GBA-AAV mitigates sleep disruptions and motor deficits in mice with REM sleep behavior disorder.

Sleep disturbances, including rapid eye movement sleep behavior disorder (RBD), excessive daytime sleepiness, and insomnia, are common non-motor manifestations of Parkinson's disease (PD). Little is known about the underlying mechanisms, partly due to the inability of current rodent models to adequately mimic the human PD sleep phenotype. Clinically, increasing studies have reported that variants of the glucocerebrosidase gene (GBA) increase the risk of PD. Here, we developed a mouse model characterized by sleep-wakefulness by injecting α-synuclein preformed fibronectin (PFF) into the sublaterodorsal tegmental nucleus (SLD) of GBA L444P mutant mice and investigated the role of the GBA L444P variant in the transition from rapid eye movement sleep behavior disorder to PD. Initially, we analyzed spectral correlates of REM and NREM sleep in GBA L444P mutant mice. Importantly, EEG power spectral analysis revealed that GBA L444P mutation mice exhibited reduced delta power during non-rapid eye movement (NREM) sleep and increased theta power (8.2-10 Hz) in active rapid eye movement (REM) sleep phases. Our study revealed that GBA L444P-mutant mice, after receiving PFF injections, exhibited increased sleep fragmentation, significant motor and cognitive dysfunctions, and loss of dopaminergic neurons in the substantia nigra. Furthermore, the over-expression of GBA-AAV partially improved these sleep disturbances and motor and cognitive impairments. In conclusion, we present the initial evidence that the GBA L444P mutant mouse serves as an essential tool in understanding the complex sleep disturbances associated with PD. This model further provides insights into potential therapeutic approaches, particularly concerning α-synuclein accumulation and its subsequent pathological consequences.

Adaptive Dynamic Event-Triggered Tracking Control for Uncertain Switched Nonlinear Systems Under State-Dependent Switching.

This article introduces an adaptive dynamic event-triggered technique for addressing the output tracking control problem of uncertain switched nonlinear systems with prescribed performance. First, a switching dynamic event-triggered mechanism (SDETM) is established to alleviate network burden and conserve computational resources. A notable aspect is the inclusion of asynchronous switching between the switching subsystems and controllers. Second, a state-dependent switching law ensuring a dwell-time constraint is designed, which avoids the frequent switching phenomenon within any finite time interval. Third, an SDETM and an adaptive dynamic event-triggered controller are developed to confine the output tracking error within predefined decaying boundaries, while ensuring that all the signals of the closed-loop switched system remain within bounded regions. Finally, the validity and applicability of the developed control scheme are demonstrated through a one-link manipulator example.

Reporting quality evaluation of the stroke clinical practice guidelines: a systematic review.

OBJECTIVES: To analyze the effectiveness and quality of stroke clinical practice guidelines (CPGs) published in recent years in order to guide future guideline developers to develop better guidelines. PARTICIPANTS: No patient involved METHOD: PubMed, China Biology Medicine (CBM), Wanfang, CNKI, and CPG-relevant websites were searched from January 2015 to December 2019 by two researchers independently. The RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was used to assess the reporting quality in terms of domains and items. Then, a subgroup analysis of the results was performed. PRIMARY AND SECONDARY OUTCOME MEASURES: RIGHT checklist reporting rate RESULTS: A total of 66 CPGs were included. Twice as many CPGs were published internationally as were published in China. More than half were updated. Most CPGs are published in journals, developed by societies or associations, and were evidence-based grading. The average reporting rate for all included CPGs was 47.6%. Basic information got the highest (71.7% ± 19.7%) reporting rate, while review and quality assurance got the lowest (22.0% ± 24.6%). Then, a cluster analysis between countries, publishing channels, and institutions was performed. There were no statistically significant differences in the reporting quality on the CPGs between publishing countries (China vs. international), publishing channels (journals vs. websites), and institutions (associations vs. non-associations). CONCLUSIONS: Current stroke CPGs reports are of low quality. We recommend that guideline developers improve the quality of reporting of key information and improve the management of conflicts of interest. We recommend that guideline developers consider the RIGHT checklist as an important tool for guideline development. TRIAL REGISTRATION: https://doi.org/10.17605/OSF.IO/PBWUX .

Clinical Epidemiology in China series. Paper 3: The methodological and reporting quality of systematic reviews and meta-analyses published by China' researchers in English-language is higher than those published in Chinese-language.

OBJECTIVE: To assess the methodological and reporting quality of Chinese- and English -language systematic reviews and meta-analyses (SRs/MAs) published by Chinese authors between 2016 and 2018. STUDY DESIGN AND SETTING: We searched MEDLINE and Chinese Science Citation Database (CSCD) for SRs/MAs led by Chinese authors published between 2016 and 2018. We used random sampling to select 10% of the eligible SRs/MAs published in each year from CSCD, and then matched the same number of SRs/MAs in MEDLINE. Reporting quality was evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and methodological quality using the Assessment of Multiple Systematic Reviews (AMSTAR-2) tool. Stratified analyses were conducted to compare the differences of quality between Chinese- and English language SRs/MAs. RESULTS: We identified 336 SRs/MAs (168 in Chinese and 168 in English). The reporting quality in Chinese-language SRs/MAs was slightly lower than English-language SRs/MAs (mean PRISMA scores: 20.58 vs. 21.71 in 2016, 19.87 vs. 21.24 in 2017, and 21.29 vs. 22.38 in 2018). Less than half of both Chinese- and English-language SRs/MAs complied with item 5 (protocol and registration), item 7 (information sources), item 8 (search) and item 27 (funding)). The methodological quality in Chinese -language SRs/MAs was also slightly lower than English -language SRs/MAs (mean AMSTAR-2 scores: 8.07 vs. 9.36 in 2016; 9.21 vs. 10.26 in 2017; 8.86 vs. 9.28 in 2018). Three items (item 2: established a protocol; item 4: use a comprehensive literature search; and item 10: report the sources of funding) were adhered to by less than 10% of both Chinese- and English -language SRs/MAs. Only one (0.6%) Chinese-language SRs/MA and nine (5.4%) English-language SRs/MAs were rated as high methodological quality. CONCLUSION: The reporting and methodological quality of English-language SRs/MAs conducted by authors from China between 2016 and 2018 were slightly better than those of Chinese -language SRs/MAs.

B4GALT3 up-regulation by miR-27a contributes to the oncogenic activity in human cervical cancer cells.

ß-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for the generation of poly-N-acetyllactosamine and is involved in tumorigenesis. However, B4GALT3-dysregulation and its role in cervical cancer cells are unknown. Herein, we found that B4GALT3 was upregulated in cervical cancer tissues compared to adjacent non-tumor tissues. B4GALT3-overexpression promoted, whereas B4GALT3-knockdown suppressed the cellular migration, invasion and EMT of HeLa and C33A cervical cancer cells. To explore the mechanism of dysregulation, B4GALT3 was predicted to be a target of miR-27a. EGFP and pGL3-promoter reporter assay showed miR-27a binds to B4GALT3 3'UTR region but enhanced its expression. RT-qPCR showed miR-27a was also upregulated and presented positive correlation with B4GALT3-expression in cervical cancer tissues. miR-27a-overexpression promoted, but blocking-miR-27a repressed these malignancies in HeLa and C33A cells. Furthermore, shR-B4GALT3 counteracted the promotion of malignancies induced by miR-27a, suggesting miR-27a upregulates B4GALT3 to enhance tumorigenic activities. In addition, we found that B4GALT3 significantly enhances ß1-integrin stability, thus mediating promotion of B4GALT3 on malignancy in cervical cancer cells. Altogether, our findings evidenced that B4GALT3 upregulated by miR-27a contributes to the tumorigenic activities by ß1-integrin pathway and might provide potential biomarkers for cervical cancer.