Working memory load recognition with deep learning time series classification.

Working memory load (WML) is one of the widely applied signals in the areas of human-machine interaction. The precise evaluation of the WML is crucial for this kind of application. This study aims to propose a deep learning (DL) time series classification (TSC) model for inter-subject WML decoding. We used fNIRS to record the hemodynamic signals of 27 participants during visual working memory tasks. Traditional machine learning and deep time series classification algorithms were respectively used for intra-subject and inter-subject WML decoding from the collected blood oxygen signals. The intra-subject classification accuracy of LDA and SVM were 94.6% and 79.1%. Our proposed TAResnet-BiLSTM model had the highest inter-subject WML decoding accuracy, reaching 92.4%. This study provides a new idea and method for the brain-computer interface application of fNIRS in real-time WML detection.

Upregulation of CIRP by its agonist prevents the development of heart failure in myocardial infarction rats.

BACKGROUND: Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI). METHODS: Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and molecular biology methods. RESULTS: Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2's antioxidant effects against oxidative injury, confirming that zr17-2's role is dependent on CIRP. CONCLUSION: Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.

maresin2 fine-tunes ULK1 O-GlcNAcylation to improve post myocardial infarction remodeling.

BACKGROUND: Myocardial infarction (MI) is one of the common causes of hospitalization and death all over the world. Maresin2 (MaR2), a specialized pro-solving mediator of inflammation, has been consolidated to be a novel cytokine fine-tuning inflammatory cascade. However, the precise mechanism is still unknown. Here, we demonstrated that maresin2 relieved myocardial damage via ULK1 O-GlcNAc modification during MI. METHODS: The myocardial infarction model was established by ligating the left anterior descending artery (LAD). Echocardiography, histopathology, transmission electron microscope, and Western blot were used to evaluate cardiac function and remodeling. Furthermore, primary neonatal rat cardiomyocytes (NRCMs) were cultivated, and immunoprecipitation (IP) assays were performed to explore the specific mechanism. RESULTS: As suggested, maresin2 treatment protected cardiac function and ameliorated adverse cardiac remodeling. Furthermore, we found that maresin2 facilitated autophagy and inhibited apoptosis under the modulation of O-GlcNAcylation-dependent ULK1 activation. Meanwhile, we discovered that maresin2 treatment ameliorated the inflammation of myocardial cells by inhibiting the interaction of TAK1 and TAB1. CONCLUSIONS: Maresin2 is likely to promote autophagy while relieving apoptosis and inflammation of myocardial cells, thereby exerting a protective effect on the heart after MI.

Sotagliflozin attenuates cardiac dysfunction and remodeling in myocardial infarction rats.

Objective: Sotagliflozin is a dual sodium-glucose co-transporter-1 and 2 (SGLT1/2) inhibitor with selectivity towards SGLT2. Previous studies showed that SGLT2 inhibitors can improve cardiac function and reduce myocardial infarction size in animal models of myocardial infarction (MI). However, it remains unknown whether the dual inhibition of SGLT1/2 by sotagliflozin has beneficial effects in this context. In this study, we investigated the potential cardioprotective effects of sotagliflozin in an animal model of MI. Methods: Sprague Dawley (SD) rats underwent left anterior descending coronary artery ligation or sham ligation then were randomly assigned to receive either sotagliflozin (10 mg/kg) or vehicle via intraperitoneal injection. Fourteen days post-MI, we assessed cardiac function using echocardiography and evaluated histological and molecular markers of cardiac remodeling and inflammation in the left ventricle. Results: Our findings indicate that sotagliflozin treatment resulted in improved cardiac function and reduced infarct size compared with the vehicle-treated group. Additionally, sotagliflozin improved cardiac remodeling as shown by the decreased cardiac hypertrophy and cardiac apoptosis in the post-MI heart. Mechanistically, an apparent reduction in the cardiac inflammatory response in sotagliflozin-treated hearts was observed in the post-MI rats. Conclusion: Overall, our results suggest that sotagliflozin may have cardioprotective effects against myocardial infarction.

Human embryonic stem cells secrete macrophage migration inhibitory factor: A novel finding.

Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and participates in important biological mechanisms. However, few studies have reported whether MIF is expressed in human Embryonic stem cells (ESCs) and its effect on human ESCs. Two human ESCs cell lines, H1 and H9 were used. The expression of MIF and its receptors CD74, CD44, CXCR2, CXCR4 and CXCR7 were detected by an immunofluorescence assay, RT-qPCR and western blotting, respectively. The autocrine level of MIF was measured via enzyme-linked immunosorbent assay. The interaction between MIF and its main receptor was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Finally, the effect of MIF on the proliferation and survival of human ESCs was preliminarily explored by incubating cells with exogenous MIF, MIF competitive ligand CXCL12 and MIF classic inhibitor ISO-1. We reported that MIF was highly expressed in H1 and H9 human ESCs. MIF was positively expressed in the cytoplasm, cell membrane and culture medium. Several surprising results emerge. The autosecreted concentration of MIF was 22 ng/mL, which was significantly higher than 2 ng/mL-6 ng/mL in normal human serum, and this was independent of cell culture time and cell number. Human ESCs mainly expressed the MIF receptors CXCR2 and CXCR7 rather than the classical receptor CD74. The protein receptor that interacts with MIF on human embryonic stem cells is CXCR7, and no evidence of interaction with CXCR2 was found. We found no evidence that MIF supports the proliferation and survival of human embryonic stem cells. In conclusion, we first found that MIF was highly expressed in human ESCs and at the same time highly expressed in associated receptors, suggesting that MIF mainly acts in an autocrine form in human ESCs.

Muscone attenuates susceptibility to ventricular arrhythmia by inhibiting NLRP3 inflammasome activation in rats after myocardial infarction.

Fibrosis and abnormal expression of connexin 43 (Cx43) in the ventricle play vital roles in ventricular arrhythmias (VAs) after myocardial infarction (MI). Muscone, an active monomer of heart-protecting musk pill, has various biological activities, but its effect on susceptibility to VAs in rats with MI has not been determined. In the present study, we investigated the effects of muscone on ventricular inflammation, fibrosis, Cx43 expression, and the occurrence of VAs after MI. An MI model was established by ligating the proximal left anterior descending coronary artery. Then, the MI model rats were administered muscone (2 mg/kg/day) or vehicle (saline)via intragastric injection for 14 days. Cardiac function was evaluated by echocardiography, and an in vivo electrophysiological study was performed on Day 14. Cardiac inflammation, fibrosis, and Cx43 expression were determined by histochemical analysis and western blot analysis. Our results indicated that muscone treatment significantly improved cardiac function and inhibited ventricular inflammation, fibrosis, and nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome activation. Electrocardiogrphy and electrophysiology studies showed that muscone shortened the QRS interval, QT interval, QTc interval, and action potential duration; prolonged the effective refractory period; and reduced susceptibility to VAs in rats after MI. Furthermore, Cx43 expression in the BZ was increased by muscone treatment, and this change was coupled by inhibition of the NLRP3/IL-1ß/p38 MAPK pathway. Taken together, our results demonstrated that muscone reduces susceptibility to VA, mainly by decreasing ventricular inflammation and fibrosis, and attenuates abnormal Cx43 expression by inhibiting NLRP3 inflammasome activation after myocardial infarction in rats.

Gefapixant, a Novel P2X3 Antagonist, Protects against Post Myocardial Infarction Cardiac Dysfunction and Remodeling Via Suppressing NLRP3 Inflammasome.

OBJECTIVE: The ATP responsive P2 purinergic receptors can be subdivided into metabotropic P2X family and ionotropic P2Y family. Among these, P2X3 is a type of P2X receptor which is specifically expressed on nerves, especially on pre-ganglionic sensory fibers. This study investigates whether gefapixant possesses the potential of inhibiting cardiac sympathetic hypersensitivity to protect against cardiac remodeling in the context of myocardial infarction. METHODS: The Sprague-Dawley rats were divided randomly into three groups: sham group-myocardial infarction group, and myocardial infarction with gefapixant treatment group. Myocardial infarction was induced by left anterior descending branch ligation. The gefapixant solution was intraperitoneally injected each time per day for 7 days and the appropriate dosage of gefapixant was determined according to the results of hematoxylin-eosin (HE) staining and myocardial injury biomarkers. Conditions of cardiac function were assessed by echocardiograph and cardiac fibrosis was evaluated by Western blotting and immunofluorescence staining of collagen I and collagen III. The sympathetic innervation was detected by norepinephrine concentration (pg/mL), in-vivo electrophysiology, and typical sympathetic biomarkers. Inflammatory cell infiltration was shown from immunofluorescence staining and pro-inflammatory signaling pathway activation was checked by immunohistology, quantitative realtime PCR (qPCR) and Western blotting. RESULTS: It was found that gefapixant injection of 10 mg/kg per day had the highest dosage-efficacy ratio. Furthermore, gefapixant treatment improved cardiac pump function as shown by increased LVEF and LVFS, and decreased LVIDd and LVIDs. The expression levels of collagen I and collagen III, and TNF-α were all decreased by P2X3 inhibition. Mechanistically, the decreased activation of nucleotide-binding and oligomerization domain-like receptors family pyrin-domain-containing 3 (NLRP3) inflammasome and subsequent cleavage of caspase-1 which modulated interleukin-1ß (IL-1ß) and IL-18 level in heart after gefapixant treatment were associated with the suppressed cardiac inflammation. CONCLUSION: It is suggested that P2X3 inhibition by gefapixant ameliorates post-infarct autonomic nervous imbalance, cardiac dysfunction, and remodeling possibly via inactivating NLRP3 inflammasome.

Multimodal Data for the Detection of Freezing of Gait in Parkinson's Disease.

Freezing of gaits (FOG) is a very disabling symptom of Parkinson's Disease (PD), affecting about 50% of PD patients and 80% of advanced PD patients. Studies have shown that FOG is related to a complex interplay between motor, cognitive and affective factors. A full characterization of FOG is crucial for FOG detection/prediction and prompt intervention. A protocol has been designed to acquire multimodal physical and physiological information during FOG, including gait acceleration (ACC), electroencephalogram (EEG), electromyogram (EMG), and skin conductance (SC). Two tasks were designed to trigger FOG, including gait initiation failure and FOG during walking. A total number of 12 PD patients completed the experiments and produced a length of 3 hours and 42 minutes of valid data including 2 hours and 14 minutes of normal gait and 1 hour and 28 minutes of freezing of gait. The FOG episodes were labeled by two qualified physicians. The multimodal data have been validated by a FOG detection task.

Change Characteristics of Negative Drainage Pressure along the Drill Hole: Theoretical Analyses and Field Tests.

A proper understanding of the change characteristics of negative drainage pressure along a drilling hole is essential since gas drainage parameters are the key parameters that influence the efficiency of gas drainage. In this study, based on the coupling of gas seepage from coal seams and the gas flow along the drilling hole, a theoretical model was established to calculate the gas pressure change law along the drilling hole with different influencing factors. Subsequently, a multibranch method was applied to test the negative pressure at different drilling holes. Finally, a field test was conducted in the Jiulishan coal mine to analyze the changed characteristics of the negative drainage pressure along the drilling hole. The results show that at a constant negative drainage pressure in the borehole, the negative pressure gradually decreased with increasing depth. With an increase in negative drainage pressure at the borehole, the negative pressure loss for every 100 m substantially increased. The gas flux had the most obvious influence on the negative pressure in the drilling hole, and the pressure loss rapidly increased with increasing gas flux. When the diameter of the borehole was small, the negative pressure loss was significant; when the drilling hole was deep, the negative pressure decreased more significantly. This study has important theoretical and practical significance for improving the gas drainage effect.

Noise exposure and its relationship with postinfarction cardiac remodeling: implications for NLRP3 inflammasome activation.

In recent years, high-decibel noise has emerged as a causative risk factor for ischemic heart disease. Massive noise overdose is associated with increased endocrine, neural, and immune stress responses. The NLRP3 (nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3) inflammasome, the most characterized supramolecular complex and a potent mediator of inflammatory signaling, has been reported to be a marker of increased ischemic heart disease vulnerability. Our study evaluated the association of noise exposure with postinfarction cardiac remodeling and its effect on NLRP3 inflammasome activation. Rats were exposed to a noisy environment (14 days, 24 h/per day, 70 ± 5 dB), and speck formation by the NLRP3 inflammasome scaffold protein ASC (apoptosis-associated speck-like protein) was assessed by confocal immunofluorescence. Echocardiography, pathological analysis, and in vivo electrophysiology were performed. Our results revealed the improved postinfarction cardiac function, mitigated fibrosis, and decreased arrhythmia vulnerability and sympathetic sprouting in low-environment noise groups. Moreover, western blotting of NLRP3, caspase-1, ASC, IL-1ß, and IL-18 and confocal microscopy of ASC speck showed that the priming and activation of NLRP3 inflammasome were higher in the NE group than in the NI group. In conclusion, our findings reveal a previously unidentified association between NLRP3 inflammasome activation and noise exposure, underscoring the significance of effective noise prevention in improving postinfarction prognosis.

Coupling Model of Stress-Damage-Seepage and Its Application to Static Blasting Technology in Coal Mine.

Most coal mine field application processes are carried out using empirical formulas because of the insufficient understanding of the fracture development law of the static blasting technology. This lack of understanding results in poor coal seam gas extraction. In this study, a stress-damage coupling model was established to investigate the construction parameters of the static blasting technology using COMSOL simulation software. Then, a stress-damage-seepage coupling model was designed to study the evolution of the fracture field (seepage field) during the static blasting process using realistic failure process analysis simulation software. Finally, the influencing factors and fracturing effects were analyzed comprehensively. The research results show the following. (1) Comparing the simulation results with previous field tests reveals that the seepage law of the numerical simulation of the static blasting technology is consistent with the field test results, verifying the rationality of the stress-damage-seepage coupling model. (2) The development of coal seam fractures is affected by the expansion pressure, elastic modulus, and guide hole arrangement; the guide hole arrangement can play a role in guiding the development direction of fractures and enhancing the effect of fracturing. (3) The coal body mainly experienced the following five stages of fracturing: coal body compaction, microdamage formation, microfracture formation, large fracture formation, and fracture propagation. In addition, because of the rapid release of soundless cracking agents during the large fracture formation stage, the gas flow decreased in a short time. (4) The static blasting technology causes the coal seam permeability coefficient to increase. Compared with conventional extraction, the effective influence radius in the horizontal direction increases by 5.1 times, and the effective influence radius in the vertical direction increases by approximately 3 times. The static blasting technology can increase the number of coal seam fractures and significantly reduce the coal seam gas pressure, thereby enhancing coal seam permeability and realizing safe coal mining.

C1q/Tumor Necrosis Factor-Related Protein-9 Attenuates Diabetic Nephropathy and Kidney Fibrosis in db/db Mice.

Diabetic nephropathy (DN) is characterized by excessive accumulation of extracellular matrix leading to early thickening of glomerular and tubular basement membrane. C1q/tumor necrosis factor (TNF)-related protein-9 (CTRP9) was recently identified as an adiponectin paralog of superior prominence. CTRP9 is an anti-inflammatory, antioxidant, vasodilation and atheroprotective adipose cytokine that share a similar metabolic regulatory function as adiponectin. Additionally, CTRP9 inhibits apoptosis of endothelial cells, decreases blood glucose level, and increases insulin sensitivity. However, the renoprotective effects of CTRP9 and the underlying molecular mechanisms in DN have not been explored. This study examined the effects of CTRP9 on DN in diabetic db/db mice through adenovirus-mediated overexpression. From the results, CTRP9 ameliorated renal dysfunction and injury at the structural and functional level in diabetic db/db mice. Additionally, CTRP9 inhibited glomerular and tubular glycogen accumulation, fibrosis, relieved hyperglycemia-mediated oxidative stress, and apoptosis. This is the first study to report on therapeutic effects of CTRP9 on DN, presenting a potentially effective clinical treatment method for DN patients.

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l+/- mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.

Clonidine adhesive patch for the treatment of tic disorders: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of clonidine adhesive patch for tic disorders (TDs). METHODS: Medline, Embase, Cochrane central register of controlled trials and Chinese databases of CBM, CNKI were searched from inception to 08.2016 for randomized controlled studies (RCTs), open-label control studies of clonidine adhesive patch versus other medications or/and placebo for TDs. The cochrane Handbook for Systematic Reviews of Interventions was used to guide our study. RESULTS: Six studies involving 1145 participants were included in this study. Among these studies, two study (N = 513 patients) used placebo as a control and four studies (N = 632 patients) used positive drug controls. The results of meta-analysis suggested that clonidine adhesive patch may be as effective as haloperidol or tiapride for TDs. Adverse events (AEs) were reported in all studies, and the most common AEs of clonidine adhesive patch were rash (8.9%), lightheadedness (8.0%), dry mouth (4.0%). The AEs of clonidine adhesive patch were slight. CONCLUSION: These data provide moderate quality evidence that clonidine adhesive patch might be an effective and safe treatment option for TDs, and results from further trials are urgently needed to extend the evidence base.

The efficacy and safety of aripiprazole for tic disorders in children and adolescents: A systematic review and meta-analysis.

The aims are to evaluate the efficacy and safety of aripiprazole for tic disorders (TDs) in children and adolescents. We searched PubMed, Embase, PsychINFO, Cochrane database as well as Chinese databases of CNKI, VIP, CBM and Wanfang from the database inception to October 2016, and 17 full-text studies (N=1305) were included in our article. The meta-analysis of 10 studies (N=817) showed that there was no significant difference in the reduction of total YGTSS score between aripiprazole and other drugs, and meta-analysis of 7 studies (n=324) which used tic symptom control ≧30% as outcome measure showed that there was no significant difference between aripiprazole and other treatments. The most common AEs of aripiprazole were the drowsiness, nausea/vomiting and increased appetite, and meta analysis which used the TESS scale as the outcome measurement showed that there was a significant difference between aripiprazole and haloperidol. In conclusion, these data provide moderate quality evidence that aripiprazole could be an effective and safe treatment option for TDs, and results from further trials are urgently needed to extend this evidence base.