Electrophysiological correlation of auditory selective spatial attention in the "cocktail party" situation.

The auditory system can selectively attend to the target source in complex environments, the phenomenon known as the "cocktail party" effect. However, the spatiotemporal dynamics of electrophysiological activity associated with auditory selective spatial attention (ASSA) remain largely unexplored. In this study, single-source and multiple-source paradigms were designed to simulate different auditory environments, and microstate analysis was introduced to reveal the electrophysiological correlates of ASSA. Furthermore, cortical source analysis was employed to reveal the neural activity regions of these microstates. The results showed that five microstates could explain the spatiotemporal dynamics of ASSA, ranging from MS1 to MS5. Notably, MS2 and MS3 showed significantly lower partial properties in multiple-source situations than in single-source situations, whereas MS4 had shorter durations and MS5 longer durations in multiple-source situations than in single-source situations. MS1 had insignificant differences between the two situations. Cortical source analysis showed that the activation regions of these microstates initially transferred from the right temporal cortex to the temporal-parietal cortex, and subsequently to the dorsofrontal cortex. Moreover, the neural activity of the single-source situations was greater than that of the multiple-source situations in MS2 and MS3, correlating with the N1 and P2 components, with the greatest differences observed in the superior temporal gyrus and inferior parietal lobule. These findings suggest that these specific microstates and their associated activation regions may serve as promising substrates for decoding ASSA in complex environments.

Lipin-1 deficiency deteriorates defect of fatty acid ß-oxidation and lipid-related kidney damage in diabetic kidney disease.

Diabetic lipo-toxicity is a fundamental pathophysiologic mechanism in DM and is now increasingly recognized a key determinant of DKD. Targeting lipid metabolic disorders is an important therapeutic strategy for the treatment of DM and its complications, including DKD. This study aimed to explore the molecular mechanism of lipid metabolic regulation in kidney, especially renal PTECs, and elucidate the role of lipid metabolic related molecule lipin-1 in diabetic lipid-related kidney damage. In this study, lipin-1-deficient db/db mouse model and STZ/HFD-induced T2DM mouse model were used to determine the effect of lipin-1 on DKD development. Then RPTCs and LPIN1 knockdown or overexpressed HK-2 cells induced by PA were used to investigate the mechanism. We found that the expression of lipin-1 increased early and then decreased in kidney during the progression of DKD. Glucose and lipid metabolic disorders and renal insufficiency were found in these 2 types of diabetic mouse models. Interestingly, lipin-1 deficiency might be a pathogenic driver of DKD-to-CKD transition, which could further accelerate the imbalance of renal lipid homeostasis, the dysfunction of mitochondrial and energy metabolism in PTECs. Mechanistically, lipin-1 deficiency resulted in aggravated PTECs injury to tubulointerstitial fibrosis in DKD by downregulating FAO via inhibiting PGC-1α/PPARα mediated Cpt1α/HNF4α signaling and upregulating SREBPs to promote fat synthesis. This study provided new insights into the role of lipin-1 as a regulator for maintaining lipid homeostasis in the kidney, especially PTECs, and its deficiency led to the progression of DKD.

The scalp time-varying network of auditory spatial attention in "cocktail-party" situations.

Sound source localization in "cocktail-party" situations is a remarkable ability of the human auditory system. However, the neural mechanisms underlying auditory spatial attention are still largely unknown. In this study, the "cocktail-party" situations are simulated through multiple sound sources and presented through head-related transfer functions and headphones. Furthermore, the scalp time-varying network of auditory spatial attention is constructed using the high-temporal resolution electroencephalogram, and its network properties are measured quantitatively using graph theory analysis. The results show that the time-varying network of auditory spatial attention in "cocktail-party" situations is more complex and partially different than in simple acoustic situations, especially in the early- and middle-latency periods. The network coupling strength increases continuously over time, and the network hub shifts from the posterior temporal lobe to the parietal lobe and then to the frontal lobe region. In addition, the right hemisphere has a stronger network strength for processing auditory spatial information in "cocktail-party" situations, i.e., the right hemisphere has higher clustering levels, higher transmission efficiency, and more node degrees during the early- and middle-latency periods, while this phenomenon disappears and appears symmetrically during the late-latency period. These findings reveal different network patterns and properties of auditory spatial attention in "cocktail-party" situations during different periods and demonstrate the dominance of the right hemisphere in the dynamic processing of auditory spatial information.

Activation of NRF2 Signaling Pathway Delays the Progression of Hyperuricemic Nephropathy by Reducing Oxidative Stress.

Hyperuricemia (HUA)-induced oxidative stress is a crucial contributor to hyperuricemic nephropathy (HN), but the molecular mechanisms underlying the disturbed redox homeostasis in kidneys remain elusive. Using RNA sequencing, together with biochemical analyses, we found that nuclear factor erythroid 2-related factor 2 (NRF2) expression and nuclear localization levels were increased in early HN progression and then gradually declined below the baseline level. We identified the impaired activity of the NRF2-activated antioxidant pathway as a driver of oxidative damage in HN progression. Through nrf2 deletion, we further confirmed aggravated kidney damage in nrf2 knockout HN mice compared with HN mice. In contrast, the pharmacological agonist of NRF2 improved kidney function and alleviated renal fibrosis in mice. Mechanistically, the activation of NRF2 signaling reduced oxidative stress by restoring mitochondrial homeostasis and reducing NADPH oxidase 4 (NOX4) expression in vivo or in vitro. Moreover, the activation of NRF2 promoted the expression levels of heme oxygenase 1 (HO-1) and quinone oxidoreductase 1 (NQO1) and enhanced the antioxidant capacity of cells. Furthermore, the activation of NRF2 ameliorated renal fibrosis in HN mice through the downregulation of the transforming growth factor-beta 1 (TGF-ß1) signaling pathway and ultimately delayed the progression of HN. Collectively, these results suggested NRF2 as a key regulator in improving mitochondrial homeostasis and fibrosis in renal tubular cells by reducing oxidative stress, upregulating the antioxidant signaling pathway, and downregulating the TGF-ß1 signaling pathway. The activation of NRF2 represents a promising strategy to restore redox homeostasis and combat HN.