L,D-转肽酶LdtMt2-厄他培南加合物的新状态Ⅰ-plus结构

具有多重耐药性和广泛耐药性的结核分枝杆菌菌株正在全球范围内传播,因此,迫切需要新的抗结核药物。结核分枝杆菌的L,D-转肽酶LdtMt2直接参与肽聚糖的形成,细菌毒性和β-内酰胺抗性。该酶是潜在的抗结核靶标,可以被碳青霉烯类抗生素抑制,碳青霉烯类抗生素是FDA批准的用于治疗肺结核的药物。据报道,LdtMt2与碳青霉烯类抗生素（如厄他培南,亚胺培南和美洛培南）相互作用时,存在两种不同的中间状态,即状态I和II。状态I被认为是初始加合物形成状态,而状态II被认为是稳定的蛋白质-配体相互作用状态,并伴有碳青霉烯类抗生素和蛋白质的局部构象排列。本文中,我们报告了一个LdMt2-ertapenem新中间状态I-plus,具有与状态II相同的碳青霉烯类抗生素构象和与状态I相似的局部蛋白质构象。该新状态是从状态I转变为状态II的中间状态,构象变化发生在厄他培南分子而不是蛋白质。我们的工作有助于阐明碳青霉烯类抗生素对LdtMt2的作用后发生的变化,并与其他报道的中间状态一起揭示L,D-转肽酶如何与碳青霉烯类抗生素相互作用。     

Migration sources and pathways of the pest species Sogatella furcifera in Yunnan,China, and across the border inferred from DNA and wind analyses

The migration sources and pathways of Sogatella furcifera (Horváth) in topologically complex regions like Yunnan, China, and adjacent montane areas have long been a challenging task and a bottleneck in effective pest forecast and control. The present research reinvestigated this issue using a combination of mtDNA and long‐term historical wind field data in an attempt to provide new insights. Genetic analyses showed that the 60 populations of S. furcufera collected across Myanmar, Thailand, Laos, Vietnam, Yunnan, Guizhou, and Sichuan lack genetic structure and geographic isolation, while spatial analysis of haplotype and diversity indices discovered geographic relevance between populations. Migration rate analysis combined with high‐resolution 10‐year wind field analysis detected the following migration sources, pathways, and impacted areas which could explain the outbreak pattern in Yunnan. (a) Dominating stepwise northward migrations originated from northern Indochina, southern Yunnan, and central‐eastern Yunnan, impacting their northern areas. (b) Concurring summer–autumn southward (return) migration originated from nearly all latitude belts of Sichuan and Yunnan mainly impacting central and southern Yunnan. (c) Regular eastward and summer–autumn westward migrations across Yunnan. The northward migration reflects the temporal rhythm of gradual outbreaks from the south to the north in a year, while the return migration may explain the repeated or very severe outbreaks in the impacted areas. To form a better pest forecast and control network, attention must also be paid to the northern part of Yunnan to suppress the impact of return migration in summers and autumns.     

Aidi injection,a traditional Chinese biomedical preparation for gynecologic tumors: a systematic review and PRISMA-compliant meta-analysis

Aidi injection (ADI), a traditional Chinese biomedical preparation, is a promising adjuvant therapy for gynecologic tumors (GTs), including cervical cancer (CC), endometrial cancer (EC), and ovarian cancer (OC). Although studies have reported positively on ADI therapy, its exact effects and safety in GT patients remain controversial. Therefore, a wide-ranging systematic search of electronic databases was performed for this meta-analysis. Data from 38 trials including 3309 GT patients were analyzed. The results indicated that the combination of conventional treatment and ADI markedly improved the patients’ overall response rate (P<0.00001), disease control rate (P<0.00001), and quality of life (P<0.05) compared with conventional treatment alone. Furthermore, patient immunity was enhanced with combined treatment, as indicated by significantly increased percentages of CD3⁺ (P=0.005) and CD4⁺ (P<0.00001) and increased CD4⁺/CD8⁺ ratio (P=0.001). Most of the adverse events caused by radiochemotherapy such as gastrointestinal issues, leukopenia, thrombocytopenia, and hepatotoxicity, (P<0.05 for all) were significantly alleviated when ADI was used in the GT patients. However, other adverse events such as nephrotoxicity, diarrhea, alopecia, and neurotoxicity did not significantly differ between the two groups. Overall, these results suggest that the combination of conventional and ADI treatment is more effective than conventional treatment alone.     

Cytotoxic,clonal fidelity,and antioxidant evaluation of in vitro propagated Vitex negundo var. cannabifolia

Plant Cell, Tissue and Organ Culture (PCTOC) - Vitex negundo L. var. cannabifolia (Sieb. et Zucc.) Hand.-Mazz. is an important medicinal plant rich in bioactive compounds. In vitro tissue culture...     

Length-weight relationships of eight fish species from the Hailang river,China

The present study reports the length-weight relationships (LWRs) for eight fish species sampled in Hailang River, a left-bank tributary of the Mudan River in Northeast China. The fishes were collected from April to October bimonthly 2017 by electrofishing (fishing 2 kilometers along the river and within 5 meters from the bank) and netting (drift gillnet: mesh size 2 cm × 3 cm; 200 m net length). The specimens were weighed (nearest 0.1 g) and measured (nearest 0.1 cm) in the laboratory. This study provides an update in maximum lengths for five species.     

Immunomodulatory effects of four polysaccharides purified from Erythronium sibiricum bulb on macrophages

Four neutral polysaccharides (ESBP1-1, ESBP1-2, ESBP2-1 and ESBP3-1) were successfully purified from the water extracted crude polysaccharides of Erythronium sibiricum bulbs through the combination of DEAE Sepharose CL-6B and Sephadex G-100 chromatography; their average molecular weights were 1.3?×?10⁴, 1.7?×?10⁴, 9.4?×?10⁵ and 4.1?×?10⁵ Da, respectively. Monosaccharide component analysis indicated that ESBP1-1 and ESBP1-2 were mainly composed of glucose (Glc). ESBP2-1 was composed of Glc, galactose (Gal) and arabinose, with a molar ratio of 24.3:1.1:1, whereas ESBP3-1 comprised Glc and Gal at a molar ratio of 14.8:1. In-vitro study showed that all of the four polysaccharides were able to considerably promote the proliferation and neutral red phagocytosis of RAW 264.7 macrophage cell. They could also stimulate the production of the cell lines’ secretory molecules [nitric oxide, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)] in a dose-dependent manner. However, ESBP1-2 was not included in IL-1β. Overall, these results suggested that polysaccharides from E. sibiricum bulbs can be developed as immunomodulatory ingredients for complementary medicines or functional foods. However, further animal or clinical studies are required.

     

Isoflurane promotes proliferation of squamous cervical cancer cells through mTOR-histone deacetylase 6 pathway

Molecular and Cellular Biochemistry - This study investigated the effect of isoflurane on the proliferation of squamous cervical cancer cells, with focus on histone deacetylase 6 that is closely...