Crisdesalazine alleviates inflammation in an experimental autoimmune encephalomyelitis multiple sclerosis mouse model by regulating the immune system.

Microglia/macrophages participate in the development of and recovery from experimental autoimmune encephalomyelitis (EAE), and the macrophage M1 (pro-inflammatory)/M2 (anti-inflammatory) phase transition is involved in EAE disease progression. We evaluated the efficacy of crisdesalazine (a novel microsomal prostaglandin E2 synthase-1 inhibitor) in an EAE model, including its immune-regulating potency in lipopolysaccharide-stimulated macrophages, and its neuroprotective effects in a macrophage-neuronal co-culture system. Crisdesalazine significantly alleviated clinical symptoms, inhibited inflammatory cell infiltration and demyelination in the spinal cord, and altered the phase of microglial/macrophage and regulatory T cells.

Four-electron reduction of benzene by a samarium(II)-alkyl without the addition of external reducing agents.

Benzene reduction by molecular complexes remains an important synthetic challenge, requiring harsh reaction conditions involving group I metals. Reductions of benzene, to date, typically result in a loss of aromaticity, although the benzene tetra-anion, a 10π-electron system, has been calculated to be stable and aromatic. Due to the lack of sufficiently potent reductants, four-electron reduction of benzene usually requires the use of group I metals.

Sex-specific mechanisms in vascular aging: exploring cellular and molecular pathways in the pathogenesis of age-related cardiovascular and cerebrovascular diseases.

Aging remains the foremost risk factor for cardiovascular and cerebrovascular diseases, surpassing traditional factors in epidemiological significance. This review elucidates the cellular and molecular mechanisms underlying vascular aging, with an emphasis on sex differences that influence disease progression and clinical outcomes in older adults. We discuss the convergence of aging processes at the macro- and microvascular levels and their contributions to the pathogenesis of vascular diseases.

Impact of perforation following self-expandable metal stent as a bridge to surgery for malignant colorectal obstruction: a multicenter study of the Research Group for Stent in the Korean Society of Gastrointestinal Endoscopy.

Background And Aims: Self-expandable metal stents (SEMS) are effective in alleviating malignant colorectal obstruction. However, bowel perforation following SEMS placement remains a significant concern, as it can adversely affect oncological outcomes. This study aimed to evaluate the recurrence and overall survival rates associated with SEMS-related bowel perforations.

Establishing bio-logging data collections as dynamic archives of animal life on Earth.

Rapid growth in bio-logging-the use of animal-borne electronic tags to document the movements, behaviour, physiology and environments of wildlife-offers opportunities to mitigate biodiversity threats and expand digital natural history archives. Here we present a vision to achieve such benefits by accounting for the heterogeneity inherent to bio-logging data and the concerns of those who collect and use them. First, we can enable data integration through standard vocabularies, transfer protocols and aggregation protocols, and drive their wide adoption.

A modeling study to define guidelines for antigen screening in schools and workplaces to mitigate COVID-19 outbreaks.

Background: In-person interaction offers invaluable benefits to people. To guarantee safe in-person activities during a COVID-19 outbreak, effective identification of infectious individuals is essential. In this study, we aim to analyze the impact of screening with antigen tests in schools and workplaces on identifying COVID-19 infections.

Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

ZIC1 is a context-dependent medulloblastoma driver in the rhombic lip.

Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).

A risk-based approach can guide safe cell line development and cell banking for scaled-up cultivated meat production.

For commercial viability, cultivated meats require scientifically informed approaches to identify and manage hazards and risks. Here we discuss food safety in the rapidly developing field of cultivated meat as it shifts from lab-based to commercial scales. We focus on what science-informed risk mitigation processes can be implemented from neighbouring fields.

Explainable artificial intelligence with UNet based segmentation and Bayesian machine learning for classification of brain tumors using MRI images.

Detecting brain tumours (BT) early improves treatment possibilities and increases patient survival rates. Magnetic resonance imaging (MRI) scanning offers more comprehensive information, such as better contrast and clarity, than any alternative scanning process. Manually separating BTs from several MRI images gathered in medical practice for cancer analysis is challenging and time-consuming.

The impact of library size and scale of testing on virtual screening.

Virtual ligand libraries for ligand discovery have recently increased 10,000-fold. Whether this has improved hit rates and potencies has not been directly tested. Meanwhile, typically only dozens of docking hits are assayed, clouding hit-rate interpretation.

Risk-based bridge life cycle cost and environmental impact assessment considering climate change effects.

To enhance sustainability and resilience against climate change in infrastructure, a quantitative evaluation of both environmental impact and cost is important within a life cycle framework. Climate change effects can lead performance deterioration in bridge components during their operational phase, highlighting the necessity for a risk-based evaluation process aligned with maintenance strategies. This study employs a two-phase life cycle assessments (LCA) framework.

Effects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.

Therapy-induced senescent cancer cells contribute to cancer progression by promoting ribophorin 1-dependent PD-L1 upregulation.

Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its transcription and glycosylation.

An updated review about the possibility of surveillance strategy in non-resected mucinous cystic neoplasms.

After the World Health Organization established a precise definition of mucinous cystic neoplasm (MCN) in 2000, based on the presence of ovarian-type stroma, its clinical features became more apparent. Surgery for MCN, which primarily affects middle-aged women with long life expectancies, is likely to negatively impact the patient's quality of life. Although recent studies have reported a low proportion of advanced neoplasia among resected MCN (≤15%), many clinicians still recommend surgery for patients with presumed MCN without considering risk stratification for advanced neoplasia.

Disruption of extracellular matrix and perineuronal nets modulates extracellular space volume and geometry.

Extracellular matrix (ECM) is a network of macromolecules which has two forms - perineuronal nets (PNNs) and a diffuse ECM (dECM) - both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility.

Protocol for optimizing robot-assisted autism therapy sessions through gaze analysis: A pilot study investigating optimal trial count for children with comorbid autism spectrum disorder and intellectual disability.

Background: Autism spectrum disorder poses challenges in social communication and behavior, while Intellectual disabilities are characterized by deficits in cognitive, social, and adaptive skills, frequently accompanied by stereotypies and challenging behaviors. Despite the progress made in autism spectrum disorder research, there is often a lack of research focusing on individuals with co-occurring autism spectrum disorder and intellectual disability. Robot-assisted autism therapies are effective in addressing these needs.

Additional Dose of Intravenous Dexamethasone Can Replace Patient-Controlled Analgesia in Pain Control after Total Knee Arthroplasty while Reducing Opioid Complications.

Purpose The purpose of this study was to evaluate whether IV dexamethasone, within the current multimodal pain management protocol, (1) could maintain postoperative pain at a comparable level without IV PCA, (2) could reduce opioids-related side effects, and (3) whether an additional dose of dexamethasone on POD 2 would offer further pain-relieving effect without increasing the risk of complications. Methods A total of 178 patients (182 knees) who underwent total knee arthroplasty (TKA) for osteoarthritis were included in the study. The patients were divided into Dexa 2 & PCA and Dexa 3 & NoPCA group.

CIROZ is dispensable in ancestral vertebrates but essential for left-right patterning in humans.

Four genes-DAND5, PKD1L1, MMP21, and CIROP-form a genetic module that has specifically evolved in vertebrate species that harbor motile cilia in their left-right organizer (LRO). We find here that CIROZ (previously known as C1orf127) is also specifically expressed in the LRO of mice, frogs, and fish, where it encodes a protein with a signal peptide followed by 3 zona pellucida N domains, consistent with extracellular localization. We report 16 individuals from 10 families with bi-allelic CIROZ inactivation variants, which cause heterotaxy with congenital heart defects.

The Effect of Adherence to a Tai Chi Intervention on Quality of Life of Older People Living With Dementia.

Background/objectives: Adherence to exercise programs is required to reap their established benefits and to sustain Quality of Life (QoL). This study explored People Living with Dementia's (PLWD) adherence to a Tai Chi exercise program and its effects on their QoL. The study included assessment of factors affecting adherence to a Tai Chi exercise intervention, causes of nonadherence, and effect of adherence on PLWD's QoL.

PFSH-Net: Parallel frequency-spatial hybrid network for segmentation of kidney stones in pre-contrast computed tomography images of dogs.

Kidney stone is a common urological disease in dogs and can lead to serious complications such as pyelonephritis and kidney failure. However, manual diagnosis involves a lot of burdens on radiologists and may cause human errors due to fatigue. Automated methods using deep learning models have been explored to overcome this limitation.

Risk assessment and monitoring of tranquilizers in live seafood: Analysis of natural essential oil and 2-phenoxyethanol by GC-MS/MS.

An analytical method for nine tranquilizer compounds, including eight major natural oil components and 2-phenoxyethanol, was developed using gas chromatography tandem mass spectrometry and validated under CODEX and National Institute of Food and Drug Safety Evaluation guidelines. Subsequently, 315 live seafood samples under Korean preference for sashimi (eight species) were monitored with sales distribution channels and place of origin. A total of 76 detection cases in 65 seafood samples contained the target tranquilizer compounds at concentrations ranging from 2.