Associations of eHealth literacy and knowledge with preventive behaviours and psychological distress during the COVID-19 pandemic: a population-based online survey.

OBJECTIVES: To compare the associations of COVID-19 preventive behaviours and depressive and anxiety symptoms with eHealth literacy and COVID-19 knowledge among Korean adults. DESIGN: A cross-sectional online survey was conducted in April 2020. SETTING: Seoul metropolitan area in South Korea. PARTICIPANTS: 1057 Korean adults were recruited. MAIN OUTCOME MEASURES: Associations between eHealth literacy, COVID-19 knowledge, COVID-19 preventive behaviours and psychological distress were computed using Pearson's correlation and logistic regression analyses. eHealth literacy, COVID-19 knowledge, COVID-19 preventive behaviours and psychological distress were weighted by sex and age distribution of the general population in Seoul Metropolitan area. RESULTS: 68.40% (n=723) perceived high eHealth literacy level (eHEALS ≥26), while 57.43% (n=605) had high levels of COVID-19 knowledge (score ≥25). No significant association between eHealth literacy and COVID-19 knowledge was identified (r=0.05, p=0.09). eHealth literacy and COVID-19 knowledge were significantly associated with COVID-19 preventive behaviours (aOR=1.99, 95% CI 1.51 to 2.62 L; aOR=1.81, 95% CI 1.40 to 2.34, respectively). High eHealth literacy was significantly associated with anxiety symptom (aOR=1.71, 95% CI 1.18 to 2.47) and depressive symptom (aOR=1.69, 95% CI 1.24 to 2.30). COVID-19 knowledge had negative and no associations with the symptoms (aOR=0.62, 95% CI 0.46 to 0.86; aOR=0.79, 95% CI 0.60 to 1.03, respectively). High eHealth literacy with low COVID-19 knowledge was positively and significantly associated with COVID-19 preventive behaviours (aOR=2.30, 95% CI 1.52 to 3.43), and anxiety (aOR=1.81, 95% CI 1.09 to 3.01) and depressive symptoms (aOR=2.24, 95% CI 1.41 to 3.55). High eHealth literacy with high COVID-19 knowledge were significantly associated with more preventive behaviours (aOR=3.66, 95% CI 2.47 to 5.42) but no significant associations with anxiety and depressive symptoms. CONCLUSION: We identified that eHealth literacy and COVID-19 knowledge were not associated each other, and differently associated with individuals' COVID-19 preventive behaviours and psychological well-being. Public health strategies should pay attention to enhancing both eHealth literacy and COVID-19 knowledge levels in the public to maximise their COVID-19 preventive behaviours and mitigate their psychological distress during COVID-19 pandemic.

Amyloid-ß Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer's Diseases.

BACKGROUND: Xanthohumol has been reported to have cytoprotection through activation of Nrf2-ARE signaling pathway and; it has capability of scavenging free radicals, suggesting its potential for the prevention of neurodegeneration. However, the bio-incompatibility and blood-brain barrier impermeability of xanthohumol hindered its in vivo efficacy potential for treating Alzheimer's disease (AD). OBJECTIVE: We designed and prepared a series of xanthohumol derivatives to enhance the desirable physical, biological and pharmacological properties in particular the blood-brain barrier permeability for intervention of AD. METHODS: We designed and synthesized a novel series of 9 xanthohumol derivatives. Their inhibitory effect on amyloid-ß (1-42), Aß1-42, oligomerization and fibrillation as well as neuroprotection against amyloid-ß induced toxicities, were explored. RESULTS: Among the 9 xanthohumol derivatives, some of them exhibited a moderate to high inhibitory effect on Aß1-42 oligomerization and fibrillation. They were biocompatible and neuroprotective to the SH-SY5Y cells by reducing the ROS generation and calcium uploading that were induced by the amyloid- ß. Importantly, two of the derivatives were found to be blood-brain barrier permeable showing promising potential for AD treatment. CONCLUSION: Two derivatives have been identified to be biocompatible, non-toxic, neuroprotective against Aß-induced toxicities and blood-brain barrier permeable highlighting their promising potential as AD drug candidates for future clinical use.

Tuning the pKa of two-photon bis-chromophoric probes for ratiometric fluorescence imaging of acidic pH in lysosomes.

Lysosomes are organelles containing many hydrolytic enzymes responsible for degrading macromolecules. Abnormal lysosomal pH changes are known to associate with dysfunction of cells linking to various diseases such as cancer and neurodegenerative disorders. Thus, it is of paramount importance to monitor lysosomal pH changes in order to investigate the pathological conditions. We report herein two novel, highly sensitive and fast responsive bis-chromophoric ratiometric two-photon fluorescent probes with different emission wavelengths, namely VP and VL for acidic pH sensing in live cells. Importantly, by adopting bis-chromophoric approach, the VP and VL probes bearing pyridyl and quinolyl as acid sensing sites exhibit pKa values of 4.62 and 5.26, respectively, which are ideal for quantitative analysis of lysosomal pH changes in live cells. These two biocompatible probes are not only highly lysosomal targeting, sensitive towards pH change with distinct emission color shifting but also highly two-photon active in cells with excellent photostability and reversibility. These probes were successfully applied to ratiometrically track and image pH fluctuation in lysosomes of HeLa cells by one- and two-photon excited fluorescence microscopy. For the first time, we have demonstrated here that the bis-chromophoric strategy is a useful tool to effectively modify and tune the pKa of a fluorescent probe.

Effective Theranostic Cyanine for Imaging of Amyloid Species in Vivo and Cognitive Improvements in Mouse Model.

We report herein an investigation of carbazole-based cyanine, (E)-4-(2-(9-(2-(2-methoxyethoxy)ethyl)-9H-carbazol-3-yl)-vinyl)-1-methyl-quinolin-1-iumiodide (SLM), as an effective theranostic agent for Alzheimer's disease (AD). This cyanine exhibited desirable multifunctional and biological properties, including amyloid-ß (Aß)-oligomerization inhibition, blood-brain barrier permeability, low neurotoxicity, neuroprotective effect against Aß-induced toxicities, high selectivity and strong binding interactions with Aß peptide/species, good biostability, as well as strong fluorescence enhancement upon binding to Aß species for diagnosis and therapy of AD. This cyanine has been successfully applied to perform near-infrared in vivo imaging of Aß species in transgenic AD mouse model. The triple transgenic AD mice intraperitoneally treated with SLM showed significant recovery of cognitive deficits. Furthermore, those SLM-treated mice exhibited a substantial decrease in both of oligomeric Aß contents and tau proteins in their brain, which was attributed to the induction of autophagic flux. These findings demonstrated for the first time that SLM is an effective theranostic agent with in vivo efficacy for diagnosis and treatment of AD in mouse models.

A Zero Cross-Talk Ratiometric Two-Photon Probe for Imaging of Acid pH in Living Cells and Tissues and Early Detection of Tumor in Mouse Model.

Acid-base disorders disrupt proper cellular functions, which are associated with diverse diseases. Development of highly sensitive pH probes being capable of detecting and monitoring the minor changes of pH environment in living systems is of considerable interest to diagnose disease as well as investigate biochemical processes in vivo. We report herein two novel high-resolution ratiometric two-photon (TP) fluorescent probes, namely, PSIOH and PSIBOH derived from carbazole-oxazolidine π-conjugated system for effective sensing and monitoring acid pH in a biological system. Remarkably, PSIOH exhibited the largest emission shift of ∼169 nm from 435 to 604 nm upon pH changing from basic to acidic with an ideal p Ka value of 6.6 within a linear pH variation range of 6.2-7.0, which is highly desirable for high-resolution tracking and imaging the minor fluctuation of pH in live cells and tissues. PSIOH also exhibits high pH sensitivity, excellent photostability, and reversibility as well as low cytotoxicity. More importantly, this probe was successfully applied to (i) sense and visualize the pH alteration in HeLa cells caused by various types of exogenous stimulation and (ii) detect and differentiate cancer and tumors in liver tissues and a mouse model, realizing its practical in vitro and in vivo applications.

Dual-Modal NIR-Fluorophore Conjugated Magnetic Nanoparticle for Imaging Amyloid-ß Species In Vivo.

Senile plaques, the extracellular deposit of amyloid-ß (Aß) peptides, are one of the neuropathological hallmarks found in Alzheimer's disease (AD) brain. The current method of brain imaging of amyloid plaques based on positron emission tomography (PET) is expensive and invasive with low spatial resolution. Thus, the development of sensitive and nonradiative amyloid-ß (Aß)-specific contrast agents is highly important and beneficial to achieve early AD detection, monitor the disease progression, and evaluate the effectiveness of potential AD drugs. Here a neuroprotective dual-modal nanoprobe developed by integrating highly Aß-specific and turn-on fluorescence cyanine sensors with superparamagnetic iron oxide nanoparticles as an effective near-infrared imaging (NIRI)/magnetic resonance imaging (MRI) contrast agent for imaging of Aß species in vivo is reported. This Aß-specific probe is found not only nontoxic and noninvasive, but also highly blood brain barrier permeable. It also shows a potent neuroprotective effect against Aß-induced toxicities. This nanoprobe is successfully applied for in vivo fluorescence imaging with high sensitivity and selectivity to Aß species, and MRI with high spatial resolution in an APP/PS1 transgenic mice model. Its potential as a powerful in vivo dual-modal imaging tool for early detection and diagnosis of AD in humans is affirmed.

Fluoro-substituted cyanine for reliable in vivo labelling of amyloid-ß oligomers and neuroprotection against amyloid-ß induced toxicity.

Alzheimer's disease (AD) is the most prevalent but still incurable neurodegenerative form of dementia. Early diagnosis and intervention are crucial for delaying the onset and progression of the disease. We herein report a novel fluoro-substituted cyanine, F-SLOH, which exhibits good Aß oligomer selectivity with a high binding affinity, attributed to the synergistic effect of strong π-π stacking and intermolecular CH···O and CH···F interactions. The selectivity towards the Aß oligomers in the brain was ascertained by in vitro labelling on tissue sections and in vivo labelling through the systemic administration of F-SLOH in 7 month APP/PS1 double transgenic (Tg) and APP/PS1/Tau triple Tg mouse models. F-SLOH also shows remarkably effective inhibition on Aß aggregation and highly desirable neuroprotective effects against Aß-induced toxicities, including the inhibition of ROS production and Ca2+ influx. Its excellent blood-brain barrier (BBB) penetrability and low bio-toxicity further support its tremendous potential as a novel theranostic agent for both early diagnosis and therapy of AD.

Quantification of Cancer Biomarkers in Serum Using Scattering-Based Quantitative Single Particle Intensity Measurement with a Dark-Field Microscope.

In this work, we developed a simple yet robust single particle scattering intensity measurement method for the quantification of cancer-related biomarkers. The design is based on the plasmonic coupling effect between noble metal nanoparticles. First, the primary and secondary antibodies were conjugated onto the surface of 60 nm gold nanoparticles (AuNPs, act as capture probes) and 50 nm silver nanoparticles (AgNPs, act as signal amplification probes) respectively. In the presence of corresponding antigen, a sandwiched immunocomplex was formed, resulting a significantly enhanced scattering intensity in contrast to that of individual probes. By measuring the intensity change of the particles with a dark-field microscope (DFM), the amount of target protein could be accurately quantified. As a proof of concept experiment, quantification of three types of antigens, including carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and alpha fetoprotein (AFP) by this platform was demonstrated with limit of detection (LOD) of 1.7, 3.3, and 5.9 pM, respectively, with a linear dynamic range of 0 to 300 pM. Furthermore, to elucidate the potential in clinical application, the content of antigens in a serum sample was also quantified directly without additional sample pretreatment. In order to validate the reliability of this method, the measured result was also compared with that obtained by regular enzyme-linked immunosorbent assay (ELISA) kit, showing good consistency between these two data sets. Therefore, owing to the simplicity and accuracy of this method, it could be potentially applied for massive disease screening in clinical assay in the future.

FRET-based modified graphene quantum dots for direct trypsin quantification in urine.

A versatile nanoprobe was developed for trypsin quantification with fluorescence resonance energy transfer (FRET). Here, fluorescence graphene quantum dot is utilized as a donor while a well-designed coumarin derivative, CMR2, as an acceptor. Moreover, bovine serum albumin (BSA), as a protein model, is not only served as a linker for the FRET pair, but also a fluorescence enhancer of the quantum dots and CMR2. In the presence of trypsin, the FRET system would be destroyed when the BSA is digested by trypsin. Thus, the emission peak of the donor is regenerated and the ratio of emission peak of donor/emission peak of acceptor increased. By the ratiometric measurement of these two emission peaks, trypsin content could be determined. The detection limit of trypsin was found to be 0.7 µg/mL, which is 0.008-fold of the average trypsin level in acute pancreatitis patient's urine suggesting a high potential for fast and low cost clinical screening.

Inhibition of ß-amyloid Aggregation By Albiflorin, Aloeemodin And Neohesperidin And Their Neuroprotective Effect On Primary Hippocampal Cells Against ß-amyloid Induced Toxicity.

Being one of the hallmarks of Alzheimer's disease, ß-amyloid (Aß) aggregates induce complicated neurotoxicity. Evidences show that the underlying mechanism of neurotoxicity involves a glutamate receptor subtype, N-methyl-D-aspartate (NMDA) receptor, an increase in intracellular calcium(II) ion loading as well as an elevation in oxidation stress. In this work, among the 35 chemical components of Chinese herbal medicines (CHMs) being screened for inhibitors of Aß aggregation, four of them, namely albiflorin, aloeemodin, neohesperidin and physcion, were found for the first time to exhibit a potent inhibitory effect on Aß(1-40) and Aß(1-42) aggregation. Their neuroprotective capability on primary hippocampal neuronal cells was also investigated by MTT assay, ROS assay and intracellular calcium(II) ion concentration measurement. It was interesting to find that physcion was rather toxic to neuronal cells while albiflorin, aloeemodin and neohesperidin reduced the toxicity and ROS induced by both monomeric and oligomeric Aß species. In addition, albiflorin was particularly powerful in maintaining the intracellular Ca(2+) concentration.