Search Results (51)

Background/Objectives: In many societies, especially in highly masculine societies like Japan, being a man, getting older, engaging in knowledge work, and earning a high annual salary are seen as conditions for success. On the other hand, an increasing number of studies have shown that incorporating kawaii-ness into our lives can help maintain and improve happiness and well-being. Methods: Therefore, in this study, we employed a variable expressing the response to kawaii-ness together with four demographic variables (sex, age, income, and knowledge work), happiness, and fractional anisotropy brain healthcare quotient (FA-BHQ) which is derived from magnetic resonance imaging (MRI) images calculations to analyze the relationship between them. Results: The results of a path analysis using data obtained from 182 healthy men and women showed that kawaii-ness mediates the association between demographic variables and happiness, which is in turn associated with FA-BHQ. Furthermore, with the correlation analysis between happiness and individual FA regions, we were able to confirm that FA regions, including the limbic-thalamo-cortical pathway, which is responsible for emotional regulation, are related to happiness. Conclusions: These results indicate the following: Men, older people, people engaged in knowledge work, and people with high annual incomes avoid kawaii-ness; As a result, they are unable to obtain the sense of happiness that they should have; as a result, they are unable to keep their brains healthy, and their brain functions, including emotional regulation, are not functioning properly; This may prevent them from maintaining or improving their performance. This study is the first attempt to clarify the relationship between demographic scales, kawaii-ness, happiness, and brain conditions. Full article

Background/Objectives: Interest in diversity is growing worldwide. Today, an understanding and social acceptance of diverse people is becoming increasingly important. Therefore, in this study, we aimed to clarify the relationship between an individual’s gray matter volume (GMV), which is thought to reflect brain health, and their understanding of diversity (gender, sexuality (LGBTQ), and origin). Methods: GMV was determined as the value of the Gray Matter Brain Healthcare Quotient (GM-BHQ) based on MRI image analysis. Meanwhile, participants’ understanding and acceptance of diversity was calculated based on their answers to the psychological questions included in the World Values Survey Wave 7 (WVS7). Results: Our analysis indicated that, in the group of participants with the highest understanding of diversity (PHUD. n = 11), not only the GMV at the whole brain level (t = 2.587, p = 0.027, Cohen’s d = 0.780) but also the GMV of the central executive network (CEN: t = 2.700, p= 0.022, Cohen’s d = 0.814) and saliency network (SN: t = 3.100, p = 0.011, Cohen’s d = 0.935) were shown to be significantly higher than the theoretical value estimated from sex, age, and BMI at the 5% level. In addition, the GMV of the default mode network (DMN: t = 2.063, p = 0.066, Cohen’s d = 0.622) was also higher than the theoretical value at the 10% level. Meanwhile, in the group of others (n = 10), there was no significant difference from the theoretical value. These differences between PHUD and others were also observed when comparing the two with and without controlling for educational and occupational covariates at the 5% or 10% levels. Conclusions: These results suggest that understanding diversity requires a healthy brain, centered on three networks that govern rational judgment, emotion regulation, other-awareness, self-awareness, and the valuing of actions. This is the first study to show that brain structure is related to an understanding and acceptance of the diversity of people. Full article

Piglet diarrhea poses significant economic losses to the pig industry, posing a worldwide challenge that urgently needs to be addressed in pig breeding practices. Porcine rotavirus (PoRV) is an important viral diarrhea pathogen in piglets, with a high incidence rate and a tendency to cause growth retardation. To enhance the sensitivity and specificity of PoRV detection, we sequenced the NSP3 gene of G5 and G9 genotypes of rotavirus A (RVA), enabling simultaneous detection of the two serotypes. Subsequently, we developed a rapid PoRV detection method using a combination of recombinase-aided amplification (RAA) and CRISPR/Cas12a. In this method, Cas12a binds to RAA amplification products, guided by CRISPR-derived RNA (crRNA), which activates its cleavage activity and releases fluorescence by cutting FAM-BHQ-labeled single-stranded DNA (ssDNA). In the optimized reaction system, the recombinant plasmid PoRV can achieve a highly sensitive reaction within 30 min at 37 °C, with a detection limit as low as 2.43 copies/μL, which is ten times higher in sensitivity compared to the qPCR method. Results from specificity testing indicate that no cross-reactivity was observed between the RAA-CRISPR/Cas12a analysis of PoRV and other viral pathogens, including PoRV G3, PoRV G4, porcine epidemic diarrhea virus (PEDV), porcine epidemic diarrhea (PDCoV), and porcine reproductive and respiratory syndrome virus (PRRSV). In the clinical sample detection using the RAA-CRISPR/Cas12a method and qPCR, Cohen’s Kappa value reached as high as 0.952. Furthermore, this approach eliminates the need for large-scale instrumentation, offering a visual result under an ultraviolet lamp through fluorescence signal output. Full article

A Black Hole Quencher-3 (BHQ-3) derivative was synthesized through an azo-coupling reaction between Methylene Violet 3RAX and a tertiary aniline functionalized with a pendant primary amine, allowing subsequent peptide conjugation. The synthesized compounds were characterized using NMR, UV–vis absorption, fluorescence spectroscopy, and mass spectrometry. The spectral properties of a Cy5/BHQ-3 amine pair were investigated through titration experiments in PBS (pH 7.4). The results confirmed Förster Resonance Energy Transfer (FRET), along with additional dynamic quenching, as evidenced by the Stern–Volmer analysis. The Stern–Volmer constant (K_SV) was determined to be 1.40 × 10⁵ M⁻¹. These findings confirm the potential of this system for use in molecular probes and bioimaging applications. Full article

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca²⁺-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca²⁺ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca²⁺ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca²⁺, permitting the differentiation of the TG-sensitive SERCA 2b Ca²⁺ store from the tBHQ-sensitive SERCA 3 Ca²⁺ store. We proceeded to test the effects of CDN1163 on Ca²⁺ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca²⁺ pools using our low-dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca²⁺ stores. Surprisingly, short-term exposure (0–30 min) to CDN1163 perturbs T cell Ca²⁺ stores by suppressing Ca²⁺ uptake with diminished Ca²⁺ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA-3 regulated store, given the observation of increased Ca²⁺ release inducible by low-dose tBHQ. Intriguingly, longer-term (>12 h) CDN1163 exposure reversed this pattern, with increased Ca²⁺ release from SERCA 2b-regulated pools yet decreased Ca²⁺ release responses from the tBHQ-sensitive SERCA 3 pool. Indeed, this remodeling of SERCA 2b Ca²⁺ stores with longer-term CDN1163 exposure also translated into the compound’s ability to protect Jurkat T lymphocytes from TG but not tBHQ-induced growth suppression. Full article

In this report, we describe a fluorescent assay for the detection of six marine toxins in water. The mechanism of detection is based on a duplex-to-complex structure-switching approach. The six aptamers specific to the targeted cyanotoxins were conjugated to a fluorescent dye, carboxyfluorescein (FAM). In parallel, complementary DNA (cDNA) sequences specific to each aptamer were conjugated to a fluorescence quencher BHQ1. In the absence of the target, an aptamer–cDNA duplex structure is formed, and the fluorescence is quenched. By adding the toxin, the aptamer tends to bind to its target and releases the cDNA. The fluorescence intensity is consequently restored after the formation of the complex aptamer–toxin, where the fluorescence recovery is directly correlated with the analyte concentration. Based on this principle, a highly sensitive detection of the six marine toxins was achieved, with the limits of detection of 0.15, 0.06, 0.075, 0.027, 0.041, and 0.026 nM for microcystin-LR, anatoxin-α, saxitoxin, cylindrospermopsin, okadaic acid, and brevetoxin, respectively. Moreover, each aptameric assay showed a very good selectivity towards the other five marine toxins. Finally, the developed technique was applied for the detection of the six toxins in spiked water samples with excellent recoveries. Full article

Activation of Nrf2—the master regulator of antioxidative response—at different stages of embryonic development has been shown to result in changes in gene expression, but the tissue-specific and downstream effects of Nrf2 activation during development remain unclear. This work seeks to elucidate the tissue-specific Nrf2 cellular localization and the downstream changes in protein S-glutathionylation during critical windows of zebrafish (Danio rerio) development. Wild-type and mutant zebrafish embryos with a loss-of-function mutation in Nrf2a were treated with two canonical activators, sulforaphane (SFN; 40 µM) or tert-butylhydroquinone (tBHQ; 1 µM), for 6 h at either pharyngula, hatching, or the protruding-mouth stage. Nrf2a protein and S-glutathionylation were visualized in situ using immunohistochemistry. At the hatching stage, Nrf2a protein levels were decreased with SFN, but not tBHQ, exposure. Exposure to both activators, however, decreased downstream S-glutathionylation. Stage- and tissue-specific differences in Nrf2a protein and S-glutathionylation were identified in the pancreatic islet and liver. Protein S-glutathionylation in Nrf2a mutant fish was increased in the liver by both activators, but not the islets, indicating a tissue-specific and Nrf2a-dependent dysregulation. This work demonstrates that critical windows of exposure and Nrf2a activity may influence redox homeostasis and highlights the importance of considering tissue-specific outcomes and sensitivity in developmental redox biology. Full article

Pyroptosis represents a type of cell death mechanism notable for its cell membrane disruption and the subsequent release of proinflammatory cytokines. The Nod-like receptor family pyrin domain containing inflammasome 3 (NLRP3) plays a critical role in the pyroptosis mechanism associated with various diseases resulting from particulate matter (PM) exposure. Tert-butylhydroquinone (tBHQ) is a synthetic antioxidant commonly used in a variety of foods and products. The aim of this study is to examine the potential of tBHQ as a therapeutic agent for managing sinonasal diseases induced by PM exposure. The occurrence of NLRP3 inflammasome-dependent pyroptosis in RPMI 2650 cells treated with PM < 4 µm in size was confirmed using Western blot analysis and enzyme-linked immunosorbent assay results for the pyroptosis metabolites IL-1β and IL-18. In addition, the inhibitory effect of tBHQ on PM-induced pyroptosis was confirmed using Western blot and immunofluorescence techniques. The inhibition of tBHQ-mediated pyroptosis was abolished upon nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown, indicating its involvement in the antioxidant mechanism. tBHQ showed potential as a therapeutic agent for sinonasal diseases induced by PM because NLRP3 inflammasome activation was effectively suppressed via the Nrf2 pathway. Full article

Under-deposit corrosion is widely present in the pipelines of oil and gas production, causing significant corrosion damage. In this paper, a novel electrochemical cathodic-polarization method was carried out to accelerate the formation of CaCO₃ scale on a X65 steel surface in a simulated solution containing scaling ions. Subsequently, pre-scaled X65 steel was placed in a high temperature and pressure autoclave to conduct corrosion weight-loss experiments and in situ electrochemical measurements. The study mainly compared the corrosion inhibition behavior of four quaternary ammonium salt corrosion inhibitors, pyridinium quaternary salt (BPC), quinolinium quaternary salt (BQC), 8-hydroxyquinolinium quaternary salt (BHQ) and pyridinium (1-chloromethyl naphthalene) quaternary salt (1-CPN), in a simulated oilfield scale under corrosive conditions. The results of the weight-loss experiments demonstrated that the inhibition efficiencies of the corrosion inhibitors from high to low were as follows: 1-CPN < BHQ < BQC < BPC. The in situ electrochemical measurements showed that the immersion time and type of corrosion inhibitor had a pronounced influence on the corrosion and corrosion inhibition behavior of X65 steel with CaCO₃ coating. It was also proved using both EIS and PC that 1-CPN shows the best inhibition performance in all. Lastly, the inhibition mechanism of corrosion inhibitors at under-deposit conditions was analyzed via a surface morphology observation of SEM. Full article

Tert-butylhydroquinone (tBHQ) has emerged as a promising candidate for mitigating the adverse effects of T-2-induced reproductive toxicity. The protective effects of tBHQ on rat sperm quality, testicular injury, apoptosis, and inflammation induced by T-2 toxin exposure were investigated. Histopathological examination of testicular tissues revealed severe damage in the T-2-treated group, characterized by disorganized germ cell arrangement, thinning of the convoluted seminiferous tubule walls, and significant cellular necrosis. However, tBHQ administration, either as a preventive or therapeutic measure, mitigated this structural damage. Image analysis confirmed an increase in the cross-sectional area and height of the convoluted seminiferous tubules in the tBHQ-treated groups compared to the T-2-treated group (p < 0.05), indicating tBHQ’s efficacy in alleviating testicular damage. Additionally, tBHQ treatment significantly inhibited T-2-induced apoptosis of testicular tissue cells, as evidenced by the results showing reduced apoptotic cell counts and downregulation of the BAX/BCL2 ratio and caspase-3 expression (p < 0.05). tBHQ significantly increased the concentrations of the antioxidant factors SOD, CAT, TAC, and GSH-PX. Furthermore, tBHQ attenuated the inflammatory response induced by T-2 exposure, as indicated by the decreased mRNA expression of the proinflammatory cytokines Tnf, Il1, and Il10 in testicular tissue (p < 0.05). Additionally, tBHQ treatment alleviated the decline in serum testosterone induced by the T-2 and promoted testosterone synthesis gene expression, including for the genes 17β-HSD and Cyp11a1, in rat testes (p < 0.05). These findings underscore tBHQ’s role as a therapeutic agent combatting T-2-induced reproductive toxicity, highlighting its antioxidative, anti-apoptotic, and anti-inflammatory properties. Further elucidation of tBHQ’s mechanisms of action may offer novel strategies for preventing and treating reproductive disorders induced by environmental toxins. Full article

In addressing the challenge of assessing healthy brain aging across diverse interventions, this study introduces the use of MRI-derived Brain Healthcare Quotients (BHQ) for comprehensive evaluation. We analyzed BHQ changes in 319 participants aged 24–69, who were allocated into dietary (collagen peptide, euglena, matcha, isohumulone, xanthophyll) and physical activity (hand massage with lavender oil, handwriting, office stretching, pink lens, clinical art) groups, alongside a control group, over a month. These interventions were specifically chosen to test the efficacy of varying health strategies on brain health, measured through BHQ indices: GM-BHQ for gray matter volume, and FA-BHQ for white matter integrity. Notably, significant improvements in FA-BHQ were observed in the collagen peptide group, with marginal increases in the hand massage and office stretching groups. These findings highlight BHQ’s potential as a sensitive tool for detecting brain health changes, offering evidence that low-intensity, easily implemented interventions can have beneficial effects on brain health. Moreover, BHQ allows for the systematic evaluation of such interventions using standard statistical approaches, suggesting its value in future brain healthcare research. Full article

Salmonella enterica serovar Indiana (S. Indiana) is among the most prevalent serovars of Salmonella and is closely associated with foodborne diseases worldwide. In this study, we combined a recombinase polymerase amplification (RPA) technique with clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated (Cas) protein Cas12b (CRISPR/Cas12b)-based biosensing in a one-pot platform to develop a novel one-step identification method for S. Indiana infection diagnosis. The entire RPA-CRISPR/Cas12b reaction can be completed at 41 °C within 1 h without the need for specific instruments. The optimal concentrations of Cas12b and single-guide RNA (sgRNA) for the reaction were the same at 250 nM. The single-stranded DNA (ssDNA) reporter 8C-FQ (5′-/6-FAM/CCCCCCCC/BHQ1/-3′) presented the best performance in the reaction compared with the other reporters. The limit of detection (LoD) of the RPA-CRISPR/Cas12b assay was 14.4 copies per reaction. As for specificity, we successfully identified four S. Indiana strains among twenty-two Salmonella strains without any false-positive results, presenting 100% accuracy for S. Indiana, and no cross-reactions were observed in eight other pathogens. Moreover, a total of 109 chicken carcasses were classified by the S. Indiana RPA-CRISPR assay and PCR methods from three processing points, including 43 post-shedding, 35 post-evisceration, and 31 post-chilling. There were 17 S. Indiana-positive samples identified during the whole processing step, consisting of nine post-shedding, five post-evisceration, and three post-chilling. The corresponding S. Indiana-positive rates of post-shedding, post-evisceration, and post-chilling were 20.93% (9/43), 14.29% (5/35), and 9.68% (3/31), respectively. Results from the S. Indiana one-step RPA-CRISPR/Cas12b assay were totally in agreement with those obtained using a traditional culture method, demonstrating 100% agreement with no false-positive or false-negative results observed. Altogether, the RPA-CRISPR/Cas12b assay developed in this study represents a promising, accurate, and simple diagnostic tool for S. Indiana detection. Full article

The NRF2 transcription factor is a master regulator of the cellular oxidant/electrophile response and a drug target for the prevention/treatment of chronic diseases. A major mechanism of NRF2 activation is its escape from rapid degradation, and newly synthesized NRF2 induces cytoprotective protein expression through its cognate antioxidant response elements (AREs). However, oxidative stress can also inhibit global protein translation, thereby potentially inhibiting NRF2 protein accumulation. H₂O₂ has been shown to be a relatively weak inducer of NRF2 in comparison with electrophiles. In the current study, we evaluated whether levels of H₂O₂ that activate the NRF2/ARE pathway inhibit NRF2 protein synthesis in HaCaT keratinocytes. A weak maximum induction was observed for H₂O₂ in comparison with electrophiles, both for NRF2 protein accumulation and ARE reporter activation (~10-fold compared to ≥100-fold activation). At similar H₂O₂ concentrations, both NRF2 protein synthesis and global protein synthesis were inhibited. The manganese porphyrin antioxidant MnTMPyP rescued both global protein synthesis and NRF2 protein synthesis from H₂O₂ inhibition and increased ARE reporter activation. Similar results were observed for the diphenol di-tert-butylhydroquinone (dtBHQ). In conclusion, induction of the NRF2/ARE pathway by H₂O₂ and dtBHQ-derived oxidative species can be limited by inhibition of NRF2 protein synthesis, likely by arrest of global protein synthesis. Full article

A capture systematic evolution of ligands by exponential enrichment (Capture-SELEX) was described to discover novel aptamers specific for 5-hydroxymethylfurfural (5-HMF), and a biosensor based on molecular beacon was constructed to detect 5-HMF. The ssDNA library was immobilized to streptavidin (SA) resin to select the specific aptamer. The selection progress was monitored using real-time quantitative PCR (Q-PCR), and the enriched library was sequenced by high-throughput sequencing (HTS). Candidate and mutant aptamers were selected and identified by Isothermal Titration Calorimetry (ITC). The FAM-aptamer and BHQ1-cDNA were designed as the quenching biosensor to detect 5-HMF in milk matrix. After the 18th round selection, the Ct value decreased from 9.09 to 8.79, indicating that the library was enriched. The HTS results indicated that the total sequence numbers for 9th, 13th, 16th, and 18th were 417054, 407987, 307666, and 259867, but the number of sequences for the top 300 sequences was gradually increased from 9th to 18th, and the ClustalX2 analysis showed that there were four families with high homology rate. ITC results indicated that the K_d values of H1 and its mutants H1-8, H1-12, H1-14, and H1-21 were 2.5 μM, 1.8 μM, 1.2 μM, 6.5 μM, and 4.7 μM. The linear range of the quenching biosensor was from 0 μM to 75 μM, and it had a similar linear range in the 0.1% milk matrix. This is the first report to select a novel aptamer specific for 5-HMF and develop quenching biosensor for the rapid detection of 5-HMF in milk matrix. Full article

Sickle cell disease (SCD) is a monogenic inheritable disease characterized by severe anemia, increased hemolysis, and recurrent, painful vaso-occlusive crises due to the polymerization of hemoglobin S (HbS)-generated oxidative stress. Up until now, only four drugs are approved for SCD in the US. However, each of these drugs affects only a limited array of SCD pathologies. Importantly, curative therapies, such as gene therapy, or hematopoietic stem cell transplantation are not available for every patient because of their high costs, availability of donor matching, and their serious adverse effects. Therefore, there is an unmet medical need for novel therapeutic strategies that target broader SCD sequelae. SCD phenotypic severity can be alleviated by increasing fetal hemoglobin (HbF) expression. This results in the inhibition of HbS polymerization and thus sickling, and a reduction in oxidative stress. The efficacy of HbF is due to its ability to dilute HbS levels below the threshold required for polymerization and to influence HbS polymer stability in RBCs. Nuclear factor-E2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1)-complex signaling is one of the most important cytoprotective signaling controlling oxidative stress. Nrf2 is present in most organs and, after dissociation from Keap1, it accumulates in the cytoplasm, then translocates to the nucleus where it binds to the antioxidant response element (ARE) sequences and increases the expression of various cytoprotective antioxidant genes. Keeping this in mind, various researchers have proposed a role of multiple agents, more importantly tert-Butylhydroquinone (tBHQ), curcumin, etc., (having electrophilic properties) in inhibiting keap1 activity, so that Nrf2 can translocate to the nucleus to activate the gamma globin gene, thus maintaining alpha-hemoglobin-stabilizing protein (AHSP) and HbF levels. This leads to reduced oxidative stress, consequently minimizing SCD-associated complications. In this review, we will discuss the role of the Keap-1–Nrf2 complex in hemoglobinopathies, especially in SCD, and how this complex might represent a better target for more effective treatment options. Full article