Small-Molecule Drug Repurposing for Counteracting Phototoxic A2E Aggregation.

Despite the well-established role of oxidative stress in the pathogenesis of age-related macular degeneration (AMD), the mechanism underlying phototoxicity remains unclear. Herein, we used a drug repurposing approach to isolate an FDA-approved drug that blocks the aggregation of the photoinducible major fluorophore of lipofuscin, the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). Our fluorescence-based screening combined with dynamic light scattering (DLS) analysis led to the identification of entacapone as a potent inhibitor of A2E fluorescence and aggregation. The entacapone-mediated inhibition of A2E aggregation blocks its photodegradation and offers photoprotection in A2E-loaded retinal pigment epithelial (RPE) cells exposed to blue light. In-depth mechanistic analysis suggests that entacapone prevents the conversion of toxic aggregates by redirecting A2E into off-pathway oligomers. These findings provide evidence that aggregation contributes to the phototoxicity of A2E.

A risk prediction score to identify patients at low risk for COVID-19 infection.

Introduction: Singapore's enhanced surveillance programme for COVID-19 identifies and isolates hospitalised patients with acute respiratory symptoms to prevent nosocomial spread. We developed risk prediction models to identify patients with low risk for COVID-19 from this cohort of hospitalised patients with acute respiratory symptoms. Methods: This was a single-centre retrospective observational study. Patients admitted to our institution's respiratory surveillance wards from 10 February to 30 April 2020 contributed data for analysis. Prediction models for COVID-19 were derived from a training cohort using variables based on demographics, clinical symptoms, exposure risks and blood investigations fitted into logistic regression models. The derived prediction models were subsequently validated on a test cohort. Results: Of the 1,228 patients analysed, 52 (4.2%) were diagnosed with COVID-19. Two prediction models were derived, the first based on age, presence of sore throat, dormitory residence, blood haemoglobin level (Hb), and total white blood cell counts (TW), and the second based on presence of headache, contact with infective patients, Hb and TW. Both models had good diagnostic performance with areas under the receiver operating characteristic curve of 0.934 and 0.866, respectively. Risk score cut-offs of 0.6 for Model 1 and 0.2 for Model 2 had 100% sensitivity, allowing identification of patients with low risk for COVID-19. Limiting COVID-19 screening to only elevated-risk patients reduced the number of isolation days for surveillance patients by up to 41.7% and COVID-19 swab testing by up to 41.0%. Conclusion: Prediction models derived from our study were able to identify patients at low risk for COVID-19 and rationalise resource utilisation.

Decompartmentalisation as a simple color manipulation of plant-based marbling meat alternatives.

Recent efforts for cell-based meat cuts focus on engineering edible scaffolds, with visual cues which are key to enhancing consumer acceptance, receiving less attention Here, we employed artificial intelligence (AI)-based screening of potential plant materials and discovered that jackfruit (Artocarpus heterophyllus) has the natural structures to recapitulate marbling visuals of meat cuts. Plant tissue compositions are exploited for its differential polyphenol adsorption to produce complex marbling patterns. A one-step colour control method by varying oxidation and incubation conditions of polyphenols was developed to produce permanent meat-like colours resembling chicken, pork, and beef. The scaffold exhibits a meat-like browning behaviour when cooked and is shown to support high-density porcine myoblasts culture without masking the marbled appearance. Surveys with 78 volunteers found that marbled jackfruit scaffolds improved consumer perception of cell-based meat by ∼8%. Our approach of combining AI, tissue engineering, and sensory science unlocks the possibility of creating a range of novel cell-based meat cuts with consumer focus.

pH changes in root dentin after intracanal placement of improved calcium hydroxide containing gutta-percha points.

The in vitro pH changes in root dentin over a period of 2 weeks was investigated in 48 extracted bicuspids after intracanal placement of either Roeko Calcium Hydroxide Plus Points, aqueous calcium hydroxide paste, or gutta-percha points (control group) after root canal preparation. Microelectrodes were placed in outer and inner root dentin at cervical, middle, and apical thirds of the root to measure the pH at 1 h, 2 h, 3 h, 1 day, 3 days, 7 days, and 14 days. Roeko Calcium Hydroxide Plus Points reached a peak inner dentine pH of 11.67 and a peak outer dentine pH of 10.82 at 3 h. In addition, Roeko Calcium Hydroxide Plus Points maintained an outer dentine pH above 9.5 for approximately 2 days, whereas the aqueous calcium hydroxide paste did not reach this pH. However, the alkalinity in dentin with Roeko Calcium Hydroxide Plus Points was maintained for 7 days only, whereas aqueous calcium hydroxide paste maintained an alkaline environment throughout the 2-week period.