Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

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.

Comparative Efficacy of Non-contrast vs. Contrast-enhanced CT Radiomics in Predicting Coronary Artery Plaques Among Patients with Low Agatston Scores.

Rationale And Objectives: Patients with a low Agatston score often present with clinical signs and symptoms suggestive of coronary artery disease, despite having minimal calcium deposits. This study aimed to compare the efficacy of low-dose non-contrast cardiac CT with coronary computed tomography angiography (CCTA) in pericoronary adipose tissue (PCAT) radiomics for predicting coronary artery plaques, using CCTA as the reference standard.

Materials And Methods: This retrospective study analyzed 459 patients with suspected coronary artery disease and a coronary artery calcium score < 100 Agatston units, who were treated between June 2021 and December 2023 at a tertiary hospital.

Spatial omics-based machine learning algorithms for the early detection of hepatocellular carcinoma.

Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.

Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).

Immunity Dynamics of Serogroups ACYW from Birth and Following Vaccination.

: Serosurveillance of epidemic cerebrospinal meningitis (ECM) in healthy individuals is crucial for assessing disease risk and evaluating the effectiveness of vaccinations. However, this practical work is rare in China. : We conducted cross-section serosurveillance in Guangzhou, Zhanjiang, and Heyuan in Guangdong Province, measuring Anti-Nm IgG with serogroups A, C, Y, and W, and analyzed the trends using a generalized additive model (GAM).

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.

Whole-Tumor Clearing and Imaging of Intratumor Microbiota in Three Dimensions with miCDaL Strategy.

Acquiring detailed spatial information about intratumor microbiota in situ is challenging, which leaves 3D distributions of microbiota within entire tumors largely unexplored. Here, a modified iDISCO-CUBIC tissue clearing and D-amino acid microbiome labeling-based (miCDaL) strategy are proposed, that integrates microbiota in situ labeling, tissue clearing, and whole-mount tissue imaging to enable 3D visualization of indigenous intratumor microbiota. Leveraging whole-mount spatial resolution and centimeter-scale imaging depth, the 3D biogeography of microbiota is successfully charted across various tumors at different developmental stages, providing quantitative spatial insights in relation to host tumors.

DNA Methylation Age Mediates Effect of Metabolic Profile on Cardiovascular and General Aging.

Background: Alterations in lipid metabolism and DNA methylation are 2 hallmarks of aging. Connecting metabolomic, epigenomic, and aging outcomes help unravel the complex mechanisms underlying aging. We aimed to assess whether DNA methylation clocks mediate the association of circulating metabolites with incident atherosclerotic cardiovascular disease (ASCVD) and frailty.

Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec.

Background:  Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy vector expressing the high-activity factor IX (FIX) variant FIX-R338L, is in development for hemophilia B. One-stage clotting (OS) assays and chromogenic substrate (CS) assays are commonly used to measure FIX-R338L variant activity. Data from ongoing trials suggest FIX activity varies between different OS and CS assays.

Survey of Pharmaceutical Industry's Best Practices around In Vitro Transporter Assessment and Implications for Drug Development: Considerations from the International Consortium for Innovation and Quality for Pharmaceutical Development Transporter Working Group.

The International Consortium for Innovation and Quality in Pharmaceutical Development Transporter Working Group had a rare opportunity to analyze a crosspharma collation of in vitro data and assay methods for the evaluation of drug transporter substrate and inhibitor potential. Experiments were generally performed in accordance with regulatory guidelines. Discrepancies, such as not considering the impact of preincubation for inhibition and free or measured in vitro drug concentrations, may be due to the retrospective nature of the dataset and analysis.

Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.

Background: The ubiquitin-proteasome system regulates protein degradation and the development of pulmonary arterial hypertension (PAH), but knowledge about the role of deubiquitinating enzymes in this process is limited. UCHL1 (ubiquitin carboxyl-terminal hydrolase 1), a deubiquitinase, has been shown to reduce AKT1 (AKT serine/threonine kinase 1) degradation, resulting in higher levels. Given that AKT1 is pathological in pulmonary hypertension, we hypothesized that UCHL1 deficiency attenuates PAH development by means of reductions in AKT1.

Synthesis of Quillaic Acid through Sustainable C-H Bond Activations.

To meet the demand for quillaic acid, a multigram synthesis of quillaic acid was accomplished in 14 steps, starting from oleanolic acid, leading to an overall yield of 3.4%. Key features include C-H activation at C-16 and C-23.

Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy.

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)-based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production.

Effect of Zr on the Microstructure and High-Temperature Phase Separation Evolution of SiOC Aerogels.

SiZrOC aerogels were synthesized through the pyrolysis of the zirconium source-doped SiOC system using zirconyl chloride octahydrate (ZrOCl·8HO) at temperatures ranging from 900 to 1300 °C. This study investigates the microstructure evolution and phase separation of SiOC and SiZrOC aerogels during the pyrolysis process. Upon pyrolysis, both aerogels exhibited a Si-O-C structure with a high thermal stability.

Polysomnography scoring-related training and quantitative assessment for improving interscorer agreement.

Study Objectives: To efficiently improve the scoring competency of scorers with varying levels of experience across regions in Taiwan, we developed a training program with a cloud-based polysomnography scoring platform to evaluate and improve interscorer agreement.

Methods: A total of 70 scorers from 34 sleep centers in Taiwan (job tenure: 0.5-39.

Developing a Nomogram to Stratify Intracranial Solitary Fibrous Tumor Recurrence.

Rationale And Objectives: To develop a nomogram to stratify tumor recurrence (TR) in intracranial solitary fibrous tumors (ISFTs) based on the clinical, radiological, and pathological features.

Materials And Methods: A total of 215 patients from Beijing Tiantan Hospital, Capital Medical University and 48 patients from Lanzhou University Second Hospital, diagnosed with ISFT based on histopathological findings, were included. The patients were randomly divided into training and test cohorts at a ratio of 8:2.

Active Ensembles in Methane Dehydroaromatization over Molybdenum/ZSM-5 Zeolite Identified by 2D H- Mo Magic Angle Spinning Nuclear Magnetic Resonance Correlation Spectroscopy.

Methane dehydroaromatization (MDA) over Mo-modified zeolite is a potential catalytic route for converting natural gas into valuable aromatics. However, the active species in this reaction are highly complex, involving diverse Mo species, acidic sites of zeolite, and organic molecules. Herein, we apply 1D Mo NMR and 2D H- Mo heteronuclear correlation solid-state NMR spectroscopy to directly observe the active ensembles in the confined channels of Mo/ZSM-5 zeolite during the MDA reaction.

Tirofiban for Stroke without Large or Medium-Sized Vessel Occlusion.

Background: The effects of the glycoprotein IIb/IIIa receptor inhibitor tirofiban in patients with acute ischemic stroke but who have no evidence of complete occlusion of large or medium-sized vessels have not been extensively studied.

Methods: In a multicenter trial in China, we enrolled patients with ischemic stroke without occlusion of large or medium-sized vessels and with a National Institutes of Health Stroke Scale score of 5 or more and at least one moderately to severely weak limb. Eligible patients had any of four clinical presentations: ineligible for thrombolysis or thrombectomy and within 24 hours after the patient was last known to be well; progression of stroke symptoms 24 to 96 hours after onset; early neurologic deterioration after thrombolysis; or thrombolysis with no improvement at 4 to 24 hours.

Two new cyclopeptides from C. Y. Wu.

Two new cyclic peptides, named as cyclogeobomptides A () and B () were isolated from the roots of C. Y. Wu.

A Novel Phytogenic Formulation, EUBIO-BPSG, as a Promising One Health Approach to Replace Antibiotics and Promote Reproduction Performance in Laying Hens.

Gut microbiota play a key role in health maintenance and disease pathogenesis in animals. Dietary phytochemicals are crucial factors shaping gut bacteria. Here, we investigated the function and mechanism of a phytogenic formulation, EUBIO-BPSG (BP), in laying hens.

Myeloid-restricted CD68 deficiency attenuates atherosclerosis via inhibition of ROS-MAPK-apoptosis axis.

In atherosclerosis, macrophages derived from blood monocytes contribute to non-resolving inflammation, which subsequently primes necrotic core formation, and ultimately triggers acute thrombotic vascular disease. Nevertheless, little is known about how inflammatory cells, especially the macrophages fuel atherosclerosis. CD68, a unique class D scavenger receptor (SRD) family member, is specifically expressed in monocytes/macrophages and remarkably up-regulated upon oxidized low-density lipoprotein (ox-LDL) stimulation.