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BACKGROUND: Empathy is important in hospice nursing clinics and may influence nurses' professional quality of life (ProQOL). However, present studies ignoring each empathic dimension, and few researches have explored the correlation between empathy and ProQOL in hospice nurses in Asia. To better understand hospice nurses' empathy abilities in China and its relationship with ProQOL, the aim of this study was to identify the latent profiles and its influencing factors of hospice nurses' empathy ability, as well as differences in ProQOL across each latent profile. METHODS: A cross-sectional study was conducted from October 2021 to September 2022, and a total of 725 hospice nurses were recruited from different geographic regions in China. Participants completed the Empathy Ability Scale for Hospice Nurses and the Brief Professional Quality of Life Scale. Latent profile analysis (LPA) was employed to identify latent profiles of empathy ability among hospice nurses in China. The predictors of hospice nurses' empathy ability in different latent profiles were assessed using multinomial logistic regression analysis. One-way ANOVA test and the Kruskal-Wallis test were used to compare the ProQOL scores in each latent profile of nurses' empathy ability. RESULTS: This study identified three latent profiles of hospice nurses' empathy ability, and those profiles labelled "poor empathy ability-high surface empathy expression" (n = 216, 29.8%), "moderate empathy ability" (n = 359, 49.5%) and "high empathy ability-high deep empathy expression" (n = 150, 20.7%). Multinomial logistic regression analysis suggested that age, hospital level, whether income meets expectations, interests in hospice care work, hospice work experience, and receiving psychological counselling were predictors of hospice nurses' profile membership of empathy ability. The scores of compassion satisfaction (CS) and burnout (BO) in ProQOL were significantly different across each profile (P < 0.001), while scores of secondary traumatic stress (STS) in ProQOL were not different across each profile (P = 0.294). CONCLUSIONS: Hospice nurses' empathy ability was divided into three latent profiles, and enhancing empathy ability may be conducive to improving hospice nurses' CS, while reducing BO, thus fostering their overall quality of life. Nursing managers should identify hospice nurses at higher risk of BO and implement targeted interventions focused on enhancing nurse's empathy abilities.

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BACKGROUND: Sepsis commonly leads to skeletal muscle atrophy, characterized by substantial muscle weakness and degeneration, ultimately contributing to an adverse prognosis. Studies have shown that programmed cell death is an important factor in the progression of muscle loss in sepsis. However, the precise role and mechanism of pyroptosis in skeletal muscle atrophy are not yet fully comprehended. Therefore, we aimed to examine the role and mechanism of action of the pyroptosis effector protein GSDMD in recognized cellular and mouse models of sepsis. METHODS: The levels of GSDMD and N-GSDMD in skeletal muscle were evaluated 2, 4, and 8 days after CLP. Sepsis was produced in mice that lacked the Gsdmd gene (Gsdmd knockout) and in mice with the normal Gsdmd gene (wild-type) using a procedure called cecal ligation and puncture (CLP). The degree of muscular atrophy in the gastrocnemius and tibialis anterior muscles was assessed 72 hours after surgery in the septic mouse model. In addition, the architecture of skeletal muscles, protein expression, and markers associated with pathways leading to muscle atrophy were examined in mice from various groups 72 hours after surgery. The in vitro investigations entailed the use of siRNA to suppress Gsdmd expression in C2C12 cells, followed by stimulation of these cells with lipopolysaccharide (LPS) to evaluate the impact of Gsdmd downregulation on muscle atrophy and the related signaling cascades. RESULTS: This study has demonstrated that the GSDMD protein, known as the "executive" protein of pyroptosis, plays a crucial role in the advancement of skeletal muscle atrophy in septic mice. The expression of N-GSDMD in the skeletal muscle of septic mice was markedly higher compared to the control group. The Gsdmd knockout mice exhibited notable enhancements in survival, muscle strength, and body weight compared to the septic mice. Deletion of the Gsdmd gene reduced muscular wasting in the gastrocnemius and tibialis anterior muscles caused by sepsis. Studies conducted in living organisms (in vivo) and in laboratory conditions (in vitro) have shown that the absence of the Gsdmd gene decreases indicators of muscle loss associated with sepsis by blocking the IL18/AMPK signaling pathway. CONCLUSION: The results of this study demonstrate that the lack of Gsdmd has a beneficial effect on septic skeletal muscle atrophy by reducing the activation of IL18/AMPK and inhibiting the UPS and autophagy pathways. Therefore, our research provides vital insights into the role of pyroptosis in sepsis-related skeletal muscle wasting, which could potentially lead to the development of therapeutic and interventional approaches for preventing septic skeletal muscle atrophy.

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Sepsis­induced myopathy (SIM) is one of the leading causes of death in critically ill patients. SIM mainly involves the respiratory and skeletal muscles of patients, resulting in an increased risk of lung infection, aggravated respiratory failure, and prolonged mechanical ventilation and hospital stay. SIM is also an independent risk factor associated with increased mortality in critically ill patients. At present, no effective treatment for SIM has yet been established. However, mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach and have been utilized in the treatment of various clinical conditions. A significant body of basic and clinical research supports the efficacy of MSCs in managing sepsis and muscle­related diseases. This literature review aims to explore the relationship between MSCs and sepsis, as well as their impact on skeletal muscle­associated diseases. Additionally, the present review discusses the potential mechanisms and therapeutic benefits of MSCs in the context of SIM.

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Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine-threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named "quadruple WT" GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

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Soil salinity pose a significant challenge to global agriculture, threatening crop yields and food security. Understanding the salt tolerance mechanisms of plants is crucial for improving their survival under salt stress. AFP2, a negative regulator of ABA signaling, has been shown to play a crucial role in salt stress tolerance during seed germination. Mutations in AFP2 gene lead to increased sensitivity to salt stress. However, the underline mechanisms by which AFP2 regulates seed germination under salt stress remain elusive. In this study, we identified a protein interaction between AFP2 and SOS2, a Ser/Thr protein kinase known to play a critical role in salt stress response. Using a combination of genetic, biochemical, and physiological approaches, we investigated the role of the SOS2-AFP2 module in regulating seed germination under salt stress. Our findings reveal that SOS2 physically interacts with AFP2 and stabilizes it, leading to the degradation of the ABI5 protein, a negative transcription factor in seed germination under salt stress. This study sheds light on previously unknown connections within salt stress and ABA signaling, paving the way for novel strategies to enhance plant resilience against environmental challenges.

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Background: The role of Ferroptosis in the course of sepsis-induced myopathy is yet unclear. The objective of our work is to identify key genes connected with Ferroptosis in sepsis-induced myopathy and investigate possible pharmaceutical targets related to this process. This research aims to provide new insights into the management of sepsis-induced myopathy. Methods: We got the GSE13205 dataset from the Gene Expression Omnibus (GEO) and extracted Ferroptosis-associated genes from the FerrDb database. After conducting a functional annotation analysis of these genes, we created a protein-protein interaction network using Cytoscape software to identify important genes. Subsequently, we employed CMap to investigate prospective pharmaceuticals that could target these crucial genes. Results: A total of 61 genes that are expressed differently (DEGs) have been found concerning Ferroptosis. These genes are involved in a wide range of biological functions, including reacting to signals from outside the cell and the availability of nutrients, programmed cell death, controlling apoptosis, and responding to peptides, chemical stressors, and hormones. The KEGG pathway study revealed that these pathways are involved in Ferroptosis, autophagy, P53 signaling, PI3K-Akt signaling, mTOR signaling, HIF-1 signaling, endocrine resistance, and different tumorigenic processes. In addition, we created a network that shows the simultaneous expression of important genes and determined the top 10 medications that have the potential to treat sepsis-induced myopathy. Conclusion: The bioinformatics research undertaken sheds insight into the probable role of Ferroptosis-associated genes in sepsis-induced myopathy. The identified critical genes show potential as therapeutic targets for treating sepsis-induced myopathy, offering opportunities for the development of tailored medicines.

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Objective: This study aims to explore the influence of dyadic coping (DC) on the quality of life (QoL) of spousal caregivers for patients with cervical cancer and to investigate the mediating role of self-efficacy in this relationship. Methods: A convenience sample of 206 spouses of cervical cancer patients from five hospitals in Jiangsu Province, China, was included in the study. The participants completed three instruments: the 12-item Short-Form Health Survey, the General Self-Efficacy Scale, and the Dyadic Coping Inventory. Structural Equation Modeling (SEM) was used to analyze the mediating effect of self-efficacy in the DC and QoL relationship. Results: The study found a positive correlation between self-efficacy and DC. Self-efficacy partially mediated the impact of DC on QoL, accounting for 16% of the total effect. Self-efficacy played a mediating role in facilitating the indirect positive effects of DC on QoL. Conclusions: Spousal caregivers of cervical cancer patients frequently experience a relatively low QoL. The results suggest that interventions aimed at enhancing DC among spousal caregivers should incorporate strategies to improve self-efficacy, given its mediating role in the positive relationship between DC and QoL.

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(Difluoromethylated cyclopropane represents an important motif, which is widely found in bioactive and functional molecules. Despite significant progress in modern chemistry, the atom-economic and enantioselective synthesis of difluoromethylated cyclopropanes is still challenging. Herein, an Rh2 (II)-catalyzed asymmetric enyne cycloisomerization is described to construct chiral difluoromethylated cyclopropane derivatives with up to 99% yield and 99% ee in low catalyst loading (0.2 mol%), which can be easily transformed into highly functionalized difluoromethylated cyclopropanes with vicinal all-carbon quaternary stereocenters by ozonolysis. Mechanistic studies and the crystal structures of alkyne-dirhodium complexes reveal that the cooperative weak hydrogen bondings between the substrates and the dirhodium catalyst may play key roles in this reaction.).

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Truncated transforming growth factor ß receptor type II (tTßRII), serving as a trap for binding excessive transforming growth factor ß1 (TGF-ß1) by means of competing with wild-type TßRII, is a promising strategy for the treatment of kidney fibrosis. Platelet-derived growth factor ß receptor (PDGFßR) is highly expressed in interstitial myofibroblasts in kidney fibrosis. This study identified the interaction between a novel tTßRII variant Z-tTßRII (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of tTßRII) and TGF-ß1. Moreover, Z-tTßRII highly targeted to TGF-ß1-activated NIH3T3 cells and UUO-induced fibrotic kidney, but less to normal cells, tissues, and organs. Furthermore, Z-tTßRII significantly inhibited cell proliferation and migration, and reduced fibrosis markers expression and phosphorylation level of Smad2/3 in activated NIH3T3 cells. Meanwhile, Z-tTßRII markedly alleviated the kidney histopathology and fibrotic responses, and inhibited the TGF-ß1/Smad signaling pathway in UUO mice. Besides, Z-tTßRII showed good safety performance in the treatment of UUO mice. In conclusion, these results demonstrated that Z-tTßRII may be a potential candidate for a targeting therapy on renal fibrosis due to the high potential of fibrotic kidney-targeting and strong anti-renal fibrosis activity.

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Background: Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PIICS) is a significant contributor to adverse long-term outcomes in severe trauma patients. Objective: The objective of this study was to establish and validate a PIICS predictive model in severe trauma patients, providing a practical tool for early clinical prediction. Patients and methods: Adult severe trauma patients with an Injury Severity Score (ISS) of ≥16, admitted between October 2020 and December 2022, were randomly divided into a training set and a validation set in a 7:3 ratio. Patients were classified into PIICS and non-PIICS groups based on diagnostic criteria. LASSO regression was used to select appropriate variables for constructing the prognostic model. A logistic regression model was developed and presented in the form of a nomogram. The performance of the model was evaluated using calibration and ROC curves. Results: A total of 215 patients were included, consisting of 155 males (72.1%) and 60 females (27.9%), with a median age of 51 years (range: 38-59). NRS2002, ISS, APACHE II, and SOFA scores were selected using LASSO regression to construct the prognostic model. The AUC of the ROC analysis for the predictive model in the validation set was 0.84 (95% CI 0.72-0.95). The Hosmer-Lemeshow test in the validation set yielded a χ2 value of 14.74, with a value of p of 0.098. Conclusion: An accurate and easily implementable PIICS risk prediction model was established. It can enhance risk stratification during hospitalization for severe trauma patients, providing a novel approach for prognostic prediction.

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AIMS: To identify N-acetyltransferase 10 (NAT10) and its downstream signaling pathways in myocytes and skeletal muscle, and to investigate its role in inflammation-induced muscle atrophy. MATERIALS AND METHODS: Cecal ligation and puncture models were used to induce sepsis in C57BL/6 mice, which were treated with either a NAT10 inhibitor or a control agent. The therapeutic effect of NAT10 inhibitor was investigated by evaluating the mass, morphology, and molecular characteristics of mouse skeletal muscle. C2C12 cells were stimulated with LPS, and the expression of the NAT10 gene, downstream protein content, and atrophy phenotype were analyzed using a NAT10 inhibitor, to further explore the atrophic effect of NAT10 on C2C12 differentiated myotubes. RESULTS: Gene set enrichment analysis revealed that NAT10 expression was elevated in the Lateral femoris muscle of patients with ICUAW. In vitro and in vivo experiments showed that sepsis or LPS induced the upregulation of NAT10 expression in skeletal muscles and C2C12 myotubes. Skeletal muscle mass, tissue morphology, gene expression, and protein content were associated with atrophic response in sepsis models. Remodelin ameliorated the LPS-induced skeletal muscle weight loss, as well as muscular atrophy, and improved survival. Remodelin reversed the atrophy program that was induced by inflammation through the downregulation of the ROS/NLRP3 pathway, along with the inhibition of the expression of MuRF1 and Atrogin-1. CONCLUSION: NAT10 is closely related to skeletal muscle atrophy during sepsis. Remodelin improves the survival rate of mice by improving the systemic inflammatory response and skeletal muscle atrophy by downregulating the ROS/NLRP3 signaling pathway.

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PURPOSE: This study aims to find candidates for testicular spermatozoa retrieval biomarkers among the seminal plasma exLncRNA pairs. MATERIALS AND METHODS: A set of exLncRNA pairs with the best potential biomarkers was selected and validated in 96 NOA samples. Weighted correlation network analysis (WGCNA) and Least Absolute Shrinkage and Selection Operator were used to identify possible biomarkers for these pairs (LASSO). These pairs' potential biomarkers were identified using receiver operating curves. Confusion matrices and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), FP, false-negative rates (FNR), and F1 scores are calculated. Through F1 scores, we selected the best threshold value. RESULTS: The relative differential expression of each pair in testicular spermatozoa retrieval (+) and testicular spermatozoa retrieval (-) men were validated. The six pairs displayed the best biomarker potential. Among them, CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair showed the most significant potential and stability for detecting testicular spermatozoa retrieval in the selected and validated cohort. CONCLUSION: CCDC37.DT-LOCI00505685 pair and LOC440934- LOCI01929088 (XR_001745218.1) pair have the potential to become new molecular biomarkers that could help to select clinical strategies for microdissection testicular sperm extraction.

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Chiral biscyclopropanes are an important skeleton in many bioactive molecules. However, there are few routes to synthesize these molecules with high stereoselectivity due to the nature of multiple stereocenters. Herein, we report the first example of Rh2 (II)-catalyzed enantioselective synthesis of bicyclopropanes with alkynes as dicarbene equivalents. The bicyclopropanes with 4-5 vicinal stereocenters and 2-3 all-carbon quaternary centers were constructed in excellent stereoselectivity. This protocol features high efficiency and excellent functional group tolerance. Moreover, the protocol was also extended to the cascaded cyclopropanation/cyclopropenation with excellent stereoselectivities. In these processes, both sp-carbons of alkyne were converted into stereogenic sp3 -carbons. Experimental and density functional theory (DFT) calculations revealed that the cooperative weak hydrogen bonds between the substrates and the dirhodium catalyst may play key roles in this reaction.

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Methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) were two core components of the N6-methyadenosine (m6A) methyltransferase complex (MTC) and played a basic role in maintaining an appropriate m6A level of target genes. In gastric cancer (GC), previous researches on the expression and role of METTL3 and METTL14 were not consistent, and their specific function and mechanism have remained elusive. In this study, the expression of METTL3 and METTL14 was evaluated based on the TCGA database, 9 paired GEO datasets, and our 33 GC patient samples, and METTL3 was highly expressed and acted as a poor prognostic factor, whereas METTL14 showed no significant difference. Moreover, GO and GSEA analyses were performed, and the results pointed out that METTL3 and METTL14 were jointly involved in multiple biological processes, while they could also take part in different oncogenic pathways independently. And BCLAF1 was predicted and identified as a novel shared target of METTL3 and METTL14 in GC. In total, we conducted a comprehensive analysis of METTL3 and METTL14 in GC including their expression, function, and role, which could provide a novel insight into the research of m6A modification in GC.

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OBJECTIVE: DDX3X is involved in various pathological processes such as infection, immunity and cell death. This study aimed to investigate the effect of RK-33, a specific inhibitor of DDX3X, on the progression of sepsis to persistent inflammation, immune suppression and catabolism syndrome(PICS). METHODS: The septic mice model was established using caecal ligation and perforation (CLP). The mice were randomly divided into four groups: sham group, sham + RK-33 group (20 mg/kg, intraperitoneal injection, once a day), CLP group and CLP + RK-33 group (20 mg/kg, intraperitoneal injection, once a day). The number of inflammatory cells in the peripheral blood, spleen and bone marrow was calculated, and inflammatory cytokines were detected using an enzyme-linked immunosorbent assay. The septic mice's body weight and skeletal muscle mass were measured, and skeletal muscle tissues were examined using eosin staining. Western blotting was performed to detect the expression levels of MuRF1, atrogin1 and NLRP3 in the skeletal muscle of septic mice. Additionally, reactive oxidative species, superoxide dismutase and malondialdehyde were measured using commercial kits. RESULTS: RK-33 reduced inflammatory cell counts and cytokine levels in CLP mice, ameliorated the decline in CD4 and CD8 T cells and prevented the loss of body weight and skeletal muscle mass in septic mice. Additionally, RX-33 reduced oxidative stress in the skeletal muscle of septic mice. CONCLUSION: In the established sepsis mouse model, RK-33 alleviated inflammation and oxidative stress, ameliorated CLP-induced immunosuppression and skeletal muscle atrophy and improved survival. These findings suggest that RK-33 could be a novel potential therapeutic agent for preventing the progression of sepsis to PICS.

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Purpose: Hedyotis diffusa Willd (HDW) is one of the most well-known herbs used in the therapy of cancer. However, the potential mechanisms of its antiangiogenic effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of HDW against liver cancer angiogenesis (LCA) and used a mouse orthotopic liver cancer model for experimental verification accordingly. Methods: The effective components, primary active compounds, and possible targets in the therapy of LCA were predicted using network pharmacology and bioinformatics. In vivo testing of the pharmacodynamic foundation of HDW in the treatment of LCA was performed. Hepa1-6 cells were implanted in C57BL/6 mice to establish an orthotopic liver cancer model to evaluate the antitumor and antiangiogenesis effects of the drug. Furthermore, protein levels were evaluated by western blotting, immunofluorescence, and immunohistochemistry. Results: We firstly confirmed the therapeutic effect of HDW on LCA and subsequently screened 7 active compounds from HDW according to their pharmacokinetic properties. Network analysis and enrichment analysis indicated that these compounds exhibit antiangiogenic effect by acting on multiple targets and thereby regulating multiple pathways mainly involved in Akt1, IL-6, IL-1ß, IL-17, hypoxia inducible factor-1α (HIF-1α), and tumor necrosis factor-α (TNF-α). Importantly, we preliminarily verified the results of the network pharmacology analysis in vivo. Conclusion: Collectively, our work initially explored the therapeutic mechanism of HDW on tumor angiogenesis, which lays an experimental reference for further exploring its pharmacological action and its clinical application.

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PURPOSE: To explore the mechanisms of action of circ_SKA3 in gastric cancer (GC), which are still not fully understood. METHODS: Subcellular localization assay was used to analyze the localization of circ_SKA3, and Actinomycin D assay was applied to confirm the stability of circ_SKA3. The levels of circ_SKA3, microRNA (miR)-520h, and cell division cycle 42 (CDC42) mRNA were gauged by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of CDC42 and proliferating cell nuclear antigen (PCNA) were assessed by western blot. Cell proliferation, colony formation, cell cycle distribution, apoptosis, migration, and invasion were detected by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT), 5-Ethynyl-2'-Deoxyuridine (EdU) incorporation, colony formation, flow cytometry, and transwell assays, respectively. Directed relationship between miR-520h and circ_SKA3 or CDC42 was verified by a dual-luciferase reporter assay. Mouse xenograft experiments were used to elucidate the impact of circ_SKA3 in vivo. RESULTS: Overexpression of circ_SKA3 was validated in GC tissues and cells. The down-regulation of circ_SKA3 suppressed proliferation, cell cycle progression, colony formation, migration, invasion, and promoted cell apoptosis in vitro, as well as weakening tumor growth in vivo. Circ_SKA3 directly bound to miR-520h, and circ_SKA3 regulated CDC42 expression through miR-520h. Circ_SKA3 exerted regulatory effects on GC cell behaviors by inhibiting miR-520h. Furthermore, CDC42 was a functional target of miR-520h in regulating GC cell behaviors. CONCLUSION: Our findings established a strong molecular mechanism, the miR-520h/CDC42 axis, at least in part, for the oncogenic role of circ_SKA3 in GC.

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Gastrointestinal stromal tumors (GISTs) are common ICC precursor sarcomas, which are considered to be a potential malignant mesenchymal tumor driven by specific KIT or PDGFRA signals in the gastrointestinal tract. The standard treatment for GIST without metastasis is surgical resection. GIST with metastasis is usually treated with tyrosine kinase inhibitors (TKIs) only but cannot be cured. The TKI imatinib is the main drug of GIST drug therapy. In adjuvant therapy, the duration of imatinib adjuvant therapy is 3 years. It has been proved that imatinib can improve the overall survival time (OS). However, many GIST patients develop drug resistance due to the long-term use of imatinib. We were forced to look for new strategies to treat GIST. The purpose of the current academic work is to study the drug-resistant genes of imatinib and their potential mechanisms. A total of 897 differentially expressed genes (DEGs) were found between imatinib-sensitive cell line GIST882 and imatinib-resistant cell line GIST430 by RNA sequencing (RNA-seq). After analyzing the DEGs, 10 top genes were selected (NDN, FABP4, COL4A1, COLEC11, MEG3, EPHA3, EDN3, LMO3, RGS4, and CRISP2). These genes were analyzed by RT-PCR, and it was confirmed that the expression trend of FABP4, COL4A1, and RGS4 in different imatinib-resistant cell lines was in accord with the GEO database. It is suggested that these genes may play a potential role in the clinical diagnosis and treatment of imatinib resistance in GIST.

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As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

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Digestive system cancers are common cancers with high cancer deaths worldwide. They have become a major threat to public health and economic burden. As one of the most universal RNA modifications in eukaryotes, the N6-methyladenosine (m6A) modification is involved in the occurrence, development, prognosis, and treatment response of various cancers, including digestive system cancers. M6A demethylases shape the m6A landscape dynamically, playing important roles in cancers. In addition, accumulating evidence reveal that many environmental toxicants are the established risk factors for digestive system cancers and associated with m6A modification. In this review, we summarize the multiple functions of M6A demethylases (fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and AlkB homolog 3 (ALKBH3)) in digestive system cancers, which are aberrantly expressed and affect cancer progression. We also discuss the potential roles of m6A demethylases in the assessment of environmental exposure, the signature for prevention and diagnosis of digestive system cancers.