A Chinese SCA36 pedigree analysis of NOP56 expansion region based on long-read sequencing

Introduction: Spinocerebellar ataxias 36 (SCA36) is the neurodegenerative disease caused by the GGCCTG Hexanucleotide repeat expansions in NOP56, which is too long to sequence using short-read sequencing. Single molecule real time (SMRT) sequencing can sequence across disease-causing repeat expansion. We report the first long-read sequencing data across the expansion region in SCA36.Methods: We collected and described the clinical manifestations and imaging features of Han Chinese pedigree with three generations of SCA36. Also, we focused on structural variation analysis for intron 1 of the NOP56 gene by SMRT sequencing in the assembled genome.Results: The main clinical features of this pedigree are late-onset ataxia symptoms, with a presymptomatic presence of affective and sleep disorders. In addition, the results of SMRT sequencing showed the specific repeat expansion region and demonstrated that the region was not composed of single GGCCTG hexanucleotides and there were random interruptions.Discussion: We extended the phenotypic spectrum of SCA36. We applied SMRT sequencing to reveal the correlation between genotype and phenotype of SCA36. Our findings indicated that long-read sequencing is well suited to characterize known repeat expansion

Roadmap on spatiotemporal light fields

Spatiotemporal sculpturing of light pulse with ultimately sophisticated structures represents the holy grail of the human everlasting pursue of ultrafast information transmission and processing as well as ultra-intense energy concentration and extraction. It also holds the key to unlock new extraordinary fundamental physical effects. Traditionally, spatiotemporal light pulses are always treated as spatiotemporally separable wave packet as solution of the Maxwell's equations. In the past decade, however, more generalized forms of spatiotemporally nonseparable solution started to emerge with growing importance for their striking physical effects. This roadmap intends to highlight the recent advances in the creation and control of increasingly complex spatiotemporally sculptured pulses, from spatiotemporally separable to complex nonseparable states, with diverse geometric and topological structures, presenting a bird's eye viewpoint on the zoology of spatiotemporal light fields and the outlook of future trends and open challenges.Comment: This is the version of the article before peer review or editing, as submitted by an author to Journal of Optics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

A fast direct locator for radiation source based on composite convolution neural network

Abstract The high spatial search complexity of the direct positioning method in passive positioning systems leads to long positioning time and high computational resource consumption. In response to this issue, this article proposes a fast localization scheme based on composite convolutional neural networks (CCNN), which can effectively explore the correlation between the position of the radiation source and the characteristics of the received signal. CCNN is a 20‐layer composite network based on fully convolutional network layer, which is composed of convolutional layers, batch normalization (BN) layers, and ReLU activation function layers with unidirectional connections. Then, CCNNs are adjusted and trained for positioning single and multiple radiation sources, respectively. Simulation results show that the computational time of the proposed method can be reduced by nearly 98% compared with the direct positioning scheme. Meanwhile, about 71.2% of positioning error's reduction is achieved

Damage-Associated Molecular Patterns and Their Signaling Pathways in Primary Blast Lung Injury: New Research Progress and Future Directions

Primary blast lung injury (PBLI) is a common cause of casualties in wars, terrorist attacks, and explosions. It can exist in the absence of any other outward signs of trauma, and further develop into acute lung injury (ALI) or a more severe acute respiratory distress syndrome (ARDS). The pathogenesis of PBLI at the cellular and molecular level has not been clear. Damage-associated molecular pattern (DAMP) is a general term for endogenous danger signals released by the body after injury, including intracellular protein molecules (HMGB1, histones, s100s, heat shock proteins, eCIRP, etc.), secretory protein factors (IL-1β, IL-6, IL-10, TNF-α, VEGF, complements, etc.), purines and pyrimidines and their derived degradation products (nucleic acids, ATP, ADP, UDPG, uric acid, etc.), and extracellular matrix components (hyaluronic acid, fibronectin, heparin sulfate, biglycan, etc.). DAMPs can be detected by multiple receptors including pattern recognition receptors (PRRs). The study of DAMPs and their related signaling pathways, such as the mtDNA-triggered cGAS-YAP pathway, contributes to revealing the molecular mechanism of PBLI, and provides new therapeutic targets for controlling inflammatory diseases and alleviating their symptoms. In this review, we focus on the recent progress of research on DAMPs and their signaling pathways, as well as the potential therapeutic targets and future research directions in PBLI

Lactobacillus reuteri mitigates hepatic ischemia/reperfusion injury by modulating gut microbiota and metabolism through the Nrf2/HO-1 signaling

Abstract Background This study seeks to investigate the impacts of Lactobacillus reuteri (L. reuteri) on hepatic ischemia-reperfusion (I/R) injury and uncover the mechanisms involved. Methods Mice in the I/R groups were orally administered low and high doses of L.reuteri (L.reuteri-low and L. reuteri-hi; 1 × 1010 CFU/d and 1 × 1011 CFU/d), for 4 weeks prior to surgery. Following this, mice in the model group were treated with an Nrf2 inhibitor (ML-385), palmitoylcarnitine, or a combination of both. Results After treatment with L. reuteri, mice exhibited reduced levels of serum aminotransferase (ALT), aspartate aminotransferase (AST), and myeloperoxidase (MPO) activity, as well as a lower Suzuki score and apoptosis rate. L. reuteri effectively reversed the I/R-induced decrease in Bcl2 expression, and the significant increases in the levels of Bax, cleaved-Caspase3, p-p65/p65, p-IκB/IκB, p-p38/p38, p-JNK/JNK, and p-ERK/ERK. Furthermore, the administration of L. reuteri markedly reduced the inflammatory response and oxidative stress triggered by I/R. This treatment also facilitated the activation of the Nrf2/HO-1 pathway. L. reuteri effectively counteracted the decrease in levels of beneficial gut microbiota species (such as Blautia, Lachnospiraceae NK4A136, and Muribaculum) and metabolites (including palmitoylcarnitine) induced by I/R. Likewise, the introduction of exogenous palmitoylcarnitine demonstrated a beneficial impact in mitigating hepatic injury induced by I/R. However, when ML-385 was administered prior to palmitoylcarnitine treatment, the previously observed effects were reversed. Conclusion L. reuteri exerts protective effects against I/R-induced hepatic injury, and its mechanism may be related to the promotion of probiotic enrichment, differential metabolite homeostasis, and the Nrf2/HO-1 pathway, laying the foundation for future clinical applications

High performance acetone sensor based on ZnO nanorods modified by Au nanoparticles

High performance acetone sensor based on ZnO nanorods modified by Au nanoparticle

Dynamic Analysis and Optimization of the Coupling System of Vibrating Flip-Flow Screen and Material Group

Vibrating flip-flow screens (VFFSs) provide an effective solution for deeply screening moist and fine-grained minerals, and an accurate dynamic model of VFFSs is critical for its dynamic analysis and optimization, thereby improving the vibration stability and symmetry of VFFSs. In this paper, uniaxial tension, uniaxial compression, plane tension, and shear stress relaxation experiments were conducted on screen panel samples to illustrate that the third-order Ogden model and the generalized Maxwell model can accurately describe the hyperelasticity and viscoelasticity of screen panels. Then, the coupling method of finite element and discrete element was adopted to establish the simulation model of the screen panel and material group coupling system, and the dynamics of the coupling system under different loading conditions were explored. Finally, the dynamic model of the coupling system of VFFSs mass, screen panel, and material group was proposed, and the non-dominated sorting genetic algorithm II was applied to optimize the system’s dynamic response. The results reveal that the use of optimized shear springs can reduce the relative amplitude change rate of the main and floating screen frame by 44.30% while maintaining the periodic motion of the VFFSs under operation conditions, greatly enhancing the stability of the VFFSs system