Monolayer V_{2}MX_{4}: A New Family of Quantum Anomalous Hall Insulators.

We theoretically propose that the van der Waals layered ternary transition metal chalcogenide V_{2}MX_{4} (M=W, Mo; X=S, Se) is a new family of quantum anomalous Hall insulators with sizable bulk gap and Chern number C=-1. The large topological gap originates from the deep band inversion between spin-up bands contributed by d_{xz}, d_{yz} orbitals of V and spin-down band from d_{z^{2}} orbital of M at the Fermi level. Remarkably, the Curie temperature of monolayer V_{2}MX_{4} is predicted to be much higher than that of monolayer MnBi_{2}Te_{4}. Furthermore, the thickness dependence of the Chern number for few multilayers shows interesting oscillating behavior. The general physics from the d orbitals here applies to a large class of ternary transition metal chalcogenide such as Ti_{2}WX_{4} with the space group P-42m. These interesting predictions, if realized experimentally, could greatly promote the research and application of topological quantum physics.

Construction of Cyan Blue Fluorescence Probe based on Nitrogen-Doped Carbon Dots for Detecting Nitrite Ion in Ham Sausage.

Nitrite ion is one of the materials widely used in human life, and the accurate, sensitive and stable detection of nitrite ions is of great significance to people's healthy life. In this study, nitrogen-doped fluorescent carbon dots (N-CDs) for detecting nitrite salt solutions were prepared using citric acid monohydrate and Chrysoidin as precursors through a one-pot hydrothermal method. Under the condition of pH = 3, a noticeable quenching phenomenon occurred in the carbon dot solution with the increase in nitrite ion concentration. This quenching effect might be attributed to the diazonium effect. N-CDs have been successfully used as fluorescence probes for NO2- detection. NO2- can effectively quench the fluorescence intensity of N-CDs, providing a linear response to fluorescence quenching efficiency with respect to NO2- concentration within the range of 0-10µM and 10-30µM, and a detection limit of 52nM, showing high sensitivity. In addition, the probe was applied to the determination of NO2- in ham sausage samples with a detection limit of 0.67µM and recoveries in the range of 99.5-102.3%, the fluorescent probe showed satisfactory reliability.

Nitrogen and Sulfur co-doped Carbon dots as an "on-off-on" Fluorescent Sensor for the Detection of Hg2+ and Ampicillin.

Herein, a fluorescent "on-off-on" nanosensor based on N,S-CDs was developed for highly precise and sensitive recognition of Hg2+ and ampicillin (AMP). Nitrogen and sulfur co-doped carbon dots with blue fluorescence were synthesized by one-pot hydrothermal method using ammonium citrate and DL-methionine as precursors. N,S-CDs exhibited a surface abundant in -OH, -COOH, and -NH2 groups, aiding in creating non-fluorescent ground state complexes when combined with Hg2+, leading to the suppression of N,S-CDs' fluorescence. Subsequent to additional AMP application, the mixed system's fluorescence was restored. Based on this N,S-CDs sensing system, the thresholds for detection for AMP and Hg2+ were discovered to be 0.121 µM and 0.493 µM, respectively. Furthermore, this methodology proved effective in identifying AMP in real samples of tap and lake water, yielding satisfactory results. Consequently, in the area of bioanalysis in intricate environmental sample work, the sensing system showed tremendous promise.

Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a serious complication of hepatic vena cava Budd-Chiari syndrome (HVC-BCS) that significantly reduces the survival time of patients. Our study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring system. METHODS: The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively analyzed. Kaplan-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the groups. Univariate and multivariate Cox regression analyses were performed to analyze the influence of biochemical, tumor, and etiological characteristics on the total survival time of patients, and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical model. The prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance index. RESULTS: Multivariate analysis showed that serum albumin level < 34 g/L [hazard ratio (HR) = 4.207, 95% confidence interval (CI): 1.816-8.932, P = 0.001], maximum tumor diameter > 7 cm (HR = 3.612, 95% CI: 1.646-7.928, P = 0.001), and inferior vena cava stenosis (HR = 8.623, 95% CI: 3.771-19.715, P < 0.001) were independent predictors of survival. A prognostic scoring system was developed according to the above-mentioned independent predictors, and patients were classified into grades A, B, C and D. Significant differences in survival were found among the four groups. CONCLUSIONS: This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC, which is helpful for clinical evaluation of patient prognosis.

Highly efficient enrichment of intact phosphoproteins by a cadmium ion-based co-precipitation strategy.

Selective separation and enrichment of phosphoproteins are essential for understanding their important functions in almost all cellular processes. Here, taking advantage of the feature that cadmium ion (Cd2+ ) has an overwhelming preference for phosphates, we developed a robust and simple Cd2+ co-precipitation strategy for the selective isolation of intact phosphoproteins. After evaluating the feasibility of Cd2+ in phosphoprotein precipitation, we compared the washing protocols for the removal of non-specific binding proteins and then used the best-performing protocol for the isolation of phosphoproteins from different complex samples. It was found that phosphoproteins can be specifically enriched from artificial protein mixtures containing α-casein, ß-casein, and bovine serum albumin or plasma, in which bovine serum albumin or plasma were served as interferences with very high molar ratios. Applying this method to enrich phosphoproteins from complex cell lysates, a high specificity was confirmed by western blotting analysis with a phosphoprotein-specific kit. Finally, we successfully applied this method to the purification of caseins from drinking milk, highlighting its potential application in the studies where purified phosphoproteins were required. In a word, this Cd2+ co-precipitation method enables universal and effective capture, enrichment, and detection of intact phosphoproteins, making it a powerful tool for the comprehensive analysis of the phosphoproteome.

Flat Chern Band from Twisted Bilayer MnBi_{2}Te_{4}.

We construct a continuum model for the moiré superlattice of twisted bilayer MnBi_{2}Te_{4}, and study the band structure of the bilayer in both ferromagnetic (FM) and antiferromagnetic (AFM) phases. We find the system exhibits highly tunable Chern bands with Chern number up to 3. We show that a twist angle of 1° turns the highest valence band into a flat band with Chern number ±1 that is isolated from all other bands in both FM and AFM phases. This result provides a promising platform for realizing time-reversal breaking correlated topological phases, such as fractional Chern insulator and p+ip topological superconductor. In addition, our calculation indicates that the twisted stacking facilitates the emergence of quantum anomalous Hall effect in MnBi_{2}Te_{4}.

Detection of Escherichia coli O157:H7 and Salmonella enterica serotype Typhimurium based on cell elongation induced by beta-lactam antibiotics.

Pathogenic bacteria such as Shiga toxigenic Escherichia coli and Salmonella can cause severe food-borne diseases. Rapid and sensitive detection of these foodborne pathogens is essential to ensure food safety. In this study, a novel method based on cell elongation induced by beta-lactam antibiotics for direct microscopic counting of Gram-negative bacteria was established. Combined with the sample preparation steps of membrane filtration and magnetic separation, the detection of E. coli O157:H7 and Salmonella enterica serotype Typhimurium was achieved by direct optical microscopic counting of the number of elongated bacteria. The limit of detection of E. coli O157:H7 and S. typhimurium could reach 20 CFU mL-1. The recovery tests for E. coli O157:H7 and S. typhimurium in water and milk samples showed acceptable recovery values between 93.6% and 106.2%. This method is sensitive, cost effective, and rapid (<2 h) and shows great potential for the detection of Gram-negative pathogens in various environmental and food samples.

Severe hyponatraemia with neurological manifestations in patients treated with terlipressin: Two case reports.

WHAT IS KNOWN AND OBJECTIVE: Terlipressin has been shown to be effective in controlling variceal bleeding and decreasing associated mortality. Terlipressin is a synthetic analogue of vasopressin and is safer than arginine vasopressin; it induces selective vasoconstriction by stimulating the vasopressin V1 receptors that are predominantly located in the splanchnic tissues. However, severe hyponatraemia may occur during terlipressin treatment, resulting in neurological manifestations. CASE SUMMARY: We describe two patients who presented a marked decrease in serum sodium levels and developed obvious neurological manifestations after receiving terlipressin therapy. Although the two patients were given sodium supplementation, their serum sodium levels continually declined. After the discontinuation of terlipressin, their serum sodium levels rapidly recovered to normal limits, and the neurological manifestations subsequently disappeared in both patients. WHAT IS NEW AND CONCLUSION: Some studies have reported hyponatraemia as a side effect of terlipressin; however, severe hyponatraemia with neurological manifestations has rarely been reported. We presented the cases of 2 patients with obvious neurological manifestations after receiving terlipressin therapy. Severe hyponatraemia may develop in patients treated with terlipressin, resulting in associated neurological symptoms. Therefore, the close monitoring of serum sodium is necessary.

TBL1XR1 predicts isolated tumor cells and micrometastasis in patients with TNM stage I/II colorectal cancer.

BACKGROUND AND AIM: A considerable number of early-stage colorectal cancer (CRC) patients may develop cancer relapse or metastasis after curative surgery. Isolated tumor cells (ITC) and micrometastasis in lymph nodes (LNMM), which are undetectable by conventional pathological examination, may be one primary reason. Detection of ITC/LNMM is time-consuming and cost-ineffective; we aimed to find biomarkers in primary CRC tissues to help predicting ITC/LNMM status. METHODS: We enrolled 137 node-negative patients with early-stage CRC in this study. Existence of ITC/LNMM was identified by immunohistological staining with cytokeratin 20 in resected lymph nodes. Expression of transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) in primary CRC tissues was also investigated. Chi-squared test was performed to reveal the correlations between ITC/LNMM and clinicopathological characteristics. Univariate and multivariate analyses were used to determine independent prognostic factors. Knockdown experiment together with proliferation and invasion assays were carried out to explore molecular mechanisms between TBL1XR1 and ITC/LNMM. RESULTS: About 29.2% (40/137) patients were identified as ITC/LNMM positive, and most of them (32/40 cases, 80%) showed high TBL1XR1 expression in primary CRC tissues. Both ITC/LNMM and TBL1XR1 expression were independent prognostic factors for disease relapse or metastasis. In vitro experiments demonstrated that TBL1XR1 can regulate the expression of vascular endothelial growth factor C and epithelial-mesenchymal transition proteins, thus mediate the process of lymph node metastasis. CONCLUSIONS: Identification of ITC/LNMM is significant in evaluating clinical outcome and guiding adjuvant chemotherapy for early-stage CRC patients. TBL1XR1 overexpression in CRC tissues can serve as an efficient biomarker to predict the status of ITC/LNMM.

Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications.

BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC.

A Predictive Model Based on the FBXO Family Reveals the Significance of Cyclin F in Hepatocellular Carcinoma.

OBJECTIVE: The F-box protein (FBXO) family plays a key role in the malignant progression of tumors. However, the biological functions and clinical value of the FBXO family in liver cancer remain unclear. Our study comprehensively assessed the clinical value of the FBXO family in hepatocellular carcinoma (HCC) and constructed a novel signature based on the FBXO family to predict prognosis and guide precision immunotherapy. METHODS: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized to investigate the expression characteristics and prognostic value of the FBXO family in HCC. A predictive model based on the FBXO family using TCGA database; and its predictive ability was validated using the ICGC database. Further analyses revealed that this predictive model can independently predict the overall survival (OS) rate of patients with HCC. We further analyzed the association of this predictive model with signaling pathways, clinical pathological features, somatic mutations, and immune therapy responses. Finally, we validated the biological functions of cyclin F (CCNF) through in vitro experiments. RESULTS: A predictive model involving three genes (CCNF, FBXO43, and FBXO45) was constructed, effectively identifying high and low-risk patients with differences in OS, clinicopathological characteristics, somatic mutations, and immune cell infiltration status. Additionally, knock-down of CCNF in HCC cell lines reduced cell proliferation in vitro, suggesting that CCNF may be a potential therapeutic target for HCC. CONCLUSIONS: The predictive model based on the FBXO family can effectively predict OS and the immune therapy response in HCC. Additionally, CCNF is a potential therapeutic target for HCC.

Ce-doping induces rapid electron transfer in a bimetallic phosphide heterostructure to achieve efficient hydrogen production.

Using electrochemical water splitting to generate hydrogen is considered a desirable approach, which is greatly impeded by the sluggish dissociation of H2O and adsorption and desorption of H*. Effective hydrogen production can be achieved by speeding up the chemical process with a suitable electrocatalyst. In this work, we designed and synthesized a rare earth element cerium (Ce) regulated iron-nickel bimetallic phosphide Ce-NiFeP@NF (here NiFeP represents Fe2P/NiP2) nanoarray with nanoflowers. For the hydrogen evolution reaction (HER), Ce-NiFeP@NF only needs an overpotential of 106 mV to provide a current density of 10 mA cm-2, compared to NiFeP@NF (175 mV@10 mA cm-2). This self-supported electrocatalyst Ce-NiFeP@NF with a composite morphology exhibits excellent performance in the HER. Specifically, the introduction of Ce promotes the electron transfer process at the Fe2P/NiP2 heterojunction interface and the Ce-NiFeP@NF nanocomposite structure with nanoflowers has a larger electrochemically active specific surface area, which is more conducive to improving the intrinsic catalytic activity. Also, a dual-electrode alkaline electrolytic cell (Ce-NiFeP@NF functions as both the anode and the cathode) operates with a cell voltage of only 1.56 V to achieve a current density of 10 mA cm-2. The synergistic effect of rare earth element doping and heterojunction engineering can improve the morphology of intrinsic catalysts to achieve more efficient electrochemical water splitting for hydrogen production.

LMNB1/CDKN1A Signaling Regulates the Cell Cycle and Promotes Hepatocellular Carcinoma Progression.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world. Lamin B1 (LMNB1) is a key component of the nuclear skeleton structure. Recent studies have found that LMNB1 is overexpressed in tumor tissues and is associated with the prognosis of patients. However, the underlying mechanism remains unclear in HCC. OBJECTIVE: This study aims to explore the clinical significance and molecular mechanisms of LMNB1 in HCC. METHODS: The expression level of LMNB1 and its clinical values were analyzed with public databases, and the level of LMNB1 in HCC tissues and adjacent normal tissues was confirmed by qRT-PCR and IHC. Functional assays were conducted to explore the impact of LMNB1 knockdown on cell proliferation both in vivo and in vitro. Additionally, Genes and Genomes enrichment analysis, recovery analysis, and ChIP assays were employed to investigate its underlying molecular mechanisms. Finally, we carried out an analysis of the relationship between LMNB1 and immune cell infiltration in HCC. RESULTS: LMNB1 was found to be overexpressed in HCC and correlated with the pathological stage and unfavorable prognosis. Functional assays demonstrated that LMNB1 promotes HCC proliferation both in vitro and in vivo. Further analysis revealed that LMNB1 promotes the progression of HCC by regulating CDKN1A expression. Furthermore, the infiltration of immune cells in HCC tissues suggests a potential correlation between immune infiltration cell markers and the expression of LMNB1. CONCLUSIONS: LMNB1 emerged as a promising therapeutic target and prognostic biomarker for HCC, with its expression showing a correlation with several immune infiltration cell markers.

[An in vitro experiment on the stability and irritant of hypochlorous acid in oral cavity].

PURPOSE: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity. METHODS: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data. RESULTS: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P＞0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P＜0.001). CONCLUSIONS: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.

Selective degradation of organic micropollutants by activation of peroxymonosulfate by Se@NC: Role of Se doping and nonradical pathway mechanism.

In this study, Se@NC-x decorated with Se was successfully prepared via two-step calcination with zeolitic imidazole framework (ZIF) as a precursor. Mechanistic studies show that PMS would be adsorbed onto the surface of Se@NC-900 to form an active complex (Se@NC-900/PMS*), and the active Se@NC-900/PMS* could oxidize phenol by the rapid decomposition of PMS. Specifically, electrons are extracted by Se@NC-900/PMS* and then transferred to the surface of Se@NC-900, which can trigger the degradation of phenol. Notably, it is found that the local charge redistribution caused by the doping of Se can activate the catalytic potential of the intrinsically inert carbon skeleton through density flooding theory (DFT) calculations. The XLogP, ΔE, VIP, and ELUMO (Se@NC/PMS)-HOMO (pollutants) and degradation rate constants of different micropollutants were correlated well linearly. This indicates that the Se@NC-900/PMS system has a great selectivity for the degradation of pollutants. Overall, these findings not only illustrate the role of Se in tuning the electronic structure of Se@NC-x to enhance the activation of PMS, but also bridge the gap in our knowledge about the physicochemical properties and degradation performance of Se@NC catalysts.

Prognostic prediction and immune infiltration analysis based on ferroptosis and EMT state in hepatocellular carcinoma.

Background: Ferroptosis is one of the main mechanisms of sorafenib against hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) plays an important role in the heterogeneity, tumor metastasis, immunosuppressive microenvironment, and drug resistance of HCC. However, there are few studies looking into the relationship between ferroptosis and EMT and how they may affect the prognosis of HCC collectively. Methods: We downloaded gene expression and clinical data of HCC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for prognostic model construction and validation respectively. The Least absolute shrinkage and selection operator (LASSO) Cox regression was used for model construction. The predictive ability of the model was assessed by Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve. We performed the expression profiles analysis to evaluate the ferroptosis and EMT state. CIBERSORT and single-sample Gene Set Enrichment Analysis (ssGSEA) methods were used for immune infiltration analysis. Results: A total of thirteen crucial genes were identified for ferroptosis-related and EMT-related prognostic model (FEPM) stratifying patients into two risk groups. The high-FEPM group had shorter overall survivals than the low-FEPM group (p<0.0001 in the TCGA cohort and p<0.05 in the ICGC cohort). The FEPM score was proved to be an independent prognostic risk factor (HR>1, p<0.01). Furthermore, the expression profiles analysis suggested that the high-FEPM group appeared to have a more suppressive ferroptosis status and a more active EMT status than the low- FEPM group. Immune infiltration analysis showed that the myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) were highly enriched in the high-FEPM group. Finally, a nomogram enrolling FEPM score and TNM stage was constructed showing outstanding predictive capacity for the prognosis of patients in the two cohorts. Conclusion: In conclusion, we developed a ferroptosis-related and EMT-related prognostic model, which could help predict overall survival for HCC patients. It might provide a new idea for predicting the response to targeted therapies and immunotherapies in HCC patients.

KIAA1429 regulates alternative splicing events of cancer-related genes in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

miR-874 ameliorates retinopathy in diabetic rats by NF-κB signaling pathway.

BACKGROUND: Increased activity of the NF-κB signaling pathway boosts the progression of retinopathy in diabetic rats. OBJECTIVES: Using a bioinformatics website, we identified a site where miR-874 binds to the NF-κB p65. Therefore, we speculated that miR-874 might improve retinopathy in diabetic rats by inhibiting the NF-κB signaling pathway. MATERIAL AND METHODS: Ten healthy rats were taken as the control group. Sixty streptozotocin (STZ; 60 mg/kg)-induced diabetes model rats were randomly divided into the model group (injection of normal saline), negative control (NC) agomir group (injection of NC mimic), miR-874 agomir group (injection of miR-874 mimic), miR-874 anti-agomir group (injection of miR-874 inhibitor), EVP4593 group (injection of NF-κB signaling pathway antagonist EVP4593), and miR-874 anti-agomir+EVP4593 group (injection of miR-874 inhibitor and EVP4593). All injections were administered into the caudal vein. RESULTS: miR-874 could target the degradation of p65. Compared with the control group, model rats had reduced miR-874 expression, increased vascular endothelial growth factor (VEGF) and Ang2 protein expression, lowered end-diastolic velocity (EDV) and peak systolic velocity (PSV) of the central retinal artery (CRA) and blood velocity of central retinal vein (CRV) and CRA, heightened plasma viscosity (PV), blood viscosity (BV) and erythrocyte sedimentation rate (ESR) at all shear rates, decreased capillary pericytes (IPCs), increased vascular endothelial cells (VECs), and ascended p65 expression in the retina (all p < 0.05). Thus, it was shown that pathological changes appeared in the retina of diabetic rats. These indices improved in diabetic rats injected with the miR-874 mimic or EVP4593, but deteriorated in those injected with miR-874 inhibitor (all p < 0.05). EVP4593 also could alleviate the aggravation of retinopathy that was caused by miR-874 inhibition in diabetic rats. CONCLUSIONS: miR-874 modulates the NF-κB signaling pathway by targeting the degradation of p65 to further improve the retina of diabetic rats, thus demonstrating the beneficial effect of miR-874 on diabetic retinopathy in rats.

Circular RNA CDR1as Exerts Oncogenic Properties Partially through Regulating MicroRNA 641 in Cholangiocarcinoma.

It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

Clinical characteristics and outcome of primary hepatic neuroendocrine tumors after comprehensive therapy.

BACKGROUND: Primary hepatic neuroendocrine tumors (PHNETs), a group of neuroendocrine neoplasms, are extremely rare. There are only few case reports about PHNETs in the literature. The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches. AIM: To discuss the clinical characteristics, diagnosis, and treatment of PHNETs and risk factors related to survival. METHODS: We retrospectively analyzed the clinical data, imaging features, immunohistochemistry data, and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1, 2014 to November 15, 2019. Finally, survival analysis was performed to identify the risk factors for survival. RESULTS: The main symptoms and signs included intermittent abdominal pain (19 patients, 47.5%) and bloating (8 patients, 20.0%). The positive rates of tested tumor markers were recorded as follows: Carbohydrate antigen 19-9 (CA19-9) (6 patients, 15.0%), CA72-4 (3 patients, 7.5%), carcinoembryonic antigen (7 patients, 17.5%), and alpha-fetoprotein (6 patients, 15.0%). Immunohistochemical staining results showed positivity for Syn in 38 (97.4%) of 39 patients, for chromogranin A in 17 (65.4%) of 26 patients, for CD56 in 35 (94.6%) of 37 patients, for AE1/AE3 in 28 (87.5%) of 32 patients, and for Ki-67 in all 40 (100.0%) patients. The overall survival rate was significantly related to the tumor grade, AE1/AE3, and Ki-67. No significant correlation was found between other parameters (age, gender, tumor number, tumor size, metastasis, and treatment) and overall survival. CONCLUSION: Higher grade, negative AE1/AE3, and higher Ki-67 are associated with a worse survival rate. Kinds of treatment and other parameters have no significant influence on overall survival.