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A new isofuranonaphthalenone, 7R,8S3,6,7,8tetrahydro4,7,8trihydroxynaphtho2,3cfuran51Hone 1, and a new benzopyran, 2R,4R3,4dihydro4methoxy2methyl2H1benzopyran5ol 2, together with four known related analogs, 3–6, were isolated from the culture of Nodulisporiumsp. A4, an endophytic fungus from the stem of Aquilaria sinensisLour. Gilg. The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature reports. The isolated compounds 1–6were evaluated for their cytotoxic activities against the NCIH460 and SF268 tumor cell lines. [ABSTRACT FROM AUTHOR]

Diseases caused by Sclerotinia sclerotiorum have caused severe losses of many economically important crops worldwide. Due to the long-term persistence of sclerotia in soil and the production of air-borne ascospores, synthetic fungicides play limited roles in controlling the diseases. The application of antagonistic microorganisms can effectively reduce the number of sclerotia and eventually eradicate S. sclerotiorum from soil, and therefore considerable interest has been focused on biological control. Streptomyces sp. NEAU-S7GS2 was isolated from the root of Glycine max and its rhizosphere soil. It showed significant inhibitory activity against the mycelial growth of S. sclerotiorum (99.1%) and completely inhibited sclerotia germination. Compared to the control, in the pot experiment the application of NEAU-S7GS2 not only demonstrated excellent potential to control sclerotinia stem rot of soybean with 77 and 38% decrease in disease incidence and disease index, respectively, but could promote the growth of soybean. The light microscopy and scanning electron microscopy showed that co-culture of NEAU-S7GS2 with S. sclerotiorum on potato dextrose agar could lead to contorted and fragmented mycelia of S. sclerotiorum, which was associated with the secretion of hydrolytic glucanase and cellulase and the production of active secondary metabolites by NEAU-S7GS2. The plant growth promoting activity of NEAU-S7GS2 was related to the solubilization of inorganic phosphate, and production of 1-aminocyclopropane-1-carboxylate (ACC) deaminase and indole acetic acid (IAA). To further explore the plant growth promoting and antifungal mechanisms, the complete genome of strain NEAU-S7GS2 was sequenced. Several genes associated with ammonia assimilation, phosphate solubilization and IAA synthesis, together with genes encoding ACC deaminase, glucanase and α-amylase, were identified. AntiSMASH analysis led to the identification of four gene clusters responsible for the biosynthesis of siderophores including desferrioxamine B and enterobactin. Moreover, the biosynthetic gene clusters of lydicamycins, phenazines, and a glycosylated polyol macrolide showing 88% gene similarity to PM100117/PM100118 were identified. These results suggested that strain NEAU-S7GS2 may be a potential biocontrol agent and biofertilizer used in agriculture.

The Wnt signalling receptor ROR2 has been identified as a possible therapeutic target in numerous cancers; however, its exact role remains unclear. The aim of this study was to investigate the role of ROR2 in endometrial cancer (EC) and the potential mechanism associated with its altered expression. The association between ROR2 mRNA expression levels and clinicopathological parameters, including overall survival (OS), in EC was analysed in The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) cohort and GEO dataset GSE17025. Four EC cell lines (KLE, MFE-296, Ishikawa and ARK-1) and eight clinical EC samples were analysed for ROR2 methylation via Combined Bisulphite Restriction Analysis (COBRA) and bisulphite genomic sequencing (BGS). In addition, the functional effects of ROR2 overexpression were investigated in Ishikawa and ARK-1 cells following ectopic ROR2 expression. ROR2 promoter methylation or reduced ROR2 expression were both found to correlate with shorter OS, high grade and serous subtype in the TCGA-UCEC and GEO datasets. ROR2 was epigenetically silenced by promoter methylation in both patient samples and cell lines. A significant correlation between ROR2 expression levels and promoter methylation was observed in patient samples (r = −0.797, p = 0.018). ROR2 restoration in ARK-1 significantly decreased invasion ability, with associated changes in epithelial-mesenchymal transition (EMT) markers. ROR2 plays a tumour-suppressor role in EC and is epigenetically suppressed with the development of disease. It may represent a diagnostic or therapeutic candidate for EC.

Sertoli cells are somatic supporting cells in spermatogenic niche and play critical roles in germ cell development, but it is yet to be understood how epigenetic modifiers regulate Sertoli cell development and contribution to spermatogenesis. BRG1 (Brahma related gene 1) is a catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex and participates in transcriptional regulation. The present study aimed to define the functions of BRG1 in mouse Sertoli cells during mouse spermatogenesis. We found that BRG1 protein was localized in the nuclei of both Sertoli cells and germ cells in seminiferous tubules. We further examined the requirement of BRG1 in Sertoli cell development using a Brg1 conditional knockout mouse model and two Amh-Cre mouse strains to specifically delete Brg1 gene from Sertoli cells. We found that the Amh-Cre mice from Jackson Laboratory had inefficient recombinase activities in Sertoli cells, while the other Amh-Cre strain from the European Mouse Mutant Archive achieved complete Brg1 deletion in Sertoli cells. Nevertheless, the conditional knockout of Brg1 from Sertoli cells by neither of Amh-Cre strains led to any detectable abnormalities in the development of either Sertoli cells or germ cells, suggesting that BRG1-SWI/SNF complex is dispensable to the functions of Sertoli cells in spermatogenesis.

The aim of this work was to compare the composition and physicochemical properties (SEM, XRD, solubility, swelling power, paste clarity, retrogradation, freeze−thaw stability, thermal property, and pasting property) of three Chinese yam (Dioscorea opposita Thunb.) starches (CYYS-1, CYYS-2, and CYYS-3) in Yunlong town, Haikou, Hainan Province, China. Our results show that all the CYYS gave a typical C-type X-ray diffraction pattern. The swelling power of CYYS varied from 10.79% to 30.34%, whereas solubility index was in the range of 7.84−4.55%. The freeze−thaw stability of each CYYS showed a contrary tendency with its amylose content. In addition, CYYS-3 showed the highest To (81.1 °C), Tp (84.8 °C), Tc (91.2 °C), and ΔH (14.1 J/g). The pasting temperature of CYYS-1 increased significantly with sucrose addition. NaCl could inhibit the swelling power of CYYS. There were significant decreases in pasting temperature and pasting time of CYYS when pH decreased.

A novel Gram staining positive, aerobic bacterium NEAU-HV1T that exhibits antifungal activity against Exserohilum turcicum was isolated from a soil collected from Gama, Hadjer lamis, Chad. It was grown at 10−45 °C (optimum 30 °C), pH 5−10 (optimum pH 8), and 0−4% (w/v) NaCl (optimum 1%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain NEAU-HV1T was closely related to Sinomonas susongensis A31T (99.24% sequence similarity), Sinomonas humi MUSC 117T (98.76%), and Sinomonas albida LC13T (98.68%). The average nucleotide identity values between NEAU-HV1T and its most closely related species were 79.34−85.49%. The digital DNA−DNA hybridization values between NEAU-HV1T and S. susongensis A31T, S. albida LC13T, and S. humi MUSC 117T were 23.20, 23.50, and 22.80%, respectively, again indicating that they belonged to different taxa. The genomic DNA G+C content was 67.64 mol%. The whole cell sugars contained galactose, mannose, and rhamnose. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, and four glycolipids. The respiratory quinone system comprised MK-9(H2), MK-10(H2), and MK-8(H2). The major cellular fatty acids (>5%) were anteiso-C15:0, anteiso-C17:0, C16:0, and iso-C15:0. Based on the polyphasic analysis, it is suggested that the strain NEAU-HV1T represents a novel species of the genus Sinomonas, for which the name Sinomonas gamaensis sp. nov. is proposed. The type strain is NEAU-HV1T (= DSM 104514T = CCTCC M 2017246T).

Variability in human taste perception is associated with both genetic and environmental factors. The influence of taste receptor expression on this variability is unknown, in part, due to the difficulty in obtaining human oral tissue that enables quantitative expression measures of taste genes. In a comparison of six current techniques (Oragene RNeasy Kit, Isohelix swab, Livibrush cytobrush, tongue saliva, cheek saliva collection, and fungiform papillae biopsy), we identify the fungiform papillae biopsy is the optimal sampling technique to analyse human taste gene expression. The fungiform papillae biopsy resulted in the highest RNA integrity, enabling amplification of all the assessed taste receptor genes (TAS1R1, TAS1R2, TAS1R3, SCNN1A and CD36) and taste tissue marker genes (NCAM1, GNAT3 and PLCβ2). Furthermore, quantitative expression was observed in a subset of taste genes assessed from the saliva collection techniques (cheek saliva, tongue saliva and Oragene RNA kit). These saliva collection techniques may be useful as a non-invasive alternative sampling technique to the fungiform papillae biopsy. Identification of the fungiform papillae biopsy as the optimal collection method will facilitate further research into understanding the effect of gene expression on variability in human taste perception.

The adsorption of Cr(III) or Cr(VI) in the absence and presence of Cu(II) onto kaolin was investigated under pH 2.0–7.0. Results indicated that the adsorption rate was not necessarily proportional to the adsorption capacity. The solutions’ pH values played a key role in kaolin zeta potential (ζ), especially the hydrolysis behavior and saturation index of heavy metal ions. In the presence of Cu(II), qmixCr(III) reached the maximum adsorption capacity of 0.73 mg·g−1 at pH 6.0, while the maximum adsorption capacity for the mixed Cr(VI) and Cu(II) system (qmixCr(VI)) was observed at pH 2.0 (0.38 mg·g−1). Comparing the adsorption behaviors and mechanisms, we found that kaolin prefers to adsorb hydrolyzed products of Cr(III) instead of Cr3+ ion, while adsorption sites of kaolin surface were occupied primarily by Cu(II) through surface complexation, leading to Cu(II) inhibited Cr(VI) adsorption. Moreover, Cr(III) and Cr(VI) removal efficiency had a positive correlation with distribution coefficient Kd. Cr(III) and Cr(VI) removal efficiency had a positive correlation with distribution coefficient Kd and that of adsorption affinities of Cr(III) or Cr(VI) on kaolin was found to be Kd Cr(III) < Kd Cr(III)-Cu(II) and Kd Cr(VI) > Kd Cr(VI)-Cu(II).

Celecoxib is a specific cyclooxygenase-2 inhibitor with poor solubility and low bioavailability. A solid selfmicroemulsifying drug delivery system of celecoxib was therefore developed to improve in vitro drug solubility and in vivo absorption. Solubility testing, compatibility testing and pseudo-ternary phase diagrams were employed in the design. Morphological observation, droplet size and in vitro release were used to characterize the formulation. The optimized celecoxib-liquid self-microemulsifying drug delivery system was determined as 10 % of celecoxib, 25 % of medium chain triglycerides, 56.25 % of emulsifier and 18.75 % of Transcutol HP. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to investigate the cytoxicity of active pharmaceutical ingredients, blank self-microemulsion and celecoxib liquid self-microemulsifying drug delivery system on Caco-2 cells. Celecoxib solid self-microemulsifying drug delivery system was prepared with Neusilin-US2 as a solid adsorbent and characterized using scanning electron microscopy, X-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry and in vitro release. Celecoxib liquid self-microemulsifying drug delivery system had a clear and transparent light-yellow appearance with average particle size of about 22.68 nm, zeta potential of -31.92 mv, and polydisperse coefficient of 0.141. 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide results showed that the formulations virtually had no cytotoxic effect on the cells. The results also showed that celecoxib existed in an amorphous state in celecoxib-solid self-microemulsifying drug delivery system, and the celecoxib-liquid self-microemulsifying drug delivery system and celecoxib-solid-self-microemulsifying drug delivery system had a dissolution degree of more than 90 % in different media with good stability. The pharmacokinetic studies showed that the area under curve of the liquid self-microemulsifying drug delivery system and self-microemulsifying drug delivery system increased by 6.59 and 6.37 folds, respectively, compared with celecoxib suspension. The findings showed that the developed solid self-microemulsion formulations improved the bioavailability of the drug with no cytotoxicity, hence the formulation can serve as a promising carrier for the oral delivery of celecoxib. [ABSTRACT FROM AUTHOR]

Purpose: To prepare ranitidine hydrochloride (RH) sustained-release suspension aimed at improving its safety, effectiveness and convenience of administration. Methods: The RH resinate suspension was prepared using bath method, with a cation- exchange resin as carrier. To obtain an ideal sustained release effect, RH resinates were coated with Eudragit®RS100 using the surface coating method, followed by optimization through a single-factor experiment and response surface analysis. The optimized RH suspension was characterized using accelerated stability test. Moreover, it was pharmacokinetically evaluated in vivo. Results: The optimized RH resin microcapsules showed relative mean deviation between the predicted and measured release values that was < 10 %, (p < 0.05) and demonstrated good reproducibility. Accelerated stability test results showed that the optimized RH suspension exhibited good stability over a period of 6 months (F > 0.9; drug content: 97 – 100 %, drug release: f2 > 50; drug leakage < 0.5 %), with good redispersibility. Results from pharmacokinetics showed that values of Tmax for RH sustainedrelease suspension and RH common tablet were 4.00 and 2.5 h, respectively (p < 0.05), while the corresponding Cmax values were 2545.78 and 3245.97 ng/mL, respectively (p < 0.05). Results of analysis of AUC0-24 showed that they were equivalent in terms of AUC0-24 (p < 0.05) and bioavailability of 101.05%. Conclusion: The optimized ranitidine hydrochloride (RH) sustained-release suspension has been successfully prepared using ion-exchange resin as a carrier and Eudragit® RS100 as a coating material. [ABSTRACT FROM AUTHOR]

Background: Black tea is fully fermented tea with abundant functional components that benefit the gastrointestinal tract. But whether black tea extract relieves constipation is unknown. Therefore, we used loperamide to induce constipation in mice to assess the therapeutical effect of extracts from aged black tea with different storage times. Design: Sixty-three C57BL/6J male mice were randomly divided into Control group (Con), Model group (Mod), Positive group (Pos), aged 6 years group (15Y), aged 4 years group (17Y), aged 2 years group (19Y), and unaged group (21Y). Mice were given loperamide (20 mg/kg, twice a day) to induce constipation for 10 days, and black tea extracts (500 mg/kg) were intragastrically given for 7 days while continuing modeling. Results: The results showed that black tea extracts relieved constipation symptoms by improving defecation weight, fecal water content, and gastrointestinal transit rate. Black tea extracts can also protect colon tissue, regulate serum neurotransmitters, increase the levels of excitatory neurotransmitters motilin (MTL) and substance P (SP), and decrease the levels of inhibitory neurotransmitters vasoactive intestinal peptide (VIP) and nitric oxide (NO). Immunohistochemistry (IHC) showed that black tea extracts were able to reduce AQP3 and AQP9 expression in the colon of constipated mice. In addition, Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showed that black tea extracts could decrease AQP3 and AQP9 mRNA expression. The relief effect of aged black tea (15Y) with the longest storage was better than that of other years, which may be due to the role of active ingredients such as thearubigins (TRs), soluble sugar, tea polysaccharide (TPS), gallic acid (GA), and catechin gallate (CG) in aged black tea. Conclusions: Based on these results, we believe that regular consumption of black tea is effective in relieving constipation, and that black tea is more effective in relieving constipation as the storage time increases. [ABSTRACT FROM AUTHOR]

Roburic acid (ROB) is a naturally occurred tetracyclic triterpenoid, and the anticancer activity of this com- pound has not been reported. Docetaxel (DOC) is the first-line chemotherapeutic agent for advanced stage prostate cancer but toxic side effects and drug resistance limit its clinical success. In this study, the potential synergistic anticancer effect and the underlying mechanisms of ROB in combination with DOC on prostate cancer were investigated. The results showed that ROB and DOC in combination synergistically inhibited the growth of prostate cancer cells. The combination also strongly induced apoptosis, and suppressed cell migration, invasion and sphere formation. Mechanistic study showed that the combined effects of ROB and DOC on prostate cancer cells were associated with inhibition of NF-κB activation, down regulation of Bcl-2 and up regulation of Bax. Knockdown of NF-κB by small interfering RNA (siRNA) significantly decreased the combined effect of ROB and DOC. Moreover, we found that esomeprazole (ESOM), a proton pump inhibitor (PPI), strongly enhanced the effectiveness of ROB and DOC on prostate cancer cells in acidic culture medium. Since acidic micro environment is known to impair the efficacy of current anticancer therapies, ESOM combined with ROB and DOC may be an effective approach for improving the treatment of prostate cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Antiviral drug-resistance patterns of hepatitis B virus (HBV) mutants are complex and currently partly understood. The aim of this study was to monitor the genotypic resistance profile in patients with chronic hepatitis B (CHB) receiving nucleos(t)ide analogues (NAs) in Huzhou, eastern China. Methodology: Serum samples of 139 CHB patients undergoing NA treatment were obtained from Huzhou Central Hospital. The full-length HBV reverse transcriptase regions were amplified and sequenced. The NA resistance mutation positions, including rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtI233, rtN236, and rtM250 were analyzed. Results: Genotypic resistance mutations were detected in 41.72% (58/139) of patients with CHB. Drug resistance mutations were detected at positions rt80, rt173, rt180, rt181, rt194, rt202, rt204, rt236, and rt250, but were not observed at positions rt169, rt184, and rt233. The prevalence of mutations at rtM204 was 54.44% in 90 patients who were treated with lamivudine (LAM) or telbivudine (LDT). RtN236 mutations were detected in 7.14% (2/28) of the patients receiving adefovir (ADV) therapy. Additionally, rtA181 mutations were observed in 4 patients with LAM, ADV, and LDT-based therapy, but not in those patients treated with entecavir (ETV). Among patients who harbored rtM204 combination mutations, rtM204I and rtM204V were significantly associated with rtL80I/V and rtL180M, respectively. Conclusions: The mutation patterns of NA-resistant HBV are complicated in CHB patients in the current clinical setting. Thus, it is necessary to persistently monitor the resistance mutations of HBV for optimizing antiviral therapy strategy and for preventing an outbreak of clinical resistance. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine the effect of age at photostimulation on sexual maturity and performance of layer breeders. A total of 192 fourteen-wk-old White Leghorn (WL) breeder hens were randomly allocated to 4 treatments of 48 birds each, with 2 replicates per treatment. The birds were photostimulated at 16 (PS16), 18 (PS18), 20 (PS20), and 22 (PS22) wk of age. Four birds per treatment were randomly selected to evaluate sexual organ development at 1 D before photostimulation and 2, 4, and 6 wk after photostimulation. The ovary weight, large yellow follicles number (LYF), oviduct weight, and oviduct length of PS18 increased sharply after photostimulation. Conversely, the increase in PS16 was not observed until 2 wk after photostimulation. There was no difference in age at sexual maturity between treatments (P > 0.05). The PS16 had the longest interval (28 D) from photostimulation to 5% egg production, while PS22 reached 5% egg production 7 D before photostimulation. The PS22 had lower peak production (P = 0.02) and less egg production (P = 0.02) than other treatments. The PS16 had more broken and abnormal eggs (P = 0.01) and lower hatchability (P = 0.04) than other treatments. In conclusion, photostimulation at 16 and 22 wk of age decreases hatchability and egg production, respectively, and photostimulation at 18 wk is appreciated for the WL breeder hens. [ABSTRACT FROM AUTHOR]

Background: As a typical representative of metabolic syndrome, obesity is also one of the extremely dangerous factors of cardiovascular diseases. Thus, the prevention and treatment of obesity has gradually become a global campaign. There have been many reports that green tea is effective in preventing obesity, but as a kind of green tea with regional characteristics, there have been no reports that Hakka stir-fried tea (HT) of different storage years has a weight loss effect. Aims: The aim was to investigate the effect of HT in diet-induced obese mice. Methods: The mice were divided into five groups as follows: the control group received normal diet; the obese model group received high-fat diet; and HT2003, HT2008, and HT2015 groups, after the induction of obesity via a high-fat diet, received HT of different storage years treatment for 6 weeks, respectively. Results: It was observed that HT decreased the levels of serum and liver triglyceride; the ratio of liver to body weight; accumulation of epididymal, perirenal, and mesenteric fat; the degree of hepatic steatosis; and adipocyte hypertrophy, with the concomitant reduction of body weight. Moreover, HT decreased the expression levels of proinflammatory cytokines tumor necrosis factor α (TNF α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and reduced fatty acid synthase (FAS) activity in liver tissue of obese mice. In addition, HT treatment also increased the phosphorylation of AMP-activated protein kinase (AMPK) and its direct downstream proteins, acetyl coenzyme A carboxylase (ACC), and carnitine palmitoyltransferase I (CPT-1), which participate in FAS pathway. Conclusions: These findings demonstrate that HT treatment has a potential protection on high-fat diet-induced obesity mice via activating the AMPK/ACC/CPT1 pathway, and to a certain extent, it has nothing to do with the storage time of three kinds of HT. [ABSTRACT FROM AUTHOR]