Mitochondrial flashes (mitoflashes) are recently discovered excitable mitochondrial events in many cell types. Here we investigate their occurrence in the context of structural long-term potentiation (sLTP) at hippocampal synapses. At dendritic spines stimulated by electric pulses, glycine, or targeted glutamate uncaging, induction of sLTP is associated with a phasic occurrence of local, quantized mitochondrial activity in the form of one or a few mitoflashes, over a 30-min window. Low-dose nigericin or photoactivation that elicits mitoflashes stabilizes otherwise short-term spine enlargement into sLTP. Meanwhile, scavengers of reactive oxygen species suppress mitoflashes while blocking sLTP. With targeted photoactivation of mitoflashes, we further show that the stabilization of sLTP is effective within the critical 30-min time-window and a spatial extent of ~2 μm, similar to that of local diffusive reactive oxygen species. These findings indicate a potential signaling role of dendritic mitochondria in synaptic plasticity, and provide new insights into the cellular function of mitoflashes.

Proteinuria and decline of renal function are associated with progression of kidney disease. The Renin Angiotensin Aldosterone System (RAAS) plays an important role in blood pressure regulation, fluid volume, and sodium balance. Overactivity of RAAS contributes to the pathogenesis of a variety of clinical conditions including progress of chronic kidney disease (CKD). This review summarizes the use of RAAS inhibitors as dual therapy or monotherapy in different stages of kidney disease. Experimental and clinical studies have demonstrated RAAS inhibitors prevent proteinuria, kidney fibrosis and slow decline of renal function and thus play a protective role in both early and end stages of kidney disease. While combination use of RAAS inhibitors showed higher efficiency compared with monotherapy, it is also associated with higher incidence of adverse events. Besides ACEI/ARBs, more mechanism research of mineralocorticoid receptor antagonists in kidney disease should be performed.

In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.

Background/Aims: There is an increasing risk of end-stage renal disease (ESRD) among Asian people with immunoglobulin A nephropathy (IgAN). A computer-aided system for ESRD prediction in Asian IgAN patients has not been well studied. Methods: We retrospectively reviewed biopsy-proven IgAN patients treated at the Department of Nephrology of the Second Xiangya Hospital from January 2009 to November 2013. Demographic and clinicopathological data were obtained within 1 month of renal biopsy. A random forest (RF) model was employed to predict the ESRD status in IgAN patients. All cases were initially trained and validated, taking advantage of the out-of-bagging(OOB) error. Predictors used in the model were selected according to the Gini impurity index in the RF model and verified by logistic regression analysis. The area under the receiver operating characteristic(ROC) curve (AUC) and F-measure were used to evaluate the RF model. Results: A total of 262 IgAN patients were enrolled in this study with a median follow-up time of 4.66 years. The importance rankings of predictors of ESRD in the RF model were first obtained, indicating some of the most important predictors. Logistic regression also showed that these factors were statistically associated with ESRD status. We first trained an initial RF model using gender, age, hypertension, serum creatinine, 24-hour proteinuria and histological grading suggested by the Clinical Decision Support System for IgAN (CDSS, www.IgAN.net). This 6-predictor model achieved a F-measure of 0.8 and an AUC of 92.57%. By adding Oxford-MEST scores, this model outperformed the initial model with an improved AUC (96.1%) and F-measure (0.823). When C3 staining was incorporated, the AUC was 97.29% and F-measure increased to 0.83. Adding the estimated glomerular filtration rate (eGFR) improved the AUC to 95.45%. We also observed improved performance of the model with additional inputs of blood urea nitrogen (BUN), uric acid, hemoglobin and albumin. Conclusion: In addition to the predictors in the CDSS, Oxford-MEST scores, C3 staining and eGFR conveyed additional information for ESRD prediction in Chinese IgAN patients using a RF model.

Accurate precipitation data is crucial in many applications such as hydrology, meteorology, and ecology. Compared with ground observations, satellite-based precipitation estimates can provide much more spatial information to characterize precipitation. In this study, the satellite-based precipitation products of Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) and Tropical Rainfall Measurement Mission (TRMM) Multisatellite Precipitation Analysis (TMPA) were firstly evaluated over the Tibetan Plateau (TP) in 2015 against ground observations at both annual and monthly scales. Secondly, random forest algorithm was used to obtain the annual downscaled results (~1 km) based on IMERG and TMPA data and the downscaled results were examined against rain gauge data. Thirdly, a disaggregation algorithm was used to obtain the monthly downscaled results based on those at annual scale. The results indicated that (1) IMERG performed better than TMPA at both annual and monthly scales; (2) IMERG had few anomalies while TMPA displayed significant numbers of outliers in central and western parts of the TP; (3) random forest was a promising algorithm in acquiring high resolution precipitation data with improved accuracy; (4) the downscaled results based on IMERG had better performances than those based on TMPA.

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In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D 3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.

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