Location-specific net water uptake and malignant cerebral edema in acute anterior circulation occlusion ischemic stroke.

Background And Purpose: Early identification of malignant cerebral edema (MCE) in patients with acute ischemic stroke is crucial for timely interventions. We aimed to identify regions critically associated with MCE using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) to evaluate the association between location-specific-net water uptake (NWU) and MCE.

Materials And Methods: This multicentre, retrospective cohort study included patients with acute ischemic stroke following large anterior circulation occlusion.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

Enhancing Neuron Activity Promotes Functional Recovery by Inhibiting Microglia-Mediated Synapse Elimination After Stroke.

Background: Activating glutamatergic neurons in the ipsilesional motor cortex can promote functional recovery after stroke. However, the underlying molecular mechanisms remain unclear. Clarifying key molecular mechanisms involved in recovery could help understand the development of neuromodulation strategies after stroke.

Deficiency of Endothelial Impairs Pulmonary Vascular Angiogenesis and Predisposes Pulmonary Hypertension.

Background: Mechanosensitive Piezo1 channel plays a key role in pulmonary hypertension (PH). However, the role of Piezo2 in PH remains unclear.

Methods: Endothelial cell (EC)-specific knockout (, Tek-Cre; ) rats and primarily cultured pulmonary microvascular ECs were used to determine the role of Piezo2 in PH.

Chromatin State Maps of Blood Pressure-Relevant Renal Segments Reveal Potential Regulatory Role for SNPs.

Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.

Transcriptional Reprogramming Deploys a Compartmentalized 'Timebomb' in Catharanthus roseus to Fend Off Chewing Herbivores.

The evolutionary arms race between plants and insects has led to key adaptive innovations that drive diversification. Alkaloids are well-documented anti-herbivory compounds in plant chemical defences, but how these specialized metabolites are allocated to cope with both biotic and abiotic stresses concomitantly is largely unknown. To examine how plants prioritize their metabolic resources responding to herbivory and cold, we integrated dietary toxicity bioassay in insects with co-expression analysis, hierarchical clustering, promoter assay, and protein-protein interaction in plants.

The First Case of Serogroup Y and An Expanded Investigation of Healthy Carriers - Shijiazhuang City, Hebei Province, China, 2023.

What Is Already Known About This Topic?: (Nm) is a bacterial pathogen that causes meningococcal disease. Serogroups A, B, C, W, X, and Y account for the vast majority of cases. However, invasive meningococcal disease (IMD) caused by NmY is rare in China and has been reported only in Tianjin, Guangdong, Shanghai, and Hunan provinces and cities.

Uncovering latent infections in kidneys: A novel molecular approach for differential detection.

Leptospirosis, a re-emerging zoonotic disease caused by spp., poses significant global health and veterinary challenges. Long-term colonization of renal tubules by in asymptomatic hosts highlights the need for sensitive detection methods.

The Impact of Sleep Disorders on Glymphatic Function in Parkinson's Disease Using Diffusion Tensor MRI.

Rationale And Objectives: To investigate the impact of sleep disorders on glymphatic system in Parkinson's disease (PD) using a non-invasive imaging technique called diffusion tensor image analysis along perivascular space (DTI-ALPS).

Materials And Methods: A total of 114 PD patients and 54 healthy controls (HCs) underwent sleep questionnaires and MRI examinations as part of data collection from the Parkinson's Progression Markers Initiative cohort. An automated pipeline was proposed for ALPS calculation to reduce biases from manually region delineation.

Engineered extracellular vesicles as nanosponges for lysosomal degradation of PCSK9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the degradation of the low-density lipoprotein receptor (LDLR), and PCSK9 inhibition emerges as an attractive strategy for atherosclerosis management. In this study, extracellular vesicles (EVs) were engineered to nanosponges, which could efficiently adsorb and deliver PCSK9 into lysosomes for degradation. Briefly, nanosponges were engineered by modifying EVs with EGF-A/PTGFRN fusion protein (PCSK9 binding domain EGF-A from the mutant LDLR with higher affinity was fused to the C terminus of prostaglandin F2 receptor negative regulator).

CRISPRi/a screens in human iPSC-cardiomyocytes identify glycolytic activation as a druggable target for doxorubicin-induced cardiotoxicity.

Doxorubicin is limited in its therapeutic utility due to its life-threatening cardiovascular side effects. Here, we present an integrated drug discovery pipeline combining human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs), CRISPR interference and activation (CRISPRi/a) bidirectional pooled screens, and a small-molecule screening to identify therapeutic targets mitigating doxorubicin-induced cardiotoxicity (DIC) without compromising its oncological effects. The screens revealed several previously unreported candidate genes contributing to DIC, including carbonic anhydrase 12 (CA12).

Application of deep learning reconstruction in abdominal magnetic resonance cholangiopancreatography for image quality improvement and acquisition time reduction.

Purpose: To compare deep learning (DL)-based and conventional reconstruction through subjective and objective analysis and ascertain whether DL-based reconstruction improves the quality and acquisition speed of clinical abdominal magnetic resonance imaging (MRI).

Methods: The 124 patients who underwent abdominal MRI between January and July 2021 were retrospectively studied. For each patient, two-dimensional axial T-weighted single-shot fast spin-echo MRI images with or without fat saturation were reconstructed using DL-based and conventional methods.

Multiscale drug screening for cardiac fibrosis identifies MD2 as a therapeutic target.

Cardiac fibrosis impairs cardiac function, but no effective clinical therapies exist. To address this unmet need, we employed a high-throughput screening for antifibrotic compounds using human induced pluripotent stem cell (iPSC)-derived cardiac fibroblasts (CFs). Counter-screening of the initial candidates using iPSC-derived cardiomyocytes and iPSC-derived endothelial cells excluded hits with cardiotoxicity.

ASGR1 Deficiency Inhibits Atherosclerosis in Western Diet-Fed Mice by Regulating Lipoprotein Metabolism and Promoting Cholesterol Efflux.

Background: Atherosclerosis is the most common cause of cardiovascular diseases. Clinical studies indicate that loss-of-function ASGR1 (asialoglycoprotein receptor 1) is significantly associated with lower plasma cholesterol levels and reduces cardiovascular disease risk. However, the effect of ASGR1 on atherosclerosis remains incompletely understood; whether inhibition of ASGR1 causes liver injury remains controversial.

Interleukin-11 causes alveolar type 2 cell dysfunction and prevents alveolar regeneration.

In lung disease, persistence of KRT8-expressing aberrant basaloid cells in the alveolar epithelium is associated with impaired tissue regeneration and pathological tissue remodeling. We analyzed single cell RNA sequencing datasets of human interstitial lung disease and found the profibrotic Interleukin-11 (IL11) cytokine to be highly and specifically expressed in aberrant KRT8 basaloid cells. IL11 is similarly expressed by KRT8 alveolar epithelial cells lining fibrotic lesions in a mouse model of interstitial lung disease.

Gastrointestinal microbiota and metabolites responses to dietary cereal grains in an adult pig model.

Corn (C), wheat (W), and paddy rice (PR) are important energy sources and are commonly used in feed production for swine. This study mainly focuses on the variation and regularities of microbiota and metabolites in the gastrointestinal tract (GIT) of pigs in response to C, W, and PR. A total of 18 pigs were allotted into three dietary groups with six replicated pigs and received diets containing C, W, or PR as the sole energy source, respectively.

Stapokibart (CM310) targets IL-4Rα for the treatment of type 2 inflammation.

Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab.

Rapid synthesis and screening of natively paired antibodies against influenza hemagglutinin stem via oPool display.

Antibody discovery is crucial for developing therapeutics and vaccines as well as understanding adaptive immunity. However, the lack of approaches to synthesize antibodies with defined sequences in a high-throughput manner represents a major bottleneck in antibody discovery. Here, we presented oPool display, which combines oligo pool synthesis and mRNA display to construct and characterize many natively paired antibodies in parallel.

Fugacity model covering abiotic and biotic matrices to investigate the transfer and fate of perfluoroalkyl acids in a large shallow lake of eastern China.

Solving the challenges faced during the measurement of the cross-interface transfer of perfluoroalkyl acids (PFAAs) in lakes is crucial for clarifying environmental behaviours of these chemicals and their efficient governance. This study developed a multimedia fugacity model based on the quantitative water-air-sediment interaction (QWASI) covering abiotic/biotic matrices to investigate the cross-interface transfer and fate of PFAAs in Luoma Lake, a typical PFAA-contaminated shallow lake in eastern China. The accuracy and reliability of the established model were confirmed using Percent bias and Monte Carlo simulation, respectively.