BioStructNet: Structure-Based Network with Transfer Learning for Predicting Biocatalyst Functions.

Enzyme-substrate interactions are essential to both biological processes and industrial applications. Advanced machine learning techniques have significantly accelerated biocatalysis research, revolutionizing the prediction of biocatalytic activities and facilitating the discovery of novel biocatalysts. However, the limited availability of data for specific enzyme functions, such as conversion efficiency and stereoselectivity, presents challenges for prediction accuracy.

Space Analogs and Behavioral Health Performance Research review and recommendations checklist from ESA Topical Team.

Space analog research has increased over the last few years with new analogs appearing every year. Research in this field is very important for future real mission planning, selection and training of astronauts. Analog environments offer specific characteristics that resemble to some extent the environment of a real space mission.

Expanding the toolbox of Baeyer-Villiger and flavin monooxygenase biocatalysts for the enantiodivergent green synthesis of sulfoxides.

Two new monooxygenase biocatalysts, the Baeyer-Villiger monooxygenase BVMO145 and the flavin monooxygenase FMO401 from Almac library, have been found to catalyse the enantiodivergent oxidation of sulfides bearing N-heterocyclic substituents into sulfoxides under mild and green conditions. The biocatalyst BVMO145 provides ()-sulfoxides while the flavin monooxygenase FMO401 affords ()-sulfoxides with good conversions and high ee.

Papain-Mediated Conjugation of Peptide Nucleic Acids to Delivery Peptides: A Density Functional Theory/Molecular Mechanics Metadynamics Study in Aqueous and Organic Solvent.

Enzymatic peptide synthesis is a powerful alternative to solid-phase methods, as enzymes can have high regio- and stereoselectivity and high yield and require mild reaction conditions. This is beneficial in formulation research due to the rise of nucleic acid therapies. Peptide nucleic acids (PNAs) have a high affinity toward DNA and RNA, and their solubility and cellular delivery can be improved via conjugation to peptides.

Programmable Interfacial Band Configuration in WS/BiOSe Heterojunctions.

van der Waals heterojunctions based on transition-metal dichalcogenides (TMDs) offer advanced strategies for manipulating light-emitting and light-harvesting behaviors. A crucial factor determining the light-material interaction is in the band alignment at the heterojunction interface, particularly the distinctions between type-I and type-II alignments. However, altering the band alignment from one type to another without changing the constituent materials is exceptionally difficult.

Application of rational enzyme engineering in a new route to etonogestrel and levonorgestrel: carbonyl reductase bioreduction of ethyl secodione.

Women in developing countries still face enormous challenges when accessing reproductive health care. Access to voluntary family planning empowers women allowing them to complete their education and join the paid workforce. This effectively helps to end poverty, hunger and promotes good health for all.

Chemical reversion of age-related oocyte dysfunction fails to enhance embryo development in a bovine model of postovulatory aging.

Purpose: There are no clinical treatments to prevent/revert age-related alterations associated with oocyte competence decline in the context of advanced maternal age. Those alterations have been attributed to oxidative stress and mitochondrial dysfunction. Our study aimed to test the hypothesis that in vitro maturation (IVM) medium supplementation with antioxidants (resveratrol or phloretin) may revert age-related oocyte competence decline.

Mitochondrial Dysfunction in Advanced Maternal Aged Cumulus Cells: A Possible Link to ATP Synthase Impairment?

Age-related changes in the mitochondrial status of human cumulus cells (hCCs) impact oocyte quality; however, the relationship between hCC mitochondrial (dys)function and reproductive aging remains poorly understood. This study aimed to establish the interplay between hCC mitochondrial dysfunction and women's reproductive potential. In this investigation, 266 women were enrolled and categorized into two groups based on their age: a young group (<35 years old) and an advanced maternal age (AMA) group (≥35 years old).

Optimization of Platelet-Rich Plasma Preparation for Regenerative Medicine: Comparison of Different Anticoagulants and Resuspension Media.

Platelet-rich plasma (PRP) has emerged as a promising therapy in regenerative medicine. However, the lack of standardization in PRP preparation protocols presents a challenge in achieving reproducible and accurate results. This study aimed to optimize the PRP preparation protocol by investigating the impact of two different anticoagulants, sodium citrate (SC) and ethylenediaminetetraacetic acid (EDTA), and resuspension media, plasma versus sodium chloride (NaCl).

Near-Infrared Light Activated Formulation for the Spatially Controlled Release of CRISPR-Cas9 Ribonucleoprotein for Brain Gene Editing.

The CRISPR/Cas9 system has emerged as a promising platform for gene editing; however, the lack of an efficient and safe delivery system to introduce it into cells continues to hinder clinical translation. Here, we report a rationally designed gene-editing nanoparticle (NP) formulation for brain applications: an sgRNA:Cas9 ribonucleoprotein complex is immobilized on the NP surface by oligonucleotides that are complementary to the sgRNA. Irradiation of the formulation with a near-infrared (NIR) laser generates heat in the NP, leading to the release of the ribonucleoprotein complex.

Designing Cell Delivery Peptides and SARS-CoV-2-Targeting Small Interfering RNAs: A Comprehensive Bioinformatics Study with Generative Adversarial Network-Based Peptide Design and Assays.

Nucleic acid technologies with designed intracellular delivery systems are some of the most promising therapies of the future. Small interfering (si)RNAs inhibit gene expression and protein synthesis and may complement current vaccines with faster design and production. Although successful delivery remains an issue, delivery peptides may help to fill this gap.

Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review.

The majority of animal studies on methylphenidate (MP) use intraperitoneal (IP) injections, subcutaneous (SC) injections, or the oral gavage route of administration. While all these methods allow for delivery of MP, it is the oral route that is clinically relevant. IP injections commonly deliver an immediate and maximum dose of MP due to their quick absorption.

Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides.

Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8-64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies.

Association Between Follicle-Stimulating Hormone Receptor (FSHR) rs6166 and Estrogen Receptor 1 (ESR1) rs2234693 Polymorphisms and Polycystic Ovary Syndrome Risk, Phenotype, and Reproductive Outcomes in an Infertile Portuguese Population.

Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder often leading to anovulatory infertility. PCOS pathophysiology is still unclear and several potential genetic susceptibility factors have been proposed. The effect of polymorphisms in two genesrelated to follicular recruitment and development, the follicle-stimulating hormone receptor () and the estrogen receptor 1 (), have been studied in different populations with contradictory results.

Nucleotides Entrapped in Liposome Nanovesicles as Tools for Therapeutic and Diagnostic Use in Biomedical Applications.

The use of nucleotides for biomedical applications is an old desire in the scientific community. As we will present here, there are references published over the past 40 years with this intended use. The main problem is that, as unstable molecules, nucleotides require some additional protection to extend their shelf life in the biological environment.

Using Markov chains and temporal alignment to identify clinical patterns in Dementia.

In the healthcare sector, resorting to big data and advanced analytics is a great advantage when dealing with complex groups of patients in terms of comorbidities, representing a significant step towards personalized targeting. In this work, we focus on understanding key features and clinical pathways of patients with multimorbidity suffering from Dementia. This disease can result from many heterogeneous factors, potentially becoming more prevalent as the population ages.

Insights into the Degradation of Polymer-Drug Conjugates by an Overexpressed Enzyme in Cancer Cells.

Intensive efforts have been made to provide better treatments to cancer patients. Currently, nanoparticle-based drug delivery systems have gained propulsion, as they can overcome the drawbacks of free drugs. However, drug stability inside the nanocapsule must be ensured to prevent burst release.

Zgli: A Pipeline for Clustering by Compression with Application to Patient Stratification in Spondyloarthritis.

The normalized compression distance (NCD) is a similarity measure between a pair of finite objects based on compression. Clustering methods usually use distances (e.g.

Direct calculation of the ionic mobility in superionic conductors.

We describe an approach based on non-equilibrium molecular dynamics (NEMD) simulations to calculate the ionic mobility of solid ion conductors such as solid electrolytes from first-principles. The calculations are carried out in finite slabs of the material, where an electric field is applied and the dynamic response of the mobile ions is measured. We compare our results with those obtained from diffusion calculations, under the non-interacting ion approximation, and with experiment.

Antidotal effect of cyclosporine A against α-amanitin toxicity in CD-1 mice, at clinical relevant doses.

Amanita phalloides is one of the most toxic mushrooms worldwide, being responsible for the majority of human fatal cases of mushroom intoxications. α-Amanitin, the most deleterious toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and renal failure.

Nanocarriers for the topical treatment of psoriasis - pathophysiology, conventional treatments, nanotechnology, regulatory and toxicology.

Psoriasis is a chronic inflammatory non-contagious disease normally characterized by a multisystemic inflammation with reddish plaques and whitish scales with greater incidence in the knees, feet and hands, elbow, scalp, and sacral areas. The global incidence of psoriasis rounds about 2% of the population and it is established that the pathophysiology of this skin disease is quite complex and still misunderstood. Nowadays, this pathology still has no cure, however, efforts are being made to find more effective and safe treatments as well as trying to decrease the occurrence of crises and complications.

An injectable, naproxen-conjugated, supramolecular hydrogel with ultra-low critical gelation concentration-prepared from a known folate receptor ligand.

Short peptides capped on the N-terminus with aromatic groups are often able to form supramolecular hydrogels-self-assembled networks of fibrils able to trap water molecules. Typically, these hydrogelators can form stiff gels at concentrations of 0.1 to 1.

Dynamic Bayesian networks for stratification of disease progression in amyotrophic lateral sclerosis.

Background And Purpose: Progression rate is quite variable in amyotrophic lateral sclerosis (ALS); thus, tools for profiling disease progression are essential for timely interventions. The objective was to apply dynamic Bayesian networks (DBNs) to establish the influence of clinical and demographic variables on disease progression rate.

Methods: In all, 664 ALS patients from our database were included stratified into slow (SP), average (AP) and fast (FP) progressors, according to the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) rate of decay.

Degradation Chemistry and Kinetic Stabilization of Magnetic CrI.

The discovery of the intrinsic magnetic order in single-layer chromium trihalides (CrX, X = I, Br, and Cl) has drawn intensive interest due to their potential application in spintronic devices. However, the notorious environmental instability of this class of materials under ambient conditions renders their device fabrication and practical application extremely challenging. Here, we performed a systematic investigation of the degradation chemistry of chromium iodide (CrI), the most studied among CrX families, a joint spectroscopic and microscopic analysis of the structural and composition evolution of bulk and exfoliated nanoflakes in different environments.