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Abstract Background Recent study showed that individuals with type 2 diabetes have a high risk of developing colorectal cancer (CRC), in which Receptor for Advanced Glycation End Products (RAGE) plays a pivotal role. We conducted a cross-sectional study to examine the relationships of circulating sRAGE, CRC and other clinical factors in type2 diabetes patients. Methods A total of 150 type 2 diabetes patients aged 50 years and older were enrolled, including 50 patients with CRC and 100 patients without CRC. We measured Serum levels of sRAGE and interleukin-6(IL-6) using an enzyme-linked immunosorbent assay (ELISA). In addition, other clinical parameters were also measured during hospitalization. Results Type 2 diabetes patients with CRC had higher triglyceride, total cholesterol, IL-6, and circulating sRAGE levels and lower use of medicines than type 2 diabetes patients without CRC. Circulating sRAGE was associated with an increased risk for CRC (OR = 2.289 for each SD increase in sRAGE, 95% CI = 1.037–5.051; P = 0.04) among Type 2 diabetes patients after adjustment for confounders. Furthermore, circulating sRAGE levels among type 2 diabetes patients were positively correlated with triglyceride (r = 0.377, P

ObjectiveAbdominal adipose is closely related to many endocrine and metabolic diseases. The aim of this study was to analyze the distribution of abdominal adipose tissue in a healthy population in northern China determined by abdominal computed tomography (CT).MethodsData for this study were obtained from a multicenter, retrospective, cross-sectional study that collected abdominal CT scans of 1787 healthy individuals from 4 representative cities in northern China. Areas of visceral adipose tissue (VATA) and subcutaneous adipose tissue (SATA) were obtained by measuring CT images at the level of the 3rd lumbar vertebra. Visceral adipose tissue index (VATI) and subcutaneous adipose index (SATI) were obtained by normalizing the square of height to analyze the distribution of the above indexes and visceral obesity among different body mass index (BMI), gender and age.ResultsThe mean age of this healthy population was 45.3 ± 15.2 years and the mean BMI was 23.5 ± 3.2 kg/m2, with 902 men and 885 women. Compared with women, men had a significantly higher median VATA (120.9 vs. 67.2 cm2), VATI (39.1 vs. 25.6 cm2/m2) and a significantly higher percentage of visceral adiposity (VATA ≥ 100 cm2) (60.8 vs. 30.4%), while women had significantly higher SATA (116.9 vs. 146.7 cm2) and SATI (38.8 vs. 55.8 cm2/m2) than men. Whether men or women, VATI was positively correlated with age. Interestingly, SATI was weakly positively correlated with age in women, while SATI was weakly negatively correlated with age in men. In persons with a normal BMI, the proportion of visceral adiposity increases with age, whereas in men with a normal BMI, the proportion of visceral adiposity decreases after the age of 60 years but remains >50%.ConclusionsThe distribution of abdominal visceral and subcutaneous adipose tissue parameters measured by CT differed among gender, age, and BMI. Even men and women with normal BMI have a high proportion of visceral obesity.

Abstract Future coastal flood hazard at many locations will be impacted by both tropical cyclone (TC) change and relative sea‐level rise (SLR). Despite sea level and TC activity being influenced by common thermodynamic and dynamic climate variables, their future changes are generally considered independently. Here, we investigate correlations between SLR and TC change derived from simulations of 26 Coupled Model Intercomparison Project Phase 6 models. We first explore correlations between SLR and TC activity by inference from two large‐scale factors known to modulate TC activity: potential intensity (PI) and vertical wind shear. Under the high emissions SSP5‐8.5, SLR is strongly correlated with PI change (positively) and vertical wind shear change (negatively) over much of the western North Atlantic and North West Pacific, with global mean surface air temperature (GSAT) modulating the co‐variability. To explore the impact of the joint changes on flood hazard, we conduct climatological–hydrodynamic modeling at five sites along the US East and Gulf Coasts. Positive correlations between SLR and TC change alter flood hazard projections, particularly at Wilmington, Charleston and New Orleans. For example, if positive correlations between SLR and TC changes are ignored in estimating flood hazard at Wilmington, the average projected change to the historical 100 years storm tide event is under‐estimated by 12%. Our results suggest that flood hazard assessments that neglect the joint influence of these factors and that do not reflect the full distribution of GSAT change may not accurately represent future flood hazard.

Silicon is regarded as the most promising anode candidate for improving the energy density of next‐generation Li‐ion batteries (LIBs) because of the high specific capacity of 4200 mAh g−1, low working voltage, and natural abundance. It is well demonstrated that the serious issues such as huge volume expansion and intrinsic low conductivity of Si anode can be addressed by nanoengineering and compositing strategies. An important step toward fully realizing the practical application of the Si‐containing electrode lies in producing high‐quality materials on large scale. Therefore, a controllable, high‐efficient, low‐cost, and environment‐friendly synthetic methodology is required to fabricate Si‐containing anode materials with high tap density, low specific surface area, high conductivity, chemical and structural stability, and high purity, thus leading to high Coulombic efficiency, high specific capacity, long cycling stability, and superior rate capability. In this review, the effects and bottlenecks of synthetic methodologies for the developments of Si anode are emphasized. The well‐developed physical and chemical synthetic approaches of nano‐ and microstructured Si, Si‐based composites, and Si–graphite hybrid electrode materials are summarized. In each category, the main merits and limitations of different synthetic methods are discussed from both academic and industrial points of view. Finally, this review ends with a conclusion of these synthetic routes, and a brief perspective on the future direction of Si‐containing Li‐storage materials for practical LIBs.

The mechanisms by which deubiquitinases modulate tumour progression are not fully understood. Here, the authors perform an RNAi screen and identify that the deubiquitinase OTUD5 suppresses cancer growth in a TRIM25 dependent manner, which in turn controls the expression of tumour suppressor protein, PML.

Abstract Background The mid-upper arm circumference (MUAC) is a proxy for subcutaneous fat in the upper body and is a reliable screening measure for identifying individuals with abnormal regional fat distribution. The purpose of this study was to evaluate the association between MUAC and metabolic syndrome (MetS) in middle-aged and elderly individuals. Methods We measured the MUAC in a cross-sectional sample with a total of 9787 subjects aged 40 years and older. The measurement of MUAC is performed on the right arm using a non-elastic tape held midway between the acromion and the olecranon processes in duplicate, with the arm hanging loosely at the side of the body. The MetS was defined according to the Joint Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Results MUAC was positively correlated with waist circumference (r = 0.437, P

Objective: A small thigh circumference is associated with an increased risk of diabetes, cardiovascular diseases, and total mortality. The purpose of this study was to evaluate the association between thigh circumference and hypertension in the middle-aged and elderly population. Methods: A total of 9520 individuals aged 40 years and older with measurement of thigh circumference were available for analysis. The measurement of thigh circumference was performed directly below the gluteal fold of the thigh. The association of thigh circumference with hypertension was tested in logistic regression analyses and reported as odds ratio (OR) with 95% CI. Results: Thigh circumference was negatively correlated with systolic blood pressure, diastolic blood pressure, fasting glucose, and total cholesterol. Compared with the lowest thigh circumference tertile group, the risk of hypertens ion was significantly lower in the highest tertile group, both in overweight individuals (OR 0.68; 95% CI 0.59–0.79, P < 0.001) and obese individuals (OR 0.51; 95% CI 0.38–0.70, P < 0.001). Conclusion: In the present study, large thigh circumference is associated with lower risk of hypertension in overweight and obese Chinese individuals.

System-level electromagnetic transient (EMT) simulation of large-scale power converters with high-order nonlinear semiconductor switch models remains a challenge albeit it is essential for design preview. In this work, a multi-layer hierarchical modeling methodology is proposed for high-performance computing of the modular multilevel converter involving device-level IGBT/diode models. The computational burden induced by converter scale and model complexity is dramatically alleviated following the proposal of topological reconfiguration and network equivalence, which create a substantial number of identical circuit units that facilitate massively parallel processing on the graphics processing unit (GPU), using the kernel-based single-instruction multi-threading computing architecture. As the DC system brings significant inhomogeneity which dilutes parallelism, heterogeneous computing is investigated and the computational tasks are properly assigned to CPU and GPU to fully exploit their respective features. The separation of nonlinear device-level models from the rest of the system enables multi-rate implementation for further efficiency enhancement since the two parts allow distinct time-steps. A remarkable acceleration of over 50 times is achieved by the hybrid CPU/GPU platform over conventional CPU simulation, and the validity of the proposed modeling and computing method is confirmed by commercial EMT tools ANSYS/Simplorer and PSCAD/EMTDC.

Objective To investigate the application value of acoustic radiation force impulse imaging in preoperative prediction for efficacy of High-Intensity Focused Ultrasound uterine fibroids ablation Methods A prospective study was conducted on 32 women (41 fibroids) undergoing HIFU uterine fibroids ablation between January 2019 and September 2019. The virtual touch tissue quantification (VTQ) technique was used for the preoperative determination of uterine fibroids shear wave velocity (SWV). The stiffness of the preoperative uterine fibroids was graded on a virtual touch tissue image (VTI). All uterine fibroids were ablated with a single point ablation acoustic power of 400 W. All patients underwent pelvic cavity MRI examination for the measurement of the size, volume and non-perfused volume (NPV) of fibroids within the first month after HIFU ablation. The ablation rate of uterine fibroids was calculated according to the formula: ablation rate = NPV × 100/target fibroid volume. The patients were divided into two groups based on the postoperative ablation rate: ≥70% ablation rate group, and＜70% ablation rate group. The preoperative SWV and VTI grade of uterine fibroids were compared between the two groups. The correlation of preoperative uterine fibroids’ SWV and VTI grade with HIFU ablation rate were analyzed using the Spearman’s correlation coefficient. The optimal cutoff points in preoperative uterine fibroids SWV of 70% ablation rate were determined by receiver operating curve (ROC) analysis. Results A total of 30 patients (73.17%, 30/41) showed ablation rate ≥70%, with preoperative uterine fibroids’ SWV values of (3.42 ± 0.71) m/s. Of these, 24 patients (80%, 24/30) had VTI grades II–III. On the other hand, 26.83% (11/41) showed ablation rate

Objective To explore correlations between the therapeutic effect of high intensity focused ultrasound (HIFU) and histopathological characteristics of uterine fibroids with different Shear Wave Velocity (SWV) values. Methods A retrospective study was conducted on 36 women (43 fibroids) who had undergone high intensity focused ultrasound (HIFU) uterine fibroids ablation between January 2019 and January 2020. Preoperative fibroids tissue sections were obtained for histopathological examination. The pathological sections were stained with Masson-trichrome, and were observed and imaged under a Low-power microscope (4 × 10), while the smooth muscle cell (SMC) and collagen fiber content were semi-quantitatively measured. Preoperative fibroid SWV was measured using the Virtual Touch tissue quantification (VTQ) technique. Within one month after HIFU ablation, all patients had undergone a pelvic cavity MRI examination, which measured the size, volume, and non-perfused volume (NPV) of the fibroids. The formula: the ablation rate = NPV/target fibroid volume × 100% was used to calculate the ablation rate of the uterine fibroids. Correlation analysis of SWV values, HIFU ablation rate, along with the smooth muscle cell (SMC) and collagen fiber content, were conducted using the Spearman’s correlation test. Results The collagen fiber and SMC content of the preoperative fibroids were 32.09 ± 15.90%/view and 37.61 ± 15.32%/view, respectively. Preoperative fibroid SWV value was 3.56 ± 0.71 m/s. Preoperative fibroid SWV was negatively correlated with SMC content (r = −0.445, p = 0.003), but positively correlated with collagen fiber content (r = 0.454, p = 0.002). The ablation rate was negatively correlated with collagen fiber content (r = −0.377, p = 0.013), but positively correlated with SMC content (r = 0.402, p = 0.007). Conclusion Differences in histopathological characteristics may be important factors that induce differences in the therapeutic effects of HIFU ablation on uterine fibroids with different SWV values.

The mismatch between the supply and demand of religious places has resulted from a lack of management, population mobility, and urban socio-spatial differentiation. Furthermore, the identity of religious groups and the localized characteristics of their behavioral practices continue to dominate the evolution of religious places. Therefore, this study analyzed the spatio-temporal patterns of Christian activity places, and further studied the characteristics and mechanisms of various influencing factors on the spatial distribution of places using a geographically weighted regression model from a socio-spatial perspective. The following results were obtained: (1) Christian activity places form a distribution pattern of circling aggregation within the core area and polycentric dispersion outside the core area. There is a certain coupling relationship between spatio-temporal patterns of places and marketization in Yiwu City. (2) The spatial differentiation pattern of influencing factors has an obvious circle-layer characteristic. The regression coefficients of population mobility, age structure, public services, and jobs-housing space are larger, and social structure and spatial resource allocation are becoming the main driving forces of spatial differentiation. (3) Due to the differences in spatial resource allocation and believers' behavioral choices, the above factors have distinct differences in urban core areas, urban-rural transition areas and rural areas.

Preparedness for adverse events is critical to building urban resilience to climate-related risks. While most extant studies investigate preparedness patterns based on survey data, this study explores the potential of big digital footprint data (i.e. population visits to points of interest (POI)) to investigate preparedness patterns in the real case of Hurricane Ida (2021). We further investigate income and racial inequality in preparedness by combining the digital footprint data with demographic and socioeconomic data. A clear pattern of preparedness was seen in Louisiana with aggregated visits to grocery stores, gasoline stations, and construction supply dealers increasing by nearly 9%, 12%, and 10% respectively, representing three types of preparedness: survival, mobility planning, and hazard mitigation. Preparedness for Hurricane Ida was not seen in New York and New Jersey states. Inequality analyses for Louisiana across census block groups (CBGs) demonstrate that CBGs with higher income have more (nearly 8% greater) preparedness in visiting gasoline stations, while CBGs with a larger percentage of the white population have more preparedness in visiting grocery stores (nearly 12% more) in the lowest income groups. The results indicate that income and racial inequality differ across different preparedness in terms of visiting different POIs.

Extraosseous Ewing’s sarcoma (EES) is a malignant tumor that is classified as a rare disease. EES is common in children and adolescents, with a rarer incidence being present in the elderly. ES of the primary intestine is rare, with only a few reports described in the literature. Here we report a case of a 69-year-old male patient who was experiencing abdominal pain for over 3 months. Ultrasonography (US) revealed a solid hypoechoic lesion with multiple irregular necrotic areas in the left lower abdomen close to the dome of the bladder. Contrast-enhanced ultrasonography (CEUS) showed that the lesion exhibited heterogeneous enhancement and quick peripheral enhanced tissue wash-out classifying this mass as malignant. PET–CT showed a high metabolic mass in the lower abdomen, multiple metabolic nodules in the mesentery, considered as a small intestinal stromal tumor with lymph nodes metastasis, and that a diagnosis of lymphoma should be excluded. Esophagogastroduodenoscopy performed at another hospital 1 month prior to CT showed an abnormal density in the pelvic cavity that was considered as a colonic diverticulum with an abscess. The endoscopy showed no obvious occupying lesions. The mass was removed and postoperative pathology confirmed ES of the small intestine. The patient avoided receiving chemotherapy. After 2 months, skull metastasis was diagnosed and surgical intervention was done. His survival was only six months after the second surgery. To our knowledge, our case is the first report of ultrasound and CEUS manifestation of EES in the small intestine in elderly.

Aims: To evaluate the prospective association of circulating PCSK9 levels with the cardiometabolic risk profiles (high LDL-cholesterol, high triglycerides, low HDL-cholesterol, hypertension, type 2 diabetes, and metabolic syndrome).Methods: A population-based prospective study was conducted among 7,104 Chinese individuals (age 56.2 ± 7.5 years; 32.0% men). Circulating PCSK9 levels were measured using ELISA.Results: Circulating PCSK9 levels were higher in women than men (286.7 ± 90.1 vs. 276.1 ± 86.4 ng/ml, p < 0.001). And circulating PCSK9 was positively correlated with LDL-cholesterol, total cholesterol, and triglycerides both in men and women (all p < 0.001). The positive correlation between PCSK9 and waist circumference, fasting glucose, insulin resistance, systolic blood pressure, diastolic blood pressure and C-reactive protein (all p < 0.01) was observed in women only. According to Cox regression analysis, circulating PCSK9 was positively associated with incidence of high LDL-cholesterol both in men (HR 1.33, 95% CI 1.09–1.65, p < 0.001) and women (HR 1.36, 95% CI 1.12–1.69, p < 0.001). Moreover, PCSK9 was significantly associated with incident high triglycerides (HR 1.31, 95% CI 1.13–1.72, p < 0.001), hypertension (HR 1.28, 95% CI 1.08–1.53, p = 0.011), type 2 diabetes (HR 1.34, 95% CI 1.09–1.76, p = 0.005), and metabolic syndrome (HR 1.30, 95% CI 1.11–1.65, p = 0.009) per SD change in women only. No statistically significant association was observed between circulating PCSK9 and incidence of low HDL-cholesterol (p > 0.1).Conclusions: Elevated circulating PCSK9 was significantly associated with cardiometabolic risk factors and independently contributed to the prediction of cardiometabolic risks in women.

Tropical cyclone-induced coastal flooding will increase under climate change. Here the authors estimate the effects of sea level rise and tropical cyclone climatology change on late–21st–century flood hazards along the US Atlantic and Gulf Coasts and find that the effect of tropical cyclone change could surpass the effect of sea level rise at some areas in the Gulf of Mexico.

Metasurfaces have powerful light field manipulation capabilities, which have been extensively studied in the past few years and have developed rapidly in various fields. At present, the focus of metasurface research has shifted to the tunable functionality. In this paper, a temperature-controllable multifunctional metasurface lens based on phase transition material is designed. First of all, by controlling the temperature of the desired working area and the polarization of the incident light, switching among multiple focus, single focus, and no focus at any position can be achieved, and the intensity and helicity of the output light can be adjusted. In addition, a polarization-sensitive intensity-tunable metalens based on the P-B phase principle is designed, when the incident light is linearly polarized light, left-handed circularly polarized light, or right-handed circularly polarized light, it has the same focal point but with different light field intensities. Therefore, the focused intensity can be tunable by the polarization state of the incident light.

ObjectiveGrowth differentiation factor 15 (GDF-15) is a member of the TGF-β superfamily that has anti-inflammatory properties. The objective of this study was to evaluate the relationship between circulating GDF-15 levels and diabetic retinopathy (DR) in patients with type 2 diabetes.Materials/MethodsA case–control study was performed in which 402 patients with type 2 diabetes were enrolled. Of these, 171 patients had DR and the remaining 231 patients without DR acted as controls. The plasma GDF-15 levels were measured using ELISA, while DR was diagnosed using the canon ophthalmic digital imaging system and the Canon EOS 10D digital camera (Canon, Tokyo, Japan) through a non-pharmacologically dilated pupil.ResultsThe levels of GDF-15 were significantly higher in patients with DR [168.9 (112.9–228.3) pg/ml vs. 127.8 (96.1–202.8) pg/ml, P < 0.001] compared to controls. Results of the Spearman correlation analysis showed that the GDF-15 levels were positively associated with the duration of diabetes morbidity, fasting plasma glucose, systolic blood pressure, albumin/creatinine ratio, creatinine, and liver enzymes, but negatively associated with eGFR (both P < 0.001). The participants in the highest GDF-15 quartile had a significantly increased risk for DR (OR = 2.15, 95% CI 1.53–3.02) after adjusting for potential cofounders.ConclusionsThe circulating GDF-15 levels are positively associated with DR independent of potential cofounders.

This paper proposes a framework for a layout evaluation of urban public sports facilities. First, the buffer analysis method is used to measure the service level of public sports facilities. The study findings indicate that the overall service level of public sports facilities presents the spatial characteristics of a central agglomeration, and the value of the service level diffuses outward from high to low. There is evident spatial heterogeneity in the layout of public sports facilities in Hangzhou. Second, the Gini coefficient, Lorenz curve, and location entropy are employed to measure the equity of the distribution among spatial units and the intradistrict disparity. The results show a mismatch between the spatial distribution of the facilities and the distribution of the permanent population. The patterns of distribution of the location entropy classes of Hangzhou can be divided into three types: balanced, alternating, and divergent districts. The method in this paper is effective in measuring spatial equity and visualizing it. it has a certain degree of systemicity, universality and operability. At the same time, this method can compare the diachronic characteristics of the same city and the synchronic characteristics of different cities, which has universal application value.

Abstract Sea level rise (SLR) and subsidence are expected to increase the risk of flooding and reliance on flood defenses for cities built on deltas. Here, we combine reliability analysis with hydrodynamic modeling to quantify the effect of projected relative SLR on dike failures and flood hazards for Shanghai, one of the most exposed delta cities. We find that flood inundation is likely to occur in low‐lying and poorly protected periurban/rural areas of the city even under the present‐day sea level. However, without adaptation measures, the risk increases by a factor of 3–160 across the densely populated floodplain under projected SLR to 2100. Impacts of frequent flood events are predicted to be more affected by SLR than those with longer return periods. Our results imply that including reliability‐based dike failures in flood simulations enables more credible flood risk assessment for global delta cities where conventional methods have assumed either overtopping only or complete failure.

Abstract The Princeton environment‐dependent probabilistic tropical cyclone (PepC) model is developed for generating synthetic tropical cyclones (TCs) to support TC risk assessment. PepC consists of three components: a hierarchical Poisson genesis model, an analog‐wind track model, and a Markov intensity model. The three model components are dependent on environmental variables that vary with the climate, including potential intensity, advection flow, vertical wind shear, relative humidity, and ocean‐cooling parameters. The present model is developed for the North Atlantic Basin. The three model components and the integrated model are verified against observations using out‐of‐sample testing. The model can generally capture the TC climatology and reproduce statistics of TC genesis, movement, rapid intensification, and lifetime maximum intensity, as well as local landfall frequency and intensity. It can be coupled with climate models and TC hazard models to quantify TC‐related wind, surge, and rainfall risks under various climate conditions. The modeling framework can be further improved when more relevant environmental variables are identified and become available in climate model outputs.

Chloroplast development and chlorophyll metabolism have been well described in model plants but not in perennial woody crops. Of particular interest is the interplay between light and hormones under shade conditions. We report that the shade induced accumulation of chlorophylls in Camellia sinensis cv. Shuchazao leaves is at least as a result of (a) positive changes in chloroplast development and (b) light/hormonal regulation of genes and transcription factors involved in the chlorophyll biosynthesis pathway. Under shade conditions, leaves developed an abundance of enlarged chloroplasts encapsulating more prominent thylakoid membranes. Four major metabolites in the chlorophyll biosynthesis pathway namely Chl a, Chl b, DPP, and Mg-Proto IX increased under shade conditions while PBG decreased significantly. Significant changes were found at the transcription level of regulators of chloroplast biogenesis (GLK1 and LHCB), the structural genes in the chlorophyll biosynthesis pathway (HEMA1, CLH1, PORA, and CAO) and potential components involved in light signaling (PHYA, CRY1, HY5, and DELLAs). Two central signal integrators (GLK1 and LHCB) between the nucleus and chloroplast showed clear responses to shade, suggesting a crucial role of light in regulating chloroplast development in tea leaves. Concurrent with the changes in gene expression, the concentrations of endogenous phytohormones (auxin, cytokinin, and gibberellins) increased significantly in the later stages of shade conditions. Two key integrators involved in the hormone signal pathways, EIN3 and EBF1/2, increased under shade conditions suggesting that shade induced changes to hormone levels may play some role in modulating chlorophyll biosynthesis in the tea leaves. Overall, this data suggests that the light and hormone influence over chloroplast development and chlorophyll biosynthesis in Camellia is similar to that of Arabidopsis. This study provides new insights into the molecular mechanisms that regulate chlorophyll biosynthesis in response to light and hormones in a commercially important woody plant such as Camellia, which may facilitate the breeding of high-chlorophyll tea cultivars for the improvement of sensory features of the green tea product.

Brown adipose tissue (BAT) can convert fatty acids and glucose into heat, exhibiting the potential to combat obesity and diabetes. The mass and activity of BAT gradually diminishes with aging. As a newly found regulator of gene expression, long non-coding RNAs (lncRNAs) exhibit a wide range of functions in life processes. However, whether long non-coding RNA (lncRNA) involves in BAT dysfunction with aging is still unclear. Here, using RNA-sequencing technology, we identified 3237 messenger RNAs (mRNAs) and 1312 lncRNAs as differentially expressed in BAT of 10-months-old mice compared with 6- to 8-week-old. The protein-protein interaction network and k-score analysis revealed that the core mRNAs were associated with two important aging-related pathways, including cell cycle and p53 signaling pathway. Gene set enrichment analysis indicated that these mRNAs might participate in lipid metabolism and brown fat dysfunction. Functional enrichment analyses demonstrated that dysregulated lncRNAs were associated with mitochondria, regulation of cellular senescence, cell cycle, metabolic and p53 signaling pathways. Moreover, we revealed that two lncRNAs (NONMMUT024512 and n281160) may involve in the regulation of their adjacent gene peroxisome proliferator-activated receptor alpha (Pparα), a thermogenesis regulator. Collectively, these results lay a foundation for extensive studies on the role of lncRNAs in age-related thermogenic degradation.

Background/Aims: MicroRNAs (miRNAs) are a novel class of small RNAs that participate in a variety of biological processes. Although miRNAs have been linked to insulin synthesis and glucose homeostasis, their role in the targeting of mitochondrial uncoupling protein 2 (UCP2), a negative modulator of insulin secretion, remains unclear. Methods: miRNA levels were determined by real-time quantitative PCR analysis using TaqMan probes, and insulin secretion from isolated islets was quantified by ELISA. Effects of miRNAs on UCP2 expression were checked with a luciferase assay and western blotting analysis. Results: An overall change in a set of miRNAs was discovered, with miR-15a, miR-424, miR-497, and miR-185 coinciding with insulin levels in islets maintained under high-glucose conditions. Moreover, experiments in MIN6 cells illustrated that miR-15a, miR-424, miR-497, and miR-185 positively regulated insulin biosynthesis by co-inhibiting UCP2 expression. Furthermore, the four miRNAs were found to post-transcriptionally repress UCP2 expression by directly targeting the 3’UTR of UCP2 mRNA. Conclusions: Thus, our results shed further light on the regulatory network in β-cells consisting of miRNAs, UCP2, and insulin and provide novel therapeutic targets for diabetes.

With the recent rising attention and debates on the role of natural gas, especially liquid natural gas, in energy transition, it is critical to have a consistent approach in assessing uncertainties and dynamics in the global gas market during the next two to three decades. There are two objectives of this paper. The first one is to estimate and discuss the impacts of the global liquified natural gas (LNG) trade under a low-carbon scenario using a partial equilibrium model. The second objective is to discuss the role of a structural economic model in empirical analysis and strategy design under a regime shift, such as an energy transition, for the global natural gas market.

Abstract Background Elevated resting heart rate (RHR) has been reported to be associated with metabolic syndrome and type 2 diabetes. The aim of this study was to explore whether a positive relationship exists between RHR and impaired glucose regulation (IGR) among middle-aged and older Chinese individuals. Methods We conducted a cross-sectional analysis that included a total of 9898 subjects (3194 men and 6704 women) in a Chinese population. The RHRs were derived from ECG recordings, and the subjects were stratified based on RHR quartiles. Results RHR levels were significantly higher in the subjects with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), IFG + IGT and diabetes than in those with normal glucose regulation. When multivariate logistic regression analyses were performed, the odds ratios were substantially higher for the subjects with IGR (odds ratio 2.19, 95% confidence interval 1.85–2.58) in the fourth RHR quartile compared with those in the first quartile after adjustment for potential confounding covariates, and the corresponding OR for the combined IGR and type 2 diabetes group was 2.56 (95% CI 2.20–2.98, p

The association between white blood cell (WBC) and nonalcoholic fatty liver disease (NAFLD) has been studied before, but whether different WBC subtypes were related to NAFLD was not detailed. The aim of our study was to investigate the relationship between WBC subtypes and NAFLD cross-sectionally and prospectively. The detailed research design has been described previously. At baseline, there were 9930 participants who had complete information, in the end a total of 8079 participants (2588 men and 5491 women) were eventually included in this study. Hepatic ultrasound examination was performed on each participant at baseline and at the end of follow-up. Alcohol abuse and hepatitis were excluded. WBC subtypes and other serum indices were measured at baseline. We found that the total WBC, neutrophil, and lymphocyte counts were independently associated with the prevalence and incidence of NAFLD. After multiple adjustments for age, gender, body mass index (BMI), insulin, HOMA-IR, TG, TC, LDL, and HDL, increased odds ratios (ORs) for new onset NAFLD were observed from the 1st to the 4th quartiles of WBC, neutrophil, and lymphocyte (all P

With 6.5 million households in the United States located in areas prone to storm surge, assessing the vulnerability of structures and residential communities to coastal flooding is an important concern. Of particular interest is understanding how the performance of structures during surge events is influenced by flood conditions, coastal defenses, and building design at both the house and community level. This study presents such a vulnerability analysis by investigating the impact of coastal flooding from Hurricane Sandy (2012) on 95 km of developed coastline across New Jersey and New York. Exterior structural damage observed from a Federal Emergency Management Agency (FEMA) aerial survey of the study area is related to (1) a hindcast simulation of flood inundation and wave action, (2) a classification of coastal defenses and storm-induced erosion, and (3) minimum building design elevations specified in FEMA’s flood hazard mapping. Findings indicate that the hardest hit communities experienced significant dune erosion, which coincided with severe flood and wave exposure. Furthermore, structures were considerably more susceptible to flood impact if Sandy’s flood level exceeded FEMA’s 100-year Base Flood Elevation dictating building design. These results are quantified by developing fragility curves relating both house and community-level performance to the considered vulnerability parameters. Findings from this study can be used to inform decision making for improving coastal resilience.

It is recently demonstrated that amorphous Ge anode shows higher reversible Na-ion storage capacity (590 mA h g−1) than crystallized Ge anode (369 mA h g−1). Here, amorphous GeOx anode is prepared by a simple wet-chemistry reduction route at room temperature. The obtained amorphous GeOx shows a porous hierarchical architecture, accompanied with a Brunauer–Emmett–Teller surface area of 159 m2 g−1 and an average pore diameter of 14 nm. This unique structure enables the GeOx anode to enhance the Na-ion/electron diffusion rate, and buffer the volume change. As anode for Na-ion battery, high reversible capacity over 400 mA h g−1, fine rate capability with a capacity of 200 mA h g−1 maintained at 3.0 A g−1 and long-term cycling stability with 270 mA h g−1 even over 1000 cycles at 1.0 A g−1 are obtained.

Objective: This study was initiated to evaluate the effects of Roux-en-Y gastric bypass surgery on renal gluconeogenesis in type 2 diabetic rats and its relationship with hormonal parameters. Methods: Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ; 35 mg/kg) combined with a high-fat diet. They were then randomly divided into three groups: diabetes model group (DM group, n = 8), sham Roux-en-Y gastric bypass group (SRYGB group, n = 8), and Roux-en-Y gastric bypass group (RYGB group, n = 14). Another 8 normal rats comprised the normal control group (NC group, n = 8). Body weight, glucose, serum lipid, insulin, glucagon-like peptide-1 (GLP-1), leptin, and adiponectin were measured pre- and postoperatively. Glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor-α (IR-α), insulin receptor-β (IR-β), and glycogen synthase kinase 3 beta (Gsk3b) were measured in renal cortex by using RT-PCR and Western immune-blot analyses on the 4th week after operation. Results: Following RYGB surgery, surgery-treated rats showed significantly improved oral glucose tolerance, dyslipidemia and insulin resistance as well as increased post-gavage insulin levels and serum circulating levels of GLP-1 and adiponectin. RT-PCR and Western immune-blot analyses showed PEPCK and G6Pase protein and mRNA to be significantly decreased in the renal cortex in the RYGB group (p Conclusion: Down-regulation of renal gluconeogenic enzymes might be a potential mechanism in hypoglycemia. An improved insulin signal pathway in the renal cortex and increased circulating adiponectin concentrations may contribute to the decline of renal gluconeogenesis following RYGB surgery.

Infrastructure located along the U.S. Atlantic and Gulf coasts is exposed to rising risk of flooding from sea level rise, increasing storm surge, and subsidence. In these circumstances coastal management commonly based on 100-year flood maps assuming current climatology is no longer adequate. A dynamic programming cost–benefit analysis is applied to the adaptation decision, illustrated by application to an energy facility in Galveston Bay. Projections of several global climate models provide inputs to estimates of the change in hurricane and storm surge activity as well as the increase in sea level. The projected rise in physical flood risk is combined with estimates of flood damage and protection costs in an analysis of the multi-period nature of adaptation choice. The result is a planning method, using dynamic programming, which is appropriate for investment and abandonment decisions under rising coastal risk.

The Sea, Lake, and Overland Surges from Hurricanes (SLOSH) model is the operational storm surge model of the National Hurricane Center (NHC). Previous studies have found that the SLOSH model estimates storm surges with an accuracy of ±20%. In this study, through hindcasts of historical storms, we assess the accuracy of the SLOSH model for four coastal regions in the Northeastern United States. We investigate the potential to improve this accuracy through modification of the wind field representation. We modify the surface background wind field, the parametric wind profile, and the maximum wind speed based on empirical, physical, and observational data. We find that on average the SLOSH model underestimates maximum storm surge heights by 22%. The modifications to the surface background wind field and the parametric wind profile have minor impacts; however, the effect of the modification to maximum wind speed is significant—it increases the variance in the SLOSH model estimates of maximum storm surges, but improves its accuracy overall. We recommend that observed values of maximum wind speed be used in SLOSH model simulations when possible.

What is the decision-making mechanism people rely upon to mitigate flood risk? Applying Bayesian Network modeling to a comprehensive survey dataset for the US Gulf Coast, we find that the overall support for flood mitigation can be inferred from flood insurance purchase behavior (i.e. without insurance versus with insurance purchased mandatorily, voluntarily, or both). Therefore, we propose a theoretical decision-making mechanism composed of two dimensions including informed flood risk and sense of insecurity. The informed flood risk is the primary determinant on one’s overall support for flood mitigation. Risk mitigation decisions are largely contingent on the level of risk that is effectively conveyed to individuals. Additionally, sense of insecurity plays a moderate role in determining individuals’ overall support for flood mitigation. The sense of insecurity can move people toward overall support for mitigation, but the effect is not as large as the informed risk. Results of this study have fundamental policy implications. The flood risk informed by Federal Emergency Management Agency’s flood maps not only provides the compulsory basis for flood insurance purchase but also determines individuals’ overall support for flood mitigation. Flood map inaccuracy can immensely mislead individuals’ overall risk mitigation decision. Meanwhile, this flood risk mitigation decision-making mechanism inferred from a survey data in the US Gulf Coast needs to be tested and validated elsewhere.

Congenital heart diseases (CHD) are among the most common birth defects in China. Environmental causes and folate metabolism changes may alter susceptibility to CHD. The aim of this study is to evaluate the relevant risk-factors of children with CHD and their mothers.138 children with CHD and 207 normal children for controls were recruited. Their mothers were also enlisted in this study and interviewed following a questionnaire about their pregnant history and early pregnancy situation. Five single nucleotide polymorphisms (SNPs) in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MS) and cystathionine β-synthase (CBS) of mothers and children were genotyped.There were significant differences in the gender of children, occupation of mothers, family history with CHD, history of abortion, history of adverse pregnancy, early pregnancy health, fetus during pregnancy, pesticide exposure and drug exposure in CHD group and control group ( P < 0.05). Logistic regression analyses showed that after adjustment for above factors, MTHFR rs1801131 were significantly associated with their offspring CHD risk in mothers. Compared with the mothers whose MTHFR were rs1801131 AA and AC genotypes, the mothers who got a mutation of MTHFR rs1801131 CC genotypes had a 267% increase in risk of given birth of a CHD children (OR = 3.67,95%CI = 1.12-12.05). Meanwhile, MTHFR rs1801131 were significantly associated with CHD susceptibility in children (OR = 1.42, 95% CI = 1.00-2.44 in additive model).Besides mothers' social and fertility characteristics, our results suggested that the genetic variants in folate metabolism pathway might be one of the most related risk-factors of CHD. MTHFR rs1801131 were identified as loci in Chinese population that were involved in CHD.

Bronchopulmonary dysplasia (BPD) is characterized by alveolar simplification with decreased alveolar number and increased airspace. Previous studies suggested that transforming growth factor-α (TGF-α) may contribute to arrested alveolar development in BPD. Histone deacetylases (HDACs) control cellular signaling and gene expression. HDAC2 is crucial for suppression of inflammatory gene expression. Here we investigated whether HDAC2 was involved in the arrest of alveolarization, as well as the ability of HDAC2 to regulate TGF-α expression in a rat model of BPD induced by intra-amniotic injection of lipopolysaccharide (LPS). Results showed that LPS exposure led to a suppression of both HDAC1 and HDAC2 expression and activity, induced TGF-α expression, and disrupted alveolar morphology. Mechanistic studies showed that overexpression of HDAC2, but not HDAC1, suppressed LPS-induced TGF-α expression. Moreover, the HDAC inhibitor TSA or downregulation of HDAC2 by siRNA both significantly increased TGF-α expression in cultured myofibroblasts. Finally, preservation of HDAC activity by theophylline treatment improved alveolar development and attenuated TGF-α release. Together, these findings indicate that attenuation of TGF-α-mediated effects in the lung by enhancing HDAC2 may have a therapeutic effect on treating BPD.

The rupture risk of unruptured intracranial aneurysms is known to be dependent on the size of the aneurysm. However, the association of morphological characteristics with ruptured aneurysms has not been established in a systematic and location specific manner for the most common aneurysm locations. We evaluated posterior communicating artery (PCoA) aneurysms for morphological parameters associated with aneurysm rupture in that location. CT angiograms were evaluated to generate 3-D models of the aneurysms and surrounding vasculature. Univariate and multivariate analyses were performed to evaluate morphological parameters including aneurysm volume, aspect ratio, size ratio, distance to ICA bifurcation, aneurysm angle, vessel angles, flow angles, and vessel-to-vessel angles. From 2005-2012, 148 PCoA aneurysms were treated in a single institution. Preoperative CTAs from 63 patients (40 ruptured, 23 unruptured) were available and analyzed. Multivariate logistic regression revealed that smaller volume (p = 0.011), larger aneurysm neck diameter (0.048), and shorter ICA bifurcation to aneurysm distance (p = 0.005) were the most strongly associated with aneurysm rupture after adjusting for all other clinical and morphological variables. Multivariate subgroup analysis for patients with visualized PCoA demonstrated that larger neck diameter (p = 0.018) and shorter ICA bifurcation to aneurysm distance (p = 0.011) were significantly associated with rupture. Intracerebral hemorrhage was associated with smaller volume, larger maximum height, and smaller aneurysm angle, in addition to lateral projection, male sex, and lack of hypertension. We found that shorter ICA bifurcation to aneurysm distance is significantly associated with PCoA aneurysm rupture. This is a new physically intuitive parameter that can be measured easily and therefore be readily applied in clinical practice to aid in the evaluation of patients with PCoA aneurysms.

BACKGROUND: Glioblastoma can be classified into four distinct molecular subtypes (Proneural, Neural, Classical and Mesenchymal), based on gene expression profiling. This study aimed to investigate the prevalence, clinicopathologic features and overall survival (OS) of the four molecular subtypes among all malignant gliomas. METHODS: A total of 941 gene expression arrays with clinical data were obtained from the Rembrandt, GSE16011 and CGGA datasets. Molecular subtypes were predicted with a prediction analysis of microarray. RESULTS: Among 941 malignant gliomas, 32.73% were Proneural, 15.09% Neural, 19.77% Classical and 32.41% Mesenchymal. The Proneural and Neural subtypes occurred largely in low-grade gliomas, while the Classical and Mesenchymal subtypes were more frequent in high-grade gliomas. A survival analysis showed that the Proneural subtype displayed a good prognosis, Neural had an intermediate correlation with overall survival, Mesenchymal had a worse prognosis than Neural, and Classical had the worst clinical outcome. Furthermore, oligodendrocytomas were preferentially assigned to the Proneural subtype, while the Mesenchymal subtype included a higher percentage of astrocytomas, compared with oligodendrocytomas. Additionally, nearly all classical gliomas harbored EGFR amplifications. Classical anaplastic gliomas have similar clinical outcomes as their glioblastoma counterparts and should be treated more aggressively. CONCLUSIONS: Molecular subtypes exist stably in all histological malignant gliomas subtypes. This could be an important improvement to histological diagnoses for both prognosis evaluations and clinical outcome predictions.

In contrast to size, the association of morphological characteristics of intracranial aneurysms with rupture has not been established in a systematic manner. We present an analysis of the morphological variables that are associated with rupture in anterior communicating artery aneurysms to determine site-specific risk variables. One hundred and twenty-four anterior communicating artery aneurysms were treated in a single institution from 2005 to 2010, and CT angiograms (CTAs) or rotational angiography from 79 patients (42 ruptured, 37 unruptured) were analyzed. Vascular imaging was evaluated with 3D Slicer© to generate models of the aneurysms and surrounding vasculature. Morphological parameters were examined using univariate and multivariate analysis and included aneurysm volume, aspect ratio, size ratio, distance to bifurcation, aneurysm angle, vessel angle, flow angle, and parent-daughter angle. Multivariate logistic regression revealed that size ratio, flow angle, and parent-daughter angle were associated with aneurysm rupture after adjustment for age, sex, smoking history, and other clinical risk factors. Simple morphological parameters such as size ratio, flow angle, and parent-daughter angle may thus aid in the evaluation of rupture risk of anterior communicating artery aneurysms.

Investigation into the association of insurance status with the outcomes of patients undergoing neurosurgical intervention has been limited: this is the first nationwide study to analyze the impact of primary payer on the outcomes of patients with aneurysmal subarachnoid hemorrhage who underwent endovascular coiling or microsurgical clipping. The Nationwide Inpatient Sample (2001-2010) was utilized to identify patients; those with both an ICD-9 diagnosis codes for subarachnoid hemorrhage and a procedure code for aneurysm repair (either via an endovascular or surgical approach) were included. Hierarchical multivariate regression analyses were utilized to evaluate the impact of primary payer on in-hospital mortality, hospital discharge disposition, and length of hospital stay with hospital as the random effects variable. Models were adjusted for patient age, sex, race, comorbidities, socioeconomic status, hospital region, location (urban versus rural), and teaching status, procedural volume, year of admission, and the proportion of patients who underwent ventriculostomy. Subsequent models were also adjusted for time to aneurysm repair and time to ventriculostomy; subgroup analyses evaluated for those who underwent endovascular and surgical procedures separately. 15,557 hospitalizations were included. In the initial model, the adjusted odds of in-hospital mortality were higher for Medicare (OR 1.23, p

The five-membered ring in the the title molecule, C24H25NO, fused with the phenylene ring, is almost planar (r.m.s. deviation = 0.023 Å), with the methylene C atom deviating most from this mean plane [0.031 (1) Å]. The tertiary N atom shows a flattened pyramidal configuration [Σ(angles at N) = 350.3 (6)°].

The molecule of the title compound, C35H27N3O2, lies on a twofold rotation axis passing through the pyridine ring. The five-membered ring is approximately flat (r.m.s. deviation = 0.065 Å) and is essentially coplanar [dihedral angle = 4.2 (2)°] with the pyridine ring.