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Background. Glucagon-like peptide 1 (GLP-1) bestows protective effects upon the cardiovascular system through direct cardiovascular interactions or by improvements to metabolic function. Both these effects are thought to be at least partly mediated by the GLP-1 receptor (GLP-1R). This case-controlled study investigated whether polymorphisms in the GLP-1R gene affect the risk of cardiovascular disease in type 2 diabetic patients in the Chinese Han population. Methods. Eleven haplotype-tagging single nucleotide polymorphisms (SNPs), distributed across 22 kb of the 39 kb GLP-1R gene, were selected and genotyped in diabetic patients from a Chinese Han population. Patients were classified based on the severity of coronary artery stenosis. Coronary artery stenosis was ≥50% in 394 patients (coronary artery disease- (CAD-) positive group), and coronary artery stenosis was <50% in 217 patients (control group). Allele and genotype frequencies were compared between the two groups at all 11 SNPs. Results. When considered in recessive inheritance mode, patients with the GG genotype at rs4714210 had a lower CAD risk than patients with other genotypes (OR = 0.442, 95% CI = 0.258–0.757, p=0.002), even when other known CAD risk factors were taken into account (ORa = 0.440, 95% CIa = 0.225–0.863, pa=0.017). In additive inheritance mode, GG genotype carriers at rs4714210 exhibited a lower risk of CAD than AA carriers (ORa = 0.475, CIa = 0.232–0.970, pa=0.041). Conclusion. In type 2 diabetic patients from a Han Chinese population, some variations in the GLP-1R gene were associated with a lower risk of developing CAD. [ABSTRACT FROM AUTHOR]

The authors explore the implications of the recent success of the Graduate Nurse Education (GNE) Demonstration for Medicare policy. They describe the effectiveness of a new model of organizing and paying for graduate nurse education that involves consortia of hospitals, health systems, community partners, and university nursing schools. They also present a graph that shows Medicare payments for hospitals for nursing and allied health training from 1991 to 2015.

Increasing insurance deductibles have prompted some medical centers to initiate transparent pricing. However, the impact of price transparency (PT) on surgical volume, revenue, and patient satisfaction is unknown, along with the barriers to achieving PT. We identified ambulatory surgical centers in the Free Market Medical Association database that publicly list prices for surgical services online. Six of eight centers (75%) responded to our data collection inquiry. Among five centers that reported their patient volume and revenue after adopting PT, patient volume increased by a median of 50 per cent (range 10-200%) at one year. Four centers (80%) reported an increase in revenue by a median of 30 per cent (range 4-75%), whereas three centers (60%) experienced an increase in third-party administrator contracts with the average increase being seven new third-party administrator contracts (range = 2-12 contracts). Three centers (50%) reported a reduction in their administrative burden and five centers (83%) reported an increase in patient satisfaction and patient engagement after PT. The leading barrier reported to making prices transparent was discouragement from another practice, hospital, or insurance company. The findings of this preliminary study may help guide medical practices in designing and implementing PT strategies. [ABSTRACT FROM AUTHOR]

Scopolia lurida , a medicinal plant native to the Tibetan Plateau, is among the most effective producers of pharmaceutical tropane alkaloids (TAs). The hyoscyamine 6β-hydroxylase genes of Hyoscyamus niger ( HnH6H ) and S. lurida ( SlH6H ) were cloned and respectively overexpressed in hairy root cultures of S. lurida , to compare their effects on promoting the production of TAs, especially the high-value scopolamine. Root cultures with SlH6H / HnH6H overexpression were confirmed by PCR and real-time quantitative PCR, suggesting that the enzymatic steps defined by H6H were strongly elevated at the transcriptional level. Tropane alkaloids, including hyoscyamine, anisodamine and scopolamine, were analyzed by HPLC. Scopolamine and anisodamine contents were remarkably elevated in the root cultures overexpressing SlH6H / HnH6H , whereas that of hyoscyamine was more or less reduced, when compared with those of the control. These results also indicated that SlH6H and HnH6H promoted anisodamine production at similar levels in S. lurida root cultures. More importantly, HnH6H -overexpressing root cultures had more scopolamine in them that did SlH6H -overexpressing root cultures. This study not only provides a feasible way of overexpressing H6H to produce high-value scopolamine in engineered root cultures of S. lurida but also found that HnH6H was better than SlH6H for engineering scopolamine production. [ABSTRACT FROM AUTHOR]

Aims. Protein kinase-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 alpha (eIF2α) pathway mutations lead to failure of β-cell function. The aim of this article was to assess the association between eIF2α and the risk of glucose metabolism abnormalities. Methods. Two eIF2α SNPs (rs9840992 T>C and rs13072593 A>G) were selected based on CHB data from HapMap, and 1466 unrelated nondiabetes individuals were genotyped. All subjects were examined by the 75 g oral glucose tolerance test, and 733 participated in a subsequent insulin release test. Various indicators of insulin resistance and islet β-cell function were examined. Results. There were no significant differences in genotype distribution and allele frequency between the prediabetes and controls. CC genotype carriers at rs9840992 showed higher insulin levels at 120 min after a 75 g glucose load than noncarriers. Also, CC homozygotes had higher ΔI30/ΔG30 and ΔI120/ΔG120 than noncarriers, even after adjusting for insulin resistance. CC homozygotes had greater AUCi values than noncarriers. Subjects aged ≥ 65 yrs, those with a BMI ≥ 24 kg/m2 and those carrying the rs9840992 risk allele, had a 2.5-fold higher risk of glucose abnormalities than subjects who had none of these risk factors. Conclusion. The eIF2α polymorphism is associated with islet β-cell function in a Chinese population. [ABSTRACT FROM AUTHOR]

The present study, seasonal pollution of heavy metals (Pb, Cd, Cr and Cu) in water, sediment, tissues of fish Carassius carassius and oyster Crassostrea gigas were determined at seven sampling sites from Meiliang Bay, Taihu Lake during one year calendar, 2016. The total heavy metal concentrations in water samples were higher in winter and summer than in spring and autumn season, whereas in sediment they were higher in winter and summer seasons, respectively. The trend of metal mean contents found in the fish and oyster were in decreasing order of Pb > Cu > Cr > Cd and Pb > Cu > Cr > Cd, respectively. The tissues of fish and oyster captured during winter and summer accumulated a higher significant different amount of metals relative to other season, which was attributed to a higher influx of agricultural waste, sewage and sludge by heavy rainfall and floods. In addition, the pollution load index (PLI) values were above one (>1), indicating an advanced decline of the sediment quality, and contamination factor (CF) confirmed that the sediment samples were moderate to high contamination by Pb and Cr. Thus, comparative studies with seasonal pollution of heavy metals in Meiliang Bay of Lake Taihu regions indicate considerable heavy metal enrichment in water, sediments as well as in various organs of fish and oyster. Finally, our results indicated that the metal concentration values increased statistically significant different related to season (p < 0.001). The determination of heavy metal stress biomarkers in fish along with seasonal variations may serve as a convenient approach during pollution bio-monitoring programme. [ABSTRACT FROM AUTHOR]

Background: As the most populous nation in the world, China has now becoming an emerging ageing society. Shanghai is the first city facing the challenge of ageing demographics. Against this background, a study that employs self-rated health (SRH) assessment system was designed to explore the health status of Shanghai elders, and learn their attitudes toward health issues; as well as to investigate the determinants of SRH among Shanghai elders. Understanding SRH is crucial for finding appropriate solutions that could effectively tackle the increasing eldercare demand.Methods: This study adopted a quantitative research strategy. Using a multistage stratified cluster sampling method, we conducted a questionnaire survey in August 2011 in Shanghai, which collected 2001 valid survey responses. SRH assessments were categorized by five levels: very good, fairly good, average, fairly poor, or poor. The respondents' functional status was evaluated using the Barthel index of activities for daily living. In the data analysis, we used chi-squared test to determine differences in socio-demographic characteristics among various groups. Along with statistics, several logistic regression models were designed to determine the associations between internal influence factors and SRH.Results: Younger age (χ2 = 27.5, p < 0.05), male sex (χ2 = 11.5, p < 0.1), and living in the suburbs (χ2 = 55.1, p < 0.05) were associated with better SRH scores. Higher SRH scores were also linked with health behaviour of the respondents; namely, do not smoke (χ2 = 18.0, p < 0.1), do not drink (χ2 = 18.6, p < 0.1), or engage in regular outdoor activities (χ2 = 69.3, p < 0.05). The respondents with better social support report higher SRH scores than those without. Respondents' ability to hear (χ2 = 38.7, p < 0.05), speak (χ2 = 16.1, p < 0.05) and see (χ2 = 78.3, p < 0.05) impacted their SRH scores as well. Meanwhile, chronic illness except asthma was a major influence factor in low SRH score. Applying multiple regression models, a series of determinants were analysed to establish the extent to which they contribute to SRH. The impact of these variables on SRH scores were 6.6% from socio-demographic and health risk behaviours, 2.4% from social support, 8.5% from mental health, 20% from physical conditions, and13% from chronic diseases.Conclusions: This is the first study that examines the determinants of SRH among Shanghai elders. Nearly 40% of our study's respondents reported their health status as "good". The main determinants of SRH among elders include living condition, health risk behaviour, social support, health status, and the economic status of the neighbourhood. [ABSTRACT FROM AUTHOR]

Based on the continuous online measurements of volatile organic compounds (VOCs) at a suburban site in Jinan, Shandong province in the wintertime of 2021, characteristics, chemical transformations and sources of VOCs were analyzed. The total mixing ratio of VOCs was 30.35 ± 19.9 ppbv, with alkanes being the most abundant species. Alkenes and aromatics were the major contributors to the hydroxyl radical loss rate (L OH) and the ozone formation potential (OFP), accounting for 44.9% and 32.7% to L OH , and 43.2% and 33.4% to OFP, respectively. Aromatics had the primary contribution (98.1%) to the secondary organic aerosol potential (SOAP), and the high correlation between SOAP and PM 2.5 concentrations (R = 0.70) suggested that VOCs were critical precursors of PM 2.5. Coal/biomass burning and motor vehicle emissions were the main sources of VOCs (24.6% and 23.8%, respectively), followed by petrochemical and fuel evaporation (19.9%), industrial sources (16.9%), and liquefied petroleum gas/natural gas use (14.8%). Backward trajectories and the potential source contribution function (PSCF) analysis results suggested that short-range transport from the southeast was the primary potential source of VOC concentrations in suburban Jinan. The results can provide theoretical support for local governments to develop VOC emission control strategies in suburban areas. • Daytime VOCs were significantly influenced by strong localized emissions. • SOAP of VOCs and PM 2.5 were highly correlated. • Coal/biomass burning and vehicle emissions were the most significant sources of VOCs. • Short-distance transport from the southeast was important for VOCs control. [ABSTRACT FROM AUTHOR]

Metal ion doping is an efficient method to achieve high photocatalytic performance of semiconductors. However, the current synthetic methods by using inorganic salts as doped sources in the precursor reaction system might suffer from ion waste and second pollution. Herein, we developed a novel method by employing electrospun nanofibers as ion reservoir to release metal ions for the synthesis of ion-doped semiconductors with high photocatalytic activity. As demonstrated, Co/Fe co-doped BiOCl photocatalyst (Co/Fe-BOC) was facilely prepared in the presence of CoFe 2 O 4 nanofibers as Co and Fe ion reservoir via a simple solvothermal method. Compared with BiOCl, the resulted Co/Fe-BOC shows increased specific surface area, visible light response as well as separation and transportation efficiencies of photogenerated carriers. Thus, the Co/Fe-BOC exhibits significantly enhanced visible light photocatalytic activity to degrade 99.4% rhodamine B (RhB) within 4 min. This new doping approach not only avoids the ion waste and pollution during the reaction process but also facilitates the separation of the photocatalyst. Moreover, the CoFe 2 O 4 nanofibers could be repeatedly used as ion reservoir to prepare high-performance Co/Fe-BOC. This nanofiber-based ion doping approach provides a novel, universal and promising insight to obtain doped semiconductors with high photocatalytic activity. [Display omitted] • CoFe 2 O 4 nanofibers were used as ion reservoir for the first time to prepare ion doped semiconductor photocatalyst. • The Co/Fe-BOC displays significantly improved visible light photocatalytic activity to degrade rhodamine B. • The CoFe 2 O 4 nanofibers could be repeatedly used as ion reservoir to prepare high-performance Co/Fe-BOC. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous syndrome. Airway inflammation and remodeling are the two key processes involved in COPD pathogenesis. However, the key pathogenic genes driving COPD development have not been revealed. This study aims to identify and validate hub gene(s) underlying COPD development through bioinformatics analysis and experimental validation. Three lung tissue sequencing datasets of the COPD (including GSE38974, GSE103174, and GSE106986) were analyzed. Further, differentially expressed genes (DEGs) were used to compare patients with COPD with non-COPD individuals, and the Robust Rank Aggregation (RRA) analysis was also performed. Results revealed a series of potential pathogenic genes of COPD. DEGs were subjected to KEGG, GO, and GSEA analyses. The scRNA dataset of human lung tissues (Human Lung Cell Atlas), and human primary airway epithelial cells (GSE134147) were used to identify the cell subtype localization. The qRT-PCR assay was performed in the human lung tissues, COPD mice model, and primary bronchial epithelial cells at the air-liquid interface (ALI) under cigarette smoke extract (CSE) stimulation to verify the expression of the hub genes. LASSO and GLM analysis with the hub genes were performed to identify the most critical gene. RNA-seq was performed after knocking down the critical gene using siRNA in HBECs at ALI. The potential role of the critical gene was confirmed through qRT-PCR, Western blot, and Immunofluorescence (IF) assays. A total of 98 genes were significantly and differently expressed in 3 GEO datasets. The KEGG and GO analyses showed that most of these genes are responsible for inflammation, immunity, and cell proliferation. The core gene set including 15 genes was screened out and consequently, the MMP1 was the most likely responsible for the progression of COPD. Moreover, we confirmed that MMP1 is significantly related to inflammatory effects and cilia function in human bronchial epithelial cells cultured at the air-liquid interface (ALI). In summary, we confirmed that inflammation and cell proliferation are potentially critical processes in COPD occurrence and development. A total of 15 potential hub genes were identified among which MMP1 was the most likely gene responsible for the development of COPD. Therefore, MMP1 is a potential molecular target of COPD therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

• Phytosterols showed greater bioaccessibility when loaded in solid lipid nanoparticles. • Amounts of phytosterols in micelle was positively correlated with lipid lipolysis. • Affinities of phytosterols and lipids affected the arrangement of nanoparticles. • Compact arrangements were conducive to greater stability and slower release. The lipid matrix plays a key role in solid lipid nanoparticles (SLNs) embedding active ingredients. To investigate the influence of lipid matrix structure on arrangement, release, and stability of solid lipid nanoparticles, three phytosterols formulations with different carrier glycerides [glycerol monostearate (GMS), glycerol distearate (GDS), and glycerol tristearate (GTS)] were prepared and evaluated. X-ray diffraction and differential scanning calorimetry revealed the lowest crystallinity of phytosterols in the GMS matrix, corresponding to the maximum bioaccessibility (40.2%) in vitro experiments. Sustained release and better stability were observed from GDS and GTS matrices, which could be attributed to strong molecular interactions or a core-rich structure inside the nanoparticles. Molecular dynamics simulations demonstrated that the affinity between phytosterols and glycerides decreased in the order GDS > GTS > GMS, as well as explaining the release and storage capacities of the three nanoparticles. This study would facilitate the rational design of SLNs in functional foods. [ABSTRACT FROM AUTHOR]

Drought is one of the most severe forms of abiotic stresses that threaten the survival of plants, including crops. In turn, plants dramatically change their physiology to increase drought tolerance, including reconfiguration of proteomes. Here, we studied drought-induced proteomic changes in leaves of cultivated tobacco ( Nicotiana tabacum ), a solanaceous plant, using the isobaric tags for relative and absolute quantitation (iTRAQ)-based protein labeling technology. Of identified 5570 proteins totally, drought treatment increased and decreased abundance of 260 and 206 proteins, respectively, compared with control condition. Most of these differentially regulated proteins are involved in photosynthesis, metabolism, and stress and defense. Although abscisic acid (ABA) levels greatly increased in drought-treated tobacco leaves, abundance of detected ABA biosynthetic enzymes showed no obvious changes. In contrast, heat shock proteins (HSPs), thioredoxins, ascorbate-, glutathione-, and hydrogen peroxide (H 2 O 2 )-related proteins were up- or down-regulated in drought-treated tobacco leaves, suggesting that chaperones and redox signaling are important for tobacco tolerance to drought, and it is likely that redox-induced posttranslational modifications play an important role in modulating protein activity. This study not only provides a comprehensive dataset on overall protein changes in drought-treated tobacco leaves, but also shed light on the mechanism by which solanaceous plants adapt to drought stress. [ABSTRACT FROM AUTHOR]

Background: This study aimed to construct a working model for detecting the mitochondrial damage and expression of Mfn2. It furthermore explored the pathogenesis of premature ovarian failure (POF) induced by cisplatin. Method: Forty young female mice were divided randomly into two groups. The first was the treatment group intraperitoneally administered cisplatin (1.5mg/kg). The untreated control group was likewise injected with physiological saline for 10 days. One month later, we observed the ovarian weight and morphological changes, particularly the development of follicles and concentration of sex hormones. Immunohistochemistry and western blotting were used to measure the two groups. We later evaluated ovarian cell apoptosis with TUNEL and analyzed Bcl-2 and Bax levels. We used transmission electron microscopy in order to observe the ultrastructure of ovarian cells. The phosphomolybdic acid colorimetric method was used to measure the ATP content in the ovarian tissue. Finally, the mitochondrial membrane potential of ovarian cells was detected with JC-1 dye. Results: The cisplatin resulted in a decline of body weight, reduced ovarian weight significantly, and resulted in disorders of the extrous cycle. The follicles’ number decreased within the tissue’s stromal hyperplasia. Moreover, E2 levels were reduced, and elevated gonadotropin levels were observed. However, Mfn2 was present in the cell’s cytoplasm in both groups. Nevertheless, the Mfn2 levels and the expression of Bcl-2 were significantly decreased (p<0.05), but the expression of Bax and the apoptosis index (AI) was increased. In addition, the ATP levels (35.2 ±5.7μmol/g) of the control group were significantly higher (13.5 ± 3.8 μmol/g). Lastly, an obvious impairment of mitochondrial function and structure was observed. Conclusion: The intreperitoneal injection of cisplatin, when administered for 10 days, establishes a POF model. Thus, the above results suggest that lower expression of Mfn2 may be involved in the mechanism of premature ovarian failure by affecting both the mitochondria’s energy metabolism and its apoptosis. This decides the termination of the follicles’ development. [ABSTRACT FROM AUTHOR]

The protein α-synuclein (α-Syn) has a central role in the pathogenesis of Parkinson’s disease (PD) and immunotherapeutic approaches targeting this molecule have shown promising results. In this study, novel antibodies were generated against specific peptides from full length human α-Syn and evaluated for effectiveness in ameliorating α-Syn-induced cell death and behavioral deficits in an AAV-α-Syn expressing rat model of PD. Fisher 344 rats were injected with rAAV vector into the right substantia nigra (SN), while control rats received an AAV vector expressing green fluorescent protein (GFP). Beginning one week after injection of the AAV-α-Syn vectors, rats were treated intraperitoneally with either control IgG or antibodies against the N-terminal (AB1), or central region (AB2) of α-Syn. An unbiased stereological estimation of TH+, NeuN+, and OX6 (MHC-II) immunostaining revealed that the α-Syn peptide antibodies (AB1 and AB2) significantly inhibited α-Syn-induced dopaminergic cell (DA) and NeuN+ cell loss (one-way ANOVA (F (3, 30) = 5.8, p = 0.002 and (F (3, 29) = 7.92, p = 0.002 respectively), as well as decreasing the number of activated microglia in the ipsilateral SN (one-way ANOVA F = 14.09; p = 0.0003). Antibody treated animals also had lower levels of α-Syn in the ipsilateral SN (one-way ANOVA F (7, 37) = 9.786; p = 0.0001) and demonstrated a partial intermediate improvement of the behavioral deficits. Our data suggest that, in particular, an α-Syn peptide antibody against the N-terminal region of the protein can protect against DA neuron loss and, to some extent behavioral deficits. As such, these results may be a potential therapeutic strategy for halting the progression of PD. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways. [ABSTRACT FROM AUTHOR]

A new strategy is proposed to identify the tangling characteristics of Raman spectra for the subnanometric cluster under reactive atmosphere, by which different SACs, SMDs and SSCs with similar metal/molecule architecture can be distinguished. [Display omitted] • A new strategy is proposed to identify the tangling characteristics of Raman spectra. • Simulated Raman spectra was use to distinguish different SACs and SMDs catalysts. • Characteristic Raman signal was originated from different vibrational polarizability. To date, using either state-of-the-art direct image or indirect spectroscopic techniques to simultaneously identify the surface fine structure of heterogeneous catalyst and predict the chemical state of surface species under operando conditions, particularly down to subnanometry and even atomic scale, remains a substantial challenge. Nevertheless, reducing the size of the heterogeneous catalyst from bulk down to atomic level, the spectroscopic characteristics responsible for the unique interaction between metal and adsorbed molecules will thereby be tuned, giving rise to non-coherent spectroscopic characteristics for even the same metal/molecule combination, as repeatedly witnessed in literatures. This work details a new chemical strategy to identify the tangling characteristics of Raman spectra derived from the subnanometric cluster and even single atom catalysts under reactive atmosphere, a long-standing issue that impeded the further implementation of Raman techniques in miniaturized heterogeneous catalysis. We illustrate this concept through the use of a density functional theory (DFT) approach to simulate the Raman spectra of three typical Pt x /CeO 2 (x = 1, 2, 9) systems of increasing sizes which represent isolated atom, layered clusters, and multiple layer clusters, respectively, under CO atmosphere to acquire the spectroscopic characteristics, usually masked by multiple interferences from the inevitable CO/Pt interaction circulated in relevant experimental studies. The novel approach explored in this manuscript should open up a new avenue for the use of theoretical chemistry method as a general tool to complement the current experimental method in identifying the intrinsic spectroscopic features masked by multiple interferences originated from complex chemical environment. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel enzymatic method for preparing phytosterol polyol esters was developed. • Phytosterol polyol esters possessed enhanced water solubility and thermal stability. • Bioaccessibility in vitro and cellular uptake of phytosterols were improved. A novel enzyme-catalyzed method was developed for the synthesis of phytosterol polyol esters from β -sitosterol and polyols (sorbitol, mannitol and xylitol) by two-step transesterification using divinyl adipate (DVA) as a link. A high conversion (exceeding 94%) of β -sitosterol with a vinyl group was achieved, in the presence of Candida rugosa lipase (CRL), at low temperature (35 °C) within 30 min. Subsequently, the maximum conversion of phytosterol polyol esters (>94%) was obtained using alkaline protease from Bacillus subtilis at 65 °C. Phytosterol polyol esters had enhanced thermal stability (up to an above 355 °C) and excellent water solubility (4.6–7.9 mM at 35 °C). Moreover, obvious increases in the bioaccessibility (41.5–63.6%) and intestinal uptake (5.2–6.5%) were observed using a simulated gastrointestinal digestion/Caco-2 cell model. These results highlighted the key role of hydrophilic structural modifications on physicochemical properties and absorption of phytosterols. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-β protein precursor (AβPP) cells were incubated with THC and assayed for amyloid-β (Aβ) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aβ level in N2a/AβPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aβ aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3β (GSK-3β) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aβ levels in N2a/AβPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aβ peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3β levels and phosphorylated GSK-3β in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways. [ABSTRACT FROM AUTHOR]

Background: Insulin and glucagon-like peptide 1 (GLP-1), converted by proprotein convertase 1 (PC1/3) from proinsulin and proglucagon, are associated with type 2 diabetes (T2DM) and coronary artery disease (CAD). The aim of this study is to investigate the association of PCSK1 gene, which encodes PC1/3, with the risk of CAD in Chinese patients with T2DM. Methods: We selected and genotyped 5 haplotype-tagging single nucleotide polymorphisms (SNPs) at PCSK1 gene (across 39873bp locus) in a case-control study of Chinese Han population involving 425 diabetic patients (62.1% male, mean age 63.2 years) with CAD as positive cases and 258 diabetic patients (44.2% male, mean age 62.0 years) without CAD as controls. Results: The allele frequencies at rs3811951 were significantly different between cases and controls (30.7% vs. 37.2%), with the allele G associated with decreased risk for CAD (OR = 0.75, 95% CI = 0.59–0.94, p = 0.013). In recessive inheritance mode, the carriers of GG had a lower risk (OR = 0.50, 95%CI = 0.31–0.82, p = 0.005), even after adjusted for gender, age, BMI and smoking (OR = 0.43, 95%CI = 0.24–0.77, p = 0.004). The carriers of the minor allele A at rs156019 had a higher risk (OR = 1.66, 95%CI = 1.10–2.50, p = 0.016 after adjustment) in dominant inheritance mode. The SNP rs6234 was also significantly associated with CAD risk in women, with the carriers of the minor allele G at rs6234 associated with a reduced CAD risk in recessive inheritance mode (OR = 0.42, 95% CI = 0.18–0.95, p = 0.036 after adjustment). Conclusions: Our results found that common genetic variants in PCSK1 were associated with CAD in Chinese patients with T2DM. [ABSTRACT FROM AUTHOR]

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65-88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2-4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (-51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 μM) in MCI subjects were associated with no conversion to dementia during the ensuing 2-4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. [ABSTRACT FROM AUTHOR]

Previously, our lab was the first to report the use of antigen-sensitized dendritic cells as a vaccine against Alzheimer's disease (AD). In preparation of this vaccine, we sensitized the isolated dendritic cells ex vivo with Ab peptide, and administered these sensitized dendritic cells as a therapeutic agent. This form of cell therapy has had success in preventing and/or slowing the rate of cognitive decline when administered prior to the appearance of Aβ plaques in PDAPP mice, but has not been tested in 2×Tg models. Herein, we test the efficacy and safety of this vaccine in halting and reversing Alzheimer's pathology in 9-month-old APP+PS1 mice. The results showed that administration of this vaccine elicits a longlasting antibody titer, which correlated well with a reduction of Aβ burden upon histological analysis. Cognitive function in transgenic responders to the vaccine was rescued to levels similar to those found in non-transgenic mice, indicating that the vaccine is capable of providing therapeutic benefit in APP+PS1 mice when administered after the onset of AD pathology. The vaccine also shows indications of circumventing past safety problems observed in AD immunotherapy, as Th1 pro-inflammatory cytokines were not elevated after long-term vaccine administration. Moreover, microhemorrhaging and T-cell infiltration into the brain are not observed in any of the treated subjects. All in all, this vaccine has many advantages over contemporary vaccines against Alzheimer's disease, and may lead to a viable treatment for the disease in the future. [ABSTRACT FROM AUTHOR]

There is increasing demand to develop antimicrobial peptides(AMPs)as next generation antibiotic agents, as they have the potential tocircumvent emerging drug resistance against conventional antibiotictreatments. Non-natural antimicrobial peptidomimetics are an idealexample of this, as they have significant potency and in vivo stability.Here we report for the first time the design of lipidated γ-AApeptidesas antimicrobial agents. These lipo-γ-AApeptides show potentbroad-spectrum activities against fungi and a series of Gram-positiveand Gram-negative bacteria, including clinically relevant pathogensthat are resistant to most antibiotics. We have analyzed their structure–functionrelationship and antimicrobial mechanisms using membrane depolarizationand fluorescent microscopy assays. Introduction of unsaturated lipidchain significantly decreases hemolytic activity and thereby increasesthe selectivity. Furthermore, a representative lipo-γ-AApeptidedid not induce drug resistance in S. aureus, evenafter 17 rounds of passaging. These results suggest that the lipo-γ-AApeptideshave bactericidal mechanisms analogous to those of AMPs and have strongpotential as a new class of novel antibiotic therapeutics. [ABSTRACT FROM AUTHOR]

Tags associated with social images are valuable information source for superior image search and retrieval experiences. Although various heuristics are valuable to boost tag-based search for images, there is a lack of general framework to study the impact of these heuristics. Specifically, the task of ranking images matching a given tag query based on their associated tags in descending order of relevance has not been well studied. In this article, we take the first step to propose a generic, flexible, and extensible framework for this task and exploit it for a systematic and comprehensive empirical evaluation of various methods for ranking images. To this end, we identified five orthogonal dimensions to quantify the matching score between a tagged image and a tag query. These five dimensions are: (i) tag relatedness to measure the degree of effectiveness of a tag describing the tagged image; (ii) tag discrimination to quantify the degree of discrimination of a tag with respect to the entire tagged image collection; (iii) tag length normalization analogous to document length normalization in web search; (iv) tag-query matching model for the matching score computation between an image tag and a query tag; and (v) query model for tag query rewriting. For each dimension, we identify a few implementations and evaluate their impact on NUS-WIDE dataset, the largest human-annotated dataset consisting of more than 269K tagged images from Flickr. We evaluated 81 single-tag queries and 443 multi-tag queries over 288 search methods and systematically compare their performances using standard metrics including Precision at top- K, Mean Average Precision ( MAP), Recall, and Normalized Discounted Cumulative Gain (NDCG). [ABSTRACT FROM AUTHOR]

Abstract: A novel super-hydrophobic coating was prepared by chemical modification on the anodized aluminum alloy surface. The surface structure was characterized by water contact angle measurement, scanning electron microscopy (SEM), and the composition was measured by X-ray photoelectron spectroscopy (XPS). The corrosion behavior of the super-hydrophobic coating was evaluated by the polarization curve and the electrochemical impedance spectroscopy (EIS). It was found that the static water contact angle on the surface of super-hydrophobic coating was as high as 167.7±1.2°, and the sliding angle was 5°. The super-hydrophobic coating resulted in excellent corrosion resistance property and the super-hydrophobic coating showed a good stability. [Copyright &y& Elsevier]

Retrospective and prospective epidemiologic studies suggest that enhanced coffee/caffeine intake during aging reduces risk of Alzheimer's disease (AD). Underscoring this premise, our studies in AD transgenic mice show that long-term caffeine administration protects against cognitive impairment and reduces brain amyloid-β levels/deposition through suppression of both β- and γ-secretase. Because coffee contains many constituents in addition to caffeine that may provide cognitive benefits against AD, we examined effects of caffeinated and decaffeinated coffee on plasma cytokines, comparing their effects to caffeine alone. In both AβPPsw+PS1 transgenic mice and non-transgenic littermates, acute i.p. treatment with caffeinated coffee greatly and specifically increased plasma levels of granulocyte-colony stimulating factor (GCSF), IL-10, and IL-6. Neither caffeine solution alone (which provided high plasma caffeine levels) or decaffeinated coffee provided this effect, indicating that caffeine synergized with some as yet unidentified component of coffee to selectively elevate these three plasma cytokines. The increase in GCSF is particularly important because long-term treatment with coffee (but not decaffeinated coffee) enhanced working memory in a fashion that was associated only with increased plasma GCSF levels among all cytokines. Since we have previously reported that long-term GCSF treatment enhances cognitive performance in AD mice through three possible mechanisms (e.g., recruitment of microglia from bone marrow, synaptogenesis, and neurogenesis), the same mechanisms could be complimentary to caffeine's established ability to suppress Aβ production. We conclude that coffee may be the best source of caffeine to protect against AD because of a component in coffee that synergizes with caffeine to enhance plasma GCSF levels, resulting in multiple therapeutic actions against AD. [ABSTRACT FROM AUTHOR]

Abstract: Counter-current chromatography (CCC) combined with pre-separation by ultrasonic solvent extraction was successively used for the separation of series bioactive compounds from the crude extract of Hypericum perforatum L. The petroleum ether extract was separated by the solvent system of n-heptane–methanol–acetonitrile (1.5:0.5:0.5, v/v) and n-heptane–methanol (1.5:1, v/v) in gradient elution, yielding a phloroglucinol compound, hyperforin with HPLC purity over 98%. The ethyl acetate extract was separated by using the solvent system composed of hexane–ethyl acetate–methanol–water (1:1:1:1 and 1:3:1:3, v/v) in gradient through both reverse phase and normal phase elution mode, yielding a naphthodianthrone compound, hypericin with HPLC purity about 95%. The n-butanol extract was separated with the solvent system composed of n-butanol–ethyl acetate–water (1:4:5 and 1.5:3.5:5, v/v) in elution and back-extrusion mode, yielding two of flavones, rutin and hyperoside, with HPLC purity over 95%. HPLC–MS, reference sample and UV spectrum were selectively used in separation to search for target compounds from HPLC-DAD profiles of different sub-extracts. The structures of isolated compounds were further identified by ESI-MS, 1HNMR and 13CNMR. [Copyright &y& Elsevier]

Abstract: The Himalayan Mianning–Dechang REE belt, western Sichuan, SW China, is approximately 270 km long and 15 km wide, and contains total reserves of >3 Mt of LREE, including one giant (Maoniuping), one large (Dalucao) and a number of small-medium REE deposits (Muluozhai, Lizhuang) and occurrences. The belt is tectonically located within a continental collision zone, i.e., the eastern Indo-Asian collision zone. REE mineralization is associated with Himalayan carbonatite–alkaline complexes, which consist of carbonatitic sills or dykes and associated alkaline syenite stocks. Available dating data define a Himalayan metallogenic epoch (40–10 Ma). The magmatic–hydrothermal REE systems were controlled by Cenozoic large-scale strike-slip faulting and the resultant tensional fissure zones, developed in a transform phase from a transpressional to a transtensional regime. Alteration is characterized by fenitization, which formed fenite halos enveloping the REE orebodies. Associated REE mineralization occurs as complex vein systems consisting of various veinlets, stringer and stockwork zones, and breccia-pipe systems. The REE orebodies show various shapes from plate-like, lenticular to pipe-like in different districts. Ore types are dominated by pegmatitic, carbonatitic, breccia, and stringer (stockwork), and disseminated ores, mainly composed of barite + fluorite + aegirine-augite + calcite + bastnaesite assemblages. Bastnaesite precipitation (275–325 °C) appears in three assemblages: early clastics-bearing barite + arfvedsonite + calcite + bastnaesite; intermediate quartz + fluorite + barite + bastnaesite; and late fluorite + barite + bastnaesite assemblages. These were followed by low-temperature pyrite + galena + sphalerite assemblages. Fluid inclusion studies indicate that gangue quartz and fluorite hosts numerous melt/fluid inclusions with a large proportion of sulfate (i.e., BaSO4, K2SO4, and CaSO4), in addition to CaCO3 and CaF2, yielding abnormally high (up to 750 °C) but wide-ranging homogenization temperatures (750–125 °C). The similarity of Sr–Nd isotopic compositions for gangue minerals with those of the host carbonatite–syenite suggests that ore-forming fluids, especially the F−, HCO3 2−, SO4 2− components, were derived from carbonatite–syenite magmas. The O–D–C isotopic data from gangue calcite, fluorite and quartz indicate that the fluids were of orthomagmatic origin, but also involved mixing with an external fluid. On the basis of our synthesis, we propose a possible genetic model for REE mineralization, in which the hydrothermal system temporally underwent a complicated evolution from separation of high-T sulfate-bearing NaCl–KCl brine resulting in effective precipitation of REE-fluorocarbonate and sulfate, to subsequent mixing with low-temperature meteoric water precipitating minor sulfide assemblages. Spatially, this sequence of events generated a three-tier REE mineralized architecture, in which pipe-like breccia orebodies grade downwards from shallow to deep structural levels into large veinlet ore systems, and veinlet-disseminated orebodies. [Copyright &y& Elsevier]

• NiFe layered double hydroxide (LDH) is synthesized by flash nano-precipitation method. • La-doped NiFe LDH is prepared via a mechanical strategy. • La-NiFe LDH exhibited boosting water splitting with high HER and OER activity. Electrolysis of water can directly produce hydrogen and oxygen, providing the possibility to expand the production of high purity hydrogen. It consists of two half reactions: anodic oxygen evolution reaction (OER) and cathodic hydrogen evolution reaction (HER). Developing electrocatalysts is an effective way to improve the efficiency of water splitting. Two-dimensional layered double hydroxides (LDHs), as abundant, cheap and bifunctional catalysts, have the similar electrocatalytic performance as precious metals, thereby receiving pretty much attention. Here, a facile flash nano-precipitation (FNP) synthetic strategy is presented to acquire NiFe LDH. Based on it, La-NiFe LDH is obtained by adding rare earth element lanthanum (La) with different contents using mechanical method. Owing to the synergistic effect between La and laminate metal, La-NiFe LDH shows an excellent water splitting performance, where the overpotential of OER activity is 340 mV and HER performance is 57 mV at the current density of 10 mA∙cm−2. Combined with characterization, performance and theoretical calculation, it is confirmed that the electronic structure of LDH laminates can be adjusted by La doping, reducing the Gibbs free energy in the reaction accordingly, which is beneficial to the water splitting reaction. In general, an easy-to-implement and rapid preparation method provides a convenient and green way to obtain water splitting catalyst with enhanced performance. [Display omitted] [ABSTRACT FROM AUTHOR]

• Four NtWRKY11 genes were identified from Nicotiana tabacum , among which NtWRKY11b exhibited the strongest transcriptional activity. • Silencing or overexpression of the NtWRKY11b gene significantly changed the content of flavonols in tobacco leaves. • Overexpression of NtWRKY11b significantly upregulated the expression levels of eight flavonoids related genes. • The transcription of four flavonoids related genes was significantly induced by posttranslational activation of NtWRKY11b. • ChIP assays demonstrated that NtWRKY11b could bind to the promoter regions of NtMYB12 , NtFLS , NtGT5 , and NtUFGT genes. The biosynthesis of flavonols and anthocyanins is precisely regulated by different transcription factors in plants. WRKY11 promotes the biosynthesis of flavonoids in apple, but the molecular mechanism of WRKY11 regulating flavonols biosynthesis, and whether WRKY11 plays the same roles in other plants species remains to be further studied. Here, we cloned four NtWRKY11 genes from tobacco, which all contained the conserved WRKYGQK heptapeptide and a zinc-finger motif. The NtWRKY11b showed higher expression levels than the other NtWRKY11 genes in all the tobacco tissues examined, especially in tobacco leaves. Silencing of NtWRKY11b in tobacco leaves reduced the content of flavonols to 45.2 %–69.8 % of that in the WT plants, but overexpression of NtWRKY11b increased the flavonols content by 37.8 %–80.7 %. Transcriptome analysis revealed 8 flavonoids related differentially expressed genes (DEGs) between NtWRKY11b -OE and WT plants, among which the transcription of NtMYB12 , NtFLS , NtGT5 , and NtUFGT was significantly induced by posttranslational activation of NtWRKY11b with the presence of protein synthesis inhibitor, indicating a putative direct promotion of NtWRKY11b on the transcription of these flavonoids related genes. Chromatin immunoprecipitation assays further demonstrated that NtWRKY11b could bind to the promoter regions of NtMYB12 , NtFLS , NtGT5 , and NtUFGT to activate the transcription of these genes. Moreover, ectopic expression of NtWRKY11b also promoted the expression levels of NtCML38 , NtCTL1 , NtWRKY44 , and NtCML37 genes, which have been shown to enhance plant resistance to various stresses. Our findings revealed the molecular mechanism of NtWRKY11b regulating flavonols biosynthesis, and provided a promising target for increasing flavonols content in tobacco. [ABSTRACT FROM AUTHOR]

We report the identification of a new class of antimicrobial peptidomimetics-γ-AApeptides with potent and broad-spectrum activity, including clinically-relevant strains that are unresponsive to most antibiotics. They are also not prone to select for drug-resistance. [ABSTRACT FROM AUTHOR]

We report a new class of peptide mimetics, α-AApeptides, that display broad-spectrum activity against both Gram-negative and Gram-positive bacteria and fungi. With non-hemolytic activity, resistance to protease hydrolysis, and easy sequence programmability, α-AApeptides may emerge as a novel class of antibiotics. [ABSTRACT FROM AUTHOR]

Ciprofloxacin, a third-generation fluoroquinolones (FQs) antibiotic, is observed to increasingly pollute the environment. In this study, a three-dimensional reduced graphene oxide-attapulgite-based catalyst Fe2O3/RGO-ATP was prepared and used to analyze the degradation of ciprofloxacin in a heterogeneous Fenton reaction. The heterogeneous catalyst Fe2O3/RGO-ATP was prepared by a one-step hydrothermal method, and the samples were characterized using BET(Brunauer-Emmett-Teller) surface area, Raman spectroscopy, X-ray diffraction (XRD), Fourier infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The effect of reaction time, temperature, pH, initial concentration, H2O2 dosage and reuse time on the degradation of ciprofloxacin by the catalyst Fe2O3/RGO-ATP was investigated. The optimum conditions of degradation of ciprofloxacin are observed to be 60 °C, pH 5, H2O2 concentration of 2.9724 mmol/L, and initial ciprofloxacin concentration of 50 mg/L. The catalyst could be reused several times with a decline in catalytic capacity. Fourier-transform ion cyclotron resonance mass spectrometer (FT) was also employed to study the degradation products of ciprofloxacin in the aqueous solution. The results show that the heterogeneous catalyst Fe2O3/RGO-ATP possessed an excellent ability for the catalytic degradation of ciprofloxacin. Direct hydroxyl oxidation is noted to be the main pathway of degradation of ciprofloxacin, and no defluorination reaction is observed during the degradation process. [ABSTRACT FROM AUTHOR]

Background: In vivo pig liver xenotransplantation preclinical trials appear to have poor efficiency compared to heart or kidney xenotransplantation because of xenogeneic rejection, including coagulopathy, and particularly thrombocytopenia. In contrast, ex vivo pig liver (wild type) perfusion systems have been proven to be effective in "bridging" liver failure patients until subsequent liver allotransplantation, and transgenic (human CD55/CD59) modifications have even prolonged the duration of pig liver perfusion. Despite the fact that hepatocyte cell lines have also been proposed for extracorporeal blood circulation in conditions of acute liver failure, porcine hepatocyte cell lines, and the GalT‐KO background in particular, have not been developed and applied in this field. Herein, we established immortalized wild‐type and GalT‐KO porcine hepatocyte cell lines, which can be used for artificial liver support systems, cell transplantation, and even in vitro studies of xenotransplantation. Methods: Primary hepatocytes extracted from GalT‐KO and wild‐type pigs were transfected with SV40 LT lentivirus to establish immortalized GalT‐KO porcine hepatocytes (GalT‐KO‐hep) and wild‐type porcine hepatocytes (WT). Hepatocyte biomarkers and function‐related genes were assessed by immunofluorescence, periodic acid‐Schiff staining, indocyanine green (ICG) uptake, biochemical analysis, ELISA, and RT‐PCR. Furthermore, the tumorigenicity of immortalized cells was detected. In addition, a complement‐dependent cytotoxicity (CDC) assay was performed with GalT‐KO‐hep and WT cells. Cell death and viability rates were assessed by flow cytometry and CCK‐8 assay. Results: GalT‐KO and wild‐type porcine hepatocytes were successfully immortalized and maintained the characteristics of primary porcine hepatocytes, including albumin secretion, ICG uptake, urea and glycogen production, and expression of hepatocyte marker proteins and specific metabolic enzymes. GalT‐KO‐hep and WT cells were confirmed as having no tumorigenicity. In addition, GalT‐KO‐hep cells showed less apoptosis and more viability than WT cells when exposed to complement and xenogeneic serum. Conclusions: Two types of immortalized cell lines of porcine hepatocytes with GalT‐KO and wild‐type backgrounds were successfully established. GalT‐KO‐hep cells exhibited higher viability and injury resistance against a xenogeneic immune response. [ABSTRACT FROM AUTHOR]

Hepatic ischemia-reperfusion (I/R) injury is inevitable during hepatectomy and may cause both postoperative morbidity and mortality. Regenerative medicine suggested adipose-derived stem cells (ADSCs) as an attractive tool for the treatment of liver diseases. In this study, we investigated the effect of ADSCs in an I/R model combined with laparoscopic hepatectomy in swine. Eighteen Bama miniature pigs were randomly divided into Sham, IRI, and ADSCs groups. ADSCs (1 × 106/kg) were injected through liver parenchyma immediately after hemihepatectomy. The apoptosis-related role of ADSCs was studied. The results showed that ADSCs transplantation reduced both pathological and ultrastructural changes and decreased the number of apoptotic-positive cells. In the ADSCs group, Fas, Fas ligand (FasL) protein, and mRNA were downregulated and the enzyme activities of Caspase3, Caspase8, and Caspase9 were significantly decreased. In addition, ADSC therapy significantly increased the ratio of Bcl-2/Bax protein and mRNA compared to the IRI group. In conclusion, ADSCs attenuated both I/R and hepatectomy-induced liver apoptosis in a porcine model, and offers a potential therapeutic option for hepatic I/R and hepatectomy. [ABSTRACT FROM AUTHOR]