Enhancing Proton-Coupled Electron Transfer in Blue Light Using FAD Photoreceptor AppA.

The Blue Light Using FAD (BLUF) photoreceptor utilizes a noncovalently bound FAD to absorb light and trigger the initial ultrafast events in receptor activation. FAD undergoes 1 and 2 electron reduction as an enzyme redox cofactor, and studies on the BLUF photoreceptor PixD revealed the formation of flavin radicals (FAD and FADH) during the photocycle, supporting a general mechanism for BLUF operation that involves PCET from a conserved Tyr to the oxidized FAD. However, no radical intermediates are observed in the closely related BLUF proteins AppA and BlsA, and replacing the conserved Tyr with fluoro-Tyr analogs that increase the acidity of the phenol OH has a minor effect on AppA photoactivation in contrast to PixD where the photocycle is halted at FAD.

STARD7 maintains intestinal epithelial mitochondria architecture, barrier integrity, and protection from colitis.

Susceptibility to inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) is linked with loss of intestinal epithelial barrier integrity and mitochondria dysfunction. Steroidogenic acute regulatory (StAR) protein-related lipid transfer (START) domain-containing protein 7 (STARD7) is a phosphatidylcholine-specific (PC-specific) lipid transfer protein that transports PC from the ER to the mitochondria, facilitating mitochondria membrane stabilization and respiration function. The aim of this study was to define the contribution of STARD7 in the regulation of the intestinal epithelial mitochondrial function and susceptibility to colitis.

The Comparative Effectiveness of Potent P2Y12 Inhibitors Versus Clopidogrel in Patients with Acute Myocardial Infarction Undergoing PCI: National Registry Data.

Dual antiplatelet therapy (DAPT), which is essential in AMI management, combines aspirin with a P2Y12 receptor antagonist. This study compared the effectiveness of potent P2Y12 inhibitors versus clopidogrel in AMI patients treated with percutaneous coronary intervention (PCI). 65,986 AMI patients included in a nationwide prospective registry who underwent PCI and received DAPT were studied.

No practice effect on the classification accuracy of the response time concealed information test.

The Response Time Concealed Information Test can reveal that a person recognizes a relevant item (probe, e.g., a murder weapon) among other, irrelevant items (controls), based on slower responses to the probe compared to the controls.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium.

Crystal structure of a bacterial photoactivated adenylate cyclase determined by serial femtosecond and serial synchrotron crystallography.

OaPAC is a recently discovered blue-light-using flavin adenosine dinucleotide (BLUF) photoactivated adenylate cyclase from the cyanobacterium Oscillatoria acuminata that uses adenosine triphosphate and translates the light signal into the production of cyclic adenosine monophosphate. Here, we report crystal structures of the enzyme in the absence of its natural substrate determined from room-temperature serial crystallography data collected at both an X-ray free-electron laser and a synchrotron, and we compare these structures with cryo-macromolecular crystallography structures obtained at a synchrotron by us and others. These results reveal slight differences in the structure of the enzyme due to data collection at different temperatures and X-ray sources.

Pre-Conception Androgen Levels and Obstetric Outcomes in Polycystic Ovary Syndrome: A Single-Center Retrospective Study.

Unlabelled: Hyperandrogenism is a determining diagnostic factor for PCOS. If pregnancy is conceived, it is considered high-risk due to several potential complications, but the correlation between pre-pregnancy androgen levels and obstetric outcomes is poorly characterized.

Objective: To determine if pre-pregnancy serum androgen concentrations and androgen indexes differed when certain obstetric and neonatal outcomes appeared in PCOS.

Artificial Urinary Sphincter Implants in Men: A National Health Care Data System-Based Study to Assess Reinterventions in France.

Purpose: Significant concerns remain regarding the long-term outcomes of AMS 800 artificial urinary sphincter (AUS) implants in men. The objective was to assess the long-term AUS reintervention (replacement or removal) rates after a first-ever AUS implantation.

Materials And Methods: This population-based retrospective cohort study included all men age ≥ 18 years in France who underwent a first-ever AUS implantation (identified using a unique device identifier) for male stress urinary incontinence (SUI) after prostate cancer (PCa) or benign prostatic hyperplasia (BPH) treatment, between January 1, 2006, and December 31, 2018.

The psychosocial background of dental care avoidance: A qualitative study.

Introduction: Dental care avoidance affects individuals' oral health status. There is limited literature examining the context of dental avoidance behavior.

Aim: The aim of the study is to examine attitudes toward dental care services among adults.

How is recovery defined and measured in patients with low back pain? A mixed study systematic review.

Background: Despite the burden of low back pain (LBP) there is no currently accepted definition for its recovery, nor is there a gold standard for measurement. In addition, it is currently unclear how the perspective of patients are used in making recovery determinations. The purpose of this mixed study systematic review across both quantitative and qualitative literature was to (1) explore how recovery has been defined and measured for patients experiencing LBP, and (2) examine how the perspectives of patients and providers for recovery of LBP align or differ.

Endocrine Characteristics and Obstetric Outcomes of PCOS Patients with Successful IVF and Non-IVF Pregnancies.

Infertility affects an estimated 40-50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment.

Variability of theory of mind versus pragmatic ability in typical and atypical development.

Introduction: Numerous studies have linked deficits in Theory of Mind (ToM) with language problems. We aimed to explore the similarities and differences between children's patterns of performance on a ToM task that requires minimal linguistic skill and a pragmatic inference task that relies on both ToM and language. We assessed variability in pragmatic inference skills and ToM across populations of children (8-14 years) displaying varying cognitive profiles.

Quality Assessment of Reconstructed Cow, Camel and Mare Milk Powders by Near-Infrared Spectroscopy and Chemometrics.

Milk powders are becoming a major attraction for many industrial applications due to their nutritional and functional properties. Different types of powdered milk, each with their own distinct chemical compositions, can have different functionalities. Consequently, the development of rapid monitoring methods is becoming an urgent task to explore and expand their applicability.

Standardizing the diagnosis of necrotizing enterocolitis in infants with congenital heart disease.

Objective: This quality improvement initiative aimed to standardize the diagnosis of necrotizing enterocolitis (NEC) in infants with congenital heart disease (CHD).

Study Design: A multidisciplinary team developed clinical practice guidelines for the diagnosis and treatment of NEC within the Cardiac Intensive Care Unit (CICU). The diagnosis rate of NEC per 100 at-risk admissions was the primary outcome measure.

SARS-CoV-2 envelope protein alters calcium signaling via SERCA interactions.

The clinical management of severe COVID-19 cases is not yet well resolved. Therefore, it is important to identify and characterize cell signaling pathways involved in virus pathogenesis that can be targeted therapeutically. Envelope (E) protein is a structural protein of the virus, which is known to be highly expressed in the infected host cell and is a key virulence factor; however, its role is poorly characterized.

Microbiome modifications by steroids during viral exacerbation of asthma and in healthy mice.

In the present studies, the assessment of how viral exacerbation of asthmatic responses with and without pulmonary steroid treatment alters the microbiome in conjunction with immune responses presents striking data. The overall findings identify that although steroid treatment of allergic animals diminished the severity of the respiratory syncytial virus (RSV)-induced exacerbation of airway function and mucus hypersecretion, there were local increases in IL-17 expression. Analysis of the lung and gut microbiome suggested that there are differences in RSV exacerbation that are further altered by fluticasone (FLUT) treatment.

RSV enhances bacterial growth in the lung.

Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages.

Synthesis and Biological Evaluation of Pyrazole-Pyrimidones as a New Class of Correctors of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).

Cystic fibrosis (CF) is caused by the functional expression defect of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Despite the recent success in CFTR modulator development, the available correctors only partially restore the F508del-CFTR channel function, and several rare CF mutations show resistance to available drugs. We previously identified compound that synergistically rescued the F508del-CFTR folding defect in combination with the existing corrector drugs VX-809 and VX-661.

Exploring the Role of Neuropeptide PACAP in Cytoskeletal Function Using Spectroscopic Methods.

The behavior and presence of actin-regulating proteins are characteristic of various clinical diseases. Changes in these proteins significantly impact the cytoskeletal and regenerative processes underlying pathological changes. Pituitary adenylate cyclase-activating polypeptide (PACAP), a cytoprotective neuropeptide abundant in the nervous system and endocrine organs, plays a key role in neuron differentiation and migration by influencing actin.