Molecular engineering of a theranostic molecule that detects Aβ plaques, inhibits Iowa and Dutch mutation Aβ self-aggregation and promotes lysosomal biogenesis for Alzheimer's disease.

Extracellular clustering of amyloid-β (Aβ) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aβ, Iowa mutation Aβ, Dutch mutation Aβ fibrils and oligomers exhibiting enhanced emission with high affinity.

Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aβ pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy.

Alternative Splicing, An Overlooked Defense Frontier of Plants with Respect to Bacterial Infection.

Disease represents a major problem in sustainable agricultural development. Plants interact closely with various microorganisms during their development and in response to the prevailing environment. In particular, pathogenic microorganisms can cause plant diseases, affecting the fertility, yield, and longevity of plants.

Fe65-engineered neuronal exosomes encapsulating corynoxine-B ameliorate cognition and pathology of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the predominant impairment of neurons in the hippocampus and the formation of amyloid plaques, hyperphosphorylated tau protein, and neurofibrillary tangles in the brain. The overexpression of amyloid-β precursor protein (APP) in an AD brain results in the binding of APP intracellular domain (AICD) to Fe65 protein via the C-terminal Fe65-PTB2 interaction, which then triggers the secretion of amyloid-β and the consequent pathogenesis of AD. Apparently, targeting the interaction between APP and Fe65 can offer a promising therapeutic approach for AD.

Efficacy and safety of intraurethral Erbium:YAG laser treatment in women with stress urinary incontinence following failed intravaginal laser therapy: a retrospective study.

Urinary incontinence (UI) is a prevalent condition affecting 25-45% of women and is linked to factors such as menopause, parity, high body mass index, and radical pelvic surgery. Among the three types of UI, stress incontinence (SUI) is the most common, accounting for almost 50% of cases, followed by urgency and overflow incontinence. UI has been found to be associated with reduced quality of life and mental stress.

PPARɑ Ligand Caudatin Improves Cognitive Functions and Mitigates Alzheimer's Disease Defects By Inducing Autophagy in Mice Models.

The autophagy-lysosomal pathway (ALP) is a major cellular machinery involved in the clearance of aggregated proteins in Alzheimer disease (AD). However, ALP is dramatically impaired during AD pathogenesis via accumulation of toxic amyloid beta (Aβ) and phosphorylated-Tau (phospho-Tau) proteins in the brain. Therefore, activation of ALP may prevent the increased production of Aβ and phospho-Tau in AD.

Eukaryotic splicing machinery in the plant-virus battleground.

Plant virual infections are mainly caused by plant-virus parasitism which affects ecological communities. Some viruses are highly pathogen specific that can infect only specific plants, while some can cause widespread harm, such as tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). After a virus infects the host, undergoes a series of harmful effects, including the destruction of host cell membrane receptors, changes in cell membrane components, cell fusion, and the production of neoantigens on the cell surface.

Bromo-protopine, a novel protopine derivative, alleviates tau pathology by activating chaperone-mediated autophagy for Alzheimer's disease therapy.

Emerging evidence from Alzheimer's disease (AD) patients suggests that reducing tau pathology can restore cognitive and memory loss. To reduce tau pathology, it is critical to find brain-permeable tau-degrading small molecules that are safe and effective. HDAC6 inhibition has long been considered a safe and effective therapy for tau pathology.

Fast Healthcare Interoperability Resources for Inpatient Deterioration Detection With Time-Series Vital Signs: Design and Implementation Study.

Background: Vital signs have been widely adopted in in-hospital cardiac arrest (IHCA) assessment, which plays an important role in inpatient deterioration detection. As the number of early warning systems and artificial intelligence applications increases, health care information exchange and interoperability are becoming more complex and difficult. Although Health Level 7 Fast Healthcare Interoperability Resources (FHIR) have already developed a vital signs profile, it is not sufficient to support IHCA applications or machine learning-based models.

Optimal timing of biliary drainage based on the severity of acute cholangitis: A single-center retrospective cohort study.

Background: Biliary decompression is well known to greatly decrease the risks of mortality in acute cholangitis (AC). Although early biliary drainage is recommended by the treatment guidelines for AC, the best time for performing this procedure is yet to be established. Furthermore, since the clinical outcomes of patients with severe AC vary dramatically, screening for patients that could benefit the most from early drainage would be more beneficial than the drainage performed based on the severity grade criteria.

Risks of posterior segment ocular ischaemic events in patients with systemic lupus erythematosus: a population-based cohort study in Taiwan.

Backgroud/aim: Ocular involvement in systemic lupus erythematosus (SLE) is often primarily recognised by ophthalmologists rather than internists. This study aims to investigate the incidence and risk factors for the occurrence of posterior ocular ischaemic events (OIE), including retinal vein occlusion (RVO), retinal artery occlusion (RAO) and ischaemic optic neuropathy (ION), in patients with SLE.

Methods: A national database in Taiwan was used to identify 24 472 patients newly diagnosed with SLE and 244 720 age-matched and sex-matched controls between 1997 and 2012.

Improved inpatient deterioration detection in general wards by using time-series vital signs.

Although in-hospital cardiac arrest is uncommon, it has a high mortality rate. Risk identification of at-risk patients is critical for post-cardiac arrest survival rates. Early warning scoring systems are generally used to identify hospitalized patients at risk of deterioration.

Klotho an Autophagy Stimulator as a Potential Therapeutic Target for Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is an age-associated neurodegenerative disease; it is the most common cause of senile dementia. Klotho, a single-pass transmembrane protein primarily generated in the brain and kidney, is active in a variety of metabolic pathways involved in controlling neurodegeneration and ageing. Recently, many studies have found that the upregulation of Klotho can improve pathological cognitive deficits in an AD mice model and have demonstrated that Klotho plays a role in the induction of autophagy, a major contributing factor for AD.

Corynoxine B derivative CB6 prevents Parkinsonian toxicity in mice by inducing PIK3C3 complex-dependent autophagy.

Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD.

[Performance of point-of-care testing for cervical cancer screening].

To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists.

Protopine promotes the proteasomal degradation of pathological tau in Alzheimer's disease models via HDAC6 inhibition.

Background: Collective evidences have indicated that intracellular accumulation of hyperphosphorylated tau forms neurofibrillary tangles in the brain, which impairs memory, cognition and affects social activities in Alzheimer's disease (AD).

Purpose: To investigate the tau-reducing, and memory-enhancing properties of protopine (PRO), a natural alkaloid isolated from Chinese herbal medicine Corydalis yanhusuo (Yanhusuo in Chinese).

Study Design: By using Histone deacetylase 6 (HDAC6) profiling and immunoprecipitation assays, we assessed that PRO mediated the heat shock protein 90 (HSP90) chaperonic activities for the degradation of pathological tau in AD cell culture models.

Epidemiology and risk of invasive fungal infections in systemic lupus erythematosus: a nationwide population-based cohort study.

Introduction: Infections are a leading cause of mortality in patients with systemic lupus erythematosus (SLE). Among various infections, invasive fungal infections (IFIs) have a particularly high mortality rate; however, studies examining IFIs in patients with SLE are limited.

Methods: Patients diagnosed as having SLE between 1997 and 2012 were enrolled from Taiwan's National Health Insurance Research Database along with age- and sex-matched non-SLE controls at a ratio of 1:10.