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Abstract The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis. Here, we present four cases of ICI-related fulminant myocarditis (FM). Three of the four cases resulted in fatal outcomes despite aggressive treatment with mechanical circulatory support and immunosuppressive therapy with corticosteroids. Given the poor prognosis of ICI-FM, the establishment of rapid and adequate therapeutic interventions on the basis of clinical and pathological evaluation is imperative.

Owls are popular pets in Japan, with the country being the largest importer of live owls in the world. Although several studies have looked at the welfare implications of the country's “owl cafés,” the scale and scope of the Japanese owl trade, and its potential consequences for conservation, remain largely unexplored. Here we present an overview of the volumes and species of owl found in a selection of Japanese pet stores and cafés, based on two physical surveys, an online survey, and an analysis of CITES import data. We found a high number of owls (n = 1914) from a large variety of species (n = 49) across a total of 92 establishments. CITES import records show that species variety has highly increased over time. Although the majority of owls in Japanese pet stores and cafés are likely to be of captive-bred origin, trade histories are often difficult to trace, and the legality of parent stock is impossible to determine. Further complicating monitoring efforts are gaps in international trade data, the mislabeling of species, selective breeding, and the use of outdated taxonomy. Considering the large scale of the Japanese market, efforts to facilitate the improved monitoring of the owl trade are highly warranted to ensure its legality and sustainability.

Joshua Runtuwene,1,2 Kai-Chun Cheng,1 Akihiro Asakawa,1 Haruka Amitani,1 Marie Amitani,1 Akinori Morinaga,1 Yoshiyuki Takimoto,3 Bernabas Harold Ralph Kairupan,2 Akio Inui1 1Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; 2Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia; 3Department of Biomedical Ethics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan Background: Rosmarinic acid (RA) is a natural substance that may be useful for treating diabetes mellitus. The present study investigated the effects of RA on glucose homeostasis and insulin regulation in rats with streptozocin (STZ)-induced type 1 diabetes or high-fat diet (HFD)-induced type 2 diabetes.Methods: Glucose homeostasis was determined using oral glucose tolerance tests and postprandial glucose tests, and insulin activity was evaluated using insulin tolerance tests and the homeostatic model assessment for insulin resistance. Additionally, the protein expression levels of PEPCK and GLUT4 were determined using Western blot analysis.Results: RA administration exerted a marked hypoglycemic effect on STZ-induced diabetic rats and enhanced glucose utilization and insulin sensitivity in HFD-fed diabetic rats. These effects of RA were dose-dependent. Meanwhile, RA administration reversed the STZ- and HFD-induced increase in PEPCK expression in the liver and the STZ- and HFD-induced decrease in GLUT4 expression in skeletal muscle.Conclusion: RA reduces hyperglycemia and ameliorates insulin sensitivity by decreasing PEPCK expression and increasing GLUT4 expression. Keywords: diabetes mellitus, STZ, HFD, HOMA-IR, PEPCK, GLUT4

ABSTRACTSmall non-coding RNAs (sncRNAs) are non-coding RNA molecules that play various roles in metazoans. Among the sncRNAs, microRNAs (miRNAs) guide post-translational gene regulation during cellular development, proliferation, apoptosis, and differentiation, while PIWI-interacting RNAs (piRNAs) suppress transposon activity to safeguard the genome from detrimental insertion mutagenesis. While an increasing number of piRNAs are being identified in the soma and germlines of various organisms, they are scarcely reported in molluscs. To unravel the small RNA (sRNA) expression patterns and genomic function in molluscs, we generated a comprehensive sRNA dataset by sRNA sequencing (sRNA-seq) of eight mollusc species. Abundant miRNAs were identified and characterized in all investigated molluscs, and ubiquitous piRNAs were discovered in both somatic and gonadal tissues in six of the investigated molluscs, which are more closely associated with transposon silencing. Tens of piRNA clusters were also identified based on the genomic mapping results, which varied among different tissues and species. Our dataset serves as important reference data for future genomic and genetic studies on sRNAs in these molluscs and related species, especially in elucidating the ancestral state of piRNAs in bilaterians.

The developmental activation of the corpus luteum (CL) structurally and functionally is critical for the temporally regulated establishment, maintenance, and termination of pregnancy in rats. In this study, we have investigated the possible involvement of autophagy in the regulation of the CL during pregnancy in rats. The expression ratio of microtubule-associated protein light chain 3 (LC3)-II/-I, a widely used indicator of autophagic activity, in the CL remained relatively stable until day 15 of pregnancy. Subsequently, it progressively increased until day 21, and then declined until day 3 postpartum. This fluctuation was closely associated with the tissue weight of the CL rather than progesterone (P4) production activity. Light and electron microscopy revealed the presence of immunoreactive LC3 aggregates and irregularly shaped autolysosome-like microstructures in the cytoplasm of luteal cells during late pregnancy. Notably, a bolus intrabursal injection of the autophagy inhibitor bafilomycin A1 on day 15 of pregnancy resulted in a significant reduction in luteal cell size and disrupted the normal alteration of circulating P4 levels. Consequently, treatment with this inhibitor increased the likelihood of the varied timing (both advanced and delayed) of delivery and led to reduced body weight in neonates when compared with the vehicle-treated control group. Our findings suggest that autophagy in the rat CL contributes to luteal tissue growth, influences P4 production, and thereby fine-tunes the regulation of gestation length in rats.

Objectives: The suppression of antimicrobial-resistant bacteria (ARB) is an important issue worldwide. In recent years, the presence of various ARB in the oral cavity has been reported, but the details remain unclear. Therefore, we aimed to isolate ARB from the oral cavity and investigate the factors affecting ARB colonization. Methods: Third-generation cephalosporin- or carbapenem-resistant gram-negative bacteria (GN-ARB) were isolated from the oral and nasal cavities of 514 participants who visited the dental clinic, and the whole-genome sequences of all the isolates were obtained. Additionally, the tongue microbiota was analysed by 16S rRNA sequencing. The correlations of GN-ARB isolation with clinical status and the tongue microbiota were subsequently investigated. Results: Among 514 participants, 131 and 13 GN-ARB strains were isolated from the oral cavities of 93 participants (18.1 %) and from the nasal cavities of 12 participants (2.3 %). The ARB were mainly affiliated with Acinetobacter spp. (39.7 %), Pseudomonas spp. (14.5 %) and Stenotrophomonas maltophilia (18.3 %). We found a correlation between the isolation of oral GN-ARB and ageing/the number of teeth. There were no significant correlations between the presence of GN-ARB and tongue microbiota composition. Conclusions: Our results suggest that the oral cavity is an important potential reservoir of GN-ARB and that ageing and tooth loss are risk factors for the presence of GN-ARB in the oral cavity.

Key Clinical Message Aerobic exercise may be an effective treatment for knee osteoarthritis and central sensitization, but no interventional studies have examined its effects. In this study, the patient showed improvement in central sensitization, pain, and autonomic nervous system activity after aerobic exercise using an arm ergometer.

Key Clinical Message A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events.

Abstract We present two cases of middle‐aged men who developed Fanconi syndrome and renal dysfunction after consuming “foods with functional claims (FFC)” containing red yeast rice. In the first case, the patient had consumed an FFC for 1 year and another FFC suspected to have contained nephrotoxin for 3 weeks; kidney biopsy performed during the acute phase of renal injury showed severe acute tubular necrosis and tubular cell regeneration. He achieved near‐complete recovery 40 days after the FFC was discontinued. In the second case, the patient had consumed FFC for 4 years and stopped 70 days prior to presentation; kidney biopsy revealed significant tubular recovery, persistent tubular injuries, and interstitial fibrosis. Although the manifestations of Fanconi syndrome subsided, mild renal dysfunction persisted. These cases suggest that FFC with nephrotoxins may induce Fanconi syndrome owing to acute tubular necrosis. Recovery is possible after discontinuing the FFC; while short‐term ingestion of FFC allows for tubular regeneration, its long‐term ingestion may cause irreversible damage and lead to chronic kidney disease. Long‐term follow‐up is crucial for preventing further renal deterioration.

Corticotropin-releasing factor (CRF) and the urocortins (UCN1, UCN2, and UCN3) belong to the CRF family of peptides and are the major regulators of the adaptive response to internal and external stresses. The actions of CRF and UCNs are mediated through two receptor subtypes: CRF receptor 1 (CRFR1) and CRFR2. Their physiological roles, among other functions, include the regulation of food intake and anxiety-like behavior. In this review, we describe the progress that has been made towards understanding how anxiety- and depression-like behavior and food intake are regulated by CRF, UCN1, UCN2, and UCN3.

Mermithidae is a family of nematodes that parasitize a wide range of invertebrates worldwide. Herein, we report nematodes that were unexpectedly found in three of 486 adult stable flies (Stomoxys calcitrans) captured from three farms (F1, F2, and F3) in different regions of Gifu Prefecture, Japan. We aimed to characterize these nematodes both at the morphological and molecular level. Morphological studies revealed that the nematodes were juveniles of Mermithidae. Phylogenetic analysis based on 18S and 28S rDNA indicated that the mermithids from farms F1 and F2 could be categorized into the same cluster as Ovomermis sinensis and Hexamermis sp., whereas the mermithid from farm F3 clustered with Amphimermis sp. Additionally, these mermithids could be categorized within the same clusters as related mermithids detected in Japan that parasitize various arthropod orders. Our findings suggest that these stable flies may have been parasitized by mermithids already present in the region and that genetically distinct species of mermithids occur across Japan. To the best of our knowledge, this is the first report of mermithids parasitizing adult stable flies in Japan.

Summary: Tandem quadrupole inductively coupled plasma mass spectrometry has the potential capability to measure 129I at extremely low concentration if spectral interferences from 129Xe and 127I1H2 can be eliminated effectively. Ozone was introduced as the reaction gas, resulting significantly improved reactions of (129I+→129I16O+) and (129I+→129I16O2+), and permitted the highly sensitive measurement of 129I+ as 129I16O+ and 129I16O2+, helping eliminate spectral interferences related to 129Xe+ and 127I1H2+. In isotopic ratio (129I/127I) analysis by measuring (129I+→129I16O2+)/(127I+→127I16O2+), a blank ratio of 6.7 × 10−10 can be realized for a solution of 500 μg/mL natural iodine, improved by one order of magnitude than the best performance previous reported. This technique contributes to the measurement of trace level 129I, a radionuclide of iodine attracting attentions as a geochemical tracer related to the development and civilian use of nuclear energy as well as a regulated radionuclide with guidance levels in drinking water established by the World Health Organization.

Cancer cachexia, which encompasses a range of sickness behaviors such as anorexia, reduced locomotor activity, and depression, diminishes quality of life and increases mortality in cancer patients. Rubiscolin-6 is a hexapeptide derived from ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), a major plant leaf protein. Previous reports have demonstrated that rubiscolin-6 functions as an agonist of the δ opioid receptor, inducing diverse effects such as orexigenic, antinociceptive, and antidepressant-like effects. In this study, we investigated the effects of rubiscolin-6 on sickness behavior in colon26-bearing cachexia model mice. Intraperitoneal administration of rubiscolin-6 enhanced food intake in cachexic mice with chronic anorexia. It also increased locomotor activity, which decreased in cachexic mice, as assessed by the open field test. Moreover, the tail suspension test revealed that rubiscolin-6 alleviated depression-like behavior in mice with cachexia. These findings imply that rubiscolin-6 could be used to ameliorate the sickness behavior associated with cancer cachexia.