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Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have shown neuroprotective effects in obese mice. However, whether SGLT2i can ameliorate high-fat diet (HFD)-related ovulation disorders remains unknown. The aim of this research was to investigate whether dapagliflozin improves HFD-induced ovulatory dysfunction by attenuating microglia-mediated hypothalamic inflammation. Methods: C57BL/6J female mice fed HFD were treated with dapagliflozin (1 mg/kg) for 22 weeks. Plasma insulin, leptin, luteinizing hormone (LH), estradiol (E2), and IL-1β levels were also tested. Microglial morphology, cell numbers, and SGLT2 expression were evaluated using immunofluorescence. The expression of IL-1β, NLRP3, kisspeptin, gonadotropin-releasing hormone (GnRH), SGLT2, insulin, and leptin receptors in the hypothalamus was determined using immunohistochemical staining. We also examined the effects of dapagliflozin on glucose metabolism and the release of inflammatory factor in palmitic acid (PA)-treated HMC3 cells. Results: As expected, dapagliflozin improved HFD-induced metabolic disturbances, peripheral versus central insulin and leptin resistance and also restored the regular estrous cycle. Furthermore, dapagliflozin blunted microglia activation, NLRP3 inflammasome priming, hypothalamic inflammation, and increased the expression of GnRH and kisspeptin at proestrus in the hypothalamus. Additionally, dapagliflozin markedly reduced IL-6 and NO release and fat accumulation, decreased lactic acid production and glucose consumption, and inhibited mammalian target of rapamycin (mTOR) and hexokinase 2 (HK2) expression in PA-treated HMC3 cells. These effects suggest that dapagliflozin reduced the mTOR/HK2-mediated aerobic glycolysis. Conclusions: Dapagliflozin improved HFD-related ovulation disorders by regulating glucose metabolism through mTOR/HK2 signaling and attenuating microglia-mediated hypothalamic inflammation. These results validate the novel role for the neuroprotection of SGLT2i in HFD-induced obesity and ovulation disorders. [ABSTRACT FROM AUTHOR]

Abstract: ZmSTK2_USP, Located on the long arm of chromosome 4, belongs to the serine/threonine kinase gene in maize. The sequence analysis of 2100 bp upstream from the start codon ATG [...]

Summary: Ubiquitination is a fundamental mechanism regulating the stability of target proteins in eukaryotes; however, the regulatory mechanism in seed longevity remains unknown. Here, we report that an uncharacterized E3 ligase, ARABIDOPSIS TÓXICOS EN LEVADURA 5 (ATL5), positively regulates seed longevity by mediating the degradation of ACTIVATOR OF BASAL TRANSCRIPTION 1 (ABT1) in Arabidopsis.Seeds in which ATL5 was disrupted showed faster accelerated aging than the wild‐type, while expressing ATL5 in atl5‐2 basically restored the defective phenotype. ATL5 was highly expressed in the embryos of seeds, and its expression could be induced by accelerated aging.A yeast two‐hybrid screen identified ABT1 as an ATL5 interacting protein, which was further confirmed by bimolecular fluorescence complementary assay and co‐immunoprecipitation analysis. In vitro and in vivo assays showed that ATL5 functions as an E3 ligase and mediates the polyubiquitination and degradation of ABT1. Disruption of ATL5 diminished the degradation of translated ABT1, and the degradation could be induced by seed ageing and occurred in a proteasome‐dependent manner. Furthermore, disruption of ABT1 enhanced seed longevity.Taken together, our study reveals that ATL5 promotes the polyubiquitination and degradation of the ABT1 protein posttranslationally and positively regulates seed longevity in Arabidopsis. [ABSTRACT FROM AUTHOR]

Background: Scalp acupuncture has been found to be effective at improving motor function after ischemic stroke, but few studies examining its central mechanisms of action have been carried out. The aim of this study was to investigate the clinical effects of scalp acupuncture on motor dysfunction and changes in spontaneous brain activity in patients with ischemic stroke. Methods: This was an evaluator- and analyst-blinded, multi-center randomized controlled trial. A total of 108 convalescent-stage ischemic stroke patients with motor dysfunction were allocated to receive either scalp acupuncture combined with rehabilitation treatment (SR group) or rehabilitation treatment alone (RE group). Patients in both groups received treatment 5 times per week for 8 weeks. The primary outcome measure was the Fugl-Meyer assessment (FMA). Secondary outcome measures included the modified Barthel index (mBI), modified Rankin scale (mRS) and values of fractional amplitude of low frequency fluctuation (fALFF) acquired using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Results: Both groups showed significant improvements in motor function, daily life ability and degree of disability, as measured by FMA, mRS and mBI (p < 0.05), and the SR group showed a significantly greater improvement (p < 0.05). Compared with the RE group, the areas where the fALFF values increased in the SR group were located in the cerebellum, praecuneus, precentral gyrus, superior frontal gyrus and parietal lobe. The improvement in FMA scores had the strongest correlation with the baseline fALFF values of the ipsilateral precentral gyrus. Conclusion: Scalp acupuncture improved motor function in convalescent-period ischemic stroke patients, and effects were correlated with regulation of motor-relevant brain regions. The fALFF value of the ipsilateral precentral and postcentral gyri could be potential clinical indices for prognostication of motor dysfunction. Trial registration number: NCT03120650 (http://www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Motor imagery training (MIT) has been widely used to improve hemiplegic upper limb function in stroke rehabilitation. The effectiveness of MIT is associated with the functional neuroplasticity of the motor network. Currently, brain activation and connectivity changes related to the motor recovery process after MIT are not well understood. Aim: We aimed to investigate the neural mechanisms of MIT in stroke rehabilitation through a longitudinal intervention study design with task‐based functional magnetic resonance imaging (fMRI) analysis. Methods: We recruited 39 stroke patients with moderate to severe upper limb motor impairment and randomly assigned them to either the MIT or control groups. Patients in the MIT group received 4 weeks of MIT therapy plus conventional rehabilitation, while the control group only received conventional rehabilitation. The assessment of Fugl‐Meyer Upper Limb Scale (FM‐UL) and Barthel Index (BI), and fMRI scanning using a passive hand movement task were conducted on all patients before and after treatment. The changes in brain activation and functional connectivity (FC) were analyzed. Pearson's correlation analysis was conducted to evaluate the association between neural functional changes and motor improvement. Results: The MIT group achieved higher improvements in FM‐UL and BI relative to the control group after the treatment. Passive movement of the affected hand evoked an abnormal bilateral activation pattern in both groups before intervention. A significant Group × Time interaction was found in the contralesional S1 and ipsilesional M1, showing a decrease of activation after intervention specifically in the MIT group, which was negatively correlated with the FM‐UL improvement. FC analysis of the ipsilesional M1 displayed the motor network reorganization within the ipsilesional hemisphere, which correlated with the motor score changes. Conclusions: MIT could help decrease the compensatory activation at both hemispheres and reshape the FC within the ipsilesional hemisphere along with functional recovery in stroke patients. [ABSTRACT FROM AUTHOR]

Emerging evidence indicates that activity flow over resting‐state network topology allows the prediction of task activations. However, previous studies have mainly adopted static, linear functional connectivity (FC) estimates as activity flow routes. It is unclear whether an intrinsic network topology that captures the dynamic nature of FC can be a better representation of activity flow routes. Moreover, the effects of between‐ versus within‐network connections and tight versus loose (using rest baseline) task contrasts on the prediction of task‐evoked activity across brain systems remain largely unknown. In this study, we first propose a probabilistic FC estimation derived from a dynamic framework as a new activity flow route. Subsequently, activity flow mapping was tested using between‐ and within‐network connections separately for each region as well as using a set of tight task contrasts. Our results showed that probabilistic FC routes substantially improved individual‐level activity flow prediction. Although it provided better group‐level prediction, the multiple regression approach was more dependent on the length of data points at the individual‐level prediction. Regardless of FC type, we consistently observed that between‐network connections showed a relatively higher prediction performance in higher‐order cognitive control than in primary sensorimotor systems. Furthermore, cognitive control systems exhibit a remarkable increase in prediction accuracy with tight task contrasts and a decrease in sensorimotor systems. This work demonstrates that probabilistic FC estimates are promising routes for activity flow mapping and also uncovers divergent influences of connectional topology and task contrasts on activity flow prediction across brain systems with different functional hierarchies. [ABSTRACT FROM AUTHOR]