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Zinc finger CCCH containing 11A (ZC3H11A) is a stress-induced protein that is upregulated in various conditions such as heat shock and virus infection. It has also been reported to be upregulated in certain cancers. The aim of this study was to evaluate the feasibility of targeting ZC3H11A as a therapeutic approach for cancer treatment, using nuclease-resistant, affinity-enhanced antisense oligonucleotide (ASO). An ASO targeting ZC3H11A was validated and evaluated in vitro and in the B16 melanoma model in vivo. Antigen presentation, interferon response, cell proliferation, and apoptosis were transcriptionally affected. These findings were validated on the protein level by the upregulation of major histocompatibility complex class I (MHC class I), an increased secretion of interferon-β (IFN-β), and induction of apoptosis observed as upregulation of caspases and annexin V. Immunogenic features of the induced apoptosis were evidenced by the surface exposure of calreticulin (CRT) and the secretion of ATP leading to enhanced dendritic cell (DC) phagocytosis, maturation, and activation. Treatment with the ZC3H11A-targeted ASO had limited efficacy in vivo, while constitutive lentiviral shRNA knockdown of ZC3H11A in murine B16 melanoma cells and human HeLa cells led to reduced tumor growth with prolonged survival of mice, validating ZC3H11A as a relevant target for cancer therapy.

Memory loss is becoming an increasingly significant health problem, largely due to Alzheimer's disease (AD), which disrupts the brain in several ways, including causing inflammation and weakening the body's defenses. This study explores the potential of medicinal plants as a source of novel therapeutic agents for AD.First, we tested various plant extracts against acetylcholinesterase (AChE) in vitro, following molecular docking simulations with key AD-related protein targets such as MAO-B, P-gp, GSK-3β, and CD14. Rosemary extract was found to be the most inhibitory towards AChE. The compounds found in rosemary (oleanolic acid), sage (pinocembrin), and cinnamon (italicene) showed promise in potentially binding to MAO-B. These chemicals may interact with a key protein in the brain and alter the production and removal of amyloid-β. Luteolin (from rosemary), myricetin (from sage), chamigrene, and italicene (from cinnamon) exhibited potential for inhibiting tau aggregation. Additionally, ursolic acid found in rosemary, sage, and chamigrene from cinnamon could modulate CD14 activity.For the first time, our findings shed light on the intricate interplay between neuroinflammation, neuroprotective mechanisms, and the immune system's role in AD. Further research is needed to validate the in vivo efficacy and safety of these plant-derived compounds, as well as their interactions with key protein targets, which could lead to the development of novel AD therapeutics.

Kafrelsheikh, situated in the middle of the Nile Delta, significantly contributes to Egypt's aquaculture and agriculture sectors. However, the local use of organochlorine pesticides (OCPs) in agriculture is often a source of OCP residues in associated drainage waters, which may threaten aquatic ecosystems. These pesticides persist in local water bodies, jeopardizing aquatic ecosystems and potentially impacting human health. This comprehensive study assessed the seasonal variations of 17 OCPs in both water sources and Nile tilapia across eight fish farming locations in Kafrelsheikh. Using gas chromatography coupled with mass spectrometry (GC-MS), we detected OCP concentrations in water that varied seasonally where winter recorded the highest levels at 22.5 ng/mL and, summer showed the lowest levels at 6.2 ng/mL. Despite water samples occasionally showing risk quotients (RQs) greater than 1, indicating a potential threat to aquatic life, the OCP levels in Nile tilapia were sufficiently low, with target hazard quotients (THQ) below 1, suggesting no significant risk for human consumption. The research highlights a pressing need for regular environmental monitoring and stricter regulatory control over pesticide use to protect aquatic life and ensure the safety of aquaculture products. These findings provide a critical basis for policy-making, aimed at balancing agricultural productivity with environmental sustainability in regions heavily dependent on both.

Diversity and homeostasis of gut bacterial composition is highly associated with the pathogenesis of insulin dysfunction and type 1 diabetes melittus (T1D), hence emerged in parallel with the activation of autoimmunity. We aimed to study the bioactive potential of essential oil from Zanthoxylum myriacanthum var. pubescens Huang (Maqian) through computational approaches. Twelve chemical constituents derived from Maqian essential oil were docked with selected proteins (i.e., 3pig, 1kho, 7dmq, 4m4d, 2z65, 4glp, and 3fxi) in which are involved in gut microbiota modulation in T1D. Subsequently, the prediction of bioavailability properties of the small molecules were evaluated. Among all chemical constituents, the post-docking interaction analysis demonstrated that α-phellandrene exhibits the strongest binding affinity and induces gut microbiota modulation with β-fructofuranosidase from Bifidobacterium longum. The current result revealed the potential of 3-Carene and α-Pinene in inducing specific changes in gut microbiota downregulating Clostridium perfringens and quenching Leptotrichia shahii respectively. β-Pinene possess exceptionally strong binding affinity that effectively disrupt the interaction between lipopolysaccharide and its cognate receptors, while α-Phellandrene was exhibited the uppermost binding affinity with TLR4/MD2 and could likely target TLR4 stimulating lipopolysaccharide. Our results are the first to report on the gut microbiota modulation effects of α-Phellandrene and β-Phellandrene via actions on LPS binding to CD14 and the TLR4 co-receptor signaling. In conclusion, our findings based on computational approaches, small molecules from Maqian present as promising agents which could regulate inflammatory response and modulate gut microbiota in type 1 diabetes mellitus.

Breast cancer is a prevalent disease that has a potential influence on the lives of countless women globally. Early diagnosis and intervention are crucial for successful treatment and better patient outcomes. Machine learning algorithms have shown promising results in developing accurate and dependable prediction models for breast cancer. In this research, we conduct an extensive overview of various machine learning (ML) techniques employed to develop breast cancer prediction models using diverse datasets. Our study explores the literature on several ML algorithms utilized for breast cancer prediction. We also examine the types of datasets used for training and testing these models, including clinical data, mammography images, and genetic data. Additionally, we evaluate the benefits and limitations of each machine learning algorithm and dataset and offer recommendations for future research. Our aim is to provide a comprehensive understanding of the current state-of-the-art in breast cancer prediction models using ML and to promote the development of precise and effective models to detect breast cancer at an early stage.

This research investigated the performance of base layer aggregates in HMA pavements using laboratory tests (standard compaction, particle size analysis, Atterberg Limits, sodium sulfate soundness, Micro-Deval abrasion, absorption, specific gravity, and soaked CBR) on existing base layer materials as well as pavement surface visual and automated distress surveys. The purpose of this research was to investigate potential degradation of aggregate bases, strength variations over time, and the likely causes for both.Analysis of laboratory and field test results indicated significant variability in the properties and characteristics of base layer aggregate materials in various pavement test sections. Based on the results of the laboratory and field tests, the research team believes that the long-term performance of the base layer aggregates impacted the overall pavement performance of the corresponding test sections. While base aggregate materials in general did not exhibit severe degradation or disintegration – as demonstrated by laboratory tests – nor significant contamination from subgrade, the performance of such materials was lower compared with typical crushed stone materials.