Pleozymes: Pleiotropic Oxidized Carbon Nanozymes Enhance Cellular Metabolic Flexibility.

Our group has synthesized a pleiotropic synthetic nanozyme redox mediator we term a "pleozyme" that displays multiple enzymatic characteristics, including acting as a superoxide dismutase mimetic, oxidizing NADH to NAD, and oxidizing HS to polysulfides and thiosulfate. Benefits have been seen in acute and chronic neurological disease models. The molecule is sourced from coconut-derived activated charcoal that has undergone harsh oxidization with fuming nitric acid, which alters the structure and chemical characteristics, yielding 3-8 nm discs with broad redox potential.

Molecular epidemiology and clinical characterization of carbapenemase-producing Enterobacter spp. from an international cohort.

Background: Despite the global public health threat posed by carbapenem-resistant Enterobacter spp., clinical and molecular epidemiological studies on international isolates remain scarce. Historically, the taxonomy of Enterobacter has been challenging, limiting our understanding of the clinical characteristics and outcomes of carbapenemase-producing Enterobacter spp.

Comprehensive Assessment of Initial Adaptation of ESBL Positive ST131 Escherichia coli to Carbapenem Exposure.

Background: It remains unclear how high-risk Escherichia coli lineages, like sequence type (ST) 131, initially adapt to carbapenem exposure in their progression to carbapenem resistance.

Methods: Carbapenem mutation frequency was measured in multiple subclades of extended-spectrum β-lactamase (ESBL) positive ST131 clinical isolates using a fluctuation assay followed by whole genome sequencing (WGS) characterization. Genomic, transcriptomic, and porin analyses of ST131 C2/H30Rx isolate, MB1860, under prolonged, increasing carbapenem exposure was performed using two experimental evolutionary platforms to measure fast vs.

Sex Differences in Response to Diet Enriched with Glutathione Precursors in the Aging Heart.

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function.

Concordance of Chest Radiography and Chest Computed Tomography Findings in Patients with Hematologic Malignancy and Invasive Mucormycosis: What Are the Prognostic Implications?

Invasive pulmonary mucormycosis (IPM) is a deadly opportunistic mold infection in patients with hematological malignancies (HM). Radiologic imaging is essential for its timely diagnosis. Here, we compared IPM lesions visualized by chest computed tomography (CCT) and chest X-ray (CXR) and determined the prognostic significance of discordant imaging.

Increased mortality in hospital- compared to community-onset carbapenem-resistant enterobacterales infections.

Background: The CDC reported a 35% increase in hospital-onset (HO) carbapenem-resistant Enterobacterales (CRE) infections during the COVID-19 pandemic. We evaluated patient outcomes following HO and community-onset (CO) CRE bloodstream infections (BSI).

Methods: Patients prospectively enrolled in CRACKLE-2 from 56 hospitals in 10 countries between 30 April 2016 and 30 November 2019 with a CRE BSI were eligible.

Refining GFR estimation: a quest for the unobservable truth?

Assessing glomerular filtration rate (GFR), which is central to evaluating kidney health, remains challenging. Measured GFR is not widely available and lacks standardization. Estimated GFR can be highly inaccurate for some patients and has limited applicability to many patient populations, such as those who are acutely ill.

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA.

Methods: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019.

Impact of Hyperglycemia and Diabetes Mellitus on Breakthrough Mucormycosis Outcomes in Patients with Hematologic Malignancies-Complex and Intriguing Associations.

Mucormycosis (MCR) is frequently associated with diabetic ketoacidosis and hyperglycemia, as well as hematologic malignancies (HMs) and hematopoietic stem cell transplantation (HSCT). However, little is known about the effect of hyperglycemia on MCR outcomes in patients with HMs. We therefore conducted a retrospective cohort study of adult patients hospitalized with MCR and HM or HSCT (n = 103) at MD Anderson Cancer Center from April 2000 through to April 2020.

IL-9 and Th9 cells in health and diseases-From tolerance to immunopathology.

CD4+ T cells have the capacity to differentiate into various T helper (Th) cell subsets after activation, and by acquiring distinct cytokine profiles and effector functions, they regulate the nature as well as the outcomes of immune responses. Th9 cells are a relatively new member in the Th cell family. The signature cytokine for Th9 cells is IL-9, a cytokine in the IL-2Rγc-chain family.

Graft-Infiltrating Macrophages Adopt an M2 Phenotype and Are Inhibited by Purinergic Receptor P2X7 Antagonist in Chronic Rejection.

Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection.

CRISPR-Cas9 delivery to hard-to-transfect cells via membrane deformation.

The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) nuclease system represents an efficient tool for genome editing and gene function analysis. It consists of two components: single-guide RNA (sgRNA) and the enzyme Cas9. Typical sgRNA and Cas9 intracellular delivery techniques are limited by their reliance on cell type and exogenous materials as well as their toxic effects on cells (for example, electroporation).

Human NLRP3 inflammasome senses multiple types of bacterial RNAs.

Inflammasomes are multiprotein platforms that activate caspase-1, which leads to the processing and secretion of the proinflammatory cytokines IL-1β and IL-18. Previous studies demonstrated that bacterial RNAs activate the nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome in both human and murine macrophages. Interestingly, only mRNA, but neither tRNA nor rRNAs, derived from bacteria could activate the murine Nlrp3 inflammasome.

Significant publications on infectious diseases pharmacotherapy in 2013.

Purpose: The most important articles on infectious diseases (ID) pharmacotherapy published in the peer-reviewed literature in 2013, as nominated and selected by panels of pharmacists and others with ID expertise, are summarized.

Summary: Members of the Houston Infectious Diseases Network were asked to nominate articles published last year in prominent biomedical journals that had a major impact in the field of ID pharmacotherapy. A list of 27 nominated articles on ID-related topics in general and 26 articles specifically focused on human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) was compiled.

The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-induced NLRP3 inflammasome activation.

NLRP3 is a key component of caspase-activating macromolecular protein complexes called inflammasomes. It has been found that DHX33 is a cytosolic dsRNA sensor for the NLRP3 inflammasome, which induces caspase-1-dependent production of IL-1β and IL-18 upon activation. However, how the cytosolic dsRNAs induce the interaction between DHX33 and the NLRP3 inflammasome remains unknown.

PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus isolates.

Ceftaroline is the first member of a novel class of cephalosporins approved for use in the United States. Although prior studies have identified eight ceftaroline-resistant methicillin-resistant Staphylococcus aureus (MRSA) isolates in Europe and Asia with MICs ranging from 4 to 8 mg/liter, high-level resistance to ceftaroline (>32 mg/liter) has not been described in MRSA strains isolated in the United States. We isolated a ceftaroline-resistant (MIC > 32 mg/liter) MRSA strain from the blood of a cystic fibrosis patient and five MRSA strains from the respiratory tract of this patient.

A cancer cell-activatable aptamer-reporter system for one-step assay of circulating tumor cells.

The current antibody-mediated numeration assays of circulating tumor cells (CTCs) require multiple steps and are time-consuming. To overcome these technical limitations, a cancer cell-activatable aptamer-reporter was formulated by conjugating a biomarker-specific aptamer sequence with paired fluorochrome-quencher molecules. In contrast to the antibody probes, the intact aptamer-reporter was optically silent in the absence of cells of interest.

DHX15 senses double-stranded RNA in myeloid dendritic cells.

Many members of the DEXD/H box helicase family play important roles in the innate immune system against viral infection. Therefore, we isolated dsRNA complex in myeloid dendritic cells. We found that DHx15, a DEXDc helicase family member, is one of the components of this complex.