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This paper comprehensively perfects the sensitive node transient detection feedback latch (SNTDFL) technique, subsequently conceptualizes an ideal hardening structure for the pre‐amplification stage, and proposes a radiation hardened by design (RHBD) strategy to cope with the severe single‐event transient (SET) effects of high‐precision voltage comparators in a space radiation environment. Analysis and verification results show that the hardening strategy exhibits excellent SET hardening performance, which can not only detect extremely small transient voltage disturbances at sensitive nodes but also effectively resist transient current pulses of various intensities generated by SETs. Compared with an unhardened high‐precision comparator, the proposed one, hardened with a hybrid strategy of SNTDFL and triple modular redundancy (TMR) techniques, can greatly preserve the original electrical properties and remarkably improve the tolerance of SET with little overhead. In addition, the proposed high‐precision comparator significantly reduces static power consumption compared with the one hardened with the TMR technique alone and has a smaller area overhead. [ABSTRACT FROM AUTHOR]

Impaired extinction of fear memory is one of the most common symptoms in post‐traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD‐ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle‐based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD‐related impaired extinction of fear memory and provide therapeutic insights into Kv3.2‐targeted RNA therapy for PTSD. [ABSTRACT FROM AUTHOR]

Summary: To reduce the impact of the single‐event transient (SET) effect on the high‐precision comparator, based on the common high‐gain pre‐amplification stage structure of the comparator, a new radiation hardened by design (RHBD) method, namely, the sensitive node transient detection feedback latch (SNTDFL) technique, is proposed. The hardening technique avoids comparator erroneous output by detecting the sensitive nodes of the high‐gain pre‐amplification stage. The detection circuit receives the response generated by the high energy particle impacts and feeds the high level back to the sensitive nodes to latch the current comparator state. In this paper, a novel high‐precision SET hardened voltage comparator based on this technique is developed. Through detailed circuit principle and simulation analysis, the functional characteristics and the hardening performance of the high‐precision hardened comparator are verified. Compared with the unhardened and the TMR technique hardened comparator, the SNTDFL technique hardened comparator effectively avoids the erroneous output caused by the SET effect with less overhead and still has excellent functional characteristics. [ABSTRACT FROM AUTHOR]

Summary: In this paper, a highly stable and low‐cost 12T (HSLC12T) radiation hardened static‐random‐access‐memories (SRAM) cell is proposed in 55 nm CMOS technology. Based on polarity reversal design and read/write separation structure, the proposed HSLC12T cell can recover from any single event upsets (SEUs) induced at all its sensitive nodes and even single event double‐node‐upsets (SEDNUs) induced at its internal storage node pair Q‐QN, while also having the maximum read static noise margin (RSNM) and lower static hold power, as well as excellent write speed and write‐ability. Though the HSLC12T cell exhibits a larger read delay, it has the best overall performance of all other cells. This is proven by having the highest electrical quality metric (EQM) value, thus making the proposed HSLC12T cell a better choice for aerospace applications. [ABSTRACT FROM AUTHOR]

Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus. [Display omitted] • Quercetin ameliorated memory impairment induced by PSD stress in a dose-dependent manner. • Quercetin restored the dynamics of the gamma band in PSD mice while the mice performed novel object recognition. • Quercetin significantly alleviated microglia activation caused by PSD. • Quercetin inhibited the abnormal activation of microglia by suppressing the TLR4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Aging is a natural and complex biological process that is associated with widespread functional declines in numerous physiological processes, terminally affecting multiple organs and tissues. Fibrosis and neurodegenerative diseases (NDs) often occur with aging, imposing large burdens on public health worldwide, and there are currently no effective treatment strategies for these diseases. Mitochondrial sirtuins (SIRT3-5), which are members of the sirtuin family of NAD + -dependent deacylases and ADP-ribosyltransferases, are capable of regulating mitochondrial function by modifying mitochondrial proteins that participate in the regulation of cell survival under various physiological and pathological conditions. A growing body of evidence has revealed that SIRT3-5 exert protective effects against fibrosis in multiple organs and tissues, including the heart, liver, and kidney. SIRT3-5 are also involved in multiple age-related NDs, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Furthermore, SIRT3-5 have been noted as promising targets for antifibrotic therapies and the treatment of NDs. This review systematically highlights recent advances in knowledge regarding the role of SIRT3-5 in fibrosis and NDs and discusses SIRT3-5 as therapeutic targets for NDs and fibrosis.

Posttraumatic stress disorder (PTSD) is a highly prevalent and debilitating psychiatric disease often accompanied by severe defensive behaviors, preventing individuals from integrating into society. However, the neural mechanisms of defensiveness in PTSD remain largely unknown. Here, we identified that the higher-order thalamus, the posteromedial complex of the thalamus (PoM), was overactivated in a mouse model of PTSD, and suppressing PoM activity alleviated excessive defensive behaviors. Moreover, we found that diminished thalamic inhibition derived from the thalamic reticular nucleus was the major cause of thalamic hyperactivity in PTSD mice. Overloaded thalamic innervation to the downstream cortical area, frontal association cortex, drove abnormal defensiveness. Overall, our study revealed that the malfunction of the higher-order thalamus mediates defensive behaviors and highlighted the thalamocortical circuit as a potential target for treating PTSD-related overreactivity symptoms.

Objective: This study aimed to analyze the characteristics of patients with pericardial effusion requiring pericardiocentesis and to evaluate the safety of pericardiocentesis without discontinuation of anticoagulant or antiplatelet drugs., Methods: We performed a retrospective study of patients undergoing pericardiocentesis in our hospital between 2012 and 2022. Patients were categorized into the Antithrombotic Group if they had used any antiplatelet or anticoagulant drugs on the day of pericardiocentesis; otherwise they were categorized into the Non-antithrombotic Group. All procedures were performed by experienced cardiologists with echocardiographic guidance. Bleeding events were defined using the National Institutes of Health scale of adverse events., Results: A total of 501 consecutive patients were identified and 70 cases were under antithrombotic drugs (Antithrombotic Group). Patients in Antithrombotic Group were older, had more comorbidities, presented with lower platelet counts and prolonged activated partial thromboplastin time (all p < 0.05). Malignancy was the most common etiology for pericardial effusion in both groups (28.6% in Antithrombotic Group and 54.7% in Non-antithrombotic Group) and tuberculosis was the second etiology in the Non-antithrombotic Group (21.9%), while procedure-related effusion (17.1%) accounted for the second cause in the Antithrombotic Group. Two patients in the Antithrombotic Group had mild oozing at the puncture site that resolved without interventions (2.9 vs. 0%, p = 0.019), and no bleeding events higher than Grade 1 occurred in either group., Conclusion: Although antiplatelet or anticoagulant drugs may put patients undergoing pericardiocentesis at theoretically higher risk of bleeding, our study demonstrated that they are not associated with increased major bleeding complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Zhang, Xie, Sasmita, Xiang, Jiang, Gong, Wang, Chen, Luo and Huang.)