Neuropathology-based approach reveals novel Alzheimer's Disease genes and highlights female-specific pathways and causal links to disrupted lipid metabolism: insights into a vicious cycle.

Dementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer's disease (AD) being the most common type. Neuropathological examination remains the gold standard for accurate AD diagnosis, however, most that we know about AD genetics is based on Genome-Wide Association Studies (GWAS) of clinically defined AD. Such studies have identified multiple AD susceptibility variants with a significant portion of the heritability unexplained and highlighting the phenotypic and genetic heterogeneity of the clinically defined entity.

Decoding the protein methylome: Identification, validation, and functional insights.

Protein methylation regulates diverse cellular processes including gene expression and DNA repair. This review discusses the methods of identifying and validating substrates for protein methyltransferases (MTases), as well as the biological roles of methylation. Meanwhile, we outline continued efforts necessary to fully map MTase-substrate pairs and uncover the complex regulatory roles of protein methylation in cellular function.

Continental drift triggered the Early Permian aridification of North China.

The boundary between wet and arid climate zones in the Tethys Ocean remains challenging to trace, complicating our understanding of global aridification pattern during the Late Carboniferous to Early Permian transition. The North China Block (NCB), situated in the Tethys Ocean, underwent a transition from humid to arid climate during the Early Permian, providing a rare opportunity to trace this climate boundary across this region. Here, we present paleomagnetic evidence indicating that the NCB underwent rapid northward drift between 290 and 281 million years ago.

Supramolecular Entrapping and Extraction of Selenate, Molybdate and Tungstate Ions from Water by Nanojars.

The supramolecular binding exclusively by H-bonds of SeO, MoO and WO ions to form nanojars of the formula [EO⊂{-Cu(μ-OH)(μ-pz)}] (; E = Se, Mo, W; = 28-34; pz = pyrazolate) was studied in solution by electrospray ionization mass spectrometry, variable temperature, paramagnetic H NMR and UV-vis spectroscopy, and in the solid state by single-crystal X-ray crystallography. These large anions allow for the observation of a record nanojar size, (E = Mo, W). Six crystal structures are described of nanojars of varying sizes with either SeO, MoO or WO entrapped ions, including the first example of a cocrystal of two different nanojars in crystallographically unique positions, and .

Effect of sign language learning on temporal resolution of visual attention.

The visual environment of sign language users is markedly distinct in its spatiotemporal parameters compared to that of non-signers. Although the importance of temporal and spectral resolution in the auditory modality for language development is well established, the spectrotemporal parameters of visual attention necessary for sign language comprehension remain less understood. This study investigates visual temporal resolution in learners of American Sign Language (ASL) at various stages of acquisition to determine how experience with sign language affects perceptual sampling.

Basic Science and Pathogenesis.

Background: Alzheimer's disease (AD) is the leading cause of dementia, affecting 50 million people globally. Current AD animal models mainly focus on familial or inherited AD. These models often carry the APP and PSEN gene mutations from familial AD patients, or introduce microtubule-associated protein tau (MAPT) mutations, which can cause frontotemporal dementia but are not linked to AD.

Basic Science and Pathogenesis.

Background: The infectious hypothesis of Alzheimer's disease (AD) suggests that microbes may play a role in pathogenesis by triggering the pathologic cascade or contributing to disease progression. Herpesviruses, such as Epstein-Barr virus (EBV), have been of high interest in AD and related neurodegenerative diseases, in part due to their ability to establish lifelong latent infection and potentially reactivate. However, further research is needed to fully understand the role of herpesviruses in these diseases.

Basic Science and Pathogenesis.

Background: Tau aggregates, a hallmark of Alzheimer's disease (AD) and other tauopathies, spread throughout the brain, contributing to neurodegeneration. How this propagation occurs remains elusive. Previous research suggests that tau-seed interactors play a crucial role.

Glial Biologist's Guide to Mass Spectrometry-Based Lipidomics: A Tutorial From Sample Preparation to Data Analysis.

Neurological diseases are associated with disruptions in the brain lipidome that are becoming central to disease pathogenesis. Traditionally perceived as static structural support in membranes, lipids are now known to be actively involved in cellular signaling, energy metabolism, and other cellular activities involving membrane curvature, fluidity, fusion or fission. Glia are critical in the development, health, and function of the brain, and glial regulation plays a major role in disease.

Basic Science and Pathogenesis.

Background: Dysfunctional microglial activity has recently been identified as a potential mechanism leading to accumulation of amyloid beta and pTau and subsequent neurodegeneration in Alzheimer's Disease. The CX3CR1/fractalkine axis serves as a mechanism for bi-directional communication between microglia and neurons, respectively, to promote a resting, anti-inflammatory state in microglia. Previous studies have demonstrated that deficiency in CX3CR1 signaling leads microglia to a more pro-inflammatory phenotype, phagocytic deficits, and increased susceptibility of neurons to cell death.

Basic Science and Pathogenesis.

Background: Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) results in longitudinal decline in cognitive function and brain atrophy. In animals, chronic Pb exposure can increase brain Aβ deposition. However, it remains unclear how Pb induces different natures of amyloid depositions and underlying mechanisms to contribute to the pathogenesis of AD and related dementia.

Basic Science and Pathogenesis.

Background: Exposure to environmental chemicals such as lead (Pb) during vulnerable developmental periods and even in adult stage can result in adverse health outcomes later in life. Human cohort studies have demonstrated associations between Pb exposure and Alzheimer's Disease (AD) onset in later life which were further corroborated by findings from animal studies. The molecular pathway linking Pb exposure and increased AD risk, however, remains elusive.

Progressive iron overload in middle-aged mice impairs olfactory function, triggers lipid oxidation and induces apoptosis.

Introduction: This study aims to investigate the progressive impact of chronic iron overload on the olfactory bulb, a region significantly affected in early neurodegenerative diseases like Parkinson's and Alzheimer's. The focus is on understanding how iron accumulation leads to oxidative stress, mitochondrial dysfunction, and neuronal damage over time in middle-aged mice.

Method: The mice were continuously administered FC for a duration of 16 weeks, and the olfactory behavior of the mice was observed at intervals of 4 weeks.

Characterization and Analytical Method Validation for Potential Impurities of a Merchantability Drug Substance Fluoxetine HCl.

A new selective and sensitive high-performance liquid chromatography (HPLC) method was developed for the quantification of potential impurities in fluoxetine hydrochloride. Chromatographic separation was achieved on an end-capped octadecylsilyl silica gel (Gemini-C18 150 mm × 4.6 mm, 3.

Electro-chemo-mechanics of anode-free solid-state batteries.

Anode-free solid-state batteries contain no active material at the negative electrode in the as-manufactured state, yielding high energy densities for use in long-range electric vehicles. The mechanisms governing charge-discharge cycling of anode-free batteries are largely controlled by electro-chemo-mechanical phenomena at solid-solid interfaces, and there are important mechanistic differences when compared with conventional lithium-excess batteries. This Perspective provides an overview of the factors governing lithium nucleation, growth, stripping and cycling in anode-free solid-state batteries, including mechanical deformation of lithium, the chemical and mechanical properties of the current collector, microstructural effects, and stripping dynamics.

Childhood predictors of high school sport participation and effects of participation on young adult activity and mental health.

Introduction: In the United States, sport is a common form of youth physical activity (PA) with demonstrated health benefits. However, limited longitudinal dataexists on the psychosocial determinants and consequences of youth sport participation. This study examined grade 6 (11-12-year-old) predictors of high school organized sport participation and effects of high school sport participation on age 26 behavior, mental health and wellbeing.

An updated overview on long-acting therapeutics for the prevention and treatment of human immunodeficiency virus (HIV) from a perspective of pharmaceutics.

Conventional drug formulations release active pharmaceutical ingredients (APIs) immediately after administration, while long-acting (LA) drug products are designed for prolonged therapeutic effects, thereby reducing administration frequency and improving patient compliance. The development of LA therapeutics for chronic disease treatment has significantly helped patients adhere to their regimens, reducing the need for daily doses and easing the burden on healthcare systems. Advances in treatment have transformed Human Immunodeficiency Virus (HIV) into a manageable chronic disease, and efforts are underway to eliminate HIV in the future.

The characterization of tumor immune microenvironment after neoadjuvant immunotherapy in head and neck squamous cell cancer using multiplex immunohistochemistry.

Objective: Optimizing clinical decision-making in head and neck squamous cell carcinoma (HNSCC) is challenging due to the ambiguous understanding of the immune cell dynamics and immune checkpoints regulation in the disease after the administration of neoadjuvant immunotherapy (NIT).

Methods: HNSCC biopsy samples collected before and after the neoadjuvant treatment are classified into the pathologic response (PR) and the non-pathologic response (NPR) groups according to treatment responses and the expression of immune cells and checkpoints was labeled using multiplex immunohistochemistry (m-IHC).

Results: The populations of CD4 T cells, CD8 T cells, regulatory T cells (Treg), PD-1, and PD-L1 were particularly higher in the PR group than the NPR group in pre-treatment tissues, with the p-values of log-transformed positive cell density <0.

Release of Bisphenol A and Other Volatile Chemicals from New Epoxy Drinking Water Pipe Liners: The Role of Manufacturing Conditions.

Cured-in-place-pipe (CIPP) technology has begun to be adopted for drinking water pipe repairs, and limited information exists about its drinking water quality impacts. CIPP involves the manufacture of a new plastic pipe inside a buried damaged pipe. In this study, the chemical composition of the raw materials and CIPP water quality impacts were examined.

Medical Reference Tools and Pharmaceutical Promotion: A History of Entanglement.

Reference tools are often uncritically accepted as balanced, objective, definitive, and evidence-based guides to medical knowledge. Yet for centuries textbooks and manuals have been entangled in various ways with industry interests. This essay shows how reference tools have served as sites of pharmaceutical promotion.

Engineering CAR-T Therapeutics for Enhanced Solid Tumor Targeting.

Cancer immunotherapy, specifically Chimeric Antigen Receptor (CAR)-T cell therapy, represents a significant breakthrough in treating cancers. Despite its success in hematological cancers, CAR-T exhibits limited efficacy in solid tumors, which account for more than 90% of all cancers. Solid tumors commonly present unique challenges, including antigen heterogeneity and complex tumor microenvironment (TME).

Molecular insights into the composition, sources, and aging of atmospheric brown carbon.

The light-absorbing chemical components of atmospheric organic aerosols are commonly referred to as Brown Carbon (BrC), reflecting the characteristic yellowish to brown appearance of aerosol. BrC is a highly complex mixture of organic compounds with diverse compositions and variable optical properties of its individual chromophores. BrC significantly influences the radiative budget of the climate and contributes to adverse air pollution effects such as reduced visibility and the presence of inhalable pollutants and irritants.

Tunable mechanical properties of PDMS-TMPTMA microcapsules for controlled release in coatings.

Within coating formulations, microcapsules serve as vehicles for delivering compounds like catalysts and self-healing agents. Designing microcapsules with precise mechanical characteristics is crucial to ensure their contents' timely release and minimize residual shell fragments, thereby avoiding adverse impacts on the coating quality. With these constraints in mind, we explored the use of 1 cSt PDMS oil as a diluent (porogen) in trimethylolpropane trimethacrylate (TMPTMA)-based to fabricate microcapsules with customized mechanical properties and submicrometer debris size after shell breakup that can encapsulate a wide range of compounds.