Serum MYCN as a predictive biomarker of prognosis and therapeutic response in the prevention of hepatocellular carcinoma recurrence.

The proto-oncogene MYCN expression marked a cancer stem-like cell population in hepatocellular carcinoma (HCC) and served as a therapeutic target of acyclic retinoid (ACR), an orally administered vitamin A derivative that has demonstrated promising efficacy and safety in reducing HCC recurrence. This study investigated the role of MYCN as a predictive biomarker for therapeutic response to ACR and prognosis of HCC. MYCN gene expression in HCC was analyzed in the Cancer Genome Atlas and a Taiwanese cohort (N = 118). Serum MYCN protein levels were assessed in healthy controls (N = 15), patients with HCC (N = 116), pre- and post-surgical patients with HCC (N = 20), and a subset of patients from a phase 3 clinical trial of ACR (N = 68, NCT01640808). The results showed increased MYCN gene expression in HCC tumors, which positively correlated with HCC recurrence in non-cirrhotic or single-tumor patients. Serum MYCN protein levels were higher in patients with HCC, decreased after surgical resection of HCC, and were associated with liver functional reserve and fibrosis markers, as well as long-term HCC prognosis (>4 years). Subgroup analysis of a phase 3 clinical trial of ACR identified serum MYCN as the risk factor most strongly associated with HCC recurrence. Patients with HCC with higher serum MYCN levels after a 4-week treatment of ACR exhibited a significantly higher risk of recurrence (hazard ratio 3.27; p = .022). In conclusion, serum MYCN holds promise for biomarker-based precision medicine for the prevention of HCC, long-term prognosis of early-stage HCC, and identification of high-response subgroups for ACR-based treatment.

Regioselective Deacetylation of Peracetylated Deoxy-C-glycopyranosides by Boron Trichloride (BCl3).

A general approach for regioselective deacetylation at sugar 3-OH of peracetylated 6-deoxy-C-glucopyranosides mediated by BCl3 was developed. The approach could be extended to other sugar-derived 6-deoxy-C-glycopyranosides, such as those derived from mannose, galactose, and rhamnose, with deacetylation occurring at varied sugar hydroxyl groups, and further extended to 4-deoxy-C-glucopyranosides with deacetylation occurring at sugar 3-OH. The approach would enable access to synthetically challenging carbohydrate derivatives. A possible mechanism of the regioselectivity was proposed.

MMP1, IL-1ß, sTNFR-1, and IL-6 are prognostic factors for patients with unresectable or metastatic renal cell carcinoma treated with immune checkpoint inhibitors.

BACKGROUND: Few studies have reported reliable prognostic factors for immune checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC). Therefore, we investigated prognostic factors in patients treated with ICIs for unresectable or metastatic RCC. METHODS: We included 43 patients who received ICI treatment for RCC between January 2018 and October 2021. Blood samples were drawn before treatment, and 73 soluble factors in the plasma were analyzed using a bead-based multiplex assay. We examined factors associated with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAE) using the Chi-squared test, Kaplan-Meier method, and the COX proportional hazards model. RESULTS: Patients exhibited a median PFS and OS of 212 and 783 days, respectively. Significant differences in both PFS and OS were observed for MMP1 (PFS, p < 0.001; OS, p = 0.003), IL-1ß (PFS, p = 0.021; OS, p = 0.008), sTNFR-1 (PFS, p = 0.017; OS, p = 0.005), and IL-6 (PFS, p = 0.004; OS, p < 0.001). Multivariate analysis revealed significant differences in PFS for MMP1 (hazard ratio [HR] 5.305, 95% confidence interval [CI], 1.648-17.082; p = 0.005) and OS for IL-6 (HR 23.876, 95% CI, 3.426-166.386; p = 0.001). Moreover, 26 patients experienced irAE, leading to ICI discontinuation or withdrawal. MMP1 was significantly associated with irAE (p = 0.039). CONCLUSION: MMP1 may be associated with severe irAE, and MMP1, IL-1ß, sTNFR-1, and IL-6 could serve as prognostic factors in unresectable or metastatic RCC treated with ICIs. MMP1 and IL-6 were independent predictors of PFS and OS, respectively. Thus, inhibiting these soluble factors may be promising for enhancing antitumor responses in patients with RCC treated with ICIs.

Clinical roles of soluble PD-1 and PD-L1 in plasma of NSCLC patients treated with immune checkpoint inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of non-small cell lung cancer (NSCLC). However, only a limited proportion of patients can benefit from this therapy, and clinically useful predictive biomarkers remain to be elucidated. METHODS: Blood was collected from 189 patients with NSCLC before and six weeks after the initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Soluble PD-1 (sPD-1) and PD-L1 (sPD-L1) in plasma before and after treatment were analyzed to evaluate their clinical significance. RESULTS: Cox regression analysis demonstrated that higher sPD-L1 levels before treatment significantly predicted unfavorable progression-free survival (PFS; HR 15.4, 95% CI 1.10-86.7, P = 0.009) and overall survival (OS; HR 11.4, 95% CI 1.19-52.3, P = 0.007) in NSCLC patients treated with ICI monotherapy (n = 122) but not in those treated with ICIs combined with chemotherapy (n = 67: P = 0.729 and P = 0.155, respectively). In addition, higher sPD-1 levels after treatment were significantly associated with better OS (HR 0.24, 95% CI 0.06-0.91, P = 0.037) in patients treated with anti-PD-1 monotherapy, whereas higher sPD-L1 levels after treatment were significantly associated with worse PFS (HR 6.09, 95% CI 1.42-21.0, P = 0.008) and OS (HR 42.6, 95% CI 6.83-226, P < 0.001). The levels of sPD-L1 at baseline closely correlated with those of other soluble factors, such as sCD30, IL-2Ra, sTNF-R1, and sTNF-R2, which are known to be released from the cell surface by zinc-binding proteases ADAM10/17. CONCLUSIONS: These findings suggest the clinical significance of pretreatment sPD-L1 as well as posttreatment sPD-1 and sPD-L1 in NSCLC patients treated with ICI monotherapy.

CircRNA CircABCB1 Diminishes the Sensitivity of Breast Cancer Cells to Docetaxel by Sponging MiR-153-3p.

Resistance to docetaxel is a major problem to the success of docetaxel-based therapies for breast cancer. The present study was to identify the role of circABCB1 in altering the docetaxel resistance properties. Reverse transcription-quantitative PCR (qRT-PCR) was performed to quantify circABCB1 and miR-153-3p. The effects of circABCB1 on the viability, apoptosis and migration/invasion of docetaxel-resistant and -sensitive cells were investigated by cell function experiments, including Cell Counting Kit-8 and Transwell assays. Correlation between circABCB1 and the docetaxel-treated outcome was analyzed by multivariate Cox regression analysis, in addition to Kaplan-Meier analysis of time to treatment failure (TTF). The targeting relationship between circABCB1 and miR-153-3p was predicted and verified by dual-luciferase reporter assay and RNA immunoprecipitation. CircABCB1 was highly expressed in cancerous tissues, as well as the docetaxel-sensitive group and cells. The overexpression of circABCB1 contributed to cell viability, docetaxel-resistance and migration/invasion, but inhibited apoptosis. CircABCB1 can sponge miR-153-3p. CircABCB1 contributed to the docetaxel resistance of breast cancer, maybe via the miR-153-3p.

Iodine-Modified Ag NPs for Highly Sensitive SERS Detection of Deltamethrin Residues on Surfaces.

It is essential to estimate the indoor pesticides/insecticides exposure risk since reports show that 80% of human exposure to pesticides occurs indoors. As one of the three major contamination sources, surface collected pesticides contributed significantly to this risk. Here, a highly sensitive liquid freestanding membrane (FSM) SERS method based on iodide modified silver nanoparticles (Ag NPs) was developed for quantitative detection of insecticide deltamethrin (DM) residues in solution phase samples and on surfaces with good accuracy and high sensitivity. The DM SERS spectrum from 500 to 2500 cm-1 resembled the normal Raman counterpart of solid DM. Similar bands at 563, 1000, 1165, 1207, 1735, and 2253 cm-1 were observed as in the literature. For the quantitative analysis, the strongest peak at 1000 cm-1 that was assigned to the stretching mode of the benzene ring and the deformation mode of C-C was selected. The peak intensity at 1000 cm-1 and the concentration of DM showed excellent linearity from 39 to 5000 ppb with a regression equation I = 649.428 + 1.327 C (correlation coefficient R2 = 0.991). The limit of detection (LOD) of the DM was found to be as low as 11 ppb. Statistical comparison between the proposed and the HPLC methods for the analysis of insecticide deltamethrin (DM) residues in solution phase samples showed no significant difference. DM residue analysis on the surface was mimicked by dropping DM pesticide on the glass surface. It is found that DM exhibited high residue levels up to one week after exposure. This proposed SERS method could find application in the household pesticide residues analysis.

Large-Scale Evaluation of Major Soluble Macromolecular Components of Fish Muscle from a Conventional 1H-NMR Spectral Database.

Conventional proton nuclear magnetic resonance (1H-NMR) has been widely used for identification and quantification of small molecular components in food. However, identification of major soluble macromolecular components from conventional 1H-NMR spectra is difficult. This is because the baseline appearance is masked by the dense and high-intensity signals from small molecular components present in the sample mixtures. In this study, we introduced an integrated analytical strategy based on the combination of additional measurement using a diffusion filter, covariation peak separation, and matrix decomposition in a small-scale training dataset. This strategy is aimed to extract signal profiles of soluble macromolecular components from conventional 1H-NMR spectral data in a large-scale dataset without the requirement of re-measurement. We applied this method to the conventional 1H-NMR spectra of water-soluble fish muscle extracts and investigated the distribution characteristics of fish diversity and muscle soluble macromolecular components, such as lipids and collagens. We identified a cluster of fish species with low content of lipids and high content of collagens in muscle, which showed great potential for the development of functional foods. Because this mechanical data processing method requires additional measurement of only a small-scale training dataset without special sample pretreatment, it should be immediately applicable to extract macromolecular signals from accumulated conventional 1H-NMR databases of other complex gelatinous mixtures in foods.

Significance of MUC2 gene methylation detection in pancreatic cancer diagnosis.

PURPOSE: This study was conducted to explore the diagnostic value of MUC2 gene methylation in pancreatic cancer. METHODS: Methylation restriction enzyme digestion (Msp I/Hap II) and polymerase chain reaction (PCR) were performed to detect methylation of the MUC2 gene in fecal and blood specimens from seven study subjects with pancreatic cancer (PC), chronic pancreatitis (CP), or normal controls (CON). Simultaneously, blood CA 19-9 levels were detected as a positive indicator of PC. RESULTS: MUC2 methylation was detected in 50% of PC cell lines. In fecal samples, the MUC2 methylation rate in PC (n = 30) was 43.3%, which was significantly higher than those in CP (n = 8, 0%, P < 0.05) and CON (n = 20, 5.0%, P < 0.05). In blood samples, the MUC2 methylation rate in PC (n = 40) was 52.5%, which was significantly higher than those in CP (n = 15, 0%, P < 0.01) and CON (n = 25, 4.0%, P < 0.01). For PC diagnosis, MUC2 gene methylation in blood samples showed higher specificity and positive predictive value than CA 19-9. The combined detection in the feces and blood showed a 60% MUC2 methylation rate in PC (n = 10), which was higher than those in the CP (n = 5, 0%, P < 0.01) and CON (n = 12, 0%, P < 0.01). CONCLUSIONS: The study can clearly indicate that combined detection of MUC2 gene methylation in the peripheral blood and feces could be used as a new screening and early diagnosis method for pancreatic cancer.

[Remote sensing extraction method of Codonopsis pilosula planting area in Weiyuan county].

Due to the large amount of Codonopsis pilosula planted in Weiyuan county,and the arable land area,the local medicinal materials office uses a large amount of manpower,financial resources and material resources to estimate its area every year. In order to extract the information of local Chinese medicinal materials more quickly and simply,we try to apply remote sensing technology to the extraction of Chinese medicinal materials. This paper will use Weiyuan county of Gansu province as the research area,and use the domestic ZY-3 Satellite multi-spectral remote sensing image as the data source to find out the spectral characteristics of the party's participation in other remote sensing images. The visual interpretation method was used to extract the planting area of the C. pilosula in Weiyuan county. The estimated value of the planting area of C. pilosula using satellite remote sensing technology was 75 965 mu( 1 mu≈667 m2),which was basically consistent with the field survey data of the local medicinal materials office. After the accuracy verification,it was found that the precision of C. pilosula planted by visual interpretation was more than 70%. It is concluded that the satellite remote sensing technology can be used to extract the information of C. pilosula and it can provide the relevant information of the planting area of Chinese medicinal materials quickly and accurately.

[Extraction of distribution information of Angelicae sinensis plants in Weiyuan county based on remote sensing technology].

Due to the large amount of nutrients required during the cultivation of Angelica sinensis and in order to prevent the occurrence of pests and diseases,and the annual reduction of the planting area of Angelica and the balance of supply and demand of A. sinensis,the A. sinensis plantation adopts the rotation mode. This paper takes Wuyuan county of Gansu province as the research scope and use GF-1 Satellite data as the data source,using remote sensing technology combined with field survey results,to explore the effective method of visual interpretation for the extraction of A. sinensis planting area. A sample was selected to generate a spectrum according to different feature types. The different characteristics of A. sinensis and other features were analyzed and distinguished in remote sensing images,so that the A. sinensis planting plots were extracted and verified in remote sensing images. The results showed that the accuracy verification value of the visual interpretation method was 95. 85%. It is determined that the visual interpretation method can effectively extract the A. sinensis planting plots within the research scope and realize the comprehensive grasp of the spatial distribution information of A. sinensis.

The Impact of Insurance Gain and Discussions with Healthcare Providers on Quitting Smoking.

Tobacco use is the leading preventable cause of death in the United States. Analyzing the ability for different mechanisms to reduce smoking rates can provide healthcare systems with information to establish the most effective smoking cessation efforts. Health insurance provides individuals with direct mechanisms to curb smoking behavior, such as access to smoking cessation resources. Gaining insurance may additionally indirectly influence smoking cessation by altering risk perceptions. Behavioral economic theory suggests that gaining health insurance may reduce current smokers' rate of discounting on the future, which could increase smoking cessation. This article aimed to evaluate the impact of insurance status (i.e., gaining any private (n = 681), gaining only public (n = 647), or remaining uninsured (n = 5,056)) as well as the impact of having a discussion with a healthcare provider about quitting smoking on smoking cessation among current adult smokers who were uninsured at the beginning of their data collection. Data for this study came from the Medical Expenditure Panel Survey 2003 to 2014 database. The study found that while individuals gaining public insurance was not statistically associated with smoking cessation, individuals who gained private insurance were more likely to stop smoking than individuals who remained uninsured (OR: 1.330; 95% CI: 1.019,1.737; p = 0.036). Having a discussion with a healthcare provider about quitting smoking was not associated with smoking cessation. These findings indicate that gaining private insurance may impact smoking behavior through mechanisms other than direct access to physician services.

Application of Two-Dimensional Nuclear Magnetic Resonance for Signal Enhancement by Spectral Integration Using a Large Data Set of Metabolic Mixtures.

Nuclear magnetic resonance (NMR) spectroscopy has tremendous advantages of minimal sample preparation and interconvertibility of data among different institutions; thus, large data sets are frequently acquired in metabolomics studies. Previously, we used a novel analytical strategy, named signal enhancement by spectral integration (SENSI), to overcome the low signal-to-noise ratio (S/N ratio) problem in (13)C NMR by integration of hundreds of spectra without additional measurements. In this letter, the development of a SENSI 2D method and application to >1000 2D JRES NMR spectra are described. Remarkably, the obtained SENSI 2D spectrum had an approximate 14-fold increase in the S/N ratio and 80-250 additional peaks without any additional measurements. These results suggest that SENSI 2D is a useful method for assigning weak signals and that the use of coefficient of variation values can support the assignment information and extraction of features from the population characteristics among large data sets.

Association of non-alcoholic fatty liver disease with impaired endothelial function by flow-mediated dilation: A meta-analysis.

AIM: Endothelial dysfunction was observed in patients with non-alcoholic fatty liver disease. The aim of the present study was to evaluate the extent of endothelial function impairment in patients with non-alcoholic fatty liver disease. METHODS: We systematically searched through the PubMed, Embase, China National Knowledge Infrastructure and Wanfang databases for studies dated up to January 2015. All observational studies that compared endothelial function between non-alcoholic fatty liver disease patients and healthy controls were included. Endothelial function was measured by brachial artery flow-mediated dilation and nitrate-induced dilatation techniques. RESULTS: Eleven observational studies were identified. Meta-analysis indicated that non-alcoholic fatty liver disease patients were associated with a reduction in brachial artery flow-mediated dilation (weighted mean difference, -4.82%; 95% confidence interval [CI], -5.63 to -4.00) compared with the healthy controls. Subgroup analysis indicated that the patients with non-alcoholic steatohepatitis or a body mass index of more than 30 kg/m(2) appeared to have a greater reduction in their flow-mediated dilation. However, no significant differences were observed in the nitrate-induced dilation (weighted mean difference, -0.4%; 95% confidence interval, -2.19 to 1.39). CONCLUSION: Non-alcoholic fatty liver disease is associated with a greater risk of endothelial dysfunction as indicated by the decreased brachial artery flow-mediated dilation. Assessment of endothelial function may be recommended to identify subclinical atherosclerosis and to create subgroups of non-alcoholic fatty liver disease patients who are at higher risk of future cardiovascular events.

Emergency transport of stroke suspects in a rural state: opportunities for improvement.

INTRODUCTION: Time delay is the key obstacle for receiving successful stroke treatment. Alteplase therapy must start within 4.5 hours from stroke occurrence. Rapid transport to a primary stroke center (PSC) or acute stroke-ready hospital (ASRH) by the emergency medical system (EMS) paramedics is vital. We determined transport time and destination data for EMS-identified and -delivered stroke suspects in Arkansas during 2013. Our objective was to analyze transport time and the hospital qualification for stroke care across the state. METHODS: The state's 75 counties were placed into 8 geographical regions (R1-R8). Transport time and hospital qualification were determined for all EMS-identified strokes. Each hospital's stroke care status was categorized as PSC, ASRH, a nonspecialty or unknown care facility (NSCF), out-of-state, or nonapplicable designation facilities. RESULTS: There were 9588 EMS stroke ground transports with median within-region transport times of 29-40 minutes. Statewide, only 65% of EMS-transported stroke patients were transported to either PSC (12%) or ASRH (53%) facilities. One-third of the patients (30.6%) were delivered to NSCFs, where acute stroke therapy may rarely be performed. Regions with the highest suspected-stroke cases per capita also had the highest percentage of transports to NSCFs. CONCLUSION: With only a few PSCs in Arkansas, EMS agencies should prioritize transporting stroke patients to ASRHs when PSCs are not regionally located.

NMR-based analysis of the chemical composition of Japanese persimmon aqueous extracts.

Japanese persimmon (Diospyros kaki L.) is recognized as an outstanding source of biologically active compounds relating to many health benefits. In the present study, NMR spectroscopy provided a comprehensive metabolic overview of Japanese persimmon juice. Detailed signal assignments of Japanese persimmon juice were carried out using various 2D NMR techniques incorporated with broadband water suppression enhanced through T1 effects (BB-WET) or WET sequences, and 26 components, including minor components, were identified. In addition, most components were quantitatively evaluated by the integration of signals using conventional (1) H NMR and BB-WET NMR. This is the first detailed analysis combined with quantitative characterization of chemical components using NMR for Japanese persimmon. Copyright © 2015 John Wiley & Sons, Ltd.

Pretreatment and integrated analysis of spectral data reveal seaweed similarities based on chemical diversity.

Extracting useful information from high dimensionality and large data sets is a major challenge for data-driven approaches. The present study was aimed at developing novel integrated analytical strategies for comprehensively characterizing seaweed similarities based on chemical diversity. The chemical compositions of 107 seaweed and 2 seagrass samples were analyzed using multiple techniques, including Fourier transform infrared (FT-IR) and solid- and solution-state nuclear magnetic resonance (NMR) spectroscopy, thermogravimetry-differential thermal analysis (TG-DTA), inductively coupled plasma-optical emission spectrometry (ICP-OES), CHNS/O total elemental analysis, and isotope ratio mass spectrometry (IR-MS). The spectral data were preprocessed using non-negative matrix factorization (NMF) and NMF combined with multivariate curve resolution-alternating least-squares (MCR-ALS) methods in order to separate individual component information from the overlapping and/or broad spectral peaks. Integrated analysis of the preprocessed chemical data demonstrated distinct discrimination of differential seaweed species. Further network analysis revealed a close correlation between the heavy metal elements and characteristic components of brown algae, such as cellulose, alginic acid, and sulfated mucopolysaccharides, providing a componential basis for its metal-sorbing potential. These results suggest that this integrated analytical strategy is useful for extracting and identifying the chemical characteristics of diverse seaweeds based on large chemical data sets, particularly complicated overlapping spectral data.

Wide field super-resolution surface imaging through plasmonic structured illumination microscopy.

We experimentally demonstrate a wide field surface plasmon (SP) assisted super-resolution imaging technique, plasmonic structured illumination microscopy (PSIM), by combining tunable SP interference (SPI) with structured illumination microscopy (SIM). By replacing the laser interference fringes in conventional SIM with SPI patterns, PSIM exhibits greatly enhanced resolving power thanks to the unique properties of SP waves. This PSIM technique is a wide field, surface super-resolution imaging technique with potential applications in the field of high-speed biomedical imaging.

[Subcellular localization of ataxin-3 and its effect on the morphology of cytoplasmic organoids].

OBJECTIVE: To explore the subcellular localization of ataxin-3 and the effect of polyglutamine (polyQ) expansion mutation on the morphology of mitochondrion, golgi apparatus and endoplasmic reticulum. METHODS: Transient transfection was employed to build cell models expressing wild-type or mutant ataxin-3 proteins. Indirect immunofluorescence was applied to identify markers of organelle membrane. The results were observed under a laser scanning confocal microscope. RESULTS: No co-localization was observed for ataxin-3 protein and mitochondrial marker TOM20, but the percentage of cells with mitochondrial fragmentation has increased in cells expressing mutant ataxin-3 (P<0.05). No co-localization was observed for ataxin-3 protein and golgi marker GM130, and mutant ataxin-3 did not cause golgi fragmentation. Wide type and polyQ-expanded ataxin-3 both showed partial co-localization with ER marker calnexin. The latter showed more overlap with calnexin, and the overlapping signals were mostly located in the places where aggregates were situated. CONCLUSION: PolyQ-expanded ataxin-3 protein may indirectly affect the integrity of mitochondria, but may cause no effect on the structure and functions of golgi apparatus. Endoplasmic reticulum may be another place where extended ataxin-3 protein can induce cytotoxicity in addition to the nucleus.

Thymic carcinoid with multiple bone metastases: A case report.

BACKGROUND: Thymic carcinoid (TC) is a rare entity among anterior mediastinal malignancies. TCs are neuroendocrine carcinomas that constitute approximately 2%-5% of all thymic epithelial tumors. CASE SUMMARY: The study reported a rare TC with multiple bone metastases. A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 kg. Magnetic resonance imaging scans revealed damage to the lumbar spine, sacrocaudal vertebrae and iliac crest, suggesting bone metastasis; computed tomography (CT) scan of the thorax showed a calcified anterior mediastinal mass; positron emission tomography-CT demonstrated multiple abnormal bone signals; and laboratory work-up showed no endocrine abnormalities. Fine-needle aspiration biopsy revealed predominantly single small, round to oval cells with scant cytoplasm and some loose clusters, suggesting endocrine manifestations. The pathological diagnosis was atypical carcinoid, which tend to originate from the thymus and was classified as intermediate-highly invasive. The patient underwent anlotinib-targeted therapy. Anlotinib (12 mg) was administered daily for 2 wk, after which the patient was allowed to rest for 21 d. Follow-up CT after one year demonstrated that the tumor had shrunk by approximately 29% after therapy. Treatment has a long stable disease benefit of more than 2.5 years. CONCLUSION: These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.