Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

AbstractA novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71 (EV71) and the coxsackievirus B3 (CVB3) and B6 (CVB6) were evaluated. Compounds 7d and 9b showed potent antiviral activities against EV71 with IC50 values of 8.27 and 5.48μM, respectively. Compound 7f, which has been synthesized for the first time in this work, showed the highest level of inhibitory activity against both CVB3 and CVB6 with an IC50 value of 0.62 and 0.87μM. Compounds 4b, 7a, 9c and 9e also showed strong inhibitory activities against both the CVB3 and CVB6 at low concentrations (IC50=1.42−7.15μM), whereas compounds 4d, 7c, 7e and 7g showed strong activity against CVB6 (IC50=2.91–3.77μM) together with low levels of activity against CVB3. Compound 7d exhibited stronger inhibitory activity against CVB3 (IC50=6.44μM) than CVB6 (IC50>8.29μM). The thioflavone derivatives 7a, 7c, 7d, 7e, 7f and 7g, represent a new class of lead compounds for the development of novel antiviral agents

Synthesis and antiviral activity of some novel indole-2-carboxylate derivatives

A series of novel indole-2-carboxylate derivatives were synthesized and assayed to determine their in vitro broad-spectrum antiviral activities. The biological results showed that some of the synthesized compounds exhibited potent broad-spectrum antiviral activity. Notably, compound 8f showed the highest SI value (17.1) to Cox B3 virus. Compound 14f showed both potent inhibitory activity against influenza A (IC50=7.53 μmol/L) and the highest SI value (12.1). SAR results showed that the alkyloxy at the 4-position of indole ring was not crucial to the antiviral activities. Incorporation of an acetyl substituent at the amino group disfavored antiviral activity towards RNA viruses

Complete Genome Sequence and Function Gene Identify of Prometryne-Degrading Strain Pseudomonas sp. DY-1

The genus Pseudomonas is widely recognized for its potential for environmental remediation and plant growth promotion. Pseudomonas sp. DY-1 was isolated from the agricultural soil contaminated five years by prometryne, it manifested an outstanding prometryne degradation efficiency and an untapped potential for plant resistance improvement. Thus, it is meaningful to comprehend the genetic background for strain DY-1. The whole genome sequence of this strain revealed a series of environment adaptive and plant beneficial genes which involved in environmental stress response, heavy metal or metalloid resistance, nitrate dissimilatory reduction, riboflavin synthesis, and iron acquisition. Detailed analyses presented the potential of strain DY-1 for degrading various organic compounds via a homogenized pathway or the protocatechuate and catechol branches of the β-ketoadipate pathway. In addition, heterologous expression, and high efficiency liquid chromatography (HPLC) confirmed that prometryne could be oxidized by a Baeyer-Villiger monooxygenase (BVMO) encoded by a gene in the chromosome of strain DY-1. The result of gene knock-out suggested that the sulfate starvation-induced (SSI) genes in this strain might also involve in the process of prometryne degradation. These results would provide the molecular basis for the application of strain DY-1 in various fields and would contribute to the study of prometryne biodegradation mechanism as well

Robust tracking with per‐exemplar support vector machine

The authors extend exemplar representation to the field of tracking and propose a robust tracking algorithm with per‐exemplar support vector machine (SVM) classifiers. First, the authors train the simple yet effective exemplar SVM classifier using the target object as the single positive and mining its surroundings as hard negatives. Second, the authors propose an online ensemble tracker, which integrates the useful ‘key historical templates’ of the target to refine the current template, leading to better discriminative power of tracker and effectively decreasing the risk of drift. Experiments on challenging sequences demonstrate that the tracker performs well in accuracy and robustness, especially under the sequences with strong illumination variation and scale variation, as well as pose change and partial occlusion in the long‐time sequence

Comparative Proteomic Analyses within Three Developmental Stages of the Mushroom White Hypsizygus marmoreus

(1) Background: The Hypsizygus marmoreus is a popular edible mushroom in East Asian markets. In a previous study, we reported the proteomic analyses of different developmental stages of H. marmoreus, from primordium to mature fruiting body. However, the growth and protein expression changes from scratching to primordium are unclear. (2) Methods: A label-free LC-MS/MS quantitative proteomic analysis technique was adopted to obtain the protein expression profiles of three groups of samples collected in different growth stages from scratching to the tenth day after scratching. The Pearson’s correlation coefficient analysis and principal component analysis were performed to reveal the correlation among samples. The differentially expressed proteins (DEPs) were organized. Gene Ontology (GO) analysis was performed to divide the DEPs into different metabolic processes and pathways. (3) Results: From the 3rd day to the 10th day after scratching, mycelium recovered gradually and formed primordia. Compared with the Rec stage, 218 highly expressed proteins were identified in the Knot stage. Compared with the Pri stage, 217 highly expressed proteins were identified in the Rec stage. Compared with the Pri stage, 53 highly expressed proteins were identified in the Knot stage. A variety of the same highly expressed proteins were identified in these three developmental stages, including: glutathione S-transferase, acetyltransferase, importin, dehydrogenase, heat-shock proteins, ribosomal proteins, methyltransferase, etc. The key pathways in the development of H. marmoreus are metabolic process, catabolic process, oxidoreductase activity and hydrolase activity. DEPs in the Knot or Pri stages compared with the Rec stage were significantly decreased in the metabolic-, catabolic- and carbohydrate-related process; and the oxidoreductase, peptidase, and hydrolase activity, which can serve as targets for selectable molecular breeding in H. marmoreus. A total of 2000 proteins were classified into eight different modules by WGCNA, wherein 490 proteins were classified into the turquoise module. (4) Conclusions: Generally, from the 3rd day to the 10th day after scratching, mycelium recovered gradually and formed primordia. Importin, dehydrogenase, heat-shock proteins, ribosomal proteins, transferases were all highly expressed in these three developmental stages. DEPs in the Rec stage compared with the Knot or Pri stages were significantly enriched in the metabolic-, catabolic- and carbohydrate-related process; and in oxidoreductase, peptidase and hydrolase activities. This research contributes to the understanding of the mechanisms of the development changes before primordium of H. marmoreus

Chinese Herbal Formula Feilin Vaginal Gel Prevents the Cervicitis in Mouse Model

Cervicitis is a common sexually transmitted disease. In recent years, the abuse of antibiotic in the treatment of cervicitis results in the emergence of antibiotic-resistant bacteria; alternative strategies are needed to be developed. In this research, we investigated the effects of Feilin Vaginal Gel (FVG), a Chinese herbal formula, on the treatment of cervicitis. Two cervicitis models were optimized using BALB/c mouse; one in vitro model was established in HeLa cells. In Chlamydia trachomatis-induced cervicitis model, the high level of bacterial loads, the inflammation in tissue, and the cytokines in serum could be observed. With the administration of FVG, the bacterial loads in cervical mucus and cervix tissue could be significantly inhibited in dose-dependent manners. The pathological injury of cervix and vagina, as well as the levels of IL-2, IL-17, and MCP-1 in serum, could be mitigated by FVG. FVG reduced the number of inclusion induced by C. trachomatis in HeLa cells. In addition, the histological damage in Escherichia coli and Staphylococcus aureus-induced cervicitis model could be reduced by FVG. These results suggest that FVG is capable of treating cervicitis through the inhibition of pathogens and the regulation of host immune responses. FVG may contribute as an alternative agent for the treatment of cervicitis

Total Syntheses of (−)-Spirooliganones A and B and Their Diastereoisomers: Absolute Stereochemistry and Inhibitory Activity against Coxsackie Virus B3

To investigate the effects of configuration on bioactivity, spirooliganones A and B and their six diastereoisomers (<b>1</b>–<b>8</b>) were synthesized in 11 steps. The key benzopyran core was assembled by intermolecular [4 + 2] hetero-Diels–Alder cycloaddition between (−)-sabinene and <i>o</i>-quinone methide, which was generated from the corresponding <i>o</i>-hydroxybenzyl alcohol. After establishing the absolute configuration, the inhibitory activities of spirooliganones <b>1</b>–<b>8</b> against Coxsackie virus B3 were evaluated, and the primary structure–activity relationships were analyzed. Compound <b>3</b> was the most potent compound, with an IC₅₀ of 0.41 μM

Accuracy of Xpert® MTB/RIF Ultra test for posterior oropharyngeal saliva for the diagnosis of paucibacillary pulmonary tuberculosis: a prospective multicenter study

ABSTRACTBackground: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. Methods: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. Findings: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8–83.8] and 56.4% (95% CI: 49.7–62.9), respectively; the specificities were 96.6% (95% CI: 94.3–98.1) for X-Ultra and 97.6 (95CI: 95.5–98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5–61.2; 193/345) and 40.0% (95% CI: 34.8–45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. Conclusions: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care