GAC-SleepNet: A dual-structured sleep staging method based on graph structure and Euclidean structure.

Sleep staging is a precondition for the diagnosis and treatment of sleep disorders. However, how to fully exploit the relationship between spatial features of the brain and sleep stages is an important task. Many current classical algorithms only extract the characteristic information of the brain in the Euclidean space without considering other spatial structures. In this study, a sleep staging network named GAC-SleepNet is designed. GAC-SleepNet uses the characteristic information in the dual structure of the graph structure and the Euclidean structure for the classification of sleep stages. In the graph structure, this study uses a graph convolutional neural network to learn the deep features of each sleep stage and converts the features in the topological structure into feature vectors by a multilayer perceptron. In the Euclidean structure, this study uses convolutional neural networks to learn the temporal features of sleep information and combine attention mechanism to portray the connection between different sleep periods and EEG signals, while enhancing the description of global features to avoid local optima. In this study, the performance of the proposed network is evaluated on two public datasets. The experimental results show that the dual spatial structure captures more adequate and comprehensive information about sleep features and shows advancement in terms of different evaluation metrics.

Spatiotemporal dynamic of subtropical forest carbon storage and its resistance and resilience to drought in China.

Subtropical forests are rich in vegetation and have high photosynthetic capacity. China is an important area for the distribution of subtropical forests, evergreen broadleaf forests (EBFs) and evergreen needleleaf forests (ENFs) are two typical vegetation types in subtropical China. Forest carbon storage is an important indicator for measuring the basic characteristics of forest ecosystems and is of great significance for maintaining the global carbon balance. Drought can affect forest activity and may even lead to forest death and the stability characteristics of different forest ecosystems varied after drought events. Therefore, this study used meteorological data to simulate the standardized precipitation evapotranspiration index (SPEI) and the Biome-BGC model to simulate two types of forest carbon storage to quantify the resistance and resilience of EBF and ENF to drought in the subtropical region of China. The results show that: 1) from 1952 to 2019, the interannual drought in subtropical China showed an increasing trend, with five extreme droughts recorded, of which 2011 was the most severe one; 2) the simulated average carbon storage of the EBF and ENF during 1985-2019 were 130.58 t·hm-2 and 78.49 t·hm-2, respectively. The regions with higher carbon storage of EBF were mainly concentrated in central and southeastern subtropics, where those of ENF mainly distributed in the western subtropic; 3) The median of resistance of EBF was three times higher than that of ENF, indicating the EBF have stronger resistance to extreme drought than ENF. Moreover, the resilience of two typical forest to 2011 extreme drought and the continuous drought events during 2009 - 2011 were similar. The results provided a scientific basis for the response of subtropical forests to drought, and indicating that improve stand quality or expand the plantation of EBF may enhance the resistance to drought in subtropical China, which provided certain reference for forest protection and management under the increasing frequency of drought events in the future.

Methylprednisolone Inhibits Autophagy of Vascular Endothelial Cells in Rat Femoral Head Via PI3K/Akt/mTOR Pathway.

OBJECTIVE: To study the relationship between vascular endothelial cells (VEC) and autophagy, and its regulatory mechanism in steroid-induced avascular necrosis of the femoral head (SANFH). METHODS: In cell experiment, VEC were isolated and cultured from the femoral head of Sprague-Dawley rats and divided into three groups: blank control group (Ctrl), methylprednisolone group (MP), and methylprednisolone+mTOR-shRNA group (MP + shmTOR). The autophagy formation was observed by transmission electron microscope. The mRNA expression of PI3K, Akt, mTOR, Beclin1 and MAP1LC3 was detected by RT-PCR and the protein expression was detected by Western blot and immunofluorescence. Expression of the damage marker 6-keto-PGF1α was detected by the ELISA method. In vivo experiment, after establishing the model, the grouping method was the same as cell experiment. Autophagosomes were observed by same method, and the expression of related factors was detected by the same method in cell experiment. RESULTS: In the cell experiment, autophagosomes in the MP group were significantly lower than in the Ctrl group, and the autophagosomes in the MP + shmTOR group were intermediate between two groups (P < 0.05). The mRNA expression levels of PI3K, Akt and mTOR in the MP group were significantly higher than in the Ctrl group, while the MP+ shmTOR group presented intermediate levels between these groups (average gray value were 3837.90, 2996.30, 3005.60, F = 428.64, P < 0.05). MRNA expression levels of Beclin1 and MAP1LC3 in the MP group were significantly lower than that in Ctrl group (P < 0.05). The content of 6-keto-PGF1α in the MP + shmTOR group was higher than in the Ctrl group and lower than in the MP group at the evaluated time intervals (average absorbance value were 104.98, 206.83, 145.91, F = 352.83, P < 0.01). In vivo experiment, the content of 6-Keto-PGF1α in the hormone group increased as time went on; the mTOR-si group was higher than that in control group, but lower than that in the hormone group (P < 0.01). The mRNA expressions of Beclin1 and MAP1LC3 in the control group were higher than those in the hormone group, while the mRNA expressions of PI3K, Akt and mTOR were lower than those in the mTOR-si group (P < 0.05). CONCLUSION: The steroid inhibited the physiological protective effect of autophagy on SANFH by increasing the expression of PI3K/Akt/mTOR signaling pathway related factors and decreasing the expression of Beclin1 and MAP1LC3 in the femoral head VEC.

Solvent-free, B(C6 F5 )3 -Catalyzed S-H Insertion of Thiophenols and Thiols with α-Diazoesters.

Described herein is a B(C6 F5 )3 -catalyzed S-H insertion reaction of thiophenols and thiols with α-diazoesters to access valuable α-thioesters. With the established protocol, an array of α-thioester products are generated in moderate to good yields with broad scope and functional group tolerance. In addition, this reaction maintains its high efficiency on gram scale and the product can be easily transformed into other useful motifs. This reaction proceeds under solvent-free conditions at room temperature, and generally finishes in twenty minutes upon magnet stirring, which offers an expedient way for the synthesis of thioether-containing compounds.

Catalyst-Free 1,2-Dibromination of Alkenes Using 1,3-Dibromo-5,5-dimethylhydantoin (DBDMH) as a Bromine Source.

A direct 1,2-dibromination method of alkenes is realized using 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) as a bromine source. This reaction proceeds under mild reaction conditions without the use of a catalyst and an external oxidant. Various sorts of alkene substrates are transformed into the corresponding 1,2-dibrominated products in good to excellent yields with broad substrate scope and exclusive diastereoselectivity. This method offers a green and practical approach to synthesize vicinal dibromide compounds.

Research on application of ReliefF and improved RVM in water quality grade evaluation.

ReliefF algorithm was used to analyze the weight of each water quality evaluation factor, and then based on the Relevance Vector Machine (RVM), Particle Swarm Optimization (PSO) was used to optimize the kernel width factor and hyperparameters of RVM to build a water quality evaluation model, and the experimental results of RVM, PSO-RVM, ReliefF-RVM and PSO-ReliefF-RVM were compared. The results show that ReliefF algorithm, combined with threshold value, selects 5 evaluation factors with significant weight from eight evaluation factors, which reduces the amount of data used in the model, CSI index is used to calculate the separability of each evaluation factor combination. The results show that the overall separability of the combination is best when the evaluation factor with significant weight is reserved. When different water quality evaluation factors were included, the evaluation accuracy of PSO-ReliefF-RVM model reached 95.74%, 14.23% higher than that of RVM model, which verified the effectiveness of PSO algorithm and ReliefF algorithm, and had a higher guiding significance for the study of water quality grade evaluation. It has good practical application value.

Cyclophosphamide inhibits the progression of Meniere's disease by reducing the generation of circulating immune complex.

Endolymphatic hydrops is a characteristic pathological manifestation of Meniere's disease (MD) that has been previously associated with autoimmunity. Interest in the circulating immune complex (CIC) has increased due to its reported role in the occurrence of MD. The present study aimed to investigate the potential value of serum CIC concentration in the diagnosis of MD and the therapeutic potential of cyclophosphamide (CTX) for the treatment of MD. In the present study, guinea pigs were immunized with isologous crude inner ear antigens to establish an autoimmune MD model. Pure tone audiometry, Vestibular-evoked myogenic potential test, electrocochleography test and auditory brainstem response was applied in this study for assessing the severity of MD in guinea pigs. ELISA was applied to measure CIC, tumor necrosis factor α (TNF-α) and heat shock protein 70 (HSP70) expression levels in the serum samples of different groups of patients. Western blotting was applied to detect the protein expression of HSP70 in inner ear tissues in guinea pigs. Hematoxylin and eosin staining was applied to visualize the spiral ganglions in spiral ganglions models. CIC expression in the inner ear was detected by immunohistochemistry. In vivo experiments were performed to confirm the therapeutic effects of CTX in MD. Serum concentrations of CIC, TNF-α and HSP70 were found to be significantly higher in patients with MD, which were also associated with increases in hearing classification and the severity of endolymphatic hydrops. Using a guinea pig MD model, ELISA results revealed significantly increased serum CIC, TNF-α and HSP70 concentrations compared with those in the control group. ABR results showed that the thresholds in the CTX group were notably decreased compared with that in the dexamethasone group, whereas CIC concentrations in the serum were reduced following dexamethasone and CTX treatments compared with those after saline treatment. In the inner ear tissues, the CIC concentration in CTX group was lower than that in the dexamethasone group. Similarly, reductions in HSP70 and TNF-α concentrations was also observed in a similar manner. Immunohistochemistry staining found notably lower CIC deposition in the inner ear tissues following CTX treatment than that in dexamethasone group. Taken together, higher CIC expression can be used as a biomarker for MD diagnosis. The efficacy of CTX in MD was found to be higher compared with that in dexamethasone, which may be associated with the effective inhibition of CIC, HSP70 and TNF-α generation.

Downregulation of VDR in benign paroxysmal positional vertigo patients inhibits otolith­associated protein expression levels.

Benign paroxysmal positional vertigo (BPPV) is the most common peripheral vertigo­associated disease. Vitamin D (VD) helps maintain normal otolith function and may be associated with BPPV. VD exerts its biological functions primarily via the VD receptor (VDR). The present study demonstrated that serum VD levels were significantly decreased in patients with BPPV compared with in controls. VDR, otolith­associated protein otoconin­90 (OC90) and NADPH oxidase 3 (NOX3) expression levels were also significantly decreased in patients with BPPV compared with in controls. Furthermore, a positive correlation was observed between VD levels and VDR expression. Receiver operating characteristic curve analysis identified VDR expression levels as a potential diagnostic marker for BPPV. OC90 and NOX3 expression levels were notably lower in the inner ear tissue of VDR knockout mice compared with in those of wild­type mice. In mice overexpressing VDR, OC90 and NOX3 were also overexpressed. Following intravenous injection of VD in VDR knockout mice, expression levels of OC90 and NOX3 were not significantly different from those in VDR knockout mice injected with saline. This indicated that VDR may be underexpressed in patients with BPPV and was associated with the expression levels of otolith­associated proteins. Moreover, VDR mediated VD activation, leading to otolith protein formation. The present study provided a novel theoretical basis for BPPV onset that may facilitate the development of more effective diagnostic and treatment options.

Simultaneous Fluorescence Imaging Reveals N-Methyl-d-aspartic Acid Receptor Dependent Zn2+/H+ Flux in the Brains of Mice with Depression.

Depression is immensely attributed to the overactivation of N-methyl-d-aspartic acid (NMDA) receptor in the brains. As regulatory binding partners of NMDA receptor, both Zn2+ and H+ are intimately interrelated to NMDA receptor's activity. Therefore, exploring synergistic changes on the levels of Zn2+ and H+ in brains will promote the knowledge and treatment of depression. However, the lack of efficient, appropriate imaging tools limits simultaneously tracking Zn2+ and H+ in living mouse brains. Thus, a well-designed dual-color fluorescent probe (DNP) was fabricated for the simultaneous monitoring of Zn2+ and H+ in the brains of mice with depression. Encountering Zn2+, the probe evoked bright blue fluorescence at 460 nm. Meanwhile, the red fluorescence at 680 nm was decreased with H+ addition. With blue/red dual fluorescence signal of DNP, we observed the synchronous increased Zn2+ and H+ in PC12 cells under oxidative stress. Notably, in vivo imaging for the first time revealed the simultaneous reduction of Zn2+ and pH in brains of mice with depression-like behaviors. Further results implied that the NMDA receptor might be responsible for the coinstantaneous fluctuation of Zn2+ and H+ during depression. Altogether, this work is conducive to the knowledge of neural signal transduction mechanisms, advancing our understanding of the pathogenesis in depression.

The correlation of physicochemical properties and combustion performance of hydrochar with fixed carbon index.

Hydrothermal carbonization (HTC) is effective method for improving fuel properties of biomass. Investigating the relationship between the HTC severity and the physicochemical properties of hydrochar is beneficial for the large-scale utilization. The fixed carbon index (FCI) based on the hydrothermal carbonization severity is introduced to predict the physicochemical properties, pelletization and combustion performance of hydrochar. The results showed the relationship between decarbonization, dehydrogenation, deoxygenation and FCI fits exponential function. It was predicted that the hydrochar pellets with FCI = 0.15-0.45 possessed the highest bulk density (>1175 kg/m3), the lowest specific energy consumption (<16.07 kJ/kg) and the strongest radial compressive strength (>10.7Mpa). Moreover, the activation energy of hydrochar combustion in FCI (0.15-0.25) is higher (the maximum is 216 kJ/mol). The study provides based datas for predicting the fuel properties of hydrochar and obtains high quality solid fuel.

Active immunization using hand-push emulsification method increases the operator's risk of transcutaneous immunization.

Setting up an animal model by using active immunization methods is a common means of studying immune-related diseases or producing antibodies with high titer and high activities. However, the security during the process of pathogen emulsification remains unclear. In a physical examination, we unexpectedly noticed high levels of angiotensin II type 1 receptor autoantibody (AT1-AA) specific to the immunizing antigen in the sera of some researchers who had participated in setting up active immunization animal models, and we were puzzled about the cause of AT1-AA production. In this study, we intended to investigate whether the emulsified antigen was the source of infection in these researchers, and if so, how to prevent it from occurring. AT1-AA was detected by advanced ELISA method. The participants presented higher levels of AT1-AA compared with non-participants of the same laboratory. This phenomenon remained that some factors during the process of rat model establishment may contribute to AT1-AA production. Animal and glove penetration studies indicated the emulsified antigen infection was attributed to neither aerosol or fur touch nor penetrating through gloves. However, AT1-AA level was largely decreased in the participants after they used an automatic emulsification device. Because of the strong permeability of the adjuvant, we speculated that emulsified antigen might get access to the unprotected skin of the participants accidentally during the immunization process. These results demonstrated that accidental contacts of emulsified antigens may infect researchers during the process of traditional hand-push emulsification, resulting in high specific autoantibody levels, which can be prevented by using appropriate tools.

Proliferation in cardiac fibroblasts induced by ß1-adrenoceptor autoantibody and the underlying mechanisms.

Chronic sustained stimulation of ß-adrenoceptor is closely related to cardiac fibrosis which is bad for cardiac function. Growing evidence showed that the high prevalence of ß1-adrenoceptor autoantibody (ß1-AA) in the sera of patients with various types of cardiovascular diseases decreased cardiac function. In the current study, we demonstrated that ß1-AA impaired the cardiac function evaluated by echocardiography and that ß1-AA triggered cardiac fibrosis in terms of increased expression of α-smooth muscle actin as the marker of myofibroblast and collagen deposition in a passive ß1-AA immunized mice model during 16 weeks. Further, we showed that ß1-AA activated ß1-AR/cAMP/PKA pathway and promoted proliferation in primary cardiac fibroblasts through specific binding to ß1-AR but not to ß2-AR. Moreover, ß1-AA was also likely to promote proliferation in cardiac fibroblasts through activating p38MAPK and ERK1/2 as p38MAPK inhibitor SB203580 and ERK1/2 inhibitor PD98059 partially reversed the proliferative effect. The persistent activating signalling of PKA and P38MAPK in 1 h induced by ß1-AA was associated with lacking agonist-induced desensitization phenomena. The conditioned medium from ß1-AA-stimulated cardiac fibroblasts induced cardiomyocyte apoptosis, which indicated that ß1-AA changed the secretion of cardiac fibroblasts contributing to cardiac injury. These findings will contribute to our understanding of the pathological mechanisms of ß1-AA.

Autoantibodies against ß1-adrenoceptor induce blood glucose enhancement and insulin insufficient via T lymphocytes.

Diabetes mellitus is a chronic metabolic disorder with a high morbidity and mortality, but its pathogenesis is not fully understood. An increasing amount of evidence indicates that an immune mechanism plays an important role in the pathogenesis of diabetes. We demonstrated previously that the long-term presence of autoantibodies against the second extracellular loop of the ß1-adrenoceptor (ß1-AA) could change the ratio of peripheral CD4+T/CD8+T in rats, which was accompanied by lymphocytes infiltration in the rat heart, liver, and kidneys. To investigate whether ß1-AA is involved in the pathogenesis of diabetes, BALB/c or nude mice were passively immunized with monoclonal antibodies against ß1-AR (ß1-AR mAb). Compared with vehicle control mice, ß1-AA-positive BALB/c mice exhibited significantly increased blood glucose (P < 0.01) and increased fasting insulin (P < 0.05). However, the same changes did not occur in the nude mice. And altered islet morphology was found at week 28 in ß1-AA immunization group compared with vehicle control. The basal insulin level of NIT-1 ß-cells was decreased markedly (P < 0.01), and the lactate dehydrogenase level was increased (P < 0.01) after the administration of conditioned media from T lymphocytes that had been treated with ß1-AA alone. However, these effects were reversed by treatment with metoprolol or peptides of the second extracellular loop of ß1-adrenoceptor (ß1-AR-ECII). These results suggest that ß1-AA could induce hyperglycemia in both rats and mice, and also impair insulin secretion and change islet structure. T lymphocytes may play a key role in the pathogenesis of these changes in the islets.

[Interstitial lung disease as an initial manifestation of dermatomyositis].

OBJECTIVE: To explore the clinical features and prognosis of dermatomyositis patients with interstitial lung disease (ILD) as an initial manifestation. METHODS: Medical records of 184 dermatomyositis inpatients complicated with ILD, admitted into Peking Union Medical College Hospital from January 1999 to January 2013, were retrospectively analyzed. The clinical features, biochemical parameters, positive rates of autoantibodies, radiology, pulmonary function tests, pathology, treatments and prognosis were compared between two subgroups of ILD-initial and non-ILD-initial dermatomyositis. RESULTS: The incidence of ILD of dermatomyositis inpatients was 17%. The average age was 48 ± 12 years and the gender ratio of male-to-female was 63: 121. Eighty eight (47.8%) dermatomyositis patients had ILD as an initial manifestation, including (n = 42, 22.8%) of ILD concomitant dermatomyositis (within 1 month) and (n = 46, 25.0%) of ILD before dermatomyositis with an average ahead time of (11 ± 3) months. Patients of ILD-initial dermatomyositis had a higher incidence of dyspnea on exertion, cough and lung crackles, but there were lower incidences of heliotrope rash, chest V area rash, shawl sign and joint involvement than non-ILD-initial dermatomyositis (P < 0.05). The positive rate of anti-Jo-1 antibodies of ILD-initial dermatomyositis group was 13.6%. The main performances of ILD-initial dermatomyositis on pulmonary function tests were diffusing and restrictive ventilation impairment. And there was a lower diffusing rate of carbon monoxide than non-ILD-initial dermatomyositis group (P < 0.01). Organic and non-specific interstitial pneumonias were the major clinical pathology types of ILD-initial dermatomyositis. The mortality rate of ILD-initial dermatomyositis patients was 19.3% and there was no significant difference from non-ILD-initial dermatomyositis (P > 0.05). The main course of ILD-initial dermatomyositis was respiratory failure due to progressive ILD (n = 13, 76.5%). CONCLUSIONS: ILD as an initial manifestation is a common complication and a major mortality cause of dermatomyositis inpatients. And the frequent clinical pathology types are organic and non-specific interstitial pneumonias. Symptoms of skin and muscle, creatine kinase and anti-synthetase antibodies should be closely monitored.