Association Between Genetic Variant in the Promoter of Pri-miR-34b/c and Risk of Glioma

Growing evidence indicates that p53 can regulate the expression of miRNAs, particularly the miR-34 family members, which are described as potential tumor suppressors. Loss of miR-34 suppresses TP53-mediated cell death, whereas over expression of miR-34 induced apoptosis. The study designed to investigate the association between the pir-miR-34b/c rs4938723, TP53 Arg72Pro and the risk of glioma. We genotyped the two polymorphisms in175 glioma patients and 235 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing assay. Association analysis showed that the CC genotype of the pir-miR-34b/c rs4938723 was associated with a significantly decreased risk of glioma compared to the TT genotype (CC vs. TT: adjusted OR = 0.43;95% CI, 0.21–0.87,P = 0.02). Moreover, a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 0.41; 95% CI, 0.21–0.81, P = 0.007). In contrast, the CC genotype of the TP53 Arg72Pro was associated with a significantly increased risk of glioma compared to the GG genotype (CC vs. GG: adjusted OR = 1.73;95% CI, 1.04–2.89,P = 0.04), and a significant association between the patients with glioma and controls was also observed in a recessive model (OR = 2.00; 95% CI, 1.26–3.18, P = 0.003). These findings suggest that the pri-miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be associated with the risk of glioma

Inhibition of ANGPT2 activates autophagy during hypertrophic scar formation via PI3K/AKT/mTOR pathway

Abstract Background Hypertrophic scar (HS), a fibroproliferative disorder caused by aberrant wound healing following skin injuries such as burns, lacerations and surgery, is characterized by invasive proliferation of fibroblasts and excessive extracellular matrix (ECM) accumulation. The dysregulation of autophagy is the pathological basis of HS formation. Previously, angiopoietin-2 (ANGPT2) was found to be overexpressed in HS fibroblasts (HSFs) compared with normal skin fibroblasts. However, whether ANGPT2 participates in the process of HS formation and the potential molecular mechanisms are not clear. Objective This study is intended to figure out the role of ANGPT2 and ANGPT2-mediated autophagy during the development of HS. Methods RT-qPCR was used to detect ANGPT2 expression in HS tissues and HSFs. HSFs were transfected with sh-ANGPT2 to knock down ANGPT2 expression and then treated with MHT1485, the mTOR agonist. The effects of sh-ANGPT2 or MHT1485 on the proliferation, migration, autophagy and ECM accumulation of HSFs were evaluated by CCK-8 assay, Transwell assay and western blotting. The expression of PI3K/Akt/mTOR pathway-related molecules (p-PI3K, p-Akt and p-mTOR) was assessed by western blotting. Results ANGPT2 expression was markedly upregulated in HS tissues and HSFs. ANGPT2 knockdown decreased the expression of p-PI3K, p-Akt and p-mTOR. ANGPT2 knockdown activated autophagy and inhibited the proliferation, migration, and ECM accumulation of HSFs. Additionally, the treatment of MHT1485, the mTOR agonist, on ANGPT2-downregulated HSFs, partially reversed the influence of ANGPT2 knockdown on HSFs. Study limitations The study lacks the establishment of more stable in vivo animal models of HS for investigating the effects of ANGPT2 on HS formation in experimental animals. Conclusions ANGPT2 downregulation represses growth, migration, and ECM accumulation of HSFs via autophagy activation by suppressing the PI3K/Akt/mTOR pathway. Our study provides a novel potential therapeutic target for HS

Shifting as an executive function separate from updating and inhibition in old age: Behavioral and genetic evidence

This study aimed to examine the organization of executive functions (EFs), specifically working memory updating, prepotent response inhibition, and mental-set shifting in old age, with a particular focus on determining whether the shifting function was behaviorally and genetically separated from the other functions. A total of 248 healthy older Chinese individuals participated, and multiple measures of executive functions were collected. Additionally, measures of fluid intelligence were included to explore the varying relationships between the three executive functions and this higher-order cognitive ability. Furthermore, genetic data were gathered and analyzed to investigate the associations between EFs and six candidate single-nucleotide polymorphisms (SNPs) mapped to dopaminergic, serotonergic, or glutamatergic genes. The results indicated that both the three-factor model and the two-factor model, which combined updating and inhibition, demonstrated a good fit. Furthermore, shifting was found to be behaviorally separated from the other two functions, and the correlation between shifting and fluid intelligence was smaller compared to the correlations between updating and inhibition with fluid intelligence. Moreover, the DRD2 SNPs showed significant associations with shifting, rather than with updating and inhibition. These findings provide evidence that shifting is distinct and separate from updating and inhibition, highlighting the diversity of EFs among older adults

A review of aerodynamic and wake characteristics of floating offshore wind turbines

International audienceWind-generated electricity has effectively promoted the net-zero carbon emission plan, and gradually developed to the deeper ocean, which leads to the emergence of rotating equipment with both rigidity and flexibility: floating offshore wind turbines (FOWT). This review presents crucial determinants for the FOWT's power generation, namely aerodynamics and wakes, which are strongly coupled to the hydrodynamics of the floating platform. The selection of different platforms leads to unique performances, and technology and cost are direct constraints for global floating projects. In the experimental study, the scale model based on some similarity criteria is used to reflect aerodynamic characteristics of the prototype under the multi-degree of freedom motions, but with the contradiction between the Froude number and Reynolds number. Wave basin and wind tunnel are two typical research forms, but the premise is the model scaling to obtain similar dynamic thrust and power. Besides, a cyclic pitch control method is discussed, which is expected to effectively reduce the fatigue load of the spindle and gears. As for the numerical simulation, Blade Element Momentum, Computational Fluid Dynamics, Free-Vortex Wake and Boundary Element behave in different calculation capacities and costs. The power, thrust and wake are obtained under specific platform and motion conditions, and the calculation results lack comparisons and verifications. It is necessary to ignore the extremely limited power increase caused by pitch and surge motion in the design process, to make the platform more stable for dynamic performances and significantly reduce fatigue loads. As a review article, this paper could provide a meaningful reference for those engaged in the aerodynamics of FOWT

Epidemiological Characteristics and Spatial-Temporal Clusters of Hand, Foot, and Mouth Disease in Zhejiang Province, China, 2008-2012.

Hand, foot and mouth disease (HFMD) is one of the major public health concerns in China. Being the province with high incidence rates of HFMD, the epidemiological features and the spatial-temporal patterns of Zhejiang Province were still unknown. The objective of this study was to investigate the epidemiological characteristics and the high-incidence clusters, as well as explore some potential risk factors. The surveillance data of HFMD during 2008-2012 were collected from the communicable disease surveillance network system of Zhejiang Provincial Center for Disease Control and Prevention. The distributions of age, gender, occupation, season, region, pathogen's serotype and disease severity were analyzed to describe the epidemiological features of HFMD in Zhejiang Province. Seroprevalence survey for human enterovirus 71 (EV71) in 549 healthy children of Zhejiang Province was also performed, as well as 27 seroprevalence publications between 1997 and 2015 were summarized. The spatial-temporal methods were performed to explore the clusters at county level. Furthermore, pathogens' serotypes such as EV71 and coxsackievirus A16 (Cox A16) and meteorological factors were analyzed to explore the potential factors associated with the clusters. A total of 454,339 HFMD cases were reported in Zhejiang Province during 2008-2012, including 1688 (0.37%) severe cases. The annual average incidence rate was 172.98 per 100,000 (ranged from 72.61 to 270.04). The male-to-female ratio for mild cases was around 1.64:1, and up to 1.87:1 for severe cases. Of the total cases, children aged under three years old and under five years old accounted for almost 60% and 90%, respectively. Among all enteroviruses, the predominant serotype was EV71 (49.70%), followed by Cox A16 (26.05%) and other enteroviruses (24.24%) for mild cases. In severe cases, EV71 (82.85%) was the major causative agent. EV71 seroprevalence survey in healthy children confirmed that occult infection was common in children. Furthermore, literature summary for 26 seroprevalence studies during 1997-2015 confirmed that 0-5 years group showed lowest level of EV71 seroprevalence (29.1% on average) compared to the elder children (6-10 years group: 54.6%; 11-20 years group: 61.8%). Global positive spatial autocorrelation patterns (Moran's Is>0.25, P<0.05) were discovered not only for mild cases but also for severe cases, and local positive spatial autocorrelation patterns were revealed for counties from the eastern coastal and southern regions. The retrospective space-time cluster analysis also confirmed these patterns. Risk factors analyses implied that more EV71 and less sunshine were associated with the clusters of HFMD in Zhejiang Province. Our study confirmed that Zhejiang Province was one of the highly epidemic provinces in China and that the epidemiological characteristics of HFMD were similar to other provinces. Occult infection in elder children and adults was one of the important reasons why most HFMD cases were children aged under-five. Combining the results of spatial autocorrelation analysis and the space-time cluster analysis, the major spatial-temporal clusters were from the eastern coastal and southern regions. The distribution of pathogens' serotypes and the level of sunshine could be risk factors for, and serve as an early warning of, the outbreak of HFMD in Zhejiang Province

The results of space-time cluster analysis for mild cases of Zhejiang Province, 2008–2012.

<p>The results of space-time cluster analysis for mild cases of Zhejiang Province, 2008–2012.</p

Age-specific EV71 seroprevalence summary in healthy children.

<p>Age-specific EV71 seroprevalence summary in healthy children.</p

The incidence rates of counties in Zhejiang Province, 2008–2012.

<p>The incidence rates of counties in Zhejiang Province, 2008–2012.</p

The partial correlations between the monthly proportions of EV71/Cox A16 and the case-severity rate.

<p>The partial correlations between the monthly proportions of EV71/Cox A16 and the case-severity rate.</p