Prediction of cytotoxicity of polycyclic aromatic hydrocarbons from first principles.

Ligand-specific binding interactions of xenobiotics with receptor proteins form the basis of cytotoxicity-based hazard assessment. Computational approaches enable predictive hazard assessment for a large number of chemicals in a high-throughput manner, minimizing the use of animal testing. However, in silico models for predicting mechanisms of toxic actions and potencies are difficult to develop because toxicity datasets or comprehensive understanding of the complicated kinetic process of ligand-receptor interactions are needed for model development.

Asthma prescribing trends, inhaler adherence and outcomes: a Real-World Data analysis of a multi-ethnic Asian Asthma population.

Inhaled corticosteroid (ICS) is the mainstay therapy for asthma, but general adherence is low. There is a paucity of real-world inhaler prescribing and adherence data from Asia and at the population level. To address these gaps, we performed a real-world data analysis of inhaler prescribing pattern and adherence in a multi-ethnic Asian asthma cohort and evaluated the association with asthma outcomes.

Mechanistic insight into airborne particulate matter PM10 as an environmental hazard for hemorrhagic stroke: Evidence from in vitro and in vivo studies.

Airborne particulate matter less than 10 µm in diameter (PM10) is recognized as a significant environmental risk factor for hemorrhagic stroke (HS), as evidenced by epidemiological studies that link PM10 with the heightened cerebrovascular mortality related to HS. Nonetheless, the molecular mechanisms underlying this association remain unknown. Cerebral aneurysm (CA), an etiological factor of HS, is characterized by a bulge resulting from the abnormal loss of the muscular layer of a cerebral artery, comprising brain vascular endothelial cell (BVEC) and vascular smooth muscle cell (VSMC).

Herbicides as fungicides: Targeting heme biosynthesis in the maize pathogen Ustilago maydis.

Pathogens must efficiently acquire nutrients from host tissue to proliferate, and strategies to block pathogen access therefore hold promise for disease control. In this study, we investigated whether heme biosynthesis is an effective target for ablating the virulence of the phytopathogenic fungus Ustilago maydis on maize plants. We first constructed conditional heme auxotrophs of the fungus by placing the heme biosynthesis gene hem12 encoding uroporphyrinogen decarboxylase (Urod) under the control of nitrogen or carbon source-regulated promoters.

Correlations between the long noncoding RNA MEG3 and clinical characteristics for diabetic kidney disease in type 2 diabetes mellitus.

Background And Aims: Diabetic kidney disease (DKD) is a common complication of type 2 diabetes mellitus (T2DM) that leads to systemic inflammation. Maternally expressed gene 3 (MEG3) is a tumor suppressor that is involved in inflammation regulation. The current study investigated the association between DKD and the prevalence of the single-nucleotide polymorphisms (SNPs) of MEG3.

Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses.

Kirsten rat sarcoma virus (KRAS)-G12C inhibition causes remodeling of the lung tumor immune microenvironment and synergistic responses to anti-PD-1 treatment, but only in T cell infiltrated tumors. To investigate mechanisms that restrain combination immunotherapy sensitivity in immune-excluded tumors, we used imaging mass cytometry to explore cellular distribution in an immune-evasive KRAS mutant lung cancer model. Cellular spatial pattern characterization revealed a community where CD4 and CD8 T cells and dendritic cells were gathered, suggesting localized T cell activation.

Shifts in embryonic oxygen levels cue heterochrony in limb initiation.

Heterochrony, or the alteration of developmental timing, is an important mechanism of evolutionary change. Avian species display synchronized growth of the forelimbs and hindlimbs, while mammalian species show delayed hindlimb development. We find that mammalian limb heterochrony is evident from the start of limb bud formation, and is associated with heterochronic expression of T-box transcription factors.

CFD investigations of a shape-memory polymer foam-based endovascular embolization device for the treatment of intracranial aneurysms.

The hemodynamic and convective heat transfer effects of a patient-specific endovascular therapeutic agent based on shape memory polymer foam (SMPf) are evaluated using computational fluid dynamics studies for six patient-specific aneurysm geometries. The SMPf device is modeled as a continuous porous medium with full expansion for the flow studies and with various degrees of expansion for the heat transfer studies. The flow simulation parameters were qualitatively validated based on the existing literature.

A Unique Case of Vascular Variations in the Upper Limbs: A Brachioradial Artery and Bilateral Persistent Median Arteries With Incomplete Superficial Palmar Arches.

Numerous vascular variations were observed in the upper limbs of a 109-year-old female donor to the Gift Body Program of Saint Louis University School of Medicine. Variations in the right upper limb included the presence of a brachioradial artery (BRA), persistent median artery (PMA), and an ulnar-dominant incomplete type B superficial palmar arch (SPA). In the left upper limb, the brachial artery bifurcated normally into the ulnar artery (UA) and radial artery (RA).

Hyperglycemia-triggered lipid peroxidation destabilizes STAT4 and impairs anti-viral Th1 responses in type 2 diabetes.

Patients with type 2 diabetes (T2D) are more susceptible to severe respiratory viral infections, but the underlying mechanisms remain elusive. Here, we show that patients with T2D and coronavirus disease 2019 (COVID-19) infections, and influenza-infected T2D mice, exhibit defective T helper 1 (Th1) responses, which are an essential component of anti-viral immunity. This defect stems from intrinsic metabolic perturbations in CD4 T cells driven by hyperglycemia.

2-[F]Fluoropropionic Acid PET Imaging of Doxorubicin-induced Cardiotoxicity.

Purpose: Treatment of pediatric cancers with doxorubicin is a common and predictable cause of cardiomyopathy. Early diagnosis of treatment-induced cardiotoxicity and intervention are major determinants for the prevention of advanced disease. The onset of cardiomyopathies is often accompanied by profound changes in lipid metabolism, including an enhanced uptake of short-chain fatty acids (SCFA).

Health risks of environmentally persistent free radicals in atmospheric particulate matter during the spring festival travel season in Tainan, Taiwan.

Environmentally persistent free radicals (EPFRs) and polycyclic aromatic hydrocarbons (PAHs) are persistent pollutants in atmospheric particulate matter that are detrimental to human health. This study collected atmospheric particulate matter during and after the spring festival travel season in Tainan, Taiwan, from various locations and analyzed the carbon composition and PAH isomeric ratios to identify the sources. In this study, EPFR concentrations were measured using electron paramagnetic resonance spectroscopy, with the highest concentration found to be 3.

Biochemical analysis of soft tissue infectious fluids and its diagnostic value in necrotizing soft tissue infections: a 5-year cohort study.

Background: Necrotizing soft tissue infections (NSTI) are rapidly progressing and life-threatening conditions that require prompt diagnosis. However, differentiating NSTI from other non-necrotizing skin and soft tissue infections (SSTIs) remains challenging. We aimed to evaluate the diagnostic value of the biochemical analysis of soft tissue infectious fluid in distinguishing NSTIs from non-necrotizing SSTIs.

Surgical anatomy of the carotid sympathetic plexus in endoscopic endonasal approaches: strategies for preventing Horner syndrome.

Objective: Endoscopic endonasal approaches (EEAs) specifically for procedures involving manipulation of the internal carotid artery (ICA), such as the transcavernous and translacerum approaches, confer a potential risk of carotid sympathetic plexus injury, potentially leading to postganglionic Horner syndrome. The primary aim of this study was to delineate the surgical anatomy of the carotid sympathetic plexus from an endoscopic endonasal perspective, offering insights to facilitate intraoperative anatomical identification and injury prevention.

Methods: A comprehensive dissection was conducted on 20 silicone-injected, lightly embalmed postmortem human heads.

The Pharmacogenomics Global Research Network Implementation Working Group: global collaboration to advance pharmacogenetic implementation.

Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

Characterization of insecticide resistance and their mechanisms in field populations of the German cockroach (Blattodea: Ectobiidae) in Taiwan under different treatment regimes.

This study investigated how management strategies influence resistance profiles in German cockroach (Blattella germanica (L.)) populations and their impact on the performance of commercial gel baits containing fipronil, imidacloprid, and indoxacarb. Field populations from premises managed under 3 different strategies: Baiting, random insecticide (RI) used, and insecticide rotation (IR) were tested.

Seq-Scope: repurposing Illumina sequencing flow cells for high-resolution spatial transcriptomics.

Spatial transcriptomics technologies aim to advance gene expression studies by profiling the entire transcriptome with intact spatial information from a single histological slide. However, the application of spatial transcriptomics is limited by low resolution, limited transcript coverage, complex procedures, poor scalability and high costs of initial setup and/or individual experiments. Seq-Scope repurposes the Illumina sequencing platform for high-resolution, high-content spatial transcriptome analysis, overcoming these limitations.

Prenatal diagnosis of 9q34.3 microdeletion-associated Kleefstra syndrome in a pregnancy complicated by polyhydramnios: A case report and literature review.

Objective: Kleefstra Syndrome (KS) is a rare genetic disorder caused by a deletion at 9q34.3. Studies showed that various heart defects are observed in 41-43% of patients and abnormal features on brain imaging in 58-63%.