Astrocyte priming enhances microglial Aβ clearance and is compromised by APOE4.

The innate immune system can develop a form of memory called priming, where prior exposure to a stimulus enhances subsequent responses. While well-characterized in peripheral immunity, its function in brain-resident cells such as astrocytes under non-disease conditions remains unclear. Here we show that human astrocytes derived from the induced pluripotent stem cells of healthy female donors, but not microglia, acquire a primed state following transient immune stimulations.

Improved Depression Symptoms Among Low-Income Mexican Americans Participating in a Community-Clinical Diabetes Intervention.

Background: Adults with type 2 diabetes mellitus and comorbid depression face complex disease management. Salud y Vida, a diabetes management intervention for Mexican Americans in the Rio Grande Valley of Texas, may mitigate depression through social support and community-clinic referrals.

Methods: In a cohort study, 292 Salud y Vida participants completed the patient health questionnaire (PHQ-9) at baseline, month 6, and month 12.

Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.

Genetic mutations in the progranulin gene, GRN, cause frontotemporal dementia and a lysosomal storage disorder. Using single-nuclei RNA sequencing of the post-mortem brain tissue from adult heterozygous pathogenic granulin variant (GRN+/-) carriers we find dysregulation of microglia, phagocytosis and the phagocytic receptors MERTK and AXL. Exogenous progranulin regulates MERTK and AXL RNA expression in human microglia induced from iPSCs irrespective of GRN mutation status, without directly binding to MERTK or AXL proteins.

The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway.

The Christchurch mutation (R136S) in the APOE3 (E3S/S) gene is associated with attenuated tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high amyloid burden in the carrier. However, the molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse Apoe with wild-type human APOE3 or APOE3S/S on a tauopathy background.

Application of instant assembly of collagen to bioprint cardiac tissues.

Advancing cardiac tissue engineering requires innovative fabrication techniques, including 3D bioprinting and tissue maturation, to enable the generation of new muscle for repairing or replacing damaged heart tissue. Recent advances in tissue engineering have highlighted the need for rapid, high-resolution bioprinting methods that preserve cell viability and maintain structural fidelity. Traditional collagen-based bioinks gel slowly, limiting their use in bioprinting.

Instant assembly of collagen for tissue engineering and bioprinting.

Engineering functional cellular tissue components holds great promise in regenerative medicine. Collagen I, a key scaffolding material in bodily tissues, presents challenges in controlling its assembly kinetics in a biocompatible manner in vitro, restricting its use as a primary scaffold or adhesive in cellular biofabrication. Here we report a collagen fabrication method termed as tunable rapid assembly of collagenous elements that leverages macromolecular crowding to achieve the instant assembly of unmodified collagen.

High-Performance Oxide Thin-Film Transistors with Atomic Layer Deposition-Grown HfO/BeO Hetero-Dielectric.

Atomic layer deposition-grown beryllium oxide (BeO) is gaining attention as a dielectric material that can minimize device power consumption because of its high dielectric constant, high thermal conductivity, and low leakage current enabled by its wide bandgap energy. In this study, the impact of BeO dielectrics on InSnZnO (ITZO) thin-film transistors (TFTs) was investigated, revealing that adding a hafnium dioxide (HfO) layer can enhance electrical performance and bias stress reliability. Time-of-flight secondary-ion mass spectrometry and X-ray photoelectron spectroscopy confirmed that the single-BeO dielectric-based ITZO TFTs exhibited a low mobility of 27.

Imaging lipid rafts reveals the principle of ApoE4-induced Aβ upregulation in human neurons.

Lipid rafts in plasma membranes are thought to provide a platform for regulating signaling pathways by increasing the expression or proximity of proteins in the same pathway. Despite this understanding, the absence of direct, simultaneous observations of lipid rafts and their affiliated proteins has hindered a comprehensive assessment of their roles across various biological contexts. Amyloid-β (Aβ), a hallmark of Alzheimer's disease (AD), is generated from the sequential cleavage of amyloid precursor proteins (APPs) by β- and -secretases, primarily within endosomes after APP endocytosis by canonical clathrin-mediated endocytosis in neurons.

ITZO-Based Self-Aligned Top Gate Thin-Film Transistor with Minimum Parasitic Capacitance for Long-Retention 2T0C DRAM.

We developed a two-transistor, zero-capacitor (2T0C) gain-cell memory featuring a self-aligned top-gate-structured thin-film transistor (TFT) for the first time. The proposed indium tin zinc oxide (ITZO) channel-incorporated architecture was specifically engineered to minimize parasitic capacitance for achieving long-retention 2T0C memory operations. A typical 2T0C structure features five types of parasitic capacitances; however, the proposed SATG design effectively used an essential gate insulator capacitance ( ) and reduced four nonessential capacitances ( , , , and ) to virtually zero.

Pituitary Gland Macroadenoma with Associated Hearing Loss.

Pituitary macroadenomas are benign neoplasms that can cause a range of symptoms due to a mass effect on surrounding structures. This case report describes a 51-year-old male presenting with progressive bilateral hearing impairment and significant deterioration in speech discrimination over several years. Examination revealed normal tympanic membranes and no neurological deficits, while pure tone audiometry indicated mild to moderate sensorineural hearing loss.

Thermal Dehydrogenation Impact on Positive Bias Stability of Amorphous InSnZnO Thin-Film Transistors.

Recently, the growing demand for amorphous oxide semiconductor thin-film transistors (AOS TFTs) with high mobility and good stability to implement ultrahigh-resolution displays has made tracking the role of hydrogen in oxide semiconductor films increasingly important. Hydrogen is an essential element that contributes significantly to the field effect mobility and bias stability characteristics of AOS TFTs. However, because hydrogen is the lightest atom and has high reactivity to metal and oxide materials, elucidating its impact on AOS thin films has been challenging.

- mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition.

The Christchurch mutation (R136S) on the ( ) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal mutation and high levels of amyloid beta pathology in the carrier. However, the specific molecular mechanisms enabling the mutation to mitigate tau-induced neurodegeneration remain unclear. Here, we replaced mouse with wild-type human or on a tauopathy background.

HDAC6 preserves BNIP3 expression and mitochondrial integrity by deacetylating p53 at lysine 320.

HDAC6 has been reported as a deacetylase of p53 at multiple lysine residues, associated with the canonical functions of p53, such as apoptosis and tumor suppression. We have previously reported that p53 acetylation at the lysine 320 site accumulates due to the genetic ablation of HDAC6 in mice liver. However, the biological processes affected by K320 acetylation of p53 are yet to be elucidated.

Instant Assembly of Collagen for Scaffolding, Tissue Engineering, and Bioprinting.

Controllable assembly of cells and tissues offers potential for advancing disease and development modeling and regenerative medicine. The body's natural scaffolding material is the extracellular matrix, composed largely of collagen I. However, challenges in precisely controlling collagen assembly limit collagen's applicability as a primary bioink or glue for biofabrication.

ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes.

Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer's disease (AD). Among them, genetic variant ε4 of the APOE gene (APOE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD.

Silicone engineered anisotropic lithography for ultrahigh-density OLEDs.

Ultrahigh-resolution patterning with high-throughput and high-fidelity is highly in demand for expanding the potential of organic light-emitting diodes (OLEDs) from mobile and TV displays into near-to-eye microdisplays. However, current patterning techniques so far suffer from low resolution, consecutive pattern for RGB pixelation, low pattern fidelity, and throughput issue. Here, we present a silicone engineered anisotropic lithography of the organic light-emitting semiconductor (OLES) that in-situ forms a non-volatile etch-blocking layer during reactive ion etching.

SIRT1 suppresses in vitro decidualization of human endometrial stromal cells through the downregulation of forkhead box O1 expression.

SIRT1 regulates survival, DNA repair, and metabolism in human cells and has pleiotropic effects on age-related diseases through either deacetylating target proteins or inhibiting gene transcription. Forkhead box O1 (FOXO1) is one of the most important transcription factors during decidualization. Prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) are well-known FOXO1-dependent genes in decidualizing cells.

Vacuum-free solution-based metallization (VSM) of a-IGZO using trimethylaluminium solution.

This research demonstrates a method to reduce the resistance of amorphous indium-gallium-zinc-oxide (a-IGZO) using a "vacuum-free solution-based metallization" (VSM) process, which revolutionizes the metallization process thanks to its simplicity, by simply dipping the a-IGZO into trimethyl aluminium (TMA, (CH)Al) solution. From the XPS results, it was found that oxygen vacancies were generated after the VSM process, resulting in the enhanced conductivity. Various metallization time and solution temperature conditions were investigated, and the measured conductivity of the a-IGZO could be enhanced up to 20.

APOE4-carrying human astrocytes oversupply cholesterol to promote neuronal lipid raft expansion and Aβ generation.

The ε4 allele of APOE-encoding apolipoprotein (ApoE) is one of the strongest genetic risk factors for Alzheimer's disease (AD). One of the overarching questions is whether and how this astrocyte-enriched risk factor initiates AD-associated pathology in neurons such as amyloid-β (Aβ) accumulation. Here, we generate neurons and astrocytes from isogenic human induced pluripotent stem cells (hiPSCs) carrying either APOE ε3 or APOE ε4 allele and investigate the effect of astrocytic ApoE4 on neuronal Aβ production.

A Synthetic CPP33-Conjugated Active Domain Peptide Inhibits Invasion Ability of Non-Small Lung Cancer Cells.

Homeobox A9 () expression is associated with the aggressive growth of cancer cells and poor prognosis in lung cancer. Previously, we showed that can serve as a potential therapeutic target for the treatment of metastatic non-small cell lung cancer (NSCLC). In the present study, we have carried out additional studies toward the development of a peptide-based therapeutic agent.

Decursinol from Angelica gigas Nakai enhances endometrial receptivity during implantation.

Background: Embryo implantation is essential for a successful pregnancy, and an elaborate synchronization between the receptive endometrium and trophoblast is required to achieve this implantation. To increase 'endometrial receptivity', the endometrium undergoes transformation processes including responses of adhesion molecules and cellular and molecular cell to cell communication. Many natural substances from traditional herbs have been studied to aid in the achievement of successful implantation.

Postmortem proteomics to discover biomarkers for forensic PMI estimation.

The assessment of postmortem degradation of skeletal muscle proteins has emerged as a novel approach to estimate the time since death in the early to mid-postmortem phase (approximately 24 h postmortem (hpm) to 120 hpm). Current protein-based methods are limited to a small number of skeletal muscle proteins, shown to undergo proteolysis after death. In this study, we investigated the usability of a target-based and unbiased system-wide protein analysis to gain further insights into systemic postmortem protein alterations and to identify additional markers for postmortem interval (PMI) delimitation.

Whole grain cereal attenuates obesity-induced muscle atrophy by activating the PI3K/Akt pathway in obese C57BL/6N mice.

Whole grain comprises starchy endosperm, germ, and bran tissues, which contain fibers, minerals, vitamins, and several phytochemicals. Whole grain cereal (WGC)-based food products supply beneficial nutrients (essential for health care) and macronutrients (essential for body maintenance and support). The present study investigated the inhibitory effect of WGC on obesity-induced muscle atrophy in obese C57BL/6N mice.

HDAC6 regulates thermogenesis of brown adipocytes through activating PKA to induce UCP1 expression.

Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics.

HDAC6 deficiency induces apoptosis in mesenchymal stem cells through p53 K120 acetylation.

The acetylation of p53 is critical in modulating its pro-apoptotic roles. However, its regulatory mechanism and physiological significance are unclear. Here, we show HDAC6 negatively regulates pro-apoptotic acetylation of p53 at lysine residue 120 (K120) in mesenchymal stem cells (MSCs).