Fatty liver, diagnosed by ultrasound, significantly predicts the 5-year incidence of type 2 diabetes regardless of insulin resistance status in 11,091 healthy Koreans.
Context:
Although fatty liver ...and insulin resistance are known to be associated, the relationship between the two in the development of type 2 diabetes mellitus (T2DM) is unclear.
Objective:
We investigated the 5-yr risk of developing T2DM in individuals diagnosed with fatty liver using ultrasound and stratified by insulin sensitivity using quartiles of fasting insulin concentration.
Design and Methods:
We examined the clinical and laboratory data of 11,091 Koreans who had a medical evaluation including fasting insulin concentration and abdominal ultrasound at baseline and had a follow-up after 5 yr.
Results:
At baseline, 27% of the population had fatty liver. Almost half (47%) of the individuals with fatty liver had baseline insulin concentration in the highest quartile compared with 17% in those without fatty liver (P < 0.001). Regardless of baseline insulin concentration, individuals with fatty liver had significantly (P < 0.001) more baseline clinical and metabolic abnormalities, including higher glucose and triglyceride concentration and lower high-density lipoprotein cholesterol concentration. In addition, regardless of baseline insulin concentration, individuals with fatty liver had a significantly increased risk for incident T2DM compared with those without fatty liver crude odds ratio, 5.05 (95% confidence interval, 2.08–12.29) in the lowest insulin quartile and 6.34 (3.58–11.21) in the highest quartile. In individuals in the highest insulin quartile, the odds ratio for developing T2DM remained significant even after multivariate adjustment including baseline glucose concentration 2.42 (1.23–4.75).
Conclusion:
Although associated with insulin resistance, fatty liver diagnosed by ultrasound appears to independently increase the risk of T2DM.
Cogging torque, inherent in permanent magnet machines, is closely related to the airgap flux density harmonic contents. The third harmonic can be utilized in combination with the fundamental one to ...increase the average torque, whilst its relationship with cogging torque is uncertain. The aim of this paper is to investigate the effect of third harmonic in airgap flux density on cogging torque in surface-mounted permanent magnet (SPM) machines considering different slot/pole (S/P) combinations. First, based on the simplified expressions of cogging torque in machines with sinusoidal plus third harmonic (Sine+3rd) airgap flux density, S/P combinations are classified into four cases for discussion. It is found that when N s /GCD ( N s , N p ) ≥ 4 ( N s : slot number; N p : pole number; GCD: great common divisor), third harmonic in airgap flux density has no effect on cogging torque. Otherwise, cogging torque will be generated. Furthermore, two approaches for obtaining the Sine and Sine+3rd airgap flux density, i.e., Sine/Sine+3rd h m and Sine/Sine+3rd B r , are validated, based on which finite-element analyses are carried out on four machines, i.e., 12-slot/10-pole (12S12P), 12S6P, 12S8P, and 12S10P to verify the conclusion. Finally, the 12S8P and 12S10P Sine+3rd SPM machines are prototyped and tested for validation.
Anti-interferon- γ (IFN-γ) autoantibodies (anti-IFN-γ Abs) have been increasingly recognized as an important cause of disseminated nontuberculous mycobacterial (DNTM) infection, and identification of ...this immunodeficiency impacts clinical management. However, the protean disease manifestations and inaccessibility to diagnostic tests in clinical settings hamper its early diagnosis. Here, we sought to determine whether QuantiFERON-TB Gold In-tube (QFT-GIT), a commercialized IFN-γ release assay, could be used to screen for neutralizing anti-IFN-γ Abs among previously healthy adults with DNTM infection.
Non-HIV patients with DNTM infection were prospectively enrolled for the QFT-GIT assays. We measured their plasma concentration of anti-IFN-γ Abs and their neutralizing capacity through enzyme-linked immunosorbent assay and flow cytometry. We then analysed the correlation between QFT-GIT results and the presence of neutralizing anti-IFN-γ Abs among patients with and without previously recognized immunosuppression, respectively.
Irrespective of the autoantibody concentration or disease activity, all patients with neutralizing anti-IFN-γ Abs (100%, 30/30) had indeterminate QFT-GIT results because of extremely low or undetectable IFN-γ levels in the mitogen tubes. None of the four DNTM patients who were previously healthy and tested negative of anti-IFN-γ Abs had an indeterminate QFT-GIT result, and their IFN-γ levels in the mitogen tube were significantly higher than those of the patients with anti-IFN-γ Abs (8.28 IU/mL vs. 0.05 IU/mL, p 0.001).
An indeterminate QFT-GIT result because of undetectable or extremely low IFN-γ level in the mitogen tube suggests the presence of neutralizing anti-IFN-γ Abs in a previously healthy patient with DNTM infection.
It has long been known that males are more susceptible than females to hepatocellular carcinoma (HCC), but the reason remains elusive. In this study, we investigated the expression and function of ...the long noncoding RNA FTX (lnc-FTX), an X-inactive-specific transcript (XIST) regulator transcribed from the X chromosome inactivation center, in both HCC and HCC gender disparity. lnc-FTX is expressed at higher levels in female livers than in male livers and is significantly downregulated in HCC tissues compared with normal liver tissues. Patients with higher lnc-FTX expression exhibited longer survival, suggesting that lnc-FTX is a useful prognostic factor for HCC patients. lnc-FTX inhibits HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, lnc-FTX represses Wnt/β-catenin signaling activity by competitively sponging miR-374a and inhibits HCC cell epithelial-mesenchymal transition and invasion. In addition, lnc-FTX binds to the DNA replication licensing factor MCM2, thereby impeding DNA replication and inhibiting proliferation in HCC cells. In conclusion, these findings suggest that lnc-FTX may act as a tumor suppressor in HCC through physically binding miR-374a and MCM2. It may also be one of the reasons for HCC gender disparity and may potentially contribute to HCC treatment.
Enhancing battery safety and thermal behaviour are critical for electric vehicles (EVs) because they affect the durability, energy storage, lifecycle, and efficiency of the battery. Prior studies of ...using air, liquid or phase change materials (PCM) to manage the battery thermal environment have been investigated over the last few years, but only a few take heat pipes into account. This paper aims to provide a full experimental characterisation of heat pipe battery cooling and heating covering a range of battery ‘off-normal’ conditions. Two representative battery cells and a substitute heat source ranging from 2.5 to 40 W/cell have been constructed. Results show that the proposed method is able to keep the battery surface temperature below 40 °C if the battery generates less than 10 W/cell, and helps reduce the battery temperature down to 70 °C under uncommon thermal abuse conditions (e.g. 20–40 W/cell). Additionally, the feasibility of using sintered copper-water heat pipes under sub-zero temperatures has been assessed experimentally by exposing the test rig to −15 °C/−20 °C for more than 14 h. Data indicates that the heat pipe was able to function immediately after long hours of cold exposure and that sub-zero temperature conditions had little impact on heat pipe performance. We therefore conclude that the proposed method of battery cooling and heating via heat pipes is a viable solution for EVs.
Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% ...of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.
We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.
Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.
HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
The present study was conducted to assess rumen bacteria in lactating cows with different milk protein yield, aiming to understand the role of rumen bacteria in this trait. Cows with high milk ...protein yield (high milk yield and high milk protein content, HH; n = 20) and low milk protein yield (low milk yield and low milk protein content, LL; n = 20) were selected from 374 mid-lactation Holstein dairy cows fed a high-grain diet. Measurement of the rumen fermentation products showed that the concentrations of ruminal total volatile fatty acids, propionate, butyrate, and valerate and the proportion of isobutyrate were higher in the HH cows than in the LL cows. Amplicon sequencing analysis of the rumen bacterial community revealed that the richness (Chao 1 index) of rumen microbiota was higher in the LL cows than in the HH cows. Among the 10 predominant bacterial phyla (relative abundance being >0.10%, present in >60% of animals within each group), the relative abundance of Proteobacteria was 1.36-fold higher in the HH cows than in the LL cows. At the genus level, the relative abundance of Succinivibrio was significantly higher and that of Clostridium tended to be higher in the LL cows than in the HH cows. Sharpea was 2.28-fold enriched in the HH cows compared with the LL cows. Different relationships between the relative abundances of rumen microbial taxa and volatile fatty acid concentrations were observed in the HH and the LL animals, respectively. Succinivibrio and Prevotella were positively correlated with acetate, propionate, and valerate in the LL cows, whereas Sharpea was positively correlated with propionate and valerate concentrations in the HH cows. Collectively, our results revealed that rumen bacterial richness and the relative abundances of several bacterial taxa significantly differed between dairy cows with high and low milk protein yields, suggesting the potential roles of rumen microbiota contributing to milk protein yield in dairy cows.
Previous studies have established the link between aberrant microRNA (miRNA) expression and hypoxia in various neoplasms. However, how these hypoxia-related miRNAs modulate tumor progression is still ...unclear. Therefore, the patterns of miRNA in colorectal carcinoma cell lines in response to hypoxia or not were first screened and the hypoxia-induced repression of the miR-15-16 cluster was confirmed. Then, this repression was found to be associated with high tumor stage and poor prognosis in colorectal carcinoma and is shown to promote tumor angiogenesis and metastasis by the loss of restriction of its target gene, fibroblast growth factor-2 (FGF2). Moreover, the general and alterative promoters of the miR-15-16 host (deleted in lymphocytic leukemia 2, DLEU2) were mapped, and three c-Myc/Max binding sites in response to the hypoxia-induced repression of miR-15-16 were further identified. Finally, an enhanced stability of c-Myc/Max heterodimer promoted by increased hypoxia-inducible factor-2α (HIF-2α) was validated, and we also verified that the enhancement contributed to the hypoxia-induced repression of miR-15-16. In brief, the c-Myc-mediated transcriptional repression of miR-15-16 in hypoxia is induced by increased HIF-2α and promoted tumor angiogenesis and hematogenous metastasis by the further loss of post-transcriptional inhibition of FGF2. Our study provides a better understanding of the coping mechanisms in response to tumor hypoxia and may be helpful in developing an effective prognostic marker or treatment target against solid tumors.
We present the charge-changing cross sections (CCCS) of 11−15C, 13−17N, and 15,17−18O at around 300 MeV/nucleon on a carbon target, which extends to p-shell isotopes with N<Z for the first time. The ...Glauber model, which considers only the proton distribution of projectile nuclei, underestimates the cross sections by more than 10%. We show that this discrepancy can be resolved by considering the contribution from the charged-particle evaporation process (CPEP) following projectile neutron removal. Using nucleon densities from the deformed relativistic Hartree-Bogoliubov theory in continuum, we investigate the isospin-dependent CPEP contribution to the CCCS for a wide range of neutron-to-proton separation energy asymmetry. Our calculations, which include the CPEP contribution, agree well with existing systematic data and reveal an “evaporation peak” at the isospin symmetric region where the neutron-to-proton separation energy is close to zero. These results suggest that analysis beyond the Glauber model is crucial for accurately determining nuclear charge radii from CCCSs.
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