Total Synthesis and Bioactivity Profile of (+)-Ieodomycins A and B and their Stereoisomers.

Herein, we report the first- and second-generation syntheses of (+)-ieodomycins A and B and their stereoisomers via the late-stage elaboration of their conjugated E-diene side chains. Key steps for successful synthesis included Keck asymmetric allylation to introduce a hydroxyl group at the C5 position, consecutive Wipf's carboalumination modification, iodination, Sharpless asymmetric dihydroxylation, one-carbon homologation via cyanation, Mukaiyama lactonization, and Stille cross-coupling to form the conjugated E-diene moiety. Further, the preliminary in vitro bioactivity profile against various disease-related molecular targets and cell lines was investigated. Results indicated that compounds 30b and 30c, diastereoisomers of (+)-ieodomycin B (2), serve as α-glucosidase inhibitors, while compounds 30b and 30d inhibit the angiotensin-converting enzyme.

Association between body mass index and atopic dermatitis among adolescents: Findings from a national cross-sectional study in Korea.

BACKGROUND: The association between atopic dermatitis and childhood overweight and obesity has been studied extensively, but the results are inconclusive; most studies have focused on body mass index as a measure of obesity, with few investigating the relationship with underweight. Therefore, this study aimed to investigate the association between body mass index levels and atopic dermatitis in Korean adolescents. METHODS: 3-year (2019-2021) of Korea Youth Risk Behavior Web-based Survey were used. Body mass index was used to measure obesity and a recent diagnosis within the past year was used as the criterion for atopic dermatitis. Multiple logistic regression analyses were performed to explore the associations. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: A total of 144,183 adolescents aged 12-18 years were included in this study (74,704 males and 69,479 females). Over the past year, 5.4% of males and 7.3% of females were diagnosed with atopic dermatitis in the study population. Adolescents with normal weight (males [OR: 1.19, CI: 1.02-1.38]; females [OR: 1.26, CI: 1.10-1.43]) and overweight (males [OR: 1.37, CI: 1.16-1.61]; females [OR: 1.37, CI: 1.19-1.58]) were more likely to develop atopic dermatitis than underweight. CONCLUSION: Increased degree of obesity may contribute to the development of atopic dermatitis. The normal-weight and obese adolescents had higher likelihood of developing atopic dermatitis compared with the underweight adolescents.

Association between living alone and generalized anxiety disorder in Korean adults.

BACKGROUND: Globally, the rise in single-person households poses a potential risk to mental health, with generalized anxiety disorder (GAD) being a prominent concern. The proliferation of single-person households may exacerbate social isolation and foster loneliness and anxiety. Notably, research investigating the association between single-person households and GAD remains limited. Therefore, this study aimed to investigate the association between single-person households and GAD across sexes in Korea. METHODS: We utilized data from the Korea National Health and Nutrition Examination Survey conducted in 2021 and 2022, comprising a sample of 9936 participants aged 19 or older. The Generalized Anxiety Disorder Screening Tool (GAD-7) was employed to assess anxiety levels in adults. Multiple logistic regression analysis was conducted to investigate the correlation between single-person households and GAD. RESULTS: The reference variable used in the analysis was multi-person households (consisting of two or more individuals). The association between single-person households and GAD was statistically significant across sexes (male: odds ratio [OR]: 1.92, 95 % CI: 1.15-3.20; female: OR: 1.56, 95 % CI: 1.03-2.36). Participants in single-person households exhibited higher scores on the GAD-7 compared with those in multi-person households. Notably, marital status and education level displayed disparate effects based on sex, whereas physical activity demonstrated consistent effects irrespective of sex. LIMITATIONS: Given the use of cross-sectional data, only correlations could be established. CONCLUSION: The findings indicate an elevated risk of GAD in single-person households compared with multi-person households. Furthermore, promoting physical activity emerged as a potential strategy for mitigating GAD in single-person households.

High-molecular-weight Fucoidan exerts an immune-enhancing effect in RAW 264.7 cells and cyclophosphamide-induced immunosuppression rat by altering the gut microbiome.

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.

Association between watching eating shows and unhealthy food consumption in Korean adolescents.

BACKGROUND: Eating habits formed during adolescence greatly influence the maintenance of health in adulthood. With the recent development of social media and easy access to the Internet, adolescents watch plenty of food videos, particularly Mukbang and Cookbnag(eating show)content. This media genre's impact on food choices has been covered in several studies; however, studies on unhealthy eating habits directly related to adolescents' exposure to eating shows are insufficient. METHODS: For this study, we used data from the 18th Korea Youth Risk Behavior Survey conducted in 2022 and finalized 50,451 participants. The extent of exposure to eating show media over the course of a week, as well as the consumption of fast food, sugar-sweetened beverages (SSBs), and high caffeinated beverages within that week were measured through self-reporting questionnaires. We classified the participants into two groups based on their frequency of watching eating shows. A multiple logistic regression analysis was performed to investigate the association between eating show and unhealthy food consumption. RESULTS: For both males and females, eating show exposure was strongly associated with the consumption of fast food (male: OR:1.37, 95% CI:1.26-1.49; female: OR:1.46, 95% CI:1.36-1.57), SSB (male: OR:1.42, 95% CI:1.26-1.60; female: OR:1.51, 95% CI:1.35-1.70), and high caffeinated beverage (male: OR:1.30, 95% CI:1.23-1.37; female: OR:1.24, 95% CI:1.18-1.31). It was observed that both sexes were more likely to frequently eat unhealthy food than students who did not watch eating shows. CONCLUSION: Among Korean adolescents, students exposed to eating shows, which primarily aim to entertain, were more likely to consume fast food, SSBs, and high caffeinated beverages. Therefore, this study's findings suggest that eating show could influence adolescents' food choices, highlighting the need for interest in emerging cultures and corresponding health policies.

Tissue specific stem cell therapy for airway regeneration.

Secondary atrophic rhinitis (AR), a consequence of mucosal damage during nasal surgeries, significantly impairs patient quality of life. The lack of effective, lasting treatments underscores the need for alternative therapeutic strategies. A major impediment in advancing research is the scarcity of studies focused on secondary AR. Our study addresses this gap by developing an animal model that closely mirrors the histopathological changes observed in patients with secondary AR. These changes include squamous metaplasia, goblet cell hyperplasia, submucosal fibrosis, and glandular atrophy. Upon administering human nasal turbinate stem cells embedded in collagen type I hydrogel in these models, we observed ciliary regeneration. This finding suggests the potential therapeutic benefit of this approach. Our animal models not only emulate the clinical manifestations of secondary AR but also serve as valuable tools for evaluating the efficacy of cell-based biotechnological interventions.

Long-Term Tumor-Targeting Effect of E. coli as a Drug Delivery System.

To overcome the limitations of current nano/micro-scale drug delivery systems, an Escherichia coli (E. coli)-based drug delivery system could be a potential alternative, and an effective tumor-targeting delivery system can be developed by attempting to perform chemical binding to the primary amine group of a cell membrane protein. In addition, positron emission tomography (PET) is a representative non-invasive imaging technology and is actively used in the field of drug delivery along with radioisotopes capable of long-term tracking, such as zirconium-89 (89Zr). The membrane proteins were labeled with 89Zr using chelate (DFO), and not only was the long-term biodistribution in tumors and major organs evaluated in the body, but the labeling stability of 89Zr conjugated to the membrane proteins was also evaluated through continuous tracking. E. coli accumulated at high levels in the tumor within 5 min (initial time) after tail intravenous injection, and when observed after 6 days, 89Zr-DFO on the surface of E. coli was found to be stable for a long period of time in the body. In this study, we demonstrated the long-term biodistribution and tumor-targeting effect of an E. coli-based drug delivery system and verified the in vivo stability of radioisotopes labeled on the surface of E. coli.

Phf7 has impacts on the body growth and bone remodeling by regulating testicular hormones in male mice.

PHD finger protein 7 (Phf7) is a member of the PHF family proteins, which plays important roles in spermiogenesis. Phf7 is expressed in the adult testes and its deficiency causes male infertility. In this study, we tried to find the causal relationship between Phf7 deficiency and reduced growth retardation which were found in null knock-out (Phf7-/-) mice. Phf7-/- mice were born normally in the Mendelian ratio. However, the Phf7-/- males showed decreased body weight gain, bone mineral density, and bone mineral content compared to those in wild-type (WT) mice. Histological analysis for tibia revealed increased number of osteoclast cells in Phf7-/- mice compared with that in WT mice. When we analyzed the expressions for marker genes for the initial stage of osteoclastogenesis, such as receptor activator of nuclear factor kappa B (Rank) in tibia, there was no difference in the mRNA levels between Phf7-/- and WT mice. However, the expression of tartrate-resistant acid phosphatase (Trap), a mature stage marker gene, was significantly higher in Phf7-/- mice than in WT mice. In addition, the levels of testosterone and dihydrotestosterone (DHT), more potent and active form of testosterone, were significantly reduced in the testes of Phf7-/- mice compared to those in WT mice. Furthermore, testicular mRNA levels for steroidogenesis marker genes, namely Star, Cyp11a1, Cyp17a1 and 17ß-hsd, were significantly lower in Phf7-/- mice than in WT mice. In conclusion, these results suggest that Phf7 deficiency reduces the production of male sex hormones and thereby impairs associated bone remodeling.

Ultra-Fast Vitrification: Minimizing the Toxicity of Cryoprotective Agents and Osmotic Stress in Mouse Oocyte Cryopreservation.

Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.

Moderate-to-Vigorous Physical Activity Changes with the Risk of SARS-CoV-2 Infection: A Nested Case-Control Study.

We identified the association of changes in moderate-to-vigorous physical activity (MVPA) with SARS-CoV-2 infection. From 6,396,500 patients, we performed a nested case-control study who participated in both biennial check-ups. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression. From physically inactive patients at period I, the odds increased when engaged in 1-2, 3-4, or ≥5 times of MVPA/week at period II. This study found that MVPA was directly associated with SARS-CoV-2 infection.

Association between alcohol use disorder and risk of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a common sleep disorder characterised by recurrent upper airway collapse during sleep. Alcohol consumption has been linked to an increased risk of OSA due to its effects on the upper airway and body mass index (BMI). We aimed to investigate the correlation between alcohol use disorders and OSA. We used 11,859 participants data from Korean National Health and Nutrition Examination Surveys. The variable of interest was alcohol use disorder, measured using the Alcohol Use Disorders Identification Test, and the dependent variable was the risk of OSA, measured using the Snoring, Tiredness, Observed apnea, high blood Pressure, BMI, age, neck circumference, and male gender questionnaires. Multiple logistic regression was used to assess the association between alcohol use disorder and OSA risk after adjusted analysis. A significant association was found between alcohol use disorder and OSA (adjusted odds ratio [aOR] 2.14, 95% confidence interval [CI] 1.93-2.37). In the unemployed group, those with alcohol use disorder had the highest odds of being at risk of OSA compared with those who did not have this disorder (aOR 2.45, 95% CI 2.04-2.95). The OSA risk increased as the snoring frequency, amount of alcohol consumed, and frequency of binge drinking increased. This study suggests an association between alcohol use disorders and the risk of OSA. The frequency of alcohol consumption, quantity of alcohol consumed, and snoring frequency were associated with the risk of OSA. Therefore, ceasing alcohol consumption is recommended as an effective approach to enhancing sleep quality.

A hypothalamus-habenula circuit regulates psychomotor responses induced by cocaine.

Administration of cocaine increases synaptic dopamine levels by blocking dopamine reuptake and leads to increased locomotor activity and compulsive drug-seeking behaviour. It has been suggested that the lateral hypothalamus (LH) or lateral habenula (LHb) is involved in drug-seeking behaviours. To explore the role of the LH and the LHb in cocaine-induced psychomotor responses, we tested whether modulation of the LH or the LH-LHb circuit affects cocaine-induced locomotion. Cocaine-induced locomotor activity and dopamine release were suppressed by the activation of the LH with 2-[2,6-difluoro-4-[[2-[(phenylsulfonyl)amino]ethyl]thio]phenoxy]acetamide (PEPA), an AMPA receptor agonist. When the LH was inhibited by microinjection of a GABA receptor agonists mixture prior to cocaine injection, the cocaine's effects were enhanced. Furthermore, optogenetic activation of the LH-LHb circuit attenuated the cocaine-induced locomotion, while optogenetic inhibition of the LH-LHb circuit increased it. In vivo extracellular recording found that the LH sent a glutamatergic projection to the LHb. These findings suggest that the LH glutamatergic projection to the LHb plays an active role in the modulation of cocaine-induced psychomotor responses.

Pharmacokinetics and clinical efficacy of 6'-sialyllactose in patients with GNE myopathy: Randomized pilot trial.

GNE myopathy, caused by biallelic mutations in the GNE gene, is characterized by initial ankle dorsiflexor weakness and rimmed vacuoles in the muscle histopathology, resulting in reduced sialic acid production. Sialyllactose is a source of sialic acid. We performed a pilot clinical trial to analyze the pharmacokinetic properties of 6'-sialyllactose (6SL) and evaluated the safety, and efficacy of oral 6SL in patients with GNE myopathy. Ten participants were in the pharmacokinetic study, and 20 in the subsequent clinical trial. For the pharmacokinetic study, participants were administered either 3 g (low-dose) or 6 g (high-dose) of 6SL in a single dose. Plasma concentrations of 6SL, sialic acid, and sialic acid levels on the surface of red blood cells were periodically assessed in blood samples. Patients were randomly allocated to test (low- and high-dose groups) or placebo groups for the trial. Motor function, ambulation, plasma 6SL and sialic acid concentrations, GNE myopathy-functional activity scale scores, and MRI findings were assessed. 6SL was well tolerated, except for self-limited gastrointestinal discomfort. Free sialic acid in both low- and high-dose groups significantly increased at 6 and 12 weeks, but not in the placebo group. In the high-dose group, proximal limb powers improved with daily 6SL. Considering the fat fraction on muscle MRI, results in the high-dose group were superior to those in the low-dose group. 6SL may be a good candidate for GNE myopathy therapeutics as it induces an increase or reduces the decrease in limb muscle power, attenuates muscle degeneration, and improves the biochemical properties of sialic acid.

Production of Feline Universal Erythrocytes with Methoxy Polyethylene Glycol.

Blood group mismatch in veterinary medicine is a significant problem in blood transfusion, sometimes leading to severe transfusion reactions and even patient death. Blood groups vary from species to species and there are three known blood groups in cats: A, B and AB. While A-type cats are most common, there is a shortage of feline B-type blood groups in cats. By using methoxy polyethylene glycol (mPEG) to protect antigenic epitopes on red blood cells (RBCs), we aimed to find the optimal conditions for the production of feline universal RBCs. The surfaces of feline A-type RBCs were treated with mPEG at various molecular weights and concentrations. Agglutination tests showed that the coating of feline A-type RBCs with mPEG of 20 kDa and 2 mM blocked hemagglutination to feline anti-A alloantibodies over 8 h. While no differences in RBC size and shape between intact and mPEG-treated RBCs were seen, coating RBCs with mPEG inhibited the binding of feline anti-A alloantibodies. Furthermore, the mPEG-treated RBCs did not cause spontaneous hemolysis or osmotic fragility, compared to control RBCs. According to a monocyte monolayer assay, mPEG treatment significantly reduced feline anti-A antibody-mediated phagocystosis of RBCs. These results confirm the potential of using activated mPEG on feline A-type RBC to create universal erythrocytes for transfusion to B-type cats.

Ensembles of Metal Triflate Additives in Gold(I)-Catalyzed Formal [2 + 2 + 2] Cycloaddition of Carbonyls with Activated Terminal Alkynes: One-Pot Synthesis of 2H-Pyrans.

Herein, we describe a gold(I)-catalyzed intermolecular formal [2 + 2 + 2] cycloaddition of a carbonyl compound and a propiolate. A series of highly substituted 2H-pyrans are accessed regioselectively from acyclic and cyclic ketones and aldehydes with various substituted propiolates using Ph3PAuCl (0.1-1 mol %) with two distinct metal triflate additives [0.75-7.5 mol %; In(OTf)3/Cu(OTf)2 for ketones, Bi(OTf)3/Hf(OTf)4 for aldehydes]. This method should provide an opportunity for further development of synthetic access to other heterocyclic compounds.

Association between anti-smoking campaign types and smoking cessation attempts.

Objective: This study explored the association between anti-smoking campaign types and smoking cessation attempts. Methods: This study included 4,594 individuals (3,292 male and 1,302 female) from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) in 2018 and 2020. The methods of anti-smoking promotion were divided into online, offline, online and offline, and none. Attempts to quit smoking were classified as yes or no. Multiple logistic regression was performed to examine the association between antismoking campaign type and smoking cessation attempts. Results: Those who saw anti-smoking advertisements both online and offline were found to have tried to quit smoking more than those who did not. (Online & offline: male, odds ratio [OR] 1.36; 95% confidence interval [95% CI], 1.08-1.71; female, OR, 1.75; 95% CI 1.21-2.54) In a subgroup analysis of the independent variables into which smoking cessation advertisements were subdivided, males were found to have the highest OR for smoking cessation attempts when they encountered advertisements in newspapers. (Newspaper: male, OR, 2.25; 95% CI, 1.00-5.02) Females had the highest OR for smoking cessation attempts when accessed via the Internet. (Internet: female, OR, 1.93; 95% CI, 1.07-3.50). Conclusion: This study showed that there is a correlation between smoking cessation advertisements and adolescents' smoking cessation attempts. The possibility of smoking cessation attempts is high when encountering smoking cessation advertisements both online and offline. Although offline smoking cessation advertisements have a great effect on adolescents' smoking cessation attempts, it can be confirmed that the frequency of exposure for offline advertisements is less than that for online advertisements.

Hepatic Cdkal1 deletion regulates HDL catabolism and promotes reverse cholesterol transport.

BACKGROUND AND AIMS: Associations between CDKAL1 variants and cholesterol efflux capacity (CEC) have been reported. This study aimed to investigate the effects of Cdkal1 deficiency on high-density lipoprotein (HDL) metabolism, atherosclerosis, and related pathways. METHODS: Lipid and glucose metabolic profiles, CEC, and in vivo reverse cholesterol transport (RCT) were compared in liver-specific Alb-Cre:Cdkal1fl/fl and Cdkal1fl/fl mice. Aortic atherosclerosis was compared in Apoe-/-Alb-Cre:Cdkal1fl/fl and Apoe-/- mice fed high-fat diets. HDL subclasses and mediators of HDL metabolism from Alb-Cre:Cdkal1fl/fl mice were examined. RESULTS: HDL-cholesterol level tended to be higher in the Alb-Cre:Cdkal1fl/fl mice (p = 0.050). Glucose and other lipid profiles were similar in the two groups of mice, irrespective of diet. The mean CEC was 27% higher (p = 0.007) in the Alb-Cre:Cdkal1fl/fl mice, as were the radioactivities of bile acids (mean difference 17%; p = 0.035) and cholesterol (mean difference 42%; p = 0.036) from faeces. The radioactivity tendency was largely similar in mice fed a high-fat diet. Atherosclerotic lesion area tended to be smaller in the Apoe-/-Alb-Cre:Cdkal1fl/fl mice than in the Apoe-/- mice (p = 0.067). Cholesterol concentrations in large HDLs were higher in the Alb-Cre:Cdkal1fl/fl mice (p = 0.024), whereas in small HDLs, they were lower (p = 0.024). Endothelial lipase (mean difference 39%; p = 0.002) and hepatic lipase expression levels (mean difference 34%; p < 0.001) were reduced in the Alb-Cre:Cdkal1fl/fl mice, whereas SR-B1 expression was elevated (mean difference 35%; p = 0.007). CONCLUSIONS: The promotion of CEC and RCT in Alb-Cre:Cdkal1fl/fl mice verified the effect of CDKAL1 seen in human genetic data. These phenotypes were related to regulation of HDL catabolism. This study suggests that CDKAL1 and associated molecules could be targets for improving RCT and vascular pathology.

Development of Hydrophobically Modified Casein Derivative-Based Delivery System for Docosahexaenoic Acids by an Acid-Induced Gelation.

Although omega-3 fatty acids including docosahexaenoic acid (DHA) contain various health-promoting effects, their poor aqueous solubility and stability make them difficult to be induced in dairy foods. The aims of this research were to manufacture casein derivative-based delivery system using acid-induced gelation method with glucono-σ-lactone and to investigate the effects of production variables, such as pH and charged amount of linoleic acid, on the physicochemical properties of delivery systems and oxidative stability of DHA during storage in model milk. Covalent modification with linoleic acid resulted in the production of casein derivatives with varying degrees of modification. As pH was reduced from 5.0 to 4.8 and the charged amount of linoleic acid was increased from 0% to 30%, an increase in particle size of casein derivative-based delivery systems was observed. The encapsulation efficiency of DHA was increased with decreased pH and increased charged amount of linoleic acid. The use of delivery system for DHA resulted in a decrease in the development of primary and secondary oxidation products. An increase in the degree of modification of casein derivatives with linoleic acid resulted in a decrease in the formation of primary and secondary oxidation products than of free DHA indicating that delivery systems could enhance the oxidative stability of DHA during storage in model milk. In conclusions, casein derivatives can be an effective delivery system for DHA and charged amount of linoleic acid played a key role determining the physicochemical characteristics of delivery system and oxidative stability of DHA.

Natural-product-based fluorescent probes: recent advances and applications.

Fluorescent probes are attractive tools for biology, drug discovery, disease diagnosis, and environmental analysis. In bioimaging, these easy-to-operate and inexpensive probes can be used to detect biological substances, obtain detailed cell images, track in vivo biochemical reactions, and monitor disease biomarkers without damaging biological samples. Over the last few decades, natural products have attracted extensive research interest owing to their great potential as recognition units for state-of-the-art fluorescent probes. This review describes representative natural-product-based fluorescent probes and recent discoveries, with a particular focus on fluorescent bioimaging and biochemical studies.

Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge.

Recurrent spillovers of α- and ß-coronaviruses (CoV) such as severe acute respiratory syndrome (SARS)-CoV, Middle East respiratory syndrome-CoV, SARS-CoV-2, and possibly human CoV have caused serious morbidity and mortality worldwide. In this study, six receptor-binding domains (RBDs) derived from α- and ß-CoV that are considered to have originated from animals and cross-infected humans were linked to a heterotrimeric scaffold, proliferating cell nuclear antigen (PCNA) subunits, PCNA1, PCNA2, and PCNA3. They assemble to create a stable mosaic multivalent nanoparticle, 6RBD-np, displaying a ring-shaped disk with six protruding antigens, like jewels in a crown. Prime-boost immunizations with 6RBD-np in mice induced significantly high Ab titers against RBD antigens derived from α- and ß-CoV and increased interferon (IFN-γ) production, with full protection against the SARS-CoV-2 wild type and Delta challenges. The mosaic 6RBD-np has the potential to induce intergenus cross-reactivity and to be developed as a pan-CoV vaccine against future CoV spillovers.