Regulation of the Nur77-P2X7r Signaling Pathway by Nodakenin: A Potential Protective Function against Alcoholic Liver Disease.

Alcoholic liver disease (ALD) is the main factor that induces liver-related death worldwide and represents a common chronic hepatopathy resulting from binge or chronic alcohol consumption. This work focused on revealing the role and molecular mechanism of nodakenin (NK) in ALD associated with hepatic inflammation and lipid metabolism through the regulation of Nur77-P2X7r signaling. In this study, an ALD model was constructed through chronic feeding of Lieber-DeCarli control solution with or without NK treatment. Ethanol (EtOH) or NK was administered to AML-12 cells, after which Nur77 was silenced. HepG2 cells were exposed to ethanol (EtOH) and subsequently treated with recombinant Nur77 (rNur77). Mouse peritoneal macrophages (MPMs) were treated with lipopolysaccharide/adenosine triphosphate (LPS/ATP) and NK, resulting in the generation of conditioned media. In vivo, histopathological alterations were markedly alleviated by NK, accompanied by reductions in serum triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and the modulation of Lipin-1, SREBP1, and Nur77 levels in comparison to the EtOH-exposed group (p < 0.001). Additionally, NK reduced the production of P2X7r and NLRP3. NK markedly upregulated Nur77, inhibited P2X7r and Lipin-1, and promoted the function of Cytosporone B, a Nur77 agonist (p < 0.001). Moreover, Nur77 deficiency weakened the regulatory effect of NK on P2X7r and Lipin-1 inhibition (p < 0.001). In NK-exposed MPMs, cleaved caspase-1 and mature IL-1ß expression decreased following LPS/ATP treatment (p < 0.001). NK also decreased inflammatory-factor production in primary hepatocytes stimulated with MPM supernatant. NK ameliorated ETOH-induced ALD through a reduction in inflammation and lipogenesis factors, which was likely related to Nur77 activation. Hence, NK is a potential therapeutic approach to ALD.

Exciplex-Forming Cohost Systems with 2,3-Dicyanopyrazinophenanthrene-based Acceptors to Achieve Efficient Near Infrared OLEDs.

Two new 2,3-dicyanopyrazinophenanthrene-based acceptors (A) p-QCN and m-QCN were synthesized to blend with a donor (D) CPTBF for the exciplex formation. The energy levels of p-QCN and m-QCN are modulated by the peripheral substituents 4- and 3-benzonitrile, respectively. Exciplex-forming blends were identified by the observation of the red-shifted emissions from various D : A blends with higher ratios of donor for suppressing the aggregation of acceptor. The two-component relaxation processes observed by time-resolved photoluminescence support the thermally activated delayed fluorescence (TADF) character of the exciplex-forming blends. The device employing CPTBF : p-QCN and (2 : 1) and CPTBF : m-QCN (2 : 1) blend as the emitting layer (EML) gave EQEmax of 1.76 % and 5.12 %, and electroluminescence (EL) λmax of 629 nm and 618 nm, respectively. The device efficiency can be further improved to 4.32 % and 5.57 % with CPTBF : p-QCN and (4 : 1) and CPTBF : m-QCN (4 : 1) as the EML, which is consistent with their improved photoluminescence quantum yields (PLQYs). A new fluorescent emitter BPBBT with photoluminescence (PL) λmax of 726 nm and a high PLQY of 67 % was synthesized and utilized as the dopant of CPTBF : m-QCN (4 : 1) cohost system. The device employing CPTBF : m-QCN (4 : 1): 5 wt.% BPBBT as the EML gave an EQEmax of 5.02 % and EL λmax centered at 735 nm, however, the weak residual exciplex emission remains. By reducing the donor ratio, the exciplex emission can be completely transferred to BPBBT and the corresponding device with CPTBF : m-QCN (2 : 1): 5 wt.% BPBBT as the EML can achieve EL λmax of 743 nm and EQEmax of 4.79 %. This work manifests the high efficiency near infrared (NIR) OLED can be realized by triplet excitons harvesting of exciplex-forming cohost system, followed by the effective energy transfer to an NIR fluorescent dopant.

Carbon nanodots constructed by ginsenosides and their high inhibitory effect on neuroblastoma.

BACKGROUND: Neuroblastoma is one of the common extracranial tumors in children (infants to 2 years), accounting for 8 ~ 10% of all malignant tumors. Few special drugs have been used for clinical treatment currently. RESULTS: In this work, herbal extract ginsenosides were used to synthesize fluorescent ginsenosides carbon nanodots via a one-step hydrothermal method. At a low cocultured concentration (50 µg·mL- 1) of ginsenosides carbon nanodots, the inhibition rate and apoptosis rate of SH-SY5Y cells reached ~ 45.00% and ~ 59.66%. The in vivo experiments showed tumor volume and weight of mice in ginsenosides carbon nanodots group were ~ 49.81% and ~ 34.14% to mice in model group. Since ginsenosides were used as sole reactant, ginsenosides carbon nanodots showed low toxicity and good animal response. CONCLUSION: Low-cost ginsenosides carbon nanodots as a new type of nanomedicine with good curative effect and little toxicity show application prospects for clinical treatment of neuroblastoma. It is proposed a new design for nanomedicine based on bioactive carbon nanodots, which used natural bioactive molecules as sole source.

Successful management of camrelizumab-induced immune-checkpoint-inhibitors-related myocarditis.

INTRODUCTION: Immune checkpoint inhibitors can cause immune-related toxicity in various systems, with myocarditis being the most severe and life-threatening manifestation. This report presents a case in which myocarditis developed following administration of programmed cell death protein-1 (PD-1) inhibitors therapy. We describe the diagnosis and treatment of this patient in detail. CASE REPORT: We present the case of a 59-year-old female diagnosed with post-operative esophageal cancer and hepatic metastases. The patient underwent second-line treatment with domestically-made PD-1 inhibitor, camrelizumab, in combination with paclitaxel (albumin-bound) and carboplatin for two cycles. During the course of treatment, an electrocardiogram (ECG) revealed ST segment elevation in leads II, III, aVF, V2, V3, and V4, along with T wave changes in leads I and aVL. Laboratory examinations showed abnormal levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT). Despite the absence of clinical symptoms, the patient was routinely hospitalized three weeks later. Based on the findings from the ECG, cardiac biomarkers, echocardiography, echocardiogram, cardiac magnetic resonance, and angiography, she was diagnosed with immune-checkpoint-inhibitors-related myocarditis. MANAGEMENT AND OUTCOME: The patient received immunoglobulin (0.5 g/kg/day) and was initially given methylprednisolone (1000 mg/day). Methylprednisolone was gradually reduced to 40 mg/day in 2 weeks. During this time, the levels of biomarkers indicative of myocardial injury also exhibited a simultaneous decline. DISCUSSION: This case highlights the importance of early detection and prompt intervention, including initiating appropriate steroid therapy and discontinuing of immune checkpoint inhibitors. Such measures can effectively prevent morbidity and mortality, ultimately leading to an improved prognosis.

Corosolic acid ameliorates non-alcoholic steatohepatitis induced by high-fat diet and carbon tetrachloride by regulating TGF-ß1/Smad2, NF-κB, and AMPK signaling pathways.

Hawthorn (Crataegus pinnatifida Bunge. var. major) is an edible and medicinal fruit that is very common in food and traditional Chinese medicine. Corosolic acid (CA), a pentacyclic triterpenoid, which is an active component of hawthorn (Crataegus pinnatifida Bunge. var. major), has been exhibiting various pharmacological activities such as antidiabetic, antibacterial, anticancer, antiinflammatory, and antioxidant effects. The study aimed to evaluate the effect of CA on non-alcoholic steatohepatitis (NASH) in mice induced by 60 kcal% high-fat diet (HFD) and carbon tetrachloride (CCl4 ). CA lowered liver index and serum AST, ALT, TG, and TC levels compared to those in the model group. Histological analyses of the liver tissues of mice treated with CA revealed significantly decreased number of lipid droplets and alleviated inflammation and fibrosis. CA inhibited the transcripts of pro-fibrogenic markers (including α-SMA, collagen I, and TIMP-1) and the levels of pro-inflammatory cytokines (including TNF-α, IL-1ß, caspase-1, and IL-6) associated with hepatic fibrosis, and NF-κB translocation and TGF-ß1/Smad2 and AMPK pathways. In addition, CA reduced lipid accumulation via the regulation of AMPK and NF-κB activation in FFA-induced steatotic HepG2 cells. CA also decreased α-SMA, collagen I expressions, and Smad2 phosphorylation, which were reduced by TGF-ß1 treatment in LX2 cells. Our results suggested that CA ameliorated NASH through regulating TGF-ß1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.

Tumor-associated macrophages derived CCL18 promotes metastasis in squamous cell carcinoma of the head and neck.

BACKGROUND: Alternatively activated macrophages in tumor microenvironment is defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer progression. However, communicative mechanisms between M2 TAMs and cancer cells in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown. METHODS: Quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and flow cytometry were applied to quantify mRNA and protein expression of genes related to M2 TAMs, epithelial-mesenchymal transition (EMT) and stemness. Wounding-healing and Transwell invasion assays were performed to detect the invasion and migration. Sphere formation assay was used to detect the stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis were used to determine the alterations of transcriptome. RESULTS: THP-1 monocytes were successfully polarized into M2-like TAMs, which was manifested by increased mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2-like TAMs promoted the migration and invasion of SCCHN cells, which was accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18 neutralizing antibody partially abrogated these effects that caused by conditional medium from M2-like TAMs. In addition, recombinant human CCL18 (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down-regulated genes stimulated by rhCCL18, which were statistically enriched in 10 cancer associated signaling pathways. CONCLUSION: These findings indicate that CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer stemness in SCCHN in vitro.

How Can Synergism of Traditional Medicines Benefit from Network Pharmacology?

Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks. Comprehensive, systematic research into network pharmacology is consistent with the perspective of holisticity, which is a main characteristic of many TMs. By means of network pharmacology, research has demonstrated that many a TM show a synergistic effect by acting at different levels on multiple targets and pathways. This approach effectively bridges the gap between modern medicine and TM, and it greatly facilitates studies into the synergistic actions of TMs. There are different kinds of synergistic effects with TMs, such as synergy among herbs, effective parts, and pure compounds; however, for various reasons, new drug discovery should at present focus on synergy among pure compounds.

Highly sensitive detection of okadaic acid in seawater by magnetic solid-phase extraction based on low-cost metal/nitrogen-doped carbon nanotubes.

Algae toxins pose a severe threat to human health all over the world. In this study, magnetic metal/nitrogen-doped carbon nanotubes (M-NCNTs) were facilely synthesized based on one-step carbonization and applied for magnetic solid-phase extraction of okadaic acid (OA) from seawater followed by high performance liquid chromatographic tandem mass spectrometry (HPLC-MS/MS) analyses. Differences in the physicochemical properties of the three prepared materials (Fe/Co/Ni-NCNTs) were investigated to confirm the best extraction material. Among them, Ni-NCNTs demonstrated a faster extraction rate (10 min) and higher adsorption capacity (223.5 mg g-1), mainly due to the higher specific surface area, suitable pore structure and more abundant pyridine nitrogen ring. Under the optimal conditions, the calibration curve was linear over the range (1.0-800.0 pg mL-1) with good determination coefficients (R) of 0.9992. The limit of detection (LOD) obtained in multiple replicates was 0.4 pg mL-1. Three seawater samples were measured by the developed method, 12.3 pg mL-1 of OA was detected with a satisfying recovery (88.6%-106.7%) and acceptable repeatability (RSD ≤ 4.8%, n = 6). The results demonstrate that M-NCNTs materials are a promising candidate for magnetic solid-phase extraction. Benefiting from its high extraction and interference resistance, the established analytical method is expected to be extended to detect other marine environmental pollutions.

Mitochondrial-related genes markers that predict survival in patients with head and neck squamous cell carcinoma affect immunomodulation through hypoxia, glycolysis, and angiogenesis pathways.

Mitochondria play a crucial role in the occurrence and development of tumors. We used mitochondria-related genes for consistent clustering to identify three stable molecular subtypes of head and neck squamous cell carcinoma (HNSCC) with different prognoses, mutations, and immune characteristics. Significant differences were observed in clinical characteristics, immune microenvironment, immune cell infiltration, and immune cell scores. TP53 was the most significantly mutated; cell cycle-related pathways and tumorigenesis-related pathways were activated in different subtypes. Risk modeling was conducted using a multifactor stepwise regression method, and nine genes were identified as mitochondria-related genes affecting prognosis (DKK1, EFNB2, ITGA5, AREG, EPHX3, CHGB, P4HA1, CCND1, and JCHAIN). Risk score calculations revealed significant differences in prognosis, immune cell scores, immune cell infiltration, and responses to conventional chemotherapy drugs. Glycolysis, angiogenesis, hypoxia, and tumor-related pathways were positively correlated with the RiskScore. Clinical samples were subjected to qPCR to validate the results. In this work, we constructed a prognostic model based on the mitochondrial correlation score, which well reflects the risk and positive factors for the prognosis of patients with HNSCC. This model can be used to guide individualized adjuvant and immunotherapy in patients with HNSCC.

High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population.

Background: This study sought to examine the expression and mutation status of fibroblast growth factor receptor 3 (FGFR3) in non-small cell lung cancer (NSCLC) tissues and explore the prognostic potential of FGFR3 in NSCLC. Methods: Immunohistochemistry (IHC) was used to evaluate the FGFR3 protein expression of 116 NSCLC tissues. Sanger sequencing was used to examine the mutation status of exons 7, 10, and 15 in FGFR3. A Kaplan­Meier survival analysis was conducted to evaluate the association between the expression level of FGFR3 and the overall survival (OS) and disease-free survival (DFS) of NSCLC patients. Univariate and multivariate Cox analyses were conducted to examine the association between the risk score and clinical features. Results: FGFR3 was immunoreactive in 26 of the 86 NSCLC cases. Further, FGFR3 was positively expressed in 84.6% of the lung adenocarcinoma (AC) cases and 15.4% of the lung squamous cell carcinoma (SCC) cases. FGFR3 mutations were detected in 2 NSCLC patients (2/72, 2.8%), who both harbored the T450M mutation, a novel mutation in exon 10 of FGFR3. In NSCLC, a high expression of FGFR3 was positively correlated with gender, smoking, histology type, T stage, and the epidermal growth factor receptor (EGFR) mutation (P<0.05). FGFR3 expression was also correlated with better OS and DFS. The multivariate analysis revealed that FGFR3 served as an independent prognostic factor (P=0.024) for the OS of NSCLC patients. Conclusions: This study showed that FGFR3 was highly expressed in NSCLC tissues, and the frequency rate for the FGFR3 mutation at T450 M in NSCLC tissues was low. The survival analysis suggested that FGFR3 may be a useful prognostic biomarker in NSCLC.

[Application progress of covalent organic framework materials in extraction of toxic and harmful substances].

Toxic and hazardous substances constitute a category of compounds that are potentially hazardous to humans, other organisms, and the environment. These substances include pesticides (benzoylureas, pyrethroids, neonicotinoids), persistent organic pollutants (polycyclic aromatic hydrocarbons, polychlorinated biphenyls, perfluorinated compounds), plasticizers (phthalate esters, phenolic endocrine disruptors), medicines (sulfonamides, non-steroid anti-inflammatory drugs, tetracyclines, fluoroquinone antibiotics), heterocyclic aromatic amines, algal toxins, and radioactive substances. Discharge of these toxic and harmful substances, as well as their possible persistence and bioaccumulation, pose a major risk to human health, often to the extent of being life-threatening. Therefore, it is important to analyze and detect toxic and hazardous substances in the environment, drinking water, food, and daily commodities. Sample pretreatment is an imperative step in most of the currently used analytical methods, especially in the analysis of trace toxic and harmful substances in complex samples. An efficient and fast sample pretreatment technology not only helps improve the sensitivity, selectivity, reproducibility, and accuracy of analytical methods, but also avoids contamination of the analytical instruments and even damages the performance and working life of instruments. Sample pretreatment techniques widely used in the extraction of toxic and hazardous substances include solid-phase extraction (SPE), solid-phase microextraction (SPME), and dispersed solid-phase extraction (DSPE). The adsorbent material plays a key role in these pretreatment techniques, thereby determining their selectivity and efficiency. In recent years, covalent organic frameworks (COFs) have attracted increasing attention in sample pretreatment. COFs represent an exciting new class of porous crystalline materials constructed via the strong covalent bonding of organic building units through a reversible condensation reaction. COFs present four advantages: (1) precise control over structure type and pore size by consideration of the target molecular structure based on the connectivity and shape of the building units; (2) post-synthetic modification for chemical optimization of the pore interior toward optimized interaction with the target; (3) straightforward scalable synthesis; (4) feasible formation of composites with magnetic nanoparticles, carbon nanotubes, graphene, silica, etc., which is beneficial to enhance the performance of COFs and meet the requirement of diverse pretreatment technologies. Because of the well-defined crystalline porous structures and tailored functionalities, COFs have excellent potential for use in target extraction. However, some issues need to be addressed for the application of COFs in the extraction of toxic and hazardous substances. (1) For the sample matrix, most of the reported COFs are highly hydrophobic, which limits their dispersibility in water-based samples, leading to poor extraction performance. COFs with good dispersibility in water-based samples are urgently required. (2) Besides, COFs rely on hydrophobic interaction, size repulsion, π-π stacking, and Van der Waals forces to extract target substances, but they are not effective for some polar targets. Thus, it is necessary to develop COFs with high affinity for polar toxic and hazardous substances. (3) Methods for the synthesis of COFs have evolved from solvothermal methods to room-temperature methods, mechanical grinding, microwave-assisted synthesis, ion thermal methods, etc. Most of the existing methods are time-consuming, laborious, and environmentally unfriendly. The starting materials are too expensive to prepare COFs in large quantities. More effort is required to improve the synthesis efficiency and overcome the obstacles in the application of COFs for extraction. This article summarizes and reviews the research progress in COFs toward the extraction of toxic and hazardous substances in recent years. Finally, the application prospects of COFs in this field are summarized, which serves as a reference for further research into pretreatment technologies based on COFs.

Identification and validation of a prognostic model based on ferroptosis-associated genes in head and neck squamous cancer.

Ferroptosis is that under the action of ferrous iron or ester oxygenase, unsaturated fatty acids highly expressed on the cell membrane are catalyzed to undergo lipid peroxidation, thereby inducing cell death. In this study, we used ferroptosis marker genes to identify 3 stable molecular subtypes (C1, C2, C3) with distinct prognostic, mutational, and immune signatures by consensus clustering; TP53, CDKN2A, etc. Have higher mutation frequencies in the three subtypes. C3 has a better prognosis, while the C1 subtype has a worse prognosis. WGCNA is used to identify molecular subtype-related gene modules.After filting, we obtained a total of 540 genes related to the module feature vector (correlation>0.7).We performed univariate COX regression analysis on these genes, and identified a total of 97 genes (p < 0.05) that had a greater impact on prognosis, including 8 ''Risk" and 89 ''Protective" genes. After using lasso regression, we identified 8 genes (ZNF566, ZNF541, TMEM150C, PPAN, PGLYRP4, ENDOU, RPL23 and MALSU1) as ferroptosis-related genes affecting prognosis. The ferroptosis prognosis-related risk score (FPRS) was calculated for each sample in TCGA-HNSC dataset. The results showed that FPRS was negatively correlated with prognosis.The activated pathways in the PFRS-high group mainly include immune-related pathways and invasion-related pathways. We assessed the extent of immune cell infiltration in patients in our TCGA-HNSC cohort by using the expression levels of gene markers in immune cells. The FPRS-high group had a higher level of immune cell infiltration. We found that the expression of immune checkpoints was significantly up-regulated in the FPRS-low group and the FPRS-high group had a higher probability of immune escape and a lower probability of benefiting from immunotherapy. In this work, we constructed a scoring Ferroptosis-related prognostic model that can well reflect risk and positive factors for prognosis in patients with head and neck squamous cell carcinoma. It can be used to guide individualized adjuvant therapy and chemotherapy for patients with head and neck cancer. Therefore, it has a good survival prediction ability and provides an important reference for clinical treatment.

Preliminary Exploration on the Value of Shear Wave Elastography in Evaluating the Effectiveness of Microwave Ablation on Hepatic Malignancies.

ABSTRACT: Shear wave elastography (SWE) is a new type of ultrasonic elastography that can quantitatively assess the elasticity and stiffness of tissues. This study aimed to investigate the value of SWE in evaluating the effectiveness of microwave ablation in hepatic malignancies. A total of 24 patients (including 30 lesions) with liver malignancies receiving microwave ablation treatment at the Cancer Hospital of Guangzhou Medical University from April 2018 to January 2019 were enrolled. The elastography was performed within 1 week before and after ablation. The SWE values in the central zone, the marginal zone of the lesion, and peripheral liver parenchyma were collected and analyzed. Before ablation, the mean of SWE value was 65.80 ± 13.37 kPa for the central zone of the tumor and 39.93 ± 7.87 kPa for the marginal zone, both of which were significantly greater than that for the perinatal liver parenchyma (12.85 ± 2.67 kPa, both P < 0.05). In the central and marginal zone of the lesions, the SWE value was significantly elevated after ablation (both P < 0.001) but not in the peripheral liver parenchyma (P = 0.444). Receiver operating characteristic curve analysis showed that the cutoff value for ablation in the marginal zone was 53.87 kPa, suggesting that an SWE exceeding 53.87 kPa is an index guaranteeing the ablation effectiveness. These results suggested that SWE has the potential to be used in evaluating the effectiveness of microwave ablation in liver cancers.

Pharmacological Properties of Ginsenoside Re.

Ginsenoside Re is a protopanaxatriol-type saponin extracted from the berry, leaf, stem, flower bud, and root of Panax ginseng. In recent years, ginsenoside Re (Re) has been attracting attention as a dietary phytochemical. In this review, studies on Re were compiled by searching a combination of keywords, namely "pharmacology," "pharmacokinetics," and "toxicology," in the Google Scholar, NCBI, PubMed, and Web of Science databases. The aim of this review was to provide an exhaustive overview of the pharmacological activities, pharmacokinetics, and toxicity of Re, focusing on clinical evidence that has shown effectiveness in specific diseases, such as diabetes mellitus, nervous system diseases, inflammation, cardiovascular disease, and cancer. Re is also known to eliminate virus, enhance the immune response, improve osteoporosis, improve skin barrier function, enhance intracellular anti-oxidant actions, regulate cholesterol metabolism, alleviate allergic responses, increase sperm motility, reduce erectile dysfunction, promote cyclic growth of hair follicles, and reduce gastrointestinal motility dysfunction. Furthermore, this review provides data on pharmacokinetic parameters and toxicological factors to examine the safety profile of Re. Such data will provide a theoretical basis and reference for Re-related studies and future applications.

Facile mechanochemistry synthesis of magnetic covalent organic framework composites for efficient extraction of microcystins in lake water samples.

Easy-preparation magnetic solid-phase extraction (MSPE) adsorbents with excellent extraction performance are very indispensable for MSPE techniques. Herein, a magnetic carbon nanotube covalent organic framework composite (MCNTs@TpPa-1) was prepared simply and rapidly through mechanochemical synthesis as MSPE adsorbent for enriching microcystins (MCs). The synthesized MCNTs@TpPa-1 exhibited well water dispersibility, high affinity with MCs and large surface area, resulting in outstanding extraction performance for MCs. Subsequently, combined with high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), an efficient, sensitive and convenient MSPE method was set up for the determination of trace MCs from aqueous sample, which exhibited acceptable repeatability (RSDs (relative standard deviations) ≤ 6.8%, n = 6), low limits of detection (LODs, 0.8-1.5 pg mL-1), reliable linearity (R ≥ 0.9991) and broad range of linearity (2.0-1000 pg mL-1). Furthermore, the developed method was applied to lake samples and trace MCs (9.6-24.6 pg mL-1) were found with satisfactory recovery (85.0-106.0%). The results indicated powerfully MCNTs@TpPa-1 was of significant potential as an MSPE sorbent for detection of trace MCs in water. Moreover, considering the complexity of traditional preparation methods, novel prospects for preparing magnetic covalent organic frameworks (COFs) with excellent extraction properties were opened up.

Six Glycolysis-Related Genes as Prognostic Risk Markers Can Predict the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is one of the worst-prognosis malignant tumors. This study used bioinformatic analysis of the transcriptome sequencing data of HNSCC and the patients' survival and clinical data to construct a prediction signature of glycolysis-related genes as the prognostic risk markers. METHODS: Gene expression profile data about HNSCC tissues (n = 498) and normal tissues in the head and neck (n = 44) were got from The Cancer Genome Atlas (TCGA), as well as patients' survival and clinical data. Then, we obtained core genes; their expression in head and neck squamous cell carcinoma tissues is significantly different from that in normal head and neck tissues. The predicted glycolysis-related genes are screened through univariate Cox regression analysis, and then, the prognostic risk markers were constructed through further correction of multivariate Cox regression analysis. The Kaplan-Meier curve and receiver operating characteristic curve are used to analyze the potential value of these risk markers in diagnosis and prognosis. We also evaluated that the glycolysis-related prognostic risk markers composed of 6 oncogenes are correlated with clinical features, such as age, gender, grade, and clinical stage of the tumor, by univariate and multivariate Cox regression analyses. RESULTS: Differentially expressed glycolytic genes in HNSCC tissues and normal head and neck tissues were screened from TCGA databases using the bioinformatic method. We confirmed a set of six glycolytic genes that were significantly associated with OS in the test series. According to our analysis, the prognostic risk markers composed of HPRT1, STC2, PLCB3, GPR87, PYGL, and SLC5A12 may be an independent risk factor for the prognosis of HNSCC. CONCLUSIONS: Through this analysis, we constructed new prognostic risk markers related to glycolysis as a prognostic risk marker for patients with HNSCC and provided new ideas and molecular targets for the research and individualized treatment of HNSCC.

Evaluation of Microwave Ablation Efficacy by Strain Elastography and Shear Wave Elastography in ex Vivo Porcine Liver.

The aim of this study was to evaluate the efficacy of microwave ablation by ultrasound (US), strain elastography (SE) and shear-wave elastography (SWE). An ex vivo model of porcine liver was adopted. According to ablation power and duration, 30 samples were divided into three groups: group 1 (45 W, 30 s), group 2 (45 W, 15 s) and group 3 (30 W, 30 s). US was used to measure the largest transverse diameter (D1), vertical diameter (D2) and anteroposterior diameter (D3) of the ablated area. SE was used to measure the largest transverse diameter (SEL1), vertical diameter (SEL2) and anteroposterior diameter (SEL3). The actual size of the ablated area was measured as the largest transverse diameter (L1), vertical diameter (L2) and anteroposterior diameter (L3). SWE values and temperatures were measured in the central lesion (region a), marginal area (region b) and unablated area (region c). At 1 h post-ablation, the values measured by US (D1, D2, D3) were all significantly smaller than the ablated area (L1, L2, L3) in all three groups. Except for SEL2 in group 1, there was no significant difference in the results between SEL and L among the three groups. All SWE results were significantly higher post-ablation than pre-ablation in the central lesion (region a) and marginal area (region b, all p values <0.05). In regions a, b and c, the temperatures measured immediately and 5 min post-ablation were all higher than that measured pre-ablation. These results suggest that SE and SWE can be used to evaluate the ablation efficacy of liver tissue.

Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma.

BACKGROUND: Metastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated. METHODS: PLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU's association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis. RESULTS: PLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all p < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU's function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell. CONCLUSIONS: PLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU's oncogene role in HNSCC.

Efficacy of nedaplatin combined with docetaxel in patients with nasopharyngeal carcinoma and its influence on ECRG4 and VEGF expressions.

PURPOSE: To explore the efficacy of nedaplatin combined with docetaxel in patients with nasopharyngeal carcinoma and its influence on the expressions of esophageal cancer-related gene 4 (ECRG4) and vascular endothelial growth factor (VEGF). METHODS: 86 patients with nasopharyngeal carcinoma, admitted to and treated in our hospital from March 2016 to February 2018, were selected and randomly divided into control group (n=43) and observation group (n=43). Chemotherapy combining cisplatin with fluorouracil was administered in the control group, while nedaplatin combined with docetaxel was given in the observation group. Then the efficacy, adverse reactions, the levels of serum hypoxia-inducible factor-1α (HIF-1α) and VEGF in patients before and after treatment, and the change in the expression level of ECRG4 in foci after treatment were compared between the two groups. After 1-year follow-up, the improvement in quality of life was compared between the two groups of patients. RESULTS: The objective remission rate and disease control rate in the observation group were obviously higher than in the control group (p<0.05), and the total incidence rate of adverse reactions in the observation group was evidently lower than in the control group (p<0.05). At 2, 4, and 6 weeks after treatment, the two groups of patients had substantially decreased levels of serum HIF-1α and VEGF, and the declines were more apparent in the observation group (p<0.05). The expression level of ECRG4 in foci in the observation group was remarkably higher than in the control group (p<0.05). The observation group exhibited more apparent improvement in quality of life than the control group (p<0.05). CONCLUSIONS: Nedaplatin combined with docetaxel has better short-term efficacy in nasopharyngeal carcinoma, with milder adverse reactions, and it can reduce the levels of serum HIF-1α and VEGF, and up-regulate ECRG4 expression in patients, exerting an anti-carcinoma effect.

Research on two-dimensional external magnetic drive method of maglev ball based on force imbalance.

In this paper, an external magnetic driving method of a maglev ball based on force imbalance is first proposed to meet the requirement that the maglev ball is moved linearly in the axis direction of the electromagnetic actuator in the non-liquid environment. This method is expected to be better applied in the fields of industrial and medical miniature curved tube. The maglev ball is a magnetic levitated object. Based on the interpolation algorithm, the two-dimensional stepwise levitation motion trajectory of the maglev ball is designed as the target curve of the motion. The maglev ball can be driven with a large range along a specified motion path. Compared with the 1.0 mm step input, the overshoot of a 0.2 mm step input is decreased by 73.7% and 73.6% in the descending phase and the ascending phase, respectively. Therefore, fluctuation of the step response of the maglev ball is improved by smaller step control. However, the larger the step input, the faster the speed and the larger the levitation gap. Under the condition of a 1.0 mm step input, the maximum levitation gap can be up to 20.487 mm, and the speed of the maglev ball can reach 3.086 mm/s. Compared with static levitation control, the position of the maglev ball is fluctuated severely due to radial runout under motion control conditions, and the position accuracy can reach ±0.03 mm.