Research Progress on the Correlation Between Hypertension and Gut Microbiota.

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.

Graded decisions in the human brain.

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior.

FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage.

Nasal septal cartilages (NSCs) and mandibular condyle cartilages (MCCs) are two important cartilages for craniomaxillofacial development. However, the role of FLRT2 in the formation of NSCs and MCCs remains undiscovered. NSCs and MCCs were used for immunocytochemistry staining of collagen II, toluidine blue staining, and alcian blue staining. Quantitative reverse transcription­PCR and western blot were used to detect mRNA and protein expressions of FLRT2, N-cadherin, collagen II, aggrecan, and SOX9. Cell proliferation of MCCs and NSCs was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell counting kit­8 assay. Cell migration of MCCs and NSCs was examined by wound healing assay and Transwell. Chondrogenesis of MCCs and NSCs were similar in morphological characteristics, while different in cell proliferation, migration, and extracellular matrix. FLRT2 promotes the proliferation and migration of NSCs. There were up-regulation of N-cadherin and down-regulation of collagen II, aggrecan, and SOX9 in NSC with knock down FLRT2. The current study, as demonstrated by Xie et al., reveals that FLRT2 overexpression in Sprague-Dawley neonatal rats promotes the proliferation and migration of NSCs and MCCs, decreases N-cadherin while increases collagen II, aggrecan, and SOX9 in NSC and MCCs. Altogether, FLRT2 mediates chondrogenesis of NSCs and MCCs.

Comparative transcriptome analysis identifies candidate genes related to sucrose accumulation in longan (Dimocarpus longan Lour.) pulp.

Sucrose content is one of the important factors to determine longan fruit flavor quality. To gain deep insight of molecular mechanism on sucrose accumulation in longan, we conducted comparative transcriptomic analysis between low sucrose content longan cultivar 'Qingkebaoyuan' and high sucrose content cultivar 'Songfengben'. A total of 12,350 unique differentially expressed genes (DEGs) were detected across various development stages and different varieties, including hexokinase (HK) and sucrose-phosphate synthase (SPS), which are intricately linked to soluble sugar accumulation and metabolism. Weighted gene co-expression network analysis (WGCNA) identified magenta module, including DlSPS gene, was significantly positively correlated with sucrose content. Furthermore, transient expression unveiled DlSPS gene play crucial role in sucrose accumulation. Moreover, 5 transcription factors (MYB, ERF, bHLH, C2H2, and NAC) were potentially involved in DlSPS regulation. Our findings provide clues for sucrose metabolism, and lay the foundation for longan breeding in the future.

GPR65 sensing tumor-derived lactate induces HMGB1 release from TAM via the cAMP/PKA/CREB pathway to promote glioma progression.

BACKGROUND: Lactate has emerged as a critical regulator within the tumor microenvironment, including glioma. However, the precise mechanisms underlying how lactate influences the communication between tumor cells and tumor-associated macrophages (TAMs), the most abundant immune cells in glioma, remain poorly understood. This study aims to elucidate the impact of tumor-derived lactate on TAMs and investigate the regulatory pathways governing TAM-mediated tumor-promotion in glioma. METHODS: Bioinformatic analysis was conducted using datasets from TCGA and CGGA. Single-cell RNA-seq datasets were analyzed by using UCSC Cell Browser and Single Cell Portal. Cell proliferation and mobility were evaluated through CCK8, colony formation, wound healing, and transwell assays. Western blot and immunofluorescence staining were applied to assess protein expression and cell distribution. RT-PCR and ELISA were employed to identify the potential secretory factors. Mechanistic pathways were explored by western blotting, ELISA, shRNA knockdown, and specific inhibitors and activators. The effects of pathway blockades were further assessed using subcutaneous and intracranial xenograft tumor models in vivo. RESULTS: Elevated expressions of LDHA and MCT1 were observed in glioma and exhibited a positive correlation with M2-type TAM infiltration. Lactate derived from glioma cells induced TAMs towards M2-subtype polarization, subsequently promoting glioma cells proliferation, migration, invasion, and mesenchymal transition. GPR65, highly expressed on TAMs, sensed lactate-stimulation in the TME, fueling glioma cells malignant progression through the secretion of HMGB1. GPR65 on TAMs triggered HMGB1 release in response to lactate stimulation via the cAMP/PKA/CREB signaling pathway. Disrupting this feedback loop by GPR65-knockdown or HMGB1 inhibition mitigated glioma progression in vivo. CONCLUSION: These findings unveil the intricate interplay between TAMs and tumor cells mediated by lactate and HMGB1, driving tumor progression in glioma. GPR65, selectively highly expressed on TAMs in glioma, sensed lactate stimulation and fostered HMGB1 secretion via the cAMP/PKA/CREB signaling pathway. Blocking this feedback loop presents a promising therapeutic strategy for GBM.

Elevated serum irisin levels in boys with central precocious puberty independent of BMI.

INTRODUCTION: Central precocious puberty (CPP) is a prevalent endocrine disorder. Research has indicated that pubertal development is linked to nutritional metabolism. Irisin, a novel myokine/adipokine, has been identified as a potential predictor of CPP in girls. This study aims to examine the relationship between serum irisin levels and CPP in boys. MATERIAL AND METHODS: An enzyme-linked immunosorbent assay (ELISA) was used to measure serum irisin levels in 32 boys diagnosed with CPP and 33 prepubertal age-matched boys as normal controls (NC). To assess the impact of body mass index (BMI) on irisin levels, both the CPP and NC groups were divided into overweight/obese and normal-weight subgroups. Spearman correlation analysis was employed to assess the connection between irisin and clinical and biochemical parameters. Additionally, a receiver operating characteristic curve was utilised to determine the optimal threshold value for irisin. RESULTS: In the normal-weight subgroups, boys with CPP exhibited elevated irisin levels compared to controls, but not in the overweight/obese subgroups. The optimal cut-off value for irisin levels to predict CPP in the normal-weight groups was 93.09 ng/mL, yielding a sensitivity of 47.6% and a specificity of 100%. Furthermore, a positive correlation was noted between irisin levels and bone age (BA), bone age advancement (BA-CA), and BMI. CONCLUSIONS: Serum irisin levels correlate with BMI and pubertal development. Given its limited sensitivity, irisin level can only be utilised as a supplementary rather than a standalone diagnostic indicator for CPP.

Inducing spin polarization via Co doping in the BiVO4 cell to enhance the built-in electric field for promotion of photocatalytic CO2 reduction.

The efficiency of CO2 photocatalytic reduction is severely limited by inefficient separation and sluggish transfer. In this study, spin polarization was induced and built-in electric field was strengthened via Co doping in the BiVO4 cell to boost photocatalytic CO2 reduction. Results showed that owing to the generation of spin-polarized electrons upon Co doping, carrier separation and photocurrent production of the Co-doped BiVO4 were enhanced. CO production during CO2 photocatalytic reduction from the Co-BiVO4 was 61.6 times of the BiVO4. Notably, application of an external magnetic field (100 mT) further boosted photocatalytic CO2 reduction from the Co-BiVO4, with 68.25 folds improvement of CO production compared to pristine BiVO4. The existence of a built-in electric field (IEF) was demonstrated through density functional theory (DFT) simulations and kelvin probe force microscopy (KPFM). Mechanism insights could be elucidated as follows: doping of magnetic Co into the BiVO4 resulted in increased the number of spin-polarized photo-excited carriers, and application of a magnetic field led to an augmentation of intrinsic electric field due to a dipole shift, thereby extending carrier lifetime and suppressing charges recombination. Additionally, HCOO- was a crucial intermediate in the process of CO2RR, and possible pathways for CO2 reduction were proposed. This study highlights the significance of built-in electric fields and the important role of spin polarization for promotion of photocatalytic CO2 reduction.

Transarterial chemoembolization with molecular targeted therapies plus camrelizumab for recurrent hepatocellular carcinoma.

BACKGROUND: The safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC. METHODS: A total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs). RESULTS: TACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3-4 adverse events. CONCLUSIONS: A combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.

PSE-Net: Channel pruning for Convolutional Neural Networks with parallel-subnets estimator.

Channel Pruning is one of the most widespread techniques used to compress deep neural networks while maintaining their performances. Currently, a typical pruning algorithm leverages neural architecture search to directly find networks with a configurable width, the key step of which is to identify representative subnet for various pruning ratios by training a supernet. However, current methods mainly follow a serial training strategy to optimize supernet, which is very time-consuming. In this work, we introduce PSE-Net, a novel parallel-subnets estimator for efficient channel pruning. Specifically, we propose a parallel-subnets training algorithm that simulate the forward-backward pass of multiple subnets by droping extraneous features on batch dimension, thus various subnets could be trained in one round. Our proposed algorithm facilitates the efficiency of supernet training and equips the network with the ability to interpolate the accuracy of unsampled subnets, enabling PSE-Net to effectively evaluate and rank the subnets. Over the trained supernet, we develop a prior-distributed-based sampling algorithm to boost the performance of classical evolutionary search. Such algorithm utilizes the prior information of supernet training phase to assist in the search of optimal subnets while tackling the challenge of discovering samples that satisfy resource constraints due to the long-tail distribution of network configuration. Extensive experiments demonstrate PSE-Net outperforms previous state-of-the-art channel pruning methods on the ImageNet dataset while retaining superior supernet training efficiency. For example, under 300M FLOPs constraint, our pruned MobileNetV2 achieves 75.2% Top-1 accuracy on ImageNet dataset, exceeding the original MobileNetV2 by 2.6 units while only cost 30%/16% times than BCNet/AutoAlim.

Vitexin enhances radiosensitivity of mouse subcutaneous xenograft glioma by affecting the miR-17-5p/miR-130b-3p/PTEN/HIF-1α pathway.

PURPOSE: Vitexin can cooperate with hyperbaric oxygen to sensitize the radiotherapy of glioma by inhibiting the hypoxia-inducible factor (HIF)-1α. However, whether vitexin has a direct radiosensitization and how it affects the HIF-1α expression remain unclear. This study investigated these issues. METHODS: The SU3 cells-inoculated nude mice were divided into control, radiation, and vitexin + radiation groups. The vitexin + radiation-treated mice were intraperitoneally injected with 75 mg/kg vitexin daily for 21 days. On the 3rd, 10th, and 17th days during the vitexin treatment, the radiation-treated mice were locally irradiated with 10 Gy, respectively. In vitro, the microRNA (miR)-17-5p or miR-130b-3p mimics-transfected SU3 cells were used to examine the effects of vitexin plus radiation on expression of miR-17-5p- or miR-130b-3p-induced radioresistance-related pathway proteins. The effects of vitexin on miR-17-5p and miR-130b-3p expression in SU3 cells were also evaluated. RESULTS: Compared with the radiation group, the tumor volume, tumor weight, and expression of HIF-1α, vascular endothelial growth factor, and glucose transporter-1/3 proteins, miR-17-5p, and miR-130b-3p in tumor tissues in the vitexin + radiation group decreased, whereas the expression of phosphatase and tensin homolog (PTEN) protein increased. After treatment of miR-17-5p or miR-130b-3p mimics-transfected SU3 cells with vitexin plus radiation, the PTEN protein expression also increased, the HIF-1α protein expression decreased correspondingly. Moreover, vitexin decreased the miR-17-5p and miR-130b-3p expression in SU3 cells. CONCLUSION: Vitexin can enhance the radiosensitivity of glioma, and its mechanism may partly be related to the attenuation of HIF-1α pathway after lowering the inhibitory effect of miR-17-5p and miR-130b-3p on PTEN.

Reprogramming Photoresponsive Liquid Crystalline Elastomer via Force-Directed Evaporation.

Incorporating photothermal agents into thermoresponsive liquid crystalline elastomers (LCEs) offers remote and spatio-temporal control in actuation. Typically, both the light responsiveness and actuation behaviors are fixed since the agent doping and mesogen alignment are conducted before network formation. Here, we report an approach that enables programming photoresponsive LCEs after synthesis via force-directed evaporation. Different photothermal agents can be doped or removed by swelling the fully cross-linked LCEs in a specific solution, achieving the introduction and erasing of the photoresponsiveness. Moreover, the network swelling deletes the registered alignment, which allows for redefining the molecular order via re-evaporating the solvent with force imposed. This "one stone, two birds" strategy paves the way to simultaneously program/reprogram the actuation mode and responsiveness of LCEs, even in a spatio-selective manner to achieve complex actuations. Our approach is expandable to three-dimensional (3D) printed LCEs to access geometrically sophisticated shape-changing.

In pursuit of feedback activation: New insights into redox-responsive hydropersulfide prodrug combating oxidative stress.

Redox-responsive hydropersulfide prodrugs are designed to enable a more controllable and efficient hydropersulfide (RSSH) supply and to thoroughly explore their biological and therapeutic applications in oxidative damage. To obtain novel activation patterns triggered by redox signaling, we focused on NAD(P)H: quinone acceptor oxidoreductase 1 (NQO1), a canonical antioxidant enzyme, and designed NQO1-activated RSSH prodrugs. We also performed a head-to-head comparison of two mainstream structural scaffolds with solid quantitative analysis of prodrugs, RSSH, and metabolic by-products by LC-MS/MS, confirming that the perthiocarbamate scaffold was more effective in intracellular prodrug uptake and RSSH production. The prodrug was highly potent in oxidative stress management against cisplatin-induced nephrotoxicity. Strikingly, this prodrug possessed potential feedback activation properties by which the delivered RSSH can further escalate the prodrug activation via NQO1 upregulation. Our strategy pushed RSSH prodrugs one step further in the pursuit of efficient release in biological matrices and improved druggability against oxidative stress.

Endoscopic Supracerebellar Infratentorial Transpineal Approach for Posterior-Medial Thalamic Lesions: Surgical Technique and Clinical Experience.

BACKGROUND AND OBJECTIVES: Accessing lesions in the posterior-medial thalamus can be challenging because of their deep location and intricate neurovascular anatomy. This study aims to describe the techniques and feasibility of the endoscopic supracerebellar infratentorial transpineal approach for treating posterior-medial thalamus lesions. METHODS: We reviewed and analyzed the clinical outcomes and endoscopic surgical experience of 11 patients with posterior-medial thalamic lesions. The first 4 cases used the endoscopic midline supracerebellar infratentorial transpineal approach, whereas the subsequent 7 cases used the endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach. All cases involved the upward transposition of the pineal gland to access the posterior-medial thalamus. The extent of resection and the endoscopic techniques were the main focus of analysis. Neurological examinations and MRI/computed tomography follow-up were conducted for 3-12 months after surgery. RESULTS: The pathology of the group included 6 gliomas, 1 cavernous malformation, 1 inflammation, 1 melanoma, and 2 hematomas. All 11 patients achieved gross total resection (6 patients, 54.5%) or subtotal resection (5 patients, 45.5%) with no new neurological deficits. Most patients (9 patients, 81.8%) experienced improvement in Karnofsky Performance Status after surgery. Postoperative hydrocephalus occurred in 2 patients (18.2%) and was relieved by endoscopic third ventriculostomy. CONCLUSION: The endoscopic supracerebellar infratentorial transpineal approach is an effective approach for removing posterior-medial thalamic lesions that require access through the third ventricle surfaces of the thalamus. The endoscopic contralateral paramedian supracerebellar infratentorial transpineal approach provides a more superior and lateral view of the posterior-medial thalamic lesions.

LncRNAs act as modulators of macrophages within the tumor microenvironment.

Long non-coding RNAs (lncRNAs) have been established as pivotal players in various cellular processes, encompassing the regulation of transcription, translation, post-translational modulation of proteins, thereby influencing cellular functions. Notably, lncRNAs exert a regulatory influence on diverse biological processes, particularly in the context of tumor development. Tumor-associated macrophages (TAMs) exhibit the M2 phenotype, exerting significant impact on crucial processes such as tumor initiation, angiogenesis, metastasis, and immune evasion. Elevated infiltration of TAMs into the tumor microenvironment (TME) is closely associated with a poor prognosis in various cancers. LncRNAs within TAMs play a direct role in regulating cellular processes. Functioning as integral components of tumor-derived exosomes, lncRNAs prompt the M2-like polarization of macrophages. Concurrently, reports indicate that lncRNAs in tumor cells contribute to the expression and release of molecules that modulate TAMs within the TME. These actions of lncRNAs induce the recruitment, infiltration, and M2 polarization of TAMs, thereby providing critical support for tumor development. In this review, we survey recent studies elucidating the impact of lncRNAs on macrophage recruitment, polarization, and function across different types of cancers.

Genomic nursing science revealed the prolyl 4-hydroxylase subunit alpha 2 as a significant biomarker involved in osteosarcoma.

Backgrounds: This study aims to explore the clinical value of P4HA2 (prolyl 4-hydroxylase subunit alpha 2) in Osteosarcoma (OSC), and assess its potential to provide directions and clues for the practice of precision nursing. Methods: The GSE73166 and GSE16088 datasets were used to explore the P4HA2 expression in OSC. We then used the clinical data of patients obtaining from TARGET database to assess the prognostic value of P4HA2 in OSC. We also evaluated the predictive value of prognostic model based on P4HA2-related genes. Further, GSEA analysis was performed to explore related pathways. Results: The P4HA2 mRNA expression was higher in OSC than that in normal tissues and other bone cancer samples. Survival analysis found that P4HA2 high expression caused poor overall survival (OS) of patients with OSC and P4HA2 presented a favorable performance for predicting OS. Specifically, P4HA2 high expression statistically influenced the OS of patients with age≥15 years old and those with or without metastasis. Cox regression analysis indicated the independent prognostic value of P4HA2 in OSC, and nomogram analysis revealed its significant contribution to the survival probability of patients. We further established a prognostic model based on P4HA2-related genes, finding that prognostic model had a good prediction ability on OS. These results supported the clinical significance of P4HA2 in OSC. GSEA analysis suggested that P4HA2 was significantly related to the MAPK signaling pathway. In addition, P4HA2-associated natural killer cell-mediated cytotoxicity and T cell receptor signaling pathway were also predicted. Conclusions: This study revealed that P4HA2 can serve as an important prognostic biomarker for OSC patients, and it may become a promising therapeutic target in OSC treatment.

Discovery of Novel PD-L1 Small-Molecular Inhibitors with Potent In Vivo Anti-tumor Immune Activity.

Programmed death-ligand 1 (PD-L1) has surfaced as a promising therapeutic target for various cancers due to its pivotal role in facilitating tumor immune evasion. Herein, we report a series of novel small-molecule PD-L1 inhibitors exhibiting remarkable inhibitory activity against the PD-1/PD-L1 interaction (X18: IC50 = 1.3 nM) and reinstating the suppressive effect of PD-L1 on T cells (X18: EC50 = 152.8 nM). Crystallographic studies revealed the binding mode of X18 and PD-L1. Through a rational prodrug design approach, we have successfully optimized the oral pharmacokinetic properties of X22, effectively addressing the poor oral pharmacokinetic profile of PD-L1 small-molecule inhibitors. Notably, X22 demonstrated significant antitumor efficacy in murine models of MC38 and CT26 colon cancer through the upregulation of tumor infiltration and cytotoxicity of CD8+ T cells partially. These findings offer promising prospects for the advancement of PD-L1 inhibitors as innovative agents in cancer immunotherapy.

Multimodal Autonomous Locomotion of Liquid Crystal Elastomer Soft Robot.

Self-oscillation phenomena observed in nature serve as extraordinary inspiration for designing synthetic autonomous moving systems. Converting self-oscillation into designable self-sustained locomotion can lead to a new generation of soft robots that require minimal/no external control. However, such locomotion is typically constrained to a single mode dictated by the constant surrounding environment. In this study, a liquid crystal elastomer (LCE) robot capable of achieving self-sustained multimodal locomotion, with the specific motion mode being controlled via substrate adhesion or remote light stimulation is presented. Specifically, the LCE is mechanically trained to undergo repeated snapping actions to ensure its self-sustained rolling motion in a constant gradient thermal field atop a hotplate. By further fine-tuning the substrate adhesion, the LCE robot exhibits reversible transitions between rolling and jumping modes. In addition, the rolling motion can be manipulated in real time through light stimulation to perform other diverse motions including turning, decelerating, stopping, backing up, and steering around complex obstacles. The principle of introducing an on-demand gate control offers a new venue for designing future autonomous soft robots.

Altering Spin Distribution of Tb2Pc3 via Molecular Chirality Manipulation.

Manipulating the chirality of the spin-polarized electronic state is pivotal for understanding many unusual quantum spin phenomena, but it has not been achieved at the single-molecule level. Here, using scanning tunneling microscopy and spectroscopy (STM/STS), we successfully manipulate the chirality of spin distribution in a triple-decker single-molecule magnet tris(phthalocyaninato)bis(terbium(III)) (Tb2Pc3), which is evaporated on a Pb(111) substrate via molecular beam epitaxy. The otherwise achiral Tb2Pc3 becomes chiral after being embedded into the self-assembled monolayer films of bis(phthalocyaninato)terbium(III) (TbPc2). The chirality of the spin distribution in Tb2Pc3 is manifested via the spatial mapping of its Kondo resonance state from its ligand orbital. Our first-principles calculations revealed that the spin and molecular chirality are associated with a small rotation followed by a structural distortion of the top Pc, consistent with the experimental observation. By constructing tailored molecular clusters with the STM tip, a single Tb2Pc3 molecule can be manipulated among achiral and differently handed chiral configurations of spin distributions reversibly. This paves the way for designing chiral spin enantiomers for fundamental studies and developing functional spintronic devices.

A novel theta-controlled vibrotactile brain-computer interface to treat chronic pain: a pilot study.

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain.