Strategic Acyl Carrier Protein Engineering Enables Functional Type II Polyketide Synthase Reconstitution In Vitro.

Microbial polyketides represent a structurally diverse class of secondary metabolites with medicinally relevant properties. Aromatic polyketides are produced by type II polyketide synthase (PKS) systems, each minimally composed of a ketosynthase-chain length factor (KS-CLF) and a phosphopantetheinylated acyl carrier protein (-ACP). Although type II PKSs are found throughout the bacterial kingdom, and despite their importance to strategic bioengineering, type II PKSs have not been well-studied .

Effects of flow lamination on aerosolized drug delivery through spatial barriers.

In this study we evaluated the effects of flow lamination on aerosol flow dynamics and deposition at the exit point in testing models with spatial barriers (narrowing or curving).We compared ModiFlow (MF) to an idealized Standard Spacer (SS) in their efficiency of delivery of aerosolized medication (fluticasone) across different types of spatial barriers. Fluticasone propionate HFA Inhaler from Prasco Labs 220 µg per actuation was used to deliver 1 spray in each test tube.

Systematic review: differences in complete blood count component rhythms.

Study Objectives: The complete blood count (CBC) is one of the most commonly ordered blood tests with a large range of reference values that does not consider time of day for interpretation. Our objective was to systematically review this topic to report on peak and trough timing of CBC values.

Methods: A systematic search was performed for studies evaluating any component of the CBC with at least three collections over 24 hours.

Prevalence of Intersex/Differences in Sex Development and Primary Gonadal Insufficiency in a Pediatric Transgender Population.

Purpose: This study aims to assess the prevalence of intersex variations/differences in sex development (I/DSDs), associated adrenal conditions, and primary gonadal insufficiency in children with gender dysphoria.

Methods: We performed a comprehensive review of the medical records for individuals who carried the diagnostic codes for gender dysphoria in addition to intersex and/or other conditions associated with sex steroid variations among patients evaluated by pediatric endocrinologists from 2013 to 2022.

Results: We found that 9 of 612 (1.

Microbial adaptive pathogenicity strategies to the host inflammatory environment.

Pathogenic microorganisms can infect a variety of niches in the human body. During infection, microbes can only persist if they adapt adequately to the dynamic host environment and the stresses imposed by the immune system. While viruses entirely rely on host cells to replicate, bacteria and fungi use their pathogenicity mechanisms for the acquisition of essential nutrients that lie under host restriction.

Identification and Characterization of Two Aryl Sulfotransferases from Deep-Sea Marine Fungi and Their Implications in the Sulfation of Secondary Metabolites.

Sulfation plays a critical role in the biosynthesis of small molecules, regulatory mechanisms such as hormone signaling, and detoxification processes (phase II enzymes). The sulfation reaction is catalyzed by a broad family of enzymes known as sulfotransferases (SULTs), which have been extensively studied in animals due to their medical importance, but also in plant key processes. Despite the identification of some sulfated metabolites in fungi, the mechanisms underlying fungal sulfation remain largely unknown.

The second phase of tumor invasion driven by immune cells: A study on doxorubicin-loaded PLG nanoparticles.

Poly(lactide-co-glycolide) (PLG) nanoparticles loaded with doxorubicin have reached phase-I clinical trials for treating advanced solid tumors. This study explores cell hitchhiking, where nanoparticles associate with blood cells and investigates the impact on pharmacokinetics and tumor migration. Previous findings highlighted the early post-injection phase dominated by nonspecific nanoparticle-cell interactions and burst release.

Treatment of Complicated Gram-Positive Bacteremia and Infective Endocarditis.

The Gram-positive cocci Staphylococcus aureus, Streptococcus spp., and Enterococcus spp. are the most frequent causative organisms of bloodstream infections and infective endocarditis.

Role of amino acid substitutions on proteolytic stability of histatin 5 in the presence of secreted aspartyl proteases and salivary proteases.

Histatin 5 (Hst5) is a 24-amino-acid peptide naturally present in human saliva that has been proposed as a potential antifungal therapeutic. However, Hst5 is susceptible to degradation by secreted aspartyl proteases (Saps) produced by Candida albicans, which could limit its efficacy as a therapeutic. To better understand the role of the lysine residues of Hst5 in proteolysis by C.

tRNA hypomodification facilitates 5-fluorocytosine resistance via cross-pathway control system activation in Aspergillus fumigatus.

Increasing antifungal drug resistance is a major concern associated with human fungal pathogens like Aspergillus fumigatus. Genetic mutation and epimutation mechanisms clearly drive resistance, yet the epitranscriptome remains relatively untested. Here, deletion of the A.

Right ventricular coupling predicts cardiopulmonary fitness in cardiac transthyretin amyloidosis.

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt) is an infiltrative disease leading to restrictive cardiomyopathy. We aimed to characterise exercise capacity in ATTRwt and to identify predictors of cardiopulmonary fitness, focusing on echocardiographic and clinical parameters.

Methods: We studied 110 ATTRwt patients from a prospective single-centre registry (2020-2024) by cardiopulmonary exercise testing (CPET).

Feels Like Home: A Biobased and Biodegradable Plastic Offers a Novel Habitat for Diverse Plant Pathogenic Fungi in Temperate Forest Ecosystems.

Poly(butylene succinate-co-adipate) (PBSA), a biodegradable plastic, is significantly colonized and degraded by soil microbes under natural field conditions, especially by fungal plant pathogens, raising concerns about potential economic losses. This study hypothesizes that the degradation of biodegradable plastics may increase the presence and abundance of plant pathogens by serving as an additional carbon source, ultimately posing a risk to forest ecosystems. We investigated (i) fungal plant pathogens during the exposure of PBSA in European broadleaved and coniferous forests (two forest types), with a specific focus on potential risk to tree health, and (ii) the response of such fungi to environmental factors, including tree species, soil pH, nutrient availability, moisture content, and the physicochemical properties of leaf litter layer.

GRK5 regulates endocytosis of FPR2 independent of β-Arrestins.

The formyl-peptide receptor 2 (FPR2) is a G-protein-coupled receptor (GPCR) that responds to pathogen-derived peptides and regulates both pro-inflammatory and pro-resolution cellular processes. While ligand selectivity and G-protein-signalling of FPR2 have been well characterized, molecular mechanisms controlling subsequent events such as endocytosis and recycling to the plasma membrane are less understood. Here we show the key role of the GPCR kinase 5 (GRK5) in facilitating FPR2 endocytosis and post-endocytic trafficking.

The palmitoyl-CoA ligase Fum16 is part of a fumonisin subcluster involved in self-protection.

produces the mycotoxin fumonisin B (FB), which disrupts sphingolipid biosynthesis by inhibiting ceramide synthase and affects the health of plants, animals, and humans. The means by which protects itself from its own mycotoxin are not completely understood. Some fumonisin () cluster genes do not contribute to the biosynthesis of the compound, but their function has remained enigmatic.

Survival outcomes of apalutamide as a starting treatment: impact in real-world patients with metastatic hormone sensitive prostate cancer (OASIS).

Background: Androgen receptor pathway inhibitors (apalutamide [APA], enzalutamide [ENZ], abiraterone acetate plus prednisone [AAP]) combined with androgen-deprivation therapy (ADT) are effective life-prolonging treatment options for metastatic hormone-sensitive prostate cancer (mHSPC). We evaluated the impact of upfront therapy for mHSPC on outcomes in real-world clinical practice in the United States.

Methods: This retrospective, observational cohort study used electronic healthcare records from the ConcertAI RWD 360 Prostate Cancer Dataset.

Cardiac findings in a phase II double-blind randomized placebo-controlled trial of combination therapy (HAZDPac) to treat COVID-19 patients.

Objective: Hydroxychloroquine paired with Azithromycin, Vitamin C, Vitamin D, and Zinc (HAZDPac), was used as a multidrug therapy method to treat COVID-19 illness and superimposed secondary bacterial pneumonia. Concerns have been raised though about such combinations regarding cardiac QTc interval prolongation and risks of arrhythmias, which we set out to address in this study.

Design: We evaluated cardiac safety in a Phase II Double-Blind Randomized Placebo-Controlled Trial of Combination Therapy to Treat COVID-19 Infections study, conducted by ProgenaBiome.

Engineering of insect juvenile hormone III biosynthesis in the plant Nicotiana benthamiana.

Juvenile hormones (JHs) are farnesoic acid-derived sesquiterpenoids that play a crucial role in regulating various developmental processes in insects. Based on these reported biological activities, JHs and their synthetic analogs have been utilized as insecticides with significant commercial success over the past years. Here we describe the engineering of the JH pathway of the yellow fever mosquito (Aedes aegypti) by transient gene expression in the plant Nicotiana benthamiana.

Physical Frailty and Functional Status in Kidney Transplantation: A Systematic Review.

Background: Frailty and functional decline are being recognized as important conditions in kidney transplant candidates. However, the ideal measures of functional status and frailty remain unknown as there is not a complete understanding of the relationship between these conditions and important post-transplant outcomes.

Objective: The objective was to examine the association between different measures of frailty and functional status evaluated before or at the time of transplant with adverse clinical outcomes post-transplantation.

High-power versus low-power laser settings during endoscopic stone disease management: a systematic review from the EAU endourology section.

Purpose: Optimal laser settings during endoscopic stone disease management still represents a debatable issue. The aim of this systematic review is to summarize all existing evidence regarding the comparison of high-power (HP) versus low-power (LP) laser settings during different endoscopic lithotripsy procedures.

Methods: PubMed, Scopus and Cochrane databases were systematically screened, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines.

A Catch-Release Strategy for the Genomics-Driven Discovery of Antiproliferative Furan-Functionalized Peptides.

Furan-functionalized peptides are of significant pharmacological interest due to their pronounced bioactivities and unique potential for orthogonal bioconjugation and derivatization. However, naturally occurring peptides with furyl side chains are exceedingly rare. This study presents a streamlined method to predict and assess the microbial production of peptides incorporating 3-furylalanine (Fua) moieties.

Volitional processes in changing physical activity: A randomized controlled trial with individuals with knee osteoarthritis.

Objective: A health action process approach (HAPA)-based intervention was designed to support moderate-to-vigorous physical activity (MVPA) in individuals with osteoarthritis of the knee (OAK). In secondary analyses of the randomized controlled trial "preventing the impairment of primary osteoarthritis by high-impact long-term physical exercise regimen-psychological adherence program," we examined long-term effects of the intervention on HAPA determinants and MVPA, and explored the former as mediators of change.

Method: = 241 individuals with OAK (63% women, aged 44-80 years) were randomly assigned to the 12-month intervention condition (IC) or active control condition (CC).

Motion-Guided Deep Image Prior for Cardiac MRI.

Cardiovascular magnetic resonance imaging is a powerful diagnostic tool for assessing cardiac structure and function. Traditional breath-held imaging protocols, however, pose challenges for patients with arrhythmias or limited breath-holding capacity. We introduce Motion-Guided Deep Image prior (M-DIP), a novel unsupervised reconstruction framework for accelerated real-time cardiac MRI.

Modeling Grid Cell Distortions with a Grid Cell Calibration Mechanism.

The medial entorhinal cortex of rodents is known to contain grid cells that exhibit precise periodic firing patterns based on the animal's position, resulting in a distinct hexagonal pattern in space. These cells have been extensively studied due to their potential to unveil the navigational computations that occur within the mammalian brain and interesting phenomena such as so-called grid cell distortions have been observed. Previous neuronal models of grid cells assumed their firing fields were independent of environmental boundaries.