Endothelial Cpt1a Inhibits Neonatal Hyperoxia-Induced Pulmonary Vascular Remodeling by Repressing Endothelial-Mesenchymal Transition.

Pulmonary hypertension (PH) increases the mortality of preterm infants with bronchopulmonary dysplasia (BPD). There are no curative therapies for this disease. Lung endothelial carnitine palmitoyltransferase 1a (Cpt1a), the rate-limiting enzyme of the carnitine shuttle system, is reduced in a rodent model of BPD.

Preclinical evaluation of the efficacy and safety of AAV8-TNAP-D10 in Alpl-/- and AlplPrx1/Prx1 mouse models for the treatment of early and late-onset hypophosphatasia.

We previously documented successful resolution of skeletal and dental disease in the infantile and late-onset murine models of hypophosphatasia (HPP), with a single injection of an adeno-associated serotype 8 vector encoding mineral-targeted TNAP (AAV8-TNAP-D10). Here, we conducted dosing studies in both HPP mouse models. A single escalating dose from 4x108 up to 4x1010 (vg/b) was intramuscularly injected into 4-day-old Alpl-/- mice (an infantile HPP model) and a single dose from 4x106 up to 4x109 (vg/b) was administered to 8-week-old AlplPrx1/Prx1 mice (a late-onset HPP model).

Controlled Inflammation Drives Neutrophil-Mediated Precision Drug Delivery in Heterogeneous Tumors.

Tumor heterogeneity remains a formidable obstacle in targeted cancer therapy, often leading to suboptimal treatment outcomes. This study presents an innovative approach that harnesses controlled inflammation to guide neutrophil-mediated drug delivery, effectively overcoming the limitations imposed by tumor heterogeneity. By inducing localized inflammation within tumors using lipopolysaccharide, it significantly amplify the recruitment of drug-laden neutrophils to tumor sites, irrespective of specific tumor markers.

Methodological standards for comparative effectiveness research: considerations for evidentiary review for medicare drug price negotiation.

Introduction: The 2022 Inflation Reduction Act (IRA) is expected to result in lower drug prices for Medicare beneficiaries in the United States (US). The Centers for Medicare & Medicaid Services (CMS) released the most recent draft guidance for the Medicare Drug Price Negotiation (DPN) program in May 2024.

Areas Covered: In August 2023, the list of 10 drugs selected for the DPN were published and the first round of negotiations are now complete.

Granting Permission: Toward Embracing Grief.

Grief, unavoidable and often excruciating, is rarely sufficiently acknowledged or supported in Western society. It is not granted to exist without barriers. By considering and evaluating grief experiences through the lens of their access to , clinicians can collectively imagine and promote inclusivity in grief.

A novel MRI-based radiomics for preoperative prediction of lymphovascular invasion in rectal cancer.

Background: To develop and validate a clinical-radiomics model for preoperative prediction of lymphovascular invasion (LVI) in rectal cancer.

Methods: This retrospective study included data from 239 patients with pathologically confirmed rectal adenocarcinoma from two centers, all of whom underwent MRI examinations. Cases from the first center (n = 189) were randomly divided into a training set and an internal validation set at a 7:3 ratio, while cases from the second center (n = 50) constituted the external validation set.

Correlation between sarcopenia and hypertrophy of the future liver remnant in patients undergoing portal vein embolization before liver resection.

Objectives: To study the correlation between sarcopenia and hypertrophy of the future liver remnant(FLR) in patients undergoing portal vein embolization(PVE) before liver resection, and to assess the outcomes after resection.

Methods: This retrospective study examined patients underwent PVE from May 2012 to May 2023. Demographic, clinical and laboratory features were documented and total liver volumes(TLV) and FLR volumes were measured before and 2-4 weeks after PVE.

Resinacein S ameliorates the obesity in mice via activating the brown adipose tissue.

Brown adipose tissue (BAT) is an ideal target organ for obesity treatment. Resinacein S is extracted from Ganoderma lucidum and can elevate Uncoupling protein 1 (UCP1) in cells, but its related effects at the animal level are not clear. The mice were fed with high-fat diet to construct obesity models and treated with Resinacein S.

Analysis of Chemical Components of Penicillium chrysogenum Crude Extract Using Liquid Chromatography Coupled With Q-Exactive Orbitrap Mass Spectrometry Combined With GNPS Molecular Networking.

A Chinese isolate of the fungus Penicillium chrysogenum was analyzed using liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry combined with Global Natural Products Social Networking (GNPS) on culture condition leading to the rapid identification of 20 secondary metabolites. Among them are eight polyketones, two phthalides, six diketopiperazine alkaloids, and others. A meleagrine network was examined and proposed as a promising candidate for new natural products.

Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe ornithine transcarbamylase deficiency.

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model, and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver.

Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress.

Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis.

Background: Ferroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.

Methods: Micro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371.

Role of sirtuins in obesity and osteoporosis: molecular mechanisms and therapeutic targets.

The prevalence of obesity and osteoporosis (OP) represents a significant public health concern on a global scale. A substantial body of evidence indicates that there is a complex relationship between obesity and OP, with a correlation between the occurrence of OP and obesity. In recent years, sirtuins have emerged as a prominent area of interest in the fields of aging and endocrine metabolism.

Global surgery and climate change: how global surgery can prioritise both the health of the planet and its people.

Climate change is an emerging global health crisis, disproportionately affecting low- and middle-income countries (LMICs) where health outcomes are increasingly compromised by environmental stressors such as pollution, natural disasters, and human migration. With a focus on promoting health equity, Global Surgery advocates for expanding access to surgical care and enhancing health outcomes, particularly in resource-limited and disaster-affected areas like LMICs. The healthcare industry-and more specifically, surgical care-significantly contributes to the global carbon footprint, primarily through resource-intensive settings, i.

Young, Empowered & strong (YES): a study protocol paper for a randomized controlled trial of an mHealth symptom monitoring and self-management intervention for adolescent and young adult (AYA) breast cancer survivors.

Background: Compared to older adults with breast cancer (BC), adolescents and young adults (AYAs) develop more aggressive disease necessitating more intensive therapy with curative intent, which is disruptive to planned life trajectories. The burden of unmet needs among AYA BC survivors exists in two domains: (1) symptoms (e.g.

Promoted read-through and mutation against pseudouridine-CMC by an evolved reverse transcriptase.

Pseudouridine (Ψ) is an abundant RNA chemical modification that plays critical biological functions. Current Ψ detection methods are limited in identifying Ψs at base-resolution in U-rich sequence contexts, where Ψ occurs frequently. Here we report "Mut-Ψ-seq" that utilizes the classic N-cyclohexyl N'-(2-morpholinoethyl)carbodiimide (CMC) agent and an evolved reverse transcriptase ("RT-1306") for Ψ mapping at base-resolution.

Response of overlying masonry structure induced by double track EPBM cutting through cemented soil composite pile foundation field measurements and numerical analysis.

This article uses the engineering background of the Zhengzhou Metro Line 5 with a cement-soil group pile composite foundation. It simplifies the composite foundation using the area-weighted composite modulus method and establishes a finite element model of a double-line EPBM passing beneath the cement-soil group pile composite foundation building. The calculation results were compared and validated against monitoring data.

Small molecules that targeting p53 Y220C protein: mechanisms, structures, and clinical advances in anti-tumor therapy.

The p53 protein is regarded as the "Guardian of the Genome," but its mutation is tumor progression and present in more than half of malignant tumors. The pro-metastatic property of mutant p53 makes a strong argument for targeting mutant p53 with new therapeutic strategies. However, mutant p53 was considered as a challenging target for drug discovery due to the lack of small molecular binding pockets.

Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.

The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results.

Energy optimization and plant comfort management in smart greenhouses using the artificial bee colony algorithm.

Agriculture is an essential component of human sustenance in this world. These days, with a growing population, we must significantly increase agricultural productivity to meet demand. Agriculture moved toward technologies as a result of the demand for higher yields with less resources.

Preparation and mechanical performance of fluorite tailings geopolymer precursor under alkaline heat activation.

As one of the bulk solid wastes in the Yellow River basin in China, fluorite tailings urgently need to be utilized as resources. In this paper, NaOH and NaCO were used for alkali thermal activation of ground fluorite tailings under different temperature conditions, and the reactivity was analyzed by XRD, SEM and compressive strength after hydration, so as to evaluate the feasibility of fluorite tailings as geopolymer precursor. The results show that the fluorite tailings can exhibit certain reactivity under alkaline heat excitation, and significant amorphous glass phase can be detected.