Integrator complex subunit 6 promotes hepatocellular steatosis via ß-catenin-PPARγ axis.

Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, ß-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r2 = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of ß-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via ß-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH.

Effects of the Coronavirus disease 2019 pandemic on mortality in patients with lung cancer: A multiple mediation analysis in Japan.

COVID-19 pandemic has had a substantial effect on healthcare systems worldwide, including the care of patients with lung cancer. The impact of healthcare disruptions and behavioral changes on lung cancer mortality is unclear. Patients newly diagnosed with lung cancer during the pandemic period 2020-2021 were compared with those diagnosed in the pre-pandemic 2018-2019. The primary outcome was all-cause mortality within 1 year. Cox proportional hazards regression analyses were conducted to estimate the changes in mortality between pandemic and pre-pandemic. Multiple mediation analyses were performed to determine the factors that accounted for the changes in mortality. In total, 5785 patients with lung cancer were included in this study. The overall mortality rate was significantly higher during the pandemic compared with the pre-pandemic (crude hazard ratio [HR]: 1.19, 95% confidence interval [CI]: 1.05, 1.29). Mediation analyses showed that not receiving tumor-directed treatment, diagnosis at an older age, and decreased diagnosis through cancer screening significantly accounted for 17.5% (95%CI: 4.2, 30.7), 13.9% (95%CI: 0.8, 27.0), and 12.4% (95%CI: 3.0, 21.8) of the increased mortality, respectively. This study revealed a significant increase in mortality risk in patients with lung cancer who have not received tumor-directed treatment or cancer screening, despite potential selection bias for follow-up status. Efforts should be focused on ensuring timely access to healthcare services, optimizing treatment delivery, and addressing the unique challenges faced by patients with lung cancer during the pandemic to mitigate the impact of the pandemic on lung cancer outcomes and provide clinical care to vulnerable populations.

Assessing the Influence of the COVID-19 Pandemic on Gastric Cancer Mortality Risk.

BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic on public health has been significant. Upper gastrointestinal endoscopy for screening and diagnosis decreased along with new gastric cancer (GC) diagnoses. METHODS: This study assesses how the pandemic affected GC mortality using data from Hiroshima Prefecture, comparing mortality rates between patients diagnosed during the pandemic (2020 and 2021) and pre-pandemic (2018 and 2019) periods. The crude hazard ratios (HRs) and HRs adjusted for age, sex, clinical stage, treatment status, and travel distance to the nearest GC screening facility were estimated using Cox regression models. Subgroup and sensitivity analyses were also performed. RESULTS: A total of 9571 patients were diagnosed, with 4877 eligible for follow-up. The median age was 74 years, and 69% were male. The median follow-up period was 157 days, with events per 1000 person-years at 278 and 374 in the pre-pandemic and pandemic periods, respectively (crude HR, 1.37; adjusted HR, 1.17). The sensitivity and subgroup analyses yielded consistent results. CONCLUSIONS: The COVID-19 pandemic increased mortality risk in patients with GC. Further studies are required to observe long-term outcomes and identify the disparities contributing to the increased mortality risk.

Impact of the COVID-19 pandemic on the mortality among patients with colorectal cancer in Hiroshima, Japan: A large cancer registry study.

BACKGROUND: This retrospective cohort study aimed to evaluate the impact of the COVID-19 pandemic on colorectal cancer care and mortality using a large cancer registry in Hiroshima Prefecture, Japan. The study aimed to estimate the all-cause mortality rates within 1 year of diagnosis among colorectal cancer patients diagnosed during the pandemic period (2020 and 2021) compared to those diagnosed during the pre-pandemic period (2018 and 2019). METHODS: The day of diagnosis was set as Day 0 and Cox regression models were utilized to estimate crude hazard ratios (HRs) and adjusted HRs, accounting for age, sex, cancer stage, and treatment status. Two sensitivity analyses of overall survival were performed with different cutoffs of the pre-pandemic/pandemic periods and year-to-year comparisons. Subgroup analyses were performed using likelihood ratio tests. RESULTS: A total of 15,085 colorectal cancer patients were included, with 6499 eligible for follow-up. A median age of included patients was 72 years old, of which 59% were male. The distribution of cancer stages showed little variation between the pre-pandemic and pandemic periods. With a median follow-up of 177 days, the number of events was 316/3111 (173 events per 1000 person-years [E/1000PY], 95% confidence interval [CI]: 154-192 E/1000PY) in the pre-pandemic period, and 326/2746 (245 E/1000PY, 95% CI: 220-274 E/1000PY) in the pandemic period (crude HR: 1.42, 95% CI: 1.22-1.66; adjusted HR: 1.25, 95% CI: 1.07-1.46). The two sensitivity analyses and subgroup analyses consistently supported these findings. CONCLUSIONS: The study revealed an increased colorectal cancer mortality during the pandemic period, suggesting a continuous impact of the COVID-19 pandemic on the known and unknown risk factors for colorectal cancer for several years. Further studies are necessary to mitigate the adverse effects on patient outcomes.

Granulocyte Colony-stimulating Factor-induced Aortitis with Lung Injury, Splenomegaly, and a Rash During Treatment for Recurrent Extraosseous Mucinous Chondrosarcoma.

We herein report a case of aortitis induced by granulocyte colony-stimulating factor (G-CSF) that coincided with lung injury, splenomegaly, and cutaneous manifestations during treatment for recurrent extraosseous mucinous chondrosarcoma. Computed tomography revealed large-vessel vasculitis, splenomegaly, and pulmonary interstitial changes. Treatment with prednisolone was successful. Because sarcoma is a rare disease, this case is valuable for showing clinicians that G-CSF preparations could cause aortitis regardless of the patient's underlying diseases or therapeutic pharmacological backgrounds.

Two new species of Fauveliopsidae (Annelida, Sedentaria) from submarine caves and deep sea, Japan.

Two new species of fauveliopsid annelids, Fauveliopsis antri sp. nov. and Laubieriopsis soyoae sp. nov., are described based on specimens collected from Japanese waters. Fauveliopsis antri sp. nov. inhabits submarine caves and can be discriminated from the other congeners by the following features: i) 32 chaetigers, ii) chaetigers 1-3 with stout hooks, iii) minute body (about 1 mm in length), iv) all parapodia with same number of chaetae (2 notochaetae; 2 neurochaetae), and v) presence of dorsal and ventral papillae. Laubieriopsis soyoae sp. nov. inhabits deep water sediments and can be distinguished from the other congeners by: i) 24 chaetigers, ii) chaetigers 1-3 without annulations, and iii) acicular chaetae with tips entire, without denticles.

Correlation of proline, hydroxyproline and serine content, denaturation temperature and circular dichroism analysis of type I collagen with the physiological temperature of marine teleosts.

Fish products are a promising source of collagen; however, these extracts are biochemically unstable. Acid-soluble collagen (ASC) was isolated from the skin of eleven fish species at various physiological temperatures (Tp). Structural features of these samples were analysed in detail using Circular Dichroism (CD) and compared to their biochemical characteristics. Positive correlation (r = 0.74, p < 0.01) between the Tp and ratio of positive peak intensity to negative peak intensity (Rpn) in CD analysis suggested a higher thermal stability of ASC from warm-water fish, owing to a higher content of cyclic imino acids, such as proline and hydroxyproline (Hyp). Conversely, cold-water fish ASCs contain significantly higher levels of acyclic, hydroxyl groups carrying Ser. These results indicated that CD spectrum techniques including Rpn measurement are concise and helpful for direct detection of the triple helix structure of fish collagens, and that this structure is tightly linked to thermostability of this molecule.

Two Patients with Paget-Schroetter Syndrome That Were Successfully Diagnosed by Doppler Ultrasonography: Case Studies with a Literature Review.

We herein report on two male patients (age, 22 and 44 years) who were referred to our department with swelling of the upper right arm after attending other hospitals. Right subclavian vein thrombosis was demonstrated by ultrasonography and they were then further evaluated by contrast-enhanced computed tomography (CT). Successful treatment involved venous thrombectomy in one patient and anticoagulant therapy in the other. Paget-Schhroetter syndrome was confirmed using standard vascular ultrasonography. Despite the accuracy of this method for diagnosing Paget-Schroetter syndrome, some cases are difficult to confirm. We reviewed 29 previously published case reports of Paget-Schroetter syndrome and analyzed the patient baseline characteristics, time to diagnosis, and the diagnostic methods used.

Complete Genome Sequence of Ichthyobacterium seriolicida JBKA-6T, Isolated from Yellowtail (Seriola quinqueradiata) Affected by Bacterial Hemolytic Jaundice.

Ichthyobacterium seriolicida is a fish bacterial pathogen that causes hemolytic jaundice in farmed yellowtail in Japan. To understand more about the characteristics of this bacterium, we determined its complete genome sequence. Two hemolysin genes which may be important for its pathogenicity were identified in the I. seriolicida genome.

Use of otolith for detecting strontium-90 in fish from the harbor of Fukushima Dai-ichi Nuclear Power Plant.

To clarify the level of contamination with radioactive cesium (radiocesium) discharged from Fukushima Dai-ichi Nuclear Power Plant (FDNPP), three fish species caught in the main harbor of FDNPP were subjected to γ-ray analysis. The concentration of radiocesium in muscle differed among individual fish, even those of similar size of the same species, and showed little relation to the standard length of fish. The maximum concentration of radiocesium (202 kBq/kg wet) was detected from fat greenling samples. A comparison to data from outside the port indicated that the level of radiocesium contamination inside the port was higher than that outside. We found that ß-rays were emitted from otoliths of fishes caught in the port of FDNPP. ß-ray intensities were correlated with the concentrations of radiocesium in muscles of the three fish species. In Japanese rockfish, the ß-ray count rates from otoliths were significantly correlated with the concentration of radiocesium and (90)Sr in the whole body without internal organs of Japanese rockfish. However, no ß-rays were detected from brown hakeling samples collected around FDNPP, suggesting that the detection of ß-rays from otoliths may indicate living in the main harbor of FDNPP.

Complete genome sequence analysis of two Pseudomonas plecoglossicida phages, potential therapeutic agents.

Pseudomonas plecoglossicida is a lethal pathogen of ayu (Plecoglossus altivelis) in Japan and is responsible for substantial economic costs to ayu culture. Previously, we demonstrated the efficacy of phage therapy against P. plecoglossicida infection using two lytic phages (PPpW-3 and PPpW-4) (S. C. Park, I. Shimamura, M. Fukunaga, K. Mori, and T. Nakai, Appl Environ Microbiol 66:1416-1422, 2000, http://dx.doi.org/10.1128/AEM.66.4.1416-1422.2000; S. C. Park and T. Nakai, Dis Aquat Org 53:33-39, 2003, http://dx.doi.org/10.3354/dao053033). In the present study, the complete genome sequences of these therapeutic P. plecoglossicida phages were determined and analyzed for deleterious factors as therapeutic agents. The genome of PPpW-3 (myovirus) consisted of 43,564 bp with a GC content of 61.1% and 66 predicted open reading frames (ORFs). Approximately half of the genes were similar to the genes of the Escherichia coli phage vB_EcoM_ECO1230-10 (myovirus). The genome of PPpW-4 (podovirus) consisted of 41,386 bp with a GC content of 56.8% and 50 predicted ORFs. More than 70% of the genes were similar to the genes of Pseudomonas fluorescens phage ϕIBB-PF7A and Pseudomonas putida phage ϕ15 (podoviruses). The whole-genome analysis revealed that no known virulence genes were present in PPpW-3 and PPpW-4. An integrase gene was found in PPpW-3, but other factors used for lysogeny were not confirmed. The PCR detection of phage genes in phage-resistant variants provided no evidence of lysogenic activity in PPpW-3 and PPpW-4. We conclude that these two lytic phages qualify as therapeutic agents.

Radiocesium contamination of greenlings (Hexagrammos otakii) off the coast of Fukushima.

We measured the radiocesium ((134)Cs and (137)Cs) contamination of 236 greenlings (Hexagrammos otakii) off the coast of Fukushima Prefecture in Japan, following the accident at the Fukushima Daiichi Nuclear Power Plant in March 2011. The radiocesium concentrations of greenlings caught approximately 40 km south of the power plant were significantly higher than those of greenlings caught approximately 50 km north of the power plant. The radiocesium concentrations of greenlings caught in southern waters were significantly higher in shallow than in deep waters. Meanwhile, two outlier specimens of greenlings with higher (137)Cs concentrations, 16,000 Bq/kg-wet on 1 August 2012 and 1,150 Bq/kg-wet on 8 May 2013, were caught approximately 20 km from the power plant. Our calculations suggest that the probability of two such outlier specimens being found off the coast of Fukushima is exceedingly low. By contrast, extremely contaminated greenlings were frequently caught in the power plant port (geometric mean of (137)Cs = 17,364 Bq/kg-wet). Our results suggest that the two outlier greenlings with higher (137)Cs concentrations migrated from the power plant port. Continued close monitoring of radiocesium concentrations in the area should be done to ensure the safety of food supplies.

Five-minute resolved spatial distribution of radiocesium in sea sediment derived from the Fukushima Dai-ichi Nuclear Power Plant.

The spatial distributions of radiocesium concentration in sea sediment to a core depth of 14 cm were investigated in the offshore region from the Fukushima Prefecture to the northern part of the Ibaraki Prefecture in February and July 2012, at a spatial resolution of 5 min of latitude and longitude. The concentrations in the area south of the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) were generally higher than those in the area north of it. In the southern area, a band of especially high concentration with a width about 20 km was present in the region shallower than 100 m, and a narrow minimal concentration band was found along the 200-m isobaths. In more than half of all cases, the vertical core profiles of radiocesium concentration generally showed an exponential decreasing trend with depth. However, in the area north of the FDNPP, where the radiocesium concentrations tended to be very low, radiocesium concentrations that had similar or larger magnitude compared with those of the most-surface layer were often found in deeper layers. Relatively good correlations were found between radiocesium concentrations and grain sizes of the most-surface sediment. The vertical profile of radiocesium concentration also had a relationship with grain size. In other case, the radiocesium concentration in the sediment seems to have had a dependence on the radiocesium concentration in bottom seawater, suggesting that the quantity of radiocesium supplied and the grain size were major factors determining the spatial distribution pattern of the radiocesium concentration after the FDNPP accident.

Southwest intrusion of 134Cs and 137Cs derived from the Fukushima Dai-ichi nuclear power plant accident in the Western North Pacific.

Enormous quantities of radionuclides were released into the ocean via both atmospheric deposition and direct release as a result of the Fukushima Dai-ichi Nuclear Power Plant (FNPP) accident. This study discusses the southward dispersion of FNPP-derived radioactive cesium (Cs) in subsurface waters. The southernmost point where we found the FNPP-derived (134)Cs (1.5-6.8 Bq m(-3)) was 18 °N, 135 °E, in September 2012. The potential density at the subsurface peaks of (134)Cs (100-500 m) and the increased water column inventories of (137)Cs between 0 and 500 m after the winter of 2011-2012 suggested that the main water mass containing FNPP-derived radioactive Cs was the North Pacific Subtropical Mode Water (NPSTMW), formed as a result of winter convection. We estimated the amount of (134)Cs in core waters of the western part of the NPSTMW to be 0.99 PBq (decay-corrected on 11 March 2011). This accounts for 9.0% of the (134)Cs released from the FNPP, with our estimation revealing that a considerable amount of FNPP-derived radioactive Cs has been transported to the subtropical region by the formation and circulation of the mode water.

Molecular and morphological discrimination between an invasive ascidian, Ascidiella aspersa, and its congener A. scabra (Urochordata: Ascidiacea).

The solitary ascidian Ascidiella aspersa (Müller, 1776) has sometimes been regarded as conspecific with A. scabra (Müller, 1776), although previous detailed morphological comparisons have indicated that the two are distinguishable by internal structures. Resolution of this taxonomic issue is important because A. aspersa has been known as a notoriously invasive ascidian, doing much damage to aquaculture e.g. in Hokkaido, Japan. We collected many specimens from European waters (including the Swedish coast, near the type localities of these two species) and Hokkaido, Japan (as an alien population) and made molecular phylogenetic analyses using the mitochondrial cytochrome c oxidase subunit I (COI) gene, and found that in terms of COI sequences all the analyzed specimens were clustered into two distinct groups, one of which is morphologically referable to A. aspersa and the other to A. scabra. Thus, these two species should be regarded as distinct from each other.

Evolutionary changes of multiple visual pigment genes in the complete genome of Pacific bluefin tuna.

Tunas are migratory fishes in offshore habitats and top predators with unique features. Despite their ecological importance and high market values, the open-ocean lifestyle of tuna, in which effective sensing systems such as color vision are required for capture of prey, has been poorly understood. To elucidate the genetic and evolutionary basis of optic adaptation of tuna, we determined the genome sequence of the Pacific bluefin tuna (Thunnus orientalis), using next-generation sequencing technology. A total of 26,433 protein-coding genes were predicted from 16,802 assembled scaffolds. From these, we identified five common fish visual pigment genes: red-sensitive (middle/long-wavelength sensitive; M/LWS), UV-sensitive (short-wavelength sensitive 1; SWS1), blue-sensitive (SWS2), rhodopsin (RH1), and green-sensitive (RH2) opsin genes. Sequence comparison revealed that tuna's RH1 gene has an amino acid substitution that causes a short-wave shift in the absorption spectrum (i.e., blue shift). Pacific bluefin tuna has at least five RH2 paralogs, the most among studied fishes; four of the proteins encoded may be tuned to blue light at the amino acid level. Moreover, phylogenetic analysis suggested that gene conversions have occurred in each of the SWS2 and RH2 loci in a short period. Thus, Pacific bluefin tuna has undergone evolutionary changes in three genes (RH1, RH2, and SWS2), which may have contributed to detecting blue-green contrast and measuring the distance to prey in the blue-pelagic ocean. These findings provide basic information on behavioral traits of predatory fish and, thereby, could help to improve the technology to culture such fish in captivity for resource management.

Complete Genome Sequence of a Novel Myovirus Which Infects Atypical Strains of Edwardsiella tarda.

We present the genome sequence of a novel Edwardsiella tarda-lytic bacteriophage, MSW-3, which specifically infects atypical E. tarda strains. The morphological and genomic features of MSW-3 suggest that this phage is a new member of the dwarf myoviruses, which have been much less studied than other groups of myoviruses.

The first symbiont-free genome sequence of marine red alga, Susabi-nori (Pyropia yezoensis).

Nori, a marine red alga, is one of the most profitable mariculture crops in the world. However, the biological properties of this macroalga are poorly understood at the molecular level. In this study, we determined the draft genome sequence of susabi-nori (Pyropia yezoensis) using next-generation sequencing platforms. For sequencing, thalli of P. yezoensis were washed to remove bacteria attached on the cell surface and enzymatically prepared as purified protoplasts. The assembled contig size of the P. yezoensis nuclear genome was approximately 43 megabases (Mb), which is an order of magnitude smaller than the previously estimated genome size. A total of 10,327 gene models were predicted and about 60% of the genes validated lack introns and the other genes have shorter introns compared to large-genome algae, which is consistent with the compact size of the P. yezoensis genome. A sequence homology search showed that 3,611 genes (35%) are functionally unknown and only 2,069 gene groups are in common with those of the unicellular red alga, Cyanidioschyzon merolae. As color trait determinants of red algae, light-harvesting genes involved in the phycobilisome were predicted from the P. yezoensis nuclear genome. In particular, we found a second homolog of phycobilisome-degradation gene, which is usually chloroplast-encoded, possibly providing a novel target for color fading of susabi-nori in aquaculture. These findings shed light on unexplained features of macroalgal genes and genomes, and suggest that the genome of P. yezoensis is a promising model genome of marine red algae.

Complete Genome Sequences of Edwardsiella tarda-Lytic Bacteriophages KF-1 and IW-1.

We report the complete genome sequences of two Edwardsiella tarda-lytic bacteriophages isolated from flounder kidney (KF-1) and seawater (IW-1). These newly sequenced phage genomes provide a novel resource for future studies on phage-host interaction mechanisms and various applications of the phages for control of edwardsiellosis in aquaculture.

Population subdivision of Japanese flounder Paralichthys olivaceus in the Pacific Coast of Tohoku Japan detected by means of mitochondrial phylogenetic information.

This study deals with mitochondrial phylogenetic information of Japanese flounder in the Pacific coast of Tohoku Japan to estimate the genetic population subdivision that was undetectable by conventional population statistics. We determined complete sequences of mitochondrial NADH dehydrogenase subunit-2 (ND2) and subunit-5 (ND5) genes for 151 individuals from northern (Aomori and Iwate prefectures, 40-41°N) and southern (Miyagi and Fukushima prefectures, 37-38°N) waters. Samples from both waters showed high genetic diversity, including 126 haplotypes. These haplotypes were located at mixed and nested positions on an inferred phylogenetic tree, and traditional F-statistics indicated no significant population divergence (φ(ST) = -0.00335, p > 0.05), corroborating our previous study. Three variable sites, however, showed significant base composition heterogeneity between samples from the northern and southern waters (Fisher's exact-test, p < 0.01). Nucleotide substitutions at the three sites converged on an apical clade, which consisted of the five southern individuals, whereas its sister clade consisted only of the three northern individuals. This phylogenetic information corroborates previous ecological studies indicating the presence of separate stocks in the northern and southern waters.