Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation.

PIM2, part of the PIM kinase family along with PIM1 and PIM3, is often overexpressed in hematologic cancers, fueling tumor growth. Despite its significance, there are no approved drugs targeting it. In response to this challenge, we devised a thorough virtual screening workflow for discovering novel PIM2 inhibitors. Our process includes molecular docking and diverse scoring methods like molecular mechanics generalized born surface area, XGBOOST, and DeepDock to rank potential inhibitors by binding affinities and interaction potential. Ten compounds were selected and subjected to an adequate evaluation of their biological activity. Compound 2 emerged as the most potent inhibitor with an IC50 of approximately 135.7 nM. It also displayed significant activity against various hematological cancers, including acute myeloid leukemia, mantle cell lymphoma, and anaplastic large cell lymphoma (ALCL). Molecular dynamics simulations elucidated the binding mode of compound 2 with PIM2, offering insights for drug development. These results highlight the reliability and efficacy of our virtual screening workflow, promising new drugs for hematologic cancers, notably ALCL.

A database for risk assessment and comparative genomic analysis of foodborne Vibrio parahaemolyticus in China.

Vibrio parahaemolyticus is a major foodborne pathogen worldwide. The increasing number of cases of V. parahaemolyticus infections in China indicates an urgent need to evaluate the prevalence and genetic diversity of this pathogenic bacterium. In this paper, we introduce the Foodborne Vibrio parahaemolyticus genome database (FVPGD), the first scientific database of foodborne V. parahaemolyticus distribution and genomic data in China, based on our previous investigations of V. parahaemolyticus contamination in different kinds of food samples across China from 2011 to 2016. The dataset includes records of 2,499 food samples and 643 V. parahaemolyticus strains from supermarkets and marketplaces distributed over 39 cities in China; 268 whole-genome sequences have been deposited in this database. A spatial view on the risk situations of V. parahaemolyticus contamination in different food types is provided. Additionally, the database provides a functional interface of sequence BLAST, core genome multilocus sequence typing, and phylogenetic analysis. The database will become a powerful tool for risk assessment and outbreak investigations of foodborne pathogens in China.

[Assessment of preclinical cognition impairment in hypertension patients with functional magnetic resonance imaging].

OBJECTIVE: To explore whether the hypertension patients with no clinical cognitive impairment manifestations have certain brain dysfunctions. METHODS: Twenty-five moderately to severely hypertensive patients, males and females, aged 63.0 +/- 1.6 (60 approximately 65), with a disease history if 5 to 10 years, and 25 sex, age, and educational level-matched healthy persons underwent tests by mini-mental status examination (MMSE) scales, state anxiety inventory (STAI-S) and trait anxiety inventory (STAI-T), and then underwent two functional magnetic resonance imaging (fMRI) studies. In Experiment 1, the subjects were demanded to listen actively to the meaningless words (pseudowords) and in Experiment 2 the subjects listened actively to real words and make the valence (abstract or concrete) of the words in silence. The subjects were told to listen passively the noise from the MR scanners during the resting period, which was used as the control task. The fMRI data were analyzed with statistical parametric mapping (SPM99) software. RESULTS: The MMSE score of the patient group was 29.3 +/- 1.1, not significantly different from that of the control group (29.6 +/- 0.5, P > 0.05). The STAI-S score of the patient group was 47 +/- 5.3748, significantly higher than that of the control group (41.6 +/- 4.9777, P < 0.05). The STAI-S score of the patient group was 45 +/- 3, not significantly different from that of the control group (43 +/- 4, t = 1.0619, P = 0.3032). In Experiment 1, the activated patterns and deactivated patterns were nearly similar for the patient and control groups. The activated regions included the bilateral superior temporal lobe, bilateral inferior frontal cortex and supplementary motor areas. In Experiment 2, the activated patterns were also nearly similar for these 2 groups. The regions included the bilateral superior temporal lobe, bilateral inferior frontal cortex, left angular gyrus, bilateral superior frontal cortex, bilateral cerebellum, premotor areas, and supplementary motor areas. The deactivation patterns were similar for the patients and controls both in Experiment 1 and Experiment 2. These regions were medial prefrontal cortex, posterior cingulate and bilateral inferior parietal cortex, which nearly overlapping with the default model network proposed by Raichle et al. However, the activation and deactivation magnitude and extent of the brain were significantly greater for the patients than for the controls both in Experiment 1 and Experiment 2. CONCLUSION: Some brain dysfunction may have already existed in patients with moderately to severely hypertension disorders, though their behavior performance scores are within the normal range of ages. The fMRI technique can be a useful tool to detect the preclinical brain abnormalities.