Replacement of a single residue changes the primary specificity of thrombin.

Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown.

Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189.

Radiology resident competency in orthopedic trauma detection in simulated on-call scenarios.

Purpose: To evaluate radiology residents' ability to accurately identify three specific types of orthopedic trauma using radiographic imaging within a simulated on-call environment.

Methods: We utilized the Wisdom in Diagnostic Imaging Emergent/Critical Care Radiology Simulation (WIDI SIM) to assess residents' preparedness for independent radiology call. The simulation included 65 cases, with three focusing on orthopedic trauma: sacral ala, femoral neck, and pediatric tibial/Toddler's fractures.

Extending beyond traditional forage: potential nutritional benefits of native plants in extreme arid insular regions.

The scarcity, unstable nutritional quality and environmental cost of imported forages in arid insular regions like Fuerteventura in the Canary Islands (Spain) need exploring sustainable local alternatives. This study evaluated the nutritional quality of twelve native and endemic plant species categorized into legumes, grasses, and a mixed group, cultivated under controlled conditions. The bromatological profiles, focusing on fiber, protein, lipids, and minerals, showed significant differences among plants in key parameters of forage quality: neutral detergent fiber (NDF; 24.

Chronic Jet Lag Disrupts Circadian Rhythms and Induces Hyperproliferation in Murine Lacrimal Glands via ROS Accumulation.

Purpose: Chronic jet lag (CJL) is known to disrupt circadian rhythms, which regulate various physiological processes, including ocular surface homeostasis. However, the specific effects of CJL on lacrimal gland function and the underlying cellular mechanisms remain poorly understood.

Methods: A CJL model was established using C57BL/6J mice.

Essential tremor with tau pathology features seeds indistinguishable in conformation from Alzheimer's disease and primary age-related tauopathy.

Neurodegenerative tauopathies are characterized by the deposition of distinct fibrillar tau assemblies, whose rigid core structures correlate with defined neuropathological phenotypes. Essential tremor (ET) is a progressive neurological disorder that, in some cases, is associated with cognitive impairment and tau accumulation. In this study, we explored tau assembly conformation in ET patients with tau pathology using cytometry-based tau biosensor assays.

Repeated 5-aminolevulinic acid mediated sonodynamic therapy using magnetic resonance guided focused ultrasound in rat brain tumour models.

Sonodynamic therapy is an emerging therapeutic approach against brain tumours. However, the treatment scheme and ultrasound parameters have yet to be explored for clinical translation. Our study aimed to optimize ultrasound parameters for sonodynamic therapy (SDT) with 5-ALA as a sonosensitizing agent and to evaluate its therapeutic outcome on the rodent 9L gliosarcoma and the human U87 glioblastoma models.

Antitumor immunostimulatory effect via cell-killing action of a novel extracorporeal blood circulating photodynamic therapy system using 5-aminolevulinic acid.

This study investigated whether intravenous administration of tumor cells killed by photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) had antitumor effects on distal tumors. Furthermore, a novel extracorporeal blood circulating 5-ALA/PDT system was developed. 5-ALA/PDT- (low or high irradiation) or anticancer drug-treated cells were intravenously administered to rats in a glioma cancer model.

Biodegradable Tenebrio molitor antifreeze protein modified kinetic hydrate inhibitor: Insights into molecular interactions and structural flexibility.

The formation of natural gas hydrates presents significant economic and safety challenges to the petroleum and gas industry, necessitating the development of effective prevention strategies. This study investigates an environmentally sustainable Tenebrio molitor antifreeze protein (TmAFP) modified to be a potential kinetic hydrate inhibitor. The aim of this study was to enhance the inhibitory activity of TmAFP by systematically substituting threonine (Thr) residues with glycine (Gly), alanine (Ala), or serine (Ser) at positions 29, 39, and 53.

CFTR as a therapeutic target for severe lung infection.

Lung infection is one of the leading causes of morbidity and mortality worldwide. Even with appropriate antibiotic and antiviral treatment, mortality in hospitalized patients often exceeds 10%, highlighting the need for the development of new therapeutic strategies. Of late, cystic fibrosis transmembrane conductance regulator (CFTR) is - in addition to its well-established roles in the lung airway and extrapulmonary organs - increasingly recognized as a key regulator of alveolar homeostasis and defense.

Rational Design Engineering of 5-Aminolevulinate Synthase with Activity and Stability Enhancement.

5-Aminolevulinic acid synthase (ALAS) is the key rate-limiting enzyme in the synthesis of the vital biosynthetic intermediate 5-aminolevulinic acid (ALA). However, its catalytic efficiency is compromised due to its low activity and poor stability. Here, we obtained the mutant I325M/V390Y/H391I (T6), which exhibited a 7.

sp. nov., a Gram-Positive, Spore-Forming Rod Isolated from a Pharmaceutical Facility Production Environment and Added to the MALDI Biotyper Database.

A Gram-positive, aerobic, rod-shaped and spore-forming bacterium strain designation, B190/17, was isolated from an air monitoring sample of a Brazilian immunobiological production facility in 2017. The strain was not identifiable by biochemical methodology VITEK 2 or by MALDI-TOF MS with VITEK MS RUO and MALDI Biotyper. The 16S rRNA gene sequencing results showed 98.

Carotenoid Interactions with PCSK9: Exploring Novel Cholesterol-Lowering Strategies.

: This study investigated the potential of green algae-derived carotenoids as natural inhibitors of the proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism. PCSK9 promotes the degradation of low-density lipoprotein receptors (LDLR), thereby increasing blood cholesterol levels and elevating the risk of cardiovascular diseases. /: We screened the pharmacophore fit score of 27 carotenoids with PCSK9 and identified 14 that were analyzed for binding affinity and molecular interactions.

In Vitro Study of Antiviral Properties of Compounds Based on 1,4-Dioxane Derivative of Closo-Decaborate Anion with Amino Acid Ester Residues Against Influenza Virus A/IIV-Orenburg/83/2012(H1N1)pdm09.

New derivatives of the -decaborate anion [BH-O(CH)O(CH)C(O)-L-OCH] (An) (: L = Trp; : L = His; : L = Met; : L = Ala(2-oxopyrrolidin-3-yl) (Pld) were synthesized and isolated as tetraphenylphosphonium salts (PhP)An. Anions ; ; , and contain a pendant functional group from the L-tryptophan methyl ester, L-histidine methyl ester, L-methionine methyl ester, or methyl 2-amino-3-(2-oxopyrrolidin-3-yl)propanoate (-Trp-OCH, -His-OCH, -Met-OCH, or -Pld-OCH) residue, respectively, bonded with the boron cluster anion through the oxybis[(ethane-2,1-diyl)oxy] spacer. This pacer is formed as a result of the nucleophilic opening of the attached dioxane molecule in the [BHO(CH)O] starting derivative.

Yeast Glucan Remodeling Protein Bgl2p: Amyloid Properties and the Mode of Attachment in Cell Wall.

Bgl2p is a major, conservative, constitutive glucanosyltransglycosylase of the yeast cell wall (CW) with amyloid amino acid sequences, strongly non-covalently anchored in CW, but is able to leave it. In the environment, Bgl2p can form fibrils and/or participate in biofilm formation. Despite a long study, the question of how Bgl2p is anchored in CW remains unclear.

Enhancing Rats' Diet with Ethyl Esters Derived from Linseed Oil and Examining the Resulting Changes in Their Blood Fatty Acid Profile.

Omega-3 fatty acids are an important factor contributing to the prevention and cure of numerous diseases, and therefore their supplementation with diet is a significant issue. There are numerous supplements on the market containing omega-3 acids, of both plant and animal origin. In our study, we compared an effect of linseed oil, ethyl esters of linseed oil and fish oil supplementation to rats' diet on their blood serum and erythrocyte fatty acid profile.

Nano-LC with New Hydrophobic Monolith Based on 9-Antracenylmethyl Methacrylate for Biomolecule Separation.

In this study, new monolithic poly(9-anthracenylmethyl methacrylate-co-trimethylolpropane trimethacrylate (TRIM) columns, referred as ANM monoliths were prepared, for the first time, and were used for the separation media for biomolecules and proteomics analysis by nano-liquid chromatography (nano-LC). Monolithic columns were prepared by in situ polymerization of 9-anthracenylmethyl methacrylate (ANM) and trimethylolpropane trimethacrylate (TRIM) in a fused silica capillary column of 100 µm ID. Polymerization solution was optimized in relation to monomer and porogenic solvent.

Interaction of Cyclosporin C with Dy Ions in Acetonitrile and in Complex with Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

The spectral characteristics of cyclosporin C (CsC) with the addition of Dy ions in acetonitrile (CDCN) and CsC with Dy incorporated into dodecylphosphocholine (DPC) micelle in deuterated water were investigated by high-resolution NMR spectroscopy. The study was focused on the interaction between Dy ions and CsC molecules in different environments. Using a combination of one-dimensional and two-dimensional NMR techniques, we obtained information on the spatial features of the peptide molecule and the interaction between CsC and the metal ion.

Kallistatin as a Potential Marker of Therapeutic Response During Alpha-Lipoic Acid Treatment in Diabetic Patients with Sensorimotor Polyneuropathy.

Diabetic sensorimotor neuropathy (DSPN) is strongly associated with the extent of cellular oxidative stress and endothelial dysfunction in type 2 diabetes (T2DM). Alpha-lipoic acid (ALA) attenuates the progression of DSPN through its antioxidant and vasculoprotective effects. Kallistatin has antioxidant and anti-inflammatory properties.

Alterations in the Microbiomes and Metabolic Profiles of the Ileal Between the Hu Sheep and East Friesian Sheep.

The East Friesian sheep is a dairy breed known for its high fertility and high milk production and is currently one of the best dairy sheep breeds in the world. This breed is known to have a poor disease-resistant phenotype compared to Hu sheep. Gut microbiota and metabolites play a role in host disease resistance.

In Situ Light-Source Delivery During 5-Aminulevulinic Acid-Guided High-Grade Glioma Resection: Spatial, Functional and Oncological Informed Surgery.

Background/objectives: 5-aminulevulinic acid (5-ALA)-guided surgery for high-grade gliomas remains a challenge in neuro-oncological surgery. Inconsistent fluorescence visualisation, subjective quantification and false negatives due to blood, haemostatic agents or optical impediments from the external light source are some of the limitations of the present technology.

Methods: The preliminary results from this single-centre retrospective study are presented from the first 35 patients operated upon with the novel Nico Myriad Spectra System©.

Erlotinib Improves the Response of Glioblastoma Cells Resistant to Photodynamic Therapy.

Glioblastoma (GBM) is the most common and deadly type of brain cancer in adults. Dysregulation of receptor tyrosine kinase pathways, such as the epidermal growth factor receptor (EGFR), contributes to therapeutic resistance. Drugs that inhibit tyrosine kinase activity and monoclonal antibodies against EGFR are strategies used in clinical trials.

Noninvasive Ultra Low Intensity Light Photodynamic Treatment of Glioblastoma with Drug Augmentation: LoGlo PDT Regimen.

This paper presents the basis for LoGlo PDT, a new treatment for glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide, and ionizing irradiation. Mortality in 2024 remains over 80% within several years from diagnosis.

-GlcNAcylation of Focal Adhesion Kinase Regulates Cell Adhesion, Migration, and Proliferation via the FAK/AKT Pathway.

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase pivotal in cellular signal transduction, regulating cell adhesion, migration, growth, and survival. However, the regulatory mechanisms of FAK during tumorigenesis and progression still need to be fully understood. Our previous study demonstrated that -GlcNAcylation regulates integrin-mediated cell adhesion.

O-Arm Navigation-Guided Unilateral Biportal Endoscopic Decompression of Far-Out Syndrome.

The main aim of this video article is to demonstrate the combined use of O-arm navigation and unilateral biportal endoscopy (UBE) to manage far-out syndrome (FOS). In FOS there is entrapment and compression of the fifth lumbar nerve beyond the foramen and between L5 transverse process and the sacral ala at the lumbosacral junction. Conventional microscopic decompression using a paraspinal approach had been the gold standard for its management.