High-frequency trading now plays out at microsecond and even nanosecond granularity, and profitability is shaped jointly by adversarial market dynamics and by acute sensitivity to execution latency. Most existing frameworks, somewhat surprisingly, still treat these two pressures in isolation, leaving robustness and timing largely uncoupled. This study sets out to unify adversarial robustness training with latency-aware policy optimization inside a single strategy-design framework, hereafter referred to as MAGAT - a multi-agent game-theoretic adversarial trading system. Methodologically, MAGAT pits a Protagonist Agent - trained by multi-agent proximal policy optimization under centralized training with decentralized execution - against an Adversary Agent that searches for worst-case perturbations using gradient-free evolution strategies; the two roles alternate in a minimax loop whose fixed point is interpreted as an approximate, not certified, equilibrium, and the approximation is itself diagnosed by tracking the joint best-response gap. A Latency-Aware Reward Shaping (LARS) term penalizes aggressive orders in proportion to the logarithm of realized delay, while an FPGA, INT8-GPU, and kernel-bypass pipeline targets sub-700-nanosecond tick-to-order latency. Performance is assessed entirely through event-driven simulation: matching-engine replay over Level-3 LOBSTER limit order book data for three U.S. equities (AAPL, MSFT, INTC, 2022), with a configurable delay-injection platform reproducing uniform, Pareto, and bursty latency profiles. Across the four stress scenarios MAGAT sustains Sharpe ratios of 1.97-2.31 (95% bootstrap CI ± 0.06) and survival rates of 89-96% (± 2.1pp), against 1.18 and 69% for the strongest single-agent baseline; latency elasticity falls roughly fourfold (from 0.54 to 0.12) and the measured 99th-percentile execution latency stays near 683 nanoseconds. These results refer strictly to simulation and should not, on their own, be read as evidence of deployable live performance.
Adults with attention-deficit/hyperactivity disorder (ADHD) often report excessive daytime sleepiness, but the relationship between subjective sleepiness and objective sleep propensity remains unclear. We examined this relationship in adults referred for Multiple Sleep Latency Test (MSLT) evaluation, using a clinical comparison group with excessive daytime sleepiness (EDS) but without ADHD. In this retrospective cross-sectional study, we analyzed medical records of 130 adults aged 18 years or older who underwent MSLT between January and December 2021, including 68 adults in the ADHD group and 62 in the EDS-only group. Subjective sleepiness was assessed by the Epworth Sleepiness Scale (ESS) and objective sleep propensity by mean MSLT sleep latency, with MSLT positivity defined as mean sleep latency ≤ 480 s. Associations between ESS scores and mean sleep latency were assessed within each group, and correlation coefficients were compared between groups using Fisher's r-to-z transformation. ESS scores did not differ significantly between groups, with median scores of 14.0 in the ADHD group and 13.0 in the EDS-only group. In contrast, objective sleep propensity differed significantly: median mean sleep latency was longer in the ADHD group than in the EDS-only group (432.0 s vs 322.0 s, p = 0.008), and MSLT positivity was less frequent in the ADHD group (61.8% vs 87.1%, p = 0.001). Within the ADHD group, ESS scores were not significantly correlated with mean sleep latency, including among MSLT-positive cases. A significant inverse correlation was observed in the MSLT-positive EDS-only subgroup, although formal comparison of correlation coefficients did not demonstrate a statistically significant between-group difference in the ESS-MSLT relationship. SOREMP frequencies were numerically higher in the EDS-only group but did not differ significantly between groups. These findings suggest that subjective sleepiness complaints and objective sleep propensity may not closely align in adults with ADHD referred for sleep evaluation, and support the need for integrated psychiatric and sleep-medicine assessment when such patients present with excessive daytime sleepiness.
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To evaluate the agreement between a contactless ballistocardiography (BCG) based sleep monitoring device and polysomnography (PSG) in assessing sleep macrostructure and respiratory parameters in older adults. Seventeen male participants (aged 50-80 years) underwent overnight PSG, while being simultaneously monitored using the BCG device. Parameters assessed included sleep latency, total sleep time (TST), durations of light sleep (N1 + N2), deep sleep (N3), rapid eye movement (REM) sleep, and derived non rapid eye movement (NREM) sleep, along with apnoea-hypopnea index (AHI). Paired t-tests and Bland Altman analysis were done to evaluate agreement. A P -value < 0.05 was considered statistically significant, with Bonferroni correction applied for multiple comparisons. Significant differences were observed for TST, REM, deep sleep, wake time, and sleep latency. Dozee overestimated TST by + 83.00 min (95% LoA: -42.88 to + 208.7) and light sleep by + 39.88 min (LoA: -197.0 to + 117.2), while underestimating deep sleep (-29.53 min; LoA: -99.20 to + 40.14), REM sleep (-45.63 min; LoA: -137.7 to + 46.43), and time in bed (-69.41 min; LoA: -236.0 to + 97.21). Sleep latency was slightly underestimated (-8.94 min; LoA: -28.20 to + 10.32), and wake time after sleep onset was overestimated (+35.24 min; LoA: -37.21 to + 107.7). AHI was modestly overestimated by + 7.18 events/hour (LoA: -18.09 to + 32.44). While the BCG based device shows potential for non-invasive, unobtrusive sleep monitoring, it demonstrated substantial discrepancies when compared to PSG. These limitations may compromise the clinical utility of such devices, especially in older adults with fragmented sleep or respiratory abnormalities. BCG based devices may offer value in large scale or home-based screening contexts if future algorithmic refinements improve its staging and respiratory event detection capabilities.
Second malignant neoplasms (SMNs) represent a devastating late complication of central nervous system (CNS) tumor, particularly in pediatric and young adult populations. While improved treatments have increased survival rates, the risk and characteristics of SMNs in contemporary cohorts remain poorly characterized. The purpose of this study is to characterize the clinicopathological and molecular features of therapy-related high-grade gliomas(t-HGGs), and to explore their multifactorial etiology involving radiation, chemotherapy, and potential genetic susceptibility. We analyzed seven cases of histologically confirmed SMNs developing after treatment for primary CNS tumors. We collected and analyzed key clinical information from patients, including gender, age, time to second tumor onset (latency), treatment modalities, and outcomes. Additionally, we examined imaging findings, histopathological features using hematoxylin-eosin (H&E) staining and immunohistochemistry, as well as molecular marker characteristics. The cohort consisted of seven patients (5 males, 2 females). The median age at primary tumor diagnosis was 5 years (range: 3-21 years), and at SMN diagnosis was 12 years (range: 7-27 years), with a median latency of 6 years (range: 2-9 years). All patients received radiotherapy. Exploratory analysis revealed no significant relationship between radiation dose and latency period. Histological transformation was universal, most commonly from medulloblastoma to high-grade glioma (3/7 cases) and germ cell tumors (3/7 cases, including 2 germinomas and 1 non-germinomatous germ cell tumor (NGGCT)). Molecular analysis in sequenced cases revealed distinct profiles, including NF1/PDGFRA alterations. Outcomes were poor. This study delineates a rare yet distinct clinicopathological entity-therapy-related high-grade glioma, which may arise from the complex interplay of prior radiotherapy, chemotherapy, and underlying genetic susceptibility. Recognition of this multifactorial etiology is critical for risk stratification and long-term surveillance.
Internet of Things-based wireless sensor networks (IoT-WSNs) face persistent challenges related to energy consumption, latency, and network congestion under dynamic and heterogeneous topologies. Conventional reinforcement learning approaches rely on static reward formulations, which limit adaptability and hinder effective multi-objective optimization. This study proposes a dynamic reward structuring framework within deep reinforcement learning to enable adaptive and balanced routing in IoT-WSNs. The proposed approach employs real-time reward recalibration to jointly optimize energy efficiency, delay, and throughput under varying network conditions. A hybrid deep reinforcement learning architecture is developed by integrating value-based, policy-based, and actor-critic methods, along with multi-agent coordination and attention mechanisms to prioritize critical nodes and links. Furthermore, a hierarchical learning structure decomposes global and local routing objectives, improving scalability and decision efficiency in complex network environments. Experimental results demonstrate that the proposed framework achieves significant performance gains, including approximately 30% improvement in energy efficiency, 25% reduction in latency, and 35% increase in network throughput compared with baseline methods. These findings highlight the effectiveness of dynamic reward adaptation for scalable and robust multi-objective optimization in IoT-WSN routing.
This study investigated developmental differences in motor execution and inhibition by comparing somatosensory event-related potentials (ERPs) between adolescents and young adults. Thirty-seven adolescents (14.7 ± 0.2 years) and thirty-seven adults (21.1 ± 1.4 years) performed a somatosensory Go/No-go task while ERPs were recorded at Fz, Cz, and Pz electrodes. We analyzed the latency and amplitude of N2, additional negativity (AN), and P3 components together with behavioral indices including reaction time (RT), RT variability, omission errors, and commission errors, and also examined the scalp distribution of the P3 amplitude. Adolescents showed significantly higher commission error rates than adults, whereas other behavioral indices were comparable. ERP analyses revealed enhanced AN amplitude at Fz and shorter N2 latency at Fz, Cz, and Pz only in adolescents compared with adults. Moreover, No-go-P3 in adolescents was more parietally distributed, whereas adults exhibited a more anterior distribution, suggesting greater prefrontal involvement in adults. These findings suggest that although the speed of sensory-cognitive processing reaches an adult-like level by adolescence, inhibitory control and its underlying neural mechanisms continue to mature during this period. While adolescents exhibit ERP-behavior relationships comparable with those of adults, they may rely on broader and less specialized neural networks, particularly for frontal inhibitory control. Overall, the present results highlight adolescence as a key transitional stage in the development of cognitive control, with important implications for understanding age-related changes in sensorimotor processing and inhibitory functions.
Persistent post-concussion symptoms (PPCS) affect 35% of children and adolescents with concussion. This study aimed to characterise sleep patterns in children and adolescents with PPCS and explore the effect of sleep disturbance on clinical concussion outcomes. A prospective longitudinal study was conducted in participants with PPCS (n = 20, aged 11-18 years) presenting to a tertiary referral clinic. Participants completed a battery of concussion assessments at their initial consultation and at 4 weeks follow-up to assess and monitor symptom burden, cognition, balance, mental health, and exercise tolerance. The Insomnia Severity Index (ISI) was used to identify participants with post-concussion clinical insomnia (PCCI). Wrist actigraphy was used to objectively characterise sleep patterns, including total sleep time, sleep latency, wake after sleep onset and sleep efficiency, over a 14-day period. Participants were followed until they were recovered from concussion. Forty-five percent of participants with PPCS also had PCCI. Objective mean ± SD sleep parameters of participants were: total sleep time 452.1 ± 53.8 min, sleep latency 32.2 ± 16.3 min, wake after sleep onset 76.9 ± 21.4 min, and sleep efficiency 85.9 ± 3.7%. Mood disturbance was a significant predictor of sleep disturbance at the 4-week follow-up (P = 0.01). Recovery time was three times greater for participants with PCCI than those with no PCCI (median (interquartile range): 150 (91-247) vs 47 (30-58) days, P = 0.04). Sleep disturbance is significantly associated with poorer mental health and prolonged recovery time in children and adolescents with PPCS.
University students regularly report insufficient sleep, with almost one-third of students achieving less than 6.5 hours per night. Social media is one behaviour shown to negatively influence sleep. However, there has been a reliance on self-report measures of both processes, which may not reflect objective behaviour. The aim was to determine if there is a relationship between social media use and sleep outcomes when measured objectively, and if so, which sleep outcomes were associated with social media use. A longitudinal repeated measures design was used to assess daily social media use and sleep outcomes over 14 days. Participants wore accelerometers to measure their sleep, with total daily social media use derived from smartphone data. Sixty-two participants (Mage = 22.11 years, SD = 5.82 years) completed the study. Linear mixed models revealed no between or within-participant effects of daily social media on sleep duration, sleep onset latency, sleep efficiency and bedtime. However, TikTok showed a positive between-participants effect on bedtime. A generalized linear mixed model also revealed that Snapchat had a negative between-participants effect on sleep onset latency. Findings indicate that the duration of time spent on social media does not impact sleep across this sample. However, interactions with different social media platforms such as TikTok and Snapchat may play an important role in influencing sleep quality. These findings suggest that behavioural measures do not reflect the same pattern of effects observed with self-report, highlighting the need for future research to corroborate findings derived from self-report.
Theoretical perspectives suggest that pre-sleep cognitive processes, including cognitive arousal, rumination, and stress can impair sleep. However, previous studies have relied on cross-sectional designs, limiting insight into how these cognitive processes relate to sleep on a night-to-night basis. In addition, anticipatory stress has received little empirical attention, despite its relevance for poor sleep. To address these gaps, the present study examined the associations of pre-sleep cognitive arousal, pre-sleep rumination, and anticipatory stress with sleep quality, sleep duration, and sleep onset latency both when averaged across 7 days (between-person level) and on a day-to-day basis (within-person level). A total of 166 emerging adults (Mage  = 20.36 years, 80.1% female) completed smartphone-based surveys during 7 consecutive days, reporting on pre-sleep cognitive processes (cognitive arousal, rumination, anticipatory stress) each evening and sleep outcomes each morning. Linear mixed-effects models showed that, at the between-person level, higher average levels of all three pre-sleep cognitive processes across the week were associated with poorer sleep quality and shorter sleep duration. No significant associations were found for sleep onset latency. At the within-person level, all three pre-sleep cognitive processes were not related to next-morning sleep outcomes. Overall, the findings suggest that stable individual differences in pre-sleep cognitive processes, rather than short-term changes, are linked to sleep quality and duration in emerging adults.
Epstein-Barr virus (EBV) infects more than 90% of the population and establishes a lifelong persistence in memory B cells, passing through several latency stages (I-III). In immunocompromised patients, EBV infections and reactivations can lead to severe complications, such as post-transplant lymphoproliferative disorder (PTLD), a malignant B cell lymphoproliferation. The EBV latent membrane protein 2A (LMP2A) induces activation and proliferation of infected B cells and is expressed in latency stages II/III, that are associated with several EBV malignancies. Here, T cell receptor (TCR)-engineered T cells based on a TCR recognizing the clinically relevant HLA-A∗02:01-restricted LMP2A-derived peptide CLGGLLTMV (A∗02_LMP2ACLG) and equipped with a TCR-inducible cassette for IL-18 release (iIL-18_LMP2A_TCR-T cells) aiming to prevent exhaustion and promote remodeling of the immunosuppressive tumor microenvironment (TME) were developed. The iIL-18_LMP2A_TCR-T cells exhibited improved cytotoxicity against HLA-A∗02:01+ EBV-infected B-lymphoblastoid cell lines (EBV+ B-LCLA∗02:01) serving as in vitro PTLD model, when compared to LMP2A_TCR-T cells without iIL-18. The superior functionality of iIL-18_LMP2A_TCR-T cells was further confirmed in multicellular tumor spheroid (MCTS) models, where they mediated sustained control of EBV+ B-LCLA∗02:01 growth, highlighting their potential as an effective therapeutic approach for the immune-mediated eradication of EBV-associated malignancies, including PTLD.
Trigeminal involvement in multiple sclerosis (MS) may remain clinically silent despite measurable functional disturbance. Subclinical dysfunction of afferent pathways can precede overt neurological findings. We aimed to investigate whether pulp sensibility testing can detect subclinical trigeminal afferent dysfunction in patients with MS who have no clinical evidence of trigeminal neuropathy. Thirty-nine patients with MS (19 relapsing-remitting and 20 progressive) and 27 healthy controls were included. Electric pulp testing (EPT) and cold stimulation were applied to the right maxillary central incisor in all participants. For EPT, sensory threshold values were recorded. For the cold test, response latency was measured in seconds. Correlation analyses were performed to assess associations with age and disease duration. Compared with controls, patients with MS demonstrated higher EPT thresholds and prolonged cold response times. Within the MS cohort, both measures were greater in progressive disease. The difference reached statistical significance for cold testing (7.15±3.60 vs 4.89±2.58 s, p=0.038), whereas EPT values showed a similar but non-significant trend (9.80±4.15 vs 7.84±4.59, p=0.084). Age correlated weakly with cold response latency (rs=0.321, p=0.046) and EPT values (rs=0.326, p=0.043). Disease duration showed a weak correlation with EPT (rs=0.334, p=0.037), but not with cold responses. Despite the limitations of our study, our results indicate that pulp sensibility testing may provide meaningful information regarding the functional status of trigeminal afferent pathways. The more pronounced alterations observed in the progressive disease subgroup are consistent with cumulative conduction disturbance along the trigeminal system. Further studies directly comparing this approach with trigeminal SEP and high-resolution brainstem MRI are needed to better define its diagnostic value and clinical relevance.
Sleep disturbances during adolescence heighten risk for physical and behavioral health problems, yet sleep physiological markers critical to health outcomes are rarely assessed in pediatric care. Wearable single-channel electroencephalography (EEG) devices may offer scalable, ecologically valid methods for assessing sleep physiology in home settings. This study evaluated whether single-channel sleep-EEG metrics were associated with physical and behavioral health in adolescents. Eighty-five community-derived adolescents (ages 11-17, 50% female) completed seven consecutive nights of at-home, single-channel sleep-EEG, physical health assessments (i.e., body mass index and blood pressure), and subjective sleep and behavioral health measures. Parents provided psychiatric diagnosis history. Odds of being overweight/obese decreased with greater REM duration (- 2.72% per minute) and higher REM percentage (- 100% per 1%). Odds of hypertension decreased with greater time spent in stage 3 (N3) (- 4.78% per minute). Multivariate analyses showed reduced N3 sleep was associated with parent-reported ADHD symptoms, whereas shorter total sleep time, lower sleep efficiency (SE), and longer sleep onset latency (SOL) were associated with higher adolescent-reported ADHD and conduct problems (p's < .05). Odds of an ADHD diagnosis increased with longer SOL (+ 1.92% per minute) and slower N3 decline (+ 89.4% per 0.01 units) but decreased with higher SE (- 7.78% per 1%). Odds of an internalizing disorder increased with higher SE (+ 12.4% per 1%) and greater wake after sleep onset (+ 3.18% per minute), but decreased with more REM sleep (- 9.62% per minute). Findings highlight the clinical value of wearable sleep-EEG for detecting sleep-related risk processes during adolescence. By capturing physiological features not accessible through self-report, at-home sleep-EEG may flag youth who could benefit from sleep-focused interventions, complementing routine care in identifying risk of future health problems. Integrating such tools into pediatric settings could support more precise, developmentally informed approaches to prevention and intervention. Sleep disturbances are common during adolescence and increase risk for physical conditions such as obesity and hypertension, as well as behavioral health problems, yet sleep physiology is rarely adequately assessed in pediatric care. Wearable single-channel EEG offers an accessible way to capture sleep architecture and continuity that subjective reports cannot provide. This study shows that EEG-derived sleep features, including REM, N3 sleep, sleep efficiency, and sleep-onset latency, are associated with physical and behavioral health outcomes above and beyond adolescent and caregiver reports. These findings highlight the potential value of integrating wearable EEG into routine care to identify sleep-related vulnerabilities and support targeted prevention efforts.
The renin-angiotensin system (RAS) has been increasingly recognized as potent modulator of cognitive and affective functions, with angiotensin II type 1 receptor (AT1R) antagonists emerging as repurposing candidate for anxiety and stress-related disorders. However, it remains unclear whether transient AT1R blockade modulates emotional attentional control and whether these effects are sex-dependent. We conducted a preregistered, randomized, double-blind, placebo-controlled pharmacological eye-tracking study in 79 healthy adults (males and females) and determined effects of transient AT1R blockade via losartan (50 mg) on emotional attention control using a validated anti-saccade paradigm with social (emotional faces) and non-social stimuli. Treatment effects on state anxiety and oculomotor responses were characterized using traditional metrics and a novel trial-history informed dynamic control framework. Losartan reduced state anxiety irrespective of sex but induced sexually dimorphic effects of attentional control. In females, losartan enhanced performance by reducing endpoint error without altering latency. Conversely, in males, losartan increased endpoint error and prolonged latency of the first correct saccade. Trial-history analyses revealed losartan reduced error probabilities following errors and repeat trials in both sexes. Yet, following correct trials, females receiving losartan maintained lower error probabilities, while males exhibited higher errors, potentially reflecting failure to disengage from effortful control. The RAS modulates anxiety and attentional control, the latter sex-dependently. AT1R blockade reconfigures attentional processing and adaptive control, suggesting sex-specific therapeutic potential in disorders characterized by excessive anxiety and attentional dysregulation. ClinicalTrials.gov; https://clinicaltrials.gov/;NCT06329050.
The therapeutic potential of lavender aroma is well documented, with proven results in reducing stress and facilitating mental repose. However, its effects on specific domains of executive function, such as cognitive flexibility, have not been sufficiently studied. This gap is significant for understanding how nonpharmacological interventions can influence complex cognition. This study investigates these effects by employing task-switching paradigms to assess cognitive flexibility. The neural correlates were measured via electroencephalography (EEG), focusing on P300 event-related potentials (ERPs). P300 latency and amplitude, a key ERP component reflecting cognitive processing, were measured at EEG electrodes Cz and FCz. The data revealed that lavender inhalation induced specific neural changes. Following lavender inhalation, the P300 peak amplitude at the Cz electrode increased during switch trials, which could indicate improved cognitive control in demanding situations. At the FCz electrode, the latency of P300 was significantly reduced during switch trials, which could suggest the importance of this area in processing speed. The findings of the current study verify the neuromodulatory effects of lavender aroma in improving processes related to cognitive flexibility. This provides a physiological basis for its benefits, suggesting it could be effectively applied in future clinical interventions for cognitive enhancement.
Circadian rhythm disruption (CRD) exacerbates epileptic seizures, yet the underlying molecular mechanisms remain unclear. Using a pentylenetetrazol (PTZ) kindling rat model combined with continuous light exposure, we found that CRD significantly shortened seizure latency and increased seizure frequency. 16S rRNA sequencing revealed that CRD substantially increased the abundance of Ruminococcus gnavus (R. gnavus) in the gut microbiota. Antibiotic-mediated microbiota depletion, fecal microbiota transplantation (FMT), and R. gnavus monocolonization experiments confirmed that R. gnavus enrichment is a critical factor driving seizure aggravation. Metabolomic analysis demonstrated that elevated R. gnavus suppressed the expression of argininosuccinate synthase 1 (ASS1), a key enzyme for arginine biosynthesis in the kidney, leading to impaired L-citrulline-to-L-arginine conversion and consequently decreased L-arginine levels in serum and hippocampal tissues. Arginine deficiency subsequently activated NADPH oxidase 4 (NOX4) upregulation in the hippocampus, triggering enhanced oxidative stress (elevated malondialdehyde (MDA) and reduced superoxide dismutase (SOD) activity), which ultimately induced ferroptosis (characterized by mitochondrial cristae reduction, acyl-CoA synthetase long-chain family member 4 (ACSL4) upregulation, and glutathione peroxidase 4 (GPX4) downregulation). Pharmacological intervention with the NOX4-specific inhibitor GLX351322 ameliorated oxidative stress, suppressed ferroptosis, and alleviated seizure severity. Importantly, L-arginine supplementation significantly prolonged seizure latency and reduced seizure frequency by reversing ferroptosis activation through downregulating NOX4-ACSL4 expression and upregulating GPX4 expression. This study unveils a complete signaling axis whereby CRD promotes epileptic seizures through the R. gnavus-ASS1-arginine-NOX4-ferroptosis cascade, providing novel therapeutic targets for clinical intervention.
To observe the effects of moxibustion at the points of governor vessel on cognitive function and gut microbiota in Alzheimer's disease (AD) model mice, and explore the mechanism of moxibustion at governor vessel in treatment of AD. Eighteen APP/PS1 mice were randomly divided into a model group and a moxibustion group, with 9 mice in each group; and the other 9 C57BL/6J mice were collected as a blank group. In the moxibustion group, mild-warm moxibustion was operated at "Baihui" (GV20), suspended moxibustion was at "Fengfu" (GV16) and "Dazhui" (GV14), 20 min in each intervention. Moxibustion was delivered once daily for 2 weeks. The water maze test and the novel object recognition experiment were employed to evaluate the cognitive function of mice, and the contents of β-amyloid 40 (Aβ40), β-amyloid 42 (Aβ42), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the hippocampus of mice were detected by ELISA, the morphology of hippocampal tissues was observed by HE staining, and the structure of fecal gut microbiota in mice was analyzed by 16S rRNA gene sequencing. The correlation of gut microbiota with the hippocampal Aβ40, Aβ42, TNF-α and IL-6 contents was analyzed. Compared with the blank group, in the model group, the escape latency was extended (P<0.01), the number of platform crossings decreased (P<0.01), the target quadrant residence time ratio was reduced (P<0.01); the preference index in the novel object experiment increased (P<0.001), and the discrimination coefficient decreased (P<0.001). The contents of Aβ40, Aβ42, TNF-α and IL-6 in the hippocampus rose (P<0.05), the hippocampal neuron structure was imcomplete, with irregular size and arrangement, the neurons were vacuolar and some showed pyknosis and were reduced in number. ACE, Chao1 and Shannon indexes decreased (P<0.001) and the Simpson index rose (P<0.001). The relative abundance of Proteobacteria and Deferribacteres was reduced (P<0.001), that of Lactobacillus and Pasteurella was elevated (P<0.01), while that of Alistipes decreased (P<0.01). Compared with the model group, in the moxibustion group, the escape latency was shortened (P<0.05), the number of crossing the platform increased (P<0.05), and the target quadrant residence time ratio was higher (P<0.05); the preference index decreased (P<0.001), and the discrimination coefficient increased (P<0.001). The contents of Aβ40, Aβ42, TNF-α and IL-6 in the hippocampus decreased (P<0.01). Hippocampal tissue injury was attenuated. ACE, Chao1 and Shannon indexes increased (P<0.05), and Simpson index decreased (P<0.05). The relative abundance of Proteobacteria and Deferribacteres increased (P<0.05), that of Lactobacillus decreased (P<0.001). The correlation was presented between gut microbiota and the contents of hippocampal Aβ40, Aβ42, TNF-α and IL-6 in the moxibustion group. Moxibustion at governor vessel points can improve cognitive function in AD mice, reduce Aβ accumulation, inhibit neuroinflammation, which may be related to the recovery of gut microbiota homeostasis. 目的:观察艾灸督脉穴对阿尔茨海默病(AD)模型小鼠认知功能和肠道菌群的影响,探讨艾灸督脉治疗AD的作用机制。 方法:将18只APP/PS1双转基因雄性小鼠随机分为模型组和艾灸组,每组9只,另取9只C57BL/6J雄性小鼠作为空白组。艾灸组予以实按灸“百会”、悬灸“风府”和“大椎”,每次20 min,每日1次,干预2周。采用水迷宫实验和新事物识别实验评估小鼠认知功能,ELISA法检测小鼠海马β淀粉样蛋白40(Aβ40)、β淀粉样蛋白42(Aβ42)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)含量,HE染色法观察小鼠海马组织形态,16S rRNA基因测序分析小鼠粪便肠道菌群结构。并分析艾灸组肠道菌群与海马Aβ40、Aβ42、TNF-α、IL-6含量的相关性。 结果:与空白组比较,模型组小鼠水迷宫实验逃避潜伏期延长(P<0.01),穿越平台次数减少(P<0.01),目标象限停留时间比减少(P<0.01);新事物识别实验偏好指数升高(P<0.001),辨别系数降低(P<0.001);海马Aβ40、Aβ42、TNF-α、IL-6含量升高(P<0.001);海马神经细胞结构不完整、大小不均匀、排列紊乱,神经细胞呈空泡样变,部分出现核固缩,数量减少;ACE、Chao1、Shannon指数下降(P<0.001),Simpson指数升高(P<0.001);变形菌门和脱铁杆菌门相对丰度降低(P<0.001);乳酸菌属和巴氏杆菌属相对丰度升高(P<0.01),另枝菌属相对丰度降低(P<0.01)。与模型组比较,艾灸组小鼠水迷宫实验逃避潜伏期缩短(P<0.05),穿越平台次数增加(P<0.05),目标象限停留时间比增加(P<0.05);新事物识别实验偏好指数降低(P<0.001),辨别系数升高(P<0.001);海马Aβ40、Aβ42、TNF-α、IL-6含量降低(P<0.01);海马组织损伤改善;ACE、Chao1、Shannon指数升高(P<0.05),Simpson指数降低(P<0.05);变形菌门和脱铁杆菌门相对丰度升高(P<0.05);乳酸菌属相对丰度降低(P<0.001)。艾灸组肠道菌群与海马Aβ40、Aβ42、TNF-α、IL-6含量存在相关性。 结论:艾灸督脉穴可改善AD小鼠的认知功能,减轻Aβ积累,抑制神经炎症,可能与恢复肠道菌群稳态有关。.
Abnormalities in visual search and navigational tasks were recognized in Parkinson's Disease (PD), mainly related to top-down mechanisms. The aim of the present study was to assess the possible independent effects of bottom-up mechanisms on visual exploration and perceptual decision-making in PD by using synthetic entropy-based visual inputs, in order to minimize their semantic value and possible top-down biases. Binocular eye movements were recorded at 1000 Hz using the Eyelink 1000 Plus system. Participants were shown pairs of grey-scale images with varying entropic properties and they were asked to choose between them while their gaze patterns were recorded. Latency of first saccade and choice together with entropy of both image at first saccade and chosen image were extracted. Data were obtained from both PD subjects and Healthy Controls (HCs). An age-related tendency towards high entropic choice together with a first saccade direction towards high entropic images were observed in PD subjects as compared to HCs. These two parameters resulted directly correlated. A direct correlation between latency of choice and disease severity was also observed among PD subjects. Results support the role of the visual scene's intrinsic entropic value in visual exploration and choice. Bottom-up mechanisms regulating visual and motor choice seem related to bradykinesia in PD subjects. An overall increase in choosing and fixating high entropic figures as age increases was found in PD with respect to HCs, indicating a progressive pathological basal ganglia dysfunction in mechanisms controlling visual-attention and motor targeting of high-entropic images.
Comorbid insomnia and sleep apnea (COMISA) presents a greater clinical burden than obstructive sleep apnea (OSA) alone. We investigated the association between body composition and insomnia to identify the body composition phenotype of COMISA. This cross-sectional study included 2915 patients with moderate-to-severe OSA (apnea-hypopnea index ≥15) who underwent polysomnography and body composition analysis. Participants were categorized into OSA (Insomnia Severity Index [ISI] < 15) and COMISA (ISI ≥15). Skeletal muscle mass (SMM), visceral fat area (VFA), and the SMM/VFA ratio were assessed via bioelectrical impedance analysis. Of the participants, 865 (29.7%) were classified as COMISA. Compared to the OSA-only group, COMISA patients were older, more frequently female, and exhibited poorer sleep parameters, namely shorter total sleep time, prolonged sleep onset latency, increased wake after sleep onset, and lower sleep efficiency, despite comparable body mass index and apnea-hypopnea index. Notably, the COMISA group showed lower SMM, alongside higher VFA. The SMM/VFA ratio was inversely associated with ISI scores (β = -0.08, p = 0.001) and COMISA status (OR = 0.29, p = 0.004), particularly in males. These associations persisted across confounder adjustments and strengthened progressively with stepwise increments in depression severity thresholds. Patients with COMISA exhibit a more vulnerable body composition profile, characterized by lower muscle-to-fat ratios, compared with those with OSA alone. These findings suggest that clinicians should consider detailed body composition assessments to stratify insomnia risk during the evaluation of patients with OSA.
Electricity markets depend on centralized clearing mechanisms that require participants to trust that submitted bids are preserved and accurately incorporated into the market-clearing process. Current blockchain-based energy market solutions either decentralize the auction mechanism or utilize the blockchain solely as a transaction log, lacking verifiable assurances that off-chain clearing employs the complete and unaltered set of submitted bids. This work introduces a hybrid blockchain-based governance architecture that enables verifiable bid integrity for centralized electricity market clearing while maintaining conventional off-chain clearing procedures. The architecture records cryptographic commitments of submitted orders on a permissioned Hyperledger Fabric blockchain, stores clear-text bids in restricted private collections, and anchors settlement outputs on-chain via an oracle interface. This design allows independent post-clearing verification that the orders used in clearing correspond precisely to those committed before auction closure, without disclosing confidential bid information. The system is evaluated using a real intraday electricity market dataset containing 46,643 orders from a full trading day in the Spanish market. Experimental results show that the architecture maintains one-to-one correspondence between submitted orders and on-chain commitments, enforces correct market lifecycle transitions, and detects inconsistencies between committed bids and the inputs used during clearing, providing tamper-evident guarantees of input integrity in adversarial scenarios. Performance benchmarking against a centralized database baseline shows that the blockchain implementation introduces additional latency and achieves 176.5 transactions per second under the evaluated configuration, reflecting a throughput-limited regime while remaining compatible with realistic intraday auction time windows. These findings demonstrate that blockchain technology can serve as a practical governance layer for electricity markets by shifting trust from unverifiable operator actions to cryptographically auditable input integrity, without requiring modifications to existing clearing algorithms. The approach does not verify the correctness of the clearing algorithm itself but ensures that its inputs are cryptographically auditable.