Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Hypoxia-related diseases,such as altitude sickness,acute lung injury,and heart failure,have emerged as significant public health challenges worldwide and are strongly associated with increased mortality risks.These conditions tend to cause functional impairment and structural alterations in multiple organs,primarily due to inadequate oxygen supply or the inability of tissues to utilize oxygen effectively.To elucidate the pathophysiological mechanisms underlying hypoxia-associated diseases and to explore potential therapeutic strategies,researchers have employed animal models to conduct extensive mechanistic studies and drug development trials.In this review,we provide a comprehensive overview of the methods used to construct animal models for various hypoxia-related diseases.We made a thorough evaluation of the strengths,weaknesses,limitations,and applicability of each approach.In particular,we focus on modeling strategies for key pathologies such as altitude sickness,acute lung injury,pulmonary hypertension,and heart failure,discussing their respective advantages and restrains.Furthermore,we examined the potential application of gene editing technologies in optimizing animal models,especially its role in enhancing the accuracy and reproducibility of the models.The integration of these advanced technologies holds great promise for developing animal models with improved specificity and simulation of key features of diseases,which will serve as a solid foundation for basic research,drug screening,and preclinical trials concerning hypoxia-related diseases.Herein,we present a systematic summary and future outlook of animal models for hypoxia-related diseases,ultimately providing theoretical support for developing clinical treatment strategies and improving patient outcomes.

Objective:To summarize the clinical characteristics of focal cerebral arteriopathy (FCA) in children, and to analyze its influencing factor of prognosis.Methods:A retrospective cohort study was conducted. Clinical data from 40 children with FCA who were hospitalized at the Department of Neurology, Beijing Children′s Hospital, Capital Medical University, from September 2015 to August 2024 were collected. A centralized follow-up was conducted in October 2024 via outpatient clinics or the internet. The pediatric stroke outcome measure (PSOM) was used to evaluate their outcomes. Based on the PSOM, the children were further divided into a group with normal neurological function and another group with abnormal neurological function. Differences between groups were analyzed using the Mann-Whitney U test and Fisher exact test. Univariate Logistic regression analysis was performed to identify the influencing factors for neurological outcomes in children with FCA. Results:A total of 40 children were included, with 20 males and 20 females, and the onset age of 9.2 (6.8, 12.5) years. Among them, 12 cases (30%) had a history of varicella within 1 year before onset. There were 23 cases (58%) presenting with transient ischemic attack (TIA) or recurrent fluctuating symptoms of onset, while 3 cases (8%) developed progressive stroke within the first month of onset. The M1 segment of the middle cerebral artery was the most commonly affected vascular site, with a total of 16 cases (40%). Arterial occlusion occurred in 8 cases (20%). Lumbar puncture was completed in 36 children, and white blood cell counts in cerebrospinal fluid was increased in 6 cases. All 23 patients who completed magnetic resonance vessel wall imaging (VWI) showed circular enhancement of the arterial wall. A total of 28 patients (70%) received antiplatelet or anticoagulation therapy, and 16 patients (40%) received hormone therapy. At admission, the pediatric National Institute of Health Stroke Scale (PedNIHSS) score was 6.0 (2.0, 8.8) points, which decreased to 0.5 (0, 3.0) points at discharge. The follow-up duration was 1.6 (0.8, 4.9) years, with 1 case lost to follow-up. There was 1 case presenting with recurrence course manifesting as TIA. Among the 39 cases who completed the follow-up, 23 cases (59%) were assessed as neurologically normal by PSOM, while 16 cases (41%) were assessed as neurologically abnormal. Among the 29 cases who completed the imaging review, magnetic resonance angiography (MRA) review in 23 cases indicated stability or improvement in the original arterial stenosis, with 6 cases experiencing transient worsening of arterial stenosis early in the disease course (within 2 months), which later improved. Arterial stenosis progression occurred in 6 cases at the final review of 29 cases who completed the imaging review, with 1 case developing progressive cerebral arteriopathy. The proportion of patients with headache, altered consciousness, and aphasia in the abnormal neurological function group, as well as the PedNISS scores at admission and discharge, were all higher than those in the normal neurological function group (all P<0.05). Univariate Logistic regression analysis revealed that only a PedNISS score>6 points at onset was an influencing factor for abnormal neurological function ( OR=20.58, 95% CI 3.93-107.70, P<0.001). Conclusions:Childhood FCA often presents with fluctuating onset, and the proximal segment of the middle cerebral artery is frequently affected. Progression of arterial stenosis is common within 2 months of the disease course, but clinical progression and new ischemic lesions are uncommon. Most patients have a favorable long-term prognosis. PedNIHSS score>6 points at admission is related to abnormal neurological function outcomes.

In recent years，with the increase in environmental pollution，organisms are exposed to more internal and external oxidative stress factors than ever before.Nuclear factor erythroid 2-related factor 2（nuclear factor erythroid 2-related factor 2，NRF2），as a core transcription factor in response to oxidative stress，maintains cellular redox homeostasis by inducing the expression of various antioxidant factors.The nasal cavity，as the "gateway" of the respiratory tract，is often accompanied by oxidative stress（oxidative stress，OS）damage，leading to the occurrence of allergic rhinitis（allergic rhinitis，AR）.Recent studies have revealed some associations between the NRF2 signaling pathway and the mechanism of AR development.Activation of NRF2 provides a potential protective effect against AR，and some natural NRF2 activators have shown therapeutic potential in clinical experiments.Therefore，this article briefly reviews the relationship between NRF2 and AR，aiming to provide a new therapeutic target and perspective for the treatment of AR.
NF-E2-Related Factor 2/metabolism* ; Humans ; Rhinitis, Allergic/metabolism* ; Signal Transduction ; Oxidative Stress

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Early correction of childhood malocclusion is timely managing morphological, structural, and functional abnormalities at different dentomaxillofacial developmental stages. The selection of appropriate imaging examination and comprehensive radiological diagnosis and analysis play an important role in early correction of childhood malocclusion. This expert consensus is a collaborative effort by multidisciplinary experts in dentistry across the nation based on the current clinical evidence, aiming to provide general guidance on appropriate imaging examination selection, comprehensive and accurate imaging assessment for early orthodontic treatment patients.
Humans ; Malocclusion/diagnostic imaging* ; Child ; Consensus

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective:To explore the impact and underlying mechanisms of social support on illness uncertainty among parents of children with autism.Methods:A convenience sample of 312 parents of children with autism was recruited from the outpatient clinic of Peking University Sixth Hospital between September 2023 and January 2024. Data were collected using a general information questionnaire, the Chinese version of the Parent's Perception Uncertainty Scale (PPUS), the Social Support Scale for Families with Children with Autism, the Generalized Anxiety Disorder-7 (GAD-7), and the Questionnaire on Caregiving Issues and Service Needs of Parents of Children with Autism. Independent samples t-tests or one-way ANOVA were used to compare illness uncertainty scores across different characteristics. Pearson correlation analysis examined relationships among illness uncertainty, social support, caregiving issues and service needs, and anxiety. Chain mediation analysis was conducted using the SPSS macro PROCESS v4.1 to test the mediating roles of caregiving issues and service needs and anxiety. Results:The illness uncertainty score of the 307 valid respondents was (82.40±14.09). Mediation analysis indicated a direct effect of social support on illness uncertainty (effect value=-1.040), accounting for 72.27% of the total effect (-1.040/-1.439). A chain-mediated effect through caregiving issues and service needs and anxiety was also observed (effect value=-0.065), accounting for 4.50% of the total effect (-0.065/-1.439) .Conclusions:Parents of children with autism experience a relatively high level of illness uncertainty. Enhancing social support, addressing caregiving issues and service needs, alleviating parental anxiety may reduce their illness uncertainty.