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Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3′ untranslated region of the DMPK gene, thus leading to the expression of transcripts containing expanded CUG repeats (CUGexp). The pathophysiology is explained by a toxic RNA gain of function where CUGexp RNAs form nuclear aggregates that sequester and alter the function of MBNL splicing factors, triggering splicing misregulation linked to the DM1 symptoms. There is currently no cure for DM1, and most therapeutic strategies aim at eliminating CUGexp-DMPK transcripts. Here, we investigate a DMPK-promoter silencing strategy using CRISPR interference as a new alternative approach. Different sgRNAs targeting the DMPK promoter are evaluated in DM1 patient muscle cells. The most effective guides allowed us to reduce the level of DMPK transcripts and CUGexp-RNA aggregates up to 80%. The CUGexp-DMPK repression corrects the overall transcriptome, including spliceopathy, and reverses a physiological parameter in DM1 muscle cells. Its action is specific and restricted to the DMPK gene, as confirmed by genome-wide expression analysis. Altogether, our findings highlight DMPK-promoter silencing by CRISPRi as a promising therapeutic approach for DM1.

Background: The effect of imaging selection paradigms on endovascular thrombectomy outcomes in patients with acute ischemic stroke with large vessel occlusion remains uncertain. The study aimed to assess the effect of basic imaging (noncontrast computed tomography with or without computed tomographic angiography) versus advanced imaging (magnetic resonance imaging or computed tomography perfusion) on clinical outcomes following thrombectomy in patients with stroke with large vessel occlusion in the early and extended windows using a pooled analysis of patient-level data from 2 pivotal randomized clinical trials done in China. Methods: This post hoc analysis used data from 1182 patients included in 2 multicenter, randomized controlled trials in China that evaluated adjunct therapies to endovascular treatment for acute ischemic stroke (Direct Endovascular Treatment for Large Artery Anterior Circulation Stroke performed from May 20, 2018, through May 2, 2020, and Intravenous Tirofiban Before Endovascular Treatment in Stroke from October 10, 2018, through October 31, 2021). Patients with occlusion of the intracranial internal carotid artery or proximal middle cerebral artery (M1/M2 segments) were categorized according to baseline imaging modality (basic versus advanced) as well as treatment time window (early, 0–6 hours versus extended, 6–24 hours from last known well to puncture). The primary outcome was the proportion of patients with functional independence (modified Rankin Scale score of 0–2) at 90 days. Multivariable Poisson regression analysis was performed to determine the association between imaging selection modality and outcomes after endovascular treatment at each time windows. Results: A total of 1182 patients were included in this cohort analysis, with 648 in the early (471 with basic imaging versus 177 advanced imaging) and 534 in the extended (222 basic imaging versus 312 advanced imaging) time window. There were no differences in 90-day functional independence between the advanced and basic imaging groups in either time windows (early window: adjusted relative risk, 0.99 [95% CI, 0.84–1.16]; P =0.91; extended window: adjusted relative risk, 1.00 [95% CI, 0.84–1.20]; P =0.97). Conclusions: In this post hoc analysis of 2 randomized clinical trial pooled data involving patients with large vessel occlusion stroke, an association between imaging selection modality and clinical or safety outcomes for patients undergoing thrombectomy in either the early or extended windows was not detected. Our study adds to the growing body of literature on simpler imaging paradigms to assess thrombectomy eligibility across both the early and extended time windows. Registration: URL: http://www.chictr.org.cn ; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Effects of two different modified treatments were investigated relative to the chemical and mechanical properties of pretreated corn stalk particles and their composites prepared with a modified lignosulfonate (ML) binder. Corn stalk particles (CP) first were prepared by treating corn stalk particles with oxalic acid in ultrasonic conditions (pretreated corn stalk particles, PCP). These particles were then modified by treatment with either laccase-vanillin system with ultrasound (LU) or polyethylenimine-glutaraldehyde with ultrasound (PU), and the surface chemistries of the modified PCP and mechanical properties of LU-PCP/ML composites and PU-PCP/ML composites, such as modulus of rupture (MOR), modulus of elasticity (MOE), internal bonding strength (IB), 24-h thickness swelling (TS), and crystallinity were compared. Both modified treatments dramatically enhanced the mechanical properties of the composites. The MOR, MOE, and IB of the PU-PCP/ML composites were improved by up to 148%, 81%, and 62%, respectively, compared to LU-PCP/ML. Moreover, the 24-h TS of the LU-PCP/ML composites was reduced by 16%. These results show that the pretreatment method of CP and ultrasonic collaborative treatment of PCP can effectively improve the properties of its composites. Modified PCP with PU was more favorable for surface chemical and mechanical properties.

Non-controlling shareholders' withdrawal threat means that by showing the withdrawal tendency to the controlling shareholders, the controlling shareholders are forced to make compromises and improve the accounting soundness of the company. At present, the existing literatures mainly discuss the impact of exit threat on corporate finance and corporate performance, but few literatures study the causal relationship between exit threat and accounting conservatism, and the research field of its correlation is not perfect. Based on this, this paper takes the sample of China's A-share listed companies from 2010 to 2021 as the research object, studies the influence mechanism of the withdrawal threat of non-controlling shareholders on accounting conservatism, puts forward theoretical assumptions from the opposite angle, makes descriptive statistics and benchmark regression, and draws a conclusion; The robustness of benchmark regression conclusion is tested by PSM tendency score matching method and replacement variable method. Finally, based on the perspective of differences, this paper studies the heterogeneous influence of company size, long-term solvency and profitability on accounting conservatism, and finds that the withdrawal threat of non-controlling shareholders is significantly positively correlated with accounting conservatism, which expands the related research of withdrawal threat on corporate governance, and has reference significance for the check and balance governance mechanism of non-controlling shareholders of listed companies in China.

Navigation and positioning is a new growth point of wireless services. And seamless positioning is the current development trend of navigation and positioning services. In view of the problems that dynamic handover cannot be performed during site movement, STA only selects the optimal AP according to the indication of received signal strength, and the handover delay is too long. This paper proposes a research on indoor and outdoor seamless positioning technology based on artificial intelligence and intelligent switching algorithm. The purpose is to study the influence of reducing the positioning data with too large error on the final positioning result. The method of this paper is to propose an intelligent switching algorithm and then discuss the research status and development direction of indoor positioning technology and outdoor positioning technology, respectively, and point out the switching methods between them. The role of these methods is to analyze the current situation of indoor and outdoor navigation technology, especially the development route of seamless positioning technology. It determines the strategy of integrating heterogeneous positioning systems to build a seamless positioning system to maximize the use of existing positioning system resources. This paper studies the design and implementation of the seamless positioning system through the simulation experiment of the intelligent switching algorithm and finally tests the system through the experimental vehicle. The online experiment results show that the system can achieve high positioning accuracy in indoor and outdoor environments, especially at its junction, and the positioning errors in all directions are within 0.2 m.

Autism spectrum disorder (ASD) affects nearly 1 in 44 children younger than 8 years old in the United States, and the situation may be even worse in remote areas of the world. However, it is difficult to utilize existing approaches to screen patients with ASD in remote areas due to the lack of professionals and high-tech instruments. To address this problem, we develop a fast and accurate scalable method for screening children with ASD.A deep weakly supervised artificial intelligence model is proposed for ASD screening based on the dynamic viewing patterns (DVP) over viewing time and visual stimuli. In training, we utilized a long short-term memory (LSTM) network to learn the mapping between the autoencoder-based encoded dynamic patterns and the labels. In testing, we fed the encoded DVP of each undiagnosed child into the trained network and predicted the diagnosis category based on the score on all stimuli.Based on the multi-center evaluation on 165 subjects (95 typically developing children and 70 children with ASD) aged 3-6 years from different areas of China, our method achieves an average recognition accuracy of 96.73% (sensitivity 96.85% and specificity 96.63%).The DVP is a discriminating attribute to identify the atypical performance of ASD. The DVP-based model is an effective platform for enhancing auxiliary ASD screening accuracy.We explored and validated the importance of dynamic information on between-group differences and classification. Additionally, the evaluation results suggest that the proposed model can provide an objective and accessible tool for scalable ASD screening applications.