Identification of Alzheimer's disease susceptibility genes by integrating eight human brain single-cell transcriptomes with genome-wide association studies.

To date, several studies have integrated genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL) data from bulk tissues to identify novel Alzheimer's disease (AD) genetic variants and susceptibility genes. However, there is highly cell-type-specific nature in different bulk eQTL data. Until now, eQTL data from different brain single cells have been reported.

Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition.

Background: NLRP3 inflammasome-related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti-inflammatory agents in improving severe CVT prognosis remains controversial.

Methods: A total of 94 male Sprague-Dawley rats were used.

Causal association between insulin sensitivity index and Alzheimer's disease.

Evidence from observational and Mendelian randomization (MR) studies suggested that insulin resistance (IR) was associated with Alzheimer's disease (AD). However, the causal effects of different indicators of IR on AD remain inconsistent. Here, we aim to assess the causal association between the insulin sensitivity index (ISI), a measure of post-prandial IR, and the risk of AD.

Blood-derived factors to brain communication in brain diseases.

Brain diseases, mainly including acute brain injuries, neurodegenerative diseases, and mental disorders, have posed a significant threat to human health worldwide. Due to the limited regenerative capability and the existence of the blood-brain barrier, the brain was previously thought to be separated from the rest of the body. Currently, various cross-talks between the central nervous system and peripheral organs have been widely described, including the brain-gut axis, the brain-liver axis, the brain-skeletal muscle axis, and the brain-bone axis.

Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era.

Stroke remains the leading cause of death and disability in some countries, predominantly attributed to acute ischemic stroke (AIS). While intravenous thrombolysis and endovascular thrombectomy are widely acknowledged as effective treatments for AIS, boasting a high recanalization rate, there is a significant discrepancy between the success of revascularization and the mediocre clinical outcomes observed among patients with AIS. It is now increasingly understood that the implementation of effective cerebral protection strategies, serving as adjunctive treatments to reperfusion, can potentially improve the outcomes of AIS patients following recanalization therapy.

Causal relationships between dyslexia and the risk of eight dementias.

Observational and genetic studies have reported the relationship between dyslexia and Alzheimer's disease (AD). Until now, the causal effect of dyslexia on AD risk has remained unclear. We conducted a two-sample univariable Mendelian randomization (MR) analysis to determine the causal association between dyslexia and the risk of AD, vascular dementia (VD), Lewy body dementia (LBD), and frontotemporal dementia (FTD) and its four subtypes.

A Neural Network-Based Scoring System for Predicting Prognosis and Therapy in Breast Cancer.

Breast cancer is a prevalent malignancy affecting women worldwide. Currently, there are no precise molecular biomarkers with immense potential for accurately predicting breast cancer development, which limits clinical management options. Recent evidence has highlighted the importance of metastatic and tumor-infiltrating immune cells in modulating the antitumor therapy response.

Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease.

Background: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2.

Genetic evidence for causal association between migraine and dementia: a mendelian randomization study.

Background: There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer's disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB).

Methods: Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia.

Interpretation of 10 years of Alzheimer's disease genetic findings in the perspective of statistical heterogeneity.

Common genetic variants and susceptibility loci associated with Alzheimer's disease (AD) have been discovered through large-scale genome-wide association studies (GWAS), GWAS by proxy (GWAX) and meta-analysis of GWAS and GWAX (GWAS+GWAX). However, due to the very low repeatability of AD susceptibility loci and the low heritability of AD, these AD genetic findings have been questioned. We summarize AD genetic findings from the past 10 years and provide a new interpretation of these findings in the context of statistical heterogeneity.

Adversarial learning-based domain adaptation algorithm for intracranial artery stenosis detection on multi-source datasets.

Intracranial arterial stenosis (ICAS) is characterized by the pathological narrowing or occlusion of the inner lumen of intracranial blood vessels. However, the retina can indirectly react to cerebrovascular disease. Therefore, retinal fundus images (RFI) serve as valuable noninvasive and easily accessible screening tools for early detection and diagnosis of ICAS.

Mendelian randomization study supports the causal effects of air pollution on longevity via multiple age-related diseases.

Growing evidence suggests that exposure to fine particulate matter (PM) may reduce life expectancy; however, the causal pathways of PM exposure affecting life expectancy remain unknown. Here, we assess the causal effects of genetically predicted PM concentration on common chronic diseases and longevity using a Mendelian randomization (MR) statistical framework based on large-scale genome-wide association studies (GWAS) (>400,000 participants). After adjusting for other types of air pollution and smoking, we find significant causal relationships between PM concentration and angina pectoris, hypercholesterolaemia and hypothyroidism, but no causal relationship with longevity.

Causal Effect of Lipoprotein-Associated Phospholipase A2 Activity on Ischemic Stroke: A Mendelian Randomization Study.

Background: The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization (MR) was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes.

Methods: Based on information from a meta-analysis of genome-wide association studies, which included 13,664 European people, five single nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables.

rs56405341 Variant Associates with Expression of C4orf33 and C4orf33 Was Downregulated in Alzheimer's Disease and Progressive Supranuclear Palsy.

The first primary age-related tauopathy (PART) genome-wide association study confirmed significant associations of Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) genetic variants with PART, and highlighted a novel genetic variant rs56405341. Here, we perform a comprehensive analysis of rs56405341. We found that rs56405341 was significantly associated with C4orf33 mRNA expression, but not JADE1 mRNA expression in multiple brain tissues.

Genetic correlation, causal relationship, and shared loci between vitamin D and COVID-19: A genome-wide cross-trait analysis.

Observational studies have shown that vitamin D supplementation reduces the risk of COVID-19 infection, yet little is known about the shared genomic architectures between them. Leveraging large-scale genome-wide association study (GWAS) summary statistics, we investigated the genetic correlation and causal relationship between genetically determined vitamin D and COVID-19 using linkage disequilibrium score regression and Mendelian randomization (MR) analyses, and conducted a cross-trait GWAS meta-analysis to identify the overlapping susceptibility loci of them. We observed a significant genetic correlation between genetically predicted vitamin D and COVID-19 (r  = -0.

Potential of Secondary Metabolites of Species Associated with Terrestrial and Marine Origins.

species produce versatile secondary metabolites (SMs), including terpenoids, fatty acids, polyketides, steroids, and alkaloids. These structurally diverse SMs exhibit a wide range of biological activities, including cytotoxic, antifungal, antibacterial, antiviral, antioxidant, anti-inflammatory, and phytotoxic activities, which could be exploited in the medical, agricultural, and other modern industries. This review comprehensively covers the production and biological potencies of isolated natural products from the genus associated with terrestrial and marine origins.

Heterologous Expression, Purification and Characterization of an Alkalic Thermophilic β-Mannanase CcMan5C from .

A endo-1,4-β-mannanase (CcMan5C) gene was cloned from and heterologously expressed in , and the recombinant enzyme was purified by Ni-affinity chromatography and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). CcMan5C hydrolyzed only locust bean gum galactomannan (LBG) but not α-mannan from or Avicel cellulose, oat spelt xylan, or laminarin from . CcMan5C exhibited distinctive catalytic features that were different from previously reported β-mannanases.

Branched-chain amino acids and risk of stroke: A Mendelian randomization study.

Background: The causality between plasma branched-chain amino acids (BCAAs) levels and stroke remains uncertain and the stratified research on the association between BCAAs levels and subtypes of stroke is not well studied. Therefore, the association of genetically proxied circulating BCAA levels with the risks of stroke and its subtypes was explored by Mendelian randomization (MR) in this study.

Methods: Summary-level data derived from the published genome-wide association studies (GWAS) were employed for analyses.

Chemical Investigation of Endophytic YSP3 Reveals New Antibacterial and Cytotoxic Agents.

Chemical investigation of the plant-derived endophytic fungus YSP3 led to the isolation of four new compounds (-), including two new xanthones (phomopthane A and B, and ), one new alternariol methyl ether derivative () and one α-pyrone derivative (phomopyrone B, ), together with eight known compounds (-). The structures of new compounds were interpreted on the basis of spectroscopic data and single-crystal X-ray diffraction analysis. All new compounds were assessed for their antimicrobial and cytotoxic potential.

Causal association of genetically determined circulating vitamin D metabolites and calcium with multiple sclerosis in participants of European descent.

Background: Vitamin D is an important regulator of calcium. Mendelian randomization (MR) studies exclusively focused on the circulating total 25-hydroxyvitamin D (25(OH)D) as a biomarker of vitamin D status, and have found the causal association between 25(OH)D and the risk of multiple sclerosis (MS). However, it currently remains unclear about the causal association of the 25(OH)D subtypes including 25(OH)D3 and C3-epi-25(OH)D3, as well as calcium with the risk of MS.

Regional transcriptional vulnerability to basal forebrain functional dysconnectivity in mild cognitive impairment patients.

Nucleus basalis of Meynert (NbM), one of the earliest targets of Alzheimer's disease (AD), may act as a seed for pathological spreading to its connected regions. However, the underlying basis of regional vulnerability to NbM dysconnectivity remains unclear. NbM functional dysconnectivity was assessed using resting-state fMRI data of health controls and mild cognitive impairment (MCI) patients from the Alzheimer's disease Neuroimaging Initiative (ADNI2/GO phase).

Single-Cell RNA-Seq Reveals a Population of Smooth Muscle Cells Responsible for Atherogenesis.

Understanding the regional propensity differences of atherosclerosis (AS) development is hindered by the lack of animal models suitable for the study of the disease process. In this paper, we used 3S-ASCVD dogs, an ideal large animal human-like models for AS, to interrogate the heterogeneity of AS-prone and AS-resistant arteries; and at the single-cell level, identify the dominant cells involved in AS development. Here we present data from 3S-ASCVD dogs which reliably mimic human AS pathophysiology, predilection for lesion sites, and endpoint events.