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C-P bond formation has typically been achieved by a single-electron transfer process. Herein, a novel class of oxime ester bifunctionalization reagents were first applied to the photocatalytic β-aminophosphorylation of modular olefins. The bifunctional reagents generate two distinct radical species (imine and phosphoryl radicals) that exhibit excellent regioselectivity. Subsequently, these radicals are attached to the olefins through a single-step EnT catalytic process, establishing a novel synthetic pathway. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility to facilitate the diversity-oriented synthesis of β-aminophosphorylated complex molecule scaffolds.

A rhodaelectro-catalyzed double dehydrogenative Heck reaction of indole-2-carboxylic acids with alkenes has been developed for the synthesis of pyrano[3,4- b ]indol-1(9 H )-ones. The weakly coordinating carboxyl group is utilized twice as a directing group to activate the C-H bonds throughout the reaction. This reaction precedes an acceptorless dehydrogenation under exogenous oxidant-free conditions in an undivided cell with a constant current.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer. In recent years, researchers have found a close relationship between microRNAs (miRNAs) and OSCC. In addition, miRNAs are highly stable in tissues and circulation, and are also considered potential biomarkers for cancer detection and prognosis. Among a variety of tools for miRNAs with low abundance, single red-emitting UCNP-based biosensors have attracted special interest due to their unique properties, including deep organizational penetration, weak radiation damage, and low autofluorescence. Additionally, the measurement of low-abundance analytes via enzyme-free signal amplification is also an effective means. Herein, by taking advantage of red-emitting UCNPs and an enzyme-toehold-mediated strand displacement cascade, a dual-signal amplification biosensor was constructed. The recycled miRNA can be regarded as a catalyst for the assembly of multiple H1/H2 duplexes, which promoted the response signal of augmented analyte expression. Moreover, the proposed biosensors improved the measurement accuracy via a dual-signal response to obviously avert false-positive signals. The proposed method was applied to measure miRNA-222 (a model analyte) in serum samples, and the results were similar to those of polymerase chain reaction (PCR), with spiked recoveries ranging from 91.2% to 101.7%. The proposed assay has the merits of high sensitivity, strong recognition, and low background, indicating broad potential for the measurement of diverse analytes in biological samples., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Objective: This study aimed to identify a quantitative index for optical coherence tomography (OCT) images to discriminate tumours from surrounding tissues., Subjects and Methods: Based on OCT measurements, mean grey values were determined from 432 locations on fifty-four human tissue specimens (eighteen cancerous, para-cancerous, and normal tissues each). These results were histologically evaluated by hematoxylin and eosin staining (H&E)., Results: The mean grey values of oral squamous cell carcinoma (OSCC) measurements were significantly different from those of the surrounding healthy tissue (p value < 0.0001), with the former being higher. The sensitivity and specificity of detecting tumourous tissue using this approach were 93 and 94%, respectively., Conclusions: OCT as a non-invasive, real-time imaging method, correlates well with H&E pathological images. It can effectively distinguish squamous cell carcinoma from normal tissues with high sensitivity and specificity and is thus expected to assist and guide tumour margin evaluation., Clinical Relevance: This discovery highlights the potential of OCT in the objective evaluation of tumour margin during surgery., (© 2024. The Author(s).)

Background: Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied., Methods: Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB., Results: UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels., Conclusions: The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function., (© 2024. The Author(s).)

Objective: Differentially expressed genes (DEGs) in lung adenocarcinoma (LUAD) tumor stem cells were screened, and the biological characteristics of NR5A2 gene were investigated., Methods: The expression and prognosis of NR5A2 in human LUAD were predicted and analyzed through bioinformatics analysis from a human cancer database. Gene expression and clinical data of LUAD tumor and normal lung tissues were obtained from The Cancer Genome Atlas (TCGA) database, and DEGs associated with lung cancer tumor stem cells (CSCs) were screened. Univariate and multivariate Cox regression models were used to screen and establish prognostic risk prediction models. The immune function of the patients was scored according to the model, and the relative immune functions of the high- and low-risk groups were compared to determine the difference in survival prognosis between the two groups. In addition, we calculated the index of stemness based on the transcriptome of the samples using one-class linear regression (OCLR)., Results: Bioinformatics analysis of a clinical cancer database showed that NR5A2 was significantly decreased in human LUAD tissues than in normal lung tissues, and the decrease in NR5A2 gene expression shortened the overall survival and progression-free survival of patients with LUAD., Conclusion: The NR5A2 gene may regulate LUAD tumor stem cells through selective splicing mutations, thereby affecting the survival and prognosis of patients with lung cancer, and the NR5A2 gene may regulate CSCs through single nucleotide polymorphism., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is sexually dimorphic, with increased incidence in females. A genome-wide association study identified a female-specific AIS susceptibility locus near the PAX1 gene. Here, we use mouse enhancer assays, three mouse enhancer knockouts, and subsequent phenotypic analyses to characterize this region. Using mouse enhancer assays, we characterize a sequence, PEC7, which overlaps the AIS-associated variant, and find it to be active in the tail tip and intervertebral disc. Removal of PEC7 or Xe1, a known sclerotome enhancer nearby, or deletion of both sequences lead to a kinky tail phenotype only in the Xe1 and combined (Xe1+PEC7) knockouts, with only the latter showing a female sex dimorphic phenotype. Extensive phenotypic characterization of these mouse lines implicates several differentially expressed genes and estrogen signaling in the sex dimorphic bias. In summary, our work functionally characterizes an AIS-associated locus and dissects the mechanism for its sexual dimorphism., Competing Interests: Declaration of interests N.A. is a co-founder and on the scientific advisory board of Regel Therapeutics. N.A. receives funding from BioMarin Pharmaceutical Incorporated., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A gentle and effective method for the photocatalytic dual functionalization of allenes with high regio- and stereoselectivity using a nonmetallic catalyst is described. Inexpensive and easily available sulfinates and TMSN 3 were employed as sulfone and azido sources, respectively. The method is characterized by satisfactory substrate compatibility and tolerance toward functional groups. The straightforward initial mechanistic experiments suggested that the reaction could follow a radical pathway. The synthesis of vinylsulfone azide derivatives presented here offers a promising scaffold for the future development of vinyl sulfone-based drugs and functional bioorthogonal reagents.

Objective: The RNA-binding protein RBM10 can regulate apoptosis during the proliferation and migration of pancreatic cancer, endometrial cancer, and osteosarcoma cells; however, the molecular mechanism underlying lung adenocarcinoma is rarely reported. Recent studies have detected multiple truncated and missense mutations in RBM10 in lung adenocarcinoma, but the role of RBM10 in lung adenocarcinoma is unclear. This study mainly explored the immune regulation mechanism of RBM10 in the development of lung adenocarcinoma and its influence on sensitivity to targeted therapy drugs., Methods: The transcriptome data of CGAP were used to analyze the RNA-seq data of lung adenocarcinoma patients from different subgroups by using the CIBERSORT algorithm to infer the relative proportion of various immune infiltrating cells, and Spearman correlation analysis was performed to determine the gene expression and immune cell content. In addition, this study utilized drug trial data from the GDSC database. The IC50 estimates for each specific targeted therapy were obtained by using a regression method, and the regression and prediction accuracy were tested via ten cross-validations with the GDSC training set. An immunohistochemical test was performed on the samples of 20 patients with lung adenocarcinoma in the subcomponent analysis of immune cells, and the protein expression of RBM10 in lung adenocarcinoma tissues was verified by cellular immunofluorescence assays. Nucleic acids were extracted at low temperatures, and qRT-PCR was used to verify the expression levels of the mRNA of RBM10 in lung adenocarcinoma tissues and normal tissues ( p < 0.05)., Results: After screening and inclusion using a machine language, the results showed that RBM10 was significantly highly expressed in the lung adenocarcinoma tissues. The related signaling pathways were mainly concentrated in ncRNA processing, rRNA metabolic processes, ribosome biogenesis, and the regulation of translation. The qRT-PCR for 20 lung adenocarcinoma tissues showed that the expression of RBM10 in these tissues was significantly different from that in normal tissues ( p = 0.0255). Immunohistochemistry analysis and cell immunofluorescence staining also confirmed that RBM10 was involved in the immune regulation of lung adenocarcinoma tissues, and the number of immune cell aggregations was significantly higher than that of the control group. RBM10 regulates B cell memory-CIBERSORT ( p = 0.042) and B cell memory-CIBERSOTRT-abs ( p = 0.027), cancer-associated fibroblast-EPIC ( p = 0.001), cancer-associated fibroblast- MCPCounter ( p = 0.0037), etc. The risk score was significantly associated with the sensitivity of patients to lapatinib ( p = 0.049), nilotinib ( p = 0.015), pazopanib ( p = 0.001), and sorafenib ( p = 0.048)., Conclusions: RBM10 can inhibit the proliferation and invasion of lung adenocarcinoma cells through negative regulation and promote the apoptosis of lung adenocarcinoma cells through immunomodulatory mechanisms. The expression level of RBM10 affects the efficacy of targeted drug therapy and the survival prognosis of lung adenocarcinoma patients, which has a certain guiding significance for the clinical treatment of these patients.

Background: COVID-19 is a global pandemic. Currently, the predominant strain is SARS-CoV-2 Omicron subvariant BA.2 in many countries. Understanding its infection characteristics can facilitate clinical management., Objectives: This study aimed to characterize the clinical, laboratory, and high-resolution computed tomography (HRCT) findings in patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2., Methods: We performed a retrospective study on patients infected with SARS-CoV-2 Omicron subvariant BA.2 between April 4th and April 17th, 2022. The clinical characteristics, laboratory features, and HRCT images were reviewed., Results: A total of 805 patients were included (411 males and 394 females, median age 33 years old). The infection was mild, moderate, severe, and asymptomatic in 490 (60.9%), 37 (4.6%), 0 (0.0%), and 278 (34.5%) patients, respectively. Notably, 186 (23.1%), 96 (11.9%), 265 (32.9%), 11 (3.4%), 7 (0.9%), and 398 (49.4%) patients had fever, cough, throat discomfort, stuffy or runny nose, fatigue, and no complaint, respectively. Furthermore, 162 (20.1%), 332 (41.2%), and 289 (35.9%) patients had decreased white blood cell counts, reduced lymphocytes, and elevated C-reactive protein levels, respectively. HRCT revealed pneumonia in 53 (6.6%) patients. The majority of the lung involvements were ground-glass opacity (50, 94.3%) mostly in the subpleural area. The grade of lung injury was mainly mild (90.6%). Short-term follow-ups showed that most patients with pneumonia recovered., Conclusion: Most patients with mild or moderate infection from SARS-CoV-2 Omicron subvariant BA.2 were adults, with fever and upper respiratory symptoms as the main clinical presentations. Lower respiratory infection was mild, with ground-glass opacity in the subpleural area as the main finding., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of this study was to find the application value of selective polyadenylation in immune cell infiltration, biological transcription function and risk assessment of survival and prognosis in lung adenocarcinoma (LUAD). The processed original mRNA expression data of LUAD were downloaded, and the expression profiles of 594 patient samples were collected. The (APA) events in TCGA-NA-SEQ data were evaluated by polyadenylation site use Index (PDUI) values, and the invasion of stromal cells and immune cells and tumor purity were calculated to group and select the differential genes. Lasso regression and stratified analysis were used to examine the role of risk scores in predicting patient outcomes. The study also used the GDSC database to predict the chemotherapeutic sensitivity of each tumor sample and used a regression method to obtain an IC50 estimate for each specific chemotherapeutic drug treatment. Then CIBERSORT algorithm was used to conduct Spearman correlation analysis, immune regulatory factor analysis and TIDE immune system function analysis for gene expression level and immune cell content. Finally, the Kaplan-Meier curve was used to analyze the correlation between stromal score and the immune score of LUAD. In this study, APA's LUAD risk score prognostic model was constructed. KM survival analysis showed that immune score affected the prognosis of LUAD patients ( P  = 0.027) but the matrix score was not statistically significant ( P  = 0.1). We extracted 108 genes with APA events from 827 different genes and based on PUDI clustering and heat map, the survival rate of patients in the four groups was significantly different ( P  = 0.05). Multiple omics studies showed that risk score was significantly positively correlated with Macrophages M0, T cells Follicular helper, B cells naive and NK cells resting. It is significantly negatively correlated with dendritic cells resting, mast cells resting, monocyte, T cells CD4 memory resting and B cells memory. We further explored the relationship between the expression of immunosuppressor genes and risk score and found that ADORA2A, BTLA, CD160, CD244, CD274, CD96, CSF1R and CTLA4 genes were highly correlated with the risk score. Selective poly adenylation plays an important role in the development and progression of LUAD, immune invasion, tumor cell invasion and metastasis and biological transcription, and affects the survival and prognosis of LUAD patients., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

[ Objective ] Using multi-omics research methods to explore cytolytic activity-related genes through the immunoregulatory factors HAVCR2 (TIM3) affecting the survival and prognosis of lung adenocarcinoma. [ Methods ] We combined Cox single factor regression and lasso regression feature selection algorithm to screen out the key genes of cytolytic activity in lung adenocarcinoma, and applied multi-omics research to explore the clinical predictive value of the model, including onset risk, independent prognosis, clinical relevance, signal transduction pathways, drug sensitivity, and the correlation of immune regulatory factors, etc. TCGA data are used as the experimental group, and GEO data is used as the external data control group to verify the stability of the model. The survival curve was generated by the Kaplan-Meier method and compared by log-rank, and the Cox proportional hazard model was used for multivariate analysis. In this study, 10 fresh tissue samples of lung adenocarcinoma were collected for cellular immunohistochemical experiments to analyze the expression of immunoregulatory factors in cancer tissues, and the key immunoregulatory factors were verified and screened out. [ Results ] A total of 450 genes related to cytolytic activity were differentially expressed, of which 273 genes were up-regulated and 177 genes were down-regulated. A total of 91 key genes related to cytolytic activity related to the prognosis of lung adenocarcinoma were screened through Cox single factor regression. The ROC curve results showed that the AUC values of 1, 3, and 5 years in the training set and test set were all greater than 0.7, indicating that the model has a valid verification. The level of risk score is significantly related to the sensitivity of patients to AKT inhibitor VIII, Lenalidomide, and Tipifarnib. In addition, our study also found that receptor and MHC genes related to immunomodulatory, and chemokines, including HAVCR2, are more highly expressed in the low-risk group. [ Conclusions ] HAVCR2 (TIM3) immunoregulatory factors affect the expression of key genes that affect cytolytic activity in lung adenocarcinoma cells, and to some extent indirectly affect the survival and prognosis of patients with lung adenocarcinoma.

For the Honghe Bridge project located in Yunnan Province, Southwest China, a steel/ultrahigh-performance concrete (UHPC) composite deck is used in the suspension bridge with a 700 m main span, and the steel stud connectors are used in the 50 mm-thick UHPC layer. To investigate the shrinkage behavior of UHPC and the relevant influence, the in situ time-dependent strain is measured continuously, and within the 20-day curing time, the material behavior is summarized based on test results. This paper proposes a prediction model for UHPC shrinkage which is refined from the widely used B3 model for normal concrete material, and the parameter values are modified and optimized by experimental comparison. Combining the numerical model and the finite element analysis model of the composite deck, the detailed mechanical state in structural parts is studied. For the practical construction, the simulation results indicate that the small thickness of UHPC above the stud and weak bond strength can influence the eventual structural performance greatly. In the discussion of stress distribution at different locations of the deck, the potential crack on the edge and the corner of the UHPC-steel interface and the mechanical damage on the stud connector around are also indicated.

The vegetable greenhouse soils in Yanglou Town, Ruzhou City, Henan Province were taken as the research object in the present study to explore the difference in soil physical and chemical properties and the total and fraction of heavy metals of different planting years. The potential ecological risks of heavy metals in greenhouse soils with different planting years were assessed by using single and comprehensive potential ecological risk index methods. The results showed that the soil pH of vegetable greenhouses increased, and fertility factors such as organic matter, available phosphorus, and alkali-hydrolyzable nitrogen accumulated to a certain extent compared to the control group, whereas catalase showed a decreasing trend. Correlation analysis showed that the planting years were significant positively correlated with pH ( P <0.05) and organic matter ( P <0.01) and significant negatively correlated with catalase ( P <0.01). The amount of heavy metals in the vegetable greenhouse soils increased with the increase in planting years, among which Cu, Zn, and Cd increased most obviously, with maximum increases of 129.14%, 204.17%, and 161.11%, respectively. The proportion of acid-soluble and reducible heavy metals in the vegetable greenhouse soils also increased gradually with the planting years, and the proportion of residual heavy metals decreased correspondingly, which resulted in the heavy metals transforming into fractions easily absorbed by plants. The results of the single potential ecological risk index showed that Cd in vegetable greenhouse soils had a strong ecological risk with the increase in planting years, whereas Cu, Pb, Zn, and Ni were in the mild risk category. The comprehensive potential ecological risk index showed that the heavy metals in the vegetable greenhouse soils of different planting years have reached a strong or very strong ecological risk.

Introduction: Vehicle weight is deterministic to the impact force in collision, and thus the injury risk of vehicle occupants. In China, involvement of heavy vehicles in overall and fatal crashes are prevalent, even though heavy vehicles only constitute a small proportion of overall registered motor vehicles. However, vehicle weight is rarely considered in the existing traffic conflict risk prediction and assessment models because of the unavailability of required data., Method: Novel risk indicators for the diagnosis of traffic conflict risk map, considering the effect of vehicle weight, are proposed, with the advantage of comprehensive traffic flow characteristics and vehicle weight data using Weigh-in-Motion (WIM) technique. Weight-incorporated risk level (WRL) and weight integrated risk level (WIRL) are established to quantify the traffic conflict risk, at an instant and over a specified time period, respectively, by extending the conventional traffic conflict risk measures including time-to-collision (TTC) and modified potential collision energy (PCE). Then, a microscopic traffic simulation model is adopted to estimate the traffic conflict risk map along a highway segment that has partial lane closure. The traffic conflict risk performances, between the risk indicators with and without considering the vehicle weight, are compared., Results: The traffic conflict risks estimated using conventional risk indicators without considering the vehicle weight are generally lower than that based on WRL and WIRL. The difference is more profound when the proportion of heavy vehicles in the traffic stream increases., Conclusions: The finding is indicative to remedial engineering measures including variable message sign, speed limit, and ramp metering that can mitigate the real-time crash risks on highways, especially in adverse environmental and weather conditions, with due consideration of vehicle composition and crash worthiness of vehicles., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 National Safety Council and Elsevier Ltd. Published by Elsevier Ltd. All rights reserved.)

Autophagy-related long-chain noncoding ribonucleic acids play a vital role in the development of esophageal adenocarcinoma. This study aimed to construct a prognostic model of autophagy-related long-chain noncoding ribonucleic acids and identify potential therapeutical targets for esophageal adenocarcinoma. We downloaded 261 long-chain noncoding RNA transcript samples and clinical data of 87 esophageal adenocarcinoma patients from the Cancer Genome Atlas and 307 autophagy-related genes from www.autophagy.com. We performed Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses and Gene Set Enrichment Analysis to determine risk characteristics and bioinformatics functions of signal transduction pathways. Univariate and multivariate Cox regression analyses were used to determine the correlation between autophagy-related long-chain noncoding ribonucleic acids and independent risk factors. The receiver operating characteristic analysis was used to evaluate the feasibility of the prognostic model. Finally, we performed survival analysis, risk analysis and independent prognostic analysis to verify the prognostic model of esophageal adenocarcinoma. We identified 22 autophagic long-chain noncoding ribonucleic acids that were highly correlated with the overall survival of esophageal adenocarcinoma patients. The areas under the receiver operating characteristic curve (0.941) and the calibration curve were significantly similar. Moreover, univariate and multivariate Cox regression analyses indicated that autophagy-related long-chain noncoding ribonucleic acids were independent predictors of esophageal adenocarcinoma. We found that autophagy-related long-chain noncoding ribonucleic acids might affect tumor development and prognosis in esophageal adenocarcinoma patients. The findings indicate that the prognostic model of esophageal adenocarcinoma has potential therapeutic applications in patients with esophageal adenocarcinoma., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Protein acetylation has emerged to play pivotal roles in alcoholic liver disease (ALD). Sirutin 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase involved in the regulation of aging, metabolism, and stress. However, the role of SIRT2 in ALD remains unclear. Here, we report that the SIRT2-mediated deacetylation-deubiquitination switch of CCAAT/enhancer-binding protein beta (C/EBPβ) prevents ALD. Our results showed that hepatic SIRT2 protein expression was negatively correlated with the severity of alcoholic liver injury in ALD patients. Liver-specific SIRT2 deficiency sensitized mice to ALD, whereas transgenic SIRT2 overexpression in hepatocytes significantly prevented ethanol-induced liver injury via normalization of hepatic steatosis, lipid peroxidation, and hepatocyte apoptosis. Mechanistically, we identified C/EBPβ as a critical substrate of SIRT2 implicated in ALD. SIRT2-mediated deacetylation at lysines 102 and 211 decreased C/EBPβ ubiquitination, resulting in enhanced protein stability and subsequently increased transcription of C/EBPβ-target gene LCN2. Importantly, hepatic deacetylated C/EBPβ and LCN2 compensation reversed SIRT2 deletion-induced ALD aggravation in mice. Furthermore, C/EBPβ protein expression was positively correlated with SIRT2 and LCN2 expression in the livers of ALD patients and was inversely correlated with ALD development. Therefore, activating SIRT2-C/EBPβ-LCN2 signaling pathway is a potential therapy for ALD., (© 2021. The Author(s).)

It is currently difficult for pathologists to diagnose pancreatic cancer (PC) using biopsy specimens because samples may have been from an incorrect site or contain an insufficient amount of tissue. Thus, there is a need to develop a platform-independent molecular classifier that accurately distinguishes benign pancreatic lesions from PC. Here, we developed a robust qualitative messenger RNA signature based on within-sample relative expression orderings (REOs) of genes to discriminate both PC tissues and cancer-adjacent normal tissues from non-PC pancreatitis and healthy pancreatic tissues. A signature comprising 12 gene pairs and 17 genes was built in the training datasets and validated in microarray and RNA-sequencing datasets from biopsy samples and surgically resected samples. Analysis of 1,007 PC tissues and 257 non-tumor samples from nine databases indicated that the geometric mean of sensitivity and specificity was 96.7%, and the area under receiver operating characteristic curve was 0.978 (95% confidence interval, 0.947-0.994). For 20 specimens obtained from endoscopic biopsy, the signature had a diagnostic accuracy of 100%. The REO-based signature described here can aid in the molecular diagnosis of PC and may facilitate objective differentiation between benign and malignant pancreatic lesions., (Copyright © 2020 Zhou, Lu, Meng, Wang, Ruan, Yang, Wang, Chen, Gao, Yan and Li.)

Main Conclusion: In Hordeum vulgare, nine differentially expressed novel miRNAs were induced by colchicine. Five novel miRNA in colchicine solution showed the opposite expression patterns as those in water. Colchicine is a commonly used agent for plant chromosome set doubling. MicroRNA-mediated responses to colchicine treatment in plants have not been characterized. Here, we characterized new microRNAs induced by colchicine treatment in Hordeum vulgare using high-throughput sequencing. Our results showed that 39 differentially expressed miRNAs were affected by water treatment, including 34 novel miRNAs and 5 known miRNAs; 42 miRNAs, including 37 novel miRNAs and 5 known miRNAs, were synergistically affected by colchicine and water, and 9 differentially expressed novel miRNAs were induced by colchicine. The novel&#95;mir69, novel&#95;mir57, novel&#95;mir75, novel&#95;mir38, and novel&#95;mir56 in colchicine treatment showed the opposite expression patterns as those in water. By analyzing these 9 differentially expressed novel miRNAs and their targets, we found that novel&#95;mir69, novel&#95;mir56 and novel&#95;mir25 co-target the genes involving the DNA repair pathway. Based on our results, microRNA-target regulation network under colchicine treatment was proposed, which involves actin, cell cycle regulation, cell wall synthesis, and the regulation of oxidative stress. Overall, the results demonstrated the critical role of microRNAs mediated responses to colchicine treatment in plants.

In this study, nitrogen transformation strains, including three ammonium transformation strains, one nitrite strain and one nitrogen fixer, were inoculated at different swine carcass composting stages to regulate the nitrogen transformation and control the nitrogen loss. The final total nitrogen content was significantly increased (p < 0.01). The bacterial communities were assessed by amplicon sequencing and association analysis. Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes were the four most dominant phyla.,Brevibacterium, Streptomyces and Ochrobactrum had a significant (p < 0.05) and positive correlation with total nitrogen and ammonium nitrogen content in both groups. The quantitative results of nitrogen transformation genes showed that ammonification, nitrification, denitrification and nitrogen fixation were simultaneously present in the composting process of swine carcasses, with the latter two accounting for a higher proportion. The ammonium transformation strains significantly (p < 0.05) strengthened nitrogen fixation and remarkably (p < 0.01) weakened nitrification and denitrification, which, however, were notably (p < 0.05) enhanced by the nitrite strain and nitrogen fixer. In this research, the inoculated strains changed the bacterial structure by regulating the abundance and activity of the highly connected taxa, which facilitated the growth of nitrogen transformation bacteria and regulated the balance/symbiosis of nitrogen transformation processes to accelerate the accumulation of nitrogen., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The mitochondrial dysfunction in the pathogenesis of myocardial damage associated with high fat diet (HFD)-induced obesity remains largely unknown. Transmembrane protein 126B (TMEM126B), as a complex I assembly factor, plays a key role in regulating mitochondrial function. In the present study, the effects of TMEM126B on mitochondrial function were investigated using genetic knockout approach in HFD-induced mouse models with obesity. We found that TMEM126B was significantly increased in HFD-treated cardiac samples. Genetic ablation of TMEM126B alleviated HFD-mediated metabolic disorder and heart injury. TEM results suggested that cardiac mitochondrial integrity was improved in TMEM126B knockout mice compared with the wild type (WT) mice after HFD challenge. Additionally, the mitochondrial dysfunction induced by HFD was alleviated in mice with TMEM126B knockout, as evidenced by the decreased protein expression levels of dynamic-related protein-1 (DRP1) and fission-1 (FIS1) and increased expression of mitofusin-1 (MFN1). The mitochondrial impairments were further confirmed in palmitic acid (PA)-incubated cardiomyocytes, as evidenced by the down-regulated membrane potential and ATP levels, and by the up-regulated mitochondrial reactive oxygen species (ROS) production and DNA damage, which were significantly reversed by TMEM126B knockdown in vitro. Finally, TMEM126B ablation suppressed mitochondrial-dependent apoptotic death in the hearts of HFD mice. Therefore, TMEM126B led to mitochondrial impairments, contributing to the pathogenesis of HFD-induced cardiac injury, and blockage of TMEM126B could inhibit mitochondrial dysfunction, paving the road to new therapeutic modalities for the prevention of obesity-associated heart injury., (Copyright © 2019. Published by Elsevier Inc.)

We present a theoretical study on the adsorption and spin transport properties of magnetic Fe@C 28 using Ab initio calculations based on spin density functional theory and non-equilibrium Green's function techniques. Fe@C 28 tends to adsorb on the bridge sites in the manner of C-C bonds, and the spin-resolved transmission spectra of Fe@C 28 molecular junctions exhibit robust transport spin polarization (TSP). Under small bias voltage, the transport properties of Fe@C 28 are mainly determined by the spin-down channel and exhibit a large spin polarization. When compressing the right electrode, the TSP is decreased, but high spin filter efficiency (SFE) is still maintained. These theoretical results indicate that Fe@C 28 with a large magnetic moment has potential applications in molecular spintronics.

Background and Objective: Inositol polyphosphate 4-phosphatase type II (INPP4B) is over-expressed in CRC tissues, and emerges as an oncogene. However, the mechanism by which INPP4B regulates CRC cell proliferation remains largely unclear. In this study, we aimed to investigate the regulatory mechanisms of INPP4B in CRC., Materials and Methods: The expression levels of mRNA were detected by qRT-PCR. The expression levels of protein were determined by Western blot. Cell Counting Kit-8 (CCK-8) assays and BrdU incorporation assays were performed to evaluate cell proliferation abilities. Bicistronic luciferase assays and the m7GTP pull down assay were performed to measure the cap-dependent translation in cells., Results: INPP4B promotes CRC cell proliferation by increasing mTORC1 activity. Furthermore, it was shown that the activation of mTORC1 signaling by INPP4B led to increased cap-dependent translation, which is essential for INPP4B-mediated CRC cell proliferation. Finally, it was demonstrated that increased AKT and serum and glucocorticoid-inducible kinase 1 activity contributed to the activation of cap-dependent translation induced by INPP4B., Conclusion: Collectively, the present study reveals INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation., Competing Interests: Disclosure The authors report no conflicts of interest in this work. SW620 and HCT116 cell lines were obtained from commercial companies.

Surface farmland soil samples were collected from 135 different sites in a 64 km 2 area around a lead and zinc smelter in Jiaozuo City, China. The concentration of the selected heavy metals (Cu, Zn, Pb, Cr, Cd, Ni, V, and Co) was analyzed and the spatial distribution of these heavy metals in the farmland was determined using the kriging interpolation technique (ArcGis 10.1). The enrichment factor, potential ecological risk model, and potential health risk model were used to assess the contamination level and potential risk of heavy metals in farmland surface soil. The results show that the average contents of Cd, Pb, Cr, and Zn in farmland soil are higher than the background content of these metals in the Henan Province and the average content of Cd is 2.8 times higher than that of class Ⅱ of the environmental quality standard for soils in China (GB 15618-1995). The heavy metal contamination in the west of the study area is higher than that in the east and the soil around the lead and zinc smelter (within 3 km) is severely contaminated with Pb and Cd, which is consistent with the location of the industries causing the pollution. The enrichment factors show that the soil is severely contaminated with Cd; partial sampling points are seriously contaminated with Pb, Cu, and Zn; the Cr and Co pollution is small; and Ni and V are almost not affected by human activities. The results of the risk assessment indicate that Cd poses serious ecological and health risks, Pb and Cu pose serious ecological risks, and Cr poses a serious cancer risk.

The preparation of folic acid-dextran-coenzyme Q 10 (FA-DEX-CoQ 10 ) nanopreparation was optimized by high-pressure homogenization to improve the dissolution and oral bioavailability of CoQ 10 . The preparation conditions of FA-DEX-CoQ 10 nanopreparation were optimized by single-factor and orthogonal experimental design. The properties of CoQ 10 raw materials, CoQ 10 physical mixtures, and FA-DEX-CoQ 10 nanopreparation were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The concentration of CoQ 10 in rat plasma was determined by high-performance liquid chromatography, and the corresponding pharmacokinetic parameters were calculated. The optimal preparation method is as follows: mass ratio of CoQ 10 /FA-DEX of 1:18, mass ratio of stabilizer/CoQ 10 of 0.4:1, 6 homogenization cycles, and homogenization pressure of 800 bar. These conditions resulted in a mean particle size of 87.6 nm. SEM showed that the particles was spherical. DSC and XRD analyses showed that the crystallinity of FA-DEX-CoQ 10 nanopreparation decreased. FA-DEX-CoQ 10 possesses long-term stability. By single-factor and orthogonal experiments, the dissolution rate, C max , and area under the curve (AUC) of the optimized FA-DEX-CoQ 10 nanopreparation were 3.95, 2.7, and 2.4 times as much as those of the raw materials. The results showed that FA-DEX-CoQ 10 nanopreparation had better oral bioavailability.

Mitochondria play an essential part in guaranteeing normal cellular physiological functions through providing ATP and participating in diverse processes and signaling pathways. Recently, more and more studies have revealed the vital roles of mitochondria in coping with stressors in the aging process, metabolic disturbances and neurological disorders. Mitochondrial stress responses, including the mitochondrial unfolded protein response (UPR mt ), antioxidant defense, mitochondrial fission, mitochondrial fusion and mitophagy, are induced to maintain cellular integrity in response to stress. The sirtuin family, a group of NAD + -dependent deacetylases, has been the focus of much attention in recent years for their multiple regulatory functions, especially in aging and metabolism. Recent reports validated the significant link between mitochondrial stress responses and the sirtuin family, which may help to elucidate the pathogenesis and therapies for diseases such as Alzheimer's disease or Parkinson's disease. This review will summarize recent related studies and illuminate the interplay between sirtuins and mitochondrial stress., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose : The aim of this study was to evaluate microstructural changes of major white matter (WM) tracts in patients with vascular cognitive impairment (VCI). Method : Diffusion tensor imaging (DTI) data were obtained from 24 subjects with subcortical ischemic vascular disease (SIVD), including 13 subjects with VCI-no dementia (VCIND) and 11 subjects with normal cognition (as a control group). A tract-based spatial statistics approach was performed to investigate WM microstructure in VCIND by integrating multiple indices including fractional anisotropy (FA) and mean diffusivity (MD), which are intra-voxel metrics, and local diffusion homogeneity (LDH), which is an inter-voxel metric. Results : The VCIND group had decreased FA and increased MD values throughout widespread WM areas predominately in the corpus callosum, bilateral internal capsule/corona radiata/posterior thalamic radiation/inferior fronto-occipital fasciculus and right inferior/superior longitudinal fasciculus. There was a slight discrepancy between the distribution of areas with decreased FA and LDH. The FA, MD and LDH values were significantly correlated with cognitive test results. According to a WM tract atlas, 10 major tracts were identified as tracts of interest in which three diffusion metrics simultaneously differed between groups, including bilateral anterior thalamic radiation, forceps minor, right corticospinal tract, bilateral inferior fronto-occipital fasciculus, left inferior and superior longitudinal fasciculus, and bilateral uncinate fasciculus. Receiver operating characteristic (ROC) analysis demonstrated the feasibility of using diffusion metrics along the forceps minor and left anterior thalamic radiation for separating two groups. Conclusion : The results suggest WM microstructural abnormalities contribute to cognitive impairments in SIVD patients. DTI parameters may be potential biomarkers for detecting VCIND from SIVD.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease which leads to elevated pulmonary arterial pressure and right heart failure. 3,7-Bis(2-hydroxyethyl)icaritin (ICT), an icariin derivatives, was reported to have potent inhibitory activity on phosphodiesterase type 5 (PDE5) which plays a crucial role in the pathogenesis of PAH. The present study was designed to investigate the effects of ICT on monocrotaline (MCT)-induced PAH rat model and reveal the underlying mechanism. MCT-induced PAH rat models were established with intragastric administration of ICT (10, 20, 40 mg/kg/d), Icariin (ICA) (40 mg/kg/d) and Sildenafil (25 mg/kg/d). The mean pulmonary arterial pressure (mPAP) and right ventricle hypertrophy index (RVHI) were measured. Pulmonary artery remodeling was assessed by H&E staining. Blood and lung tissue were collected to evaluate the level of endothelin 1 (ET-1), nitric oxide (NO), and cyclic guanosine monophosphate (cGMP). The expressions endothelial nitric oxide synthase (eNOS) and PDE5A in lung tissues were determined by Western blot analysis. The results showed that ICT reduced RVHI and mPAP, and reversed lung vascular remodeling in rats with MCT-induced PAH. ICT also reversed MCT-induced ET-1 elevation, NO and cGMP reduction in serum or lung tissue. Moreover, ICT administration significantly induced eNOS activation and PDE5A inhibition. ICT with lower dose had better effects than ICA. In summary, ICT is more effective in preventing MCT-induced PAH in rats via NO/cGMP activation compared with ICA. These findings demonstrate a novel mechanism of the action of ICT that may have value in prevention of PAH., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Renal renin-angiotensin system (RAS) plays a pivotal role in the development of diabetic nephropathy (DN). Angiotensin II (Ang II) type 1 receptor (AT 1 R) blockade elevates (pro)renin, which may bind to (pro)renin receptor (PRR) and exert receptor-mediated, angiotensin-independent profibrotic effects. We therefore investigated whether PRR activation leads to the limited anti-fibrotic effects of AT 1 R blockade on DN, and whether PRR inhibition might ameliorate progression of DN. Methods: To address the issue, the expression of RAS components was tested in different stages of streptozotocin (STZ)-induced diabetic rats (6, 12, and 24 weeks) and 6-week AT 1 R blockade (losartan) treated diabetic rats. Using the blocker for PRR, the handle region peptide (HRP) of prorenin, the effects of PRR on high glucose or Ang II-induced proliferative and profibrotic actions were evaluated by measurement of cell proliferation, matrix metalloproteinase-2 (MMP-2) activity, activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and transforming growth factor-β1 (TGF-β1) expression in rat mesangial cells (MCs). Results: PRR was downregulated in the kidneys of different stages of diabetic rats (6, 12, and 24 weeks). Moreover, 6-week losartan treatment further suppressed PRR expression via upregulating AT 2 R, and ameliorated diabetic renal injury. HRP inhibited high glucose and Ang II-induced proliferative and profibrotic effects in MCs through suppressing TGF-β1 expression and activating MMP-2. Meanwhile, HRP enhanced losartan's anti-fibrotic effects through further inhibiting phosphorylation of ERK1/2 and TGF-β1 expression. Moreover, the inhibitive effect of HRP on Ang II-induced TGF-β1 expression depended on the regulation of PRR expression by AT 2 R. Conclusions: Our findings suggest that inhibition of PRR contributes to renoprotection against diabetic nephropathy by AT 1 R blockade.

The present study aims to evaluate the diagnostic value of four-dimensional CT angiography (4D-CTA) in the diagnosis of arterial erectile dysfunction (ED) using 320-detector row dynamic volume CT. Arterial ED patients attributed to arterial insufficiency were enrolled. To induce penile erection, an intracavernous injection (ICI) of corpus cavernosum with a vasoactive drug was administered. Patients were assigned into the erection hardness score (EHS) 1/2 group or EHS 3/4 group. Color duplex Doppler ultrasound (CDDU) was used to analyze blood flow spectrum. Each patient was examined using 4D-CTA. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of 4D-CTA in arterial ED. According to Irwin Goldstein, the EHS 3/4 group ( n =38) had a shorter course of ED and low proportion with history of hypertension, hyperlipidemia, and diabetes than the EHS 1/2 group ( n =35). The peak systolic velocity (PSV), end diastolic velocity (EDV), and resistant index (RI) in the EHS 3/4 group were lower than those of the EHS 1/2 group. 4D-CTA showed there were a total of 35 cases in the EHS 1/2 group (two cases missed) and 38 cases in the EHS 3/4 group (seven cases misdiagnosed). Using 4D-CTA to diagnose arterial ED, the area under the ROC curve yielded a value of 0.879, with a specificity of 93.9% and a sensitivity of 82.5%. These findings indicated that 4D-CTA using 320-detector row dynamic volume CT is a promising and reliable utility in diagnosing arterial ED., (© 2017 The Author(s).)

To provide scientific basis for reasonable application of nitrogen and create varieties with high N use-efficiency, an experiment was carried out to study the effects of nitrogen fertilizer application rate on grain yield, N use rate and quality of different rice varieties. Four different genotypic rice varieties, Nipponbare, N70, N178 and OM052 were used as tested material and three levels of nitrogen application rate (0, 120, 270 kg·hm -2 ) were conducted. Urea as nitrogen source was applied as basal (70%) and panicle (30%) fertilizer. The results showed that nitrogen fertilizer could raise yield mainly because of the increased effective panicles and filled grains per panicle. When the N application rate was 120 and 270 kg·hm -2 , OM052 had the largest grain yield among four varieties, being 41.1% and 76.8% higher, respectively compared with control. Difference in grain yield among four varieties was due to the difference of nitrogen use efficiency. Under 120 and 270 kg·hm -2 nitrogen levels, Nipponbare had the lowest grain yield and N agronomic efficiency (NAE, 40.90 g·g -1 and 18.56 g·g -1 ), which was a variety with low N use-efficiency. On the contrary, OM052 had the highest grain yield and NAE (145.9 g·g -1 and 81.24 g·g -1 ), was a variety with high N use-efficiency. N fertilizer application increased the amylose content and protein content, lengthened gel consistency, reduced chalky kernel, chalkiness, and alkali digestion value. With the increase of N fertilizer application, hot paste viscosity, peak viscosity, consistence viscosity and breakdown viscosity were decreased gradually, and setback viscosity was increased. Correlation analysis showed that the yield and yield components had more significant correlations with appearance quality, cooking and eating quality under low N level. This study confirmed that OM052 was a double high variety with extremely high N agronomic efficiency and yield. Reasonable application of nitrogen fertilizer could significantly increase effective panicles and filled grains per panicle, improve rice quality, and ensure high yield and superior quality simultaneously.

Aim: To establish a severe acute cholangitis (SAC) model in mice., Methods: Cholecystic catheterization was performed under the condition of bile duct ligation (BDL). Trans-cholecystic injection of lipopolysaccharide (LPS) was defined as the SAC animal model. Sham operation group, intraperitoneal injection of LPS without BDL group, intraperitoneal injection of LPS with BDL group and trans-cholecystic injection of normal saline with BDL group were defined as control groups. The survival rates and tissue injuries in liver, lungs and kidney were evaluated., Results: Mice in the SAC group showed a time-dependent mortality and much more severe tissue injuries in liver, lungs and kidney, compared with other groups. However, relieving biliary obstruction could effectively reduce mortality and attenuate liver injury in the SAC mouse model., Conclusion: Trans-cholecystic injection of LPS under the condition of biliary obstruction could establish a repeatable and reversible mouse model of SAC., Competing Interests: Conflict-of-interest statement: The authors declare that there are no other conflicts of interest.

In this study, the effect of seasonal variations on Crataegus pinnatifida, changes in antioxidant activity and active components in C. pinnatifida leaves, roots, twigs, and fruits from May to October were investigated. Through correlation analysis of climatic factors and 7 phenolic compounds yield, the phenolic compounds content was positively correlated with temperatures and daytime. The correlation coefficient of temperatures and daytime were 0.912 and 0.829, respectively. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging and reducing power tests were employed to evaluate the antioxidant activity of the C. pinnatifida. C. pinnatifida leaves exhibited significant advantages in terms of higher phenolic contents and excellent antioxidant activities. Principal component analysis (PCA) revealed that 2 main PC characterize the C. pinnatifida phenolic composition (82.1% of all variance). C. pinnatifida leaves in September possessed remarkable antioxidant activity. The results elucidate that C. pinnatifida leaves, as renewable parts, are suitable for application as antioxidant ingredients., (© 2016 Institute of Food Technologists®)

Background and Aim of the Study: The prosthesis of choice for a tricuspid valve replacement is still unkown. This meta-analysis was undertaken to review the results of mechanical and bioprosthetic valves in the tricuspid position., Methods: We identified all relevant studies published in the past 20 years (from January 1, 1995 to December 31, 2014) through the Embase, Current Contents, and PubMed databases. The hazard ratio and its 95% confidence limits were utilized to evaluate time-to-event related effects of surgical procedures. The Q-statistic, Index of Inconsistency test, funnel plots, and Egger's test were used to assess the degree of heterogeneity and publication bias. Random effects models were used, and study quality was also assessed., Results: In our meta-analysis, 22 studies published from 1995 to 2014 were reviewed and 2630 patients and 14,694 follow-up years were analyzed. No statistically significant difference was identified between mechanical and biological valves in terms of survival, reoperation, and prosthetic valve failure. The respective pooled hazard ratio estimates were 0.95 (0.79 to 1.16, p = 0.62, I(2)  = 29%), 1.20 (0.84 to 1.71, p = 0.33, I(2)  = 0%), and 0.35 (0.06 to 2.01, p = 0.24, I(2)  = 0%). A higher risk of thrombosis was found in mechanical tricuspid valve prostheses (3.86, 1.38 to 10.82, p = 0.01, I(2)  = 0%)., Conclusions: No statistically significant difference was identified between mechanical and biological valves in terms of survival, reoperation, or prosthetic valve failure, but mechanical tricuspid valve prostheses had a higher risk of thrombosis. doi: 10.1111/jocs.12730 (J Card Surg 2016;31:294-302)., (© 2016 Wiley Periodicals, Inc.)

Cases of gastric fistula secondary to drainage tube penetration have rarely been reported. The current study presents a case of gastric penetration caused by misplacement of a drainage tube after a splenectomy. The patient was admitted to the Department of Hepatobiliary Surgery, (Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, Zhejiang, China) for blunt abdominal trauma due to injuries sustained in an automobile accident. A ruptured spleen was found and successfully removed surgically. On post-operative day 7, the patient complained of slight discomfort and tenderness in the left upper quadrant of the abdomen. In addition, 500 ml of bile-colored fluid with small food particles was noted in the drainage tube. Barium X-ray revealed a gastric fistula in the upper gastrointestinal tract. Gastroscopy indicated infiltration of the drainage tube into the gastric cavity. No significant peritoneal effusion was observed, as revealed by abdominal ultrasound examination. These results confirmed the diagnosis of a gastric fistula secondary to perforation by the drainage tube. Following conservative treatment with antibiotics and total parenteral nutrition, the general condition of the patient improved significantly. The drainage tube was withdrawn progressively, as the amount of fluid being discharged was decreasing. Gastroenterography confirmed perforation closure and the tube was finally removed on post-operative day 44.

Purpose: The purpose of this study was to evaluate the anticancer, apoptotic and antioxidant properties of Bupleurum chinense (B.C) root extract against human epithelial ovarian cancer cells (HO-8910) in vitro., Methods: MTT assay was used to evaluate the cell viability of HO-8910 cells after treatment with different B.C extract doses. Apoptotic and morphological effects induced by the extract were demonstrated by inverted phase contrast microscopy and fluorescence microscopy. The percentage of apoptotic cells was quantified by Annexin V/PI double staining assay. Flow cytometry using rhodamine-123 dye was used to measure disruption of mitochondrial membrane potential (Δψm). Gel electrophoresis was used to study the effects of the extract on DNA fragmentation. The antioxidant activity of the extract using 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging assays was also evaluated., Results: The results showed that B.C extract could induce potent and dose-dependent cytotoxic effects on the HO-8910 cells as demonstrated by MTT assay. The extract also induced cell shrinkage, chromatin condensation and membrane blebbing which are the hallmark of apoptosis. The average proportion of Annexin V-staining positive cells (total apoptotic cells) significantly increased from 9.4% in control cells to 18.5, 28.2 and 50.5% in 20, 80 and 120 μg/ml B.C extract-treated cells respectively. Different doses of the extract (20, 80 and 120 μg/ml) after 48 hrs exposure led to a substantial increase in DNA fragmentation.The number of cells with disrupted Δψm increased from 6.6% in untreated (control cells) to 14.2, 42.1 and 73.4% in 20, 80 and 120 μg/ml in extract-treated cells, respectively, Conclusion: The anticancer effects of Bupleurum chinense extract were mediated through the induction of apoptosis, DNA fragmentation and disruption of mitochondrial membrane potential.

Fifty-two dust samples were collected from four parks [Longting Park (P(L)), Tieta Park (P(T)), Qingmingshanghe Park (P(Q)), Xiangguosi Park (P(X))] located in Kaifeng City, China. Concentrations of Hg and As in dusts were measured by atomic fluorescence spectrometry (AFS), while Cr, Cu, Zn, Pb, Ni and Cd were analyzed by inductively coupled plasma mass-spectrometry (ICP-MS). The heavy metal pollution of dust was assessed using Geo-accumulation index (Igeo) and pollution load index (PLI). The health risk due to exposure to heavy metals in dust was assessed using the model recommended by USEPA. The non-carcinogen (HI) and carcinogen health risks (TCR) were also calculated to evaluate the potential risks to adults. The results showed that the average contents of Hg, Cu, Zn, Cd and Pb were much higher than those in control samples and the background values of fluvo-aquic soil in China. The samples were seriously polluted by Hg and Pb, besides, there was.moderate pollution, slight pollution of Cu and Zn, and no pollution of As, Cr and Ni. The PLI from the 4 Parks indicated that there was serious heavy metals pollution of dust in P(X), moderate pollution in P%, and slight pollution in P(T) and P(Q). The average HI of heavy metals in the four Parks was lower than one. The average HI decreased in the order of P(L) > P(X), > P(T) > P(Q), while the average TCR decreased in the order of P(L) > P(Q) > P(x) > P(T). The contribution rate of HQ(As) to HI was about 43.51% , and that of CR(As) to TCR was about 70.11%.

Recent studies indicate that absence of the consideration of risk attitudes of decisionmakers in the risk matrix establishment process has become a major limitation. In order to evaluate risk in a more comprehensive manner, an approach to establish risk matrices that integrates risk attitudes based on utility theory is proposed. There are three main steps within this approach: (1) describing risk attitudes of decisionmakers by utility functions, (2) bridging the gap between utility functions and the risk matrix by utility indifference curves, and (3) discretizing utility indifference curves. A complete risk matrix establishment process based on practical investigations is introduced. This process utilizes decisionmakers' answers to questionnaires to formulate required boundary values for risk matrix establishment and utility functions that effectively quantify their respective risk attitudes., (© 2015 Society for Risk Analysis.)

Purpose: The gut is in direct contact with BDE-99 (2,2',4,4',5-pentabromodiphenyl ether), one of the most abundant PBDE congeners in the environment and in human tissues. The objective of the present study was to investigate the effects of BDE-99 on colorectal cancer (CRC) cells., Methods: The effects of BDE-99 on cell proliferation were measured by CCK-8 assay in the CRC cell line HCT-116. Wound healing and transwell migration/invasion assays were used to test the migration and invasion of CRC cells. Factors related to epithelial-to-mesenchymal transition (EMT) were measured by real-time PCR and Western blot analysis for mRNA and protein levels, respectively., Results: BDE-99 was found to increase migration and invasion and trigger EMT in HCT-116 cells; EMT was characterized by cells acquiring mesenchymal spindle-like morphology and by increased expression of N-cadherin with a concomitant decrease in E-cadherin. BDE-99 treatment also increased the protein and mRNA levels of the transcription factor Snail, but not Slug, Twist, and ZEB1. Knockdown of Snail by siRNA significantly attenuated BDE-99-induced EMT in HCT-116 cells, suggesting that Snail plays a crucial role in BDE-99-induced EMT. The PI3K/Akt inhibitor LY294002 completely blocked BDE-99-induced Snail and invasion of HCT-116 cells., Conclusions: Our results revealed that BDE-99 can trigger the EMT of colon cancer cells via the PI3K/AKT/Snail signaling pathway. This study provides new insight into the tumorigenesis and metastasis of CRC stimulated by BDE-99 and possibly other PBDE congeners.

The present study was conducted to investigate the antinociceptive action of relationship between Herba Epimedium (HE) and 5-HT1A receptor, between Herba Epimedium (HE) and 5-HT2A receptor. We used the hot-plate method and the writhing assay in mice by the intracerebroventricular (i.c.v.) injection and observed the analgesic effect of HE. Furthermore, through the i.c.v. injection, 5-HT1A receptor partial agonist Buspirone, antagonist Propranolol, the adrenaline β 1-receptor selective blocking agent Metoprolol, and 5-HT2A receptor agonist hydrochloride DOI and antagonist Ketanserin were used, and, 5 min later, HE was used to investigate the impacts of drugs on the analgesic effect in the same way. Results showed that HE had fast and significant antinociception in nervous system, and the effects can persist for a long time. Buspirone and Hydrochloride DOI can remarkably increase the antinociception of HE in nervous system. Ketanserin leads to a significant decrease in its antinociception in nervous system; Metoprolol also has antinociceptive action in nervous system, but it can inhibit the antinociceptive effect of Herba Epimediumin peripheral region. These results suggest that HE has significant antinociception effect and its mechanism is related with 5-HT1A receptor, 5-HT2A receptor, and adrenaline β 1-receptor.

Percutaneous coronary intervention (PCI) is widely used in clinical treatment of coronary artery disease. However, the effects of PCI on preventing restenosis after revascularization and improving the quality of life were not satisfying. Huxin Formula is formulated by modifying an experienced Chinese medicine formula and has been widely used in clinical practice due to its marked effects on coronary heart disease. A multicentre double-blind randomized controlled clinical trial was designed to evaluate the effects and safety of Huxin Formula in patients undergoing PCI. Our results showed that there was no significant difference between the two groups in main outcomes. For patients with ejection fraction (EF) >50%, score of the quality of life scale was higher in treatment group compared with control group. For patients with unstable angina, score of the quality of life scale in 360 days was significantly higher in treatment group compared with control group (P < 0.05). No obvious adverse reaction was found in the use of Huxin Formula. In conclusion, Huxin Formula, believed to be a safe treatment for patients after PCI, has benefits in improving the quality of life in patients with unstable angina though it failed to show superiority in primary and secondary outcomes.

Background: Coronary artery bypass grafting (CABG) is widely used in the treatment of coronary artery disease. A multicenter, double-blind, randomized, controlled clinical trial was designed to evaluate the efficacy and safety of Huxin Formula post CABG., Patients and Methods: 270 inpatients with coronary heart disease participated in this study. CABG patients in the control group were treated with placebo, while patients in the experimental group were treated with Huxin Formula 1 week after the surgery. All patients were treated for 6 months and followed up for another 6 months. The main outcomes (death, nonfatal myocardial infarction, repeat revascularization, and readmission) were assessed 360 days after treatment, and secondary outcomes (frequency and scores of angina pectoris, etc.) were assessed 0, 90, 180, 270, and 360 days after treatment., Results: Our results showed no significant difference between the 2 groups for the primary endpoints. In patients with cardiac function class II (New York Heart Association), the score of angina pectoris was significantly lower (3.88 ± 3.86 vs. 5.45 ± 3.59) and the frequency of angina pectoris attacks was less (0.96 ± 1.01 vs. 1.36 ± 0.94) after 90 days of treatment with Huxin Formula compared to placebo (p < 0.05). In patients with 3 coronary vessel lesions, the cardiac function class (1.14 ± 0.35 vs. 1.05 ± 0.21) after 360 days was significantly higher in the control group compared to the treatment group (p < 0.05). There were no obvious adverse reactions., Conclusion: Huxin Formula may improve cardiac function of patients with 3 coronary vessel lesions and relieve symptoms of patients with cardiac function class II but failed to show superiority in primary outcomes., (© 2015 S. Karger GmbH, Freiburg.)

Objective: To observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice., Methods: Thirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method., Results: As compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups., Conclusion: HXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Background: The role of somatostatin analogues in advanced hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to examine the effect of octreotide on the survival of patients with advanced HCC., Material/methods: Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science and PubMed (updated to Dec 2010) and manual bibliographical searches were conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing octreotide versus placebo or no treatment was performed., Results: Eleven RCTs including 802 patients were assessed and 9 were included in the meta-analysis. Meta-analysis showed that the 6-mo and 12-mo survival rates in the octreotide group were significantly higher than those of the control group (6-mo: RR 1.41, 95%CI 1.12-1.77, P=0.003; 12-mo: RR 2.66, 95%CI 1.30-5.44, P=0.008). When including the studies using no treatment as control, with high quality, being performed in China, including >50 patients and with follow-up >2 years, the sensitivity analyses tended to confirm the primary meta-analysis. Whereas, when including the studies using placebo as control or being performed in western countries, the difference was not significant., Conclusions: This meta-analysis demonstrates that octreotide could improve the survival of patients with advanced HCC, but possibly not in western countries. The role of detecting SSTR expression in the administration of octreotide in advanced HCC needs further investigation.

Background: It is a surgical dilemma when patients present with both severe heart disease and neoplasms. The best surgical treatment remains controversial. This study aimed to analyze the early and long-term results of simultaneous surgical treatment of severe heart disease and neoplasms., Methods: We reviewed the clinical records of 15 patients who underwent simultaneous neoplastic resection and cardiac surgery between September 2006 and January 2011. There were 5 male and 10 female patients. The mean age was (59.2 ± 12.5) years and the mean left ventricular ejection fraction was (57.4 ± 11.0)%. All patients were followed up completely for a period of 12 to 51 months (mean, (33.1 ± 11.2) months)., Results: Fifteen patients underwent simultaneous cardiac surgery and neoplastic resection. Cardiac procedures consisted of off pump coronary artery bypass grafting (n = 7), aortic valve replacement (n = 3), mitral valve replacement (n = 3), mitral valve replacement with coronary artery bypass grafting (n = 1) and left atrial myxoma resection (n = 1). Neoplastic resection consisted of lung cancer resection (n = 5), colonic cancer resection (n = 3), gallbladder resection (n = 1), colonic cancer resection with gallbladder resection (n = 1), hysterectomy (n = 2), hysterectomy with bilateral salpingo-oophorectomy (n = 2) and left ovariectomy (n = 1). Pathological examination confirmed malignant disease in 10 patients and benign disease in 5 patients. There were no perioperative myocardial infarctions, stroke, pericardial tamponade, renal failure or hospital deaths. The most frequent complications were atrial fibrillation (33.3%), pneumonia (26.7%), low cardiac output syndrome (6.7%) and delayed healing of surgical wounds (6.7%). There was 1 late death 42 months after surgery for recurrent malignant disease. At 1 and 3 years, survival rates were 100% (Kaplan-Meier method)., Conclusions: Simultaneous cardiac surgery and neoplastic resection was not associated with increased early or late morbidity or mortality. Cardiopulmonary bypass does not appear to adversely affect survival in patients with malignant disease. The long-term survival was determined by tumor stage.