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The therapeutic efficacy of lung adenocarcinoma (LUAD), the most prevalent histological subtype of primary lung cancer, remains inadequate, with accurate prognostic assessment posing significant challenges. This study sought to elucidate the prognostic significance of mitochondrial-related genes in LUAD through an integrative multi-omics approach, aimed at developing personalized therapeutic strategies. Utilizing transcriptomic and single-cell RNA sequencing (scRNA-seq) data, alongside clinical information from publicly available databases, we first applied dimensionality reduction and clustering techniques to the LUAD single-cell dataset, focusing on the subclassification of fibroblasts, epithelial cells, and T cells. Mitochondrial-related prognostic genes were subsequently identified using TCGA-LUAD data, and LUAD cases were stratified into distinct molecular subtypes through consensus clustering, allowing for the exploration of gene expression profiles and clinical feature distributions across subtypes. By leveraging an ensemble of machine learning algorithms, we developed an Artificial Intelligence-Derived Prognostic Signature (AIDPS) model based on mitochondrial-related genes and validated its prognostic accuracy across multiple independent datasets. The AIDPS model demonstrated robust predictive power for LUAD patient outcomes, revealing significant differences in responses to immunotherapy and chemotherapy, as well as survival outcomes between risk groups. Furthermore, we conducted comprehensive analyses of tumor mutation burden (TMB), immune microenvironment characteristics, and genome-wide association study (GWAS) data, providing additional insights into the mechanistic roles of mitochondrial-related genes in LUAD pathogenesis. This study not only offers a novel approach to improving prognostic assessments in LUAD but also establishes a strong foundation for the development of personalized therapeutic interventions.

CD8+ T cells play a central role in anti-tumor immunity. Naïve CD8+ T cells are active upon tumor antigen stimulation, and then differentiate into functional cells and migrate towards the tumor sites. Activated CD8+ T cells can directly destroy tumor cells by releasing perforin and granzymes and inducing apoptosis mediated by the death ligand/death receptor. They also secrete cytokines to regulate the immune system against tumor cells. Mitochondria are the central hub of metabolism and signaling, required for polarization, and migration of CD8+ T cells. Many studies have demonstrated that mitochondrial dysfunction impairs the anti-tumor activity of CD8+ T cells through various pathways. Mitochondrial energy metabolism maladjustment will cause a cellular energy crisis in CD8+ T cells. Abnormally high levels of mitochondrial reactive oxygen species will damage the integrity and architecture of biofilms of CD8+ T cells. Disordered mitochondrial dynamics will affect the mitochondrial number and localization within cells, further affecting the function of CD8+ T cells. Increased mitochondria-mediated intrinsic apoptosis will decrease the lifespan and quantity of CD8+ T cells. Excessively low mitochondrial membrane potential will cause the release of cytochrome c and apoptosis of CD8+ T cells, while excessively high will exacerbate oxidative stress. Dysregulation of mitochondrial Ca2+ signaling will affect various physiological pathways in CD8+ T cells. To some extent, mitochondrial abnormality in CD8+ T cells contributes to cancer development. So far, targeting mitochondrial energy metabolism, mitochondrial dynamics, mitochondria-mediated cell apoptosis, and other mitochondrial physiological processes to rebuild the anti-tumor function of CD8+ T cells has proved effective in some cancer models. Thus, mitochondria in CD8+ T cells may be a potential and powerful target for cancer treatment in the future.

Background Non-suicidal self-injury (NSSI) by adolescent patients with depression has become a serious public health problem. This cross-sectional study aims to identify subgroups of adolescents based on NSSI and explore the factors related to these subgroups. Methods The study recruited 326 in- and out-patient adolescents (263 girls and 63 boys) aged 12 to 18 years (mean = 14.7, SD = 1.6) who had self-injured in the past year. Latent class indicators included 12 NSSI variables, as well as suicidal ideation. Logistic regression examined associations between identified classes and related factors. Results In this study, two distinct subgroups were identified: a “high suicidal ideation NSSI group” (n = 129, 39.6%) and a “low suicidal ideation NSSI group” (n = 197, 60.4%). Depression (OR = 1.10; 95% CI, 1.05–1.16), female (OR = 2.01; 95% CI, 1.09–3.69), left-behind experience (OR = 2.08; 95% CI, 1.17–3.71), single-parent family (OR = 1.84; 95% CI, 1.11–3.04) and peer victimization (OR = 1.04; 95% CI, 1.02–1.05) increases the probability of belonging to the “high suicidal ideation NSSI group”. A high level of perceived social support (OR = 0.99; 95% CI, 0.97–0.99) was a protective factor towards NSSI. Conclusions This study identifies two subgroups of NSSI and the factors associated with each subgroup. The early identification of high-risk groups for major NSSI in adolescents diagnosed with depression is possible due to the identification of correlating factors. Different treatment plans can be developed for different subtypes of NSSI to improve the effectiveness of prevention and intervention, promoting the healthy physical and mental development of adolescents with depression.

Surgery is the common treatment for early lung cancer with multiple pulmonary nodules, but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas. In this study, we found that a combined treatment of local radiofrequency ablation (RFA) and melatonin (MLT) greatly improved clinical outcomes for early lung cancer patients with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas. Mechanically, as demonstrated in an associated mouse lung tumor model, RFA not only effectively remove treated tumors but also stimulate antitumor immunity, which could inhibit tumor growth in non-ablated areas. MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA. Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment, which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT. Analysis of residual tumor further revealed the depressed activity of MAPK, NF-kappa B, Wnt, and Hedgehog pathways and upregulated P53 pathway in tumors, which was in line with the inhibited tumor growth. Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy. These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules. Trial registration: www.chictr.org.cn , identifier ChiCTR2100042695, http://www.chictr.org.cn/showproj.aspx?proj=120931 .

Background Childhood and peer experiences can influence adolescents’ perceptions of interpersonal relationships, which can, in turn, influence their emotional states and behavior patterns. Non-suicidal self-injury (NSSI) is now a common problem behavior among adolescents. The present study examined the role of childhood trauma and peer victimization in adolescents’ NSSI. Methods A cross-sectional survey was conducted among 1783 adolescents (1464 girls and 318 boys) in the psychiatric outpatient clinics or wards of 14 psychiatric hospitals or general hospitals in nine provinces in China. Data were collected using the Multidimensional Peer Victimization Scale (MPVS), Short-form Childhood Trauma Questionnaire(CTQ-SF), and Functional Assessment of Self-Mutilation (FASM). Structural equation modeling (SEM) with latent variables was used to demonstrate the mediating role of peer victimization in the association between childhoodtrauma and NSSI. Results The SEM analysis demonstrated that peer victimization plays a partial mediating role in the relationship between childhood trauma and NSSI. In addition, several covariates (such as age, gender, education level, and place of residence) effectively regulated the relationship between peer victimization and NSSI. Conclusion In future studies of NSSI among Chinese adolescents, attention should be paid to the roles of childhood trauma and peer bullying; there is a temporal sequence between these two variables and, to some extent, childhood trauma can have an impact on bullying during adolescence which, in turn, influences NSSI behavior.

The overall incidence of cancer is increasing in recent years. Despite advances in various comprehensive treatments, the mortality of advanced malignant tumors remains at a high level. Numerous pharmacological studies have confirmed that many Chinese herbal medicines possess remarkable antitumor activities. Amygdalin, mainly existing in bitter almond, is reported to have antitumor properties in addition to the antioxidative, antibacterial, anti‐inflammatory and immunoregulatory activities. This article summarizes the structural characteristics of amygdalin, its antitumor mechanisms, and recent progress and achievement in the research of amygdalin, hoping that it could provide theoretical clues for exploring the clinical value of amygdalin against tumors. Amygdalin is known to have an antitumor effect in solid tumors such as lung cancer, bladder cancer and renal cell carcinoma by affecting cell cycle, inducing apoptosis and cytotoxicity, and regulating immune function. Further research is needed to elucidate the pharmacological mechanisms of amygdalin in terms of the optimal dosage, the feasibility of combined use of amygdalin with other antitumor drugs, and even artificial synthesis of the active components in amygdalin, for the sake of enhancing its antitumor activities and reducing its adverse effects for clinical use. Amygdalin is known to have an antitumor effect in solid tumors such as lung cancer, bladder cancer, and renal cell carcinoma by affecting cell cycle, inducing apoptosis and cytotoxicity, and regulating immune function. Further research is needed to elucidate the pharmacological mechanisms of amygdalin in terms of the optimal dosage, the feasibility of combined use of amygdalin with other antitumor drugs, and even artificial synthesis of the active components in amygdalin, for the sake of enhancing its antitumor activities and reducing its adverse effects for clinical use.

Ethylene oxide (EO) is a reactive epoxide. However, the association between EO exposure and the risk of developing asthma in humans is unknown. The aim of this study was to investigate the relationship between EO exposure and the risk of developing asthma in the general US population. In this cross-sectional study, data of 2542 patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016 were obtained and analyzed. Hemoglobin adducts of EO (HbEO) level be used as the main factor for predicting EO exposure. The association between the level of EO exposure and the risk of developing asthma was evaluated with logistic regression models and dose–response analysis curves of restricted cubic spline function. Mediation analysis and linear regression analysis were utilized to evaluate the association between EO exposure and inflammation indicators. According to the quartiles of HbEO level, the patients were divided into four groups. The results indicated that an increased HbEO level was associated with a higher risk of asthma onset. Compared with the lowest quartile, the odds ratio (OR) with the 95% confidence interval (CI) for the highest quartile was 1.960 (95% CI: 1.348–2.849, P  = 0.003). After being adjusted for numerous potential confounders, the OR of quartile 4 relative to quartile 1 was 1.991 (95% CI: 1.359–2.916, P  = 0.001). Consistent results were also obtained in most subgroup analyses and dose–response analysis curves. In addition, EO levels were positively correlated with the inflammatory indicators ( P  = 0.006 for WBC, P  = 0.015 for lymphocyte, and P  = 0.015 for neutrophil). This study revealed a positive correlation between the level of EO exposure and the risk of asthma in a representative US population. In addition, inflammatory response may prove to be a potential biological mechanism underlying EO-induced asthma.

Background Non-suicidal self-injury (NSSI) and suicide attempts (SAs) by adolescent patients with depression have become serious public health problems. There is still insufficient research evidence on the effects of NSSI and SAs on neurocognitive functioning in adolescents. Cognitive function alterations may be associated with SAs and self-injury. NSSI and SAs have different influencing factors. Methods Participants were recruited from outpatient clinics and included 142 adolescent patients with depression (12–18 years old). This cohort included the SAs group (n = 52), NSSI group (n = 65), and depression without SAs/NSSI control group (n = 25). All participants underwent a clinical interview and neuropsychological assessment for group comparisons, and post-hoc tests were performed. Finally, partial correlation analysis was used to explore factors related to changes in cognitive function. Results The SAs group performed significantly worse than the control group in executive function and working memory. The depression score was directly proportional to the executive function of the SAs group, whereas cognitive functioning in the NSSI group was associated with borderline traits and rumination. Conclusions These findings suggest that impairment of executive function and working memory may be a common pattern in adolescent depressed patients with SAs. However, borderline traits and rumination may be indicative of NSSI but not SAs.

Objective Major depressive disorder (MDD) is often accompanied by psychotic symptoms. However, few studies have examined the relationship between psychotic symptoms and endocrine factors in adolescent patients with MDD. Therefore, this study aimed to investigate the prevalence and related endocrine clinical factors of psychotic symptoms in Chinese adolescent patients with MDD. Methods In total, 601 patients (aged 12–18) with MDD were recruited. The Patient Health Questionnaire – 9 items (PHQ – 9) was utilized for assessing depressive symptoms. Psychotic symptoms were assessed through clinical interviews. Prolactin (PRL), thyroid-stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (FT3), thyroxine (T4), and free thyroxine (FT4) were also measured. Results The incidence of psychotic symptoms in adolescent patients with MDD was 22.6%. The findings demonstrated that age, self-harming behavior, PHQ-9 score, FT4, and normalized PRL were independently associated with psychotic symptoms in patients with MDD (All p  < 0.05). Conclusions PRL and FT4 levels are more likely to be abnormally elevated in major depressive adolescents with psychotic symptoms. Prolactin and thyroid hormones in patients with MDD should be paid more attention.

Background Non-suicidal self-injury (NSSI) is prevalent among adolescents. Adverse psychosocial factors (e.g., childhood trauma, peer bullying) and altered pain hyposensitivity are core risk factors for NSSI. These factors have been associated with structural changes in brain regions involved in pain processing, which may relate to differences in pain perception. However, the specific relationship between cortical structure and pain perception in NSSI adolescents remains unclear. This study aims to investigated cortical structure and structural covariance network alterations in NSSI adolescents, analyzing associations with pain sensitivity changes and adverse psychosocial factors. Method 44 NSSI adolescents and 37 healthy controls underwent MRI scans and clinical assessments. Cortical thickness (CT) and surface area (CSA) values per brain region were obtained for both groups and used to generate a structural covariance matrix. Group comparisons of cortical structure and network properties were performed, followed by correlation analyses integrating psychosocial questionnaires and pain sensitivity metrics. Results The NSSI group showed significantly reduced CT in the right cingulate isthmus cortex. This reduction negatively correlated with the severity of peer bullying and childhood trauma, as well as the bilateral pain tolerance. Regarding structural covariance networks, the NSSI group exhibited reduced global properties, alongside two key nodal alterations: a decrease in nodal betweenness centrality in the rostral left middle frontal gyrus (based on CT), which correlated with childhood trauma severity, and an increase in nodal degree centrality in the left lingual gyrus (based on CSA), which was associated with experiences of physical bullying. Conclusions This study revealed brain structure and structural network alterations in NSSI adolescents, linked to changed pain perception and adverse psychosocial factors. Our findings suggest associations between adverse psychosocial factors and altered pain perception in NSSI, which coincide with brain structural and network changes and may reflect heightened vulnerability to NSSI behavior. Trial registration Clinical trial number: not applicable.