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Abstract Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

Abstract Background Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG). Methods Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test. Results Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction. Conclusions These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity. Trial registration ChiCTR2000032245.

Abstract Background Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear. Methods Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R. Results Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation. Conclusions These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes. Graphical abstract

Diabetic nephropathy, a common and severe complication of diabetes, is the leading cause of end-stage renal disease, ultimately leading to renal failure and significantly affecting the prognosis and lives of diabetics worldwide. However, the complexity of its developmental mechanisms makes treating diabetic nephropathy a challenging task, necessitating the search for improved therapeutic targets. Intercellular communication underlies the direct and indirect influence and interaction among various cells within a tissue. Recently, studies have shown that beyond traditional communication methods, tunnel nanotubes, exosomes, filopodial tip vesicles, and the fibrogenic niche can influence pathophysiological changes in diabetic nephropathy by disrupting intercellular communication. Therefore, this paper aims to review the varied roles of intercellular communication in diabetic nephropathy, focusing on recent advances in this area.

IntroductionMetabolic syndrome (MetS) is significantly associated with osteoarthritis (OA), especially in MetS patients with blood glucose abnormalities, such as elevated fasting blood glucose (FG), which may increase OA risk. Dietary modifications, especially the intake of polyunsaturated fatty acids (PUFAs), are regarded as a potential means of preventing MetS and its complications. However, regarding the effects of FG, Omega-3s, and Omega-6s on OA, the research conclusions are conflicting, which is attributed to the complexity of the pathogenesis of OA. Therefore, it is imperative to thoroughly evaluate multiple factors to fully understand their role in OA, which needs further exploration and clarification.MethodsTwo-sample univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) were employed to examine the causal effect of metabolic related factors on hip OA (HOA) or knee OA (KOA). The exposure and outcome datasets were obtained from Open GWAS IEU. All cases were independent European ancestry data. Three MR methods were performed to estimate the causal effect: inverse-variance weighting (IVW), weighted median method (WMM), and MR-Egger regression. Additionally, the intercept analysis in MR-Egger regression is used to estimate pleiotropy, and the IVW method and MR-Egger regression are used to test the heterogeneity.ResultsThe UVMR analysis revealed a causal relationship between FG and HOA. By MVMR analysis, the study discovered a significant link between FG (OR = 0.79, 95%CI: 0.64∼0.99, p = 0.036) and KOA after accounting for body mass index (BMI), age, and sex hormone-binding globulin (SHBG). However, no causal effects of FG on HOA were seen. Omega-3s and Omega-6s did not have a causal influence on HOA or KOA. No significant evidence of pleiotropy was identified.DiscussionThe MR investigation showed a protective effect of FG on KOA development but no causal relationship between FG and HOA. No causal effect of Omega-3s and Omega-6s on HOA and KOA was observed. Shared genetic overlaps might also exist between BMI and age, SHBG and PUFAs for OA development. This finding offers a novel insight into the treatment and prevention of KOA from glucose metabolism perspective. The FG cutoff value should be explored in the future, and consideration should be given to demonstrating the study in populations other than Europeans.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive fat deposition in hepatocytes and a major cause of end-stage liver disease. Autophagy is a metabolic pathway responsible for degrading cytoplasmic products and damaged organelles, playing a pivotal role in maintaining the homeostasis and functionality of hepatocytes. Recent studies have shown that pharmacological intervention to activate or restore autophagy provides benefits for liver function recovery by promoting the clearance of lipid droplets (LDs) in hepatocytes, decreasing the production of pro-inflammatory factors, and inhibiting activated hepatic stellate cells (HSCs), thus improving liver fibrosis and slowing down the progression of NAFLD. This article summarizes the physiological process of autophagy, elucidates the close relationship between NAFLD and autophagy, and discusses the effects of drugs on autophagy and signaling pathways from the perspectives of hepatocytes, kupffer cells (KCs), and HSCs to provide assistance in the clinical management of NAFLD.

Background and aimMetabolic-associated fatty liver disease (MAFLD) has gradually become one of the main health concerns regarding liver diseases. Postmenopausal women represent a high-risk group for MAFLD; therefore, it is of great importance to identify and intervene with patients at risk at an early stage. This study established a predictive nomogram model of MAFLD in postmenopausal women and to enhance the clinical utility of the new model, the researchers limited variables to simple clinical and laboratory indicators that are readily obtainable.MethodsData of 942 postmenopausal women from January 2023 to October 2023 were retrospectively collected and divided into two groups according to the collection time: the training group (676 cases) and the validation group (226 cases). Significant indicators independently related to MAFLD were identified through univariate logistic regression and stepwise regression, and the MAFLD prediction nomogram was established. The C-index and calibration curve were used to quantify the nomogram performance, and the model was evaluated by measuring the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).ResultsOf 37 variables, 11 predictors were identified, including occupation (worker), body mass index, waist-to-hip ratio, number of abortions, anxiety, hypertension, hyperlipidemia, diabetes, hyperuricemia, and diet (meat and processed meat). The C-index of the training group predicting the related risk factors was 0.827 (95% confidence interval [CI] 0.794–0.860). The C-index of the validation group was 0.787 (95% CI 0.728–0.846). Calibration curves 1 and 2 (BS1000 times) were close to the diagonal, showing a good agreement between the predicted probability and the actual incidence in the two groups. The AUC of the training group was 0.827, the sensitivity was 0.784, and the specificity was 0.735. The AUC of the validation group was 0.787, the sensitivity was 0.674, and the specificity was 0.772. The DCA curve showed that the nomogram had a good net benefit in predicting MAFLD in postmenopausal women.ConclusionsA predictive nomogram for MAFLD in postmenopausal women was established and verified, which can assist clinicians in evaluating the risk of MAFLD at an early stage.

Abstract With the rapid advancements in deep learning technology, the Transformer-based attention neural network has shown promising performance in keyword spotting (KWS). However, this method suffers from high computational cost since the excessive parameters in the Transformer model and the computational burden of global attention, which limit its applicability in a resource-constrained KWS scenario. To overcome this issue, we propose a novel Swin-Transformer based KWS method. In this approach, first extract dynamic features using Temporal Convolutional Network (TCN) from input Mel-Frequency Cepstral Coefficients (MFCCs). Then, the Swin-Transformer is employed to capture hierarchical multi-scale features, where a window attention is designed to grasp dynamic time–frequency features. Furthermore, to enhance the extraction of contextual information from the spectrogram, a frame-level shifted window attention mechanism is proposed to enhance the inter-window interaction, thus extracting more contextual information from the spectrogram. Experimental results on the speech command V1 dataset verify the effectiveness of the proposal, which achieves a recognition accuracy of 98.01% with less model parameters, outperforming existing KWS methods.

Abstract Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

BackgroundPrevious observational studies have demonstrated a link between diabetes mellitus(DM) and primary biliary cholangitis (PBC). Nevertheless, since these relationships might be confused, whether there is any causal connection or in which direction it exists is unclear. Our investigation aimed to identify the causal associations between DM and PBC.MethodsWe acquired genome-wide association study (GWAS) datasets for PBC, Type 1 diabetes(T1DM), and Type 2 diabetes(T2DM) from published GWASs. Inverse variance-weighted (IVW), MR-Egger, weighted median (WM), Simple mode, and weighted mode methods were used to determine the causal relationships between DM(T1DM or T2DM) and PBC. Sensitivity analyses were also carried out to ensure the results were robust. To determine the causal relationship between PBC and DM(T1DM or T2DM), we also used reverse MR analysis.ResultsT1DM was associated with a higher risk of PBC (OR 1.1525; 95% CI 1.0612-1.2517; p = 0.0007) in the IVW method, but no evidence of a causal effect T2DM on PBC was found (OR 0.9905; 95% CI 0.8446-1.1616; p = 0.9071) in IVW. Results of the reverse MR analysis suggested genetic susceptibility that PBC was associated with an increased risk of T1DM (IVW: OR 1.1991; 95% CI 1.12-1.2838; p = 1.81E-07), but no evidence of a causal effect PBC on T2DM was found (IVW: OR 1.0101; 95% CI 0.9892-1.0315; p = 0.3420).ConclusionThe current study indicated that T1DM increased the risk of developing PBC and vice versa. There was no proof of a causal connection between PBC probability and T2DM. Our results require confirmation through additional replication in larger populations.

AbstractBackground Hepatocellular carcinoma lacks ideal diagnostic biomarkers. There is a lack of scientific evaluation of relevant promising biomarkers as well. Therefore this study reanalyzes the related studies of 11 blood biomarkers of HCC, and compares the diagnostic value of these biomarkers for HCC systematically.Methods The relevant literatures on the diagnostic value in HCC of 11 blood indexes in recent 5 years were searched in PubMed, Embase, and Cochrane libraries. Data were extracted and analyzed.Results Finally, 83 literature studies were brought into meta-analysis. The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The AUC and sum of sensitivity and specificity of the combination of AFP and other biomarkers were all significantly higher than that of AFP, including AFP + AFP-L3 + DCP, AFP + DCP, AFP/DCP, AFP + GPC3. Among other biomarkers, the AUC and sum of sensitivity and specificity of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN were significantly higher than that of AFP. In this study, GP73 had the highest sum of sensitivity and specificity (1.78) and AUC (0.95).Conclusions The pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency. The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP. GP73 had the best diagnostic value for HCC with the highest sum of sensitivity and specificity (1.78) and AUC (0.95).KEY MESSAGESThe pooled sensitivity and specificity of AFP were 0.61 and 0.87, respectively. The AUC of AFP were 0.78. The combination of AFP and other biomarkers improved the diagnostic efficiency of HCC.The diagnostic value of biomarkers including DCP, GPC3, GP73, Hsp90alpha, midkine, and OPN was higher than that of AFP.GP73 had the best diagnostic value for HCC.

ObjectiveThis study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice.MethodsA systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool.ResultsA total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-β1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant.ConclusionThe analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.

Abstract Background The cause of aggravation of diabetic myocardial damage is yet to be elucidated; damage to mitochondrial function has been a longstanding focus of research. During diabetic myocardial ischaemia–reperfusion (MI/R), it remains unclear whether reduced mitochondrial fusion exacerbates myocardial injury by generating free damaged mitochondrial DNA (mitoDNA) and activating the cGAS-STING pathway. Methods In this study, a mouse model of diabetes was established (by feeding mice a high-fat diet (HFD) plus a low dose of streptozotocin (STZ)), a MI/R model was established by cardiac ischaemia for 2 h and reperfusion for 30 min, and a cellular model of glycolipid toxicity induced by high glucose (HG) and palmitic acid (PA) was established in H9C2 cells. Results We observed that altered mitochondrial dynamics during diabetic MI/R led to increased mitoDNA in the cytosol, activation of the cGAS-STING pathway, and phosphorylation of the downstream targets TBK1 and IRF3. In the cellular model we found that cytosolic mitoDNA was the result of reduced mitochondrial fusion induced by HG and PA, which also resulted in cGAS-STING signalling and activation of downstream targets. Moreover, inhibition of STING by H-151 significantly ameliorated myocardial injury induced by MFN2 knockdown in both the cell and mouse models. The use of a fat-soluble antioxidant CoQ10 improved cardiac function in the mouse models. Conclusions Our study elucidated the critical role of cGAS-STING activation, triggered by increased cytosolic mitoDNA due to decreased mitochondrial fusion, in the pathogenesis of diabetic MI/R injury. This provides preclinical insights for the treatment of diabetic MI/R injury. Video Abstract Graphical Abstract

The diabetic kidney disease (DKD) is chronic kidney disease caused by diabetes and one of the most common comorbidities. It is often more difficult to treat end-stage renal disease once it develops because of its complex metabolic disorders, so early prevention and treatment are important. However, currently available DKD therapies are not ideal, and novel therapeutic strategies are urgently needed. The potential of stem cell therapies partly depends on their ability to secrete exosomes. More and more studies have shown that stem cell-derived exosomes take part in the DKD pathophysiological process, which may offer an effective therapy for DKD treatment. Herein, we mainly review potential therapies of stem cell-derived exosomes mainly stem cell-derived exosomal microRNAs in DKD, including their protective effects on mesangial cells, podocytes and renal tubular epithelial cells. Using this secretome as possible therapeutic drugs without potential carcinogenicity should be the focus of further research.

Abstract A longstanding theory indicates that the threat of a common enemy can mitigate conflict between members of rival groups. We tested this hypothesis in a pre-registered experiment where 1670 Republicans and Democrats in the United States were asked to complete an online social learning task with a bot that was labeled as a member of the opposing party. Prior to this task, we exposed respondents to primes about (a) a common enemy (involving Iran and Russia); (b) a patriotic event; or (c) a neutral, apolitical prime. Though we observed no significant differences in the behavior of Democrats as a result of priming, we found that Republicans—and particularly those with very strong conservative views—were significantly less likely to learn from Democrats when primed about a common enemy. Because our study was in the field during the 2020 Iran Crisis, we were able to further evaluate this finding via a natural experiment—Republicans who participated in our study after the crisis were even less influenced by the beliefs of Democrats than those Republicans who participated before this event. These findings indicate common enemies may not reduce inter-group conflict in highly polarized societies, and contribute to a growing number of studies that find evidence of asymmetric political polarization in the United States. We conclude by discussing the implications of these findings for research in social psychology, political conflict, and the rapidly expanding field of computational social science.

The gibberellic acid-stimulated Arabidopsis (GASA) gene family plays a crucial role in growth, development, and stress response, and it is specific to plants. This gene family has been extensively studied in various plant species, and its functional role in pineapple has yet to be characterized. In this study, 15 AcGASA genes were identified in pineapple through a genome-wide scan and categorized into three major branches based on a phylogenetic tree. All AcGASA proteins share a common structural domain with 12 cysteine residues, but they exhibit slight variations in their physicochemical properties and motif composition. Predictions regarding subcellular localization suggest that AcGASA proteins are present in the cell membrane, Golgi apparatus, nucleus, and cell wall. An analysis of gene synteny indicated that both tandem and segmental repeats have a significant impact on the expansion of the AcGASA gene family. Our findings demonstrate the differing regulatory effects of these hormones (GA, NAA, IAA, MeJA, and ABA) on the AcGASA genes. We analyzed the expression profiles of GASA genes in different pineapple tissue parts, and the results indicated that AcGASA genes exhibit diverse expression patterns during the development of different plant tissues, particularly in the regulation of floral organ development. This study provides a comprehensive understanding of GASA family genes in pineapple. It serves as a valuable reference for future studies on the functional characterization of GASA genes in other perennial herbaceous plants.

Abstract Background Gait disability affects the daily lives of patients with stroke in both home and community settings. An abnormal foot–ankle position can cause instability on the supporting surface and negatively affect gait. Our research team explored the ability of a portable peroneal nerve-targeting electrical stimulator to improve gait ability by adjusting the foot–ankle position during walking in patients with chronic stroke undergoing home-based rehabilitation. Methods This was a double-blinded, parallel-group randomized controlled trial. Thirty-one patients with chronic stroke and ankle–foot motor impairment were randomized to receive 3 weeks of gait training, which involved using the transcutaneous peroneal nerve stimulator while walking (tPNS group; n = 16, mean age: 52.25 years), or conventional home and/or community gait training therapy (CT group; n = 15, mean age: 54.8 years). Functional assessments were performed before and after the 3-week intervention. The outcome measures included spatiotemporal gait parameters, three-dimensional kinematic and kinetic data on the ankle–foot joint, and a clinical motor and balance function assessment based on the Fugl–Meyer Assessment of Lower Extremity (FMA-LE) and Berg Balance scales (BBS). Additionally, 16 age-matched healthy adults served as a baseline control of three-dimensional gait data for both trial groups. Results The FMA-LE and BBS scores improved in both the tPNS groups (p = 0.004 and 0.001, respectively) and CT groups (p = 0.034 and 0.028, respectively) from before to after training. Participants in the tPNS group exhibited significant differences in spatiotemporal gait parameters, including double feet support, stride length, and walking speed of affected side, and the unaffected foot off within a gait cycle after training (p = 0.043, 0.017, 0.001 and 0.010, respectively). Additionally, the tPNS group exhibited significant differences in kinematic parameters, such as the ankle angle at the transverse plane (p = 0.021) and foot progression angle at the frontal plane (p = 0.009) upon initial contact, and the peak ankle joint angle at the transverse plane (p = 0.023) and foot progression angle (FPA) at the frontal and transverse planes (p = 0.032 and 0.046, respectively) during gait cycles after 3 weeks of training. Conclusions Use of a portable tPNS device during walking tasks appeared to improve spatiotemporal gait parameters and ankle and foot angles more effectively than conventional home rehabilitation in patients with chronic stroke. Although guidelines for home-based rehabilitation training services and an increasing variety of market devices are available, no evidence for improvement of motor function and balance was superior to conventional rehabilitation. Trial registration Chictr, ChiCTR2000040137. Registered 22 November 2020, https://www.chictr.org.cn/showproj.aspx?proj=64424

In order to explore the best preparation technology and release performance of Artemisia selengensis flavonoids microcapsules, the molecular embedding method was used with Artemisia selengensis flavonoids as the core material, β-Cyclodextrin as the wall material, and the preparation technology of microcapsules was optimized by single factor and response surface methodology. By measuring the retention rate of flavonoids in microcapsules at different temperatures and relative humidity, Avrami’s formula was used to fit the release kinetics of microcapsules under different conditions. Meanwhile, the release rate constant and release mechanism parameters were analyzed. The results showed that the optimal preparation parameters of Artemisia selengensis flavonoids microcapsule were as follows: Embedding time 65 min, embedding temperature 55 ℃, core/wall material quality ratio 1:3 (g/g), the embedding rate of microcapsule could reach 89.52%. The release kinetics of microcapsules was between diffusion limited kinetics and first-order kinetics under the conditions of 4, 25, 45 ℃ and 50%, 70%, 90% relative humidity. In addition, the release rate constant increased with the increase of temperature and humidity. Therefore, low temperature and humidity will be more conducive to the preservation and sustained release of Artemisia selengensis flavonoids microcapsules. The results provide the theoretical basis for the research and development of Artemisia selengensis flavonoids and related functional food.

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked to cellular differences, the molecular identity and spatial distribution of PVT cell types remain unclear. To address this gap, here we used single nucleus RNA sequencing (snRNA-seq) and identified five molecularly distinct PVT neuronal subtypes in the mouse brain. Additionally, multiplex fluorescent in situ hybridization of top marker genes revealed that PVT subtypes are organized by a combination of previously unidentified molecular gradients. Lastly, comparing our dataset with a recently published single-cell sequencing atlas of the thalamus yielded novel insight into the PVT’s connectivity with the cortex, including unexpected innervation of auditory and visual areas. This comparison also revealed that our data contains a largely non-overlapping transcriptomic map of multiple midline thalamic nuclei. Collectively, our findings uncover previously unknown features of the molecular diversity and anatomical organization of the PVT and provide a valuable resource for future investigations.

BackgroundRoutine rehabilitation services were disrupted by the COVID-19 pandemic outbreak. Telehealth was identified as an alternative means to provide access to these services. This bibliometric study aimed to analyze the scientific literature to discover trends and topics in the potential applications of telerehabilitation for patients with stroke.MethodsThe Web of Science electronic database was searched to retrieve relevant publications on telerehabilitation. Bibliometric data, including visual knowledge maps of authors, countries, institutions, and references, were analyzed in CiteSpace. Visualization maps were generated in VOSviewer to illustrate recurrent keywords and countries actively involved in this research area.ResultsThe analysis was performed based on 6,787 publications. The number of publications peaked between 2019 and 2021, coinciding with the years of the COVID-19 outbreak. A total of 113 countries in Europe, North America, Asia, and Oceania had at least one publication in this research field, implying global attention in this research area. Nine of the top 10 most productive countries are developed countries, indicating a potentially higher capability to implement a telerehabilitation program.ConclusionThe potential benefits and diversity of telerehabilitation are already highly visible from clinical studies, and further improvements in these technologies are expected to enhance functionality and accessibility for patients. More relevant research is encouraged to understand the barriers to increased adaptation of telerehabilitation services, which will finally translate into a significant therapeutic or preventive impact.

BackgroundStroke is among the leading causes of disability of worldwide. Gait dysfunction is common in stroke survivors, and substantial advance is yet to be made in stroke rehabilitation practice to improve the clinical outcome of gait recovery. The role of the upper limb in gait recovery has been emphasized in the literature. Recent studies proposed that four limbs coordinated interventions, coined the term “interlimb-coordinated interventions,” could promote gait function by increasing the neural coupling between the arms and legs. A high-quality review is essential to examine the clinical improvement and neurophysiological changes following interlimb-coordinated interventions in patients with stroke.MethodsSystematic review and meta-analysis will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The literature will be retrieved from the databases of OVID, MEDLINE, PubMed, Web of Science, EMBASE, and PsycINFO. Studies published in English over the past 15 years will be included. All of the clinical studies (e.g., randomized, pseudorandomized and non-randomized controlled trials, uncontrolled trials, and case series) that employed interlimb intervention and assessed gait function of patients with stroke will be included. Clinical functions of gait, balance, lower limb functions, and neurophysiologic changes are the outcome measures of interest. Statistical analyses will be performed using the Comprehensive Meta-Analysis version 3.DiscussionThe findings of this study will provide insight into the clinical benefits and the neurophysiological adaptations of the nervous system induced by interlimb-coordinated intervention in patients with stroke. This would guide clinical decision-making and the future development of targeted neurorehabilitation protocol in stroke rehabilitation to improve gait and motor function in patients with stroke. Increasing neuroplasticity through four-limb intervention might complement therapeutic rehabilitation strategies in this patient group. The findings could also be insightful for other cerebral diseases.

Objective: This study aimed to evaluate the intervention effect of curcumin in myocardial infarction rodent models.Methods: A systematic retrieval of relevant studies on curcumin intervention in rats or mice myocardial infarction models was conducted, and the data were extracted. The outcome indicators included biochemical blood indicators, such as creatine kinase (CK), creatine kinase isoenzyme (CK-MB), malondialdehyde (MDA), lactate dehydrogenase (LDH) and superoxide dismutase (SOD), as well as cardiac tissue structure indicators, such as left ventricular weight to body weight ratio (LVW/BW), apoptosis index, left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), and myocardial infarction area, and hemodynamic indexes, such as systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular end-diastolic pressure (LVEDP), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), maximum rate of left ventricular pressure rise (+dp/dtmax), and maximum rate of left ventricular pressure decline (–dp/dtmax). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle’s bias risk tool.Results: A total of 24 studies were included in the meta-analysis. The quality assessment of included studies revealed that the evidence was low quality and none of studies was judged as having a low risk of bias across all domains. The results revealed that curcumin could reduce CK-MB, CK, LDH, and MDA levels. They also revealed that it could lower SBP, DBP, LVEDP, LVW/BW, apoptosis index, LVEDD, LVESD, and myocardial infarction area and increase LVEF, LVFS, +dp/dtmax, and–dp/dtmax. However, it had no significant impact on the heart rate and the levels of SOD in the models.Conclusion: Curcumin alleviates myocardial injury and oxidative stress in myocardial infarction rodent models in terms of blood biochemistry indicators, improves the diastolic and systolic capacity of the ventricle in terms of hemodynamic indexes, and reduces the necrosis and apoptosis of cardiomyocytes in terms of tissue structure. The methodological quality of the studies was low and additional research is warranted.

Abstract The purpose of this study was to investigate whether inhibition of DNA (cytosine-5)-methyltransferase 1 (DNMT-1) alleviated ferroptosis through nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy during diabetes myocardial (DM) ischemia/reperfusion (I/R) injury (IRI). Rat DM + sham (DS), I/R, and DM + I/R (DIR), H9c2 cell high glucose (HG), hypoxia reoxygenation (H/R), and high-glucose hypoxia reoxygenation (HH/R) models were established. DNMT-1 inhibitor 5-Aza-2’-deoxycytidine (5-aza-CdR) was administered to rat and cell models. The protein level of DNMT-1, NCOA4, FTH, GPX4, Beclin-1, and P62 was detected by western blotting. Compared with normal sham (NS) group, myocardial tissue was injured in DS and I/R models. The level of DNMT-1, NCOA4, and ferroptosis was increased. Moreover, the cell injury was more serious in rat DIR or HH/R model. 5-Aza-CdR could reduce NCOA4-mediated ferritinophagy and myocardial injury in DIR and HH/R models. Moreover, the siRNA for NCOA4 could also reduce the level of ferritinophagy and cell injury in HH/R model. 5-Aza-CdR enhanced the protective effect for NCOA4-siRNA in the process of cell injury. Inhibition of DNMT-1 could reduce ferroptosis during DIR, which the NCOA4-mediated ferritinophagy might be regulated.

Abstract Beyond the physical structures that contain daily routines, urban city dwellers repeatedly encounter strangers that similarly shape their environments. Familiar strangers are neither formal acquaintances nor completely anonymous faces in daily urban life. Due to data limitations, there is a lack of research focused on uncovering the structure of the “Familiar Stranger” phenomenon at a large scale while simultaneously investigating the social relationships between such strangers. Using countrywide mobile phone records from Andorra, we empirically show the existence of such a phenomenon as well as details concerning these strangers’ relative social relations. To understand the social and spatial components of familiar strangers more deeply, we study the temporal regularity and spatial structure of collective urban mobility to shed light on the mechanisms that guide these interactions. Furthermore, we explore the relationship between social distances and the number of encounters to show that more significant physical encounters correspond to a shorter social distance. Understanding these social and physical networks has essential implications for epidemics spreading, urban planning, and information diffusion.

BackgroundStroke is among the leading causes of long-term disability worldwide. Motor impairments after stroke not only impact the individuals quality of life but also lay substantial burdens on the society. Motor planning is a key component of cognitive function that impacts motor control. Hand movements such as grasping or reaching to grasp require the application of correct force and the coordination of multiple limb segments. Successful completion of hand motor task requires a certain degree of cognitive function to anticipate the requirement of the task. Cognitive function may thus be a confounding factor to rehabilitation outcomes. ObjectiveThis study aims to explore the impact of cognitive function on functional outcomes in people with subacute stroke after VR intervention. MethodsPatients with stroke were first stratified into cognitively normal (CN) and cognitively impaired (CI), followed by allocation to the VR or control group (CG). Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Barthel Index (BI), and Instrumental Activities of Daily Living (IADL) were recorded at baseline, 3 weeks after the intervention, and 3 and 6 months after the intervention. The between-group and within-group differences were assessed by repeated-measures analysis of variance (ANOVA). ResultsThe between-group comparison indicated that FMA-UE, BI, and IADL (time effect P

Abstract Diversity has tremendous value in modern society. Economic theories suggest that cultural and ethnic diversity may contribute to economic development and prosperity. To date, however, the correspondence between diversity measures and the economic indicators, such as the Consumer Price Index, has not been quantified. This is primarily due to the difficulty in obtaining data on the micro behaviors and macroeconomic indicators. In this paper, we explore the relationship between diversity measures extracted from large-scale and high-resolution mobile phone data, and the CPIs in different sectors in a tourism country. Interestingly, we show that diversity measures associate strongly with the general and sectoral CPIs, using phone records in Andorra. Based on these strong predictive relationships, we construct daily, and spatial maps to monitor CPI measures at a high resolution to complement existing CPI measures from the statistical office. The case study on Andorra used in this study contributes to two growing literature: linking diversity with economic outcomes, and macro-economic monitoring with large-scale data. Future study is required to examine the relationship between the two measures in other countries.

Probiotics are known to contribute to the anti-oxidation, immunoregulation, and aging delay. Here, we investigated the extension of lifespan by fermented pickles-origin Pediococcus acidilactici (PA) in Caenorhabditis elegans (C. elegans), and found that PA promoted a significantly extended longevity of wild-type C. elegans. The further results revealed that PA regulated the longevity via promoting the insulin/IGF-1 signaling, JNK/MAPK signaling but not TOR signaling in C. elegans, and that PA reduced the reactive oxygen species (ROS) levels and modulated expression of genes involved in fatty acids uptake and lipolysis, thus reducing the fat accumulation in C. elegans. Moreover, this study identified the nrfl-1 as the key regulator of the PA-mediated longevity, and the nrfl-1/daf-18 signaling might be activated. Further, we highlighted the roles of one chloride ion exchanger gene sulp-6 in the survival of C. elegans and other two chloride ion channel genes clh-1 and clh-4 in the prolonged lifespan by PA-feeding through the modulating expression of genes involved in inflammation. Therefore, these findings reveal the detailed and novel molecular mechanisms on the longevity of C. elegans promoted by PA.

Catecholaminergic neurons of the ventrolateral medulla are known to drive diverse glucose counterregulatory responses to hypoglycemia. Here, the authors show that projections from these neurons onto nucleus accumbens-targeting neurons of the midline thalamus selectively mediate hypoglycemic feeding.

Background: To determine whether abnormal coagulation parameters are associated with disease severity and poor prognosis in patients with 2019 Corona Virus Disease (COVID-19). Methods: A systematic literature search was conducted using the databases PubMed, Embase, and Web of sciences until April 25, 2020. We included a total of 15 studies with 2277 patients. Platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer (D-D), and fibrinogen (FIB) were collected and analyzed. The statistical results were expressed as the effect measured by mean difference (MD) with the related 95% confidence interval (CI). Results: The PLT level of severe cases was lower than that of mild cases, while the levels of PT, D-D, and FIB were higher than those of mild cases (P < 0.05). The level of APTT had no statistical difference between two groups (P > 0.05). PT of ICU patients was significantly longer (P < 0.05) than that of non-ICU patients. In non-survivors, PT and D-D were higher, yet PLT was lower than that of survivors (P < 0.05). There was no significant difference in APTT between survivors and non-survivors (P > 0.05). The funnel plot and Egger's regression test demonstrated that there was no publication bias. Conclusions: Our data support the notion that coagulopathy could be considered as a risk factor for disease severity and mortality of COVID-19, which may help clinicians to identify the incidence of poor outcomes in COVID-19 patients.

Since ancient times, dance has been widely loved by people. The history of dance has a long history, and people’s pursuit of dance has never stopped. However, with the development of modern technology, traditional dance has been unable to keep up with the pace of the times. Therefore, this article studies the influence of multimedia interaction on the development of dance. This article proposes that multimedia interaction has a great influence on the status quo of dance development. This article aims to study the role of multimedia interaction in dance development. In the eleven years since 2010, the technology of stage effects has developed rapidly. As you can imagine, not only the stage effects can bring a visual feast, but also the development space of dancers has been greatly improved. It can be seen that multimedia interaction is of great significance to the development of dance; with the rapid development of science and technology, multimedia technologies such as computer networks are widely used in all walks of life. The application in the field of dance art is gradually popularized, in which dance teaching and stage performance methods have undergone great changes with the in-depth popularization of multimedia. Therefore, this article must analyze the influence of multimedia interaction on the development of dance.

The overhead caused by broadcast schemes cannot be neglected in mobile ad hoc networks. It is known that the probabilistic broadcast scheme is an effective approach to reduce overhead, in which nodes forward packets with a probability to reduce redundant retransmissions. In hostile environments, malicious nodes degrade network efficiency, and they should be prevented from route discovery and data transmission. In this case, routing packets forwarded by malicious nodes are redundant. This paper presents a Trust-based Probabilistic Broadcast scheme (TPB) focusing on reducing overhead, especially caused by malicious nodes, in which rebroadcast probability is determined based on nodes' trustworthiness. In order to obtain nodes' trust level, a light-weight trust management model is designed based on direct and recommended trust evidence. According to nodes' trust level, rebroadcast delay is calculated for rearranging the rebroadcast order of routing packets. Furthermore, a novel method based on nodes' trustworthiness is proposed to calculate rebroadcast probability, which prevents untrusted nodes from route discovery. The proposed trust-based probabilistic broadcast scheme is incorporated with existing routing protocol and its performance is evaluated by simulations. The numerical results show that the proposed scheme can secure network communication and reduce the routing overhead.

Abstract This paper studies the Cauchy problem to a class of coupled nonlinear parabolic systems and investigates the asymptotic behavior of solutions to the problem. The blow-up theorem of Fujita type is established by the integral estimation and suitable supersolutions. Moreover, the critical Fujita exponent determined by the diffusion and the spatial dimension is given.

Edge computing is an important tool for smart computing, which brings convenience to data processing as well as security problems. In particular, the security of data storage under edge computing has become an obstacle to its widespread use. To solve the problem, the mechanism combing blockchain with regeneration coding is proposed to improve the security and reliability of stored data under edge computing. Our contribution is as follows. 1) According to the three-tier edge computing architecture and data security storage requirements, we proposed hybrid storage architecture and model specifically adapted to edge computing. 2) Making full use of the data storage advantages of edge network devices and cloud storage servers, we build a global blockchain in the cloud service layer and local blockchain is built on the terminals of the Internet of things. Moreover, the regeneration coding is utilized to further improve the reliability of data storage in blockchains. 3) Our scheme provides a mechanism for periodically validating hash values of data to ensure the integrity of data stored in global blockchain.

Background: This study combined neuromechanical modeling analysis, muscle tone measurement from mechanical indentation and electrical impedance myography to assess the neural and peripheral contribution to spasticity post stroke at wrist joint. It also investigated the training effects and explored the underlying mechanism of radial extracorporeal shock wave (rESW) on spasticity.Methods: People with first occurrence of stroke were randomly allocated to rESW intervention or control group. The intervention group received one session of rESW therapy, followed by routine therapy which was the same frequency and intensity as the control group. Outcome measures were: (1) NeuroFlexor method measured neural component (NC), elastic component (EC) and viscosity component (VC), and (2) myotonometer measured muscle tone (F) and stiffness (S), (3) electrical impedance myography measured resistance (R), reactance (X) and phase angle (θ); (4) modified Asworth scale; (5) Fugl Meyer Upper limb scale. All outcome measures were recorded at baseline, immediately post rESW and at 1-week follow-up. The differences between the paretic and non-paretic side were assessed by t-test. The effectiveness of rESW treatment were analyzed by repeated-measures one-way analysis of variance (ANOVA) at different time points.Results: Twenty-seven participants completed the study. NC, EC, and VC of the Neuroflexor method, F and S from myotonometer were all significantly higher on the paretic side than those from the non-paretic side. R, X, and θ from electrical impedance were significantly lower on the paretic side than the non-paretic side. Immediately after rESW intervention, VC, F, and S were significantly reduced, and X was significantly increased. The clinical scores showed improvements immediate post rESW and at 1-week follow-up.Conclusions: The observed changes in upper limb muscle properties adds further support to the theory that both the neural and peripheral components play a role in muscle spasticity. ESW intervention may be more effective in addressing the peripheral component of spasticity in terms of muscle mechanical properties changes. The clinical management of post stroke spasticity should take into consideration of both the neural and non-neural factors in order to identify optimal intervention regime.

Spasticity is a major contributor to pain, disabilities and many secondary complications after stroke. Investigating the effect of spasticity on neuromuscular function in stroke patients may facilitate the development of its clinical treatment, while the underlying mechanism of spasticity still remains unclear. The aim of this study is to explore the difference in the neuromuscular response to passive stretch between healthy subjects and stroke patients with spasticity. Five healthy subjects and three stroke patients with spastic elbow flexor were recruited to complete the passive stretch at four angular velocities (10°/s, 60°/s, 120°/s, and 180°/s) performed by an isokinetic dynamometer. Meanwhile, the 64-channel electromyography (EMG) signals from biceps brachii muscle were recorded. The root mean square (RMS) and fuzzy entropy (FuzzyEn) of EMG recordings of each channel were calculated, and the relationship between the average value of RMS and FuzzyEn over 64-channel was examined. The two groups showed similar performance from results that RMS increased and FuzzyEn decreased with the increment of stretch velocity, and the RMS was negatively correlated with FuzzyEn. The difference is that stroke patients showed higher RMS and lower FuzzyEn during quick stretch than the healthy group. Furthermore, compared with the healthy group, distinct variations of spatial distribution within the spastic muscle were found in the EMG activity of stroke patients. These results suggested that a large number of motor units were recruited synchronously in the presence of spasticity, and this recruitment pattern was non-uniform in the whole muscle. Using a combination of RMS and FuzzyEn calculated from high-density EMG (HD-EMG) recordings can provide an innovative insight into the physiological mechanism underlying spasticity, and FuzzyEn could potentially be used as a new indicator for spasticity, which would be beneficial to clinical intervention and further research on spasticity.

Patients with lung cancer are presumed to be at high risk from COVID-19 infection due to underlying malignancy. A total of 31 COVID-19 patients with pre-diagnosed lung cancer and 186 age and sex matched COVID-19 patients without cancer in 6 hospitals in Wuhan, China were identified in our study. There was a significantly higher level of IL-6 in lung cancer group showed by multifactorial analysis. The restricted mean survival time in 10, 20, and 53 days in COVID-19 patients with lung cancer were ealier than non-cancer COVID-19 patients in the same observation time (all P values < 0.05). Our results indicated that pre-diagnosed lung cancer was associated with higher morbidity and mortality in COVID-19 patients.

Objective The mechanism underlying the benefit of nonsurgical spinal decompression (NSSD) on low back pain is unclear. This study was performed to investigate the immediate impact of NSSD on the mechanical properties and morphology of the paraspinal muscles. Methods Participants with low back pain were recruited. NSSD therapy was provided on one occasion. A myotonometer was placed perpendicularly on the skin surface over the paraspinal muscle at the level of L 3 /L 4 to measure the mechanical muscle properties. The multifidus thickness was measured using B-mode ultrasound and defined as the distance between the transverse process and subcutaneous tissue fascia. The difference between before and after NSSD was analyzed by a paired t-test. Results Thirty participants (mean age, 20.9 ± 0.8 years; 9 male, 21 female) were recruited. No significant difference was observed in the muscle mechanical properties or morphology between before and after the intervention. Conclusions NSSD intervention did not induce immediate changes in the paraspinal muscle mechanical properties or multifidus thickness in young adults with low back pain. NSSD might produce benefits by stimulating mechanical receptors rather than inducing morphological changes or mechanical property alterations of the muscle fibers. These parameters may not be suitable outcome measures for NSSD intervention.

Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P

Background: The efficacy of interlimb-coordinated training on gait and upper limb functional improvement remains unclear. The latest published randomized controlled trials have supported the potential benefits of interlimb-coordinated training to enhance gait function. Upper limb functional recovery may also benefit from interlimb-coordinated training since most everyday activities require the coordinated use of both hands to complete a task. This study investigates the efficacy of interlimb-coordinated training on gait and upper limb functional recovery over a short-medium term period. Methods: A total of 226 acute stroke patients will be recruited from four centres over four years. Patients will be randomly allocated to either conventional therapy or conventional therapy plus interlimb-coordinated training. Outcomes will be recorded at baseline, after 2 weeks of intervention, and at 3- and 6-months post-intervention. Gait speed is the primary outcome measure. Secondary outcome measures include Fugl–Meyer Assessment of Motor Recovery, Berg Balance Scale, Timed Up and Go test, Action Research Arm Test, electroencephalography, and magnetic resonance imaging. Conclusion: The results of this trial will provide an in-depth understanding of the efficacy of early interlimb-coordinated intervention on gait and upper functional rehabilitation and how it may relate to the neural plasticity process.

Abstract Purpose: To investigate whether the neuroprotective effect of TSA on cerebral ischemia reperfusion injury is mediated by the activation of Akt/GSK-3β signaling pathway. Methods: Mice were randomly divided into four groups (n=15): sham group (S); ischemia reperfusion group (IR); ischemia reperfusion and pretreated with TSA group (IR+T); ischemia reperfusion and pretreated with TSA and LY294002 group (IR+T+L). The model of cerebral ischemia reperfusion was established by 1h of MCAO following 24h of reperfusion. TSA (5mg/kg) was intraperitoneally given for 3 days before MCAO, Akt inhibitor, LY294002 (15 nmol/kg) was injected by tail vein 30 min before the MCAO. Results: TSA significantly increased the expression of p-Akt, p-GSK-3β proteins and the levels of SOD, Bcl-2, reduced the infarct volume and the levels of MDA, ROS, TNF-α, IL-1β, Bax, Caspase-3, TUNEL and attenuated neurological deficit in mice with transient MCAO, LY294002 weakened such effect of TSA dramatically. Conclusions: TSA could significantly decrease the neurological deficit and reduce the cerebral infarct volume, oxidative stress, inflammation, as well as apoptosis during cerebral ischemia reperfusion injury, which was achieved by activation of the Akt/GSK-3β signaling pathway.

A critical question relevant to the increasing importance of crowd-sourced-based finance is how to optimize collective information processing and decision-making. Here, we investigate an often under-studied aspect of the performance of online traders: beyond focusing on just accuracy, what gives rise to the trade-off between risk and accuracy at the collective level? Answers to this question will lead to designing and deploying more effective crowd-sourced financial platforms and to minimizing issues stemming from risk such as implied volatility. To investigate this trade-off, we conducted a large online Wisdom of the Crowd study where 2037 participants predicted the prices of real financial assets (S&P 500, WTI Oil and Gold prices). Using the data collected, we modeled the belief update process of participants using models inspired by Bayesian models of cognition. We show that subsets of predictions chosen based on their belief update strategies lie on a Pareto frontier between accuracy and risk, mediated by social learning. We also observe that social learning led to superior accuracy during one of our rounds that occurred during the high market uncertainty of the Brexit vote.

This study aims to quantify passive muscle stiffness of spastic wrist flexors in stroke survivors using shear wave elastography (SWE) and to correlate with neural and non-neural contributors estimated from a biomechanical model to hyper-resistance measured during passive wrist extension. Fifteen hemiplegic individuals after stroke with Modified Ashworth Scale (MAS) score larger than one were recruited. SWE were used to measure Young's modulus of flexor carpi radialis muscle with joint from 0° (at rest) to 50° flexion (passive stretch condition), with 10° interval. The neural (NC) and non-neural components i.e., elasticity component (EC) and viscosity component (VC) of the wrist joint were analyzed from a motorized mechanical device NeuroFlexor® (NF). Combining with a validated biomechanical model, the neural reflex and muscle stiffness contribution to the increased resistance can be estimated. MAS and Fugl-Meyer upper limb score were also measured to evaluate the spasticity and motor function of paretic upper limb. Young's modulus was significantly higher in the paretic side of flexor carpi radialis than that of the non-paretic side (p < 0.001) and it increased significantly from 0° to 50° of the paretic side (p < 0.001). NC, EC, and VC on the paretic side were higher than the non-paretic side (p < 0.05). There was moderate significant positive correlation between the Young's Modulus and EC (r = 0.565, p = 0.028) and VC (r = 0.645, p = 0.009) of the paretic forearm flexor muscle. Fugl-Meyer of the paretic forearm flexor has a moderate significant negative correlation with NC (r = −0.578, p = 0.024). No significant correlation between MAS and shear elastic modulus or NF components was observed. This study demonstrated the feasibility of combining SWE and NF as a non-invasive approach to assess spasticity of paretic muscle and joint in stroke clinics. The neural and non-neural components analysis as well as correlation findings of muscle stiffness of SWE might provide understanding of mechanism behind the neuromuscular alterations in stroke survivors and facilitate the design of suitable intervention for them.

Diabetes aggravates myocardial ischemia-reperfusion (I/R) injury because of the combination effects of changes in glucose and lipid energy metabolism, oxidative stress, and systemic inflammatory response. Studies have indicated that myocardial I/R may coincide and interact with sepsis and inflammation. However, the role of LPS in hypoxia/reoxygenation (H/R) injury in cardiomyocytes under high glucose conditions is still unclear. Our objective was to examine whether lipopolysaccharide (LPS) could aggravate high glucose- (HG-) and hypoxia/reoxygenation- (H/R-) induced injury by upregulating ROS production to activate NLRP3 inflammasome-mediated pyroptosis in H9C2 cardiomyocytes. H9C2 cardiomyocytes were exposed to HG (30 mM) condition with or without LPS, along with caspase-1 inhibitor (Ac-YVAD-CMK), inflammasome inhibitor (BAY11-7082), ROS scavenger N-acetylcysteine (NAC), or not for 24 h, then subjected to 4 h of hypoxia followed by 2 h of reoxygenation (H/R). The cell viability, lactate dehydrogenase (LDH) release, caspase-1 activity, and intracellular ROS production were detected by using assay kits. The incidence of pyroptosis was detected by calcein-AM/propidium iodide (PI) double staining kit. The concentrations of IL-1β and IL-18 in the supernatants were assessed by ELISA. The mRNA levels of NLRP3, ASC, and caspase-1 were detected by qRT-PCR. The protein levels of NF-κB p65, NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18 were detected by western blot. The results indicated that pretreatment LPS with 1 μg/ml not 0.1 μg/ml could efficiently aggravate HG and H/R injury by activating NLRP3 inflammasome to mediate pyroptosis in H9C2 cells, as evidenced by increased LDH release and decreased cell viability in the cells, and increased expression of NLRP3, ASC, cleaved caspase-1 (p10), IL-1β, and IL-18. Meanwhile, Ac-YVAD-CMK, BAY11-7082, or NAC attenuated HG- and H/R-induced H9C2 cell injury with LPS stimulated by reversing the activation of NLRP3 inflammasome-mediated pyroptosis. In conclusion, LPS could increase the sensitivity of H9C2 cells to HG and H/R and aggravated HG- and H/R-induced H9C2 cell injury by promoting ROS production to induce NLRP3 inflammasome-mediated pyroptosis.

Background: Stroke survivors may lack the cognitive ability to anticipate the required control for palmar grasp execution. The cortical mechanisms involved in motor anticipation of palmar grasp movement and its association with post-stroke hand function remains unknown.Aims: To investigate the cognitive anticipation process during a palmar grasp task in subacute stroke survivors and to compare with healthy individuals. The association between cortical excitability and hand function was also explored.Methods: Twenty-five participants with hemiparesis within 1–6 months after first unilateral stroke were recruited. Twenty-five matched healthy individuals were recruited as control. Contingent negative variation (CNV) was measured using electroencephalography recordings (EEG). Event related potentials were elicited by cue triggered hand movement paradigm. CNV onset time and amplitude between pre-cue and before movement execution were recorded.Results: The differences in CNV onset time and peak amplitude were statistically significant between the subacute stroke and control groups, with patients showing earlier onset time with increased amplitudes. However, there was no statistically significant difference in CNV onset time and peak amplitude between lesioned and non-lesioned hemisphere in the subacute stroke group. Low to moderate linear associations were observed between cortical excitability and hand function.Conclusions: The earlier CNV onset time and higher peak amplitude observed in the subacute stroke group suggest increased brain computational demand during palmar grasp task. The lack of difference in CNV amplitude between the lesioned and non-lesioned hemisphere within the subacute stroke group may suggest that the non-lesioned hemisphere plays a role in the motor anticipatory process. The moderate correlations suggested that hand function may be associated with cortical processing of motor anticipation.

Most daily movements require some degree of collaboration between the upper limbs. The neural mechanisms are bimanual-condition specific and therefore should be different between different activities. In this study, we aimed to explore intraregional activation and interregional connectivity during bimanual movement by functional magnetic resonance imaging (fMRI). Ten right-handed, normal subjects were recruited. The neural correlates of unimanual (right side) and bimanual (in-phase and antiphase) upper limb movements were investigated. Connectivity analyses were carried out using the psychophysiological interaction (PPI) model. The cerebellum was strongly activated in both unimanual and bimanual movements, and the cingulate motor area (CMA) was the most activated brain area in antiphase bimanual movement. Moreover, compared with unimanual movement, CMA activation was also observed in antiphase bimanual movement, but not in in-phase bimanual movement. In addition, we carried out the PPI model to study the differences of effective connectivity and found that the cerebellum was more connected with the CMA during antiphase bimanual movement than in-phase bimanual movement. Our findings elucidate the differences of the cerebellar-cerebral functional connectivity between antiphase and in-phase bimanual movements, which could be used to facilitate the development of a neuroscience perspective on bimanual movement control in patients with motor impairments.

Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

Choline plays a lipotropic role in lipid metabolism as an essential nutrient. In this study, we investigated the effects of choline (5, 35 and 70 μM) on DNA methylation modifications, mRNA expression of the critical genes and their enzyme activities involved in hepatic lipid metabolism, mitochondrial membrane potential (Δψm) and glutathione peroxidase (GSH-Px) in C3A cells exposed to excessive energy substrates (lactate, 10 mM; octanoate, 2 mM and pyruvate, 1 mM; lactate, octanoate and pyruvate-supplemented medium (LOP)). Thirty five micromole or 70 μM choline alone, instead of a low dose (5 μM), reduced hepatocellular triglyceride (TG) accumulation, protected Δψm from decrement and increased GSH-Px activity in C3A cells. The increment of TG accumulation, reactive oxygen species (ROS) production and Δψm disruption were observed under LOP treatment in C3A cells after 72 h of culture, which were counteracted by concomitant treatment of choline (35 μM or 70 μM) partially via reversing the methylation status of the peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, upregulating PPARα, carnitine palmitoyl transferase-I (CPT-I) and downregulating fatty acid synthase (FAS) gene expression, as well as decreasing FAS activity and increasing CPT-I and GSH-Px activities. These findings provided a novel insight into the lipotropic role of choline as a vital methyl-donor in the intervention of chronic metabolic diseases.

Wireless body area networks (WBANs) are expected to play a vital role in the field of patient-health monitoring shortly. They provide a convenient way to collect patient data, but they also bring serious problems which are mainly reflected in the safe storage of the collected data. The privacy and security of data storage in WBAN devices cannot meet the needs of WBAN users. Therefore, this paper adopts blockchain technology to store data, which improves the security of the collected data. Moreover, a storage model based on blockchain in WBAN is proposed in our solution. However, blockchain storage brings new problems, for example, that the storage space of blockchain is small, and the stored content is open to unauthorized attackers. To solve the problems above, this paper proposed a sequential aggregate signature scheme with a designated verifier (DVSSA) to ensure that the user’s data can only be viewed by the designated person and to protect the privacy of the users of WBAN. In addition, the new signature scheme can also compress the size of the blockchain storage space.