Scyllatoxin-based peptide design for E. coli expression and HIV gp120 binding.

Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins.

The Biodistribution of Replication-Defective Simian Adenovirus 1 Vector in a Mouse Model.

The administration route affects the biodistribution of a gene transfer vector and the expression of a transgene. A simian adenovirus 1 vector carrying firefly luciferase and GFP reporter genes (SAdV1-GFluc) were constructed, and its biodistribution was investigated in a mouse model by bioluminescence imaging and virus DNA tracking with real-time PCR. Luciferase activity and virus DNA were mainly found in the liver and spleen after the intravenous administration of SAdV1-GFluc.

Radiation Dose Does Not Affect the Predictive Value of Thyroid Biopsy for Diagnosing Papillary Thyroid Cancer in a Belarusian Cohort Exposed to Chernobyl Fallout.

Introduction: The Chernobyl nuclear accident exposed residents of contaminated territories to substantial quantities of radioiodines and was followed by an increase in thyroid cancer, primarily papillary thyroid cancer (PTC), among exposed children and adolescents. Although thyroid biopsy is an essential component of screening programs following accidental exposure to radioiodines, it is unknown whether the predictive value of biopsy is affected by different levels of environmental exposure.

Methods: A cohort of 11,732 Belarusians aged ≤18 years at the time of the Chernobyl accident with individual thyroid radiation dose estimates was screened at least once 11-22 years later.

Virtual screening and identification of promising therapeutic compounds against drug-resistant β-ketoacyl-acyl carrier protein synthase I (KasA).

The emergence of new () strains resistant to the key drugs currently used in the clinic for tuberculosis treatment can substantially reduce the probability of therapy success, causing the relevance and importance of studies on the development of novel potent antibacterial agents targeting different vulnerable spots of . In this study, 28,860 compounds from the library of bioactive molecules were screened to identify novel potential inhibitors of β-ketoacyl-acyl carrier protein synthase I (KasA), one of the key enzymes involved in the biosynthesis of mycolic acids of the cell wall. In doing so, we used a structure-based virtual screening approach to drug repurposing that included high-throughput docking of the C171Q KasA enzyme with compounds from the library of bioactive molecules including the FDA-approved drugs and investigational drug candidates, assessment of the binding affinity for the docked ligand/C171Q KasA complexes, and molecular dynamics simulations followed by binding free energy calculations.

Repurposing Navitoclax to block SARS-CoV-2 fusion and entry by targeting heptapeptide repeat sequence 1 in S2 protein.

Along with the long pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has come the dilemma of emerging viral variants of concern (VOC), particularly Omicron and its subvariants, able to deftly escape immune surveillance and the otherwise protective effect of current vaccines and antibody drugs. We previously identified a peptide-based pan-CoV fusion inhibitor, termed as EK1, able to bind the HR1 region in viral spike (S) protein S2 subunit. This effectively blocked formation of the six-helix bundle (6-HB) fusion core and, thus, showed efficacy against all human coronaviruses (HCoVs).

Recall of residential history and dietary habits during pregnancy and lactation in the distant past: reliability of questionnaire-based radiation doses for persons exposed in utero and early life.

This study evaluates the reliability of information obtained by standardized questionnaires used in by personal interviews for estimation of radiation thyroid doses of 1065 individuals in the Belarusian cohort of individuals who were exposed in utero and early life following the Chernobyl accident in April 1986. Data from two interviews conducted in 2012-2017 and in 2018-2022 with mothers, who were pregnant or gave birth shortly after the Chernobyl accident, were analysed. The most reliable answers dealt with various attributes related to residential history.

AI-Driven De Novo Design and Molecular Modeling for Discovery of Small-Molecule Compounds as Potential Drug Candidates Targeting SARS-CoV-2 Main Protease.

Over the past three years, significant progress has been made in the development of novel promising drug candidates against COVID-19. However, SARS-CoV-2 mutations resulting in the emergence of new viral strains that can be resistant to the drugs used currently in the clinic necessitate the development of novel potent and broad therapeutic agents targeting different vulnerable spots of the viral proteins. In this study, two deep learning generative models were developed and used in combination with molecular modeling tools for de novo design of small molecule compounds that can inhibit the catalytic activity of SARS-CoV-2 main protease (Mpro), an enzyme critically important for mediating viral replication and transcription.

Cost minimizing planning of container inspection and repair in multiple facilities.

A problem of optimal mid-term or long-term planning of inspection and repair of freight containers in multiple facilities is introduced and investigated. The containers are of different types and quality levels, which define their repair costs and workforce requirements. The objective function includes the total holding, inspection, repair, transportation and rejection costs.

Doses from external irradiation and ingestion of Cs, Cs and Sr of the population of Belarus accumulated over 35 years after the Chernobyl accident.

This study considers the exposure of the population of the most contaminated Gomel and Mogilev Oblasts in Belarus to prolonged sources of irradiation resulting from the Chernobyl accident. Dose reconstruction methods were developed and applied in this study to estimate the red bone-marrow doses (RBMs) from (i) external irradiation from gamma-emitting radionuclides deposited on the ground and (ii) Cs, Cs and Sr ingestion with locally produced foodstuffs. The mean population-weighted RBM doses accumulated during 35 years after the Chernobyl accident were 12 and 5.

Evaluation of I transfer in the environment based on the available measurements made in Belarus after the Chernobyl accident.

This study evaluates the I transfer from ground deposition to the human thyroid gland after the Chernobyl accident using measurements of I concentrations in 1,252 soil, 124 grass, and 136 cow's milk samples as well as I thyroid activity measured in 3,100 individuals included in the Belarusian-American cohort. The following parameters of an I environmental transfer model used to calculate thyroid doses were evaluated in this study: (i) the interception factor of I by pasture grass, which was described by a purely empirical equation, (ii) the removal rate of I from pasture grass due to weathering and growth dilution, estimated to be 0.0676 d (half-life of 10.

Aberrant IKZF1 gene as relapse predictor in standard-risk pediatric patients with B-cell precursor acute lymphoblastic leukaemia.

Introduction: Worldwide, the B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) treatment protocols are based on risk-adaptive therapy, that is on the search for biological markers for stratification by risk groups for optimal management. Depending on the treatment protocol, deletions and overexpression of non-functional IKZF1 isoforms act as relapse predictors in ALL. We investigated the IKZF1 gene aberrations as the substantive marker for predicting the development of relapse or adverse events when using risk stratification from ALL-MB-2002/2008 protocols.

In silico design and computational evaluation of novel 2-arylaminopyrimidine-based compounds as potential multi-targeted protein kinase inhibitors: application for the native and mutant (T315I) Bcr-Abl tyrosine kinase.

An integrated computational approach to drug discovery was used to identify novel potential inhibitors of the native and mutant (TI) Bcr-Abl tyrosine kinase, the enzyme playing a key role in the pathogenesis of chronic myeloid leukemia (CML). This approach included i) design of chimeric molecules based on the 2-arylaminopyrimidine fragment, the main pharmacophore of the Abl kinase inhibitors imatinib and nilotinib used in the clinic for the CML treatment, ii) molecular docking of these compounds with the ATP-binding site of the native and mutant Abl kinase, iii) refinement of the ligand-binding poses by the quantum chemical method PM7, iv) molecular dynamics simulations of the ligand/Abl complexes, and v) prediction of the ligand/Abl binding affinity in terms of scoring functions of molecular docking, machine learning, quantum chemistry, and molecular dynamics. As a result, five top-ranking compounds able to effectively block the enzyme catalytic site were identified.

Small-molecule HIV-1 entry inhibitors targeting the epitopes of broadly neutralizing antibodies.

Highly active antiretroviral therapy currently used for HIV/AIDS has significantly increased the life expectancy of HIV-infected individuals. It has also improved the quality of life, reduced mortality, and decreased the incidence of AIDS and HIV-related conditions. Currently, however, affected individuals are typically on a lifetime course of several therapeutic drugs, all with the potential for associated toxicity and emergence of resistance.

Intelligent Mining of Urban Ventilation Corridors Based on High-Precision Oblique Photographic Images.

With the advancement of urbanization and the impact of industrial pollution, the issue of urban ventilation has attracted increasing attention. Research on urban ventilation corridors is a hotspot in the field of urban planning. Traditional studies on ventilation corridors mostly focus on qualitative or simulated research on urban climate issues such as the intensified urban heat island effect, serious environmental pollution, and insufficient climate adaptability.

Comparative pathological characteristics of papillary thyroid carcinoma with second primary non-thyroid malignancies in the region affected by the Chernobyl accident.

The aim was to study the pathological features of papillary thyroid carcinoma diagnosed with or before second primary malignancy in patients exposed to post-Chernobyl exposure. The patients selected (n = 6559) were those exposed to radiation at the age of ≤ 18 years old and developed papillary thyroid carcinoma during the years 1990-2020. Of these, 2.

Thyroid dose estimates for the genome-wide association study of thyroid cancer in persons exposed in Belarus to 131I after the Chernobyl accident.

The Chernobyl accident on 26 April 1986 led to a sharp increase in thyroid cancer (TC) incidence in the individuals exposed to radiation in childhood. The major risk factor for TC was exposure to Iodine-131 (131I). Here, we estimated the thyroid doses due to 131I intake for 2041 participants of the genome-wide association study of TC in Belarusian people exposed to radioactive fallout from the Chernobyl accident.

Integration of complete ensemble empirical mode decomposition with deep long short-term memory model for particulate matter concentration prediction.

The atmospheric particulate matter (PM) with a diameter of 2.5 μm or less (PM2.5) is one of the key indicators of air pollutants.

Clinical benefits of single vs repeated courses of mesenchymal stem cell therapy in epilepsy patients.

Purpose: Epilepsy is defined as "drug-resistant" when existing anti-epileptic drugs (AED) are found to have minimal to no effect on patient's condition. Therefore the search and testing of new treatment strategies is warranted. This study focuses on the effects of autologous mesenchymal stem cells (MSC) in drug-resistant epilepsy patients within a Phase I/II open-label registered clinical trial NCT02497443.

Rapid Artificial Intelligence Solutions in a Pandemic - The COVID-19-20 Lung CT Lesion Segmentation Challenge.

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of the disease. We organized an international challenge and competition for the development and comparison of AI algorithms for this task, which we supported with public data and state-of-the-art benchmark methods. Board Certified Radiologists annotated 295 public images from two sources (A and B) for algorithms training (n=199, source A), validation (n=50, source A) and testing (n=23, source A; n=23, source B).

A survey on applications of deep learning in microscopy image analysis.

Advanced microscopy enables us to acquire quantities of time-lapse images to visualize the dynamic characteristics of tissues, cells or molecules. Microscopy images typically vary in signal-to-noise ratios and include a wealth of information which require multiple parameters and time-consuming iterative algorithms for processing. Precise analysis and statistical quantification are often needed for the understanding of the biological mechanisms underlying these dynamic image sequences, which has become a big challenge in the field.

Hyperthermic intraperitoneal chemotherapy in prevention of gastric cancer metachronous peritoneal metastases: a systematic review.

Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various options of preventing metachronous peritoneal metastases in radically operated gastric cancer patients. Also examined are different hyperthermic intraperitoneal chemotherapy (HIPEC) regimens employed in gastric cancer treatment, postoperative morbidity and mortality rates and long-term treatment outcomes.