Long-duration spaceflight characterized by microgravity adversely affects operator proficiency postlanding, yet the mechanisms by which microgravity induces cerebral dysfunction refractory to short-term recovery among astronauts remain poorly defined. Here, we demonstrate that simulated microgravity (SMG) leads to chronic behavior disorders and cognitive deficits via a microbiota-metabolite-brain axis. Fecal microbiota transplantation (FMT) from long-term SMG-treated donor rats to recipients (n = 5 per group) under normal gravity (NG) induces anxiety-like behaviors and spatial working memory disturbances by impairing synaptic plasticity in the hippocampus, reproducing the phenotype of SMG-exposed rats. SMG destroys intestinal barriers and alters the gut microbiota to a proinflammatory state with an increased abundance of Proteobacteria but decreased production of linoleic acid (LA) and LA-derived metabolites, which is highly associated with neuroinflammation in the hippocampus. Mechanistically, LA can be taken up by the hippocampus under NG conditions, and then block inflammatory microglial activation by interacting with signal transducer and activator of transcription 1 (STAT1) and inhibiting its phosphorylation at Tyr 701 and Ser 727. However, the Proteobacteria, especially Pseudomonas aeruginosa, tend to be the dominant phylum in gut microbiota under SMG conditions and consume large amounts of LA, breaking LA-dependent immune homeostasis in the central nervous system (CNS). Dietary supplementation with LA significantly mitigated SMG-induced neuroinflammation and cognitive impairment. Taken together, our findings in SD rats models reveal a critical role for gut microbiota dysbiosis in simulated microgravity-associated encephalopathy, offering a novel strategy for LA replenishment to improve brain function during spaceflight.

Atherosclerosis and aortic aneurysms are prevalent aortic disorders. Significantly, atherosclerosis frequently impacts the common carotid artery (CA), whereas aortic aneurysms typically involve the abdominal aorta (AA), indicating possible heterogeneity between CA and AA with an ambiguous underlying mechanism. Sphingolipids, a crucial branch of lipid metabolism, has increasingly garnered attention in vascular diseases by influencing the phenotypic regulation of vascular smooth muscle cells (VSMCs). Nevertheless, whether sphingolipids play a role in the heterogeneity between CA and AA and in disease susceptibility remains uncertain. Public transcriptomics were employed to clarify the distinctions in contractility and calcification of VSMCs in relation to the vulnerability of human AA and CA to aortic aneurysms and atherosclerosis, respectively. Bulk RNA-seq revealed transcriptomic variances in the biology of VSMCs between AA and CA from rats. Primary VSMCs from AA (AASMC) and CA (CASMC) were isolated for further validation. The specific variations in sphingolipid metabolism (comprising 8 classes of sphingolipids with 169 species) between AA and CA from rats were further characterized using UPLC–QTOF-MS-based lipidomics. Most sphingolipids, except sphingomyelin, were significantly elevated in CA compared to AA. Ceramides were the major contributor to these differences, which was further confirmed by in situ immunofluorescence of AA and CA from rats and healthy humans. The differential expression of genes involved in ceramide biosynthesis (Cers1-4), transport (Cert1), and metabolic processes (Smpd1, Sgpp1, Sphk2, and Sgms1/2), along with variations in subcellular organelles in VSMCs, contributed to the heterogeneity of sphingolipid metabolism between AA and CA. The effects of ceramides on VSMC biology were subsequently assessed using primary VSMCs. Specifically, AASMC exhibited greater contractility and lower susceptibility to calcification compared to CASMC. Exogenous ceramides heightened the susceptibility to calcification in both CASMC and AASMC, whereas the inhibition of ceramide synthases engendered an opposing consequence. Notably, in CA from patients with atherosclerosis but not AA from aortic aneurysms, the activation of sphingolipid metabolism (including ceramides) was positively correlated with calcification and negatively correlated with the regulatory processes of VSMC contraction. Furthermore, the ceramide metabolism was activated along with calcification in CA, which corresponded with the accumulation of ceramide in atherosclerotic plaques of human. In this study, we identified ceramides, a major class of sphingolipid metabolites, as a promising determinant in unequal biology and susceptibility to calcification of CA and AA. Our results reveal the previously unappreciated role of sphingolipid metabolism, particularly ceramides, in regional vascular pathology. These findings provide novel insights that inform our understanding of disease mechanisms and highlight potential ways for future therapeutic exploration. Sphingolipids' role in vascular heterogeneity between common carotid artery (CA) and abdominal aorta (AA) have been elucidated through a comprehensive approach involving public transcriptomics, RNA sequencing, and lipidomics. Ceramides, key in sphingolipid metabolism, modulate contractility and calcification differences in vascular smooth muscle cells (VSMCs) between CA and AA.

Real or simulated microgravity induces a senescence-like modification of carotid artery in both human and animal observations, with the mechanisms not fully elucidated. Here, we aim to elucidate the role of sterol regulatory element-binding protein 1 (SREBP1, encoded by Srebf1) mediated lipogenesis in the process. Pharmacological activation of SREBP1 directly triggers senescence-like transformation in vascular smooth muscle cells (VSMC), while silencing Srebf1 exerts an opposite effect. Mechanistically, SREBP1-mediated lipogenesis upregulates acetyl-CoA pool to increase histone acetylation, modifying the chromatin accessibility which limiting recruitment of SRF/myocardin complexes to CArG boxes of contractile genes and opening the chromatin accessibility of aging genes. Srebf1 knockdown and local delivery of lentivirus or AAV-mediated VSMC specific expressing sh-Srebf1 significantly attenuates the senescence-like transformation of VSMC both in vitro and in vivo. Our findings reveal a previously unrecognized feature of SREBP1-mediated lipogenesis in vascular biology and SM-induced carotid artery remodeling. Microgravity triggers carotid artery aging via SREBP1. This lipid regulator remodels chromatin by boosting acetyl-CoA, silencing contractile genes while activating aging pathways. Targeting SREBP1 blocks senescence, revealing a therapeutic strategy for spaceflight-associated vascular remodeling.

Background:Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM.Methods:Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed.Results:The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic.Conclusion:SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.

Background: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1. Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early. Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP). Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA. Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.

Although haemoglobin is a known carrier of oxygen in erythrocytes that functions to transport oxygen over a long range, its physiological roles outside erythrocytes are largely elusive 1 , 2 . Here we found that chondrocytes produced massive amounts of haemoglobin to form eosin-positive bodies in their cytoplasm. The haemoglobin body (Hedy) is a membraneless condensate characterized by phase separation. Production of haemoglobin in chondrocytes is controlled by hypoxia and is dependent on KLF1 rather than the HIF1/2α pathway. Deletion of haemoglobin in chondrocytes leads to Hedy loss along with severe hypoxia, enhanced glycolysis and extensive cell death in the centre of cartilaginous tissue, which is attributed to the loss of the Hedy-controlled oxygen supply under hypoxic conditions. These results demonstrate an extra-erythrocyte role of haemoglobin in chondrocytes, and uncover a heretofore unrecognized mechanism in which chondrocytes survive a hypoxic environment through Hedy.

Background and objectiveSudden unexpected death in epilepsy (SUDEP) has been regarded as a leading cause of premature death in patients with epilepsy (PWE). Although patients, relatives and caregivers have the right to be informed of SUDEP, neurologists prefer not to release the facts for fear of associated anxiety. In the study, a Chinese questionnaire survey was carried out to elucidate effect of SUDEP disclosure on anxiety in PWE and variables determining the anxiety of patients and provided suggestions for SUDEP disclosure.MethodsA survey study in China was conducted. We recruited 305 PWE from 3 tertiary epilepsy centers who attended outpatient clinic from December 2021 to February 2022. Two hundred and thirty-two PWE completed the screening evaluation, survey and Hamilton anxiety rating scale (HAMA) twice with 171 PWE completing third HAMA at follow-up. HAMA scores at baseline, T1, T2 were compared using analysis of variance and dependent samples t-test. The variables related to anxiety were screened out by univariate analysis and used for multivariate logistic regression.ResultWe found 127 (54.7%) among the 232 participants experienced anxiety after SUDEP disclosure. HAMA scores at T1 were significantly higher than at baseline and T2, while there was no statistical difference between baseline and T2. Medical insurance, seizure severity, and whether the PWE supported SUDEP being disclosed to their relatives and caregivers only were associated with the occurrence of anxiety.ConclusionSUDEP disclosures may cause short-term acute anxiety, but have no long-term effects in PWE. Acute anxiety caused by SUDEP disclosure may be more common in PWE with NCMI and severe seizures. Meanwhile, compared with indirect SUDEP disclosure to their relatives and caregivers, direct SUDEP disclosure to PWE reduces the risk of anxiety. Recommendations are provided to avoid anxiety caused by SUDEP disclosure.

睡眠是人体必需的生命活动,良好的睡眠有助于β-淀粉样蛋白、腺苷和毒素等代谢物的清除、脑力和体力恢复.随着社会高速发展,睡眠障碍的发生率迅速增高,同时,心血管疾病的比例及严重程度也显著增加,并与睡眠障碍有密切关系,其机制涉及下丘脑、交感神经、脑干网状结构、免疫系统和激素等神经-体液因素,本文总结了二者关系、作用机制及相关治疗研究进展.

青少年肌阵挛性癫痫(juvenile myoclonic epilepsy,JME)是一种从青春期开始的终生疾病.JME患者的认知水平下降,异常的网络连接被认为是引起认知功能障碍的原因.基于功能磁共振成像(functional magnetic resonance imaging,fMRI)的研究对揭示JME患者脑功能网络异常及认知功能障碍已取得显著成果,在阐明JME生理病理方面具有重大潜力.功能网络连接研究阐明了JME患者脑网络的改变并帮助理解JME的神经机制.非传统脑电-功能磁共振成像(electroencephalography-functional magnetic resonance imaging,EEG-fMRI)联合研究EEG的动态网络相关联的血氧水平依赖(blood oxygen level dependent,BOLD)活动,从新的角度揭示JME神经机制.JME内表型的fMRI研究可帮助提供临床特征和潜在遗传特征之间的联系.本文将对fMRI在JME脑网络、EEG的动态网络相关联的BOLD活动及内表型研究进展进行综述.

目的 研究四周尾部悬吊模拟失重大鼠胸主动脉(thoracic aorta,TA)和腹主动脉(abdominal aorta,AA)溶酶体相关分子的基因和蛋白表达改变.方法 采用4周尾部悬吊大鼠模拟失重对心血管系统的影响,通过Western blot技术、免疫组织化学染色和实时定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)检测溶酶体相关膜蛋白1(lysosomal associated membrane protein 1,LAMP1),调控溶酶体合成的转录因子EB(transcription factor EB,TFEB)、转录因子 E3(transcription factor E3,TFE3)以及溶酶体相关基因包括 LAMP1、酸性神经酰胺酶(N-acylsphingosine amidohydrolase 1,ASAH1)、液泡型 ATP 酶转运协助蛋白 1(adenosine triphosphatase(ATPase)H+transporting accessory protein 1,ATP6AP1)、液泡型 ATP 酶 H 亚基(ATPase H+transporting V1 subunit H,ATP6V1H)以及粘脂蛋白 1(mucolipin 1,MCOLN1)的蛋白表达、分布和 mRNA 水平变化.结果 Western blot 显示,与对照(control,CTR)组相比,悬吊(hindlimb unloading tail suspension,HU)组大鼠TA和AA的LAMP1蛋白表达均显著降低(P＜0.05).免疫组化则显示LAMP1主要分布于TA和AA的内膜和中膜;CTR大鼠TA内膜、中膜的LAMP1蛋白表达均显著高于AA(P＜0.05);与CTR组相比,HU组大鼠TA、AA内膜LAMP1表达无明显变化,但在TA中膜呈现均匀的表达降低,而在AA中膜则呈现不均匀的表达降低(P＜0.05);qRT-PCR显示,与CTR组比较,溶酶体相关基因表达在HU组大鼠TA显著增加(P＜0.05),但在AA则显著降低(P＜0.05).转录因子TFEB和TFE3呈现与溶酶体相关基因相同变化,蛋白表达在HU组大鼠TA和AA中均显著降低(P＜0.05),但基因表达在TA增加,在AA降低(P＜0.05).结论 HU组大鼠TA和AA溶酶体相关蛋白表达均降低,但基因转录及转录因子表达呈现部位特异性改变,可能参与动脉重塑过程.

Objective To analyze the risk factors inducing hyperuricemia (HUA) in helicopter pilots and put forward the corresponding intervention measures. Methods A total of 190 male helicopter pilots, aged 20-50 years and with more than 100 hours of flight time, were recruited from April to October 2020 in a flight brigade. A self-designed questionnaire was used, by which the basic information of subjects were collected including eating habits, physical exercise, smoking and drinking, exposure to noise and vibration at work, mood, disease, work performance, sleep status, genetic factors, and so on. At the same time, 28 SPF grade 6-week-old male C57BL/6J mice were randomly divided into 7 groups (4 each): control group, noise group, noise + vitamin C (Vit C) group, noise + multivitamin (Multi Vit) group, noise + hyperbaric oxygen (HBO) group, noise + HBO + Vit C group, and noise + HBO + Multi Vit group. After continuous intervention for 7 days, Multiskan Ascent was used to detect the uric acid (UA) level in mice sera. Results Finally, 186 subjects, aged 22-50 years and with (1378±569) hours of flight time, were included in present study. Of whom 17 (9.14%) were self-reported with HUA (HUA group) and 169 (9.14%) were with normal uric acid (NUA group). No significant difference existed between the two groups in age, height, body mass index and the proportion of hyperglycemia. The proportions of hyperlipidemia and fatty liver were significantly higher in HUA group (17.6% and 29.4%, respectively) than those in NUA group (4.7% and 10.1%, respectively) with statistically significant difference (P 0.05) in the other 8 dimensions. Noise and vibration exposure were closely related to the occurrence of HUA. Among them, strong noise and long daily exposure, great influence on emotion, the poor effect and low use frequency of protective measures would significantly increase the risk of HUA; Long daily exposure and great influence on emotion of vibration would also increase the risk of HUA. Compared with the control group, the serum UA level in noise group increased significantly [(38.710±10.201) μmol/L vs. (191.935±9.542) μmol/L] with significant difference (P 0.05). Conclusions HUA in helicopter pilots is related to noise and vibration exposure in working environment. Hyperbaric oxygen and dietary vitamin supplementation can effectively reduce the increase of serum uric acid level caused by noise exposure. DOI: 10.11855/j.issn.0577-7402.2021.02.08

目的 研究某新型运输机(简称A)和已列装运输机(简称B)飞行人员本场及长航时飞行作业负荷特点规律,为制定相关的航卫保障措施提供参考依据.方法 采用自认劳累负荷量表(RPE)、斯坦福嗜睡感量表(SSS)、NASA任务负荷指数(NASA-TLX)结合心率监测及心率变异性分析的方法,以32名两型运输机飞行人员(A13人,B19人)为研究对象,于飞行前、中、后开展主观负荷程度、生理参数的变化情况分析比较,探讨两型运输机飞行人员的作业负荷变化特点.结果 飞行后,两型运输机飞行人员RPE、SSS评分增加非常显著(P<0.01),着陆阶段NASA-TLX评分非常显著高于其他飞行阶段(P＜0.01).飞行中,A型运输机飞行人员心率变异性指标RMSSD、VLF、HFnorm显著低于B型运输机飞行人员(P＜0.05),LFnorm、LF/HF非常显著高于B型运输机飞行人员(P＜0.01),A型运输机飞行人员各心率值显著高于B型运输机飞行人员(P＜0.05).不同飞行阶段中,着陆阶段飞行人员VLF、TP显著高于起飞阶段(P＜0.05),巡航阶段各心率值显著低于起飞、着陆阶段(P＜0.05).结论 两型运输机飞行人员的作业负荷具有共性,精神紧张度在巡航阶段均减轻,着陆阶段均增加;但A型运输机飞行人员心率、交感神经张力、精神紧张度均高于B型,提示现阶段A型运输机飞行人员的作业负荷强度高于B型运输机飞行人员.

OBJECTIVE:Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects.METHODS:Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining.RESULTS:HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism.CONCLUSION:These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo.

Aims: Weightlessness exposure conduces to substantial vascular remodeling, mechanisms behind which remain unclear. Acid sphingomyelinase (ASM) catalyzed ceramide (Cer) generation accounts for multiple vascular disorders, so the role of it in adjustment of cerebral artery (CA) and small mesenteric artery (MA) was investigated in simulated weightless rats. Main methods: Rats were hindlimb unloaded tail suspended (HU) to simulate the effect of weightlessness. Arterial morphology was examined by hematoxylin-eosin staining. Cer abundance was measured by immunohistochemistry. Western blotting was used to detect protein content. Apoptosis was detected by transferase-mediated dUTP nick end labeling. Key findings: During 4 weeks of tail suspension, intima-media thickness (IMT) and media cross section area (CSA) were increased gradually in CA but decreased gradually in MA (P < 0.05). Correspondingly, the apoptosis and proliferation of vascular smooth muscle cells were reduced and enhanced respectively in CA (P < 0.05), while promoted and restrained in MA (P < 0.05). As compared to control, both ASM protein expression and Cer content were lowered in CA and elevated in MA of HU rats (P < 0.05). Permeable Cer incubation reversed the change of apoptosis and proliferation in CA of HU rats, while ASM inhibition recapitulated it in control rats. On the contrary, ASM inhibitors restored the alteration of apoptosis and proliferation in MA of HU. Significance: The results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer exerts an important role in structural adaptation of CA and MA to simulated weightlessness.

Noise exposure relates to various pathological disorders including liver damage, preventive measures of which are being demanded. Hyperbaric oxygen treatment (HBOT), as a non-invasive procedure, exerts convincing therapeutic potency on multiple liver diseases. The efficacy of HBOT in mitigating noise induced liver damage (NILD) and associated mechanisms would be elucidated here. Mice were subject to broad band noise (20-20k Hz, 90-110 dB) for 5 days by 3 hours/day. HBOT with 2.5 atmosphere absolute (ata) was employed before noise exposure. Morphology of liver tissue was examined by hematoxylin-eosin (HE) staining. Oil Red O (ORO), transferase-mediated dUTP nick end labelling (TUNEL) test and western blot were utilized to detect lipid accumulation, apoptotic cells and protein expression, respectively. Ceramide (Cer) level was assayed by immunohistochemistry (IHC) analysis. With noise exposure, conspicuous structural derangement and lipid deposition occurred in liver tissue of mice, which was alleviated significantly by the application of HBOT. Meanwhile, HBOT reduced the proportion of apoptotic hepatocytes, restraining the superoxide production in noise exposed mice. In view of underlying mechanisms, noise enhanced the acid sphingomyelinase (ASM) protein expression and the Cer generation in liver tissue of mice which was reversed substantially by HBOT. Altogether, HBOT ameliorates the structural and functional derangement of liver by neutralizing the ASM/Cer pathway in noise exposed mice.

目的 研究尾部悬吊模拟失重大鼠颈总动脉(carotid aorta,CA)平滑肌细胞溶酶体数量、分布及相关分子的基因和蛋白表达改变.方法 采用4周尾部悬吊大鼠模拟失重对心血管系统的影响,通过电镜、Western blot技术、免疫组织化学染色和实时定量聚合酶链反应(quantitative real-time polymerase chain reaction,qRT-PCR)检测CA平滑肌细胞溶酶体数量和分布、溶酶体相关膜蛋白(lysosomal associated membrane protein,LAMP)1,驱动蛋白kinesin-1,转录因子(transcription factor,TF)EB、TFE3以及溶酶体相关基因的蛋白表达、分布和mRNA水平变化.结果 电镜结果显示,与对照(control,CTR)组相比,悬吊(hindlimb unloading tail suspension,HU)组大鼠CA平滑肌细胞溶酶体数量明显减少;Western blot和免疫组化则显示CA的LAMP1蛋白表达显著降低(P＜0.05),且主要为中膜改变(P＜0.05),内膜无明显变化;kinesin-1蛋白表达显著增加(P＜0.05).qRT-PCR显示,溶酶体相关基因表达显著增加(P＜0.05).与CTR相比,TFEB和TFE3蛋白表达在HU大鼠CA中显著降低(P＜0.05),基因表达显著增加(P＜0.05).结论 HU大鼠CA平滑肌细胞溶酶体数量减少,相关蛋白表达降低,但基因转录水平增加,可能参与动脉重构改变.

Military flying labor hygiene is a discipline that focuses on influences of special flight environment and labor condition on human body and related prevent measures,with the core of flight fatigue.Health information and technique training can help flight surgeons to enhance professional competency and improve the prevention and recovery of military flying fatigue.The course construction of teaching system in this study included survey of demand,arrangement of content,identification of strategy,determination of evaluation,and feedback of results.Meanwhile,the textbook compilation,cultivation of teaching team and construction of laboratory were also needed.After a 4-year practice,a formal teaching system has been established and its teaching effectiveness has basically fulfilled the professional requirement for flight surgeons.

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP's curative effect on hearing loss and neuronal damage in noise-exposed mice.

Previous studies have demonstrated cardiac and vascular remodeling induced by microgravity exposure. Yet, as the most important branch of vasculatures circulating the heart, the coronary artery has been seldomly studied about its adaptations under microgravity conditions. Large‐conductance Ca2+‐activated potassium channel (BKCa) and the Ras homolog family member A (RhoA)/Rho kinase (ROCK) pathway play key roles in control of vascular tone and mediation of microgravity‐induced vascular adjustments. Therefore, we investigated the adaptation of coronary vasoreactivity to simulated microgravity and the role of BKCa and the RhoA/ROCK pathway in it. Four‐week‐old hind‐limb unweighted (HU) rats were adopted to simulate effects of microgravity. Right coronary artery (RCA) constriction was measured by isometric force recording. The activity and expression of BKCa and the RhoA/ROCK pathway were examined by Western blot, patch‐clamp recordings, and immunoprecipitation. We found HU significantly decreased RCA vasoconstriction to KCl, serotonin, and U‐46619, but increased protein expression and current densities of BKCa, inhibition of which by iberiotoxin (IBTX) further decreased RCA vasoconstriction (P < 0.05). Expression of RhoA and ROCK as well as active RhoA and phosphorylation of myosin light chain (MLC) at Ser19 and MLC phosphatase target‐1 at Thr696 were significantly increased by HU, and ROCK inhibitor Y‐27632 exerted greater suppressing effect on HU RCA vasoconstriction than that of control (P < 0.05). BKCa opener NS1619 increased HU RCA vasoconstriction, which was blocked by both RhoA and ROCK inhibitor, similar to the effect of IBTX. These results indicate that HU impairs coronary vasoconstriction but enhances BKCa activity acting as a protective mechanism avoiding excessive decrease of coronary vasoreactivity through activation of the RhoA/ROCK pathway.—Wu, Y., Yue, Z., Wang Q., Lv, Q., Liu, H., Bai, Y. Li S. Xie M. Bao J. Ma J. Zhu X. Wang Z. BKCa compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind‐limb unweighted rats. FASEB J. 33, 13358–13366 (2019). www.fasebj.org