ALKBH5-mediated m6A modification of circFOXP1 promotes gastric cancer progression by regulating SOX4 expression and sponging miR-338-3p.

Circular RNAs (circRNAs) have recently been suggested as potential functional modulators of cellular physiology processes in gastric cancer (GC). In this study, we demonstrated that circFOXP1 was more highly expressed in GC tissues. High circFOXP1 expression was positively associated with tumor size, lymph node metastasis, TNM stage, and poor prognosis in patients with GC. Cox multivariate analysis revealed that higher circFOXP1 expression was an independent risk factor for disease-free survival (DFS) and overall survival (OS) in GC patients. Functional studies showed that increased circFOXP1 expression promoted cell proliferation, cell invasion, and cell cycle progression in GC in vitro. In vivo, the knockdown of circFOXP1 inhibited tumor growth. Mechanistically, we observed ALKBH5-mediated m6A modification of circFOXP1 and circFOXP1 promoted GC progression by regulating SOX4 expression and sponging miR-338-3p in GC cells. Thus, our findings highlight that circFOXP1 could serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for GC.

A Multi-Scale Anti-Multipath Algorithm for GNSS-RTK Monitoring Application.

During short baseline measurements in the Real-Time Kinematic Global Navigation Satellite System (GNSS-RTK), multipath error has a significant impact on the quality of observed data. Aiming at the characteristics of multipath error in GNSS-RTK measurements, a novel method that combines improved complete ensemble empirical mode decomposition with adaptive noise (ICEEMDAN) and adaptive wavelet packet threshold denoising (AWPTD) is proposed to reduce the effects of multipath error in GNSS-RTK measurements through modal function decomposition, effective coefficient sieving, and adaptive thresholding denoising. It first utilizes the ICEEMDAN algorithm to decompose the observed data into a series of intrinsic mode functions (IMFs). Then, a novel IMF selection method is designed based on information entropy to accurately locate the IMFs containing multipath error information. Finally, an optimized adaptive denoising method is applied to the selected IMFs to preserve the original signal characteristics to the maximum possible extent and improve the accuracy of the multipath error correction model. This study shows that the ICEEMDAN-AWPTD algorithm provides a multipath error correction model with higher accuracy compared to singular filtering algorithms based on the results of simulation data and GNSS-RTK data. After the multipath correction, the accuracy of the E, N, and U coordinates increased by 49.2%, 65.1%, and 56.6%, respectively.

FASN promotes gallbladder cancer progression and reduces cancer cell sensitivity to gemcitabine through PI3K/AKT signaling.

Lipid metabolism plays an important role in the growth and development of tumors. However, the role of lipid metabolism in gallbladder cancer (GBC) has not been clearly clarified. Here, we demonstrated that fatty acid synthase (FASN), a key enzyme in de novo fatty acid biosynthesis, had upregulated expression in GBC samples both at protein and mRNA levels. Analysis of clinical data indicated the association between elevated FASN expression and poorer histology grades. Furthermore, FASN activity impairment through FASN knockdown or treatment with orlistat resulted in the inhibition of cell proliferation and migration, as well as increased sensitivity to gemcitabine. Both FASN knockdown and orlistat treatment induced cell apoptosis. Mechanistically, impairment of FASN activity suppressed the activation of the PI3K/AKT signaling pathway, which led to increased cell apoptosis and sensitivity to gemcitabine. These findings were also validated through nude mouse xenograft models, thus highlighting the potential of targeting FASN as a clinical treatment strategy. Collectively, the present study underscores the crucial role of FASN in the progression of gallbladder cancer via the PI3K/AKT pathway.

Drug resistance and new therapies in gallbladder cancer.

Gallbladder cancer (GBC) is a highly aggressive malignancy, which poses significant challenges for timely diagnosis, resulting in a dismal prognosis. Chemotherapy serves as a primary treatment option in cases where surgery is not feasible. However, the emergence of chemoresistance poses a significant challenge to the effectiveness of chemotherapy, ultimately resulting in a poor prognosis. Despite extensive research on mechanisms of chemotherapeutic resistance in oncology, the underlying mechanisms of chemoresistance in GBC remain poorly understood. In this review, we present the findings from the last decade on the molecular mechanisms of chemotherapeutic resistance in GBC. We hope that these insights may provide novel therapeutic and experimental targets for further investigations into this lethal disease.

CircRNA MBOAT2 promotes intrahepatic cholangiocarcinoma progression and lipid metabolism reprogramming by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export.

The carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well-established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression, such as circRNAs, regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism-related circRNA, circMBOAT2 (hsa_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. CircMBOAT2 knockdown inhibits the growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protects PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.

A Partial Ambiguity Resolution Algorithm Based on New-Breadth-First Lattice Search in High-Dimension Situations.

With the development and integration of GNSS systems in the world, the positioning accuracy and reliability of GNSS navigation services are increasing in various fields. Because the current multisystem fusion leads to an increase in the ambiguity dimension and the ambiguity parameters have discrete characteristics, the current conventional search algorithm leads to low search efficiency when the ambiguity dimension is large. Therefore, this paper describes a new algorithm that searches the optimal lattice points by lattice theory through the breadth-first algorithm and reduces the search space of ambiguity by calculating and judging the Euclidean distance between each search variable and the target one so as to propose a new lattice ambiguity search algorithm based on the breadth-first algorithm. The experimental results show that this method can effectively improve the search efficiency of ambiguity in high-dimension situations.

New Advances in Nano-Drug Delivery Systems: Helicobacter pylori and Gastric Cancer.

With the development of materials science and biomedicine, the application of nanomaterials in the medical field is further promoted. In the process of the diagnosis and treatment of diseases, a variety of drugs need to be used. It is an ideal state to make these drugs arrive at a specific location at a specific time and release at a specific speed, which can improve the bioavailability of drugs and reduce the adverse effects of drugs on normal tissues. Traditional drug delivery methods such as tablets, capsules, syrups, and ointments have certain limitations. The emergence of a new nano-drug delivery system further improves the accuracy of drug delivery and the efficacy of drugs. It is well known that the development of the cancer of the stomach is the most serious consequence for the infection of Helicobacter pylori. For the patients who are suffering from gastric cancer, the treatments are mainly surgery, chemotherapy, targeted and immune therapy, and other comprehensive treatments. Although great progress has been made, the diagnosis and prognosis of gastric cancer are still poor with patients usually diagnosed with cancer at an advanced stage. Current treatments are of limited benefits for patients, resulting in a poor 5-year survival rate. Nanomaterials may play a critical role in early diagnosis. A nano-drug delivery system can significantly improve the chemotherapy, targeted therapy, and immunotherapy of advanced gastric cancer, reduce the side effects of the original treatment plan and provide patients with better benefits. It is a promising treatment for gastric cancer. This article introduces the application of nanomaterials in the diagnosis and treatment of H. pylori and gastric cancer.

Updated genetic studies of Marfan syndrome in China.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disease that affects multiple systems such as the ocular, skeletal, and cardiovascular systems. This disease is relatively rare and has no effective treatment except for symptomatic treatment. As a result, early detection, early intervention, and preventing the occurrence of adverse cardiovascular outcomes are crucial to the diagnosis and treatment of MFS. The rapid development of gene sequencing technology has facilitated the detection of MFS at the genetic level, allowing a more accurate and efficient diagnosis of the disease. Therefore, research on MFS-related genes has become a topic of interest. This article reviews the recent progress of genetic research on MFS in China.

CircTP63 promotes cell proliferation and invasion by regulating EZH2 via sponging miR-217 in gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis in patients with GBC. CircRNA TP63 (circTP63) has been implicated in cell proliferation and invasion in some tumor progress. The study aims to investigate the clinical significance and functional role of circTP63 expression in GBC. METHODS: The expression of circTP63 in GBC tissues or cells was detected by qRT-PCR and the association between circTP63 expression and prognosis of GBC patients was analyzed. CCK8 assay, flow cytometry analysis, transwell assay and in vivo studies were used to evaluate the cell proliferation and invasion abilities after circTP63 knockdown in GBC cells. Luciferase reporter assays and RNA pull-down assay were used to determine the correlation between circTP63 and miR-217 expression. Besides, western blot analysis was also performed. RESULTS: In the present study, we showed that circTP63 expression was upregulated in GBC tissues and cells. Higher circTP63 expression was associated with lymph node metastasis and short overall survival (OS) in patients with GBC. In vitro, knockdown of circTP63 significantly inhibited cell proliferation, cell cycle progression, migration and invasion abilities in GBC. Besides, we demonstrated that knockdown of circTP63 inhibited GBC cells Epithelial-Mesenchymal Transition (EMT) process. In vivo, knockdown of circTP63 inhibited tumor growth in GBC. Mechanistically, we demonstrated that circTP63 competitively bind to miR-217 and promoted EZH2 expression and finally facilitated tumor progression. CONCLUSIONS: Our findings demonstrated that circTP63 sponged to miR-217 and regulated EZH2 expression and finally facilitated tumor progression in GBC. Thus, targeting circTP63 may be a therapeutic strategy for the treatment of GBC.

Circß-catenin promotes tumor growth and Warburg effect of gallbladder cancer by regulating STMN1 expression.

Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circß-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circß-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circß-catenin overexpression had the opposite effects. In vivo, silencing of circß-catenin inhibited tumor growth. Furthermore, we also found that circß-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circß-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circß-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circß-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circß-catenin might be a potential therapeutic strategy for GBC.

CircPVT1 promotes gallbladder cancer growth by sponging miR-339-3p and regulates MCL-1 expression.

Circular RNAs (circRNAs) have been implicated in modulating biological processes in some tumors. However, the contributions and molecular mechanisms of circRNAs to gallbladder cancer (GBC) remain largely unknown. In the present study, our results showed circPVT1 expression was significantly upregulated in GBC tissues and cells. Higher circPVT1 expression was correlated with lymph node metastasis, advanced TNM stage, and poor overall survival (OS) in patients with GBC. Subsequently, knockdown of circPVT1 significantly impeded GBC cell proliferation, migration, invasion, while induced cell apoptosis in vitro. However, upregulated circPVT1 had the opposite effects. In vivo, we also demonstrated that knockdown of circPVT1 inhibited tumor growth. Furthermore, we confirmed that circPVT1 could regulate Myeloid cell leukemia-1 (MCL-1) expression by sponging to miR-339-3p, which affected tumor progression in GBC cells. In summary, our findings indicated that circPVT1 may serve as a promising prognostic marker and therapeutic target for GBC.

Long Non-coding RNA FIRRE Acts as a miR-520a-3p Sponge to Promote Gallbladder Cancer Progression via Mediating YOD1 Expression.

OBJECTIVES: The role of lncRNAs in gallbladder cancer (GBC) remains poorly understood. In this study, we explored the function of functional intergenic repeating RNA element (FIRRE) in GBC. MATERIALS AND METHODS: Whole transcriptome resequencing was performed in three pairs of GBC tissues and adjacent non-tumor tissues. lncRNA FIRRE expression was verified by real-time PCR. The function of FIRRE in GBC was evaluated by experiments in vitro and in vivo. The mechanism of FIRRE was investigated via fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter assays, and RNA immunoprecipitation. RESULTS: FIRRE level was dramatically increased in GBC tissues compared to that in the adjacent non-tumor tissues. High expression of FIRRE was closely related to clinical stage and poor prognosis in GBC patients. Moreover, FIRRE remarkably enhanced proliferation and migration, and inhibited apoptosis of GBC cells. Mechanistically, FIRRE modulated YOD1 expression by sponging miR-520a-3p, thus contributing to the development of GBC. CONCLUSION: Our data revealed that FIRRE might act as a novel mediator in GBC progression by sponging miR-520a-3p and regulating YOD1. FIRRE might be regarded as a potential diagnostic marker or target for GBC treatment.

Orphan drugs in different countries and development of new drugs to treat biliary tract cancer.

Biliary tract cancer (BTC), which includes cholangiocarcinoma and gallbladder carcinoma, is a rare malignancy. Due to its low incidence, drugs treating these diseases are scarce, so they can be considered orphan drugs. The main treatment choice for BTC is chemotherapy with gemcitabine or cisplatin or combined use of both, but patients fail to significantly benefit from established chemotherapy. Advancements in immunotherapy and targeted therapy will shed light on ways to improve clinical outcomes for patients with BTC. In conjunction, more new drugs will come onto the market. This article compares the conditions for development of orphan drugs in different countries and it describes several types of new drugs that were recently approved to treat BTC.

The immunological characteristics of gallbladder carcinoma and advances in immunotherapy practices.

Gallbladder carcinoma (GBC) is one of the most common malignant tumors in the biliary system, ranking sixth among gastrointestinal malignancies. In addition, the incidence of GBC has recently increased in China. GBC metastasizes early and invades adjacent organs such as the liver, making patients with GBC ineligible for radical surgery and giving them a poor prognosis. What is more, GBC is more inclined to develop chemo-resistance, which requires new strategies for clinical intervention. Cancer immunotherapy has made great advances over the past few years, with improved clinical efficacy against multiple malignancies, including GBC. This review summarizes the immunological characteristics of GBC as well as current advances in immunotherapies for GBC in order to provide new insights into future treatment and prevention of GBC.