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BackgroundGait impairments including shuffling gait and hesitation are common in people with Parkinson’s disease (PD), and have been linked to increased fall risk and freezing of gait. Nowadays the gait metrics mostly focus on the spatiotemporal characteristics of gait, but less is known of the angular characteristics of the gait, which may provide helpful information pertaining to the functional status and effects of the treatment in PD. ObjectiveThis study aimed to quantify the angles of steps during walking, and explore if this novel step angle metric is associated with the severity of PD and the effects of the treatment including the acute levodopa challenge test (ALCT) and deep brain stimulation (DBS). MethodsA total of 18 participants with PD completed the walking test before and after the ALCT, and 25 participants with PD completed the test with the DBS on and off. The walking test was implemented under two conditions: walking normally at a preferred speed (single task) and walking while performing a cognitive serial subtraction task (dual task). A total of 17 age-matched participants without PD also completed this walking test. The angular velocity was measured using wearable sensors on each ankle, and three gait angular metrics were obtained, that is mean step angle, initial step angle, and last step angle. The conventional gait metrics (ie, step time and step number) were also calculated. ResultsThe results showed that compared to the control, the following three step angle metrics were significantly smaller in those with PD: mean step angle (F1,48=69.75, P

Autophagy has been implicated in stroke. Our previous study showed that the FoxO3 transcription factor promotes autophagy after transient cerebral ischemia/reperfusion (I/R). However, whether the Akt/FoxO3 signaling pathway plays a regulatory role in autophagy in cerebral I/R-induced oxidative stress injury is still unclear. The present study aims to investigate the effects of the Akt/FoxO3 signaling pathway on autophagy activation and neuronal injury in vitro and in vivo. By employing LY294002 or insulin to regulate the Akt/FoxO3 signaling pathway, we found that insulin pretreatment increased cell viability, decreased reactive oxygen species production, and enhanced the expression of antiapoptotic and autophagy-related proteins following [H.sub.2][O.sub.2] injury in HT22 cells. In addition, insulin significantly decreased neurological deficit scores and infarct volume and increased the expression of antiapoptotic and autophagy-related proteins following I/R injury in rats. However, LY294002 showed the opposite effects under these conditions. Altogether, these results indicate that Akt/FoxO3 signaling pathway activation inhibited oxidative stress-mediated cell death through activation of autophagy. Our study supports a critical role for the Akt/FoxO3 signaling pathway in autophagy activation in stroke. Key words: Akt/FoxO3 signaling pathway, autophagy, apoptosis, hydrogen peroxide, stroke, Introduction Stroke, which is widely considered to be a leading cause of disability and death, causes a tremendous global health and economic burden (Virani et al. 2021). Cerebral ischemia/reperfusion (I/R) [...]

Autophagy has been implicated in neurodegenerative diseases. Forkhead box O3 (FoxO3) transcription factors promote autophagy in heart and inhibit oxidative damage. Here we investigate the role of FoxO3 transcription factors in regulating autophagy after oxidative stress injury in immortalized mouse hippocampal cell line (HT22). The present study confirms that hydrogen peroxide ([H.sub.2][O.sub.2]) injury could induce autophagy and FoxO3 activation in HT22 cells. In addition, overexpression of FoxO3 enhanced [H.sub.2][O.sub.2]-induced autophagy activation and suppressed neuronal cell damage, while knockdown of FoxO3 reduced [H.sub.2][O.sub.2]-induced autophagy activation and exacerbated neuronal cell injury. Inhibition of autophagy by 3- methyladenine (3-MA) resulted in reduced cell viability, increased production of reactive oxygen species (ROS), promoted nuclear condensation, and decreased expression of antiapoptotic and autophagy-related proteins, indicating that autophagy may have protective effects on [H.sub.2][O.sub.2]-induced injury in HT22 cells. Moreover, overexpression of FoxO3 prevented exacerbation of brain damage induced by 3-MA. Taken together, these results show that activation of FoxO3 could induce autophagy and inhibit [H.sub.2][O.sub.2]-induced damage in HT22 cells. Our study demonstrates the critical role of FoxO3 in regulating autophagy in brain. Key words: FoxO3 transcription factors, autophagy, apoptosis, hydrogen peroxide, oxidative stress, neurodegenerative diseases, HT22 cells. On a implique l'autophagie dans les maladies neurodegeneratives. Les facteurs de transcription FoxO3 (pour << Forkhead box O3 >>) favorisent l'autophagie dans le coeur et entrainent une inhibition des dommages oxydatifs. Dans les presents travaux, nous etudions le role des FoxO3 dans la regulation de l'autophagie apres des lesions liees au stress oxydatif dans des lignees cellulaires d'hippocampe de souris (HT22). La presente etude confirme que des lesions causees par le peroxyde d'hydrogene ([H.sub.2][O.sub.2]) peuvent engendrer de l'autophagie et l'activation des FoxO3 dans les cellules HT22. De plus, la surexpression des FoxO3 entrainait une augmentation de l'activation de l'autophagie engendree par le [H.sub.2][O.sub.2] et une inhibition complete des dommages dans les cellules neuronales, tandis que la repression (<< knockdown >>) des FoxO3 entrainait une diminution de l'activation de l'autophagie engendree par le [H.sub.2][O.sub.2] et une exacerbation des lesions dans les cellules neuronales. L'inhibition de l'autophagie par le 3-methyladenine (3-MA) entrainait une diminution de la viabilite des cellules, une augmentation de la production de derives reactifs de l'oxygene, une aggravation de la condensation des noyaux et une diminution de l'expression de proteines antiapoptotiques et liees a l'autophagie, ce qui montre que l'autophagie pourrait avoir des effets protecteurs contre les effets des lesions engendrees par le [H.sub.2][O.sub.2] dans les cellules HT22. En outre, la surexpression des FoxO3 permettait de prevenir l'exacerbation des dommages engendres par le 3-MA dans le cerveau. Dans leur ensemble, ces resultats montrent que l'activation des FoxO3 pourrait engendrer de l'autophagie et attenuer les dommages engendres par le [H.sub.2][O.sub.2] dans les cellules HT22. Notre etude montre le role essentiel des FoxO3 dans la regulation de l'autophagie dans le cerveau. [Traduit par la Redaction] Mots-cles : facteurs de transcription FoxO3, autophagie, apoptose, peroxyde d'hydrogene, stress oxydatif, maladies neurodegeneratives, cellules HT22., Introduction Neurodegenerative diseases are associated with irreversible and progressive damage to the nervous system (Rekatsina et al. 2020). These diseases are primarily prevalent in the elderly, and the incidence rate [...]

In conjunction with Earth's ongoing global warming, the Southwest China (SWC) region has become a fascinating case study on the control of local climate change. Moreover, an entire period of climate change may partially mask the patterns in some stages. Therefore, in this research, we investigated the spatial patterns of the significant turning years of climatic factor change, and determined the heterogeneity of the spatial patterns of climate change before and after the significant turning years. We used the long time-series of the CRU datasets (CRU_TS4.02) from 1901 to 2017 with a piecewise linear regression model to explore the significant turning-year distribution characteristics of inter-annual and inter-seasonal climate factor changes, and further describe and quantize the differences in the spatio-temporal patterns of climate factors before and after the significant turning years on the grid scale in SWC. Overall, the trends in temperature and precipitation factors in SWC were segmented over the last 120 years, with significant turning years with different regional and stepwise characteristics. In terms of timing, temperature and precipitation factors changed significantly in 1954 and 1928, respectively, and overall temporal variability (0.04 °C/(10 a) (p < 0.05), −0.48 mm/(10 a)) masked the magnitude or direction of variability (0.13 °C/(10 a) and 0.16 °C/(10 a) both at the level of p < 0.05 before the turning year, 19.56 mm/(10 a) (p < 0.05) and 1.19 mm/(10 a) after the turning year) around the watershed years. Spatially, the significant turning years were concentrated in the periods 1940–1993 (temperature) and 1910–2008 (precipitation), and the distribution pattern of the turning years was patchy and concentrated. The turning years of temperature factors were gradually delayed from east to west, and the variability of climate factors before and after the turning years exhibited significant shifts in location (e.g., temperature decreased from southeast to northwest before the turning year and increased after the turning year). After the turning year, the warming variability of the temperature factor increased, while the increasing variability of the precipitation factor decreased. Further integrated analysis revealed that the increase in variability of the climate factor after the turning year was mainly due to the increase in winter and autumn variability (0.05 °C/(10 a), 7.30 mm/(10 a) in autumn; and 0.12 °C/(10 a), 1.97 mm/(10 a) in winter). To the extent that this study provides a necessary academic foundation for efficiently unveiling the spatio-temporal variability properties of climate factors against the background of modern global climate change, more attention should be paid to the location and phase of the study. [ABSTRACT FROM AUTHOR]

Although previous studies have reported correlations between alpha oscillations and the "retention" subprocess of working memory (WM), causal evidence has been limited in human neuroscience due to the lack of delicate modulation of human brain oscillations. Conventional transcranial alternating current stimulation (tACS) is not suitable for demonstrating the causal evidence for parietal alpha oscillations in WM retention because of its inability to modulate brain oscillations within a short period (i.e., the retention subprocess). Here, we developed an online phase-corrected tACS system capable of precisely correcting for the phase differences between tACS and concurrent endogenous oscillations. This system permits the modulation of brain oscillations at the target stimulation frequency within a short stimulation period and is here applied to empirically demonstrate that parietal alpha oscillations causally relate to WM retention. Our experimental design included both in-phase and anti-phase alpha-tACS applied to participants during the retention subprocess of a modified Sternberg paradigm. Compared to in-phase alpha-tACS, anti-phase alpha-tACS decreased both WM performance and alpha activity. These findings strongly support a causal link between alpha oscillations and WM retention and illustrate the broad application prospects of phase-corrected tACS. With its capacity to correct for its phase differences relative to concurrent brain oscillations, an online phase-corrected tACS system provides the possibility to both up- and down-regulate targeted brain oscillations within a short period; using such a system, this study shows that parietal alpha oscillations exert causal impacts on working memory retention. [ABSTRACT FROM AUTHOR]

Climate change is known to significantly affect vegetation development in the terrestrial system. Because Southwest China (SW) is affected by westerly winds and the South and East Asian monsoon, its climates are complex and changeable, and the time lag effect of the vegetation's response to the climate has been rarely considered, making it difficult to establish a link between the SW region's climate variables and changes in vegetation growth rate. This study revealed the characteristics of the time lag reaction and the phased changes in the response of vegetation to climate change across the entire SW and the typical climate type core area (CA) using the moving average method and multiple linear model based on the climatic information of CRU TS v. 4.02 from 1982 to 2017 together with the annual maximum (P100), upper quarter quantile (P75), median (P50), lower quarter quantile (P25), minimum (P5), and mean (Mean) from GIMMS NDVI. Generally, under the single and combined effects of temperature and precipitation, taking the time lag effect (annual and interannual delay effect) into account significantly improved the average prediction rates of temperature and precipitation, which increased by 18.48% and 25.32%, respectively. The optimal time delay was 0–4 months when the annual delay was taken into consideration, but it differed when considering the interannual delay, and the delaying effect of precipitation was more significant than that of temperature. Additionally, the response intensity of vegetation to temperature, precipitation, and their interaction was significantly more robust when the annual delay was taken into account than when it was not (p < 0.05), with corresponding multiple correlation coefficients of 0.87 and 0.91, respectively. However, the degree of response to the combined effect of individual effects and climate factors tended to decrease regardless of whether time delay effects were taken into account. A more comprehensive analysis of the effects of climate change on vegetation development dynamics suggested that the best period for synthesizing NDVI annual values might be the P25 period. Our study could provide a new theoretical framework for analyzing, predicting, and evaluating the dynamic response of vegetation growth to climate change. [ABSTRACT FROM AUTHOR]