Metals with nanometer-sized grains are strong but often suffer from poor thermal stability. Herein, nanolaminated (NL) structure with an average thickness of 110 nm and a low angle grain boundaries ...(LAGBs) fraction of 80% was obtained in an Al-1Mn (in wt%) alloy produced by high strain rate deformation at cryogenic temperature. The NL structures are thermally stable up to 523 K, which can effectively suppress GB precipitation during aging, thus improving the pitting corrosion resistance in 0.6 M NaCl solution. The high thermal stability of NL structures can be mainly attributed to the formation of a large fraction (80%) of LAGBs.
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•LAGBs fraction of 80% was introduced in an Al-1Mn alloy by high strain rate deformation at cryogenic temperature.•The NL structure exhibits a good combination of thermal stability and hardness.•NL structure has excellent pitting resistance even when aged up to 523 K.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: The triglyceride glucose (TyG) index reflects insulin resistance; the latter being associated with mild cognitive impairment (MCI). Objective: To investigate the clinical value of the TyG ...index to identify MCI in patients living with type 2 diabetes (T2D) using a cross-sectional study. Methods: This cross-sectional study was performed on 517 patients with T2D. The diagnosis of MCI was based on criteria established by the National Institute on Aging-Alzheimer's Association workgroup, and patients were divided into the MCI group and the normal cognitive function (NCF) group. The logistic regression analysis determines whether the TyG index is related to MCI. Subsequently, we constructed the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). The nomogram model of the influence factor was established and verified. Results: Compared to the type 2 diabetes-normal cognitive function (T2D-NCF) group, the MCI subjects were olderand had higher TyG indexes, lower cognitive scores, and lower education levels (p < 0.01). After adjusting for the confounders, the TyG index was associated with MCI (OR = 7.37, 95% CI = 4.72-11.50, p < 0.01), and TyG-BMI was also associated with MCI (OR = 1.02, 95% CI = 1.01-1.02, p<0.01). The TyG index AUC was 0.79 (95% CI = 0.76-0.83). The consistency index of the nomogram was 0. 8395% CI (0. 79, 0. 86). Conclusion: Our results indicate that the TyG index and TyG-BMI are associated with MCI in T2D patients, and the TyG index is an excellent indicator of the risk of MCI in T2D patients. The nomogram incorporating the TyG index is useful to predict MCI risk in patients with T2D. Keywords: triglyceride glucose index, TyG, mild cognitive impairment, MCI, insulin resistance, IR, type 2 diabetes, T2D
RNA interference screening identified XPO1 (exportin 1) among the 55 most vulnerable targets in multiple myeloma (MM). XPO1 encodes CRM1, a nuclear export protein. XPO1 expression increases with MM ...disease progression. Patients with MM have a higher expression of XPO1 compared with normal plasma cells (P<0.04) and to patients with monoclonal gammopathy of undetermined significance/smoldering MM (P<0.0001). The highest XPO1 level was found in human MM cell lines (HMCLs). A selective inhibitor of nuclear export compound KPT-276 specifically and irreversibly inhibits the nuclear export function of XPO1. The viability of 12 HMCLs treated with KTP-276 was significantly reduced. KPT-276 also actively induced apoptosis in primary MM patient samples. In gene expression analyses, two genes of probable relevance were dysregulated by KPT-276: cell division cycle 25 homolog A (CDC25A) and bromodomain-containing protein 4 (BRD4), both of which are associated with c-MYC pathway. Western blotting and reverse transcription-PCR confirm that c-MYC, CDC25A and BRD4 are all downregulated after treatment with KPT-276. KPT-276 reduced monoclonal spikes in the Vk*MYC transgenic MM mouse model, and inhibited tumor growth in a xenograft MM mouse model. A phase I clinical trial of an analog of KPT-276 is ongoing in hematological malignancies including MM.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aims to assess the risk factors of cardiovascular disease (CVD) and to determine the association of traditional and biologic disease-modifying anti-rheumatic drugs (DMARDs) with risk for ...CVD in Chinese rheumatoid arthritis (RA) patients. A cross-sectional cohort of 2013 RA patients from 21 hospitals around China was established. Medical history of CVD was documented. The patients’ social background, clinical manifestations, comorbidities, and medications were also collected. Of the 2013 patients, 256 had CVD with an incidence of 12.7%. Compared with non-CVD controls, RA patients with CVD had a significantly advanced age, long-standing median disease duration, more often male and more deformity joints. Patients with CVD also had higher rates of smoking, rheumatoid nodules, interstitial lung disease, and anemia. The prevalence of comorbidities, including hypothyroidism, diabetes mellitus (DM), hypertension, and hyperlipidemia, was also significant higher in the CVD group. In contrast, patients treated with methotrexate, hydroxychloroquine (HCQ), and TNF blockers had lower incidence of CVD. The multivariate analysis showed that the use of HCQ was a protective factor of CVD, while hypertension, hyperlipidemia, and interstitial lung disease were independent risk factors of CVD. Our study shows that the independent risk factors of CVD include hypertension, hyperlipidemia, and interstitial lung disease. HCQ reduces the risk of CVD in patients with RA.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The latest research confirms that cytotoxic lymphocytes rely on pyroptosis to kill tumor cells, suggesting that pyroptosis plays a vital role in immune response. However, the influence of pyroptosis ...on tumor microenvironment (TME) remodeling and immunotherapy is still unclear. We analyzed the variations in the expression of 28 pyroptosis-related molecules in pan-cancer tissues and normal tissues and the influence of genome changes. We investigated 2,214 bladder cancer samples and determined that there are three pyroptosis phenotypes in bladder cancer, and there are significant differences in cell infiltration characteristics in different pyroptosis phenotypes. Phenotypes with high expression of pyroptosis-related molecules are "hot tumors" with better immune function. We used a principal component analysis to measure the level of pyroptosis in patients with PyroScore, and confirmed that the PyroScore can predict the prognosis of bladder cancer patients, the sensitivity of the immune phenotype to chemotherapy, and the response to immunotherapy. Patients with a high PyroScore are more sensitive to chemotherapeutics such as cisplatin and gemcitabine, and have a better prognosis (HR = 0.7; 95%CI = 0.51-0.97, P = 0.041). Our study suggests a significant correlation between the expression imbalance of pyroptosis-related molecules and genome variation in various cancers and suggests pyroptosis plays an important role in modeling the TME. Evaluating pyroptosis modification patterns contributes to enhancing our understanding of TME infiltration and can guide more effective immunotherapy strategies.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Insulin resistance (IR) is a complex metabolic disorder that underlies several human diseases, including type 2 diabetes and cardiovascular disease. Despite extensive research, the precise mechanisms ...underlying IR development remain poorly understood. Previously we showed that deficiency of coenzyme Q (CoQ) is necessary and sufficient for IR in adipocytes and skeletal muscle (Fazakerley et al., 2018). Here, we provide new insights into the mechanistic connections between cellular alterations associated with IR, including increased ceramides, CoQ deficiency, mitochondrial dysfunction, and oxidative stress. We demonstrate that elevated levels of ceramide in the mitochondria of skeletal muscle cells result in CoQ depletion and loss of mitochondrial respiratory chain components, leading to mitochondrial dysfunction and IR. Further, decreasing mitochondrial ceramide levels in vitro and in animal models (mice, C57BL/6J) (under chow and high-fat diet) increased CoQ levels and was protective against IR. CoQ supplementation also rescued ceramide-associated IR. Examination of the mitochondrial proteome from human muscle biopsies revealed a strong correlation between the respirasome system and mitochondrial ceramide as key determinants of insulin sensitivity. Our findings highlight the mitochondrial ceramide-CoQ-respiratory chain nexus as a potential foundation of an IR pathway that may also play a critical role in other conditions associated with ceramide accumulation and mitochondrial dysfunction, such as heart failure, cancer, and aging. These insights may have important clinical implications for the development of novel therapeutic strategies for the treatment of IR and related metabolic disorders.
Abstract
The defects dispersed in a spar cap often lead to the failure of large-scale wind turbine blades. To predict the residual service life of the blade and make the repair, it is necessary to ...detect the depth of spar cap defects. Step-heating thermography (SHT) is a common infrared technique in this domain. However, the existing methods of SHT on defect depth detection are generally based on 1D models, which are unable to accurately detect the depth of spar cap defects due to ignoring material anisotropy and in-plane heat flow. To improve the depth detection accuracy of spar cap defects, a 3D model based on the theory of heat transfer is established by using the equivalent source method (ESM), and a defect depth criterion is proposed based on the analytical solution of the heat conduction equation. The modeling process is as follows. The heat conduction model of SHT was established by ESM. Then, coordinate transformation, variables separation, and Laplace transformation were utilized to solve the 3D heat conduction equation. A defect depth criterion was proposed based on emerging contrast Cr. A glass fiber reinforced plastic composite plate containing 12 square flat-bottom holes with different sizes and depths was manufactured to represent a spar cap with large thermal resistance defects, such as delamination and cracks. The experimental results demonstrate the validity of the 3D model. Then, the model was applied to an on-site SHT test of a 1.5 MW wind turbine blade. The test results prove that the depth detection accuracy of spar cap defects can be significantly improved by using the 3D model. In addition, by using an improved principle component analysis (PCA) method containing a contrast enhancement factor, artifacts can be reduced and the recognition time of defects can be shortened. The 3D model provides a tool for detecting the depth of deep-lying defects in a thick composite structure, and the SHT technology is optimized by improved PCA.
ABSTRACT
Fast transitions between different types of power density spectra (PDS) happening over time-scales of several tens of seconds are rare phenomena in black hole X-ray binaries. In this paper, ...we report a broad-band spectral-timing analysis of the fast transitions observed in the 2021 outburst of GX 339−4 using NICER and Insight-HXMT observations. We observe transitions between band-limited noise-dominated PDS and type-B quasi-periodic oscillations (QPOs), and their rapid appearance or disappearance. We also make a detailed comparison between the fast transitions in GX 339−4 with those seen in MAXI J1820+070 and MAXI J1348−630. By comparing the spectra of the periods with and without type-B QPOs, we find that the spectral ratios above 10 keV are nearly constant or slightly decreasing, and the values are different between sources. Below 10 keV, the flux change of the Comptonization component is inversely proportional to the flux change of the thermal component, suggesting that the appearance of type-B QPOs is associated with a redistribution of the accretion power between the disc and the Comptonizing emission region. The spectral ratios between the periods with type-B QPO and those with broad-band noise are significantly different from that with type-B QPO and without type-B QPO, where the ratios (type-B QPO/broad-band noise) show a maximum at around 4 keV and then decrease gradually towards high energies. Finally, we discuss the possible change of the geometry of the inner accretion flow and/or jet during the transitions.
Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. ...However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC–MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition,
l
-isoleucine,
l
-lysine, and
l
-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that
l
-isoleucine,
l
-lysine, and
l
-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
The flare-associated stellar coronal mass ejections (CMEs) of solar-like and late-type stars profoundly impact the habitability of any expolanets in the systems. In this paper, we report the ...detection of flare-associated CMEs for two M-dwarfs, thanks to a high-cadence survey carried out by the Ground Wide-angle Camera system and fast photometric and spectroscopic follow-ups. The flare energies in the
R
band are determined to be 1.6 × 10
35
erg and 8.1 × 10
33
erg based on modeling of their light curves. The time-resolved spectroscopic observations start at about 20 and 40 minutes after the trigger in both cases. The large projected maximum velocity of ∼500–700 km s
−1
suggests that the high-velocity wings of their H
α
emission lines most likely result from CME events in both stars, after excluding the possibility of chromospheric evaporation and coronal rain. The masses of the CMEs are estimated to be 1.5–4.5 × 10
19
g and 7.1 × 10
18
g.
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