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Abstract Radiative cooling by molecules is a crucial process for hydrodynamic escape, as it can efficiently remove the thermal energy driving the outflow, acquired through X-ray and extreme UV absorption. Carbon oxides, such as CO and CO2, and their photochemical products are anticipated to serve as vital radiative cooling sources not only in atmospheres dominated by carbon oxides but also in H2-rich atmospheres. However, their specific effects on the hydrodynamic escape, especially in H2-rich atmospheres, have been inadequately investigated. In this study, we conduct 1-D hydrodynamic escape simulations for H2-rich atmospheres incorporating CO, CO2, and their chemical products on an Earth-mass planet. We consider detailed radiative cooling processes and chemical networks related to carbon oxides to elucidate their impacts on the hydrodynamic escape. In the escape outflow, CO2 undergoes rapid photolysis, producing CO and atomic oxygen, while CO exhibits photochemical stability compared to CO2. The H2 oxidation by atomic oxygen results in the production of OH and H2O. Consequently, the hydrodynamic escape is significantly suppressed by the radiative cooling effects of CO, H2O, OH, and H3 + even when the basal mixing fraction of CO and CO2 is lower than ~ 0.01. These mechanisms extend the lifetime of H2-rich atmospheres by about one order of magnitude compared to the case of pure hydrogen atmospheres on early Earth, which also results in negligible escape of heavier carbon- and nitrogen-bearing molecules and noble gases.

Abstract Genetic backgrounds of patients with pulmonary arterial hypertension (PAH) were not fully investigated. A variant of c.14429G > A (p.Arg4810Lys) in the ring finger protein 213 gene (RNF213) was recently identified as a risk allele for poor treatment response and poor clinical prognosis in patients with PAH. However, the molecular mechanisms of the RNF213 p.Arg4810Lys variant in development of PAH are unknown. We investigated the underlying molecular mechanisms of RNF213-associated vasculopathy using an in vivo mouse model. RNF213 +/p.Arg4828Lys mice, harboring the heterozygous RNF213 p.Arg4828Lys variant corresponding to the p.Arg4810Lys variant in humans, were created using the CRISPR-Cas9 system to recapitulate the genetic status of PAH patients. RNF213 +/p.Arg4828Lys mice had a significant elevation of the right ventricular systolic pressure, hypertrophy of the right ventricle, and increased thickness of the pulmonary arterial medial wall compared with wild-type mice after 3 months of exposure to a hypoxic environment. C-X-C motif chemokine ligand 12 (CXCL12), a C-X-C chemokine receptor type 4 (CXCR4) ligand, was significantly elevated in the lungs of RNF213 +/p.Arg4828Lys mice, and PAH was ameliorated by the administration of a CXCR4 antagonist. CXCL12-CXCR4 is an angiogenic chemokine axis, and immunohistochemistry demonstrated an increase in CXCR4 in vimentin-positive spindle-shaped cells in adventitia and interstitial lesions in RNF213 +/p.Arg4828Lys mice and lung specimens from severe PAH patients with the RNF213 p.Arg4810Lys variant. We confirmed a cause-and-effect relationship between the RNF213 p.Arg4810Lys variant and PAH via the CXCL12-CXCR4 pathway. The findings in this study suggest that targeting this pathway might be a novel therapeutic strategy for RNF213-associated vasculopathy.

Neuroaxonal dystrophy (NAD) is a neurodegenerative disease characterized by spheroid (swollen axon) formation in the nervous system. In the present study, we focused on a newly established autosomal recessive mutant strain of F344-kk/kk rats with hind limb gait abnormalities and ataxia from a young age. Histopathologically, a number of axonal spheroids were observed throughout the central nervous system, including the spinal cord (mainly in the dorsal cord), brain stem, and cerebellum in F344-kk/kk rats. Transmission electron microscopic observation of the spinal cord revealed accumulation of electron-dense bodies, degenerated abnormal mitochondria, as well as membranous or tubular structures in the axonal spheroids. Based on these neuropathological findings, F344-kk/kk rats were diagnosed with NAD. By a positional cloning approach, we identified a missense mutation (V95E) in the Hspa8 (heat shock protein family A (Hsp70) member 8) gene located on chromosome 8 of the F344-kk/kk rat genome. Furthermore, we developed the Hspa8 knock-in (KI) rats with the V95E mutation using the CRISPR-Cas system. Homozygous Hspa8-KI rats exhibited ataxia and axonal spheroids similar to those of F344-kk/kk rats. The V95E mutant HSC70 protein exhibited the significant but modest decrease in the maximum hydrolysis rate of ATPase when stimulated by co-chaperons DnaJB4 and BAG1 in vitro, which suggests the functional deficit in the V95E HSC70. Together, our findings provide the first evidence that the genetic alteration of the Hspa8 gene caused NAD in mammals.

Resulta difícil entender por qué en el Perú, una actividad productiva característica y en líneas generales tan exitosa a nivel macroeconómico como lo es la agricultura está subdividida en un subsector altamente productivo -agroexportador, que posiciona sus productos en los mercados más exigentes a nivel global- y una agricultura de familiar que mantiene a su actor principal, el agricultor tradicional, en un estado de subsistencia. Este último parece haberse estancado en el tiempo, conservando una matriz productiva centrada en cultivos transitorios de baja rentabilidad, sin acceso a tecnología o a asistencia técnica que le permita incrementar su competitividad, autonomía y poder de negociación, este fortalecimiento de capacidades les permitiría afrontar de una mejor manera las perturbaciones de mercado como la inflación postpandemia o la crisis de fertilizantes, dichas situaciones adversas no están delimitadas a una región o país por el contrario se encuentran generalizadas debido a la presión por la demanda mundial de alimentos por lo que es propicia la presente oportunidad para explorar cómo es que se aborda la temática de la innovación, el incremento de la productividad y la evolución del sector agrícola alrededor del mundo desde la perspectiva académica a través del análisis bibliométrico y el análisis estructural.

Intracellular potassium ion (K+) concentration is higher than extracellular K+ concentration. Some cells maintain intracellular potassium levels by taking up extracellular potassium. However, investigating these details requires techniques to measure intracellular potassium concentrations. We established a method to easily measure intracellular potassium concentrations using a simpler electrode. The LAQUAtwin K-11 was capable of linearly quantifying potassium concentrations and was not affected by cellular constituents other than nucleic acids; however, it did not tolerate low temperatures. Interference caused by a high concentration of nucleic acids was eliminated by the addition of cations. It was also suggested that the concentration of nucleic acids in the cell suspension was not sufficiently high to interfere with the measurements. Intracellular potassium concentrations increased and decreased in response to extracellular potassium concentrations. Exposure to valinomycin did not decrease the potassium concentration, suggesting that re-uptake of the potassium released outside the cells occurred immediately. Additionally, potassium concentrations could be measured in the brain tissue homogenates using the device. This measurement method can track the relative changes in potassium concentration in cells under various conditions and in tissues of various disease models.

This study investigates whether the present bias influences the payment behavior of credit card holders in Japan. We hypothesize that credit card holders with present bias prefer to delay bill payment, even at the cost of accepting interest charges. To test this hypothesis, we utilize a dataset comprising 128,032 observations from a leading securities company. Our analysis reveals that a significant number of respondents indeed delayed credit card bill payments, suggesting a potential association with present bias behavior. Probit regression models further confirm the link between impatience, impulsivity, and credit card payment behavior. Specifically, impatience and impulsivity exhibit a positive association with credit card payments, indicating that impatient and impulsive credit card users are more likely to postpone payment, even when interest charges are incurred. The implications of this study extend to both credit card users and issuers, highlighting the influential role of impulsivity in the timely payment of bills.

Objectives: To compare the characteristics and prognosis of patients with nontuberculous mycobacterial (NTM) pulmonary disease (PD) with pleuroparenchymal fibroelastosis (PPFE) with those of patients with nodular/bronchiectatic (NB) and fibrocavitary (FC) NTM-PD. Methods: This multicenter, retrospective, observational study enrolled 32 patients with NTM-PPFE (median age: 70.5 years, 15 females) from six institutions in Japan from January 2003 to December 2018. Their clinical characteristics and response to therapy were compared with age- and sex-matched cohorts of patients with noncavitary NB and cavitary NB/FC NTM-PD. Results: Patients with NTM-PPFE had a lower body mass index and a higher standard NTM-PD therapy initiation rate than patients with other NTM-PD types. Sputum culture conversion rates were comparable between groups; however, patients with NTM-PPFE had a higher incidence of treatment-related adverse events, including optic neuropathy associated with high-dose ethambutol therapy, lower percent predicted forced vital capacity values, higher serum Krebs von den Lungen-6 (KL-6) levels, and poorer treatment outcomes than the other groups. Cox regression revealed that NTM-PPFE was an independent risk factor for death/pneumothorax (adjusted hazard ratio: 35.3, 95% confidence interval: 3.90-4692). Conclusion: NTM-PPFE is a unique NTM-PD phenotype with a poorer prognosis than the NB and FC phenotypes.

Abstract Background We previously identified Il17RB, a member of the IL17 superfamily, as a candidate marker gene for endometrial aging. While IL17RB has been linked to inflammation and malignancies in several organ systems, its function in the endometrium has not been investigated and is thus poorly understood. In the present study, we performed a functional analysis of this receptor with the aim of determining the effects of its age-associated overexpression on the uterine environment. Methods We analyzed IL17RB-related signaling pathways and downstream gene expression in an immortalized human endometrial glandular epithelial cell line (“hEM”) forced to express the receptor via lentiviral transduction (“IL17RB-hEM”). We also prepared endometrial organoids from human endometrial tissue sourced from hysterectomy patients (“patient-derived EOs”) and exposed them to cytokines that are upregulated by IL17RB expression to investigate changes in organoid-forming capacity and senescence markers. We analyzed RNA-seq data (GEO accession number GSE132886) from our previous study to identify the signaling pathways associated with altered IL17RB expression. We also analyzed the effects of the JNK pathway on organoid-forming capacity. Results Stimulation with interleukin 17B enhanced the NF-κB pathway in IL17RB-hEM, resulting in significantly elevated expression of the genes encoding the senescence associated secretory phenotype (SASP) factors IL6, IL8, and IL1β. Of these cytokines, IL1β inhibited endometrial organoid growth. Bioinformatics analysis showed that the JNK signaling pathway was associated with age-related variation in IL17RB expression. When IL17RB-positive cells were cultured in the presence of IL17B, their organoid-forming capacity was slightly but non-significantly lower than in unexposed IL17RB-positive cells, but when IL17B was paired with a JNK inhibitor (SP600125), it was restored to control levels. Further, IL1β exposure significantly reduced organoid-forming capacity and increased p21 expression in endometrial organoids relative to non-exposure (control), but when IL1β was paired with SP600125, both indicators were restored to levels comparable to the control condition. Conclusions We have revealed an association between IL17RB, whose expression increases in the endometrial glandular epithelium with advancing age, and cellular senescence. Using human endometrial organoids as in vitro model, we found that IL1β inhibits cell proliferation and leads to endometrial senescence via the JNK pathway.

Abstract Mechanical circulatory support (MCS) devices, including veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and Impella, have been widely used for patients with cardiogenic shock (CS). However, hemodynamics with each device and combination therapy is not thoroughly understood. We aimed to elucidate the hemodynamics with MCS using a pulsatile flow model. Hemodynamics with Impella CP, VA-ECMO, and a combination of Impella CP and VA-ECMO were assessed based on the pressure and flow under support with each device and the pressure–volume loop of the ventricle model. The Impella CP device with CS status resulted in an increase in aortic pressure and a decrease in end-diastolic volume and end-diastolic pressure (EDP). VA-ECMO support resulted in increased afterload, leading to a significant increase in aortic pressure with an increase in end-systolic volume and EDP and decreasing venous reservoir pressure. The combination of Impella CP and VA-ECMO led to left ventricular unloading, regardless of increase in afterload. Hemodynamic support with Impella and VA-ECMO should be a promising combination for patients with severe CS.

Objectives: In patients with stable ischemic heart disease, there is no evidence for the effect of revascularization treatment timing on the need for repeat procedures. We aimed to determine if repeat revascularizations differed among patients who received coronary artery bypass graft surgery after the time recommended by physicians compared with those who had timely percutaneous coronary intervention. Methods: We identified 25,520 British Columbia residents 60 years or older who underwent first-time nonemergency revascularization for angiographically proven, stable left main or multivessel ischemic heart disease between January 1, 2001, and December 31, 2016. We estimated unadjusted and adjusted cumulative incidence functions for repeat revascularization, in the presence of death as a competing risk, after index revascularization or last staged percutaneous coronary intervention for patients undergoing delayed coronary artery bypass grafting compared with timely percutaneous coronary intervention. Results: After adjustment with inverse probability of treatment weights, at 3 years, patients who underwent delayed coronary artery bypass grafting had a statistically significant lower cumulative incidence of a repeat revascularization compared with patients who received timely percutaneous coronary intervention (4.84% delayed coronary artery bypass grafting, 12.32% timely percutaneous coronary intervention; subdistribution hazard ratio, 0.16, 95% CI, 0.04-0.65). Conclusions: Patients who undergo delayed coronary artery bypass grafting have a lower cumulative incidence of repeat revascularization than patients who undergo timely percutaneous coronary intervention. Patients who want to wait to receive coronary artery bypass grafting will see the benefit of lower repeat revascularization over percutaneous coronary intervention unaffected by a delay in treatment.

Abstract A 12‐year‐old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2‐week history of pruritus and raw/bleeding skin from self‐trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0–2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2–2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib.

IntroductionSpinal cord injury (SCI) leads to severe disabilities and remains a significant social and economic challenge. Despite advances in medical research, there are still no effective treatments for SCI. Human amnion-derived mesenchymal stem cells (hAMSCs) have shown potential due to their anti-inflammatory and neuroprotective effects. This study evaluates the therapeutic potential of intravenously administered hAMSCs in SCI models.MethodsThree days after induction of SCI with forceps calibrated with a 0.2 mm gap, hAMSCs or vehicle were administered intravenously. Up to 4 weeks of SCI induction, motor function was assessed by scores on the Basso Mouse Locomotor Scale (BMS) and the Basso-Beattie-Bresnahan Scale (BBB), and sensory function by hindlimb withdrawal reflex using von Frey filaments. Six weeks after SCI induction, gait function was assessed using three-dimensional motion analysis. Immunohistochemistry, polymerase chain reaction (PCR), flow cytometry, and ELISA assay were performed to clarify the mechanisms of functional improvement.ResultsThe hAMSC treatment significantly improved sensory response and gait function. In the SCI site, immunohistochemistry showed a reduction in Iba1-positive cells and PCR revealed decreased TNFα and increased BDNF levels in the hAMSC-treated group. In assessing the systemic inflammatory response, hAMSC treatment reduced monocytic bone marrow-derived suppressor cells (M-MDSCs) and Ly6C-positive inflammatory macrophages in the bone marrow by flow cytometry and serum NO levels by ELISA assay.DiscussionThis study demonstrates the therapeutic potential of the hAMSC in SCI, with improvements in gait and sensory functions and reduced inflammation both locally and systemically. The findings support further investigation of the hAMSC as a potential treatment for SCI, focusing on their ability to modulate inflammation and promote neuroprotection.

The importance of non-financial capital in firm valuation has been increasing. Non-financial capital comprises intellectual, human, social, relational, natural, and manufactured capital. This study proposes a clustered corporate value model to identify financial and non-financial factors influencing firm value. We cluster a group of companies and build a principal component regression model for each cluster, using the Bayesian Information Criterion for evaluation, with financial and non-financial factors as explanatory variables. We also considered the time lag in the impact of financial and non-financial factors on corporate value. In other words, we consider the impact of financial and non-financial factors on corporate value over multiple years, not just a single year. We propose an algorithm that identifies clusters and constructs a regression model for each, optimizing the combination of cluster divisions and explanatory variables using adjusted R-squared as the evaluation criterion. The cluster-specific corporate value model shows higher explanatory power than the industry-specific cluster-based corporate value model for the electrical, chemical, food, construction, and service industries.