Exploring the natural products chemical space through a molecular search to discover potential inhibitors that target the hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD).

Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.

Public Anxiety, Attitudes, and Practices towards COVID-19 Infection in the Eastern Province of Saudi Arabia: A Cross-Sectional Study.

Coronavirus disease 2019, or COVID-19, still has a terrifying potential due to its continuous genetic variation. Although vaccines have been created, adherence to preventive measures remains a privileged choice to tackle the pandemic. This study aims to investigate the anxiety, attitudes, and practices (KAPs) towards COVID-19 infection in the Eastern Province of Saudi Arabia. In this cross-sectional study, data were collected from 400 participants via an online self-structured questionnaire. Anxiety, attitude, and practice scores were calculated by summing the points of the statements under the corresponding domain multiplied by 100 over 12, 21, or 15, respectively. Chi-square and one-way analysis of variance were used to investigate the relationships between vaccination, anxiety, attitude, practice scores, and demographic characteristics. More than half of the participants were female (58.5%; mean age of 29.5 years; the majority in the age groups of <20 years and 21-30 years). Only 21.5% of the participants were suffering from or previously had chronic diseases. Notably, 22.3% of the male participants were vaccinated (p = 0.000). The old age groups (41-50 years and >50 years) were more vaccinated (16.3% and 24.1%, respectively, p = 0.000), as well as the unemployed (36.4%; p = 0.000). The mean scores of anxiety, attitude, and practice were 66.8, 72.3, and 85.2, respectively. Females had an anxiety score of 68.5% (p = 0.008) and a higher attitude score of 68.5% (p = 0.008). Infected male participants had a lower practice score of 80% (p = 0.038), while females recorded higher practice scores (85.7 ± 11.6). The results highlight the importance of reliable communication from health representatives and legislators in educating the public and promoting their knowledge about non-therapeutic interventions. Efficient intervention approaches are required to fill the gap during the implementation of non-therapeutic measures. Also, it is recommended that awareness programs, during COVID-19 or any other similar pandemics, should be tailored to target Eastern Province inhabitants, especially males.

Deep Monocular Depth Estimation Based on Content and Contextual Features.

Recently, significant progress has been achieved in developing deep learning-based approaches for estimating depth maps from monocular images. However, many existing methods rely on content and structure information extracted from RGB photographs, which often results in inaccurate depth estimation, particularly for regions with low texture or occlusions. To overcome these limitations, we propose a novel method that exploits contextual semantic information to predict precise depth maps from monocular images. Our approach leverages a deep autoencoder network incorporating high-quality semantic features from the state-of-the-art HRNet-v2 semantic segmentation model. By feeding the autoencoder network with these features, our method can effectively preserve the discontinuities of the depth images and enhance monocular depth estimation. Specifically, we exploit the semantic features related to the localization and boundaries of the objects in the image to improve the accuracy and robustness of the depth estimation. To validate the effectiveness of our approach, we tested our model on two publicly available datasets, NYU Depth v2 and SUN RGB-D. Our method outperformed several state-of-the-art monocular depth estimation techniques, achieving an accuracy of 85%, while minimizing the error Rel by 0.12, RMS by 0.523, and log10 by 0.0527. Our approach also demonstrated exceptional performance in preserving object boundaries and faithfully detecting small object structures in the scene.

Effects of spray dried yeast (Saccharomyces cerevisiae) on growth performance and carcass characteristics, gut health, cecal microbiota profile and apparent ileal digestibility of protein, amino acids and energy in broilers.

The aim of present study was to determine the effects of supplementation of either synbiotic or probiotic on growth performance and carcass characteristics, gut health, cecal microbiota prolife and apparent ileal digestibility of protein, amino acids, and energy in broilers. Two hundred and forty-day-old straight-run broilers (Ross 308) were allotted randomly to 1 of 5 dietary treatments including basal diet (control), supplemented with either synbiotic (Nutromax P) or probiotic (Actera), each at 0.5 and 1 g/kg of the diet for 5 weeks. The overall findings of the study indicated better (p < 0.05) growth performance of broilers by synbiotic supplementation (1 g/kg) compared with those fed probiotic (1 g/kg) supplemented and control diets. The broilers consuming diet supplemented with 1 g/kg synbiotic has an increased carcass yield in comparison with those fed control diet. The findings of gut health indicated significantly increased villus height and goblet cells, by synbiotic supplementation (1 g/kg), compared with control diet in broilers. The broilers fed 1 g/kg synbiotic supplemented diets had 18% increased protein, 9 to 31% higher amino acid, and 34% better energy digestibility, whereas 8.4% decreased protein digestibility in broilers fed probiotic (1 g/kg) supplemented compared with control diet in broilers. The broilers fed synbiotic (1 g/kg) supplemented diets had increased cecal Lactobacillus and decreased Salmonella, E. coli, and Clostridium count compared with those fed control diet. In conclusion, synbiotic supplementation (1 g/kg) resulted in improved production performance, balanced cecal microbial composition, and better digestibility of nutrients in broilers compared with those fed control and diets supplemented with probiotics.

Genetic Structure of Field Populations of Begomoviruses and of Their Vector Bemisia tabaci in Pakistan.

ABSTRACT The genetic structure of field populations of begomoviruses and their whitefly vector Bemisia tabaci in Pakistan was analyzed. Begomoviruses and B. tabaci populations were sampled from different crops and weeds in different locations in Punjab and Sindh provinces, in areas where cotton leaf curl disease (CLCuD) occurs or does not occur. Phylogenetic analysis based on nucleotide sequences of the intergenic region in the viral DNA-A provided evidence of two clusters of isolates: viruses isolated from species in the family Malvaceae, and viruses isolated from other dicotyledon families. Analysis of the capsid protein (CP) open reading frame grouped isolates into three geographical clusters, corresponding to isolates collected in Punjab, Sindh, or both provinces. Random amplified polymorphic DNA analyses of the B. tabaci population showed that intrapopulation diversity was high at both the local and regional scales. Sequence analysis of the mitocondrial cytochrome oxydase I (mt COI) gene showed that the B. tabaci population was structured into at least three genetic lineages corresponding to the previously described Indian, Southeast Asian, and Mediterranean-African clades. The Indian clade was present only in Punjab, the Mediterranean-African only in Sindh, and the Southeast Asian in both provinces. B. tabaci haplotypes of the Indian clade were found only in the Punjab, where CLCuD occurs. Hence, the geographical distribution of virus and vector genotypes may be correlated, because similar phylogenetic relationships were detected for the viral CP and the vector mt COI genes.