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ObjectiveThis systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer’s disease, and other neurological disorders.MethodsA systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords “vagus nerve stimulation,” “cognitive enhancement,” “emotional processing,” “executive function,” “learning and memory,” “epilepsy,” “depression,” “Alzheimer’s disease,” “neurological disorders,” “attention-deficit/hyperactivity disorder,” “sleep disorders,” and “long COVID.” The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.ResultsA comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer’s disease.ConclusionVNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.

Abstract To establish and evaluate an intestinal microbiota dysbiosis-induced obesity mouse model. 50 C57BL/6 J male healthy mice were randomly divided into an obesity model group and the control group. The body weight, body length, and Lee’s index of the two groups of mice at week 1 and week 10 were compared. Serum glucose (GLU), total cholesterol (TC) and triglyceride (TG) were measured by enzyme-labeled colorimetric methods. Illumina HiSeq 16S rDNA high-throughput sequencing technology was used to characterize intestinal microbiota in feces. The success rate of model establishment in obese mice was 52%. The body weight, body length, Lee’s index, and abdominal fat (wet weight) in the obese model group were all higher than those in the control group, and the differences were statistically significant (P 0.05). The control group contained more abundant intestinal microbiota phyla and genera than did the obesity model group; the differences between the two groups were significant (FDR ≤ 0.05, P ≤ 0.05). Intestinal microbiota dysbiosis can be used to generate an obesity model in mice.

The effects of face immersion and concurrent exercise on the diving reflex evoked by breath-hold (BH) differ, yet little is known about the combined effects of different BH conditions on aerobic fitness in elite athletes. This study aimed to assess the acute effects of various BH conditions on 18 male elite rugby players (age: 23.5 ± 1.8 years; height: 183.3 ± 3.4 cm; body mass: 84.8 ± 8.5 kg) and identify the BH condition eliciting the greatest aerobic fitness activation. Participants underwent five warm-up conditions: baseline regular breathing, dynamic dry BH (DD), static dry BH (SD), wet dynamic BH (WD), and wet static BH (WS). Significant differences (p < 0.05) were found in red blood cells (RBCs), red blood cell volume (RGB), and hematocrit (HCT) pre- and post-warm-up. Peak oxygen uptake (VO2peak) and relative oxygen uptake (VO2/kgpeak) varied significantly across conditions, with BH groups showing notably higher values than the regular breathing group (p < 0.05). Interaction effects of facial immersion and movement conditions were significant for VO2peak, VO2/kgpeak, and the cardiopulmonary optimal point (p < 0.05). Specifically, VO2peak and peak stroke volume (SVpeak) were significantly higher in the DD group compared to that in other conditions. Increases in VO2peak were strongly correlated with changes in RBCs and HCT induced by DD warm-up (r∆RBC = 0.84, r∆HCT = 0.77, p < 0.01). In conclusion, DD BH warm-up appears to optimize subsequent aerobic performance in elite athletes.

Abstract Aged microglia display augmented inflammatory activity after neural injury. Although aging is a risk factor for poor outcome after brain insults, the precise impact of aging-related alterations in microglia on neural injury remains poorly understood. Microglia can be eliminated via pharmacological inhibition of the colony–stimulating factor 1 receptor (CSF1R). Upon withdrawal of CSF1R inhibitors, microglia rapidly repopulate the entire brain, leading to replacement of the microglial compartment. In this study, we investigated the impact of microglial replacement in the aged brain on neural injury using a mouse model of intracerebral hemorrhage (ICH) induced by collagenase injection. We found that replacement of microglia in the aged brain reduced neurological deficits and brain edema after ICH. Microglial replacement-induced attenuation of ICH injury was accompanied with alleviated blood-brain barrier disruption and leukocyte infiltration. Notably, newly repopulated microglia had reduced expression of IL-1β, TNF-α and CD86, and upregulation of CD206 in response to ICH. Our findings suggest that replacement of microglia in the aged brain restricts neuroinflammation and brain injury following ICH.

BackgroundThe Composite Dietary Antioxidant Index (CDAI), a composite score of multiple dietary antioxidants (including vitamin A, C, and E, selenium, zinc, and carotenoids), represents an individual’s comprehensive dietary antioxidant intake profile. CDAI was developed based on its combined effect on pro-inflammatory markers Tumor Necrosis Factor-α (TNF-α) and anti-inflammatory effects of Interleukin-1β (IL-1β), which are associated with many health outcomes, including depression, all-cause mortality, colorectal cancer, etc. Handgrip strength is used as a simple measure of muscle strength, not only is it highly correlated with overall muscle strength, but also serves as a diagnostic tool for many adverse health outcomes, including sarcopenia and frailty syndromes.PurposeThe association between CDAI and Handgrip strength (HGS) is currently unclear. This study investigated the association between CDAI (including its components) and HGS in 6,019 American adults.MethodThe research data were selected from the 2011–2014 National Health and Nutrition Survey (NHANES), and a total of 6,019 American adults were screened and included. A weighted generalized linear regression model was used to evaluate CDAI (including its components) and HGS.Results(1) CDAI was significantly positively correlated with HGS (β = 0.009, 0.005∼0.013, P < 0.001), and the trend test showed that compared with the lowest quartile of CDAI, the highest quartile of CDAI was positively correlated with HGS (β = 0.084, 0.042∼0.126, P = 0.002) and significant in trend test (P for trend < 0.0100). Gender subgroup analysis showed that male CDAI was significantly positively correlated with HGS (β = 0.015, 0.007∼0.023, P = 0.002), and the trend test showed that compared with the lowest quartile of CDAI, the highest quartile of CDAI was positively correlated with HGS (β = 0.131, 0.049∼0.213, P = 0.006) and the trend test was significant (P for trend < 0.0100). There was no correlation between female CDAI and HGS, and the trend test was not statistically significant (P > 0.05). (2) The intake of dietary vitamin E, Zinc and Selenium showed a significant positive correlation with HGS (β = 0.004, 0.002∼0.007, P = 0.006; β = 0.007, 0.004∼0.009, P < 0.001; β = 0.001, 0.001∼0.001, P < 0.001), vitamin A, vitamin C and carotenoid were significantly associated with HGS in the Crude Model, but this significant association disappeared in the complete model with the increase of control variables. Gender subgroup analysis showed that in model 3, male dietary intake levels of vitamin E, Zinc, and Selenium were significantly positively correlated with HGS (β = 0.005, 0.002∼0.009, P = 0.011; β = 0.007, 0.004∼0.011, P = 0.001; β = 0.001, 0.001∼0.001, P = 0.004), the rest of the indicators had no significant correlation with HGS. Among the female subjects, dietary zinc intake was significantly positively correlated with HGS (β = 0.005, 0.001∼0.008, P = 0.008), and there was no significant correlation between other indicators and HGS (P > 0.05).ConclusionThere was an association between the CDAI and HGS, but there was a gender difference, and there was an association between the CDAI and HGS in male, but the association was not significant in female. Intake of the dietary antioxidants vitamin E, selenium, and zinc was associated with HGS in male, but only zinc was associated with HGS among dietary antioxidants in female.

Objective: Although regular and moderate physical activity has been shown to improve the cardiovascular and autonomic nervous systems, little has been done to study the effects of postural changes in the movement on the heart and autonomic nervous system. To uncover changes in cardiac function and autonomic nerves induced by different underlying posture transitions and explore which trunk postures lead to chronic sympathetic activation. Therefore, this study investigated the effects of trunk posture on the cardiovascular and autonomic nervous systems.Methods: Twelve male subjects (age 24.7 ± 1.3) underwent this study. The non-invasive cardiac output NICOM monitoring equipment and the FIRSTBEAT system are used to dynamically monitor seven trunk postures in the sitting position simultaneously (neutral position, posterior extension, forward flexion, left lateral flexion, right lateral flexion, left rotation, right rotation). Each posture was maintained for 3 min, and the interval between each movement was 3 min to ensure that each index returned to the baseline level. Repeated analysis of variance test was used to compare and analyze the differences in human cardiac function, heart rate variability index, and respiratory rate under different postures.Results: Compared with the related indicators of cardiac output in a neutral trunk position: the cardiac index (CI) was significantly reduced in forwarding flexion and left rotation (3.48 ± 0.34 vs. 3.21 ± 0.50; 3.48 ± 0.34 vs. 3.21 ± 0.46, Δ L/(min/m2)) (p = 0.016, p = 0.013), cardiac output decreased significantly (6.49 ± 0.78 vs. 5.93 ± 0.90; 6.49 ± 0.78 vs. 6.00 ± 0.96, Δ L/min) (p = 0.006, p = 0.014), the stroke volume (stroke volume)decreased significantly (87.90 ± 15.10 vs. 81.04 ± 16.35; 87.90 ± 15.10 vs. 79.24 ± 16.83, Δ ml/beat) (p = 0.017, p = 0.0003); heart rate increased significantly in posterior extension (75.08 ± 10.43 vs. 78.42 ± 10.18, Δ beat/min) (p = 0.001); left rotation stroke volume index (SVI) decreased significantly (47.28 ± 7.97 vs. 46.14 ± 8.06, Δ ml/m2) (p = 0.0003); in the analysis of HRV-related indicators, compared with the neutral trunk position, the LF/HF of the posterior extension was significantly increased (1.90 ± 1.38 vs. 3.00 ± 1.17, p = 0.037), and the LF/HF of the forward flexion was significantly increased (1.90 ± 1.38 vs. 2.85 ± 1.41, p = 0.041), and the frequency-domain index LF/HF of right rotation was significantly increased (1.90 ± 1.38 vs. 4.06 ± 2.19, p = 0.008). There was no significant difference in respiratory rate (p > 0.05).Conclusion: A neutral trunk is the best resting position, and deviations from a neutral trunk position can affect the cardiovascular and autonomic nervous systems, resulting in decreased stroke volume, increased heart rate, and relative activation of sympathetic tone.

Oxygen uptake (VO2) is an important parameter in sports medicine, health assessment and clinical treatment. At present, more and more wearable devices are used in daily life, clinical treatment and health care. The parameters obtained by wearables have great research potential and application prospect. In this paper, an instantaneous VO2 estimation model based on XGBoost was proposed and verified by using data obtained from a medical-grade wearable device (Beijing SensEcho) at different posture and activity levels. Furthermore, physiological characteristics extracted from single-lead electrocardiogram, thoracic and abdominal respiration signal and tri-axial acceleration signal were studied to optimize the model. There were 29 healthy volunteers recruited for the study to collect data while stationary (lying, sitting, standing), walking, Bruce treadmill test and recuperating with SensEcho and the gas analyzer (Metalyzer 3B). The results show that the VO2 values estimated by the proposed model are in good agreement with the true values measured by the gas analyzer (R2 = 0.94 ± 0.03, n = 72,235), and the mean absolute error (MAE) is 1.83 ± 0.59 ml/kg/min. Compared with the estimation method using a separate heart rate as input, our method reduced MAE by 54.70%. At the same time, other factors affecting the performance of the model were studied, including the influence of different input signals, gender and movement intensity, which provided more enlightenment for the estimation of VO2. The results show that the proposed model based on cardio-pulmonary physiological signals as inputs can effectively improve the accuracy of instantaneous VO2 estimation in various scenarios of activities and was robust between different motion modes and state. The VO2 estimation method proposed in this paper has the potential to be used in daily life covering the scenario of stationary, walking and maximal exercise.

Abstract Background Previous studies have shown that changes in intestinal microfloras are associated with both gastrointestinal (GI) and non-GI tumors. It is not clear whether there is an association between GI microflora changes and hematological malignancies. Methods In the current study, we used 16S rDNA gene sequencing techniques to profile the GI microbiome in children with lymphoblastic leukemia (ALL, n = 18) and matched healthy control (n = 18). Using multiple specialized software [Heatmap, Principal coordinates analysis (PCoA), Claster and Metastates], we analyzed the sequencing data for microfloral species classification, abundance and diversity. Results A total of 27 genera between the ALL and control groups (FDR ≤ 0.05 and/or P ≤ 0.05) showed significantly different abundance between ALL patients and healthy controls: 12 of them were predominant in healthy group and other 15 species were significantly higher in ALL group. In addition, we compared the abundance and diversity of microfloral species in ALL patients prior to and during remission stage after chemotherapy, and no significant difference was detected. Conclusions Compared to healthy controls, ALL patient showed significant changes of GI microfloras. Further explorations of the intestinal micro-ecology in ALL patients may provide important information to understand relationship between microfloras and ALL.

Background: Curcumin is a major active ingredient extracted from powdered dry rhizome of Curcuma longa. In Ayurveda and traditional Chinese medicine, it has been used as a hepatoprotective agent for centuries. However, the underlying mechanisms are not clear. Objective: The present study is to investigate the hepatoprotective effects of curcumin in chronic alcohol-induced liver injury and explore its mechanism. Design: Alcohol-exposed Balb/c mice were treated with curcumin (75 and 150 mg/kg) once per day for 8 weeks. Tissue from individual was fixed with formaldehyde for pathological examination. The activities of mitochondrial antioxidant enzymes, Na+/k+-ATPase, Ca2+-ATPase, and Ca2+Mg2+-ATPase, were determined. The level of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (MPTP) opening was also determined. The expression of PGC-1α, NRF1, Mn-SOD, GRP78, PERK, IRE1α, nuclear NF-κB, and phosphorylated IκBα was quantified by western blot. The contents of TNF-α, IL-1β, and IL-6 in the liver were measured using the ELISA method. Results: Curcumin significantly promoted hepatic mitochondrial function by reducing the opening of MPTP, thus increasing the MMP, promoting the activity of Na+/k+-ATPase, Ca2+-ATPase, and Ca2+/Mg2+-ATPase, and attenuating oxidative stress. Curcumin upregulated the expression of PGC-1α, NRF1, and Mn-SOD, and downregulated the expression of GRP78, PERK, and IRE1α in hepatic tissue. Curcumin also attenuated inflammation by inhibiting the IκBα–NF-κB pathway, which reduced the production of TNF, IL-1β, and IL-6. Conclusion: Curcumin attenuates alcohol-induced liver injury via improving mitochondrial function and attenuating endoplasmic reticulum stress and inflammation. This study provides strong evidence for the beneficial effects of curcumin in the treatment of chronic alcohol-induced liver injury.

Cigarette smoke is a major preventable risk factor of ischemic stroke. Cigarette smoke induces a significant increase in circulating leukocytes. However, it remains unclear to what extent and by what mechanisms smoke priming influences stroke severity. Here we report that exposure to cigarette smoke exacerbated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion (MCAO). The augmentation of neurodeficits and brain infarction was accompanied by increased production of pro-inflammatory factors and brain infiltration of neutrophils and monocytes. Prior to brain ischemia, exposure to cigarette smoke induced mobilization of peripheral neutrophils, and monocytes. Furthermore, the detrimental effects of smoke priming on ischemic brain injury were abolished either by pharmacological inhibition of the recruitment of neutrophils and monocytes or by blockade of the NLRP3 inflammasome, an effector protein of neutrophils and monocytes. Our findings suggest that cigarette smoke-induced mobilization of peripheral neutrophils and monocytes augments ischemic brain injury.

Accumulating evidence has shown that preeclampsia (PE) was associated with an aberrant maternal-fetal inflammatory response. In the present study, we first found that in human PE placentas levels of toll-like receptor 4 (TLR4), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and inflammatory cytokines IL-6 and MCP-1 were significantly upregulated. Next, we demonstrated a notable increase in systolic blood pressure (SBP) and proteinuria in lipopolysaccharide (LPS)-treated pregnant rats and concomitant high levels of TLR4 and p-p38 in these PE-like rat placentas, which led to aberrant overexpression of both IL-6 and MCP-1, as well as deficient trophoblast invasion and spiral artery (SA) remodeling, and these abnormalities were ameliorated by SB203580, a reported inhibitor of p38. In vitro we further confirmed that LPS triggered the activation of TLR4/p38 signaling pathway, which promoted trophoblast apoptosis and damaged trophoblastic invasion via downstream effectors IL-6 and MCP-1; these mutations were rectified by silencing this signaling pathway. These findings elaborated potential mechanisms that aberrant TLR4/p38 signaling might contribute to PE and LPS-induced PE-like symptom by damaging trophoblast invasion and SA remodeling via activating inflammatory cytokines including IL-6 and MCP-1.

Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs). Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down-regulated the expression of β-catenin in HTR-8/SVneo cells, demonstrating that β-catenin is a downstream effector of Rac1 in trophoblast invasion. Conclusion: Our data suggest that Rac1-mediated activation of β-catenin might regulate Snail and MMP9 expression subsequently promoting trophoblast invasion in pregnancy.