Precious2GPT: the combination of multiomics pretrained transformer and conditional diffusion for artificial multi-omics multi-species multi-tissue sample generation.

Synthetic data generation in omics mimics real-world biological data, providing alternatives for training and evaluation of genomic analysis tools, controlling differential expression, and exploring data architecture. We previously developed Precious1GPT, a multimodal transformer trained on transcriptomic and methylation data, along with metadata, for predicting biological age and identifying dual-purpose therapeutic targets potentially implicated in aging and age-associated diseases. In this study, we introduce Precious2GPT, a multimodal architecture that integrates Conditional Diffusion (CDiffusion) and decoder-only Multi-omics Pretrained Transformer (MoPT) models trained on gene expression and DNA methylation data.

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease with a high mortality rate. Putative drug targets in IPF have failed to translate into effective therapies at the clinical level. We identify TRAF2- and NCK-interacting kinase (TNIK) as an anti-fibrotic target using a predictive artificial intelligence (AI) approach.

PandaOmics: An AI-Driven Platform for Therapeutic Target and Biomarker Discovery.

PandaOmics is a cloud-based software platform that applies artificial intelligence and bioinformatics techniques to multimodal omics and biomedical text data for therapeutic target and biomarker discovery. PandaOmics generates novel and repurposed therapeutic target and biomarker hypotheses with the desired properties and is available through licensing or collaboration. Targets and biomarkers generated by the platform were previously validated in both and studies.

Biomedical generative pre-trained based transformer language model for age-related disease target discovery.

Target discovery is crucial for the development of innovative therapeutics and diagnostics. However, current approaches often face limitations in efficiency, specificity, and scalability, necessitating the exploration of novel strategies for identifying and validating disease-relevant targets. Advances in natural language processing have provided new avenues for predicting potential therapeutic targets for various diseases.

Precious1GPT: multimodal transformer-based transfer learning for aging clock development and feature importance analysis for aging and age-related disease target discovery.

Aging is a complex and multifactorial process that increases the risk of various age-related diseases and there are many aging clocks that can accurately predict chronological age, mortality, and health status. These clocks are disconnected and are rarely fit for therapeutic target discovery. In this study, we propose a novel approach to multimodal aging clock we call Precious1GPT utilizing methylation and transcriptomic data for interpretable age prediction and target discovery developed using a transformer-based model and transfer learning for case-control classification.

Kinetic Intricacies of the Light Emission and Antiradical Influence of Exogenous Bioantioxidants Transformation Products in the Chemiluminescence Bioantioxidant Assay.

The subject matter of the reported work refers to studying the interactions followed by the excited-state generation, which are chemical models of oxidative processes leading to a weak light emission emerging from living cells, and to explore the possibilities of using them as tools for evaluating the activity of oxygen-metabolism modulators, most prominently, natural bioantioxidants of biomedical value in particular. Methodologically, major attention is paid to analyzing the shapes of the time profiles of the light emission derived from a model sensory system in the presence of lipid samples of vegetable and animal (fish) origin rich in bioantioxidants. As a result, a modified reaction mechanism involving 12 elementary steps is proposed to rationalize the light-emission kinetics in the presence of natural bioantioxidants.

AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor.

The application of artificial intelligence (AI) has been considered a revolutionary change in drug discovery and development. In 2020, the AlphaFold computer program predicted protein structures for the whole human genome, which has been considered a remarkable breakthrough in both AI applications and structural biology. Despite the varying confidence levels, these predicted structures could still significantly contribute to structure-based drug design of novel targets, especially the ones with no or limited structural information.

COVIDomic: A multi-modal cloud-based platform for identification of risk factors associated with COVID-19 severity.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in December 2019 in Wuhan, China. It was quickly established that both the symptoms and the disease severity may vary from one case to another and several strains of SARS-CoV-2 have been identified. To gain a better understanding of the wide variety of SARS-CoV-2 strains and their associated symptoms, thousands of SARS-CoV-2 genomes have been sequenced in dozens of countries.

Optimization of small RNA extraction and comparative study of NGS library preparation from low count sperm samples.

Recent studies demonstrate that sperm epigenome is a vehicle that conveys paternal experiences to offspring phenotype. That evidence triggers interest of both experimental and epidemiological studies of epigenetic markers in sperm. Since samples are often unique in epidemiological studies, a careful and efficient use of the material is a critical requirement.

Aging Induces Profound Changes in sncRNA in Rat Sperm and These Changes Are Modified by Perinatal Exposure to Environmental Flame Retardant.

Advanced paternal age at fertilization is a risk factor for multiple disorders in offspring and may be linked to age-related epigenetic changes in the father's sperm. An understanding of aging-related epigenetic changes in sperm and environmental factors that modify such changes is needed. Here, we characterize changes in sperm small non-coding RNA (sncRNA) between young pubertal and mature rats.

Comparative analysis of novel MGISEQ-2000 sequencing platform vs Illumina HiSeq 2500 for whole-genome sequencing.

The MGISEQ-2000 developed by MGI Tech Co. Ltd. (a subsidiary of the BGI Group) is a new competitor of such next-generation sequencing platforms as NovaSeq and HiSeq (Illumina).

Rat liver epigenome programing by perinatal exposure to 2,2',4'4'-tetrabromodiphenyl ether.

Perinatal exposures to polybrominated diphenyl ethers permanently reprogram liver metabolism and induce a nonalcoholic fatty liver disease-like phenotype and insulin resistance in rodents. To test if these changes are associated with altered liver epigenome. Expression of small RNA and changes in DNA methylation in livers of adult rats were analyzed following perinatal exposure to 2,2',4,4'-tetrabromodiphenyl ether, the polybrominated diphenyl ether congener most prevalent in human tissues.

Comparative Whole-Transcriptome Profiling of Liver Tissue from Wistar Rats Fed with Diets Containing Different Amounts of Fat, Fructose, and Cholesterol.

Differential expression of 30,003 genes was studied in the liver of female Wistar rats fed with isocaloric diets with the excess of fat, fructose, or cholesterol, or their combinations for 62 days using the method of whole-transcriptome profiling on a microchip. Relative mRNA expression levels of the Asah2, Crot, Crtc2, Fmo3, GSTA2, LOC1009122026, LOC102551184, NpY, NqO1, Prom1, Retsat, RGD1305464, Tmem104, and Whsc1 genes were also determined by RT-qPCR. All the tested diets affected differently the key metabolic pathways (KEGGs).

[Role of contrast enhancement in ultrasound examination of the aortic abdominal portion].

Analysed herein are the data of scientific literature over several last years concerning the use of contrast-enhanced ultrasonography (CEUS) of the abdominal portion of the aorta. Based on the results of Russian and foreign studies, the authors analyse feasibility of using CEUS in various pathological conditions of the aorta, as well as sensitivity, specificity, and prognostic value of the method. Also discussed are advantages and limitations of CEUS compared with other imaging techniques.

Bromination of bis-(pyridin-2-yl) diselenide in methyl-ene chloride: the reaction mechanism and crystal structures of 1-pyridine-2-selenenyl dibromide and its cyclo-adduct with cyclo-pentene (3a,9a)-2,3,3a,9a-tetra-hydro-1-cyclo-penta-[4,5][1,3]selenazolo[3,2-]pyridinium bromide.

1-Pyridine-2-selenenyl dibromide, CHNSeBr, , is a product of the bromination of bis-(pyridin-2-yl) diselenide in methyl-ene chloride recrystallization from methanol. Compound is essentially zwitterionic: the negative charge resides on the SeBr moiety and the positive charge is delocalized over the pyridinium fragment. The C-Se distance of 1.

Analysis of excitatory and inhibitory neuron types in the inferior colliculus based on properties.

The inferior colliculus (IC) is a large midbrain nucleus that integrates inputs from many auditory brainstem and cortical structures. Despite its prominent role in auditory processing, the various cell types and their connections within the IC are not well characterized. To further separate GABAergic and non-GABAergic neuron types according to their physiological properties, we used a mouse model that expresses channelrhodopsin and enhanced yellow fluorescent protein in all GABAergic neurons and allows identification of GABAergic cells by light stimulation.

Dissolution of chitosan nanocrystals in aqueous media of different acidity. Molecular dynamic study.

The process of dissolution of chitosan nanocrystals with molecular mass of polymer up to 12.8 kDa in aqueous media of various pH was studied by molecular dynamic simulations with the use of the improved force field GROMOS 56A specially developed for the chitosan polymers description. The effect of the media acidity and polymer molecular weight on the dissolution process kinetics has been studied and the regression expressions for kinetic parameters were established.

Updating the Chemiluminescence Oxygen-Aftereffect Method for Determining the Rate Constant of the Peroxy-Radical Self-Reaction: Oxidation of Cyclohexene.

Updating the facile chemiluminescence oxygen-aftereffect method, most suitable for determining the rate constant (k ) of the peroxy-radical self-reaction (main chemiluminescence channel), pertained to considering the sensitivity of such a method toward a disturbing influence of the peroxy radicals of the initiator of the chain oxidation process. Such a disturbance may derive from the side chemiluminescent reaction, which involves peroxy radicals of both hydrocarbon and initiator. To examine the applicability and limitations of the chemiluminescence method under present scrutiny, cyclohexene was used as the model oxidizable hydrocarbon substrate.

How to reconcile wood production and biodiversity conservation? The Pan-European boreal forest history gradient as an "experiment".

There are currently competing demands on Europe's forests and the finite resources and services that they can offer. Forestry intensification that aims at mitigating climate change and biodiversity conservation is one example. Whether or not these two objectives compete can be evaluated by comparative studies of forest landscapes with different histories.

Transcription profile analysis of the endometrium revealed molecular markers of the personalized 'window of implantation' during in vitro fertilization.

To determine the most informative markers for assessing the functional state of endometrium during the 'window of implantation' and creating a model for assessment of the readiness of endometrium for embryo implantation. Forty-seven women with tubal infertility and a successful IVF pregnancy participated in the study. Pipelle endometrial sample was performed during the supposed 'window of implantation' in natural cycle with subsequent histological study, and transcriptional profile of genes GPX3, PAEP, DPP4, TAGLN, HABP2, IMPA2, AQP3, HLA-DOB, MSX1, POSTN determined by real-time quantitative polymerase chain reaction (qRT-PCR).

Method of Selection of Bacteria Antibiotic Resistance Genes Based on Clustering of Similar Nucleotide Sequences.

A new method for selection of bacterium antibiotic resistance genes is proposed and tested for solving the problems related to selection of primers for PCR assay. The method implies clustering of similar nucleotide sequences and selection of group primers for all genes of each cluster. Clustering of resistance genes for six groups of antibiotics (aminoglycosides, β-lactams, fluoroquinolones, glycopeptides, macrolides and lincosamides, and fusidic acid) was performed.

Modification of 56A force field for molecular dynamic calculations of chitosan and its derivatives.

The GROMOS 56A force field for the description of carbohydrates was modified for calculations of chitosan (poly-1,4-(N-acetyl)-β-D-glucopyranosamine-2) with protonated and non-protonated amino groups and its derivatives. Additional parameterization was developed on the basis of quantum chemical calculations. The modified force field (56A) allows performing the molecular dynamic calculations of chitosans with different degrees of protonation corresponding to various acidity of medium.

Green infrastructure development at European Union's eastern border: Effects of road infrastructure and forest habitat loss.

The functionality of forest patches and networks as green infrastructure may be affected negatively both by expanding road networks and forestry intensification. We assessed the effects of (1) the current and planned road infrastructure, and (2) forest loss and gain, on the remaining large forest landscape massifs as green infrastructure at the EU's eastern border region in post-socialistic transition. First, habitat patch and network functionality in 1996-98 was assessed using habitat suitability index modelling.

The expanding repertoire of G4 DNA structures.

The definition of DNA and RNA G-quadruplexes (G4s) has recently been broadened to include structures with certain defects: bulges, G-vacancies or mismatches. Despite the striking progress in computational methods for assessing G4 folding propensity, predicting G4s with defects remains problematic, reflecting the enhanced sequential diversity of these motifs. "Imperfect" G4 motifs, i.

Does Frailty Predict Health Care Utilization in Community-Living Older Romanians?

Background. The predictive value of frailty assessment is still debated. We analyzed the predictive value of frailty of independent living elderly.