The CHEK2 gene serves a canonical role in the DNA damage response (DDR) pathway encoding the regulatory kinase CHK2 in the homologous recombination (HR) repair of double-strand breaks (DSB). Although CHEK2 is traditionally considered a tumor suppressor gene, recent studies suggest additional functions. Across several cohort studies, CHEK2 expression was negatively correlated with the efficacy of immune checkpoint inhibitors (ICI), which target the interaction between effector immune and tumor cells. This review explores two possible explanations for this observed phenomenon: the first relating to the canonical role of CHEK2, and the second introducing a novel role of the CHEK2 gene in immunomodulation of the tumor microenvironment (TME). DDR mutations have been implicated in increased levels of tumor mutation burden (TMB), often manifesting as neoepitope expression on the tumor cell surface recognized by effector immune cells. As a result, impaired DNA repair due to CHEK2 loss of function, either from germline deleterious variants or acquired mutations, results in the recruitment of CD8+ cytotoxic T-cells and subsequent efficacy of ICI treatment. However, functional loss of CHEK2 may be directly involved in potentiating the immune response through canonical inflammatory and anti-tumor pathways, acting through the cGAS-STING pathway. Although the exact mechanism by which CHEK2 modulates immune responses is still under investigation, combination therapy with CHEK1/2 inhibition and ICI immunotherapy has shown benefit in preclinical studies of several solid tumors.

Radiation therapy (RT) is the standard of care for glioblastoma but is not curative. Triggering the cGAS/stimulator of interferon genes (STING) pathway with potent agonists, such as 8803, exerts activity across high-grade glioma preclinical models. To determine if the combination of 8803 with RT warrants consideration in the up-front treatment setting and to clarify the underlying mechanisms of therapeutic activity, C57BL/6J mice harboring intracerebral CT-2A or QPP8v gliomas were treated with RT, intratumoral 8803, or both. The treatment with the combination resulted in 80% long-term survival in the CT-2A model but not in the radiation-resistant QPP8v model. This therapeutic effect was maintained in Sting^–/– CT-2A cells, highlighting the direct role of the immune system in mediating the survival benefit. Single-cell RNA-Seq identified increased nitric oxide synthase 2 (Nos2) in inflammatory tumor-associated macrophages; however, the therapeutic effect was maintained in Nos2^–/– mice. Additionally, 8803 reprogrammed the blood-brain barrier (BBB) by altering the Pecam and Cd147 pathways in endothelial cells; intracranial injection of 8803 induced bihemispheric BBB opening for up to 24 hours. Sting activation was visualized longitudinally using 3’-deoxy-3’-[¹⁸F]-fluorothymidine ([¹⁸F]-FLT) PET, which peaked 72–96 hours after 8803 administration. In summary, 8803 combined with RT triggers distinctive antiglioma immune reactivity, facilitates BBB opening, and warrants consideration for up-front clinical trials in glioblastoma, where treatment effects can be monitored using [¹⁸F]-FLT PET imaging.

Abstract

Flash floods are among the most dangerous natural hazards, especially in arid and semi-arid regions, where their sudden onset can lead to devastating impacts. This study presents an integrated assessment of flash flood hazards and risks in the Wadi Feiran Basin, a hyper-arid region in Egypt’s Sinai Peninsula that experiences recurring flood events. Surface runoff was estimated using the Soil Conservation Service Curve Number (SCS-CN) method, incorporating spatial datasets on hydrology, topography, and land use. A comprehensive risk assessment was then carried out by integrating the Analytic Hierarchy Process (AHP) within a Geographic Information System (GIS) framework to generate three key models: a Flood Hazard Index (FHI), a Vulnerability Index (VI), and a combined Flood Risk Index (FRI). Results show that approximately 14.5% of the basin falls in the high flood hazard zone, and nearly 30% is classified as very highly vulnerable. The FRI model highlights that 14.5% of the area is at very high risk, while 23.5% is at high risk. Critically exposed zones include urban settlements in Feiran city, northeastern Saint Catherine, and main roads connecting to Dahab and Abu Zenima. The region's cultural and touristic significance further amplifies the consequences of such hazards. This study offers essential spatial tools and decision-support data for policymakers, urban planners, and disaster risk managers to prioritize mitigation, strengthen infrastructure resilience, and guide sustainable development in Wadi Feiran and similar arid, flood-prone regions.

High-voltage (HV) terminations are commonly used in HV connections, such as cable-to-transformer connections, to limit local electric field intensifications that may result in electrical breakdown. The termination contains a conductor and multiple dielectric layers with an embedded semiconductive (SC) layer, which is essential for reliable insulation design and breakdown prevention. The traditional charge simulation method (CSM) for electric field calculation is limited to two pure dielectric media. The present paper is aimed at proposing a new formulation of the traditional CSM for calculation of the electric field in HV terminations with more than two dielectric layers, including an SC layer. The conductor, dielectric interfaces, and surrounding air are modeled using sets of fictitious ring charges. By considering the governing pertinent boundary conditions, namely the Dirichlet condition on the conductor surface, and the continuity of both the electric potential and the normal electric flux density at the dielectric interfaces, the simulation charges are evaluated, and hence the electric field. To account for the presence of SC layers with relatively high conductivity, a hybrid numerical approach combining the CSM and the finite difference method (FDM) is developed, where the SC region is solved using FDM and coupled to the CSM domain through the continuity conditions of potential and normal flux density. The proposed formulation is validated through comparison with COMSOL Multiphysics simulations. The results demonstrate excellent agreement in the potential and electric field distributions across all dielectric layers, including in regions near to the interfaces and sheds. The newly-formulated CSM with hybrid CSM–FDM provides an efficient and accurate tool for electric field calculation in complex plasma reactors and HV cable terminations, accommodating multi-dielectric layers, including SC ones 
 

Introduction:

Blood parasitism is a significant clinical disease that silently undermines the livestock industry, particularly affecting camels. This study aimed to assess the prevalence of Trypanosoma evansi in Arabian camels (Camelus dromedarius) and its impact on infertility by examining serum protein fractions, lipids, reproductive indices, and the expression of heat shock protein (HSP70) during breeding season.

Methods:

A total of 107 male post-pubertal camels, aged between 5 and 10 years, were collected randomly from slaughtering house in Assiut Governorate, Egypt.

Results:

Microscopic and serological examinations revealed that 23.4% (25/107) of the camels were infected with T. evansi. Infected camels exhibited a highly significant increase in total serum protein. The assessment of dyslipidemia, measure as binary variables for lipid profiles (cholesterol, triglycerides, HDL, and LDL), indicated a nonsignificant increase in risk of dyslipidemia in infected camels compared to healthy camels. Proteomic analysis identified four major protein fractions in the infected camels compared to healthy camels with molecular weights of 181.72, 87.59, 30.5, and 19.5 kDa using SDS electrophoresis. Testicular tissue of the infected camels showed degeneration and necrotic changes in seminiferous tubules and interstitial tissue, along with edema and congestion. There was a significant reduction in the diameter of seminiferous tubules and germinal epithelium height. A marked reduction in testosterone levels and a high expression of HSP70 in spermatogonia, spermatocytes, Sertoli cells, and Leydig cells were observed.

The morphology and host-parasite data of Schistorchis carneus Lühe, 1906 indicate low host specificity and geographical range variation, accompanied by a large scale of intraspecific variability and ambiguous molecular phylogeny, confusing in determining biodiversity extent and specificity to a particular host and/or locality. To address the challenging circumstances of records of S. carneus, a detailed morphological description, molecular characterization and species delimitation analyses were conducted using a combination of comparative morphology, molecular phylogeny, multivariate analyses, and hostparasite data. Several morphological features exhibited an extensive intra-variation, as well as a wide morphometric range in many measurements within and across records. Phylogenetic analyses showed that the classification of schistorchiines is highly correlated with the morphology/nature of the oral sucker and highlighted the limitations of ribosomal 28S rDNA and ITS2 rDNA in distinguishing morphologically close/related taxa. Species delimitation analyses reflected the critical importance of host distinction in schistorchiines recognition/differentiation, even those that are indistinct morphologically. The clustering of schistorchiines into certain groups was driven by host differences. Additionally, host variation typically corresponds to a distinct schistorchiine species, even if it is morphologically identical to another. Cluster analysis associated with host-parasite data revealed high morphometric convergence and significant diversity among Egyptian and Sri-Lankan records of S. carneus. It also confirmed the distinction between Indian records from the Bay of Bengal and those from the Gulf of Mannar (previously mentioned as Manaar), each in their own distant group. In conclusion, the records of S. carneus represent a repository for a group of closely related cryptic species. The restricted concept of S. carneus should include only records from the white-spotted puffer, Arothron hispidus (Linnaeus) and the stellate puffer, Arothron stellatus (Anonymous). The Australian specimens from the narrow-lined puffer, Arothron manilensis (Marion de Procé) and the Indian record from the lunartail puffer, Lagocephalus lunaris (Bloch & Schneider) likely represent a free-standing cryptic species with limited distribution, requiring further characterization.