Explore the vast range of titles available.

Sapphire is widely used as a new generation of optoelectronic chips. In this article, single-sided chemical mechanical polishing (SS-CMP) and double-sided chemical mechanical polishing (DS-CMP) were conducted polishing experiments on sapphire wafers. Polishing pressure, relative rotational speed, and polishing time were investigated on material removal rate (MRR), surface roughness (SR), and parallelism of sapphire wafers under the two methods. The results demonstrate both MRR and SR of DS-CMP are significantly better than SS-CMP under the same parameters. Sapphire DS-CMP can obtain a relatively stable average MRR increment of 14.016 nm/min comparing to SS-CMP and can also obtain better surface quality when subjected to greater polishing pressure. Additionally, the parallelism after SS-CMP is about 3 times that of DS-CMP under one-time processing. Finally, sapphire CMP material removal equations are established empirically and theoretically to demonstrate the exponential equation of nonlinear relationship is more suitable for the material removal of sapphire CMP, and the mean error between the theoretical and experimental results of SS-CMP and DS-CMP is within 10%, providing a quantitative and efficient solution for manufacturing sapphire wafers.

Spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) is a progressive autosomal dominantly inherited cerebellar ataxia characterized by the aggregation of polyglutamine-expanded protein within neuronal nuclei in the brain, which can lead to brain damage that precedes the onset of clinical manifestations. Magnetic resonance (MR) imaging techniques such as morphometric MRI, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) have gained increasing attention as noninvasive and quantitative methods for the assessment of structural and functional alterations in clinical SCA3/MJD patients as well as preclinical carriers. Morphometric MRI has demonstrated typical patterns of atrophy or volume loss in the cerebellum and brainstem with extensive lesions in some supratentorial areas. DTI has detected widespread microstructural alterations in brain white matter, which indicates disrupted brain anatomical connectivity. Task-related fMRI has presented unusual brain activation patterns within the cerebellum and some extracerebellar tissue reflecting decreased functional connectivity of these brain regions in SCA3/MJD subjects. MRS has revealed abnormal neurochemical profiles, such as the levels or ratios of N-acetyl aspartate (NAA), choline (Cho) and creatine (Cr), in both clinical cases and preclinical cases before the alterations in brain anatomical structure. Moreover, a number of studies have reported correlations of MR imaging alterations with clinical and genetic features. The utility of these MR imaging techniques can help to identify preclinical SCA3/MJD carriers, monitor disease progression, evaluate response to therapeutic interventions and illustrate the pathophysiological mechanisms underlying the occurrence, development and prognosis of SCA3/MJD.

Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a progressive autosomal dominant neurodegenerative disease caused by abnormal CAG repeats in the exon 10 of ATXN3. The accumulation of the mutant ataxin-3 proteins carrying expanded polyglutamine (polyQ) leads to selective degeneration of neurons. Since the pathogenesis of SCA3 has not been fully elucidated, and no effective therapies have been identified, it is crucial to investigate the pathogenesis and seek new therapeutic strategies of SCA3. Induced pluripotent stem cells (iPSCs) can be used as the ideal cell model for the molecular pathogenesis of polyQ diseases. Abnormal CAG expansions mediated by CRISPR/Cas9 genome engineering technologies have shown promising potential for the treatment of polyQ diseases, including SCA3. In this study, SCA3-iPSCs can be corrected by the replacement of the abnormal CAG expansions (74 CAG) with normal repeats (17 CAG) using CRISPR/Cas9-mediated homologous recombination (HR) strategy. Besides, corrected SCA3-iPSCs retained pluripotent and normal karyotype, which can be differentiated into a neural stem cell (NSCs) and neuronal cells, and maintained electrophysiological characteristics. The expression of differentiation markers and electrophysiological characteristics were similar among the neuronal differentiation from normal control iPSCs (Ctrl-iPSCs), SCA3-iPSCs, and isogenic control SCA3-iPSCs. Furthermore, this study proved that the phenotypic abnormalities in SCA3 neurons, including aggregated IC2-polyQ protein, decreased mitochondrial membrane potential (MMP) and glutathione expressions, increased reactive oxygen species (ROS), intracellular Ca2+ concentrations, and lipid peroxidase malondialdehyde (MDA) levels, all were rescued in the corrected SCA3-NCs. For the first time, this study demonstrated the feasibility of CRISPR/Cas9-mediated HR strategy to precisely repair SCA3-iPSCs, and reverse the corresponding abnormal disease phenotypes. In addition, the importance of genetic control using CRISPR/Cas9-mediated iPSCs for disease modeling. Our work may contribute to providing a potential ideal model for molecular mechanism research and autologous stem cell therapy of SCA3 or other polyQ diseases, and offer a good gene therapy strategy for future treatment.

Background Spinocerebellar ataxia type 3 (SCA3) is the most common subtype of SCA without effective treatment. This study aimed to evaluate the comparative efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) and intermittent Theta Burst Stimulation (iTBS) in a larger cohort of SCA3 patients. Methods One hundred and twenty patients with SCA3 were randomly assigned to the 3 groups: 40 patients in the 1 Hz rTMS, 40 in the iTBS and 40 in the sham group. Patients underwent 10 sessions of rTMS targeting the cerebellum delivering for 5 consecutive days per week for 2 weeks (a total of 1200 pulses per session). Primary outcomes included the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). Secondary outcomes included 10-m walking test (10MWT), nine-hole peg test (9-HPT), and PATA Rate Test (PRT). Outcome assessments were performed at baseline and on the last day of rTMS intervention. Results This study revealed that active rTMS outperformed sham in reducing the SARA and ICARS scores in SCA3 patients, but with no difference between the 1 Hz rTMS and iTBS protocol. Moreover, no significant differences were observed in SARA and ICARS scores between the mild and moderate to severe groups after the 1 Hz rTMS/iTBS therapy. Additionally, no severe adverse events were recorded in this study. Conclusions The study concluded that both 1 Hz rTMS and iTBS interventions targeting the cerebellum are effective to improve the symptoms of ataxia in patients with SCA3.

Background Transcranial sonography (TCS) plays a crucial role in diagnosing Parkinson's disease. However, the intricate nature of TCS pathological features, the lack of consistent diagnostic criteria, and the dependence on physicians' expertise can hinder accurate diagnosis. Current TCS-based diagnostic methods, which rely on machine learning, often involve complex feature engineering and may struggle to capture deep image features. While deep learning offers advantages in image processing, it has not been tailored to address specific TCS and movement disorder considerations. Consequently, there is a scarcity of research on deep learning algorithms for TCS-based PD diagnosis. Methods This study introduces a deep learning residual network model, augmented with attention mechanisms and multi-scale feature extraction, termed AMSNet, to assist in accurate diagnosis. Initially, a multi-scale feature extraction module is implemented to robustly handle the irregular morphological features and significant area information present in TCS images. This module effectively mitigates the effects of artifacts and noise. When combined with a convolutional attention module, it enhances the model's ability to learn features of lesion areas. Subsequently, a residual network architecture, integrated with channel attention, is utilized to capture hierarchical and detailed textures within the images, further enhancing the model's feature representation capabilities. Results The study compiled TCS images and personal data from 1109 participants. Experiments conducted on this dataset demonstrated that AMSNet achieved remarkable classification accuracy (92.79%), precision (95.42%), and specificity (93.1%). It surpassed the performance of previously employed machine learning algorithms in this domain, as well as current general-purpose deep learning models. Conclusion The AMSNet proposed in this study deviates from traditional machine learning approaches that necessitate intricate feature engineering. It is capable of automatically extracting and learning deep pathological features, and has the capacity to comprehend and articulate complex data. This underscores the substantial potential of deep learning methods in the application of TCS images for the diagnosis of movement disorders. Graphical Abstract

Carbon nanotubes (CNTs) were added into the electrolyte to improve electrolytic dressing grinding performance of a brazed multi-layer diamond wheel containing titanium. The effect of CNTs on the electrolytic dressing performance of the grinding wheel was studied. The grinding force, residual stress, roughness and morphology of the machined surfaces were recorded in the grinding experiment of cemented carbides, and the grinding performance was evaluated based on these. The experiment results expressed that the CNTs improved the electrolytic dressing performance of the grinding wheel, which allows the worn grits to smoothly fall off and maintain the sharpness. The grinding force and residual stress were reduced when the CNTs were added into the electrolyte. Moreover, there was a grand advancement in the machined surface quality when the CNTs were used as an additive to the electrolyte. The machined surfaces produced by the brazed wheel using an electrolyteadded CNTs showed predominantly smooth grinding marks. Ductile-mode removal was predominantly observed in the grinding experiments. Adding CNTs to an electrolyte can help achieve high-precision grinding of difficult-to-cut materials with a brazed multi-layer diamond wheel.

Lactylation, a new epigenetic modification, is an important way in which lactate exerts physiological functions. There is a close relationship between increased lactylations caused by lactate and glycolysis, which can interact and play a role in disease through lactate as an intermediate mediator. Current research on lactylations has focused on histone lactylation, but non-histone lactylation also has greater research potential. Due to the ubiquity of lactate modifications in mammalian cells, an increasing number of studies have found that lactate modifications play important roles in tumour cell metabolism, gene transcription and immunity. A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria. Many literatures have reported that the lactylation of protein plays an important role in human diseases and is involved in the occurrence and development of human diseases. This article summary the correlation between lactylation and glycolysis, histones and non-histone proteins; the relationship between lactonation modifications and tumour development; and the current existence of lactylation-related inhibitors, with a view to provide new basic research ideas and clinical therapeutic tools for lactylation-related diseases.

Background Third-generation EGFR-TKIs (TGETs) have demonstrated improved clinical outcomes compared to first-generation EGFR-TKIs (FGETs) in patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Nonetheless, the comparative safety and efficacy of TGETs as a first-line option for Asian patients with advanced EGFR-mutant NSCLC remain unclear. This meta-analysis aims to compare the survival outcomes, response rates, and adverse events (AEs) of TGETs versus FGETs in this population. Methods We systematically searched 6 databases for eligible phase 3 randomized controlled trials (RCTs). Eligible studies included those comparing TGETs with FGETs in previously untreated Asian patients with EGFR-mutant advanced NSCLC. Pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), risk ratios (RRs) for response rates, and AEs were calculated and analyzed. Results Seven phase 3 RCTs comprising 2434 Asian patients were included. TGETs significantly improved PFS (HR: 0.47 [0.42, 0.52], P  < 0.00001) and central nervous system-PFS (HR: 0.57 [0.40, 0.80], P  = 0.001) compared to FGETs. A trend toward improved OS was also observed with TGETs (HR: 0.88 [0.75, 1.03], P  = 0.10). The advantages of PFS in the TGET group were confirmed in all subgroups. The objective response rate (ORR) (RR: 1.05 [1.01, 1.09], P  = 0.03) and duration of response (DOR) (HR: 0.41 [0.34, 0.48], P  < 0.00001) were also better in the TGET group. Total/grade 3–5 treatment-emergent AEs (TEAEs) and Total/grade 3–5 treatment-related AEs (TRAEs) were similar between the two groups. The top 3 TEAEs of TGET group were diarrhea (31.72%), rash (30.90%), and platelet count decreased (27.97%). Conclusion Compared with FGETs, TGETs significantly improve PFS, CNS control, response outcomes, and maintain a comparable safety profile for Asian patients with advanced EGFR-mutated NSCLC.

A study of a noncircular workpiece grinding mechanism for improving the quality of noncircular grinding was conducted. By combining the principle of heat transfer, the geometry, and the kinematics in the high-speed grinding of noncircular workpiece, a variable heat flow distribution model was developed to evaluate the temperature field. Through a reasonable hypothesis and simplification, a three-dimensional (3D) finite element (FE) simulation model was established based on the variable heat source distribution model. The temperature field in the workpiece was simulated with a 3D transient thermal FE code. The grinding temperature test platform using an infrared thermal imager was established. Experimental results were compared with the results of a simulation; the comparison results showed that the temperature field obtained from ANSYS and the infrared thermal imager were nearly identical, the maximum error was 5.91%, and the simulation results truly reflected noncircular high-speed grinding heat conditions. Based on the analysis of experimental and simulation results, the influence of grinding process parameters on the grinding temperature in high-speed grinding of the noncircular workpiece was revealed. This work should be helpful in solving the problem of thermal damage on the surface of noncircular workpieces during high-speed grinding.

Glaucoma, long considered an ocular-limited, age-dependent and hypoxia-driven neurodegeneration, is here reframed as a systemic erythroid–inosine axis failure that originates in the bone marrow yet culminates in retinal ganglion cell (RGC) death. By mining UK Biobank datasets ( n  = 127,028) and validating our findings in an independent clinical cohort ( n  = 178), we reveal that glaucoma is preceded by dyserythropoiesis and a compensatory, AMPK-driven metabolic rewiring of mature erythrocytes that hypercatabolizes inosine to enhance oxygen unloading. This adaptation collapses when accelerated erythrocyte inosine metabolism drains systemic pools, starving high-energy demand hematopoietic progenitors, driving retinal microenvironment hypoxia and accelerating RGC loss. Genetic ablation of murine erythroid equilibrative nucleoside transporter 1 (ENT1) recapitulates the hallmark features of patients with glaucoma, including impaired erythropoiesis, reduced oxygen delivery, retinal hypoxia and RGC apoptosis in both age and intraocular pressure-induced glaucoma models. Conversely, inosine repletion reconstitutes erythroid output, restores oxygen delivery from mature erythrocytes and halts neurodegeneration in inducible glaucoma models. A ten-metabolite erythrocyte signature centered on inosine metabolism offers diagnostic potential. Altogether, our work redefines glaucoma as the first treatable systemic erythroid-driven hypoxic syndrome, positioning inosine as a pleiotropic metabolic rescue factor for neurodegeneration and a powerful biomarker for intercepting hypoxia-driven pathologies across organs. Targeting inosine offers new hope for glaucoma treatment Glaucoma is a major cause of blindness. It involves damage to the optic nerve and is often linked to high eye pressure. However, even with controlled pressure, vision can worsen. Recent studies suggest that systemic issues, such as problems with red blood cells (RBCs), might play a role. Researchers studied RBCs in patients with glaucoma to understand their role in the disease. They analyzed blood samples from patients and healthy individuals to compare RBC function and metabolism. They found that patients with glaucoma had fewer RBCs and these cells showed signs of metabolic stress. The study revealed that RBCs in patients with glaucoma have altered metabolism, relying more on a compound called inosine for energy. This change might be a response to low oxygen levels in the eye. The findings suggest that improving RBC function could help manage glaucoma. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.