CircRNA hsa_circ_0069,399 as a potential clinical prognostic marker in laryngeal squamous cell carcinoma.

Objective: Circular RNAs (circRNAs) significantly influence the invasion, metastasis, gene expression, proliferation, and apoptosis of tumor cells. However, the roles of circRNAs in laryngeal squamous cell carcinoma (LSCC) remain largely unexplored. This study aims to examine circRNA expression patterns in LSCC and adjacent non-tumorous tissues, with the goal of uncovering potential biomarkers for LSCC. Methods: Tissue samples were collected from both the tumor and adjacent normal tissues of ten patients who had undergone surgical resection. The profiling of circRNAs was conducted through transcriptomic sequencing and analytical bioinformatics approaches. A ternary regulatory network based on the competitive endogenous RNA (ceRNA) hypothesis was established, linking target circRNAs to clinical immunohistochemical parameters for comparison. Verification of target circRNAs in LSCC tissues was performed using quantitative real-time PCR (RT-qPCR), whereas target mRNAs were analyzed through immunohistochemistry. Results: A total of 126 significantly different circRNAs were identified, including 40 up-regulated genes and 86 down-regulated genes. Furthermore, 92 circRNA-miRNA-mRNA regulatory relationship axes related to clinical immunohistochemical indicators were found based on 5 candidate circRNAs. Interestingly, all axes related to the target genes MKI67 and TP53 were found to compete with the same circRNA: hsa_circ_0069,399. Further verification confirmed that the hsa_circ_0069,399 expression was overtly upregulated in tumor tissues from LSCC patients, which was consistent with the sequencing results. Conclusion: hsa_circ_0069,399 could be a potential prognostic marker for LSCC.

Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multi-Parametric MRI.

PURPOSE: This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage, leveraging advanced imaging techniques to explore the relationship between tumor characteristics, glymphatic function, and aquaporin 4 (AQP4) expression. EXPERIMENTAL DESIGN: In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including Diffusion Tensor Imaging Analysis Along the Perivascular Space (DTI-ALPS) index and Multiparametric MRI (MTP) for quantitative brain mapping. Tumor and peri-tumor tissues were analyzed for AQP4 expression via immunofluorescence. Correlations between imaging parameters, glymphatic function (DTI-ALPS index), and AQP4 expression were statistically assessed. RESULTS: Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), brain tumor patients exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; p = 0.001) and increased cerebrospinal fluid (CSF) volume (201.376 cm³ vs. 115.957 cm³; p = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, p < 0.001), while AQP4 expression correlated positively with peritumoral brain edema (PTBE) volume (r: 0.989; p < 0.001) and negatively with PD in PTBE areas (ρ: -0.506; p < 0.001). CONCLUSIONS: Our findings highlight the interplay between tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, showing the utility of DTI-ALPS and MTP in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system.

Development of a Specific Aptamer-Modified Nano-System to Treat Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a prevalent gastrointestinal cancer characterized by high mortality and an unfavorable prognosis. While combination therapies involving surgery, chemotherapy, and radiation therapy are advancing, targeted therapy for ESCC remains underdeveloped. As a result, the overall five-year survival rate for ESCC is still below 20%. Herein, ESCC-specific DNA aptamers and an innovative aptamer-modified nano-system is introduced for targeted drug and gene delivery to effectively inhibit ESCC. The EA1 ssDNA aptamer, which binds robustly to ESCC cells with high specificity and affinity, is identified using cell-based systematic evolution of ligands by exponential enrichment (cell-SELEX). An EA1-modified nano-system is developed using a natural egg yolk lipid nanovector (EA1-EYLNs-PTX/siEFNA1) that concurrently loads paclitaxel (PTX) and a small interfering RNA of Ephrin A1 (EFNA1). This combination counters ESCC's proliferation, migration, invasion, and lung metastasis. Notably, EFNA1 is overexpressed in ESCC tumors with lung metastasis and has an inverse correlation with ESCC patient prognosis. The EA1-EYLNs-PTX/siEFNA1 nano-system offers effective drug delivery and tumor targeting, resulting in significantly improved therapeutic efficacy against ESCC tumors. These insights suggest that aptamer-modified nano-systems can deliver drugs and genes with superior tumor-targeting, potentially revolutionizing targeted therapy in ESCC.

Coupling Process between Droplet and Iron Investigated by Reactive Molecular Dynamics Simulations.

The droplet-to-iron electrochemical reaction is common in nature and industrial production, and it causes damage to the economy, safety, and the environment. The electrochemical reaction of droplet-to-iron is a coupling process of wetting and corrosion. Presently, investigations into electrochemical reactions mainly focus on the corrosions caused by a solution, and wetting is rarely considered. However, for the droplet-to-iron electrochemical reaction, the mechanism of charge transfer in the process is still unclear. In this paper, a reactive molecular dynamics simulation model for the droplet-to-iron electrochemical reaction is developed for the first time. The electrochemical reaction of droplet-to-iron is studied, and the interaction between droplet wetting and corrosion on iron is investigated. The effects of temperature, electric field strength, and salt concentration on the electrochemical reaction are explored. Results show that droplet wetting on the iron surface and the formation of a single-molecular-layer ordered structure are prerequisites for corrosion. The hydroxyl radicals that penetrate the ordered structure acquire electrons from iron atoms on the substrate surface under the action of Coulomb forces and form iron-containing oxides with these iron atoms. The corrosion products and craters lead to a reduced droplet height, which promotes droplet wetting on iron and further intensifies the droplet-to-iron electrochemical reaction.

[Application of metal cushion block combined with Jumbo cup in reconstruction of acetabular bone defect in revision of artificial hip joint].

OBJECTIVE: To investigate the application effect and imaging changes of metal cushion block combined with Jumbo cup in the reconstruction of acetabular bone defect after revision of artificial hip joint. METHODS: Retrospective analysis was made on the clinical data of 83 patients who underwent revision acetabular bone defect reconstruction of the artificial hip joint in our hospital from September 2019 to October 2021. They were divided into group A and group B according to different surgical methods. There were 42 patients in group A, including 26 males and 16 females, aged from 44 to 72 years old with an average of (60.57±4.62) years, who underwent revision with metal cushion block and Jumbo cup. There were 41 patients in group B, including 22 males and 19 females, aged from 42 to 71 years old with an average of (58.74±4.25) years, who underwent revision with metal cushion block and bone cement mortar cup. The operation related indexes, Harris hip function score and visual analogue scale (VAS) of pain before operation, 1 month and 12 month after operation were compared between two groups. The results of X-ray imaging examination (hip rotation center height, acetabular abduction angle, femoral eccentricity and imaging standard qualification rate) before and 12 month after operation were evaluated, and the incidence of complications was compared between two groups. RESULTS: There was no significant difference in operation time, intraoperative bleeding volume and postoperative drainage volume between two groups (P>0.05). Both groups were followed up for 12 to 36 months with an average of (25.36±3.59) months. The scores of pain, function, deformity and Harris' total score in the two groups at 1 month after operation were higher than those before operation (P<0.05), and the scores of pain, function, deformity, joint activity and Harris' total score in two groups at 1 year after operation were higher than those before operation and 1 month after operation (P<0.05), and the above scores in group A were higher than those in group B at 1 year after operation (P<0.05). The VAS of two groups decreased successively at 1 month and 1 year after operation (P<0.05), but there was no significant difference in both groups at each time point (P>0.05). The femoral eccentricity increased in both groups at 1 year after operation (P<0.05), and group A was higher than group B (P<0.05). The height of rotation center and acetabular abduction angle decreased in both groups at 1 year after operation (P<0.05), and the height of rotation center in group A was lower than that in group B (P<0.05), but there was no significant difference in acetabular abduction angle between two groups (P>0.05). The imaging qualification rate of group A was higher than that of group B (P<0.05). There was no significant difference in the incidence of adverse reactions between two groups (P>0.05). CONCLUSION: Metal cushion block combined with Jumbo cup in the treatment of acetabular bone defects can provide the hip joint function, and restore the hip joint rotation center, femoral eccentricity and acetabular abduction angle, with obvious clinical effect.

[Hip joint biomechanical analysis of the acetabular anatomical reconstruction and nonanatomical reconstruction in total hip arthroplasty for Crowe type â ¢ developmental dysplasia of the hip by finite element method].

OBJECTIVE: To analyze the hip joint biomechanics of the acetabular anatomical reconstruction and nonanatomical reconstruction in total hip arthroplasty (THA) for Crowe type Ⅲ developmental dysplasia of the hip (DDH) by finite element method, which provided theoretical foundation and experimental basis for the anatomical acetabular reconstruction during THA in clinical practice. METHODS: One patient with left end-stage hip arthritis secondary to Crowe type Ⅲ DDH was selected in this study, who underwent total hip arthroplasty in the orthopedic department of the First Affiliated Hospital of Bengbu Medical College in April 2020. This patient was female, 57 years old. The preoperative and postoperative three dimentional CT scan of the patient's pelvis were performed. Fourteen acetabular cup models with different anteversion, inclination and rotation center height were established in Mimics and 3-Matic software. The boundary and load conditions were set in Abaqus software. The Von Mises and stress distribution of the hip joint were calculated and observed. RESULTS: In the Crowe type Ⅲ DDH THA, if the hip rotation center was restored anatomically and the acetabular cup's inclination was set as 40°, the cup's anteversion varied from 5° to 25°, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 20°anteversioin;if the hip rotation center was restored anatomically and the acetabular cup's anteversion was set as 15°, the cup's inclination varied from 35° to 55°, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 35° inclination;if the acetabular cup's anteversion and inclination were set as 15°and 40°respectively, the up migration of hip rotaion center varied from 0 mm to 20 mm, the lowest Von Mises value of acetabular cup and polyethylene liner occured in 10 mm up migration. In all fourteen models, the Von Mises value of the acetabulum, acetabulum cup and polyethylene liner were lowest when the acetabular cup's anteversion and inlcination were 15°, 35° respectively, as well as the rotation center was restored anatomically. CONCLUSION: In total hip arthroplasty for Crowe type Ⅲ DDH, the anatomical restoration of hip rotation center with 15° anteversion and 35° inclination of the acetabular cup are suggested, bone graft above the acetabular cup and additional screws are recommended simultaneously to further reduce the Von Mises of hip joint.

Clinical relevance of somatic mutations in Chinese lung adenocarcinoma and their prognostic implications for survival.

BACKGROUND: To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. METHODS: A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis-related genes and establish a predictive model for stratifying patients with LUAD. RESULTS: In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK-RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic-Related Genes (CCRGs) were found to closely related to the clinical high-risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM-low group showed significantly better overall survival (OS) compared to the MPGM-high group (p < 0.0001, area under the curve (AUC) = 0.754). The robust performance was validated in 55 LUAD patients from the DPH cohort and another LUAD dataset. Immune characteristics analysis revealed a higher proportion of primarily DCs and mononuclear cells in the MPGM-low risk group, while the MPGM-high risk group showed lower immune cells and higher tumor cell infiltration. CONCLUSION: This study provides a comprehensive genomic landscape of Chinese LUAD patients and develops an MPGM risk model for LUAD prognosis stratification. Further follow-up will be performed for the patients in the DPH cohort consistently to explore the resistance and prognosis genetic features.

C634Y mutation in RET-induced multiple endocrine neoplasia type 2A: A case report.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners. CASE SUMMARY: Herein, we present RET proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the RET proto-oncogene was conducted. The C634Y mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the C634Y mutation, and the corresponding treatments administered based on test results and associated clinical guidelines. CONCLUSION: Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.

Evaluating the predictive value of angiogenesis-related genes for prognosis and immunotherapy response in prostate adenocarcinoma using machine learning and experimental approaches.

Background: Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a crucial role in the development and advancement of cancer. Although blocking angiogenesis has shown success in treating different types of solid tumors, its relevance in prostate adenocarcinoma (PRAD) has not been thoroughly investigated. Method: This study utilized the WGCNA method to identify angiogenesis-related genes and assessed their diagnostic and prognostic value in patients with PRAD through cluster analysis. A diagnostic model was constructed using multiple machine learning techniques, while a prognostic model was developed employing the LASSO algorithm, underscoring the relevance of angiogenesis-related genes in PRAD. Further analysis identified MAP7D3 as the most significant prognostic gene among angiogenesis-related genes using multivariate Cox regression analysis and various machine learning algorithms. The study also investigated the correlation between MAP7D3 and immune infiltration as well as drug sensitivity in PRAD. Molecular docking analysis was conducted to assess the binding affinity of MAP7D3 to angiogenic drugs. Immunohistochemistry analysis of 60 PRAD tissue samples confirmed the expression and prognostic value of MAP7D3. Result: Overall, the study identified 10 key angiogenesis-related genes through WGCNA and demonstrated their potential prognostic and immune-related implications in PRAD patients. MAP7D3 is found to be closely associated with the prognosis of PRAD and its response to immunotherapy. Through molecular docking studies, it was revealed that MAP7D3 exhibits a high binding affinity to angiogenic drugs. Furthermore, experimental data confirmed the upregulation of MAP7D3 in PRAD, correlating with a poorer prognosis. Conclusion: Our study confirmed the important role of angiogenesis-related genes in PRAD and identified a new angiogenesis-related target MAP7D3.

Exploring the Common Genetic Underpinnings of Chronic Pulmonary Disease and Esophageal Carcinoma Susceptibility.

Background: Pulmonary diseases and esophageal cancer are highly prevalent conditions with rising incidence worldwide. Prior evidence supports shared environmental and behavioral factors, but less is known regarding potential genetic links underlying this comorbidity. This study aimed to elucidate the complex genetic relationship between chronic lung diseases and esophageal cancer risk. Methods: Linkage disequilibrium score regression assessed the genetic correlation between esophageal cancer and asthma, COPD, and idiopathic pulmonary fibrosis leveraging extensive GWAS datasets. Pleiotropic analysis, gene-set enrichment, eQTL mapping, and mendelian randomization causality analyses were then conducted to identify specific shared genetic variants, enriched pathways, causal relationships and gene regulatory mechanisms connecting lung disease and cancer susceptibility. Results: Significant genetic correlations were observed between esophageal cancer and both COPD and asthma, but not idiopathic pulmonary fibrosis. Further analyses identified 13 pleiotropic loci and 6 shared genes including CHRNA4, ERBB3, and SMAD3, as well as pathways related to immune function. eQTL integration highlighted 53 genes like SOCS1, FGF2, and CHRNA5 with tissue-specific regulatory effects on disease risk. Bidirectional relationships were noted, whereby genetic predisposition to asthma and COPD increased esophageal cancer risk, while cancer liability reciprocally raised pulmonary fibrosis risk. Conclusions: These genomic analyses provide initial evidence that shared genetic factors may underpin the comorbidity between lung conditions and esophageal malignancy. The genes and pathways identified offer insights into biological mechanisms linking both diseases, aiding future screening, prevention and therapeutic efforts to mitigate this growing comorbidity burden.

Expression and diagnostic value of interleukin-22 in rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is characterized by a high incidence and mortality rate, highlighting the need for biomarkers to detect ILD early in RA patients. Previous studies have shown the protective effects of Interleukin-22 (IL-22) in pulmonary fibrosis using mouse models. This study aims to assess IL-22 expression in RA-ILD to validate foundational experiments and explore its diagnostic value. The study included 66 newly diagnosed RA patients (33 with ILD, 33 without ILD) and 14 healthy controls (HC). ELISA was utilized to measure IL-22 levels and perform intergroup comparisons. The correlation between IL-22 levels and the severity of RA-ILD was examined. Logistic regression analysis was employed to screen potential predictive factors for RA-ILD risk and establish a predictive nomogram. The diagnostic value of IL-22 in RA-ILD was assessed using ROC. Subsequently, the data were subjected to 30-fold cross-validation. IL-22 levels in the RA-ILD group were lower than in the RA-No-ILD group and were inversely correlated with the severity of RA-ILD. Logistic regression analysis identified IL-22, age, smoking history, anti-mutated citrullinated vimentin antibody (MCV-Ab), and mean corpuscular hemoglobin concentration (MCHC) as independent factors for distinguishing between the groups. The diagnostic value of IL-22 in RA-ILD was moderate (AUC = 0.75) and improved when combined with age, smoking history, MCV-Ab and MCHC (AUC = 0.97). After 30-fold cross-validation, the average AUC was 0.886. IL-22 expression is dysregulated in the pathogenesis of RA-ILD. This study highlights the potential of IL-22, along with other factors, as a valuable biomarker for assessing RA-ILD occurrence and progression.

S100A16 is a potential target for reshaping the tumor microenvironment in the hypoxic context of liver cancer.

BACKGROUND: The research on the S100 family has garnered significant attention; however, there remains a dearth of understanding regarding the precise role of S100A16 in the tumor microenvironment of liver cancer. METHOD: Comprehensive analysis was conducted on the expression of S100A16 in tumor tissues and its correlation with hypoxia genes. Furthermore, an investigation was carried out to examine the association between S100A16 and infiltration of immune cells in tumors as well as immunotherapy. Relevant findings were derived from the analysis of single cell sequencing data, focusing on the involvement of S100A16 in both cellular differentiation and intercellular communication. Finally, we validated the expression of S100A16 in liver cancer by Wuhan cohort and multiplexed immunofluorescence to investigate the correlation between S100A16 and hypoxia. RESULT: Tumor tissues displayed a notable increase in the expression of S100A16. A significant correlation was observed between S100A16 and genes associated with hypoxic genes. Examination of immune cell infiltration revealed an inverse association between T cell infiltration and the level of S100A16 expression. The high expression group of S100A16 exhibited a decrease in the expression of genes related to immune cell function. Single-cell sequencing data analysis revealed that non-immune cells predominantly expressed S100A16, and its expression levels increased along with the trajectory of cell differentiation. Additionally, there were significant variations observed in hypoxia genes as cells underwent differentiation. Cellular communication identified non-immune cells interacting with immune cells through multiple signaling pathways. The Wuhan cohort verified that S100A16 expression was increased in liver cancer. The expression of S100A16 and HIF was simultaneously elevated in endothelial cells. CONCLUSION: The strong association between S100A16 and immune cell infiltration is observed in the context of hypoxia, indicating its regulatory role in shaping the hypoxic tumor microenvironment in liver cancer.

PA28γ coordinates the cross-talk between cancer-associated fibroblasts and tumor cells to promote OSCC progression via HDAC1/E2F3/IGF2 signaling.

PA28γ overexpression is aberrant and accompanied by poor patient prognosis in various cancers, the precise regulatory mechanism of this crucial gene in the tumor microenvironment remains incompletely understood. In this study, using oral squamous cell carcinoma as a model, we demonstrated that PA28γ exhibits high expression in cancer-associated fibroblasts (CAFs), and its expression significantly correlates with the severity of clinical indicators of malignancy. Remarkably, we found that elevated levels of secreted IGF2 from PA28γ+ CAFs can enhance stemness maintenance and promote tumor cell aggressiveness through the activation of the MAPK/AKT pathway in a paracrine manner. Mechanistically, PA28γ upregulates IGF2 expression by stabilizing the E2F3 protein, a transcription factor of IGF2. Further mechanistic insights reveal that HDAC1 predominantly mediates the deacetylation and subsequent ubiquitination and degradation of E2F3. Notably, PA28γ interacts with HDAC1 and accelerates its degradation via a 20S proteasome-dependent pathway. Additionally, PA28γ+ CAFs exert an impact on the tumor immune microenvironment by secreting IGF2. Excitingly, our study suggests that targeting PA28γ+ CAFs or secreted IGF2 could increase the efficacy of PD-L1 therapy. Thus, our findings reveal the pivotal role of PA28γ in cell interactions in the tumor microenvironment and propose novel strategies for augmenting the effectiveness of immune checkpoint blockade in oral squamous cell carcinoma.

Reliability and validity tests of the Chinese version of the Geriatric Locomotive Function Scale (GLFS-25) in tumor survivors.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.

Characterizing Glycosylation of Adeno-Associated Virus Serotype 9 Capsid Proteins Generated from HEK293 Cells through Glycopeptide Mapping and Released Glycan Analysis.

Recombinant adeno-associated viral (AAV) vectors have emerged as prominent gene delivery vehicles for gene therapy. AAV capsid proteins determine tissue specificity and immunogenicity and play important roles in receptor binding, the escape of the virus from the endosome, and the transport of the viral DNA to the nuclei of target cells. Therefore, the comprehensive characterization of AAV capsid proteins is necessary for a better understanding of the vector assembly, stability, and transduction efficiency of AAV gene therapies. Glycosylation is one of the most common post-translational modifications (PTMs) and may affect the tissue tropism of AAV gene therapy. However, there are few studies on the characterization of the N- and O-glycosylation of AAV capsid proteins. In this study, we identified the N- and O-glycosylation sites and forms of AAV9 capsid proteins generated from HEK293 cells using liquid chromatography-tandem mass spectrometry (LC-MS)-based glycopeptide mapping and identified free N-glycans released from AAV9 capsid proteins by PNGase F using hydrophilic interaction (HILIC) LC-MS and HILIC LC-fluorescence detection (FLD) methods. This study demonstrates that AAV9 capsids are sprinkled with sugars, including N- and O-glycans, albeit at low levels. It may provide valuable information for a better understanding of AAV capsids in supporting AAV-based gene therapy development.

Plant-Derived Vesicle-like Nanoparticles: The Next-Generation Drug Delivery Nanoplatforms.

A wide variety of natural bioactive compounds derived from plants have demonstrated significant clinical relevance in the treatment of various diseases such as cancer, chronic disease, and inflammation. An increasing number of studies have surfaced that give credence to the potential of plant-derived vesicle-like nanoparticles (PDVLNs) as compelling candidates for a drug delivery system (DDS). PDVLNs are cost-effective production, non-toxicity and non-immunogenicity and fascinating bi-ocompatibility. In this review, we attempt to comprehensively review and consolidate the position of PDVLNs as next-generation drug delivery nanoplatforms. We aim to give a quick glance to readers of the current developments of PDVLNs, including their biogenesis, characteristic features, composition, administration routes, advantages, and application. Further, we discuss the advantages and limitations of PDVLNs. We expect that the role of PDVLNs in drug delivery will be significantly enhanced, thus positioning them as the next generation of therapeutic modalities in the foreseeable future.

SOX13 is a novel prognostic biomarker and associates with immune infiltration in breast cancer.

Background: The transcription factor, SOX13 is part of the SOX family. SOX proteins are crucial in the progression of many cancers, and some correlate with carcinogenesis. Nonetheless, the biological and clinical implications of SOX13 in human breast cancer (BC) remain rarely known. Methods: We evaluated the survival and expression data of SOX13 in BC patients via the UNLCAL, GEPIA, TIMER, and Kaplan-Meier plotter databases. Immunohistochemistry (IHC) was used to verify clinical specimens. The gene alteration rates of SOX13 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between SOX13 mRNA expression and copy number alterations (CNA) and methylation was determined. LinkedOmics was used to identify the genes that co-expressed with SOX13 and the regulators. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuCellAI and TIMER2.0 databases. SOX13 correlated drug resistance analysis was performed using the GDSC2 database. Results: Higher SOX13 expression was discovered in BC tissues in comparison to normal tissues. Moreover, increased gene mutation and amplification of SOX13 were found in BC. Patients with increased SOX13 expression levels showed worse overall survival (OS). Cox analysis showed that SOX13 independently served as a prognostic indicator for poor survival in BC. Further, the expression of SOX13 was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells. In terms of drug sensitivity analysis, we found higher expression level of SOX13 predicts a high IC50 value for most of 198 drugs which predicts drug resistance. Conclusion: The present findings demonstrated that high expression of SOX13 negatively relates to prognosis and SOX13 plays an important role in cancer immunity. Therefore, SOX13 may potentially be adopted as a biomarker for predicting BC prognosis and infiltration of immune cells.

The Ideal Proportion of the Auricle Exposure via a Morphometric Analysis in Asian Women.

BACKGROUND: Ears are an important aesthetic feature that is vital to the overall attractiveness of the face. Although there have been many studies on the aesthetics of the auricle, there is currently a lack of consensus on the ideal proportion of auricle exposure for Asian women in frontal view. OBJECTIVES: This study aimed to investigate ideal proportion of auricle exposure in Asian women. METHODS: An observational study was carried out on the photographs of 84 women on the list of the 100 most beautiful faces in Asia (published by TCC Asia in 2020). The proportion of the distance between the outer canthus and the outermost point of auricle to the distance between the inner canthus and the outermost point of auricle was calculated as the auricle exposure proportion. Evaluators were asked to rank a set of photographs of the volunteer with varying auricle exposure proportions from most attractive to least attractive. RESULTS: Measurements of the photographs of the 84 women showed a mean ear exposure proportion of 0.600. With 487 questionnaire responses received, the proportion of auricle exposure that the evaluators considered most attractive was 0.600. People with aesthetic experience considered 0.625 the most attractive proportion, while the general group considered 0.600 the most attractive. CONCLUSIONS: The ideal proportion of the auricle exposure for Asian women is in the range of 0.60-0.625, which may help surgeons reconstruct aesthetically pleasing ears. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

ODF3B affects the proliferation and apoptosis of glioma via the JAK/STAT pathway.

The pathogenesis of glioma has remained unclear. In this study, it was found that high expression of the outer dense fibers of sperm tail 3B (ODF3B) in gliomas was positively correlated with the grade of glioma. The higher the grade, the worse the prognosis. ODF3B is closely related to the growth and apoptosis of glioma. In terms of mechanism, ODF3B was found to affect the proliferation and apoptosis of glioma through the JAK1 and JAK2/STAT3 pathways. ODF3B was also found to affect the growth and apoptosis of glioma in vivo. We conclude that ODF3B affects glioma proliferation and apoptosis via the JAK/STAT pathway and is a potential therapeutic target.