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.

Use of the Neuroform Atlas Stent or LVIS Jr Stent for Treatment of Unruptured Intracranial Aneurysms in Parent Arteries of <2 mm in Diameter: A Multicenter Experience.

Background And Purpose: The Neuroform Atlas stent and the LVIS Jr stent are intracranial microstent systems for the treatment of wide-neck intracranial aneurysms. Hence, this study aimed to compare the efficacy and safety of the Neuroform Atlas stent and the LVIS Jr stent for the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter.

Materials And Methods: From March 2022 to April 2023, the clinical and imaging data of 135 patients with unruptured intracranial aneurysms treated with stent-assisted coiling using the Neuroform Atlas or LVIS Jr stent in parent arteries of <2 mm in diameter were retrospectively analyzed.

The W195 Residue of the Newcastle Disease Virus V Protein Is Critical for Multiple Aspects of Viral Self-Regulation through Interactions between V and Nucleoproteins.

The transcription and replication of the Newcastle disease virus (NDV) strictly rely on the viral ribonucleoprotein (RNP) complex, which is composed of viral NP, P, L and RNA. However, it is not known whether other viral non-RNP proteins participate in this process for viral self-regulation. In this study, we used a minigenome (MG) system to identify the regulatory role of the viral non-RNP proteins V, M, W, F and HN.

Increased Ca Transient Underlies RyR2-Related Left Ventricular Noncompaction.

Background: A loss-of-function cardiac ryanodine receptor (RyR2) mutation, I4855M, has recently been linked to a new cardiac disorder termed RyR2 Ca release deficiency syndrome (CRDS) as well as left ventricular noncompaction (LVNC). The mechanism by which RyR2 loss-of-function causes CRDS has been extensively studied, but the mechanism underlying RyR2 loss-of-function-associated LVNC is unknown. Here, we determined the impact of a CRDS-LVNC-associated RyR2-I4855M loss-of-function mutation on cardiac structure and function.

Expression of RNA polymerase I catalytic core is influenced by RPA12.

RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a subunit with functions in RNA cleavage, transcription initiation and elongation.

Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization.

WD repeat domain 5 (WDR5) is a nuclear scaffolding protein that forms many biologically important multiprotein complexes. The WIN site of WDR5 represents a promising pharmacological target in a variety of human cancers. Here, we describe the optimization of our initial WDR5 WIN-site inhibitor using a structure-guided pharmacophore-based convergent strategy to improve its druglike properties and pharmacokinetic profile.

A phylogenetic overview of the (, ) with new taxa from China.

The family (, ) is a group of fungi found worldwide which exhibit stichic nuclear division. The group is highly diverse in morphology, ecology, and phylogeny, and includes some edible species which are popular all over the world. Traditionally, together with , and are four families in the The four families were combined and redefined as "", however, a comprehensive phylogeny based on multiple-marker dataset for the entire is still lacking and the delimitation is also unclear.

Reference Standards for Newborn Screening of Metabolic Disorders by Tandem Mass Spectrometry: A Nationwide Study on Millions of Chinese Neonatal Populations.

The major clinical problem presently confronting the Chinese newborn screening (NBS) programs by tandem mass spectrometry (MS/MS) is the lack of comprehensive reference intervals (RIs) for disease biomarkers. To close this gap, the Chinese National Center for Clinical Laboratories (NCCL) launched a nationwide study to investigate the dynamic pattern of 35 MS/MS NBS biomarkers and establish accurate and robust RIs. Blood spot samples from 4,714,089 Chinese neonates were tested in participating centers/laboratories and used for study analysis.

6-month follow-up of VIALE-C demonstrates improved and durable efficacy in patients with untreated AML ineligible for intensive chemotherapy (141/150).

VIALE-C compared the safety and efficacy of venetoclax or placebo plus low-dose cytarabine (+LDAC) in patients with untreated AML ineligible for intensive chemotherapy. Overall, 211 patients were enrolled (n = 143, venetoclax; n = 68, placebo). At the primary analysis, the study did not meet its primary endpoint of a statistically significant improvement in overall survival (OS), however, ~60% of patients had been on study for ≤6-months.

Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

Background: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis.

Methods: This was a multicenter, open-label, randomized controlled trial.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

Objective: To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT).

Methods: A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization.

Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics.

The conventional outflow pathway is a complex tissue responsible for maintaining intraocular pressure (IOP) homeostasis. The coordinated effort of multiple cells with differing responsibilities ensures healthy outflow function and IOP maintenance. Dysfunction of one or more resident cell types results in ocular hypertension and risk for glaucoma, a leading cause of blindness.

Ablation at Right Coronary Cusp as an Alternative and Favorable Approach to Eliminate Premature Ventricular Complexes Originating From the Proximal Left Anterior Fascicle.

Background: Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC's characteristics.

Methods: Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC.

Leveraging gene expression subgroups to classify DLBCL patients and select for clinical benefit from a novel agent.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, commonly described by cell-of-origin (COO) molecular subtypes. We sought to identify novel patient subgroups through an unsupervised analysis of a large public dataset of gene expression profiles from newly diagnosed de novo DLBCL patients, yielding 2 biologically distinct subgroups characterized by differences in the tumor microenvironment. Pathway analysis and immune deconvolution algorithms identified higher B-cell content and a strong proliferative signal in subgroup A and enriched T-cell, macrophage, and immune/inflammatory signals in subgroup B, reflecting similar biology to published DLBCL stratification research.

Multi-input chemical control of protein dimerization for programming graded cellular responses.

Chemical and optogenetic methods for post-translationally controlling protein function have enabled modulation and engineering of cellular functions. However, most of these methods only confer single-input, single-output control. To increase the diversity of post-translational behaviors that can be programmed, we built a system based on a single protein receiver that can integrate multiple drug inputs, including approved therapeutics.

Wool/Acrylic Blended Fabrics as Next-Generation Photodynamic Antimicrobial Materials.

The adoption of self-sterilizing materials to reduce infection transmission in hospitals and related healthcare facilities has been hampered by the availability of scalable, cost-effective, and potent antimicrobial textiles. Here, we investigated whether photodynamic materials comprising photosensitizer-embedded wool/acrylic blends were able to mediate the photodynamic inactivation of Gram-positive and Gram-negative bacteria. A small library of wool/acrylic (W/A) blended fabrics was constructed wherein the wool fibers were embedded with rose Bengal (RB) as a photosensitizer and the acrylic fibers were dyed with a traditional cationic yellow X-8GL dye, thereby enabling a broader color palette than was achievable with a single photosensitizer.

Integrating Data From Randomized Controlled Trials and Observational Studies to Assess Survival in Rare Diseases.

Background Conducting randomized controlled trials to investigate survival in a rare disease like pulmonary arterial hypertension has considerable ethical and logistical constraints. In many studies, such as the Study with an Endothelin Receptor Antagonist in Pulmonary Arterial Hypertension to Improve Clinical Outcome (SERAPHIN) randomized controlled trial, evaluating survival is further complicated by bias introduced by allowing active therapy among placebo-treated patients who clinically deteriorate. Methods and Results SERAPHIN enrolled and followed patients in the same time frame as the US Registry to Evaluate Early And Long-term PAH Disease Management, providing an opportunity to compare observed survival for SERAPHIN patients with predicted survival had they received real-world treatment as in the Registry to Evaluate Early And Long-term PAH Disease Management.

Prospective Clinical Sequencing of Adult Glioma.

Malignant gliomas are a group of intracranial cancers associated with disproportionately high mortality and morbidity. Here, we report ultradeep targeted sequencing of a prospective cohort of 237 tumors from 234 patients consisting of both glioblastoma (GBM) and lower-grade glioma (LGG) using our customized gene panels. We identified 2,485 somatic mutations, including single-nucleotide substitutions and small indels, using a validated in-house protocol.

KDM4B-mediated reduction of H3K9me3 and H3K36me3 levels improves somatic cell reprogramming into pluripotency.

Correct reprogramming of epigenetic marks is essential for somatic cells to regain pluripotency. Repressive histone (H) lysine (K) methylation marks are known to be stable and difficult to reprogram. In this study, we generated transgenic mice and mouse embryonic fibroblasts (MEFs) for the inducible expression of KDM4B, a demethylase that removes H3 K9 and H3K36 trimethylation (me3) marks (H3K9/36me3).

Liver X Receptor α Is Involved in Counteracting Mechanical Allodynia by Inhibiting Neuroinflammation in the Spinal Dorsal Horn.

Background: Liver X receptors, including α and β isoforms, are ligand-activated transcription factors. Whether liver X receptor α plays a role in neuropathic pain is unknown.

Methods: A spared nerve injury model was established in adult male rats and mice.