MicroRNA-148a Targets DNMT1 and PPARGC1A to Regulate the Viability, Proliferation, and Milk Fat Synthesis of Ovine Mammary Epithelial Cells.

In this study, the expression profiles of miR-148a were constructed in eight different ovine tissues, including mammary gland tissue, during six different developmental periods. The effect of miR-148a on the viability, proliferation, and milk fat synthesis of ovine mammary epithelial cells (OMECs) was investigated, and the target relationship of miR-148a with two predicted target genes was verified. The expression of miR-148a exhibited obvious tissue-specific and temporal-specific patterns. miR-148a was expressed in all eight ovine tissues investigated, with the highest expression level in mammary gland tissue (p < 0.05). Additionally, miR-148a was expressed in ovine mammary gland tissue during each of the six developmental periods studied, with its highest level at peak lactation (p < 0.05). The overexpression of miR-148a increased the viability of OMECs, the number and percentage of Edu-labeled positive OMECs, and the expression levels of two cell-proliferation marker genes. miR-148a also increased the percentage of OMECs in the S phase. In contrast, transfection with an miR-148a inhibitor produced the opposite effect compared to the miR-148a mimic. These results indicate that miR-148a promotes the viability and proliferation of OMECs in Small-tailed Han sheep. The miR-148a mimic increased the triglyceride content by 37.78% (p < 0.01) and the expression levels of three milk fat synthesis marker genes in OMECs. However, the miR-148a inhibitor reduced the triglyceride level by 87.11% (p < 0.01). These results suggest that miR-148a promotes milk fat synthesis in OMECs. The dual-luciferase reporter assay showed that miR-148a reduced the luciferase activities of DNA methyltransferase 1 (DNMT1) and peroxisome proliferator-activated receptor gamma coactivator 1-A (PPARGC1A) in wild-type vectors, suggesting that they are target genes of miR-148a. The expression of miR-148a was highly negatively correlated with PPARGC1A (r = -0.789, p < 0.001) in ovine mammary gland tissue, while it had a moderate negative correlation with DNMT1 (r = -0.515, p = 0.029). This is the first study to reveal the molecular mechanisms of miR-148a underlying the viability, proliferation, and milk fat synthesis of OMECs in sheep.

Molecular Characteristics of JAK2 and Its Effect on the Milk Fat and Casein Synthesis of Ovine Mammary Epithelial Cells.

In addition to its association with milk protein synthesis via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, JAK2 also affects milk fat synthesis. However, to date, there have been no reports on the effect of JAK2 on ovine mammary epithelial cells (OMECs), which directly determine milk yield and milk contents. In this study, the coding sequence (CDS) region of ovine JAK2 was cloned and identified and its tissue expression and localization in ovine mammary glands, as well as its effects on the viability, proliferation, and milk fat and casein levels of OMECs, were also investigated. The CDS region of ovine JAK2, 3399 bp in length, was cloned and its authenticity was validated by analyzing its sequence similarity with JAK2 sequences from other animal species using a phylogenetic tree. JAK2 was found to be expressed in six ovine tissues, with the highest expression being in the mammary gland. Over-expressed JAK2 and three groups of JAK2 interference sequences were successfully transfected into OMECs identified by immunofluorescence staining. When compared with the negative control (NC) group, the viability of OMECs was increased by 90.1% in the pcDNA3.1-JAK2 group. The over-expression of JAK2 also increased the number and ratio of EdU-labeled positive OMECs, as well as the expression levels of three cell proliferation marker genes. These findings show that JAK2 promotes the viability and proliferation of OMECs. Meanwhile, the triglyceride content in the over-expressed JAK2 group was 2.9-fold higher than the controls and the expression levels of four milk fat synthesis marker genes were also increased. These results indicate that JAK2 promotes milk fat synthesis. Over-expressed JAK2 significantly up-regulated the expression levels of casein alpha s2 (CSN1S2), casein beta (CSN2), and casein kappa (CSN3) but down-regulated casein alpha s1 (CSN1S1) expression. In contrast, small interfered JAK2 had the opposite effect to JAK2 over-expression on the viability, proliferation, and milk fat and milk protein synthesis of OMECs. In summary, these results demonstrate that JAK2 promotes the viability, proliferation, and milk fat synthesis of OMECs in addition to regulating casein expression in these cells. This study contributes to a better comprehension of the role of JAK2 in the lactation performance of sheep.

Noninvasive Models to Assess Liver Inflammation and Fibrosis in Chronic HBV Infected Patients with Normal or Mildly Elevated Alanine Transaminase Levels: Which One Is Most Suitable?

The prevalence of substantial inflammation or fibrosis in treatment-naïve patients with chronic hepatitis B (CHB) and normal alanine transaminase (ALT) levels is high. A retrospective analysis was conducted on 559 consecutive patients with hepatitis B virus infection, who underwent liver biopsy, to investigate the value of noninvasive models based on routine serum markers for evaluating liver histology in CHB patients with normal or mildly elevated ALT levels and to provide treatment guidance. After comparing 55 models, we identified the top three models that exhibited excellent performance. The APGA model, based on the area under the receiver operating characteristic curve (AUROC), demonstrated a superior ability to evaluate significant (AUROC = 0.750) and advanced fibrosis (AUROC = 0.832) and demonstrated a good performance in assessing liver inflammation (AUROCs = 0.779 and 0.874 for stages G ≥ 2 and G ≥ 3, respectively). APGA also exhibited significant correlations with liver inflammation and fibrosis stage (correlation coefficients, 0.452 and 0.405, respectively (p < 0.001)). When the patients were stratified into groups based on HBeAg status and ALT level, APGA consistently outperformed the other 54 models. The other top two models, GAPI and XIE, also outperformed models based on other chronic hepatitis diseases. APGA may be the most suitable option for detecting liver fibrosis and inflammation in Chinese patients with CHB.

Fructus choerospondiatis: A comprehensive review of its traditional uses, chemical composition, pharmacological activities, and clinical studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Choerospondiatis is the dried and mature fruit of Choerospondias axillaris (Roxb.) Burtt et Hill. It has been used for a long time in Tibetan and Mongolian medicine, first recorded in the ancient Tibetan medicine book "Medicine Diagnosis of the King of the Moon" in the early 8th century. Fructus Choerospondiatis shows multiple pharmacological activities, especially in treating cardiovascular diseases. AIM OF THIS REVIEW: This paper reviews the progress in research on the botanical characteristics, traditional uses, chemical constituents, pharmacological activity, clinical studies, and quality control of Fructus Choerospondiatis. This review aims to summarize current research and provide a reference for further development and utilization of Fructus Choerospondiatis resources. METHOD: The sources for this review include the Pharmacopeia of the People's Republic of China (2020), theses, and peer-reviewed papers (in both English and Chinese). Theses and papers were downloaded from electronic databases including Web of Science, PubMed, SciFinder, Scholar, Springer, and China National Knowledge Infrastructure.The search terms used were "Choerospondias axillaris", "C. axillaris", "Choerospondias axillaris (Roxb.) Burtt et Hill", "Fructus choerospondiatis", "Guangzao", "Lapsi", and "Lupsi". RESULTS: Fructus Choerospondiatis contains polyphenols, organic acids, amino acids, fatty acids, polysaccharides, and other chemical components. These ingredients contribute to its diverse pharmacological activities such as antioxidant activity, protection against myocardial ischemia-reperfusion injury, anti-myocardial fibrosis, heart rhythm regulation, anti-tumor, liver protection, and immunity enhancement. It also affects the central nervous system, with the ability to repair damaged nerve cells. CONCLUSION: Fructus Choerospondiatis, with its various chemical compositions and pharmacological activities, is a promising medicinal resource. However, it remains under-researched, particularly in pharmacodynamic material basis and quality control. These areas require further exploration by researchers in the future.

Interaction between Rumen Epithelial miRNAs-Microbiota-Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep.

Tibetan sheep are already well adapted to cold season nutrient stress on the Tibetan Plateau. Rumen, an important nutrient for metabolism and as an absorption organ in ruminants, plays a vital role in the cold stress adaptations of Tibetan sheep. Ruminal microbiota also plays an indispensable role in rumen function. In this study, combined multiomics data were utilized to comprehensively analyze the interaction mechanism between rumen epithelial miRNAs and microbiota and their metabolites in Tibetan sheep under nutrient stress in the cold season. A total of 949 miRNAs were identified in the rumen epithelium of both cold and warm seasons. A total of 62 differentially expressed (DE) miRNAs were screened using FC > 1.5 and p value < 0.01, and a total of 20,206 targeted genes were predicted by DE miRNAs. KEGG enrichment analysis revealed that DE miRNA-targeted genes were mainly enriched in axon guidance(ko04360), tight junction(ko04530), inflammatory mediator regulation of TRP channels(ko04750) and metabolism-related pathways. Correlation analysis revealed that rumen microbiota, rumen VFAs and DE miRNAs were all correlated. Further study revealed that the targeted genes of cold and warm season rumen epithelial DE miRNAs were coenriched with differential metabolites of microbiota in glycerophospholipid metabolism (ko00564), apoptosis (ko04210), inflammatory mediator regulation of TRP channels (ko04750), small cell lung cancer (ko05222), and choline metabolism in cancer (ko05231) pathways. There are several interactions between Tibetan sheep rumen epithelial miRNAs, rumen microbiota, and microbial metabolites, mainly through maintaining rumen epithelial barrier function and host homeostasis of choline and cholesterol, improving host immunity, and promoting energy metabolism pathways, thus enabling Tibetan sheep to effectively respond to cold season nutrient stress. The results also suggest that rumen microbiota have coevolved with their hosts to improve the adaptive capacity of Tibetan sheep to cold season nutrient stress, providing a new perspective for the study of cold season nutritional stress adaptation in Tibetan sheep.

Attention-based generative adversarial networks improve prognostic outcome prediction of cancer from multimodal data.

The prediction of prognostic outcome is critical for the development of efficient cancer therapeutics and potential personalized medicine. However, due to the heterogeneity and diversity of multimodal data of cancer, data integration and feature selection remain a challenge for prognostic outcome prediction. We proposed a deep learning method with generative adversarial network based on sequential channel-spatial attention modules (CSAM-GAN), a multimodal data integration and feature selection approach, for accomplishing prognostic stratification tasks in cancer. Sequential channel-spatial attention modules equipped with an encoder-decoder are applied for the input features of multimodal data to accurately refine selected features. A discriminator network was proposed to make the generator and discriminator learning in an adversarial way to accurately describe the complex heterogeneous information of multiple modal data. We conducted extensive experiments with various feature selection and classification methods and confirmed that the CSAM-GAN via the multilayer deep neural network (DNN) classifier outperformed these baseline methods on two different multimodal data sets with miRNA expression, mRNA expression and histopathological image data: lower-grade glioma and kidney renal clear cell carcinoma. The CSAM-GAN via the multilayer DNN classifier bridges the gap between heterogenous multimodal data and prognostic outcome prediction.

Characterization of the Heat Shock Transcription Factor Family in Medicago sativa L. and Its Potential Roles in Response to Abiotic Stresses.

Heat shock transcription factors (HSFs) are important regulatory factors in plant stress responses to various biotic and abiotic stresses and play important roles in growth and development. The HSF gene family has been systematically identified and analyzed in many plants but it is not in the tetraploid alfalfa genome. We detected 104 HSF genes (MsHSFs) in the tetraploid alfalfa genome ("Xinjiangdaye" reference genome) and classified them into three subgroups: 68 in HSFA, 35 in HSFB and 1 in HSFC subgroups. Basic bioinformatics analysis, including genome location, protein sequence length, protein molecular weight and conserved motif identification, was conducted. Gene expression analysis revealed tissue-specific expression for 13 MsHSFs and tissue-wide expression for 28 MsHSFs. Based on transcriptomic data analysis, 21, 11 and 27 MsHSFs responded to drought stress, cold stress and salt stress, respectively, with seven responding to all three. According to RT-PCR, MsHSF27/33 expression gradually increased with cold, salt and drought stress condition duration; MsHSF6 expression increased over time under salt and drought stress conditions but decreased under cold stress. Our results provide key information for further functional analysis of MsHSFs and for genetic improvement of stress resistance in alfalfa.

Metformin inhibits neutrophil extracellular traps-promoted pancreatic carcinogenesis in obese mice.

Obesity has been linked to a higher risk of pancreatic cancer. However, the mechanism by which obesity promote pancreatic carcinogenesis is still unclear. We investigated the effect of obesity on pancreatic carcinogenesis in Pdx1-Cre; LSL-KrasG12D+/- (KC) mice. Metformin was administrated to rescue the effects of obesity and NETs. The pro-tumorigenic effects of neutrophil extracellular traps (NETs) were further evaluated in vivo and vitro. We found that obesity significantly promoted the progression of murine pancreatic ductal intraepithelial neoplasia (mPanIN). The proliferation rate and epithelial-mesenchymal transition (EMT) of mPanIN ductal cells were increased in obese mice. More visceral adipocytes, PD-L1+ neutrophil infiltration and NETs formation were found in the pancreas of obese mice and visceral adipocytes could recruit neutrophils and promote NETs formation. The latter could induce an inflammatory response in ductal cells via TLR4-dependent pathways both in vivo and vitro, as demonstrated by upregulation of IL-1ß. Metformin and DNase I significantly reversed the pro-tumorigenic effects of obesity and NETs in vivo and in vitro. Our study provides causal evidence for the contribution of obesity in promoting pancreatic carcinogenesis in genetic model and reveals the mechanism by NETs to regulate mPanIN progression.

MicroRNA-200c Affects Milk Fat Synthesis by Targeting PANK3 in Ovine Mammary Epithelial Cells.

Milk fat is the foremost nutrient of milk and a vital indicator in evaluating milk quality. Accumulating evidence suggests that microRNAs (miRNAs) are involved in the synthesis of milk fat. The miR-200c is closely related to lipid metabolism, but little is known about its effect on the synthesis of milk fat in MECs of ewes. Herein, the effect of miR-200c on the proliferation of ovine mammary epithelial cells (MECs) and its target relationship with a predicted target gene were investigated. The regulatory effects of miR-200c on the expression of the target genes and the content of triglycerides in ovine MECs were further analyzed. The results revealed that the expression level of miR-200c was differentially expressed in both eight tissues selected during lactation and in mammary gland tissues at different physiological periods. Overexpression of miR-200c inhibited the viability and proliferation of ovine MECs, while inhibition of miR-200c increased cell viability and promoted the proliferation of ovine MECs. Target gene prediction results indicated that miR-200c would bind the 3'UTR region of pantothenate kinase 3 (PANK3). Overexpression of miR-200c reduced the luciferase activity of PANK3, while inhibition of miR-200c increased its luciferase activity. These findings illustrated that miR-200c could directly interact with the target site of the PANK3. It was further found that overexpression of miR-200c reduced the expression levels of PANK3 and, thus, accelerated the synthesis of triglycerides. In contrary, the inhibitor of miR-200c promoted the expression of PANK3 that, thus, inhibited the synthesis of triglycerides in ovine MECs. Together, these findings revealed that miR-200c promotes the triglycerides synthesis in ovine MECs via increasing the lipid synthesis related genes expression by targeting PANK3.

A histopathological study of artery wall involvement in pancreatic cancer surgery.

PURPOSE: This study aims to study the depth of artery wall tumour invasion in patients undergoing surgery for pancreatic ductal adenocarcinoma. METHODS: Specimens from 47 pancreatic cancer patients with major arterial (splenic, SA; celiac, CA; common hepatic, CHA) invasion were examined: 45 left (distal) pancreatectomies, including 11 celiac artery resections, and two total pancreatectomies. Dissection of tumour-invaded arteries in 25 fresh specimens was attempted ex vivo using the sub-adventitial dissection technique (SDT). Tumour invasion of 66 arteries was graded using the tumour-free distance (TFD) from the external elastic lamina (EEL): 0 = no arterial invasion; I = TFD ≥ 1 mm; II = TFD < 1 mm; and grade III = EEL invasion. RESULTS: AJCC TNM staging was IA = 1 (2%), IB = 4 (9%), IIA = 5 (11%), IIB = 17(36%) and III = 20 (43%). Grade III tumour invasion was found in 17/47(36%) SAs, in 5/11 (45%) CAs and in 1/8 (13%) CHAs (p = 0.318). Attempted ex vivo SDT undertaken in 33 arteries from 25 specimens was complete in 16 and incomplete in 17 arteries. The median (IQR) TFD was 0.97 (0.11-2.54) mm in dissected and 0.14 (0.10, 0.14) mm in non-dissected SAs (p = 0.034). EEL tumour invasion occurred in 0/12 (0%) dissected compared to 7/13 (54%) non-dissected SAs (p = 0.005). Grades 0, I, II and III invasion were found in four (33%), two (17%) and six (50%), respectively, of 12 dissected SAs and grades II and III in six 6 (46%) and seven (54%), respectively, of 13 non-dissected SAs (p = 0.002). CONCLUSIONS: The grading system described may form the basis for classification to further develop arterial dissection techniques for pancreatic cancer.

Carex rigescens caffeic acid O-methyltransferase gene CrCOMT confer melatonin-mediated drought tolerance in transgenic tobacco.

Melatonin is an important, multifunctional protective agent against a variety of abiotic and biotic stressors in plants. Caffeic acid O-methyltransferase (COMT) catalyzes the last step of melatonin synthesis in plants and reportedly participates in the regulation of stress response and tolerance. However, few studies have reported its function in melatonin-mediated drought resistance. In this study, CrCOMT was identified and was strongly induced by drought stress in Carex rigescens. CrCOMT overexpression in transgenic tobacco increased tolerance to drought stress with high levels of seed germination, relative water content, and survival rates. CrCOMT overexpression in tobacco improved membrane stability, and plants exhibited lower relative electrolytic leakage and malondialdehyde content, as well as higher photochemical efficiency than the wildtype (WT) under drought stress. The transgenic plants also had higher levels of proline accumulation and antioxidant enzyme activity, which decreased oxidative stress damage due to reactive oxygen species (ROS) hyperaccumulation under drought stress. The transcription of drought stress response and ROS scavenging genes was significantly higher in the CrCOMT overexpression plants than in the WT plants. In addition, CrCOMT transgenic tobacco plants exhibited higher melatonin content under drought stress conditions. Exogenous melatonin was applied to C. rigescens under drought stress to confirm the function of melatonin in mediating drought tolerance; the relative water content and proline content were higher, and the relative electrolytic leakage was lower in melatonin-treated C. rigescens than in the untreated plants. In summary, these results show that CrCOMT plays a positive role in plant drought stress tolerance by regulating endogenous melatonin content.

The genetic landscape of pancreatic head ductal adenocarcinoma in China and prognosis stratification.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is the major subtype of pancreatic cancer and head PDACs show distinct characteristics from body/tail PDACs. With limited studies based on Asian population, the mutational landscape of Asian PDAC remains unclear. METHODS: One hundred fifty-one Chinese patients with head PDAC were selected and underwent targeted 425-gene sequencing. Genomic alterations, tumor mutational burden, and microsatellite instability were analyzed and compared with a TCGA cohort. RESULTS: The genomic landscape of Chinese and Western head PDAC had identical frequently-mutated genes including KRAS, TP53, SMAD4, and CDKN2A. KRAS hotspot in both cohorts was codon 12 but Chinese PDACs containing more G12V but fewer G12R variants. Potentially pathogenic fusions, CHD2-BRAF and KANK1-MET were identified in two KRAS wild-type patients. Serum cancer antigens CA125 and CA19-9 were positively associated with SMAD4 alterations while high CEA was enriched in wild-type CDKN2A subgroup. The probability of vascular invasion was lower in patients with RNF43 alterations. The nomogram developed including histology grade, the mutation status of SMAD4, TGFBR2, and PREX2 could calculate the risk score of prognoses validated by Chinese and TCGA cohort. CONCLUSIONS: Chinese head PDAC contained more KRAS G12V mutation than Western population. The well-performed nomogram may improve post-operation care in real-world practice.

Sub-adventitial divestment technique for resecting artery-involved pancreatic cancer: a retrospective cohort study.

PURPOSE: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated. METHODS: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery. RESULTS: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively. CONCLUSIONS: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

Prognostic Nomogram for Resected Pancreatic Adenocarcinoma: A TRIPOD-Compliant Retrospective Long-Term Survival Analysis.

BACKGROUND: Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors. METHODS: From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre. RESULTS: Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram). CONCLUSION: Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.

Comprehensive analysis of human IgG Fc N-glycopeptides and construction of a screening model for colorectal cancer.

Currently, analyzing intact glycopeptides remains a challengeable task. Considerable progress has been achieved in the knowledge of immunoglobulin G (IgG) glycans in patients with colorectal cancer (CRC), whereas data on IgG Fc N-glycopeptides are scarce in the literature. To fill this gap in knowledge, we developed a rapid and effective method to obtain and analyze IgG Fc N-glycopeptides in the plasma from 46 CRC patients and 67 healthy individuals using chitosan@poly (glycidyl methacrylate) @iminodiacetic acid (CS@PGMA@IDA) nanomaterial in combination with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). A total of 29 N-glycopeptides were detected and analyzed. Compared with healthy individuals, CRC patients had increased levels of N-acteylglucosamine, yet decreased levels of galactosylation, fucosylation and sialylation. Further, a multivariate logistic regression model was developed using the levels of IgG Fc N-glycopeptides to distinguish CRC patients from healthy individuals, and the prediction performance was good, with an average AUC of the ROC curves of 0.893. SIGNIFICANCE: In this study, we proposed a strategy for obtaining and analyzing IgG glycopeptides using CS@PGMA@IDA nanomaterial in combination with MALDI-TOF-MS. Using this strategy, IgG Fc N-glycopeptides were analyzed in the plasma of CRC patients, and our findings indicated that glycosylation levels in the IgG Fc region were closely related to CRC. By using the IgG N-glycopeptide enrichment method and screening model designed in this study, early large-scale colorectal cancer screening can be implemented easily and fast.

Correlation between radiologic features on contrast-enhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms.

Contrast-enhanced computed tomography (CT) contributes to the increasing detection of pancreatic neuroendocrine neoplasms (PNENs). Nevertheless, its value for differentiating pathological tumor grades is not well recognized. In this report, we have conducted a retrospective study on the relationship between the 2017 World Health Organization (WHO) classification and CT imaging features in 94 patients. Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2, including tumor size, shape, margin, heterogeneity, intratumoral blood vessels, vascular invasion, enhancement pattern in both contrast phases, enhancement degree in both phases, tumor-to-pancreas contrast ratio in both phases, common bile duct dilatation, lymph node metastases, and liver metastases. Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve (AUC) of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis. The portal enhancement ratio (PER) was shown the highest AUC of 0.855 in terms of quantitative features. Our data suggest that the traditional contrast-enhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

Up-regulation of lipid metabolism and glycine betaine synthesis are associated with choline-induced salt tolerance in halophytic seashore paspalum.

Choline may affect salt tolerance by regulating lipid and glycine betaine (GB) metabolism. This study was conducted to determine whether alteration of lipid profiles and GB metabolism may contribute to choline regulation and genotypic variations in salt tolerance in a halophytic grass, seashore paspalum (Paspalum vaginatum). Plants of Adalayd and Sea Isle 2000 were subjected to salt stress (200-mM NaCl) with or without foliar application of choline chloride (1 mM). Genotypic variations in salt tolerance and promotive effects of choline application on salt tolerance were associated with both the up-regulation of lipid metabolism and GB synthesis. The genotypic variations in salt tolerance associated with lipid metabolism were reflected by the differential accumulation of phosphatidylcholine and phosphatidylethanolamine between Adalayd and Sea Isle 2000. Choline-induced salt tolerance was associated with of the increase in digalactosyl diacylglycerol (DGDG) content including DGDG (36:4 and 36:6) in both cultivars of seashore paspalum and enhanced synthesis of phosphatidylinositol (34:2, 36:5, and 36:2) and phosphatidic acid (34:2, 34:1, and 36:5), as well as increases in the ratio of digalactosyl diacylglycerol: monogalactosyl diacylglycerol (DGDG:MGDG) in salt-tolerant Sea Isle 2000. Choline regulation of salt tolerance may be due to the alteration in lipid metabolism in this halophytic grass species.

Gastric mixed adenoneuroendocrine carcinoma: correlation of histologic characteristics with prognosis.

Gastric mixed adenoneuroendocrine carcinomas (MANECs) are rare, with both the exocrine and neuroendocrine components exceeding 30% volume. Several classifications for MANECs have been proposed, yet they have not been clinically evaluated. The aim of this study was to evaluate the correlation between tumor grade, histologic characteristics, and prognosis of gastric MANECs. We collected eligible 14 cases in our series and 31 cases in the literature and compared the prognostic difference among gastric MANECs with different histologic characteristics. Gastric MANECs could be divided into subgroups according to tumor grade of the neuroendocrine component and adenocarcinoma types. The high grade and large proportion of neuroendocrine component correlated with aggressive behavior and a tendency of poor clinical outcome. Gastric MANECs with a poorly differentiated adenocarcinoma showed a significant lower survival rate than did MANECs with a differentiated adenocarcinoma or mucin-producing carcinoma (P = .0008). Gastric MANECs were a heterogeneous group with different tumor grades, histologic subtypes, combination patterns, and patient outcomes. Previous classifications were evaluated. This study proves that histologic characteristics correlate with clinical outcomes. Our findings are complements to the latest prognostic classification.

Prevalence of metastasis in T1b esophageal squamous cell carcinoma: a retrospective analysis of 258 Chinese patients.

BACKGROUND: There is controversy regarding the impact of different depths of submucosal invasion on lymph node metastasis (LNM) and overall survival (OS). We evaluated the impact of depth of submucosal invasion on the presence of metastatic lymphadenopathy and survival in a Chinese population with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 258 patients who underwent esophagectomy from November 2009 to March 2014 were studied. Demographics of patients, tumor characteristics, and surgical information were retrospectively collected through medical records. Submucosal invasion was equally categorized into inner one-third (sm1), middle one-third (sm2), and deep one-third (sm3) invasion by pathologists. The patients were observed at the outpatient department in accordance with appointed time and recurrence, and deaths were recorded. The median follow-up duration was 26 months and the deadline was April 2015. Cancer characteristics and its association with LNM and OS were analyzed. RESULTS: The study included 75 (29.1%) sm1, 73 (28.3%) sm2, and 110 (42.6%) sm3 patients, and the rates of LNM were 12% (9/75), 11% (8/73), and 20.9% (23/110), respectively. sm3 might be associated with regional LNM (univariate analysis, P=0.041). Tumor volume >1.856 cm(3) (P=0.022) and lymphovascular invasion (LVI) (P=0.004) predicted LNM using multivariate analysis. No significant differences in distant metastases were observed according to the depth of invasion. Only metastatic lymph nodes predicted OS (P<0.001) rather than the depth of invasion. CONCLUSIONS: Submucosal ESCC showed a substantial rate of LNM. In T1b ESCC, after adjusting for possible covariates, depth of invasion does not predict LNM or OS.

Forkhead box A1 (FOXA1) tagging polymorphisms and esophageal cancer risk in a Chinese population: a fine-mapping study.

Esophageal cancer was the fifth most commonly diagnosed cancer and the fourth leading cause of cancer-related death in China in 2009. Esophageal squamous cell carcinoma (ESCC) accounts for more than 90% of esophageal cancers. Besides environmental risk factors, genetic factors such as single-nucleotide polymorphisms (SNPs) play an important role in ESCC carcinogenesis. We performed a hospital-based case-control study to evaluate the Forkhead-box protein A1 (FOXA1) rs12894364 C > T, rs2145146 C > A and rs7144658 T > C tag SNPs in the risk of developing ESCC. We recruited 629 ESCC cases and 686 controls. Genotypes were determined using ligation detection reaction. Logistic regression analyses revealed that the three FOXA1 SNPs were not associated with ESCC risk. However, there was significantly decreased ESCC risk associated with the FOXA1 rs12894364 C > T and rs2145146 C > A polymorphisms among older patients. There was significantly increased ESCC risk associated with the FOXA1 rs7144658 T > C polymorphism among male patients. This study demonstrates an association between FOXA1 polymorphisms and ESCC susceptibility. Additional larger studies are required to confirm our findings.