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.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Tailoring Polyelectrolyte Multilayer Nanofiltration Membranes by Aerosol-Assisted Printing: Insights into Membrane Formation Mechanisms.

Polyelectrolyte multilayer (PEM) membranes, with advantageous features of versatile chemistry and structures, are driving the development of advanced nanofiltration (NF) membranes with exceptional performance. While developing a printing method holds great promise for the eventual mass production of these membranes, reports on the printing method and the underlying mechanisms of membrane formation are currently scarce. Herein, we develop an aerosol-assisted printing (AAP) system for fabricating PEM NF membranes with highly tunable separation characteristics.

Facile preparation of marine carrageenan hydrogel-coated steel mesh with superhydrophilic and underwater superoleophobic performance for highly efficient oil-water separation.

The discharge of oil-laden wastewater from industrial processes and the frequent occurrence of oil spills pose severe threats to the ecological environment and human health. Membrane materials with special wettability have garnered attention for their ability to achieve efficient oil-water separation by leveraging the differences in wettability at the oil-water interface. These materials are characterized by their simplicity, energy efficiency, environmental friendliness, and reusability.

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Reduced graphene oxide membrane with small nanosheets for efficient and ultrafast removal of both microplastics and small molecules.

The clogging of sieving pores due to the complex sewage system of mixed molecules and nanoparticles of different scales is a difficulty in the membrane-based separation process. When the holes are reduced to the point where they can repel small molecules in the contaminants, large-molecule contaminants can adsorb to the holes and decrease the permeability. A similar question remains in new promising graphene oxide (GO) membranes.

Evaluating Neoadjuvant Immunochemotherapeutic Response for Bladder Carcinoma Using Amide Proton Transfer-Weighted MRI.

Rationale And Objectives: To investigate the feasibility of amide proton transfer-weighted (APTw) and diffusion-weighted MRI in evaluating the response of bladder cancer (BCa) to neoadjuvant immunochemotherapy.

Materials And Methods: From June 2021 to July 2023, participants with pathologically confirmed BCa were prospectively recruited to undergo MRI examinations, including APTw and diffusion-weighted MRI before and after neoadjuvant immunochemotherapy. Histogram analysis features (mean, median, and entropy) were extracted from pre- and post-treatment APTw and apparent diffusion coefficient (ADC) maps, respectively.

Facile Preparation of Sulfonated Polysulfone Composite Membranes with High Hydrophilicity and Visible-Light Driving Self-Cleaning Performance.

The photo-Fenton reaction can efficiently degrade organic pollutants and thus is applied intensively for clearing out membrane fouling. However, the pollutant removal efficiency is greatly limited by the redox cycle rate of Fe/Fe and the rapid recombination rate of the photogenerated electrons and holes. In order to overcome these drawbacks, a sulfonated polysulfone composite membrane was designed and prepared by incorporating titanium dioxide (TiO) nanoparticles into a sulfonated polysulfone membrane and sequentially forming β-FeOOHs on the membrane surface.

A Gravity-Driven Membrane Bioreactor in Treating Real Fruit Juice Wastewater: Response Relationship Between Filtration Behavior and Microbial Community Evolution.

The issue of environmental pollution caused by wastewater discharge from fruit juice production has attracted increasing attention. However, the cost-effectiveness of conventional treatment technology remains insufficient. In this study, a gravity-driven membrane bioreactor (GDMBR) was developed to treat real fruit juice wastewater from secondary sedimentation at pressures ranging from 0.

Correlation Analysis Between Cortical Structural Features and Acoustic Features in Patients With Parkinson's Disease.

Purpose: Parkinson disease (PD) is a progressive neurodegenerative disease. The aim of this study is to investigate the association between acoustic and cortical brain features in Parkinson's disease patients.

Methods: We recruited 19 (eight females, 11 males) Parkinson's disease patients and 19 (eight females, 11 males) healthy subjects to participate in the experiment.

Severe fever with thrombocytopenia syndrome virus was found in Northern Jiangxi Province, China.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. SFTS monitoring has been carried out since 2010 in mainland China. In recent years, human infection with SFTS virus (SFTSV) has frequently been detected in Jiujiang of Jiangxi Province, Central China.

Do emergency Medicaid programs improve post-discharge health care access for trauma patients? A statewide mixed-methods study.

Background: Hospital presumptive eligibility (HPE) emergency Medicaid programs offset patient bills at hospitalization and can provide long-term Medicaid coverage. We characterized postdischarge outpatient health care utilization among HPE Medicaid trauma patients and identified patient access facilitators and barriers once newly insured. We hypothesized utilization would be increased among HPE trauma patients compared with other HPE patients, but that challenges in access to care would remain.

A robust benchmark for detecting low-frequency variants in the HG002 Genome In A Bottle NIST reference material.

Somatic mosaicism is an important cause of disease, but mosaic and somatic variants are often challenging to detect because they exist in only a fraction of cells. To address the need for benchmarking subclonal variants in normal cell populations, we developed a benchmark containing mosaic variants in the Genome in a Bottle Consortium (GIAB) HG002 reference material DNA from a large batch of a normal lymphoblastoid cell line. First, we used a somatic variant caller with high coverage (300x) Illumina whole genome sequencing data from the Ashkenazi Jewish trio to detect variants in HG002 not detected in at least 5% of cells from the combined parental data.

Continuous motion tracking for accurate and efficient color vision assessment.

The assessment of color vision is crucial in both fundamental visual research and clinical diagnosis. However, existing tools for color vision assessment are limited by various factors. This study introduces a novel, efficient method for color vision assessment, which is based on a continuous motion tracking task and a Kalman filter model.

Optimization of border irrigation variables based on a correction factor for irrigation quota.

The optimization of surface irrigation variables, i.e., the selection of the optimal combination of the inflow rate per unit width (q) and cutoff time (tco), is essential for obtaining high performance.

Mineralized Nanofiber Substrates Enabling High-Performance Dually Charged Nanofiltration Membranes with Enhanced Permeability.

Nanofiltration membranes (NFMs) with superior permeability and high rejection of both divalent anions and cations are highly desirable to meet the increasing separation demands of complex systems. Herein, we propose a three-in-one strategy to develop a state-of-the-art dually charged thin-film composite (TFC) nanofiltration membrane consisting of a positively charged electrospun nanofiber substrate (NFS) with surface mineralization and a negatively charged polyamide (PA) selective layer prepared by interfacial polymerization (IP). The highly hydrophilic mineralized nanofiber substrate not only effectively reduces the thickness of the PA selective layer but also crumples its structures by the abundant zirconia nanoparticles on the substrate surface, resulting in excellent water flux (15.

Nivolumab plus Ipilimumab in Microsatellite-Instability-High Metastatic Colorectal Cancer.

Background: Patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer have poor outcomes with standard chemotherapy with or without targeted therapies. Nivolumab plus ipilimumab has shown clinical benefit in nonrandomized studies of MSI-H or dMMR metastatic colorectal cancer.

Methods: In this phase 3 open-label trial, we randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive, in a 2:2:1 ratio, nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies.

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.

Carbapenem-resistant Enterobacterales in solid organ transplant recipients.

Carbapenem-resistant Enterobacterales (CRE) are an important threat to the health of solid organ transplant recipients (SOTr); data comparing outcomes of SOTr with CRE to non-SOTr with CRE are lacking. A matched cohort study was performed within 2 prospective, multicenter, cohort studies (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales and Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales 2). The epidemiology, desirability of outcome rankings outcomes, and mortality of SOTr and non-SOTr hospitalized in the United States (December 2011-August 2017) with clinical isolates with Centers for Disease Control and Prevention-defined CRE were compared.

Individually addressed entangling gates in a two-dimensional ion crystal.

Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.

Co-doped Zr-UiO-66-NH@carboxylated cellulose nanocrystals/PAN membrane for oil/water separation with photocatalysis-PMS synergistic self-cleaning and antibacterial activity.

The development of superwetting membranes is a promising approach for separating emulsified oily wastewater. However, challenges such as low flux without external pressure and membrane fouling have hindered membrane performance. Herein, we fabricated a novel nanofibrous membrane by grafting Co-doped Zr-UiO-66-NH (UiO(Zr/Co)) nanoparticles onto carboxylated cellulose nanocrystals (CCNC)-polyacrylonitrile (PAN) mixed matrix electrospinning membrane via chemical bonds through EDC/NHS reaction.

A heterogeneous polyurethane hybrid foam with enhanced demulsification and dynamic oil cleaning for continuous emulsion separation.

Here, a top-down strategy was presented to fabricate a heterogeneous polyurethane hybrid foam with independent oil-absorbing frameworks and uninterrupted water transport channels for continuous emulsion separation. A commercial polyurethane foam (PUF) was hydrophobically modified to develop oil-absorbing frameworks (HPUF). Superhydrophilic carbon nanotubes/cellulose nanofibers (CNTs/CNFs) aerogels were assembled in the voids of the HPUF to establish independent water transport channels, forming a heterogeneous polyurethane hybrid foam (CHPUF).

The biological mechanism of a lower carbon/nitrogen ratio increases methane emissions during vegetable waste composting.

The initial carbon/nitrogen (C/N) ratio is one of the most important factors impacting composting processes, such as methane (CH) emissions. However, the effects of the C/N ratio on CH emissions and the associated biological mechanisms during vegetable waste composting are largely unknown. In this study, a lab-scale experiment was conducted to investigate the effects of different C/N ratios on CH emissions and the mechanisms associated with methane-metabolizing microorganisms (methanogens and methanotrophs) during capsicum straw composting.