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Reinforced concrete structures are subject to exposure to chloride ions in the air, leading to chloride penetration, and carbonation attacks resulting from exposure to carbon dioxide. This chemical degradation process induces corrosion of reinforcing bars within concrete, significantly impacting durability. Structures situated in coastal areas, such as nuclear power plants, are particularly susceptible to rapid chloride penetration due to the high chloride concentration in the air. This study utilizes existing experimental data to forecast the chloride diffusion coefficient employing artificial neural network (ANN technology). The total number of experimental data was 535 gathered from 18 papers. Through analysis of the chloride coefficient and predicted degradation depth, the effective cross-sectional area of concrete is examined, and the deterioration of wall performance is forecasted.

Background: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. Methods: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. Results: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. Conclusion: The diagnostic yield of WES was 48.8 %. We conclude that patients’ characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.

Summary: Purpose: This methodological study evaluated the psychometric properties of the Self-Care of Coronary Heart Disease Inventory version 3 (SC-CHDI v3) in a Korean context. Methods: The SC-CHDI v3 was translated into Korean following a rigorous translation process. Participants were 452 patients who had experienced coronary heart disease (CHD), all recruited from a tertiary hospital in Korea. Exploratory and confirmatory factor analyses were performed to test construct validity. Concurrent validity was examined by correlating scores from the Korean version of the SC-CHDI v3 with those from the Cardiac Self-Efficacy Scale. Internal consistency was analyzed using Cronbach's alpha and McDonald's omega. Results: The Korean version of the SC-CHDI v3 consists of 21 items, excluding two from the original instrument. The self-care maintenance subscale identified a two-factor structure: “treatment adherence” and “health-promoting behaviors.” The goodness-of-fit indices were satisfied: χ2 = 18.19, p = .110, comparative fit index (CFI) = .97, Tucker-Lewis Index (TLI) = .95, and standardized root mean square residual (SRMR) = .04. The self-care monitoring subscale consisted of a one-dimensional structure (“monitoring behaviors”) and the goodness-of-fit indices were satisfied: χ2 = 19.19, p = .059, CFI = .99, TLI = .99, and SRMR = .04. The self-care management subscales had a two-factor structure of “consulting behaviors” and “problem-solving behaviors.” The goodness-of-fit indices were satisfied: χ2 = 16.44, p = .037, CFI = .99, TLI = .98, and SRMR = .03. Scores from the Cardiac Self-Efficacy Scale showed a positive correlation with the Korean version of SC-CHDI v3 subscales. Reliability estimates were ≥ .80 for all subscales except for the self-care maintenance subscale. Conclusions: The Korean version of the SC-CHDI v3 consists of 21 items in 3 subscales and is a valid and reliable instrument. Therefore, healthcare providers can effectively utilize it to assess the self-care levels of patients with CHD.

Wire and arc additive manufacturing (WAAM) technique has introduced a novel approach for producing complex Ti–6Al–4V parts with metric dimensions. However, the produced part leads to the development of a strong texture and anisotropic mechanical properties due to the formation of large columnar β grains. To resolve this issue, the plastic deformation of each deposited track through hammer peening was developed as a means to refine these large β grains. In this study, we have investigated an innovative approach to further enhance the efficiency of β grain refinement by minimizing the arc heat input associated with previous deposited layer, which is achieved by employing a C-type filler wire. Our findings reveal a notable enhancement in grain refinement efficiency through the utilization of a C-type filler wire with peening process, as compared to available conventional commercial round shape filler wire. Specifically, the employment of the C-type filler wire results in a reduced melt pool penetration depth of WAAM Ti–6Al–4V (3.3 mm), compared to the commercially available round shape (R-Type) filler wire (4.48 mm). Within the plastically deformed region by peening, fine and randomly oriented β grains are observed, extending to a depth of deformation reaching 844 ± 32.65 μm. Peening WAAM Ti–6Al–4V with the C-type filler wire leads to the development of isotropic mechanical properties in both horizontal and vertical directions, offering high strength due to the presence of small equiaxed β grains and thin α laths (0.56 ± 0.18 μm), in contrast to the use of conventional commercial round shape filler wire.

Background: Several biologics have been developed and used to treat severe asthma. However, commercialized biologics have limitations in treating T2-low asthma because their main target is the T2 inflammation marker. Therefore, there is an unmet need for treating T2-low severe asthma. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is an auxiliary protein in the mammalian multi-aminoacyl-tRNA synthetase complex. AIMP1 also acts as a cytokine and induces the secretion of proinflammatory cytokines. Since anti-AIMP1 has been shown to reduce interleukin (IL)-6, tumor necrosis factor-α, and IL-17A levels in a mouse model, it could be effective in the treatment of T2-low severe asthma. Methods: Wild-type BALB/c mice were sensitized and challenged with intranasal inoculation of a crude HDM extract. Atliximab, a chimeric AIMP1 antibody, was administered once (20 μg, 40 μg, 100 μg) on Day 14. We evaluated airway hyperresponsiveness (AHR), performed cellular analyses of the bronchoalveolar lavage fluid (BALF), measured inflammatory cytokine levels, and examined peribronchial histological features. Results: Atliximab reduced AIMP1 levels in asthmatic mice in a dose-dependent manner. AHR and Inflammatory cells such as neutrophils and eosinophils in the BALF decreased in asthmatic mice treated with atliximab. The levels of IL-6, IL-13, and transforming growth factor-β (TGF-β) in the lung tissue decreased in asthmatic mice treated with a high dose of atliximab (100 μg). Atliximab also reduced goblet cell hyperplasia and peribronchial fibrosis. Conclusions: Atliximab improved asthmatic airway inflammation including neutrophilic inflammation in HDM-induced asthma mice. These data suggest that anti-AIMP1 plays an important role in the treatment of severe T2-low asthma.

Background: Korean red ginseng extract (KRGE) (Family: Araliaceae) is one of the most widely used traditional herbs in Asia. Multiple studies have shown that KRGE has anti-inflammation, anti-fatigue, anti-obesity, anti-oxidant, and anti-cancer effects. Methods: Sprague-Dawley rats were divided into five groups for PTU-induced hypothyroidism and six groups for LT4-induced hyperthyroidism. At the experiment's conclusion, rats were sacrificed, and blood, thyroid gland, and liver samples were collected. Body weight was recorded weekly, and serum hormone levels were assessed using enzyme-linked immunoassay. Thyroid gland and liver tissues were stained with hematoxylin and eosin. KRGE was prepared in 0.5% CMC and stored at 4 °C before administration. Results: In the LT4-induced hyperthyroidism model, KRGE prevented decreases in body weight, thyroid gland weight, liver weight, serum glucose, and thyroid hormone levels compared to the PTU group. It also reduced increases in T3, T4, and serum aspartate aminotransferase levels after LT4 treatment. Additionally, KRGE improved thyroid gland and liver histopathology, effects not observed in the PTU-induced hypothyroidism model. Conclusion: All things considered, our research points to KRGE's potential protective role in rat hyperthyroidism caused by LT4 by lowering thyroid hormone production.

Objective: Currently, little is known about the mechanism(s) regulating global and specific protein translation during metabolic dysfunction-associated steatohepatitis (MASH; previously known as non-alcoholic steatohepatitis, NASH). Methods: Unbiased label-free quantitative proteome, puromycin-labelling and polysome profiling were used to understand protein translation activity in vitro and in vivo. Results: We observed a global decrease in protein translation during lipotoxicity in human primary hepatocytes, mouse hepatic AML12 cells, and livers from a dietary mouse model of MASH. Interestingly, proteomic analysis showed that Rplp1, which regulates ribosome and translation pathways, was one of the most downregulated proteins. Moreover, decreased Esrra expression and binding to the Rplp1 promoter, diminished Rplp1 gene expression during lipotoxicity. This, in turn, reduced global protein translation and Esrra/Rplp1-dependent translation of lysosome (Lamp2, Ctsd) and autophagy (sqstm1, Map1lc3b) proteins. Of note, Esrra did not increase its binding to these gene promoters or their gene transcription, confirming its regulation of their translation during lipotoxicity. Notably, hepatic Esrra-Rplp1-dependent translation of lysosomal and autophagy proteins also was impaired in MASH patients and liver-specific Esrra knockout mice. Remarkably, alternate day fasting induced Esrra-Rplp1-dependent expression of lysosomal proteins, restored autophagy, and reduced lipotoxicity, inflammation, and fibrosis in hepatic cell culture and in vivo models of MASH. Conclusions: Esrra regulation of Rplp1-mediated translation of lysosome/autolysosome proteins was downregulated during MASH. Alternate day fasting activated this novel pathway and improved MASH, suggesting that Esrra and Rplp1 may serve as therapeutic targets for MASH. Our findings also provided the first example of a nuclear hormone receptor, Esrra, to not only regulate transcription but also protein translation, via induction of Rplp1.

Background: Recently, plant-derived exosome-like nanoparticles (PDENs) have been isolated, and active research was focusing on understanding their properties and functions. In this study, the characteristics and molecular properties of ginseng root-derived exosome-like nanoparticles (GrDENs) were examined in terms of skin protection. Methods: HPLC-MS protocols were used to analyze the ginsenoside contents in GrDENs. To investigate the beneficial effect of GrDENs on skin, HaCaT cells were pre-treated with GrDENs (0–2 × 109 particles/mL), and followed by UVB irradiation or H2O2 exposure. In addition, the antioxidant activity of GrDENs was measured using a fluorescence microscope or flow cytometry. Finally, molecular mechanisms were examined with immunoblotting analysis. Results: GrDENs contained detectable levels of ginsenosides (Re, Rg1, Rb1, Rf, Rg2 (S), Gyp17, Rd, C-Mc1, C–O, and F2). In UVB-irradiated HaCaT cells, GrDENs protected cells from death and reduced ROS production. GrDENs downregulated the mRNA expression of proapoptotic genes, including BAX, caspase-1, -3, -6, -7, and -8 and the ratio of cleaved caspase-8, -9, and -3 in a dose-dependent manner. In addition, GrDENs reduced the mRNA levels of aging-related genes (MMP2 and 3), proinflammatory genes (COX-2 and IL-6), and cellular senescence biomarker p21, possibly by suppressing activator protein-1 signaling. Conclusions: This study demonstrates the protective effects of GrDENs against skin damage caused by UV and oxidative stress, providing new insights into beneficial uses of ginseng. In particular, our results suggest GrDENs as a potential active ingredient in cosmeceuticals to promote skin health.

Summary: Purpose: This study explored the work adjustment trajectory and its predictors and characteristics among newly registered nurses. Methods: A total of 245 newly registered nurses working in a university hospital provided general baseline characteristics and completed a work adjustment questionnaire along with self-report measures of clinical competency, psychological capital, preceptor exchange, social support, and role conflict when they started working independently (baseline) and at 7 and 12 months after employment. Data were collected from July 2020 to August 2022. The collected data were subjected to a group-based trajectory model, χ2 test, F test, one-way ANOVA, and multiple logistic regression using SAS 9.4, and SPSS 25.0. Results: Group-based trajectory modeling classified three newly registered nurse groups: nurses with a high work adjustment level in all subscales from the beginning of employment (early adjustment group, 16.1%), nurses with a moderate level of adjustment from beginning to end (standard adjustment group, 60.6%), and nurses with a low level of work adjustment from early to mid-term, rising later (delayed adjustment group, 23.3%). Higher hope, optimism, and emotional support predicted early and standard adjustments. Conclusions: Based on the trajectory characteristics, newly registered nurses need to improve their work adjustment. The early and standard adjustment groups should continuously monitor their levels of work adjustment while monitoring their hopes, optimism, and emotional support. In particular, the delayed adjustment group required customized educational programs and strengthened peer support.

This paper gives an extensive analysis on the characterization of xenon isotopic ratios for various nuclear reactors and nuclear explosions through neutronic depletion codes. The results of the characterization can be used for discriminating the sources of the xenon isotopes’ release among the nuclear explosions and nuclear reactors. The considered sources of the xenon radionuclides do not only include PWR, CANDU, and nuclear explosions using uranium and plutonium bombs, but also IRT-200 and 5MWe Yongbyon (MAGNOX reactor) research reactors operated in North Korea. A new data base (DB) on xenon isotopic activity ratios was produced using the results of the characterization, which can be used in discrimination of the sources of xenon isotopes. The results of the study show that 5MWe Yongbyon reactor has quite different characteristics in 135Xe/133Xe ratio from the PWRs and the nuclear reactors have different characteristics in 135Xe/133Xe ratios from the nuclear explosions.

Our study was to explore the effects of subchronic particulate matter (PM) exposure on lung injury induced by polyhexamethylene guanidine phosphate (PHMG-p) in a rat model. Specifically, we investigated pulmonary inflammation, fibrosis, and tumor formation using chest computed tomography (CT), and histopathologic examination. PHMG-p was administered intratracheally to 20 male rats. After an initial week of PHMG-p treatment, the experimental group (PM group) received intratracheal administration of PM suspension, while the control group received normal saline. This regimen was continued for 10 weeks to induce subchronic PM exposure. Chest CT scans were conducted on all rats, followed by the extraction of both lungs for histopathological analysis. All CT images underwent comprehensive quantitative and qualitative analyses. Pulmonary inflammation was markedly intensified in rats subjected to subchronic PM exposure in the PM group compared to those in the control. Similarly, lung fibrosis was more severe in the PM group as observed on both chest CT and histopathologic examination. Quantitative chest CT analysis revealed that the mean lesion volume was significantly greater in the PM group than in the control group. Although the incidence of bronchiolo-alveolar hyperplasia was higher in the PM group compared to the control group, this difference was not statistically significant. In summary, subchronic PM exposure exacerbated pulmonary inflammation and fibrosis underlying lung injury induced by PHMG-p.

Hemophilia B is a congenital bleeding disorder caused by factor IX (FIX) deficiency. Generation of recombinant FIX (rFIX) is required for detecting a Hemophilia B indicator, anti-FIX antibody. In this study, we described a method for producing recombinant FIX (rFIX) using Escherichia coli. We constructed a FIX-expressing plasmid without a fusion tag protein-encoding gene and produced rFIX as a soluble form within five days. Dose-dependent curve was obtained from ELISA using anti-FIX antibody, indicating that the rFIX can be used as an antigen to detect anti-FIX antibody with high affinity and sensitivity.

Rheumatoid arthritis (RA) is known to be caused by autoimmune disorders and can be partially alleviated through Disease-Modifying Antirheumatic Drugs (DMARDs) therapy. However, due to significant variations in the physical environment and condition of each RA patient, the types and doses of DMARDs prescribed can differ greatly. Consequently, there is a need for a platform based on patient-derived cells to determine the effectiveness of specific DMARDs for individual patient. In this study, we established an RA three-dimensional (3D) spheroid that mimics the human body's 3D environment, enabling high-throughput assays by culturing patient-derived synovial cells on a macroscale-patterned polycaprolactone (PCL) scaffold. Fibroblast-like synoviocytes (FLSs) from patient and human umbilical vein endothelial cells (HUVECs) were co-cultured to simulate vascular delivery. Additionally, RA characteristics were identified at both the genetic and cytokine levels using real-time polymerase chain reaction (RT-qPCR) and dot blot assay. The similarities in junctions and adhesion were demonstrated in both actual RA patient tissues and 3D spheroids. The 3D RA spheroid was treated with representative DMARDs, observing changes in reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) levels, and inflammatory cytokine responses to confirm the varying cell reactions depending on the DMARDs used. This study underscores the significance of the 3D drug screening platform, which can be applied to diverse inflammatory disease treatments as a personalized drug screening system. We anticipate that this platform will become an indispensable tool for advancing and developing personalized DMARD treatment strategies.

The development and deployment of deep learning models are currently limited to expert developers due to the requirement for programming expertise, posing challenges for non-expert or inexperienced developers. In this paper, we present VELCRO, a visual-based programming tool that enables intuitive construction, modification, analysis, and generation of deep learning models for both expert and non-expert developers. VELCRO allows users to understand and modify complex architectures of deep learning models using architecture abstraction, and verify architectures through automated architecture validation. Finally, users can convert the user-configured architecture into deep learning code and deploy it in target environments.

Asplenium L. is a sub-cosmopolitan genus of ferns comprising approximately 700 species. It includes various ploidy-leveled taxa, and, in particular, polyploid species occupy a higher proportion than diploid species within the genus. In addition, it is regarded as an essential process to confirm the cytotype of taxa because the ploidy level is sometimes used to identify a particular taxon in Asplenium. In the case of A. prolongatum, two cytotypes, tetraploid and hexaploid, have been reported in Japanese and Chinese populations. However, to date, there have been no attempts to confirm the ploidy of the Korean species. In the present study, we investigated the cytotype of Korean A. prolongatum using chromosome counting and genome size measurements, and we found that two cytotypes, hexaploid (2n = 6x = 216) and octaploid (2n = 8x = 288), were distributed in Jeju Island, Korea. To the best of our knowledge, this is the first report of a neo-cytotype of A. prolongatum. The hexaploids mostly had empty, shrunken sporangia, which is one of the traits observed in sterile hybrid ferns. From these results, it was concluded that A. prolongatum has three cytotypes: tetraploid, hexaploid, and octaploid.

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

Recently, with the development of non-invasive human health monitoring technology including wearable devices, a flexible sensor that monitors ‘human sound and movement signals’ such as human voice and muscle movement is attracting attention. In this experiment, electrospun nanofibers were mixed with highly conductive nanoparticles and coated with polyaniline to detect the patient's electrical signals. Due to the high piezoelectric effect, nanofiber-based sensors do not require charging through a separate battery, so they can be used as self-powered devices. In addition, the LCR meter test confirmed that the sensor has a high capacitance due to its high conductivity and high sensitivity to electrical signals. The sensor produced in this study can visually estimate the electrical signal of the actual human body through real-time comparison with electromyography (EMG) measuring equipment, and it was confirmed that the error is small. This sensor is expected to be widely used in the medical field, from simple sound and movement signals to disease monitoring.

A poly(p-phenylene)-based multiblock polymer is developed with an oligomeric chain extender and cerium (CE-sPP-PPES + Ce3+) to realize better performance and durability in proton exchange membrane fuel cells. The membrane performance is evaluated in single cells at 80 °C and at 100% and 50% relative humidity (RH). The accelerated stability test is conducted 90 °C and 30% RH, during which linear sweep voltammetry and hydrogen permeation detection are monitored periodically. Results demonstrate that the proton conductivity of the pristine hydrocarbon membranes is superior to that of PFSA membranes, and the hydrogen crossover is significantly lower. In addition, a composite membrane containing cerium performs similarly to a pristine membrane, particularly at low RH levels. Adding cerium to CE-sPP-PPES + Ce3+ membranes improves their chemical durability significantly, with an open circuit voltage decay rate of only 89 μV/h for 1000 h. The hydrogen crossover is maintained across accelerated stability tests, as confirmed by hydrogen detection and crossover current density. The short-circuit resistance indicates that membrane thinning is less likely to occur. Collectively, these results demonstrate that a hydrocarbon membrane with cerium is a potential alternative for fuel cell applications.

Summary: We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1β and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.

The cultivar of red pepper used in kimchi contributes to spiciness, red color, and fermentation characteristics. Capsaicinoids are the main components of red pepper. Therefore, understanding changes in metabolites during kimchi fermentation according to capsaicinoid concentration is necessary to control the quality of kimchi. The purpose of this study was to investigate the effect of capsaicinoids on metabolites during kimchi fermentation. To profile the effect of capsaicinoid concentrations on kimchi fermentation, five kimchi samples were prepared using different concentrations of capsaicinoids (4, 12, 30.7, 40.9, and 50.3 mg/kg) and stored at 4 °C for 28 days. During kimchi fermentation, pH, titratable acidity, capsaicinoid concentration, total viable and lactic acid bacteria, free sugars, amino acids, and microbial community were evaluated. Each result was statistically analyzed for changes in capsaicin concentration and fermentation time. The capsaicinoid concentration did not change during kimchi fermentation but the growth of lactic acid bacteria changed. According to the growth of lactic acid bacteria, free sugar, amino acids, and microbial community changed with the capsaicinoid concentration. Overall, the results of this study provide preliminary information on the use of red pepper and capsaicinoids in the kimchi industry.

Garlic, a key ingredient in kimchi, is an indispensable source of lactic acid bacteria, which are essential for fermentation. This study explored the effects of various garlic varieties on kimchi fermentation, focusing on changes in microbial communities and metabolite profiles. We observed that the type of garlic used did not significantly alter the microbial community. However, the presence of garlic itself made a significant difference. Specifically, kimchi with garlic showed higher abundance of Leuconostoc and Weissella, which are bacteria primarily responsible for kimchi fermentation. Additionally, kimchi containing garlic had increased levels of mannitol and fructose, which significantly influence taste; however, lactic acid and putrescine levels were decreased. Therefore, the addition of garlic directly contributes to the flavor profile of kimchi. Sixty-two metabolites were identified using gas chromatography and mass spectrometry. The variety of garlic added influenced the metabolite profiles of kimchi, particularly in the later stages of fermentation. These profiles were categorized based on the garlic's origin, whether from southern or northern ecotypes (R2X = 0.933, R2Y = 0.986, Q2 = 0.878). These findings confirm that both the presence and the variety of garlic significantly impact the microbial ecology and metabolites during kimchi fermentation, underscoring its essential role in the process.

Aim: The role of regional nodal irradiation (RNI) after preoperative systemic treatment (PST) with targeted therapy for HER2-positive breast cancer remains uncertain. This study aimed to investigate the impact of RNI on locoregional recurrence (LRR) and disease-free survival (DFS) outcomes after docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP) for PST. Methods: We retrospectively analyzed 255 patients who were treated with six cycles of TCHP between 2016 and 2019. The patients were divided into four groups based on clinical nodal involvement: group A, with no nodal disease; group B, with axillary lymph node (AXL) level I; group C, with AXL level I with II/III; and group D, with supraclavicular or internal mammary nodes. Results: The RNI group had more advanced nodal disease (C/D) than the no RNI group (56.9 % vs. 6.8 %). With a median follow-up of 51.3 months, there were two (0.8 %), three (1.2 %), and 15 (5.9 %) local, regional, and distant metastases, respectively. LRR did not differ significantly according to the RNI (2.6 % vs. 1.0 %, p = 0.651). Group D had the most frequent distant metastases (17.5 %; p = 0.005). The 4-year DFS rate was 92.7 %, and DFS did not improve significantly after RNI (p = 0.074). When stratified by clinical nodal groups and pathological axillary response, RNI had no effect on LRR/DFS outcomes. Conclusion: With a rare incidence of LRR, RNI did not significantly affect LRR or DFS in patients with HER2-positive breast cancer after with PST-TCHP. However, intensive systemic treatment is required for advanced diseases (C/D). Selective de-intensified RNI and intensified systemic treatment should be investigated in future studies.

Hydrogel electrolytes, where water solvents and salts are confined in the porous networks of polymeric or inorganic solids, are attractive because they can resolve technical challenges of liquid electrolytes such as leakage, water decomposition, and mechanical instability. Herein, we demonstrate polyacrylic acid tethered onto the surface of vinyl functionalized silica nanoparticles (PAA-VSNP) hydrogel electrolytes through a sol-gel and radical polymerization process. The synthesis chemistry, the associated chemical structure, and the morphology of PAA-VSNP hydrogel electrolytes were comprehensively characterized analyzing FTIR, XPS and 13C and 29Si solid-state MAS NMR spectroscopies. The resulting PAA-VSNP hydrogel electrolytes were mechanically stable as verified by the stretchability up to 1122.75% of original length as well as ionically conductive as demonstrated by higher ionic conductivity of 20.23 mS cm−1 and lower activation energy of 0.106 eV than those of PVA counterparts. Integrating this PAA-VSNP hydrogel electrolytes with activated carbon and Na3V2(PO4)3/carbon composite and, flexible sodium ion hybrid supercapacitors (AC//PAA-VSNP //NVP@C SHSC SHSC) full cells could be fabricated. The as-fabricated AC//PAA-VSNP//NVP@C SHSC achieved a long-term cyclability over 4000 cycles and flexibility, delivering the larger energy and power densities 86.95 W h kg−1 and 19.94 kW kg−1 than those of AC//PVA//NVP@C and other works using hydrogel electrolytes.

Cancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients’ quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer.In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and μCT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bone microenvironment and their role in pain and disease progression associated with bone metastatic prostate cancer.

This study aimed to derive mature oocytes from murine preantral follicles cultured in a biomimetic ovary with a porcine scaffold using decellularization technology. We evaluated the DNA content and the presence of cell and extracellular matrix (ECM) components, including collagen, elastin, and glycosaminoglycans (GAGs), in decellularized (decell) porcine ovaries. The DNA content inthe decell ovarian tissues was approximately 94 % less than that in native tissues (66 ± 9.8 ng/mg vs. 1139 ± 269 ng/mg). Furthermore, the ECM component integrity was maintained in the decell ovarian tissue. The soluble collagen concentration of native ovarian tissue (native) was 195.34 ± 15.13 μg/mg (dry wt.), which was less than 878.6 ± 8.24 μg/mg for the decell ovarian tissue due to the loss of cellular mass. Hydrogels derived from decell porcine ovaries were prepared to develop an in vitro biomimetic ovary with appropriate ECM concentration (2−6 mg/mL). Scanning electron microscope (SEM) imagining revealed that the complex fiber network and porous structure were maintained in all groups treated with varying ECM concentration (2–6 mg/mL). Furthermore, rheometer analysis indicated that mechanical strength increased with ECM concentration in a dose-dependently. The preantral follicles cultured with 4 mg/mL ECM showed high rates of antral follicle (66 %) and mature oocyte (metaphase II) development (47 %). The preantral follicles cultured in a biomimetic ovary with a decell porcine scaffold showed a higher rate of antral follicle and mature oocytes than those cultured in other biomaterials such as collagen and Matrigel. In mature oocytes derived from antral follicles, meiotic spindles and nuclei were stained using a tubulin antibody and Hoechst, respectively. Two-cell embryos were developed from MII oocytes following parthenogenetic activation. Preantral follicles were cultured in a biomimetic ovary derived from the ECM of a decell porcine ovary, and embryos were generated from MII oocytes. This biomimetic ovary could contribute to restoring fertility in infertile women with reduced ovarian function, benefit mating efforts for endangered species, and maintain animals with valuable genetic traits.

Transcranial focused ultrasound (tFUS), in which acoustic energy is focused on a small region in the brain through the skull, is a non-invasive therapeutic method with high spatial resolution and depth penetration. Image-guided navigation has been widely utilized to visualize the location of acoustic focus in the cranial cavity. However, this system is often inaccurate because of the significant aberrations caused by the skull. Therefore, acoustic simulations using a numerical solver have been widely adopted to compensate for this inaccuracy. Although the simulation can predict the intracranial acoustic pressure field, real-time application during tFUS treatment is almost impossible due to the high computational cost. In this study, we propose a neural network-based real-time acoustic simulation framework and test its feasibility by implementing a simulation-guided navigation (SGN) system. Real-time acoustic simulation is performed using a 3D conditional generative adversarial network (3D-cGAN) model featuring residual blocks and multiple loss functions. This network was trained by the conventional numerical acoustic simulation program (i.e., k-Wave). The SGN system is then implemented by integrating real-time acoustic simulation with a conventional image-guided navigation system. The proposed system can provide simulation results with a frame rate of 5 Hz (i.e., about 0.2 s), including all processing times. In numerical validation (3D-cGAN vs. k-Wave), the average peak intracranial pressure error was 6.8 ± 5.5%, and the average acoustic focus position error was 5.3 ± 7.7 mm. In experimental validation using a skull phantom (3D-cGAN vs. actual measurement), the average peak intracranial pressure error was 4.5%, and the average acoustic focus position error was 6.6 mm. These results demonstrate that the SGN system can predict the intracranial acoustic field according to transducer placement in real-time.

Background: The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods: Thirty-eight rats were randomly assigned to five groups: sham (n...=...6), ischemic (n...=...8), chelerythrine (a PKC inhibitor; 5...mg.kg-1 IV administered 30...min before cerebral ischemia) (n...=...8), dexmedetomidine (100.....g.kg-1 IP administered 30...min before cerebral ischemia (n...=...8), and dexmedetomidine...+...chelerythrine (n...=...8). Global transient cerebral ischemia (10...min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24...hours after ischemia insult. Results: We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p...

Background: To investigate whether intrarectal local anesthesia with heated lidocaine gel (IRLAH) is non-inferior to periprostatic nerve block (PNB) for reducing pain in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy. Methods: We performed a randomized controlled non-inferiority trial with 100 participants who underwent systematic TRUS-guided, 12-core prostate biopsy from August 2019 to July 2020. These participants were randomly assigned to a group receiving intrarectal local anesthesia with 20 mL of heated (40°C) 2% lidocaine gel (n = 50) or PNB (n = 50). The primary outcome was a pain score on a 0–10 visual analogue scale (VAS) at four time points with the non-inferiority margin of 1; VAS-1: during local anesthesia application; VAS-2: during probe insertion; VAS-3: during biopsy; VAS-4: 30 minutes after the procedure. The secondary outcome included complications during and after the procedure. Results: The IRLAH group (0.1) met non-inferiority as well as superiority criteria for mean VAS-1 score vs. the PNB group (2.33) (P

The study presents a controlled nanoscale drug delivery system mediated by polymeric magnetic nanoparticles. Under an alternating magnetic field (AMF), the magnetic nanoparticles act as internal heating sources that increase the surrounding temperature, provoking polymer transitions and thereby releasing the entrapped drug. We explain the drug-release mechanism using different mathematical models including Higuchi, Korsmeyer–Peppas, Hixson–Crowell, and Kopcha. Our results indicate that doxorubicin (DOX) release follows the Hixson–Crowell model with R2 = 0.99, revealing that the changes in the surface areas of the particles are the main driving force for drug release from poly(N-isopropylacrylamide)/N (hydroxymethyl) acrylamide coated SPIONs (SPNH/DOX) at 43 °C. However, at 37 °C, the drug release occurs by the diffusion mechanism. Moreover, in vitro cell culture assays including CCK-8, FACS, confocal and BIO-TEM images have confirmed cytotoxicity and cellular uptake of SPNH/DOX in CT26 cancer cells. Through a synergetic effect between chemotherapy triggered by AMF application and intracellular hyperthermia, significant tumoricidal effects were achieved in the initial 24 h after treatment.

Agricultural byproducts are intermediate products generated during food processing and contain functional ingredients that are suitable for use in the green circular economy. This study aimed to demonstrate the skin-whitening effect of pumpkin tendril extract (PTE) using a mushroom tyrosinase assay, L-DOPA staining, qRT-PCR, western blotting, a zebrafish model, and a reconstituted 3D human skin model. PTE dose-dependently scavenged DPPH free radicals and inhibited melanogenesis stimulated by α-MSH without exhibiting cytotoxicity in 2D- and 3D-cultured B16F10 cells. Interestingly, PTE significantly reduced melanogenesis in zebrafish and 3D-pigmented human skin models. In addition, PTE notably downregulated the expression of proteins related to melanogenesis, such as MITF, TRP-1, TRP-2, and tyrosinase. Phosphorylation of CREB, an upregulator of MITF, was also attenuated by PTE treatment. Component analysis revealed that rutin is an active compound in PTE affecting melanogenesis. These results suggest that PTE suppresses melanogenesis and tyrosinase activity by regulating the CREB/MITF signaling pathway.

Food-borne bacteria have frequently been detected in kimchi, a representative and traditional fermented ethnic food of Korea. This study investigated the effect of atmospheric dielectric barrier discharge (DBD) plasma treatment (1.1 kV, 43 kHz, N2: 1.5 m/s, 5–60 min) on reduction of Yersinia enterocolitica and Staphylococcus aureus and on quality parameters in Geotjeroi, a non-fermented kimchi. A decrease of 0.12/0.09, 0.19/0.19, 0.34/0.45, 0.64/0.72, and 1.13/1.12 log10 CFU/g was observed by 5, 10, 20, 30, and 60 min of DBD plasma, respectively. D-value of 52.83 and 51.95 min was determined for Y. enterocolitica (R2 = 0.99) and S. aureus (R2 = 0.98) using the first order kinetics model. The quality parameters (pH, Brix, and hardness) were not significantly different (P > 0.05) between treated and untreated Geotjeori. Moreover, a decrease of >1 log10 CFU/g, for both bacteria was observed without any change in the quality of Geotjeori. These findings imply that DBD plasma treatment enhances Geotjeori safety and protects product from microbial risk.

Air pollution is a risk factor that increases cardiovascular morbidity and mortality. In this study, we investigated the cardiotoxicity of particulate matter (PM) exposure using a zebrafish embryo model. We found that PM exposure induced cardiotoxicity, such as arrhythmia, during cardiac development. PM exposure caused cardiotoxicity by altering the expression levels of cardiac development (T-box transcription factor 20, natriuretic peptide A, and GATA-binding protein 4)- and ion-channel (scn5lab, kcnq1, kcnh2a/b, and kcnh6a/b)-related genes. In conclusion, this study showed that PM induces the aberrant expression of cardiac development- and ion channel-related genes, leading to arrhythmia-like cardiotoxicity in zebrafish embryos. Our study provides a foundation for further research on the molecular and genetic mechanisms of cardiotoxicity induced by PM exposure.

Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.

Background & Aims: Binge drinking in patients with metabolic syndrome accelerates the development of alcohol-associated liver disease. However, the underlying mechanisms remain elusive. We investigated if oxidative and nonoxidative alcohol metabolism pathways, diet-induced obesity, and adipose tissues influenced the development of acute liver injury in a single ethanol binge model. Methods: A single ethanol binge was administered to chow-fed or high-fat diet (HFD)-fed wild-type and genetically modified mice. Results: Oral administration of a single dose of ethanol induced acute liver injury and hepatic endoplasmic reticulum (ER) stress in chow- or HFD-fed mice. Disruption of the Adh1 gene increased blood ethanol concentration and exacerbated acute ethanol-induced ER stress and liver injury in both chow-fed and HFD-fed mice, while disruption of the Aldh2 gene did not affect such hepatic injury despite high blood acetaldehyde levels. Mechanistic studies showed that alcohol, not acetaldehyde, promoted hepatic ER stress, fatty acid synthesis, and increased adipocyte death and lipolysis, contributing to acute liver injury. Increased serum fatty acid ethyl esters (FAEEs), which are formed by an enzyme-mediated esterification of ethanol with fatty acids, were detected in mice after ethanol gavage, with higher levels in Adh1 knockout mice than in wild-type mice. Deletion of the Ces1d gene in mice markedly reduced the acute ethanol-induced increase of blood FAEE levels with a slight but significant reduction of serum aminotransferase levels. Conclusions: Ethanol and its nonoxidative metabolites, FAEEs, not acetaldehyde, promoted acute alcohol-induced liver injury by inducing ER stress, adipocyte death, and lipolysis.

We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.

We developed a predictive growth model of Yersinia enterocolitica for fresh Kimchi cabbages as a function of storage temperature (5–20 °C). The Baranyi equation used for primary modeling at these storage temperatures was suitable as a model for obtaining lag time (LT) and specific growth rate (SGR) (R2 = 0.97–0.98). As the temperature increased, the growth of Y. enterocolitica tended to increase, with SGR values of 0.33, 0.40, 0.60 and 0.68 log colony-forming units/h at 8, 11, and 15 °C, and LT values of 5.63, 3.54, 2.23 and 1.09 h, respectively. The secondary model was determined by the non-linear regression analysis. The suitability of the modeling results for the SGR and LT value was verified by determining the mean square error (

Summary: DHPS deficiency is a rare genetic disease caused by biallelic hypomorphic variants in the Deoxyhypusine synthase (DHPS) gene. The DHPS enzyme functions in mRNA translation by catalyzing the post-translational modification, and therefore activation, of eukaryotic initiation factor 5A (eIF5A). The observed clinical outcomes associated with human mutations in DHPS include developmental delay, intellectual disability, and seizures. Therefore, to increase our understanding of this rare disease, it is critical to determine the mechanisms by which mutations in DHPS alter neurodevelopment. In this study, we have generated patient-derived lymphoblast cell lines and demonstrated that human DHPS variants alter DHPS protein abundance and impair enzyme function. Moreover, we observe a shift in the abundance of the post-translationally modified forms of eIF5A; specifically, an increase in the nuclear localized acetylated form (eIF5AAcK47) and concomitant decrease in the cytoplasmic localized hypusinated form (eIF5AHYP). Generation and characterization of a mouse model with a genetic deletion of Dhps in the brain at birth shows that loss of hypusine biosynthesis impacts neuronal function due to impaired eIF5AHYP-dependent mRNA translation; this translation defect results in altered expression of proteins required for proper neuronal development and function. This study reveals new insight into the biological consequences and molecular impact of human DHPS deficiency and provides valuable information toward the goal of developing treatment strategies for this rare disease.

Kimchi cabbage is a well-known glucosinolate (GLS)-containing vegetable, but its by-products are discarded despite the presence of GLS. The aim of this study was the optimization of the extraction and nanoencapsulation of GLS from kimchi cabbage by-products to enhance the intestinal absorption of GLS. The optimal GLS extraction conditions included steaming thrice as pretreatment, utilizing 70% methanol, and ultrasonication at 20% amplitude for 15 min. Under these conditions, 80.11 ± 4.40 mg/100 g of GLS extraction was obtained and the extraction yield was 81.70 ± 4.73%. The optimized kimchi cabbage by-product extract (KCE) was coated with chitosan-lipid nanoparticles (KCE-NPs) and their stability and release under simulated in vitro gastrointestinal conditions were evaluated. KCE-NPs protected the encapsulated GLS under acidic gastric conditions and released 91.63 ± 0.76% of GLS in the simulated intestinal medium. Therefore, the proposed KCE-NPs are a promising delivery system for increasing GLS absorption.

Rationale & Objective: The platelet-to-lymphocyte ratio (PLR) is a marker of inflammation and a predictor of mortality in a variety of diseases. However, the effectiveness of PLR as a predictor of mortality in patients with severe acute kidney injury (AKI) is uncertain. We evaluated the association between the PLR and mortality in critically ill patients with severe AKI who underwent continuous kidney replacement therapy (CKRT). Study Design: Retrospective cohort study. Setting & Participants: A total of 1,044 patients who underwent CKRT in a single center, from February 2017 to March 2021. Exposures: PLR Outcomes: In-hospital mortality. Analytical Approach: The study patients were classified into quintiles according to the PLR values. A Cox proportional hazards model was used to investigate the association between PLR and mortality. Results: The PLR value was associated with in-hospital mortality in a nonlinear manner, showing a higher mortality at both ends of the PLR. The Kaplan-Meier curve revealed the highest mortality with the first and fifth quintiles, whereas the lowest mortality occurred with the third quintile. Compared with the third quintile, the first (adjusted HR, 1.94; 95% CI, 1.44-2.62; P

ABSTRACT: Avian metapneumovirus (aMPV) causes respiratory and reproductive diseases in birds, including chickens. In the chicken industry, live vaccines against aMPV subtypes A and B, which are the major aMPV subtypes, are widely used to control disease caused by aMPV. In this study, we evaluated the cross protective efficacy of a live aMPV subtype B vaccine administered via 3 different routes (nasal, spray, and oral) against virulent aMPV subtype A in chickens. At 3 wk after vaccination of 1-wk-old specific-pathogen-free chickens, we measured the serological responses. On the same day, we challenged the birds with aMPV subtype A. Protection was evaluated by viral gene detection and histopathological examination at 3 and 5 days postchallenge. Although there were differences in the serological responses according to administration route, all vaccinated birds showed complete protection at 5 days postchallenge. Regardless of administration route, genome of challenge virus was not detected in vaccinated group, and there were significant differences between vaccinated birds and control group. Overall, our results demonstrated that a subtype B aMPV vaccine can provide cross protection against virulent subtype A aMPV in chickens.

ABSTRACT: Objectives: Antimicrobial resistance is one of the most urgent global health threats. The need for the qualitative evaluation of antibiotic use at the national level is increasing. To identify areas for improvement, we aimed to assess the prevalence and appropriateness of antibiotic prescriptions during hospitalization and ambulatory care in Korea. Methods: The prevalence and appropriateness of antibiotic prescriptions on 29 August 2018 were assessed for 20 hospitals in Korea. Infectious disease specialists determined appropriateness. Except for antiviral and anti-tuberculosis agents, all antibacterial or antifungal agent prescriptions during hospitalization or ambulatory care were evaluated. Results: The prevalence of antibiotic prescription was 14.1% (8,400/59 216 patients) on the study date. Antibiotics were prescribed for 50.8% of inpatients (6557/12 902), with two or more antibiotics prescribed for 27.4% (1798/6557) of patients. A total of 10 948 prescriptions (7999 therapeutic, 2105 surgical prophylaxes, and 844 medical prophylaxes) were included in the final analysis, and 27.7% of these were inappropriate. Surgical prophylaxis was inadequately prescribed most frequently (54.4%), followed by medical prophylaxis (29.5%) and therapeutic antibiotics (20.5%). The most common indications for therapeutic antibiotics were respiratory (29.1%, n=2332), gastrointestinal (22.4%, n=1791), and urinary tract infections (13.1%, n=1050). The most frequently prescribed antibiotics were cephalosporins (52.0%, n=5490), followed by beta lactam/beta lactamase inhibitors (13.7%, n=1373), fluoroquinolones (9.1%, n=957), and metronidazole (6.6%, n=699). Conclusion: This was the first nationwide qualitative antibiotic prescription adequacy evaluation in Korea. A significant proportion of antibiotic prescriptions were inappropriate. Therefore, interventions for high-frequency infections and prescription antibiotics are needed.

Objective: This study aimed to examine the characteristics of research conducted on nonpharmacological interventions for cognitive impairment in patients with breast cancer and identify the primary effects of nonpharmacological interventions through a systematic review and meta-analysis. Methods: Five electronic databases were searched to identify all randomized controlled trial studies until September 30, 2022, using the key terms “breast cancer,” “cognitive disorders,” and their possible variations. The Cochrane Risk of Bias tool was used to assess risk of bias. The effect sizes were calculated in Hedges’ g. Potential moderators influencing the intervention effects were explored. Results: Twenty-three studies were included in the systematic review, and 17 studies were included in the meta-analysis. Among the nonpharmacological interventions for patients with breast cancer, cognitive rehabilitation and physical activity were the most common, followed by cognitive behavioral therapy. The meta-analysis indicated that nonpharmacological interventions had a significant effect on attention (g ​= ​0.83; 95% CI: 0.14 to 1.52; I2 ​= ​76%), immediate recall (g ​= ​0.33; 95% CI: 0.18 to 0.49; I2 ​= ​0%), executive function (g ​= ​0.25; 95% CI: 0.13 to 0.37; I2 ​= ​0%), and processing speed (g ​= ​0.44; 95% CI: 0.14 to 0.73; I2 ​= ​51%) among objective cognitive functions, as well as subjective cognitive function (g ​= ​0.68; 95% CI: 0.40 to 0.96; I2 ​= ​78%). Intervention type and mode of delivery were potential moderators for the effects of nonpharmacological interventions on cognitive functions. Conclusions: Nonpharmacological interventions can improve subjective and objective cognitive functioning among patients with breast cancer undergoing cancer treatment. Therefore, it is necessary to provide nonpharmacological interventions by screening patients at high risk of cancer-related cognitive impairment. Systematic review registration: CRD42021251709.

Biogenic silica nanoparticle is a superb alternative to synthetic silica because of their highly active, polar, and porous nanostructure with a large interior area. Among the available agricultural bioresources, biogenic silica extracted from rice husks could be a simple, easily available, and cost-effective resource to use as the stationary phase for the column chromatographic technique. In the present study, highly pure amorphous biogenic silica nanoparticles (bSNPs) were synthesized using rice husk by a controlled combustion route followed by the sol-gel method. The bSNPs show better performance for the separation and isolation of ortho- and para-nitrophenol and nitroaniline. The outstanding performance of the as-synthesized bSNPs is attributed to the high surface area, high porosity, and presence of Si–OH polar bonds. These preliminary findings imply that rice husk, an agricultural waste, could be an alternative source of silica and applicable as a stationary phase in column chromatography.

Background: Palbociclib plus endocrine therapy (ET) demonstrated significant progression-free survival (PFS) benefit in Young Pearl, a randomized phase ll trial comparing palbociclib + ET versus capecitabine in premenopausal women with hormone receptor positive, HER2 negative metastatic breast cancer (MBC). This exploratory analysis investigated potential biomarkers of palbociclib plus ET on PFS. Patients and methods: Of 178 patients randomized (92 palbociclib plus ET; 86 capecitabine), we performed targeted sequencing (141 patients) and whole transcriptome sequencing (165 patients) using baseline tumor samples to examine genomic alteration in relation to drug response on PFS. Hazard ratios (HRs) were estimated using unstratified Cox proportional hazards models. Results: PIK3CA (41%) and TP53 (33%) mutations and CCND1 copy number variation (29%) were found most frequently in targeted sequencing of 141 patients. ESR1 mutations were found only in 3.5% of patients of this population. Luminal type showed better prognosis in palbociclib + ET arm but no impact on PFS difference in capecitabine arm. High TMB, TP53 mutation, PTEN loss of function mutation and RB1 pathway alteration showed worse prognosis in palbociclib plus ET arm. Patients with BRCA2 pathogenic mutations showed worse prognosis regardless of PAM50 subtypes. AURKA mutation/amplification, BRIP1/MYC/RAD51C amplification were significantly associated to the patients with short PFS

Background: The genetic polymorphisms of the alpha-2A adrenergic receptor (ADRA2A), which plays a significant role in sedation, anxiety relief, and antinociception, particularly in dexmedetomidine, may differ in the degree of sedation. This study aimed to investigate the effect of the genetic polymorphisms of ADRA2A (rs11195418, rs1800544, rs2484516, rs1800545, rs553668, rs3750625) on the sedative effects of dexmedetomidine. Methods: A total of 131 patients aged 50 years or more from May 2018 to August 2019 were included in this study. The ADRA2A gene variants were evaluated using the TaqMan Assay. Dexmedetomidine diluted in normal saline to a concentration of 4 μg.mL-1 was infused at a dose of 2 μg.kg-1 to achieve procedural sedation (modified Ramsay sedation scale 4 [mRSS 4]). Results: A total of 131 patients were evaluated. The genetic polymorphisms (rs11195418) of the ADRA2A receptor gene demonstrated no variation in our participants. The ADRA2A receptor gene polymorphisms (rs1800544, rs2484516, rs1800545, rs553668, and rs3750625) exhibited no differences in total dexmedetomidine doses (p > 0.217), bispectral index at mRSS 4 (p > 0.620), and time to obtain mRSS 4 (p > 0.349). Conclusion: This study suggested that the genetic polymorphisms of ADRA2A did not affect the sedative efficacy of dexmedetomidine.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease, characterized by steatosis and hallmark liver neutrophil infiltration. NASH also is associated with adipose tissue inflammation, but the role of adipose tissue inflammation in NASH pathogenesis remains obscure. The aim of this study was to investigate the interplay between neutrophil recruitment in adipose tissue and the progression of NASH. Methods: A mouse model of NASH was obtained by high-fat diet (HFD) feeding plus adenovirus-Cxcl1 overexpression (HFD+AdCxcl1). Genetic deletion of E-selectin (Sele) and treatment with an S100A9 inhibitor (Paquinimod) were investigated using this model. Results: By analyzing transcriptomic data sets of adipose tissue from NASH patients, we found that E-selectin, a key adhesion molecule for neutrophils, is the highest up-regulated gene among neutrophil recruitment-related factors in adipose tissue of NASH patients compared with those in patients with simple steatosis. A marked up-regulation of Sele in adipose tissue also was observed in HFD+AdCxcl1 mice. The HFD+AdCxcl1-induced NASH phenotype was ameliorated in Sele knockout mice and was accompanied by reduced lipolysis and inflammation in adipose tissue, which resulted in decreased serum free fatty acids and proinflammatory adipokines. S100A8/A9, a major proinflammatory protein secreted by neutrophils, was highly increased in adipose tissue of HFD+AdCxcl1 mice. This increase was blunted in the Sele knockout mice. Therapeutically, treatment with the S100A9 inhibitor Paquinimod reduced lipolysis, inflammation, and adipokine production, ameliorating the NASH phenotype in mice. Conclusions: E-selectin plays an important role in inducing neutrophil recruitment in adipose tissue, which subsequently promotes inflammation and lipolysis via the production of S100A8/A9, thereby exacerbating the steatosis-to-NASH progression. Targeting adipose tissue inflammation therefore may represent a potential novel therapy for treatment of NASH.

As NPPs continue to operate, liquid waste continues to be generated, and containers are needed to store and transport them at low cost and high capacity. To transport and store liquid phase very low-level radioactive waste (VLLW), a container is designed by considering related regulations. The design was constructed based on the existing container design, which easily transports and stores liquid waste. The radiation shielding calculation was performed according to the composition change of barium sulfate (BaSO4) using the Monte Carlo N-Particle (MCNP) code. High-density polyethylene (HDPE) without mixing the additional BaSO4, represented the maximum dose of 1.03 mSv/hr (