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Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1. Results: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG. Conclusion: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.

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Hydrogel, as a promising material for a wide range of applications, has demonstrated considerable potential for use in flexible wearable devices and engineering technologies. However, simultaneously realizing the ultrastretchability, low hysteresis, and high toughness of hydrogels is still a great challenge. Here, we present a dual physically cross-linked polyacrylamide (PAM)/sodium hyaluronate (HA)/montmorillonite (MMT) hydrogel. The introduction of HA increases the degree of chain entanglement, and the addition of MMT acts as a stress dissipation center and cross-linking agent, resulting in a hydrogel with high toughness and low hysteretic properties. This hydrogel synthesized by a simple strategy exhibited ultrahigh stretchability (3165%), high breaking stress (228 kPa), high toughness (4.149 MJ/m3), and ultralow hysteresis (≈2% at 100% of strain). The fabricated hydrogel flexible strain sensors possessed fast response and recovery times (62.5:75 ms), a wide strain detection range (2000%), a strain detection limit of 1%, and excellent cycling stability over 500 cycles. Furthermore, the hydrogel flexible strain sensor can be used for human motion monitoring, gesture recognition, and pressure recognition assisted by deep learning algorithms, showing enormous promise for applications.

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BACKGROUND: Magnolol (MAG) exhibits hepatoprotective activity, however, whether and how MAG regulates the gut microbiota to alleviate fatty liver hemorrhagic syndrome (FLHS) remains unclear. Therefore, we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis. We randomly divided 540 56-week-old Hy-line white laying hens with FLSH into 4 groups. The birds were fed a high-fat low-protein (HFLP) diet (CON) or HELP diets supplemented with 200, 400, and 600 mg/kg of MAG (M1, M2, and M3, respectively) for 9 weeks. RESULTS: Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism, improving intestinal barrier function, and shaping the gut microbiota and tryptophan metabolic profiles. Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees. The intestinal barrier function was improved by 200 and 400 mg/kg of MAG supplementation, as evidenced by the increased villus height and mRNA expression of tight junction related genes. Microbiological profile information revealed that MAG changed the gut microbiota, especially by elevating the abundances of Lactobacillus, Faecalibacterium, and Butyricicoccus. Moreover, non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites, which was positively correlated with the MAG-enriched gut microbiota. The increased tryptophan metabolites could activate aryl hydrocarbon receptor (AhR) and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in the liver. The fecal microbiota transplantation (FMT) experiments further confirmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites. CONCLUSIONS: Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism, improving the intestinal barrier function, and relieving hepatic inflammation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk. These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.

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Nonylphenol (NP) is a ubiquitous endocrine disruptor that persists in the environment and can significantly contribute to serious health hazards, particularly intestinal barrier injury. Plant essential oils (EOs) have recently gained widespread interest due to their potential for improving intestinal health. However, the precise mechanism and protective effects of EOs ameliorating the intestinal damages induced by NP exposure remain unclear. To clarify the potential mechanism and protective impact of EOs against intestinal injury induced by NP, a total of 144 one-day-old male ducks were randomly allocated to four groups: CON (basal diet), EO (basal diet + 200 mg/kg EOs), NP (basal diet + 40 mg/kg NP), and NPEO (basal diet + 200 mg/kg EOs + 40 mg/kg NP). The data revealed that NP exposure significantly damaged intestinal barrier, as evidenced by a reduction in the levels of tight junction gene expression and an increase in intestinal permeability. Additionally, it disturbed gut microbiota, as well as interfered with tryptophan (Trp) metabolism. The NP-induced disorder of Trp metabolism restrained the activation of aryl hydrocarbon receptor (AhR) and resulted in decreased the expression levels of CYP1A1, IL-22, and STAT3 genes, which were alleviated after treatment with EOs. Taken together, NP exposure resulted in impairment of the intestinal barrier function, disruption of gut microbiota, and disturbances in Trp metabolism. Dietary EOs supplementation alleviated the intestinal barrier injury induced by NP through the Trp/AhR/IL-22 signaling pathway.

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Polysaccharides extracted from Hericium erinaceus (HEP) exhibit hepatoprotective activity in the alleviation of non-alcoholic fatty liver disease (NAFLD); however, the mechanisms underlying whether and how HEP regulation of the gut microbiota to alleviate liver-associated metabolic disorders are not well understood. This study used an aged laying hen model to explore the mechanisms through which HEP alleviates NAFLD, with a focus on regulatory function of HEP in the gut microbiome. The results showed that HEP ameliorated hepatic damage and metabolic disorders by improving intestinal barrier function and shaping the gut microbiota and tryptophan metabolic profiles. HEP increased the abundance of Lactobacillus and certain tryptophan metabolites, including indole-3-carboxylic acid, kynurenic acid, and tryptamine in the cecum. These metabolites upregulated the expression of ZO-1 and Occludin by activating the AhR and restoring the intestinal barrier integrity. The increased intestinal barrier functions decreased LPS transferring from the intestine to the liver, inhibited hepatic LPS/TLR4/MyD88/NF-κB pathway activation, and reduced hepatic inflammatory response and apoptosis. Fecal microbiota transplantation experiments further confirmed that the hepatoprotective effect is likely mediated by HEP-altered gut microbiota and their metabolites. Overall, dietary HEP could ameliorate the hepatic damage and metabolic disorders of NAFLD through regulating the "gut-liver" axis.

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Little information is available on the effect of Hericium erinaceus polysaccharides (HEP) on laying hens, especially on improving liver and ovarian health and function. Therefore, this study was conducted to investigate the impacts of HEP on liver and ovarian function to delay the decline in the laying performance of aged hens. A total of 360 fifty-eight-wk-old laying hens were randomly allocated to 4 treatments, with 6 replicates of 15 birds each. After 2 wk of adaptation, the birds were fed basal diet (CON) or basal diets supplemented with 250, 500, and 750 mg/kg of HEP (HEP250, HEP500, and HEP 750, respectively) for 12 wk. The results showed that, compared with CON, hens fed HEP had significantly increased laying performance (P < 0.05) and promoted follicle development, as evidenced by the increased numbers of hierarchical follicles, small follicles, and total follicles (P < 0.05). Birds fed 500 mg/kg of HEP improved the liver function by increasing T-AOC activity (P < 0.05) and decreasing hepatic oxidative stress and inflammatory responses (inflammatory cell infiltration) caused by aging. The lipid metabolism was improved, and yolk precursor synthesis was promoted in the liver of HEP-treated laying hens by upregulating the mRNA expression of FAS, MTTP, PPAR-α, APOVLDL-Ⅱ, and VTG-Ⅱ (P < 0.05). In addition, HEP significantly decreased ovarian inflammation by regulating the mRNA levels of NF-κB, IL-1ß, IL-6, and TNF-α (P < 0.05). As a result, the contents of E2, LH, and FSH in serum and the gene expression of ERα of the liver and FSHR of the ovary increased in HEP-treated hens (P < 0.05). In conclusion, dietary HEP supplementation exhibited potential hepatic and ovarian protective effects, thereby increasing the laying performance of aged hens by enhancing reproductive hormone secretion hormone secretion and promoting yolk precursor synthesis and follicle development via the liver-blood-ovary axis. The optimal supplementation level of HEP in aged hens was 500 mg/kg.

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Pain is a complex experience that remains largely unexplored in naturalistic contexts, hindering our understanding of its neurobehavioral representation in ecologically valid settings. To address this, we employed a multimodal, data-driven approach integrating intracranial electroencephalography, pain self-reports, and facial expression quantification to characterize the neural and behavioral correlates of naturalistic acute pain in twelve epilepsy patients undergoing continuous monitoring with neural and audiovisual recordings. High self-reported pain states were associated with elevated blood pressure, increased pain medication use, and distinct facial muscle activations. Using machine learning, we successfully decoded individual participants' high versus low self-reported pain states from distributed neural activity patterns (mean AUC = 0.70), involving mesolimbic regions, striatum, and temporoparietal cortex. High self-reported pain states exhibited increased low-frequency activity in temporoparietal areas and decreased high-frequency activity in mesolimbic regions (hippocampus, cingulate, and orbitofrontal cortex) compared to low pain states. This neural pain representation remained stable for hours and was modulated by pain onset and relief. Objective facial expression changes also classified self-reported pain states, with results concordant with electrophysiological predictions. Importantly, we identified transient periods of momentary pain as a distinct naturalistic acute pain measure, which could be reliably differentiated from affect-neutral periods using intracranial and facial features, albeit with neural and facial patterns distinct from self-reported pain. These findings reveal reliable neurobehavioral markers of naturalistic acute pain across contexts and timescales, underscoring the potential for developing personalized pain interventions in real-world settings.

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Poaceae members shared a whole-genome duplication called rho. However, little is known about the evolutionary pattern of the rho-derived duplicates among Poaceae lineages and implications in adaptive evolution. Here we present phylogenomic/phylotranscriptomic analyses of 363 grasses covering all 12 subfamilies and report nine previously unknown whole-genome duplications. Furthermore, duplications from a single whole-genome duplication were mapped to multiple nodes on the species phylogeny; a whole-genome duplication was likely shared by woody bamboos with possible gene flow from herbaceous bamboos; and recent paralogues of a tetraploid Oryza are implicated in tolerance of seawater submergence. Moreover, rho duplicates showing differential retention among subfamilies include those with functions in environmental adaptations or morphogenesis, including ACOT for aquatic environments (Oryzoideae), CK2ß for cold responses (Pooideae), SPIRAL1 for rapid cell elongation (Bambusoideae), and PAI1 for drought/cold responses (Panicoideae). This study presents a Poaceae whole-genome duplication profile with evidence for multiple evolutionary mechanisms that contribute to gene retention and losses.

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Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T-cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore -specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV-specific T cells. In line with Taiwanese dominant HLA-alleles, we also evaluated ex vivo HBVcore -specific T cells by pMHC-tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD-1. Our parallel study showed HBV-specific CD8 T cells were more activated with greater PD-1 expression than CMV-specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD-1 fluctuation pattern of HBVcore -specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen-mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD-1 levels of HBVcore -specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.

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Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.

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Source mask optimization (SMO) is a widely used computational lithography technique for compensating lithographic distortion. However, line-end shortening is still a key factor that cannot be easily corrected and affects the image fidelity of lithography at advanced nodes. This paper proposes a source mask optimization method that suppresses line-end shortening and improves lithography fidelity. An adaptive hybrid weight method is employed to increase the weights of the line end during the optimization, which adaptively updates the weights in each iteration according to the edge placement error (EPE). A cost function containing a penalty term based on the normalized image log slope (NILS) is established to ensure the fidelity of the overall feature when paying more attention to the line-end region. The scope of this penalty term is regulated by widening and extending the split contour to further reduce the line-end shortening. Simulation results show that the proposed method can effectively suppress the line-end shortening and improve the lithography fidelity compared with the traditional SMO method.

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Implantable electrodes have raised great interest over the last years with the increasing incidence of neurodegenerative disorders. For brain implant devices, some key factors resulting in the formation of glial scars, such as mechanical mismatch and acute injury-induced inflammation, should be considered for material design. Therefore, in this study, a new biocompatible flexible electrode (e-SgG) with arbitrary shapes on a positive electrode was developed via electrogelation by applying a direct electrical voltage on a silk fibroin/gelatin/reduced graphene oxide composite hydrogel. The implantable flexible e-SgG-2 film with 1.23% rGO content showed high Young's modulus (11-150 MPa), which was sufficient for penetration under dried conditions but subsequently became a biomimetic brain tissue with low Young's modulus (50-3200 kPa) after insertion in the brain. At the same time, an anti-inflammatory drug (DEX) incorporated into the e-SgG-2 film can be electrically stimulated to exhibit two-stage release to overcome tissue inflammation during cyclic voltammetry via degradation by applying an AC field. The results of cell response to the SF/gelatin/rGO/DEX composite film showed that the released DEX could interrupt astrocyte growth to reduce the inflammatory response but showed non-toxicity toward neurons, which demonstrated a great potential for the application of the biocompatible and degradable e-SgG-D electrodes in the improvement of nerve tissue repair.

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OBJECTIVE: A brain-computer interface (BCI) can be used to translate neuronal activity into commands to control external devices. However, using noninvasive BCI to control a robotic arm for movements in three-dimensional (3D) environments and accomplish complicated daily tasks, such as grasping and drinking, remains a challenge. APPROACH: In this study, a shared robotic arm control system based on hybrid asynchronous BCI and computer vision was presented. The BCI model, which combines steady-state visual evoked potentials (SSVEPs) and blink-related electrooculography (EOG) signals, allows users to freely choose from fifteen commands in an asynchronous mode corresponding to robot actions in a 3D workspace and reach targets with a wide movement range, while computer vision can identify objects and assist a robotic arm in completing more precise tasks, such as grasping a target automatically. RESULTS: Ten subjects participated in the experiments and achieved an average accuracy of more than 92% and a high trajectory efficiency for robot movement. All subjects were able to perform the reach-grasp-drink tasks successfully using the proposed shared control method, with fewer error commands and shorter completion time than with direct BCI control. SIGNIFICANCE: Our results demonstrated the feasibility and efficiency of generating practical multidimensional control of an intuitive robotic arm by merging hybrid asynchronous BCI and computer vision-based recognition.

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BACKGROUND: Approximately 10-40% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI). METHODS: The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib/RT/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM). RESULTS: At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib/RT/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% (p < 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib/RT/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM (p < 0.001) in patients who received multiple therapeutic modalities. CONCLUSION: Multimodality therapy with sorafenib/RT/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials.

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Extreme climate events constitute a major risk to global food production. Among these, extreme rainfall is often dismissed from historical analyses and future projections, the impacts and mechanisms of which remain poorly understood. Here we used long-term nationwide observations and multi-level rainfall manipulative experiments to explore the magnitude and mechanisms of extreme rainfall impacts on rice yield in China. We find that rice yield reductions due to extreme rainfall were comparable to those induced by extreme heat over the last two decades, reaching 7.6 ± 0.9% (one standard error) according to nationwide observations and 8.1 ± 1.1% according to the crop model incorporating the mechanisms revealed from manipulative experiments. Extreme rainfall reduces rice yield mainly by limiting nitrogen availability for tillering that lowers per-area effective panicles and by exerting physical disturbance on pollination that declines per-panicle filled grains. Considering these mechanisms, we projected ~8% additional yield reduction due to extreme rainfall under warmer climate by the end of the century. These findings demonstrate that it is critical to account for extreme rainfall in food security assessments.

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The preparation of diimidazolium salt HBDIM 1, a precursor for a di-NHCs ligand, from cheap and easily available agent hexabenzylhexaazaisowurtzitane (HBIW) is reported. Under basic conditions, HBDIM undergoes facile deprotonation to in situ generate CageCarbene, which could efficiently coordinate to transition-metals, such as, Au, Cu or Pd, to give the corresponding bimetallic complexes 2-4. These complexes were isolated and fully characterized, including X-ray diffraction of their single crystals. It was found that the steric hinderance of CageCarbene is similar to that of SIMes but smaller than that of IPr, and electronically, CageCarbene is a strong σ-donator similar to SIMes and a stronger σ-donator than IPr. Further studies showed that complexes 2-4 were highly reactive to catalyze up to 17 reactions. Control experiments utilizing a N-benzyl-substituted monoimidazolium salt showed much lower catalytic reactivity when it was bound to Au or Cu, but exhibited similar reactivity for the Pd complex. Kinetic studies showed that the low reactivity of the monodentate carbene-ligated Au or Cu complex was due to the low stability of the complex under the reaction conditions.

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1-Aryl-substituted bicyclo[1.1.1]pentanes (BCPs) are an important class of BCP derivatives with widespread application in drug development. Most syntheses of these materials require multiple chemical steps via BCP electrophiles or nucleophiles derived from [1.1.1]propellane. Although one-step, multicomponent radical cross-coupling reactions could provide a more sustainable and rapid route to access diverse heteroarylated BCPs, current approaches are limited to tertiary alkyl radicals, leading to a decrease in their practical value. In this study, a conceptually different approach enabled by a radical multicomponent heteroarylation of [1.1.1]propellane to access functionalized heteroarylated BCPs is described. Importantly, this protocol is compatible with primary-, secondary-, and tertiary aliphatic radicals, as well as various fluoroalkyl radical sources, thus enabling rapid library generation of sought-after BCP derivatives for drug development.

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A brain-computer interface (BCI) measures and analyzes brain activity and converts it into computer commands to control external devices. Traditional BCIs usually require full calibration, which is time-consuming and makes BCI systems inconvenient to use. In this study, we propose an online P300 BCI spelling system with zero or shortened calibration based on a convolutional neural network (CNN) and big electroencephalography (EEG) data. Specifically, three methods are proposed to train CNNs for the online detection of P300 potentials: (i) training a subject-independent CNN with data collected from 150 subjects; (ii) adapting the CNN online via a semisupervised learning/self-training method based on unlabeled data collected during the user's online operation; and (iii) fine-tuning the CNN with a transfer learning method based on a small quantity of labeled data collected before the user's online operation. Note that the calibration process is eliminated in the first two methods and dramatically shortened in the third method. Based on these methods, an online P300 spelling system is developed. Twenty subjects participated in our online experiments. Average accuracies of 89.38%, 94.00% and 93.50% were obtained by the subject-independent CNN, the self-training-based CNN and the transfer learning-based CNN, respectively. These results demonstrate the effectiveness of our methods, and thus, the convenience of the online P300-based BCI system is substantially improved.

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