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BACKGROUND: Lactic acid (LA) can promote the malignant progression of tumors through the crosstalk with the tumor microenvironment (TME). However, the function of long non-coding RNAs (lncRNAs) related to LA metabolism in Wilms tumor (WT) remains unclear. METHODS: Gene expression data and clinical data of WT patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Through the ESTIMATE algorithm and Pearson correlation analysis, lncRNAs related to tumor immunity and LA metabolism were screened. Subsequently, Cox regression analysis and Lasso Cox regression analysis were used to construct a model. Furthermore, candidate genes were identified and a competitive endogenous RNA (ceRNA) network was conducted to explore the specific mechanism of characteristic genes. Finally, based on the strong clinical relevance of UNC5B-AS1, its expression and function were experimentally verified. RESULTS: The immune score and stromal score were found to be closely related to the prognosis of WT. Eventually, a prognostic model (TME-LA-LM) consisting of 6 lncRNAs was successfully identified. The model demonstrated favorable predictive ability and accuracy, with significant variation in immune infiltration and drug susceptibility observed between risk groups. Additionally, the study revealed the involvement of 2 candidate genes and 5 microRNAs (miRNAs) in the tumor's development. Notably, UNC5B-AS1 was highly expressed and found to promote the proliferation and migration of tumor cells. CONCLUSION: This study, for the first time, elucidated the prognostic signatures of WT using lncRNAs related to TME and LA metabolism. The fundings of this research offer valuable insights for future studies on immunotherapy, personalized chemotherapy and mechanism research.

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Lung squamous cell carcinoma (LUSC), a subset of non-small cell lung cancer (NSCLC), accounts for about 30% of all lung cancers (LC) and exhibits a dismal response to current therapeutic protocols. Existed studies have indicated that aberrations in fibroblast growth factor receptors (FGFRs) play a pivotal role in the progression of LUSC, rendering them as attractive targets for therapeutic intervention in this cancer type. This study found that Erdafitinib (Erda), a novel pan-FGF receptor tyrosine kinase inhibitor (TKI), exerted a cytotoxic effect on LUSC cells. However, STAT3, the downstream target of FGFRs, remained still activated despite Erdafitinib treatment. Then, a STAT3 inhibitor, Stattic (Sta), was concurrently used with Erdafitinib, and the combined treatment demonstrated a synergistic efficacy in both in vitro and in vivo models of LUSC when compared to that of the treatment of the Erdafitinib or Stattic alone. Further molecular studies showed that such an effect of Erdafitinib and Stattic was associated with their concurrently inhibitory effect on FGFR1 and STAT3 signaling in LUSC cells. Therefore, the findings of this study indicated that the concurrent use of Erdafitinib and Stattic is a promising therapeutic approach for the treatment of FGFR1-positive LUSC.

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Parnassius butterflies have significantly advanced our understanding of biogeography, insect-plant interactions, and other fields of ecology and evolutionary biology. However, to date, little is known about the gene expression patterns related to the high-altitude adaptation of Parnassius species. In this study, we obtained high-throughput RNA-seq data of 48 adult Parnassius individuals covering 10 species from 12 localities in China, and deciphered their interspecific and intraspecific expression patterns based on comparative transcriptomic analyses. Though divergent transcriptional patterns among species and populations at different altitudes were found, a series of pathways related to genetic information processing (i.e., recombination, repair, transcription, RNA processing, and ribosome biogenesis), energy metabolism (i.e., oxidative phosphorylation, thermogenesis, and the citrate cycle), and cellular homeostasis were commonly enriched, reflecting similar strategies to cope with the high-altitude environments by activating energy metabolism, enhancing immune defense, and concurrently inhibiting cell growth and development. These findings deepen our understanding about the molecular mechanisms of adaptative evolution to extreme environments, and provide us with some theoretical criteria for the biodiversity conservation of alpine insects.

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Liver oncogenesis is accompanied by discernible protein changes in the bloodstream. By employing plasma proteomic profiling, we can delve into the molecular mechanisms of liver cancer and pinpoint potential biomarkers. In this nested case-control study, we applied liquid chromatography-tandem mass spectrometry for proteome profiling in baseline plasma samples. Differential protein expression was determined and was subjected to functional enrichment, network, and Mendelian randomization (MR) analyses. We identified 193 proteins with notable differential levels between the groups. Of these proteins, MR analysis offered a compelling negative association between apolipoprotein B (APOB) and liver cancer. This association was further corroborated in the UK Biobank cohort: genetically predicted APOB levels were associated with a 31% (95% CI 19-42%) decreased risk of liver cancer; and phenotypic analysis indicated an 11% (95% CI 8-14%) decreased liver cancer risk for every 0.1 g/L increase of circulating APOB levels. Multivariable MR analysis suggested that the hepatic fat content might fully mediate the APOB-liver cancer connection. In summary, we identified some plasma proteins, particularly APOB, as potential biomarkers of liver cancer. Our findings underscore the intricate link between lipid metabolism and liver cancer, offering hints for targeted prophylactic strategies and early detection.

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Background: Male urethral stricture disease (USD) is predominantly characterized by scar formation. There are few effective therapeutic drugs, and comprehensive molecular characterizations of USD formation remain undefined. Methods: The proteomic profiling of twelve scar tissues and five matched normal adjacent tissues (NATs). Proteomic analysis methods were applied to explore the molecular characterizations of USD formation, including uncovering mechanistic pathways and providing novel biomarkers for scar formation. Results: Comparative proteomic analysis showed that the extracellular matrix (ECM) and complement cascade signaling were predominant in scar tissues. COL11A1 and CD248 significantly contributed to the accumulation of ECM components. Our study presented diverse molecular mechanisms of scar formation across different ages and suggested the potential effects of PXK in Age 1 (<45) patients. Furthermore, immune infiltration studies indicated the therapeutic potential of inhibiting the complement system (C4A, C4B) in Age 2 (≥45) patients, providing a potential clinical strategy for USD. Conclusion: This study illustrated the pathogenesis of USD formation and the diverse characteristics of USD patients with different ages, enhancing our understanding of the disease's pathogenesis and providing a valuable resource for USD treatment.

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BACKGROUND/AIM: Autophagy and immunity play important roles in the growth of malignant tumors and are promising targets for tumor therapy. This study was conducted to identify differentially expressed immune genes related to autophagy in Wilms' tumor (WT) and analyze their correlation with the disease prognosis. MATERIALS AND METHODS: The public data of WT and normal kidney tissues were downloaded from TCGA, ImmPort, and GeneCards databases to obtain differentially expressed immune genes associated with autophagy. Survival analysis, ROC curve, and clinical relevance filtering were used to screen the key gene plasminogen activator urokinase (PLAU). The univariable and multivariable Cox regression model analyses were used to analyze the prognostic factors of overall survival (OS) in patients with WT. Then, GO enrichment, KEGG pathway analysis and GSEA were used to enrich and analyze differentially expressed genes. The relationship between PLAU gene expression and tumor microenvironment and infiltration of immune cells was analyzed, as well as between the expression of PLAU and epigenetic modifications. RESULTS: PLAU gene expression was associated with survival and prognosis in WT patients and was an independent prognostic indicator of OS in patients. The GO, KEGG, and GSEA analysis results suggested that PLAU may be involved in RNA transcription and epithelial cell migration. High expression of PLAU was also associated with increased immune cell infiltration and a higher presence of antitumor immune cells. The low expression of PLAU in WT was related to DNA methylation and may be also co-regulated by miR-342-3p. CONCLUSION: PLAU can be used as an independent prognostic biomarker for WT. Low expression of PLAU is associated with poor prognosis in WT patients. Evidence on the prognostic value of PLAU gene and the pathways that may be associated with its expression is invaluable for the development of new therapies for WT.

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Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affect the dental stromal tissue homeostasis and impair the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mTOR signaling pathway (ILK, MAPK3, mTOR, STAT1 and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-ß-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.

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Pecan (Carya illinoinensis) is an economically important nut crop known for its genetic diversity and adaptability to various climates. Understanding the growth variability, phenological traits, and population structure of pecan populations is crucial for breeding programs and conservation. In this study, plant growth and phenological traits were evaluated over three consecutive seasons (2015-2017) for 550 genotypes from 26 provenances. Significant variations in plant height, stem diameter, and budbreak were observed among provenances, with Southern provenances exhibiting faster growth and earlier budbreak compared to Northern provenances. Population structure analysis using SNP markers revealed eight distinct subpopulations, reflecting genetic differentiation among provenances. Notably, Southern Mexico collections formed two separate clusters, while Western collections, such as 'Allen 3', 'Allen 4', and 'Riverside', were distinguished from others. 'Burkett' and 'Apache' were grouped together due to their shared maternal parentage. Principal component analysis and phylogenetic tree analysis further supported subpopulation differentiation. Genetic differentiation among the 26 populations was evident, with six clusters highly in agreement with the subpopulations identified by STRUCTURE and fastSTRUCTURE. Principal components analysis (PCA) revealed distinct groups, corresponding to subpopulations identified by genetic analysis. Discriminant analysis of PCA (DAPC) based on provenance origin further supported the genetic structure, with clear separation of provenances into distinct clusters. These findings provide valuable insights into the genetic diversity and growth patterns of pecan populations. Understanding the genetic basis of phenological traits and population structure is essential for selecting superior cultivars adapted to diverse environments. The identified subpopulations can guide breeding efforts to develop resilient rootstocks and contribute to the sustainable management of pecan genetic resources. Overall, this study enhances our understanding of pecan genetic diversity and informs conservation and breeding strategies for the long-term viability of pecan cultivation.

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EMT dysfunction is a dominant mechanisms of hypospadias. Thus, identification of EMT-related lncRNAs based on transcriptome sequencing data of hypospadias might provide novel molecular markers and therapeutic targets for hypospadias. First, the microarray data related to hypospadias were downloaded from Gene Expression Omnibus (GEO). Besides, the differentially expressed lncRNAs and messenger RNAs (mRNAs) related to EMT were screened to construct lncRNA-mRNA co-expression interaction pairs. In addition, the microRNA (miRNA) prediction analysis was performed through bioinformatics methods to construct a ceRNA network. Moreover, function prediction and function enrichment and pathway analyses were also performed. Finally, the core EMT-related lncRNAs were verified based on mRNA expression changes and cell functions. A total of 6 EMT-related lncRNAs were identified and 123 mRNA-lncRNA co-expression interaction pairs were screened in this study. Additionally, a ceRNA regulatory network comprising 17 mRNAs, 4 lncRNAs, and 28 miRNAs was constructed based on the prediction of hypospadias-related miRNAs. The validation results of the dataset GSE121712 revealed that only BEX1 was positively correlated with the expression of the lncRNA GNAS-AS1 (r = 0.874, P < 0.01), both of which had high expression. The cell experiment results demonstrated that interfering with the expression of GNAS-AS1 significantly promoted the proliferation, migration, and EMT of cells. Importantly, it was confirmed that GNAS-AS1 can serve as a ceRNA and play an important role in the EMT of hypospadias. Hence, it may be considered as a potential target in the treatment of this disease.

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Cell cycle regulation is largely abnormal in cancers. Molecular understanding and therapeutic targeting of the aberrant cell cycle are essential. Here, we identified that an underappreciated serine/threonine kinase, cyclin-dependent kinase-like 3 (CDKL3), crucially drives rapid cell cycle progression and cell growth in cancers. With regard to mechanism, CDKL3 localizes in the nucleus and associates with specific cyclin to directly phosphorylate retinoblastoma (Rb) for quiescence exit. In parallel, CDKL3 prevents the ubiquitin-proteasomal degradation of cyclin-dependent kinase 4 (CDK4) by direct phosphorylation on T172 to sustain G1 phase advancement. The crucial function of CDKL3 in cancers was demonstrated both in vitro and in vivo. We also designed, synthesized, and characterized a first-in-class CDKL3-specific inhibitor, HZ1. HZ1 exhibits greater potency than CDK4/6 inhibitor in pan-cancer treatment by causing cell cycle arrest and overcomes acquired resistance to CDK4/6 inhibitor. In particular, CDKL3 has significant clinical relevance in colon cancer, and the effectiveness of HZ1 was demonstrated by murine and patient-derived cancer models. Collectively, this work presents an integrated paradigm of cancer cell cycle regulation and suggests CDKL3 targeting as a feasible approach in cancer treatment.

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Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.

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Microphthalmia transcription factor (MiT) family translocation renal cell carcinoma (tRCC) is a rare, aggressive, and heterogeneous subtype of kidney cancer, which is not well characterized. Since genetic alterations are always associated with carcinogenesis, and proteins are the major executors of biological features, multi-omics studies can reveal the systematic tRCC biological process comprehensively. Here, we describe the proteogenomic workflow for characterization of tRCC in detail to provide the knowledge foundation for integrated proteogenomic analysis of tRCC and other malignant tumors in the future.

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Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas (n = 27), and nevi (n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis-effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.

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Novel reprocessable thermosetting adhesives (RTAs), which combine high adhesive strength, reusability, disassembly, and recyclability features, have attracted increasing attention. However, developing RTAs with a rapidly adhesive rate while ensuring high adhesive strength and self-healing ability is still a significant challenge. Here, we prepared a novel vitrimer called DAx-DTSAy, which can be used as an RTA. First, by adjusting the ratio of rigid and flexible segments, maximum tensile strength reached 35.92 MPa. Second, the combined effect of dynamic hydroxyl ester bonds and dynamic disulfide bonds resulted in a rapid stress relaxation behavior, with a complete relaxation time 13.6 times shorter than a vitrimer only cross-linked with hydroxy ester bonds. This feature endowed its good self-healing and reprocessing capabilities. After self-healing at 180 °C, the maximum healing rate of mechanical properties was 91.8%. After three reprocesses, the maximum recovery rate of tensile strength was 120.2%. Furthermore, the combination of rigid and flexible segments and the synergistic effect of dual dynamic covalent bonds made DAx-DTSAy capable of use as a high-performance RTA. The lap shear strength of a DAx-DTSAy film on stainless steel reached 18.18 MPa after 15 min, with a recovery rate of 91.9% after 5 rebonding cycles. Additionally, DAx-DTSAy can be disassembled in chemical agents and exhibited better insulation properties compared to traditional epoxy resins. DAx-DTSAy can be employed as a novel high-performance adhesive in applications such as electronic devices and transportation, contributing to the development of thermosetting adhesives toward recyclability and sustainability.

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PURPOSE: Cervical disc arthroplasty (CDA) is widely employed for patients diagnosed with cervical degenerative disc disease (CDDD). Postoperative bone loss (BL) represents a radiological alteration that is a relatively novel consideration in the realm of CDA. This study endeavors to examine the risk factors associated with BL following CDA, aiming to elucidate the underlying mechanisms and the impact of BL on surgical outcomes. METHODS: A retrospective study was undertaken, encompassing consecutive patients subjected to one-level CDA, two-level CDA, or two-level hybrid surgery (HS) for the treatment of CDDD at our institution. Patient demographic and perioperative data were systematically recorded. Radiological images obtained preoperatively, at 1-week post-operation, and during the last follow-up were collected and evaluated, following with statistical analyses. RESULTS: A total of 295 patients and 351 arthroplasty segments were involved in this study. Univariate logistic regressions indicated that age ≥ 45 years and two-level HS was associated with lower risk of BL; and a greater ΔDA (change of disc angle before and after surgery) was correlated with an increased risk of BL. Multivariate logistic regression determined that two-level HS and greater ΔDA were independent preventative and risk factors for BL, respectively. Further analysis revealed that severe BL significantly elevated the risk of implant subsidence compared to non-BL and mild BL. CONCLUSIONS: This study posited bone remodeling and micromotion as potential underlying mechanisms of BL. Subsequent research endeavors should delve into the divergent mechanisms and progression observed between lower- and higher-grade BL, aiming to prevent potential adverse outcomes associated with severe BL.

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Cryptococcosis imposes a considerable burden on public health, and emerging drug responses to anticryptococcal drugs remain to be addressed. In this forum article we discuss the emerging drug responses of Cryptococcus, focusing on the critical nature of understanding such responses in order to improve the effectiveness of anticryptococcal therapeutics.

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CONTEXT: Cachexia is associated with poor survival rates. In the clinical setting, the diagnosis of cancer cachexia is challenging. The cachexia index (CXI), a new index for predicting survival time, is a promising tool for diagnosing cancer cachexia; however, its efficacy in predicting patient survival has not been validated. OBJECTIVE: This meta-analysis and systematic review aimed to explore the CXI's prognostic value in patients with cancer. DATA SOURCES: The PubMed, Embase, MEDLINE, and Cochrane Library databases were searched for relevant studies to determine the association between CXI findings and prognosis. DATA EXTRACTION: The outcomes were overall survival (OS), progression-, disease-, and recurrence-free survival (PFS/DFS/RFS) rates, and the rate of complete response. DATA ANALYSIS: The QUality In Prognostic Studies (QUIPS) tool was used to evaluate the quality of the included trials. This meta-analysis comprised 14 studies involving 2777 patients. A low CXI was associated with decreased OS (hazard ratio [HR] 2.34, 95% confidence interval [CI] 2.01-2.72; P < .001), PFS/DFS/RFS (HR 1.93, 95% CI 1.68-2.22; P < .001), and complete response (odds ratio [OR] 0.49, 95% CI 0.36-0.66; P < .001). Patients with a low CXI had a lower body mass index (mean difference [MD] -0.75, 95% CI -1.00 to 0.50; P < .001), skeletal muscle index (standardized MD -0.80, 95% CI -0.98 to -0.61; P < .001), and serum albumin level (MD -0.23, 95% CI -0.26 to -0.20; P < .001); and a higher neutrophil-lymphocyte ratio (MD 1.88, 95% CI 1.29-2.47; P < .001) and more advanced disease stages (OR 0.80, 95% CI 0.71-0.91; P = .001). CONCLUSION: A low CXI was found to be associated with poor survival in patients with cancer. While the CXI is a promising marker for predicting cancer cachexia, further studies are required to verify its usefulness.

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OBJECTIVE: To investigate (1) lateral atlantoaxial articulation (LAA) morphology in patients with basilar invagination (BI) with atlantoaxial dislocation (AAD) and healthy individuals and its relationship with the severity of dislocation and (2) the effect of the LAA morphology on reduction degree (RD) after surgery. METHODS: In this retrospective propensity score matching case-control study, imaging and baseline data of 62 patients with BI and AAD from 2011 to 2022 were collected. Six hundred thirteen  participants without occipitocervical junctional deformity served as controls. Logistic regression and receiver operating characteristic (ROC) curve were used for analysis. RESULTS: The age, BMI and sex did not differ significantly between the two groups after propensity score matching. Sagittal slope angle (SSA) and coronal slope angle (CSA) was lower and greater, respectively, in the patient group than in the control group. A negative SSA value usually indicates anteverted LAA. Regression analysis revealed a significant negative correlation between SSA and severity of dislocation. However, no relationship was found between CSA and the severity of dislocation. The multivariate logistic regression analysis revealed that minimum-SSA emerged as an independent predictor of satisfactory reduction (RD ≥ 90%). The ROC curve demonstrated an area under the curve of 0.844, with a cut-off value set at -40.2. CONCLUSION: SSA in patients group was significantly smaller and more asymmetric than that in the control group. Dislocation severity was related to SSA but not to CSA. Minimum-SSA can be used as a predictor of horizontal RD after surgery.

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Background: Long non-coding RNA (lncRNA), a crucial regulator in breast cancer (BC) development, is intricately linked with cellular senescence. However, there is a lack of cellular senescence-related lncRNAs (CSRLs) signature to evaluate the prognosis of BC patients. Methods: Correlation analysis was conducted to identify lncRNAs associated with cellular senescence. Subsequently, a CSRL signature was crafted in the training cohort. The model's accuracy was evaluated through survival analysis and receiver operating characteristic curves. Furthermore, prognostic nomograms amalgamating cellular senescence and clinical characteristics were devised. Tumor microenvironment and checkpoint disparities were compared between low-risk and high-risk groups. The correlation between these signatures and treatment response in BC patients was also investigated. Finally, functional experiments were conducted for validation. Results: A signature comprising nine CSRLs was devised, which demonstrated adept prognostic capability in BC patients. Functional enrichment analysis revealed that tumor and immune-related pathways were predominantly enriched. Compared to the low-risk group, the high-risk group could benefit more from immunotherapy and certain chemotherapeutic agents. The expression of the 9 CSRLs was validated through in vitro experiments in different subtypes of BC cell lines and tissues. AC098484.1 was specifically verified for its association with senescence-associated secretory phenotypes. Conclusion: The CSRLs signature emerges as a promising prognostic biomarker for BC, with implications for immunological studies and treatment strategies. AC098484.1 has potential relevance in the treatment of BC cell senescence, and these findings improve the clinical treatment levels for BC patients.

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Background: The correlation between hypoxia and tumor development is widely acknowledged. Meanwhile, the foremost organelle affected by hypoxia is mitochondria. This study aims to determine whether they possess prognostic characteristics in lung adenocarcinoma (LUAD). For this purpose, a bioinformatics analysis was conducted to assess hypoxia and mitochondrial scores related genes, resulting in the successful establishment of a prognostic model. Methods: Using the single sample Gene Set Enrichment Analysis algorithm, the hypoxia and mitochondrial scores were computed. Differential expression analysis and weighted correlation network analysis were employed to identify genes associated with hypoxia and mitochondrial scores. Prognosis-related genes were obtained through univariate Cox regression, followed by the establishment of a prognostic model using least absolute shrinkage and selection operator Cox regression. Two independent validation datasets were utilized to verify the accuracy of the prognostic model using receiver operating characteristic and calibration curves. Additionally, a nomogram was employed to illustrate the clinical significance of this study. Results: 318 differentially expressed genes associated with hypoxia and mitochondrial scores were identified for the construction of a prognostic model. The prognostic model based on 16 genes, including PKM, S100A16, RRAS, TUBA4A, PKP3, KCTD12, LPGAT1, ITPRID2, MZT2A, LIFR, PTPRM, LATS2, PDIK1L, GORAB, PCDH7, and CPED1, demonstrates good predictive accuracy for LUAD prognosis. Furthermore, tumor microenvironments analysis and drug sensitivity analysis indicate an association between risk scores and certain immune cells, and a higher risk scores suggesting improved chemotherapy efficacy. Conclusion: The research established a prognostic model consisting of 16 genes, and a nomogram was developed to accurately predict the prognosis of LUAD patients. These findings may contribute to guiding clinical decision-making and treatment selection for patients with LUAD, ultimately leading to improved treatment outcomes.