Analyses of NOTCH3 variants in Chinese patients with clinically diagnosed Alzheimer's disease and frontotemporal dementia.

Background: A pathogenic variant in the NOTCH3 gene has been identified as the cause of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Studies focusing on variants in NOTCH3 in Alzheimer's disease (AD) and frontotemporal dementia (FTD) cohorts have been limited. We aim to screen clinically diagnosed AD and FTD patients with unknown etiology for pathogenic variants in NOTCH3 in the Chinese population.

Gut-derived bacterial vesicles carrying lipopolysaccharide promote microglia-mediated synaptic pruning.

Introduction: Growing evidence links gut microbiota (GM) to Alzheimer's disease (AD). Elevated lipopolysaccharide (LPS) levels, a Gram-negative bacteria component, are found in AD brains, but how LPS breaches the blood-brain barrier (BBB) remains unclear. Hypotheses suggest that bacteria-derived extracellular vesicles (bEVs) may transport LPS across the BBB.

Cohort profile: China healthy aging cohort study (China-Aging).

BackgroundAs China undergoes a demographic transition towards an aging society, the prevalence and incidence of age-related disabilities, Alzheimer's disease, and various geriatric syndromes are steadily rising.ObjectiveThe China Healthy Aging Cohort Study (China-Aging) aims to investigate the prevalence and associated risk factors of disability and cognitive impairment, and to develop predictive models for these conditions by combining traditional risk factors with artificial intelligence-derived metrics (such as gait, speech, vision, etc.).

Serum lipidomic analysis identifies potential therapeutic targets for neurodegeneration.

Introduction: Circulating very-long-chain saturated fatty acids (VLSFAs) may attenuate age-related cognitive decline, but their direct association with neurodegeneration biomarkers and the underlying mechanisms remain unclear.

Methods: This cross-sectional study examined associations between circulating fatty acid profiles, neurodegeneration (assessed by serum neurofilament light chain, NfL), cognitive function, and hypertension in 1,677 U.S.

A novel 8-octapeptide repeat insertion in causing Huntington disease-like 1 in a Chinese family: a case report and literature review.

Background: Approximately 1-3% of patients with Huntington disease (HD) present with HD-like phenotype but test negative for the HD gene, suggesting other causes.

Methods: This study presents the first case of Huntington disease-like 1 (HDL-1) in a Chinese family and summarises the clinical features of previously reported HDL-1 cases and patients with octapeptide repeat insertion (OPRI) mutations.

Results: The proband, a 36-year-old woman, presented with progressive involuntary movements, bradykinesia, cognitive decline and personality changes over 6 years, worsening over the past year.

Exploring the causal association between fatty acid-binding proteins and anaphylactic shock due to adverse reactions to medications: A two-sample Mendelian randomization study.

Previous studies have identified a relationship between fatty acid-binding proteins (FABPs) and immune diseases. This study aimed to investigate whether a causal relationship exists between FABPs and anaphylactic shock resulting from adverse drug reactions. Single nucleotide polymorphisms associated with FABPs were utilized as instrumental variables, sourced from the National Human Genome Research Institute-European Bioinformatics Institute Catalog of human genome-wide association studies.

Smoking alters effective connectivity of resting-state brain networks in mild cognitive impairment.

BackgroundSmoking, a modifiable risk factor for Alzheimer's disease (AD), is associated with impaired functional connectivity in resting-state networks (RSNs). This study investigates how smoking affects brain effective connectivity (EC).ObjectiveInvestigate smoking-associated EC alterations.

Zmynd11 is essential for neurogenesis by coordinating H3K36me3 modification of Epha2 and PI3K signaling pathway.

10p15.3 deletion syndrome is caused by the deficiency of MYND-type zinc finger domain-containing protein 11 (ZMYND11) and featured by global developmental delay, intellectual disability, behavioral abnormalities, etc. Although the roles of Zmynd11 is intensively studied in cancer, the function and associated mechanisms of Zmynd11 in neurodevelopment remain largely unknown.

Qingkailing injection induces pseudo-allergic reactions via the MRGPRX2 pathway.

Objective: Qingkailing Injection (QKLI) is a traditional Chinese medicine injection mainly used for sedation, heat clearing, and other treatments. However, recent clinical studies have shown a risk of pseudo-allergic reactions. The purpose of this study is to elucidate the underlying mechanism of QKLI-induced mast cell degranulation in Laboratory of Allergic Diseases 2 (LAD2) and to validate QKLI-induced activation of guinea pig IgE-independent allergic responses.

Molecular pathways and diagnosis in spatially resolved Alzheimer's hippocampal atlas.

We employed Stereo-seq combined with single-nucleus RNA sequencing (snRNA-seq) to investigate the gene expression and cell composition changes in human hippocampus with or without Alzheimer's disease (AD). The transcriptomic map, with single-cell precision, unveiled AD-associated alterations with spatial specificity, which include the following: (1) elevated synapse pruning gene expression in the fimbria of AD, with disrupted microglia-astrocyte communication likely leading to disorganized synaptic structure; (2) a globally increased energy generation in the cornu ammonis (CA) region, with varying degrees across its subregions; (3) a significant reduction in the number of CA1 neurons in AD, while CA4 neurons remained largely unaffected, potentially due to gene alterations in CA4 conferring resilience to AD; and (4) aggravated amyloid-beta (Aβ) plaques in CA1 and stratum lucidum, radiatum, and moleculare (SLRM), and integration of Stereo-seq map with Aβ staining revealed a sequential enrichment of microglia and astrocytes around Aβ plaques. Finally, reduced brain-derived extracellular vesicles carrying cholecystokinin (CCK) and peripheral myelin protein 2 (PMP2) in AD plasma highlighted their diagnostic potential for clinical applications.

Mechanistic exploration of licorice reconciling Medicine:Huangqi Guizhi Wuwu decoction and Shaoyao Gancao decoction compatibility as an example.

Ethnopharmacological Relevance: Glycyrrhiza uralensis Fisch. (GU) is a pivotal botanical in traditional Chinese medicine (TCM), because of its ability to reconcile various herbs, and its crucial role in numerous formulas. Huanggui Shaogan decoction (HSGD) is an empirical formula, developed by Huangqi Guizhi Wuwu decoction (HGD) and Shaoyao Gancao decoction (SGD), and prepared by adding GU to HGD.

Taraxasterol attenuates inflammatory responses in a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model via inactivation of the MAPK and NF-κB pathways.

Atopic dermatitis (AD) is an inflammatory skin disease. Taraxasterol has anti-inflammatory effects in various pathological processes. In this study, our goal is to detect the biological functions of taraxasterol and its related mechanisms in AD development.

Immunomodulation of Polysaccharides In Vivo Based on Microbiome and Metabolomics Approaches.

is a medicinal herb that can be added to food to provide therapeutic effects and reduce the burden of medications. Herein, the immunomodulatory effects of polysaccharides (GPs) were verified and illustrated by intervening immunocompromised rats treated with different doses of GPs, which were reflected for adjusting the composition and structure of the intestinal microbiota and altering the metabolic profile. The immunomodulatory effects of GPs were exerted by regulating the intestinal microenvironment.

Peripheral Single-Cell Immune Characteristics Contribute to the Diagnosis of Alzheimer's Disease and Dementia With Lewy Bodies.

Objective: Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are common neurodegenerative diseases with distinct but overlapping pathogenic mechanisms. The clinical similarities between these diseases often result in high misdiagnosis rates, leading to serious consequences. Peripheral blood mononuclear cells (PBMCs) are easy to collect and can accurately reflect the immune characteristics of both DLB and AD.

Border-associated macrophages: From physiology to therapeutic targets in Alzheimer's disease.

Border-associated macrophages (BAMs) constitute a highly heterogeneous group of central nervous system-resident macrophages at the brain boundaries. Despite their significance, BAMs have mainly been overlooked compared to microglia, resulting in a limited understanding of their functions. However, recent advancements in single-cell immunophenotyping and transcriptomic analyses of BAMs have revealed a previously unrecognized complexity in these cells, in addition to their critical roles under non-pathological conditions and diseases like Alzheimer's disease (AD), Parkinson's disease, glioma, and ischemic stroke.

Lipopolysaccharide aggravating anaphylactoid reactions caused by traditional Chinese Medicine injections via p38/ERK/NF-κB signaling pathways.

Ethnopharmacological Relevance: Currently, adverse reactions limit the development of traditional Chinese medicine injections (TCMI), and severe anaphylactoid shock is one of the serious adverse reactions, which presents a significant challenge. The presence of abnormal inflammatory mediators before the administration of TCMI will most likely result in severe anaphylactoid reactions. Not only that, the lack of clinically relevant safety evaluations impedes the widespread use of TCMI, and there is an urgent need for studies to reveal the mechanisms of anaphylactoid shock caused by TCMI.

Alzheimer's disease and sleep disorders: A bidirectional relationship.

Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) and nonrapid eye movement sleep (NREM), plays a key role in consolidating social and spatial memory. Emerging evidence has revealed that sleep disorders such as circadian disturbances and disruption of neuronal rhythm activity are considered as both candidate risks and consequence of AD, suggesting a bidirectional relationship between sleep and AD. This review will firstly grasp basic knowledge of AD pathogenesis, then highlight macrostructural and microstructural alteration of sleep along with AD progression, explain the interaction between accumulation of Aβ and hyperphosphorylated tau, which are two critical neuropathological processes of AD, as well as neuroinflammation and sleep, and finally introduce several methods of sleep enhancement as strategies to reduce AD-associated neuropathology.

Comprehensive Comparison of Three Different Medicinal Parts of DC. Using the RRLC-Q-TOF-MS-Based Metabolic Profile and In Vitro Anti-Inflammatory Activity.

DC. (EL) is a traditional Chinese herb known for its phlegm-reducing, cough-relieving and asthma-calming properties. It is widely used for treating cough and bronchitis.

Advances in Blood Biomarkers for Alzheimer's Disease: Ultra-Sensitive Detection Technologies and Impact on Clinical Diagnosis.

Alzheimer's disease has escalated into a critical public health concern, marked by its neurodegenerative nature that progressively diminishes cognitive abilities. Recognized as a continuously advancing and presently incurable condition, AD underscores the necessity for early-stage diagnosis and interventions aimed at delaying the decline in mental function. Despite the proven efficacy of cerebrospinal fluid and positron emission tomography in diagnosing AD, their broader utility is constrained by significant costs and the invasive nature of these procedures.

Rapid evaluation of the quality of Smilax glabra Roxb. using QADS based on FT-NIR combined with multiple intelligent algorithms.

Smilax glabra Roxb. (SGR) is known for its high nutritional and therapeutic value. However, the frequent appearance of counterfeit products causes confusion and inconsistent quality among SGR varieties.

An efficient method for rapid screening of triterpenoid saponins in three Glycyrrhiza species using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry combined with mass defect filtering.

Triterpenoid saponins, a major bioactive component of liquorice, possess high hydrophilicity and often co-occur with other impurities of similar polarity. Additionally, subtle structural differences of some triterpenoid saponins bring challenges to comprehensive characterisation. In this study, triterpenoid saponins of three Glycyrrhiza species were systematically analysed using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) coupled with mass defect filtering (MDF).

Cognitive Impairment in the Post-Acute Phases of COVID-19 and Mechanisms: An Introduction and Narrative Review.

Cognitive impairment is a primary manifestation of neurological symptoms associated with COVID-19 and may occur after disease resolution. Although cognitive impairment has been extensively reported in the literature, its duration and rate of remission remain controversial. This study discusses the various factors that influence cognitive impairment, including demographic characteristics, genetics, as well as disease course and severity.