Rutaecarpine Alleviates Early Brain Injury-Induced Inflammatory Response Following Subarachnoid Hemorrhage via SIRT6/NF-[Formula: see text]B Pathway.

Subarachnoid hemorrhage (SAH), a specific subtype of cerebrovascular accident, is characterized by the extravasation of blood into the interstice between the brain and its enveloping delicate tissues. This pathophysiological phenomenon can precipitate an early brain injury (EBI), which is characterized by inflammation and neuronal death. Rutaecarpine (Rut), a flavonoid compound discovered in various plants, has been shown to have protective effects against SAH-induced cerebral insult in rodent models. In our study, we used a rodent SAH model to evaluate the effect of Rut on EBI and investigated the effect of Rut on the inflammatory response and its regulation of SIRT6 expression in vitro. We found that Rut exerts a protective effect on EBI in SAH rats, which is partly due to its ability to inhibit the inflammatory response. Notably, Rut up-regulated Sirtuin 6 (SIRT6) expression, leading to an increase in H3K9 deacetylation and inhibition of nuclear factor-kappa B (NF-[Formula: see text]B) transcriptional activation, thereby mediating the inflammatory response. In addition, further data showed that SIRT6 was proven to mediate the regulation of Rut on the microglial inflammatory response. These findings highlight the importance of SIRT6 in the regulation of inflammation and suggest a potential mechanism for the protective effect of Rut on EBI. In summary, Rut may have the potential to prevent and treat SAH-induced brain injury by interacting with SIRT6. Our findings may provide a new therapeutic strategy for the treatment of SAH-induced EBI.

Periodic static compression of micro-strain pattern regulates endochondral bone formation.

Introduction: Developmental engineering based on endochondral ossification has been proposed as a potential strategy for repairing of critical bone defects. Bone development is driven by growth plate-mediated endochondral ossification. Under physiological conditions, growth plate chondrocytes undergo compressive forces characterized by micro-mechanics, but the regulatory effect of micro-mechanical loading on endochondral bone formation has not been investigated. Methods: In this study, a periodic static compression (PSC) model characterized by micro-strain (with 0.5% strain) was designed to clarify the effects of biochemical/mechanical cues on endochondral bone formation. Hydrogel scaffolds loaded with bone marrow mesenchymal stem cells (BMSCs) were incubated in proliferation medium or chondrogenic medium, and PSC was performed continuously for 14 or 28 days. Subsequently, the scaffold pretreated for 28 days was implanted into rat femoral muscle pouches and femoral condylar defect sites. The chondrogenesis and bone defect repair were evaluated 4 or 10 weeks post-operation. Results: The results showed that PSC stimulation for 14 days significantly increased the number of COL II positive cells in proliferation medium. However, the chondrogenic efficiency of BMSCs was significantly improved in chondrogenic medium, with or without PSC application. The induced chondrocytes (ichondrocytes) spontaneously underwent hypertrophy and maturation, but long-term mechanical stimulation (loading for 28 days) significantly inhibited hypertrophy and mineralization in ichondrocytes. In the heterotopic ossification model, no chondrocytes were found and no significant difference in terms of mineral deposition in each group; However, 4 weeks after implantation into the femoral defect site, all scaffolds that were subjected to biochemical/mechanical cues, either solely or synergistically, showed typical chondrocytes and endochondral bone formation. In addition, simultaneous biochemical induction/mechanical loading significantly accelerated the bone regeneration. Discussion: Our findings suggest that microstrain mechanics, biochemical cues, and in vivo microenvironment synergistically regulate the differentiation fate of BMSCs. Meanwhile, this study shows the potential of micro-strain mechanics in the treatment of critical bone defects.

Blended BA.5 infection within 8 days after a boosted bivalent mRNA vaccination strengthens and lengthens the host immunity.

The impact of SARS-CoV-2 infection shortly after vaccination on vaccine-induced immunity is unknown, which is also one of the concerns for some vaccinees during the pandemic. Here, based on a cohort of individuals who encountered BA.5 infection within 8 days after receiving the fourth dose of a bivalent mRNA vaccine, preceded by three doses of inactivated vaccines, we show that booster mRNA vaccination provided 48% protection efficacy against symptomatic infections. At Day 7 postvaccination, the level of neutralizing antibodies (Nabs) against WT and BA.5 strains in the uninfected group trended higher than those in the symptomatic infection group. Moreover, there were greater variations in Nabs levels and a significant decrease in virus-specific CD4+ T cell response observed in the symptomatic infection group. However, symptomatic BA.5 infection significantly increased Nab levels against XBB.1.9.1 and BA.5 (symptomatic > asymptomatic > uninfected group) at Day 10 and resulted in a more gradual decrease in Nabs against BA.5 compared to the uninfected group at Day 90. Our data suggest that BA.5 infection might hinder the early generation of Nabs and the recall of the CD4+ T cell response but strengthens the Nab and virus-specific T cell response in the later phase. Our data confirmed that infection can enhance host immunity regardless of the short interval between vaccination and infection and alleviate concerns about infections shortly after vaccination, which provides valuable guidance for developing future vaccine administration strategies.

Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization study.

BACKGROUND: This study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot's foot. METHODS: GM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications. RESULTS: After multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors. CONCLUSION: Extensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.

Effect of short-term exposure to air pollution on hospital admission for cardiovascular disease: A time-series study in Xiangyang, China.

BACKGROUND: Data on the relationship between short-term exposure to air pollution and cardiovascular diseases (CVDs) and the potential modifying factors are limited and inconsistent. OBJECTIVE: To explore the relationship between short-term exposure to air pollution and CVD risk, and potential modification effect factors. METHOD: A time series study was conducted on 52,991 hospital admissions for CVD from 2015 to 2019 in Xiangyang City, China. Air pollution data from four national fixed monitoring stations were collected to estimate exposure level in Xiangyang City. A quasi-Poisson generalized additive model incorporating a distributed lag nonlinear model was applied to evaluate the association between air pollution and CVD risk. The potential modification effect of sex, age, and season on the above associations was also evaluated. RESULTS: CVD risk was positively associated with air pollution. Peak associations in single lag day structures were observed for particulate matter ≤10 µm in aerodynamic (PM10; RR: 1.040, 95 % CI: 0.996-1.087), PM2.5 (1.025, 1.004-1.045), nitrogen dioxide (NO2; 1.074, 1.039-1.111), and sulfur dioxide (SO2; 1.079, 1.019-1.141) at Lag 0 and ozone (O3; 1.018, 1.004-1.031) at Lag 4. In cumulative lag day structures, the highest RRs were 1.225 (1.079,1.392) for PM10 at Lag 06, 1.054 (1.013, 1.098) for PM2.5 at Lag 03, 1.200 (1.119, 1.287) for NO2 at Lag 04, and 1.135 (1.025, 1.257) for SO2 at Lag 02. Moreover, the association between air pollution and CVD risk was modified by sex and age (P < 0.05). Females and individuals aged ≤65 years were more vulnerable to NO2 and had a higher CVD risk. CONCLUSION: Short-term exposure to air pollution was positively associated with CVD risk. Moreover, sex and age could modify the effect of air pollution on CVD risk. Females and individuals aged ≤65 years had a higher NO2 exposure-induced CVD risk.

P-coumaric Acid: Advances in Pharmacological Research Based on Oxidative Stress.

P-coumaric acid is an important phenolic compound that is mainly found in fruits, vegetables, grains, and fungi and is also abundant in Chinese herbal medicines. In this review, the pharmacological research progress of p-coumaric acid in recent years was reviewed, with emphasis on its role and mechanism in oxidative stress-related diseases, such as inflammation, cardiovascular diseases, diabetes, and nervous system diseases. Studies have shown that p-coumaric acid has a positive effect on the prevention and treatment of these diseases by inhibiting oxidative stress. In addition, p-coumaric acid also has anti-tumor, antibacterial, anti-aging skin and other pharmacological effects. This review will provide reference and inspiration for further research on the pharmacological effects of p-coumaric acid.

Toxicity and Toxicokinetics of a Four-Week Repeated Gavage of Levamisole in Male Beagle Dogs: A Good Laboratory Practice Study.

Levamisole (LVM) is considered an immunomodulatory agent that has the potential to treat various cancer and inflammation diseases. However, there is still much debate surrounding the toxicokinetic and toxicological information of LVM. Therefore, it is crucial to assess its toxicity to provide useful data for future human LVM risk assessments. In this study, a barrier environment was established under the guidance of good laboratory practice (GLP) at the Fujian Center for New Drug Safety Evaluation. Male beagle dogs were orally administered with 5, 15, and 30 mg/kg of LVM daily for four weeks. Toxicity assessment was based on various factors such as mortality, clinical signs, food and water consumption, body weight, body temperature, electrocardiogram, ophthalmological examination, hematology, serum biochemistry, organ/body coefficients, histopathological study, and toxicokinetic analysis. The results of this study showed that LVM did not exhibit any significant toxicological effects on beagle dogs at the exposure levels tested. A no observed adverse effect level (NOAEL) of LVM was set at 30 mg/kg/day for male beagle dogs, which is equivalent to a 12-fold clinical dose in humans. Moreover, the repeated exposure to LVM for four weeks did not lead to any bioaccumulation. These findings provide valuable insights for future human LVM risk assessments.

The integration of multidisciplinary approaches revealed PTGES3 as a novel drug target for breast cancer treatment.

BACKGROUND: The main challenge in personalized treatment of breast cancer (BC) is how to integrate massive amounts of computing resources and data. This study aimed to identify a novel molecular target that might be effective for BC prognosis and for targeted therapy by using network-based multidisciplinary approaches. METHODS: Differentially expressed genes (DEGs) were first identified based on ESTIMATE analysis. A risk model in the TCGA-BRCA cohort was constructed using the risk score of six DEGs and validated in external and clinical in-house cohorts. Subsequently, independent prognostic factors in the internal and external cohorts were evaluated. Cell viability CCK-8 and wound healing assays were performed after PTGES3 siRNA was transiently transfected into the BC cell lines. Drug prediction and molecular docking between PTGES3 and drugs were further analyzed. Cell viability and PTGES3 expression in two BC cell lines after drug treatment were also investigated. RESULTS: A novel six-gene signature (including APOOL, BNIP3, F2RL2, HINT3, PTGES3 and RTN3) was used to establish a prognostic risk stratification model. The risk score was an independent prognostic factor that was more accurate than clinicopathological risk factors alone in predicting overall survival (OS) in BC patients. A high risk score favored tumor stage/grade but not OS. PTGES3 had the highest hazard ratio among the six genes in the signature, and its mRNA and protein levels significantly increased in BC cell lines. PTGES3 knockdown significantly inhibited BC cell proliferation and migration. Three drugs (gedunin, genistein and diethylstilbestrol) were confirmed to target PTGES3, and genistein and diethylstilbestrol demonstrated stronger binding affinities than did gedunin. Genistein and diethylstilbestrol significantly inhibited BC cell proliferation and reduced the protein and mRNA levels of PTGES3. CONCLUSIONS: PTGES3 was found to be a novel drug target in a robust six-gene prognostic signature that may serve as a potential therapeutic strategy for BC.

The Causal Association between Alcohol, Smoking, Coffee Consumption, and the Risk of Arthritis: A Meta-Analysis of Mendelian Randomization Studies.

Objective: To evaluate the genetic causality between alcohol intake, smoking, coffee consumption, and arthritis. Methods: Mendelian randomization (MR) studies with alcohol, smoking, and coffee consumption behaviors as exposures, and osteoarthritis (OA) and rheumatoid arthritis (RA) as outcomes were retrieved from up to July 2023. Two researchers with relevant professional backgrounds independently assessed the quality and extracted data from the included studies. Meanwhile, we applied MR analyses of four lifestyle exposures and five arthritis outcomes (two for OA and three for RA) with gene-wide association study (GWAS) data that were different from the included studies, and the results were also included in the meta-analysis. Statistical analyses were performed using Stata 16.0 and R software version 4.3.1. Results: A total of 84 studies were assessed. Of these, 11 were selected for meta-analysis. As a whole, the included studies were considered to be at a low risk of bias and were of high quality. Results of the meta-analysis showed no significant genetic causality between alcohol intake and arthritis (odds ratio (OR): 1.02 (0.94-1.11)). Smoking and arthritis had a positive genetic causal association (OR: 1.44 (1.27-1.64)) with both OA (1.44 (1.22-1.71)) and RA (1.37 (1.26-1.50)). Coffee consumption and arthritis also had a positive genetic causal association (OR: 1.02 (1.01-1.03)). Results from the subgroup analysis showed a positive genetic causality between coffee consumption and both OA (OR: 1.02 (1.00-1.03)) and RA (OR: 1.56 (1.19-2.05)). Conclusion: There is positive genetic causality between smoking and coffee consumption and arthritis (OA and RA), while there is insufficient evidence for genetic causality between alcohol intake and arthritis.

Transfer Learning for Indoor Localization Algorithm Based on Deep Domain Adaptation.

In application, training data and test data collected via indoor positioning algorithms usually do not come from the same ideal conditions. Changes in various environmental conditions and signal drift can cause different probability distributions between the data sets. Existing positioning algorithms cannot guarantee stable accuracy when facing these issues, resulting in dramatic reduction and the infeasibility of the positioning accuracy of indoor location algorithms. Considering these restrictions, domain adaptation technology in transfer learning has proven to be a promising solution in past research in terms of solving the inconsistent probability distribution problems. However, most localization algorithms based on transfer learning do not perform well because they only learn a shallow representation feature, which can only slightly reduce the domain discrepancy. Based on the deep network and its strong feature extraction ability, it can learn more transferable features for domain adaptation and achieve better domain adaptation effects. A Deep Joint Mean Distribution Adaptation Network (DJMDAN) is proposed to align the global domain and relevant subdomain distributions of activations in multiple domain-specific layers across domains to achieve domain adaptation. The test results demonstrate that the performance of the proposed method outperforms the comparison algorithm in indoor positioning applications.

Causal associations between common musculoskeletal disorders and dementia: a Mendelian randomization study.

Introduction: Dementia and musculoskeletal disorders (MSDs) are major public health problems. We aimed to investigate the genetic causality of common MSDs and dementia. Methods: Two-sample Mendelian randomization (MR) was used in this study. MR analysis based on gene-wide association study (GWAS) data on osteoarthritis (OA), dementia with Lewy bodies, and other MSDs and dementia types were obtained from the Genetics of Osteoarthritis consortium, IEU-open GWAS project, GWAS catalog, and FinnGen consortium. Rigorously selected single-nucleotide polymorphisms were regarded as instrumental variables for further MR analysis. Inverse-variance weighted, MR-Egger regression, weight median, simple mode, and weight mode methods were used to obtain the MR estimates. Cochran's Q test, MR-Egger and MR-Pleiotropy Residual Sum and Outlier analysis, and the leave-one-out test were applied for sensitivity testing. Results: The inverse-variance weighted method showed that hip OA was genetically associated with a lower risk of dementia, unspecified dementia, dementia in Alzheimer's disease, and vascular dementia. Kneehip OA was inversely associated with unspecified dementia and vascular dementia. Rheumatoid arthritis, juvenile idiopathic arthritis and seronegative rheumatoid arthritis were inversely associated with frontotemporal dementia, and rheumatoid arthritis was inversely associated with unspecified dementia. Simultaneously, ankylosing spondylitis was an independent risk factor for dementia, dementia with Lewy bodies, and dementia in Alzheimer's disease. Sensitivity tests showed that heterogeneity and horizontal pleiotropy did not exist in these associations. The leave-one-out test showed that these associations were stable. Conclusion: We found that some MSDs were associated with the risk of dementia and provide evidence for the early detection of dementia in patients with MSDs and for the impact of inflammation on the central nervous system.

Study on the Mechanical Properties and Mechanism of a Nickel-Iron Slag Cement-Based Composite under the Action of Sodium Sulfate.

The accumulated amount of nickel-iron slag has increased with the rapid development of the nickel-iron industry. To determine a method for comprehensively utilizing nickel-iron slag, triaxial compression tests of nickel-iron slag cement-based composite materials under the action of sodium sulfate were conducted, and the effects of the sodium sulfate concentration on the stress-strain relation, shear strength, cohesion, and internal friction angle of the composite materials were analyzed. In addition, the influence mechanism of the nickel-iron slag content and sodium sulfate concentration on the composite was examined. The results revealed that the stress-strain curve of the nickel-iron slag cement-based composites reflected softening. With the increase in the sodium sulfate concentration, the brittleness increased, while the shear strength, cohesion, and internal friction angle decreased; the addition of nickel-iron slag slowed down the rate at which these parameters decrease. Scanning electron microscopy images revealed that nickel-iron slag can improve the internal structure of the cement composite soil, enhance its compactness, and improve its corrosion resistance. The optimum nickel-iron slag content of 14% can improve the cementitious composites' resistance to sodium sulfate erosion in terms of solid waste utilization and cementitious soil performance. The results obtained can provide technical parameters for preparing and designing cement-based composite materials as well as certain theoretical significance and engineering reference value.

Executive function elevated by long term high-intensity physical activity and the regulation role of beta-band activity in human frontal region.

The importance of physical activity (PA) to people's health has become a consensus around the world, and regular long-term PA has been accepted as an alternative preventive measure for many chronic medical conditions. Although the daily PA have several benefits for the public, the systematic research on its effect in human physiology, cognition and cerebral nerve level is not fully studied. Hence, in this study, we aim to investigate this question in several specific aspects: basal heart rate, executive function, and neural oscillatory activity in the brain. A total of 146 subjects participated in this study and they were divided into two groups. One group (SG) is the long-term training (more than 8 years) subjects in soccer (n = 31), and the other group (CG) is a normal control group (n = 115). The heart rate was monitored with a portable equipment. Besides, 24 subjects (14 in SG and 10 in CG) participated the Go/No-Go task and EEG recording before and after exercise fatigue task. In the physiology level, we found that in the non-training time, the heart rate in CG group is significantly higher than that of the SG group (P < 0.001). In the cognition level, we found that the SG group has a faster reaction time that that of CG group (P < 0.01), while for the accuracy, two groups did show significant difference. In the neural level in the brain, we found a significant abnormal increased beta-band (around 25 Hz) activity in CG group after the exercise fatigue task immediately. Long-term high-intensity physical activity reduces basal heart rate, improves executive function, and improve the central tolerance of the body under the stimulation of fatigue and stress. These benefits of long-term activity could be used as a manual to guide people's healthy life.

Wet cupping with rehabilitation training for upper-limb poststroke spasticity: A systematic review and meta-analysis of randomized controlled trials.

Background: Upper-limb poststroke spasticity (PSS) negatively impacts on patients' quality of life. An increasing number of clinical trials have indicated that wet cupping with rehabilitation training is conductive to alleviate spastic muscle tone, thereby to improve upper-limb function. However, related evidence base is insufficient. This study systematically investigates the efficacy and safety of wet cupping with rehabilitation training on stroke patients with upper-limb spasticity. Methods: Eight separate databases and two clinical trial registries were searched from their inception to December 6, 2022. Two reviewers extracted the data and assessed the quality of the literature, independently. The mean difference (MD) or risk ratio (RR) were used as measure of effect size in meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used for the certainty of evidence. Results: Eight randomized controlled trials (RCTs) were quantified for meta-analysis. The results indicated that in comparison with the control group, wet cupping with rehabilitation training was more effective in reducing modified Ashworth scale score (MD = -0.60, 95% CI: -0.74, -0.46; P < 0.00001) and the integral electromyography value of biceps muscle (MD = -4.71, 95% CI: -6.74, -2.67; P < 0.00001), but improving effective rate (RR = 1.28, 95% CI: 1.15, 1.41; P < 0.00001), Fugl-Myer Assessment score (MD = 4.84, 95% CI: 3.05, 6.64; P < 0.00001) as well as Barthel Index score (MD = 6.38, 95% CI: 2.20, 10.57; P = 0.003). However, no significant difference was found regarding the integral electromyography value of triceps muscle between groups (MD = 1.72, 95% CI: -2.05, 5.48; P = 0.37). Conclusion: Wet cupping with rehabilitation training should be included in a comprehensive therapeutic regimen for stroke patients with upper-limb spasticity. However, these results need to be further verified by more RCTs with rigorous design and large sample size.

Electrophysiological mechanisms of motion-style scalp acupuncture for treating poststroke spasticity in rats. / è¿åŠ¨å¤´é’ˆæ³•æŠ—å’ä¸­åŽç—‰æŒ›æ•ˆåº”çš„ç”µç”Ÿç†æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of motion-style scalp acupuncture (MSSA) on H-reflex in rats with post-stroke spasticity (PSS), so as to explore the electrophysiological mechanisms of MSSA against spasticity. METHODS: A total of 36 male SD rats were randomly divided into sham operation, model and MSSA groups, with 12 rats in each group. The stroke model was established by occlusion of the middle cerebral artery. After modeling, rats in the MSSA group were treated by scalp acupuncture (manipulated every 15 min, 200 r/min) at ipsilesional "parietal and temporal anterior oblique line" (MS6) for a total of 30 min, the treadmill training (10 m/min) was applied during the needling retention, once daily for consecutive 7 days. The neurological deficits, muscle tone and motor function were assessed by Zea Longa score, modified modified Ashworth scale (MMAS) score and screen test score before and after treatment, respectively. The H-reflex of spastic muscle was recorded by electrophysiological recordings and the frequency dependent depression (FDD) of H-reflex was also recorded. The cerebral infarction volume was evaluated by TTC staining. RESULTS: Compared with the sham operation group, the Zea longa score, MMAS score, cerebral infarction volume, motion threshold, Hmax/Mmax ratio and FDD of H-reflex were significantly increased (P<0.01), while the screen test score was significantly decreased (P<0.01) in the model group. Intriguingly, compared with the model group, the above results were all reversed (P<0.01) in the MSSA group. CONCLUSIONS: MSSA could exert satisfactory anti-spastic effects in rats with PSS, the underlying mechanism may be related to the improvement of nerve function injury, the reduction of spastic muscle movement threshold, Hmax/Mmax ratio and H-reflex FDD.

Optic disc detection based on fully convolutional network and weighted matrix recovery model.

Eye diseases often affect human health. Accurate detection of the optic disc contour is one of the important steps in diagnosing and treating eye diseases. However, the structure of fundus images is complex, and the optic disc region is often disturbed by blood vessels. Considering that the optic disc is usually a saliency region in fundus images, we propose a weakly-supervised optic disc detection method based on the fully convolution neural network (FCN) combined with the weighted low-rank matrix recovery model (WLRR). Firstly, we extract the low-level features of the fundus image and cluster the pixels using the Simple Linear Iterative Clustering (SLIC) algorithm to generate the feature matrix. Secondly, the top-down semantic prior information provided by FCN and bottom-up background prior information of the optic disc region are used to jointly construct the prior information weighting matrix, which more accurately guides the decomposition of the feature matrix into a sparse matrix representing the optic disc and a low-rank matrix representing the background. Experimental results on the DRISHTI-GS dataset and IDRiD dataset show that our method can segment the optic disc region accurately, and its performance is better than existing weakly-supervised optic disc segmentation methods. Graphical abstract of optic disc segmentation.

Performance evaluation of a liquid-sodium thermoacoustic engine with magnetohydrodynamic electricity generation based upon the Swift model.

Liquid sodium is an attractive working fluid for thermoacoustic conversion. Herein, a numerical study on a standing-wave thermoacoustic electricity generation system with liquid sodium as the working fluid is presented, based upon the Swift model. The characteristics of the thermoacoustic conversion and the output performance of the system have been investigated. The results show that the sodium engine can reach a power density much higher than the classical gas engine. Due to the strong acoustic coupling between components, the electricity output is significantly affected by the input heating power, the magnetic flux density, and the load ratio. In a typical case, the thermal-to-electric efficiency and the relative Carnot efficiency can reach 4.6% and 7.8%, respectively, with a temperature difference of 563 K and an input heat of 5 kW. More importantly, the output electricity density reaches 150 kW/m3, higher than some commercially available technologies. These results demonstrate the potential of such technology for small-scale electricity generation. Its extremely simple structure without any mechanical moving part endows the system with high reliability and long lifetime, if risks of corrosion and exposure to air and water can be avoided.

Dopamine Release Impairments Accompany Movement Vigor Deficiency in an Exercise-Induced Fatigue Mouse Model.

Fatigue is a common symptom in neurological diseases with a complex cause, involving the influence of events occurring in both the central and peripheral nervous systems. When people suffer from fatigue, a general decline in their movement performance typically occurs. The neural representation of dopamine signaling in the striatum plays a crucial role in movement regulation. Movement vigor is regulated by dopamine-dependent neuron activity in the striatum. However, whether exercise-induced fatigue alters stimulated dopamine release and further affects movement vigor has not been described. Here, for the first time, we used fast-scan cyclic voltammetry to demonstrate the effect of exercise-induced fatigue on stimulated dopamine release in the striatum in combination with a fiber photometry system to observe the excitability of striatal neurons. The movement vigor of mice was reduced, and after fatigue, the balance of excitability of striatal neurons regulated by dopamine projections was disturbed, which was induced by a reduction in dopamine release. Additionally, D2DR regulation may serve as a targeted intervention to alleviate exercise-induced fatigue and promote fatigue recovery.

Immune-related biomarkers predict the prognosis and immune response of breast cancer based on bioinformatic analysis and machine learning.

Breast cancer (BC) is the malignancy with the highest mortality rate among women, identification of immune-related biomarkers facilitates precise diagnosis and improvement of the survival rate in early-stage BC patients. 38 hub genes significantly positively correlated with tumor grade were identified based on weighted gene coexpression network analysis (WGCNA) by integrating the clinical traits and transcriptome analysis. Six candidate genes were screened from 38 hub genes basing on least absolute shrinkage and selection operator (LASSO)-Cox and random forest. Four upregulated genes (CDC20, CDCA5, TTK and UBE2C) were identified as biomarkers with the log-rank p < 0.05, in which high expression levels of them showed a poor overall survival (OS) and recurrence-free survival (RFS). A risk model was finally constructed using LASSO-Cox regression coefficients and it possessed superior capability to identify high risk patients and predict OS (p < 0.0001, AUC at 1-, 3- and 5-years are 0.81, 0.73 and 0.79, respectively). Decision curve analysis demonstrated risk score was the best prognostic predictor, and low risk represented a longer survival time and lower tumor grade. Importantly, multiple immune cell types and immunotherapy targets were observed increase in expression levels in high-risk group, most of which were significantly correlated with four genes. In summary, the immune-related biomarkers could accurately predict the prognosis and character the immune responses in BC patients. In addition, the risk model is conducive to the tiered diagnosis and treatment of BC patients.

New insights into acupuncture techniques for poststroke spasticity.

With the trend of aging population getting more obvious, stroke has already been a major public health problem worldwide. As a main disabling motor impairment after stroke, spasticity has unexpected negative impacts on the quality of life and social participation in patients. Moreover, it brings heavy economic burden to the family and society. Previous researches indicated that abnormality of neural modulation and muscle property corelates with the pathogenesis of poststroke spasticity (PSS). So far, there still lacks golden standardized treatment regimen for PSS; furthermore, certain potential adverse-events of the mainstream therapy, for example, drug-induced generalized muscle weakness or high risk related surgery somehow decrease patient preference and compliance, which brings challenges to disease treatment and follow-up care. As an essential non-pharmacological therapy, acupuncture has long been used for PSS in China and shows favorable effects on improvements of spastic hypertonia and motor function. Notably, previous studies focused mainly on the research of antispastic acupoints. In comparison, few studies lay special stress on the other significant factor impacting on acupuncture efficacy, that is acupuncture technique. Based on current evidences from the clinic and laboratory, we will discuss certain new insights into acupuncture technique, in particular the antispastic needling technique, for PSS management in light of its potential effects on central modulations as well as peripheral adjustments, and attempt to provide some suggestions for future studies with respect to the intervention timing and course, application of acupuncture techniques, acupoint selection, predictive and aggravating factors of PSS, aiming at optimization of antispastic acupuncture regimen and improvement of quality of life in stroke patients. More innovations including rigorous study design, valid objective assessments for spasticity, and related experimental studies are worthy to be expected in the years ahead.