Trends in adherence to recommended physical activity and its association with cardiovascular risk factors in US adults with cardiovascular disease: a cross-sectional study.

BACKGROUND: Being physically active is important for cardiovascular health. This study aimed to examine the trend in adherence to the physical activity guidelines (PAG) for aerobic activity among US adults with a history of cardiovascular disease (CVD) and evaluated its association with cardiovascular risk factors. METHODS: We studied participants from the national health and nutrition examination survey 2007-08 to 2017-18. Regression models were used to evaluate the significance of the trend and the association between adherence to the PAG with cardiovascular risk factors. RESULTS: A total of 3638 participants were reported to have a history of CVD. The proportion of adherence to PAG significantly increased from 41.5% in 2007-08 to 54.3% in 2017-18. Males had a higher proportion of adherence compared to the females, while the trend in adherence was only significant in females. Adherence to the PAG was significantly associated with decreased levels of waist circumference, body mass index, hemoglobin A1c, and triglycerides. CONCLUSIONS: There is a significant increase in the proportion of adherence to the PAG among US adults with a history of CVD from 2007-08 to 2017-18, and adherence to the PAG was associated with improvement in cardiovascular risk factors.

Design of Rational JAK3 Inhibitors Based on the Parent Core Structure of 1,7-Dihydro-Dipyrrolo [2,3-b:3',2'-e] Pyridine.

JAK3 differs from other JAK family members in terms of tissue distribution and functional properties, making it a promising target for autoimmune disease treatment. However, due to the high homology of these family members, targeting JAK3 selectively is difficult. As a result, exploiting small changes or selectively boosting affinity within the ATP binding region to produce new tailored inhibitors of JAK3 is extremely beneficial. PubChem CID 137321159 was used as the lead inhibitor in this study to preserve the characteristic structure and to collocate it with the redesigned new parent core structure, from which a series of 1,7-dihydro-dipyrrolo [2,3-b:3',2'-e] pyridine derivatives were obtained using the backbone growth method. From the proposed compounds, 14 inhibitors of JAK3 were found based on the docking scoring evaluation. The RMSD and MM/PBSA methods of molecular dynamics simulations were also used to confirm the stable nature of this series of complex systems, and the weak protein−ligand interactions during the dynamics were graphically evaluated and further investigated. The results demonstrated that the new parent core structure fully occupied the hydrophobic cavity, enhanced the interactions of residues LEU828, VAL836, LYS855, GLU903, LEU905 and LEU956, and maintained the structural stability. Apart from this, the results of the analysis show that the binding efficiency of the designed inhibitors of JAK3 is mainly achieved by electrostatic and VDW interactions and the order of the binding free energy with JAK3 is: 8 (−70.286 kJ/mol) > 11 (−64.523 kJ/mol) > 6 (−51.225 kJ/mol) > 17 (−42.822 kJ/mol) > 10 (−40.975 kJ/mol) > 19 (−39.754 kJ/mol). This study may provide a valuable reference for the discovery of novel JAK3 inhibitors for those patients with immune diseases.

8-O-ß-D-Glucopyranosyl-2-methylchromone, a new chromone glycoside from the Tibetan medicine plant of Swertia punicea Hemsl.

A new chromone glycoside, 8-O-ß-D-Glucopyranosyl-2-methylchromone (1), together with eight known compounds (2-9) were isolated from the Tibetan medicine plant of Swertia punicea. All compounds of this plant were reported for the first time. The structures of these metabolites were elucidated by analysis of their HR-ESI-MS, 1D and 2D NMR spectroscopic data and comparison with data reported in the literature. In vitro test, all compounds were evaluated for their anti-inflammatory activity through the determination of nitric oxide production. Compounds 1-2 were evaluated for cytotoxic activities against three human cancer cell lines (HeLa, MDA-MB-231 and A375) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Furthermore, the chemotaxonomic significance of these compounds has also been described.

Involvement of PaSNF1 in Fungal Development, Sterigmatocystin Biosynthesis, and Lignocellulosic Degradation in the Filamentous Fungus Podospora anserina.

The sucrose non-fermenting 1/AMP-activated protein kinase (SNF1/AMPK) is a central regulator of carbon metabolism and energy production in the eukaryotes. In this study, the functions of the Podospora anserina SNF1 (PaSNF1) ortholog were investigated. The ΔPaSNF1 mutant displays a delayed development of mycelium and fruiting bodies and fails to form ascospores. The expression of the PaSNF1 gene in the strain providing female organs in a cross is sufficient to ensure fertility, indicating a maternal effect. Results of environmental stress showed that ΔPaSNF1 was hypersensitive to stress, such as osmotic pressure and heat shock, and resistant to fluconazole. Interestingly, the knockout of PaSNF1 significantly promoted sterigmatocystin (ST) synthesis but suppressed cellulase [filter paperase (FPA), endoglucanase (EG), and ß-glucosidase (BG)] activity. Further, transcriptome analysis indicated that PaSNF1 made positive regulatory effects on the expression of genes encoding cellulolytic enzymes. These results suggested that PaSNF1 may function in balancing the operation of primary and secondary metabolism. This study suggested that SNF1 was a key regulator concerting vegetative growth, sexual development, and stress tolerance. Our study provided the first genetic evidence that SNF1 was involved in the ST biosynthesis and that it may also be a major actor of lignocellulose degradation in P. anserina.

Structure Elucidation of Two New Norlignans from Anemone vitifolia and Their Anti-Inflammatory Activities.

Two new norlignans together with two known phenylpropanoids were isolated from the whole herb of Anemone vitifolia. All compounds were reported from this plant for the first time. The structures of these compounds were identified by comprehensive HR-ESI-MS, 1D and 2D NMR spectroscopic data analysis and comparison with literature data. Additionally, bioactivity study results showed that two new compounds have potential anti-inflammatory activity. The plausible biosynthetic pathway for these compounds were also speculated in this article.

Three new phenylacetamide glycosides from Dracocephalum tanguticum Maxim and their anti-hyperglycemic activity.

Three new phenylacetamide glycosides (1-3) together with one known phenylacetamide glycoside (4) and two known flavonoid glycosides (5-6) were isolated from whole plants of Dracocephalum tanguticum. The structure of all compounds were elucidated based on spectroscopic data analysis and comparison with data reported in related literature. Compounds (1-3) were evaluated for their anti-hyperglycemic and anti-fungal (Candida albicans) activities, the results revealed that all of them showed moderate activity with 3T3-L1 adipocytes glucose consumption rate of 20.80 ± 1.47%, 21.48 ± 2.44%, and 21.57 ± 1.35%, respectively at the final concentration of 25 µM. However, none of them showed obvious Candida albicans inhibitory activity.

Trans-acting non-synonymous variant of FOXA1 predisposes to hepatocellular carcinoma through modulating FOXA1-ERα transcriptional program and may have undergone natural selection.

Interplay of pioneer transcription factor forkhead box A1 (FOXA1) and estrogen receptor has been implicated in sexual dimorphism in hepatocellular carcinoma (HCC), but etiological relevance of its polymorphism was unknown. In the case control study (1152 patients versus1242 controls), we observed significant increase in HCC susceptibility in hepatitis B virus carriers associated with a non-synonymous Thr83Ala variant of FOXA1 (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.11-1.48, for Ala83-containing genotype, after validation in an independent population with 933 patients versus 1030 controls), a tightly linked (CGC)5/6or7 repeat polymorphism at its promoter (OR 1.32; 95% CI 1.10-1.60, for (CGC)6or7-repeat-containing genotype), and their combined haplotype (OR 1.50; 95% CI 1.24-1.81, for (CGC)6or7-Ala83 haplotype). The susceptible FOXA1-Ala83 impairs its interaction with ERα, attenuates transactivation toward some of their dual target genes, such as type 1 iodothyronine deiodinase, UDP glucuronosyltransferase 2 family, polypeptide B17 and sodium/taurocholate cotransporting polypeptide, but correlates with strengthened cellular expression of α-fetoprotein (AFP) and elevated AFP serum concentration in HCC patients (n = 1096). The susceptible FOXA1 cis-variant with (CGC)6or7 repeat strengthens the binding to transcription factor early growth response 1 and enhances promoter activity and gene expression. Evolutionary population genetics analyses with public datasets reveal significant population differentiation and unique haplotype structure of the derived protective FOXA1-Thr83 and suggest that it may have undergone positive natural selection in Chinese population. These findings epidemiologically highlight the functional significance of FOXA1-ERα transcriptional program and regulatory network in liver cancer development.

Two new xanthone glycosides from Swertia punicea Hemsl. and their anti-inflammatory activity.

Two new xanthone glycosides (1-2), together with seven known analogues (3-9), were isolated from whole herb of Swertia punicea. The structures of these metabolites were established on the basis of detailed spectroscopic analysis and comparison with data reported in the literature. In an in vitro test, all isolates were evaluated for their anti-inflammatory activity. The results revealed that all of them showed significant anti-inflammatory activity with IC50 values ranging from 1.237 to 3.319 mM. Compounds 3, 4, and 5 (IC50 values in the range 1.237-1.987 mM) displayed more potent anti-inflammatory activity than the positive control, indomethacin (IC50 value of 2.004 mM).

Mechanical modulation of terahertz wave via buckled carbon nanotube sheets.

Manipulation of terahertz (THz) wave plays an important role in THz imaging, communication, and detection. The difficulty in manipulating the THz wave includes single function, untunable, and inconvenient integration. Here, we present a mechanically tunable THz polarizer by using stretchable buckled carbon nanotube sheets on natural rubber substrate (BCNTS/rubber). The transmittance and degree of polarization of THz wave can be modulated by stretching the BCNTS/rubber. The experiments showed that the degree of polarization increased from 17% to 97%, and the modulation depth reached 365% in the range of 0.2-1.2 THz, as the BCNTS/rubber was stretched from 0% to 150% strain. These changes can be also used for high strain sensing up to 150% strain, with a maximum sensitivity of 2.5 M/S. A spatial modulation of THz imaging was also realized by stretching and rotating BCNTS/rubber. The theoretical analysis and numerical modeling further confirm the BCNTS/rubber changes from weak anisotropic to highly anisotropic structure, which play key roles in THz wave modulation. This approach for active THz wave manipulation can be widely used in polarization imaging, wearable material for security, and highly sensitive strain sensing.

Long non-coding RNA HNF1A-AS1 promotes hepatocellular carcinoma cell proliferation by repressing NKD1 and P21 expression.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Recent evidences have demonstrated that long non-coding RNAs (lncRNAs) act as key regulators of tumor development and progression including HCC. In the study, we showed that the expression level of HNF1A-AS1 was up-regulated in HCC cell lines. Furthermore, CCK-8 cell proliferation assays and cell cycle analysis showed that HNF1A-AS1 over-expression facilitated HCC cell proliferation by promoting the cell proliferation and S-phase progression, whereas HNF1A-AS1 knockdown had the opposite effect. Western-blotting analysis revealed that knockdown of HNF1A-AS1 inhibited the cycle-relative protein cyclin-D1 and PCNA expression in HCC cells. Mechanism, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that by interacting with enhancer of zeste homolog 2 (EZH2), HNF1A-AS1 promoted HCC cell proliferation by repressing the NKD1 and p21 expression. These results suggested that HNF1A-AS1 may contribute to HCC progression, which may be an effective therapeutic target for patients.

Methylated of genes behaving as potential biomarkers in evaluating malignant degree of glioblastoma.

Abnormal methylation genes usually act as oncogenes or anti-oncogenes in the occurrence and development of tumor, indicating their potential role as biomarkers in the evaluation of malignant tumor. However, the research on methylation's association with glioblastoma was rare. We attempted to figure out whether the methylation of genes could serve as the biomarker in evaluating the malignant degree of GBM. Methylation microarray data of 275 GBM patients have been downloaded from The Cancer Genome Atlas (TCGA) dataset. Logistic regression was used to find the methylated genes associated with the malignant degree of patients with the tumor. Functional enrichment analysis and network analysis were further performed on these selected genes. A total of 668, 412, 470, and 620 genes relevant with the methylation or demethylation were found to be associated with the malignant degree, Grades 1-4 of tumor. The higher the degree of malignant tumor, the higher of its methylation degree of its corresponding genes. GO and KEGG analysis results showed that these methylated genes were enriched in many functions as cell adhesion, abnormal transcription, and cell cycle disorder, etc. Of note, CCL11 and LCN11 were found to be significantly related to the progression of GBM. Critical genes associated with cell cycle as CCL11 and LCN1 may play essential roles in the occurrence, development, and transition of glioblastoma. More research was needed to explore its potential molecular mechanism.

Three new xanthones from Swertia bimaculata and their anti-5α-reductase activity.

Three new xanthones (1-3), together with five known ones (4-8), were isolated from whole herb of Swertia bimaculata. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New isolates were evaluated for their anti-5α-reductase activity. The results revealed that all new compounds showed weak activity with reductase inhibitions of 40.5 ± 2.8, 38.6 ± 2.5, and 48.9 ± 3.0%, respectively.

Two new phenylpropanoids from Swertia atroviolacea and their anti-5α-reductase activity.

Two new phenylpropanoids (1-2), together with two known lignans (3-4), were isolated from whole herb of Swertia atroviolacea. The structures of the new metabolites were established on the basis of detailed spectroscopic analysis. Compounds 1 and 2 were evaluated for their anti-5α-reductase activity. The results revealed that 1 and 2 showed weak activity with reductase inhibitions of 45.6 ± 2.8% and 38.4 ± 2.5%, respectively.

[(3) H]-L685,458 binding sites are abundant in multiple peripheral organs in rats: implications for safety assessment of putative γ-secretase targeting drugs.

γ-Secretase is a multimeric enzyme complex that carries out proteolytic processing to a variety of cellular proteins. It is currently explored as a therapeutic target for Alzheimer's disease (AD) and cancer. Mechanism-based toxicity needs to be thoroughly evaluated for γ-secretase inhibitory and/or modulatory drugs. This study comparatively assessed putative γ-secretase catalytic sites in rat peripheral tissues relative to brain and explored an effort of its pharmacological inhibition on hair regeneration. Using [(3) H]-labelled L685,458, a potent γ-secretase inhibitor, as probe, we found more abundant presence of γ-secretase binding sites in the liver, gastrointestinal tract, hair follicle, pituitary gland, ovary and testis, as compared to the brain. Local application of L658,458 delayed vibrissal regrowth following whisker removal. These results suggest that γ-secretase may execute important biological functions in many peripheral systems, as in the brain. The development of γ-secretase inhibitors/modulators for AD and cancer therapy should include close monitoring of toxicological panels for hepatic, gastrointestinal, endocrinal and reproductive functions.

A new chitin-binding lectin from rhizome of Setcreasea purpurea with antifungal, antiviral and apoptosis-inducing activities.

A 48 kDa, chitin-binding lectin with antifungal, antiviral and apoptosis-inducing activities was isolated from the rhizomes of Setcreasea purpurea Boom, a member of family Commelinaceae. Setcreasea purpurea lectin (designated as SPL) is a homotetrameric protein consisting of 12031.9 Da subunits linked by non-covalent bonds as determined by SDS-PAGE, gel filtration and MS. The N-terminal 25 amino-acid sequence of SPL, NVLGRDAYCGSQNPGATCPGLCCSK was determined and homology analysis suggested that SPL belongs to the family of chitin-binding plant lectins composed of hevein domains. The lectin exhibited strong hemagglutinating activity towards rabbit erythrocytes at 0.95 µg/ml and the activity could be reversed exclusively by chitin hydrolysate (oligomers of GlcNAc). Its hemagglutinating activity was stable in pH range of 2.0-9.0 and it showed excellent thermal tolerance. SPL showed antifungal activity against Rhizoctonia solani, Sclerotinia sclerotiorum, Penicillium italicum and Helminthosporiun maydis. It also exhibited inhibitory effect on HIV-1 (IIIB) and HIV-2 (ROD), with an EC50 of 13.8 ± 1.3 and 57.1 ± 15 µg/ml, respectively. Subsequently, MTT method, cell morphological analysis and LDH activity-based cytotoxicity assays demonstrated that SPL was highly cytotoxic to CNE-1 cells and induced apoptosis in a dose-dependent manner. Moreover, due to the caspase inhibitors analyses, caspase was also found to play an important role in the potential apoptotic mechanism of SPL.

[The pulmonary arterial oxygen saturation monitoring via trachea in hypoxia dogs].

This study was aimed to assess the agreement between pulse pulmonary arterial oxygen saturation (StO2) by oximetry in trachea and the mixed venous oxygen saturation (SvO2) by fiberoptic pulmonary arterial catheter, and to evaluate the accuracy of StO2 monitoring during hypoxia. 10 mongred dog's were used. After anesthesia was induced and thorax was opened, we placed a fiberoptic pulmonary artery catheter directly through the dog's right ventricular outlet. Then, we placed and adjusted the trachea catheter, attached the oximetry probe to trachea carina till the high quality StO2 PPG signal was obtained, and till the readings were stable at about +/-2% from fiberoptic catheter. The pair readings of StO2 and SvO2 were recorded at every minute interval in 10 minutes when circulation was stable. Decreasing the inhaled oxygen concentration till the tongue's SpO2 decreased to 60%; recording the changes of StO2 and SvO2 in every 5% drop of tongue's SpO2 when the tongue's SpO2 decreased from 100% to 50%. The results showed that there was a good agreement between the two methods for pulmonary arterial oxygen saturation measurement. However, the difference between the two methods was great and unacceptable during the presence of hypoxia.

Role of Toll-like receptor 4/NF-kappaB pathway in monocyte-endothelial adhesion induced by low shear stress and ox-LDL.

TLR4 plays an important role in atherosclerosis, but little is known about the precise mechanism. Herein, we investigated the role of TLR4/NF-kappaB signaling pathway in monocyte-endothelial adhesion induced by low shear stress and Ox-LDL. We found that low shear stress up-regulated TLR4 expression in endothelial cells, and that ox-LDL exerted an obvious synergistic action as revealed by RT-PCR and Western blotting analysis. Low shear stress also significantly up-regulated IL-8 expression in endothelial cells. Meanwhile, NF-kappaB activity and the adhesion force of monocytes were increased, and there was a synergetic action of ox-LDL. However, following transfection with a functional mutant of TLR4 (C3H/HeJ, TLR4 Dicd) or addition of anti-human TLR4 mAb, IL-8 expression was obviously decreased, NF-kappaB activity in cells remarkably inhibited, and the adhesion force of monocyte significantly reduced. Nevertheless, anti-human TLR2 mAb had no similar effects. These findings suggest that TLR4 may be involved in the early stages of atherosclerosis, associating ox-LDL, inflammation/infection, and low shear stress. Therefore, TLR4 is expected to be a new target for preventing and treating atherosclerosis.