Pharmacokinetics of a Fixed-Dose Combination Product of Amlodipine, Losartan, Ezetimibe, and Rosuvastatin and Its Comparison with Co-administration of Four Individual Components in Healthy Participants.

BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Tonic excitation by astrocytic GABA causes neuropathic pain by augmenting neuronal activity and glucose metabolism.

Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (EGABA) via the downregulation of the neuronal K+/Cl- cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET imaging demonstrated increased regional glucose metabolism in the ipsilateral dorsal horn, reflecting neuronal hyperexcitability. Importantly, inhibiting MAOB restored the entire astrocytic GABA-mediated cascade and abrogated the increased glucose metabolism and mechanical allodynia. Overall, astrocytic GABA-mediated tonic excitation is critical for neuronal hyperexcitability, leading to mechanical allodynia and neuropathic pain.

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer.

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Relation between textural attributes and surface leachate structural and compositional characteristics of cooked rice.

The objective of this study was to evaluate the leachate and textural characteristics of cooked rice, and the correlations between the leachate properties and texture attributes were also investigated. Cooked waxy rice had much higher total solids and amylopectin amount in leachate than the normal and high-amylose rice. For all varieties, the amylopectin chain length of the leachate was similar, excluding Dodam cultivar. The rheological characteristics of the leachate solutions were highly dependent on the amylopectin amount of the leachate. Regarding the textural characteristics, Dodam had the highest hardness and the lowest adhesiveness. The principal component analysis showed substantial differences in leachate and textural characteristics of Korean cooked rice according to its amylose content. The adhesiveness was positively and negatively correlated with amylopectin amount of leachate and the proportion of long amylopectin chains, respectively. These results indicated that the leachate characteristics of cooked rice significantly influenced its textural attributes. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01446-3.

Ecological predictors of cultural competence among nurses in the neonatal intensive care unit: A cross-sectional descriptive study.

Active migration and globalization have led to increased opportunities for critical care nurses to care for patients from diverse racial and cultural backgrounds. This study thus aimed to identify the individual, interpersonal, and organizational factors affecting cultural competence levels among neonatal intensive care unit (NICU) nurses based on an ecological model. This was a cross-sectional descriptive study that included 135 NICU nurses in South Korea. A hierarchical multiple linear regression analysis was conducted using the proposed ecological model, and a regression model for each of the four subdomains of cultural competence was constructed and compared. NICU nurses' cultural competencies were influenced not only by the "necessity of multicultural education" and "ethnocultural empathy" at the individual level but by the "hospital's readiness and support for cultural competencies" at the organizational level. To promote the cultural competence of nurses in critical care settings, environmental and organizational support should be improved, along with developing strategies that focus on nurses' individual characteristics. It is also necessary to investigate the "intersectionality" of the effects of individual and environmental factors on cultural competence.

Ginkgo biloba extract ameliorates skin fibrosis in a bleomycin-induced mouse model of systemic sclerosis.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-ß signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.

Laparoscopic treatment of paraprostatic cyst in two dogs - complete resection, and partial resection with omentalization: a case report.

Two intact male dogs were evaluated for symptoms, including hematuria, prostatomegaly, anuria, lethargy, and abdominal mass. Presurgical evaluations, including complete physical examinations, blood examinations, abdominal radiography with contrast (only in Case 2), ultrasonography, and computed tomography and magnetic resonance imaging (only in Case 1), were performed. A paraprostatic cyst was diagnosed initially, and laparoscopic exploration and surgery were performed. Complete resection was performed in case 1, whereas partial resection with omentalization was performed in case 2. Histopathological examination of the tissue samples confirmed the presence of paraprostatic pseudocysts in both cases, with no evidence of an epithelial lining. These two cases represent the first documented instances of laparoscopic treatment for extraparenchymal prostatic cysts. The laparoscopic treatment proved feasible even in the case of a giant cyst causing anuria (Case 2). Paraprostatic cysts should be considered a potential differential diagnosis for abnormal urination accompanied by an abdominal mass, and long-term postoperative follow-up is necessary.

Design of dissimilar material joint for defect-free multi-material additive manufacturing via laser-directed energy deposition.

Additive manufacturing technology has advanced beyond creating optimized features, from strengthening materials to make them lightweight to fabricating multi-material combinations that offer functionalities beyond the capabilities of individual materials. In this study, a lamination method for laser-directed energy deposition (LDED) is developed to achieve dense multi-material features, and a design that combines different and dissimilar materials is developed. To evaluate these novel developments, two materials-AISI 316L stainless steel and Inconel 625-are introduced. Tensile specimens, fabricated via multi-material additive manufacturing using LDED, are subjected to tensile tests that are recorded on video for digital image correlation. After the tests, fracture surface analyses of the fractured specimens are performed via scanning electron microscopy, and optical monitoring analyses are performed on the specimens that are not subjected to the tensile tests. The results indicate that the specimens demonstrate varied mechanical properties due to the influence of lamination direction and order, which affect the formation of critical cracks and pores.

XPA tumor variant leads to defects in NER that sensitize cells to cisplatin.

Nucleotide excision repair (NER) reduces efficacy of treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss of the NER genes Excision Repair Cross Complementation Group 1 and 2 (ERCC1 and ERCC2) leads to improved patient outcomes after treatment with Pt-based chemotherapies. Although most NER gene alterations found in patient tumors are missense mutations, the impact of mutations in the remaining nearly 20 NER genes is unknown. Towards this goal, we previously developed a machine learning strategy to predict genetic variants in an essential NER protein, Xeroderma Pigmentosum Complementation Group A (XPA), that disrupt repair. In this study, we report in-depth analyses of a subset of the predicted variants, including in vitro analyses of purified recombinant protein and cell-based assays to test Pt agent sensitivity in cells and determine mechanisms of NER dysfunction. The most NER deficient variant Y148D had reduced protein stability, weaker DNA binding, disrupted recruitment to damage, and degradation. Our findings demonstrate that tumor mutations in XPA impact cell survival after cisplatin treatment and provide valuable mechanistic insights to improve variant effect prediction. Broadly, these findings suggest XPA tumor variants should be considered when predicting chemotherapy response.

Creating a Rehabilitation Sports Public Service Information Systems Using Service Design Thinking: Physical Activity Management of the Disabled after Discharge in the Republic of Korea.

The Republic of Korea has established an institutional framework to expedite the provision of rehabilitation sports public services to individuals with disabilities post-hospital discharge (Act on Guarantee of Right to Health and Access to Health Services for People with Disabilities in December 2017). Regrettably, this service remains non-operational to date. This study employs a service design approach to identify and develop essential elements for the effective implementation of public rehabilitation sports services in Korea. Adopting the service design method, including the empathize-define-ideate-prototype phases, co-creation activities were conducted with three teams comprising people with disabilities, caregivers, rehabilitation physicians, specialized sports instructors, facility managers, and government officials, emphasizing equitable distribution. By leveraging the experiences of people with disabilities, these teams collaboratively engaged in creative activities to formulate strategies for delivering prompt and user-friendly rehabilitation sports public services post-hospital discharge. Contributions from each team were meticulously collected and organized, incorporating diverse perspectives into the development of the Korean Rehabilitation Sports Public Service Information System (KRSPSIS). Additionally, we presented a scenario illustrating the practical application of the KRSPSIS. Through this system, we anticipate providing more efficient and convenient rehabilitation sports public services to individuals with disabilities during the critical early stages following hospital discharge.

Impact of exercise training and diet therapy on the physical fitness, quality of life, and immune response of people living with HIV/AIDS: a randomized controlled trial.

BACKGROUND: Exercise and dietary nutrition are considered crucial in human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) treatment protocols and people living with HIV/AIDS (PLWHA) rehabilitation care. However, there is no well-studied research evaluating the effects of combined interventions on the fitness and immune systems of PLWHA. Therefore, this study aimed to analyze the effects of exercise and dietary intervention on physical fitness, quality of life and immune response in PLWHA. METHODS: This was an experimental study, with a sample of 25 male PLWHA divided into two groups: the intervention group (IG: 12 participants) and the control group (CG: 13 participants). All participants have not had any exercise habits and nutritional supplements in the past six months. The participants in the IG completed 45 min of exercise (60-80% HRmax) 4 times per week for 4 weeks. The exercise was in the form of brisk walking or running. They were also given a nutritional dietary supplement 3 times a day for 4 weeks. The 13 individuals in the CG continued their normal daily life (physical activity and diet). The following parameters were evaluated before and after the intervention: body composition, physical fitness, immune response, quality of life (QoL), stress, dietary behavior, dietary habits, exercise motivation, and physical self-efficacy. RESULTS: The significant changes were observed in burnout of stress variables and physical efficiency index (PEI) of physical fitness in the IG (p =.023). Moreover, in the saliva samples, sal-T levels significantly increased only after the intervention in the IG (p =.012). Additionally, regarding the analysis of the interaction (group × time), there was a significant improvement in the reaction speed (p =.001) and grip strength (left: p =.002, right: p =.030) and a significant difference in physical satisfaction in QoL (p =.001), stress burnout (p =.043), self-confidence in physical efficacy (p =.045), external display (p =.008), and fulfillment (p =.047) in exercise motivation. Moreover, the significant effect of the intervention on emotional eating in dietary behavior was shown in the comparison of the IG before and after intervention (p =.001) and in the comparison of the IG group with the CG after the experiment (p =.013). However, there was no significant effect of time or interaction between the condition and time on body composition. CONCLUSIONS: In conclusion, exercise training and diet therapy caused changes in physical fitness and Sal-T levels, which had positive effects on the health promotion of PLWHA.

Successful interventional occlusion of muscular ventricular septal defect in a dog.

Ventricular septal defect (VSD) is a rare congenital heart disease in dogs. Hemodynamically important interventricular defects must be closed to improve the prognosis. This case report describes successful interventional transcatheter closure of a muscular VSD in a young Maltese and poodle mixed-breed dog with a large muscular interventricular defect (~5 mm in diameter) with a high rate of left-to-right shunt flow. The VSD was closed with a customized Amplatzer-type VSD occluder via a percutaneous transvenous (jugular) approach. We concluded that interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs. A regular follow-up study for this dog is ongoing and has not detected complications. Key clinical message: Interventional occlusion of a muscular VSD with an Amplatzer-type occluder is a viable treatment option for dogs.

Occlusion interventionnelle réussie d'une communication interventriculaire musculaire chez un chien. La communication interventriculaire (VSD) est une maladie cardiaque congénitale rare chez le chien. Les anomalies interventriculaires hémodynamiquement importantes doivent être fermées pour améliorer le pronostic. Ce rapport de cas décrit la fermeture interventionnelle réussie par cathéter d'un VSD musculaire chez un jeune chien de race mixte (maltais et caniche) présentant un défaut interventriculaire musculaire important (~5 mm de diamètre) avec un débit de shunt élevé de gauche à droite. Le VSD a été fermé avec un obturateur VSD personnalisé de type Amplatzer via une approche trans-veineuse percutanée (jugulaire). Nous avons conclu que l'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens. Une étude de suivi régulière de ce chien est en cours et aucune complication n'a été détectée.Message clinique clé :L'occlusion interventionnelle d'un VSD musculaire avec un obturateur de type Amplatzer est une option de traitement viable pour les chiens.(Traduit par Dr Serge Messier).

Comparative analysis of malt quality and starch characteristics of three South Korean barley cultivars.

In this study, malt was produced in pilot-scale facilities and conditioned using three barley (Hordeum vulgare L.) cultivars in South Korea (Heugho, Hopum, and Kwangmaeg). Quality and starch characteristics were compared. The starch content was considerably reduced in all malts. Coleoptile elongation was higher in Heugho (HHM; 85.7% ± 12.6%) and Hopum (HPM; 83.9% ± 10.7%) than in Kwangmaeg (KMM; 78.1% ± 9.9%) malt. Malt yield ranged from 81.8 to 84.9%, with no significant difference. All samples presented type A crystallinity, and granules showed discoid shapes. After malting, the mono- and di-saccharide contents (not including sucrose) were increased. The fermentable sugar level was the highest in HHM, whereas non-fermentable sugar was the highest in KMM. These results suggest that HPM enables efficient scarification based on the rapid degradation of starch, while Heugho barley and HHM have a high potential for beer and malt production, respectively. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01419-6.

Eco-friendly natural mineral biotite as a cesium adsorbent: Utilizing low-concentration acid and hydrogen peroxide.

Biotite, a phyllosilicate mineral, possesses significant potential for cesium (Cs) adsorption owing to its negative surface charge, specific surface area (SSA), and frayed edge sites (FES). Notably, FES are known to play an important role in the adsorption of Cs. The objectives of this study were to investigate the Cs adsorption capacity and behavior of artificially weathered biotite and identify mineralogical characteristics for the development of an eco-friendly geologically-based Cs adsorbent. Through various analyses, it was confirmed that the FES of biotite was mainly formed by mineral structural distortion during artificial weathering. The Cs adsorption capacity is improved by approximately 39% (from 20.53 to 28.63 mg g-1) when FES are formed in biotite through artificial weathering using a low-concentration acidic solution mixed with hydrogen peroxide (H2O2). Especially, the Cs selectivity in Cs-containing seawater, including high concentrations of cations and organic matter, was significantly enhanced from 203.2 to 1707.6 mL g-1, an increase in removal efficiency from 49.5 to 89.2%. These results indicate that FES of artificially weathered biotite play an essential role in Cs adsorption. Therefore, this simple and economical weathering method, which uses a low-concentration acidic solution mixed with H2O2, can be applied to natural minerals for use as Cs adsorbents.

Augmented interpretation of HER2, ER, and PR in breast cancer by artificial intelligence analyzer: enhancing interobserver agreement through a reader study of 201 cases.

BACKGROUND: Accurate classification of breast cancer molecular subtypes is crucial in determining treatment strategies and predicting clinical outcomes. This classification largely depends on the assessment of human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR) status. However, variability in interpretation among pathologists pose challenges to the accuracy of this classification. This study evaluates the role of artificial intelligence (AI) in enhancing the consistency of these evaluations. METHODS: AI-powered HER2 and ER/PR analyzers, consisting of cell and tissue models, were developed using 1,259 HER2, 744 ER, and 466 PR-stained immunohistochemistry (IHC) whole-slide images of breast cancer. External validation cohort comprising HER2, ER, and PR IHCs of 201 breast cancer cases were analyzed with these AI-powered analyzers. Three board-certified pathologists independently assessed these cases without AI annotation. Then, cases with differing interpretations between pathologists and the AI analyzer were revisited with AI assistance, focusing on evaluating the influence of AI assistance on the concordance among pathologists during the revised evaluation compared to the initial assessment. RESULTS: Reevaluation was required in 61 (30.3%), 42 (20.9%), and 80 (39.8%) of HER2, in 15 (7.5%), 17 (8.5%), and 11 (5.5%) of ER, and in 26 (12.9%), 24 (11.9%), and 28 (13.9%) of PR evaluations by the pathologists, respectively. Compared to initial interpretations, the assistance of AI led to a notable increase in the agreement among three pathologists on the status of HER2 (from 49.3 to 74.1%, p < 0.001), ER (from 93.0 to 96.5%, p = 0.096), and PR (from 84.6 to 91.5%, p = 0.006). This improvement was especially evident in cases of HER2 2+ and 1+, where the concordance significantly increased from 46.2 to 68.4% and from 26.5 to 70.7%, respectively. Consequently, a refinement in the classification of breast cancer molecular subtypes (from 58.2 to 78.6%, p < 0.001) was achieved with AI assistance. CONCLUSIONS: This study underscores the significant role of AI analyzers in improving pathologists' concordance in the classification of breast cancer molecular subtypes.

Implementation of a Childcare-Based Obesity Prevention Program for Vulnerable Families During the COVID-19 Pandemic: Lessons for School Nurses.

COVID-19 brought significant changes to the role of school nurses, necessitating the development of remote health education programs. However, there is a lack of evidence and pedagogical lessons for digitally transforming education for socially vulnerable children. This qualitative study analyzes the health educational needs and barriers faced by children and service providers in a childcare-based obesity prevention program during the pandemic in South Korea. Through a thematic content analysis, four core themes emerged: (a) heightened concerns about obesity and the pandemic's impact on facilities, (b) unexpected positive outcomes of the program, (c) digital readiness gaps, and (d) insufficient program satisfaction (better than nothing). When designing a digital-based health education program for vulnerable children, assessing individual readiness and facility suitability is crucial. Additionally, school nurses should incorporate hybrid pedagogy, integrating technology-mediated activities. By leveraging technology effectively and considering individual and environmental factors, educators can provide comprehensive and accessible health education.

Exploration of MELK as a downstream of Del-1 and druggable targets in triple-negative breast cancer.

PURPOSE: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer. METHODS: To investigate Del-1 downregulation effect on breast cancer, we performed transcriptome analysis using RNA sequencing of Del-1 knockdowned MDA-MB-231 cell line Plus, to investigate the expression of Del-1 and Maternal embryonic leucine zipper kinase (MELK), mRNA levels in eight different triple-Negative Breast Cancer (TNBC) cell lines were analyzed. High-throughput sequencing was performed on total RNA isolated. OTS167 was used for MELK inhibition. The effects of MELK on cell proliferation and invasion were determined using the MTT and Matrigel transwell assays. Furthermore, we examined MELK expression in breast cancer tissue. RESULTS: Del-1 and MELK mRNA expression levels were significantly higher in the TNBC cell lines, MDA-MB-468, HCC-1806, and MBA-MB-231. Knocking down Del-1 with siRNA in HCC-1806 and MBA-MB-231 cells significantly decreased MELK expression and thus suggested a possible relationship between Del-1 and MELK. In MDA-MB-468 cells, a basal-like 1 TNBC cell line, OTS167 significantly inhibited breast cancer cell proliferation and promoted cell apoptosis. To further investigate the relationship between Del-1 and MELK, dual inhibition of both Del-1 and MELK was performed, which significantly reduced the viability of MDA-MB-468 and MBA-MB-231 cells. CONCLUSION: We found that MELK acts downstream of Del-1 and is a promising druggable target, especially in basal-like and mesenchymal stem-like subtype.

Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates.

In mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.

Evaluation of Physicochemical Changes in Hard-Boiled Eggs Stored at Different Temperatures.

Eggs that have been hard-boiled are frequently used as ready-to-eat food. Refrigerated and frozen storage of hard-boiled eggs causes issues, such as customer rejection owing to textural changes. The objective of this research is to ascertain how storage temperature affects hard-boiled eggs' alteration in texture over time. Medium-sized brown shell eggs were acquired from a local market, boiled at 100°C for 15 min, and then stored at room temperature (25°C), refrigeration (4°C), and freezing (-18°C) conditions for 0, 12, 24, and 48 h. Fourier transform infrared spectroscopy (FTIR), texture profile, visual observation using a gemological microscope, free amino acid content, and color were measured. Freezing had a substantial impact on the eggs' hardness, gumminess, chewiness, and cohesiveness (p<0.05). The FTIR spectrums confirmed the textural changes in bonds of amide A (3,271 cm-1), amide I (1,626.2 cm-1), amide II (1,539.0 cm-1), C=O stretch of COO- (1,397 cm-1), asymmetric PO2- stretch (1,240 cm-1). Microscopic images confirmed structural changes in eggs stored at -18°C. The free amino acid content was lower in fresh and frozen eggs than in the rest (p<0.05). However, there was no discernible variation in the egg white's color when eggs were kept at 4°C (p>0.05). Salmonella spp. was found exclusively in eggs kept at room temperature. In conclusion, hard-boiled eggs did not exhibit structural or chemical changes when stored at 4°C for up to 48 h compared to freezing and room temperature conditions.

FAM3C in Cancer-Associated Adipocytes Promotes Breast Cancer Cell Survival and Metastasis.

Adipose tissue within the tumor microenvironment (TME) plays a critical role in supporting breast cancer progression. In this study, we identified FAM3 metabolism-regulating signaling molecule C (FAM3C) produced by cancer-associated adipocytes (CAA) as a key regulator of tumor progression. FAM3C overexpression in cultured adipocytes significantly reduced cell death in both adipocytes and cocultured breast cancer cells while suppressing markers of fibrosis. Conversely, FAM3C depletion in CAAs resulted in adipocyte-mesenchymal transition (AMT) and increased fibrosis within the TME. Adipocyte FAM3C expression was driven by TGFß signaling from breast cancer cells and was reduced upon treatment with a TGFß-neutralizing antibody. FAM3C knockdown in CAAs early in tumorigenesis in a genetically engineered mouse model of breast cancer significantly inhibited primary and metastatic tumor growth. Circulating FAM3C levels were elevated in patients with metastatic breast cancer compared with those with nonmetastatic breast cancer. These results suggest that therapeutic inhibition of FAM3C expression levels in CAAs during early tumor development could be a promising approach in the treatment of patients with breast cancer. SIGNIFICANCE: High FAM3C levels in cancer-associated adipocytes contribute to tumor-supportive niches and are tightly associated with metastatic growth, indicating that FAM3C inhibition could be beneficial for treating patients with breast cancer.