Magnetic aptamer copper nanoclusters fluorescent biosensor for the visual detection of zearalenone based on docking-aided rational tailoring.

To address the food safety issues caused by toxins, we established a fluorescent copper nanocluster biosensor based on magnetic aptamer for the visual and quantitative detection of ZEN. Specifically, we utilized the docking-aided rational tailoring (DART) strategy to analyze intermolecular force and interaction sites between zearalenone (ZEN) and the aptamer, and optimize the long-chain aptamer step by step to enhance the binding affinity by 3.4 times. The magnetic bead-modified aptamer underwent conformational changes when competing with complementary sequences to bind with ZEN. Then, the released complementary sequences will be amplified in template-free mode with the presence of the terminal deoxynucleotidyl transferase (TdT), and generating T-rich sequences as the core sequences for the luminescence of copper nanoclusters. The luminescence could be visualized and quantitatively detected through ultraviolet irradiation. The proposed label-free aptasensor exhibited high sensitivity and specificity, with a low limit of detection (LOD) of 0.1 ng/mL.

Mitoquinone mesylate as post-exposure prophylaxis against SARS-CoV-2 infection in humans: an exploratory single center pragmatic open label non-randomized pilot clinical trial with matched controls.

BACKGROUND: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice. METHODS: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure). FINDINGS: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant. INTERPRETATION: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted. FUNDING: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK).

Light and the City: Breast Cancer Risk Factors Differ Between Urban and Rural Women in Israel.

Women are exposed to indoor and outdoor artificial light at night (ALAN) in urban and rural environments. Excessive exposure to hazardous ALAN containing short wavelength light may suppress pineal melatonin production and lead to an increased breast cancer (BC) risk. Our objective was to address the differences in BC risks related to light exposure in urban and rural communities. We examined indoor and outdoor light habits of BC patients and controls that had lived in urban and rural areas in a 5-year period, 10 to 15 years before the time of the study. Individual data, night time sleeping habits and individual exposure to ALAN habits were collected using a questionnaire. A total of 252 women (110 BC patients and 142 controls) participated in this study. The sample was divided to subgroups according to dwelling area and disease status. Age matching was completed between all subgroups. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated for urban and rural women separately, using binary logistic regression. OR results of urban population (92 BC patients and 72 control) revealed that BC risk increases with daily use of cellphone (OR = 2.13, 95% CI = 1.01-4.49, P < .05) and residence near strong ALAN sources (OR = 1.51, 95% CI = 0.99-2.30, P < .06). Nevertheless, BC risk decreases if a woman was born in Israel (OR = 0.44, 95% CI = 0.21-0.93, P < .03), longer sleep duration (OR = 0.75, 95% CI = 0.53-1.05, P < .1), and reading with bed light illumination before retiring to sleep (OR = 0.77, 95% CI = 0.61-0.96, P < .02). Furthermore, in the rural population (18 BC patients and 66 control) BC risk increases with the number of years past since the last menstruation (OR = 1.12, 95% CI = 1.03-1.22, P < .01). However, BC risk decreases with longer sleep duration (OR = 0.53, 95% CI = 0.24-1.14, P < .1), reading with room light illumination before retiring to sleep (OR = 0.55, 95% CI = 0.29-1.06, P < .07), and sleeping with closed shutters during the night (OR = 0.66, 95% CI = 0.41-1.04, P < .08). These data support the idea that indoor and outdoor nighttime light exposures differ between urban and rural women. Therefore, we suggest that women can influence BC risk and incidence by applying protective personal lighting habits. Further studies with larger sample sizes are needed to strengthen the results.

Illuminating a Risk for Breast Cancer: A Preliminary Ecological Study on the Association Between Streetlight and Breast Cancer.

Artificial light at night (ALAN) for elongating photophase is a new source of pollution. We examined the association between measured ALAN levels and breast cancer (BC) standard morbidity ratio (SMR) at a statistical area (SA) level in an urban environment. Sample size consisted of 266 new BC cases ages 35-74. Light measurements (lux) were performed in 11 SAs. A new calculated variable of morbidity per SA size (SMR35-74/km2) was correlated with the light variables per road length, using Pearson correlations (P < .05, 1-tailed). Looking for a light threshold, we correlated percentage of light points above SA light intensity median with SMR35-74/km2. SMR35-74/km2 was significantly and positively strongly correlated with mean, median, and standard-deviation (SD) light intensity per road length (r = .79, P < .01, R2 = .63; r = .77, P < .01, R2 = .59; and r = .79, P < .01, R2 = .63). Light threshold results demonstrate a marginally significant positive moderate correlation between percentage of points above 16.3 lux and SMR35-74/km2 (r = .48, P < .07; R2 = .23). In situ results support the hypothesis that outdoor ALAN illumination is associated with a higher BC-SMR in a specific area and age group. Moreover, we suggest an outdoor light threshold of approximately 16 lux as the minimal intensity to affect melatonin levels and BC morbidity. To the best of our knowledge, our attempt is the first to use this method and show such association between streetlight intensity and BC morbidity and therefore should be further developed.

Can Avoiding Light at Night Reduce the Risk of Breast Cancer?

Excessive exposure to artificial light at night (ALAN) suppresses nocturnal melatonin (MLT) production in the pineal gland and is, therefore, associated with an increased risk of breast cancer (BC). We examined indoor and outdoor light habits of 278 women, BC patients (n = 93), and controls (n = 185; 2010-2014). Cases and controls were age and residential area matched. Data regarding behavior in the sleeping habitat in a 5-year period, 10 to 15 years prior to disease diagnosis, were collected using a questionnaire. Sleep quality, bedtime, sleep duration, TV watching habits, presleeping reading habits, subjective illumination intensity, and type of illumination were collected. Binary logistic regression models were used to calculate odds ratios with 95% confidence intervals (ORs with 95% CIs) for BC patients in relation to those habits. OR results revealed that women who had slept longer (controls), 10 to 15 years before the time of the study, in a period of 5 years, had a significant (OR = 0.74; 95% CI = 0.57-0.97; P < .03) reduced BC risk. Likewise, women who had been moderately exposed to ALAN as a result of reading using bed light (reading lamp) illumination and women who had slept with closed shutters reduced their BC risk: OR = 0.81, 95% CI = 0.67-0.97, P < .02, and OR = 0.82, 95% CI = 0.68-0.99, P < .04, respectively. However, women who had been exposed to ALAN as a result of living near strong illumination sources were at a significantly higher BC risk (OR = 1.52; 95% CI = 1.10-2.12; P < .01). These data support the hypothesis that diminishing nighttime light exposure will diminish BC risk and incidence. This hypothesis needs to be tested directly using available testing strategies and technologies that continuously measure an individual's light exposure, its timing, and sleep length longitudinally and feed this information back to the individual, so that BC risk can be distinguished prospectively.