Alkalinity exposure induced growth inhibition, intestinal histopathological changes, and down-regulated nutrient transporter expression in Nile Tilapia: The ameliorative role of dietary camel whey protein hydrolysates.

Alkaline stress impairs fish productivity and performance and, therefore, is considered one of the major challenges facing aquaculture. In this work, the effects of supplementing diets with camel whey protein hydrolysates (WPH) on growth, digestion, antioxidant capacity, and gene expression were investigated in Nile tilapia (Oreochromis niloticus) under alkaline stress. A total of 160 fish (16.

Chalcogen dihydrobenzofuran compounds as potential neuroprotective agents: an in vitro and in silico biological investigation.

Oxidative stress arises from an imbalance between reactive species (RS) production and the antioxidant defense, increasing the brain susceptibility to neurodegenerative and psychiatric diseases. Besides, changes in the expression or activity of neurotransmitter metabolism enzymes, such as monoamine oxidases (MAO), are also associated with mental disorders, including depression. Considering this, antioxidant and MAO-A activity inhibitory potential of six 2,3-chalcogenodihydrobenzofurans (2,3-DHBF) was investigated through in vitro and in silico tests.

The comparison of pathogenic role and mechanism of Kallistatin and PEDF in tumors.

Tumors are diseases caused by abnormal cell division and growth, which can be life-threatening if not treated properly. Serpin inhibitors play a crucial role in regulating pathophysiological process and are promising drug targets. Kallistatin (SERPINA4) and Pigment Epithelium-Derived Factor (PEDF, SERPINF1) are two serpins that lack protease inhibitory activity but are abundant in blood.

The PPAR-α agonist oleoyethanolamide (OEA) ameliorates valproic acid-induced steatohepatitis in rats via suppressing Wnt3a/β-catenin and activating PGC-1α: Involvement of network pharmacology and molecular docking.

Liver damage is one of the most severe side effects of valproic acid (VPA) therapy. Research indicates that PPAR-α prevents Wnt3a/β-catenin-induced PGC-1α dysregulation, which is linked to liver injury. Although PPAR-α activation has hepatoprotective effects, its role in preventing VPA-induced liver injury remains unclear.

Derivatization of ophiobolin A and cytotoxicity toward breast and glioblastoma cancer stem cells: Varying the ketone and unsaturated aldehyde moieties.

To gain further insights into the importance of the unsaturated 1,4-ketoaldehyde moiety of ophiobolin A (OpA) for the potency and selectivity observed toward cancer stem cells, several derivatives were synthesized through controlled reduction and oxidations of the unsaturated aldehyde and ketone moieties. Structure elucidation of these new OpA derivatives was achieved through detailed NMR studies and comparison to OpA and known isolated congeners possessing variations in these regions. The relative stereochemistry of the newly generated stereocenters was determined by coupling constants in conjunction with conformational analyses (DFT) of the synthetic derivatives.

Occurrence and allele frequencies of genetic variants associated with Varroa drone brood resistance (DBR) in African Apis mellifera subspecies.

The ectoparasite Varroa destructor is a major contributor to the global decline of honeybee colonies (Apis mellifera), especially in the Northern Hemisphere. However, Varroa-resistant honeybee populations have been reported in various regions around the globe, including Europe and Africa. This resistance is primarily attributed to the trait known as Suppressed Mite Reproduction (SMR), which significantly reduces the reproductive success of Varroa mites within these colonies.

Structure and self-association of Arrestin-1.

Arrestins halt cell signaling by binding to phosphorylated activated G protein-coupled receptors. Arrestin-1 binds to rhodopsin, arrestin-4 binds to cone opsins, and arrestins-2,3 bind to the rest of GPCRs. In addition, it has been reported that arrestin-1 is functionally expressed in mouse cone photoreceptors.

A conserved chaperone protein is required for the formation of a non-canonical type VI secretion system spike tip complex.

Type VI secretion systems (T6SS) are dynamic protein nanomachines found in Gram-negative bacteria that deliver toxic effector proteins into target cells in a contact-dependent manner. Prior to secretion, many T6SS effector proteins require chaperones and/or accessory proteins for proper loading onto the structural components of the T6SS apparatus. However, despite their established importance, the precise molecular function of several T6SS accessory protein families remains unclear.

A novel FOXM1-BCL2A1 axis determines unfavourable response to venetoclax in AML.

Forkhead box M1 (FOXM1), a Forkhead family transcription factor, is often overexpressed in a variety of human cancers, including AML and strongly associated with therapy resistance and unfavourable outcomes. In AML with NPM1 mutations NPM1/FOXM1 complex sequesters FOXM1 in the cytoplasm and confers favourable treatment outcomes for AML patients, because of FOXM1 inactivation. Inhibition of FOXM1 in AML cell lines and animal models of AML sensitizes AML cells to the Bcl2-inhibitor, venetoclax.

Localized K63 ubiquitin signaling is regulated by VCP/p97 during oxidative stress.

Under stress conditions, cells reprogram their molecular machineries to mitigate damage and promote survival. Ubiquitin signaling is globally increased during oxidative stress, controlling protein fate and supporting stress defenses at several subcellular compartments. However, the rules driving subcellular ubiquitin localization to promote concerted response mechanisms remain understudied.

Molecular basis of vitamin K driven γ-carboxylation at membrane interface.

The γ-carboxylation of glutamate residues enables Ca-mediated membrane assembly of protein complexes that support broad physiological functions including hemostasis, calcium homeostasis, immune response, and endocrine regulation. Modulating γ-carboxylation level provides prevalent treatments for hemorrhagic and thromboembolic diseases. This unique posttranslational modification requires vitamin K hydroquinone (KH) to drive highly demanding reactions catalyzed by the membrane-integrated γ-carboxylase (VKGC).

A cis-regulatory element controls expression of histone deacetylase 9 to fine-tune inflammasome-dependent chronic inflammation in atherosclerosis.

Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are a major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association and its proinflammatory properties, we examined the mechanisms whereby HDAC9 regulates vascular inflammation. HDAC9 bound and mediated deacetylation of NLRP3 in the NACHT and LRR domains leading to inflammasome activation and lytic cell death.

Projection-targeted photopharmacology reveals distinct anxiolytic roles for presynaptic mGluR2 in prefrontal- and insula-amygdala synapses.

Dissecting how membrane receptors regulate neural circuits is critical for deciphering principles of neuromodulation and mechanisms of drug action. Here, we use a battery of optical approaches to determine how presynaptic metabotropic glutamate receptor 2 (mGluR2) in the basolateral amygdala (BLA) controls anxiety-related behavior in mice. Using projection-specific photopharmacological activation, we find that mGluR2-mediated presynaptic inhibition of ventromedial prefrontal cortex (vmPFC)-BLA, but not posterior insular cortex (pIC)-BLA, connections produces a long-lasting decrease in spatial avoidance.

Analysis of serum natalizumab concentrations obtained during routine clinical care in patients with multiple sclerosis: A cross-sectional study.

Background: Natalizumab is a humanized monoclonal antibody administered at a fixed dose of 300 mg intravenously or subcutaneously every 4-6 weeks to treat relapsing-remitting multiple sclerosis. In this prospective cross-sectional study, natalizumab serum concentrations obtained during routine healthcare were measured, and the relationships between different routes of administration, sampling times, body characteristics, changes in blood count, and presence of anti-natalizumab antibodies were evaluated.

Methods: Ninety-two patients were included in this study.

Design, synthesis, and antiviral activity of fragmented-lapatinib aminoquinazoline analogs towards SARS-CoV-2 inhibition.

The severe impact of COVID-19 on global health and economies highlights the critical need for innovative treatments. Recently, lapatinib, a drug initially used for breast cancer, has been identified as a potential inhibitor of the main protease (Mpro) of SARS-CoV-2, meriting further investigation. Utilizing rational design strategies and guided by MD simulations, we developed novel aminoquinazoline analogs based on fragmented lapatinib's structure.

Transforming growth factor beta induces interleukin-11 expression in osteoarthritis.

Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and possesses both pro- and anti-inflammatory properties. IL-11 activates its target cells via binding to a membrane-bound IL-11R and subsequent formation of a homodimer of the signal-transducing receptor gp130. Thus, the expression pattern of the IL-11R determines which cells can be activated by IL-11.

Ultrasound-assisted enhancement of bioactive compounds in hawthorn vinegar: A functional approach to anticancer and antidiabetic effects.

In this study, the effects of ultrasound treatment on bioactive components and functional properties of hawthorn vinegar (Crataegus tanacetifolia) were investigated. Parameters such as total phenolic compound (TPC), total flavonoid content (TFC), ascorbic acid (AA), DPPH radical scavenging activity and CUPRAC reducing capacity were optimised by surface response method (RSM) and 14 min duration and 61.40 % amplitude were determined as the most suitable treatment conditions.

Exploring wood-derived biochar potential for electrochemical sensing of fungicides mancozeb and maneb in environmental water samples.

The sustainable material, biochar (BC) from a hardwood source, was synthesized via pyrolysis process at 400 °C (BC400) and 700 °C (BC700) and used as a modifier during the electrochemical sensor design. The prepared BCs were characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, and elemental analysis (CHNS). The development of rapid analytical techniques for detecting pesticides employing a low-cost carbon paste electrode (CPE) modified with BC is a novel strategy to provide a sensitive response to water pollution.

Potential for application of direct thrombin inhibitors isolated from Euphorbia resinifera O.Berg latex in fibrin clot formation.

Direct thrombin inhibitors (designated as EuRL-DTIs) were partially purified from ethanol extracts of Euphorbia resinifera O.Berg latex. The obtained EuRL-DTIs comprised four major compounds: two isomers of phenolic compounds (CHO) and two amide compounds (tentatively identified as CHNO and CHNO), as identified by liquid chromatography and electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, and/or nuclear magnetic resonance (NMR) spectroscopy.

The secreted protease ADAMTS18 links early isoform transformation and maturation of glomerular basement membrane macromolecules to the integrity of the glomerular filtration barrier.

The glomerular filtration barrier (GFB) has a unique spatial structure, including porous capillary endothelial cells, glomerular basal membrane (GBM) and highly specialized podocytes. This special structure is essential for the hemofiltration process of nephrons. GBM is the central meshwork structure of GFB formed by the assembly and fusion of various extracellular matrix (ECM) macromolecules, such as laminins and collagens, which undergo isoform transformation and maturation that may require precise regulation by metalloproteinases.

Plasma phosphorylated tau217 strongly associates with memory deficits in the Alzheimer's disease spectrum.

Plasma phosphorylated tau biomarkers open unprecedented opportunities for identifying carriers of Alzheimer's disease pathophysiology in early disease stages using minimally invasive techniques. Plasma p-tau biomarkers are believed to reflect tau phosphorylation and secretion. However, it remains unclear to what extent the magnitude of plasma p-tau abnormalities reflects neuronal network disturbance in the form of cognitive impairment.

An alternative approach to biokinetic modelling for phenol pollutant degradation and microbial growth using Genetic Programming.

Biokinetic models can optimise pollutant degradation and enhance microbial growth processes, aiding to protect ecosystem protection. Traditional biokinetic approaches (such as Monod, Haldane, etc.) can be challenging, as they require detailed knowledge of the organism's metabolism and the ability to solve numerous kinetic differential equations based on the principles of micro, molecular biology and biochemistry (first engineering principles) which can lead to discrepancies between predicted and actual degradation rates.

Discovery of a MET-driven monogenic cause of steatotic liver disease.

Background Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about a third of adults worldwide and is projected soon to be the leading cause of cirrhosis. It occurs when fat accumulates in hepatocytes and can progress to metabolic dysfunction-associated steatohepatitis (MASH), liver cirrhosis, and hepatocellular carcinoma. MASLD pathogenesis is believed to involve a combination of genetic and environmental risk factors.

Acute encephalopathy without hyperammonemia has a different presentation than overt hepatic encephalopathy and displays similarly severe prognosis.

Background And Aims: In cirrhosis, some patients display acute encephalopathy without hyperammonemia (NonHep E) which is not considered as overt hepatic encephalopathy (OHE). We aimed to assess the prevalence and characteristics of NonHep E and OHE in cirrhotic patients displaying acute encephalopathy, assess their respective prognosis and compare it to other causes of acute decompensation (AD) with/without hyperammonemia.

Approach And Results: We conducted a retrolective analysis from a prospective cohort of patients hospitalized for AD.