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AR/VR and other immersive technologies are creating dynamic, learner-centred, and engaging language-learning environments. In these ever-changing situations, judging someone’s language abilities is difficult. Managing multimodal learner inputs, understanding model predictions, and protecting user data across distributed systems are some of the most prominent challenges. This paper proposes TriNet-AQ, a federated, interpretable deep learning architecture for classifying English competency in AR/VR platforms. This technique addresses the difficulties raised. This work employs Quantum Sinusoidal Encoding (QSE), Triaxial Attention Fusion (TAF) for multimodal feature alignment, and Quantum Modulated Integration (QMI) to enhance context-aware learning by optimizing temporal representation. Hybrid Slime Gorilla Optimisation (HSGO) aids optimization. It accelerates convergence and improves performance and economy. TriNet-AQ provides decentralized training to many clients via federated learning, enhancing privacy and flexibility. TriNet-AQ outperforms classical, fuzzy, and hybrid baselines in real-world augmented and virtual reality instructional datasets. Its accuracy is 98.5%, AUC is 0.95, and EPES is 0.89. Even when it loses 3.5% accuracy on new data, it can generalize effectively. Another SHAP-based interpretability finding is the presence of obvious feature attributions and consistent relevance across users. Statistical analysis, including Cohen’s d = 0.89 (p < 0.001), confirms the model’s significance and reliability. TriNet-AQ provides robust, easy-to-understand, and private real-time, tailored language evaluation in next-generation immersive learning environments.

Integrins are considered the main cell-adhesion transmembrane receptors that play multifaceted roles as extracellular matrix (ECM)-cytoskeletal linkers and transducers in biochemical and mechanical signals between cells and their environment in a wide range of states in health and diseases. Integrin functions are dependable on a delicate balance between active and inactive status via multiple mechanisms, including protein-protein interactions, conformational changes, and trafficking. Due to their exposure on the cell surface and sensitivity to the molecular blockade, integrins have been investigated as pharmacological targets for nearly 40 years, but given the complexity of integrins and sometimes opposite characteristics, targeting integrin therapeutics has been a challenge. To date, only seven drugs targeting integrins have been successfully marketed, including abciximab, eptifibatide, tirofiban, natalizumab, vedolizumab, lifitegrast, and carotegrast. Currently, there are approximately 90 kinds of integrin-based therapeutic drugs or imaging agents in clinical studies, including small molecules, antibodies, synthetic mimic peptides, antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapy, imaging agents, etc. A serious lesson from past integrin drug discovery and research efforts is that successes rely on both a deep understanding of integrin-regulatory mechanisms and unmet clinical needs. Herein, we provide a systematic and complete review of all integrin family members and integrin-mediated downstream signal transduction to highlight ongoing efforts to develop new therapies/diagnoses from bench to clinic. In addition, we further discuss the trend of drug development, how to improve the success rate of clinical trials targeting integrin therapies, and the key points for clinical research, basic research, and translational research.

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients’ paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a “cancer-primed” premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF -like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications. The characterisation of the papillary thyroid carcinoma (PTC) tumour microenvironment remains crucial. Here, the authors perform single-cell RNA sequencing in 11 patients and identify potential opportunities for the use of immunotherapy and its combination with anti-angiogenic therapy in PTC.

Background Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. Methods Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. Results Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. Conclusions These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

Background The impact of smokeless tobacco (SLT) use on the risk of oral cavity cancer (OCC) has been confirmed; however, the sex-based difference in this association remains inconclusive. Therefore, this study aimed to estimate the association between SLT use and OCC risk in women and compared it to that in men. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies from their inception up to August 2020. Studies reporting the effect estimates of SLT use on OCC risk in men and women, were eligible for inclusion. The relative risk ratio (RRR) was applied to calculate the sex-based difference in the relationship between SLT use and OCC risk, and pooled analysis was conducted using a random-effects model with inverse variance weighting. Results Nineteen studies reporting a total of 6593 OCC cases were included in the final meta-analysis. The pooled relative risk (RR) suggested that SLT use was associated with an increased risk of OCC in both men (RR, 2.94; 95% confidence interval [CI], 2.05–4.20; P  < 0.001) and women (RR, 6.39; 95%CI, 3.16–12.93; P  < 0.001). Moreover, the SLT-use-related risk of OCC was higher in women than that in men (RRR,1.79; 95%C, 1.21–2.64; P  = 0.003). The risk of OCC related to SLT use in women was still significantly higher than that in men (RRR, 1.75; 95%CI, 1.15–2.66; P  = 0.008) after excluding indirect comparison results. Finally, a subgroup analysis suggested significant sex-based differences only in individuals who received chewed smokeless products, regardless of the control definition. Pooled analysis of studies with high design quality confirmed the notably higher risk of OCC in women than in men. Conclusions This study found that SLT use was associated with a higher risk of OCC in women than in men. Further large-scale prospective cohort studies should be conducted to verify sex-based differences in the association between use of specific smokeless products and OCC risk.

Background Diabetic peripheral neuropathy (DPN) is a major complication of diabetes. This study aimed to investigate the therapeutic effects and molecular mechanisms of Compound Qiying Granules (CQYG) for DPN. Methods Rats and RSC96 cells of DPN models were established to evaluate the therapeutic effects of CQYG. Then the morphology and apoptotic changes of sciatic nerves were detected. Further, tandem mass tag based quantitative proteomics technology was used to identify differentially expressed proteins (DEPs) and the underlying molecular mechanisms. Protein expression of key signaling pathways was also detected. Results CQYG treatment significantly improved blood glucose and oxidative stress levels, and further reduced nerve fiber myelination lesions, denervation, and apoptosis in DPN rats. Further, 2176 DEPs were found in CQYG treated DPN rats. Enrichment analysis showed that protein processing in the endoplasmic reticulum (ER), and apoptosis were all inhibited after CQYG treatment. Next, CQYG treatment reduced inflammatory factor expression, mitochondrial damage, and apoptosis in RSC96 cells which induced by high glucose. Transmission electron microscopy results found that CQYG treatment improved the morphology of nerve myelin, mitochondria, and ER. CQYG treatment decreased ER stress and apoptosis pathway proteins that were highly expressed in DPN models. In addition, we also predicted the potential targets of CQYG in DEPs. Conclusions CQYG exerts neuroprotective effects in experimental diabetic neuropathy through anti-ER stress and anti-apoptosis.

Background Postoperative eccentric macular hole (MH) formation is a relatively rare complication after pars plana vitrectomy (PPV) with internal limiting membrane(ILM) peeling for epiretinal membrane (ERM) or MH treatment. Herein, we report a case of eccentric MH formation following PPV with ILM peeling for MH. Case presentation A 62-year-old male presented with a 3-month history of blurred vision and metamorphopsia in the left eye. Preoperative optical coherence tomography (OCT) confirmed a full-thickness MH (minimum linear diameter: 675 μm). The patient underwent 25-gauge PPV with ILM peeling using indocyanine green (ICG, 0.25%) and inverted ILM flap placement. Postoperative OCT at one week confirmed MH closure. However, subsequent follow-ups revealed progressive inner retinal disorganization, atrophy, and cavitation. At five months, a parafoveal full-thickness eccentric macular hole (EMH) developed inferiorly. No additional interventions were pursued due to stable hole size and absence of retinal detachment. Conclusions This case highlights rare postoperative retinal atrophy and EMH formation following ILM peeling for MH repair. Potential contributors include ICG-induced photochemical toxicity, Müller cell damage from ILM peeling, and fluid shear stress. The findings underscore the need to optimize ICG protocols (reduced concentration, shorter exposure) and prioritize safer alternatives like brilliant blue G (BBG). Long-term postoperative monitoring is critical to detect delayed complications, emphasizing the balance between surgical efficacy and minimizing iatrogenic retinal injury.

Deep geothermal reservoirs have great potential for exploitation and are characterized by high temperatures, high stress, and strong heterogeneity. However, these reservoirs contain widely and continuously distributed dominant flow channels with high permeability, predisposing these reservoirs to the formation of dominant flow, which notably decreases the efficiency of heat extraction. Focusing on the dominant flow in fractures, this study provides a definite concept, systematically reviews current studies, and puts forward suggestions for future research. It is expected that this study will serve as a reference for the sustainable, high-quality development of deep geothermal resources.

There is a continuous debate regarding the classification of thyroid follicular lesions and the term “well‐differentiated tumor of uncertain malignant potential (WDT‐UMP)” was recently introduced to cover this problematic spectrum of tumors. The objective of this study was to reappraise WDT‐UMP using morphological, immunochemical, and molecular analysis and to shed more light on encapsulated thyroid follicular‐patterned tumors. A total of 30 cases of WDT‐UMP with equivocal papillary thyroid carcinoma‐type nuclear changes (PTC‐N) or focal unequivocal PTC‐N were examined. As a control, follicular adenoma (n = 29), follicular carcinoma (n = 8), hyalinizing trabecular adenoma (n = 5), and PTC (n = 48) were included. HBME‐1, cytokeratin 19, and galectin‐3 were positive in 12 (40.0%), 10 (33.3%) and 11 (36.7%) cases of WDT‐UMP, respectively. According to the positivity of those markers, significant differences were obtained between WDT‐UMP and PTC encapsulated common type (P = 0.028, 0.010, and 0.004, respectively), infiltrative follicular variant (P = 0.020, 0.026, and 0.008, respectively), and infiltrative common type (P = 0.004, 0.001, and 0.005, respectively), but not between WDT‐UMP and follicular adenoma or follicular carcinoma. BRAFV600E mutation was absent but RET/PTC1 rearrangement was found in only two (6.7%) cases of WDT‐UMP. None of the 20 patients with WDT‐UMP developed recurrence, with an average follow‐up of 80 months. These findings indicate that WDT‐UMP has a favorable outcome and is distinct from PTC in morphological, immunohistochemical, and molecular characteristics. We propose that WDT‐UMP should be classified as “well‐differentiated tumor with uncertain behavior”. (Cancer Sci 2011; 102: 288–294)

Benign prostatic hyperplasia (BPH) is a common condition in middle-aged and elderly men. Disrupted circadian rhythms (CRD) can directly influence aging, inflammation, metabolic syndrome, and hormonal changes—all of which are closely linked to BPH. This study aimed to investigate whether CRD accelerates prostatic hyperplasia in rats. Twenty male Sprague-Dawley (SD) rats were divided into two batches. A BPH model was established using mixed slow-release pellets of testosterone (T) and estradiol (E2). CRD was induced by continuous light exposure (Cle), while a 12-hour light/12-hour dark cycle defined the control (Con) group.