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When traditional grid-forming converters directly participate in the grid-connected operation of the power grid, due to the lack of a pre-synchronization control system, the voltage amplitude and initial phase on both sides of the grid-connected point will deviate, resulting in voltage and current distortion during grid-connected mode. An active support phase-locked loop free pre-synchronization control strategy based on the third-order model of a synchronous generator is proposed to address the grid-connected problem of the grid-forming converter mentioned above. First, a model of active support control with frequency integral feedback at small signal levels was constructed. The root locus method was employed to examine how system parameters affect the stability of the active support control system. Second, by adding phase pre-synchronization controllers and amplitude pre-synchronization controllers to the active frequency loop and excitation voltage loop of the third-order model, it was ensured that the frequency, phase, and voltage amplitude of the unit are consistent with the power grid, achieving a fast and smooth grid-connected mode of the unit. Finally, by using a DC source to simulate all types of new energy power generation equipment, the active support pre-synchronization control system based on the three-order model of synchronous generator is built in the MATLAB/Simulink simulation environment, and the accuracy and effectiveness of the control strategy in this paper is verified. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea syndrome (OSAS), characterized by chronic intermittent hypoxia (CIH), is an independent risk factor for aggravating non‐alcoholic steatohepatitis (NASH). The prevailing mouse model employed in CIH research is inadequate for the comprehensive exploration of the impact of CIH on NASH development due to reduced food intake observed in CIH‐exposed mice, which deviates from human responses. To address this issue, a pair‐feeding investigation with CIH‐exposed and normoxia‐exposed mice is conducted. It is revealed that CIH exposure aggravates DNA damage, leading to hepatic fibrosis and inflammation. The analysis of genome‐wide association study (GWAS) data also discloses the association between Eepd1, a DNA repair enzyme, and OSAS. Furthermore, it is revealed that CIH triggered selective autophagy, leading to the autophagic degradation of Eepd1, thereby exacerbating DNA damage in hepatocytes. Notably, Eepd1 liver‐specific knockout mice exhibit aggravated hepatic DNA damage and further progression of NASH. To identify a therapeutic approach for CIH‐induced NASH, a drug screening is conducted and it is found that Retigabine dihydrochloride suppresses CIH‐mediated Eepd1 degradation, leading to alleviated DNA damage in hepatocytes. These findings imply that targeting CIH‐mediated Eepd1 degradation can be an adjunctive approach in the treatment of NASH exacerbated by OSAS. [ABSTRACT FROM AUTHOR]

Introduction: Lysosomes are degradative organelles that maintain cellular homeostasis and protein quality control. Transcription factor EB (TFEB)–mediated lysosome biogenesis enhances lysosome‐dependent degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB regulation and modification are still poorly understood. Methods: By screening novel small‐molecule compounds, we identified a group of lysosome‐enhancing compounds (LYECs) that promote TFEB activation and lysosome biogenesis. Results: One of these compounds, LH2‐051, significantly inhibited the function of the dopamine transporter (DAT) and subsequently promoted lysosome biogenesis. We uncovered cyclin‐dependent kinase 9 (CDK9) as a novel regulator of DAT‐mediated lysosome biogenesis and identified six novel CDK9‐phosphorylated sites on TFEB. We observed that signal transduction by the DAT‐CDK9‐TFEB axis occurs on lysosomes. Finally, we found that LH2‐051 enhanced the degradation of amyloid beta plaques and improved the memory of amyloid precursor protein (APP)/Presenilin 1 (PS1) mice. Discussion: We identified the DAT‐CDK9‐TFEB signaling axis as a novel regulator of lysosome biogenesis. Our study sheds light on the mechanisms of protein quality control under pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Background: Acute cerebral infarction (ACI) is one of the most common ischemic cerebrovascular diseases in neurology, with high morbidity, mortality, and disability. Early thrombolytic treatment of ACI has significant efficacy, but intraprocedural complications of hypoxemia can significantly reduce the efficacy. This study aims to analyze the risk factors for intraprocedural hypoxemia in patients with ACI, so as to take effective measures in advance to reduce the likelihood of adverse patient outcomes., Methods: We retrospectively analyzed a total of 238 patients with ACI treated with vascular interventions from May 2017 to May 2022. To assess and collate the patients' characteristics, factors associated with the development of intraprocedural hypoxemia. The independent risk factors for the development of intraprocedural hypoxemia were analyzed by binary logistic regression., Results: A total of 238 patients were included in this study. Of these, intraprocedural hypoxemia occurred in 89 (37.4%). The results showed that old age (odds ratio [OR] = 2.666, P = 0.009), obesity (OR = 3.029, P = 0.003), smoking history (OR = 2.655, P = 0.010), preoperative oxygen saturation (SpO 2 ) (OR = 0.001, P = 0.042), preoperative C-reactive protein (OR = 1.216, P = 0.002), and time from puncture to vascular recanalization (OR = 1.135, P = 0.000) were independent risk factors for intraprocedural hypoxemia in patients. The prognosis of the patients was assessed according to the modified Rankin scale, and the prognosis of the nonhypoxemia group was significantly better than that of the hypoxemia group. Regression analysis showed that intraprocedural hypoxemia (OR = 0.360, P = 0.001), postoperative lower extremity vein thrombosis (OR = 0.187, P = 0.018), hydrocephalus (OR = 0.069, P = 0.015), intracranial hemorrhage (OR = 0.116, P = 0.002), and reocclusion (OR = 0.217, P = 0.036) were independent risk factors for poor prognosis., Conclusions: Currently, intravascular hypoxemia in patients with ACI has a serious impact on prognosis. Clinical work should attach great importance to the clinical characteristics of patients, identify relevant risk factors, and aggressively take personalized therapeutic actions to improve patients' prognosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Brain Circulation.)

Twenty-eight imidazo[1,2- c ]pyrimidin-5(6 H )-one nucleoside derivatives incorporating a sulfonamide scaffold with preferable inactivating activities on pepper mild mottle virus (PMMoV) were designed and synthesized. Then, compound B29 with illustrious inactivating activity against PMMoV was received on the basis of the three-dimensional quantitative structure-activity relationship (3D-QSAR) model, with the EC 50 of 11.4 μg/mL, which was superior to ningnanmycin (65.8 μg/mL) and template molecule B16 (15.3 μg/mL). Furthermore, (1) transmission electron microscopy (TEM) indicated that B29 could cause severe fracture of virions; (2) microscale thermophoresis (MST) and molecular docking further demonstrated that B29 had faintish binding affinities with PMMoV CP R62A ( K d = 202.84 μM), PMMoV CP L144A ( K d = 141.57 μM), and PMMoV CP R62A,L144A ( K d = 332.06 μM) compared to PMMoV CP ( K d = 4.76 μM); and (3) western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results of pCB-GFP-PMMoV CP R62A , pCB-GFP-PMMoV CP L144A , and pCB-GFP-PMMoV CP R62A,L144A were consistent with MST and confocal. In brief, the above results indicated that the amino acids at positions 62 and 144 of PMMoV CP might be the key amino acid sites of B29 acted on.

Introduction: Lysosomes are degradative organelles that maintain cellular homeostasis and protein quality control. Transcription factor EB (TFEB)-mediated lysosome biogenesis enhances lysosome-dependent degradation and alleviates neurodegenerative diseases, but the mechanisms underlying TFEB regulation and modification are still poorly understood., Methods: By screening novel small-molecule compounds, we identified a group of lysosome-enhancing compounds (LYECs) that promote TFEB activation and lysosome biogenesis., Results: One of these compounds, LH2-051, significantly inhibited the function of the dopamine transporter (DAT) and subsequently promoted lysosome biogenesis. We uncovered cyclin-dependent kinase 9 (CDK9) as a novel regulator of DAT-mediated lysosome biogenesis and identified six novel CDK9-phosphorylated sites on TFEB. We observed that signal transduction by the DAT-CDK9-TFEB axis occurs on lysosomes. Finally, we found that LH2-051 enhanced the degradation of amyloid beta plaques and improved the memory of amyloid precursor protein (APP)/Presenilin 1 (PS1) mice., Discussion: We identified the DAT-CDK9-TFEB signaling axis as a novel regulator of lysosome biogenesis. Our study sheds light on the mechanisms of protein quality control under pathophysiological conditions., (© 2022 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)