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Background Coccomorphan mitochondrial genomes (mitogenomes) exhibit a suite of unconventional genomic features. However, the insufficient mitogenomic data from Coccomorpha, which includes numerous economically important plant pests, hampers not only the investigation of mitogenome evolution but also the molecular identification and population origin tracing of pest species. Results Here, we sequenced the complete mitogenomes of five invasive coccomorphans and compared the performances of short-read- and long-read-based assemblies. Moreover, the newly generated and 16 previously reported mitogenomes were subjected to comparative genomic and phylogenetic analyses. We found that an extremely high A + T content, large-scale tRNA gene truncation and frequent gene rearrangement were ubiquitous among the coccomorphan mitogenomes. Notably, our data reveal that massive tRNA arm loss and gene rearrangements provide informative phylogenetic characteristics within Coccomorpha. The rapid evolution of ATP8 , driven by relaxed purifying selection, has resulted in divergent ATP8 gene lengths and relative genomic positions. Furthermore, long-read sequencing data revealed the heteroplasmic landscape of the repeat sequence copy numbers in two Icerya species, indicating that repeat sequences drive rapid intraspecific evolution of genome size, gene content, and gene rearrangement and increase mitogenomic plasticity. Conclusions Our study supports the use of long-read sequencing as an efficient and useful approach for resolving complex genomic architectures and heteroplasmy. This study also identifies several potential genome-level phylogenetic markers and advances our understanding of mitogenome evolution within Coccomorpha.

HOX transcript antisense RNA (HOTAIR) is upregulated in glioblastoma (GBM) and associated with temozolomide (TMZ) resistance. However, the mechanisms underlying HOTAIR-mediated TMZ resistance remains poorly understood. HOTAIR expression in glioma-related public datasets and drug response estimation were analyzed using bioinformatics. These findings were verified by overexpressing HOTAIR in TMZ-sensitive U251 cells and/or silencing HOTAIR in resistant U251 cells (U251R). The cytotoxic effects were evaluated using cell viability assay and flow cytometry analysis of cell cycle and apoptosis. In this study, we found that HOTAIR was upregulated in TMZ-resistant GBM cell lines and patients with high HOTAIR expression responded poorly to TMZ therapy. HOTAIR knockdown restored TMZ sensitivity in U251R cells, while HOTAIR overexpression conferred TMZ resistance in U251 cells. Wnt/β-catenin signaling was enriched in patients with high HOTAIR expression; consistently, HOTAIR positively regulated β-catenin expression in U251 cells. Moreover, HOTAIR-mediated TMZ resistance was associated with increased MGMT protein level, which resulted from the HOTAIR/miR-214-3p/β-catenin network. Besides, GBM with high HOTAIR expression exhibited sensitivity to methotrexate. Methotrexate enhanced TMZ sensitivity in U251R cells, accompanied by reduced expression of HOTAIR and β-catenin. Thus, we conlcude that HOTAIR is a risk factor for TMZ resistance and methotrexate may represent a potential therapeutic drug for patients with high HOTAIR expression level.

Objective To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. Methods A retrospective analysis with pair matching of 81 patients who received FNS or cannulated screw internal fixation for Pauwels type‐3 femoral neck fracture in our hospital from January 2019 to December 2019 was conducted. Patients who received FNS were the test group, and those who received cannulated screws comprised the control group. Matching requirements were as follows: same sex, similar age, and similar body mass index (BMI). A total of 30 pairs were successfully matched at a 1:1 ratio, including 12 males and 18 females. The average age of the patients in the FNS group was 54.53 ± 6.71 years. In the cannulated screw group, the average age of the patients was 53.14 ± 7.19 years. The operation time, intraoperative blood loss, hospital stay, hospitalization cost, postoperative visual analog scale (VAS) score, time to walking without crutches, Harris score, femoral head necrosis rate, and complication rate were compared between the groups. Results Postoperative re‐examination of radiographs showed satisfactory reduction in all patients, and all patients were followed up for 10–22 months. Those in the FNS group had lower postoperative VAS scores, earlier times to walking without crutches, higher Harris scores at the last follow‐up, and lower complication rates (P < 0.05). VAS scores were lower in the FNS group (3.13 ± 1.07 scores) than in the cannulated screw group (3.77 ± 1.04 scores) (P = 0.018). Patients in the FNS group (5.23 ± 1.33 months) recovered to walking without crutches earlier than did those in the cannulated screw group (6.03 ± 1.45 months) (P<0.001). In addition, a statistically higher postoperative Harris score was detected in the FNS group (86.16 ± 7.26) than in the cannulated screw group (82.37 ± 7.52) (P = 0.039). Overall, a higher incidence of complications was observed in the cannulated screw group (9/30) than in the FNS group (2/30) (P = 0.042). However, intraoperative blood loss and hospitalization costs were greater in the FNS group (P < 0.05). Intraoperative blood loss was greater in the FNS group (99.73 ± 4.69) than in the cannulated screw group (30.27 ± 9.04) (P<0.001). In addition, patients in the FNS group (46976 ± 2270 ¥) spent more on hospitalization costs than did those in the cannulated screw group (15626 ± 1732 ¥) (P<0.001). No statistically significant difference in operation time, hospital stay, or femoral head necrosis rate was observed between the two groups (P > 0.05). Conclusion For patients with unstable femoral neck fractures, FNS has better clinical efficacy than cannulated screws, though it is also more expensive. To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. We designed a retrospective analysis with pair matching. This study found that compared with cannulated screws, FNS is a suitable option for the treatment of Pauwels type‐3 femoral neck fractures. This approach is characterized by its accurate efficacy, simple procedure, reduced trauma, faster recovery, and fewer complications, though it is more expensive. FNS's excellent biomechanical performance and clinical efficacy make it a new choice for the treatment of unstable femoral neck fractures.

Nowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated. The RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis. Four glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1-IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1-IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype. ANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.

The CHI3L1 signaling pathway significantly influences glioma angiogenesis, but its role in the tumor microenvironment (TME) remains elusive. We propose a novel CHI3L1‐associated vascular phenotype classification for glioma through integrative analyses of multiple datasets with bulk and single‐cell transcriptome, genomics, digital pathology, and clinical data. We investigated the biological characteristics, genomic alterations, therapeutic vulnerabilities, and immune profiles within these phenotypes through a comprehensive multi‐omics approach. We constructed the vascular‐related risk (VR) score based on CHI3L1‐associated vascular signatures (CAVS) identified by machine learning algorithms. Utilizing unsupervised consensus clustering, gliomas were stratified into three distinct vascular phenotypes: Cluster A, marked by high vascularization and stromal activation with a relatively low levels of tumor‐infiltrating lymphocytes (TILs); Cluster B, characterized by moderate vascularization and stromal activity, coupled with a high density of TILs; and Cluster C, defined by low vascularization and sparse immune cell infiltration. We observed that the CAVS effectively indicated glioma‐associated angiogenesis and immune suppression by single‐cell RNA‐seq analysis. Moreover, the high‐VR‐score group exhibited enhanced angiogenic activity, reduced immune response, resistance to immunotherapy, and poorer clinical outcomes. The VR score independently predicted glioma prognosis and, combined with a nomogram, provided a robust clinical decision‐making tool. Potential drug prediction based on transcription factors for high‐risk patients was also performed. Our study reveals that CHI3L1‐associated vascular phenotypes shape distinct immune landscapes in gliomas, offering insights for optimizing therapeutic strategies to improve patient outcomes. We propose a novel CHI3L1‐associated vascular phenotype classification for glioma, each characterized by unique tumor features, including immune cell infiltration, metabolic reprogramming, and genomic alterations. We identified CHI3L1‐associated vascular signatures that reflect tumor angiogenesis and immunosuppression. We devised a vascular‐related risk (VR) score, with the high‐VR‐score group exhibiting enhanced angiogenic activity, reduced immune response, immunotherapy resistance, and poorer clinical outcomes.

Metastasis is the trigger of death in anaplastic thyroid cancer (ATC) patients, yet the specific mechanisms at play are still largely enigmatic. While the involvement of LARP1 in the metastatic process of various cancers has been documented, there is a noticeable gap in the literature regarding its potential influence on ATC metastasis. Molecular studies probed LARP1 expression within ATC cells, with subsequent in vitro experiments examining the effects of LARP1 on ATC cell metastasis and the mTOR signaling cascade. A suite of assays, including colony formation, scratch wound healing, transwell invasion, and cell adhesion, was used to assess cell growth, movement, invasion, and attachment. Western Blot determined the expression levels of epithelial–mesenchymal transition (EMT) markers (E‐cadherin, Vimentin, N‐cadherin) and proteins implicated in metastasis (MMP‐2, MMP‐9), along with mTOR and p‐mTOR. The affinity of Telocinobufagin (TBG) from Yuanhua Toad Essence for LARP1 was investigated through molecular docking, with CETSA assays providing subsequent validation. Further cellular experiments substantiated the influence of TBG on ATC cell metastasis and modulation in the mTOR pathway. LARP1 levels were heightened in ATC cells, and its depletion effectively curbs their proliferative, migratory, invasive, and adhesive activities. With LARP1 knockdown, we also observed that the onset of EMT and metastatic processes was thwarted, as was the mTOR pathway. Subsequent research has uncovered that TBG formed a physical complex with LARP1, allowing it to target and suppress the mTOR pathway, thus preventing the metastasis of ATC. The simultaneous overexpression of LARP1, however, lessened the ability of TBG to inhibit ATC metastasis. This study highlights the importance of TBG binding to LARP1 in the mediation of the mTOR signaling pathway, a key process in the inhibition of ATC cell metastasis. This discovery introduces a new target for the diagnosis of ATC and enlightens the consideration of TBG as a treatment for ATC metastasis.

Aims High immune cell infiltration in gliomas establishes an immunosuppressive tumor microenvironment, which in turn promotes resistance to immunotherapy. Hence, it is important to identify novel targets associated with high immune cell infiltration in gliomas. Our previous study showed that serum levels of beta‐2 microglobulin (B2M) in lower‐grade glioma patients were lower than those in glioblastoma patients. In the present study, we focused on exploring the roles of B2M in glioma immune infiltration. Methods A large cohort of patients with gliomas from the TCGA, CGGA, and Gravendeel databases was included to explore differential expression patterns and potential roles of B2M in gliomas. A total of 103 glioma tissue samples were collected to determine the distributions of B2M protein levels by immunofluorescent assays. Kaplan‐Meier survival analysis and meta‐analysis were used for survival analysis. GO(Gene‐ontology) enrichment analysis, co‐expression analysis, KEGG(Kyoto Encyclopedia of Genes and Genomes) pathway analysis, and immune infiltration analysis were performed to explore roles and related mechanisms of B2M in glioma. Results We found that both B2M mRNA and protein levels were abnormally upregulated in glioma samples compared with those from normal brain tissue. B2M expression was correlated with tumor grade and was downregulated in IDH1 mutant samples. Furthermore, B2M was a moderately sensitive indicator for predicting the mesenchymal molecular subtype of gliomas. Interestingly, glioma patients with lower B2M expression had remarkably longer survival times than those with higher B2M expression. Moreover, meta‐analysis showed that B2M was an independent predictive marker in glioma patients. The results of GO enrichment analysis revealed that B2M contributed to immune cell infiltration in glioma patients. In addition, results of KEGG pathway analysis and co‐expression analysis suggested that B2M may mediate glioma immune infiltration via chemokines. Conclusions We conclude that B2M levels are critical for the survival times of glioma patients, at least in part due to mediating high immune infiltration. Beta‐2 microglobulin (B2M) is a potential marker for the prognosis of glioma patients. Forest plot shows that high B2M expression corresponded to a poor survival time compared to that of low B2M expression in glioma patients from three databases.

The clinical necessity of lymph node dissection in papillary thyroid carcinoma (PTC) surgery remains contentious. This study compared four logistic regression (LR) models (with distinct feature selection strategies) and four machine learning (ML) models to preoperatively predict lymph node metastasis (LNM) risk in PTC patients, with emphasis on multidimensional evaluation and cross-populational generalizability. Data from 3,175 PTC patients (2021 cohort) were randomly split into training (70%) and testing (30%) subsets, with external validation performed using a Chinese (2024, n = 104) and a Canadian (2019–2022, n = 412) cohort. Twelve predictors were screened, and models were evaluated using metrics of discrimination (AUC), calibration (Brier Score), classification accuracy, and clinical utility. The prevalence of LNM was 34.48%, 36.54%, and 30.10% in the internal, Chinese, and Canadian cohorts, respectively. Among ML models, Random Forest achieved the highest internal AUC (0.767), whereas XGBoost demonstrated superior generalization (external AUCs: 0.785 and 0.725). LR models, particularly BestSubset-GLM, outperformed these ML models with an internal AUC of 0.770 and external AUCs of 0.831 and 0.785. Notably, BestSubset-GLM exhibited high specificity (0.86), precision (0.59), favorable calibration (Brier Score < 0.20), and robust clinical utility across the approximately 15–90% threshold probability range. Extrathyroidal extension, tumor size above 1.00 cm, younger age, and male gender were identified as key LNM risk factors. Bethesda classification and molecular aberrations were integrated into models. BestSubset-GLM balanced parsimony, interpretability, and generalizability, thereby supporting clinical decision-making through dynamic nomograms. Comprehensive evaluation beyond AUC is crucial.

Background Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. Methods Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). Results Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05–3.50, P  = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. Conclusions High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.