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Glycyl-tRNA synthetase ( GARS1 ) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan–Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.

Cancer stem-like cells (CSLCs) acquire enhanced immune checkpoint responses to evade immune cell killing and promote tumor progression. Here we showed that signal regulatory protein γ (SIRPγ) determined CSLC properties and immune evasiveness in a small population of lung adenocarcinoma (LUAD) cancer cells. A SIRPγhi population displayed CSLC properties and transmitted the immune escape signal through sustaining CD47 expression in both SIRPγhi and SIRPγlo/- tumor cells. SIRPγ bridged MST1 and PP2A to facilitate MST1 dephosphorylation, resulting in Hippo/YAP activation and leading to cytokine release by CSLCs, which stimulated CD47 expression in LUAD cells and consequently inhibited tumor cell phagocytosis. SIRPγ promoted tumor growth and metastasis in vivo through YAP signaling. Notably, SIRPγ targeting with genetic SIRPγ knockdown or a SIRPγ-neutralizing antibody inhibited CSLC phenotypes and elicited phagocytosis that suppressed tumor growth in vivo. SIRPG was upregulated in human LUAD and its overexpression predicted poor survival outcome. Thus, SIRPγhi cells serve as CSLCs and tumor immune checkpoint-initiating cells, propagating the immune escape signal to the entire cancer cell population. Our study identifies Hippo/YAP signaling as the first mechanism by which SIRPγ is engaged and reveals that targeting SIRPγ represents an immune- and CSLC-targeting strategy for lung cancer therapy.

Background The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. Methods In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. Results We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. Conclusion Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.

Background: Computer-aided detection (CADe) of colon polyps has been demonstrated to improve colon polyp and adenoma detection during colonoscopy by indicating the location of a given polyp on a parallel monitor. The aim of this study was to investigate whether embedding the CADe system into the primary colonoscopy monitor may serve to increase polyp and adenoma detection, without increasing physician fatigue level. Methods: Consecutive patients presenting for colonoscopies were prospectively randomized to undergo routine colonoscopy with or without the assistance of a real-time polyp detection CADe system. Fatigue level was evaluated from score 0 to 10 by the performing endoscopists after each colonoscopy procedure. The main outcome was adenoma detection rate (ADR). Results: Out of 790 patients analyzed, 397 were randomized to routine colonoscopy (control group), and 393 to a colonoscopy with computer-aided diagnosis (CADe group). The ADRs were 20.91% and 29.01%, respectively (OR = 1.546, 95% CI 1.116–2.141, p = 0.009). The average number of adenomas per colonoscopy (APC) was 0.29 and 0.48, respectively (Change Folds = 1.64, 95% CI 1.299–2.063, p < 0.001). The improvement in polyp detection was mainly due to increased detection of non-advanced diminutive adenomas, serrated adenoma and hyperplastic polyps. The fatigue score for each procedure was 3.28 versus 3.40 for routine and CADe group, p = 0.357. Conclusions: A real-time CADe system employed on the primary endoscopy monitor may lead to improvements in ADR and polyp detection rate without increasing fatigue level during colonoscopy. The integration of a low-latency and high-performance CADe systems may serve as an effective quality assurance tool during colonoscopy. www.chictr.org.cn number, ChiCTR1800018058.

The burgeoning complexity of space missions has amplified the research focus on robots that are capable of assisting astronauts in accomplishing tasks within space stations. Nevertheless, these robots grapple with substantial mobility challenges in a weightless environment. This study proposed an omnidirectional continuous movement method for a dual-arm robot, inspired by the movement patterns of astronauts within space stations. On the basis of determining the configuration of the dual-arm robot, the kinematics and dynamics model of the robot during contact and flight phases were established. Thereafter, several constraints are determined, including obstacle constraints, prohibited contact area constraints, and performance constraints. An optimization algorithm based on the artificial bee colony algorithm was proposed to optimize the trunk motion law, contact point positions between the manipulators and the inner wall, as well as the driving torques. Through the real-time control of the two manipulators, the robot is capable of achieving omnidirectional continuous movement across various inner walls with complex structures while maintaining optimal comprehensive performance. Simulation results demonstrate the correctness of this method. The method proposed in this paper provides a theoretical basis for the application of mobile robots within space stations.

Background Schwannomas can occur in the body where nerve sheaths are present. Genitourinary schwannomas are very rare, especially primary bladder schwannomas. They account for only 0.1% of bladder tumours. The literature reports that simple surgical resection has a good effect and prognosis. Case presentation A 39-year-old man had no significant improvement in symptoms due to frequent urination and urgency for 1 month following the treatment of prostatitis for 2 weeks. Ultrasound and computed tomography (CT) showed a mass in the left side wall of the bladder (size approximately 2.0 × 1.9 cm) that had clear boundaries and protruded outward from the bladder. After the extraperitoneal space was dilated with a balloon, a minimally invasive laparoscopic partial cystectomy was performed in this space to remove the tumour. The pathological diagnosis was bladder schwannoma. Immunohistochemical staining showed that it was strongly S100 protein positive. There was no recurrence after 2 years follow-up by cystoscopy and CT. Conclusions Bladder schwannomas are clinically rare benign bladder lesions and no specific clinical manifestations. Laparoscopic partial cystectomy through the extraperitoneal space is a safe and feasible treatment option.

Objectives The objective of this study was to analyse trends in the burden of multiple myeloma (MM) in the five permanent members of the United Nations Security Council (China, the United States of America, the Russian Federation, England, and France) to understand country differences and factors. Methods The Global Burden of Disease Study 2021 was utilised to analyse the incidence and mortality trends of MM from 1990 to 2021. An age‐period‐cohort model was employed to evaluate the disparities among nations, while an autoregressive integrated moving average (ARIMA) model was employed to forecast the impending developments over the subsequent 15 years. Results The study found the burden of MM continues to increase in China and the Russian Federation, with significant increases particularly in older age groups. In the United States of America, age‐standardised incidence rates (ASIR) and age‐standardised death rates (ASDR) showed a downward trend, reflecting a reduction in the burden of disease. In England and France, ASIR increased overall, but ASDR remained stable. The burden of MM was found to be significantly correlated with age, period effect, and birth cohort through age‐period‐cohort analysis. The ARIMA model predictions indicated an increasing trend in ASIR and a stable ASDR in China and the Russian Federation, while in England, France, and the United States of America, there was an overall stabilisation of ASIR and ASDR. Conclusions Significant differences in the burden of MM were found among the five countries. China and the Russian Federation are facing an increasing MM burden, particularly in older age groups, while the United States of America, England and France have made progress through early screening and treatment. The study suggests focusing on older populations, promoting early diagnosis and personalised treatment, and addressing lifestyle and environmental factors. Future research should examine risk factors across countries to inform public health policy.

Hepatocellular carcinoma is associated with high mortality, and tumor metastasis is an important reason for poor prognosis. However, metastasis has not been effectively prevented in clinical therapy and the mechanisms underlying metastasis have not been fully characterized. CCAAT/enhancer-binding protein-α (C/EBPα) is a transcriptional regulator with an essential role in tumor metastasis. We used short-activating RNAs (saRNA) to enhance expression of C/EBPα. Intravenous injection of C/EBPα-saRNA in a nude mouse liver orthotopic xenograft tumor model inhibited intrahepatic and distant metastasis. C/EBPα-saRNA-treated mice showed increased serum levels of albumin and decreased alanine aminotransferase (ALT), glutamic-oxalacetic transaminase (AST), indicating a role of C/EBPα in improving liver function. Migration and invasion were inhibited in hepatoma cell lines transfected with C/EBPα-saRNA. We also observed an inhibition of epithelial-mesenchymal transition (EMT) and suppression of epidermal growth factor receptor (EGFR), EGFR phosphorylation, and β-catenin in C/EBPa-saRNA-transfected cells. Our results suggested that C/EBPα-saRNA successfully inhibited HCC metastasis by inhibiting EGFR/β-catenin signaling pathway mediated EMT in vitro and in vivo.

Bladder cancer (BC) exhibits significant gender disparities in incidence and prognosis, with women experiencing worse prognosis despite lower incidence rates. This study aims to elucidate the molecular mechanisms underlying these gender-specific differences, focusing on the role of the long non-coding RNA XIST. Comprehensive bioinformatics analysis was performed using TCGA and GSE13507 cohorts to identify gender-differential gene expression. Functional experiments including cell proliferation, migration, and invasion assays were conducted in bladder cancer cell lines. Molecular interactions were investigated through gene knockdown, overexpression, and luciferase reporter assays. A zebrafish model was employed to validate findings. Our study revealed that XIST expression is significantly higher in female bladder cancer tissues and strongly associated with poor prognosis in female patients. The XIST/miR-15a-5p/MN1/FZD2 signaling axis was found to play a critical role in promoting bladder cancer progression. Specifically, XIST upregulates MN1 by sponging miR-15a-5p, which in turn enhances FZD2 expression. Functional experiments demonstrated that XIST knockdown significantly inhibited bladder cancer cell proliferation, migration, and invasion, effects which could be reversed by FZD2 overexpression. The XIST/miR-15a-5p/MN1 signaling axis plays a critical role in the gender disparity observed in bladder cancer prognosis, particularly in women. Targeting this pathway may offer new therapeutic strategies for improving outcomes in female BC patients.