The cysteine protease legumain decreases glucose metabolism and enhances fatty acid uptake in human myotubes.

Skeletal muscle has an important role in whole body energy metabolism and various proteases are involved in skeletal muscle functions. We have previously identified the cysteine protease legumain in cultured human skeletal muscle cells. However, the potential role of legumain in regulation of energy metabolism remains unexplored.

Combination of Coevolutionary Information and Supervised Learning Enables Generation of Cyclic Peptide Inhibitors with Enhanced Potency from a Small Data Set.

Computational generation of cyclic peptide inhibitors using machine learning models requires large size training data sets often difficult to generate experimentally. Here we demonstrated that sequential combination of Random Forest Regression with the pseudolikelihood maximization Direct Coupling Analysis method and Monte Carlo simulation can effectively enhance the design pipeline of cyclic peptide inhibitors of a tumor-associated protease even for small experimental data sets. Further studies showed that such -evolved cyclic peptides are more potent than the best peptide inhibitors previously developed to this target.

Detection of Putative Ligand Dissociation Pathways in Proteins Using Site-Identification by Ligand Competitive Saturation.

Drug efficacy often correlates better with dissociation kinetics than binding affinity alone. To study binding kinetics computationally, it is necessary to identify all of the possible ligand dissociation pathways. The site identification by ligand competitive saturation (SILCS) method involves the precomputation of a set of maps (FragMaps), which describe the free energy landscapes of typical chemical functionalities in and around a target protein or RNA.

Titanium Dioxide Nanoparticles Negatively Influence Gill Metabolism in .

Background: In recent years, titanium dioxide (TiO) nanoparticles (NPs) have been widely used in various industries due to their favorable chemical properties, and their contamination of the environment has attracted much attention, especially to aquatic animals.

Methods: Therefore, we assessed the impact of TiO NPs (5 mg/L) on the marine bivalve, pearl oyster (), especially gill metabolism. Pearl oysters were exposed to seawater containing 5 mg/L TiO NPs for 14 days, followed by 7 days of recovery in untreated seawater.

Influence of Different Measuring Backgrounds on the Classification of Multilayer Polyolefin Films Using a Near-Infrared Handheld Spectrometer.

The low thickness of plastic films poses a challenge when using near-infrared (NIR) spectroscopy as it affects the spectral quality and classification. This research focuses on offering a solution to the challenge of classifying multilayer plastic film materials with a focus on polyolefin multilayer plastics. It presents the importance of spectral quality on accurate classification.

A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer.

Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).

Deciphering regulatory architectures of bacterial promoters from synthetic expression patterns.

For the vast majority of genes in sequenced genomes, there is limited understanding of how they are regulated. Without such knowledge, it is not possible to perform a quantitative theory-experiment dialogue on how such genes give rise to physiological and evolutionary adaptation. One category of high-throughput experiments used to understand the sequence-phenotype relationship of the transcriptome is massively parallel reporter assays (MPRAs).

Identification and occurrence of microcystins in freshwaters and fish from a eutrophic dam through LC-HRMS.

Microcystins (MCs) are cyclic heptapeptides originating from various cyanobacteria in eutrophic aquatic environments. Their potential consequences on ecosystems and public health underscores the need to explore MCs' occurrence. In this study, liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) analysis and a suspect screening workflow supported by open-source tools were employed for the determination of MCs in freshwater and biota samples from a eutrophic dam in Uruguay.

In situ characterization of amine-forming enzymes shows altered oligomeric state.

Enzyme stability can be measured in a number of ways, including melting temperature, activity retention, and size analysis. However, these measurements are often conducted in an idealized storage buffer and not in the relevant enzymatic reaction media. Particularly for reactions that occur in alkaline, volatile, and high ionic strength media, typical analyses using differential scanning calorimetry, light scattering, and sodium dodecyl-sulfate polyacrylamide gel electrophoresis are not satisfactory to track the stability of these enzymes.

Renewable energy transition in Europe in the context of renewable energy transition processes in the world. A review.

Both the global and European energy sectors have been undergoing a deep transition for several years, associated with a reduction in the overall share of conventional coal-based energy in favor of new technologies, especially energy from renewable sources (RES). This transition is moving from centralized production towards distributed technologies and from providing only energy to end users towards combining innovative products and services with it. Electricity consumers are becoming prosumers connected to the grid and generating an increasing amount of energy.

A comprehensive review on nanoparticle-based photo acoustic: current application and future prospective.

In vivo, molecular imaging is prevalent for biology research and therapeutic practice. Among advanced imaging technologies, photoacoustic (PA) imaging and sensing is gaining interest around the globe due its exciting features like high resolution and good (~ few cm) penetration depth. PA imaging is a recent development in ultrasonic technology that generates acoustic waves by absorbing optical energy.

Fractionated alpha and mixed beam radiation promote stronger pro-inflammatory effects compared to acute exposure and trigger phagocytosis.

Introduction And Methods: Aiming to evaluate safety aspects of a recently proposed approach to target Alzheimer's disease, we mimicked a complex boron neutron capture therapy field using a mixed beam consisting of high- and low-linear energy transfer (LET) radiation, Am alpha particles (α) and/or X-ray radiation respectively, in human microglial (HMC3) cells.

Results: Acute exposure to 2 Gy X-rays induced the strongest response in the formation of γH2AX foci 30 min post irradiation, while α- and mixed beam-induced damage (α:X-ray = 3:1) sustained longer. Fractionation of the same total dose (0.

Surface-enhanced Raman spectroscopy: a half-century historical perspective.

Surface-enhanced Raman spectroscopy (SERS) has evolved significantly over fifty years into a powerful analytical technique. This review aims to achieve five main goals. (1) Providing a comprehensive history of SERS's discovery, its experimental and theoretical foundations, its connections to advances in nanoscience and plasmonics, and highlighting collective contributions of key pioneers.

Guiding Competitive Binding Assays Using Protein-Protein Interaction Prediction: The HER2-Affitin Use Case.

Affitins are a class of small artificial proteins, designed as alternatives to antibodies for therapeutic, diagnostic, and biotechnological applications. Recent patents by Bracco Imaging S.p.

Additive CHARMM Force Field for Pterins and Folates.

Folates comprise a crucial class of biologically active compounds related to folic acid, playing a vital role in numerous enzymatic reactions. One-carbon metabolism, facilitated by the folate cofactor, supports numerous physiological processes, including biosynthesis, amino acid homeostasis, epigenetic maintenance, and redox defense. Folates share a common pterin heterocyclic ring structure capable of undergoing redox reactions and existing in various protonation states.

The effect of cancer cell-derived exosomal proteins on macrophage polarization: An in-depth review.

Cancer is characterized by unregulated cell proliferation, enabling it to invade and spread to different organs and tissues in the body. Cancer progression is intricately influenced by the complex dynamics within the tumor microenvironment (TME). The TME is a composite and dynamic network comprising cancer cells and various immune cells, including tumor-associated macrophages.

Exploring the role of pomalidomide in androgen-dependent prostate cancer: a computational analysis.

Prostate cancer (PC) is among the most prevalent cancers in males. It is the leading cause of death in men, in around 48 out of 185 countries. Increased androgen receptor (AR) activity is the key factor contributing to the development or progression of newly diagnosed cases of prostate cancer.

Investigating cognitive impairments and hippocampal proteome alterations in aged male rats with TAA-Induced minimal hepatic encephalopathy.

The aging population faces a gradual decline in physical and mental capacities, with an increased risk of liver cirrhosis and chronic liver diseases leading to hepatic encephalopathy (HE). The intertwining of physiological manifestations of aging with the pathophysiology of HE significantly impairs cognitive ability, reduces quality of life, and increases mortality. Hence, effective therapeutic intervention is imperative.

Effects of perfluorooctanoic acid and nano titanium dioxide on the immune response and energy allocation in Mytilus coruscus.

Perfluorooctanoic acid (PFOA) functions as a surfactant, while nano-titanium dioxide (nano-TiO) serves as an antibacterial agent. These substances are extensively utilized in industrial production and, upon release into aquatic environments, pose significant threats to the viability and development of marine organisms. However, research into the effects of PFOA and nano-TiO on the immune functions and cellular energy allocation (CEA) of bivalves remains limited.

CRISPR-Cas12a bends DNA to destabilize base pairs during target interrogation.

RNA-guided endonucleases are involved in processes ranging from adaptive immunity to site-specific transposition and have revolutionized genome editing. CRISPR-Cas9, -Cas12 and related proteins use guide RNAs to recognize ∼20-nucleotide target sites within genomic DNA by mechanisms that are not yet fully understood. We used structural and biochemical methods to assess early steps in DNA recognition by Cas12a protein-guide RNA complexes.

Altered metabolic function induced by Aβ-oligomers and PSEN1 mutations in iPSC-derived astrocytes.

Altered energy metabolism in Alzheimer's disease (AD) is a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are implicated in multiple neurodegenerative diseases. Although numerous studies have investigated global changes in brain metabolism, redox status, gene expression and epigenetic markers in AD, the intricate interplay between different metabolic processes, particularly in astrocytes, remains poorly understood.

Dynamic quinone repertoire accompanied the diversification of energy metabolism in Pseudomonadota.

It is currently unclear how Pseudomonadota, a phylum that originated around the time of the Great Oxidation Event, became one of the most abundant and diverse bacterial phyla on Earth, with metabolically versatile members colonizing a wide range of environments with different O2 concentrations. Here, we address this question by studying isoprenoid quinones, which are central components of energy metabolism covering a wide range of redox potentials. We demonstrate that a dynamic repertoire of quinone biosynthetic pathways accompanied the diversification of Pseudomonadota.

Electrified Enhanced Recovery of Lithium from Unconventional Sources.

Demand for lithium is expected to quadruple by the end of the decade. Without new sources of production, the supply-demand curve is expected to invert. Traditional geological reserves will not be able to meet the anticipated gap, thus unconventional sources of lithium will need to be utilized, setting the stage for fierce competition for perhaps the most critical of mineral resources required for the energy transition.