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We use three-dimensional culture systems of human pluripotent stem cells for differentiation into pituitary organoids. Three-dimensional culture is inherently characterized by its ability to induce heterogeneous cell populations, making it difficult to maintain constant differentiation efficiency. That is why the culture process involves empirical aspects. In this study, we use deep-learning technology to create a model that can predict from images of organoids whether differentiation is progressing appropriately. Our models using EfficientNetV2-S or Vision Transformer, employing VENUS-coupled RAX expression, predictively class bright-field images of organoids into three categories with 70% accuracy, superior to expert-observer predictions. Furthermore, the model obtained by ensemble learning with the two algorithms can predict RAX expression in cells without RAX::VENUS, suggesting that our model can be deployed in clinical applications such as transplantation., Competing Interests: Competing interests: The authors declare the following competing interests: Sumitomo Pharma employs S.T. The authors are co-inventors on patent applications., (© 2024. The Author(s).)

A high-fat diet (HFD) causes inflammation with an increase in microglial activity in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA), resulting in insulin resistance in both regions. This leads to a deterioration in glucose and energy metabolism. The effect of voluntary exercise on HFD-induced inflammation in the central nervous system (CNS) remains unclear. To clarify the effects of voluntary exercise on the CNS, 8-week-old male C57BL6 mice were fed a chow diet (CHD) or HFD for 4 weeks; each group was further divided into running exercise (EX+) on a wheel and no exercise (EX-) groups. The expression of the inflammatory cytokine, tumor necrosis factor alpha (TNFα), in the ARC and VTA was significantly increased in the HFD/EX- group, with an increase of microglial activity noted, compared to the CHD/EX- group. The expression of TNFα was significantly suppressed, with a decrease of microglial activity, in the HFD/EX+ compared to HFD/EX- group. Insulin resistance in the ARC and VTA was improved with the suppression of TNFα expression. The HFD/EX- group showed significant weight gain and impaired glucose metabolism compared to the CHD/EX- group. The HFD/EX+ group showed an improvement in glucose and energy metabolism compared to the HFD/EX- group. In addition, voluntary wheel running suppressed HFD-induced inflammation in the ARC, with a decrease in microglial activity observed independently of weight changes. Our data suggest that voluntary exercise prevents obesity and improves glucose metabolism by suppressing inflammation in the ARC and VTA under HFD conditions., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

To date, only a few studies have assessed the dietary preferences, lifestyle habits, and risk factors of patients with acute myocardial infarction. This study aimed to investigate the dietary preferences and lifestyle habits of these patients to reflect on the implementation of an effective comprehensive diet therapy in the future.In total, 117 patients who were admitted to Fukuoka University Nishijin Hospital due to acute myocardial infarction from April 2014 to January 2020 were enrolled. Test values, dietary preferences, and lifestyle habits as well as specificity were investigated in patients aged < 70 years (n = 62) and ≥ 70 years (n = 55).Of the patients < 70 years of age, 56.5% preferred high-fat foods and 29.0% preferred high-salt foods, whereas of the patients ≥ 70 years of age, 41.8% preferred high-sugar foods and 32.7% preferred high-salt foods (P < 0.01). The percentages of patients who tended to eat out and drink were 60.7% and 34.2%, respectively. The percentage of patients with a smoking habit was 31.6%.Since improved lipid levels are an important target in nutritional guidance, we should consider adjusting the diet and guiding patients to stop drinking and smoking among young people and reducing sugar and salt intake in the elderly.

Background: Immune-related adverse events (irAEs) are reported to be associated with better overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. However, there may be a bias in that patients who develop irAEs must survive long enough to experience the irAEs, and no prospective studies adjusting for immortal time bias (ITB) have examined the relationship between OS and pituitary dysfunction or the two different types of thyroid dysfunction: destructive thyroiditis and hypothyroidism without prior thyrotoxicosis (isolated hypothyroidism)., Methods: Patients with NSCLC who received nivolumab or pembrolizumab at Nagoya University Hospital between November 2, 2015 and February 1, 2023 were enrolled. Endocrine irAEs were prospectively assessed during scheduled evaluations of hormone levels. The association between irAE development and survival when considering ITB was examined by time-dependent Cox regression analysis., Results: Of the 194 patients included, 11 (5.7%), 10 (5.2%), and 5 (2.6%) developed pituitary dysfunction, destructive thyroiditis, and isolated hypothyroidism, respectively. The development of pituitary dysfunction (HR 0.36, 95% CI 0.13-0.98, p = 0.045) and destructive thyroiditis (HR 0.31, 95% CI 0.10-0.97, p = 0.044), but not isolated hypothyroidism (HR 1.15, 95% CI 0.42-3.20, p = 0.786), was significantly associated with longer OS., Conclusion: NSCLC patients developing pituitary dysfunction and destructive thyroiditis showed better OS even after adjusting for ITB, suggesting that these irAEs indicate a better prognosis., Competing Interests: HA received grants from Ono Pharmaceutical Co., Ltd. and MSD K.K., and personal fees from Ono Pharmaceutical Co., Ltd. and MSD K.K. outside of this study. SI received personal fees from Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb, and MSD K.K. outside of this study. THas received personal fees from AstraZeneca KK, Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., MSD K.K., Merck Biopharma Co. Ltd., Pfizer Inc., and Eli Lilly Japan KK, and grants from Novartis Pharma KK, AstraZeneca KK, BeiGene Inc., AbbVie Inc., Amgen Co. Ltd., and Chugai Pharmaceutical Co. Ltd., outside of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Suzuki, Kobayashi, Izuchi, Otake, Ando, Handa, Miyata, Sugiyama, Onoue, Hagiwara, Suga, Banno, Hase, Inoue, Ishii, Arima and Iwama.)

Cerium oxide (CeO2) nanoparticles, as a metal oxide nanomaterial, are increasingly used for various industrial and biomedical applications. Although their cytotoxicity to bacteria and the associated mechanisms have attracted particular attention, the mechanisms behind their antifungal effects have remained unclear. This study investigated the antifungal properties of CeO2, focusing on Aspergillus oryzae. CeO2 inhibited fungal spore germination on solid substrates, and the effect was fungistatic rather than fungicidal. CeO2 inhibited fungal growth, especially under UV irradiation, and induced reactive oxygen species (ROS) production. Tocopherol reduced the intracellular ROS levels and the growth-inhibitory effects of CeO2, suggesting that ROS are involved in these growth-inhibitory effects. Transcriptomic analysis revealed upregulated expression of genes related to phospholipases and phosphate metabolism. CeO2 affected phosphate ion concentration in the medium, potentially influencing cellular responses. This research provided valuable insights into the antifungal effects of CeO2 application, which differ from those of conventional photocatalysts like TiO2., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Rhizopus microsporus is a species in the order Mucorales that is known to cause mucormycosis, but it is poorly understood as a host of viruses. Here, we examined 25 clinical strains of R. microsporus for viral infection with a conventional double-stranded RNA (dsRNA) assay using agarose gel electrophoresis (AGE) and the recently established fragmented and primer-ligated dsRNA sequencing (FLDS) protocol. By AGE, five virus-infected strains were detected. Then, full-length genomic sequences of 12 novel RNA viruses were revealed by FLDS, which were related to the families Mitoviridae, Narnaviridae, and Endornaviridae, ill-defined groups of single-stranded RNA (ssRNA) viruses with similarity to the established families Virgaviridae and Phasmaviridae, and the proposed family "Ambiguiviridae." All the characterized viruses, except a potential phasmavirid with a negative-sense RNA genome, had positive-sense RNA genomes. One virus belonged to a previously established species within the family Mitoviridae , whereas the other 11 viruses represented new species or even new genera. These results show that the fungal pathogen R. microsporus harbors diverse RNA viruses and extend our understanding of the diversity of RNA viruses in the fungal order Mucorales, division Mucoromycota. Identifying RNA viruses from clinical isolates of R. microsporus may expand the repertoire of natural therapeutic agents for mucormycosis in the future.IMPORTANCEThe diversity of mycoviruses in fungal hosts in the division Mucoromycota has been underestimated, mainly within the species Rhizopus microsporus . Only five positive-sense RNA genomes had previously been discovered in this species. Because current sequencing methods poorly complete the termini of genomes, we used fragmented and primer-ligated double-stranded RNA sequencing to acquire the full-length genomes. Eleven novel mycoviruses were detected in this study, including the first negative-sense RNA genome reported in R. microsporus . Our findings extend the understanding of the viral diversity in clinical strains of Mucoromycota, may provide insights into the pathogenesis and ecology of this fungus, and may offer therapeutic options., Competing Interests: The authors declare no conflict of interest.

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1., Competing Interests: SI received personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb, and MSD KK outside of this study. MA received a grant from Kyowa Kirin Co Ltd, outside of this study. THas received personal fees from Ono Pharmaceutical Company, Bristol-Myers Squibb, and MSD KK. TOn received personal fees from MSD KK outside of this study. YA received grants and personal fees from Ono Pharmaceutical Company, and personal fees from Bristol Myers Squibb and MSD KK outside of this study. HA received grants from Ono Pharmaceutical Company and MSD KK and personal fees from Ono Pharmaceutical Company, Bristol Myers Squibb, and MSD KK outside of this study. The remaining authors have nothing to disclose.