Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study.

Our study aimed to investigate the association between the transition of the TXNIP gene methylation level and the risk of incident type 2 diabetes mellitus (T2DM). This study included 263 incident cases of T2DM and 263 matched non-T2DM participants. According to the methylation levels of five loci (CpG1-5; chr1:145441102-145442001) on the TXNIP gene, the participants were classified into four transition groups: maintained low, low to high, high to low, and maintained high methylation levels. Compared with individuals whose methylation level of CpG2-5 at the TXNIP gene was maintained low, individuals with maintained high methylation levels showed a 61-87% reduction in T2DM risk (66% for CpG2 [OR: 0.34, 95% CI: 0.14, 0.80]; 77% for CpG3 [OR: 0.23, 95% CI: 0.07, 0.78]; 87% for CpG4 [OR: 0.13, 95% CI: 0.03, 0.56]; and 61% for CpG5 [OR: 0.39, 95% CI: 0.16, 0.92]). Maintained high methylation levels of four loci of the TXNIP gene are associated with a reduction of T2DM incident risk in the current study. Our study suggests that preserving hypermethylation levels of the TXNIP gene may hold promise as a potential preventive measure against the onset of T2DM.

Association of traditional and novel obesity indicators with stroke risk: Findings from the Rural Chinese cohort study.

BACKGROUND AND AIMS: Few researchers have compared the effectiveness of traditional and novel obesity indicators in predicting stroke incidence. We aimed to evaluate the associations between six obesity indices and stroke risk, and to further identify the optimal indicator. METHODS AND RESULTS: A total of 14,539 individuals from the Rural Chinese Cohort Study were included in the analyses. We used the Cox proportional hazards regression models to evaluate the association between six obesity indices (including body mass index [BMI], waist circumference [WC], conicity index [C-index], lipid accumulation product [LAP], visceral adiposity index [VAI], and Chinese visceral adiposity index [CVAI]) and stroke risk. Receiver operating characteristic curves were employed to compare their predictive ability on stroke risk. During a median follow-up period of 11.13 years, a total of 1257 cases of stroke occurred. In the multiple-adjusted Cox regression model, WC, BMI, C-index, and CVAI were positively associated with ischemic stroke (P < 0.01) rather than hemorrhagic stroke risk. Dose-response analyses showed a linear correlation of WC, BMI, C-index, and LAP (Poverall <0.05, and Pnonlinear >0.05), but a non-linear correlation of CVAI (Poverall <0.05, and Pnonlinear <0.05) with the risk of ischemic stroke. CVAI demonstrates the highest areas under the curves (AUC: 0.661, 95% CI: 0.653-0.668), indicating a superior predictive ability for ischemic stroke occurrence compared to other five indices (P < 0.001). CONCLUSION: WC, BMI, C-index, LAP, and CVAI were all positively related to the risk of ischemic stroke, among which CVAI exhibited stronger predictive ability for ischemic stroke.

A first-principles study of bilayered black phosphorene as a potential anode material for sodium-ion batteries.

Black phosphorene has attracted widespread attention because of its great potential as a high-performance anode material for sodium-ion batteries (SIBs). However, almost all theoretical studies on sodium (Na) atom adsorption and diffusion in it have not taken temperature into account. Actually, the structural stability of an anode material at room temperature is vital in practical applications. In this work, employing first-principles calculations, we investigate the stability of AA-, AB-, AC- and AD-stacked bilayered black phosphorene (BBP) at ground state, and Na adsorption and diffusion within BBPs. Using ab initio molecular-dynamics (AIMD) calculations, dynamic stabilities of pristine BBP and Na-adsorbed BBP systems at room temperature are discussed. Our calculations show that only AB-stacked BBP is stable. Na atoms generally prefer to intercalate within BBP, making all BBPs exhibit metallic properties, which provides good electrical conductivity required for an ideal anode of SIBs. In particular, our AIMD results indicate that the temperature effect on the structural stability of Na-adsorbed BBP could not be neglected. It increases Na capacity loss at room temperature. This provides an important reference for further theoretical and experimental exploration of anode materials for SIBs. Additionally, the AC-stacked structure facilitates Na intercalation within BBP, and Na diffusion exhibits a strong directional preference, diffusing very fast along the zigzag direction. Our results suggest that AC-stacked BBP is a potential anode material of SIBs.

Correlation of heavy metals' exposure with the prevalence of coronary heart disease among US adults: findings of the US NHANES from 2003 to 2018.

We sought to explore the association between heavy metal exposure and coronary heart disease (CHD) based on data from the US National Health and Nutrition Examination Survey (NHANES, 2003-2018). In the analyses, participants were all aged > 20 and had participated in heavy metal sub-tests with valid CHD status. The Mann-Kendall test was employed to assess the trends in heavy metals' exposure and the trends in CHD prevalence over 16 years. Spearman's rank correlation coefficient and a logistics regression (LR) model were used to estimate the association between heavy metals and CHD prevalence. 42,749 participants were included in our analyses, 1802 of whom had a CHD diagnosis. Total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine, and cadmium, lead, and total mercury in blood all showed a substantial decreasing exposure level tendency over the 16 years (all Pfor trend < 0.05). CHD prevalence varied from 3.53 to 5.23% between 2003 and 2018. The correlation between 15 heavy metals and CHD ranges from - 0.238 to 0.910. There was also a significant positive correlation between total arsenic, monomethylarsonic acid, and thallium in urine and CHD by data release cycles (all P < 0.05). The cesium in urine showed a negative correlation with CHD (P < 0.05). We found that exposure trends of total arsenic, dimethylarsonic acid, monomethylarsonic acid, barium, cadmium, lead, and antimony in urine and blood decreased. CHD prevalence fluctuated, however. Moreover, total arsenic, monomethylarsonic acid, and thallium in urine all showed positive relationships with CHD, while cesium in urine showed a negative relationship with CHD.

Volatiles Accumulation during Young Pomelo (Citrus maxima (Burm.) Merr.) Fruits Development.

As widely planted fruits with high nutritional and medical values, pomelos are managed systematically to achieve the largest economic benefits. But the annual shedding of young pomelos, which could be applied as feedstocks for essential oil extraction with their abundant volatiles, leads to a waste of source. The present study selected two commonly planted pomelo (Citrus maxima (Burm.) Merr.) varieties in Southern China, to investigate the volatile profiles during young pomelo fruits development. Combing transcriptomic analysis, this study aimed at identifying the prominent volatile components in young pomelo fruits in order to preferably extract profitable volatiles, as well, increasing the knowledge concerning regulatory roles of transcription factors (TFs) on volatiles accumulation in young pomelos. Totally 29 volatiles were identified, including 14 monoterpenoids and 13 sesquiterpenoids. Diprene was the principal component with the highest amount. Volatiles were generally decreased during fruits development but preferable stages were figured out for volatile collections. 12 and 17 TFs were related to developing time while ERF003 and MYC2 were highly correlated to monoterpenoids. These findings put forward the comprehensive usages of young pomelos and enriched the regulatory roles of TFs on both fruit development and volatiles metabolism.

Persistent Helicobacter pylori infection for more than 3 years leads to elevated serum homocysteine concentration: A retrospective cohort study based on a healthy Chinese population.

BACKGROUND AND AIM: The relationship between the Helicobacter pylori (H. pylori) infection and homocysteine is unclear. We evaluated the effect of H. pylori on serum homocysteine in a healthy Chinese population. METHODS: A total of 21 184 individuals aged over 18 years underwent 13 C/14 C urease breath test (13 C/14 C-UBT) and blood tests and 5042 individuals with follow-up intervals greater than 6 months. Homocysteine levels are classified according to the Chinese expert consensus. RESULTS: The rates of H. pylori infection of normal level, mild level, moderate level, and severe level were 40.9%, 43.8%, 45.8%, and 46.6%, respectively (P = 0.000). H. pylori infection increased the risk of higher homocysteine concentration (OR = 1.406, P = 0.000). In the case-control study, the rates of persistent negative, new infection, persistent infection, and eradication infection were 43.6%, 11.2%, 22.9%, and 22.3%, respectively. The percentage of changes in serum homocysteine levels varied significantly among the different H. pylori infection statuses only in mild level (P = 0.024). Mean changed homocysteine values were higher in the subgroup of persistent infection than in the persistent negative subgroup (P = 0.004) and the eradication infection subgroup (P = 0.034). Serum homocysteine values were elevated only in the subgroup with over 3 years interval time and persistent infection (n = 107, mean paired differences = 1.1 ± 4.6 µmol/L, P = 0.014). CONCLUSIONS: There is a relationship between H. pylori and serum homocysteine, and persistent infection leads to elevation of the latter.

Compressed Video Quality Index Based on Saliency-Aware Artifact Detection.

Video coding technology makes the required storage and transmission bandwidth of video services decrease by reducing the bitrate of the video stream. However, the compressed video signals may involve perceivable information loss, especially when the video is overcompressed. In such cases, the viewers can observe visually annoying artifacts, namely, Perceivable Encoding Artifacts (PEAs), which degrade their perceived video quality. To monitor and measure these PEAs (including blurring, blocking, ringing and color bleeding), we propose an objective video quality metric named Saliency-Aware Artifact Measurement (SAAM) without any reference information. The SAAM metric first introduces video saliency detection to extract interested regions and further splits these regions into a finite number of image patches. For each image patch, the data-driven model is utilized to evaluate intensities of PEAs. Finally, these intensities are fused into an overall metric using Support Vector Regression (SVR). In experiment section, we compared the SAAM metric with other popular video quality metrics on four publicly available databases: LIVE, CSIQ, IVP and FERIT-RTRK. The results reveal the promising quality prediction performance of the SAAM metric, which is superior to most of the popular compressed video quality evaluation models.

Evaluation of Carotenoids Accumulation and Biosynthesis in Two Genotypes of Pomelo (Citrus maxima) during Early Fruit Development.

Pomelo is rich in bioactive compounds (carotenoids, phenolics and essential oil) in the early stage of fruit development, but it is often wasted in the cultivation and management process. To gain an insight into the carotenoid metabolism pathway in pomelo, the carotenoid profiles and the expression patterns of carotenogenic genes were investigated in two genotypes of pomelo during early fruit development. The results showed that a higher carotenoid content was observed in honey pomelo as compared with golden pomelo, which may be related to different gene regulation mechanisms. Lutein, α-carotene, and ß-carotene were the main carotenoids in pomelo young fruit, and lutein was the highest one. The accumulation of carotenoids during fruit early development in honey pomelo is related to the transcriptional regulation of ZISO and LUT5. In golden pomelo, the rate-limiting gene for carotenoids is PDS and ZDS. In addition, the expression of seven genes except CRTISO in honey pomelo was higher than that in golden pomelo. The results are helpful to further clarify the regulatory mechanism of carotenoid accumulation during early fruit development and provide a direction for the high-value utilization of young fruits in pomelo.

A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design.

Aggregation of polypeptides and proteins is commonly associated with human and other vertebrate diseases. For example, amyloid plaques consisting of amyloid-ß proteins are frequently identified in Alzheimer's disease and islet amyloid formed by islet amyloid polypeptide (IAPP, amylin) can be found in most patients with type 2 diabetes (T2D). Although many fluorescent dyes have been developed to stain amyloid fibrils, very few examples have been designed for IAPP. In this study, a series of environmentally sensitive fluorescent probes using flavonoid as a scaffold design are rationally designed and synthesized. One of these probes, namely 3-HF-ene-4'-OMe, can bind to IAPP fibrils but not nonfibrillar IAPP by exhibiting a much stronger fluorescent enhancement at 535 nm. In addition, this probe shows better detection sensitivity to IAPP fibrils compared with that of conventionally used thioflavin-T. We demonstrate that 3-HF-ene-4'-OMe can be used to monitor the kinetics of IAPP fibril formation in vitro even in the presence an amyloid inhibitor. To test the specificity of the probe, we attempt to incubate this probe with amyloid fibrils formed from other amyloidogenic proteins. Interestingly, this probe shows different responses when mixed with these fibrils, suggesting the mode of binding of this probe on these fibrils could be different. Moreover, we show that this probe is not toxic to pancreatic mouse ß-cells. Further structural optimization based on the structure of 3-HF-ene-4'-OMe may yield a specific probe for imaging islet amyloid in the pancreas. That would improve our understanding of the relationship between islet amyloid and T2D.

Persistent infection of Helicobacter pylori affects weight loss in obese population compared with persistent negative: A case-control study based on healthy Chinese.

BACKGROUND: The relationship between Helicobacter pylori (H pylori) and body mass index (BMI) is still inconclusive. Not only the high rate of H pylori infection but also the increasing higher BMI levels are endangering Chinese today. METHODS: The aim of this research was to evaluate the association between different situations of H pylori infection and BMI values or levels in Chinese healthy population. A total of 39 091 individuals aged from 18 years to 80 years, performed healthy examination including a 13 C/14 C urease breath test (13 C/14 C-UBT), were included. Among them, 30 224 individuals only had one time of health examination, and 8867 had two or more times. A case-cohort data of 8752 with an interval time more than 6 months, collected by the first and the last time, were established from the latter. BMI groups are classified according to the China recommendation: low weight (<18.5 kg/m2 ), normal weight (18.5 ~ 23.9 kg/m2 ), overweight (24.0 ~ 27.9 kg/m2 ), and obesity (≥28.0 kg/m2 ). RESULTS: The rate of H pylori infection among low weight, normal weight, overweight, and obesity was 43.2%, 44.7%, 46.4%, and 48.0%, respectively (P = .000). H pylori infection increased the risk of higher level of BMI (OR = 1.077, 95% confidence interval = 1.036-1.119, χ2  = 14.048, P = .000) with adjustments for sex and age. In the case-control study, the rate of persistent negative, persistent infection, new infection, and eradicated infection was 39.5%, 25.8%, 15.8%, and 18.9%, respectively, with a median interval time of 13 months. The mean obesity BMI descend values in the persistent negative subgroup were lower than those in the persistent infection subgroup (-0.21 ± 1.19 kg/m2 vs -0.003 ± 1.01 kg/m2 , P = .021). But the change of BMI classifications had no difference between the subgroups of H pylori infection in different BMI levels. CONCLUSIONS: H pylori infection was positively correlated with higher BMI levels. And H pylori persistent infection had a negative effect on the fall of BMI values in Chinese obese population.

Assessing left ventricular systolic function in children with a history of Kawasaki disease.

BACKGROUND: The incidence of Kawasaki disease (KD) is increasing. Indeed, KD has become the most common cause of acquired heart disease in children. Previous studies have well summarized the acute phase left ventricular (LV) systolic dysfunction using speckle tracking echocardiography (STE); however, changes in LV systolic function after long-term follow-up remain unclear. METHODS: One hundred children with a history of KD, but without coronary artery aneurysms, were enrolled. These children were divided into two subgroups based on the presence or absence of coronary artery dilatation (CAD). The duration of follow-up was > 7 years. The control group consisted of 51 healthy children. The LV myocardial strain were measured by two- and three-dimensional STE. RESULTS: Two-dimensional STE not only revealed that LV longitudinal strain decreased in part of segments in both KD groups, but also showed that global strain decreased in the KD group with CAD compared to the controls (P < 0.05). Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) were obtained by 3D STE. Compared to the controls, GLS and GAS decreased in both KD groups (P < 0.05). GCS and GRS decreased in the KD group with CAD, but was unchanged in the KD group without CAD (P < 0.05). CONCLUSIONS: LV systolic dysfunction in children with KD and CAD was more severe than KD children without CAD compared to healthy children. This dysfunction can be assessed by LV regional and global myocardial strain using two- and three-dimensional STE.

Investigating behavior inhibition in obsessive-compulsive disorder: Evidence from eye movements.

We investigated the role of inhibition failure in Obsessive Compulsive Disorder (OCD) through an eye tracking experiment. Twenty-five subjects with OCD were recruited, as well as 25 with Generalized Anxiety Disorder (GAD) and 25 healthy controls. A 3 (group: OCD group, GAD group and control group) × 2 (target eccentricity: far and near) × 2 (saccade task: prosaccade and antisaccade) mixed design was used, with all participants completing two sets of tasks involving both prosaccade (eye movement towards a target) and antisaccade (eye movement away from a target). The main outcome was the eye movement index, including the saccade latency (the time interval from the onset of the target screen to the first saccade) and the error rate of saccade direction. The antisaccade latency and antisaccade error rates for OCDs were much higher than those for GADs and healthy controls. OCDs had longer latency and error rates for antisaccades than for prosaccades, and for far-eccentricity rather than near-eccentricity stimuli. These results suggest that OCDs experience difficulty with behavior inhibition, and that they have higher visual sensitivity to peripheral stimuli. In particular, they show greatest difficulty in inhibiting behavior directed towards peripheral stimuli.

Sideband amplitude modulation absorption spectroscopy of CH4 at 1170 nm.

We report on the method of the sideband amplitude modulation (SAM) to achieve high-sensitivity spectroscopy with a fiber electro-optic modulator (fiber-EOM). This method increases the signal to noise ratio (SNR) by a factor of forty, comparing with conventional absorption spectroscopy. It is a temporal balanced detection to eliminate the intensity noise of the light source, and capable of preserving an undistorted Doppler profile for further quantitative analysis. Taking advantage of the newly developed fiber-EOM, SAM is applicable for various spectroscopies with a simple experimental setup. We performed SAM on CH43ν3 overtone band at 1170 nm using an external cavity Quantum dot laser. We demonstrated that one of the absorption lines buried in the other ten times stronger nearby lines was clearly extracted. SAM shows great potential on the molecular spectroscopy, where the spectrum is complicated and quantitative analysis is required.

Application of two-dimensional fractional-order convolution and bounding box pixel analysis for rapid screening of pleural effusion.

Pleural effusion is a pathologic symptom in which there is accumulation of body fluids around the lungs. A chest radiograph is a rapid examination technique and does not require complex setup for making a preliminary diagnosis of lung and heart diseases. In radiographic visualization, the symptom patterns appear as light or dark areas in the lung cavity. Computer-aided diagnosis is an automatic manner that can rapidly highlight the object region by preanalyzing medical images. It can improve the problems of manual inspection and allow diagnosis in remote medical facilities. Based on the ratios of lung anatomy, the automatic screening manner based on pattern recognition can be viewed as pixel value detection in the bilateral lung cavities. In this study, a fractional-order convolution (FOC) process is used to enhance the original image for an accurate extrapolation of the desired object in an image. The specific object image feature can be improved, and an accurate quantification of the pleural effusion region can be obtained using the suitable ranges of fractional-order parameters. Based on the boundaries of homogeneous regions, the pixel ratios of the lung anatomy between normal and abnormal conditions can be computed. The pleural effusion sizes and volumes can be rapidly estimated through the number of pixel changes. The experimental results reveal that the feature maps are similar and stable on image enhancement and segmentation with two fractional-order enhancement masks, as fractional-order v = 0.05 to 0.20 for mask 1# and v = 0.80 to 0.95 for mask 2#, respectively. The results also demonstrate the feasibility of the study on combining two-dimensional image FOC-process and bounding box pixel analysis to estimate the moderate and large effusion sizes from 500-2,000 mL.

HIF-1α triggers long-lasting glutamate excitotoxicity via system xc- in cerebral ischaemia-reperfusion.

Hypoxia-inducible factor 1α (HIF-1α) controls many genes involved in physiological and pathological processes. However, its roles in glutamatergic transmission and excitotoxicity are unclear. Here, we proposed that HIF-1α might contribute to glutamate-mediated excitotoxicity during cerebral ischaemia-reperfusion (CIR) and investigated its molecular mechanism. We showed that an HIF-1α conditional knockout mouse displayed an inhibition in CIR-induced elevation of extracellular glutamate and N-methyl-d-aspartate receptor (NMDAR) activation. By gene screening for glutamate transporters in cortical cells, we found that HIF-1α mainly regulates the cystine-glutamate transporter (system xc- ) subunit xCT by directly binding to its promoter; xCT and its function are up-regulated in the ischaemic brains of rodents and humans, and the effects lasted for several days. Genetic deletion of xCT in cortical cells of mice inhibits either oxygen glucose deprivation/reoxygenation (OGDR) or CIR-mediated glutamate excitotoxicity in vitro and in vivo. Pharmaceutical inhibition of system xc- by a clinically approved anti-cancer drug, sorafenib, improves infarct volume and functional outcome in rodents with CIR and its therapeutic window is at least 3 days. Taken together, these findings reveal that HIF-1α plays a role in CIR-induced glutamate excitotoxicity via the long-lasting activation of system xc- -dependent glutamate outflow and suggest that system xc- is a promising therapeutic target with an extended therapeutic window in stroke. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease.

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe3O4-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe3O4-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7 days compared to the non-treated leg that showed no evidence of the blood recovery.

Randomization and resilience of brain functional networks as systems-level endophenotypes of schizophrenia.

Schizophrenia is increasingly conceived as a disorder of brain network organization or dysconnectivity syndrome. Functional MRI (fMRI) networks in schizophrenia have been characterized by abnormally random topology. We tested the hypothesis that network randomization is an endophenotype of schizophrenia and therefore evident also in nonpsychotic relatives of patients. Head movement-corrected, resting-state fMRI data were acquired from 25 patients with schizophrenia, 25 first-degree relatives of patients, and 29 healthy volunteers. Graphs were used to model functional connectivity as a set of edges between regional nodes. We estimated the topological efficiency, clustering, degree distribution, resilience, and connection distance (in millimeters) of each functional network. The schizophrenic group demonstrated significant randomization of global network metrics (reduced clustering, greater efficiency), a shift in the degree distribution to a more homogeneous form (fewer hubs), a shift in the distance distribution (proportionally more long-distance edges), and greater resilience to targeted attack on network hubs. The networks of the relatives also demonstrated abnormal randomization and resilience compared with healthy volunteers, but they were typically less topologically abnormal than the patients' networks and did not have abnormal connection distances. We conclude that schizophrenia is associated with replicable and convergent evidence for functional network randomization, and a similar topological profile was evident also in nonpsychotic relatives, suggesting that this is a systems-level endophenotype or marker of familial risk. We speculate that the greater resilience of brain networks may confer some fitness advantages on nonpsychotic relatives that could explain persistence of this endophenotype in the population.

Wenshen Zhuanggu formula effectively suppresses breast cancer bone metastases in a mouse Xenograft model.

Wenshen Zhuanggu formula (WSZG) is a traditional Chinese medicine used as an adjuvant for the prevention of bone metastases in breast cancer patients. In this study we investigated the efficacy of WSZG in preventing bone metastases and the potential mechanisms in a mouse xenograft model of breast cancer bone metastases. This model was established by injection of human MDA-MB-231BO-Luc breast cancer cells alone or a mixture of the cancer cells with bone marrow-derived mesenchymal stem cells (BMSCs) into left ventricle of the heart in female nude mice. Then the mice were treated with WSZG (3.25, 6.5 or 13.0 mg·kg-1·d-1, ig) for four weeks, whereas zoledronic acid (100 µg/kg per week, ig) was used as a positive control. The occurrence and development of bone metastases were monitored via bioluminescent imaging, and bone lesions were assessed using micro-CT. Intracardiac injection of the mixture of MDA-MB-231BO-Luc breast cancer cells with BMSCs significantly facilitated the bone metastatic capacity of the breast cancer cells, and aggravated bone lesions in the mouse xenograft model of breast cancer bone metastases. Administration of WSZG dose-dependently inhibited the incidence and intensity of bone metastases and protected against bone lesions by suppressing osteoclast formation and tumor cell infiltration. Furthermore, administration of WSZG caused a marked reduction in the expression of CCL5/CCR5 and IL-17B/IL-17BR in bone metastatic tissues. The results demonstrate that WSZG exerts potential therapeutic effects in a mouse xenograft model of breast cancer bone metastases, which are partially mediated by weakening the interaction between BMSCs and breast cancer cells in the tumor microenvironment.

Apparatus for Comparison of Pullout Forces for Various Thoracic Stent Grafts at Varying Neck Angulations and Oversizes.

BACKGROUND: The purpose of this study is to provide an apparatus for comparison of pullout forces for various thoracic stent grafts at varying neck angulations and oversizes. METHODS: An in vitro platform capable of performing pullout tests was used on stent grafts in angulated silicone tubes designed for this study (0°, 45°, 90°, and 135° with a 32-mm inner diameter) in a temperature-controlled chamber (37 ± 2°C). Three commercial stent grafts with sizes commonly used in Taiwan (Valiant: 34, 36, 38, and 40 mm; Zenith TX2: 34, 36, 38, and 40 mm; and TAG: 34, 37, and 40 mm) were used, and each size was tested 8 times for each angulation condition. RESULTS: The mean dislodgement forces (DFs) at 0° angulation within 10-20% oversize were approximately 22.7, 9.6, and 9.0 N for the Valiant, Zenith TX2, and TAG devices, respectively, whereas the mean DFs decreased by 46%, 38%, and 50% to 12.3, 5.9, and 4.5 N when the angulation reached 135°. Regression analysis shows that neck angulation was a significant factor for the Valiant and Zenith TX2 devices (P < 0.0001 and P < 0.0001, respectively) but not for the TAG device (P = 0.483). In addition, oversize and interactions between variables (angulation × oversize) exhibited significant effects on the DFs for all devices (P < 0.0001). CONCLUSIONS: We successfully built up an apparatus for comparison of pullout forces for various thoracic stent grafts at varying neck angulations and oversizes. With the empirical comparative data of different brand stent grafts under various conditions shown and compared, our findings suggest that aortic neck angulation has a negative correlation with stent-graft fixation. To have better stent-graft fixation and seal in the aortic arch for thoracic endovascular aortic repair, a longer landing zone with cautiously selected oversize is a more suitable selection.

MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus.

We previously reported that the G allele of rs3853839 at 3'untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P = 6.5×10(-10), odds ratio (OR) (95%CI) = 1.27 (1.17-1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta = 7.5×10(-11), OR = 1.24 [1.18-1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 3'UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R(2) = 0.255, P = 0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 3'UTR segment bearing the C allele (P = 0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta  = 2.0×10(-19), OR = 1.25 [1.20-1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148.