Abstract To verify the reliability and accuracy of wall thickness ratio analysis to determine the degree of bone healing, fracture models were established with 6 beagles. X-ray, micro-CT, and CT scans were performed at 24 weeks. The healthy side and the affected side were used to simulate the three-dimensional geometric model after internal fixation, and the mesh was divided. The mean and median CT wall thickness values were obtained through the wall thickness analysis. X-ray, CT, micro-CT, and gross appearance were used to determine the degree of bone healing, which was compared with wall thickness analysis. There was a positive correlation between the average CT value and the median wall thickness. The correlation coefficient analysis of the median wall thickness ratio (R2) and healing index ratio (R3) showed a positive correlation. The results of the wall thickness ratio (R2) and the healing index ratio (R3) were used to determine bone healing, and the results were consistent with the results of the actual mechanical test and image analysis. The results of wall thickness ratio analysis were significantly correlated with the degree of bone healing. This method is simple, rapid, and practical to analyze and judge the degree of bone healing.
Huntington disease (HD) is a neurological disorder caused by polyglutamine expansions in mutated Huntingtin (mHtt) proteins, rendering them prone to form inclusion bodies (IB). We report that in yeast, such IB formation is a factor-dependent process subjected to age-related decline. A genome-wide, high-content imaging approach, identified the E3 ubiquitin ligase, Ltn1 of the ribosome quality control complex (RQC) as a key factor required for IB formation, ubiquitination, and detoxification of model mHtt. The failure of ltn1∆ cells to manage mHtt was traced to another RQC component, Tae2, and inappropriate control of heat shock transcription factor, Hsf1, activity. Moreover, super-resolution microscopy revealed that mHtt toxicity in RQC-deficient cells was accompanied by multiple mHtt aggregates altering actin cytoskeletal structures and retarding endocytosis. The data demonstrates that spatial sequestration of mHtt into IBs is policed by the RQC-Hsf1 regulatory system and that such compartmentalization, rather than ubiquitination, is key to mHtt detoxification.
BACKGROUND: Increasing evidence reveals that aberrant microRNAs (miRNAs) expression play a crucial role in the tumorigenesis of cancers, including hepatocellular carcinoma (HCC), whereas the role of miR-654-3p in HCC remains unclear. This study aimed to investigate the role of miR-654-3p in HCC. ME THODS: Real-time quantitative PCR was performed to detect miR-654-3p expression in HCC tissues and cell lines. The association of miR-654-3p expression with clinical characteristics of HCC patients were analyzed. And the prognostic value of miR-654-3p was examined using Kaplan-Meier curve and Cox regression analysis. CCK-8 and Transwell assays were used to observe the effects of miR-654-3p on proliferation, migration, and invasion of HCC cells. RESULTS: The miR-654-3p expression was downregulated in both HCC tissues and cell lines, which was significantly associated with lymph node metastasis and TNM stage. Downregulation of miR-654-3p predicted poor prognosis of HCC patients. Overexpression of miR-654-3p inhibited HCC cell proliferation, migration, and invasion, while knockdown of miR-654-3p promoted these cellular behaviors in vitro. CONCLUSION: Our study suggested that miR-654-3p expression was downregulated in HCC and might serve as a potential prognostic marker and therapeutic target for the survival of HCC patients. miR-654-3p might exert a suppressor role in HCC through inhibiting tumor cell proliferation, migration, and invasion.
The finite element method provides a powerful tool for nonlinear numerical analysis of engineering structures. Although significant progress in the constitutive modeling of concrete and shotcrete behaviour has been made, very few of these models deal with the effect of high temperature on concrete or shotcrete. This research work developed a relatively comprehensive and sophisticated model, the Willam-Wranke five-parameter model, to describe concrete as well as shotcrete deformational and strength behavior under normal and high temperatures. A highly sophisticated Isoparametric Sandwich Shell Element (ISSQ) model that can have many layers is very useful for simulating the behavior of the shell structures, because it has the ability to separately specify a different material as well as different properties for each layer. The model also has the ability to specify a different temperature for each layer as well as constant or linear temperature distribution through the element thickness, which will be helpful for fires in tunnel structures. The model was applied to a tunnel for the case of fire loading. This helps answer many questions about the safety of tunnels in case of fire. The results show that taking fire loading into consideration is of great importance when designing concrete tunnel lining, because very high temperatures can cause total failure in some parts of the tunnel lining.
Affymetrix GeneChips were used to measure RNA abundance for ≈13,500 Drosophila genes in young, old, and 100% oxygen-stressed flies. Data were analyzed by using a recently developed background correction algorithm and a robust multichip model-based statistical analysis that dramatically increased the ability to identify changes in gene expression. Aging and oxidative stress responses shared the up-regulation of purine biosynthesis, heat shock protein, antioxidant, and innate immune response genes. Results were confirmed by using Northerns and transgenic reporters. Immune response gene promoters linked to GFP allowed longitudinal assay of gene expression during aging in individual flies. Immune reporter expression in young flies was partially predictive of remaining life span, suggesting their potential as biomonitors of aging.
Objective: To investigate the influenza vaccination and its influencing factors among the clinical staff in Xining, Qinghai province, in the 2016-2017 influenza season, and to explore the promoting strategies to encourage the target population for influenza vaccination. Methods: Four sample hospitals were randomly selected from the total 11 tertiary hospitals in Xining city. Clinical staff that worked in the four hospitals and agreed to participate were recruited for investigation via a self-administered questionnaire. Results: During the 2016-2017 influenza season, the coverage rate of influenza vaccines among the clinical staff was 5.14% (95%CI: 4.80%-5.49%). Multivariate logistic regression showed that knowing the priority of vaccination, the frequency of vaccination, effect of vaccination, and possessing higher professional qualifications were major influencing factors for influenza vaccination. The intention on recommendation of seasonal influenza vaccine was higher in vaccinated group than that in the unvaccinated group (χ(2)=99.57, P<0.001). Conclusion: The lower coverage rate was primarily associated with the lack of knowledge about influenza vaccine among the clinical staff of the hospital. Tailored information should be provided to the clinical staff through effective methods to improve vaccination and the recommendation of influenza vaccine.目的： 了解青海省西宁市临床医护人员2016－2017年度流感疫苗的接种情况及影响因素，初步探索推动西宁市临床医护人员流感疫苗接种措施。 方法： 随机抽取西宁市4家三级医院，在知情同意的原则下自愿参与完成自填式问卷调查，并访谈医院相关负责人。 结果： 西宁市三级医院临床医护人员2016－2017年度流感疫苗接种率为5.14%（95%CI：4.80%~5.49%），多因素分析显示，流感疫苗优先推荐接种人群、接种频次，接种效果的知晓以及职称是主要影响因素。接种组向他人推荐流感疫苗的意愿高于未接种组（χ(2)=99.57，P<0.001）。 结论： 西宁市医院临床医护人员流感疫苗接种率低，主要与流感疫苗的认知不足有关。应开展宣传教育，充分发挥示范和影响作用。.
Huntington disease (HD) manifests a unique macroautophagy/autophagy defect: the presense of cytosolic autophagosomes without substrates or so-called "empty" autophagosomes. It was proposed that mutant HTT (huntingtin; mHTT) disrupts cargo recognition by the selective autophagy receptor SQSTM1/p62 thus leading to the failure of cargo sequestration by phagophores, the precursors to autophagosomes. Here we looked at recent discoveries that liquid-like SQSTM1 droplets can serve as platforms for autophagosome formation, and discussed possible alternative mechanisms for "empty" autophagosome formation in HD inspired by these findings.
Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood. Mechanistic target of rapamycin (mTOR), a lysosome-localized protein kinase that acts as a critical regulator of cellular growth, is believed to mediate most Rap actions. Here, we identified mucolipin 1 (transient receptor potential channel mucolipin 1 [TRPML1], also known as MCOLN1), the principle Ca2+ release channel in the lysosome, as another direct target of Rap. Patch-clamping of isolated lysosomal membranes showed that micromolar concentrations of Rap and some rapalogs activated lysosomal TRPML1 directly and specifically. Pharmacological inhibition or genetic inactivation of mTOR failed to mimic the Rap effect. In vitro binding assays revealed that Rap bound directly to purified TRPML1 proteins with a micromolar affinity. In both healthy and disease human fibroblasts, Rap and rapalogs induced autophagic flux via nuclear translocation of transcription factor EB (TFEB). However, such effects were abolished in TRPML1-deficient cells or by TRPML1 inhibitors. Hence, Rap and rapalogs promote autophagy via a TRPML1-dependent mechanism. Given the demonstrated roles of TRPML1 and TFEB in cellular clearance, we propose that lysosomal TRPML1 may contribute a significant portion to the in vivo neuroprotective and anti-aging effects of Rap via an augmentation of autophagy and lysosomal biogenesis.
Formation of intracellular mutant Huntingtin (mHtt) aggregates is a hallmark of Huntington's disease (HD). The mechanisms underlying mHtt aggregation, however, are still not fully understood. A few recent studies indicated mHtt undergoes phase transition, bringing new clues to understand how mHtt aggregates assemble. Here in this mini review, we will summarize these findings with a focus on the factors that affect mHtt phase transition. We will also discuss the possible pathological roles of mHtt phase separation in HD.
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