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Background The FDA-approved small-molecule drug ibrutinib is an effective targeted therapy for patients with chronic lymphocytic leukemia (CLL). Ibrutinib inhibits Bruton’s tyrosine kinase (BTK), a kinase involved in B cell receptor signaling. However, the potential regulation of neuroinflammatory responses in the brain by ibrutinib has not been comprehensively examined. Methods BV2 microglial cells were treated with ibrutinib (1 μM) or vehicle (1% DMSO), followed by lipopolysaccharide (LPS; 1 μg/ml) or PBS. RT-PCR, immunocytochemistry, and subcellular fractionation were performed to examine the effects of ibrutinib on neuroinflammatory responses. In addition, wild-type mice were sequentially injected with ibrutinib (10 mg/kg, i.p.) or vehicle (10% DMSO, i.p.), followed by LPS (10 mg/kg, i.p.) or PBS, and microglial and astrocyte activations were assessed using immunohistochemistry. Results Ibrutinib significantly reduced LPS-induced increases in proinflammatory cytokine levels in BV2 microglial and primary microglial cells but not in primary astrocytes. Ibrutinib regulated TLR4 signaling to alter LPS-induced proinflammatory cytokine levels. In addition, ibrutinib significantly decreased LPS-induced increases in p-AKT and p-STAT3 levels, suggesting that ibrutinib attenuates LPS-induced neuroinflammatory responses by inhibiting AKT/STAT3 signaling pathways. Interestingly, ibrutinib also reduced LPS-induced BV2 microglial cell migration by inhibiting AKT signaling. Moreover, ibrutinib-injected wild-type mice exhibited significantly reduced microglial/astrocyte activation and COX-2 and IL-1β proinflammatory cytokine levels. Conclusions Our data provide insights on the mechanisms of a potential therapeutic strategy for neuroinflammation-related diseases.

Resistin-like alpha (Retnla) is a member of the resistin family and known to modulate fibrosis and inflammation. Here, we investigated the role of Retnla in the cardiac injury model. Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and was significantly preserved in the KO mice, while worsened in the TG group. Angiogenesis was substantially increased in the KO mice, and cardiomyocyte apoptosis was markedly suppressed in the KO mice. By Retnla treatment, the expression of p21 and the ratio of Bax to Bcl2 were increased in cardiomyocytes, while decreased in cardiac fibroblasts. Interestingly, the numbers of cardiac macrophages and unsorted bone marrow cells (UBCs) were higher in the KO mice than in the WT mice. Besides, phosphorylated histone H3(+) cells were more frequent in bone marrow of KO mice. Moreover, adiponectin in UBCs was notably higher in the KO mice compared with WT mice. In an adoptive transfer study, UBCs were isolated from KO mice to transplant to the WT infarcted heart. Cardiac function was better in the KO-UBCs transplanted group in the WT-UBCs transplanted group. Taken together, proliferative and adiponectin-rich bone marrow niche was associated with substantial cardiac recovery by suppression of cardiac apoptosis and proliferation of cardiac fibroblast.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0–122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3–4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

This study presents a metric selection framework and a normalization method for the quantitative assessment of cyber resilience, with a specific focus on availability as a core dimension. To develop a generalizable evaluation model, service types from 1124 organizations were categorized, and candidate metrics applicable across diverse operational environments were identified. Ten quantitative metrics were derived based on five core selection criteria—objectivity, reproducibility, scalability, practicality, and relevance to resilience—while adhering to the principles of mutual exclusivity and collective exhaustiveness. To validate the framework, two availability-oriented metrics—Transactions per Second (TPS) and Connections per Second (CPS)—were empirically evaluated in a simulated denial-of-service environment using a TCP SYN flood attack scenario. The experiment included three phases: normal operation, attack, and recovery. An Area Under the Curve (AUC)-based Normalized Resilience Index (NRI) was introduced to quantify performance degradation and recovery, using each organization’s Recovery Time Objective (RTO) as a reference baseline. This approach facilitates objective, interpretable comparisons of resilience performance across systems with varying service conditions. The findings demonstrate the practical applicability of the proposed metrics and normalization technique for evaluating cyber resilience and underscore their potential in informing resilience policy development, operational benchmarking, and technical decision-making.

Aims Increased red cell distribution width (RDW) is a poor prognostic factor in patients with heart failure (HF). However, only a few large‐scale studies have identified the clinical utility of RDW after adjusting for covariates affecting RDW. Methods and results From January 2010 to April 2021, we retrospectively enrolled patients diagnosed with HF from three referral hospitals with available RDW data (taken within 3 months of HF diagnosis) using an integrated clinical data system. Patients with an ejection fraction (EF) < 50% or HFA‐PEFF (Heart Failure Association Pre‐test assessment, Echocardiography and natriuretic peptide, Functional testing, Final aetiology) score ≥ 2 without severe valvular heart disease or coronary revascularization were enrolled. The primary endpoint was all‐cause mortality, and cardiovascular mortality was also collected. Multivariable Cox regression analysis and stabilized inverse probability of treatment weighting (IPTW) were used to identify any association between RDW and all‐cause death by balancing covariates or compounding factors. The global χ2 score was calculated and discrimination analysis was performed to evaluate the incremental value of RDW in predicting prognosis. Among the 6599 participants enrolled in this study, 1256 (19.0%) cases of all‐cause death occurred, and the median duration of follow‐up was 887 (interquartile range 351–1589) days. Elevated RDW at the initial diagnosis was associated with poor prognosis [cumulative incidence: 819 (30.2%) vs. 437 (11.2%), relative risk 1.58, 95% confidence interval (CI) 1.51–1.67, log‐rank P < 0.001]. Multivariable Cox analysis showed that elevated RDW was a poor prognostic factor for the primary endpoint [hazard ratio (HR) 1.11, 95% CI 1.06–1.16, P < 0.001], independent of clinical risk factors, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and EF, which was concordant with the stabilized IPTW (HR 1.29, 95% CI 1.10–1.49, P < 0.001). Adding RDW to model composed of traditional risk factors, NT‐proBNP, and echocardiographic parameters showed incremental prognostic value for predicting poor prognosis (area under the receiver operating characteristic curve, 0.799–0.826; P < 0.001). Conclusions Increased RDW at the time of diagnosis is associated with poor prognosis in patients with HF, independent of clinical risk factors, such as NT‐proBNP, and echocardiographic parameters. Therefore, RDW may aid in the management of these patients beyond traditional risk factors.

Bone marrow-derived mesenchymal stem cells (BMMSCs) are used extensively for cardiac repair and interact with immune cells in the damaged heart. Macrophages are known to be modulated by stem cells, and we hypothesized that priming macrophages with BMMSCs would enhance their therapeutic efficacy. Rat bone marrow-derived macrophages (BMDMs) were stimulated by lipopolysaccharide (LPS) with or without coculture with rat BMCs. In the LPS-stimulated BMDMs, induction of the inflammatory marker iNOS was attenuated, and the anti-inflammatory marker Arg1 was markedly upregulated by coculture with BMMSCs. Myocardial infarction (MI) was induced in rats. One group was injected with BMMSCs, and a second group was injected with MIX (a mixture of BMMSCs and BMDMs after coculture). The reduction in cardiac fibrosis was greater in the MIX group than in the BMC group. Cardiac function was improved in the BMMSC group and was substantially improved in the MIX group. Angiogenesis was better in the MIX group, and anti-inflammatory macrophages were more abundant in the MIX group than in the BMMSC group. In the BMMSCs, interferon regulatory factor 5 (IRF5) was exclusively induced by coculture with macrophages. IRF5 knockdown in BMMSCs failed to suppress inflammatory marker induction in the macrophages. In this study, we demonstrated the successful application of BMDMs primed with BMMSCs as an adjuvant to cell therapy for cardiac repair. Heart attacks: mixed cell therapy for heart regeneration A tailored technique involving stem cells and anti-inflammatory immune cells shows promise for repairing heart tissue damage. Immune cells called anti-inflammatory macrophages are vital for healing of the heart following a heart attack. Youngkeun Ahn, Yong Sook Kim and co-workers at Chonnam National University Hospital in Gwangju, South Korea trialed a novel stem cell therapy on rats to improve cardiac repair. They took bone marrow-derived macrophages and stem cells from each rat and incubated the two cell types together to create individualized treatments. Following induced heart attacks, they injected one group of rats with both cell types, and another group with stem cells only. While heart function improved in both groups, the group treated with both cell types showed significant improvements with a greater reduction in cardiac fibrosis and increased the reparative activity of macrophages.

Stevioside (ST) and rebaudioside A (Reb A) are 250 times sweeter than sucrose, but their bitterness and low water solubility limit their application. Rebaudioside Aα (Reb Aα) was synthesized using dextransucrase. Reb Aα exhibited 80-fold greater water solubility and lower thermal mass loss than Reb A and had melting point >180 °C. Reb Aα was stable within pH range 1.4–10 and exhibited excellent storage stability in aqueous solution. In vitro digestion revealed that Reb Aα was hydrolyzed into ST and glucose. In vivo, Reb Aα administration did not affect body weight gain, glucose tolerance, energy homeostasis, or liver histology. Also, in the Reb Aα group, inflammatory crown-like structures were not observed in white adipose tissue and uncoupling protein 1 was significantly upregulated in brown adipose tissue. Gut microbiota analysis revealed no significant differences in microbial composition between the control and Reb A or Reb Aα groups.

Ensuring animal welfare is essential for both the well-being of zoo animals and the effective management of zoological facilities. This study introduces the Simplified Animal Welfare Assessment Grid (S-AWAG), a streamlined adaptation of the original AWAG framework that integrates the Five Domains Model with an observation-based approach. Designed for non-expert users, S-AWAG focuses on easily observable welfare indicators—such as health and environmental conditions—making it particularly suitable for small, private zoos, including petting zoos, roadside zoos, indoor zoos, and animal cafés. We conducted welfare assessments on 304 animals from 11 species across nine zoos in South Korea. The results revealed significant differences in welfare standards between accredited and non-accredited zoos, with accredited facilities consistently demonstrating better welfare conditions ( p  < 0.05). The tool exhibited high inter-rater reliability (IRR = 0.839), confirming its consistency across assessors with varying levels of expertise and ensuring reliable and accurate results. Pearson correlation analysis identified strong positive associations between health and environmental factors, reinforcing the comprehensive nature of the tool’s evaluation approach. With its user-friendly, efficient, and adaptable design, S-AWAG has the potential to improve animal welfare standards not only in South Korea but also globally, particularly in smaller, resource-constrained facilities.

Background Neoadjuvant treatment is recommended for large GISTs due to their friability and risk of extensive operations; however, studies on the indications and long-term results of this approach are lacking. Methods Patients with large (≥ 10 cm) gastric GISTs were enrolled from multiple centers in Korea and Japan after a pathologic confirmation of c-KIT ( +) GISTs. Imatinib (400 mg/d) was given for 6–9 months preoperatively, and R0 resection was intended. Postoperative imatinib was given for at least 12 months and recommended for 3 years. Results A total of 56 patients were enrolled in this study, with 53 patients receiving imatinib treatment at least once and 48 patients undergoing R0 resection. The 5-year overall survival and progression-free survival rates were 94.3% and 61.6%, respectively. Even patients with stable disease by RECIST criteria responded well to preoperative imatinib treatment and could undergo R0 resection, with most being evaluated as partial response by CHOI criteria. The optimal reduction in tumor size was achieved with preoperative imatinib treatment for 24 weeks or more. No resumption of imatinib treatment was identified as an independent prognostic factor for recurrence after R0 resection. No additional size criteria for a higher risk of recurrence were identified in this cohort with a size of 10 cm or more. Conclusions Neoadjuvant imatinib treatment is an effective treatment option for gastric GISTs 10 cm or larger. Postoperative imatinib treatment is recommended even after R0 resection to minimize recurrence.

Various assessment tools that have been proposed thus far have disadvantages in that they are complex, time-consuming, non-objective, and not convenient for assessing multiple zoos. This study aimed to develop a simple, objective, and reliable welfare assessment tool, the modified Animal Welfare Assessment Grid (AWAG), that can be applied in South Korea, where there is no licensing system for zoos. The AWAG has four main sections: physical, psychological, environmental, and procedural. These four sections include 23 welfare factors like general conditions, behaviors, housing, and restraints, for which each individual or group of animals is given a score. The modified AWAG system was applied by converting the 10-point rating scale of the original AWAG to a 6-point Likert scale. Sixteen zoos in Korea were selected based on the zoos with the most animals. Three inspectors assessed the scores of each animal and then averaged the results. The total data surveyed included 16,065 items. Zoos were largely classified into four grades based on the size of the zoo, animal species, and operating organization. In a relatively short period of 14 days, all the zoos were successfully assessed. Despite the shortened and modified assessment tool, the inter-rater reliability among inspectors was 0.942 with high objectivity. The modified AWAG could identify welfare differences between grades of Korean zoos. There were large differences between zoos in most environmental sections and some zoos were evaluated as having inadequate welfare levels. The modified AWAG showed high usability and objectivity. In addition, it was possible to determine which environmental or procedural sections could potentially help improve physical and psychological scores. The modified AWAG is an objective method that could set the direction for the improvement of zoo welfare in the future.