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We propose a new non-parametric conditional independence test for a scalar response and a functional covariate over a continuum of quantile levels. We build a Cramer-von Mises type test statistic based on an empirical process indexed by random projections of the functional covariate, effectively avoiding the "curse of dimensionality" under the projected hypothesis, which is almost surely equivalent to the null hypothesis. The asymptotic null distribution of the proposed test statistic is obtained under some mild assumptions. The asymptotic global and local power properties of our test statistic are then investigated. We specifically demonstrate that the statistic is able to detect a broad class of local alternatives converging to the null at the parametric rate. Additionally, we recommend a simple multiplier bootstrap approach for estimating the critical values. The finite-sample performance of our statistic is examined through several Monte Carlo simulation experiments. Finally, an analysis of an EEG data set is used to show the utility and versatility of our proposed test statistic.
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Simulación por Computador , Modelos Estadísticos , Método de Montecarlo , Humanos , Electroencefalografía/estadística & datos numéricos , Interpretación Estadística de Datos , Biometría/métodos , Estadísticas no ParamétricasRESUMEN
Long-term weightlessness in animals can cause changes in myocardial structure and function, in which mitochondria play an important role. Here, a tail suspension (TS) Kunming mouse (Mus musculus) model was used to simulate the effects of weightlessness on the heart. We investigated the effects of 2 and 4 weeks of TS (TS2 and TS4) on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling. Our study revealed significant changes in the ultrastructural features of cardiomyocytes in response to TS. The results showed: (1) mitochondrial swelling and disruption of cristae in TS2, but mitochondrial recovery and denser cristae in TS4; (2) an increase in the total number of mitochondria and number of sub-mitochondria in TS4; (3) no significant changes in the nuclear ultrastructure or DNA fragmentation among the two TS groups and the control group; (4) an increase in the bax/bcl-2 protein levels in the two TS groups, indicating increased activation of the bax-mediated apoptosis pathway; (5) no change in the phosphorylation ratio of dynamin-related protein 1 in the two TS groups; (6) an increase in the protein levels of optic atrophy 1 and mitofusin 2 in the two TS groups; and (7) in comparison to the TS2 group, an increase in the phosphorylation ratio of parkin and the ratio of LC3II to LC3I in TS4, suggesting an increase in autophagy. Taken together, these findings suggest that mitochondrial autophagy and fusion levels increased after 4 weeks of TS, leading to a restoration of the bax-mediated myocardial apoptosis pathway observed after 2 weeks of TS. NEW FINDINGS: What is the central question of this study? What are the effects of 2 and 4 weeks of tail suspension on myocardial mitochondrial ultrastructure and oxidative respiratory function and on the molecular mechanisms of apoptosis and mitochondrial fission, autophagy and fusion-related signalling? What is the main finding and its importance? Increased mitochondrial autophagy and fusion levels after 4 weeks of tail suspension help to reshape the morphology and increase the number of myocardial mitochondria.
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Suspensión Trasera , Mitocondrias Cardíacas , Ratones , Animales , Mitocondrias Cardíacas/metabolismo , Dinámicas Mitocondriales/genética , Proteína X Asociada a bcl-2/metabolismo , Apoptosis/fisiología , Autofagia , Miocitos Cardíacos/metabolismoRESUMEN
In this study, we investigated the mitochondrial energy supply capacity and molecular mechanisms of apoptosis, mitochondrial fission, and mitophagy in regulating mitochondrial degeneration in testis of striped dwarf hamsters (Cricetulus barabensis) under mild low temperature (15°C) and short daylight (10 h:14 h) conditions. Results showed that under moderate daylight and mild low temperature (ML), short daylight and moderate temperature (SM), short daylight and mild low temperature (SL) conditions, the mitochondria were swollen and cristae were disrupted. Compared with the moderate daylight & moderate temperature group (MM; 12 h:12 h, 22°C), the number of mitochondria was significantly decreased in the SM and SL groups. Both short daylight and mild low temperature reduced the protein expression of citrate synthase, thus the energy supply capacity of mitochondria may be weakened. Compared with the MM group, bax/bcl2 protein expression was higher in three treatment groups, and caspase3 activity increased in SM and SL groups, suggesting that short daylight can induce apoptosis. DRP1 protein expression showed no difference in four groups, while the FIS1 protein expression was significantly decreased in three treatment groups, this indicates that short daylight and mild low temperature can increase mitochondrial fission level. PINK1 protein expression was significantly increased in ML and SL groups, indicates that mild low temperature will lead to increased mitophagy level. Generally, short daylight induced degeneration of mitochondria in the testis of hamsters mainly by increasing apoptosis, while under mild low temperature, balanced regulation of mitophagy and mitochondrial fission appear to contribute to the protection of mitochondria.
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Mitocondrias , Testículo , Animales , Citrato (si)-Sintasa/metabolismo , Citrato (si)-Sintasa/farmacología , Cricetinae , Cricetulus , Masculino , Mitocondrias/metabolismo , Proteínas Quinasas/metabolismo , Proteínas Quinasas/farmacología , Temperatura , Testículo/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
OBJECTIVE: To establish the solid three-dimensional fluorescence fingerprint spectra for the main root and branch root of Panax notoginseng. METHODS: With the Xuesaitong power as a control, the solid three-dimensional fluorescence technique was employed to establish the fingerprint spectra. RESULTS: The fluorescence peaks of Xuesaitong power were at 230 nm/330 nm,280 nm/660 nm,300 nm/340 nm, 370 nm/590 nm, 440 nm/550 nm, and 490 nm/610 nm. Among of them, the 300 nm/340 nm peak was the strongest. The fluorescence peaks of Panax notoginseng main root power were at 230 nm/340 nm,290 nm/340 nm,370 nm/480 nm,and 430 nm/540 nm. Among of them, the peak at 290 nm/340 nm was the strongest. The branch root of Panax notoginseng was at 280 nm/450 nm,290 nm/350 nm and 350 nm/440 nm,and the peak at 350 nm/440 nm was the strongest. All of them had the peak at 290-300 nm/340-350 nm, this peak was the strongest in Xuesaitong and Panax notoginseng main root power, but 350 nm/440 nm was the strongest in the branch root of Panax notoginseng. Only the peak at 230 nm/330-340 nm was not detected in the branch root of Panax notoginseng. CONCLUSION: The solid three-dimensional fluorescence fingerprints spectra are established. Using peaks at 290-300 nm/340-350 nm and 230 nm/330-340 nm as characteristics of the fluorescence peak can efficiently identify main root and branch root of Panax notoginseng.
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Panax notoginseng/química , Fluorescencia , Imagenología Tridimensional , Raíces de Plantas , Control de CalidadRESUMEN
Photoperiod regulates the functions and development of gonadal organs of seasonally breeding animals, resulting in breeding peaks in specific seasons. miRNA plays an important role in the regulation of testicular physiological functions. However, the relationship between photoperiods and miRNA levels in testes has yet to be conclusively determined. We investigated testicular miRNA of striped dwarf hamster (Cricetulus barabensis) responses to different photoperiods (long daylength [LD], moderate daylength [MD], and short daylength [SD]) and the potential pathways involved in photoperiod regulated reproduction. Testicular weights and reproductive hormone levels were measured in each of photoperiod treatments after 30 days. The concentrations of testosterone (T) and dihydrogen testosterone (DHT) in testes and Gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in serum were higher in MD than in the other two groups. Testicular weights were heaviest in MD. Small RNA-seq was performed for the testes of hamsters in three groups. A total of 769 miRNAs were identified, of which 83 were differentially expressed between LD, MD, and SD. GO and KEGG analysis of target genes revealed that some miRNAs influence testicular activities by regulating the pathways related to cell apoptosis and metabolism. Gene expression pattern analysis showed that the MAPK signaling pathway may be the core pathway for photoperiodic regulation of reproduction. These results suggest that moderate daylength is more suitable for hamster reproduction while long daylength and short daylength may regulate reproduction through different molecular pathways.
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An antitumor peptide from Musca domestica pupae (MATP) was seen to inhibit proliferation and induce apoptosis in cancer cells in our previous investigation. However, the molecular mechanisms involved in MATP-induced apoptosis are still uncharacterized in the human liver cancer cell line HepG2. The present study was undertaken to elucidate the signaling events in MATP-induced apoptosis of HepG2 cells. In this study, the sustained activation of phosphorylated c-Jun N-terminal kinase (JNK) and the obvious inactivation of phosphorylated Akt(Ser473), which prevented IκBα from degeneration, were induced by MATP. Simultaneously, the apoptosis induced by MATP was reversed by SP600125 (a JNK inhibitor) whereas it was aggravated by LY294002 (an Akt inhibitor). These results proved that JNK and Akt independently participated in the apoptosis of HepG2 cells, which were treated with MATP. Moreover, the activation of phosphorylated JNK together with the inactivation of phosphorylated Akt(Ser473) restrained nuclear factor-κB (NF-κB p65) from entering the nucleus. The apoptosis induced by MATP was increased by pyrrolidine dithiocarbamate (NF-κB p65 inhibitor) and the restriction of NF-κB p65 from entering the nucleus induced the decrease of Bcl-2. Simultaneously, MATP induced the increase of Bax, but this mechanism did not depend on the decrease of NF-κB p65 in the nucleus. The release of cytochrome c from the mitochondria, which intensified the expression of caspase-9 and caspase-3, was enhanced by the increase in Bax-to-Bcl-2 expression ratio. The apoptosis of HepG2 cells was induced ultimately by the increase in caspase-3. Taken together, these findings suggest that MATP-induced apoptosis through a JNK-mediated and Akt-mediated NF-κB pathway.