Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss.

JOURNAL/nrgr/04.03/01300535-202505000-00030/figure1/v/2024-07-28T173839Z/r/image-tiff Noise-induced hearing loss is the primary non-genetic factor contributing to auditory dysfunction. However, there are currently no effective pharmacological interventions for patients with noise-induced hearing loss. Here, we present evidence suggesting that the lysine-specific demethylase 1 inhibitor-tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss, and elucidate its underlying regulatory mechanisms. We established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 dB for 4 hours. We found that tranylcypromine treatment led to the upregulation of Sestrin2 (SESN2) and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with tranylcypromine. The noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click, 4, 8, and 16 kHz frequencies compared with the noise exposure group treated with saline. These findings indicate that tranylcypromine treatment resulted in increased SESN2, light chain 3B, and lysosome-associated membrane glycoprotein 1 expression after noise exposure, leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3, thereby reducing noise-induced hair cell loss. Additionally, immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy pathway. Tranylcypromine treatment also reduced the production of NOD-like receptor family pyrin domain-containing 3 (NLRP3) production. In conclusion, our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2, which induced autophagy, thereby restricting NLRP3-related inflammasome signaling, alleviating cochlear hair cell loss, and protecting hearing function. These findings suggest that inhibiting lysine-specific demethylase 1 is a potential therapeutic strategy for preventing hair cell loss and noise-induced hearing loss.

Soil colloids can significantly enhance spreading of polybromodiphenyl ethers in groundwater by serving as an effective carrier.

Polybromodiphenyl ethers (PBDEs), the widely used flame retardants, are common contaminants in surface soils at e-waste recycling sites. The association of PBDEs with soil colloids has been observed, indicating the potential risk to groundwater due to colloid-facilitated transport. However, the extent to which soil colloids may enhance the spreading of PBDEs in groundwater is largely unknown. Herein, we report the co-transport of decabromodiphenyl ester (BDE-209) and soil colloids in saturated porous media. The colloids released from a soil sample collected at an e-waste recycling site in Tianjin, China, contain high concentration of PBDEs, with BDE-209 being the most abundant conger (320 ± 30 mg/kg). The colloids exhibit relatively high mobility in saturated sand columns, under conditions commonly observed in groundwater environments. Notably, under all the tested conditions (i.e., varying flow velocity, pH, ionic species and ionic strength), the mass of eluted BDE-209 correlates linearly with that of eluted soil colloids, even though the mobility of the colloids varies markedly depending on the specific hydrodynamic and solution chemistry conditions involved. Additionally, the mass of BDE-209 retained in the columns also correlates strongly with the mass of retained colloids. Apparently, the PBDEs remain bound to soil colloids during transport in porous media. Findings in this study indicate that soil colloids may significantly promote the transport of PBDEs in groundwater by serving as an effective carrier. This might be the reason why the highly insoluble and adsorptive PBDEs are found in groundwater at some PBDE-contaminated sites.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Misdiagnosis of hemangioma of left triangular ligament of the liver as gastric submucosal stromal tumor: Two case reports.

BACKGROUND: Extragastric lesions are typically not misdiagnosed as gastric submucosal tumor (SMT). However, we encountered two rare cases where extrinsic lesions were misdiagnosed as gastric SMTs. CASE SUMMARY: We describe two cases of gastric SMT-like protrusions initially misdiagnosed as gastric SMTs by the abdominal contrast-enhanced computed tomography (CT) and endoscopic ultrasound (EUS). Based on the CT and EUS findings, the patients underwent gastroscopy; however, no tumor was identified after incising the gastric wall. Subsequent surgical exploration revealed no gastric lesions in both patients, but a mass was found in the left triangular ligament of the liver. The patients underwent laparoscopic tumor resection, and the postoperative diagnosis was hepatic hemangiomas. CONCLUSION: During EUS procedures, scanning across different layers and at varying degrees of gastric cavity distension, coupled with meticulous image analysis, has the potential to mitigate the likelihood of such misdiagnoses.

Advancements in the Transdermal Drug Delivery Systems Utilizing Microemulsion-based Gels.

Microemulsion gel, as a promising transdermal nanoparticle delivery system, addresses the limitations of microemulsions and enhances their performance in drug delivery and release. This article aims to discuss the advantages of microemulsion gel, including improved drug bioavailability, reduced drug irritation, enhanced drug penetration and skin adhesion, and increased antimicrobial properties. It explores the methods for selecting microemulsion formulations and the general processes of microemulsion preparation, as well as commonly used oil phases, surfactants, and co-surfactants. Additionally, the biomedical applications of microemulsion gel in treating conditions, such as acne and psoriasis, are also discussed. Overall, this article elucidates the significant potential of microemulsion gel in topical drug delivery, providing insights into future development and clinical applications.

Characterization of an RR-2 cuticle protein DcCP8 and its potential application based on SPc nanoparticle-wrapped dsRNA in Diaphorina citri.

BACKGROUND: The insect cuticle consists of chitin fibers and a protein matrix, which plays an important role in protecting the body from invasion of various pathogens and prevents water loss. Periodic synthesis and degradation of the cuticle is required for the growth and development of insects. Key genes involved in cuticle formation have long been considered a potential target for pest control. RESULTS: In this study, a member of the RR-2 subfamily of cuticular protein 8 (DcCP8) was identified from the Diaphorina citri genome database. Immunofluorescence analysis suggested that DcCP8 was mainly located in the Diaphorina citri exocuticle and can be induced to up-regulate 12 h following 20-hydroxyecdysone (20E) treatment. Silencing of DcCP8 by RNA interference (RNAi) significantly disrupted the metamorphosis to the adult stage, and improved the permeability of the cuticle. Transmission electron microscopy (TEM) analysis revealed that the synthesis of the exocuticle was impressed after silencing of DcCP8. Furthermore, the recombinant DcCP8 protein exhibited chitin-binding properties in vitro, down-regulation of DcCP8 significantly inhibited expression levels of chitin metabolism-related genes. Additionally, a sprayable RNAi method targeting DcCP8 based on star polycation (SPc) nanoparticles-wrapped double-stranded RNA (dsRNA) significantly increased Diaphorina citri mortality. Transcriptome sequencing further confirmed that genes associated with the endocytic pathway and immune response were up-regulated in Diaphorina citri after SPc treatment. CONCLUSIONS: The current study indicated that DcCP8 is critical for the formation of Diaphorina citri exocuticles, and lays a foundation for Diaphorina citri control based on large-scale dsRNA nanoparticles. © 2024 Society of Chemical Industry.

A study on the effect of clinical intervention of evidence-based nursing measures on complications in patients after breast-conserving surgery.

BACKGROUND: Breast-conserving surgery is an important treatment for breast cancer, which not only eradicates the disease, but also protects the integrity of the breast, however, postoperative nausea and vomiting often bother patients. OBJECTIVE: This study examines the effects of evidence-based nursing practices on nausea and vomiting in patients after breast-conserving surgery, with the aim of providing new perspectives for clinical nursing practice. METHODS: One hundred and sixty patients who underwent breast-conserving surgery from January 2023 to December 2023 in Fudan University Shanghai Cancer Center were enrolled. The patients were divided into an intervention group (evidence-based nursing group) and a control group (conventional nursing group) using the random number table method, both groups comprised 80 patients. The control group used conventional nursing methods, and the intervention group added evidence-based nursing intervention on this basis. Comparative analysis focused on the incidence of nausea and vomiting, quality of life metrics, and postoperative satisfaction. RESULTS: In the intervention group, notably lower incidence rates of postoperative nausea and vomiting were observed compared to the control group within both the 0-24 hour and 24-48-hour postoperative periods (P< 0.05). Furthermore, the intervention group exhibited significantly higher scores across all five dimensions as well as the overall score of the FACT-B scale in comparison to the control group (P< 0.05), accompanied by heightened satisfaction with the nursing staff. CONCLUSION: This study demonstrated the positive clinical intervention effects of evidence-based nursing measures and emphasized their importance in improving postoperative nausea and vomiting and quality of life. Future studies are expected to incorporate evidence-based nursing practices into nursing care to improve patient recovery and overall quality of care.

Incremental prognostic value of cardiovascular magnetic resonance imaging in patients with severe LV dysfunction undergoing coronary artery bypass grafting.

BACKGROUND: Coronary artery disease (CAD) remains a significant global health issue, particularly when complicated by left ventricular ejection fraction (LVEF) < 35%. Although coronary artery bypass grafting (CABG) is recommended for such cases, the unclear prognosis necessitates further investigation. METHOD: This retrospective study aimed to determine whether cardiovascular magnetic resonance (CMR) imaging provides additional prognostic value in guiding effective clinical management. The study included patients with CAD and LVEF < 35% who underwent CABG surgery after enhanced CMR between March 2016 and March 2023. CMR was performed using a 3.0T scanner with steady-state free precession and phase-sensitive inversion recovery sequences. Prognostic analysis of clinical and CMR data was conducted, with the endpoint defined as cardiovascular death, revascularization, hospitalization for heart failure, or stroke. Statistical analysis included Student's t-test, chi-squared test, univariate and multivariate Cox regression analysis, receiver operating characteristic analysis, Harrell C statistical analysis, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) analysis. RESULT: The study included 152 patients (mean age 58.6 ± 9.7 years; 138 men). During a mean follow-up of 2.0 years, 8 patients experienced cardiovascular death, while 1 case had revascularization, 13 had hospitalization for heart failure, and 11 had a stroke. Left atrial diameter index (LADi) (hazard ratio [HR], 1.08 [95% confidence interval (CI): 1.02-1.15]; P = 0.04) and late gadolinium enhancement (LGE) mass (HR, 1.03 [95% CI: 1.01-1.06]; P < 0.001) were associated with the endpoint, even after adjusting for multiple clinical variables. Adding LADi and LGE mass improved risk prediction for adverse events, as indicated by the C-index (0.738, p < 0.01), IDI (0.36), and NRI (0.13). CONCLUSION: Left atrial diameter index (LADi) and scar burden are valuable prognostic indicators in patients with LVEF < 35% undergoing CABG. They offer enhanced risk stratification beyond traditional clinical factors, highlighting their importance in guiding clinical management.

Manipulating electron redistribution between iridium and Co6Mo6C bridging with a carbon layer leads to a significantly enhanced overall water splitting performance at industrial-level current density.

Nowadays, alkaline water electrocatalysis is regarded as an economical and highly effective approach for large-scale hydrogen production. Highly active electrocatalysts functioning under large current density are urgently required for practical industrial applications. In this work, we present a meticulously designed methodology to anchor Ir nanoparticles on Co6Mo6C nanofibers (Co6Mo6C-Ir NFs) bridging with nitrogen-doped carbon as efficient bifunctional electrocatalysts with both excellent hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity and stability in alkaline media. With a low Ir content of 5.9 wt%, Co6Mo6C-Ir NFs require the overpotentials of only 348 and 316 mV at 1 A cm-2 for the HER and OER, respectively, and both maintain stability for at least 500 h at ampere-level current density. Consequently, an alkaline electrolyzer based on Co6Mo6C-Ir NFs only needs a voltage of 1.5 V to drive 10 mA cm-2 and possesses excellent durability for 500 h at 1 A cm-2. Density functional theory calculations reveal that the introduction of Ir nanoparticles is pivotal for the enhanced electrocatalytic activity of Co6Mo6C-Ir NFs. The induced interfacial electron redistribution between Ir and Co6Mo6C bridging with nitrogen-doped carbon dramatically modulates the electron structure and activates inert atoms to generate more highly active sites for electrocatalysis. Moreover, the optimized electronic structure is more conducive to the balance of the adsorption and desorption energies of reaction intermediates, thus significantly promoting the HER, OER and overall water splitting performance.

Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei.

Spiral ganglia neurons (SGNs) impairment can cause deafness. One important therapeutic approach involves utilizing stem cells to restore impaired auditory circuitry. Nevertheless, the inadequate implementation of research methodologies poses a challenge in accurately assessing the functionality of derived cells within the circuit. Here, we describe a novel method for converting human embryonic stem cells (hESCs) into otic neurons (ONs) and assess their functional connectivity using an optogenetic approach with cells or an organotypic slice of rat cochlear nucleus (CN) in coculture. Embryonic stem cell-derived otic neurons (eONs) exhibited SGN marker expression and generated functional synaptic connection when cocultured with cochlear nucleus neurons (CNNs). Synapsin 1 and VGLUT expression are found in the cochlear nucleus of brain slices, where eONs projected processes during the coculture of eONs and CN brain slices. Action potential spikes and INa+/IK+ of CNNs increased in tandem with light stimulations to eONs. These findings provide further evidence that eONs may be a candidate source to treat SGN-deafness.

Application of MXene composites for target gas detection in food safety.

Food contamination has long plagued agriculture, posing significant health risks to consumers. The use of volatile gases for food safety detection has proven highly effective, with composite gas sensors that leverage the two-dimensional material MXene exhibiting notable advancements in detecting various target gases. This paper reviews the progress of MXene-based composite gas sensors in the detection of food safety-related gases. The review begins by examining MXene material synthesis methods and then presents an overview of techniques aimed at enhancing MXene-based sensor detection capabilities. Recently, advancements in MXene composite gas sensors tailored for food safety gases have been highlighted. Finally, challenges encountered in gas-sensing applications of MXene-based composites are outlined, alongside predictions for their future development, aiming to offer insights for the application and advancement of intelligent gas sensors for target gases in food safety.

Machine learning-based analysis of heavy metal contamination in Chinese lake basin sediments: Assessing influencing factors and policy implications.

Sediments are important heavy metal sinks in lakes, crucial for ensuring water environment safety. Existing studies mainly focused on well-studied lakes, leaving gaps in understanding pollution patterns in specific basins and influencing factors.We compiled comprehensive sediment contamination data from literature and public datasets, including hydro-geomorphological, climatic, soil, landscape, and anthropogenic factors. Using advanced machine learning, we analyzed typical pollution factors to infer potential sources and migration pathways of pollutants and predicted pollution levels in basins with limited data availability. Our analysis of pollutant distribution data revealed that Cd had the most extensive pollution range, with the most severe pollution occurring in the Huaihe and Yangtze River basins. Furthermore, we identified distinct groups of driving factors influencing various heavy metals. Cd, Cr, and Pb were primarily influenced by human activities, while Cu and Ni were affected by both anthropogenic and natural factors, and Zn tended more towards natural sources. Our predictions indicated that, in addition to the typical highly polluted areas, the potential risk of Cd, Cu and Ni is higher in Xinjiang, and in Tibet and Qinghai, the potential risk of Cd, Cr, Cu and Ni is higher. Pb and Zn presented lower risks, except in the Huaihe and Yangtze River Basins. Temperature, wind, precipitation, precipitation rate, and the cation exchange capacity of soil significantly impacted the predictions of heavy metal pollution in sediments, suggesting that particulate migration, rainfall runoff, and soil erosion are likely the main pathways for pollutant migration into sediments. Considering the migration, pathways, and sources of pollutants, we propose strategies such as low-impact development and promoting sustainable transportation to mitigate pollution. This study provides the latest insights into heavy metal pollution in Chinese lake sediments, offering references for policy-making and water resource management.

The Effect of Global Spinal Alignment on the Cervical Degeneration in Patients with Degenerative Lumbar Scoliosis.

PURPOSE: To elucidate the effect of global spinal alignment on the cervical degeneration in Patients with Degenerative Lumbar Scoliosis (DLS). METHODS: A total of 117 patients with DLS and 42 controls were analysed. DLS patients (study group) were categorized according to the SRS-Schwab classification. Patients with lumbar spinal stenosis were reviewed as a control group. Spinopelvic parameters were measured in cervical and full-length spine radiographs. Cervical degeneration was assessed using the Cervical Degeneration Index (CDI) scoring system. RESULTS: There were significant differences in C2-7 sagittal vertical axis, T1 Slope, thoracic kyphosis, Lumbar Lordosis (LL), and pelvic tilt between DLS and control groups. Although the DLS and control groups did not differ significantly with regard to CDI scores, a striking difference was noted when sagittal spinopelvic modifiers were considered individually. Patients with a Pelvic Incidence minus Lumbar Lordosis (PI-LL) modifier grade of ++ had significantly higher CDI scores than those with 0, and patients with a PI-LL or Sagittal Vertical Axis (SVA) modifier grade of ++ had significantly higher CDI scores than control group. Disk narrowing scores were highest in patients with a PI-LL modifier grades of ++ followed by those with +. Additionally, CDI scores were more associated with LL rather than cervical lordosis. CONCLUSIONS: Patients with DLS may be at greater risk of cervical spine degeneration, especially those with a PI-LL or SVA modifier grade of ++. Surgical strategy for DLS patients should be more carefully selected considering the restoration of LL.

Light regulates widespread plant alternative polyadenylation through the chloroplast.

Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage, and polyadenylation (CPA), and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3' untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover, and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways, and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial and TOR kinase activities are necessary for the effect of light. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by histone deacetylase inhibition. Instead, regulation seems to correlate with changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.

Emotion recognition of EEG signals based on contrastive learning graph convolutional model.

Electroencephalogram (EEG) signals offer invaluable insights into the complexities of emotion generation within the brain. Yet, the variability in EEG signals across individuals presents a formidable obstacle for empirical implementations. Our research addresses these challenges innovatively, focusing on the commonalities within distinct subjects' EEG data.We introduce a novel approach named Contrastive Learning Graph Convolutional Network (CLGCN). This method captures the distinctive features and crucial channel nodes related to individuals' emotional states. Specifically, CLGCN merges the dual benefits of Contrastive Learning's synchronous multisubject data learning and the Graph Convolutional Network's proficiency in deciphering brain connectivity matrices.Understanding multifaceted brain functions and their information interchange processes is realized as CLGCN generates a standardized brain network learning matrix during a dataset's learning process. Our model significantly streamlines the retraining process for new subjects, requiring only 5% of the initial sample size for fine-tuning to attain a remarkable 92.8% accuracy rate. Additionally, our model has undergone extensive testing on the DEAP and SEED datasets, demonstrating the effectiveness of our model. .

Discovery of FO-4-15, a novel 1,2,4-oxadiazole derivative, ameliorates cognitive impairments in 3×Tg mice by activating the mGluR1/CaMKIIα pathway.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive impairments. Despite the limited efficacy of current treatments for AD, the 1,2,4-oxadiazole structure has garnered significant attention in medicinal chemistry due to its potential impact on mGluR1 and its association with AD therapy. In this study, a series of novel 1,2,4-oxadiazole derivatives were designed, synthesized, and evaluated for the neuroprotective effects in human neuroblastoma (SH-SY5Y) cells. Among all the derivatives tested, FO-4-15 (5f) existed the lowest cytotoxicity and the highest protective effect against H2O2. Based on these in vitro results, FO-4-15 was administered to 3×Tg mice and significantly improved the cognitive impairments of the AD mice. Pathological analysis showed that FO-4-15 significantly reduced Aß accumulation, Tau hyper-phosphorylation, and synaptic impairments in the 3×Tg mice. Dysfunction of the CaMKIIα/Fos signaling pathway in 3×Tg mice was found to be restored by FO-4-15 and the necessity of the CaMKIIα/Fos for FO-4-15 was subsequently confirmed by the use of a CaMKIIα inhibitor in vitro. Beyond that, mGluR1 was identified to be a potential target of FO-4-15, and the interaction of FO-4-15 and mGluR1 was displayed by Ca2+ flow increase, molecular docking, and interaction energy analysis. The target of FO-4-15 was further confirmed in vitro by JNJ16259685, a nonselective inhibitor of mGluR1. These findings suggest that FO-4-15 may hold promise as a potential treatment for Alzheimer's disease.

Delicate and thin fibrous septa indicate a regression tendency in metabolic dysfunction-associated steatohepatitis patients with advanced fibrosis.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis is reversible. However, the dynamic morphology change in fibrosis regression remains unclear. We aim to explore the morphological characteristics of fibrosis regression in advanced MASH patients. METHODS: Clinical and histological data of 79 biopsy-proved MASH patients with advanced fibrosis (F3-F4) were reviewed. The second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) image technology was used to quantitatively identify the R (regressive) septa from P (progressive) septa and PS (perisinusoidal) fibrosis. Non-invasive tests were used to compare the fibrosis level with and without R septa groups. Transcriptomics was used to explore hub genes and the underlying mechanism of the formation of R septa. RESULTS: The R septa were different from the P septa and PS fibrosis in detail collagen quantitation identified by SHG/TPEF technology. The R septa were found in MASH fibrosis-regressed patients, which met the definition of the "Beijing classification". Therefore, patients were divided into two groups according to septa morphology: with R septa (n = 10, 12.7%), and without R septa (n = 69, 87.3%). Patients with R septa had lower values in most non-invasive tests, especially for liver stiffness assessed by TE (12.3 vs. 19.4 kPa, p = 0.010) and FAST (FibroScan®-AST) score (0.43 vs. 0.70, p = 0.003). Transcriptomics analysis showed that the expressions of five hub fibrogenic genes, including Col3A1, BGN, Col4A1, THBS2, and Col4A2 in the R septa group, were significantly lower. CONCLUSIONS: The R septa can be differentiated from the P septa and PS fibrosis by quantitative assessment of SHG/TPEF, and it represents a tendency of fibrosis regression in MASH patients. TRIAL REGISTRATION: NCT03386890, 29/12/2017.

Attention-based CNN-BiLSTM for sleep state classification of spatiotemporal wide-field calcium imaging data.

BACKGROUND: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired. NEW METHOD: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and a bidirectional long short-term memory network (BiLSTM) with attention mechanism to identify temporal dependencies among different time points was proposed to classify WFCI data into states of wakefulness, NREM and REM sleep. RESULTS: Sleep states were classified with an accuracy of 84 % and Cohen's κ of 0.64. Gradient-weighted class activation maps revealed that the frontal region of the cortex carries more importance when classifying WFCI data into NREM sleep while posterior area contributes most to the identification of wakefulness. The attention scores indicated that the proposed network focuses on short- and long-range temporal dependency in a state-specific manner. COMPARISON WITH EXISTING METHOD: On a held out, repeated 3-hour WFCI recording, the CNN-BiLSTM achieved a κ of 0.67, comparable to a κ of 0.65 corresponding to the human EEG/EMG-based scoring. CONCLUSIONS: The CNN-BiLSTM effectively classifies sleep states from spatiotemporal WFCI data and will enable broader application of WFCI in sleep research.