Prevalence of excessive daytime sleepiness (EDS) and its association with quality of life in patients with obstructive sleep apnea (OSA): data from a sleep-center in Shenzhen, a single-center cross-sectional study.

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.

Differential Connectivity Patterns of Mild Cognitive Impairment in Alzheimer's and Parkinson's Disease: A Large-scale Brain Network Study.

Rationale And Objectives: Cognitive disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), significantly impact the quality of life in older adults. Mild cognitive impairment (MCI) is a critical stage for intervention and can predict the development of dementia. The causes of these two diseases are not fully understood, but there is an overlap in their neuropathology.

Social contact patterns and their impact on the transmission of respiratory pathogens in rural China.

Introduction: 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.

Optimized circular RNA vaccines for superior cancer immunotherapy.

Circular 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.

Small molecule inhibits KCNQ channels with a non-blocking mechanism.

Voltage-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.

In vivo base editing extends lifespan of a humanized mouse model of prion disease.

Prion disease is a fatal neurodegenerative disease caused by the misfolding of prion protein (PrP) encoded by the PRNP gene. While there is currently no cure for the disease, depleting PrP in the brain is an established strategy to prevent or stall templated misfolding of PrP. Here we developed in vivo cytosine and adenine base strategies delivered by adeno-associated viruses to permanently modify the PRNP locus to achieve PrP knockdown in the mouse brain.

DNA origami-based composite nanosandwich for iteratively potentiated chemo-immunotherapy.

Developing 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.

Time in Target Range for Blood Pressure and Adverse Health Outcomes: A Systematic Review.

Background: Blood pressure (BP) time in target range (TTR) reflects the proportion of time that BP measurement is within a specified target range. We aim to summarize the evidence for relationships between TTR and adverse health outcomes.

Methods: Seven databases were searched.

Aqueous Proteomic and Metabolomic Profiles in Low-Energy vs High-Energy Femtosecond Laser-Assisted Cataract Surgery.

Purpose: To investigate the aqueous proteomics and metabolomics in low-energy and high-energy femtosecond laser-assisted cataract surgery (FLACS).

Methods: In this prospective observational study, 72 patients were randomized to 3 groups: low-energy FLACS, high-energy FLACS, and conventional phacoemulsification (controls). Aqueous was collected after femtosecond laser treatment or at the beginning of surgery (controls).

SEAD reference panel with 22,134 haplotypes boosts rare variant imputation and genome-wide association analysis in Asian populations.

Limited 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.

Optimized Adsorption of H and OH over Amorphous SrRuPtOH Nanobelts towards Efficient Alkaline Fuel Cell Catalysis.

PtRu-based catalysts toward hydrogen oxidation reaction (HOR) suffer from low efficiency, CO poisoning and over-oxidation at high potentials. In this work, an amorphization strategy is adopted for preparation of amorphous SrRuPtOH nanobelts (a-SrRuPtOH NBs). The a-SrRuPtOH NBs has optimized adsorption of intermediates (H and OH), increased number of active sites, highly weakened CO poisoning and enhanced anti-oxidation ability owing to the special amorphous structure.

Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis.

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene cause Rett syndrome, a severe childhood neurological disorder. MeCP2 is a well-established transcriptional repressor, yet upon its loss, hundreds of genes are dysregulated in both directions. To understand what drives such dysregulation, we deleted Mecp2 in adult mice, circumventing developmental contributions and secondary pathogenesis.

General anesthesia induces acute cell-free DNA methylation changes in peripheral blood.

Background: 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).

Feasibility of Sub-milliSievert Low-dose Computed Tomography with Deep Learning Image Reconstruction in Evaluating Pulmonary Subsolid Nodules: A Prospective Intra-individual Comparison Study.

Rationale And Objectives: To comprehensively assess the feasibility of low-dose computed tomography (LDCT) using deep learning image reconstruction (DLIR) for evaluating pulmonary subsolid nodules, which are challenging due to their susceptibility to noise.

Materials And Methods: Patients undergoing both standard-dose CT (SDCT) and LDCT between March and June 2023 were prospectively enrolled. LDCT images were reconstructed with high-strength DLIR (DLIR-H), medium-strength DLIR (DLIR-M), adaptive statistical iterative reconstruction-V level 50% (ASIR-V-50%), and filtered back projection (FBP); SDCT with FBP as the reference standard.

Canonical androgen response element motifs are tumor suppressive regulatory elements in the prostate.

The androgen receptor (AR) is central in prostate tissue identity and differentiation, and controls normal growth-suppressive, prostate-specific gene expression. It also drives prostate tumorigenesis when hijacked for oncogenic transcription. The execution of growth-suppressive AR transcriptional programs in prostate cancer (PCa) and the potential for reactivation remain unclear.

An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.

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.

Integrative mapping of human CD8 T cells in inflammation and cancer.

CD8 T cells exhibit remarkable phenotypic diversity in inflammation and cancer. However, a comprehensive understanding of their clonal landscape and dynamics remains elusive. Here we introduce scAtlasVAE, a deep-learning-based model for the integration of large-scale single-cell RNA sequencing data and cross-atlas comparisons.

Unraveling the Diffusion MRI-Based Glymphatic System Alterations in Children with Rolandic Epilepsy.

Rationale And Objectives: Although dysfunction of the glymphatic system in adult epilepsy has been extensively studied, there is a lack of research on the changes in this system during childhood development, particularly in children with Rolandic epilepsy (RE). This study aimed to investigate the changes in diffusion MRI measures related to the glymphatic function in children with RE.

Materials And Methods: A total of thirty-eight children with RE and thirty-six demographically matched healthy children were enrolled in the study.

Middle Meningeal Artery Embolization for Nonacute Subdural Hematoma.

Background: 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.

Coordinated inheritance of extrachromosomal DNAs in cancer cells.

The chromosomal theory of inheritance dictates that genes on the same chromosome segregate together while genes on different chromosomes assort independently. Extrachromosomal DNAs (ecDNAs) are common in cancer and drive oncogene amplification, dysregulated gene expression and intratumoural heterogeneity through random segregation during cell division. Distinct ecDNA sequences, termed ecDNA species, can co-exist to facilitate intermolecular cooperation in cancer cells.

Design of customized coronavirus receptors.

Although coronaviruses use diverse receptors, the characterization of coronaviruses with unknown receptors has been impeded by a lack of infection models. Here we introduce a strategy to engineer functional customized viral receptors (CVRs). The modular design relies on building artificial receptor scaffolds comprising various modules and generating specific virus-binding domains.

5'-tRNA halves generated by IRE1α are linked to the ER stress response.

Transfer RNA halves (tRHs) have various biological functions. However, the biogenesis of specific 5'-tRHs under certain conditions remains unknown. Here, we report that inositol-requiring enzyme 1α (IRE1α) cleaves the anticodon stem-loop region of tRNA to produce 5'-tRHs (5'-tRH-Gly) with highly selective target discrimination upon endoplasmic reticulum (ER) stress.

Tailoring smart hydrogels through manipulation of heterogeneous subdomains.

The mechanical interactions among integrated cellular structures in soft tissues dictate the mechanical behaviors and morphogenetic deformations observed in living organisms. However, replicating these multifaceted attributes in synthetic soft materials remains a challenge. In this work, we develop a smart hydrogel system featuring engineered stiff cellular patterns that induce strain-driven heterogeneous subdomains within the hydrogel film.

CAR-Macrophage Therapy Alleviates Myocardial Ischemia-Reperfusion Injury.

Background: Given the growing acknowledgment of the detrimental effects of excessive myocardial fibrosis on pathological remodeling after myocardial ischemia-reperfusion injury (I/R), targeting the modulation of myocardial fibrosis may offer protective and therapeutic advantages. However, effective clinical interventions and therapies that target myocardial fibrosis remain limited. As a promising chimeric antigen receptor (CAR) cell therapy, whether CAR macrophages (CAR-Ms) can be used to treat I/R remains unclear.