A logic-incorporated gene regulatory network deciphers principles in cell fate decisions.

Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven). Under the noise-driven mode, we distilled the relationship among fate bias, regulatory logic, and noise profile. Under the signal-driven mode, we bridged regulatory logic and progression-accuracy trade-off, and uncovered distinctive trajectories of reprogramming influenced by logic motifs. In differentiation, we characterized a special logic-dependent priming stage by the solution landscape. Finally, we applied our findings to decipher three biological instances: hematopoiesis, embryogenesis, and trans-differentiation. Orthogonal to the classical analysis of expression profile, we harnessed noise patterns to construct the GRN corresponding to fate transition. Our work presents a generalizable framework for top-down fate-decision studies and a practical approach to the taxonomy of cell fate decisions.

Maternal exposure to deltamethrin during pregnancy and lactation impairs neurodevelopment of male offspring.

Deltamethrin (DM) is a highly effective and widely used pyrethroid pesticide. It is an environmental factor affecting public and occupational health and exerts direct toxic effects on the central nervous system. As the major target organs for neurotoxicity of DM, the hippocampus and the cerebellum are critical to the learning and motor function. Pregnant Wistar rats were randomly divided into four groups and gavaged at doses of 0, 1, 4or 10 mg/kg/d DM from gestational day (GD) 0 to postnatal day (PN) 21. The PC12 cells were selected to further verify the regulatory mechanisms of DM on the neurodevelopmental injury. We found that maternal exposure to DM caused learning, memory and motor dysfunction in male offspring. Maternal exposure to DM induced the decrease in the density of hippocampal dendritic spines in male offspring through the reduced expression of M1 mAchRs, which in turn reduced the mediated AKT/mTOR signaling pathway, contributing to the inhibition of dynamic changes of GluA1. Meanwhile, DM exposure inhibited the BDNF/TrkB signaling pathway, thereby reducing phosphorylation of stathmin and impairing cerebellar purkinje cell dendrite growth and development. Taken together, maternal exposure to DM during pregnancy and lactation could impair neurodevelopment of male offspring.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation.

BACKGROUND: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. METHOD: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. RESULT: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. CONCLUSION: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Causal Association of Cytokines and Growth Factors with Stroke and Its Subtypes: a Mendelian Randomization Study.

Cytokines and growth factors contribute to nerve growth and angiogenesis and are associated with the development of vascular disease. This Mendelian randomization (MR) study was designed to examine the causal relationship between factors associated with stem cell paracrine mechanisms and with stroke and its subtypes. We used pooled statistics on cytokine levels from three studies (INTERIAL, Olink Proseek CVD array, and KORA) encompassing 7795 participants in Europe. Data for stroke and its subtypes were pooled from these European populations (40,585 cases and 406,111 controls) in a multiprogenitor genome-wide association study (GWAS). MR was performed using established analytical methods, including inverse variance weighting (IVW), weighted median (WM), and MR-Egger. Genetically determined high IGF-1 levels were found to associate negatively with risk of stroke, ischemic stroke (large-artery atherosclerosis), and ischemic stroke (cardiogenic embolism). Meanwhile, high IL-13 levels had a positive causal relationship with ischemic stroke (large-artery atherosclerosis). An additional 27 cytokines were found to have a causal association with stroke or its subtypes. However, these results should be interpreted with caution given that the power efficacy was <80%. This MR study supports the concept of a causal relationship of 29 cytokines with stroke or its subtypes. Our genetic analysis provides new insights into stroke prevention and treatment by demonstrating an association of stem cell paracrine-related cytokines with stroke risk.

Effects of pyrethroids on the cerebellum and related mechanisms: a narrative review.

Pyrethroids (PYRs) are a group of synthetic organic chemicals that mimic natural pyrethrins. Due to their low toxicity and persistence in mammals, they are widely used today. PYRs exhibit higher lipophilicity than other insecticides, which allows them to easily penetrate the blood-brain barrier and directly induce toxic effects on the central nervous system. Several studies have shown that the cerebellum appears to be one of the regions with the largest changes in biomarkers. The cerebellum, which is extremely responsive to PYRs, functions as a crucial region for storing motor learning memories. Exposure to low doses of various types of PYRs during rat development resulted in diverse long-term effects on motor activity and coordination functions. Reduced motor activity may result from developmental exposure to PYRs in rats, as indicated by delayed cerebellar morphogenesis and maturation. PYRs also caused adverse histopathological and biochemical changes in the cerebellum of mothers and their offspring. By some studies, PYRs may affect granule cells and Purkinje cells, causing damage to cerebellar structures. Destruction of cerebellar structures and morphological defects in Purkinje cells are known to be directly related to functional impairment of motor coordination. Although numerous data support that PYRs cause damage to cerebellar structures, function and development, the mechanisms are not completely understood and require further in-depth studies. This paper reviews the available evidence on the relationship between the use of PYRs and cerebellar damage and discusses the mechanisms of PYRs.

Ectopic Expression of BcCUC2 Involved in Sculpting the Leaf Margin Serration in Arabidopsis thaliana.

Leaf margin serration is a morphological characteristic in plants. The CUC2 (CUP-SHAPED COTYLEDON 2) gene plays an important role in the outgrowth of leaf teeth and enhances leaf serration via suppression of growth in the sinus. In this study, we isolated the BcCUC2 gene from Pak-choi (Brassica rapa ssp. chinensis), which contains a 1104 bp coding sequence, encoding 367 amino acid residues. Multiple sequence alignment exhibited that the BcCUC2 gene has a typical conserved NAC domain, and phylogenetic relationship analysis showed that the BcCUC2 protein has high identity with Cruciferae plants (Brassica oleracea, Arabidopsis thaliana, and Cardamine hirsuta). The tissue-specific expression analysis displayed that the BcCUC2 gene has relatively high transcript abundance in floral organs. Meanwhile, the expression profile of BcCUC2 was relatively higher in the '082' lines with serrate leaf margins than the '001' lines with smooth leaf margins in young leaves, roots, and hypocotyls. In addition, the transcript level of BcCUC2 was up-regulated by IAA and GA3 treatment, especially at 1-3 h. The subcellular localization assay demonstrated that BcCUC2 was a nuclear-target protein. Furthermore, leaf serration occurred, and the number of the inflorescence stem was increased in the transgenic Arabidopsis thaliana plants' overexpressed BcCUC2 gene. These data illustrated that BcCUC2 is involved in the development of leaf margin serration, lateral branches, and floral organs, contributing to further uncovering and perfecting the regulation mechanism of leaf serration in Pak-choi.

A novel four-dimensional prediction model of soil heavy metal pollution: Geographical explanations beyond artificial intelligence "black box".

The current artificial intelligence (AI)-based prediction approaches of soil pollutants are inadequate in estimating the geospatial source-sink processes and striking a balance between the interpretability and accuracy, resulting in poor spatial extrapolation and generalization. In this study, we developed and tested a geographically interpretable four-dimensional AI prediction model for soil heavy metal (Cd) contents (4DGISHM) in Shaoguan city of China from 2016 to 2030. The 4DGISHM approach characterized spatio-temporal changes in source-sink processes of soil Cd by estimating spatio-temporal patterns and the effects of drivers and their interactions of soil Cd at local to regional scales using TreeExplainer-based SHAP and parallel ensemble AI algorithms. The results demonstrate that the prediction model achieved MSE and R2 values of 0.012 and 0.938, respectively, at a spatial resolution of 1 km. The predicted areas exceeding the risk control values for soil Cd across Shaoguan from 2022 to 2030 increased by 22.92% at the baseline scenario. By 2030, enterprise and transportation emissions (SHAP values 0.23 and 0.12 mg/kg, respectively) were the major drivers. The influence of driver interactions on soil Cd was marginal. Our approach surpasses the limitations of the AI "black box" by integrating spatio-temporal source-sink explanation and accuracy. This advancement enables geographically precise prediction and control of soil pollutants.

In-Tumor Biosynthetic Construction of Upconversion Nanomachines for Precise Near-Infrared Phototherapy.

Targeted construction of therapeutic nanoplatforms in tumor cells with specific activation remains appealing but challenging. Here, we design a cancer-motivated upconversion nanomachine (UCNM) based on porous upconversion nanoparticles (p-UCNPs) for precise phototherapy. The nanosystem is equipped with a telomerase substrate (TS) primer and simultaneously encapsulates 5-aminolevulinic acid (5-ALA) and d-arginine (d-Arg). After coating with hyaluronic acid (HA), it can readily get into tumor cells, where 5-ALA induces efficient accumulation of protoporphyrin IX (PpIX) via the inherent biosynthetic pathway, and the overexpressed telomerase prolonged the TS to form G-quadruplexes (G4) for binding the resulting PpIX as a nanomachine. This nanomachine can respond to near-infrared (NIR) light and promote the active singlet oxygen (1O2) production due to the efficiency of Förster resonance energy transfer (FRET) between p-UCNPs and PpIX. Intriguingly, such oxidative stress can oxidize d-Arg into nitric oxide (NO), which relieves the tumor hypoxia and in turn improves the phototherapy effect. This in situ assembly approach significantly enhances targeting in cancer therapy and might be of considerable clinical value.

The impact of strain, constraints, and morality on different cyberbullying roles: A partial test of Agnew's general strain theory.

The strain has been well studied in traditional bullying, and recent research has begun to explore it in cyberbullying behavior. Drawing from General Strain Theory, the current study empirically examined the relationship between strain and the cyberbullying behavior of perpetrators and bully-victims, respectively. Meanwhile, this study also considered the influences of the protective variables (e.g., constraints and morality) on the strain, which may potentially reduce the risks of participating in cyberbullying. The sample comprised 928 Chinese internet users (Male = 490, Female = 438) aged between 16 to 50. We identified the prevalence of cyberbullying in China, in which the percentages of cyberbullying perpetrators, cyberbullying victims, and cyber bully-victims were 23.40, 23.20, and 37.40%, respectively. This study mentioned a noteworthy phenomenon: cyberbullying victims quickly became cyberbullying perpetrators when they were cyberbullied. Secondly, according to the binary logistic regression, we hold that the strain was significantly related to cyberbullying behaviors, as individuals with low levels of self-control showed a higher tendency to participate in cyberbullying. As for protective factors, the results showed that constraints and morality can reduce the negative consequences of strain and then against cyberbullying, exploring the possibilities of using constraints and morality as variables to decrease strain and prevent cyberbullying. Thus, the unique values of this study are using the GST theory to investigate the empirical link between strain and cyberbullying between different roles in a new cultural and social background, demonstrating that negative emotion and low self-control had influences on strain and cyberbullying behaviors. Meanwhile, this study also contributes by discussing the implications for future research and practicing efforts targeting how to decrease the risks of cyberbullying engagement, for example, we suggest that the prevention and intervention of cyberbullying should adopt a cross-sectoral response to help individuals to view cyberbullying, vent dissatisfaction and relieve strain in the right way.

Effects of repetitive transcranial magnetic stimulation on sequelae in patients with chronic stroke: A systematic review and meta-analysis of randomized controlled trials.

Background: Stroke is the second leading cause of death worldwide, with a large proportion of survivors suffering from motor dysfunction and neuropsychiatric sequelae. Repetitive transcranial magnetic stimulation (rTMS) is a promising stroke rehabilitation intervention and is effective in improving neurological system function in stroke patients. In the current systemic review and meta-analysis, an overview of the most recent studies regarding the effectiveness of rTMS's potential to help chronic stroke patients recover from sequelae was provided. Methods: Relevant randomized controlled trials were retrieved from three online databases (Web of Science, Medline, and Embase). A total of 25 RCTs (N = 535 participants) were included. A meta-analysis was performed using a fixed-effects model or a random-effects model, and effect sizes were reported as weighted mean differences or standardized mean differences. Results: Administration of rTMS significantly improved upper limb function, hand function, and muscle tone in stroke patients throughout the chronic phase [≥6 months], but not lower limb mobility and strength. In terms of cognitive function, rTMS has a considerable positive impact on patients' cognitive performance. rTMS also alleviated apathy in stroke patients more than post-stroke depressive symptoms regarding mental functioning. Balance and walking function, as well as functional activities of daily living, of patients were dramatically improved by rTMS. However, the current conclusions should be taken carefully due to the small sample size of the meta-analysis. Conclusions: This is the first meta-analysis of rTMS treatment in patients with chronic stroke to inform the selection of the optimal treatment strategy for patients with chronic stroke, which demonstrated that rTMS treatment has the potential to improve the effects of sequelae by improving upper limb function, hand function, and muscle tone. Systematic review registration: https://inplasy.com/inplasy-2022-7-0095/, identifier: INPLASY202270095.

Effects of repetitive transcranial magnetic stimulation on upper-limb and finger function in stroke patients: A systematic review and meta-analysis of randomized controlled trials.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising intervention for stroke rehabilitation. Several studies have demonstrated the effectiveness of rTMS in restoring motor function. This meta-analysis aimed to summarize the current evidence of the effect of rTMS in improving upper limb function and fine motor recovery in stroke patients. Methods: Three online databases (Web of Science, PubMed, and Embase) were searched for relevant randomized controlled trials. A total of 45 studies (combined n = 2064) were included. Random effects model was used for meta-analysis and effect size was reported as standardized mean difference (SMD). Results: rTMS was effective in improving fine motor function in stroke patients (SMD, 0.38; 95% CI 0.19-0.58; P = 0). On subgroup analyses, for post-stroke functional improvement of the upper extremity, bilateral hemisphere stimulation was more effective than unilateral stimulation during the acute phase of stroke, and a regimen of 20 rTMS sessions produced greater improvement than <20 sessions. In the subacute phase of stroke, affected hemispheric stimulation with a 40-session rTMS regimen was superior to unaffected hemispheric stimulation or bilateral hemispheric stimulation with <40 sessions. Unaffected site stimulation with a 10-session rTMS regimen produced significant improvement in the chronic phase compared to affected side stimulation and bilateral stimulation with >10 rTMS sessions. For the rTMS stimulation method, both TBS and rTMS were found to be significantly more effective in the acute phase of stroke, but TBS was more effective than rTMS. However, rTMS was found to be more effective than TBS stimulation in patients in the subacute and chronic phases of stroke. rTMS significantly improved upper limb and fine function in the short term (0-1-month post-intervention) and medium term (2-5 months), but not for upper limb function in the long term (6 months+). The results should be interpreted with caution due to significant heterogeneity. Conclusions: This updated meta-analysis provides robust evidence of the efficacy of rTMS treatment in improving upper extremity and fine function during various phases of stroke. Systematic Review Registration: https://inplasy.com/inplasy-2022-5-0121/, identifier: INPLASY202250121.

Analysis of Factors Affecting Individuals' Online Consumer Credit Behavior: Evidence From China.

In the past two decades, a growing number of Chinese young adults utilize online consumer credit to satisfy their increasing consumption demand. Although it is indeed boosting consumer markets, it has also caused many serious social problems. A number of previous studies discussed the authentication mechanism and legal supervision of online lending from a legal or economic perspective, and a small number of scholars explored factors affecting individuals' online consumer credit from the perspective of behavioral psychology. Based on the Triandis model and existing studies on online lending, this paper constructs a theoretical model for the formation of individuals' online consumer credit. It then adopts SmartPLS 3.00 to analyze the data set that involves 302 respondents in total. This research found that affect, facilitating conditions, perceived consequences and social factors have a significant impact on individuals' online consumer credit. The findings of this study have political and practical implications. First, they can contribute to the rational consumption by China's young generation and promote the sound development of online consumer credit. In the meantime, this study also helps online consumer credit platforms to provide better services and improve public relations.

Microwaving released more polyphenols from black quinoa grains with hypoglycemic effects compared with traditional cooking methods.

BACKGROUND: Polyphenols were reported to exhibit inhibitory effects on digestive enzymes to regulate carbohydrates and lipid digestion. However, different cooking methods might cause differences in the composition of polyphenols in cereal grains and thus further affect their activities. RESULTS: The present study used boiling, roasting and microwaving to cook black quinoa and extracted polyphenols from them. Their total phenolic content (TPC) and total flavonoids content were determined, and phenolic composition was analyzed via high-performance liquid chromatography-mass spectrometry (HPLC-MS). Compared with other cooking methods, phenolic extract from microwaved black quinoa (PEM) showed the highest TPC value (about 2.64 mg GAE g-1 ). Microwaving released more phenolic acids (ferulic acid and gallic acid) from black quinoa grains. PEM also exhibited the strongest antioxidant and α-glucosidase inhibitory activities. Lineweaver-Burk plots showed that PEM inhibited α-glucosidase in an uncompetitive mode, which was supported by circular dichroism analysis. PEM further reduced about 20.04% of digested starch in an in vitro digestion model and suppressed postprandial blood glucose increases (about 16.91% reduction) in vivo. CONCLUSION: Collectively, our data suggested that microwaving could be an ideal method to cook quinoa in regards of its polyphenols in management of postprandial blood glucose. © 2022 Society of Chemical Industry.

IL-17A Mediates Demyelination by Activating A1 Astrocytes via SOCS3 During Angiostrongylus cantonensis Infection.

Background: Demyelinating disease of the central nervous system is one of the most common neurological diseases and effective treatment is still under in-depth research. Our previous study showed that Angiostrongylus cantonensis infection can induce demyelination injury in mouse brains and IL-17A expression was shown to be significantly increased during this process. Moreover, we found that IL-17A inhibition attenuated the demyelination caused by A. cantonensis infection. However, the underlying mechanisms have not yet been fully elucidated. Methods: IL-17A neutralizing antibodies were injected into A. cantonensis infected mice to decrease IL-17A levels. The activation of glial cells in the brain and the expression of cell markers were detected by a variety of methods, including real-time quantitative PCR, western blotting, and immunofluorescence staining. The relationship between IL-17A and astrocyte activation was further identified by in vitro experiments. The role of SOCS3 in the IL-17A stimulating process was determined using RNA-seq data collection of infected mice and the siRNA interference method. Results: Demyelination of the corpus callosum was relieved after administration of IL-17A neutralizing antibody and this was accompanied by decreased activation of A1 type astrocytes around this region. The expression of SOCS3 was attenuated and activation of astrocytes by IL-17A was mediated by the IL-17RA/STAT3/SOCS3 pathway. IL-17A not only directly damaged oligodendrocytes but also indirectly damaged oligodendrocytes through A1 astrocyte mediation. Specific siRNA inhibition of IL-17A-inducible SOCS3 in astrocytes alleviated their damaging effects on oligodendrocytes. Conclusion: IL-17A plays an important role in demyelination induced by A. cantonensis infection via the IL-17RA/STAT3/SOCS3 pathway in A1-type astrocytes, indicating that specific blockage of IL-17A and SOCS3 activity could be a therapeutic strategy for neuroinflammatory demyelinating diseases associated with astrocyte activation.

The Corticospinal Excitability Can Be Predicted by Spontaneous Electroencephalography Oscillations.

Transcranial magnetic stimulation (TMS) has a wide range of clinical applications, and there is growing interest in neural oscillations and corticospinal excitability determined by TMS. Previous studies have shown that corticospinal excitability is influenced by fluctuations of brain oscillations in the sensorimotor region, but it is unclear whether brain network activity modulates corticospinal excitability. Here, we addressed this question by recording electroencephalography (EEG) and TMS measurements in 32 healthy individuals. The resting motor threshold (RMT) and active motor threshold (AMT) were determined as markers of corticospinal excitability. The least absolute shrinkage and selection operator (LASSO) was used to identify significant EEG metrics and then correlation analysis was performed. The analysis revealed that alpha2 power in the sensorimotor region was inversely correlated with RMT and AMT. Innovatively, graph theory was used to construct a brain network, and the relationship between the brain network and corticospinal excitability was explored. It was found that the global efficiency in the theta band was positively correlated with RMT. Additionally, the global efficiency in the alpha2 band was negatively correlated with RMT and AMT. These findings indicated that corticospinal excitability can be modulated by the power spectrum in sensorimotor regions and the global efficiency of functional networks. EEG network analysis can provide a useful supplement for studying the association between EEG oscillations and corticospinal excitability.

Cardioprotective Role of SIRT5 in Response to Acute Ischemia Through a Novel Liver-Cardiac Crosstalk Mechanism.

Protein posttranslational modifications play important roles in cardiovascular diseases. The authors' previous report showed that the abundance of succinylated and glutarylated proteins was significantly lower in the serum of patients with acute myocardial infarction (AMI) than in that of healthy volunteers, suggesting a potential relationship between protein acylation and AMI. Sirtuin 5 (SIRT5) facilitates the removal of malonyl, succinyl, and glutaryl modification; however, its effects on AMI remain unknown. In this study, the levels of SIRT5 in AMI mouse model was compared. Results showed elevated hepatic SIRT5 after myocardial infarction. Hepatocyte-specific SIRT5 overexpressing mice (liver SIRT5 OE) were generated to address the possible involvement of hepatic SIRT5 in AMI. The areas of myocardial infarction, myocardial fibrosis, and cardiac function in a model of experimental myocardial infarction were compared between liver SIRT5 OE mice and wild-type (WT) mice. The liver SIRT5 OE mice showed a significantly smaller area of myocardial infarction and myocardial fibrosis than the WT mice. The fibroblast growth factor 21 (FGF21) in the blood and myocardium of liver SIRT5 OE mice after AMI was markedly elevated compared with that in WT mice. The results of mass spectrometry showed increased levels of proteins regulating tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid ß-oxidation pathways in the liver mitochondria of liver SIRT5 OE mice. These findings showed that SIRT5 may exhibit a cardioprotective effect in response to acute ischemia through a liver-cardiac crosstalk mechanism, probably by increasing the secretion of FGF21 and the improvement of energy metabolism.

Dynamic Changes of Arc Expression in Dorsal Striatum of Mice After Self-Administration of Sucrose.

Region-specific plasticity in the striatal circuit plays an important role in the development and long-term maintenance of skills and sequential movement procedures. Studies investigating the molecular substrates that contribute to the plasticity changes during motor skill processes have documented a transition in expression from the dorsomedial striatum (DMS) to the dorsolateral striatum (DLS); however, few studies have explored the expression pattern of molecular substrates in the dorsal striatum during progression of instrumental learning. To address this issue, the activity-regulated cytoskeleton-associated protein (Arc) expressions in the subregional dorsal striatum were analyzed during the early and late learning phases of the 10-day sucrose self-administration process. We found that Arc protein is primarily detected in the DMS only in the initial learning stage; however, it is expressed in the DLS during both early and late learning stages. Moreover, Arc expression in the DMS correlated with the number of rewards received later in the training. These data indicated that the Arc expression in subregions of the dorsal striatum shows region-specific transfer and that Arc expression in the DMS contributes to obtaining reward in later learning stage during the process of instrumental learning.

Parameters Indicating Development of Influenza-Associated Acute Necrotizing Encephalopathy: Experiences from a Single Center.

BACKGROUND Influenza-associated acute necrotizing encephalopathy (IANE) can be lethal and disabling and have a sudden onset and deteriorate rapidly but lacks early diagnostic indicators. We aimed to examine the early clinical diagnostic indicators in children with IANE. MATERIAL AND METHODS Acute influenza patients were grouped according to their clinical manifestations: flu alone (FA), flu with febrile seizure (FS), influenza-associated encephalopathy (IAE), and IANE. The clinical features, biomarkers, neuroelectrophysiological results, and neuroimaging examination results were compared. RESULTS A total of 31 patients were included (FA (n=4), FS (n=8), IAE (n=14), and IANE (n=5)). The IANE group, whose mean age was 3.7 years, was more likely to show rapid-onset seizure, acute disturbance of consciousness (ADOC), Babinski's sign, and death/sequela. More patients in the IANE group required tracheal intubation mechanical ventilation and received intravenous immunoglobulins (IVIG) and glucocorticoids. The alanine aminotransferase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels in the IANE group were significantly higher than in the FS and IAE groups. The aquaporin-4 (AQP-4) antibody and malondialdehyde (MDA) levels in the serum and cerebrospinal fluid (CSF) were notably higher in IANE patients in the acute stage compared with FS and IAE patients. All patients in the IANE group had positive neuroimaging findings. CONCLUSIONS Early clinical warning factors for IANE include rapid-onset seizures in patients under 4 years of age, ADOC, and pathological signs. Increased AQP-4 antibodies and MDA levels in CSF might contribute to early diagnosis. Early magnetic resonance venography (MRV) and susceptibility-weighted imaging (SWI) sequences, or thrombelastography to identify deep vein thrombosis, might indicate clinical deterioration.

Short intracortical facilitation associates with motor-inhibitory control.

The ability of motor-inhibitory control is important in daily life. Inhibitory control deficits are commonly observed in psychiatric conditions with enhanced impulsivity. The physiological mechanisms underlying the inhibitory control deficits are not well elucidated. We systematically investigated the relationship between resting-state intracortical inhibition or facilitation and inhibitory control (indicated by stop signal reaction time, SSRT) to determine whether reduced intracortical inhibition or increased intracortical facilitation was related to the poorer inhibitory control. Thirty-three healthy subjects (age: 21.46 ± 1.40 years) participated in this study. We used paired-pulse transcranial magnetic stimulation to induce short intracortical inhibition, intracortical facilitation, long intracortical inhibition, and short intracortical facilitation at rest. SSRT was derived from stop signal task. We performed all measurements in two repeat sessions conducted two weeks apart. A negative correlation between short intracortical inhibition and SSRT was only observed in session 1; however, the correlation did not persist after controlling for short intracortical facilitation. Positive correlation between short intracortical facilitation and SSRT was observed in both sessions, indicating that individuals with greater resting-state short intracortical facilitation tend to have less efficient stopping performance. Our results help explain the inconsistency with respect to the relationship between short intracortical inhibition and SSRT in the existing literature. Short intracortical facilitation may be used as a potential physiological biomarker for motor-inhibitory control, which may have clinical implications for disorders associated with inhibitory control deficits.

Influence of iTBS on the Acute Neuroplastic Change After BCI Training.

Objective: Brain-computer interface (BCI) training is becoming increasingly popular in neurorehabilitation. However, around one third subjects have difficulties in controlling BCI devices effectively, which limits the application of BCI training. Furthermore, the effectiveness of BCI training is not satisfactory in stroke rehabilitation. Intermittent theta burst stimulation (iTBS) is a powerful neural modulatory approach with strong facilitatory effects. Here, we investigated whether iTBS would improve BCI accuracy and boost the neuroplastic changes induced by BCI training. Methods: Eight right-handed healthy subjects (four males, age: 20-24) participated in this two-session study (BCI-only session and iTBS+BCI session in random order). Neuroplastic changes were measured by functional near-infrared spectroscopy (fNIRS) and single-pulse transcranial magnetic stimulation (TMS). In BCI-only session, fNIRS was measured at baseline and immediately after BCI training. In iTBS+BCI session, BCI training was followed by iTBS delivered on the right primary motor cortex (M1). Single-pulse TMS was measured at baseline and immediately after iTBS. fNIRS was measured at baseline, immediately after iTBS, and immediately after BCI training. Paired-sample t-tests were used to compare amplitudes of motor-evoked potentials, cortical silent period duration, oxygenated hemoglobin (HbO2) concentration and functional connectivity across time points, and BCI accuracy between sessions. Results: No significant difference in BCI accuracy was detected between sessions (p > 0.05). In BCI-only session, functional connectivity matrices between motor cortex and prefrontal cortex were significantly increased after BCI training (p's < 0.05). In iTBS+BCI session, amplitudes of motor-evoked potentials were significantly increased after iTBS (p's < 0.05), but no change in HbO2 concentration or functional connectivity was observed throughout the whole session (p's > 0.05). Conclusions: To our knowledge, this is the first study that investigated how iTBS targeted on M1 influences BCI accuracy and the acute neuroplastic changes after BCI training. Our results revealed that iTBS targeted on M1 did not influence BCI accuracy or facilitate the neuroplastic changes after BCI training. Therefore, M1 might not be an effective stimulation target of iTBS for the purpose of improving BCI accuracy or facilitate its effectiveness; other brain regions (i.e., prefrontal cortex) are needed to be further investigated as potentially effective stimulation targets.