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Ischemic stroke (IS) is a vascular disease group concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has been known to improve stroke, but its mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, the mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes in intestinal flora in model mice after BBR administration using 16SrRNA sequencing. Chromatography–mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes in the microglia and astroglia in the mice brains. Our findings suggest that berberine improves stroke outcomes by modulating the gut microbiota. Specifically, after MCAO/R mice were given berberine, the beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. The administration of butyric acid and an inhibitor of butyric acid synthesis, heptanoyl-CoA, showed that butyric acid improved the stroke outcomes in the model mice. In addition, butyric acid could inhibit the activation of the microglia and astrocytes in the brains of model mice, thereby inhibiting the generation of pro-inflammatory factors IL-6, IL-1β and TNF-α as well as improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment. [ABSTRACT FROM AUTHOR]

Previous studies suggested that tropical sea surface salinity (SSS) can influence tropical Pacific sea surface temperature (SST) through mixing and entrainment and thus it may be a signal for El Niño‐Southern Oscillation (ENSO) prediction. This paper explores the influence of SSS on ENSO spring predictability barrier (SPB) using an empirical dynamic model ‐ Linear Inverse Model (LIM). By coupling and decoupling SSS in the LIM, we find that tropical Pacific SSS plays a significant role in weakening both Central‐Pacific and Eastern‐Pacific ENSO SPB. The evolution of optimal initial structure also shows the importance of SSS dynamics in ENSO. We found an SSS mode that plays the dominant role in SSS impacting ENSO prediction. By the analysis of lead‐lag correlation, we find that this mode can induce easterlies during the spring, which finally leads to a La Niña‐like SST pattern in the winter through zonal advective and thermocline feedbacks. Plain Language Summary: The spring predictability barrier (SPB) is a phenomenon of forecast skill reduction of the El Niño‐Southern Oscillation (ENSO) when it comes to the boreal spring, regardless of the initial month. Sea surface salinity (SSS) can influence sea surface temperature by altering sea surface density and thus it may be a signal for ENSO prediction. Using a linear dynamical model, we find that SSS plays an important role in improving the forecast skill of ENSO and weakening SPB. We further find that SSS can induce the easterlies during the spring, which finally leads to a La Niña‐like SST pattern. Our study suggests that SSS can be used to predict ENSO about 1 year later. Key Points: A linear dynamical model suggests that taking sea surface salinity (SSS) into consideration can strongly weaken Central‐Pacific and Eastern‐Pacific El Niño‐Southern Oscillation (ENSO) spring predictability barrier (SPB)A new SSS mode is found to be important for weakening ENSO SPBThe SSS mode can predict ENSO events about 1 year earlier by inducing sea surface temperature and wind anomalies in the early spring [ABSTRACT FROM AUTHOR]

Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. Prevotella histicola is a species of Prevotella, belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of Prevotella histicola on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + Prevotella histicola group. The VaD rats (the 2VO group and 2VO + Prevotella histicola group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ Prevotella histicola group were administered with Prevotella histicola twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + Prevotella histicola group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of Prevotella histicola may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, Prevotella histicola attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of Prevotella histicola transplantation as a promising treatment of VaD. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a predictive nomogram for idiopathic rapid eye movement (REM) sleep behavior disorder (RBD) in a community population in Beijing, China. Methods: Based on the validated RBD questionnaire-Hong Kong (RBDQ-HK), we identified 78 individuals with possible RBD (pRBD) in 1,030 community residents from two communities in Beijing. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify candidate features and develop the nomogram. Internal validation was performed using bootstrap resampling. The discrimination of the nomogram was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, and the predictive accuracy was assessed via a calibration curve. Decision curve analysis (DCA) was performed to evaluate the clinical value of the model. Results: From 31 potential predictors, 7 variables were identified as the independent predictive factors and assembled into the nomogram: family history of Parkinson's disease (PD) or dementia [odds ratio (OR), 4.59; 95% confidence interval (CI), 1.35–14.45; p = 0.011], smoking (OR, 3.24; 95% CI, 1.84–5.81; p < 0.001), physical activity (≥4 times/week) (OR, 0.23; 95% CI, 0.12–0.42; p < 0.001), exposure to pesticides (OR, 3.73; 95%CI, 2.08–6.65; p < 0.001), constipation (OR, 6.25; 95% CI, 3.58–11.07; p < 0.001), depression (OR, 3.66; 95% CI, 1.96–6.75; p < 0.001), and daytime somnolence (OR, 3.28; 95% CI, 1.65–6.38; p = 0.001). The nomogram displayed good discrimination, with original AUC of 0.885 (95% CI, 0.845–0.925), while the bias-corrected concordance index (C-index) with 1,000 bootstraps was 0.876. The calibration curve and DCA indicated the high accuracy and clinical usefulness of the nomogram. Conclusions: This study proposed an effective nomogram with potential application in the individualized prediction for pRBD. [ABSTRACT FROM AUTHOR]

Detection of oligomeric α-synuclein (o-α-Syn) in red blood cells (RBCs) has been shown to be promising in diagnosing Parkinson's disease and other synucleinopathies. However, if RBC o-α-Syn derive from plasma and can reflect changes of plasma o-α-Syn remains unclear. In this study, synthetic o-α-Syn was intravenously injected into mice and dynamic changes in plasma and RBC o-α-Syn levels were investigated. Injection of o-α-Syn induced a temporary increase in plasma o-α-Syn levels, which then decreased to a relatively stable level. In contrast, levels of RBC o-α-Syn increased steadily and significantly. Besides, α-Syn-immunoreactive particles were observed in RBCs of the injected mice, suggesting that RBCs can actively take up and enrich o-α-Syn from plasma. Moreover, incubation of o-α-Syn with isolated RBCs at concentrations lower than those of endogenous o-α-Syn led to a time- and concentration-dependent o-α-Syn elevation in RBCs, which was impaired by lowering the temperature and treatment with proteinase K. The o-α-Syn accumulation in RBCs was also inhibited by specific inhibitors of receptor-dependent endocytosis, including dynamin- and clathrin-dependent endocytosis. The above results suggest that plasma o-α-Syn can be actively transported into RBCs via receptor-dependent endocytic pathways. [ABSTRACT FROM AUTHOR]

The National Center for Atmospheric Research Community Earth System Model is used to study the 'spring predictability barrier' (SPB) problem for El Niño events from the perspective of initial error growth. By conducting perfect model predictability experiments, we obtain two types of initial sea temperature errors, which often exhibit obvious season-dependent evolution and cause a significant SPB when predicting the onset of El Niño events bestriding spring. One type of initial errors possesses a sea surface temperature anomaly (SSTA) pattern with negative anomalies in the central-eastern equatorial Pacific, plus a basin-wide dipolar subsurface temperature anomaly pattern with negative anomalies in the upper layers of the eastern equatorial Pacific and positive anomalies in the lower layers of the western equatorial Pacific. The other type consists of an SSTA component with positive anomalies over the southeastern equatorial Pacific, plus a large-scale zonal dipole pattern of the subsurface temperature anomaly with positive anomalies in the upper layers of the eastern equatorial Pacific and negative anomalies in the lower layers of the central-western equatorial Pacific. Both exhibit a La Niña-like evolving mode and cause an under-prediction for Niño-3 SSTA of El Niño events. For the former initial error type, the resultant prediction errors grow in a manner similar to the behavior of the growth phase of La Niña; while for the latter initial error type, they experience a process that is similar to El Niño decay and transition to a La Niña growth phase. Both two types of initial errors cause negative prediction errors of Niño-3 SSTA for El Niño events. The prediction errors for Niño-3 SSTA are mainly due to the contribution of initial sea temperature errors in the large-error-related regions in the upper layers of the eastern tropical Pacific and/or in the lower layers of the western tropical Pacific. These regions may represent ''sensitive areas'' for El Niño-Southern Oscillation (ENSO) predictions, thereby providing information for target observations to improve the forecasting skill of ENSO. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is one of the principal causes of disability and death worldwide. Berberine (BBR), derived from the traditional Chinese herbal medicine Huang Lian, has been reported to inhibit the progression of stroke, but the specific mechanism whereby BBR modulates the progression of ischemic stroke remains unclear. N6-methyladenosine (m6A) modification is the most typical epigenetic modification of mRNA post-transcriptional modifications, among which METTL3 is the most common methylation transferase. During the study, the middle cerebral artery occlusion/reperfusion (MCAO/R) was established in mice, and the mice primary astrocytes and neurons induced by oxygen-glucose deprivation/reoxygenation (OGD/R) was simulated in vitro . Level of LncNEAT1, miR-377-3p was detected via RT-qPCR. The levels of Nampt and METTL3 were measured by Western blot. CCK8 and LDH assay was performed to detect cell viability. Here, we found that berberine alleviates MCAO/R-induced ischemic injury and up-regulates the expression of Nampt in astrocytes, miR-377-3p inhibits the expression of Nampt in astrocytes after OGD/R, thus promoting neuronal injury. NEAT1 binds to miR-377-3p in OGD/R astrocytes and plays a neuronal protective role as a ceRNA. METTL3 can enhance NEAT1 stability in OGD/R astrocytes by modulating m6A modification of NEAT1. Taken together, our results demonstrate that berberine exerts neuroprotective effects via the m6A methyltransferase METTL3, which regulates the NEAT1/miR-377-3p/Nampt axis in mouse astrocytes to ameliorate cerebral ischemia/reperfusion (I/R) injury.

Ischemic stroke (IS) is a vascular disease group concomitant with high morbidity and mortality. Berberine is a bioactive substance and it has been known to improve stroke, but its mechanism is yet to be proven. Mice were fed with BBR for 14 days. Then, the mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were detected. We tested the changes in intestinal flora in model mice after BBR administration using 16SrRNA sequencing. Chromatography-mass spectrometry was used to detect butyrate chemically. Tissue immunofluorescence was used to detect the changes in the microglia and astroglia in the mice brains. Our findings suggest that berberine improves stroke outcomes by modulating the gut microbiota. Specifically, after MCAO/R mice were given berberine, the beneficial bacteria producing butyric acid increased significantly, and the mice also had significantly higher levels of butyric acid. The administration of butyric acid and an inhibitor of butyric acid synthesis, heptanoyl-CoA, showed that butyric acid improved the stroke outcomes in the model mice. In addition, butyric acid could inhibit the activation of the microglia and astrocytes in the brains of model mice, thereby inhibiting the generation of pro-inflammatory factors IL-6, IL-1β and TNF-α as well as improving stroke outcomes. Our results suggest that berberine may improve stroke outcomes by modulating the gut flora to increase the abundance of butyric acid. These findings elucidate the mechanisms by which berberine improves stroke outcomes and provide some basis for clinical treatment.