Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Objectives: To assess the trends and disparities in the utilization of F-18 fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) in Korea between 2018 and 2022, with a focus on disease classification, patient demographics, and regional distribution. Methods: This national surveillance retrospective study uses data from the Health Insurance Review and Assessment Service (HIRA) database, which includes all FDG PET/CT examinations conducted in Korea from 2018 to 2022. Disease classifications, cancer types, age groups, gender, and geographic regions were analyzed using descriptive statistics. Utilization rates per 100,000 population were calculated for regional comparisons. Results: FDG PET/CT utilization increased by 25.4%, from 174,885 examinations in 2018 to 219,377 in 2022. Older age groups (60 years and above) accounted for the majority of examinations, with males undergoing more examinations than females. Oncology remained the primary indication, with lung, colorectal, and non-Hodgkin lymphoma leading in examination numbers. The number of examinations performed on patients aged 60 and above increased at a higher rate compared to those under 60. Significant geographic disparities were found, with Seoul reporting the highest utilization rate (1,114.3 examinations per 100,000 population), while Gyeongbuk exhibited much lower rate (26.2 examinations per 100,000 population). Conclusions This study highlights the growing utilization of FDG PET/CT in Korea, particularly among older adults, with significant gender differences in cancer types. The findings also reveal disparities in FDG PET/CT utilization across regions, indicating varying access to advanced imaging technology.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Objectives: To assess the trends and disparities in the utilization of F-18 fluorodeoxyglucose positron emission tomography/ computed tomography (FDG PET/CT) in Korea between 2018 and 2022, with a focus on disease classification, patient demographics, and regional distribution. Methods: This national surveillance retrospective study uses data from the Health Insurance Review and Assessment Service (HIRA) database, which includes all FDG PET/CT examinations conducted in Korea from 2018 to 2022. Disease classifications, cancer types, age groups, gender, and geographic regions were analyzed using descriptive statistics. Utilization rates per 100,000 population were calculated for regional comparisons. Results: FDG PET/CT utilization increased by 25.4%, from 174,885 examinations in 2018 to 219,377 in 2022. Older age groups (60 years and above) accounted for the majority of examinations, with males undergoing more examinations than females. Oncology remained the primary indication, with lung, colorectal, and non-Hodgkin lymphoma leading in examination numbers. The number of examinations performed on patients aged 60 and above increased at a higher rate compared to those under 60. Significant geographic disparities were found, with Seoul reporting the highest utilization rate (1,114.3 examinations per 100,000 population), while Gyeongbuk exhibited much lower rate (26.2 examinations per 100,000 population). Conclusions This study highlights the growing utilization of FDG PET/CT in Korea, particularly among older adults, with significant gender differences in cancer types. The findings also reveal disparities in FDG PET/CT utilization across regions, indicating varying access to advanced imaging technology.