MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma

Glioblastoma multiforme is the most aggressive and common primary brain tumor, and is virtually incurable due to its therapeutic resistance to radiation and chemotherapy. Curcumin is a well-known phytochemical exhibiting antitumor activity on many human cancers including glioblastoma multiforme. Given the unique miRNA expression profiles in cancer cells compared to non-cancerous cells, we investigated whether these miRNA could be used to cancer therapy. In this report we show that miR-378, a glioblastoma multiforme down regulated miRNA, may enhance the inhibitory effect of curcumin on this cancer growth. Our results indicated that the inhibitory effect of curcumin was enhanced in miR-378-expressing stable U87 cells in vitro and in vivo, compared to control cells. MiR-378 was found to target p-p38 expression, underlying the observed phenotypic changes. Thus, we concluded that miR-378 enhances the response of glioblastoma multiforme to curcumin treatment, by targeting p38

Beauvericin counteracted multi-drug resistant Candida albicans by blocking ABC transporters

AbstractMulti-drug resistance of pathogenic microorganisms is becoming a serious threat, particularly to immunocompromised populations. The high mortality of systematic fungal infections necessitates novel antifungal drugs and therapies. Unfortunately, with traditional drug discovery approaches, only echinocandins was approved by FDA as a new class of antifungals in the past two decades. Drug efflux is one of the major contributors to multi-drug resistance, the modulator of drug efflux pumps is considered as one of the keys to conquer multi-drug resistance. In this study, we combined structure-based virtual screening and whole-cell based mechanism study, identified a natural product, beauvericin (BEA) as a drug efflux pump modulator, which can reverse the multi-drug resistant phenotype of Candida albicans by specifically blocking the ATP-binding cassette (ABC) transporters; meantime, BEA alone has fungicidal activity in vitro by elevating intracellular calcium and reactive oxygen species (ROS). It was further demonstrated by histopathological study that BEA synergizes with a sub-therapeutic dose of ketoconazole (KTC) and could cure the murine model of disseminated candidiasis. Toxicity evaluation of BEA, including acute toxicity test, Ames test, and hERG (human ether-à-go-go-related gene) test promised that BEA can be harnessed for treatment of candidiasis, especially the candidiasis caused by ABC overexpressed multi-drug resistant C. albicans

A comparative analysis of morphology, microstructure, and volatile metabolomics of leaves at varied developmental stages in Ainaxiang (Blumea balsamifera (Linn.) DC.)

IntroductionAinaxiang (Blumea balsamifera (Linn.) DC.) is cultivated for the extraction of (-)-borneol and other pharmaceutical raw materials due to its abundant volatile oil. However, there is limited knowledge regarding the structural basis and composition of volatile oil accumulation in fresh B. balsamifera leaves.MethodsTo address this problem, we compare the fresh leaves’ morphology, microstructure, and volatile metabonomic at different development stages, orderly defined from the recently unfolded young stage (S1) to the senescent stage (S4).Results and discussionDistinct differences were observed in the macro-appearance and microstructure at each stage, particularly in the B. balsamifera glandular trichomes (BbGTs) distribution. This specialized structure may be responsible for the accumulation of volatile matter. 213 metabolites were identified through metabolomic analysis, which exhibited spatiotemporal accumulation patterns among different stages. Notably, (-)-borneol was enriched at S1, while 10 key odor metabolites associated with the characteristic balsamic, borneol, fresh, and camphor aromas of B. balsamifera were enriched in S1 and S2. Ultra-microstructural examination revealed the involvement of chloroplasts, mitochondria, endoplasmic reticulum, and vacuoles in the synthesizing, transporting, and storing essential oils. These findings confirm that BbGTs serve as the secretory structures in B. balsamifera, with the population and morphology of BbGTs potentially serving as biomarkers for (-)-borneol accumulation. Overall, young B. balsamifera leaves with dense BbGTs represent a rich (-)-borneol source, while mesophyll cells contribute to volatile oil accumulation. These findings reveal the essential oil accumulation characteristics in B. balsamifera, providing a foundation for further understanding

Microfluidic Platform for Investigating Osteocyte Mechanoregulation of Breast Cancer Bone Metastasis

Bone metastasis is a severe complication that occurs in approximately 85% of patients with advanced breast cancer. Although the potential of exercise in attenuating metastatic tumor growth in bone had been shown in vivo, the role of mechanical loading on bone in preventing bone metastasis remains unknown. Osteocytes, as the major mechanosensory bone cells, are identified regulators in mediating loading inhibited bone metastasis in vitro. However, there is no ideal platform currently available for investigating the impact and mechanism underlying loading reduced bone metastasis. To bridge the gap between in vivo and in vitro experiments, this thesis develops a novel microfluidic cancer extravasation platform that integrates bone mechanical loading and real-time bi-directional signaling between multiple cell populations within the bone metastasis environment. Using our microfluidic extravasation platform, we observed the overall effect that mechanically-stimulated osteocytes regulate breast cancer transendothelial extravasation indeed, and the specific impact is breast cancer type dependent.M.A.S

Forecasting the Volatility of European Union Allowance Futures with Climate Policy Uncertainty Using the EGARCH-MIDAS Model

We propose the EGARCH-MIDAS-CPU model, which incorporates the leverage effect and climate policy uncertainty (CPU) to model and forecast European Union allowance futures’ (EUAF) volatility. An empirical analysis based on the daily data of the EUAF price index and the monthly data of the CPU index using the EGARCH-MIDAS-CPU model shows that the EUAF’s volatility exhibits a leverage effect, and the CPU has a significantly negative impact on the EUAF’s volatility. Furthermore, out-of-sample analysis based on three loss functions and the Model Confidence Set (MCS) test suggests that EGARCH-MIDAS-CPU model yields more accurate out-of-sample volatility forecasting results than various competing models. There is room for further application of the model, such as this model could be applied to price carbon futures, so as to improve the liquidity of the carbon market and achieve carbon peak and carbon neutrality as soon as possible

Assessing Population Structure and Signatures of Selection in Wanbei Pigs Using Whole Genome Resequencing Data

Wanbei pig (WBP) is one of the indigenous pig resources in China and has many germplasm characteristics. However, research on its genome is lacking. To assess the genomic variation, population structure, and selection signatures, we resequenced 18 WBP for the first time and performed a comprehensive analysis with resequenced data of 10 Asian wild boars. In total, 590.03 Gb of data and approximately 41 million variants were obtained. Polymorphism level (θπ) ratio and genetic differentiation (fixation index)-based cross approaches were applied, and 539 regions, which harbored 176 genes, were selected. Functional analysis of the selected genes revealed that they were associated with lipid metabolism (SCP2, APOA1, APOA4, APOC3, CD36, BCL6, ADCY8), backfat thickness (PLAG1, CACNA2D1), muscle (MYOG), and reproduction (CABS1). Overall, our results provide a valuable resource for characterizing the uniqueness of WBP and a basis for future breeding

Population Structure and Selection Signatures Underlying Domestication Inferred from Genome-Wide Copy Number Variations in Chinese Indigenous Pigs

Single nucleotide polymorphism was widely used to perform genetic and evolution research in pigs. However, little is known about the effect of copy number variation (CNV) on characteristics in pigs. This study performed a genome-wide comparison of CNVs between Wannan black pigs (WBP) and Asian wild boars (AWB), using whole genome resequencing data. By using Manta, we detected in total 28,720 CNVs that covered approximately 1.98% of the pig genome length. We identified 288 selected CNVs (top 1%) by performing Fst statistics. Functional enrichment analyses for genes located in selected CNVs were found to be muscle related (NDN, TMOD4, SFRP1, and SMYD3), reproduction related (GJA1, CYP26B1, WNT5A, SRD5A2, PTPN11, SPEF2, and CCNB1), residual feed intake (RFI) related (MAP3K5), and ear size related (WIF1). This study provides essential information on selected CNVs in Wannan black pigs for further research on the genetic basis of the complex phenotypic and provides essential information for direction in the protection and utilization of Wannan black pig

Interrogation of Streptomyces avermitilis for efficient production of avermectins

AbstractThe 2015 Nobel Prize in Physiology or Medicine has been awarded to avermectins and artemisinin, respectively. Avermectins produced by Streptomyces avermitilis are excellent anthelmintic and potential antibiotic agents. Because wild-type strains only produce low levels of avermectins, much research effort has focused on improvements in avermectin production to meet the ever increasing demand for such compounds. This review describes the strategies that have been widely employed and the future prospects of synthetic biology applications in avermectin yield improvement. With the help of genome sequencing of S. avermitilis and an understanding of the avermectin biosynthetic/regulatory pathways, synthetic and systems biotechnology approaches have been applied for precision engineering. We focus on the design and synthesis of biological chassis, parts, devices, and modules from diverse microbes to reconstruct and optimize their dynamic processes, as well as predict favorable effective overproduction of avermectins by a 4Ms strategy (Mine, Model, Manipulation, and Measurement)

Relationship between perceptions of recurrence risk and depression state among first‐episode ischemic stroke patients in rural areas: The mediating role of coping style

Abstract Aims To investigate the relationship between stroke survivors' perceptions of recurrence risk, coping styles and depression state, and the role coping styles play in mediating that relationship. Design A cross‐sectional descriptive study. Methods From one hospital in Huaxian, China, 320 stroke survivors were randomly selected as a convenience sample. In this research, the Simplified Coping Style Questionnaire, the Patient Health Questionnaire‐9 and the Stroke Recurrence Risk Perception Scale were all used. Structural equation modelling and correlation analysis were used to analyse the data. This research followed the EQUATOR and STROBE checklists. Results There were 278 valid survey responses. There were mild to severe depressive symptoms in 84.8% of stroke survivors. In stroke survivors, there was a significant negative relationship (p < 0.01) between the positive coping of perceptions of recurrence risk and their depression state. Recurrence risk perception's impact on depression state was partly mediated, according to mediation studies, by coping style, with the mediation effect accounting for 44.92% of the overall effect. Conclusions The connection between perceptions of recurrence risk and depression state was mediated by the coping mechanisms of stroke survivors. A lower degree of depression state among survivors was connected with positive coping to the beliefs of recurrence risk

BTF3 sustains cancer stem-like phenotype of prostate cancer via stabilization of BMI1

Abstract Background Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Deciphering the novel molecular mechanisms underlying stem-like traits may provide important insight for developing novel therapeutics. Methods Immunohistochemistry and immunofluorescence assays in prostatic tissues; gain- and loss-of-function analyses using ectopic overexpression and shRNAs in PCa cell lines; measurements of tumorigenic and stemness properties, and transcription in vitro and in vivo; transcriptional analysis in public databases. Results We identified that overexpression of BTF3 in PCa tissues and BTF3 expression highly correlates to stem-like traits. Cancer stem-like characteristics in PCa including self-renewal and metastatic potential were impaired by BTF3 loss and promoted by BTF3 overexpression. Mechanistically, BTF3 could stabilize BMI1, which is a crucial regulator of prostate stem cell self-renewal. More importantly, our data revealed that BTF3 is highly predictive of poor prognosis and may help in risk stratification of PCa patients. Conclusions BTF3 promotes PCa progression though modeling stem-like traits in PCa. BTF3 represents a stratification marker in PCa progression and outcomes