Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

The 5-hydroxytryptamine 2A receptor (5-HT_2AR) is one of the key targets in the development of novel antidepressants. To develop new antidepressants targeting the 5-HT_2A receptor, this study established a high-throughput screening method for drugs targeting the 5-HT_2A receptor based on the principle of detecting calcium flux signals. The immunofluorescence assay and western blotting were employed to evaluate receptor expression levels in the 5-HT_2AR-CHO cell line. The reaction system parameters, including cell seeding density, DMSO concentration, and dye incubation time, were optimized with Z'-factor and signal window values as evaluation indicators. The specificity, precision, stability, and applicability of the method were assessed. Results indicated that the 5-HT_2AR-CHO cell line stably expressed high levels of the 5-HT_2A receptor. The optimized screening method involved a reaction system with 10 000 cells/well, 0.2% DMSO, and 2 h incubation with Calcium 6 dye. The method demonstrated excellent specificity, with inter-batch precision below 10% for the detection of 5-hydroxytryptamine (5-HT) at low, medium, and high concentrations. Testing four compounds that target the 5-HT_2A receptor- agonists 2,5-dimethoxy-4-iodoamphetamine (DOI), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), and lysergic acid diethylamide (LSD), along with the antagonist MDL100907-yielded Z'-factors (at EC₈₀) greater than 0.85 and signal window values over 0.91. The EC₅₀ values of these compounds were in the nanomolar range, and their potency rank order aligned with previously reported data, confirming the reliability of the established method. When being applied to the detection of 38 known active compounds, the method efficiently identified 5-HT_2A receptor agonists and antagonists while showing no response to non-target compounds. In conclusion, this study successfully constructs a high-throughput screening approach for 5-HT_2A receptor-targeting drugs based on calcium flux signals. The method possesses strong specificity, high sensitivity, and robust stability, being suitable for screening antidepressants targeting the 5-HT_2A receptor.
High-Throughput Screening Assays/methods* ; Receptor, Serotonin, 5-HT2A/metabolism* ; Animals ; CHO Cells ; Cricetulus ; Calcium Signaling/drug effects* ; Antidepressive Agents/pharmacology* ; Humans ; Serotonin 5-HT2 Receptor Antagonists/pharmacology* ; Calcium/metabolism*

Objective To study the clinical and electrophysiological characteristics about ictal facial dystonia of medial temporal lobe epilepsy.Method Data was collected from patients with mesial temporal lobe epilepsy originating from unilateral temporal lobe structures through preoperative evaluation at the Functional Neurology Department of the Second People's Hospital of Shenzhen between July 1,2019 and September 1,2023.All patients did not have seizures for at least 1 year after operation.The ictal symptoms of each patient were analyzed and the patients with ictal facial dystonia were selected and the clinical and electrophysiological characteristics of ictal facial dystonia were summarized.Results Nineteen of 47 patients diagnosed as mesial temporal lobe epilepsy had ictal facial dystonia,of which the electroencephalogram starting at the right side in 11 cases and at the left side in 8 cases.Fifteen patients had the symptom in the first 1/3 period of seizure.Fifteen patients had bilateral symmetrical muscle contraction.Thirteen patients showed with negative expression,5 with neutral expression,and 1 with negative or positive expression in different seizures.None of the patient had the drop of the corners of the mouth.Five patients underwent stereotactic-electroencephalogram(SEEG),including 3 patients with bilateral implantation and 2 patients with unilateral implantation.SEEG showed that the medial temporal structure,insula and orbital lobes were all involved in the onset of ictal facial dystonia.Conclusion The medial temporal lobe epilepsy often present ictal facial dystonia in the first 1/3 period of seizure,with bilaterally symmetrically facial contraction,often accompanied by negative expression,but without drop of the corners of the mouth.The lateralization value of ictal facial dystonia is limited and this symptom involves a wide brain network structure.

Humans ; Endovascular Aneurysm Repair ; Endovascular Procedures ; Blood Vessel Prosthesis Implantation ; Aortic Aneurysm, Abdominal/surgery* ; Treatment Outcome ; Postoperative Complications ; Risk Factors ; Aortic Rupture/surgery* ; Retrospective Studies

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Cryoablation (CRA) and microwave ablation (MWA) are two main local treatments for hepatocellular carcinoma (HCC). However, which one is more curative and suitable for combining with immunotherapy is still controversial. Herein, CRA induced higher tumoral PD-L1 expression and more T cells infiltration, but less PD-L1^highCD11b⁺ myeloid cells infiltration than MWA in HCC. Furthermore, CRA had better curative effect than MWA for anti-PD-L1 combination therapy in mouse models. Mechanistically, anti-PD-L1 antibody facilitated infiltration of CD8⁺ T cells by enhancing the secretion of CXCL9 from cDC1 cells after CRA therapy. On the other hand, anti-PD-L1 antibody promoted the infiltration of NK cells to eliminate PD-L1^highCD11b⁺ myeloid cells by antibody-dependent cell-mediated cytotoxicity (ADCC) effect after CRA therapy. Both aspects relieved the immunosuppressive microenvironment after CRA therapy. Notably, the wild-type PD-L1 Avelumab (Bavencio), compared to the mutant PD-L1 atezolizumab (Tecentriq), was better at inducing the ADCC effect to target PD-L1^highCD11b⁺ myeloid cells. Collectively, our study uncovered the novel insights that CRA showed superior curative effect than MWA in combining with anti-PD-L1 antibody by strengthening CTL/NK cell immune responses, which provided a strong rationale for combining CRA and PD-L1 blockade in the clinical treatment for HCC.

Objective To summarize the clinical,electrophysiological and imaging features of frontal opercular epilepsy.Methods A retrospective analysis was conducted on 5 cases with frontal opercular epilepsy,who were treated at the Department of Functional Neurology,Shenzhen Second People's Hospital from December 2020 to December 2022.Among these cases,4 cases were underwent stereotactic-EEG(SEEG)guided radiofrequency thermocoagulation.The clinical,electrophysiological,and imaging characteristics of these 5 cases were summarized.Results The 5 cases had an onset age ranging from 2 to 17 years and a disease duration ranging from 1 to 20 years.All of them experienced daily seizures,especially at night.The seizure duration was less than 30 seconds,and consciousness recovered rapidly.Among the cases,3 exhibited hypermotor seizures of typeⅠorⅡ,characterized by body turning along the horizontal body axis.Two of them experienced laughter during the seizures,while 1 showed a fearful expression.The remaining 2 cases presented with symmetric tonic seizures,involving the facial muscles.One case reported indescribable aura,and 2 cases had autonomic symptoms.During the interictal period,all 5 cases showed epileptic discharges predominantly in the frontal region on EEG,with lateralization value present in only 2 cases.During the ictal period,4 cases demonstrated general low volatility and fast activity(LVFA),while 1 case showed low-frequency rhythmic sharp and slow waves originating from the lesioned side.Four cases underwent SEEG,which revealed seizure starting from the frontal operculum and adjacent electrodes with LVFA,rapidly spreading to the insula,insular opercular,and medial frontal lobe.Positive changes were observed in the MRI of 4 cases,including 2 cases with possible cortical dysplasia,1 case with tuberous sclerosis,and 1 case with encephalomalacia foci.All 4 cases underwent SEEG guided radiofrequency thermocoagulation,resulting in seizure frequency reduction.Conclusions Frontal opercular epilepsy is mainly characterized by hypermotor seizure with body turning along the horizontal body axis or symmetric tonic seizure.These seizure may be accompanied by emotional symptom or facial muscle tonic,but aura and autonomic symptom are less common.The lateralization value of EEG is limited in frontal opercular epilepsy.SEEG indicates early involvement of the insula,insular opercular,and medial frontal lobe.

DNA is a biological polymer that encodes and stores genetic information in all living organism. Particularly, the precise nucleobase pairing inside DNA is exploited for the self-assembling of nanostructures with defined size, shape and functionality. These DNA nanostructures are known as framework nucleic acids (FNAs) for their skeleton-like features. Recently, FNAs have been explored in various fields ranging from physics, chemistry to biology. In this review, we mainly focus on the recent progress of FNAs in a pharmaceutical perspective. We summarize the advantages and applications of FNAs for drug discovery, drug delivery and drug analysis. We further discuss the drawbacks of FNAs and provide an outlook on the pharmaceutical research direction of FNAs in the future.

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

Objective: To examine the prevalence of allergic diseases in schoolaged children from Shanghai and to explore related factors so as to produce epidemiological data regarding allergic diseases in children. Methods: Multistage cluster sampling was used to carry out the study in Shanghai from April to June 2019. A total of 10 686 children aged 7-12 years from 17 primary schools participated in the survey. The International Study of Asthma and Allergies in Childhood (ISAAC)Scale was used to evaluate allergic diseases. Multivariate Logistic regression analysis was performed to analyze the related factors. Results: The overall prevalence of allergic diseases among schoolaged children in Shanghai was 47.0%. A higher prevalence was observed among boys (50.4% vs 43.3% in girls, χ2=54.44, P<0.01). Common allergic diseases included asthma (13.9%), allergic rhinitis (18.2%), and atopic dermatitis (34.3%). The Logistic regression analysis showed that the common risk factors of asthma, allergic rhinitis and atopic dermatitis included the following:male gender (OR=1.52,1.44,1.22); mother has a bachelors degree or above (OR=1.26,1.77,1.84); family history of allergic diseases (OR=2.87,4.24,2.57); only child (OR=1.16,1.28,1.22); curtain cleaning frequency <1 time/month (OR=1.41,1.79,1.77); room not cleaned daily (OR=1.14,1.18,1.20); and dust exposure frequency ≥1 time/month (OR=1.45,1.56,1.42), all P<0.05. These three types of allergic diseases were also associated with unique risk factors that dependent on socialenvironmentalbehavioral factors. Conclusion Compared with previous data, the prevalence of allergic diseases among schoolaged children in Shanghai increased significantly in 2019. The related influencing factors involve multiple variables including demographics, environmental exposure and behavior, which warrant further exploration.