CircRNA_0008668 Sponges miR-1301-3p to Promote the Inflammatory Response in Allergic Rhinitis by Upregulating GATA6 Expression.

AIMS: We aim to explore GATA6 modulation in allergic rhinitis (AR). BACKGROUND: Circular RNAs (circRNAs) and microRNAs (miRNAs) are involved in inflammatory responses; GATA6 is also known to regulate multiple inflammatory pathways. However, the mechanism of regulation of AR between them is unclear. OBJECTIVE: We expect that this study will provide new treatment options for AR from a GATA6 perspective. METHODS: In vitro, AR models were employed to examine the efficacy of our study, where we utilized monoclonal anti-2,4,6-dinitrophenyl immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) to induce rat basophilic leukemia cells (RBL-2H3 cells). Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to measure the expression of circ_0008668, miR-1301-3p, GATA6, and cellular inflammatory markers. Enzyme-linked immunosorbent assay (ELISA) was used to measure concentrations of beta-hexosaminidase, histamine, and cellular inflammatory factors including TNF-α, IL-1ß, IL-4, and IL-5. In addition, western blot, RNA pull-down, and luciferase assays were performed to validate the molecular mechanism by which circ_ 0008668 and miR-1301-3p interactions promote GATA6 to ameliorate the inflammatory state of RBL-2H3 cells. RESULTS: In the in vitro model of AR, the expression levels of circ_0008668 and GATA6 were elevated, whereas that of miR-1301-3p was decreased. Pull-down assays confirmed that circ_0008668 efficiently binds miR-1301-3p and its overexpression leads to upregulation of the levels of GATA6, cellular inflammatory factors (IL-4, IL-5, TNF-α, and IL-1ß), and markers associated with inflammatory signaling pathways (NLRP3, ERK1/2, and P65 protein phosphorylation). In addition, miR-inhibitor with circRNA enhanced GATA6 and NLPR3 expression and activated inflammatory pathway activity. In particular, miR-mimic was effective in reversing the onset of this inflammatory state. CONCLUSION: Our results indicate that circ_0008668 promotes the inflammatory state of mast cells by sponging miR-1301-3p to target GATA6, which in turn affects the allergic response to AR. This process could improve the current diagnosis of AR patients and clinical treatment.

Deep brain stimulation for pediatric pantothenate kinase-associated neurodegeneration with status dystonicus: A case report and literature review.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN) is a type of inherited metabolic disorder caused by mutation in the PANK2 gene. The metabolic disorder mainly affects the basal ganglia region and eventually manifests as dystonia. For patients of dystonia, their dystonic symptom may progress to life-threatening emergency--status dystonicus. OBJECTIVE: We described a case of a child with PKAN who had developed status dystonicus and was successfully treated with deep brain stimulation (DBS). Based on this rare condition, we analysed the clinical features of PKAN with status dystonicus and reviewed the reasonable management process of this condition. CONCLUSION: This case confirmed the rationality of choosing DBS for the treatment of status dystonicus. Meanwhile, we found that children with classic PKAN have a cluster of risk factors for developing status dystonicus. Once children diagnosed with similar neurodegenerative diseases are under status dystonicus, DBS can be active considered because it has showed high control rate of this emergent condition.

A robust multi-scale feature extraction framework with dual memory module for multivariate time series anomaly detection.

Although existing reconstruction-based multivariate time series anomaly detection (MTSAD) methods have shown advanced performance, most assume the training data is clean. When faced with noise or contamination in training data, they can also reconstruct the anomaly well, weakening the distinction between normal and anomaly. Some probabilistic generation-based methods have been used to address this issue because of their implicit robust structure to noise, but the training process and suppression of anomalous generalization are not stable. The recently proposed explicit method based on the memory module would also sacrifice the reconstruction effect of normal patterns, resulting in limited performance improvement. Moreover, most existing MTSAD methods use a single fixed-length window for input, which weakens their ability to extract long-term dependency. This paper proposes a robust multi-scale feature extraction framework with the dual memory module to comprehensively extract features fusing different levels of semantic information and lengths of temporal dependency. First, this paper designs consecutive neighboring windows as inputs to allow the model to extract local and long-term dependency information. Secondly, a dual memory-augmented encoder is proposed to extract global typical patterns and local common features. It ensures the reconstruction ability of normal data while suppressing the generalization of the anomaly. Finally, this paper proposes a multi-scale fusion module to fuse latent variables representing different levels of semantic information and uses the reconstructed latent variables to reconstruct samples for anomaly detection. Experimental results on five datasets from diverse domains show that the proposed method outperforms 16 typical baseline methods.

Arbuscular Mycorrhizal Fungus Alleviates Charged Nanoplastic Stress in Host Plants via Enhanced Defense-Related Gene Expressions and Hyphal Capture.

Contamination of small-sized plastics is recognized as a factor of global change. Nanoplastics (NPs) can readily enter organisms and pose significant ecological risks. Arbuscular mycorrhizal (AM) fungi are the most ubiquitous and impactful plant symbiotic fungi, regulating essential ecological functions. Here, we first found that an AM fungus, Rhizophagus irregularis, increased lettuce shoot biomass by 25-100% when exposed to positively and negatively charged NPs vs control, although it did not increase that grown without NPs. The stress alleviation was attributed to the upregulation of gene expressions involving phytohormone signaling, cell wall metabolism, and oxidant scavenging. Using a root organ-fungus axenic growth system treated with fluorescence-labeled NPs, we subsequently revealed that the hyphae captured NPs and further delivered them to roots. NPs were observed at the hyphal cell walls, membranes, and spore walls. NPs mediated by the hyphae were localized at the root epidermis, cortex, and stele. Hyphal exudates aggregated positively charged NPs, thereby reducing their uptake due to NP aggregate formation (up to 5000 nm). This work demonstrates the critical roles of AM fungus in regulating NP behaviors and provides a potential strategy for NP risk mitigation in terrestrial ecosystems. Consequent NP-induced ecological impacts due to the affected AM fungi require further attention.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors.

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

Effects of transcutaneous auricular vagus nerve stimulation and exploration of brain network mechanisms in children with high-functioning autism spectrum disorder: study protocol for a randomized controlled trial.

Background: Autism Spectrum Disorders (ASD) are a collection of neurodevelopmental diseases characterized by poor social interaction and communication, a limited range of interests, and stereotyped behavior. High-functioning autism (HFA) indicates a subgroup of individuals with autism who possess cognitive and/or language skills that are within the average to above-normal range for their age. Transcutaneous auricular vagus nerve stimulation (taVNS) holds promise in children with HFA. However, few studies have used randomized controlled trials to validate the effectiveness of taVNS. Therefore, in this study, we intend to provide a study protocol to examine the therapeutic effects of taVNS in individuals diagnosed with HFA and to investigate the process of brain network remodeling in individuals with ASD using functional imaging techniques to observe alterations in large-scale neural networks. Methods and design: We planned to employ a randomized, double-blind experimental design, including 40 children receiving sham stimulation and 40 children receiving real stimulation. We will assess clinical scales and perform functional imaging examinations before and after the stimulation. Additionally, we will include age- and gender-matched healthy children as controls and conduct functional imaging examinations. We plan first to observe the therapeutic effects of taVNS. Furthermore, we will observe the impact of taVNS stimulation on the brain network. Discussion: taVNS was a low-risk, easy-to-administer, low-cost, and portable option to modulate the vagus system. taVNS may improve the social performance of HFA. Changes in the network properties of the large-scale brain network may be related to the efficacy of taVNS. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2300074035.

Sleep-wake dependent hippocampal regulation of fear memory.

The hippocampus (HPC) plays a pivotal role in fear learning and memory. Our two recent studies suggest that rapid eye movement (REM) sleep via the HPC downregulates fear memory consolidation and promotes fear extinction. However, it is not clear whether and how the dorsal and the ventral HPC regulates fear memory differently; and how the HPC in wake regulates fear memory. By chemogenetic stimulating in the HPC directly and its afferent entorhinal cortex that selectively activated the HPC in REM sleep for 3-6 h post-fear-acquisition, we found that HPC activation in REM sleep consolidated fear extinction memory. In particular, dorsal HPC (dHPC) stimulation in REM sleep virtually eliminated fear memory by enhancing fear extinction and reducing fear memory consolidation. By contrast, chemogenetic stimulating HPC afferent the supramammillary nucleus (SUM) induced 3-hr wake with HPC activation impaired fear extinction. Finally, desipramine (DMI) injection that selectively eliminated REM sleep for >6 h impaired fear extinction. Our results demonstrate that the HPC is critical for fear memory regulation; and wake HPC and REM sleep HPC have an opposite role in fear extinction of respective impairment and consolidation.

A filter-augmented auto-encoder with learnable normalization for robust multivariate time series anomaly detection.

While existing reconstruction-based multivariate time series (MTS) anomaly detection methods demonstrate advanced performance on many challenging real-world datasets, they generally assume the data only consists of normal samples when training models. However, real-world MTS data may contain significant noise and even be contaminated by anomalies. As a result, most existing approaches easily capture the pattern of the contaminated data, making identifying anomalies more difficult. Although a few studies have aimed to mitigate the interference of the noise and anomalies by introducing various regularizations, they still employ the objective of fully reconstructing the input data, impeding the model from learning an accurate profile of the MTS's normal pattern. Moreover, it is difficult for existing methods to apply the most appropriate normalization schemes for each dataset in various complex scenarios, particularly for mixed-feature MTS. This paper proposes a filter-augmented auto-encoder with learnable normalization (NormFAAE) for robust MTS anomaly detection. Firstly, NormFAAE designs a deep hybrid normalization module. It is trained with the backbone end-to-end in the current training task to perform the optimal normalization scheme. Meanwhile, it integrates two learnable normalization sub-modules to deal with the mixed-feature MTS effectively. Secondly, NormFAAE proposes a filter-augmented auto-encoder with a dual-phase task. It separates the noise and anomalies from the input data by a deep filter module, which facilitates the model to only reconstruct the normal data, achieving a more robust latent representation of MTS. Experimental results demonstrate that NormFAAE outperforms 17 typical baselines on five real-world industrial datasets from diverse fields.

Effects of dietary supplement with licorice and rutin mixture on production performance, egg quality, antioxidant capacity, and gut microbiota in quails (Turnix tanki).

This study was conducted to evaluate the effect of licorice and rutin on production performance, egg quality, and mucosa antioxidant levels in Chinese yellow quail. A total of 240 Chinese Yellow Quail (400-day-old) were randomly distributed into 5 groups: the Control group, fed with a basic diet; the LR1 group, fed with basal diet supplemented with 300 + 100 mg licorice and rutin mixture/kg diet; the LR2 group, fed with basal diet supplemented with 300 + 200 mg licorice and rutin mixture/kg diet; the LR3 group, fed with basal diet supplemented with 600 + 100 mg licorice and rutin mixture/kg diet and the LR4 group, fed with basal diet supplemented with 600 + 200 mg licorice and rutin mixture/kg diet. Compared with the control, supplementation with the licorice and rutin mixture improved the laying rate and eggshell thickness whereas decreased the feed conversion ratio of quails. Moreover, dietary supplementation with the licorice and rutin mixture improved the antioxidant capacity by increasing the activity of the superoxide dismutase (SOD) level and decreasing the concentration of malondialdehyde (MDA) in the jejunal mucosa. The licorice and rutin mixture altered the composition of intestinal microbiota by influencing the relative abundances of Bacteroidetes and Bacteroides. The relative abundances of the Bacteroidetes were significantly related to the laying rate of quails. In addition, the mixture of licorice and rutin was also effective in reducing the relative abundance of intestinal Proteobacteria and Enterobacter in quails, reducing the accumulation of antibiotic-resistance genes. The results revealed that supplementation of licorice and rutin mixture to the diet improved production performance, egg quality, and antioxidant capacity and modified the composition of intestinal microbiota in quails. This study provides a reference for Chinese herbal additives to promote production performance by modulating quail gut microbes.

Ectopic expression of neuronal adenosine kinase, a biomarker in mesial temporal lobe epilepsy without hippocampal sclerosis.

AIMS: Mesial temporal lobe epilepsy without hippocampal sclerosis (no-HS MTLE) refers to those MTLE patients who have neither magnetic resonance imaging (MRI) lesions nor definite pathological evidence of hippocampal sclerosis. They usually have resistance to antiepileptic drugs, difficulties in precise seizure location and poor surgical outcomes. Adenosine is a neuroprotective neuromodulator that acts as a seizure terminator in the brain. The role of adenosine in no-HS MTLE is still unclear. Further research to explore the aetiology and pathogenesis of no-HS MTLE may help to find new therapeutic targets. METHODS: In surgically resected hippocampal specimens, we examined the maladaptive changes of the adenosine system of patients with no-HS MTLE. In order to better understand the dysregulation of the adenosine pathway in no-HS MTLE, we developed a rat model based on the induction of focal cortical lesions through a prenatal freeze injury. RESULTS: We first examined the adenosine system in no-HS MTLE patients who lack hippocampal neuronal loss and found ectopic expression of the astrocytic adenosine metabolising enzyme adenosine kinase (ADK) in hippocampal pyramidal neurons, as well as downregulation of neuronal A1 receptors (A1 Rs) in the hippocampus. In the no-HS MTLE model rats, the transition of ADK from neuronal expression to an adult pattern of glial expression in the hippocampus was significantly delayed. CONCLUSIONS: Ectopic expression of neuronal ADK might be a pathological hallmark of no-HS MTLE. Maladaptive changes in adenosine metabolism might be a novel target for therapeutic intervention in no-HS MTLE.

Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors.

AIMS: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A1 Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms. METHODS: Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A1 Rs were tested with histochemistry and western blot, respectively. RESULTS: Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A1 R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A1 Rs. CONCLUSION: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A1 Rs. A1 Rs might be a potential target of DBS for the treatment of epilepsy.

Factors that Influence Subdural Hemorrhage Secondary to Intracranial Arachnoid Cysts in Children.

OBJECTIVE: This study aimed to investigate factors that influence subdural haemorrhage (SDH) secondary to intracranial arachnoid cysts (IACs) in children. METHODS: Data of children with unruptured IACs (IAC group) and those with SDH secondary to IACs (IAC-SDH group) were analyzed. Nine factors, sex, age, birth type (vaginal or caesarean), symptoms, side (left, right, or midline), location (temporal or nontemporal), image type (I, II, or III), volume, and maximal diameter, were selected. IACs were classified as types I, II, and III according to their morphological changes observed on computed tomography images. RESULTS: There were 117 boys (74.5%) and 40 girls (25.5%); 144 (91.7%) patients comprised the IAC group and 13 (8.3%) comprised the IAC-SDH group. There were 85 (53.8%) IACs on the left side, 53 (33.5%) on the right side, 20 (12.7%) in the midline region, and 91 (58.0%) in the temporal region. The univariate analysis showed significant differences in age, birth type, symptoms, cyst location, cyst volume, and cyst maximal diameter (P < 0.05) between the 2 groups. Logistic regression using the synthetic minority oversampling technique model showed that image type III and birth type were independent factors that influenced SDH secondary to IACs (ß0 = 4.143; ß for image type = -3.979; ß for birth type = -2.542) and that the representative area under the receiver-operating characteristic curve value was 0.948 (95% confidence interval, 0.898-0.997). CONCLUSIONS: IACs are more common in boys than in girls. They can be divided into 3 groups according to their morphological changes on computed tomography images. Image type III and caesarean delivery were independent factors that influenced SDH secondary to IACs.

Ginsenoside Rg1 attenuates cerebral ischemia-reperfusion injury through inhibiting the inflammatory activation of microglia.

It is recognized that the cerebral ischemia/reperfusion (I/R) injury triggers inflammatory activation of microglia and supports microglia-driven neuronal damage. Our previous studies have shown that ginsenoside Rg1 had a significant protective effect on focal cerebral I/R injury in middle cerebral artery occlusion (MCAO) rats. However, the mechanism still needs further clarification. Here, we firstly reported that ginsenoside Rg1 effectively suppressed the inflammatory activation of brain microglia cells under I/R conditions depending on the inhibition of Toll-likereceptor4 (TLR4) proteins. In vivo experiments showed that the ginsenoside Rg1 administration could significantly improve the cognitive function of MCAO rats, and in vitro experimental data showed that ginsenoside Rg1 significantly alleviated neuronal damage via inhibiting the inflammatory response in microglia cells co-cultured under oxygen and glucose deprivation/reoxygenation (OGD/R) condition in gradient dependent. The mechanism study showed that the effect of ginsenoside Rg1 depends on the suppression of TLR4/MyD88/NF-κB and TLR4/TRIF/IRF-3 pathways in microglia cells. In a word, our research shows that ginsenoside Rg1 has great application potential in attenuating the cerebral I/R injury by targeting TLR4 protein in the microglia cells.

The regulatory function of lncRNA and constructed network in epilepsy.

BACKGROUND: Epilepsy is a neurological disease characterized by neural network dysfunction. Although most reports indicate that the pathological process of epilepsy is related to inflammation, synaptic plasticity, cell apoptosis, and ion channel dysfunction, the underlying molecular mechanisms of epilepsy are not fully understood. METHODS: This review summarizes the latest literature on the roles and characteristics of long noncoding RNAs (lncRNAs) in the pathogenesis of epilepsy. RESULTS: lncRNAs are a class of long transcripts without protein-coding functions that perform important regulatory functions in various biological processes. lncRNAs are involved in the regulation of the pathological process of epilepsy and are abnormally expressed in both patients and animal models. This review provides an overview of research progress in epilepsy, the multifunctional features of lncRNAs, the lncRNA expression pattern related to epileptogenesis and status epilepticus, and the potential mechanisms for the two interactions contributing to epileptogenesis and progression. CONCLUSION: lncRNAs can serve as new diagnostic markers and therapeutic targets for epilepsy in the future.

A new isolate of Streptomyces lateritius (Z1-26) with antibacterial activity against fish pathogens and immune enhancement effects on crucian carp (Carassius auratus).

The Streptomyces lateritius Z1-26 was isolated from soil samples which showed broad-spectrum antibacterial activity against a broad range of fish pathogens. The In Vivo Imaging System (IVIS) monitored that strain Z1-26 could survive and colonize in the gills and abdomen of crucian carp. The effects of dietary supplementation with strain Z1-26 were evaluated with respect to the growth performance, antioxidant capacity, and immune response of crucian carp. The results showed that the Z1-26-fed fish had a significantly higher growth rate than the fish fed the control diet. The immune and antioxidant parameters revealed that the non-specific immune indicators (AKP, SOD, and LZM) of the serum, the expression of immune-related genes (IgM, C3, and LZM), and antioxidant-related genes (Nrf2 and Keap1) of the immune organs were significantly increased, whereas the expression of pro-inflammatory factors (IL-1ß, IL-8, and TNF-α) of the immune organs was significantly down-regulated in crucian carp fed strain Z1-26 compared with fish fed a control diet. Moreover, fish fed with Z1-26 supplemented diets showed a significantly improved survival rate after Aeromonas hydrophila infection. In addition, the whole genome analysis showed that strain Z1-26 possesses 28 gene clusters, including 6 polyketide synthetase (PKS), 4 non-ribosomal peptide-synthetase (NRPS), 1 bacteriocin, and 1 lantipeptide. In summary, these results indicated that strain Z1-26 could improve the growth performance and disease resistance in crucian carp, and has the potential to be developed as a candidate probiotics for the control of bacterial diseases in aquaculture.

Chx10+V2a interneurons in spinal motor regulation and spinal cord injury.

Chx10-expressing V2a (Chx10+V2a) spinal interneurons play a large role in the excitatory drive of motoneurons. Chemogenetic ablation studies have demonstrated the essential nature of Chx10+V2a interneurons in the regulation of locomotor initiation, maintenance, alternation, speed, and rhythmicity. The role of Chx10+V2a interneurons in locomotion and autonomic nervous system regulation is thought to be robust, but their precise role in spinal motor regulation and spinal cord injury have not been fully explored. The present paper reviews the origin, characteristics, and functional roles of Chx10+V2a interneurons with an emphasis on their involvement in the pathogenesis of spinal cord injury. The diverse functional properties of these cells have only been substantiated by and are due in large part to their integration in a variety of diverse spinal circuits. Chx10+V2a interneurons play an integral role in conferring locomotion, which integrates various corticospinal, mechanosensory, and interneuron pathways. Moreover, accumulating evidence suggests that Chx10+V2a interneurons also play an important role in rhythmic patterning maintenance, left-right alternation of central pattern generation, and locomotor pattern generation in higher order mammals, likely conferring complex locomotion. Consequently, the latest research has focused on postinjury transplantation and noninvasive stimulation of Chx10+V2a interneurons as a therapeutic strategy, particularly in spinal cord injury. Finally, we review the latest preclinical study advances in laboratory derivation and stimulation/transplantation of these cells as a strategy for the treatment of spinal cord injury. The evidence supports that the Chx10+V2a interneurons act as a new therapeutic target for spinal cord injury. Future optimization strategies should focus on the viability, maturity, and functional integration of Chx10+V2a interneurons transplanted in spinal cord injury foci.

Effectiveness of vagus nerve stimulation therapy in refractory hypoxic-ischemic encephalopathy-induced epilepsy.

Background: Epilepsy is one of the important long-term sequelae of neonatal hypoxic-ischemic encephalopathy (HIE) and is typically characterized by drug resistance and poor surgical outcomes. Vagus nerve stimulation (VNS) is a promising neuromodulation therapy for refractory epilepsy. Objectives: The present study aimed to first evaluate the effectiveness of VNS in patients with refractory HIE-induced epilepsy and scrutinize potential clinical predictors. Methods: We retrospectively collected the outcomes of VNS in all patients with refractory HIE-induced epilepsy and at least 2 years of follow-up. Subgroups were classified as responders and nonresponders according to the effectiveness of VNS (⩾50% or <50% reduction in seizure frequency). Preoperative data were analyzed to screen for potential predictors of VNS effectiveness. Results: A total of 55 patients with refractory HIE-induced epilepsy who underwent VNS therapy were enrolled. Responders represented 56.4% of patients, and 12.7% of patients achieved seizure freedom at the last follow-up. In addition, the responder rate increased over time with rates of 23.6%, 38.2%, 50.9%, and 56.4% at the 3-, 6-, 12- and 24-month follow-ups, respectively. After multivariate analysis, neonatal seizure was identified as a negative predictor (OR: 4.640, 95% CI: 1.129-19.066), and a predominant seizure type of generalized onset was identified as a positive predictor (OR: 0.261, 95% CI: 0.078-0.873) of VNS effectiveness. Conclusion: VNS therapy was effective in patients with refractory HIE-induced epilepsy and was well tolerated over a 2-year follow-up period. VNS therapy demonstrated better effectiveness in patients without neonatal seizures or with a predominant seizure type of generalized onset.

A Privacy-Preserving, Two-Party, Secure Computation Mechanism for Consensus-Based Peer-to-Peer Energy Trading in the Smart Grid.

Consumers in electricity markets are becoming more proactive because of the rapid development of demand-response management and distributed energy resources, which boost the transformation of peer-to-peer (P2P) energy-trading mechanisms. However, in the P2P negotiation process, it is a challenging task to prevent private information from being attacked by malicious agents. In this paper, we propose a privacy-preserving, two-party, secure computation mechanism for consensus-based P2P energy trading. First, a novel P2P negotiation mechanism for energy trading is proposed based on the consensus + innovation (C + I) method and the power transfer distribution factor (PTDF), and this mechanism can simultaneously maximize social welfare and maintain physical network constraints. In addition, the C + I method only requires a minimum set of information to be exchanged. Then, we analyze the strategy of malicious neighboring agents colluding to attack in order to steal private information. To defend against this attack, we propose a two-party, secure computation mechanism in order to realize safe negotiation between each pair of prosumers based on Paillier homomorphic encryption (HE), a smart contract (SC), and zero-knowledge proof (ZKP). The energy price is updated in a safe way without leaking any private information. Finally, we simulate the functionality of the privacy-preserving mechanism in terms of convergence performance, computational efficiency, scalability, and SC operations.

The Effect of the KDL Active School Plan on Children and Adolescents' Physical Fitness in China.

The development of physical fitness among Chinese children and adolescents is not fundamentally improving, and an exploration of effective ways to promote it is an urgent need. Research into physical fitness promotion in schools is increasingly deepening worldwide. However, the implementation and verification of intervention programs with local characteristics in accordance with China's national conditions are relatively weak. This study conducted a randomized controlled trial to examine the effects of the KDL (Know it, Do it, Love it) Active School Plan (KDL-ASP) on children and adolescents' physical fitness. A total of 596 students from level two (2nd-grade students) to five (11th-grade students) in China were assessed in terms of their physical fitness. Of these, 308 students were randomly selected to participate in the KDL-ASP, which uses a combination of indoor and outdoor sports activities in which teachers, parents, and students participate together. The remaining 288 students performed conventional physical activities. After one school year of intervention with the KDL-ASP, the physical fitness of the children and adolescents improved. The improvements in the speed of level two girls, the strength of level four boys, and the lung capacity of level five boys were the most obvious. These results demonstrate the viability of indigenized intervention in schools to improve physical fitness and suggest that KDL-ASP needs to be considered throughout the whole progress of physical education learning for children and adolescents.