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Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia with a poor prognosis. In this study, we established a novel murine AEL model with Trp53 depletion and ERG overexpression. ERG overexpression in Trp53-deficient mouse bone marrow cells, but not in wild-type bone marrow cells, leads to AEL development within two months after transplantation with 100% penetrance. The established mouse AEL cells expressing Cas9 can be cultured in vitro, induce AEL in vivo even in unirradiated recipient mice, and enable efficient gene ablation using the CRISPR/Cas9 system. We also confirmed the cooperation between ERG overexpression and TP53 inactivation in promoting the growth of immature erythroid cells in human cord blood cells. Mechanistically, ERG antagonizes KLF1 and inhibits erythroid maturation, whereas TP53 deficiency promotes proliferation of erythroid progenitors. Furthermore, we identified HDAC7 as a specific susceptibility in AEL by the DepMap-based two-group comparison analysis. HDAC7 promotes the growth of human and mouse AEL cells both in vitro and in vivo through its non-enzymatic functions. Our study provides experimental evidence that TP53 deficiency and ERG overexpression are necessary and sufficient for the development of AEL and highlights HDAC7 as a promising therapeutic target for this disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Decitabine (DAC) is clinically used to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells indicates that mitotic regulation is critical for DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations or antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation and highlight the potent activity of DAC to disrupt mitosis through aberrant DNMT1-DNA covalent bonds., Competing Interests: Declaration of interests The authors declare no potential conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/aim: Although computed tomography (CT) is the standard modality for diagnosing lymph node metastasis (LNM), transabdominal ultrasonography (US) can be useful due to its high spatial resolution and use of Doppler signals to precisely analyse lymph nodes. This study aimed to evaluate the accuracy of US for lymph node assessment, establish US-based diagnostic criteria for LNM, and compare the capability of US with that of CT for the diagnosis of LNM., Patients and Methods: This retrospective, single-institution, cohort study included patients who underwent radical surgery for clinical stage 0-III colon cancer, between March 2012 and February 2019., Results: Overall, 34.9% (66/189) of patients had pathological LNM. The optimal US diagnostic criteria were 1) short axis ≥7 mm and short/long ratio ≥0.75 and 2) at least two of the following: the absence of hilar echoes, expansive appearance, or peripheral/mixed vascularity by the colour Doppler and/or contrast-enhanced method. Compared to CT, US showed a higher diagnostic sensitivity (54.5% vs. 43.9%; p=0.296), higher concordance with the number of pathological LNM (correlation coefficient: US, 0.42; CT, 0.27) and pathological N diagnosis (weighted ĸ: US, 0.35; CT, 0.18), and higher sensitivity for advanced LNM, including multiple LNMs (47.4% vs. 18.4%; p=0.014) and N2 stage (27.8% vs. 5.6%; p=0.177)., Conclusion: US has higher sensitivity than CT for diagnosing LNM in colon cancer, along with a more accurate preoperative diagnosis of the N stage. Additionally, US may be more helpful than CT alone for preoperatively deciding the appropriateness of neoadjuvant treatment in colon cancer with advanced LNM., Competing Interests: The Authors have no conflicts of interest directly relevant to the content of this article., (Copyright 2022, International Institute of Anticancer Research.)

Polytetrafluoroethylene (PTFE) fine powder with 93% crystallinity was irradiated by an electron beam (EB) at various temperatures under a nitrogen atmosphere. Trapped free radicals in PTFE were studied using electron spin resonance (ESR) spectroscopy. The observed spectra of the samples exposed to air after irradiation at various temperatures showed asymmetrical signals, which are middle-chain type peroxide macroradicals derived from fluoroalkyl radicals. The radical yields at each irradiation temperature increased with increasing absorbed dose, and eventually saturated. The higher irradiation temperature resulted in higher radical yields when compared at the same exposed dose. Furthermore, the G-value of the radicals (G(R·)) increases with increasing irradiation temperatures corresponding to each relaxation and transition temperature. It is concluded that the chain reaction by the fluorine extraction from the main chain due to the end-chain radical generated via β-scission after dissociative electron attachment (DEA) is enhanced by the synergistic effect of heat and radiation.

A new sustainable synthetic method for cellulose acetate was developed by a combination of I 2 -catalyzed solid-liquid acetylation of cellulose and a milling process reducing the crystallinity of cellulose within a few seconds. Milled low-crystalline cellulose was acetylated faster than the original cellulose with higher crystallinity. The plausible factors of acceleration were the conversion of the hydroxy group in hydrogen bonds into reactive ones and the efficient formation of the catalytic species I + by the enhanced formation of I 3 - assisted by the amorphous domain of the milled cellulose, while the morphological and structural changes were ignorable., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Introduction: Blakiston's fish owl (Bubo blakistoni) was previously widespread on Hokkaido Island, Japan, but is now distributed only in limited forest areas. The population size on Hokkaido decreased during the 20th century due to reduction and fragmentation of the owl's habitat. To elucidate temporal and spatial changes in population structure and genetic diversity, we analyzed 439 individuals collected over the last 100 years., Results: We detected a population bottleneck and fragmentation event indicated by mitochondrial DNA (mtDNA) haplotype and microsatellite analyses. The lowest value for effective population size, which was estimated by moment and temporal methods from microsatellite data, occurred in the 1980s. Five haplotypes were found in the mtDNA control region; most haplotypes were previously widespread across Hokkaido, but have become fixed in separate areas after the bottleneck period. Genetic differentiation among local populations, as indicated by both mtDNA and microsatellite data, likely arose through population fragmentation., Conclusions: The owl population may have been divided into limited areas due to loss of habitats via human activities, and have lost genetic variability within the local populations through inbreeding. Our mtDNA and microsatellite data show that genetic diversity decreased in local populations, indicating the importance of individuals moving between areas for conservation of this species on Hokkaido.

Red-crowned cranes (Grus japonensis) are distributed separately in the east Eurasian Continent (continental population) and in Hokkaido, Japan (island population). The island population is sedentary in eastern Hokkaido and has increased from a very small number of cranes to over 1,300, thus giving rise to the problem of poor genetic diversity. While, Hooded cranes (Grus monacha), which migrate from the east Eurasian Continent and winter mainly in Izumi, Kagoshima Prefecture, Japan, are about eight-time larger than the island population of Red-crowned cranes. We collected whole bodies of these two species, found dead or moribund in eastern Hokkaido and in Izumi, and observed skeletons with focus on vertebral formula. Numbers of cervical vertebrae (Cs), thoracic vertebrae (Ts), vertebrae composing the synsacrum (Sa) and free coccygeal vertebrae (free Cos) in 22 Red-crowned cranes were 17 or 18, 9-11, 13 or 14 and 7 or 8, respectively. Total number of vertebrae was 47, 48 or 49, and the vertebral formula was divided into three types including 9 sub-types. Numbers of Cs, Ts, vertebrae composing the Sa and free Cos in 25 Hooded cranes were 17 or 18, 9 or 10, 12-14 and 6-8, respectively. Total number of vertebrae was 46, 47, 48 or 49, and the vertebral formula was divided into four types including 14 sub-types. Our findings clearly showed various numerical vertebral patterns in both crane species; however, these variations in the vertebral formula may be unrelated to the genetic diversity.

The present study investigated a novel method for producing amorphous cellulose by milling without adding water. A new type of milling machine was developed (called a shear and cooling milling machine (SCMM)), which was capable of applying mechanical shear and cooling during the milling process. The SCMM consisted of a pair of mortars attached to a servomotor and a ring cooler. Wide-angle X-ray diffraction (WAXD) analysis was used to determine the cellulose crystallinity in samples produced using the SCMM at different milling temperatures. The results of WAXD for cellulose powder milled at lower temperatures exhibited no diffraction peaks. This experimental result demonstrates that the SCMM produces amorphous cellulose easily by cooled milling without the addition of water. The milling conditions, such as the applied shear and cooling, can be used to control the crystallinity of cellulose., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A 33 month-old male flying squirrel kept in a zoo developed progressive dyspnea and died. Macroscopically, the liver and lung were enlarged with numerous nodular vesicles. Histologically, these organs were replaced by numerous collapsed vesicles demarcated by fibrous tissues. The cysts lined by a cellular, germinal layer contained numerous brood capsules with abundant production of well-developed protoscolices. Protoscolices were about 80-100 μm in diameter, and had hooks being visible as refractive structures. This zoo locates in the east of Hokkaido where is an endemic area of Echinococcus multilocularis infection. From epidemiology and pathological findings, this animal was diagnosed as E.multilocularis infection. This report describes the pathology of the first case of E. multilocularis infection in a flying squirrel.

A 33-year-old red-crowned crane (Grus japonensis) had a diffuse intestinal thickening from the duodenum to colon. Microscopically, neoplastic cells were arranged in sheets and occasionally nests or cords without gland or squamous differentiation. Metastatic tumor cells were found in the lungs, heart, kidneys and adrenal glands. Immunohistochemically, the neoplastic cells were strongly positive for pan-cytokeratin and cytokeratin 8 and 18 and only partly positive for E-cadherin antibodies. Immunostaining for CD3 was positive in normal lymphocytes, and NSE was also positive in normal nerve fibers. But, the neoplastic cells were not immunoreactive to CD3 and NSE. Based on the histological features and the epithelial characteristics in the immunohistochemical stain, the present case was diagnosed as undifferentiated carcinoma originating from the intestine. Interestingly, the neoplastic cells showed a unique growth pattern; they never invaded the submucosa or muscularis throughout the intestine, whereas they spread lymphogenously or hematogenously to other organs.

Red-crowned (or Japanese) cranes Grus japonensis are native to eastern Hokkaido, Japan--the island population, and mainland Asia--the continental population that migrates from breeding grounds along the Amur River Basin to winter in east China and the Korean Peninsula. The island population was reduced to about 50-60 birds in early part of the 20th century. Since 1950s, the population has increased to more than 1,300 as a consequence of human-provided food in winter, resulted in change of their habitats and food resource. From the carcasses of 284 wild cranes from the island population, collected in Hokkaido since 1976 until 2010, we measured six physical parameters (body weight and lengths of body, wing, tarsus, tail and exposed culmen) and divided into groups by sex and three developmental stages (juvenile, yearling and adult). All parameters of males were larger than those of females at the same stage. Total body length of females tends to grow up earlier than males, in contrast to body weight. Obvious time trends were not observed in these all parameters during 34 years for these six categories measured, except total length of male juveniles, which showed a significant increasing trend. These results provide the first extensive data on body size and mass in the wild red-crowned cranes.

Red-crowned cranes (Grus japonensis) are native to eastern Hokkaido (island population), in contrast to the mainland, which migrates between the Amur River basin and eastern China-Korea peninsula. During the 1990s we found that Red-crowned cranes in Hokkaido were highly contaminated with mercury: however, the source was unknown. We investigated the time trend of mercury contamination in Red-crowned cranes. Total mercury levels in the livers and kidneys from cranes dead in the 2000s were lower than those dead in the 1990s. Feather is a major pathway of mercury excretion for many bird species and is used as an indicator of blood mercury level during feather growth. As internal organs from the specimens collected before 1988 were not available, we analyzed the flight feather shavings from stuffed Red-crowned cranes dead in 1959-1987 and found that the mercury level of feathers from cranes dead in the 1960s and 1970s was not more than those from the cranes dead in the 2000s. These results suggest that mercury contamination in Red-crowned cranes in Hokkaido decreased temporally during the 1990s-2000s. This indicates the possible occurrence of some mercury pollution in Red-crowned cranes' habitat in this region in the 1990s or before.

The article Lower grip strength and dynamic body balance in women with distal radial fractures, written by. K. Fujita, H. Kaburagi, A. Nimura, T. Miyamoto, Y. Wakabayashi, Y. Seki, H. Aoyama, H. Shimura, R. Kato, A. Okawa was originally published electronically on the publisher's internet portal. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the efficacy and safety of midtrimester termination of pregnancy using gemeprost in combination with laminaria in women who had previously undergone cesarean section and in women who had not., Methods: Between January 1999 and December 2006, we carried out a retrospective study of termination of pregnancy at 12-21 weeks of gestation at the University of Tsukuba Hospital. Termination of pregnancy was carried out by three-step uterine cervical dilation using laminaria followed by vaginal administration of 1 mg gemeprost every 3 h for up to four doses over 24 h., Results: A total of 173 women underwent midtrimester termination of pregnancy. The women were categorized into two groups: those who had previously undergone cesarean section (n = 26) (previous cesarean section group) and those who had not (n = 147) (control group). Seven women had undergone cesarean section at least twice. The gemeprost dose administered was 2.8 +/- 1.4 mg for the previous cesarean section group and 2.4 +/- 1.6 mg for the control group (difference in doses not significant). Although abnormal vaginal bleeding (>500 mL) was more likely to occur in the previous cesarean section group than in the control group (odds ratio, 2.61; 95% confidence interval, 0.63-10.82), none of the woman required blood transfusion. Uterine rupture and failed abortion were not observed., Conclusion: The efficacy and safety of our laminaria-gemeprost protocol for termination of pregnancy during the midtrimester are similar for women who have previously undergone cesarean section and those who have not.

The milling plays a crucial role in producing polished rice grains suitable for daily consumption. By using VOSviewer software, 522 articles on rice milling retrieved from the Web of Science database were analyzed to understand the changes in research hotspots. A novel computer simulation technology based on the discrete element method (DEM) can be utilized to simulate rice's motion state during milling. This technology can improve the parameters and configuration of rice milling machines. Furthermore, the integration of machine vision technology and near-infrared analysis enables more accurate classification of rice milling. Any form or degree of milling will bring a reduction in nutrient content. Moreover, changes occur in the proportion of starch, particle size, and structure, which in turn affect the thermal properties, pasting properties, and in vitro digestion of rice. These factors need to be taken into consideration when assessing the quality of milled rice. To improve milled rice quality, future research can focus on: (1) optimizing rice milling equipment and technology, (2) strengthening rice nutrition fortification to alleviate the loss caused by milling, (3) exploring the relationship between the degree of milling and rice composition to balance rice's health benefits and economic benefits. [ABSTRACT FROM AUTHOR]

Venous thromboembolism presenting as deep vein thrombosis or pulmonary embolism (PE) remains to be an important cause of mortality and morbidity worldwide. Despite its significance and incidence, compared to many other cardiovascular conditions there are significant gaps in knowledge in many aspects of it, including its pathophysiology. A rare sequela of PE is chronic thromboembolic pulmonary hypertension (CTEPH). This complication has a poor outcome and data is scarce in this field. Many therapeutic approaches are based solely on clinical expertise, which can be explained by the complex and not fully understood pathobiology of this disease. Over the years, many theories have been proposed regarding its genesis. Although generally acute PE is accepted as a trigger for CTEPH, this condition is multifactorial and cannot be explained by recurring PEs only. By reviewing the current evidence, we have demonstrated that thrombus non-resolution in CTEPH is due to multiple mechanisms and predisposing factors including: inflammation, small-vessel disease, impaired angiogenesis, platelet dysfunction, coagulopathies, malignancy, impaired fibrinolysis, genetics and many other components. Based on the current evidence, we aimed to explain the pathophysiology CTEPH, PE and the connection between these two important diseases. Furthermore, we highlight the negative hemodynamic effects of CTEPH and PE on the right ventricle and its role in further exacerbation of these patients. [ABSTRACT FROM AUTHOR]

The quest for sustainable space exploration and colonization is a challenge in its infancy, which faces scarcity of resources and an inhospitable environment. In recent years, advancements in space biotechnology have emerged as potential solutions to the hurdles of prolonged space habitation. Taking cues from the oceans, this review focuses on the sundry types of marine organisms and marine-derived chemicals that have the potential of sustaining life beyond planet Earth. It addresses how marine life, including algae, invertebrates, and microorganisms, may be useful in bioregenerative life support systems, food production, pharmaceuticals, radiation shielding, energy sources, materials, and other applications in space habitats. With the considerable and still unexplored potential of Earth's oceans that can be employed in developing space colonization, we allow ourselves to dream of the future where people can expand to other planets, not only surviving but prospering. Implementing the blend of marine and space sciences is a giant leap toward fulfilling man's age-long desire of conquering and colonizing space, making it the final frontier. [ABSTRACT FROM AUTHOR]

Alphaviruses are known for being model viruses for studying cellular functions related to viral infections but also for causing epidemics in different parts of the world. More recently, alphavirus-based expression systems have demonstrated efficacy as vaccines against infectious diseases and as therapeutic applications for different cancers. Point mutations in the non-structural alphaviral replicase genes have generated enhanced transgene expression and created temperature-sensitive expression vectors. The recently engineered trans-amplifying RNA system can provide higher translational efficiency and eliminate interference with cellular translation. The self-replicating feature of alphaviruses has provided the advantage of extremely high transgene expression of vaccine-related antigens and therapeutic anti-tumor and immunostimulatory genes, which has also permitted significantly reduced doses for prophylactic and therapeutic applications, potentially reducing adverse events. Furthermore, alphaviruses have shown favorable flexibility as they can be delivered as recombinant viral particles, RNA replicons, or DNA-replicon-based plasmids. In the context of infectious diseases, robust immune responses against the surface proteins of target agents have been observed along with protection against challenges with lethal doses of infectious agents in rodents and primates. Similarly, the expression of anti-tumor genes and immunostimulatory genes from alphavirus vectors has provided tumor growth inhibition, tumor regression, and cures in animal cancer models. Moreover, protection against tumor challenges has been observed. In clinical settings, patient benefits have been reported. Alphaviruses have also been considered for the treatment of neurological disorders due to their neurotrophic preference. [ABSTRACT FROM AUTHOR]

The search for substitutes for conventional fuels leads to the use of non-hydrocarbon fuels or synthetic fuels. One of them is hydrogen. The use of hydrogen in combination with a two-stage charge formation system leads to the combustion of lean (> 1) or very lean (> 3) charges. The simulation tests carried out were aimed at determining the best configuration of the chamber connecting the pre-chamber with the main combustion chamber. Three variants of the diameter of the holes connecting the chambers were selected (d = 0.5; 1.0 and 1.5 mm) in combination with different fuel doses fed to the pre-chamber. A passive chamber (qo_PC = 0 mg) and an active chamber (qo_PC = 0.4 and 1.2 mg) were used with a constant fuel dose to the main chamber (qo_MC = 6 mg). The research was conducted using AVL Fire 2022.1 software using the moving mesh of the LDV engine. Based on the simulation work, the most favourable conditions for conducting the process were determined, taking into account the thermodynamic effects of the process and acceptable levels of nitrogen oxide concentration. The resulting correlation maps of chamber hole sizes and fuel doses supplied to the prechamber can serve as a preliminary basis for selecting control options for hydrogen combustion in the TJI system. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme (ACE) plays an important role in vascular remodeling in pulmonary hypertension, and ACE gene polymorphism is associated with exercise-induced pulmonary hypertension in Japanese patients with chronic obstructive pulmonary disease. The present study was designed to investigate if ACE-insertion (I)/deletion (D) polymorphism might be related to the susceptibility, severity, and disease outcome in chronic thromboembolic pulmonary hypertension (CTEPH)., Methods and Results: ACE-I/D genotypes were determined in 95 consecutive CTEPH patients (46 underwent surgery, 49 received medical treatment) and 97 controls. The frequencies of genotypes and alleles were not significantly different between patients and controls. Clinical characteristics were compared among ACE genotypes (II, ID, DD). ACE D allele carrier (ID plus DD) was associated with a lower 6-min walk test distance compared with D allele non-carrier (II) (330+/-102 (mean +/- SD) vs 381 +/-85 m, p=0.046). Kaplan-Meier analysis in the medically treated group showed significantly deteriorated survival for D allele carriers compared with D allele non-carriers (p=0.0389). Multivariate analysis revealed that age (p=0.013), pulmonary vascular resistance (p=0.008), and D allele carrier status (p=0.021) were independent predictors of survival., Conclusion: ACE D allele carrier is possibly one of the prognostic factors for medically treated CTEPH patients.

Purpose: Recently, the application of replication-competent viruses has been studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has not been reported to induce any serious disease to humans., Experimental Design: In this study, we evaluated the feasibility of the replication-competent SIN AR339 strain as an agent for cervical and ovarian cancer therapy., Results: SIN infection was able to induce cytopathic effects and apoptosis in two cervical cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell viability, virus protein synthesis, and viral growth showed the cancer-specific cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of SIN resulted in significant regression of established cervical tumors implanted at their backs. Histologic studies revealed that systemic treatment with the single injection of SIN induces necrosis within tumors at a remote site. In the metastasis model of ovarian cancer, suppression of ascites formation was observed in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent protein imaging system, we also showed that systemic treatment with SIN targeted tumors specifically., Conclusions: Our study suggested that SIN AR339 strain has a possibility as a novel agent for human cervical and ovarian cancer therapy.

This study evaluated the influence of curing method and storage condition on the microhardness of dual-cure resin cements: Panavia F 2.0 (PF) and Nexus 2 (NX). The specimens were either light-cured (LC) or chemically cured in darkness (CC). After 24 hours of storage in dry chamber (Dry) or distilled water (DW), the specimens were sectioned and polished. The microhardness of resin cement matrix was measured using a nanoindentation tester (ENT-1100). The data (n = 6) were statistically analyzed with t-test, two-way ANOVA (p < 0.05), and Tukey HSD test (alpha = .05). It was found that the factors of curing method and storage condition had significant effect on microhardness. For both PF and NX, LC presented higher microhardness than CC, while DW showed higher microhardness than Dry. In conclusion, dual-cure resin cements could achieve high degree of cure when light-cured. In addition, the microhardness of the resin cements evaluated did not decrease when kept in water.

Background: Obesity and visceral fat accumulation (VFA) are risk factors for the development of obstructive sleep apnea-hypopnea syndrome (OSAHS), and a subgroup of OSAHS patients acquire hypoventilation. Circulating leptin, an adipocyte-derived signaling factor, increases in accordance with body mass index (BMI); under experimental conditions, leptin selectively decreases visceral adiposity and it is also a respiratory stimulant., Objective: To investigate whether the location of body fat deposits, ie, the distribution of VFA and subcutaneous fat accumulation (SFA), contributes to hypoventilation and whether circulating levels of leptin are involved in the pathogenesis of hypoventilation, which is often observed in OSAHS., Methods: We assessed VFA and SFA by abdominal CT scan, and measured lung function and circulating levels of leptin in 106 eucapnic and 79 hypercapnic male patients with OSAHS., Results: In the whole study group, circulating leptin levels correlated with BMI (r = 0.56), VFA (r = 0.24), and SFA (r = 0.47), but not with Po(2) or sleep mean arterial oxygen saturation (Sao(2)). BMI, percentage of predicted vital capacity, FEV(1)/FVC ratio, apnea-hypopnea index, sleep mean Sao(2), VFA, and SFA were not significantly different between two groups. Circulating leptin levels were higher in the hypercapnic group than in the eucapnic group. Logistic regression analysis indicated that serum leptin was the only predictor for the presence of hypercapnia (beta = 0.21, p < 0.01)., Conclusions: These results suggest that the location of body fat deposits may not contribute to the pathogenesis of hypoventilation, and circulating leptin may fail to maintain alveolar ventilation in hypercapnic patients with OSAHS.

Histological survey was made to determine nitrate toxicity on the Medaka fish, Oryzias latipes. In order to investigate the effects of short-term exposure to nitrate, one-month-old Medaka fish was exposed to NaNO3 at concentrations of 100 and 125 mg NO3-N l-1 for 96 hours. At the end of the exposure period, survival rate was found to be 30% and 10%, for the 100 and 125 mg NO3-N l-1 exposure concentrations, respectively. Histological examination of the organs showed that disruption of cell alignment was a common feature in the gills, intestinal ampulla, liver and kidney. A long-term exposure experiment was also carried out, whereby Medaka fish was exposed to NaNO3 (100 and 125 mg NO3-N l-1) for three months from its egg stage. Eggs treated with NaNO3 hatched within 10 days after fertilization. At the end of the exposure period, survival rate in the 100 and 125 mg NO3-N l-1 treatments were 40% and 30%, respectively. Fibrosis of the hepatic cells and curved spinal column were observed in the juveniles subjected to long-term nitrate exposure. The results of our experiments suggest that the high mortality resulting from short-term acute exposure to nitrate is caused by general dysfunction throughout the whole body. The chronic toxic effects attributed to nitrate, following long-term exposure, were likely to have resulted from nutrient deficiency caused by hepatic dysfunction.

Since a biological filter with nitrifying bacteria was firstly applied to aquatic animal experiments in IML-2 mission, the reactor system has been further studied to combine both nitrifying and denitrifying reactions under aerobic environment allowing an efficient removal of inorganic nitrogen from animal wastes. The isolated denitrifying bacteria had an activity under aerobic condition with rice straw providing a metabolic carbon source for the reaction. The advantage of the aerobic biological filter having both nitrifying and denitrifying activities may allow to reduce the size of the life support system and also for its manageability. The paper reports characteristics of the biological filter systems used for the IML-2 mission and the improved combined filter system having both nitrifying and denitrifying activities, and discuss its application to space experiments.

In a space environment such as Space Shuttle or Space Station, animal experiments with aquatic species in a closed system pose a crucial problem in maintaining their water quality for a long term. In nature, ammonia as an animal wastes is converted by nitrifying bacteria to nitrite or nitrate compounds, which usually become nitrogen sources for plants. Thus an application of the biological reactor with such bacteria attached on some filters has been suggested and experimentally studied for efficient waste managements of ammonia. Although some successful results were reported (Kozu et al. 1995, Nagaoka et al. 1998, Nakamura et al. 1997, 1998) in the space applications, purely empirical approaches have so far been taken to develop a biological filter having a stable nitrifying activity. In this study, we constructed a mathematical model to deal with the dynamics of the ammonia nitrifying processes in a biological reactor. The model describes population dynamics of the ammonia-oxidizing bacteria and the nitrite-oxidizing bacteria cultivated on the same filter. We estimated parameters involved in the model using the experimental data. The result shows that these estimated parameters could be applied to general cases and that the two bacteria are in a symbiotic relationship; they can better perform when both coexist, as has been empirically recognized. Based on the model analysis, we discuss how to prepare a high performance biological filter.

The feasibility of intracellular recordings under constraints for experimental conditions in outer space were tested at a telescience testbed of the National Space Development Agency of Japan. We attempted to study the dose-response relationship of adenosine-induced potential changes in the Xenopus oocyte. The testbed simulated the distance from a ground control room to oocytes in an orbital laboratory; signals were delayed and compressed from one "station" to other. A microelectrode was inserted into the oocyte using remote control on the manipulator and on the xyz-planes of the platform with stereoscopic pictures observed through a head mounted display. When the transfer rate of the visual signals was decreased from 1.5 Mbps to 128 Kbps, insertion of the electrode became almost impossible because of reduced picture quality. Once the electrode was inserted, however, dose-dependent adenosine responses could be observed with little trouble.

A bacteriocin from a subgingival plaque isolate of Capnocytophaga ochracea was purified and characterized. It was isolated from cell extract and had a molecular weight of 100,000. Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans and Propionibacterium acnes were susceptible to the bacteriocin.

Background: Understanding the potential risk factors for failure of pregnancy termination is crucial for informed clinical decision making. Such insights can assist clinicians in adjusting the dosage or route of various regimens, as well as in counseling patients and predicting the likelihood of successful outcomes. However, research on these risk factors has been limited, and existing studies have yielded inconsistent results. To address this gap, we conducted a study with a large sample size, focusing on identifying the potential risk factors for failure of second-trimester termination using misoprostol as a single agent, specifically between 14 and 28 weeks of gestation. Methods: A secondary analysis based on a database of second-trimester terminations was conducted. The inclusion criteria were a singleton pregnancy, gestational age between 14 and 28 weeks, an unfavorable cervix, no spontaneous labor pain, intact membranes, and termination with misoprostol alone. Potential risk factors for failure of termination, defined as no abortion within 48 h, were analyzed using univariate and multivariate analyses. Results: A total of 1094 cases were included in the analysis, consisting of 991 successful cases and 103 (9.4%) cases of failure. The significant risk factors for failure of termination included early gestational age, live fetuses, sublingual regimen of 400 mcg every 6 h, and high maternal pre-pregnancy BMI. Previous cesarean sections and lower Bishop scores tended to increase the risk but did not reach a significant level. Conclusions: Second-trimester termination with misoprostol as a single agent was highly effective, with a failure rate of 9.4%. The risk factors for failure included gestational age, fetal viability, misoprostol regimen, and maternal pre-pregnancy BMI, suggesting that these factors should be taken into consideration for second-trimester terminations with misoprostol. [ABSTRACT FROM AUTHOR]

In this research article, the objective is to determine the return on investment (ROI) of photovoltaic (PV) power plants by employing machine learning (ML) techniques. Special focus is done on the levelized cost of electricity (LCOE) as a pivotal economic parameter crucial for facilitating economic decision‐making and enabling quantitative comparisons among different energy generation technologies. Traditional methods of calculating LCOE often rely on fixed singular input values, which may fall short in addressing uncertainties associated with assessing the financial feasibility of PV projects. In response, a dynamic model that integrates essential demographic, energy, and policy data, is introduced encompassing factors such as interest rates, inflation rates, and energy yield, which are anticipated to undergo changes over the lifetime of a PV system. This dynamic model provides a more accurate estimation of LCOE. The comparative analysis of ML algorithms indicates that the auto‐regression integration moving average (ARIMA) model exhibits a high accuracy of 93.8% in predicting consumer electricity prices. The validation of the model is highlighted through two case studies in the United States and the Philippines underscores the potential impact on LCOE values. For instance, in California, LCOE values could vary by nearly 30% (5.03 cents kWh−1 for singular values vs 7.09 cents kWh−1 using our ML model), influencing the perceived risk or economic feasibility of a PV power plant. Additionally, the ML model estimates the ROI for a grid‐connected PV plant in the Philippines at 5.37 years, in contrast to 4.23 years using traditional methods. [ABSTRACT FROM AUTHOR]

High-performance alloy thin films and large-sized thin film wafers for infrared applications are the focus of international researchers. In this study, doped Ge1−xSnx and Ge1−yBiy semiconductor alloy films were grown on a 5-in. silicon (Si) wafer using high-quality Ge films as buffer layers. An efficient technique is presented to reduce the dark current density of near-infrared photoelectric devices. By using boron for p-type doping in Ge1−xSnx films and bismuth (Bi) for n-type doping in Ge1−yBiy films, an all-thin film planar nano-p-i-n optoelectronic device with the structure n-Ge1−yBiy/i-GeSn/p-Ge1−xSnx/Ge buffer/Si substrate has been successfully fabricated. The photoelectric performance of the device was tested, and it was found that the insertion of p-Ge1−xSnx/Ge films reduced the dark current density by 1–2 orders of magnitude. The maximum photoresponsivity reached up to 0.8 A/W, and the infrared photocurrent density ranged from 904 to 935 μA/cm2 under a +1 V bias voltage. Furthermore, the device is capable of modulating a terahertz wave using a voltage signal with a modulation bandwidth of 1.2 THz and a modulation depth of ∼83%, while the modulation rate is 0.5 MHz. This not only provides a clear demonstration of how doped alloy films and the development of nano-p-i-n heterojunctions will improve photoelectric devices' performance in the near-infrared and terahertz bands, but it also raises the possibility of optoelectronic interconnection applications being achieved through a single device. [ABSTRACT FROM AUTHOR]

Radiotherapy is a pivotal means of cancer treatment, but it often leads to radiation dermatitis, a skin injury caused by radiation-induced excess reactive oxygen species (ROS). Scavenging free radicals in the course of radiation therapy will be an effective means to prevent radiation dermatitis. This study demonstrates a novel double network hydrogel doped with MoS2 nanosheets for the prevention of radiation-induced dermatitis. The resultant SPM hydrogel constructed from polyacrylamide (PAM) and sodium alginate (SA) nanofiber presented favorable mechanical and adhesion properties. It could conform well to the human body's irregular contours without secondary dressing fixation, making it suitable for skin protection applications. The in vitro and in vivo experiments showed that the antioxidant properties conferred by MoS2 nanosheets enable SPM to effectively mitigate excessive ROS and reduce oxidative stress, thereby preventing radiation dermatitis caused by oxidative damage. Biosafety assessments indicated good biocompatibility of the composite hydrogel, suggesting SPM's practicality and potential as an external dressing for skin radiation protection. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is a refractory tumor with poor prognosis and high mortality. Many oncolytic viruses are currently being investigated for the treatment of hepatocellular carcinoma. Based on previous studies, we constructed a recombinant GM-CSF-carrying Sindbis virus, named SINV-GM-CSF, which contains a mutation (G to S) at amino acid 285 in the nsp1 protein of the viral vector. The potential of this mutated vector for liver cancer therapy was verified at the cellular level and in vivo, respectively, and the changes in the tumor microenvironment after treatment were also described. The results showed that the Sindbis virus could effectively infect hepatocellular carcinoma cell lines and induce cell death. Furthermore, the addition of GM-CSF enhanced the tumor-killing effect of the Sindbis virus and increased the number of immune cells in the intra-tumor microenvironment during the treatment. In particular, SINV-GM-CSF was able to efficiently kill tumors in a mouse tumor model of hepatocellular carcinoma by regulating the elevation of M1-type macrophages (which have a tumor-resistant ability) and the decrease in M2-type macrophages (which have a tumor-promoting capacity). Overall, SINV-GM-CSF is an attractive vector platform with clinical potential for use as a safe and effective oncolytic virus. [ABSTRACT FROM AUTHOR]

Decitabine (DAC), a well-recognized DNA hypomethylating agent, has been applied to treat acute myeloid leukemia. However, clinic investigations revealed that DNA methylation reduction does not correlate with a clinical response, and relapse is prevalent. To gain a better understanding of its anti-tumor mechanism, we perform a temporally resolved CRISPR-Cas9 screen to identify factors governing the DAC response. We show that DNA damage generated by DNMT-DNA adducts and 5-aza-dUTP misincorporation through the dCMP deaminase DCTD act as drivers of DAC-induced acute cytotoxicity. The DNA damage that arises during the next S phase is dependent on DNA replication, unveiling a trans-cell cycle effect of DAC on genome stability. By exploring candidates for synthetic lethality, we unexpectedly uncover that KDM1A promotes survival after DAC treatment through interactions with ZMYM3 and CoREST, independent of its demethylase activity or regulation of viral mimicry. These findings emphasize the importance of DNA repair pathways in DAC response and provide potential biomarkers., Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests., (© 2025. The Author(s).)

Hypermethylation of tumor suppressor genes is a hallmark of leukemia. The hypomethylating agent decitabine covalently binds, and degrades DNA (cytosine-5)-methyltransferase 1 (DNMT1). Structural similarities within DNA-binding domains of DNMT1, and the leukemic driver histone-lysine N-methyltransferase 2A (KMT2A) suggest that decitabine might also affect the latter. In acute lymphoblastic leukemia (ALL) cell lines, and xenograft models, we observed increased DNMT1, and KMT2A expression in response to decitabine-induced demethylation. Strikingly, KMT2A protein expression was diminished in all cell lines that experienced DNMT1 degradation. Moreover, only cells with reduced KMT2A protein levels showed biological effects following decitabine treatment. KMT2A wild-type, and rearranged cells were locked in G2 and G1 cell cycle phases, respectively, likely due to p27/p16 activation. Primary sample gene expression profiling confirmed different patterns between KMT2A wild-type, and translocated cells. This newly discovered decitabine mode of action via KMT2A degradation evokes anti-leukemic activity in adult ALL cells, and can act synergistically with menin inhibition. Following the successful clinical implementation of decitabine for acute myeloid leukemia, the drug should be considered a potential promising addition to the therapeutic portfolio for ALL as well., (© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Worldwide, over 2 billion children under the age of 5 experience stunting, wasting, or are underweight. Malnutrition contributes to 45% of all deaths in this age group (approximately 3.1 million deaths) [1]. Poverty, food insecurity, suboptimal feeding practices, climate change, and conflict are all contributing factors. Malnutrition causes significant respiratory problems, including increased risk of respiratory infections, impaired lung function, and increased risk of subsequent adult respiratory disease, including asthma, COPD, and lung cancer. Childhood malnutrition not only has serious consequences for children's health but it also has numerous consequences on wellbeing and educational attainment. Childhood malnutrition is a complex and multifaceted problem. However, by understanding and addressing the underlying causes, and investing in prevention and treatment programs, it is possible to maximize children's health and wellbeing on a global scale. This narrative review will focus on the impact of childhood malnutrition on lung development, the consequent respiratory disease, and what actions can be taken to reduce the burden of malnutrition on lung health. [ABSTRACT FROM AUTHOR]

Aim: The continental island system comprising Sakhalin, Hokkaido and the southern Kuril Islands (SHSK) in northeastern Asia serves as one of the southernmost habitats for many boreal and arctic organisms, with colonization via land bridges formed during glacial periods. To understand the impacts of past land‐bridge formation under Quaternary climate changes across SHSK, we investigated the demographic history of forest‐dwelling marten species. Location: Sakhalin, Hokkaido and the southern Kuril Islands in northeastern Asia. Taxon: Sable, Martes zibellina (Carnivora, Mustelidae). Methods: We employed multiplexed inter‐simple sequence repeat genotyping by sequencing (MIG‐seq) to obtain genome‐wide single nucleotide polymorphisms (SNPs). We tested possible scenarios of colonization and diversification for SHSK sables using several population genetics approaches including clustering analysis, population tree estimation and approximate Bayesian computation modelling. We also examined haplotype diversity for the mitochondrial ND2 gene. Results: The genetic diversity of the island populations and their affinity for continental populations were found to be higher in the order Sakhalin > Hokkaido > Iturup in both nuclear SNP and mitochondrial DNA analyses. Demographic analyses indicated that the sable migrated repeatedly from the continent, particularly to the neighbouring Sakhalin Island. However, only an earlier colonized lineage has persisted on marginal Iturup Island since the Middle Pleistocene. The stronger effects of repeated migrations and/or isolation influenced by the distance to the continent have shaped the contemporary genetic diversity and differentiation of sable populations in SHSK. Main Conclusions: Genome‐wide and comprehensive sampling approaches demonstrated that the forest‐dwelling sable had long‐term persistence with partial admixture of multiple lineages in SHSK, suggesting the existence of forest corridors and refugia on the islands during the last several glacial periods. The SHSK system of continental islands is valuable for understanding the impacts of Quaternary climate changes on the genetic diversity and evolutionary histories of boreal organisms. [ABSTRACT FROM AUTHOR]

PTFE coatings were manufactured using the pulsed electron beam deposition (PED) technique and deposited on Si substrates. The deposition was carried out at constant parameters: temperature 24 °C, discharge voltages 12 kV, and 5000 electron pulses with a pulse frequency of 5 Hz. Nitrogen was used as the background gas. The gas pressure varied from 3 to 11 mTorr. The coating adhesion was evaluated using micro scratch testing and the residual scratch morphology was characterized by atomic force microscopy. Detailed studies of the chemical and physical structure were conducted using infrared spectroscopy and X-ray diffraction. These analyses were then correlated with the mechanical response of the coatings observed during the scratch tests. Drawing upon a review of the literature concerning energetic beam interactions with PTFE material, hypotheses were posed to explain why only specific conditions of the PED process yielded PTFE coatings with rubber-like properties. [ABSTRACT FROM AUTHOR]

This review article provides a comprehensive overview of a novel Sindbis virus vaccine platform as potential immunotherapy for ovarian cancer patients. Ovarian cancer is the most lethal of all gynecological malignancies. The majority of high-grade serous ovarian cancer (HGSOC) patients are diagnosed with advanced disease. Current treatment options are very aggressive and limited, resulting in tumor recurrences and 50–60% patient mortality within 5 years. The unique properties of armed oncolytic Sindbis virus vectors (SV) in vivo have garnered significant interest in recent years to potently target and treat ovarian cancer. We discuss the molecular biology of Sindbis virus, its mechanisms of action against ovarian cancer cells, preclinical in vivo studies, and future perspectives. The potential of Sindbis virus-based therapies for ovarian cancer treatment holds great promise and warrants further investigation. Investigations using other oncolytic viruses in preclinical studies and clinical trials are also presented. [ABSTRACT FROM AUTHOR]

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries. Author summary: Neglected tropical diseases (NTDs) are an umbrella term for 20 diseases and disease groups recognized by the World Health Organization. Although NTDs are usually considered to be a public health problem in low- and middle-income countries, people living in high-income countries could also be affected. In this scoping review, we aimed to summarize the latest evidence and information to understand the epidemiology of and public health response to NTDs in Japan. Japan officially reported a yearly average of 340 NTD cases between 2014 and 2017; however, we found that it does not accurately reflect the current status of NTDs in the country. Our review suggests that 15 of 20 NTDs can be considered to be important public health concerns. While echinococcosis, chikungunya, dengue, and rabies are under control by law, many other NTDs are largely neglected by Japan's health systems and solely addressed by a limited number of physicians and researchers. We recommend that the Government of Japan should assume responsibility for enhancing surveillance, expanding access to diagnostics and medicines, and ensuring affordability of unapproved NTD drugs. [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of death worldwide, with breast and colorectal cancers being the two most common cancer forms. The present work was designed to investigate the probable oncolytic effect of lentogenic and velogenic Newcastle disease viruses on MCF-7 and Caco-2 cell lines compared to the commonly used chemotherapies as an in vitro preliminary study to further prelude an in vivo study. The cytotoxic effects of Newcastle disease virus strains NDV/chicken/Egypt/Giza/2015 (velogenic NDV genotype VIID) and Lasota strains, as well as the commonly used chemotherapies (Paclitaxel or Doxorubicin) were investigated on MCF-7 and Caco-2 cell lines at different concentrations. Both the human colorectal adenocarcinoma (Caco-2) and the Michigan Cancer Foundation-7 (MCF-7) human breast cancer cell lines were inoculated with NDV VIID and LaSota at concentrations of 10-2, 10-3, 10-4, and 10-5, Paclitaxel (for MCF-7) at concentrations of 0.5, 1, and 2 µM, and Doxorubicin (for Caco-2) at 0.1, 1 and 10 µM in four replicates each. The cytotoxic effect was performed using a neutral red assay for both virus strains and in combination with chemotherapeutic agents. The present study clarified that both VIID and LaSota strains of NDV, particularly at titers of 10-3 and 10-4 TCID50/ml, respectively, displayed a significant (P = 0.05) cytotoxic effect on both MCF-7 and Caco-2 cell lines. Moreover, the combined treatment of the TCID50 (Tissue Culture Infective Dose 50) doses of both NDV strains and the tested chemotherapies showed a more significant (P = 0.05) cytotoxic effect than the sole use of each. Depending on the results, we can conclude that this study opens the way for further in vivo studies aiming to provide more safe treatment for human cancers, save human lives, and avoid dramatic ends. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can lead to right heart failure and death. The pathobiology of CTEPH has been challenging to unravel due to its rarity, possible interference of results with anticoagulation, difficulty in selecting the most relevant study time point in relation to presentation with acute pulmonary embolism (PE), and lack of animal models. In this article, we review the most relevant multifaceted cross-talking pathogenic mechanisms and advances in understanding the pathobiology in CTEPH, as well as its challenges and future direction. There appears to be a genetic background affecting the relevant pathological pathways. This includes genetic associations with dysfibrinogenemia resulting in fibrinolysis resistance, defective angiogenesis affecting thrombus resolution, and inflammatory mediators driving chronic inflammation in CTEPH. However, these are not necessarily specific to CTEPH and some of the pathways are also described in acute PE or deep vein thrombosis. In addition, there is a complex interplay between angiogenic and inflammatory mediators driving thrombus non-resolution, endothelial dysfunction, and vascular remodeling. Furthermore, there are data to suggest that infection, the microbiome, circulating microparticles, and the plasma metabolome are contributing to the pathobiology of CTEPH. [ABSTRACT FROM AUTHOR]