Metabolites from Two Dominant Thermophilic Fungal Species Thermomyces lanuginosus and Scytalidium thermophilum

Thermomyces lanuginosus and Scytalidium thermophilum are among the most ubiquitous thermophilic fungi in compost and soil. Chemical study on these two prevalent strains collected from Yunnan led to isolation of 23 metabolites, including one new metabolite, therlanubutanolide, and 15 known compounds, isolated from the YGP culture broth of Thermomyces lanuginosus and 7 known compounds isolated from Scytalidium thermophilum, respectively. Therlanubutanolide shared the quite similar features of the same carbon skeleton and saturation as natural hexadecanoic acids. This was the first reported discovery of such a lactone as natural occurring metabolite. All the compounds were reported for the first time from thermophilic fungi. Among them, N‐[(2S,3R,4E,8E)‐1,3‐dihydroxy‐9‐methyloctadeca‐4,8‐dien‐2‐yl]acetamide was for the first time reported to be a naturally occurring metabolite and its NMR data was first provided in this study. A type of PKS‐derived metabolites, three 3,4‐dihydronaphthalen‐1(2H)‐ones, which were widely found in plant pathogenic fungi as phytotoxins and reported to have antimicrobial activity, were obtained from both dominant thermophilic fungi. The frequent occurrence of such PKS phytotoxins in these two thermophilic fungi might suggest particular ecological interest.     

miRNA‐182/Deptor/mTOR axis regulates autophagy to reduce intestinal ischaemia/reperfusion injury

It had been reported miR‐182 was down‐regulated after intestinal ischaemia/reperfusion (I/R) damage. However, its role and potential mechanisms are still unknown. This study was aimed to elucidate the function of miR‐182 in intestinal I/R injury and the underlying mechanisms. The model of intestinal injury was constructed in wild‐type and Deptor knockout (KO) mice. Haematoxylin‐eosin staining, Chiu's score and diamine oxidase were utilized to detect intestinal damage. RT‐qPCR assay was used to detected miR‐182 expression. Electronic microscopy was used to detect autophagosome. Western blot was applied to detect the expression of Deptor, S6/pS6, LC3‐II/LC3‐I and p62. Dual‐luciferase reporter assay was used to verify the relationship between miR‐182 and Deptor. The results showed miR‐182 was down‐regulated following intestinal I/R. Up‐regulation of miR‐182 reduced intestinal damage, autophagy, Deptor expression and enhanced mTOR activity following intestinal I/R. Moreover, suppression of autophagy reduced intestinal damage and inhibition of mTOR by rapamycin aggravated intestinal damage following intestinal I/R. Besides, damage of intestine was reduced and mTOR activity was enhanced in Deptor KO mice. In addition, Deptor was the target gene of miR‐182 and was indispensable for the protection of miR‐182 on intestine under I/R condition. Together, our research implicated up‐regulation of miR‐182 inhibited autophagy to alleviate intestinal I/R injury via mTOR by targeting Deptor.     

Rational Design of Hydroxyl‐Rich Ti3C2Tx MXene Quantum Dots for High‐Performance Electrochemical N2 Reduction

To enable an efficient and cost‐effective electrocatalytic N₂ reduction reaction (NRR) the development of an electrocatalyst with a high NH₃ yield and good selectivity is required. In this work, Ti₃C₂T_x MXene‐derived quantum dots (Ti₃C₂T_x QDs) with abundant active sites enable the development of efficient NRR electrocatalysts. Given surface functional groups play a key role on the electrocatalytic performance, density functional theory calculations are first conducted, clarifying that hydroxyl groups on Ti₃C₂T_x offer excellent NRR activity. Accordingly, hydroxyl‐rich Ti₃C₂T_x QDs (Ti₃C₂OH QDs) are synthesized as NRR catalysts by alkalization and intercalation. This material offers an NH₃ yield and Faradaic efficiency of 62.94 µg h^?1 mg^?1_cat. and 13.30% at ?0.50 V, respectively, remarkably higher than reported MXene catalysts. This work demonstrates that MXene catalysts can be mediated through the optimization of both QDs sizes and functional groups for efficient ammonia production at room temperature.     

Effect of Different Culture Systems and 3, 5, 3'-Triiodothyronine/Follicle-Stimulating Hormone on Preantral Follicle Development in Mice

The mechanical method to isolate preantral follicle has been reported for many years. However, the culture systems in vitro are still unstable. The aim of this study was to analyze the effect of the culture system of mice preantral follicles on the follicular development in vitro. The results showed that the 96-well plate system was the most effective method for mice follicle development in vitro (volume change: 51.71%; survival rate: 89%, at day 4). Follicle-stimulating hormone (FSH) and Thyroid hormone (TH) are important for normal follicular development and dysregulation of hormones are related with impaired follicular development. To determine the effect of hormone on preantral follicular development, we cultured follicle with hormones in the 96-well plate culture system and found that FSH significantly increased preantral follicular growth on day 4. The FSH-induced growth action was markedly enhanced by T₃ although T₃ was ineffective alone. We also demonstrated by QRT-PCR that T₃ significantly enhanced FSH-induced up-regulation of Xiap mRNA level. Meanwhile, Bad, cell death inducer, was markedly down-regulated by the combination of hormones. Moreover, QRT-PCR results were also consistent with protein regulation which detected by Western Blotting analysis. Taken together, the findings of the present study demonstrate that 96-well plate system is an effective method for preantral follicle development in vitro. Moreover, these results provide insights on the role of thyroid hormone in increasing FSH-induced preantral follicular development, which mediated by up-regulating Xiap and down-regulating Bad.     

Periodontal Disease and Risk of Head and Neck Cancer: A Meta-Analysis of Observational Studies

Background

Many epidemiological studies have found a positive association of periodontal disease (PD) with risk of head and neck cancer (HNC), but the findings are varied or even contradictory. In this work, we performed a meta-analysis to ascertain the relationship between PD and HNC risk.

Methods

We searched the PubMed, Embase, and Cochrane Library databases for relevant observational studies on the association between PD and HNC risk published up to March 23, 2013. Data from the included studies were extracted and analyzed independently by two authors. Meta-analysis was performed using RevMan 5.2 software.

Results

We obtained seven observational studies involving two cohort and six case-control studies. Random-effects meta-analysis indicated a significant association between PD and HNC risk (odds ratio = 2.63, 95% confidence interval = 1.1.68 - 4.14; p < 0.001), with sensitivity analysis showing that the result was robust. Subgroup analyses based on adjustment for covariates, study design, PD assessment, tumor site, and ethnicity also revealed a significant association.

Conclusions

Based on currently evidence, PD is probably a significant and independent risk factor of HNC.     

HER2 as a Promising Target for Cytotoxicity T Cells in Human Melanoma Therapy

Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu⁺ tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.     

Surface Roughness Detection of Arteries via Texture Analysis of Ultrasound Images for Early Diagnosis of Atherosclerosis

There is a strong research interest in identifying the surface roughness of the carotid arterial inner wall via texture analysis for early diagnosis of atherosclerosis. The purpose of this study is to assess the efficacy of texture analysis methods for identifying arterial roughness in the early stage of atherosclerosis. Ultrasound images of common carotid arteries of 15 normal mice fed a normal diet and 28 apoE^−/− mice fed a high-fat diet were recorded by a high-frequency ultrasound system (Vevo 2100, frequency: 40 MHz). Six different texture feature sets were extracted based on the following methods: first-order statistics, fractal dimension texture analysis, spatial gray level dependence matrix, gray level difference statistics, the neighborhood gray tone difference matrix, and the statistical feature matrix. Statistical analysis indicates that 11 of 19 texture features can be used to distinguish between normal and abnormal groups (p<0.05). When the 11 optimal features were used as inputs to a support vector machine classifier, we achieved over 89% accuracy, 87% sensitivity and 93% specificity. The accuracy, sensitivity and specificity for the k-nearest neighbor classifier were 73%, 75% and 70%, respectively. The results show that it is feasible to identify arterial surface roughness based on texture features extracted from ultrasound images of the carotid arterial wall. This method is shown to be useful for early detection and diagnosis of atherosclerosis.     

Pharmacophore Modeling and Virtual Screening for the Discovery of New type 4 cAMP Phosphodiesterase (PDE4) Inhibitors

Type 4 cAMP phosphodiesterase (PDE4) inhibitors show a broad spectrum of anti-inflammatory effects in almost all kinds of inflamed cells, by an increase in cAMP levels which is a pivotal second messenger responsible for various biological processes. These inhibitors are now considered as the potential drugs for treatment of chronic inflammatory diseases. However, some recently marketed inhibitors e.g., roflumilast, have shown adverse effects such as nausea and emesis, thus restricting its use. In order to identify novel PDE4 inhibitors with improved therapeutic indexes, a highly correlating (r = 0.963930) pharmacophore model (Hypo1) was established on the basis of known PDE4 inhibitors. Validated Hypo1 was used in database screening to identify chemical with required pharmacophoric features. These compounds are further screened by using the rule of five, ADMET and molecular docking. Finally, twelve hits which showed good results with respect to following properties such as estimated activity, calculated drug-like properties and scores were proposed as potential leads to inhibit the PDE4 activity. Therefore, this study will not only assist in the development of new potent hits for PDE4 inhibitors, but also give a better understanding of their interaction with PDE4. On a wider scope, this will be helpful for the rational design of novel potent enzyme inhibitors.