PSMD9 promotes the malignant progression of hepatocellular carcinoma by interacting with c-Cbl to activate EGFR signaling and recycling.

BACKGROUND: Mounting evidences shows that the ubiquitin‒proteasome pathway plays a pivotal role in tumor progression. The expression of 26S proteasome non-ATPase regulatory subunit 9 (PSMD9) is correlated with recurrence and radiotherapy resistance in several tumor types. However, the role and mechanism of PSMD9 in hepatocellular carcinoma (HCC) progression remain largely unclear. METHODS: PSMD9 was identified as a prognosis-related biomarker for HCC based on analysis of clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the JP Project of the International Cancer Genome Consortium (ICGC-LIRI-JP). PSMD9 expression was analyzed in cancer tissues and adjacent noncancerous tissues via immunohistochemistry and Western blotting. Multiple in vivo and in vitro experimental techniques (such as CCK-8, colony formation, EdU, and Transwell assays; flow cytometry; Western blotting; quantitative RT-PCR; Coimmunoprecipitation assay and immunofluorescence confocal imaging) were used to assess the functions of PSMD9 in the pathogenesis of HCC. RESULTS: We found that the expression of PSMD9 was upregulated and associated with a poor prognosis in HCC patients. PSMD9 promoted HCC cell proliferation, migration, invasion and metastasis. Knockdown of PSMD9 significantly inhibited HCC cell proliferation by inducing G1/S cell cycle arrest and apoptosis. Mechanistically, we demonstrated that PSMD9 promoted HCC cell proliferation and metastasis via direct interaction with the E3 ubiquitin ligase c-Cbl, suppresses EGFR ubiquitination, influenced EGFR endosomal trafficking and degradation and subsequently activated ERK1/2 and Akt signaling. In addition, we showed that PSMD9 knockdown sensitized HCC cells to the tyrosine kinase inhibitor erlotinib in vitro and in vivo. CONCLUSIONS: Collectively, our results indicate that PSMD9 drives HCC progression and erlotinib resistance by suppressing c-Cbl mediated EGFR ubiquitination and therefore can be a potential therapeutic target for HCC.

First Detection of Food-Derived Agricultural Chemicals Residues in Waste Wool Fibers by Ultrasound-Assisted Extraction-QuEChERS Cleanup-UPLC-MS/MS.

Food-derived agricultural chemical residues (FACRs) accumulate gradually in organisms and can damage their nervous system, endocrine system and reproductive system, posing significant harm. Currently, there is little literature on the detection of FACRs in waste wool fibers. In this paper, an ultrasound-assisted extraction-QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) cleanup-UPLC-Ms/Ms method was applied for the qualitative analysis and quantitative determination of trace FACRs in waste wool fibers with 0.2% formic acid-methanol as extraction solvent and multi-selective ion scanning. Using the external standard method, it was shown that the 13 target FACRs showed good linearity in the mass concentration range of 0.1-50 µg/kg. The limits of detection were 1.0- 10.0 µg/kg and the limits of quantification were 4.0-40.0 µg/kg. The recoveries of the 13 target FACRs ranged from 78 to 112.6% at the 5-, 10- and 20-fold detection limit spiked levels, and the intra- or inter-day relative standard deviations were 2.05-6.98% or 1.98-6.99%, respectively. This method satisfied the detection requirements and can be used in applications.

Development of Cu(II) 4-hydroxybenzoylhydrazone complexes that induce mitochondrial DNA damage and mitochondria-mediated apoptosis in liver cancer.

Cisplatin remains the most widely used chemotherapeutic agent in cancer treatment; however, its inherent drawbacks have fueled the development of novel metalloanticancer drugs. In this study, two novel Cu(II) complexes (Cu1 and Cu2) were designed and synthesized. Notably, these Cu(II) complexes showed higher cytotoxicity against HL-7402 cells than cisplatin. Moreover, Cu(II) complexes significantly inhibited liver cancer growth in a xenograft model. A mechanism study revealed that the Cu(II) complexes reduced the mitochondrial membrane potential of cancer cells, produced excessive reactive oxygen species (ROS), induced mitochondrial DNA (mtDNA) damage, and ultimately facilitated cancer cell apoptosis.

Cu+-doped lead-free double perovskite quantum dots for enhancing the photovoltaic performance of carbon-based Cs2AgInCl6 perovskite solar cells.

Lead-free double perovskite solar cells (PSCs) have received widespread attention because of their non-toxic nature and three-dimensional structure. However, their photovoltaic efficiency is limited by their large bandgap, including indirect or direct forbidden. Herein, Cu+ ions are incorporated into Cs2AgInCl6 double perovskite quantum dots, following which the bandgap is effectively decreased from 3.6 to 2.9 eV. Meanwhile, a facile method of drop-coating is employed to fabricate Cs2AgInCl6 films and carbon electrodes. A carbon electrode derived from a by-product of the cane sugar industry (molasses) is used to replace the expensive hole-transport materials and metal electrodes. A 0.5% Cu+-doped Cs2AgInCl6, device fabricated using carbon-based PSCs with a stacked-architecture achieves a power conversion efficiency of 1.77%, which is 2.9 times higher than that of the original device, and displays a better stability compared with that of the control one. This study provides guidance for preparing PSCs using a low-cost, facile strategy.

Research on the SAW Gyroscopic Effect in a Double-Layer Substrate Structure Incorporating Non-Piezoelectric Materials.

The SAW (surface acoustic wave) gyroscopic effect is a key parameter that reflects the sensitivity performance of SAW angular velocity sensors. This study found that adding a layer of non-piezoelectric material with a lower reflection coefficient than that of the upper-layer material below the piezoelectric substrate to form a double-layer structure significantly enhanced the SAW gyroscopic effect, and the smaller the reflection coefficient of the lower-layer material, the stronger the SAW gyroscopic effect, with values being reached that were two to three times those with single-layer substrate structures. This was confirmed using a three-dimensional model, and the experimental results also showed that the thickness of the piezoelectric layer and the type of the lower-layer material also had a significant impact on the SAW gyroscopic effect. This novel discovery will pave the way for the future development of SAW angular velocity sensors.

Anti-virulence strategy of diaryl chalcogenide compounds against Candida albicans infection.

Candida albicans is an important opportunistic pathogenic fungus that frequently causes serious systemic infection in humans. Due to the vital roles of biofilm formation and the yeast-to-hypha transition in the infection process, we have selected a series of diaryl chalcogenides and tested their efficacy against C. albicans SC5314 pathogenicity by the inhibition of biofilm formation and the yeast-to-hypha transition. The compounds 5-sulfenylindole and 5-selenylindole were found to have excellent abilities to inhibit both biofilm formation and hyphal formation in C. albicans SC5314. Intriguingly, the two leading compounds also markedly attenuated C. albicans SC5314 virulence in human cell lines and mouse infection models at micromolar levels. Furthermore, our results showed that the presence of the compounds at 100 µM resulted in a marked decrease in the expression of genes involved in the cAMP-PKA and MAPK pathways in C. albicans SC5314. Intriguingly, the compounds 5-sulfenylindole and 5-selenylindole not only attenuated the cytotoxicity of Candida species strains but also showed excellent synergistic effects with antifungal agents against the clinical drug-resistant C. albicans strain HCH12. The compound 5-sulfenylindole showed an obvious advantage over fluconazole as it could also restore the composition and richness of the intestinal microbiota in mice infected by C. albicans. Together, these results suggest that diaryl chalcogenides can potentially be designed as novel clinical therapeutic agents against C. albicans infection. The diaryl chalcogenides of 5-sulfenylindole and 5-selenylindole discovered in this study can provide new direction for developing antifungal agents against C. albicans infection.

Pose Estimation and Behavior Classification of Jinling White Duck Based on Improved HRNet.

In breeding ducks, obtaining the pose information is vital for perceiving their physiological health, ensuring welfare in breeding, and monitoring environmental comfort. This paper proposes a pose estimation method by combining HRNet and CBAM to achieve automatic and accurate detection of duck's multi-poses. Through comparison, HRNet-32 is identified as the optimal option for duck pose estimation. Based on this, multiple CBAM modules are densely embedded into the HRNet-32 network to obtain the pose estimation model based on HRNet-32-CBAM, realizing accurate detection and correlation of eight keypoints across six different behaviors. Furthermore, the model's generalization ability is tested under different illumination conditions, and the model's comprehensive detection abilities are evaluated on Cherry Valley ducklings of 12 and 24 days of age. Moreover, this model is compared with mainstream pose estimation methods to reveal its advantages and disadvantages, and its real-time performance is tested using images of 256 × 256, 512 × 512, and 728 × 728 pixel sizes. The experimental results indicate that for the duck pose estimation dataset, the proposed method achieves an average precision (AP) of 0.943, which has a strong generalization ability and can achieve real-time estimation of the duck's multi-poses under different ages, breeds, and farming modes. This study can provide a technical reference and a basis for the intelligent farming of poultry animals.

A sham-controlled randomised trial of pulmonary artery denervation for Group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial.

BACKGROUND: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported. AIMS: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH. METHODS: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death. RESULTS: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (pinteraction=0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone. CONCLUSIONS: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.

Construction of a Diagnostic Model and a lncRNA-Associated ceRNA Network Based on Apoptosis-Related Genes for Schizophrenia.

Methods: Gene expression profiles and apoptosis-related data were downloaded from the Gene Expression Omnibus and Molecular Signature databases, respectively. Apoptosis-related differentially expressed mRNAs (DEGs) and miRNAs (DEMs) from blood samples between the schizophrenia and healthy control individuals were screened. A diagnostic model was developed using the data from univariate and least absolute shrinkage and selection operator (LASSO) regression analyses, followed by validation using the GSE38485 dataset. Cases were divided into low-risk (LR) and high-risk (HR) groups based on the risk score of the model, and differences in immune gene sets and pathways between these two groups were compared. Finally, a ceRNA network was constructed by integrating long non-coding RNAs (lncRNAs), DEMs, and DEGs. Results: A diagnostic model containing 15 apoptosis-related genes was developed and its diagnostic efficiency was found to be robust. The HR group was correlated with higher immune scores of chemokines, cytokines, and interleukins; it was also significantly involved in pathways such as pancreatic beta cells and early estrogen response. A ceRNA network composed of 2 lncRNAs, 14 miRNAs, and 5 mRNAs was established. Conclusions: The established model is a potential tool to improve the diagnostic efficiency of patients with schizophrenia, and the nodes included in the ceRNA network might serve as biomarkers and therapeutic targets for schizophrenia.

m6A reader YTHDF3 is associated with clinical prognosis, related RNA signatures and immunosuppression in gastric cancer.

BACKGROUND: YTHDF3 as a N6-methyladenosine (m6A) reader participates in the development and progression of multiple cancer types, however, the prognosis, molecular biology and immune infiltration of YTHDF3 in gastric cancer (GC) have not been investigated. METHODS: The YTHDF3 expression profile and clinicopathological parameters of stomach adenocarcinoma (STAD) were downloaded from TCGA. The online websites and databases such as GEPIA2, cBioPortal, UALCAN, ImmuCellAl, xCell, TISIDB, GSCA were utilized for analysis of the association of YTHDF3 with STAD, including clinical prognosis, WGCNA and LASSO Cox regression analysis. Further functional assays such as RT-qPCR, Western blot, immunohistochemistry (IHC), immunofluorescence (IF), CCK-8, colony formation, EdU and Transwell assays were performed to determine the role of YTHDF3 in GC. RESULTS: We found that YTHDF3 was upregulated in STAD tissue samples ascribed to its copy number amplification and associated with poor prognosis in patients with STAD. GO and KEGG analyses showed that YTHDF3-related differential genes were predominantly enriched in the proliferation, metabolism and immune signaling pathways. Knockdown of YTHDF3 repressed the growth and invasion of GC cells by inhibition of PI3K/AKT signaling. We then identified YTHDF3-related lncRNAs, miRNAs and mRNAs, and constructed their prognostic signatures in patients with STAD. Moreover, YTHDF3 associated with tumor immune infiltration such as CD8+ T cells, macrophages, Tregs, MHC molecules and chemokines, upregulated PD-L1 and CXCL1 and exerted a response to the immunotherapy in GC. CONCLUSIONS: YTHDF3 upregulation indicates poor prognosis and promotes GC cell growth and invasion by activating PI3K/AKT pathway and regulating immune microenvironment. The established YTHDF3-related signatures highlight the association of YTHDF3 with the clinical prognosis and immune cell infiltration in GC.

Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures.

Centenarians are an excellent model to study the relationship between the gut microbiome and longevity. To characterize the gut microbiome signatures of aging, we conducted a cross-sectional investigation of 1,575 individuals (20-117 years) from Guangxi province of China, including 297 centenarians (n = 45 with longitudinal sampling). Compared to their old adult counterparts, centenarians displayed youth-associated features in the gut microbiome characterized by an over-representation of a Bacteroides-dominated enterotype, increase in species evenness, enrichment of potentially beneficial Bacteroidetes and depletion of potential pathobionts. Health status stratification in older individuals did not alter the directional trends for these signature comparisons but revealed more apparent associations in less healthy individuals. Importantly, longitudinal analysis of centenarians across a 1.5-year period indicated that the youth-associated gut microbial signatures were enhanced with regard to increased evenness, reduction in interindividual variation and stability of Bacteroides, and that centenarians with low microbial evenness were prone to large microbiome instability during aging. These results together highlight a youth-related aging pattern of the gut microbiome for long-lived individuals.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial.

BACKGROUND: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients. METHODS: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months. RESULTS: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up. CONCLUSIONS: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

Solution-Processed Flexible Transparent Electrodes for Printable Electronics.

Flexible transparent electrodes (FTEs) have been widely witnessed in various printable electronic devices, especially those involving light. So far, solution processes have demonstrated increasing advantages in preparing FTEs not only in their mild operation conditions and high-throughput but also in the diversity in micropatterning conductive nanomaterials into networks. For the FTEs, both high transparency and high conductivity are desirable, which therefore create requirements for the conductive network by considering the trade-off relationship between the coverage and the micropatterns of the network. In addition, the conductive networks also affect the flexibility of FTEs due to the deformation during bending/stretching. Consequently, solution processes capable of micropatterning conductive nanomaterials including nanoparticles, nanowires/polymers, and graphene/MXene play a crucial role in determining the performance of FTEs. Here, we reviewed recent research progress on solution-processed FTEs, including the solution processes, the solution-processable conductive nanomaterials and the substrates for making FTEs, and applications of FTEs in flexible electronics. Finally, we proposed several perspective outlooks of the FTEs, which aim at not only the enhanced performance but also the performances in extreme conditions and in integration. We believe that the review would offer inspiration for developing functional FTEs.

Postoperative psychological stress and expression of stress-related factors HSP70 and IFN-γ in patients with early lung cancer.

BACKGROUND: To explore the status of postoperative psychological stress and the expression of stress-related factors heat stress protein 70 (HSP70) and interferon γ (IFN-γ) in patients with early lung cancer, and to provide scientific basis for psychological rehabilitation and index detection of patients with lung cancer. METHODS: Patients with early lung cancer hospitalized in People's Hospital of Rizhao from April 2014 to March 2017 were selected as the research subjects, and a cross-sectional survey research method was used to conduct a questionnaire survey on the research subjects. The questionnaire included General Data Questionnaire and the SCL-90 Self-Assessment Scale for Health Symptoms, which were used to research the postoperative psychological stress of patients with early lung cancer. The enzyme-linked immunosorbent assay was used to detect the serum levels of HSP70 and IFN-γ. RESULTS: A total of 178 patients with early lung cancer were investigated, including 126 males (70.8%) and 52 females (29.2%). There were 52.6% of the patients with mild discomfort, 29.9% with moderate discomfort and 4.8% with severe discomfort, and the positive detection rate of psychological problems was 44.2%. The SCL-90 factors of the patients were higher than the norm, and the average scores of factors including anxiety, horror, somatization, depression, and interpersonal sensitivity were higher (P<0.05). Serum HSP70 expression level was the highest in patients with moderate discomfort of early lung cancer (P<0.05), and the serum IFN-γ expression level decreased with the increased stress level (P<0.05). HSP70 was positively correlated with somatization factors, and negatively correlated with fear factors, and IFN-γ was negatively correlated with the fear factor. CONCLUSIONS: Patients with early lung cancer have extensive postoperative psychological problems, and the timely postoperative psychological intervention is significant. There are differences in the expression levels of stress related factors HSP70 and IFN-γ in patients with different levels of psychological stress, which are of certain clinical value as the monitoring index of response psychological stress.

Identification of risk factors for incident cervical insufficiency in nulliparous and parous women: a population-based case-control study.

BACKGROUND: Cervical insufficiency is one of the underlying causes of late miscarriage and preterm birth. Although many risk factors have been identified, the relative magnitude of their association with risk in nulliparous versus parous women has not been well demonstrated, especially for incident cervical insufficiency (ICI). The aim of this study was to investigate and compare the magnitude of the association of ICI with predictive factors in nulliparous and parous women, and to further investigate various aspects of obstetric history for parous women. METHODS: Pregnant women with a first diagnosis of cervical insufficiency were compared to a random sample of control pregnancies from women with no diagnosis by using Swedish national health registers. Demographic, reproductive, and pregnancy-specific factors were compared in case and control pregnancies, and relative risks presented as odds ratios (OR), stratified by nulliparous/parous. Independent associations with ICI were estimated from multivariable logistic regression. Associations with obstetric history were further estimated for multiparous women. RESULTS: A total of 759 nulliparous ICI cases and 1498 parous cases were identified during the study period. Multifetal gestation had a strong positive association with ICI in both groups, but of much larger magnitude for nulliparous women. The number of previous miscarriages was also a much stronger predictor of risk in nulliparous women, especially for multifetal pregnancies. History of preterm delivery (<37 weeks' gestation) was an independent predictor for parous women, and for those whose most recent delivery was preterm, the association with ICI increased with each additional week of prematurity. A previous delivery with prolonged second stage of labor or delivery of a very large infant were both inversely associated with risk of ICI in the current pregnancy. CONCLUSIONS: The differences in importance of predictive risk factors for incident cervical insufficiency in nulliparous and parous women can help resolve some of the inconsistencies in the literature to date regarding factors that are useful for risk prediction. Stratifying on parity can inform more targeted surveillance of at-risk pregnancies, enable the two groups of women to be better informed of their risks, and eventually inform screening and intervention efforts.

Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized PADN-CFDA Trial.

BACKGROUND: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial. OBJECTIVES: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH. METHODS: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months. RESULTS: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up. CONCLUSIONS: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266).

Abnormal Ventral Somatomotor Network Homogeneity in Patients With Temporal Lobe Epilepsy.

Background: Abnormalities of functional connectivity in the somatomotor network have been thought to play an essential role in the pathophysiology of epilepsy. However, there has been no network homogeneity (NH) study about the ventral somatomotor network (VSN) in patients with temporal lobe epilepsy (TLE). Therefore, we explored the NH of the VSN in TLE patients in this study. Methods: The sample included 52 patients with left temporal lobe epilepsy, 83 patients with right temporal lobe epilepsy, and 68 healthy controls. The NH method was utilized to analyze the resting-state functional magnetic resonance imaging data. Results: Compared to the controls, rTLE patients had significantly higher NH in the bilateral postcentral gyrus, and significantly lower NH in the bilateral Rolandic operculum and the right superior temporal gyrus (STG). The NH values of the left postcentral gyrus were significantly higher in lTLE patients than in the healthy controls, and lTLE patients had lower NH in the right Rolandic operculum. The altered NH in the postcentral gyrus was negatively correlated with the illness duration, and the decreased NH in the left Rolandic operculum was negatively correlated with the executive control reaction time (ECRT). Conclusion: Our findings suggest that altered NH of the postcentral gyrus, Rolandic operculum and STG might be associated with the pathophysiology of TLE, and thus, highlight the contribution of the VSN to the pathophysiology of TLE.

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

Fusion of Whole Night Features and Desaturation Segments Combined with Feature Extraction for Event-Level Screening of Sleep-Disordered Breathing.

Purpose: Misdiagnosis and missed diagnosis of sleep-disordered breathing (SDB) is common because polysomnography (PSG) is time-consuming, expensive, and uncomfortable. The use of recording methods based on the oxygen saturation (SpO2) signals detected by wearable devices is impractical and inaccurate for extracting signal features and detecting apnoeic events. We propose a method to automatically detect the apnoea-based SpO2 signal segments and compute the apnoea-hypopnea index (AHI) for SDB screening and grading. Patients and Methods: First, apnoea-related desaturation segments in raw SpO2 signals were detected; global features were extracted from whole night signals. Then, the SpO2 signal segments and global features were fed into a bi-directional long short-term memory convolutional neural network model to identify apnoea-related and non-apnoea-related events. The apnoea-related segments were used to assess the AHI. Results: The model was trained on 500 individuals and tested on 8131 individuals from two public hospitals and one private centre. In the testing data, the classification accuracy for apnoea-related segments was 84.3%. Individuals with SDB (AHI 15) were identified with a mean accuracy of 88.95%. Conclusion: Using automatic SDB detection based on SpO2 signals can accurately screen for SDB.