with peak in July. R. tsutsugamushi was isolated from L. scutellare, L. palpale, L. linhuaikonense and W. pacifica . The main serotypes of R. tsutsugamushi isolated from the chigger mites were of the Gilliam type, but Karp type also existed in L. linhuaikonense . These results indicate that the surveyed area has a high probability of occurrence of tsutsugamushi disease, and L. scutellare, L. palpale, L. linhuaikonense and W. pacifica may serve as the vectors in this area. It is suggested that L. scutellare is the most important vector which has caused the endemic of this disease in Feixian County.     

非人灵长类声音通讯的研究进展

声音通讯是非人灵长类研究一个重要的研究领域,有助于了解非人灵长类的社会行为、个体关系、行为进化和社会演化等,甚至对探究人类语言起源和进化等方面也具有十分重要的意义。本文通过对非人灵长类声音通讯的研究内容、影响因素和研究方法等进行了梳理,探讨非人灵长类声音通讯研究的前景和展望,旨在进一步推动国内非人灵长类声音通讯研究的深入,同时为相关研究提供借鉴和参考。     

云南高黎贡山地区蝴蝶群落多样性

位于滇西北的高黎贡山是全球生物多样性研究和保护的热点地区之一, 然而该地区昆虫多样性缺乏系统调查和总结。本研究聚焦蝴蝶类群, 考虑该区域高山峡谷特点, 结合海拔梯度、生境类型和季节变化, 采用样线法调查、分析蝴蝶物种多样性及群落结构变化。结果显示: 共观测记录到蝴蝶2,055只, 隶属于5科85属151种, 在历史记录上新增27种, 使该地区已知蝴蝶种类达488种; 其中蛱蝶科物种多样性最高, 灰蝶科次之, 凤蝶科最低。蝴蝶群落多样性分析结果表明: 中海拔1,000-2,000 m区域种类丰富、多样性指数最高; 低海拔区蝴蝶分布明显聚集, 并且与高海拔地区空间上分离, 少有重叠。该地区不同生境中蝴蝶的种类及数量差异也较大, 物种数及多样性指数在自然保护区最高、边缘交错带居中及农业种植区最低。此外, 蝴蝶的种类和数量也存在季节差异, 春季调查到的个体数少, 夏季观察到的物种数少, 两年秋季调查到的物种丰富度、多样性均高, 但存在季节内变化。总之, 高黎贡山地区不同海拔、生境、季节间和季节内蝴蝶群落组成有自身特点, 共存物种有限, 蝴蝶群落相似性低。综合评估分布于该地区的蝴蝶保护种类, 包括易危种17种、近危种50种, 有国家二级保护蝴蝶3种。本研究弄清了高黎贡山地区蝴蝶的物种本底, 并调查获得其多样性随海拔、生境和季节变化的模式, 为加强区域物种多样性监测、保护生物多样性提供了科学依据。     

Auxin-mediated induction of GAL promoters by conditional degradation of Mig1p improves sesquiterpene production in Saccharomyces cerevisiae with engineered acetyl-CoA synthesis

The yeast Saccharomyces cerevisiae uses the pyruvate dehydrogenase-bypass for acetyl-CoA biosynthesis. This relatively inefficient pathway limits production potential for acetyl-CoA-derived biochemical due to carbon loss and the cost of two high-energy phosphate bonds per molecule of acetyl-CoA. Here, we attempted to improve acetyl-CoA production efficiency by introducing heterologous acetylating aldehyde dehydrogenase and phosphoketolase pathways for acetyl-CoA synthesis to enhance production of the sesquiterpene trans-nerolidol. In addition, we introduced auxin-mediated degradation of the glucose-dependent repressor Mig1p to allow induced expression of GAL promoters on glucose so that production potential on glucose could be examined. The novel genes that we used to reconstruct the heterologous acetyl-CoA pathways did not sufficiently complement the loss of endogenous acetyl-CoA pathways, indicating that superior heterologous enzymes are necessary to establish fully functional synthetic acetyl-CoA pathways and properly explore their potential for nerolidol synthesis. Notwithstanding this, nerolidol production was improved twofold to a titre of ˜ 900 mg l⁻¹ in flask cultivation using a combination of heterologous acetyl-CoA pathways and Mig1p degradation. Conditional Mig1p depletion is presented as a valuable strategy to improve the productivities in the strains engineered with GAL promoters-controlled pathways when growing on glucose.     

The progress and perspectives of CAR-T cell therapy

CAR-T cell therapy has already achieved world-renowned clinical effects in the treatment of hematological malignancies. Due to the tumor heterogeneity, immunosuppressive microenvironment, and other factors, CAR-T cell therapy has still not shown obvious clinical efficacy in clinical treatment of solid tumors. However, great progress has been made in the preparation of CAR-T cells in recent years, including T cells redirected for universal cytokine mediated killing, universal CAR -T cells, non-viral vector CAR-T cells, SynNotch technology, SUPRA CAR technology, regulated CAR-T cells, and bi-specific CAR-T cells, etc. Future research and development of CAR-T cell therapy will be focused on these following aspects: the combined application of CAR-T cells with different targets, known as "Cocktail CAR-T cells", is expected to increase efficiency toward solid tumors; based on systemic biology/synthetic biology theories, CAR-T cells are likely to be transformed to robot or intelligent system by introducing sensors, logic gates, and logic circuits. This article mainly comments on research progress and perspectives on CAR-T cell therapy in solid tumor treatment.