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.

Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.

Search for the Exclusive W Boson Hadronic Decays W^{±}→π^{±}γ, W^{±}→K^{±}γ and W^{±}→ρ^{±}γ with the ATLAS Detector.

A search for the exclusive hadronic decays W^{±}→π^{±}γ, W^{±}→K^{±}γ, and W^{±}→ρ^{±}γ is performed using up to 140  fb^{-1} of proton-proton collisions recorded with the ATLAS detector at a center-of-mass energy of sqrt[s]=13  TeV. If observed, these rare processes would provide a unique test bench for the quantum chromodynamics factorization formalism used to calculate cross sections at colliders. Additionally, at future colliders, these decays could offer a new way to measure the W boson mass through fully reconstructed decay products.

Conjugation of anti-HIV gp41 monoclonal antibody to a drug capable of targeting resting lymphocytes produces an effective cytotoxic anti-HIV immunoconjugate.

HIV-infected cells persisting in the face of suppressive antiretroviral therapy are the barrier to curing infection. Cytotoxic immunoconjugates targeted to HIV antigens on the cell surface may clear these cells. We showed efficacy in mouse and macaque models using immunotoxins, but immunogenicity blunted the effect.

A Single Component, Single Layer Flexile Foam Evaporator with the Higher Efficiency for Water Generation.

One of the greenest and promising ways to solve the problem of freshwater crisis is surface solar steam generation from seawater. A great number of photothermal materials with multi-component and multi-layered delicate yet complex structures often suffer from either low evaporation rate or high energy loss. Here, this work presents a single component foam evaporator with steam generation rate of up to 4.

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells.

Development of Procathepsin L (pCTS-L)-Inhibiting Lanosterol-Carrying Liposome Nanoparticles to Treat Lethal Sepsis.

The pathogenesis of microbial infections and sepsis is partly attributable to dysregulated innate immune responses propagated by late-acting proinflammatory mediators such as procathepsin L (pCTS-L). It was previously not known whether any natural product could inhibit pCTS-L-mediated inflammation or could be strategically developed into a potential sepsis therapy. Here, we report that systemic screening of a NatProduct Collection of 800 natural products led to the identification of a lipophilic sterol, lanosterol (LAN), as a selective inhibitor of pCTS-L-induced production of cytokines [e.

Urate-Lowering Therapy Inhibits Thoracic Aortic Aneurysm and Dissection Formation in Mice.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a highly lethal vascular disease without effective drug therapy. Whether elevated serum concentrations of uric acid are involved in TAAD development remains unclear.

Methods: Serum uric acid levels were detected in different TAAD mouse models and patients.

Activin Receptor-Like Kinase 3 Directly Couples Gαq (Guanine Nucleotide-Binding Protein Subunit αq)/ Gαq (Guanine Nucleotide-Binding Protein Subunit α11) to Regulate Vascular Contractility.

Background: Vascular smooth muscle cell (VSMC) contractility is critical for blood pressure regulation and vascular homeostasis. Identifying the key molecule that maintains VSMC contractility may provide a novel therapeutic target for vascular remodeling. ALK3 (activin receptor-like kinase 3) is a serine/threonine kinase receptor, and deletion of ALK3 causes embryonic lethality.

Nitrative Modification of Caveolin-3: A Novel Mechanism of Cardiac Insulin Resistance and a Potential Therapeutic Target Against Ischemic Heart Failure in Prediabetic Animals.

Background: Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning.

Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine.

SARS-CoV-2 spread in humans results in continuous emergence of new variants, highlighting the need for vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation-patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x) that contains key regions and residues across multiple SAR-CoV-2 variants. STFK1628x demonstrated high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK).

Versatile in silico modelling of microplastics adsorption capacity in aqueous environment based on molecular descriptor and machine learning.

To comprehensively evaluate the hazards of microplastics and their coexisting organic pollutants, the sorption capacity of microplastics is a major issue that is quantified through the microplastic-aqueous sorption coefficient (K). Almost all quantitative structure-property relationship (QSPR) models that describe K apply only to narrow, relatively homogeneous groups of reactants. Herein, non-hybrid QSPR-based models were developed to predict PE-water (K), PE-seawater (K), PVC-water (K) and PP-seawater (K) sorption coefficients at different temperatures, with eight machine learning algorithms.

Simulation of winter wheat response to variable sowing dates and densities in a high-yielding environment.

Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change.

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines.

COMP (Cartilage Oligomeric Matrix Protein), a Novel PIEZO1 Regulator That Controls Blood Pressure.

Background: Vascular endothelial cells are critical for maintaining blood pressure (BP) by releasing biologically active molecules, such as nitric oxide. A non-endothelial cell resident matricellular protein, COMP (cartilage oligomeric matrix protein), plays a pivotal role in maintaining cardiovascular homeostasis, but little is known about its regulatory effect on BP.

Methods: Mice were infused with AngII (angiotensin II; 450 ng/kg per minute) for 3 days via an osmotic minipump, and BP was monitored by a tail-cuff system.

Dosing Regimen Prediction and Confirmation With Rivaroxaban for Thromboprophylaxis in Children After the Fontan Procedure: Insights From the Phase III UNIVERSE Study.

Thrombosis remains an important complication for children with single-ventricle physiology following the Fontan procedure, and effective thromboprophylaxis is an important unmet medical need. To obviate conventional dose-finding studies and expedite clinical development, a rivaroxaban dose regimen for this indication was determined using a model-informed drug development approach. A physiologically based pharmacokinetic rivaroxaban model was used to predict a pediatric dosing regimen that would produce drug exposures similar to that of 10 mg once daily in adults.

Comparison of IOL Power Calculation Formulas for a Trifocal IOL in Eyes With High Myopia.

Purpose: To analyze the results of new intraocular lens (IOL) formulas (Emmetropia Verifying Optical [EVO], Kane, Olsen, and Barrett Universal II), traditional formulas (Haigis and SRK/T), and modified Wang-Koch axial length adjustment formulas with the SRK/T and Holladay 1 (SRK/T and H1) in Chinese patients with long eyes.

Methods: In this retrospective case series, patients with an axial length of 26 mm or greater having uneventful femtosecond laser-assisted cataract surgery with one trifocal IOL model were enrolled. The actual postoperative spherical equivalent of the manifest refraction was compared with the formula-predicted refraction based on the implanted IOL power.

Population pharmacokinetic analysis of rivaroxaban in children and comparison to prospective physiologically-based pharmacokinetic predictions.

Rivaroxaban has been investigated in the EINSTEIN-Jr program for the treatment of acute venous thromboembolism (VTE) in children aged 0 to 18 years and in the UNIVERSE program for thromboprophylaxis in children aged 2 to 8 years with congenital heart disease after Fontan-procedure. Physiologically-based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling were used throughout the pediatric development of rivaroxaban according to the learn-and-confirm paradigm. The development strategy was to match pediatric drug exposures to adult exposure proven to be safe and efficacious.

Quadruple-layer group-IV tellurides: low thermal conductivity and high performance two-dimensional thermoelectric materials.

Through first-principles calculations, we report the thermoelectric properties of two-dimensional (2D) hexagonal group-IV tellurides XTe (X = Ge, Sn and Pb), with quadruple layers (QL) in the Te-X-X-Te stacking sequence, as promising candidates for mid-temperature thermoelectric (TE) materials. The results show that 2D PbTe exhibits a high Seebeck coefficient (∼1996 μV K) and a high power factor (6.10 × 10 W K m s) at 700 K.

Enhanced Optical Fiber for Distributed Acoustic Sensing beyond the Limits of Rayleigh Backscattering.

We report on engineered fibers with enhanced optical backscattering that exceeds Rayleigh scattering limits by more than one order of magnitude. We measure attenuation less than 0.5 dB/km from 1,300 to 1,650 nm.

Composition-dependent thermodynamics of intracellular phase separation.

Intracellular bodies such as nucleoli, Cajal bodies and various signalling assemblies represent membraneless organelles, or condensates, that form via liquid-liquid phase separation (LLPS). Biomolecular interactions-particularly homotypic interactions mediated by self-associating intrinsically disordered protein regions-are thought to underlie the thermodynamic driving forces for LLPS, forming condensates that can facilitate the assembly and processing of biochemically active complexes, such as ribosomal subunits within the nucleolus. Simplified model systems have led to the concept that a single fixed saturation concentration is a defining feature of endogenous LLPS, and has been suggested as a mechanism for intracellular concentration buffering.