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Abstract Background Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy. Methods We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs. Results Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs. Conclusion We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies.

Abstract Processing spatiotemporal data sources with both high spatial dimension and rich temporal information is a ubiquitous need in machine intelligence. Recurrent neural networks in the machine learning domain and bio-inspired spiking neural networks in the neuromorphic computing domain are two promising candidate models for dealing with spatiotemporal data via extrinsic dynamics and intrinsic dynamics, respectively. Nevertheless, these networks have disparate modeling paradigms, which leads to different performance results, making it hard for them to cover diverse data sources and performance requirements in practice. Constructing a unified modeling framework that can effectively and adaptively process variable spatiotemporal data in different situations remains quite challenging. In this work, we propose hybrid spatiotemporal neural networks created by combining the recurrent neural networks and spiking neural networks under a unified surrogate gradient learning framework and a Hessian-aware neuron selection method. By flexibly tuning the ratio between two types of neurons, the hybrid model demonstrates better adaptive ability in balancing different performance metrics, including accuracy, robustness, and efficiency on several typical benchmarks, and generally outperforms conventional single-paradigm recurrent neural networks and spiking neural networks. Furthermore, we evidence the great potential of the proposed network with a robotic task in varying environments. With our proof of concept, the proposed hybrid model provides a generic modeling route to process spatiotemporal data sources in the open world.

Abstract Background Oral cancer is one of the most common cancers in China and seriously threaten life and health of Chinese people. We analysed the trends and disparities of oral cancer mortality rates and the disease burden of oral cancer in China from 2006 to 2021 to provide a reference for its prevention and control. Methods Annual death data for oral cancer was gleaned from the China Death Surveillance Database. The age-standardized mortality rate (ASMR), annual percentage change (APC), and average APC (AAPC) were used to analyze the trend of mortality. Loss of life expectancy (LLE) and years of life lost (YLL) were adopted to assess disease burden. Results From 2006 to 2021, the overall ASMR of oral cancer lightly declined (AAPC: − 0.97%; 95% CI: − 1.89%, − 0.04%), and the similar trend was observed among females (AAPC: − 1.22%; 95% CI: − 1.89%, − 0.55%). The ASMR of males was 2.31–3.16 times higher than that of females per year. The median of LLE for overall, males and females caused by oral cancer from 2006 to 2021 were 0.05, 0.06 and 0.03 years, respectively. There was a decrease of standardized YLL rate from 2006 to 2021 for overall (AAPC: − 1.31%, 95% CI: − 2.24% ~ − 0.37%) and for female (AAPC: − 1.63%, 95% CI: − 2.30% ~ − 0.95%). ASMR in urban areas was 1.02–1.28 times higher than that in rural areas from 2006 to2011, but 0.85–0.97 times lower in urban areas than that in rural areas from 2018 to 2021. The disease burden was higher in urban areas than in rural areas in 2006, whereas the reverse was observed in 2021. Conclusions There are severe health gaps and disparities in trends between sexes and different areas in China. Males and rural populations need to be focused on targeted interventions for the main influencing factors.

Lithium-ion batteries (LIBs) are widely used as important energy storage and energy supply devices. The porous design and heteroatomization modification of carbon-based anode materials are crucial for achieving high-capacity and reversible energy storage in LIBs. Sol-gel method and pyrolysis treatment were used to obtain silica/silver composite particles used as templates. Polyphosphazene-coated silica/silver composite composite carbon materials (SiO2/Ag@PZS-C) were synthesized through in-situ self-assembly and carbonization of polyphosphazene. The electrochemical behavior and lithium storage mechanism of SiO2/Ag@PZS-C was also studied. The results reveal that the composite exhibited high specific capacity, stable cycling and superior rate performance. The double modification of silver nanoparticles and polyphosphazene carbon significantly improves the conductivity of silica and reduces the volume change. Moreover, the carbon shell of polyphosphazene facilitated the formation of a stable solid electrolyte interface film (SEI), preventing direct contact between the active material and the electrolyte, thereby substantially enhancing lithium storage performance.

Abstract Background Glycerophospholipids (GPLs) are essential for cell membrane structure and function. Sphingomyelin and its metabolites regulate cell growth, apoptosis, and stress responses. This study aimed to investigate lipid metabolism in patients experiencing sudden sensorineural hearing loss across all frequencies (AF-SSNHL). Methods The study included 60 patients diagnosed with unilateral AF-SSNHL, among whom 30 patients had a level of hearing improvement ≥ 15 dB after 6 months of follow-up. A propensity score-matched (2:1) control group was used. Liquid chromatography‒mass spectrometry based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the lipids change. The “lipidome” R package and weighted gene co-expression network analysis (WGCNA) were utilised to assess the lipids’ structural features and the association between lipids and hearing. Results Lipidomics successfully differentiated the AF-SSNHL group from the control group, identifying 17 risk factors, mainly including phosphatidylcholine (PC), phosphatidylethanolamine (PE), and related metabolites. The ratios of lysophosphatidylcholine/PC, lysophosphatidylethanolamine/PE, and lysodimethylphosphatidylethanolamine/PE were upregulated, while some glycerophospholipid (GPL)-plasmalogens were downregulated in the AF-SSNHL group, indicating abnormal metabolism of GPLs. Trihexosylceramide (d34:1), PE (18:1e_22:5), and sphingomyelin (d40:3) were significantly different between responders and nonresponders, and positively correlated with hearing improvement. Additionally, the results of the WGCNA also suggested that partial GPL-plasmalogens were positively associated with hearing improvement. Conclusion AF-SSNHL patients exhibited abnormally high blood lipids and pronounced GPLs metabolic abnormalities. Sphingolipids and GPL-plasmalogens had an association with the level of hearing improvement. By understanding the lipid changes, clinicians may be able to predict the prognosis of hearing recovery and personalize treatment approaches.

Objective: Hashimoto’s thyroiditis is an inflammatory disease, and research suggests that a low-carbohydrate diet may have potential anti-inflammatory effects. This study aims to utilize Dixon-T2-weighted imaging (WI) sequence for a semi-quantitative assessment of the impact of a low-carbohydrate diet on the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Methods: Forty patients with Hashimoto’s thyroiditis were recruited for this study and randomly divided into two groups: one with a normal diet and the other with a low-carbohydrate diet. Antibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) were measured for all participants. Additionally, thyroid water content was semi-quantitatively measured using Dixon-T2WI. The same tests and measurements were repeated for all participants after 6 months. Results: After 6 months of a low-carbohydrate diet, patients with Hashimoto’s thyroiditis showed a significant reduction in thyroid water content (94.84 ± 1.57% vs 93.07 ± 2.05%, P < 0.05). Concurrently, a decrease was observed in levels of TPOAb and TgAb (TPOAb: 211.30 (92.63–614.62) vs 89.45 (15.9–215.67); TgAb: 17.05 (1.47–81.64) vs 4.1 (0.51–19.42), P < 0.05). In contrast, there were no significant differences in thyroid water content or TPOAb and TgAb levels for patients with Hashimoto’s thyroiditis following a normal diet after 6 months (P < 0.05). Conclusion: Dixon-T2WI can quantitatively assess the degree of thyroid inflammation in patients with Hashimoto’s thyroiditis. Following a low-carbohydrate diet intervention, there is a significant reduction in thyroid water content and a decrease in levels of TPOAb and TgAb. These results suggest that a low-carbohydrate diet may help alleviate inflammation in patients with Hashimoto’s thyroiditis.

Abstract The strain clamps and leading wires are important components that connect conductors on overhead transmission lines and conduct current. During operation, poor contact between these components can cause abnormal overheating, leading to electric failures and threatening power system reliability. Recently, the use of unmanned aerial vehicles equipped with infrared thermal imagers for strain clamp and leading wire maintenance has become increasingly popular. Deep learning‐based image recognition shows promising prospects for intelligent fault diagnosis of overheating faults. A pre‐treatment method is proposed based on dynamic histogram equalisation to enhance the contrast of infrared images. The DeepLab v3+ network, loss function, and existing networks with different backbones are compared. The DeepLab v3+ network with ResNet101 and convolutional block attention module added, and the Focal Loss function achieved the highest performance with an average pixel accuracy of 0.614, an average intersection over union (AIoU) of 0.567, an F1 score of 0.644, and a frequency weighted intersection over union of 0.594 on the test set. The optimised Atrous rates has increased the AIoU by 12.91%. Moreover, an intelligent diagnosis scheme for evaluating the defect state of the strain clamps and leading wires is proposed and which achieves a diagnostic accuracy of 91.0%.

Abstract Objective Fluorine‐18‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) is routinely used for presurgical evaluation in many epilepsy centers. Hypometabolic characteristics have been extensively examined in prior studies, but the metabolic patterns associated with specific pathological types of drug‐resistant epilepsy remain to be fully defined. This study was developed to explore the relationship between metabolic patterns or characteristics and surgical outcomes in type I and II focal cortical dysplasia (FCD) patients based on results from a large cohort. Methods Data from individuals who underwent epilepsy surgery from 2014 to 2019 with a follow‐up duration of over 3 years and a pathological classification of type I or II FCD in our hospital were retrospectively analyzed. Hypometabolic patterns were quantitatively identified via statistical parametric mapping (SPM) and qualitatively analyzed via visual examination of PET‐MRI co‐registration images. Univariate analyses were used to explore the relationship between metabolic patterns and surgical outcomes. Results In total, this study included data from 210 patients. Following SPM calculations, four hypometabolic patterns were defined including unilobar, multi‐lobar, and remote patterns as well as cases where no pattern was evident. In type II FCD patients, the unilobar pattern was associated with the best surgical outcomes (p = 0.014). In visual analysis, single gyrus (p = 0.032) and Clear‐cut hypometabolism edge (p = 0.040) patterns exhibited better surgery outcomes in the type II FCD group. Conclusions PET metabolic patterns are well‐correlated with the prognosis of type II FCD patients. However, similar correlations were not observed in type I FCD, potentially owing to the complex distribution of the epileptogenic region. Plain Language Summary In this study, we demonstrated that FDG‐PET was a crucial examination for patients with FCD, which was a common cause of epilepsy. We compared the surgical prognosis for patients with different hypometabolism distribution patterns and found that clear and focal abnormal region in PET was correlated with good surgical outcome in type II FCD patients.

Many studies have explored the effect of grouping and task distribution strategies in collaborative learning in the conventional condition, for example, grouping based on student's learning style, gender diversity, and motivation, but few studies have investigated the impact of heterogeneous grouping with mixed gender and ability factors and the distribution of roles and tasks on members' engagement and collaboration in the IVE environment. This study proposed external scripts that were composed of grouping strategies and distribution strategies. The former includes Mixed Gender and Ability Grouping (MGAG) and Mixed Gender Grouping (MGG), while the latter contains Role-based Task Distribution (RTD) and Freely Distribution (FD). The scripts serve as a heterogeneous grouping and distribution procedural guide for collaborative learning in an Immersive Virtual Environment (IVE), which has the potential to address issues such as homogeneous competencies, collaboration confusion, and conflict among group members to meet the needs of IVE-based collaborative learning. This study used a quasi-experimental research method to explore the effects of IVE-based collaborative learning on students. The results of the experiment which contained 77 junior high school participants from 2 classes showed that: (1) MGAG can stimulate students' motivation(d = 1.55); (2) RTD can improve students' engagement(d = 0.66) and reduce their cognitive load(d=-0.92); (3) There is no significant interaction between MGAG and RTD in motivation, engagement, and cognitive load. Therefore, the study recommends MGAG combined with RTD to be stressed in IVE-based collaborative learning.

Sensorineural hearing loss (SNHL) is the most common type of hearing loss worldwide. The primary mechanism is oxidative injury to the cochlea as a result of oxidative stress. Therefore, exploring antioxidant strategies is particularly important in addressing SNHL.Thioredoxin-interacting protein (TXNIP) is an upstream target of oxidative stress-induced damage, and the NOD-like receptor protein 3 (NLRP3) and NF-κB pathways may be the main downstream molecular pathways, but this has not been reported in SNHL. Therefore, we investigated the molecular mechanism and role of TXNIP in oxidative stress injury induced by H2O2 in the HEI-OC1 auditory cells. To induce oxidative stress, HEI-OC1 cells were treated with H2O2. The TXNIP expression was measured by western blotting and Immunofluorescence. Intracellular TXNIP was knocked down using small interfering RNAs (siRNAs). Cell viability was measured by CCK8, total intracellular reactive oxygen species (ROS) by DCFH-DA, mitochondrial ROS by Mito-SOX, NLRP3, pro-caspase-1, total p65 NF-κB, and phospho-p65 NF-κB expression were measured by western blotting. Statistical analyses were performed using one-way analysis of variance, and p

Abstract Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS‐associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high‐throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL‐1β/IL‐18 and the nucleotide oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome. Mechanically, RNA‐seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co‐IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase‐1/gasdermin D (GSDMD)‐mediated canonical pyroptosis through the P21‐activated kinase 4 (PAK4)/mitogen‐activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.

This study investigates the propagation of dark Alfvén solitons in low-β magnetized plasma using Hall-magnetohydrodynamic (Hall-MHD) numerical simulations. The rational solution of the nonlinear Schrödinger equation (NLSE) is presented, which is proposed as an effective tool for studying dark envelope solitons in plasma. Our results show a high degree of agreement between numerical simulations and analytical solutions derived from the NLSE via the reductive perturbation method. This agreement validates our modeling and computational approach. In addition, the simulations confirm the existence of dark Alfvén solitons in magnetized plasma. This work demonstrates the effectiveness of Hall-MHD simulations in studying complex plasma phenomena, contributing to the broader understanding of soliton propagation in plasma environments.

Objective: The purpose was to explore the effects of traditional and non-traditional lipid parameters on Sudden Sensorineural Hearing Loss (SSNHL). Methods: The study included 452 patients diagnosed with SSNHL, among whom 206 patients had a level of hearing improvement ≥10 dB after one month of follow-up. A propensity score-matched (2:1) control group was used. Conditional and unconditional logistic regression were used to analyze the risk factors for SSNHL. Results: Patients with SSNHL had a higher risk of concomitant hypertension and elevated atherosclerogenic lipid levels, with apolipoprotein B and apolipoprotein E identified as independent risk factors for the onset of SSNHL. Additionally, the Lipid Comprehensive Index (LCI) was an independent risk factor for the degree of hearing loss. A positive linear correlation was revealed between triglyceride, non-high-density lipoprotein cholesterol, atherogenic index, Castelli risk index, atherogenic index of plasma, LCI and hearing loss. However, no linear relationship was observed between hearing gain and any lipid parameters. When Total Cholesterol (TC) was in the range of borderline high, the treatment effect was the best. However, the statistical significance disappeared upon adjusting for confounding factors. Conclusion: Patients with SSNHL exhibited markedly dysregulated lipid metabolism. Elevated serum lipid levels may be a causative factor in auditory impairment and can influence the extent of hearing loss. Promptly improving cochlear microcirculation may benefit patients with borderline elevated TC. Level of evidence: 4.