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Background: Insufficient or disrupted sleep increases the risk of cardiovascular disease, including atherosclerosis. However, we know little about the molecular mechanisms by which sleep modulates atherogenesis. This study aimed to explore the potential role of circulating exosomes in endothelial inflammation and atherogenesis under sleep deprivation status and the molecular mechanisms involved. Methods: Circulating exosomes were isolated from the plasma of volunteers with or without sleep deprivation and mice subjected to 12-week sleep deprivation or control littermates. miRNA array was performed to determine changes in miRNA expression in circulating exosomes. Results: Although the total circulating exosome levels did not change significantly, the isolated plasma exosomes from sleep-deprived mice or human were a potent inducer of endothelial inflammation and atherogenesis. Through profiling and functional analysis of the global microRNA in the exosomes, we found miR-182-5p is a key exosomal cargo that mediates the proinflammatory effects of exosomes by upregulation of MYD88 (myeloid differentiation factor 88) and activation of NF-ĸB (nuclear factor kappa-B)/NLRP3 pathway in endothelial cells. Moreover, sleep deprivation or the reduction of melatonin directly decreased the synthesis of miR-182-5p and led to the accumulation of reactive oxygen species in small intestinal epithelium. Conclusions: The findings illustrate an important role for circulating exosomes in distant communications, suggesting a new mechanism underlying the link between sleep disorder and cardiovascular disease.

Objective: To explore the value of flow cytometry (FCM) in detecting the level of exfoliated cells in pleural effusion in the differential diagnosis of non-small cell lung cancer and benign lung diseases. Methods: Clinical data of patients with non-small cell lung cancer who were hospitalized in Hebei hospital from June 2019 to March 2022 were collected. A total of 98 patients were included, and 63 patients with alveolar lung disease were screened during the same period, and the two groups of patients were analyzed. Results: Compared with alveolar lung disease group, FCM detection and analysis showed that the level of exfoliated cells in the pleural effusion of non-small cell lung cancer (NSCLC) patients was 99 (3-969)/100,000, and patients with alveolar lung disease was 4 (0 ~ 19)/100,000. Additionally, compared with the alveolar lung disease group, the level of exfoliated cells in the pleural effusion of patients with non-small cell lung cancer (NSCLC) was significantly increased (P

Background: Studies on the association between cystatin C based estimated glomerular filtration rate (eGFRcys) and cognitive outcomes yielded inconsistent results. Objective: The present study aimed to examine the potential association of eGFRcys with subsequent cognitive decline rate. Methods: A total of 11,503 community-based participants were involved in our analyses, including 5,837 (aged 72.9±6.3; 58.6% women) in the Health and Retirement Study (HRS) from the US and 5,666 (aged 58.1±9.2; 49.0% women) in the China Health and Retirement Longitudinal Study (CHARLS). The association of eGFRcys with subsequent cognitive decline rate was evaluated by linear mixed models. Results: During 85,266 person-years of follow-up, both baseline elevated serum cystatin C (–0.048 standard deviation [SD]/year per mg/L; 95% confidence interval [CI], –0.060 to –0.036; p

Visual navigation involves a movable robotic agent striving to reach a point goal (target location) using vision sensory input. While navigation with ideal visibility has seen plenty of success, it becomes challenging in suboptimal visual conditions like poor illumination, where traditional approaches suffer from severe performance degradation. We propose E3VN (echo-enhanced embodied visual navigation) to effectively perceive the surroundings even under poor visibility to mitigate this problem. This is made possible by adopting an echoer that actively perceives the environment via auditory signals. E3VN models the robot agent as playing a cooperative Markov game with that echoer. The action policies of robot and echoer are jointly optimized to maximize the reward in a two-stream actor-critic architecture. During optimization, the reward is also adaptively decomposed into the robot and echoer parts. Our experiments and ablation studies show that E3VN is consistently effective and robust in point goal navigation tasks, especially under nonideal visibility.

Isothermal forging is an effective method for forming and manufacturing large-scale titanium alloy components with multi-rib. However, successive filling of the rib-grooves and reverse flow of the material are prone to occur during the forming process, which makes those rib-grooves are difficult to be filled then resulting in disturbed material flow and excessive die loading. The variability of billet sizes and fluctuation of uncertain parameters during the forging process have the great impacts on the forming results and stability. To this end, the eigenstructure with multi-rib from large titanium alloy rib-web components was extracted, and the combined method of finite element simulation and physical simulation experiment was used based on isothermal forging technique. Firstly, the finite element model for the eigenstructure under isothermal forging is established, then the behavior of the material flow and rib-grooves filling in the die cavity are analyzed. Secondly, the variation pattern and fluctuation range of rib-grooves filling are investigated by considering the deterministic factors of billet sizes, as well as the uncertainties of die draft angle, forming temperature, forming speed, billet manufacturing deviation and die manufacturing deviation. Subsequently, the significate deterministic factors and uncertainty factors are screened out and the correlation between the mean value as well as the variance of the filling consistency of the rib-grooves and the deterministic factors i.e. billet sizes are established by the dual response surface method. Then, a robust optimization model is constructed and solved. Finally, the reliability of the robust optimization solution is compared and verified, to obtain the ideal and stable fully-filling of the rib-grooves by adjusting and regulating the deterministic factors to weaken the interference of the uncertainties and achieve the simultaneous filling of the rib-grooves.

Background. Interleukin-37b is a fundamental inhibitor of innate and acquired immunity. Type 2 innate lymphoid cells (ILC2s) can secret type 2 cytokines and regulate allergic rhinitis (AR). However, the role of IL-37b in ILC2s in children with AR was not clear. Methods. We recruited 15 AR children and controls. The serum IL-37b levels and its relation with the frequency and functional phenotype of ILC2s. The regulation of IL-37b on ILC2s proliferation and function was confirmed using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The mRNA expression of IL-1R8, IL-18Rα, and ICOSL was examined using RCR. The change of IL-37b protein level in serum during subcutaneous allergen immunotherapy (SCIT) was determined by ELISA. Results. We have demonstrated that both of the frequencies of blood ILC2s, IL-5+ILC2s, and IL-13+ILC2s in AR children were elevated compared with controls. The serum protein level of IL-37b was downregulated in AR, and it was negatively related to the frequency of ILC2s, IL-5+ILC2s, and IL-13+ILC2s. IL-37b increased the mRNA levels of IL-1R8, IL-18Rα, and ICOSL expressed by ILC2s. IL-37b suppressed the proliferation of ILC2s and the secretion of IL-5 and IL-13 from ILC2s. Finally, we found that IL-37b was increased in AR children after 3 years’ SLIT, especially in the good response group. Conclusion. Our findings highlight the role of IL-37b in the suppression of ILC2s and establish a new therapeutic target in AR.

Background: Whole-exome sequencing (WES) facilitates the diagnosis of hereditary neuromuscular disorders. To achieve an accurate diagnosis, physicians should interpret the genetic report carefully along with clinical information and examinations. We described our experience with (1) clinical validation in patients with variants found using WES and (2) a diagnostic approach for those with negative findings from WES. Methods: WES was performed on patients with the clinical impression of hereditary neuromuscular disorders. Information on clinical manifestations, neurological examination, electrodiagnostic studies, histopathology of muscle and nerve, and laboratory tests were collected. Results: Forty-one patients (Male/Female: 18/23, age of onset: 34.5±15.9) accepted WES and were categorized into four scenarios: (1) patients with a positive WES result, (2) patients with an inconclusive WES result but supporting clinical data, (3) negative findings from WES, but a final diagnosis after further work-up, and (4) undetermined etiology from WES and in further work-ups. The yield rate of the initial WES was 63.4% (26/41). Among these, seventeen patients had positive WES result, while the other nine patients had inconclusive WES result but supporting clinical data. Notably, in the fifteen patients with equivocal or negative findings from WES, four patients (26.7%) achieved a diagnosis after further workup: tumor-induced osteomalacia, metabolic myopathy with pathogenic variants in mitochondrial DNA, microsatellite expansion disease, and vasculitis-related neuropathy. The etiologies remained undetermined in eleven patients (myopathy: 7, neuropathy: 4) after WES and further workup. Conclusions: It is essential to design genotype-guided molecular studies to correlate the identified variants with their clinical features. For patients who had negative findings from WES, acquired diseases, mitochondrial DNA disorders and microsatellite expansion diseases should be considered.

There exists a linear algorithm to decide whether a polyomino tessellates the plane by translation only. On the other hand, the problem of deciding whether a set of [Formula: see text] or more polyominoes can tile the plane by translation is undecidable. We narrow the gap between decidable and undecidable by showing that it remains undecidable for a set of [Formula: see text] polyominoes, which partially solves a conjecture posed by Ollinger.

Shuang Liang,1 Yan-Jun Liang,1 Zhao Li,2 Yong Wang,1 Xin-Ru Guo,1 Chao-yang Zhang,1 Chun Zhang,1 Jie Wu,1 Xiao-Long Wang,1 Yi-Sha Li,1 Guang-Yan Cai,1 Xiang-Mei Chen1 1Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China; 2Haikou People’s Hospital Affiliated to Xiangya School of Medicine, Haikou, People’s Republic of ChinaCorrespondence: Guang-Yan Cai, Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People’s Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, People’s Republic of China, Tel +86 13601062936, Fax +86 010-68130297, Email caiguangyan@sina.comPurpose: Tacrolimus is recommended by KDIGO Clinical Practice Guidelines as an initial therapy for the treatment of membranous nephropathy (MN). However, little is known about the factors that influence response and recurrence of the disease after tacrolimus therapy, and there are limited data regarding the duration of tacrolimus treatment. Here, we present a real-world retrospective cohort study of 182 MN patients treated with tacrolimus, aiming to assess the efficacy and safety of tacrolimus in the treatment of MN.Patients and Methods: The clinical data of 182 patients with MN treated with tacrolimus and followed up for at least one year were analyzed retrospectively for the efficacy and safety of tacrolimus.Results: The mean follow-up period was 27.3 (19.3– 41.6) months. A total of 154 patients (84.6%) achieved complete or partial remission, and 28 patients (15.4%) did not. Multivariate Cox regression analysis showed that male and higher baseline BMI were independently associated with lower, while higher serum albumin was associated with higher probability of remission. Among the responders, 56 patients (36.4%) relapsed. After adjustments for age and sex, Cox regression analysis revealed that the longer period of full-dose tacrolimus was administered, the lower the incidence of relapse. However, high levels of serum creatinine and proteinuria at the onset of tacrolimus discontinuation were risk factors for relapse. During the treatment of tacrolimus, a decline in renal function (≥ 50% increase in serum creatinine after the onset of tacrolimus treatment) was the most common adverse reaction, observed in 20 (11.0%) patients, followed by elevated blood glucose and infection, but the latter two occurred mostly during treatment with tacrolimus plus corticosteroids.Conclusion: Tacrolimus is effective in the treatment of MN, but the relapse rate is high. Clinical studies with larger sample sizes are needed to further explore the use of tacrolimus in the treatment of membranous nephropathy.Keywords: membranous nephropathy, tacrolimus, response, relapse, safety