Analysis of cognitive function and its related factors after treatment in Meniere’s disease

A growing body of research recently suggested the association between vestibular dysfunction and cognitive impairment. Meniere’s disease (MD), a common clinical vestibular disorder, is usually accompanied by hearing loss and emotional stress, both of which may mediate the relationship between vestibule dysfunction and cognition. It is currently unknown whether the cognitive decline in MD patients could improve through treatment and how it relates to multiple clinical characteristics, particularly the severity of vertigo. Therefore, in the present study, the MD patients were followed up for 3, 6, and 12 months after treatment, and the cognitive functions, vertigo symptoms, and related physical, functional, and emotional effects of the patients were assessed using the Montreal Cognitive Assessment (MoCA) and Dizziness Handicap Inventory (DHI), aiming to explore the change in cognition before and after therapy and the correlation with various clinical features. It was found that cognitive decline in MD patients compared to healthy controls before therapy. Importantly, this cognitive impairment could improve after effective therapy, which was related to the severity of vertigo, especially in functional and physical impacts. Our results support the view that vestibular dysfunction is a potentially modifiable risk factor for cognitive decline

Analysis of residual stresses in electron beam welding with filler wire of Ti62A alloy

Residual stress significantly affects the performance of the welded joints and the tensile residual stress easily leads to the joint fracture and failure. A three dimensional nonlinear transient thermo-mechanically coupled finite element model of Ti62A alloy electron beam welding (EBW) with filler wire was established. The influence of the welding parameters, such as welding power, groove angles and number of welding layers on the temperature and residual stress evolutions was predicted and verified against existing literature data. The calculated results indicate that the high tensile stress of heat affected zone is very likely to induce the failure of the welded joints. When the welding power is 2600 W, the longitudinal residual stress along the welding direction is more symmetrical on both sides, and the force and deformation of the weldment will be more uniform. As the groove angle decreases, the transverse residual compressive stress on the joint surface becomes larger, which results in the low risk for cracking tendency of the joint. Increasing the number of welding layers reduces the weld reinforcement and the residual stress. In addition, the decline magnitude of residual stress decreases with the increase in the number of welding layers. Both the smaller groove angle and the multi-layer welding can effectively reduce the residual stress of weldments and improve the joint performance. The findings of this study will provide a good theoretical basis for optimizing welding process

Analysis of residual stress relief for Ti62A alloy welded joints by post weld heat treatment considering creep effect

In this paper, the Arrhenius-type constitutive equation based on strain compensation was developed, and the constants of the constitutive equation were determined by linear fitting to construct the material models of Ti62A alloy. Meanwhile, the creep parameters of Ti62A alloy at high temperature were corrected by existing experiments, and the Norton creep model during post weld heat treatment (PWHT) was established. The sequential coupling finite element method was used to calculate the residual stress distribution in the welding and PWHT processes of Ti62A alloy plates. The effects of PWHT parameters on the residual stress relief of welded joints were revealed, such as creep, heating rate, and heat treatment temperature. The results reveal that the creep has an important influence on residual stress relief during PWHT. Compared with longitudinal residual stress, the effects of heating rate and heat treatment temperature on transverse residual stress are more significant. A lower heating rate or higher heat treatment temperature will be beneficial for releasing residual stress. The results of this paper will contribute to a better understanding of PWHT mechanisms and provide a good theoretical guidance for optimizing process parameters

DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming

Abstract Background DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia (AML) with Arg882His (R882H) as the hotspot mutation. It has been reported that DNMT3A mutation plays a key role in leukemogenesis through hypomethylation of some target genes associated with cell growth and differentiation. In this study, we investigated the function of DNMT3A R882H in the malignant progression of AML by regulating metabolic reprogramming. Methods Ultra-High Performance Liquid Chromatography–High Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS) was used to detect metabolites in the serum of mice harboring Dnmt3a R878H mutation and the wild-type Dnmt3a. Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) were used to analyze the levels of DNA methylation and mRNA expression of genes in mouse Gr1+ bone marrow cells respectively. The TCGA and GO databases were used to analyze the differential genes between human samples carrying the DNMT3A R882 mutation and the wild-type DNMT3A. Co-immunoprecipitation and immunoblotting were used to illustrate the binding levels of Cyclins-CDKs and CDK inhibitors including CDKN1A and CDKN1B. Flow cytometry was used to analyze the cell differentiation, division, apoptosis and cell cycle. The effect of NAMPT inhibition on leukemia was evaluated by using in vivo fluorescence imaging in NOG mouse model bearing OCI-AML3 cells. Results DNMT3A mutation caused high expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the nicotinamide adenine dinucleotide (NAD) salvage synthetic pathway, through DNA hypomethylation, and finally led to abnormal nicotinamide (NAM) metabolism and NAD synthesis. The NAM-NAD metabolic abnormalities caused accelerated cell cycle progression. Inhibition of NAMPT can reduce the binding degree between Cyclins-CDKs, and increase the binding interaction of the CDK inhibitors with Cyclins-CDKs complexes. Moreover, cells with high expression of NAMPT were more sensitive to the NAMPT inhibitor FK866 with a lower IC50. The inhibition of NAMPT can remarkably extend the survival time of tumor-bearing mice and reduce the infiltration of tumor cells. Conclusions Taken together, our data showed that DNMT3A mutation caused NAMPT overexpression to induce the reprogramming of NAM-NAD metabolism and contribute to abnormal proliferation, which provided a potential direction for targeted therapy at the metabolic level in AML with DNMT3A mutation

Modeling and analysis for group delay mismatch effect on wideband adaptive spatial interference cancellation

Abstract The adaptive interference cancellation technique has been widely utilized in radar, GPS, data link, etc., systems to address challenges from external interference, such as co-site and hostile interference. Since the anti-jamming performance of the adaptive interference cancellation technique is sensitive to group delay mismatch between channels, the group delay mismatch becomes one of the main factors that limit the system’s anti-jamming capability. However, the traditional adaptive interference cancellation system’s mathematical model cannot quantitatively characterize the group delay mismatch effect on the wideband interference cancellation performance. In this paper, the mathematical model of the wideband adaptive spatial interference cancellation (ASIC) system is established, which considers the group delay mismatch, to quantitatively analyze the impact of group delay mismatch on the hostile interference cancellation. The mathematical model utilizes the weighted multi-tone signals to fit the wideband interference, and then, delay differences are attached to each tone signal to simulate the group delay mismatch. Then, the analytic expressions of weight and interference cancellation ratio are derived, which consider the interference bandwidth and group delay mismatch, to quantitatively analyze the group delay mismatch effect on the anti-jamming performance of the wideband ASIC system. Simulation results indicate that the theoretical analysis based on the mathematical model of wideband ASIC system are accurate, which can achieve the quantitative analysis of the group delay mismatch effect on the WIC performance

Purification and Functional Characterization of a Soluble Trehalase in <i>Lissorhoptrus oryzophilus</i> (Coleoptera: Curculionidae)

Trehalase is the only enzyme known for the irreversible splitting of trehalose and plays a major role in insect growth and development. In this report, we describe a basic study of the trehalase gene fragment encoding a soluble trehalase from Lissorhoptrus oryzophilus (LoTRE1). Sequence alignment and phylogenetic analysis suggested that LoTRE1 was similar to some known insect trehalases and belongs to the Coleoptera trehalase group. Additionally, LoTRE1 was expressed mainly in the fat body. Purified protein was obtained using heterologous expression of LoTRE1 in Escherichia coli, and the recombinant protein exhibited the ability to decompose trehalose. Enzyme–substrate docking indicated the potential involvement of other residues in the catalytic activity, in addition to Asp 333. Moreover, feeding of adults on LoTRE1 dsRNA silenced the transcription of LoTRE1 and thereby reduced the activity of trehalase and increased the trehalose content; it also led to a 12% death rate. This study reveals essential molecular features of trehalase and offers insights into the structural aspects of this enzyme, which might be related to its function. Taken together, the findings demonstrate that LoTRE1 is indispensable for adults of this pest and provide a new target for the control of L. oryzophilus

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment

Background: Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST). Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors. Methods: Totally, 74 patients who were aged 22–81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2–6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST. Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P  0.05). Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL

Additional file 2 of DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming

Additional file 2: Table S2. The mRNA expression level of NAMPT in AML obtained from the Oncomine database

Additional file 1 of DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming

Additional file 1: Table S1. Primer sequences used in Q-RT-PCR