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Atherosclerosis is a potentially life-threatening cardiovascular disease characterized by chronic endothelial inflammation and the formation of atherosclerotic lesions. Circulating ox-LDL is known to induce atherosclerosis by triggering oxidative stress, the expression of inflammatory mediators and adhesion molecules, as well as downregulating the atheroprotective transcriptional factor KLF2. Aloperine is an alkaloid compound isolated from the plant Sophora alopecuroides. Here, we employed various experimental methods to determine the effects of aloperine on ox-LDL-induced markers of atherosclerosis. DHE staining revealed that aloperine may restore the oxidant/antioxidant balance in HUVECs by reducing the level of ROS and rescuing the reduction in NOQ-1 and GCLC induced by ox-LDL. Aloperine treatment reduced ox-LDL-induced expression of IL-6, MCP-1, VCAM-1, and E-selectin and rescued the reduction in KLF2. Aloperine also downregulated ox-LDL-induced expression of the LOX-1. We also demonstrate that aloperine improved cell viability and inhibited the adhesion of U937 monocytes to HUVECs. Finally, we demonstrate that the effects of aloperine are mediated through the rescue of KLF2 expression via suppression of the phosphorylation of p53 protein. Together, our results implicate the potential of aloperine as a safe and effective antiatherosclerosis treatment. [ABSTRACT FROM AUTHOR]

Although clinically associated with the progression of multiple cancers, the biological function of p21‐activated kinase 5 (PAK5) in breast cancer remains largely unknown. Here, we reveal that the PAK5–aspartyl aminopeptidase (DNPEP)–ubiquitin‐specific protease 4 (USP4) axis is involved in breast cancer progression. We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. Functionally, we demonstrate that DNPEP overexpression suppresses breast cancer cell proliferation and invasion and restricts breast cancer growth and metastasis in mice. Furthermore, we identify USP4 as a downstream target of the PAK5–DNPEP pathway; DNPEP mediates USP4 downregulation. Importantly, we verify that DNPEP expression is frequently downregulated in breast cancer tissues and is negatively correlated with PAK5 and USP4 expression. PAK5 decreases DNPEP abundance via the ubiquitin–proteasome pathway. Consistently, analyses of clinical breast cancer specimens revealed significantly increased PAK5 and USP4 levels and an association between higher PAK5 and USP4 expression and worse breast cancer patient survival. These findings suggest a pivotal role for PAK5‐elicited signaling in breast cancer progression. What's new? Increasing lines of evidence suggest that PAK5 is an oncogenic protein that is commonly overexpressed in many cancer tissues and plays multiple functions in cancer progression. However, the underlying molecular mechanisms and the biological significance of PAK5 in breast cancer remain to be fully explored. Here, the authors reveal that DNPEP links the upstream PAK5 kinase to the downstream target USP4 through a phosphorylation‐based regulatory mechanism in malignant breast cancer. Moreover, they identify an association between elements of the PAK5‐DNPEP‐USP4 pathway and clinicopathological features in breast cancer patients, altogether providing potential prognostic markers and therapeutic targets for breast cancer intervention. [ABSTRACT FROM AUTHOR]

Objectives: A significant number of researches have evidenced that occupational lead (Pb) exposure increased risks of cardiovascular disease. However, evidences about the potential effects of Pb on the cardiac conduction system are sparse and inconclusive. Besides, ryanodine receptors (RyRs) induced dysfunction of cardiac excitation contraction coupling which is considered to be one of the mechanisms in cardiovascular diseases. Therefore, we examined the association between occupational Pb exposure and ECG conduction abnormalities, as well as RyRs in Pb-induced ECG abnormalities.Methods: We investigated 529 Pb smelter workers, and measured blood lead (BPb), zinc protoporphyrin (ZPP), ECG outcomes and RyR expression levels. Based on BPb levels, the workers were divided into three groups: the BPb not elevated group, the BPb elevated group and the Pb poisoning group. Descriptive and multivariable analyses were performed.Results: Compared with the BPb not elevated group, the Pb poisoning group had a higher incidence of high QRS voltage, and a lower level of RyR1 gene expression (p<0.05). Further unconditional multivariable logistic regression analyses showed that high QRS voltage was positively related to BPb (OR=1.045, 95% CI 1.014 to 1.078) and inversely associated with RyR1 expression (OR=0.042, 95% CI 0.002 to 0.980) after adjusting for potential confounders. In addition, multiple linear regression analyses showed that the QTc interval was positively associated with ZPP (β=0.299, 95% CI 0.130 to 0.468) after adjusting for potential confounders.Conclusions: Our study provided evidences that occupational exposure to Pb may be associated with worse ECG outcomes (high QRS voltage), which might be related to decreased levels of RyR1. [ABSTRACT FROM AUTHOR]

Although all southern states provide preferential property-tax incentives to forest landowners, there are great variations in the methodology of forestry-use valuation across the states. This study gives a comparative overview of the methods for current-use valuation of forestry properties across the southern states. Major issues with current practices include inconsistencies in the valuation method and forestry properties under assessment, inconsistencies in measures of incomes and costs, the quality of data for timber growth, insufficient treatment of risks associated with forest management, and the arbitrary limits on capitalization rate. To address these issues, policymakers are advised to ensure the consistency in valuation method and forestry assets, take risks into consideration, weigh the benefits and risks of fixed measures, and introduce adjustment mechanisms to the valuation system. [ABSTRACT FROM AUTHOR]

Incorporation of quantum dots into the p-n junction of the photovoltaic device provides numerous possibilities for nanoscale control of photoelectron processes via engineering the band structure and nanoscale potential profile. The band structure is determined by the size and shape of quantum dots and width of the wetting layer. The potential profile is formed by selective doping, which leads to the built-in dot charge. To study the effects of the band structure and nanoscale potential barriers on the photovoltaic performance we fabricated and investigated 3-μm base GaAs devices with various InAs quantum dot media and selective doping. All quantum dot devices show significant improvement in conversion efficiency in comparison with the reference cell. The data obtained have been analyzed in frame of the diode model. It was found that the two-diode model with the ideality factors of and well describes the scope of data. The essential component evidences that the Shockley-Read-Hall recombination plays a substantial role in recombination losses. Further optimization of solar cells should be aimed at the formation of potential profile with large barriers that separate quantum dot areas from high mobility conducting channels. [ABSTRACT FROM AUTHOR]

Background: Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. Objectives: To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Methods: Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Results: Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. Conclusions: No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally. [ABSTRACT FROM AUTHOR]

P21-activated kinase 5 (PAK5) plays an important role in tumors. However, the functional role of PAK5 in mammary tumorigenesis in vivo remains unclear. Here, we show that PAK5 deficiency represses MMTV-PyVT -driven breast tumorigenesis. DEAD-box RNA helicase 5 (DDX5) is a substrate of PAK5, which is phosphorylated on threonine 69. PAK5-mediated DDX5 phosphorylation promotes breast cancer cell proliferation and metastasis. The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. Finally, we verify decreased expression of DDX5 phosphorylation and sumoylation and mature miR-10b in PAK5 −/− /MMTV-PyVT transgenic mice. Our findings provide insights into the function of PAK5 in microRNA (miRNA) biogenesis, which might be a potential therapeutic target for breast cancer. [Display omitted] • PAK5 deficiency represses MMTV-PyVT- driven mammary tumorigenesis • PAK5-mediated DDX5 phosphorylation enhances DDX5 sumoylation and stability • PAK5 enhances the formation of the DDX5/Drosha/DGCR8 complex leading to mature miR-10b • High expression of PAK5 and p-DDX5 is associated with poor outcomes of breast cancer Li et al. show that PAK5 deletion suppresses mammary tumorigenesis in MMTV-PyVT transgenic mice, an effect that is related to the PAK5-DDX5-miR-10b pathway. Phosphorylation-dependent sumoylation of DDX5 by PAK5 enhances formation of a DDX5/Drosha/DGCR8 complex, thus promoting miR-10b processing posttranscriptionally, suggesting a potential therapeutic avenue for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the effect of reused brine and fresh salt brine on nitrites and biogenic amines production in low-salt Paocai during fermentation, with insights into the impact of initial microbial loading and acidification. By monitoring the changes in microbial counts, physicochemical properties as well as the production of nitrites, biogenic amines and precursor amino acid nitrogen (AAN) in Paocai fermented with reused brine (RB), microorganism-reduced reused brine (MRRB), fresh salt brine (SB) and acidified fresh salt brine (ASB), the results showed that RB promoted the growth of lactic acid bacteria (LAB) and yeasts, causing a rapid consumption of reducing sugar. MRRB and RB inhibited the undesirable enterobacteria, while SB and ASB failed. Among the treatments, RB achieved highest AAN contents and lowest contents of nitrites (1.10 mg/kg), histamine (0.29 mg/kg), tyramine (0.79 mg/kg) and cadaverine (not detected) after fermentation. Comparing SB with ASB, it was found that initial acidification of salt brine eliminated cadaverine and reduced histamine contents by 33.93%. These results suggested that the initial microbial loading and acidification of brine could reduce nitrites and biogenic amines production in Paocai during fermentation, which might provide guidance for production of fermented vegetable with higher safety. [Display omitted] • Reused brine with initial microbial loading promoted the growth of LAB and yeasts. • Compared with salt brine, reused brine lead to significantly lower nitrite peak. • Reused brine and acidified salt brine eliminated cadaverine in Paocai. • Compared with salt brine, reused brine reduced tyramine and histamine in Paocai. • Initial acidification of salt brine slightly reduced nitrites and biogenic amines. [ABSTRACT FROM AUTHOR]

Density functional theory calculations were performed to examine the interaction between large aromatic molecules such as benzene and phenol and stanene nanosheets. Before we consider the adsorption process, it is very necessary to optimize the atomic structure of the bare stanene and non-adsorbed benzene and phenol molecules. Our results showed that the benzene and phenol molecules are weakly physisorbed on the surface of stanene due to their lower binding energies at the surface. Phenol adsorption strength on the surface of stanene was found to be much stronger than the adsorption of benzene. Besides, the adsorption of benzene and phenol cannot make any considerable change in the electronic properties of stanene sheets. The electron density difference calculations also indicated that the electron density moves from the benzene molecule to the surface of stanene. The change densities were largely accumulated over the stanene sheet. Thus, stanene nanosheet can be suggested as a moderate host material for sensing benzene and phenol molecules. Image 1 • Benzene and phenol molecules are weakly physisorbed on the surface of stanene. • Phenol adsorption strength on the surface of stanene was found to be much stronger than the adsorption of benzene. • It is revealed that the WF of bare stanene nanosheet after adsorption aren't altered remarkably. [ABSTRACT FROM AUTHOR]

Discerning the modular nature of human diseases through computational approaches calls for diverse data. The finding sites of diseases, like other disease phenotypes, possess rich information in understanding disease genetics. Yet, analysis of the rich knowledge of disease finding sites has not been comprehensively investigated. In this study, we built a large-scale disease organ network (DON) based on 76,561 disease-organ associations (for 37,615 diseases and 3492 organs) extracted from the United Medical Language System (UMLS) Metathesaurus. We investigated how phenotypic organ similarity among diseases in DON reflects disease gene sharing. We constructed a disease genetic network (DGN) using curated disease-gene associations and demonstrated that disease pairs with higher organ similarities not only are more likely to share genes, but also tend to share more genes. Based on community detection algorithm, we showed that phenotypic disease clusters on DON significantly correlated with genetic disease clusters on DGN. We compared DON with a state-of-art disease phenotype network, disease manifestation network (DMN), that we have recently constructed, and demonstrated that DON contains complementary knowledge for disease genetics understanding. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the risk factors of hallux valgus angle among preprofessional adolescent dancesport athletes. Methods: A total of 275 athletes, (73 males and 202 females) aged between the ages of 11 and 18 years, participated in this study. A cross‐sectional questionnaire was used to survey their demographic characteristics (sex and age), training information (starting age, weekly training time, and athletic career [number of years of training at this specific dancesport school]), and measured their height and weight. The hallux valgus angle was measured based on foot photographs. The chi‐square test was used to compare the difference with prevalence of hallux valgus between male and female athletes. A normal distribution test was performed, and based on the test results, unpaired t‐test and multiple logistic regression were conducted to identify training factors for the hallux valgus in this cohort. Results: Chi‐square test showed higher prevalence of hallux valgus in female elite adolescent dancesport athletes than males. The t‐test results did not show any significant differences between the hallux valgus group and non‐hallux valgus groups with start age, athletic career, and weekly training time. Multiple logistic regression analysis with hallux valgus as the dependent variable revealed that the female sex was a strong predictor of a higher prevalence of hallux valgus (odds ratio [OR]: 3.954, 95% confidence interval 95% CI: 2.193–7.131, and p < 0.001). Weekly training time was also entered into the multiple logistic regression model (OR: 1.033, 95% CI: 1.001–1.067, and p = 0.041). Conclusions: Our findings revealed that the prevalence of hallux valgus in adolescent dancesport athletes was higher in females than in males. Longer weekly training time was also a risk factor for hallux valgus. Training factors should be considered in preventive programs for elite adolescent dancesport athletes, and special attention should be paid to female athletes. [ABSTRACT FROM AUTHOR]

Grafting scions can significantly alter apple (Malus × Domestica) fruit quality and tree development. However, there is a lack of in-depth studies on the mechanism by which different scion varieties affect the root growth of apple rootstocks. In this study, young Malus sieversii trees were grafted with Malus sieversii , Hanfu, and Fuji scions. The effects of different scion varieties on carbon and nitrogen metabolism and the microbial community structure of the roots and rhizosphere soils of apple trees were analyzed using enzyme assay and high-throughput sequencing techniques. The three scion varieties effectively increased the root length, root surface area, and vessel diameter of the root tips of young apple trees, especially in the Hanfu treatment. Under different treatment conditions, significant differences were observed in nitrogen content and key enzyme activities involved in carbon and nitrogen metabolism in the roots and rhizosphere soil of apple rootstocks, following this order: Hanfu > Fuji > Malus sieversii. Meanwhile, the Chao1 indices of bacterial and fungal communities in the rhizosphere soil of apple rootstocks were greater than those in the roots. Further analysis revealed that the roots in the Hanfu treatment harbored abundant fungal genera such as Lasiobolidium and Penicillium , whereas the rhizosphere soil was enriched with the bacterial genus Sphingomonas and the fungal genus Humicola. Taken together, the results revealed that Hanfu scions alter carbon and nitrogen metabolism and the diversity and composition of microbial communities in the roots and rhizosphere soil, thereby enhancing root growth. Our findings provide novel insights into the impact of grafting scion varieties on underground microbial communities. • Grafted scion varieties effectively enhance the root morphology of apple trees. • Grafted scion varieties modify the structure of the apple rhizosphere microbiota. • KOs associated with amine and polyamine biosynthesis are enriched in the Hanfu. • Microbial diversity in the apple rhizosphere is closely associated with root growth. [ABSTRACT FROM AUTHOR]