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The thyme oil emulsion was prepared using a novel type of nanocellulose obtained under different hydrolysis durations. The effect of different cellulose structures on interfacial adsorption properties of emulsion and loading efficiency of thyme oil were analyzed. The results showed that the cellulose particles became more homogeneous and hydrophilic after hydrolysis duration for 10 h. The loading efficiency of thyme oil for all emulsions reached about 80%. The retention rate of thyme oil decreased during the storage period, and rising temperatures will exacerbate the loss of thyme oil. Compared to Hd2, emulsions stabilized by Hd10 exhibited better stability and higher retention at all storage conditions. Cellulose emulsion can increase the dispersion and improve the stability of thyme oil. A smaller cellulose particle could make the emulsion become more stable. The experimental results confirmed that cellulose can be used as a stabilizer to encapsulate and transport hydrophobic active ingredient. PRACTICAL APPLICATION: The study results demonstrated that the emulsion transport system was developed using cellulose nanoparticles prepared by hydrolysis. The system can be used to load hydrophobic active substances (active peptides, curcumin, β-carotene, essential oils, etc.). It can protect the active substance from environmental damage, enhance water solubility and stability, and improve the bioavailability of the active substance.

Chiral perhydroindoles are found in a number of natural products and biologically active compounds. Therefore, the development of new asymmetric methodology for rapid access to this core is of high importance. Herein, we reported a highly regio- and diastereo-selective palladium/PC-Phos-catalyzed asymmetric Heck/Tsuji-Trost reactions of readily available amino tethered 1,3-cyclohexadienes with aryl and alkenyl halides, delivering various functionalized chiral hexahydroindoles in good yields with high enantioselectivity. The application of this reaction to the concise synthesis of (-)-α-Lycorane was demonstrated. DFT computation results indicate that the difference in ΔE

The liver is an essential multifunctional organ and constantly communicates with nearly all the tissues in the body. Spaceflight or simulated microgravity has a significant impact on the livers of rodent models, including lipid accumulation and inflammatory cell infiltration. Whether similar liver lipotoxicity could occur in humans is not known, even though altered circulating cholesterol profile has been reported in astronauts. Using a 42-day head-down bed rest (HDBR) model in rhesus macaques, the present study investigated whether simulated microgravity alters the liver of non-human primates at the transcriptome and metabolome levels. Its association with stress and intestinal changes was also explored. Compared to the controls, the HDBR monkeys showed mild liver injury, elevated ANGPTL3 level in the plasma, and accumulation of fat vacuoles and inflammatory cells in the liver. Altered transcriptome signatures with up-regulation of genes in lipid metabolisms and down-regulation of genes in innate immune defense were also found in HDBR group-derived liver samples. The metabolic profiling of the liver revealed mildly disturbed fatty acid metabolism in the liver of HDBR monkeys. The intestinal dysbiosis, its associated endotoxemia and changes in the composition of bile acids, and elevated stress hormone in HDBR monkeys may contribute to the altered lipid metabolisms in the liver. These data indicate that liver metabolic functions and gut-liver axis should be closely monitored in prolonged spaceflight to facilitate strategy design to improve and maintain metabolic homeostasis.

The metastable type-II clathrate Na24-δ Ge136 was obtained from Na12 Ge17 by applying a two-step procedure. At first, Na12 Ge17 was reacted at 70 °C with a solution of benzophenone in the ionic liquid (IL) 1,3-dibutyl-2-methylimidazolium-bis(trifluoromethylsulfonyl) azanide. The IL was inert towards Na12 Ge17 , but capable of dissolving the sodium salts formed in the redox reaction. By annealing at 340 °C under an argon atmosphere, the X-ray amorphous intermediate product was transformed to crystalline Na24-δ Ge136 (δ≈2) and α-Ge in an about 1 : 1 mass ratio. The product was characterized by X-ray powder diffraction, chemical analysis, and 23 Na solid-state NMR spectroscopy. Metallic properties of Na24-δ Ge136 were revealed by a significant Knight shift of the 23 Na NMR signals and by a Pauli-paramagnetic contribution to the magnetic susceptibility. At room temperature, Na24-δ Ge136 slowly ages, with a tendency to volume decrease and sodium loss.

CRISPR/Cas9-mediated genome editing technology is a simple and highly efficient and specific genome modification approach with wide applications in the animal industry. CRISPR/Cas9-mediated genome editing combined with somatic cell nuclear transfer rapidly constructs gene-edited somatic cell-cloned pigs for the genetic improvement of traits or simulation of human diseases. Chinese Bama pigs are an excellent indigenous minipig breed from Bama County of China. Research on genome editing of Chinese Bama pigs is of great significance in protecting its genetic resource, improving genetic traits and in creating disease models. This study aimed to address the disadvantages of slow growth and low percentage of lean meat in Chinese Bama pigs and to knock out the myostatin gene (MSTN) by genome editing to promote growth and increase lean meat production. We first used CRISPR/Cas9-mediated genome editing to conduct biallelic knockout of the MSTN, followed by somatic cell nuclear transfer to successfully generate MSTN biallelic knockout Chinese Bama pigs, which was confirmed to have significantly faster growth rate and showed myofibre hyperplasia when they reached sexual maturity. This study lays the foundation for the rapid improvement of production traits of Chinese Bama pigs and the generation of gene-edited disease models in this breed.

To understand the driving environmental factors in changes of bacterial virulence and antibiotic resistance, we determined the prevalence, antibiotic resistance and antibiotic resistance and virulence genes of Vibrio harveyi isolated from diseased marine fish in south coastal China. We isolated 2, 52 and 53 V. harveyi strains from Fujian, Hainan and Guangdong, respectively, and identified them by multilocus sequence analysis of 16S rRNA-toxRVh -rctB. Nine typical virulence genes were represented at a higher average in Hainan (7.39 ± 0.24) than in Guangdong (6.91 ± 0.28). Five atypical virulence genes were detected in some isolates. In particular, flaC and vvh were detected in more than 60% of isolates. Their average number was significantly higher in Hainan (2.30 ± 0.20) than in Guangdong (1.70 ± 0.10). Multidrug resistance was widespread with an average resistance to 4.57 ± 0.18 of 15 antibiotics. Both the average number of antibiotic resistance and antibiotic resistance genes were higher in Hainan (5.25 ± 0.27 and 1.11 ± 0.15, respectively) than in Guangdong (3.87 ± 0.21 and 0.75 ± 0.10, respectively). This study demonstrated that there were more virulence genes and greater drug resistance in Hainan than in Guangdong, suggesting that warmer temperature and antibiotics pollutants probably enhance antibiotic resistance and bacterial infection.

Epoxides are widely used chemicals, the determination of which is of paramount importance. Herein, we present an enzyme-based approach for noninstrumental detection of epoxides in standard solution and environmental samples. Halohydrin dehalogenase (HheC) as a biological recognition element and epichlorohydrin as a model analyte were evaluated for sensing. The detection is based on the color change of the pH indicator dye bromothymol blue caused by the HheC-catalyzed ring-opening of the epoxide substrate. The color change is then exploited for the determination of epoxide using a smartphone as an image acquisition and data processing device, eliminating the need for computer-based image analysis software. The color parameters were systematically evaluated to determine the optimum quantitative analytical parameter. Under optimal conditions, the proposed enzyme-based detection system showed a linear range of 0.13-2 mM with a detection limit of 0.07 mM and an assay time of 8 Min. In addition, the repeatability expressed as relative standard deviation was found to be below 5% (n = 6). Validation with gas chromatographic analyses showed that the proposed enzyme-based epoxide detection could be an alternative way in the quantitative determination of epoxides, and particularly useful in resource-limited settings.

This paper investigates a novel winner-determination mechanism: multiple-winner award rules that are widely used in e-procurement auctions and crowdsourcing sites. We focus on one unique award mechanism in e-procurement auctions, in which the auctioneer (i.e., the buyer) specifies three rules before the auction starts: (1) the size of the finalist set (from which the winner[s] will be chosen), (2) the number of winners, and (3) the proportion of contract volume allocated to each winner. We examine how these three rules affect auction performance using a data set of online procurement auctions across a variety of product categories. We find that all three award rules significantly impact the suppliers’ participation decision, which is an important factor determining the economic performance of the auction (i.e., buyer's savings). Most interestingly, these three rules systematically induce opposite effects on auction participation for two types of suppliers: experienced bidders and first-time bidders. For example, enlarging the size of the finalist set or increasing the number of winners encourages experienced but discourages inexperienced suppliers to participate the auction, while raising the disparity in contract allocation among winning bidders (e.g., a 50/50 vs. 90/10 split) deters experienced but motivates inexperienced suppliers to participate. These findings provide useful guidelines for industrial buyers and crowdsourcing hosts on how to effectively make use of the three design levers to affect suppliers’ participation when designing procurement auctions and crowdsourcing contests.

AIMS HSP90, as a molecular chaperone, has numerous substrate proteins, including HIF-1α and p-AKT, but the relationships among HSP90, HIF-1α and p-AKT have not been investigated in NPC. We examined and analysed the correlation between expression of HSP90, HIF-1α and p-AKT and clinicopathological features of NPC. METHODS We collected 445 cases of NPC and 54 cases of non-cancerous nasopharyngeal epithelia tissues, detected expression of HSP90, HIF-1α and p-AKT proteins in these tissues by immunohistochemistry. RESULTS The results indicated that overexpression of HSP90, HIF-1α and p-AKT in NPC was significantly higher than that in non-cancerous nasopharyngeal epithelia (P

A simple and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of paeoniflorin, albiflorin, oxypaeoniflorin, liquiritin, liquiritigenin, glycyrrhetinic acid, and glycyrrhizin in rat plasma after oral administration of Shaoyao-Gancao decoction, which is traditionally used in the treatment of polycystic ovary syndrome. The plasma samples were pretreated with methanol as precipitant. The method exhibited good linearity (correlation coefficient (R2 ) > 0.99) with lower quantification limits of 0.595-4.69 ng/mL for all analytes. Intra- and interbatch precision, accuracy, recovery, and stability of the method were all within accepted criteria. The results showed that the pharmacokinetic behaviors of the seven compounds were altered in the pathological status of polycystic ovary syndrome. Furthermore, a total of 36 metabolites were structurally identified based on their accurate masses and fragment ions. The major metabolic pathway involves phase I metabolic reactions (such as hydroxylation), phase II metabolic reactions (such as sulfation and glucuronidation conjugation) as well as the combined multiple-step metabolism. This study is the first report on the pharmacokinetic and metabolic information of Shaoyao-Gancao decoction in both normal and model rats, which would provide scientific evidences for the bioactive chemical basis of herbal medicines and also promote the clinical application of Shaoyao-Gancao decoction for treating polycystic ovary syndrome.

Xanthanolide-type sesquiterpenoids are a diverse family of natural products isolated primarily from the genus Xanthium (Compositae). The intriguing molecular architectures and biological profiles of these natural products have rendered them attractive targets for total synthesis. This focus review aims to provide an up-to-date summary of progress in the chemical synthesis of xanthanolide-type sesquiterpenoids. Different synthetic strategies to form 5/7-cis- and 5/7-trans-bicyclic xanthanolides are presented in chronological order, with an emphasis on the key elements used to forge the characteristic 5/7-bicyclic cores of the targets. Recent advances in the total syntheses of structurally more complicated polycyclic and dimeric xanthanolides are also discussed.

Bone mineral density (BMD) at various skeletal sites have shared genetic determinants. In the present study, aiming to identify shared loci associated with BMD, we conducted a joint association study of a genomewide association study (GWAS) and a meta-analysis of BMD at different skeletal sites: (i) a single GWAS of heel BMD in 142,487 individuals from the UK Biobank, and (ii) a meta-analysis of 30 GWASs of total body (TB) BMD in 66,628 individuals from the Genetic Factors for Osteoporosis (GEFOS) Consortium. The genetic correlation coefficient of the two traits was estimated to be 0.57. We performed joint association analysis with a recently developed statistical method multi-trait analysis of GWAS (MTAG) to account for trait heterogeneity and sample overlap. The joint association analysis combining samples of up to 209,115 individuals identified 18 novel loci associated with BMD at the genomewide significance level (α = 5.0 × 10-8 ), explaining an additional 0.43% and 0.60% of heel-BMD and TB-BMD heritability, respectively. The vast majority of the identified lead SNPs or their proxies exerted local expression quantitative trait loci (cis-eQTL) activity. Credible risk variants, defined as those SNPs located within 500 kilobases (kb) of the lead SNP and with p values within two orders of magnitude of the lead SNP, were enriched in transcription factor binding sites (p = 3.58 × 10-4 ) and coding regions (p = 5.71 × 10-4 ). Fifty-six candidate genes were prioritized at these novel loci using multiple sources of information, including several genes being previously reported to play a role in bone biology but not reported in previous GWASs (PPARG, FBN2, DEF6, TNFRSF19, and NFE2L1). One newly identified gene, SCMH1, was shown to upregulate the expression of several bone biomarkers, including alkaline phosphatase (ALP), collagen type 1 (COL-I), osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), in mouse osteoblastic MC3T3-E1 cells, highlighting its regulatory role in bone formation. Our results may provide useful candidate genes for future functional investigations. © 2019 American Society for Bone and Mineral Research.

Objectives To investigate the association of aspirin resistance (AR) with the plasma 4‐hydroxynonenal (4‐HNE) level and its impact on recurrent cerebral infarction (CI) in patients with acute cerebral infarction (ACI) who were receiving aspirin therapy. Methods One hundred and fifty‐four ACI patients who previously received aspirin therapy (100 mg/day) were enrolled. Whole urine (for measuring 11dhTXB2 and creatinine) along with blood (for measuring the plasma 4‐HNE level) were collected at least 7 days after the patients received aspirin. A cutoff of 1500 pg/mg of 11dhTXB2/ creatinine was used to determine AR. A follow‐up period to monitor recurrence CI events was 1 year. In addition, blood testing was performed when the patients were first admitted to hospital. Results Forty‐six of the 154 enrolled patients (29.9%) were found to be AR. No statistical difference in age, sex, hypertension, diabetes mellitus, coronary disease, smoking status, NIHSS score, TOAST classification, platelet count, thrombocytocrit, LDL‐C, HDL‐C, TG, and TC was found between the AR and aspirin‐sensitive (AS) patients, but the plasma 4‐HNE level was found to be higher in the AR patients than AS patients (p, ACI patients with AR have a higher plasma 4‐HNE level, suggesting that 4‐HNE may be a factor contributing to aspirin resistance. And AR has a higher CI recurrence rate compared with the patients without AR.

In many global health analyses, it is of interest to examine countries' progress using indicators of socio-economic conditions based on national surveys from varying sources. This results in longitudinal data where heteroscedastic summary measures, rather than individual level data, are available. Administration of national surveys can be sporadic, resulting in sparse data measurements for some countries. Furthermore, the trend of the indicators over time is usually nonlinear and varies by country. It is of interest to track the current level of indicators to determine if countries are meeting certain thresholds, such as those indicated in the United Nations Sustainable Development Goals. In addition, estimation of confidence and prediction intervals are vital to determine true changes in prevalence and where data is low in quantity and/or quality. In this article, we use heteroscedastic penalized longitudinal models with survey summary data to estimate yearly prevalence of malnutrition quantities. We develop and compare methods to estimate confidence and prediction intervals using asymptotic and parametric bootstrap techniques. The intervals can incorporate data from multiple sources or other general data-smoothing steps. The methods are applied to African countries in the UNICEF-WHO-The World Bank joint child malnutrition data set. The properties of the intervals are demonstrated through simulation studies and cross-validation of real data.

Mucin-type O-glycosylation is the dominant form of glycosylation in eukaryotes and plays an important role in various physiological processes. The polypeptide GalNAc-transferase (GalNAc-T) catalyzes the first step in the attachment of mucin-type O-glycosylation. GalNAc-T was recently uncovered to be linked with cancer, atherogenic dyslipidemia, and X-linked hypophosphatemic rickets. Therefore, it has attracted increasing interest as a new target for exploring the underlying mechanism and developing new treatments for related diseases. Decades of studies on GalNAc-T have laid a stable foundation for understanding the catalytic mechanism, determining atom-resolution three-dimensional structures, and developing various types of biochemical assays as well as small-molecule inhibitor leads. Here, we systematically summarize this invaluable knowledge on GalNAc-T and cultivate new perspectives to foster breakthrough points for mucin-type O-glycosylation.

Background Alcohol use and its associated problems are on the rise in China. In this study, we examined the associations between alcohol use and cognitive functioning in a representative sample of adults aged 45 years and older in China. Methods Baseline data for 16,328 participants of the China Health and Retirement Longitudinal Study were analyzed. Alcohol use was measured by drinking status (never, former, moderate, and at-risk drinkers), number of standard drinks per week, and years of drinking. Cognitive functioning was assessed for visuospatial ability, episodic memory, orientation/attention, and overall cognitive functioning. Multivariate linear and logistic regressions were used to examine the independent association between alcohol use and cognitive functioning controlling for age, gender, education, domestic partner status, and depressive symptoms. Results The study participants were, on average, 66 years old (median 59, range 45 to 102). The prevalence of ever drinking during lifetime and current at-risk drinking (>14 drinks per week) in this population was 34.6 and 6.7%, respectively. Drinking was more common among men with 48.8% being ever drinkers and 14.4% current at-risk drinkers, respectively. At-risk drinkers, compared to people who never drank alcohol, had worse episodic memory (β = -0.11, p = 0.048). Moreover, number of standard drinks per week was associated with worse episodic memory (β = -0.001, p = 0.02). None of the other measures of alcohol use was associated with the overall or domain-specific cognitive functioning. Conclusions At-risk drinking status was associated with worse episodic memory. Clinicians should incorporate alcohol use assessment into routine care for middle-aged and older adults in China and provide them with resources and strategies to effectively manage their alcohol use. This may help preserve episodic memory in this population.

We report the concise total synthesis of homodimericin A (1), a recently identified fungal metabolite bearing an unprecedented molecular architecture. The success of the approach hinges on a series of rationally designed and bioinspired transformations, including a Moore rearrangement to assemble the monomeric hydroquinone precursor, homodimerization through double Michael addition to construct the planar A/B/C tricyclic framework, and a tandem Diels-Alder reaction/carbonyl-ene cyclization to forge the congested D/E/F tricyclic cage motif. Unequivocal evidence for the elucidated structure of homodimericin A was also provided by this study.