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Background: Hypertension is associated with stroke-related mortality. However, the long-term association of blood pressure (BP) and the risk of stroke-related mortality and the influence path of BP on stroke-related death remain unknown. The current study aimed to estimate the long-term causal associations between BP and stroke-related mortality and the potential mediating and moderated mediating model of the associations., Methods: This is a 45-year follow-up cohort study and a total of 1696 subjects were enrolled in 1976 and 1081 participants died by the latest follow-up in 2020. COX proportional hazard model was used to explore the associations of stroke-related death with baseline systolic blood pressure (SBP)/diastolic blood pressure (DBP) categories and BP changes from 1976 to 1994. The mediating and moderated mediating effects were performed to detect the possible influencing path from BP to stroke-related deaths. E value was calculated in the sensitivity analysis., Results: Among 1696 participants, the average age was 44.38 ± 6.10 years, and 1124 were men (66.3%). After a 45-year follow-up, a total of 201 (11.9%) stroke-related deaths occurred. After the adjustment, the COX proportional hazard model showed that among the participants with SBP ≥ 160 mmHg or DBP ≥ 100 mmHg in 1976, the risk of stroke-related death increased by 217.5% (hazard ratio [HR] = 3.175, 95% confidence interval [CI]: 2.297-4.388), and the adjusted HRs were higher in male participants. Among the participants with hypertension in 1976 and 1994, the risk of stroke-related death increased by 110.4% (HR = 2.104, 95% CI: 1.632-2.713), and the adjusted HRs of the BP changes were higher in male participants. Body mass index (BMI) significantly mediated the association of SBP and stroke-related deaths and this mediating effect was moderated by gender., Conclusions: In a 45-year follow-up, high BP and persistent hypertension are associated with stroke-related death, and these associations were even more pronounced in male participants. The paths of association are mediated by BMI and moderated by gender., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Fluralaner, a systemic pesticide, was originally registered with the US Food and Drug Administration in 2014 under the trade name Bravecto for flea treatment for pets. As a GABA antagonist, the footprint of fluralaner has expended beyond medical and veterinary pests in recent years. In this study, we examined the acute toxicity of fluralaner against three pests of Henosepilachna vigintioctopunctata, Megalurothrips usitatus, and Phyllotreta striolata in the Solanaceae, Fabaceae, and Cruciferae families, respectively, and the sublethal impact of fluralaner on Propylaea japonica, a widely distributed predatory ladybeetle. Based on LC 50 , fluralaner was effective against H. vigintioctopunctata (0.098 mg a.i. L -1 for the second instar larvae), M. usitatus (0.134 mg a.i. L -1 for adult females), and P. striolata (0.595 mg a.i. L -1 for adults). For P. japonica, however, fluralaner was substantially less effective (1.177 mg a.i. L -1 for the third instar larvae). Furthermore, the LC 10 and LC 30 of P. japonica were also consistently higher than the LC 50 of the three pests. In addition, we did not observe any significant impacts of fluralaner at LC 10 and LC 30 on the life history traits, including body weight, developmental time, pre-oviposition period, and fecundity of P. japonica. Based on our results from acute toxicities and sublethal impacts, fluralaner is effective against vegetable pests, while potentially friendly to P. japonica when employed as a biological control agent., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

RNA interference (RNAi) has emerged as a powerful tool for developing novel management strategies for controlling insect pests. The 28-spotted ladybeetle, Henosepilachna vigintioctopunctata is one of the most important pests attacking solanaceous plants in Asia. In this study, the potential of dietary RNAi to manage H. vigintioctopunctata was investigated using both in vitro synthesized and bacterially expressed double-stranded RNAs (dsRNAs) of HvvATPase A and HvvATPase E. The expression levels of HvvATPase A and HvvATPase E were higher in Malpighian tubules than in other tissue types. The silencing of HvvATPase A and HvvATPase E led to significant mortality in H. vigintioctopunctata larvae. In addition, the ingestion of HvvATPase A and HvvATPase E significantly deterred feeding behavior and subsequently arrested the development of H. vigintioctopunctata. Notably, the bacterially expressed dsRNAs consistently caused higher mortality in larvae and adults. Finally, the nontarget effects of the dsRNAs of H. vigintioctopunctata on the predatory ladybeetle Propylaea japonica were evaluated. P. japonica 1st instar larvae were administered vATPase A and vATPase E dsRNAs from H. vigintioctopunctata and P. japonica under the worst-case scenario, in which dsGFP served as negative control. There were significant effects of dsHvvATPase A on P. japonica at the transcriptional level but not at the organismal level, whereas dsHvvATPase E did not effect P. japonica at either the transcriptional or the organismal level. Collectively, the results of the study suggest that HvvATPase A and HvvATPase E can act as novel molecular targets for the control of H. vigintioctopunctata., (© 2020 Institute of Zoology, Chinese Academy of Sciences.)

Porous materials are very promising for the development of cost- and energy-efficient separation processes, such as for the purification of ethylene from ethylene/ethane mixture-an important but currently challenging industrial process. Here we report a microporous hydrogen-bonded organic framework that takes up ethylene with very good selectivity over ethane through a gating mechanism. The material consists of tetracyano-bicarbazole building blocks held together through intermolecular CN···H-C hydrogen bonding interactions, and forms as a threefold-interpenetrated framework with pores of suitable size for the selective capture of ethylene. The hydrogen-bonded organic framework exhibits a gating mechanism in which the threshold pressure required for guest uptake varies with the temperature. Ethylene/ethane separation is validated by breakthrough experiments with high purity of ethylene (99.1%) at 333 K. Hydrogen-bonded organic frameworks are usually not robust, yet this material was stable under harsh conditions, including exposure to strong acidity, basicity and a variety of highly polar solvents., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Crystalline porous materials (CPMs), exhibiting high surface areas, versatile structural topologies, and tunable functionality, have attracted much attention in the field of proton exchange membrane fuel cells (PEMFC) for their great potential in solid electrolytes. However, most hydrated CPM proton conductors suffer from the narrow working temperature and the high water/humidity dependence. Considering the practical application in different working environments, CPMs with high anhydrous conductivity from subzero to moderate temperature (>100 °C) are desirable, but it is still a huge challenge. Herein we summarized our recent research work in the anhydrous CPM proton conductors, including to rationally tune the structures of CPMs by using the strategies of pore engineering and protonic species control to achieve wide working temperature conduction, as well as to clarify the conducting mechanism. This spotlight will provide clues to flexibly design and fabricate wide-working-temperature CPM conductors with high protonic conductivity.

Objective: Epithelial-to-mesenchymal transition (EMT) is an essential biological process of cancer progression associated with increased metastatic potential and initiation. Herein, we aimed to develop and validate a robust EMT-related prognostic signature that could predict the prognosis of patients with hepatocellular carcinoma (HCC)., Methods: Messenger RNA expression matrix and clinicopathological data were retrieved from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes (DEGs) between HCC tissues and adjacent non-tumor samples. Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression analysis were performed to establish a prognosis signature. Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC), multivariate Cox regression analysis, nomogram, C-index, and decision curve analysis (DCA) were performed to investigate the prognostic performance of the signature. The prognostic performance of the new signature was further validated in an independent external cohort. A support vector machine (SVM) approach was performed to evaluate the diagnostic value of the identified genes., Results: A seven-gene signature was formulated to classify patients into high-risk and low-risk groups with discrepant overall survival (OS) in two cohorts (all P < 0.0001), and the former illustrated shorter survival time than the latter even stratified by various groups. The new signature has presented an excellent performance for predicting survival prognosis. Multivariate analysis showed that the signature was an independent risk factor for HCC. The SVM classifier based on the seven genes presented an excellent diagnostic power in differentiating early HCC and normal tissues. Gene Set Enrichment Analyses (GSEA) demonstrated multiple biological processes and pathways to provide novel insights into the development of HCC., Conclusion: We established and validated a prognostic signature based on EMT-related genes with good predictive value for HCC survival. The diagnostic performance of the signature had been demonstrated to accurately distinguish early HCC from control individuals., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

In this work, a ternary TiO 2 /Graphene oxide/Polyaniline (TiO 2 /GO/PANI) nanocomposite was synthesized by in situ oxidation and use as a filler on epoxy resin (TiO 2 /GO/PANI/EP), a bifunctional in situ protective coating has been developed and reinforced the Q235 carbon steel protection against corrosion. The structure and optical properties of the obtained composites are characterized by XRD, FTIR, and UV-vis. Compared to bare TiO 2 and bare Q235, the TiO 2 /GO/PANI/EP coating exhibited prominent photoelectrochemical properties, such as the photocurrent density increased 0.06 A/cm 2 and the corrosion potential shifted from -651 mV to -851 mV, respectively. The results show that the TiO 2 /GO/PANI nanocomposite has an extended light absorption range and the effective separation of electron-hole pairs improves the photoelectrochemical performance, and also provides cathodic protection to Q235 steel under dark conditions. The TiO 2 /GO/PANI/EP coating can isolate the Q235 steel from the external corrosive environment, and may generally be regarded a useful protective barrier coating to metallic materials. When the TiO 2 /GO/PANI composite is dispersed in the EP, the compactness of the coating is improved and the protective barrier effect is enhanced.

Soybean is one of the most commonly allergenic foods in the U.S. However, the variety of commercial soy ingredients used in the food industry makes soybean a challenging allergen to detect and quantify. The processing methods used to produce soy-derived ingredients result in protein modifications that often substantially impact detection and quantification with commonly used antibody-based methods. This study aimed to develop a mass spectrometry (MS)-based method capable of quantifying commercially processed soy ingredients in food matrices. A quantification strategy using external standards with internal calibrants was developed and evaluated, resulting in the ultimate use of a matrix-independent standard curve of non-roasted soy flour with milk proteins as carrier proteins. The method performance was evaluated by quantifying six soy-derived ingredients in incurred food matrices using three quantification strategies. Out of the twelve ingredient-matrix combinations with 10 ppm incurred total soy protein, eight had maximum recoveries between 60 and 120% using the full standard curve strategy. Other quantification strategies may be useful for internal quality control and interlaboratory calibrations. Compared with three commercial ELISA kits, the MS method showed a substantial advantage in quantifying the highly processed soy proteins in food matrices. SIGNIFICANCE: The ability to quantify undeclared soy protein in food products regardless of the soy ingredient source is essential for food allergen management, risk assessment, and regulatory enforcement. The MS-based method described here is able to reliably quantify six different soy-derived ingredients incurred in a model processed food. When compared with existing commercial ELISA methods, the MS method is much less affected by matrices and ingredient types, indicating its wider applicability to a range of soy-derived ingredients and processed products., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The aim of this study was to construct and validate a DNA repair-related gene signature for evaluating the overall survival (OS) of patients with gastric cancer (GC). Differentially expressed DNA repair genes between GC and normal gastric tissue samples obtained from the TCGA database were identified. Univariate Cox analysis was used to screen survival-related genes and multivariate Cox analysis was applied to construct a DNA repair-related gene signature. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. The prognostic model and the expression levels of signature genes were validated using an independent external validation cohort. Two genes (CHAF1A, RMI1) were identified to establish the prognostic signature and patients ware stratified into high- and low-risk groups. Patients in high-risk group presented significant shorter survival time than patients in the low-risk group in both cohorts, which were verified by the ROC curves. Multivariate analysis showed that the prognostic signature was an independent predictor for patients with GC after adjustment for other known clinical parameters. A nomogram incorporating the signature and known clinical factors yielded better performance and net benefits in calibration plot and decision curve analyses. Further, the logistic regression classifier based on the two genes presented an excellent diagnostic power in differentiating early HCC and normal tissues with AUCs higher than 0.9. Moreover, Gene Set Enrichment Analysis revealed that diverse cancer-related pathways significantly clustered in the high-risk and low-risk groups. Immune cell infiltration analysis revealed that CHAF1A and RMI1 were correlated with several types of immune cell subtypes. A prognostic signature using CHAF1A and RMI1 was developed that effectively predicted different OS rates among patients with GC. This risk model provides new clinical evidence for the diagnostic accuracy and survival prediction of GC.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus causing coronavirus disease 2019 (COVID-19), has been confirmed in cancers through binding specific mRNAs to invade human cells. Therefore, the aim of this study described here was to develop and validate novel SARS-CoV-2 proteins binding human mRNAs ( SPBRs ) signature to predict overall survival (OS) in hepatocellular carcinoma (HCC). Using multivariate Cox regression analysis, a set of SPBRs was identified to establish a multigene signature in the Cancer Genome Atlas repositories cohort. Furthermore, a nomogram was established based on the signature and clinical risk factors to improve risk stratification for individual patients. External validation was performed in the International Cancer Genome Consortium (ICGC) cohort. A six-SPBR signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all p  < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Moreover, the signature presented an excellent diagnostic power in differentiating HCC and normal tissues. Gene set enrichment analysis demonstrated that high-risk group was closely enriched in cell cycle, DNA replication, microRNAs in cancer, and cytokine-cytokine receptor interaction. The novel signature demonstrated great clinical value in predicting the OS for patients with HCC, and will provide a good reference between cancer research and SARS-CoV-2 and help individualized treatment in HCC.

Objective: The purpose of this study was to develop and validate a novel immune checkpoint-related gene signature for prediction of overall survival (OS) in hepatocellular carcinoma (HCC). Methods: mRNA expression profiles and clinical follow-up information were obtained in the International Cancer Genome Consortium database. An external dataset from The Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma database was used to validate the results. The univariate and multivariate Cox regression analyses were performed based on the differentially expressed genes. We generated a four-mRNA signature to predict patient survival. Furthermore, the reliability and validity were validated in TCGA cohort. An integrated bioinformatics approach was performed to evaluate its diagnostic and prognostic value. Results: A four-gene (epidermal growth factor, mutated in colorectal cancer, mitogen-activated protein kinase kinase 2, and NRAS proto-oncogene, GTPase) signature was built to classify patients into two risk groups using a risk score with different OS in two cohorts (all P < 0.0001). Multivariate regression analysis demonstrated the signature was an independent predictor of HCC. Furthermore, the signature presented an excellent diagnostic power in differentiating HCC and adjacent tissues. Immune cell infiltration analysis revealed that the signature was associated with a number of immune cell subtypes. Conclusion: We identified a four-immune checkpoint-related gene signature as a robust biomarker with great potential for clinical application in risk stratification and OS prediction in HCC patients and could be a potential indicator of immunotherapy in HCC. The diagnostic signature had been validated to accurately distinguish HCC from adjacent tissues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Chen and Dang.)

Objective: Flap endonuclease 1 (FEN1) overexpression has been reported to be closely associated with cancer prognosis. However, its diagnostic and prognostic significance in gastric cancer (GC) has not yet been explored., Methods: FEN1 expression, its correlation with clinical parameters, and prognostic significance were investigated by data mining of The Cancer Genome Atlas (TCGA) datasets. Patients were divided into low- and high-expression groups using the median value of FEN1 expression as the cut-off. The diagnostic value of FEN1 expression in GC tissues was determined via receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analyses were used to identify the prognostic indicators. Gene set enrichment analysis (GSEA) was used to explore FEN1-related signalling pathways in GC. Furthermore, the Human Protein Atlas (HPA) database and GSE62254 dataset were used for further external validation., Results: FEN1 was expressed at a higher level in GC tissues than in normal gastric tissues with high diagnostic accuracy (area under the ROC=0.909). Higher FEN1 expression was also validated at the protein level using the HPA database. High FEN1 expression in GC was correlated with older age (P<0.05). Patients with high FEN1 expression had a favourable prognosis compared to patients with low FEN1 expression (P=0.0048). Univariate and multivariate analyses revealed that FEN1 was an independent predictive factor associated with overall survival in both the TCGA cohort and the GSE62254 dataset (P=0.0004 and P=0.011, respectively). GSEA identified that the FEN1 expression was related to DNA replication, cell cycle, cytosolic and sensing pathways, oocyte meiosis, and the P53 signalling pathway., Conclusion: The results revealed high expression of FEN1 in GC; thus, it could be a promising early diagnostic and independent prognostic biomarker for GC., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: RNA interference (RNAi) is a potential tool for plant protection against insect pests. The great challenge for effective pest control using RNAi in the field is the development of efficient and reliable methods for the production and delivery of double-stranded RNA (dsRNA)., Results: In the present study, we investigated the potential of feeding in vitro synthesized or bacterially expressed dsRNA to populations of the 28-spotted ladybeetle Henosepilachna vigintioctopunctata as a method of biological pest control. Ingestion of in vitro synthesized dsHvRPS18 or dsHvRPL13 led to significant down-regulation of the ribosomal protein-encoding genes HvRPS18 and HvRPL13, respectively, and significantly decreased the survival of H. vigintioctopunctata. Such silencing of HvRPS18 or HvRPL13 expression appeared to be partially dose-dependent and also inhibited the growth of H. vigintioctopunctata and significantly suppressed the expression of digestive enzyme-related genes. Finally, ingestion of bacterially expressed dsHvRPS18 or dsHvRPL13 induced significant mortality in the first and third instars, and in adults., Conclusion: The effectiveness of RNAi-based gene silencing in H. vigintioctopunctata provides a powerful reverse genetic tool for the functional annotation of its genes. This study demonstrates that HvRPS18 and HvRPL13 represent candidate genes for RNAi-based biological control of H. vigintioctopunctata. © 2020 Society of Chemical Industry., (© 2020 Society of Chemical Industry.)

The chemical investigation of the fruits of a mangrove Sonneratia apetala collected from the Beibu Gulf led to the isolation of four new compounds, sonneradons A-D (1-4), as well as 18 known compounds (5-22). The structures of the new compounds were elucidated based on extensive spectroscopic analysis, and the structures of the known compounds were established by comparison of their spectroscopic data with those of related metabolites. The antiaging activities of all isolates were evaluated using the nematode Caenorhabditis elegans as a model organism. The results showed that 10 compounds could protect C. elegans by extending its lifespan. Compound 1 possessed the most potent effect in the anti-heat stress assay and significantly attenuated aging-related decreases in the pumping and bending of the nematodes in the healthspan assay. Molecular docking studies suggested that compound 1 was bound to the DNA binding domain of HSF-1 and promoted the conformation of HSF-1, thus strengthening the interaction between the HSF-1 and related DNA. GLN49, ASN-74, and LYS-80 of the binding region might be the key amino residues during the interaction., 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 © 2020 Elsevier Inc. All rights reserved.)

The development of genetic based techniques, specifically RNA interference (RNAi), has emerged as a powerful tool in novel pest management strategies for pestiferous coleoptera. The 28-spotted ladybird beetle, Henosepilachna vigintioctopunctata, is a dynamic foliar pest of solenaceous plants, primarily potato plants, and has quickly become one of the most important pests attacking many crops in Asian countries. In this study, we demonstrate the efficacy of dietary RNAi targeting vATPase B, which led to significant gene silencing. Downstream effects of vATPase B silencing appeared to be both time- and partial dose-dependent. Our results indicate that silencing of vATPase B caused a significant decrease in survival rate, as well as reduced the food stuffs consumption and inhibited the overall development of H. vigintioctopunctata. Furthermore, results demonstrate expression of insect melanism related genes, TH and DDC, was significantly up regulated under the dsvATPase B (RNAi molecule designed against vATPase B) treatment. The impact of oral dsvATPase B delivery on the survival of 1st, 3rd instars, and adults was investigated through bacterially expressed dsRNA. The effectiveness of RNAi-based gene silencing in H. vigintioctopunctata provides a powerful reverse genetic tool for the functional annotation of its genes. This study demonstrates that vATPase B may represent a candidate gene for RNAi-based control of H. vigintioctopunctata., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Although proton-conductive metal phosphonates with well-defined structure offer a favorable platform for exploring their structure-property relationship, investigating of the synergic effect of phosphonate groups and functional moieties on proton conduction is rare. In this work, we have synthesized two new copper phosphonates, [Cu(4-cppH)(4,4'-bipy)(H 2 O) 3 ] ( FJU-80 ) and [Cu(4-cppH)(4,4'-bipy)]·H 2 O·DMF ( FJU-81 ), by the method of solvent-assisted modification, giving a 1D metal coordination polymer and a 3D metal open framework, respectively. Single-crystal X-ray diffraction shows that FJU-80 is full of hydrogen-bonding sites contributed from the improved synergic effect of phosphonate groups, carboxylate groups, and coordinated water molecules, thereby facilitating continuous hydrogen-bonding networks, whereas FJU-81 only has discrete hydrogen-bonding fragments. Powder X-ray diffraction and impedance analyses confirm that FJU-80 possesses higher water stability as well as improved proton conductivity, indicating that solvent-assisted modification is effective in increasing the hydrogen-bonding sites from phosphonate groups and functional moieties and then realizing facile proton transfer.

RNA interference (RNAi) techniques have emerged as powerful tools in the development of novel management strategies for the control of insect pests, such as Henosepilachna vigintioctopunctata , which is a major solanaceous pest in Asia. Our results showed that levels of HvSnf7 expression were greater in larval midguts than in other tissues. Silencing of HvSnf7 led to greater H. vigintioctopunctata mortality rates and appeared to be time- and partially dose-dependent. Bacterially expressed dsHvSnf7 that was applied to detached plant leaves caused 98, 88, and 60% mortality in 1st and 3rd instars, and adults after 10, 12, and 14 d, respectively; when applied to living plants, bacterially expressed dsHvSnf7 led to mortality in 1st and 3rd instars, with no effect on adults. Bacterially expressed dsHvSnf7 led to improved plant protection against H. vigintioctopunctata . Ultrastructural changes caused by HvSnf7-RNAi in larval midguts showed extensive loss of cellular contents that indicate loss of membrane integrity. This study indicate that HvSnf7 potentially can be used as RNAi target gene for controlling of H. vigintioctopunctata .

Aim: To build a prognostic nomogram based on log odds of positive lymph nodes for patients with gastric carcinoma (GC) after resection, and to compare the predictive performance with the American Joint Committee on Cancer (AJCC) staging system and lymph node ratio (LNR). Methods: Multivariate analyses were performed to identify the independent variables for cancer-specific survival (CSS). A nomogram was constructed based on independent clinicopathological factors. Results: The C-indices for predicting CSS were 0.674 in development cohort and 0.647 in validation cohort, which were higher than that of the AJCC staging system and LNR. Conclusion: The nomogram was more accurate than the AJCC staging system and LNR for predicting CSS in patients undergoing resection for GC.

Chronic exposure to arsenic induces a variety of cancers, particularly in the skin. Autophagy is a highly conserved process which plays a dual role in tumorigenesis. In the present study, we found that chronic exposure to an environmentally relevant dose of arsenite induced malignant transformation of human keratinocytes (HaCaT) with dysregulated autophagy as indicated by an increased number of autophagosomes, activation of mTORC1 pathway, and elevated protein levels of p62 and LC3II. Meanwhile, arsenite-transformed cells showed lower intracellular levels of reactive oxygen species compared with control. Silencing p62 ameliorated elevation in mRNA levels of NRF2 downstream genes ( AKR1C1 and NQO1 ) and malignant phenotypes (acquired invasiveness and anchor-independent growth) induced by chronic arsenite exposure. On the other hand, silencing NRF2 abrogated the increase in mRNA and protein levels of p62 and malignant phenotypes induced by arsenite. In response to acute arsenite exposure, impaired autophagic flux with an increase in p62 protein level and interrupted autophagosome-lysosome fusion was observed. The increase in p62 protein levels in response to arsenite was not completely dependent on NRF2 activation and at least partially attributed to protein degradation. Our data indicate that accumulation of p62 by impaired autophagic flux is involved in the activation of NRF2 and contributes to skin tumorigenesis due to chronic arsenite exposure., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2019 Xiafang Wu et al.)

The gut bacteria of insects positively influence the physiology of their host, however, the dynamics of this complicated ecosystem are not fully clear. To improve our understanding, we characterized the gut prokaryotic of Henosepilachna vigintioctopunctata that fed on two host plants, Solanum melongena (referred to as QZ hereafter) and Solanum nigrum (referred to as LK hereafter), by sequencing the V3-V4 hypervariable region of the 16S rRNA gene using the Illumina MiSeq system. The results revealed that the gut bacterial composition varied between specimens that fed on different host plants. The unweighted pair group method with arithmetic mean analyses and principal coordinate analysis showed that the bacterial communities of the LK and QZ groups were distinct. Four phyla (Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria) were present in all H. vigintioctopunctata gut samples. It is noteworthy that bacteria of the phylum Cyanobacteria were only found in the LK group, with a low relative abundance. Proteobacteria and Enterobacteriaceae were the predominant phylum and family, respectively, in both the LK and QZ groups. Linear discriminant analysis effect size (LEfSe) analyses showed that the QZ group enriched the Bacilli class and Lactococcus genus; while the LK group enriched the Alphaproteobacteria class and Ochrobactrum genus. PICRUSt analysis showed that genes predicted to be involved in xenobiotic biodegradation and metabolism, metabolism of other amino acids, signaling molecules, and interaction were significantly higher in the QZ group. Genes predicted to be involved in the metabolism of cofactors and vitamins were significantly higher in the LK group. Furthermore, the complexity of the network structure and the modularity were higher in the LK group than in the QZ group. This is the first study to characterize the gut bacteria of H. vigintioctopunctat, our results demonstrate that the two host plants tested had a considerable impact on bacterial composition in the gut of H. vigintioctopunctata and that the bacterial communities were dominated by relatively few taxa., Competing Interests: The authors have declared that no competing interests exist.

Henosepilachna vigintioctopunctata (Coleoptera: Coccinellidae) is a major pest affecting Solanaceae plants in Asian countries. In this study, we sequenced the ovary and testis transcriptomes of H. vigintioctopunctata to identify gonad-related genes. Comparison of the unigene sequences in ovary and testis libraries identified 1,421 and 5,315 ovary- and testis-specific genes, respectively. Among the ovary-specific genes, we selected the RC2-like and PSHS-like genes to investigate the effects of gene silencing on the mortality, percentage infertility, pre-oviposition period, fecundity, daily number of eggs laid, and hatching rate in female adults. Although the percentage mortality and infertility of females did not differ significantly among dsRNA treatments, fecundity was significantly reduced in the dsRC2-like and dsPSHS-like treatment groups. Moreover, the pre-oviposition period was markedly prolonged in response to dsPSHS-like treatment. This is the first reported RNA sequencing of H. vigintioctopunctata . The transcriptome sequences and gene expression profiles of the ovary and testis libraries will provide useful information for the identification of gonad-related genes in H. vigintioctopunctata and facilitate further research on the reproductive biology of this species. Moreover, the gonad-specific genes identified may represent candidate target genes for inhibiting the population growth of H. vigintioctopunctata .

Reactions of an N/Al FLP-based aluminum dihydride (o-TMP-C6H4)AlH2 (1, TMP = N(CMe2CH2)2CH2) with several terminal and internal alkynes were studied. 1 reacted with HC[triple bond, length as m-dash]CR by deprotonated alumination to yield (o-TMP-C6H4)Al(C[triple bond, length as m-dash]CR)2 (R = Ph (2), 1-C4H3S (3)) and with HC[triple bond, length as m-dash]CPPh2 by deprotonated alumination followed by HC[triple bond, length as m-dash]CPPh2 C(sp)-H-activation addition to yield [o-(TMP)H-C6H4]Al(C[triple bond, length as m-dash]CPPh2)3 (4). Furthermore, 1 reacted with R1C[triple bond, length as m-dash]CR2 to produce mono-hydroalumination compounds (o-TMP-C6H4)AlH(CR1[double bond, length as m-dash]CHR2) (R1,R2 = Ph,Ph (5), Ph,Et (6) and SiHMeR',Ph (7, R' = N(SiMe2Ph)-2,6-iPr2C6H3), all as monomers, as well as {(o-TMP-C6H4)AlH[C(PPh2)[double bond, length as m-dash]CHPh]}2 (8), a dimer formed due to the intermolecular P/Al donor-acceptor interaction. Moreover, bis-hydroalumination compounds (o-TMP-C6H4)Al(CR1[double bond, length as m-dash]CHR2)2 (R1,R2 = SiHMe2,PPh2 (9) and SiHPh2,PPh2 (10)) were produced. Natural Bond Orbital (NBO) analysis was performed, which revealed the inequivalent charge distribution on the C[triple bond, length as m-dash]C carbon atoms of the alkynes that have two different substituents. The electronic matching interaction between the Al-H and C[triple bond, length as m-dash]C bonds is discussed. The hydroalumination reaction exhibits the regioselective cis-addition character.

A novel microporous metal-organic framework (FJU-44), with abundant accessible nitrogen sites on its internal surface, was constructed from the tetrapodal tetrazole ligand tetrakis(4-tetrazolylphenyl)ethylene (H 4 TTPE) and copper chloride. Notably, the CO 2 uptake capacity (83.4 cm 3 /g, at 273 K and 1 bar) in the activated FJU-44a is higher than most of tetrazolate-containing MOF materials. Particularly, FJU-44a exhibits superior adsorption selectivity of CO 2 /N 2 (278-128) and CO 2 /CH 4 (44-16), which is comparable to some well-known CO 2 capture materials. Furthermore, the fixed-bed breakthrough experiment indicates that the postcombustion flue gas flow over a packed column with FJU-44a adsorbents can be effectively separated.

The encapsulation of dyes into metal-organic frameworks (MOFs) has generated a variety of platforms for luminescence, but little attention has been paid to their application in proton conduction. Here, a cationic MOF {{[In 3 OL 1.5 (H 2 O) 3 ](NO 3 )}·(DMA) 3 ·(CH 3 CN) 6 ·(H 2 O) 30 } n (FJU-10, H 4 L = 4,4',4″,4‴-(1,4-phenylenbis(pyridine-4,2,6-triyl))-tetrabenzoic acid, DMA = N, N-dimethylacetamide) was synthesized, and the dye molecule 8-hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt (HPTS) was further added to the MOF growth solution, but during the reaction, HPTS was nitrated and nitrated HPTS was encapsulated into the FJU-10 to obtain dye@FJU-10. As a result, the intrinsic proton conductivity of dye@FJU-10 is nearly 5 times higher than that of FJU-10 at 90 °C. Dye@FJU-10 exhibits more sensitive fluorescence quenching toward aniline than FJU-10 in DMF solution (the detection limits of FJU-10 and dye@FJU-10 are as low as 0.58 and 0.62 μM, respectively). Here, it is demonstrated for the first time that intrinsic proton conductivity can be effectively improved by encapsulating a nitrated HPTS dye into an MOF.

Objective: Previous studies have reported an association between cyclooxygenase-2 (COX-2) polymorphism and gastric cancer (GC) susceptibility, but their results are controversial. This meta-analysis was intended to evaluate the relationship between the COX-2 rs20417 polymorphism and GC susceptibility in different ethnic groups., Methods: We searched PubMed, EMBASE, Web of Knowledge, and the Chinese Biomedical Database (CBM) for relevant case-control studies published up to October 6, 2018, which reported an association between the COX-2 rs20417 polymorphism and gastric cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of this association., Results: 15 papers detailing case-control studies were included in the analysis, which included a total of 2848 GC cases and 4962 healthy controls. The meta-analysis results indicated that the COX-2 rs20417 polymorphism was associated with increased GC susceptibility under allele (G vs C: OR = 1.67, 95%CI = 1.19-2.35, P = .003), heterozygous (GG vs CG: OR = 1.44, 95%CI = 1.03-2.02, P = .034), dominant (GC+CC vs GG: OR = 1.66, 95%CI = 1.18-2.34, P = .004), homozygous (GG vs CC:OR = 2.20, 95%CI = 1.07-4.54, P = .033), and recessive models (CC vs GG+CG:OR = 2.05, 95%CI = 1.09-3.85, P = .025). An analysis of ethnic subgroups revealed that the COX-2 rs20417 polymorphism was significantly associated with GC susceptibility in Asians under all 5 models (G vs C: OR = 2.22, 95%CI = 1.66-2.96, P < .001; GG vs CC: OR = 4.29, 95%CI = 1.94-9.50, P < .001; GG vs CG: OR = 1.86, 95%CI = 1.34-2.58, P < .001; CC vs GG+CG: OR = 3.73, 95%CI = 1.92-7.24, P < .001; GC+CC vs GG: OR = 2.20, 95%CI = 1.65-2.93, P < .001). Helicobacter pylori positive patients suffered a high risk of GC, compared to H pylori negative patients under the dominant model (OR = 3.09, 95%CI = 1.80-5.32, P < .001)., Conclusion: This meta-analysis of 15 case-control studies provides strong evidence that the COX-2 rs20417 polymorphism increases the risk of GC susceptibility in general populations, especially in Asians. Helicobacter pylori positive patients and those with the COX-2 rs20417 polymorphism had a higher risk of developing GC.

Soybeans are one of the major allergenic foods in many countries. Soybeans are commonly processed into different types of soy ingredients to achieve the desired properties. The processing, however, may affect the protein profiles and protein structure, thus affecting the detection of soy proteins. Mass spectrometry (MS) is a potential alternative to the traditional immunoassays for the detection of soy-derived ingredients in foods. This study aims to develop a liquid chromatography-tandem MS method that uniformly detects different types of soy-derived ingredients. Target peptides applicable to the detection of six commercial soy ingredients were identified based on the results of MS label-free quantification and a set of selection criteria. The results indicated that soy ingredient processing can result in different protein profiles. A total of six soy ingredients were then individually incurred into cookie matrices at different levels. Sample preparation methods were optimized, and a distinct improvement in peptide performance was observed after optimization. Cookies and dough incurred with different soy ingredients at 100 ppm total soy protein showed a similar level of peptide recovery (90% mean signal relative to unroasted soy flour), demonstrating the ability of the MS method to detect processed soy ingredients in a uniform manner.

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a reliable technique commonly used in molecular biology to analyze RNA expression. The selection of suitable reference genes for data normalization is a precondition for credible measurements of gene expression levels using RT-qPCR. Propylea japonica is one of the most common pests of many crop systems throughout East Asia, and has often been used in the testing of non-target impacts during environmental risk assessments of genetically engineered plants. The present study assessed the suitability of nine frequently used reference genes for comparisons of P. japonica gene expression. Expression stability was compared across developmental stages, sex, a range of tissues, and following exposure to different temperatures. Data were analyzed using RefFinder, which integrated the results obtained using NormFinder, geNorm, BestKeeper, and the ΔCt method. This led to the identification of unique sets of reference genes for each experimental condition: ribosomal protein S18 (RPS18) and elongation factor 1 α (EF1A) for developmental stage comparisons, RPS18 and EF1A for sex comparisons, EF1A and ribosomal protein L4 for tissue comparisons, and RPS18 and EF1A for analyses of temperature-mediated effects. These reference genes will help to enhance the accuracy of RT-qPCR analyses of P. japonica gene expression. This work represents an initial move towards building a standardized system for RT-qPCR analysis of P. japonica, providing a basis for the ecological risk assessment of RNAi-based insect control products., Competing Interests: The authors have declared that no competing interests exist.

Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a momentous technique for quantifying expression levels of the targeted genes across various biological processes. Selection and validation of appropriate reference genes for RT-qPCR analysis are a pivotal precondition for reliable expression measurement. Henosepilachna vigintioctopunctata is one of the most serious insect pests that attack Solanaceae plants in Asian countries. Recently, the transcriptomes of H. vigintioctopunctata were sequenced, promoting gene functional studies of this insect pest. Unfortunately, the reference genes for H. vigintioctopunctata have not been selected and validated. Here, a total of 7 commonly used reference genes, namely, Actin , GAPDH , RPL13 , RPL6 , RPL32 , RPS18 , and ATPB , were selected and assessed for suitability under four experimental conditions, namely, developmental stage, tissue, temperature, and host plant, using RefFinder , which integrates four different analytical tools ( Normfinder , geNorm , the Δ Ct method, and BestKeeper ). The results displayed that RPL13 and RPS18 were the best suitable reference genes for each experimental condition. The relative transcript levels of 2 target genes, lov and TBX1 , varied greatly according to normalization with the two most- and least-suited reference genes. Our results will be helpful for improving the accuracy of the RT-qPCR analysis for future functional investigations of target gene expression in H. vigintioctopunctata .

Although supramolecular isomerism in metal-organic frameworks (MOFs) would offer a favorable platform for in-depth exploring their structure-property relationship, the design and synthesis of the isomers are still rather a challenging aspect of crystal engineering. Here, a pair of supramolecular isomers of Co(II)-based MOFs (FJU-88 and FJU-89) can be directionally fabricated by rational tuning the additives. In spite of the fact that the isomers have the similar Co 3 secondary building units and organic linkers, they adopt distinct networks with acs and snw topologies, respectively, which derive from the conformational flexibility of the organic ligands. It is noteworthy that the porous structure of FJU-88 would be collapsed after removal of the solvent from the pores. But FJU-89a shows permanent porosity accompanied with unusual hierarchical micro- and mesopores and superior gas selective adsorption performance. In addition, FJU-89a can efficiently trap C 2 H 2 from C 2 H 2 /CO 2 and C 2 H 2 /CH 4 mixture gases through fixed-bed dynamic breakthrough experiments.

Numerous reports have been done to seek the relationship between sleep apnea hypopnea syndrome (SAHS) and the risk of atrial fibrillation (AF). However, definite conclusion has not yet been fully established. We examined whether SAHS increases AF incidence in common population and summarized all existing studies in a meta-analysis. We summarized the current studies by searching related database for potential papers of the association between SAHS and the risk of AF. Studies that reported original data or relative risks (RRs) with 95% confidence intervals (CIs) for the associations were included. Sensitivity analyses were performed by omitting each study iteratively and publication bias was detected by Begg's tests. Eight eligible studies met the inclusion criteria. Fixed effects meta-analysis showed that SAHS increased AF risk in the common population (RR = 1.70, 95% CI: 1.53-1.89, P = 0.002, I 2 = 69.2%). There was a significant association between mild SAHS and the risk of AF (RR = 1.52, 95% CI: 1.28-1.79, P = 0.01, I 2 = 78.4%), moderate SAHS (RR = 1.88, 95% CI: 1.55-2.27, P = 0.017, I 2 = 75.6%), and severe SAHS (RR = 2.16, 95% CI: 1.78-2.62, P < 0.001, I 2 = 91.0%). The results suggest that sleep apnea hypopnea syndrome could increase the risk of AF, and the higher the severity of SAHS, the higher risk of atrial fibrillation.

Background: Previous studies have reported conflicting results for the relationship between dipeptidyl peptidase-4 (DPP-4) inhibitor drugs and acute pancreatitis. The aim of this study was to investigate the association between DPP-4 inhibitors and an increased risk of acute pancreatitis using meta-analysis., Methods: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane library from inception to March 4, 2017. Original articles with data on DPP-4 inhibitors and acute pancreatitis were included. We used random-effects models or fixed-effects models to combine the relative risks (RRs), odds ratio (OR), and hazard ratio (HRs) with 95% confidence intervals (CIs) in randomized controlled studies, case-control study and cohort study, respectively., Results: Five case-control studies, 5 randomized controlled studies, and 3 cohort studies were selected of the 451 retrieved abstracts. A higher risk of acute pancreatitis was observed with the following RR/OR and 95%CI: RR 1.67 (1.08-2.59) in randomized controlled studies and OR 1.45 (1.30-1.61) in case-control studies. However, the pooled HR of the 3 cohort studies failed to confirm this association., Conclusion: There is a marginally higher risk of acute pancreatitis with DPP-4 inhibitors. However, this risk was not observed in cohort studies. Thus, further clinical trials are required to confirm this finding.

The 2-aminophenylaluminum dihydride (2-TMP-C 6 H 4 )AlH 2  (2) has been prepared and characterized for the first time. Compound 2 features an intramolecular N⋅⋅⋅Al donor-acceptor bond. 2 reacted with N-methylpyrrole and N-methylindole (both at 50 °C) by means of the elusive AlH C(sp 2 )-H dehydroalumination to aluminum heteroaryls (3 and 4). Moreover, 2 reacted with PhCCSiMe 3 (at room temperature) and Ph 2 CCNR (R=iPr or 2,6-iPr 2 C 6 H 3 , at -30 to 20 °C ) to yield aluminaindene heterocycle (8) and alumina-aza-naphthalene heterocycle (9 and 10), respectively. These reactions underwent hydroalumination followed by AlH C(sp 2 )-H dehydroalumination. The reaction mechanism has been studied by combining experiment and quantum chemical calculations, with the result that the key heteroarene or arene C(sp 2 )-H bond activation is involved under cooperative interaction by the inherent N/Al donor/acceptor pair. The reported reactions open a straightforward route to heteroaryl and unique heterocyclic aluminum compounds., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Aryl(silyl)amino group stabilized hydridosilanediols RSiH(OH)2 (R = N(SiMe2Ph)-2,6-iPr2C6H3 (), N(SiMe3)-2,6-iPr2C6H3 (), and N(SiMe2Ph)-2,4,6-Me3C6H2 ()) were prepared from the controlled hydrolysis of the related RSiHCl2 () each in the presence of aniline as the HCl acceptor. Reactions of with AlMe3, AliBu3, AlH(iBu)2, and AlH3·NMe3, respectively, yielded alumino(hydrido)siloxanes [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlMe(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAliBu(THF)]2 (), [2,6-iPr2C6H3N(SiMe2Ph)Si(H)O2]3[Al(THF)]2 (), and [2,6-iPr2C6H3N(SiMe2Ph)Si(H)OAlH(THF)]2 (). The reaction of with AlMe3 gave [2,6-iPr2C6H3N(SiMe3)Si(H)OAlMe(THF)]2 (), a compound similar to . Compounds are characterized by NMR ((1)H, (13)C, and (29)Si) and IR spectroscopy and CHN elemental analysis, of which and are further studied by X-ray crystallography. Compounds and feature cyclic structures all with the skeleton core of Si2O4Al2 while compound exhibits a bicyclic structure having a core of Si3O6Al2. Melting point measurements indicated that are thermally stable bearing the geminal SiH and SiOH groups. Compounds and are thermally stable as well with the O atom-bridged SiH and AlR (R = Me, iBu, or H) groups.

Henrich, Heine, and Norenzayan summarized cultural differences in psychology and argued that people from one particular culture are outliers: people from societies that are Western, educated, industrialized, rich, and democratic (WEIRD). This study shows that liberals think WEIRDer than conservatives. In five studies with more than 5,000 participants, we found that liberals think more analytically (an element of WEIRD thought) than moderates and conservatives. Study 3 replicates this finding in the very different political culture of China, although it held only for people in more modernized urban centers. These results suggest that liberals and conservatives in the same country think as if they were from different cultures. Studies 4 to 5 show that briefly training people to think analytically causes them to form more liberal opinions, whereas training them to think holistically causes shifts to more conservative opinions., (© 2014 by the Society for Personality and Social Psychology, Inc.)

Previous studies have suggested an association between hepatitis C virus (HCV) infection and the development of Sjögren's syndrome (SS), also known as sicca syndrome. The main objective of this study was to summarize the existing evidence and quantitatively evaluate the association between hepatitis C virus infection and SS/sicca syndrome by performing a meta-analysis of observational studies. MEDLINE and PubMed (January 1980-August 2013) were searched to identify relevant studies in English. Outcomes were calculated and are reported as odds risk (OR) and 95% CIs based on a random-effects model. Heterogeneity was assessed with I(2) statistics. Quality assessment was performed with the Newcastle-Ottawa scale. Based on meta-analysis of five cross-sectional and five cohort studies, a significant positive relationship between HCV infection and development of SS/sicca syndrome was found, the pooled random effects OR being 3.31 (95% CI, 1.46-7.48; P < 0.001). In subset analyses, the studies that used European diagnostic criteria showed a higher summary OR than did studies that adopted other diagnostic criteria. When the data were stratified by source of controls, significant associations were also observed when healthy people (OR = 9.44; 95% CI = 2.67-33.40; P = 0.204) or subjects with hepatitis B virus infection (OR = 6.57; 95% CI = 1.21-35.57; P = 0.5) were used as controls, but not when the controls were hospital-based (OR = 0.99; 95% CI = 0.61-1.61; P = 0.169). In summary, the findings suggest that HCV infection is associated with SS/sicca syndrome. The observed increased risk in studies in which European diagnostic criteria and healthy controls were used and the decreased risk in studies with hospital-based controls may be attributable to selection bias or other unknown factors., (© 2014 The Societies and Wiley Publishing Asia Pty Ltd.)

Purpose: MicroRNAs (miRNAs) play an essential role in breast malignant tumor development and progression. The development of clinically validated biomarkers for primary breast cancer (BC) has remained an insurmountable task despite other advances in the field of cancer molecular biology. The objective of this study is to investigate the differential expression of miRNAs and the potential of circulating microRNAs as novel primary breast cancer biomarkers., Methods: Our analyses were performed on 48 tissue and 100 serum samples of patients with primary BC and a set of 20 control samples of healthy women, respectively. The relative expression of ten candidate miRNAs (miR-106b, miR-125b, miR-17, miR-185, miR-21, miR-558, miR-625, miR-665, miR-92a, and miR-93) from the results of four bioinformatics approaches and literature curation was measured by real-time quantitative reverse transcription PCR (qRT-PCR)., Results: The level of miR-92a was significantly lower, while miR-21 was higher, as previous reports, in tissue and serum samples of BC than that of healthy controls (p < 0.001). Logistic regression and receiver operating characteristic curve analyses revealed the significant and independent value (p < 0.001) of the miR-92a and miR-21 expression quantification in serums. Moreover, the comparison with the clinicopathologic data of the BC patients showed that decreased levels of miR-92a and increased levels of miR-21 were associated with tumor size and a positive lymph node status (p < 0.001)., Conclusions: These findings suggest that many miRNAs expressions are altered in BC, whose expression profiling may provide a useful clue for the pathophysiological research. Circulating miR-92a has potential use as novel breast cancer biomarker, which is comparable to miR-21.

The cell surface receptor tissue factor (TF) is regarded as a common but specific target on angiogenic tumor vascular endothelial cells (VECs) and tumor cells in many types of cancer including breast cancer. The purpose of this study is to develop a selective and effective TF-targeting photodynamic therapy (PDT) by using its natural ligand factor VII (fVII)-conjugated Sn(IV) chlorin e6 (SnCe6) for the treatment of breast cancer. A cross linker EDC was used to covalently conjugate fVII protein to SnCe6, and the binding activity and phototoxicity was confirmed by ELISA and in vitro PDT. The efficacy of fVII-tPDT was assessed in vitro by crystal violet staining assay and in vivo by measuring tumor size in mice carrying murine or human breast cancer xenografts. We show that active site-mutated (K341A) fVII protein can be internalized into breast cancer cells and vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs) as angiogenic VECs. fVII-tPDT not only enhances 12-fold the in vitro efficacy but also selectively and effectively kills angiogenic HUVECs and breast cancer cells via specifically binding of fVII to TF and inducing apoptosis and necrosis as the underlying mechanism. Furthermore, fVII-tPDT can significantly inhibit the tumor growth of murine and human breast cancer without obvious toxicities in mice. We conclude that fVII-tPDT using fVII-SnCe6 conjugate can selectively and effectively kill angiogenic VECs and breast cancer cells in vitro and significantly inhibit the tumor growth of murine and human breast cancer in mice.

Background: The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia., Methods: Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested in vitro for the killing of breast cancer cells and VEGF-stimulated VEC and in vivo for inhibiting the tumour growth of breast tumours in a mouse xenograft model., Results: We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT., Conclusions: We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers and leukaemia.

Purpose: UbcH10 is the cancer-related E2 ubiquitin-conjugating enzyme, and its overexpression has been demonstrated in a variety of malignancies. The aim of this study is to investigate the association of UbcH10 gene expression with the carcinogenesis and tumor progression of colorectal cancer., Methods: The expression levels of UbcH10 in human malignant colorectal carcinoma tissues and their adjacent normal tissues were examined using real-time quantitative RT-PCR and immunohistochemical analysis. The correlations of UbcH10 expression to the clinicalpathologic characteristics of the colorectal cancer were analyzed. Cell proliferation and Matrigel invasion assays were performed in HT-29 cells transfected with UbcH10 expression plasmid pcDNA3.1-UbcH10, UbcH10 RNA interference vector pUbcH10-RNAi as well as their control vectors., Results: Our study demonstrated that the expression of UbcH10 in colorectal carcinoma tissues was significantly higher than that in non-cancerous tissues (P < 0.01), and the UbcH10 overexpression was related to the degree of tumor differentiation and lymph node metastasis of colorectal cancer patients (P < 0.05). In vitro, the overexpression of UbcH10 promoted cell proliferation and tumor invasiveness, but the downregulation of UbcH10 expression significantly reduced the growth rate and the invasiveness activity of tumor cell line., Conclusions: Our study suggests that the overexpression of UbcH10 gene plays a critical role in the carcinogenesis and tumor progression of colorectal cancer. It may be a new marker in diagnosis and prognosis of colorectal cancer, and the inhibition of UbcH10 may be a therapeutic potential for the treatment of colorectal cancer.