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This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life. Highlights: Service induced microstructure evolution and LCF life decay of a blade were investigated.Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.Accelerated decrease of residual LCF life was identified as increases of coarsening.Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life. [ABSTRACT FROM AUTHOR]

Despite the known benefits of data‐driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter‐subject correspondence limits the clinical utility of rsfMRI and its application to single‐subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi‐spatial‐scale canonical intrinsic connectivity network (ICN) templates via the use of multi‐model‐order independent component analysis (ICA). We also study the feasibility of estimating subject‐specific ICNs via spatially constrained ICA. The results show that the subject‐level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large‐scale ICNs require less data to achieve specific levels of (within‐ and between‐subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject‐level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within‐subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases. [ABSTRACT FROM AUTHOR]

In this paper, the flexible support mould is designed by using magnetorheological elastomer (MRE) to assist in the deep-drawing of magnesium alloys. Based on the magnesium alloy mechanical tensile test and magnetorheological elastomer regular force experiments, the deep-drawing process of AZ31 magnesium alloy supported by support mould was numerically simulated by finite-element analysis software ABAQUS. By varying the current input to the excitation coil to change the magnetic induction intensity and thus adjust the magnetic normal force of the magnetorheological elastomer, then using magnetic normal force to complete the auxiliary sheet metal deep-drawing. The results show that, compared with the unsupported mould, the supported mould can effectively reduce the maximum thinning rate of magnesium alloy on the original basis, thus effectively increasing the ultimate depth of magnesium alloy deep-drawing. It can replace the original buffer device, effectively solution the problem of pulling and cracking at the bottom of magnesium alloy caused by the original excessive damping force, and improve the yield rate of workpiece. [ABSTRACT FROM AUTHOR]

Background: Several research efforts have found that older schizophrenia patients are at higher risk for suicide. Related risk factors for suicide attempts in the elderly with schizophrenia are poorly understood. This study sought to assess the prevalence of suicide attempts and related risk variables in schizophrenia patients over the age of 50., Methods: We recruited 591 elderly patients over the age of 50. Demographic, clinical and blood parameters of all patients were collected. Patients with schizophrenia were evaluated for psychopathological symptoms using the Positive and Negative Syndrome Scale (PANSS)., Results: The rate of suicide attempts among elderly Chinese schizophrenia patients was 15.2%. In these elderly schizophrenia patients, those who with suicide attempts had significantly higher scores for insomnia, depression and smoking addiction, and higher levels of red blood cells, Hc1 glycosylated hemoglobin and free T3, but significantly lower levels of hypersensitive C-reactive protein and -globulin. Binary logistic regression analysis showed that higher depression scores and smoking addiction were risk factors for suicide attempts in these patients. Additionally, multiple regression analyses showed that higher BMI and insomnia scores were associated with suicide risk scores in elderly schizophrenia patients., Conclusions: Our research shows that there is a high incidence of suicide attempts in people over 50 years of age with schizophrenia. A number of clinically relevant factors and metabolic markers are associated with suicide attempts among elderly patients with schizophrenia., (© 2024 American Association of Suicidology.)

Aims: We evaluated whether Subjective Cognitive Decline (SCD) subtypes could be empirically derived within the Sino Longitudinal Study on Cognitive Decline (SILCODE) SCD cohort and examined associated neuroimaging markers, biomarkers, and clinical outcomes., Methods: A cluster analysis was performed on eight neuropsychological test scores from 124 SCD SILCODE participants and 57 normal control (NC) subjects. Structural and functional neuroimaging indices were used to evaluate the SCD subgroups., Results: Four subtypes emerged: (1) dysexecutive/mixed SCD (n = 23), (2) neuropsychiatric SCD (n = 24), (3) amnestic SCD (n = 22), and (4) cluster-derived normal (n = 55) who exhibited normal performance in neuropsychological tests. Compared with the NC group, each subgroup showed distinct patterns in gray matter (GM) volume and the amplitude of low-frequency fluctuations (ALFF). Lower fractional anisotropy (FA) values were only found in the neuropsychiatric SCD group relative to NC., Conclusion: The identification of empirically derived SCD subtypes demonstrates the presence of heterogeneity in SCD neuropsychological profiles. The cluster-derived normal group may represent the majority of SCD individuals who do not show progressive cognitive decline; the dysexecutive/mixed SCD and amnestic SCD might represent high-risk groups with progressing cognitive decline; and finally, the neuropsychiatric SCD may represent a new topic in SCD research., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

Sphingosine-1-phosphate (S1P), the circulating HDL-bound lipid mediator that acts via S1P receptors (S1PR), is required for normal vascular development. The role of this signaling axis in vascular retinopathies is unclear. Here, we show in a mouse model of oxygen-induced retinopathy (OIR) that endothelial overexpression of S1pr1 suppresses while endothelial knockout of S1pr1 worsens neovascular tuft formation. Furthermore, neovascular tufts are increased in Apom -/- mice which lack HDL-bound S1P while they are suppressed in Apom TG mice which have more circulating HDL-S1P. These results suggest that circulating HDL-S1P activation of endothelial S1PR1 suppresses neovascular pathology in OIR. Additionally, systemic administration of ApoM-Fc-bound S1P or a small-molecule Gi-biased S1PR1 agonist suppressed neovascular tuft formation. Circulating HDL-S1P activation of endothelial S1PR1 may be a key protective mechanism to guard against neovascular retinopathies that occur not only in premature infants but also in diabetic patients and aging people., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Rabies is a viral disease that is nearly 100% fatal once clinical signs and symptoms develop. Post-exposure prophylaxis can efficiently prevent rabies, and antibody (Ab) induction by vaccination or passive immunization of human rabies immunoglobulin (HRIG) or monoclonal antibodies (mAbs) play an integral role in prevention against rabies. In addition to their capacity to neutralize viruses, antibodies exert their antiviral effects by antibody-dependent cellular cytotoxicity (ADCC), which plays an important role in antiviral immunity and clearance of viral infections. For antibodies against rabies virus (RABV), evaluation of ADCC activity was neglected. Here, we developed a robust cell-based reporter gene assay (RGA) for the determination of the ADCC activity of anti-RABV antibodies using CVS-N2c-293 cells, which stably express the glycoprotein (G) of RABV strain CVS-N2c as target cells, and Jurkat cells, which stably express FcγRⅢa and nuclear factor of activated T cells (NFAT) reporter gene as effector cells (Jurkat/NFAT-luc/FcγRⅢa cells). The experimental parameters were carefully optimized, and the established ADCC assay was systematically validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 guideline. We also evaluated the ADCC activity of anti-RABV antibodies, including mAbs, HRIG, and vaccine induced antisera, and found that all test antibodies exhibited ADCC activity with varied strengths. The established RGA provides a novel method for evaluating the ADCC of anti-RABV antibodies., (© 2022 The Societies and John Wiley & Sons Australia, Ltd.)

Aberrant localization of proteins to mitochondria disturbs mitochondrial function and contributes to the pathogenesis of Huntington's disease (HD). However, the crucial factors and the molecular mechanisms remain elusive. Here, we found that heat shock transcription factor 1 (HSF1) accumulates in the mitochondria of HD cell models, a YAC128 mouse model, and human striatal organoids derived from HD induced pluripotent stem cells (iPSCs). Overexpression of mitochondria-targeting HSF1 (mtHSF1) in the striatum causes neurodegeneration and HD-like behavior in mice. Mechanistically, mtHSF1 facilitates mitochondrial fission by activating dynamin-related protein 1 (Drp1) phosphorylation at S616. Moreover, mtHSF1 suppresses single-stranded DNA-binding protein 1 (SSBP1) oligomer formation, which results in mitochondrial DNA (mtDNA) deletion. The suppression of HSF1 mitochondrial localization by DH1, a unique peptide inhibitor, abolishes HSF1-induced mitochondrial abnormalities and ameliorates deficits in an HD animal model and human striatal organoids. Altogether, our findings describe an unsuspected role of HSF1 in contributing to mitochondrial dysfunction, which may provide a promising therapeutic target for HD., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

We trace the crafting of expert narratives during the initial months of the COVID-19 pandemic in Mainland China, Hong Kong, and the United States. By expert narratives, we refer to how experts drew different lessons from past disease experiences to guide policymakers and the public amidst uncertainty. These expert narratives were mobilized in different sociopolitical contexts, resulting in varying configurations of expertise networks and allies that helped contain and mitigate COVID-19. In Mainland China, experts carefully advanced a managed narrative, emphasizing the new pandemic akin to the 2003 SARS outbreak can be managed while destressing the similar mistakes the government made during the two crises. In Hong Kong, experts invoked a distrust narrative, pointing to a potential coverup of COVID-19 similar to SARS, activating allies in civil society to pressure policymakers to act. In the United States, experts were mired in a contested narrative and COVID-19 was compared to different diseases; varying interpretations of COVID-19's consequences was exacerbated by political polarization. In expert narratives, the resonance of the past is emergent: the past becomes a site of struggle and a cultural object that is presented as potentially useful in solving problems of the present., (© 2022 The Authors. Sociological Forum published by Wiley Periodicals LLC on behalf of Eastern Sociological Society.)

New Findings: What is the central question of this study? The aim was to investigate the function of brahma-related gene-1 (BRG1) in airway remodelling epithelial-to-mesenchymal transition (EMT) of asthma and identify the transcription factor of BRG1 that binds to the protomer of E-cadherin. What is the main finding and its importance? This study highlighted an important molecular mechanism involving chromatin remodelling factor BRG1 that played a crucial role in airway remodelling EMT of asthma and demonstrated that ZEB1 was the key transcription factor recruiting BRG1. This finding might offer new insights into gene-based therapy for asthma., Abstract: Epithelial-to-mesenchymal transition (EMT) of airway remodelling happens in children with asthma. A reduction in the epithelial marker E-cadherin is reported to be one of the initiating factors of EMT. Our previous study showed that chromatin remodelling factor brahma-related gene-1 (BRG1) could regulate the expression of E-cadherin indirectly. However, the transcription factor involved in the recruitment of BRG1 in asthma is unknown. Here, we studied the function of Brg1 in an ovalbumin-induced asthma model [lung-specific conditional Brg1 knockdown (Brg1 -/- ) mice] and human bronchial epithelial 16HBE cells stably expressing BRG1 short hairpin RNA. Our results showed that Brg1 was involved in EMT in asthmatic mice by detecting the expression of EMT markers. We also identified that BRG1 participated in the transforming growth factor-β-induced EMT of 16HBE cells. We observed that zinc finger E-box binding homeobox 1 (ZEB1) and BRG1 co-localized in the EMT of TGF-β-induced 16HBE cells. Further results revealed that ZEB1 recruited BRG1 and bound to the promoter region (+3563/3715) to regulate E-cadherin expression. Thus, ZEB1 might be the key transcription factor to recruit BRG1 in airway remodelling EMT of asthma and might be a new therapeutic target., (© 2022 The Authors. Experimental Physiology © 2022 The Physiological Society.)

The four-parameter logistic (4PL) item response model, which includes an upper asymptote for the correct response probability, has drawn increasing interest due to its suitability for many practical scenarios. This paper proposes a new Gibbs sampling algorithm for estimation of the multidimensional 4PL model based on an efficient data augmentation scheme (DAGS). With the introduction of three continuous latent variables, the full conditional distributions are tractable, allowing easy implementation of a Gibbs sampler. Simulation studies are conducted to evaluate the proposed method and several popular alternatives. An empirical data set was analysed using the 4PL model to show its improved performance over the three-parameter and two-parameter logistic models. The proposed estimation scheme is easily accessible to practitioners through the open-source IRTlogit package., (© 2021 The British Psychological Society.)