A novel process for transcellular hemoglobin transport from macrophages to cancer cells.

Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163.

Systematic, computational discovery of multicomponent and one-pot reactions.

Discovery of new types of reactions is essential to organic chemistry because it expands the scope of accessible molecular scaffolds and can enable more economical syntheses of existing structures. In this context, the so-called multicomponent reactions, MCRs, are of particular interest because they can build complex scaffolds from multiple starting materials in just one step, without purification of intermediates. However, for over a century of active research, MCRs have been discovered rather than designed, and their number remains limited to only several hundred.

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.

Background And Objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.

Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).

Deconvoluting zavegepant drug-drug interactions: A phase I study to evaluate the effects of rifampin and itraconazole on zavegepant pharmacokinetics.

Zavegepant is a calcitonin gene-related peptide receptor antagonist for acute migraine treatment. This Phase I, open-label, fixed-sequence study evaluated the effects of itraconazole (a strong cytochrome P450 3A4 [CYP3A4] and P-glycoprotein [P-gp] inhibitor) on the pharmacokinetics of intranasal/oral zavegepant and the effects of rifampin (a strong inducer of CYP3A4 and P-gp; and an inhibitor of organic anion transporting polypeptide 1B3 [OATP1B3]) on oral zavegepant in healthy participants. In the intranasal/oral zavegepant-itraconazole cohort, participants received a single 10-mg dose of zavegepant nasal spray on Day 1, followed by oral zavegepant (50 mg) on Day 3.

Improved energy equations and thermal functions for diatomic molecules: a generalized fractional derivative approach.

Context: This work presents analytical expressions for ro-vibrational energy models of diatomic molecules by introducing fractional parameters to improve molecular interaction analysis. Thermodynamic models, including Helmholtz free energy, mean thermal energy, entropy, and isochoric heat capacity, are formulated for diatomic molecules such as CO (X ∑), Cs (3 ∑), K (X ∑), Li (6 Π), Li (1 Δ), Na (5 Δ), Na (C(2) Π), and NaK (c ∑). The incorporation of fractional parameters improves predictive accuracy for vibrational energies, as shown by reductions in percentage average absolute deviations from 0.

Abdominal Compared With Coronary Artery Calcification and Incident Cardiovascular Events and Mortality in Black Adults.

Background: Black adults show heightened cardiovascular risk compared with other groups despite comparable or lower coronary artery calcium (CAC) scores, indicating potential cardiovascular risk underestimation by CAC. Abdominal aortic calcification (AAC), preceding CAC, may predict cardiovascular events better in Black adults who are prone to early atherosclerotic cardiovascular disease and excess events at low CAC scores.

Methods: We included 2551 participants from the JHS (Jackson Heart Study) visit 2 examination (2005-2008) without cardiovascular disease, followed through 2016.

UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.

Background: Ang-II (angiotensin II) impairs the function of the antihypertensive enzyme ACE2 (angiotensin-converting enzyme 2) by promoting its internalization, ubiquitination, and degradation, thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified, and their role in hypertension remains unknown.

Methods: Proteomics and bioinformatic analyses were used to identify ACE2 ubiquitination partners in the brain, heart, and kidney of hypertensive C57BL6/J mice of both sexes.

Effect of Postbiotic CECT 7347 on Gastrointestinal Symptoms, Serum Biochemistry, and Intestinal Microbiota in Healthy Adults: A Randomised, Parallel, Double-Blind, Placebo-Controlled Pilot Study.

Objectives: A randomised, double-blind, placebo-controlled pilot trial was conducted to assess the effect of heat-treated CECT 7347 (HT-ES1) in healthy adults with mild to moderate digestive symptoms. A total of 60 participants were recruited and received either HT-ES1 or an identical placebo for 8 weeks with a further follow-up at week 10.

Methods: This study monitored changes in the total Gastrointestinal Symptom Rating Scale for IBS score (GSRS-IBS), Irritable Bowel Syndrome Symptom Severity Scale (IBS-SSS), IBS Quality of Life index (IBS-QoL), gut microbiome using 16S rRNA sequencing, and the Visceral Sensitivity Index, as well as a range of biochemical markers, anthropometric parameters, and adverse events.

Preclinical Validation of MIN-T: A Novel Controlled-Released Formulation for the Adjunctive Local Application of Minocycline in Periodontitis.

Adjunctive treatment of periodontitis lacks solutions which allow for enough time for wound healing in the periodontal pockets by avoiding fast re-colonization. Such a solution might be an antibiotic-containing formulation with a controlled release over a period of weeks. Here, a recently described minocycline-containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development, and degradation studies.

TERTmonitor Efficacy and Performance in Detecting Mutations by Droplet Digital PCR.

Background: The screening of TERT promoter () mutations is essential in cancer research and diagnostics, due to its prevalence in tumours associated with low self-renewal rates. TERTmonitor is a diagnosis kit primarily designed for real-time qPCR qualitative detection of -124C>T and -146C>T mutations, which are highly prevalent in several malignancies, particularly in bladder carcinoma.

Objective: This study aims to investigate TERTmonitor performance in droplet digital PCR (ddPCR) in urine samples from bladder cancer patients.

Assessing the Prognostic Value of Cytoplasmic and Stromal Caveolin-1 in Early Triple-Negative Breast Cancer Undergoing Neoadjuvant Chemotherapy.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype with limited therapeutic options, leading to higher relapse rates and mortality. Identifying prognostic biomarkers like caveolin-1 (CAV1) is crucial for personalized treatment. CAV1 influences tumor progression and chemotherapy response, particularly through its interaction with the tumor microenvironment (TME) and cancer metabolism.

Stress and the City: Mental Health in Urbanized vs. Rural Areas in Salzburg, Austria.

Background: Living in the city is associated with a higher risk of suffering from stress, anxiety, and depression. Due to an increase of migration to the city, the association between mental health and city life is highly relevant to society.

Methods: We analyzed data of 9573 participants (Ø 55.

Elovanoids, a Novel Class of Lipid Mediators, Are Neuroprotective in a Traumatic Brain Injury Model in Rats.

Background: In the United States, traumatic brain injury (TBI) contributes significantly to mortality and morbidity. Elovanoids (ELVs), a novel class of homeostatic lipid mediators we recently discovered and characterized, have demonstrated neuroprotection in experimental stroke models but have never been tested after TBI.

Methods: A moderate fluid-percussion injury (FPI) model was used on male rats that were treated with ELVs by intravenous (IV) or intranasal (IN) delivery.

Guardians of resistance and virulence: detection of mec, femA, Van, pvl, hlg and spa genes in methicillin and vancomycin-resistant Staphylococcus aureus from clinical and food samples in Southwestern Nigeria.

Background: Staphylococcus aureus strains are highly virulent and associated with an eclectic range of severe nosocomial and community-acquired infections.

Objectives: This study assessed methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA/VRSA) from clinical and ready-to-eat (RTE) food sources, screened for antibiotic resistance; and molecular determinants of antibiotic and virulence genes.

Methods: Altogether, 465 clinical and RTE food samples were analyzed via conventional microbiological techniques and S.

Elastic and magnetic characteristics of nano-spinel ferrite Co MgCuFeO.

Wet-chemical co-precipitation was used to create CoMgCuFeO nano-ferrites (x = 0.0, 0.2, 0.

Robotic MRI/CT Guided Multiregional 'smart' Biopsy for Characterization of Tumor Heterogeneity: A Prospective Development Study.

Rationale And Objectives: Intratumoral heterogeneity means single site tumor biopsy might not be representative. Here we develop and optimize an MRI-informed robotic multiregional 'smart' biopsy technique in retroperitoneal and pelvic sarcomas (RPS). We also explore the relationship between imaging and histological biomarkers.

Prolonged Venous Transit on Perfusion Imaging is Associated with Longer Lengths of Stay in Acute Large Vessel Occlusions.

Background And Purpose: Prolonged venous transit (PVT+) is a marker of venous outflow; it is defined as the presence or absence of time-to-maximum ≥10 seconds timing in either the superior sagittal sinus or torcula. This novel perfusion imaging-based metric has been associated with higher odds of mortality and lower odds of functional recovery. This study aims to assess the relationship between PVT on admission perfusion imaging and length of hospital stay in large vessel occlusion strokes successfully reperfused with mechanical thrombectomy.

Comprehensive Study of Sperm Proteins and Metabolites Potentially Associated with Higher Fertility of Zebu Cattle () in Tropical Areas.

Crossbreeding of zebu cattle () with European breeds () producing crossbred cattle was performed to overcome the low growth rates and milk production of indigenous tropical cattle breeds. However, zebu cattle fertility is higher than those of crossbred cattle and European breeds under warm conditions. Combination study of proteomics and metabolomics toward Malaysian indigenous breed Kedah × Kelantan-KK () and crossbreed Mafriwal-M ( × ) to understand physiological reasons for higher thermotolerance and fertility in Zebu cattle sperm.