Bacterial Amino Acid Auxotrophies Enable Energetically Costlier Proteomes.

The outsourcing of amino acid (AA) production to the environment is relatively common across the tree of life. We recently showed that the massive loss of AA synthesis capabilities in animals is governed by selective pressure linked to the energy costs of AA production. Paradoxically, these AA auxotrophies facilitated the evolution of costlier proteomes in animals by enabling the increased use of energetically expensive AAs.

Resveratrol-Based Carbamates as Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, Computational Study and Biometal Complexation Capability.

Considering our previous experience in the design of new cholinesterase inhibitors, especially resveratrol analogs, in this research, the basic stilbene skeleton was used as a structural unit for new carbamates designed as potentially highly selective butyrylcholinesterase (BChE) inhibitors with excellent absorption, distribution, metabolism, excretion and toxicity ADMET properties. The inhibitory activity of newly prepared carbamates - was tested toward the enzymes acetylcholinesterase (AChE) and BChE. In the tested group of compounds, the leading inhibitors were and , which achieved excellent selective inhibitory activity for BChE with IC values of 0.

Quantum-computing-enhanced algorithm unveils potential KRAS inhibitors.

We introduce a quantum-classical generative model for small-molecule design, specifically targeting KRAS inhibitors for cancer therapy. We apply the method to design, select and synthesize 15 proposed molecules that could notably engage with KRAS for cancer therapy, with two holding promise for future development as inhibitors. This work showcases the potential of quantum computing to generate experimentally validated hits that compare favorably against classical models.

Prediction of Retention Indices in LC-HRMS for Enhanced Structural Identification of Organic Micropollutants in Water: Selectivity-Based Filtration.

Addressing the global challenge of ensuring access to safe drinking water, especially in developing countries, demands cost-effective, eco-friendly, and readily available technologies. The persistence, toxicity, and bioaccumulation potential of organic pollutants arising from various human activities pose substantial hurdles. While high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-HRMS) is a widely utilized technique for identifying pollutants in water, the multitude of structures for a single elemental composition complicates structural identification.

Levothyroxine therapy reduces endocan and total cholesterol concentrations in patients with subclinical hypothyroidism.

Introduction: Subclinical hypothyroidism (SCH) is an independent risk factor for cardiovascular diseases due to endothelial dysfunction and atherosclerosis development. The aim of this study was to determine whether the levothyroxine therapy could impact the concentrations of endothelial dysfunction blood markers, namely endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA) and endocan, in patients with a mild form of SCH (thyroid-stimulating hormone (TSH) ≤ 10 mIU/L).

Materials And Methods: In this case-control prospective study, SCH patients and healthy controls were recruited during their regular health examinations.

Green Microfluidic Method for Sustainable and High-Speed Analysis of Basic Amino Acids in Nutritional Supplements.

Amino acids (AAs) have broad nutritional, therapeutic, and medical significance and thus are one of the most common active ingredients of nutritional supplements. Analytical strategies for determining AAs are high-priced and often limited to methods that require modification of AA polarity or incorporation of an aromatic moiety. The aim of this work was to develop a new method for the determination of L-arginine, L-ornithine, and L-lysine on low-cost microchip electrophoresis instrumentation conjugated with capacitively coupled contactless conductivity detection.

Synthesis of novel imino-coumarin and acrylonitrile 2-benzazole hybrids as potent anticancer agents targeting tubulin.

Building on previous research indicating the robust biological effects of coumarins, we focused on exploring imino-coumarin 2-benzazole conjugates. Compounds were tested for antiproliferative activity in vitro, with the most active ones further examined to determine the mechanism of biological action. Five derivatives exhibited significant antiproliferative activity against all tested cancer cells (IC ranging from 0.

Experimental and DFT Approaches to Physico-Chemical Properties of Bioactive Resveratrol Analogues.

Acetylcholinesterase and butyrylcholinesterase are two related enzymes that represent pharmacologically suitable targets in neurodegenerative disorders, given their physiological roles in the body. The treatment of neurodegenerative disorders currently includes common reversible cholinesterase inhibitors. Resveratrol analogues, as the molecules in focus, have shown the very strong inhibition potential of cholinesterases.

Outcomes of Ixazomib Treatment in Relapsed and Refractory Multiple Myeloma: Insights from Croatian Cooperative Group for Hematologic Diseases (KROHEM).

: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). : This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023.

Disease Activity in Pregnant and Postpartum Women With Multiple Sclerosis Receiving Ocrelizumab or Other Disease-Modifying Therapies.

Background And Objectives: Women with multiple sclerosis (MS) are at risk of disease reactivation in the early postpartum period. Ocrelizumab (OCR) is an anti-CD20 therapy highly effective at reducing MS disease activity. Data remain limited regarding use of disease-modifying therapies (DMTs), including OCR, and disease activity during peripregnancy periods.

The Additive Effect of Combinations of FSH Receptor Gene Variants in Ovarian Response to Stimulation.

To analyze whether combinations of polymorphisms within FSHR gene influence ovarian response (OR) to stimulation. A multicenter prospective cohort study was conducted from 11/2016-06/2019 in Europe and Asia including predicted normo-responders under 38y. Patients underwent ovarian stimulation using fixed-dose 150 IU rFSH in a GnRH antagonist protocol.

Quality Assessment of Cryopreserved Peripheral Blood Stem Cell Products: Evaluation of Two Methods for Flow Cytometric Viability Testing.

Introduction: The standard flow cytometry method for viability testing using 7-aminoactinomycin D (7-AAD) determines cells in necrosis and late apoptosis. The colony-forming unit (CFU) assay, which evaluates the proliferation ability of HSCs, is also used in graft quality assessment despite known deficiencies that make this assay impractical in routine clinical settings. The aim was to compare the effectiveness of the flow cytometry 7-AAD/annexin V method with the 7-AAD method in assessing the quality of HSCs in autologous and allogeneic peripheral blood stem cell (PBSC) products.

Bone marrow stromal cells enhance differentiation of acute myeloid leukemia induced by pyrimidine synthesis inhibitors.

Acute myeloid leukemia (AML) is a heterogeneous group of hematological malignancies characterized by differentiation arrest, high relapse rates, and poor survival. The bone marrow (BM) microenvironment is recognized as a critical mediator of drug resistance and a primary site responsible for AML relapse. Our previous study reported that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAr) induces AML cell differentiation by inhibiting pyrimidine synthesis and activating Checkpoint kinase 1.

Education and cooking methods in the management of calcium and PTH serum levels in patients on hemodialysis: a randomized controlled study.

Background: Chronic kidney disease associated mineral bone disorder (CKD-MBD) is one of the major causes of excess morbidity and mortality in hemodialysis patients. The purpose of this study was to investigate whether education about dietary intakes and specific food processing methods affect serum calcium and PTH concentrations in hemodialysis patients.

Methods: Forty-seven hemodialysis patients were randomly divided into a control and an intervention group.

In silico attempt to reveal the link between cancer development and combined exposure to the maize herbicides: Glyphosate, nicosulfuron, S-metolachlor and terbuthylazine.

Pesticides are crucial for crop protection and have seen a 50 % increase in use in the last decade. Besides preventing significant crop losses their use has raised health concerns due to consumer exposure through residues in food and water. The toxicity data from individual components is often used to assess overall mixture toxicity, but uncertainty persists in understanding the behaviors of individual chemicals within these mixtures.

Ocrelizumab in people with primary progressive multiple sclerosis: A real-world multicentric study.

Background: Ocrelizumab is the only disease-modifying therapy (DMT) approved for the treatment of people with primary progressive multiple sclerosis (pwPPMS).

Objectives: To provide real-world evidence of ocrelizumab effectiveness and safety in pwPPMS in Croatian MS centers.

Methods: A retrospective observational multi-center study of pwPPMS who were started on ocrelizumab in 7 MS centers in Croatia.

Protonation of palmitic acid embedded in DPPC lipid bilayers obscures detection of ripple phase by FTIR spectroscopy.

The transformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers from the gel (L) to the fluid (L) phase involves an intermediate ripple (P) phase forming a few degrees below the main transition temperature (T). While the exact cause of bilayer rippling is still debated, the presence of amphiphilic molecules, pH, and lipid bilayer architecture are all known to influence (pre)transition behavior. In particular, fatty acid chains interact with hydrophobic lipid tails, while the carboxylic groups simultaneously participate in proton transfer with interfacial water in the polar lipid region which is controlled by the pH of the surrounding aqueous medium.

Cholinesterase Inhibition and Antioxidative Capacity of New Heteroaromatic Resveratrol Analogs: Synthesis and Physico-Chemical Properties.

The targeted compounds in this research, resveratrol analogs -, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the -configuration as the biologically active -resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring.

Comparison of Clinical, Pathological, and Procedural Characteristics of Adult and Pediatric Acute Appendicitis before and during the COVID-19 Pandemic.

Background: This study aims to analyze the impact of the COVID-19 pandemic on the clinical, pathological, and surgical characteristics of acute appendicitis (AA) at the University Hospital Centre (UHC) Zagreb.

Methods: This retrospective study analyzed demographic, clinical, and surgical data from consecutive AA patients. Data were collected from an electronic database for two periods: 1 January to 31 December 2019 (pre-COVID-19), and 11 March 2020, to 11 March 2021 (COVID-19 pandemic).

Di-mannosylation enhances the adjuvant properties of adamantane-containing desmuramyl peptides .

Muramyl dipeptide (MDP) is the smallest essential peptidoglycan substructure capable of promoting both innate and adaptive immune responses. Herein, we report on the design, synthesis, and study of the adjuvant properties of two novel MDP analogs containing an achiral adamantyl moiety attached to the desmuramyl dipeptide (DMP) pharmacophore and additionally modified by one mannosyl subunit (derivative 7) or two mannosyl subunits (derivative 11). Mannose substructures were introduced in order to assess how the degree of mannosylation affects the immune response and nucleotide-binding oligomerization-domain-containing protein 2 (NOD2) binding affinity, compared to the reference compound ManAdDMP.

The HyperPed-COVID international registry: Impact of age of onset, disease presentation and geographical distribution on the final outcome of MIS-C.

Objectives: The aim of the study was to establish an international multicenter registry to collect data on patients with Multisystem Inflammatory Syndrome in Children (MIS-C), in order to highlight a relationship between clinical presentation, age of onset and geographical distribution on the clinical outcome.

Study Design: Multicenter retrospective study involving different international societies for rare immunological disorders.1009 patients diagnosed with MIS-C between March and September 2022, from 48 centers and 22 countries were collected.