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INTRODUCTION: Muscle strength is known to play an important role in the health of older adults. The health burden of cigarette smoking among older adults remains significant. We investigated the association between smoking cessation and dynapenia among older lifetime smokers in Korea. METHODS: This study is a secondary dataset analysis of cross-sectional data from theKorea National Health and Nutrition Examination Survey (KNHANES) 2016- 2019. We included 1450 participants aged 65-79 years, excluding those who had never smoked. Dynapenia was defined as grip strength <28 kg for men and <18 kg for women based on the Asian Working Group for Sarcopenia 2019 criteria. Multivariable logistic regression analysis evaluated the association between smoking cessation and dynapenia. RESULTS: Compared with current smokers, the adjusted odds ratio (AOR) of dynapenia in former smokers was 0.66 (95% CI: 0.44-0.99). The AORs for smoking cessation periods of ≤10 years, 10-20 years, 20-30 years, and >30 years were 0.67 (95% CI: 0.39-1.16), 0.61 (95% CI: 0.36-1.03), 0.65 (95% CI: 0.37-1.14), and 0.52 (95% CI: 0.25-1.06), respectively. The AOR for dynapenia significantly decreased with the years since smoking cessation (p for trend=0.043). CONCLUSIONS: Our findings suggest that smoking cessation can reduce the likelihood of dynapenia among older lifetime smokers, with a decreasing likelihood trend associated with longer cessation periods.

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Background: Although the association between smoking and health-related quality of life (HRQoL) has been established, the effects of tobacco products, including combustible cigarettes (CCs) and non-combustible nicotine or tobacco products (NNTPs), on HRQoL remain unclear. This study examined the association between tobacco use and HRQoL in Korean men. Methods: Data from the Korea National Health and Nutrition Examination Survey conducted between 2013 and 2020 were analyzed. A total of 16,429 male participants aged ≥19 years completed the European Quality of Life-5 Dimensions (EQ-5D). Impaired HRQoL was defined as scoring in the lowest 20% of the EQ-5D index and having some or extreme problems in the following five domains of the EQ-5D: mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression. Multiple logistic regression was conducted to evaluate the risk of impaired HRQoL in current tobacco users. Results: Current tobacco users exhibited a significantly higher risk of impaired HRQoL compared with never users (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.05-1.92). Compared to never users, current tobacco users reported more problems with mobility and pain/discomfort (all P<0.05). Moreover, compared with former tobacco users, current tobacco users had a higher risk of impaired HRQoL (OR, 1.60; 95% CI, 1.18-2.17). Compared to former tobacco users, current tobacco users reported more problems with mobility and pain/discomfort (all P<0.05). Conclusion: Use of CCs and NNTPs is associated with impaired HRQoL in Korean men. Therefore, further interventions for lifestyle modification and smoking cessation treatments are required to reduce the risk of impaired HRQoL among current tobacco users.

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BACKGROUND: ​​The genus Fusarium poses significant threats to food security and safety worldwide because numerous species of the fungus cause destructive diseases and/or mycotoxin contamination in crops. The adverse effects of climate change are exacerbating some existing threats and causing new problems. These challenges highlight the need for innovative solutions, including the development of advanced tools to identify targets for control strategies. DESCRIPTION: In response to these challenges, we developed the Fusarium Protein Toolkit (FPT), a web-based tool that allows users to interrogate the structural and variant landscape within the Fusarium pan-genome. The tool displays both AlphaFold and ESMFold-generated protein structure models from six Fusarium species. The structures are accessible through a user-friendly web portal and facilitate comparative analysis, functional annotation inference, and identification of related protein structures. Using a protein language model, FPT predicts the impact of over 270 million coding variants in two of the most agriculturally important species, Fusarium graminearum and F. verticillioides. To facilitate the assessment of naturally occurring genetic variation, FPT provides variant effect scores for proteins in a Fusarium pan-genome based on 22 diverse species. The scores indicate potential functional consequences of amino acid substitutions and are displayed as intuitive heatmaps using the PanEffect framework. CONCLUSION: FPT fills a knowledge gap by providing previously unavailable tools to assess structural and missense variation in proteins produced by Fusarium. FPT has the potential to deepen our understanding of pathogenic mechanisms in Fusarium, and aid the identification of genetic targets for control strategies that reduce crop diseases and mycotoxin contamination. Such targets are vital to solving the agricultural problems incited by Fusarium, particularly evolving threats resulting from climate change. Thus, FPT has the potential to contribute to improving food security and safety worldwide.

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OBJECTIVE: To explain the relationship between cartilage erosion and medial patellar luxation (MPL) and to identify risk factors in dogs. METHODS: A retrospective review was conducted on 90 dogs (103 stifles) surgically treated for MPL between January 2006 and March 2024. Data collected included signalment, side of operated stifle, patellar luxation grade, symptom duration, and lameness score. Cartilage erosion was evaluated for extent and location on the patella and femoral trochlea. Statistical analyses were conducted to identify risk factors. RESULTS: The prevalence of cartilage erosion of the patella and femoral trochlea was 47.6% (49/103) and 54.4% (56/103), respectively, increasing with a higher grade of patellar luxation. Lesions were most prevalent in the distolateral patella and proximomedial trochlea, with generalized lesions more prevalent in grade IV. The extent of both lesions was significantly associated with age, patellar luxation grade, and symptom duration, while body weight significantly correlated only with the cartilage erosion of the patella. No significant correlation was observed with sex, side of operated stifle, or lameness score. CONCLUSIONS: Many patients with MPL exhibited cartilage erosion in the patellofemoral joint, likely due to biomechanical mechanisms. Surgery can be indicated for patients with MPL, as it may prevent cartilage erosion while improving patellofemoral alignment and gait. When selecting surgical candidates, it is important to consider risk factors, such as patellar luxation grade, body weight, age, and symptom duration. CLINICAL RELEVANCE: Early surgical treatment is recommended, especially for dogs with higher body weight and higher grade of MPL, to prevent cartilage erosion and secondary osteoarthritis.

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INTRODUCTION: Ipsilateral breast tumor recurrence (IBTR) remains a concern despite standard treatments. Advances in early detection have shifted surgical paradigms towards less invasive approaches. While repeat sentinel lymph node biopsy (rSLNB) emerges as a viable option according to the 2023 National Comprehensive Cancer Network (NCCN) guidelines, its efficacy remains uncertain. This study aimed to assess lymphatic drainage patterns in IBTR and evaluate the feasibility of rSLNB, along with analyzing oncologic outcomes. METHODS: A retrospective analysis involving 78 patients with IBTR who had prior breast-conserving surgery (BCS) with sentinel lymph node biopsy (SLNB) and adjuvant whole breast irradiation (WBI) at Samsung Medical Center was conducted. Data on patient characteristics, lymphatic mapping techniques, and oncologic outcomes were collected and analyzed. RESULTS: Among 78 patients with IBTR, 82.1 % underwent successful rSLNB, predominantly detecting lymphatic drainage to the ipsilateral axilla (80.8 %). The initial tumor location correlated significantly with failed lymphatic mapping (p = 0.019). A third event occurred in 28.8 % of invasive IBTR cases, notably associated with postmenopausal status, higher T stages, and HR(-)/HER2(-) subtype (p < 0.001). The risk of a third event increased by over 50 % within a 2-year interval post-IBTR. CONCLUSION: rSLNB in patients with IBTR, particularly for tumors initially located outside the upper-outer quadrant, demonstrated technical feasibility. The combined use of blue dye with lymphoscintigraphy may enhance rSLNB success rates. Active surveillance, especially for triple negative IBTR cases, may be important due to their aggressive nature and rapid progression potential within a short interval post-IBTR.

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INTRODUCTION: PD-L1 expression and tumor-associated macrophage (TAM) status in phyllodes tumors (PT) have only been examined in a limited number of studies. This study aimed to investigate the expression of PD-L1 and TAM in breast PT and examine their implications. METHODS: Tissue microarrays were constructed from 181 PT samples, and immunohistochemistry for PD-L1 antibodies (SP142, SP263, and 22C3) and TAM markers (CD68 and CD163) were performed. The staining results were compared and analyzed with clinicopathological parameters. RESULTS: Of the 181 samples, 149 were benign, 27 were borderline, and five were malignant. The number of CD68- and/or CD163-positive TAMs increased with increasing PT grades (P < 0.001), and the number of CD68-positive TAMs was significantly positively correlated with that of CD163-positive TAMs (R = 0.704, P < 0.001). Some of the CD68- and/or CD163-positive cells exhibited positivity for actin staining, displaying hybrid characteristics that resemble both histiocytes and myofibroblasts. PD-L1 SP263 tumor cells and PD-L1 SP263 immune cells were the most expressed in malignant PTs (P < 0.001). The number of CD68- and/or CD163-positive TAMs increased when PD-L1 SP263 immune cells were expressed (P < 0.001). The number of CD68- and/or CD163-positive TAMs was positively correlated with PD-L1 22C3 immune cells (R = 0.299, P < 0.001 and R = 0.336, P < 0.001, respectively). Univariate analysis showed that PD-L1 SP263 immune cell expression (P = 0.016) was associated with shorter disease-free survival and that PD-L1 22C3 tumor cell expression (P < 0.001) was associated with shorter overall survival. CONCLUSION: The number of CD68- and/or CD163-positive cells increases with increasing PT histological grade, and these cells exhibit hybrid characteristics, resembling both histiocyte and myofibroblasts.

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BACKGROUND: Vegetal-derived protein hydrolysates (PHs) have been recognized as sustainable biostimulant products due to their beneficial effects on crops. However, most studies on PHs have been conducted at a fixed ratio of nitrate-to-ammonium (NO3 -:NH4 +) without considering other N application scenarios, leading to inconsistent results among the studies. This study compared the influences of N levels (2 or 10 mM N), NO3:NH4 ratios (100:0, 75:25, 50:50, or 25:75), and PH application methods - control, foliar spray (PH-F) or root application (PH-R) - on the yield, morphology, nutrients, and nutraceutical quality of hydroponic lettuce. RESULTS: Nitrogen level, NO3:NH4 ratio, and PH application affected plant growth, morphology, and quality significantly, highlighting the importance of the interactions among these factors. Shoot growth was influenced by NO3:NH4 ratios, PH, and their interactions. Similar trends were observed in chlorophyll content. The interactions among all three factors significantly influenced root growth and morphology. Root application (PH-R) protected lettuce from yield loss caused by low NO3:NH4 ratios and from reduced antioxidant compounds caused by high N levels. Vegetal-derived protein hydrolysates improved nutrient uptake through two-way and three-way interactions although neither PH nor any interactions affected nitrate concentrations. CONCLUSION: This study demonstrated that PH interacts with N level and NO3:NH4 ratio, affecting hydroponic lettuce yield and quality. In particular, the root application of PH was the most effective method for enhancing yield (shoot fresh weight), quality (chlorophylls, carotenoids, flavonoids, and phenols), and nutrient uptake in hydroponically grown lettuce in relation to N form and level. © 2024 Society of Chemical Industry.

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Metastatic lateral pelvic lymph nodes (LPNs) in rectal cancer significantly impact the prognosis and treatment strategies. Western practices emphasize neoadjuvant chemoradiotherapy (CRT), whereas Eastern approaches often rely on LPN dissection (LPND). This review examines the evolving role of LPND in the context of modern treatments, including total neoadjuvant therapy (TNT), and the impact of CRT on the management of clinically suspicious LPNs. We comprehensively reviewed the key literature comparing the outcomes of LPND versus preoperative CRT for rectal cancer, focusing on recent advancements and ongoing debates. Key studies, including the JCOG0212 trial and recent multicenter trials, were analyzed to assess the efficacy of LPND, particularly in conjunction with preoperative CRT or TNT. Current evidence indicates that LPND can reduce local recurrence rates compared to total mesorectal excision alone in patients not receiving radiation therapy. However, the benefit of LPND in the context of neoadjuvant CRT is influenced by the size and pretreatment characteristics of LPNs. While CRT can effectively control smaller metastatic LPNs, larger or clinically suspicious LPNs may require LPND for optimal outcomes. Advances in surgical techniques, such as robotic-assisted LPND, offer potential benefits but also present challenges and complications. The role of TNT in controlling metastatic LPNs and improving patient outcomes is emerging but remains underexplored. The decision to perform LPND should be individualized based on patient-specific factors, including LPN size, response to neoadjuvant treatment, and surgeon expertise. Future research should focus on optimizing treatment protocols and further evaluating the role of TNT in managing metastatic LPNs.

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Background: Oryeongsan (Wulingsan, Goreisan) has long been used for the treatment of impaired body fluid metabolism. However, the action mechanisms have not been clearly defined. Recently, effects of Oryeongsan on the body fluid and Na+ metabolism and the action mechanisms have been shown more clearly. The present review focuses on the recent findings on the effects of Oryeongsan in the cardio-renal system in relation with body fluid metabolism and action mechanisms leading to a decrease in blood pressure in animal models of hypertension. Methods: The new and recent findings were searched by using searching systems including PubMed-NCBI and Google-Scholar. Results: Oryeongsan induced an increase in glomerular filtration rate, and natriuresis and diuresis with a decreased osmolality and resulted in a contraction of the body fluid and Na+ balance. These findings were associated with a suppression of abundance of Na+-H +-exchanger isoform 3 expression and V2 receptor/aquaporin2 water channel signaling pathway in the kidney. Further, treatment with Oryeongsan accentuated atrial natriuretic peptide secretion in the atria from spontaneously hypertensive rats in which the secretion was suppressed. In addition, Oryeongsan ameliorated impaired vasodilation in spontaneously hypertensive rats. Conclusion: The effects of Oryeongsan in the kidney, atria, and vessel were accompanied by a suppression of AT1 receptor and concurrent accentuation of abundance of AT2/Mas receptors expression and modulation of the natriuretic peptide system in these organs from hypertensive rats. The review shows multiple sites of action of Oryeongsan and mechanisms involved in the regulation of volume and pressure homeostasis in the body.

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Prion diseases, known as a group of fatal neurodegenerative disorders caused by prions, remain incurable despite extensive research efforts. In a recent study, crude extract from Curcuma phaeocaulis Valeton (Cp) showed promising anti-prion efficacy in in vitro and in vivo models, prompting further investigation into their active compounds. We endeavored to identify the chemical constituents of the Cp extract and discover potential anti-prion agents. With the use of centrifugal partition chromatography (CPC), major constituents were isolated from the n-hexane (HX) fraction of the extract in a single step. Spectroscopic analysis confirmed the presence of curcumenone, curcumenol, and furanodienone. Subsequent efficacy testing in a cell culture model of prion disease identified curcumenol and furanodienone as active compounds. This study underscores the potential of natural products in the search for effective treatments against prion diseases.

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Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 µM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

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In the ongoing battle against coronavirus disease 2019 (COVID-19), understanding its pathogenesis and developing effective treatments remain critical challenges. The creation of animal models that closely replicate human infection stands as a critical step forward in this research. Here, we present a genetically engineered mouse model with specifically-humanized knock-in ACE2 (hiACE2) receptors. This model, featuring nine specific amino acid substitutions for enhanced interaction with the viral spike protein, enables efficient severe acute respiratory syndrome coronavirus 2 replication in respiratory organs without detectable infection in the central nervous system. Moreover, it mirrors the age- and sex-specific patterns of morbidity and mortality, as well as the immunopathological features observed in human COVID-19 cases. Our findings further demonstrate that the depletion of eosinophils significantly reduces morbidity and mortality, depending on the infecting viral dose and the sex of the host. This reduction is potentially achieved by decreasing the pathogenic contribution of eosinophil-mediated inflammation, which is strongly correlated with neutrophil activity in human patients. This underscores the model's utility in studying the immunopathological aspects of COVID-19 and represents a significant advancement in COVID-19 modeling. It offers a valuable tool for testing vaccines and therapeutics, enhancing our understanding of the disease mechanisms and potentially guiding more targeted and effective treatments.

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This study explored the use of waste from the textile industry (silkworm byproducts) as a promising raw feedstock for the production of carbon-based adsorbents (biochar). The silk excreta biochar generated at 600 and 700 °C (referred to as SEB-600 and SEB-700, respectively) were evaluated in terms of their efficacy in adsorbing cationic (methylene blue) and anionic (Congo red) textile dyes. Although the functional groups on the surfaces of SEB-600 and SEB-700 were not significantly different, the specific surface area of SEB-700 was greater than that of SEB-600. The dye adsorption capacity of SEB-700 was higher than that of SEB-600. The adsorption of methylene blue and Congo red on SEB-700 followed Freundlich isotherms (R2 ≥ 0.963) and pseudo-second-order kinetics (R2 = 0.999), indicating chemisorption with multilayer characteristics. The mechanism for the adsorption of methylene blue on SEB-700 may involve interactions with the negatively charged functional groups on the surface and the mesopores of SEB-700. For the adsorption of Congo red, the mesopores in the biochar and the electrostatic interaction between biochar (positively charged because of the dye solution pH < pHzpc) and the anionic dye could affect adsorption. The maximum adsorption capacities of SEB-700 for methylene blue and Congo red were determined to be 168.23 and 185.32 mg g-1, respectively. Utilising the waste generated from the textile industry to remove pollutants will build a sustainable loop in the industry by minimising waste generation and pollutant emissions.

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BACKGROUND: Although COVID-19 is no longer a global health emergency, it remains pervasive in Singapore, a city-state situated in Southeast Asia, with periodic waves of infection. In addition to disease management, strong communication strategies are critical in the government's response to the pandemic to keep the public updated and equip them in protecting themselves. OBJECTIVE: Grounded in the crisis and emergency risk communication (CERC) framework and emotional appeals, this study aimed to analyze public health communication strategies in Singapore during the COVID-19 pandemic. METHODS: Quantitative content analysis was conducted on 696 Facebook (Meta Platforms Inc) posts and 83 website articles published by Singapore-based public health institutions between January 2020 and September 2022. RESULTS: The results showed that increasing communication on message themes, such as inquisitive messaging and clarification, can enhance communication strategies. The use of emotional appeals also varies with time and should be carefully used as they are context-specific. CONCLUSIONS: Theoretically, this study contributes to advancements in the CERC framework and concepts of emotional appeals by exploring the applications and changes of CERC message types and emotional appeals at different phases. The findings can provide practical guidance for authorities and communication practitioners in developing effective communication strategies.

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Background In this narrative review, we assess published data on subclinical hyperthyroidism (SCHyper) and its association with cardiovascular disease (CVD) in the general population. Summary We present data on the risk of SCHyper in relation to CVD outcomes, including atrial fibrillation (AF), heart failure, stroke, coronary heart disease (CHD), major adverse cardiac events (MACE), CVD mortality, and all-cause mortality. Evidence indicates that SCHyper is associated with an elevated risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. SCHyper appears to have little association with stroke risk and has shown conflicting results regarding CHD risk. Regarding the degree of serum TSH suppression, evidence shows a higher risk of CVD in SCHyper individuals with suppressed TSH (<0.1 mIU/L) compared with those with low TSH (0.1-0.4 mIU/L). Despite evidence that older individuals are inherently at a higher risk for CVD, no studies have yet demonstrated an age-related increase in the relative risk of CVD in SCHyper. Conclusion The studies indicate that SCHyper is associated with an increased risk of AF, heart failure, MACE, CVD mortality, and all-cause mortality. Considering the importance of the degree of serum TSH suppression and age as risk factors for CVD, treatment decisions should be individualized based on their specific risk factors.

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[This corrects the article DOI: 10.3389/fendo.2024.1372397.].

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AIM: Although relationships among positive psychological capital (PsyCap), compassion fatigue, compassion satisfaction, and burnout have been reported, causal relationships among these variables have not been identified. This study examined the influence of positive PsyCap on burnout and confirmed the mediating effects of compassion fatigue and satisfaction among public hospital nurses. METHODS: This study adopted a correlational cross-sectional design. We recruited 237 nurses working at a public hospital, using convenience sampling. RESULTS: The fit of the hypothetical model was adequate. Positive PsyCap directly affected compassion fatigue and satisfaction, and burnout. It had an indirect effect on burnout. Compassion fatigue and satisfaction directly affect burnout. This finding indicates that compassion fatigue and satisfaction partially mediate between positive PsyCap and burnout. In addition, the mediating effect of compassion fatigue was greater than that of compassion satisfaction on the relationship between positive PsyCap and burnout. Finally, positive PsyCap, compassion fatigue, and compassion satisfaction explained 70.4% of the total variance in burnout scores. The effect size (f2) was 2.38 (large effect size). CONCLUSIONS: Burnout should be assessed with positive PsyCap, compassion fatigue, and compassion satisfaction among public hospital nurses. Given that the mediating effect of compassion fatigue was greater than that of compassion satisfaction, interventions for compassion fatigue may be a strategy to reduce burnout, especially among public hospital nurses with low levels of positive PsyCap.

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Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

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Reactive oxygen species (ROS) play a vital role in cellular functions but can lead to oxidative stress and contribute to degenerative diseases when produced in excess. Maintaining redox balance is essential and can be achieved through innate defense mechanisms or external antioxidants. Superoxide dismutase (SOD) is a key enzyme that mitigates intracellular oxidative stress by converting harmful free radicals into hydrogen peroxide, which is subsequently neutralized by catalase and glutathione peroxidase. Previous studies have demonstrated the antioxidant capabilities of SOD derived from Bacillus amyloquefaciens GF424 (BA-SOD) in murine models exposed to either irradiation or SOD1 gene deletion. In this study, a randomized clinical trial was conducted to evaluate the antioxidative benefits of BA-SOD in healthy individuals undergoing acute aerobic exercise (AAE). Eighty participants were randomly assigned to receive either BA-SOD or a placebo for 8 weeks. Antioxidant enzyme activities and glutathione levels were measured before, immediately after, and 30 min post-exercise. A single dose of BA-SOD significantly reduced ROS levels induced by AAE, primarily by enhancing SOD activity in erythrocytes and activating glutathione peroxidase. Continuous BA-SOD administration was associated with a sustained increase in catalase activity and elevated levels of reduced glutathione (GSH). Transcriptomic and metabolomic analyses revealed that a single BA-SOD dose facilitated GSH oxidation, as evidenced by decreased levels of serine, glutamine, and glycine, and increased pyroglutamate levels. Additionally, repeated dosing led to increased expression of genes encoding isocitrate dehydrogenase and malic enzyme, which are involved in NADPH synthesis, as well as nicotinamide phosphoribosyl transferase and NAD kinase, which are essential for NADP availability-critical for converting oxidized glutathione (GSSG) back to GSH. These molecular insights align with clinical observations, suggesting that both acute and long-term BA-SOD supplementation may effectively enhance antioxidant defenses and maintain redox balance under oxidative stress conditions.

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Aggregation of misfolded amyloid-ß (Aß) and hyperphosphorylated tau proteins to plaques and tangles, respectively, is the major drug target of Alzheimer's disease (AD), as the former is an onset biomarker and the latter is associated with neurodegeneration. Thus, we report a small molecule drug candidate, DN5355, with a dual-targeting function toward aggregates of both Aß and tau. DN5355 was selected through a series of four screenings assessing 52 chemicals for their functions to inhibit and reverse the aggregation of Aß and tau by utilizing thioflavin T. When orally administered to AD transgenic mouse model 5XFAD, DN5355 significantly reduced cerebral Aß plaques and hyperphosphorylated tau tangles. In Y-maze spontaneous alteration and contextual fear conditioning tests, 5XFAD mice showed amelioration of cognitive deficits upon the oral administration of DN5355.