Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis in a Murine Model.

OBJECTIVE: The aim of this study was to explore the pathogenesis of CLCN6-related disease and to assess whether its Cl-/H+-exchange activity is crucial for the biological role of ClC-6. METHODS: We performed whole-exome sequencing on a girl with development delay, intractable epilepsy, behavioral abnormities, retinal dysfunction, progressive brain atrophy, suggestive of neuronal ceroid lipofuscinoses (NCLs). We generated and analyzed the first knock-in mouse model of a patient variant (p.E200A) and compared it with a Clcn6-/- mouse model. Additional functional tests were performed with heterologous expression of mutant ClC-6. RESULTS: We identified a de novo heterozygous p.E200A variant in the proband. Expression of disease-causing ClC-6E200A or ClC-6Y553C mutants blocked autophagic flux and activated transcription factors EB (TFEB) and E3 (TFE3), leading to autophagic vesicle and cholesterol accumulation. Such alterations were absent with a transport-deficient ClC-6E267A mutant. Clcn6E200A/+ mice developed severe neurodegeneration with typical features of NCLs. Mutant ClC-6E200A, but not loss of ClC-6 in Clcn6-/- mice, increased lysosomal biogenesis by suppressing mTORC1-TFEB signaling, blocked autophagic flux through impairing lysosomal function, and increased apoptosis. Carbohydrate and lipid deposits accumulated in Clcn6E200A/+ brain, while only lipid storage was found in Clcn6-/- brain. Lysosome dysfunction, autophagy defects, and gliosis were early pathogenic events preceding neuron loss. INTERPRETATION: CLCN6 is a novel genetic cause of NCLs, highlighting the importance of considering CLCN6 mutations in the diagnostic workup for molecularly undefined forms of NCLs. Uncoupling of Cl- transport from H+ countertransport in the E200A mutant has a dominant effect on the autophagic/lysosomal pathway. ANN NEUROL 2024;96:608-624.

Enzymatically Mediated In Situ Generation of Z-Scheme Bi2S3/Bi2MoO6 Heterojunction-Based Organic Photoelectrochemical Transistor for METTL3/METTL14 Detection.

The OPECT biosensing platform, which connects optoelectronics and biological systems, offers significant amplification and more possibilities for research in biological applications. In this work, a homogeneous organic photoelectrochemical transistor (OPECT) biosensor based on a Bi2S3/Bi2MoO6 heterojunction was constructed to detect METTL3/METTL14 protein activity. The METTL3/METTL14 complex enzyme was used to catalyze adenine (A) on an RNA strand to m6A, protecting m6A-RNA from being cleaved by an E. coli toxin (MazF). Alkaline phosphatase (ALP) catalyzed the conversion of Na3SPO3 to H2S through an enzymatic reaction. Due to the adoption of the strategy of no fixation on the electrode, the generated H2S was easy to diffuse to the surface of the ITO electrode. The Bi2S3/Bi2MoO6 heterojunction was formed in situ through a chemical replacement reaction with Bi2MoO6, improving photoelectric conversion efficiency and realizing signal amplification. Based on this "signal on" mode, METTL3/METTL14 exhibited a wide linear range (0.00001-25 ng/µL) between protein concentration and photocurrent intensity with a limit of detection (LOD) of 7.8 fg/µL under optimal experimental conditions. The applicability of the developed method was evaluated by investigating the effect of four plasticizers on the activity of the METTL3/METTL14 protein, and the molecular modeling technique was employed to investigate the interaction between plasticizers and the protein.

Ultrahigh precision laser nanoprinting based on defect-compensated digital holography for fast-fabricating optical metalenses.

The 3D structured light field manipulated by a digital-micromirror-device (DMD)-based digital hologram has demonstrated its superiority in fast-fabricating stereo nanostructures. However, this technique intrinsically suffers from defects of light intensity in generating modulated focal spots, which prevents from achieving high-precision micro/nanodevices. In this Letter, we have demonstrated a compensation approach based on adapting spatial voxel density for fabricating optical metalenses with ultrahigh precision. The modulated focal spot experiences intensity fluctuations of up to 3% by changing the spatial position, leading to a 20% variation of the structural dimension in fabrication. By altering the voxel density to improve the uniformity of the laser cumulative exposure dosage over the fabrication region, we achieved an increased dimensional uniformity from 94.4% to 97.6% in fabricated pillars. This approach enables fast fabrication of metalenses capable of sub-diffraction focusing of 0.44λ/NA with the increased mainlobe-sidelobe ratio from 1:0.34 to 1:0.14. A 6 × 5 supercritical lens array is fabricated within 2 min, paving a way for the fast fabrication of large-scale photonic devices.

Causal Effects of Asthma on Upper Airway Diseases and Allergic Diseases: A Two-Sample Mendelian Randomization.

INTRODUCTION: Asthma is associated with upper airway diseases and allergic diseases; however, the causal effects need to be investigated further. Thus, we performed this two-sample Mendelian randomization (MR) analysis to explore and measure the causal effects of asthma on allergic rhinitis (AR), vasomotor rhinitis (VMR), allergic conjunctivitis (AC), atopic dermatitis (AD), and allergic urticaria (AU). METHODS: The data for asthma, AR, VMR, AC, AD, and AU were obtained from large-scale genome-wide association studies summarized recently. We defined single-nucleotide polymorphisms satisfying the MR assumptions as instrumental variables. Inverse-variance weighted (IVW) approach under random-effects was applied as the dominant method for causal estimation. The weighted median approach, MR-Egger regression analysis, MR pleiotropy residual sum and outlier test, and leave-one-out sensitivity analysis were performed as sensitivity analysis. Horizontal pleiotropy was measured using MR-Egger regression analysis. Significant causal effects were attempted for replication and meta-analysis. RESULTS: We revealed that asthma had causal effects on AR (IVW, odds ratio [OR] = 1.93; 95% confidence interval [CI], 1.74-2.14; p < 0.001), VMR (IVW, OR = 1.40; 95% CI, 1.15-1.71; p < 0.001), AC (IVW, OR = 1.65; 95% CI, 1.49-1.82; p < 0.001), and AD (IVW, OR = 2.13; 95% CI, 1.82-2.49; p < 0.001). No causal effect of asthma on AU was observed. Sensitivity analysis further assured the robustness of these results. The evaluation of the replication stage and meta-analysis further confirmed the causal effect of asthma on AR (IVW OR = 1.81, 95% CI 1.62-2.02, p < 0.001), AC (IVW OR = 1.44, 95% CI 1.11-1.87, p < 0.001), and AD (IVW OR = 1.85, 95% CI 1.42-2.41, p < 0.001). CONCLUSIONS: We revealed and quantified the causal effects of asthma on AR, VMR, AC, and AD. These findings can provide powerful causal evidence of asthma on upper airway diseases and allergic diseases, suggesting that the treatment of asthma should be a preventive and therapeutic strategy for AR, VMR, AC, and AD.

Severity Identification of Graves Orbitopathy via Random Forest Algorithm.

This study aims to establish a random forest model for detecting the severity of Graves Orbitopathy (GO) and identify significant classification factors. This is a hospital-based study of 199 patients with GO that were collected between December 2019 and February 2022. Clinical information was collected from medical records. The severity of GO can be categorized as mild, moderate-to-severe, and sight-threatening GO based on guidelines of the European Group on Graves' orbitopathy. A random forest model was constructed according to the risk factors of GO and the main ocular symptoms of patients to differentiate mild GO from severe GO and finally was compared with logistic regression analysis, Support Vector Machine (SVM), and Naive Bayes. A random forest model with 15 variables was constructed. Blurred vision, disease course, thyroid-stimulating hormone receptor antibodies, and age ranked high both in mini-decreased gini and mini decrease accuracy. The accuracy, positive predictive value, negative predictive value, and the F1 Score of the random forest model are 0.83, 0.82, 0.86, and 0.82, respectively. Compared to the three other models, our random forest model showed a more reliable performance based on AUC (0.85 vs. 0.83 vs. 0.80 vs. 0.76) and accuracy (0.83 vs. 0.78 vs. 0.77 vs. 0.70). In conclusion, this study shows the potential for applying a random forest model as a complementary tool to differentiate GO severity.

Architecting N-doped Carbon Nanotube-Rich Carbon Nanofibers with Biomimetic Vine-Leaf-Whisker Structure as Robust Bifunctional Electrocatalysts for Rechargeable Zn-Air Batteries.

Efficient and durable bifunctional catalysts toward oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are urgently desirable but challenging for rechargeable Zn-air batteries (ZABs), especially flexible wearable ZABs. Inspired by the vine-leaf-whisker structure in nature, we proposed a three-dimensional (3D) hierarchical bifunctional catalyst (denoted as Co-Fe-Zn@N-CNT/CNF) consisting of N-doped carbon nanotubes embedded with abundant CoFe alloy nanoparticles, leaf-shaped N-doped carbon nanoflakes, and porous carbon fibers for rechargeable ZABs. The special biomimetic structure provides a large specific surface area, allowing for high exposure of the active site and ensuring fast mass transport/charge transfer. The close combination of CoFe bimetallic alloys and N-doped carbon nanotubes delivers high electrocatalytic activity, while the coexistence of various active sites such as metal nanoparticles (NPs), metal-Nx, doped N species, and their synergistic interactions endows the catalysts with more active sites. As such, the Co-Fe-Zn@N-CNT/CNF catalyst achieves superior bifunctional catalytic activities for the ORR (a half-wave potential of 0.84 V) and the OER (an overpotential of 326 mV at 10 mA cm-2) in alkaline media, comparable to commercial Pt/C and RuO2. Remarkably, both aqueous and solid-state ZABs assembled with Co-Fe-Zn@N-CNT/CNF catalysts as air electrodes demonstrate excellent charging/discharging performance, high peak power density, and robust long-term cycling stability. More interestingly, the flexible ZAB performs well even under bending conditions, displaying satisfactory device stability and mechanical flexibility. This study presents a new collective morphological-composition-structural engineering strategy for exploiting the efficient bifunctional oxygen electrocatalysts, which is of great significance for high-performance rechargeable ZABs and wearable energy storage devices.

Efficacy and safety of ongericimab given by prefilled syringe or autoinjector in primary hypercholesterolemia and mixed hyperlipidemia.

BACKGROUND AND AIMS: Limited evidence exist regarding the association between ongericimab, a novel recombinant humanized anti-PCSK9 monoclonal antibody, and primary hypercholesterolemia and mixed dyslipidemia. This study aimed to evaluate the efficacy and safety of ongericimab administered by prefilled syringe (PFS) or autoinjector (AI) in Chinese patients with primary hypercholesterolemia and mixed dyslipidemia on stable optimized lipid-lowering therapy. METHODS AND RESULTS: A total of 255 patients on stable optimized lipid-lowering therapy were randomized in a 2:1:2:1 ratio to receive PFS for the subcutaneous injection of ongericimab 150 mg every 2 weeks (Q2W) or a matching placebo, or AI for the subcutaneous injection of ongericimab 150 mg Q2W or a matching placebo. The primary efficacy endpoint was the percent change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Safety was also evaluated. At week 12, the least squares mean percent changes were -72.7% (3.9%) for PFS and -71.1% (3.8%) for AI (all P < 0.001) compared to respective matching placebo groups. Beneficial effects were also seen for all secondary lipid parameters, notably with robust reduction in Lp (a). Treatment-emergent adverse events (TEAEs) and serious AEs with ongericimab were reported in 46.2% and 2.4% of patients, compared to 44.2% and 3.5% with placebo. CONCLUSION: In Chinese patients with primary hypercholesterolemia and mixed dyslipidemia, a 12-week treatment regimen with ongericimab administered by PFS or AI significantly reduced LDL-C and other lipid parameters, proving to be safe and well tolerated. Patients experienced consistent effects from PFS or AI devices. CLINICAL TRIAL REGISTRATION: CTR20220027; January 11, 2022; http://www.chinadrugtrials.org.cn/index.html.

Three-dimensional soft tissue reconstruction and volume measurement used for the diagnosis of dysthyroid optic neuropathy.

PURPOSE: Dysthyroid optic neuropathy (DON) leads to vision loss. This study aimed to investigate a new method that can directly evaluate the change in muscle cone inner volume (MCIV) and distinguish DON orbits from non-DONs. MATERIALS AND METHODS: This study included 54 patients (108 orbits) who were diagnosed with thyroid eye disease and treated at the Beijing Tongren Hospital between December 2019 and September 2021. The extraocular muscle volume (EOMV), orbital fat volume (OFV), and bony orbit volume (BOV) of the patients were measured using three-dimensional reconstruction. MCIV was measured using artificially defined boundaries. The associations between these volumes and clinical indicators were studied, and the diagnostic efficacy of these volumes for DON was described using receiver operating characteristic (ROC) curves. RESULTS: The ROC curve showed that the area under the curve of MCIV/BOV (%) combined with EOMV/BOV (%) reached 0.862 (p < 0.001), with a sensitivity of 85.7% and a specificity of 76.1%. CONCLUSION: The combination of MCIV/BOV (%) and EOMV/BOV (%) is a good indicator for the diagnosis of DON, which aids in the early detection and intervention of DON.

Work-family conflict among primary health workers during the COVID-19 pandemic: Its mediating role in the relationship between workload and job burnout.

AIMS AND OBJECTIVES: This study explores the situation of workload, work-family conflict and job burnout among primary health workers in China in the context of COVID-19 and identifies the mediating effect of work-family conflict between workload and job burnout. BACKGROUND: Since the breakout of the COVID-19 pandemic, primary health workers have been working on the frontline of the epidemic and may experience increasing workload, work-family conflict and job burnout. It is important to focus on the issue of how to alleviate job burnout of primary health workers. DESIGN: A cross-sectional study (STROBE) was used. METHODS: Data were collected from 785 primary health workers in China. Multiple regression analysis was used to examine the mediating effect of work-family conflict between workload and job burnout. RESULTS: 18.7%, 10.4% and 39.5% of respondents had high job burnout in the dimensions of emotional exhaustion, depersonalization and personal accomplishment, respectively. 34.6% of the respondents had high or very high workload, and 12.8% of the respondents had high or very high work-family conflict. Results of multiple regression analysis indicated that work-family conflict mediated the relationship between workload and job burnout. Workload (ß = .163, CI = .207-.549) and work-family conflict (ß = .211, CI = .311-.640) positively influenced job burnout, and workload (ß = .428, CI = .375-.508) positively influenced work-family conflict. CONCLUSION: The study indicated that primary health workers experienced a high level of job burnout, especially in the personal accomplishment dimension. Furthermore, this study verified the mediating effect of work-family conflict between workload and job burnout. RELEVANCE TO CLINICAL PRACTICE: Some interventions for alleviating workload, work-family conflict and job burnout should be taken, including workplace assistance programmes, family-friendly policies and a well-integrated healthcare system. NO PATIENT OR PUBLIC CONTRIBUTION: This study does not involve patient or public contribution in any part. IMPACT STATEMENT: Nurses and other primary health workers are health gatekeepers of residents and play a vital role in the healthcare system. Due to the breakout of COVID-19, they have taken more work and are more vulnerable to work overload, work-family conflict and the consequent job burnout. Some interventions should be taken to effectively alleviate their job burnout and improve their health and performance.

[Multi-Voiced Narrative of Home-Based Palliative Care:Report of One Case].

Terminally ill patients face multiple difficulties in home care.Home-based palliative care adhering to the concept of whole-person,whole-family,whole-team,and whole-course care is able to meet the needs of terminally ill patients and their families.In this paper,we reported the care history and home-based palliative care process of a patient with end-stage breast tumor and summarized the experience,aiming to provide reference for the future work of home-based palliative care.

Effect of the OPHN1 novel variant c.1025+1 G>A on RNA splicing: insights from a minigene assay.

This research analyzes the clinical data, whole-exome sequencing results, and in vitro minigene functional experiments of a child with developmental delay and intellectual disability. The male patient, aged 4, began experiencing epileptic seizures at 3 months post-birth and has shown developmental delay. Rehabilitation training was administered between the ages of one and two. There were no other significant family medical histories. Through comprehensive family exome genetic testing, a hemizygous variant in the 11th exon of the OPHN1 gene was identified in the affected child: c.1025 + 1G > A. Family segregation analysis confirmed the presence of this variant in the patient's mother, which had not been previously reported. According to the ACMG guidelines, this variant was classified as a likely pathogenic variant. In response to this variant, an in vitro minigene functional experiment was designed and conducted, confirming that the mutation affects the normal splicing of the gene's mRNA, resulting in a 56 bp retention on the left side of Intron 11. It was confirmed that OPHN1: c.1025 + 1G > A is the pathogenic cause of X-linked intellectual disabilities in the child, with clinical phenotypes including developmental delay and seizures.

A case of primary pulmonary angiosarcoma arising from tuberculous scar with fatal capillary bleeding.

The etiology of primary pulmonary angiosarcoma is still unknown. Here we report a case of primary pulmonary angiosarcoma originated from a tuberculous scar and presented as aggressive deterioration with uncontrolled bleeding from capillaries with angiodysplasia.

The Effect of Servant Leadership on Work Engagement: The Role of Employee Resilience and Organizational Support.

Employees suffer from low resources in the workplace because of multiple work roles in project-based organization (PBO). Based on the conservation of resources theory (COR), this study identifies both employee resilience and organizational support as critical personal and job resources. It then examines how servant leadership enhances employee work engagement in PBO through the mediating roles of employee resilience and organizational support. This study uses a questionnaire-based quantitative research design to collect data from 437 employees in PBO. The collected data were analyzed by partial least squares structural equation modeling (PLS-SEM) to test hypotheses. The research findings indicate that servant leadership positively affects work engagement. Additionally, the relationship between servant leadership and work engagement is mediated by employee resilience and organizational support. This study deepens the understanding of how servant leadership promotes work engagement in PBO by providing personal and job resources. The findings deepen our understanding of how servant leadership enhances work engagement in PBO. The findings also provide implications for PBO to enhance sustainable well-being at work and organizational productivity.

A Study on the Effect and Suppression of Hydrogen Permeation Behavior on the Friction Characteristics of PEEK/PTFE Composites via Molecular Dynamics Simulation.

To research the effect of hydrogen permeation on the friction characteristics of the seal materials on the hydrogen equipment, the molecular models of 10% PEEK/PTFE composites and its frictional models were established, respectively, and molecular dynamics (MDs) and giant canonical Monte Carlo (GCMC) methods were used to simulate the diffusion coefficient, dissolution coefficient and permeability coefficient of the hydrogen in PEEK/PTFE composites. The effect of a different amount of hydrogen on the friction and wear of PEEK/PTFE composites was also studied. The results showed that few permeations of the hydrogen gas mainly demonstrated having a positive effect on the surface of the PEEK/PTFE composites, and the wear rate of the PEEK/PTFE composites showed a slight decreasing trend. The wear rate of the PEEK/PTFE composites gradually decreased when more hydrogen molecules penetrated the matrix. With the further penetration of the hydrogen molecules, the wear rate and friction coefficient of the PEEK/PTFE composites rapidly increased, showing a negative effect. With the further penetration of the hydrogen molecule, the friction coefficient of the composite displayed a small fluctuation and then a rapid decreasing trend. Meanwhile, effective improvement measures were proposed, and the introduction of the graphene was verified to be effective to reduce the negative effect of the hydrogen permeation, thereby improving the friction performance of the PEEK/PTFE composites.

Potential molecular mechanism of exercise reversing insulin resistance and improving neurodegenerative diseases.

Neurodegenerative diseases are debilitating nervous system disorders attributed to various conditions such as body aging, gene mutations, genetic factors, and immune system disorders. Prominent neurodegenerative diseases include Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Insulin resistance refers to the inability of the peripheral and central tissues of the body to respond to insulin and effectively regulate blood sugar levels. Insulin resistance has been observed in various neurodegenerative diseases and has been suggested to induce the occurrence, development, and exacerbation of neurodegenerative diseases. Furthermore, an increasing number of studies have suggested that reversing insulin resistance may be a critical intervention for the treatment of neurodegenerative diseases. Among the numerous measures available to improve insulin sensitivity, exercise is a widely accepted strategy due to its convenience, affordability, and significant impact on increasing insulin sensitivity. This review examines the association between neurodegenerative diseases and insulin resistance and highlights the molecular mechanisms by which exercise can reverse insulin resistance under these conditions. The focus was on regulating insulin resistance through exercise and providing practical ideas and suggestions for future research focused on exercise-induced insulin sensitivity in the context of neurodegenerative diseases.

Updates on mouse models of Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial AD (FAD) patients. Newer generations of mouse models through knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, have been developed for both familial and sporadic AD risk genes with the hope to more accurately model proteinopathies without over-expression of human AD genes in mouse brains. In this review, we summarized the phenotypes of a few commonly used as well as newly developed mouse models in translational research laboratories including the presence or absence of key pathological features of AD such as amyloid and tau pathology, synaptic and neuronal degeneration as well as cognitive and behavior deficits. In addition, advantages and limitations of these AD mouse models have been elaborated along with discussions of any sex-specific features. More importantly, the omics data from available AD mouse models have been analyzed to categorize molecular signatures of each model reminiscent of human AD brain changes, with the hope to guide future selection of most suitable models for specific research questions to be addressed in the AD field.

Elevated Saliva Pepsin Concentration as a Risk Factor for Asthma in Children with Allergic Rhinitis: A Preliminary Study.

Objective: This study aimed to explore whether saliva pepsin concentration (SPC) could be regarded as a risk factor for the occurrence and unfavorable control of asthma in children with allergic rhinitis. Methods: A prospective study was conducted on a group of 20 consecutive children newly diagnosed with allergic rhinitis and asthma (referred to as the asthma group). All these children underwent fractional exhaled nitric oxide (FeNO) measurement, lung function tests, and assessment of asthma control using the 7-item Childhood Asthma Control Test (C-ACT) score. Simultaneously, a control group consisting of 20 children with simple allergic rhinitis, matched for baseline characteristics, was included. SPC measurement was performed in the two groups. Results: The SPC value was significantly higher in the asthma group than that in the control group (165.0 ± 82.8 ng/mL vs 68.4 ± 34.5 ng/mL) (P < 0.001). In the asthma group, SPC was independently associated with FeNO, the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), and forced expiratory flow at 50% and 75% of FVC (FEF50 and FEF75) (all P < 0.05). The severity of nasal symptoms evaluated by the visual analogue scale (N-VAS) was independently associated with FEF75, the maximal mid-expiratory flow (MMEF), and C-ACT score (P < 0.05). Conclusion: Direct pepsin exposure and uncontrolled nasal symptoms may play crucial roles in the pathogenesis and progression of childhood allergic asthma. The SPC value can be considered as a risk factor for asthma in children with allergic rhinitis.

MIF: Multi-Shot Interactive Fusion Model for Cancer Survival Prediction Using Pathological Image and Genomic Data.

Accurate cancer survival prediction is crucial for oncologists to determine therapeutic plan, which directly influences the treatment efficacy and survival outcome of patient. Recently, multimodal fusion-based prognostic methods have demonstrated effectiveness for survival prediction by fusing diverse cancer-related data from different medical modalities, e.g., pathological images and genomic data. However, these works still face significant challenges. First, most approaches attempt multimodal fusion by simple one-shot fusion strategy, which is insufficient to explore complex interactions underlying in highly disparate multimodal data. Second, current methods for investigating multimodal interactions face the capability-efficiency dilemma, which is the difficult balance between powerful modeling capability and applicable computational efficiency, thus impeding effective multimodal fusion. In this study, to encounter these challenges, we propose an innovative multi-shot interactive fusion method named MIF for precise survival prediction by utilizing pathological and genomic data. Particularly, a novel multi-shot fusion framework is introduced to promote multimodal fusion by decomposing it into successive fusing stages, thus delicately integrating modalities in a progressive way. Moreover, to address the capacity-efficiency dilemma, various affinity-based interactive modules are introduced to synergize the multi-shot framework. Specifically, by harnessing comprehensive affinity information as guidance for mining interactions, the proposed interactive modules can efficiently generate low-dimensional discriminative multimodal representations. Extensive experiments on different cancer datasets unravel that our method not only successfully achieves state-of-the-art performance by performing effective multimodal fusion, but also possesses high computational efficiency compared to existing survival prediction methods.

Perceived Social Support and Experiential Avoidance in Adolescents: A Moderated Mediation Model of Individual Relative Deprivation and Subjective Social Class.

Based on the integration of ecological systems theory and the risk and protective factor model, the current study tested whether individual relative deprivation mediated the association between perceived social support and adolescents' experiential avoidance and whether this mediation model was moderated by subjective social class. A sample of 582 senior high school students in China participated in the current survey. The results indicated that perceived social support was negatively related to the students' experiential avoidance. Mediation analysis showed a significant indirect effect of perceived social support on experiential avoidance, via individual relative deprivation. Moreover, the mediation effect of individual relative deprivation was moderated by subjective social class. Specifically, the negative relationship between perceived social support and individual relative deprivation, and the direct relationship between perceived social support and experiential avoidance were stronger for adolescents with low subjective social class. In contrast, the positive relationship between individual relative deprivation and experiential avoidance was stronger for adolescents with high subjective social class.

A novel signature constructed by mitochondrial function and cell death-related gene for the prediction of prognosis in bladder cancer.

Bladder urothelial carcinoma (BLCA) presents a persistent challenge in clinical management. Despite recent advancements demonstrating the BLCA efficacy of immune checkpoint inhibitors (ICI) in BLCA patients, there remains a critical need to identify and expand the subset of individuals who benefit from this treatment. Mitochondria, as pivotal regulators of various cell death pathways in eukaryotic cells, exert significant influence over tumor cell fate and survival. In this study, our objective was to investigate biomarkers centered around mitochondrial function and cell death mechanisms to facilitate prognostic prediction and guide therapeutic decision-making in BLCA. Utilizing ssGSEA and LASSO regression, we developed a prognostic signature termed mitochondrial function and cell death (mtPCD). Subsequently, we evaluated the associations between mtPCD score and diverse clinical outcomes, including prognosis, functional pathway enrichment, immune cell infiltration, immunotherapy response analysis and drug sensitivity, within high- and low-risk subgroups. Additionally, we employed single-cell level functional assays, RT-qPCR, and immunohistochemistry to validate the differential expression of genes comprising the mtPCD signature. The mtPCD signature comprises a panel of 10 highly influential genes, strongly correlated with survival outcomes in BLCA patients and exhibiting robust predictive capabilities. Importantly, individuals classified as high-risk according to mtPCD score displayed a subdued overall immune response, characterized by diminished immunotherapeutic efficacy. In summary, our findings highlight the development of a novel prognostic signature, which not only holds promise as a biomarker for BLCA prognosis but also offers insights into the immune landscape of BLCA. This paradigm may pave the way for personalized treatment strategies in BLCA management.