Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a ...potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.Deep brain stimulation (DBS) of the anterior nucleus of the thalamus is an efficacious treatment option for patients with refractory epilepsy. Our previous study demonstrates that adenosine is a potential target of DBS for the treatment of epilepsy. Equilibrative nucleoside transporters-1 (ENT1) and ectonucleotidases (CD39, CD73) function as regulators of extracellular adenosine in the brain. It is unclear whether ENT1, CD39, and CD73 are involved in the mechanism of DBS for epilepsy. A total of 48 SD male rats were divided into four groups: control (naïve rats), Pilo (pilocarpine induced rats with epilepsy), DBS (rats with epilepsy treated with DBS for 8 weeks), and sham. In the present study, video electroencephalogram monitoring, Morris water maze assays, in vivo measurements of adenosine using fiber photometry, histochemistry, and western blot were performed on the hippocampus. DBS markedly attenuated spontaneous recurrent seizures (SRSs) and enhanced spatial learning in rats with epilepsy, assessed through video-EEG and water maze assays. Fibred photometry measurements of an adenosine sensor revealed dynamic increase in extracellular adenosine during DBS. The expressions of ENT1, CD39, and CD73 in Pilo group and sham group increased compared with the control group, while the expressions of ENT1, CD39, and CD73 in DBS group decreased compared to that of Pilo group and sham group. The findings indicate that DBS reduces the number of SRSs and improves spatial memory in rats with epilepsy with concomitant decrease of ENT1, CD39, and CD73 expressions. Adenosine-modulating enzymes might be the potential targets of DBS for the treatment of epilepsy.
Background
Traumatic brain injury (TBI) has been recognized as an important and common cause of epilepsy since antiquity. Posttraumatic epilepsy (PTE) is usually associated with drug resistance and ...poor surgical outcomes, thereby increasing the burden of the illness on patients and their families. Vagus nerve stimulation (VNS) is an adjunctive treatment for medically refractory epilepsy. This study aimed to determine the efficacy of VNS for refractory PTE and to initially evaluate the potential predictors of efficacy.
Methods
We retrospectively collected the outcomes of VNS with at least a 1-year follow-up in all patients with refractory PTE. Subgroups were classified as responders and non-responders according to the efficacy of VNS (≥50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS efficacy.
Results
In total, forty-five patients with refractory PTE who underwent VNS therapy were enrolled. Responders were found in 64.4% of patients, and 15.6% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 37.8, 44.4, 60, and 67.6% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, generalized interictal epileptic discharges (IEDs) were found to be a negative predictor (OR: 4.861, 95% CI: 1.145–20.632) of VNS efficacy.
Conclusion
The results indicated that VNS therapy was effective in refractory PTE patients and was well tolerated over a 1-year follow-up period. Patients with focal or multifocal IEDs were recognized to have better efficacy after VNS therapy.
Focal cortical dysplasia (FCD), a common malformation of cortical development, is frequently associated with pharmacoresistant epilepsy in both children and adults. Adenosine is an inhibitory ...modulator of brain activity and a prospective anti-seizure agent with potential for clinical translation. Our previous results demonstrated that the major adenosine-metabolizing enzyme adenosine kinase (ADK) was upregulated in balloon cells (BCs) within FCD type IIB lesions, suggesting that dysfunction of the adenosine system is implicated in the pathophysiology of FCD. In our current study, we therefore performed a comprehensive analysis of adenosine signaling in surgically resected cortical specimens from patients with FCD type I and type II via immunohistochemistry and immunoblot analysis. Adenosine enzyme signaling was assessed by quantifying the levels of the key enzymes of adenosine metabolism, i.e., ADK, adenosine deaminase (ADA), and ecto-5'-nucleotidase (CD73). Adenosine receptor signaling was assessed by quantifying the levels of adenosine A
2A
receptor (A
2A
R) and putative downstream mediators of adenosine, namely, glutamate transporter-1 (GLT-1) and mammalian target of rapamycin (mTOR). Within lesions in FCD specimens, we found that the adenosine-metabolizing enzymes ADK and ADA, as well as the adenosine-producing enzyme CD73, were upregulated. We also observed an increase in A
2A
R density, as well as a decrease in GLT-1 levels and an increase in mTOR levels, in FCD specimens compared with control tissue. These results suggest that dysregulation of the adenosine system is a common pathologic feature of both FCD type I and type II. The adenosine system might therefore be a therapeutic target for the treatment of epilepsy associated with FCD.
Vagus nerve stimulation (VNS) is an adjunctive treatment for pharmacoresistant epilepsy. Encephalomalacia is one of the most common MRI findings in the preoperative evaluation of patients with ...pharmacoresistant epilepsy. This is the first study that aimed to determine the effectiveness of VNS for pharmacoresistant epilepsy secondary to encephalomalacia and evaluate the potential predictors of VNS effectiveness.
We retrospectively analyzed the seizure outcomes of VNS with at least 1 year of follow-up in all patients with pharmacoresistant epilepsy secondary to encephalomalacia. Based on the effectiveness of VNS (≥50% or <50% reduction in seizure frequency), patients were divided into two subgroups: responders and non-responders. Preoperative data were analyzed to screen for potential predictors of VNS effectiveness.
A total of 93 patients with epilepsy secondary to encephalomalacia who underwent VNS therapy were recruited. Responders were found in 64.5% of patients, and 16.1% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time, with 36.6, 50.5, 64.5, and 65.4% at the 3-, 6-, 12-, and 24-month follow-ups, respectively. After multivariate analysis, seizure onset in adults (>18 years old) (OR: 0.236, 95%CI: 0.059-0.949) was found to be a positive predictor, and the bilateral interictal epileptic discharges (IEDs) (OR: 3.397, 95%CI: 1.148-10.054) and the bilateral encephalomalacia on MRI (OR: 3.193, 95%CI: 1.217-8.381) were found to be negative predictors of VNS effectiveness.
The results demonstrated the effectiveness and safety of VNS therapy in patients with pharmacoresistant epilepsy secondary to encephalomalacia. Patients with seizure onset in adults (>18 years old), unilateral IEDs, or unilateral encephalomalacia on MRI were found to have better seizure outcomes after VNS therapy.
Abstract
In order to comprehensively test the low temperature cold start performance of hydraulic oil and ensure their use effectiveness to the fullest, the idea of low temperature cold start ...performance index is proposed, so as to comprehensively evaluate the low temperature capability. Firstly, the cold start performance index system of hydraulic oil tested in low temperature environment is constructed, so as to describe its low temperature capability from multiple angles and in a comprehensive manner; secondly, for different index types, the corresponding data collection methods and data analysis methods are clarified, and the low temperature cold start performance of hydraulic fluid is evaluated. Finally, using the method as an example for three oils, the index types and assessment results are given to further illustrate the scientific nature of the research method. The research content can provide some technical support for the evaluation of the low temperature cold starting performance test of hydraulic winches.
Here, upon the invitation of Matter’s editorial team, four postdocs from four Chinese institutes with various backgrounds and research expertise share their insights in seeking academic positions.
...Here, upon the invitation of Matter’s editorial team, four postdocs from four Chinese institutes with various backgrounds and research expertise share their insights in seeking academic positions.
Most of DEPs were downregulated in B-ALL patients and highly enriched in actin binding and actin cytoskeleton organization, among others (Figure 1B,C; Supplemental Figure S3). SEE PDF Given the ...significant differences in plasma molecular signatures between B-ALL patients and HC, we next performed plasma proteomic and metabolomic analyses of samples collected from the different time points relative to pretreatment samples. Actin cytoskeleton organization was identified in WPC3 (Figure 2A,C,E), suggesting that cytoskeleton organization was disrupted. An elevated plasma TGs level may result from adipose tissue lipolysis under hyperinflammatory condition.4 Free fatty acids and purine metabolites were identified in whole metabolome cluster 2 (WMC2) (Figure 2B; Supplemental Table S10). To further elucidate the dynamics of plasma proteome and metabolome during CS, we made co-expression clustering analyses in CS patients. Since IL-6 is a critical and multifunctional cytokine in CAR-T cell-mediated CS, we identified sets of covarying molecules that were implicated in epithelial mesenchymal transition, glutathione metabolism and tryptophan metabolism in concert with IL-6 (Figure 3A–D), further revealing a potential regulatory crosstalk between tissue remodeling, metabolic reprogramming and IL-6.
The Bama Xiang pig (BM) is a unique pig species in Guangxi Province, China. Compared to other breeds of domestic pig, such as the Debao pig (DB), it is smaller in size, better in meat quality, ...resistant to rough feeding and strong in stress resistance. These unique advantages of Bama Xiang pigs make them of great edible value and scientific research value. However, the differences in muscle metabolites between Bama Xiang pigs (BM) and Debao pigs (DB) are largely unexplored. Here, we identified 214 differential metabolites between these two pig breeds by LC-MS. Forty-one such metabolites are enriched into metabolic pathways, and these metabolites correspond to 11 metabolic pathways with significant differences. In Bama pigs, the abundance of various metabolites such as creatine, citric acid, L-valine and hypoxanthine is significantly higher than in Debao pigs, while the abundance of other metabolites, such as carnosine, is significantly lower. Among these, we propose six differential metabolites: L-proline, citric acid, ribose 1-phosphate, L-valine, creatine, and L-arginine, as well as four potential differential metabolites (without the KEGG pathway), alanyl-histidine, inosine 2'-phosphate, oleoylcarnitine, and histidinyl hydroxyproline, as features for evaluating the meat quality of Bama pigs and for differentiating pork from Bama pigs and Debao pigs. This study provides a proof-of-concept example of distinguishing pork from different pig breeds at the metabolite level and sheds light on elucidating the biological processes underlying meat quality differences. Our pork metabolites data are also of great value to the genomics breeding community in meat quality improvement.
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