Mechanism of Nicotiflorin in San-Ye-Qing rhizome for anti-inflammatory effect in ulcerative colitis.

BACKGROUND: The incidence of ulcerative colitis (UC) is on the rise globally and the development of drugs targeting UC is urgent. Finding the target of action of natural products is important for drug discovery, elucidation of drug action mechanism, and disease mechanism. San-Ye-Qing (SYQ), is an ancient herbal medicine, but whether the powder of its rhizome has pharmacological effects against UC and its mechanism of action are not clear. PURPOSE: To evaluate the therapeutic effectiveness of rhizome powder of SYQ in treating UC, and conduct an isolation and characterization of the chemical constituents of the powder. Further, screen the most potent compounds among them and determine the potential mechanism for treating UC. METHODS: In vivo, the therapeutic effect of SYQ's rhizome powder on UC was assessed by mice's body weight, DAI score, colon length, tissue MPO activity, serum inflammatory markers, etc. Additionally, HPLC was used to isolate and identify the specific chemical components of SYQ's rhizome powder. Then, the most effective compounds and their therapeutic targets were analysed and screened in SYQ rhizome powder using network pharmacology, combined with CCK-8 assay, NO release assay and molecular docking assay, in conjunction with CETSA, DARTS, SPR and enzyme activity assay. Finally, the biological effects of the key compound on the targets were validated using Western blot and ELISA. RESULTS: In vivo, SYQ rhizome powder effectively restored mice's body weight, lowered DAI and pathological score, downregulated the expression of inflammatory biomarkers, and restored colon length, as well as the colonic epithelial and mucus barriers. Afterward, 9 compounds were isolated and identified from the powder of the rhizomes of SYQ by HPLC. Nicotiflorin is the primary compound in SYQ with the highest concentration. According to both CCK-8 and NO release tests, Nicotiflorin is also the most efficacious compound. Combined with network pharmacological prediction, molecular docking analysis, CETSA, DARTS, SPR and enzyme activity assay, Nicotiflorin may ultimately suppress inflammation by targeting p65 and inhibiting the NF-κB pathway, thereby attenuating the activation of NLRP3 inflammasome. To verify this conclusion, Western blot and ELISA experiments were conducted. CONCLUSIONS: Our results suggest that the extract from SYQ rhizomes has therapeutic properties for UC. Its active ingredient Nicotiflorin exerted potent anti-UC effects by binding to p65 and inhibiting the activation of NF-κB and NLRP3 inflammasomes.

Comparison of endovascular interventional embolization and microsurgical clipping for ruptured cerebral aneurysms: impact on patient outcomes.

OBJECTIVE: To compare the therapeutic efficacy of endovascular interventional embolization and microsurgical clipping in patients with ruptured cerebral aneurysms and investigate their subsequent influence on inflammatory indices, neurological function, prognosis, and recovery. METHODS: The two groups were compared in terms of surgery duration, hospital stay, Hunt-Hess classification, and inflammatory indices before and after the surgery, as well as National Institutes of Health Stroke Scale (NIHSS), Baethel Index (BI), and one-year prognosis of patients affected. RESULTS: The surgery duration and hospital stay of the intervention group were (116.27 ± 12.32) min and (19.82 ± 2.26) d, respectively, and those of the clipping group was (173.87 ± 10.39) min and (24.11 ± 2.33) d, respectively (both p < 0.05). Neither the intervention nor the microscopic approach had a significant impact on the severity of the patients' conditions in terms of Hunt-Hess classification (p > 0.05). In the intervention group, CRP was changed to (5.31 ± 1.22) mg/L and PCT decreased to (1.17 ± 0.39) µg/L after the surgery, while the corresponding values in clipping group were (9.78 ± 2.35) mg/L and (2.75 ± 0.81) µg/L (p > 0.05). After surgery, both groups' NIHSS scores declined dramatically, with the intervention group scoring lower than the microscopy group (6.81 ± 1.22 vs 8.72 ± 1.27) (p < 0.05). CONCLUSION: The findings of this study support the potential advantages of endovascular interventional embolization (coiling) over microsurgical clipping for the management of ruptured cerebral aneurysms. These advantages include shorter surgical duration, reduced hospital stay, lower inflammatory response, improved neurological and functional outcomes, and better long-term prognosis.

Association of ACP5 with the tumor immune microenvironment and its role in cell proliferation and metastasis in pancreatic cancer.

BACKGROUND: Tartrate-resistant acid phosphatase (ACP5) has been implicated in the progression of most malignant tumors, but its role in pancreatic cancer (PC) remained unclear. Thus, this study aimed to elucidate the role and function of ACP5 in PC progression. METHODS: The expression of ACP5 in PC samples was assessed via R programming, TNM plot, and Gene Expression Profiling Interactive Analysis (GEPIA). Western blotting and immunohistochemistry (IHC) were performed to detect ACP5 expression in cells and tissues. The correlation between ACP5 and methylation was analyzed using the University of ALabama at Birmingham Cancer data analysis Portal (UALCAN) and cBio Cancer Genomics Portal (cBioPortal). The Database for Annotation, Visualization and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were used for the enrichment of ACP5 in PC. Subsequently, Cell Counting Kit-8 (CCK8), clonogenic, and wound healing assays were used to investigate the role of ACP5 in PC. Finally, Tumor Immune Estimation Resource (TIMER) and R programming was utilized in evaluating the association between ACP5 and immune cell infiltration in PC. RESULTS: The analyses confirmed that ACP5 was highly expressed in PC samples. According to UALCAN and cBioPortal analysis, ACP5 expression, and methylation levels were negatively correlated in PC. The enrichment analysis also revealed that ACP5 was enriched in the proliferation and migration pathways. Meanwhile, ACP5 knockout reduced PC cell proliferation and migration and impaired the cells' independent viability. This gene also positively correlated with immune cell infiltration in PC, particularly regulatory T cells (Tregs). CONCLUSION: ACP5 is crucial for proliferation, migration, and immune cell infiltration in PC. Therefore, ACP5 may be a valuable target for future PC treatment.

TeaDiseaseNet: multi-scale self-attentive tea disease detection.

Accurate detection of tea diseases is essential for optimizing tea yield and quality, improving production, and minimizing economic losses. In this paper, we introduce TeaDiseaseNet, a novel disease detection method designed to address the challenges in tea disease detection, such as variability in disease scales and dense, obscuring disease patterns. TeaDiseaseNet utilizes a multi-scale self-attention mechanism to enhance disease detection performance. Specifically, it incorporates a CNN-based module for extracting features at multiple scales, effectively capturing localized information such as texture and edges. This approach enables a comprehensive representation of tea images. Additionally, a self-attention module captures global dependencies among pixels, facilitating effective interaction between global information and local features. Furthermore, we integrate a channel attention mechanism, which selectively weighs and combines the multi-scale features, eliminating redundant information and enabling precise localization and recognition of tea disease information across diverse scales and complex backgrounds. Extensive comparative experiments and ablation studies validate the effectiveness of the proposed method, demonstrating superior detection results in scenarios characterized by complex backgrounds and varying disease scales. The presented method provides valuable insights for intelligent tea disease diagnosis, with significant potential for improving tea disease management and production.

RBM12 regulates the progression of hepatocellular cancer via miR-497-5p/CPNE1 Axis.

BACKGROUND: Hepatocellular Carcinoma (HCC), also called hepatocellular cancer, has emerged as a highly prevalent malignancy globally. By binding to specific RNA via one or more spherical RNA Domains (RBDs) or RNA Motifs (RBMs), RNA Binding Proteins (RBPs) can affect RNA modification, splicing, localization, translation, and stability. METHODS: This paper builds on previous research by further investigating the impact of RBM12 on LC progression. In order to determine the effect of RBM12 expression on the prognosis of patients with hepatocellular cancer, we first investigated its expression in liver cancer cells (LCC) and tissues. The effect of RBM12 on the malignant biological behavior of LCC was subsequently detected using cytological experiments. To explore the upstream mechanism affecting RBM12, we predicted the miRNA targeting RBM12. According to the database, miR-497-5p was the best candidate gene. The double Luciferase reporter gene experiment was executed to validate the bounding of miR-497-5p with RBM12. RESULTS: According to the cytological experiments, a high RBM12 expression promoted the propagation, migration, and invasion of LCC and impeded liver cancer cell apoptosis. By secreting TGF-ß1, RBM12 could induce the EMT process. The miR-497-5p expression is suppressed in hepatocellular cancer. As shown by the CCK8, plate cloning, Transwell, EDU, and other experiments, miR-497-5p suppressed RBM12 expression and tumor growth. The double Luciferase reporter gene system was utilized to verify the combination of miR-497-5p and RBM12. The CPNE1 is a downstream gene regulated by RBM12. A high CPNE1 expression was exhibited in LCC and tissues. The CPNE1 is essential in the process where RBM12 promotes the incidence and progression of liver cancer. CONCLUSIONS: By elucidating the exact molecular mechanism through which RBM12 promotes the initiation and progression of LC, thus, the current investigation provides some reference for the clinical management of LC.

Phosphorus partitioning contribute to phosphorus use efficiency during grain filling in Zea mays.

Introduction: Lower phosphorus (P) availability limits crop productivity in agroecosystems. The remobilization of P from the source to the sink organs plays an important role in enhancing the P-utilization efficiency of crops. During the grain filling stage, phosphorus flow to the developing grains, the primary sink, determines crop yield. However, the specific contributions of different organs to grain P throughout the post-silking period in maize remain unclear. Methods: In our study, three maize inbred lines (CIMBL89, Ji846, and CML118) with contrasting P statuses were selected and grown in a field with high P (HP, 150 kg ha-1 P2O5) and low P (LP, 0 kg ha-1 P2O5) conditions. Results: The grain yield of CIMBL89 was 69% and 169% greater under HP supply, and 83% and 309% greater than those of Ji846 and CML118 under LP supply, respectively. The ear length, ear diameter, and kernel row number of CML118 were lower than those of CIMBL89 and Ji846 under HP conditions. Most of the P (87%) in the grains of CIMBL89 came from P uptake at the LP supply, while almost all P (95%) came from P remobilization in various organs at the HP supply after silking. In contrast, 91% of the P found in the grain of CML118 came from P remobilization under LP supply, while 76% came from P uptake under HP supply after silking. Discussion: In conclusion, our findings suggest that CIMBL89, with greater P acquisition efficiency, contributes to grain formation and production during the post-silking period under LP conditions. Additionally, CIMBL89 can fully remobilize P and avoid the extravagant absorption of P in P-sufficient soil, which sets it apart from Ji846 and CML118.

Prevalence, incidence, deaths, and disability-adjusted life-years of drug use disorders for 204 countries and territories during the past 30 years.

Drug use disorders are increasingly recognized as the main cause of public health issues worldwide. The current analysis aims to provide the most comprehensive, updated estimates of the burden from drug use disorders at global, regional, and national levels during the past three decades. Prevalence, incidence, deaths, and disability-adjusted life-years (DALYs) were estimated from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 by age and sex for drug use disorder as well as its four main categories (opioid use disorders, cocaine use disorders, amphetamine use disorders, and cannabis use disorders) in 204 countries and territories between 1990 and 2019. DisMod-MR 2.1, and Bayesian meta-regression were used to analyze prevalence and incidence, while the Cause of Death Ensemble model (CODEm) was used to estimate death of diseases. Globally, the burden of drug use disorders, as measured by the average annual percentage change (AAPC) of deaths and DALYs, continues to increase. The patterns by regions of DALYs due to drug use disorders varied significantly, and it is mainly in developed countries and concentrated among young people and males. Programs for drug use disorders management should be improved, particularly in opioid use disorders. Governments will face increasing demand for treatment and support services, and effective prevention as well as control strategies are required to reduce the burden from these causes.

Biomass partitioning and ionomics of Macadamia with high manganese and low phosphorus concentrations.

Knowledge of the ionome of plant organs helps us understand a plant's nutritional status. However, the ionome of Macadamia (Proteaceae), which is an important nut-producing tree, remains unknown. We aimed to characterise the allocation of biomass and nutrient-partitioning patterns in three macadamia genotypes. We excavated 15 productive trees (three cultivars at 21years of age; two cultivars at 16years of age) in an orchard. Biomass, nutrient concentrations, and contents of roots, stems, branches, and leaves were analysed. Dry weight of roots, stems, branches and leaves accounted for 14-20%, 19-30%, 36-52%, and 12-18% of total plant weight, respectively. No significant difference was found in the total biomass among the cultivars at the same age. Compared with most crop plants, macadamia had low phosphorus (P) concentrations in all organs (<1gkg-1 ), and low leaf zinc (Zn) concentration (8mgkg-1 ). In contrast, macadamia accumulated large amounts of manganese (Mn), with a 20-fold higher leaf Mn concentration than what is considered sufficient for crop plants. Leaves exhibited the highest nutrient concentrations, except for iron and Zn, which exhibited the highest concentrations in roots. The organ-specific ionomics of Macadamia is characterised by low P and high Mn concentrations, associated with adaptation to P-impoverished habitats.

Rhizosphere engineering for sustainable crop production: entropy-based insights.

There is a growing interest in exploring interactions at root-soil interface in natural and agricultural ecosystems, but an entropy-based understanding of these dynamic rhizosphere processes is lacking. We have developed a new conceptual model of rhizosphere regulation by localized nutrient supply using thermodynamic entropy. Increased nutrient-use efficiency is achieved by rhizosphere management based on self-organization and minimized entropy via equilibrium attractors comprising (i) optimized root strategies for nutrient acquisition and (ii) improved information exchange related to root-soil-microbe interactions. The cascading effects through different hierarchical levels amplify the underlying processes in plant-soil system. We propose a strategy for manipulating rhizosphere dynamics and improving nutrient-use efficiency by localized nutrient supply with minimization of entropy to underpin sustainable food/feed/fiber production.

Differences in foliar phosphorus fractions, rather than in cell-specific phosphorus allocation, underlie contrasting photosynthetic phosphorus use efficiency among chickpea genotypes.

Although significant intraspecific variation in photosynthetic phosphorus (P) use efficiency (PPUE) has been shown in numerous species, we still know little about the biochemical basis for differences in PPUE among genotypes within a species. Here, we grew two high PPUE and two low PPUE chickpea (Cicer arietinum) genotypes with low P supply in a glasshouse to compare their photosynthesis-related traits, total foliar P concentration ([P]) and chemical P fractions (i.e. inorganic P (Pi), metabolite P, lipid P, nucleic acid P, and residual P). Foliar cell-specific nutrient concentrations including P were characterized using elemental X-ray microanalysis. Genotypes with high PPUE showed lower total foliar [P] without slower photosynthetic rates. No consistent differences in cellular [P] between the epidermis and mesophyll cells occurred across the four genotypes. In contrast, high PPUE was associated with lower allocation to Pi and metabolite P, with PPUE being negatively correlated with the percentage of these two fractions. Furthermore, a lower allocation to Pi and metabolite P was correlated with a greater allocation to nucleic acid P, but not to lipid P. Collectively, our results suggest that a different allocation to foliar P fractions, rather than preferential P allocation to specific leaf tissues, underlies the contrasting PPUE among chickpea genotypes.

Identification of key genes and infiltrating immune cells among acetaminophen-induced acute liver failure and HBV-associated acute liver failure.

Background: Acute liver failure (ALF) is a life-threatening complication that is relatively uncommon. ALF causes severe hepatocyte damage and necrosis, which can lead to liver dysfunction and even multi-organ failure. A growing body of evidence suggests that immune cell infiltration and some abnormally expressed genes are associated with ALF development. However, in ALF, they have yet to be thoroughly investigated. Methods: The Gene Expression Omnibus (GEO) database was used to obtain microarray datasets such as GSE74000, GSE120652, GSE38941, and GSE14668, which were then examined via GEO2R to determine differentially expressed genes (DEGs) associated with ALF. Metascape was employed to annotate the underlined genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The mechanism of IGF1 in 2 different kinds of ALF including acetaminophen-induced ALF and hepatitis B virus (HBV)-induced ALF was studied using gene set enrichment analysis (GSEA). Next, immune cell infiltration was investigated and differentiated in ALF using CIBERSORT. Results: Six genes (HAO2, IGF1, PLA2G7, SC5D, GNE, SLC1A1) were found to be abnormally expressed in the 2 distinct types of ALF i.e., acetaminophen-induced ALF and HBV-induced ALF. IGF1 was identified as a hub gene in ALF and was found to be associated with several developmental cascades including immune responses, inflammatory responses, and intracellular calcium homeostasis. Additionally, the number of CD4 naive T cells, CD8 T cells, and follicular helper T cells was increased in acetaminophen-induced ALF, whereas the number of activated NK cells, resting NK cells, and plasma cells was increased in HBV-induced ALF. Conclusions: The present study determined a potential molecular target, namely IGF1, in acetaminophen-induced ALF and HBV-induced ALF, which may provide novel insights into the pathophysiology and management of ALF. Concurrently, the putative immunological pathways have been found.

Validation of rib structural responses under dynamic loadings using different material properties: A finite element analysis.

In this paper, human rib finite element models were created and validated based on finite element simulations. Validation tests were conducted through replicating experimental configurations of ribs under dynamic anterior-posterior bending, and by comparing numerical rib structural responses and fracture locations against experimental data. Human rib cortical bone material properties from different loading modes (tension and compression), strain rates (0.5 strain/s and 0.005 strain/s) and ages as well as porcine rib material properties were applied. Comparison of rib structural responses with various material properties was investigated. Numerical force-displacement relationship, cortical strain, rotation and fracture location correspond well with published experimental data, which demonstrates the robustness of the finite element rib models. Numerical analysis reveals that numerical strain and rotation time histories with human rib cortical compressive material properties have a better correlation with experimental data compared to those with human rib cortical tensile material properties. Also, numerical rib structural responses were found to be sensitive to material properties from different loading modes, strain rates and ages. Therefore, it is necessary to consider the effect of material properties from different loading modes, strain rates and ages when establishing rib FE models. Meanwhile, it is also indicated that porcine rib material properties can obtain similar and reasonable results compared to human rib material properties. This was the first numerical study to apply human rib compressive material properties in investigating rib dynamic structural responses and compare the results with those from tensile material properties. The present study helps better understand human rib fractures in a high velocity impact (HVI) context in a numerical way.

Ensuring future food security and resource sustainability: insights into the rhizosphere.

Feeding the world's growing population requires continuously increasing crop yields with less fertilizers and agrochemicals on limited land. Focusing on plant belowground traits, especially root-soil-microbe interactions, holds a great promise for overcoming this challenge. The belowground root-soil-microbe interactions are complex and involve a range of physical, chemical, and biological processes that influence nutrient-use efficiency, plant growth and health. Understanding, predicting, and manipulating these rhizosphere processes will enable us to harness the relevant interactions to improve plant productivity and nutrient-use efficiency. Here, we review the recent progress and challenges in root-soil-microbe interactions. We also highlight how root-soil-microbe interactions could be manipulated to ensure food security and resource sustainability in a changing global climate, with an emphasis on reducing our dependence on fertilizers and agrochemicals.

A Retrospective Trail Investigating Temozolomide Neoadjuvant Chemotherapy Combined with Radiotherapy in Low-Grade Pituitary Tumors.

Objective: To study and analyze the clinical application of temozolomide (TMZ) combined with radiotherapy in the treatment of low-grade pituitary tumors. Methods: A retrospective trail was conducted among 67 patients with low-grade pituitary tumors who were treated in our hospital from March 2018 to June 2020. According to different treatment methods, they were assigned into a combined group (37 cases, temozolomide capsules and radiotherapy) and a control group (30 cases, radiotherapy). The changes of serum prolactin (PRL), insulin-like growth factor-1 (IGF-1), GH levels, thyroid-stimulating hormone (TSH), serum free thyroxine (FT4), and adrenocorticotropic hormone (ACTH) were compared. Results: The chi-square test reports a significantly higher total effective rate in the combined group vs. control group (91.89% vs. 70.00%). Significant reductions in serum levels of PRL, IGF-1, and GH were observed in both groups after treatment, whereas the combined group treated with radiotherapy and TMZ resulted in significantly lower levels compared with the control group (p < 0.05). After treatment, TSH decreased, and FT4 and ACTH increased in both groups, and the treatment with radiotherapy and TMZ in the combined group led to a significantly greater amplitude of variation (p < 0.05). Conclusion: The combination of temozolomide and radiotherapy might be a promising technique for the treatment of pituitary tumors, thereby meriting promotion.

Linking root exudation to belowground economic traits for resource acquisition.

The concept of a root economics space (RES) is increasingly adopted to explore root trait variation and belowground resource-acquisition strategies. Much progress has been made on interactions of root morphology and mycorrhizal symbioses. However, root exudation, with a significant carbon (C) cost (c. 5-21% of total photosynthetically fixed C) to enhance resource acquisition, remains a missing link in this RES. Here, we argue that incorporating root exudation into the structure of RES is key to a holistic understanding of soil nutrient acquisition. We highlight the different functional roles of root exudates in soil phosphorus (P) and nitrogen (N) acquisition. Thereafter, we synthesize emerging evidence that illustrates how root exudation interacts with root morphology and mycorrhizal symbioses at the level of species and individual plant and argue contrasting patterns in species evolved in P-impoverished vs N-limited environments. Finally, we propose a new conceptual framework, integrating three groups of root functional traits to better capture the complexity of belowground resource-acquisition strategies. Such a deeper understanding of the integrated and dynamic interactions of root morphology, root exudation, and mycorrhizal symbioses will provide valuable insights into the mechanisms underlying species coexistence and how to explore belowground interactions for sustainable managed systems.

Flavonoids are involved in phosphorus-deficiency-induced cluster-root formation in white lupin.

BACKGROUND AND AIMS: Initiation of cluster roots in white lupin (Lupinus albus) under phosphorus (P) deficiency requires auxin signalling, whereas flavonoids inhibit auxin transport. However, little information is available about the interactions between P deficiency and flavonoids in terms of cluster-root formation in white lupin. METHODS: Hydroponic and aeroponic systems were used to investigate the role of flavonoids in cluster-root formation, with or without 75 µm P supply. KEY RESULTS: Phosphorus-deficiency-induced flavonoid accumulation in cluster roots depended on developmental stage, based on in situ determination of fluorescence of flavonoids and flavonoid concentration. LaCHS8, which codes for a chalcone synthase isoform, was highly expressed in cluster roots, and silencing LaCHS8 reduced flavonoid production and rootlet density. Exogenous flavonoids suppressed cluster-root formation. Tissue-specific distribution of flavonoids in roots was altered by P deficiency, suggesting that P deficiency induced flavonoid accumulation, thus fine-tuning the effect of flavonoids on cluster-root formation. Furthermore, naringenin inhibited expression of an auxin-responsive DR5:GUS marker, suggesting an interaction of flavonoids and auxin in regulating cluster-root formation. CONCLUSIONS: Phosphorus deficiency triggered cluster-root formation through the regulation of flavonoid distribution, which fine-tuned an auxin response in the early stages of cluster-root development. These findings provide valuable insights into the mechanisms of cluster-root formation under P deficiency.

Dispositional mindfulness and mental health among Chinese college students during the COVID-19 lockdown: The mediating role of self-compassion and the moderating role of gender.

College students' mental health has been seriously impacted during the global COVID-19 lockdown. There is evidence that dispositional mindfulness is beneficial to mental health. However, few studies have looked at the relationship between dispositional mindfulness and mental health from the standpoint of self-compassion. Furthermore, it is unclear under what circumstances dispositional mindfulness is linked to mental health during COVID-19 lockdown. To fill this gap, the current study investigated self-compassion as a possible mediating factor and gender as a possible moderating effect between dispositional mindfulness and mental health. The sample included 1,018 Chinese university students during the COVID-19 lockdown (M age = 20.12; SD age = 1.17) who had completed self-report questionnaires on dispositional mindfulness, self-compassion, and mental health. According to the findings of mediation analysis, self-compassion partially mediated the relationship between dispositional mindfulness and mental health. The moderating analysis also revealed significant moderating effects of dispositional mindfulness, self-compassion, and mental health. Male college students' mental health was significantly better protected, and the buffering effects of dispositional mindfulness and self-compassion on their mental health were significantly stronger than those of female college students. These findings advance our understanding of the process and mechanism between dispositional mindfulness and mental health, broadened and deepened the understanding of the relationship between dispositional mindfulness and mental health, as well as the mediating role of self-compassion and the moderating role of gender, and offer practical guidance for improving college students' mental health during the COVID-19 lockdown.

The expression and prognostic value of REXO4 in hepatocellular carcinoma.

BACKGROUND: Globally, one of the dominant causes of cancer-related mortality is liver cancer. Identification of potent biomarkers for initial stage diagnosis and prognosis is a key factor to ensure efficient therapy and reduce the mortality rate in liver cancer patients. REXO4 has been reported in neuropathic pain and familial isolated pituitary adenoma (FIPA), however, its relationship with liver cancer is still elusive. METHODS: In an attempt to scrutinize the expression of REXO4 in liver cancer, the Oncomine, and TCGA databases were analyzed. Real-time PCR was employed to identify the REXO4 mRNA levels in 45 patient tissue samples and western blot was used to detect the REXO4 protein levels in hepatocellular carcinoma (HCC) cells. Evaluation of the prognostic value of REXO4 in liver cancer was made using Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots. Tumor-associated biological processes related to REXO4 were revealed by LinkedOmics. The correlation of REXO4 and immune infiltration was evaluated using the TIMER database. RESULTS: REXO4 is significantly up-regulated in liver cancer in comparison with the nontumor controls. Moreover, poor progression-free survival and overall survival is a frequent outcome related to high expression of REXO4, highlighting it as a risk factor in case of liver cancer. Additionally, the plausible role of REXO4 in tumor-immune interactions was also investigated and it was revealed that the immune infiltration and immune activation of liver cancer might have an association with REXO4. CONCLUSIONS: REXO4 has a significant expression in liver cancer and could potentially become a predictor for the prognosis of liver cancers and a biomarker for targeted therapeutic regimens. Significant overexpression of REXO4 in HCC was revealed by the bioinformatics analysis, with REXO4 overexpression being related to a negative outcome in HCC patients, in addition, REXO4 might be associated with the immune infiltration in liver cancer. Such a vital understanding of the functioning of REXO4 may furnish a foundation for new targeted drug therapy as well as a new direction for additional investigation into the underlying mechanisms of REXO4 carcinogenesis in liver cancer.

Increased RBM12 expression predicts poor prognosis in hepatocellular carcinoma based on bioinformatics.

BACKGROUND: Liver cancer is one of the major causes of cancer death worldwide, incurring high mortality and a significant financial burden on the healthcare system. Abnormal RNA-binding proteins (RBPs) have been found to be associated with carcinogenesis in liver cancer. Among these, RNA-binding motif protein 12 (RBM12) is located in the exon junction complex (EJC). The goal of this study was to determine what role RBM12 plays in hepatocellular carcinoma (HCC) from a biological perspective. METHODS: The Tumor IMmune Estimation Resource (TIMER) and the Human Protein Atlas database were used to examine the expression level of RBM12, with the UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases used to investigate the relationship between RBM12 and other noteworthy clinical features. RBM12 expression in cells and tissue samples was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. The functional network of RBM12 in HCC was studied using LinkedOmics and gene set enrichment analysis (GSEA), while the effects of hypomethylation on the expression of RBM12 in HCC was investigated using methylation databases. Finally, we used TIMER and CIBERSORT to investigate the relationship between immune cell infiltration and RBM12 in HCC. RESULTS: RBM12 is highly elevated in HCC tissues and cells, and it can be used to predict the prognosis of patients with HCC. Analysis with LinkedOmics and GSEA revealed RBM12 to be closely linked with tumor progression. Furthermore, hypomethylation was linked to an increase in RBM12 expression in HCC, while RBM12 was associated with immune cell infiltration. CONCLUSIONS: This study shows that an elevated level of RBM12 in HCC indicates a poor patient prognosis. Furthermore, according to LinkedOmics and GSEA analyses, RBM12 was implicated in the most important hallmark pathways. Our findings suggest that RBM12 overexpression is caused by hypomethylation and that RBM12 plays a key role in liver cancer tumor immunity.