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Synovial sarcoma (SS) is an aggressive soft-tissue cancer with a poor prognosis and a propensity for local recurrence and distant metastasis. In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Next, we identified that genetic depletion of Skp2 reduced mesenchymal and stemness markers, and inhibited the invasive and proliferative capacities of SS cell lines. Furthermore, Skp2 depletion markedly suppressed the growth of SS xenografts tumors. Treatment of SS cell lines with the skp2 inhibitor flavokawain A (FKA) reduced Skp2 expression in a dose-dependent manner and resulted in cell cycle arrest and apoptosis. FKA also suppressed the invasion and tumor-initiating properties in SS, similar to the effects of Skp2 knockdown. In addition, a combination of FKA and conventional chemotherapy showed a synergistic therapeutic efficacy. Taken together, our results suggest that Skp2 plays an essential role in the biology of SS by promoting the mesenchymal state and cancer stemness. Given that chemotherapy resistance is often associated with cancer stemness, strategies of combining Skp2 inhibitors with conventional chemotherapy in SS may be desirable.

Osteosarcoma (OS), the most common primary cancer of bone, exhibits a high propensity for local invasion and distant metastasis. This study sought to elucidate the role of S phase kinase-associated protein (Skp2) in osteosarcoma invasion and metastasis and to explore flavokawain A (FKA), a natural chalcone from kava extract, as a potential Skp2 targeting agent for preventing osteosarcoma progression. Skp2 was found to be overexpressed in multiple osteosarcoma cell lines, including 5 standard and 8 primary patient-derived cell lines. Patients whose tumors expressed high levels of Skp2 sustained a significantly worse metastasis-free (p = 0.0095) and overall survival (p = 0.0013) than those with low Skp2. Skp2 knockdown markedly reduced in vitro cellular invasion and in vivo lung metastasis in an orthotopic mouse model of osteosarcoma. Similar to Skp2 knockdown, treatment with FKA also reduced Skp2 expression in osteosarcoma cell lines and blocked the invasion of osteosarcoma cells in vitro and lung metastasis in vivo. Together, our findings suggest that Skp2 is a promising therapeutic target in osteosarcoma, and that FKA may be an effective Skp2-targeted therapy to reduce osteosarcoma metastasis.

Allophane and ferrihydrite are the main hosts of phosphate in allophanic Andosols, which are vital soil resources that support high human population densities. However, the sorption mechanism of phosphate on allophane has not been elucidated, unlike that of ferrihydrite. In particular, the effects of residence time on phosphate sorbed on allophane remain unclear. Therefore, the objectives of this study were to (1) understand the effect of residence time on the stability of phosphate sorbed on allophanic Andosol and allophane by desorption experiments using arsenate and (2) elucidate the sorption mechanism of phosphate on allophane using solid‐state 31P nuclear magnetic resonance (NMR). Consequently, the slow sorption of phosphate onto allophanic Andosol, allophane, and ferrihydrite continued for approximately 150 days. The ratio of total desorbable phosphate to phosphate sorbed onto the allophanic Andosol and allophane decreased with increasing residence time. In other words, phosphate sorption on allophanic Andosol and allophane was more irreversible with increasing residence time. The NMR spectra and X‐ray diffraction patterns showed that the molecular environment of phosphate sorbed onto allophane and ferrihydrite did not change at any residence time. Therefore, the slow sorption and irreversibility of phosphate were caused not by surface precipitation but by internal diffusion. In addition, the NMR spectra showed that most of the phosphate sorbed on allophane was present as inner‐sphere complexes. [ABSTRACT FROM AUTHOR]

Vital signs are crucial for assessing the condition of a patient and detecting early symptom deterioration. Noncontact sensor technology has been developed to take vital measurements with minimal burden. This study evaluated the accuracy of a mat-type noncontact sensor in measuring respiratory and pulse rates in patients with cardiovascular diseases compared to conventional methods. Forty-eight hospitalized patients were included; a mat-type sensor was used to measure their respiratory and pulse rates during bed rest. Differences between mat-type sensors and conventional methods were assessed using the Bland–Altman analysis. The mean difference in respiratory rate was 1.9 breaths/min (limits of agreement (LOA): −4.5 to 8.3 breaths/min), and proportional bias existed with significance (r = 0.63, p < 0.05). For pulse rate, the mean difference was −2.0 beats/min (LOA: −23.0 to 19.0 beats/min) when compared to blood pressure devices and 0.01 beats/min (LOA: −11.4 to 11.4 beats/min) when compared to 24-h Holter electrocardiography. The proportional bias was significant for both comparisons (r = 0.49, p < 0.05; r = 0.52, p < 0.05). These were considered clinically acceptable because there was no tendency to misjudge abnormal values as normal. The mat-type noncontact sensor demonstrated sufficient accuracy to serve as an alternative to conventional assessments, providing long-term monitoring of vital signs in clinical settings. [ABSTRACT FROM AUTHOR]

INTRODUCTION: We examined the efficacy of a multidomain intervention in preventing cognitive decline among Japanese older adults with mild cognitive impairment (MCI). METHODS: Participants aged 65‐85 years with MCI were randomized into intervention (management of vascular risk factors, exercise, nutritional counseling, and cognitive training) and control groups. The primary outcome was changes in the cognitive composite score over a period of 18 months. RESULTS: Of 531 participants, 406 completed the trial. The between‐group difference in composite score changes was 0.047 (95% CI: −0.029 to 0.124). Secondary analyses indicated positive impacts of interventions on several secondary health outcomes. The interventions appeared to be particularly effective for individuals with high attendance during exercise sessions and those with the apolipoprotein E ε4 allele and elevated plasma glial fibrillary acidic protein levels. DISCUSSION: The multidomain intervention showed no efficacy in preventing cognitive decline. Further research on more efficient strategies and suitable target populations is required. Highlights: This trial evaluated the efficacy of multidomain intervention in individuals with MCI.The trial did not show a significant difference in preplanned cognitive outcomes.Interventions had positive effects on a wide range of secondary health outcomes.Those with adequate adherence or high risk of dementia benefited from interventions. [ABSTRACT FROM AUTHOR]

High pathogenicity avian influenza is an acute zoonotic disease with high mortality in birds caused by a high pathogenicity avian influenza virus (HPAIV). Recently, HPAIV has rapidly spread worldwide and has killed many wild birds, including endangered species. Baloxavir marboxil (BXM), an anti-influenza agent used for humans, was reported to reduce mortality and virus secretion from HPAIV-infected chickens (Gallus domesticus, order Galliformes) at a dosage of ≥2.5 mg/kg when administered simultaneously with viral challenge. Application of this treatment to endangered birds requires further information on potential avian-specific toxicity caused by repeated exposure to BXM over the long term. To obtain information of potential avian-specific toxicity, a 4-wk oral repeated-dose study of BXM was conducted in chickens (n = 6 or 7 per group), which are commonly used as laboratory avian species. The study was conducted in reference to the human pharmaceutical guidelines for nonclinical repeated-dose drug toxicity studies to evaluate systemic toxicity and exposure. No adverse changes were observed in any organs examined, and dose proportional increases in systemic exposure to active pharmaceutical ingredients were noted from 12.5 to 62.5 mg/kg per day. BXM showed no toxicity to chickens at doses of up to 62.5 mg/kg per day, at which systemic exposure was approximately 71 times higher than systemic exposure at 2.5 mg/kg, the reported efficacious dosage amount, in HPAIV-infected chickens. These results also suggest that BXM could be considered safe for treating HPAIV-infected endangered birds due to its high safety margin compared with the efficacy dose. The data in this study could contribute to the preservation of endangered birds by using BXM as a means of protecting biodiversity. [ABSTRACT FROM AUTHOR]

This study develops a new dynamic general equilibrium model to explore the role of people's love of novelty as a cultural preference in innovation and innovation-based growth. The model considers (a) an infinitely lived representative consumer who has standard love-of-variety preferences for differentiated products and additional love-of-novelty preferences for new products and (b) technological progress driven by two costly and time-consuming innovation activities, new product development and existing product development. We demonstrate that consumers' love of novelty is a source of innovation-based growth, wherein economies with a moderate love of novelty can achieve innovation and long-run growth through endogenous cycles between periods in which new product development is active and those in which existing product development is active. However, if love of novelty preference is too weak or too strong, the economy is caught in an underdevelopment trap with less innovation and no long-run growth. We also provide some suggestive empirical evidence that supports our theoretical predictions. [ABSTRACT FROM AUTHOR]