Machine learning models for water safety enhancement.

Humans encounter both natural and artificial radiation sources, including cosmic rays, primordial radionuclides, and radiation generated by human activities. These radionuclides can infiltrate the human body through various pathways, potentially leading to cancer and genetic mutations. A study was conducted using random sampling to assess the concentrations of radioactive isotopes and heavy metals in mineral water from Iran, consumable at Arak City.

A machine learning decision support tool optimizes WGS utilization in a neonatal intensive care unit.

The Mendelian Phenotype Search Engine (MPSE), a clinical decision support tool using Natural Language Processing and Machine Learning, helped neonatologists expedite decisions to whole genome sequencing (WGS) to diagnose patients in the neonatal intensive care unit. After the MPSE was introduced, utilization of WGS increased, time to ordering WGS decreased, and WGS diagnostic yield increased.

Domperidone inhibits dengue virus infection by targeting the viral envelope protein and nonstructural protein 1.

Dengue is a mosquito-borne disease caused by dengue virus (DENV) infection, which remains a major public health concern worldwide owing to the lack of specific treatments or antiviral drugs available. This study investigated the potential repurposing of domperidone, an antiemetic and gastrokinetic agent, to control DENV infection. Domperidone was identified by pharmacophore-based virtual screening as a small molecule that can bind to both the viral envelope (E) and the nonstructural protein 1 (NS1) of DENV.

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib.

Genes related to neural tube defects and glioblastoma.

There are many similarities between early embryonic development and tumorigenesis. The occurrence of neural tube defects (NTDs) and glioblastoma (GBM) are both related to the abnormal development of neuroectodermal cells. To obtain genes related to both NTDs and GBM, as well as small molecule drugs with potential clinical application value.

Mendelian randomization analysis does not support a causal influence between lipoprotein(A) and immune-mediated inflammatory diseases.

Observational studies have reported an association between lipoprotein(a) (Lp(a)) and immune-mediated inflammatory diseases (IMIDs). This study used Mendelian Randomization (MR) and multivariable MR (MVMR) to explore the causal relationship between lipoprotein(a) [Lp(a)] and immune-mediated inflammatory diseases (IMIDs). We performed a bidirectional two-sample mendelian randomization analyses based on genome-wide association study (GWAS) summary statistics of Lp(a) and nine IMIDs, specifically celiac disease (CeD), Crohn's disease (CD), ulcerative colitis (UC), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis (Pso), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and summary-level data for lipid traits.

Improved constructs for bait RNA display in a bacterial three-hybrid assay.

We have previously developed a transcription-based bacterial three-hybrid (B3H) assay as a genetic approach to probe RNA-protein interactions inside of E. coli cells. This system offers a straightforward path to identify and assess the consequences of mutations in RBPs with molecular phenotypes of interest.

Alzheimer's disease may develop from changes in the immune system, cell cycle, and protein processing following alterations in ribosome function.

The prevalence of Alzheimer's disease (AD) is increasing as society ages. The details of AD pathogenesis have not been fully elucidated, and a comprehensive gene expression analysis of the process leading up to the onset of AD would be helpful for understanding the mechanism. We performed an RNA sequencing analysis on a cohort of 1227 Japanese blood samples, representing 424 AD patients, 543 individuals with mild cognitive impairment (MCI), and 260 cognitively normal (CN) individuals.

Optimized convolutional neural network using African vulture optimization algorithm for the detection of exons.

The detection of exons is an important area of research in genomic sequence analysis. Many signal-processing methods have been established successfully for detecting the exons based on their periodicity property. However, some improvement is still required to increase the identification accuracy of exons.

Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition.

We previously demonstrated that the inability of primary endothelial cilia to sense fluid shear stress can lead to nitric oxide (NO) deficiency and cause hypertension (HTN). Decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in Alzheimer's disease (AD) patients through increased deposition of amyloid beta (Aβ). However, the molecular mechanisms underlying the pathogenesis of HTN and AD are incompletely understood.

Biofabrication of zinc oxide nanoparticles using Moringa oleifera, characterization and statistical optimization for their application in crystal violet adsorption.

Crystal violet (Cry) is an essential textile dye belonging to the triphenylmethane group, that is widely used in the textile industry. It is also applied for paper printing and Gram staining. Previously, it was significant as a topical antiseptic due to its antibacterial, antifungal, and anthelmintic properties.

Comprehensive profiling of serum microRNAs in normal and non-alcoholic fatty liver disease (NAFLD) patients.

Pediatric non-alcoholic fatty liver disease (NAFLD) is emerging as a worldwide health concern with the potential to advance to cirrhosis and liver cancer. NAFLD can also directly contribute to heart problems through inflammation and insulin resistance, even in individuals without other risk factors. The pathological mechanisms of NAFLD are linked to functional differences of miRNAs in different biological environments.

Optimizing multiprocessor performance in real-time systems using an innovative genetic algorithm approach.

Due to its enormous influence on system functionality, researchers are presently looking into the issue of task scheduling on multiprocessors. Establishing the most advantageous schedules is often regarded as a difficult-to-compute issue. Genetic Algorithm is a recent tool employed by researchers to optimize scheduling tasks and boost performance, although this field of research is yet mostly unexplored.

Mitochondrial KMT9 methylates DLAT to control pyruvate dehydrogenase activity and prostate cancer growth.

Prostate cancer (PCa) growth depends on de novo lipogenesis controlled by the mitochondrial pyruvate dehydrogenase complex (PDC). In this study, we identify lysine methyltransferase (KMT)9 as a regulator of PDC activity. KMT9 is localized in mitochondria of PCa cells, but not in mitochondria of other tumor cell types.

Deep mutational scanning of the Trypanosoma brucei developmental regulator RBP6 reveals an essential disordered region influenced by positive residues.

To regain infectivity, Trypanosoma brucei, the pathogen causing Human and Animal African trypanosomiasis, undergoes a complex developmental program within the tsetse fly known as metacyclogenesis. RNA-binding protein 6 (RBP6) is a potent orchestrator of this process, however, an understanding of its functionally important domains and their mutational constraints is lacking. Here, we perform deep mutational scanning of the entire RBP6 primary structure.

Diffusion Smart-seq3 of breast cancer spheroids to explore spatial tumor biology and test evolutionary principles of tumor heterogeneity.

Combining 3D cultures such as tumor spheroids and organoids with spatial omics holds great potential for tissue biology and cancer research. Yet, this potential is presently limited by technical and financial challenges of spatial omics methods and 3D cultures. To address this, we combine dye diffusion, the Smart-seq3xpress protocol for deep single-cell gene expression profiling, and dedicated probabilistic inference methods into diffusion Smart-seq3 (Smart-seq3D), to reveal the transcriptome of single cells along with their position along the core-periphery axis of spheroids.

Chronic kidney disease.

Chronic kidney disease (CKD) is defined by persistent abnormalities of kidney function or structure that have consequences for the health. A progressive decline of excretory kidney function has effects on body homeostasis. CKD is tightly associated with accelerated cardiovascular disease and severe infections, and with premature death.

Understanding metastasis mixed-treatment responses through genomic analyses.

Early-stage and metastatic breast cancers (MBC) can exhibit genomic heterogeneity, even within the same individual. Response to therapy in metastatic breast cancer patients with multiple metastases can also be heterogeneous, with different degrees of responsiveness to the same drug(s) across metastatic sites, termed "mixed response," within the same patient. Whether this treatment response variability is influenced by factors such as intrinsic tumor characteristics of metastatic lesions and/or the microenvironment is unknown.

Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening.

Cas12a is a next-generation gene editing tool that enables multiplexed gene targeting. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a (enAsCas12a) linked to an mCherry fluorescent reporter.

Nuclear farnesoid X receptor protects against bone loss by driving osteoblast differentiation through stabilizing RUNX2.

The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis. Nuclear receptors (NRs) are now understood to be crucial in bone physiology and pathology. However, the function of the Farnesoid X receptor (FXR), a member of the NR family, in regulating bone homeostasis remains incompletely understood.

Versatile nitrate-respiring heterotrophs are previously concealed contributors to sulfur cycle.

Heterotrophic denitrifiers play crucial roles in global carbon and nitrogen cycling. However, their inability to oxidize sulfide renders them vulnerable to this toxic molecule, which inhibits the key enzymatic reaction responsible for reducing nitrous oxide (NO), thereby raising greenhouse gas emissions. Here, we applied microcosm incubations, community-isotope-corrected DNA stable-isotope probing, and metagenomics to characterize a cohort of heterotrophic denitrifiers in estuarine sediments that thrive by coupling sulfur oxidation with denitrification through chemolithoheterotrophic metabolism.

Pasteurisation temperatures effectively inactivate influenza A viruses in milk.

In late 2023 an H5N1 lineage of high pathogenicity avian influenza virus (HPAIV) began circulating in American dairy cattle Concerningly, high titres of virus were detected in cows' milk, raising the concern that milk could be a route of human infection. Cows' milk is typically pasteurised to render it safe for human consumption, but the effectiveness of pasteurisation on influenza viruses in milk was uncertain. To assess this, here we evaluate heat inactivation in milk for a panel of different influenza viruses.

Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.

Oncolytic reprogramming of tumor microenvironment shapes CD4 T-cell memory via the IL6ra-Bcl6 axis for targeted control of glioblastoma.

Oncolytic viruses (OVs) emerge as a promising cancer immunotherapy. However, the temporal impact on tumor cells and the tumor microenvironment, and the nature of anti-tumor immunity post-therapy remain largely unclear. Here we report that CD4 T cells are required for durable tumor control in syngeneic murine models of glioblastoma multiforme after treatment with an oncolytic herpes simplex virus (oHSV) engineered to express IL-12.