Background: Excessive daytime sleepiness (EDS) is considered to be one of the main clinical manifestations of obstructive sleep apnea (OSA) and is a treatment target for patients with OSA. The prevalence of EDS in patients with OSA remains unclear and there is a lack of studies on the associations of EDS with quality of life among patients with OSA in China. This study aimed to evaluate the prevalence of EDS and its association with quality of life in patients with OSA in Shenzhen, China.
View Article and Find Full Text PDFCompliant mechanisms with reconfigurable degrees of freedom are gaining attention in the development of kinesthetic haptic devices, robotic systems, and mechanical metamaterials. However, available devices exhibit limited programmability and form-customizability, restricting their versatility. To address this gap, we propose a metastructure concept featuring reconfigurable motional freedom and tunable stiffness, adaptable to various form factors and applications.
View Article and Find Full Text PDFIntroduction: Social contact patterns significantly influence the transmission dynamics of respiratory pathogens. Previous surveys have quantified human social contact patterns, yielding heterogeneous results across different locations. However, significant gaps remain in understanding social contact patterns in rural areas of China.
View Article and Find Full Text PDFCircular RNA (circRNA) has gained attention as a promising platform for mRNA vaccines due to its stability, sustained protein expression, and intrinsic immunostimulatory properties. This study aimed to design and optimize a circRNA cancer vaccine platform by screening for efficient internal ribosome entry sites (IRES) and enhancing circRNA translation efficiency for improved cancer immunotherapy. We screened 29 IRES elements to identify the most efficient one for immune cell translation, ultimately discovering the A (EV-A) IRES.
View Article and Find Full Text PDFVoltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
View Article and Find Full Text PDFDeveloping effective nanoplatforms for chemo-immunotherapy to achieve enhanced tumor suppression and systemic antitumor immunity has recently received extensive attention. Herein, we formulated a multifunctional DNA sandwich nanodevice, DSWAC/siPD-L1, based on triangular DNA origami, to implement enhanced cancer chemo-immunotherapy. Taking advantage of the tumor-targeting ability of the AS1411 aptamer, DSWAC/siPD-L1 efficiently delivered doxorubicin (DOX), CpG, and siPD-L1 into tumor cells.
View Article and Find Full Text PDFClinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).
View Article and Find Full Text PDFAims: We aimed to perform a retrospective cohort study using the Centers for Disease Control and Prevention's (CDC's) Wide-Ranging Online Data for Epidemiologic Research (WONDER) database to analyse the trends in cardiovascular disease (CVD)-related mortality in patients with myeloproliferative neoplasms (MPNs) from 1999 to 2020.
Methods And Results: We analysed the death certificate data from the CDC WONDER database from 1999 to 2020 for CVD with co-morbid myeloproliferative disorders in the US population. Age-adjusted mortality rates (AAMRs) and 95% confidence intervals (CIs) were computed per 1 million population by standardizing crude mortality rates to the 2000 US census population.
Background: Approximately half of the patients with acute ischemic stroke who receive intravenous thrombolysis (IVT) do not achieve an excellent outcome. Remote ischemic conditioning (RIC) as a promising neuroprotective treatment may improve clinical outcomes in this population. This study aimed to assess the efficacy and safety of RIC in patients with IVT.
View Article and Find Full Text PDFIt is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.
View Article and Find Full Text PDFLimited whole genome sequencing (WGS) studies in Asian populations result in a lack of representative reference panels, thus hindering the discovery of ancestry-specific variants. Here, we present the South and East Asian reference Database (SEAD) panel ( https://imputationserver.westlake.
View Article and Find Full Text PDFPurpose: To compare graft remodeling, as measured by magnetic resonance imaging (MRI), and clinical outcomes between patients who underwent isolated anterior cruciate ligament reconstruction (ACLR) versus combined anterior cruciate ligament and anterolateral ligament reconstruction (ACLR + ALLR).
Methods: A retrospective review was conducted on patients who underwent primary ACLR with quadruple hamstring grafts between January 2019 and March 2022, with a minimum follow-up period of 2 years. Patients were categorized into 2 groups on the basis of the addition of ALLR with tibialis anterior allografts: an isolated ACLR group and an ACLR + ALLR group.
Context: Medical education is moving towards competency based medical education (CBME). This provides opportunities and challenges for the field of Hospice and Palliative Medicine (HPM). The American Academy of Hospice and Palliative Medicine (AAHPM) created the Assessment Workgroup to spearhead a shared vision and process to implement high-quality assessment of fellow performance.
View Article and Find Full Text PDFFormative verbal feedback during live surgery is essential for adjusting trainee behavior and accelerating skill acquisition. Despite its importance, understanding optimal feedback is challenging due to the difficulty of capturing and categorizing feedback at scale. We propose a Human-AI Collaborative Refinement Process that uses unsupervised machine learning (Topic Modeling) with human refinement to discover feedback categories from surgical transcripts.
View Article and Find Full Text PDFBackground: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.
Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.
Metabolic syndrome (MS) is a progressive metabolic disease characterized by obesity and multiple metabolic disorders. Tryptophan (Trp) is an essential amino acid, and its metabolism is linked to numerous physiological functions and diseases. However, the mechanisms by which Trp affects MS are not fully understood.
View Article and Find Full Text PDFBackground: Short-term and long-term adverse events could occur after general anesthesia (GA) and the specific mechanism driving these effects has not yet been well-characterized. In this study, we aimed to evaluate the global effect of GA on DNA methylation in the cell-free DNA (cfDNA) of surgical lung-nodule patients.
Methods: This large retrospective cohort study enrolled 1,006 surgical lung nodule patients (529 pre-anesthesia, and 477 post-anesthesia).
Duplication of methyl-CpG-binding protein 2 (MECP2) gene causes MECP2 duplication syndrome (MDS). To normalize the duplicated MECP2 in MDS, we developed a high-fidelity Cas13Y (hfCas13Y) system capable of targeting the MECP2 (hfCas13Y-gMECP2) messenger RNA for degradation and reducing protein levels in the brain of humanized MECP2 transgenic mice. Moreover, the intracerebroventricular adeno-associated virus (AAV) delivery of hfCas13Y-gMECP2 in newborn or adult MDS mice restored dysregulated gene expression and improved behavior deficits.
View Article and Find Full Text PDFPurpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.
View Article and Find Full Text PDFOxygen evolution reaction (OER) holds vital significance for energy conversion and sustainable synthesis, but the scope of achievable reactions using active and durable electrocatalysts remains limited. Nearly all employed electrocatalyst surfaces undergo uncontrolled reconstruction processes during OER, resulting in inevitable uncertainties and randomness in the formation and evolution of the reconstituted layer. Most current efforts are confined to a single process or region, leaving the energy supply and microenvironment uncontrollable.
View Article and Find Full Text PDFThe exploration of two-dimensional (2D) metallenes is driven by their noteworthy attributes, encompassing high conductivity and substantial exposure of metal active sites, facilitating the development of nitrogen reduction reaction (NRR) electrocatalysts characterized by a low overpotential and superior selectivity. Here, employing first-principles swarm-intelligence structural search methods, we predict molybdenene as a novel and stable non-precious metallene, featuring a 2-atom-thick structure. Our findings demonstrate that the basal plane of molybdenene showcases remarkable catalytic activity with an overpotential of 0.
View Article and Find Full Text PDFBackground: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain.
Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care.