Search

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 μM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC. [Display omitted] • An integrated electrochemical POCT platform based on AuNFs/PNA modified carbon-fiber microelectrode (CFME). • Ultrasensitive circRNA detection biosensor was firstly created towards hepatocellular carcinoma. • The biosensor had great specificity and good stability. • The biosensor was verified in human serum samples and had potential utility in clinical POCT applications. [ABSTRACT FROM AUTHOR]

Most of pyruvoyl-dependent proteins observed in prokaryotes and eukaryotes are critical regulatory enzymes, which are primary targets of inhibitors for anti-cancer and anti-parasitic therapy. These proteins undergo an autocatalytic, intramolecular self-cleavage reaction in which a covalently bound pyruvoyl group is generated on a conserved serine residue. Traditional detections of the modified serine sites are performed by experimental approaches, which are often labor-intensive and time-consuming. In this study, we initiated in an attempt for the computational predictions of such serine sites with Feature Selection based on a Random Forest. Since only a small number of experimentally verified pyruvoyl-modified proteins are collected in the protein database at its current version, we only used a small dataset in this study. After removing proteins with sequence identities >60%, a non-redundant dataset was generated and was used, which contained only 46 proteins, with one pyruvoyl serine site for each protein. Several types of features were considered in our method including PSSM conservation scores, disorders, secondary structures, solvent accessibilities, amino acid factors and amino acid occurrence frequencies. As a result, a pretty good performance was achieved in our dataset. The best 100.00% accuracy and 1.0000 MCC value were obtained from the training dataset, and 93.75% accuracy and 0.8441 MCC value from the testing dataset. The optimal feature set contained 9 features. Analysis of the optimal feature set indicated the important roles of some specific features in determining the pyruvoyl-group-serine sites, which were consistent with several results of earlier experimental studies. These selected features may shed some light on the in-depth understanding of the mechanism of the post-translational self-maturation process, providing guidelines for experimental validation. Future work should be made as more pyruvoyl-modified proteins are found and the method should be evaluated on larger datasets. At last, the predicting software can be downloaded from http://www.nkbiox.com/sub/pyrupred/index.html. [ABSTRACT FROM AUTHOR]

Acquired immune deficiency syndrome (AIDS) is a severe infectious disease that causes a large number of deaths every year. Traditional anti-AIDS drugs directly targeting the HIV-1 encoded enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) usually suffer from drug resistance after a period of treatment and serious side effects. In recent years, the emergence of numerous useful information of protein-protein interactions (PPI) in the HIV life cycle and related inhibitors makes PPI a new way for antiviral drug intervention. In this study, we identified 26 core human proteins involved in PPI between HIV-1 and host, that have great potential for HIV therapy. In addition, 280 chemicals that interact with three HIV drugs targeting human proteins can also interact with these 26 core proteins. All these indicate that our method as presented in this paper is quite promising. The method may become a useful tool, or at least plays a complementary role to the existing method, for identifying novel anti-HIV drugs. [ABSTRACT FROM AUTHOR]

Colorectal cancer can be grouped into Dukes A, B, C, and D stages based on its developments. Generally speaking, more advanced patients have poorer prognosis. To integrate progression stage prediction systems with recurrence prediction systems, we proposed an ensemble prognostic model for colorectal cancer. In this model, each patient was assigned a most possible stage and a most possible recurrence status. If a patient was predicted to be recurrence patient in advanced stage, he would be classified into high risk group. The ensemble model considered both progression stages and recurrence status. High risk patients and low risk patients predicted by the ensemble model had a significant different disease free survival (log-rank test p-value, 0.0016) and disease specific survival (log-rank test p-value, 0.0041). The ensemble model can better distinguish the high risk and low risk patients than the stage prediction model and the recurrence prediction model alone. This method could be applied to the studies of other diseases and it could significantly improve the prediction performance by ensembling heterogeneous information. [ABSTRACT FROM AUTHOR]

Abstract: Ubiquitin C-terminal hydrolase 37 (UCH37) plays a crucial role in numerous biological processes and is also involved in oncogenesis. In this study, clinicopathologic data showed that UCH37 was over-expressed in hepatocellular carcinoma (HCC) cancerous tissues and was a significant predictor for time to recurrence (TTR). In vitro, we discovered that UCH37 could promote cell migration and invasion. Subsequently, we utilized Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) to identify differentially expressed proteins in UCH37 over-expressing cells compared with the control cells, and found that PRP19, an essential RNA splicing factor, was up-regulated. The relationship between UCH37, PRP19 and the capability of cell migration and invasion was further confirmed. Collectively, this study demonstrated that UCH37 could promote cell migration and invasion in HCC cell lines through interacting and deubiquitinating PRP19, and suggested that UCH37 could be a novel predictor for HCC recurrence after curative resection. [Copyright &y& Elsevier]

Abstract: The orientation and bonding of adsorbed 9,10-phenanthrenequinone (PQ) on onion-like carbon (OLC) were determined by combining spectroscopy and density functional theory (DFT) calculations. Electrochemical measurements demonstrated relatively strong bonding of PQ to the OLC as indicated by persistent and reversible features in the cyclic voltammetry. Spectra of bulk solid and adsorbed PQ were obtained by inelastic neutron scattering (INS) and Raman spectroscopy, and the bands were compared with vibrational energies calculated from DFT. At energy losses (frequencies) above 400cm−1, no band shifts in INS or Raman spectra were observed between bulk solid and adsorbed PQ. However, adsorption of PQ resulted in shifts in the lowest frequency modes (<400cm−1), compared to crystalline PQ, which could only be identified by INS. DFT calculations also provided adsorption energies and from these and comparison of computed and experimental spectra it is determined that the molecule adsorbs parallel to the onion-like carbon surface through π–π stacking interaction. [Copyright &y& Elsevier]

Purpose: To develop PEGylated multi-walled carbon nanotubes as a sustained release drug delivery system. Methods: Oxaliplatin was incorporated into inner cavity of PEGylated multi-walled carbon nanotubes (MWCNT-PEG) using nano-extraction. Oxaliplatin release rates from MWCNT-PEG-Oxaliplatin were investigated using dialysis tubing. Cytotoxicity of oxaliplatin, MWCNT-Oxaliplatin and MWCNT-PEG-Oxaliplatin were evaluated in HT29 cell by MTT assay, Pt-DNA adducts formation, γ-H2AX formation and cell apoptosis assay. Results: Loading of oxaliplatin into MWCNT-PEG was ~43.6%. Sustained release occurred to MWCNT-PEG-Oxaliplatin, with only 34% of oxaliplatin released into medium within 6 h. In MTT assay, MWCNT-PEG-Oxaliplatin showed slightly decreased cytotoxic effect when cell viability was assessed at 12 and 24 h. A drastic increase of cytotoxicity was found when cell viability was assessed at 48 and 96 h. Pt-DNA adducts formation, γ-H2AX formation and cell apoptosis assay results showed the same trend as the MTT assay, suggesting sustained-release for MWCNT-Oxaliplatin and MWCNT-PEG-Oxaliplatin formulations. Conclusions: PEGylated multi-walled carbon nanotubes can be used as sustained release drug delivery system, thus remarkably improving cytotoxicity of oxaliplatin on HT-29 cells. [ABSTRACT FROM AUTHOR]

Toxicity is a major contributor to high attrition rates of new chemical entities in drug discoveries. In this study, an order-classifier was built to predict a series of toxic effects based on data concerning chemical-chemical interactions under the assumption that interactive compounds are more likely to share similar toxicity profiles. According to their interaction confidence scores, the order from the most likely toxicity to the least was obtained for each compound. Ten test groups, each of them containing one training dataset and one test dataset, were constructed from a benchmark dataset consisting of 17,233 compounds. By a Jackknife test on each of these test groups, the 1st order prediction accuracies of the training dataset and the test dataset were all approximately 79.50%, substantially higher than the rate of 25.43% achieved by random guesses. Encouraged by the promising results, we expect that our method will become a useful tool in screening out drugs with high toxicity. [ABSTRACT FROM AUTHOR]

Background: Food-borne helminthiases (FBHs) have become increasingly important due to frequent occurrence and worldwide distribution. There is increasing demand for developing more sensitive, high-throughput techniques for the simultaneous detection of multiple parasitic diseases due to limitations in differential clinical diagnosis of FBHs with similar symptoms. These infections are difficult to diagnose correctly by conventional diagnostic approaches including serological approaches. Methodology/Principal Findings: In this study, antigens obtained from 5 parasite species, namely Cysticercus cellulosae, Angiostrongylus cantonensis, Paragonimus westermani, Trichinella spiralis and Spirometra sp., were semi-purified after immunoblotting. Sera from 365 human cases of helminthiasis and 80 healthy individuals were assayed with semi-purified antigens by both a protein microarray and the enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity and simplicity of each test for the end-user were evaluated. The specificity of the tests ranged from 97.0% (95% confidence interval (CI): 95.3–98.7%) to 100.0% (95% CI: 100.0%) in the protein microarray and from 97.7% (95% CI: 96.2–99.2%) to 100.0% (95% CI: 100.0%) in ELISA. The sensitivity varied from 85.7% (95% CI: 75.1–96.3%) to 92.1% (95% CI: 83.5–100.0%) in the protein microarray, while the corresponding values for ELISA were 82.0% (95% CI: 71.4–92.6%) to 92.1% (95% CI: 83.5–100.0%). Furthermore, the Youden index spanned from 0.83 to 0.92 in the protein microarray and from 0.80 to 0.92 in ELISA. For each parasite, the Youden index from the protein microarray was often slightly higher than the one from ELISA even though the same antigen was used. Conclusions/Significance: The protein microarray platform is a convenient, versatile, high-throughput method that can easily be adapted to massive FBH screening. Author Summary: Food-borne helminthiases (FBHs) have caused significant problems in public health and also posed socio-economic concerns. Common FBHs, such as cysticercosis, trichinellosis, paragonimiasis, sparganosis and angiostrongyliasis, have a worldwide distribution with high morbidity and even death. The objective of the present study was to develop and test a rapid assay suitable for large-scale screening for FBHs that would also allow differential diagnosis between the various parasite species. We tested archived, well-characterized serum specimens and prioritized tests for future evaluation in rapid and simultaneous screening of five different FBHs, i.e. cysticercosis, trichinellosis, paragonimiasis, sparganosis and angiostrongyliasis. This was done with a multiplex protein microarray assay equipped with semi-purified antigens capable of detecting disease-specific antibodies. Results showed that the protein microarray developed displayed a good specificity, ranging from 97.0% to 100.0%, and a sensitivity, ranging from 85.7% to 92.1%, with a Youden index variation from 0.83 to 0.92. It was concluded that the protein microarray provides a sensitive, high-throughput technique for the simultaneous detection of multiple FBHs overcoming the limitations of conventional diagnostics. [ABSTRACT FROM AUTHOR]

Background: Food-borne helminthiases (FBHs) have become increasingly important due to frequent occurrence and worldwide distribution. There is increasing demand for developing more sensitive, high-throughput techniques for the simultaneous detection of multiple parasitic diseases due to limitations in differential clinical diagnosis of FBHs with similar symptoms. These infections are difficult to diagnose correctly by conventional diagnostic approaches including serological approaches. Methodology/Principal Findings: In this study, antigens obtained from 5 parasite species, namely Cysticercus cellulosae, Angiostrongylus cantonensis, Paragonimus westermani, Trichinella spiralis and Spirometra sp., were semi-purified after immunoblotting. Sera from 365 human cases of helminthiasis and 80 healthy individuals were assayed with semi-purified antigens by both a protein microarray and the enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity and simplicity of each test for the end-user were evaluated. The specificity of the tests ranged from 97.0% (95% confidence interval (CI): 95.3–98.7%) to 100.0% (95% CI: 100.0%) in the protein microarray and from 97.7% (95% CI: 96.2–99.2%) to 100.0% (95% CI: 100.0%) in ELISA. The sensitivity varied from 85.7% (95% CI: 75.1–96.3%) to 92.1% (95% CI: 83.5–100.0%) in the protein microarray, while the corresponding values for ELISA were 82.0% (95% CI: 71.4–92.6%) to 92.1% (95% CI: 83.5–100.0%). Furthermore, the Youden index spanned from 0.83 to 0.92 in the protein microarray and from 0.80 to 0.92 in ELISA. For each parasite, the Youden index from the protein microarray was often slightly higher than the one from ELISA even though the same antigen was used. Conclusions/Significance: The protein microarray platform is a convenient, versatile, high-throughput method that can easily be adapted to massive FBH screening. [ABSTRACT FROM AUTHOR]

Background and objective: No randomized trial has been reported comparing different chemotherapy regimens on disseminated nasopharyngeal carcinoma (NPC). This study aims to compare five cisplatin-based regimens including cisplatin + 5-fluororacil (PF), paclitaxel + cisplatin (TP), gemcitabine + cisplain (GP), paclitaxel + cisplatin + 5-fluororacil (TPF), and bleomycin + cisplatin + 5-fluororacil (BPF) regimen most frequently used as the first-line protocols for metastatic NPC retrospectively. Methods: Eight hundred and twenty-two patients with metastatic NPC were divided into five groups according to the regimen they received. Then, their response rate, toxicity, and long-term survival outcome as well as the prognostic factors were analyzed. Results: The higher response rates in GP and TPF regimens comparing to PF regimen were achieved ( Χ = 4.57, P = 0.033; Χ = 7.04, P = 0.008), as well as in TPF regimen comparing to TP regimen ( Χ = 5.579, P = 0.018). The occurrence rate of the major III-IV grade toxicity was significantly different between the five groups. However, no statistically significant difference was observed in progression-free survival (PFS; P = 0.247) and overall survival ( P = 0.127) among the five groups. Cox multivariate analysis identified the following independent prognostic factors: liver metastases, plasma Epstein Barr Virus (EBV)-DNA level, cycles of chemotherapy, and second-line chemotherapy. Conclusions: PF, TP, and GP are all effective regimens as the first-line chemotherapy for metastatic NPC, which can be well tolerated. Over four cycles of chemotherapy are recommended under no contraindication. Patients should transfer to the second-line regimen after the treatment failure of the first-line chemotherapy. [ABSTRACT FROM AUTHOR]

Summary: The aim of the present study was to evaluate the correlation between excision repair cross-complementation group 1 (ERCC1) protein with the clinical outcome of nasopharyngeal carcinoma (NPC) patients treated with cisplatin-based induction chemotherapy. One hundred one Stage III–IVB nonkeratinizing NPC patients who were treated with cisplatin (DDP)+fluorouracil (5-Fu) induction chemotherapy were recruited. Pre-treatment tumor biopsy specimens were analyzed for ERCC1 by immunohistochemistry. The relationship of ERCC1 expression and chemotherapy response and survival of these NPC patients was analyzed. The objective response to induction chemotherapy of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 88.2% vs. 72% (P =0.041). The 5-year distant failure-free survival (D-FFS) of NPC patients with low ERCC1 expression compared with high ERCC1 expression was 73.5% vs. 51.3% (P =0.037). ERCC1 expression was a significant prognostic factor for overall survival and D-FFS using Cox regression analysis. High tumor ERCC1 expression predicts low chemotherapy response and poor survival mainly caused by more metastasis in locoregionally advanced NPC treated with cisplatin-based induction chemotherapy. [Copyright &y& Elsevier]

Abstract: This paper presents a new method for identifying retinoblastoma related genes by integrating gene expression profile and shortest path in a functional linkage graph. With the existing protein–protein interaction data from STRING, a weighted functional linkage graph is constructed. 119 consistently differentially expressed genes between retinoblastoma and normal retina were obtained from the overlap of two gene expression studies of retinoblastoma. Then the shortest paths between each pair of these 119 genes were determined with Dijkstra''s algorithm. Finally, all the genes present on the shortest paths were extracted and ranked according to their betweenness and the 119 shortest genes with a betweenness greater than 100 and with a p-value less than 0.05 were selected for further analysis. We also identified 53 retinoblastoma related miRNAs from published miRNA array data and most of the 238 (119 consistently differentially expressed genes and 119 shortest path genes) retinoblastoma genes were shown to be target genes of these 53 miRNAs. Interestingly, the genes we identified from both the gene expression profiles and the functional protein association network included more cancer genes than did the genes identified from the gene expression profiles alone. In addition, these genes also had greater functional similarity to the reported cancer genes than did the genes identified from the gene expression profiles alone. This study shows promising results and proves the efficiency of the proposed methods. [Copyright &y& Elsevier]

Abstract: Longevity is one of the most basic and one of the most essential properties of all living organisms. Identification of genes that regulate longevity would increase understanding of the mechanisms of aging, so as to help facilitate anti-aging intervention and extend the life span. In this study, based on the network features and the biochemical/physicochemical features of the deletion network and deletion genes, as well as their functional features, a two-layer model was developed for predicting the deletion effects on yeast longevity. The first stage of our prediction approach was to identify whether the deletion of one gene would change the life span of yeast; if it did, the second stage of our procedure would automatically proceed to predict whether the deletion of one gene would increase or decrease the life span. It was observed by analyzing the predicted results that the functional features (such as mitochondrial function and chromatin silencing), the network features (such as the edge density and edge weight density of the deletion network), and the local centrality of deletion gene, would have important impact for predicting the deletion effects on longevity. It is anticipated that our model may become a useful tool for studying longevity from the angle of genes and networks. Moreover, it has not escaped our notice that, after some modification, the current model can also be used to study many other phenotype prediction problems from the angle of systems biology. [Copyright &y& Elsevier]

Abstract: S-nitrosylation (SNO) is one of the most important and universal post-translational modifications (PTMs) which regulates various cellular functions and signaling events. Identification of the exact S-nitrosylation sites in proteins may facilitate the understanding of the molecular mechanisms and biological function of S-nitrosylation. Unfortunately, traditional experimental approaches used for detecting S-nitrosylation sites are often laborious and time-consuming. However, computational methods could overcome this demerit. In this work, we developed a novel predictor based on nearest neighbor algorithm (NNA) with the maximum relevance minimum redundancy (mRMR) method followed by incremental feature selection (IFS). The features of physicochemical/biochemical properties, sequence conservation, residual disorder, amino acid occurrence frequency, second structure and the solvent accessibility were utilized to represent the peptides concerned. Feature analysis showed that the features except residual disorder affected identification of the S-nitrosylation sites. It was also shown via the site-specific feature analysis that the features of sites away from the central cysteine might contribute to the S-nitrosylation site determination through a subtle manner. It is anticipated that our prediction method may become a useful tool for identifying the protein S-nitrosylation sites and that the features analysis described in this paper may provide useful insights for in-depth investigation into the mechanism of S-nitrosylation. [Copyright &y& Elsevier]

Abstract: Background: Whether acupuncture is effective for patients with functional constipation is still unclear. Therefore, we report the protocol of a randomized controlled trial of using acupuncture to treat functional constipation. Design: A randomized, controlled, four-arm design, large-scale trial is currently undergoing in China. Seven hundred participants are randomly assigned to three acupuncture treatment groups and Mosapride Citrate control group in a 1:1:1:1 ratio. Participants in acupuncture groups receive 16 sessions of acupuncture treatment, and are followed up for a period of 9 weeks after randomization. The acupuncture groups are: (1) Back-Shu and Front-Mu acupoints of Large Intestine meridians (Shu-Mu points group); (2) He-Sea and Lower He-Sea acupoints of Large Intestine meridians (He points group); (3) Combining used Back-Shu, Front-Mu, He-Sea, and Lower He-Sea acupoints of Large Intestine meridians (Shu-Mu-He points group). The control group is Mosapride Citrate group. The primary outcome is frequency of defecation per week at the fourth week after randomization. The secondary outcomes include Bristol stool scale, the extent of difficulty during defecating, MOS 36-item Short Form health survey (SF-36),Self-Rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). The first two of second outcomes are measured 1 week before randomization and 2, 4, and 8 weeks after randomization. Other second outcomes are measured 1 week before randomization and 2 and 4 weeks after randomization, but SF-36 is measured at randomization and 4 weeks after randomization. Discussion: The result of this trial (which will be available in 2012) will confirm whether acupuncture is effective to treat functional constipation and whether traditional acupuncture theories play an important role in it.Trials registration: Clinical Trials.gov NCT01411501 [ABSTRACT FROM AUTHOR]

AbstractAging is characterized by the interlocking decay of biological functions over time. Microarrays have been successful in elucidating some of the genome-wide changes that occur with age. Using the AGEMAP dataset that catalogs changes in gene expression as a function of age in 16 tissues in mice, we identified tissue-specific aging genes. Coordinated aging processes across different tissues then were clarified in crosstissue coexpression networks on both the gene and pathway levels. Our findings provide more concrete information about coordinated aging across different tissues. By bridging gene-level and tissue-level research, this study could help identify targets for attenuation of critical aging-related genes, pathways, or networks for antiaging intervention. [ABSTRACT FROM AUTHOR]

Abstract: Usually the functioning of a transcription factor to regulate a target gene requires a modifying enzyme. The triplet of transcription factor, mediating enzyme and target gene, MFG triplet for short, is like a switchboard that transmits signals from signaling network to gene regulatory network. Using PTM-Switchboard database, we systematically studied the MFG triplets in yeast and constructed a predictor to identify MFG triplets based on functional profiles of each element in the triplet. The sensitivity (Sn) and specificity (Sp) of Nearest Neighbor Algorithm (NNA) were 75.106% and 99.585%, respectively. Our method had higher sensitivity than Bayesian network (NaiveBayes), decision tree (J48), Random Forest (RandomForest) and k-nearest neighbor (KNN, K=3). The established predictor may be used to identify MFG triplet, which can link up cellular signaling transduction with transcriptional regulation, two major subjects in biological research. [Copyright &y& Elsevier]

Summary: Autophagy is an important intracellular catabolic mechanism that mediates the degradation of cytoplasmic proteins and organelles. We report a potent small molecule inhibitor of autophagy named “spautin-1” for specific and potent autophagy inhibitor-1. Spautin-1 promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin-specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Beclin1 is a tumor suppressor and frequently monoallelically lost in human cancers. Interestingly, Beclin1 also controls the protein stabilities of USP10 and USP13 by regulating their deubiquitinating activities. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. Our study provides a molecular mechanism involving protein deubiquitination that connects two important tumor suppressors, p53 and Beclin1, and a potent small molecule inhibitor of autophagy as a possible lead compound for developing anticancer drugs. [ABSTRACT FROM AUTHOR]

Abstract: Angiostrongylus cantonensis causes eosinophilic meningitis and eosinophilic pleocytosis in humans and is of significant socio-economic importance globally. microRNAs (miRNAs) are endogenous small non-coding RNAs that play crucial roles in gene expression regulation, cellular function and defense, homeostasis and pathogenesis. They have been identified in a diverse range of organisms. The objective of this study was to determine and characterize miRNAs of female and male adults of A. cantonensis by Solexa deep sequencing. A total of 8861,260 and 10,957,957 high quality reads with 20 and 23 conserved miRNAs were obtained in females and males, respectively. No new miRNA sequence was found. Nucleotide bias analysis showed that uracil was the prominent nucleotide, particularly at positions of 1, 10, 14, 17 and 22, approximately at the beginning, middle and the end of the conserved miRNAs. To our knowledge, this is the first report of miRNA profiles in A. cantonensis, which may represent a new platform for studying regulation of genes and their networks in A. cantonensis. [Copyright &y& Elsevier]

Abstract: Palmitoylation is a universal and important lipid modification, involving a series of basic cellular processes, such as membrane trafficking, protein stability and protein aggregation. With the avalanche of new protein sequences generated in the post genomic era, it is highly desirable to develop computational methods for rapidly and effectively identifying the potential palmitoylation sites of uncharacterized proteins so as to timely provide useful information for revealing the mechanism of protein palmitoylation. By using the Incremental Feature Selection approach based on amino acid factors, conservation, disorder feature, and specific features of palmitoylation site, a new predictor named IFS-Palm was developed in this regard. The overall success rate thus achieved by jackknife test on a newly constructed benchmark dataset was 90.65%. It was shown via an in-depth analysis that palmitoylation was intimately correlated with the feature of the upstream residue directly adjacent to cysteine site as well as the conservation of amino acid cysteine. Meanwhile, the protein disorder region might also play an import role in the post-translational modification. These findings may provide useful insights for revealing the mechanisms of palmitoylation. [Copyright &y& Elsevier]

OBJECTIVE To investigate the role of preoperative magnetic resonance tomographic angiography (MRTA) in predicting the clinical outcomes of trigeminal neuralgia (TN) patients following microvascular decompression (MVD). METHODS Preoperative MRTA imaging was performed on 167 consecutive patients with TN. The characteristics of offending vessels were determined by MRTA prior to MVD. The relationship of neurovascular contact was classified into 3 types: positive, negative, and contralateral positive, which were compared with the surgical findings and clinical outcomes. RESULTS MRTA showed obvious neurovascular compression in accordance with surgical findings in 144 patients. Among the remaining 23 patients with negative finding on preoperative MRTA images, neurovascular compression (vein alone or in combination with artery) were found in 16, no definite vascular compression in 7. The sensitivity of MRTA on the symptomatic side was therefore 90%, the specificity was 100% in our series. A correlation was found between clinical outcomes and preoperative findings on MRTA. In 144 MRTA-positive patients, 136 achieved 'excellent' or 'good' outcomes after MVD and were significantly better than the MRTA-negative group ( P < .01). The outcomes of patients with a single artery compression were significantly better than those with venous compression, vein in combination with artery compression, or without obvious neurovascular contact ( P < .01). Seven of 23 MRTA-negative patients obtained poor outcomes after operation, venous compression were identified intraoperatively in 4 of them, no definite offending vessel was found in 3 patients. CONCLUSIONS This study suggests that the curative rate of TN following MVD is higher in the MRTA-positive group. Venous compression and no neurovascular contact that were negative on MRTA image are poor prognostic factors for surgical outcome of TN. Thus, preoperative MRTA serves as a useful tool in patient selection and outcome prediction. [ABSTRACT FROM AUTHOR]

Abstract: A growing number of researchers have recognized the importance of using lipopolysaccharide (LPS) as target for the prevention and treatment of sepsis. However, no drugs targeting LPS have been applied clinically. In this study, LPS-inhibiting aptamers were screened by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and their therapeutic effects for experimental sepsis were observed. After 12 rounds of screening, 46 sequences were obtained. Primary structure analysis indicated that they had identical sequences, partly conserved sequences, or non-conserved sequences. Secondary structure analysis showed these sequences usually contained hairpin or stem–loop structures. Aptamer 19 significantly decreased NF-κB activation of monocytes challenged by LPS and reduced the IL-1 and TNF-α concentration in the media of LPS-challenged monocytes. Furthermore, aptamer 19 significantly increased the survival rate of mice with endotoxemia. The results suggest that a novel LPS antagonizing aptamer was obtained by SELEX, which successfully treated experimental sepsis. [Copyright &y& Elsevier]

Abstract: GalNAc-transferase can catalyze the biosynthesis of O-linked oligosaccharides. The specificity of GalNAc-transferase is composed of nine amino acid residues denoted by R4, R3, R2, R1, R0, R1′, R2′, R3′, R4′. To predict whether the reducing monosaccharide will be covalently linked to the central residue R0(Ser or Thr), a new method based on feature selection has been proposed in our work. 277 nonapeptides from reference [Chou KC. A sequence-coupled vector-projection model for predicting the specificity of GalNAc-transferase. Protein Sci 1995;4:1365–83] are chosen for training set. Each nonapeptide is represented by hundreds of amino acid properties collected by Amino Acid Index database (http://www.genome.jp/aaindex) and transformed into a numeric vector with 4554 features. The Maximum Relevance Minimum Redundancy (mRMR) method combining with Incremental Feature Selection (IFS) and Feature Forward Selection (FFS) are then applied for feature selection. Nearest Neighbor Algorithm (NNA) is used to build prediction models. The optimal model contains 54 features and its correct rate tested by Jackknife cross-validation test reaches 91.34%. Final feature analysis indicates that amino acid residues at position R3′ play the most important role in the recognition of GalNAc-transferase specificity, which were confirmed by the experiments [Elhammer AP, Poorman RA, Brown E, Maggiora LL, Hoogerheide JG, Kezdy FJ. The specificity of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase as inferred from a database of in vivo substrates and from the in vitro glycosylation of proteins and peptides. J Biol Chem 1993;268:10029–38; O’Connell BC, Hagen FK, Tabak LA. The influence of flanking sequence on the O-glycosylation of threonine in vitro. J Biol Chem 1992;267:25010–8; Yoshida A, Suzuki M, Ikenaga H, Takeuchi M. Discovery of the shortest sequence motif for high level mucin-type O-glycosylation. J Biol Chem 1997;272:16884–8]. Our method can be used as a tool for predicting O-glycosylation sites and for investigating the GalNAc-transferase specificity, which is useful for designing competitive inhibitors of GalNAc-transferase. The predicting software is available upon the request. [Copyright &y& Elsevier]

Identifying whether and when the southern continental margin of the South China Sea (SCS) was part of the South China Block (SCB) is important for Mesozoic–Cenozoic paleogeographic reconstructions of Southeast Asia. In this paper, we present geochronological and geochemical data for dacites from Well NK-1 in the Nansha Block (Dangerous Grounds) of the southern SCS margin to investigate their petrogenesis and tectonic affinity. Zircon U Pb and 40Ar/39Ar datings show that these dacites formed during the Late Triassic (218–217 Ma). The dacites have high total alkali (K 2 O + Na 2 O = 7.39–8.42 wt%) and relatively low CaO contents (1.87–3.38 wt%), and show geochemical affinities with A-type granites, with high Zr saturation temperatures (806–855 °C), FeOTot/MgO ratios (5.22–7.48), Zr + Nb + Ce + Y contents (530–680 ppm) and 10,000 × Ga/Al values (2.40–2.94), and relatively low A/CNK values (0.86–1.04). The primitive magma for the dacites was likely generated by partial melting of ancient crustal materials. Late Triassic dacites in the Nansha Block and Triassic A-type granites in the SCB formed in an extensional setting at the continental margin of the SCB. This setting was probably related to the Paleo-Pacific plate subduction that restarted prior to the Early Triassic. Therefore, the southern SCS margin was part of the SCB continental margin during the early Mesozoic, which provides more detailed insights into the paleogeography of SE Asia since the Mesozoic. • Triassic dacites were drilled from Well NK-1 in Nansha Block, South China Sea (SCS). • These dacites formed in an extensional setting due to Paleo-Pacific plate subduction. • The southern SCS margin was attached to the South China Block (SCB) in Early Mesozoic. • Most blocks in the southern SCS margin were affiliated with the SCB in Mesozoic. • Palawan Block was separated from the SCB and drifted southeastward in Late Cretaceous. [ABSTRACT FROM AUTHOR]

The possibility of using EPR spectroscopy to monitor the current concentration of polyaniline and control the kinetics of aniline polymerization is shown. Kinetic measurements were carried out for various temperatures, initial concentrations of reagents. Autocatalysis was detected in all cases. It was shown that the order of polyaniline-catalyzed oxidation of aniline changes from the first to the second as a result of a decrease in the monomer concentration. A new approach to deriving an equation for the rate of oxidative polymerization of aniline and its derivatives is proposed taking into account the physical adsorption and chemisorption of the monomer, and the reaction mechanism is considered. [Display omitted] • Derived an equation for the rate of polymerization of aniline and its derivatives. • EPR method allows you to monitor the current concentration of polymerization products. • Chemisorption of aniline on polyaniline limits the rate of the catalytic stage. • The order of the catalytic stage depends on the concentration of the monomer. • Methods for calculating the kinetic parameters of aniline polymerization are proposed. [ABSTRACT FROM AUTHOR]

Abstract: Lipopolysaccharide (LPS) is a major constituent of the outer membrane of Gram-negative bacteria. Binding of LPS to the CD14+ murine macrophage cell line RAW264.7 results in pro-inflammatory cytokine secretion. In extreme cases, it leads to septic shock in vivo. Therefore, the pursuit for molecules with antiendotoxin properties is urgent. In this study, we investigated the efficacy of antibacterial peptide CM4 in binding Escherichia coli LPS in vitro. CM4 avidly bound to E. coli LPS, as proven by the limulus amoebocyte lysate assay. Furthermore, the killing activity of CM4 against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide''s affinity for endotoxin. Flow cytometric analysis revealed that CM4 inhibited the binding of FITC-conjugated LPS to RAW264.7 cells. Likewise, the inhibition of peptide to LPS-dependent cytokine induction was analyzed. CM4 suppressed LPS-induced TNF-α and IL-6 mRNA expression and blocked release of TNF-α and NO following LPS challenge in RAW264.7 cells. Together these observations indicate that antibacterial peptide CM4 probably exerts protective actions against endotoxin shock by blocking the binding of LPS to CD14+ cells. [Copyright &y& Elsevier]

Non-small cell lung cancer is a major lethal subtype of epithelial lung cancer, with high morbidity and mortality. The single-cell sequencing technique plays a key role in exploring the pathogenesis of non-small cell lung cancer. We proposed a computational method for distinguishing cell subtypes from the different pathological regions of non-small cell lung cancer on the basis of transcriptomic profiles, including a group of qualitative classification criteria (biomarkers) and various rules. The random forest classifier reached a Matthew's correlation coefficient (MCC) of 0.922 by using 720 features, and the decision tree reached an MCC of 0.786 by using 1880 features. The obtained biomarkers and rules were analyzed in the end of this study. [ABSTRACT FROM AUTHOR]

Abstract: A new isolated dibenzothiophene (DBT) desulfurizing bacterium, identified as Mycobacterium sp. ZD-19 can utilize a wide range of organic sulfur compounds as a sole sulfur source. Thiophene (TH) or benzothiophene (BTH) was completely degraded by strain ZD-19 within 10h or 42h, and 100% DBT or 4,6-dimethyldibenzothiophene (4,6-DMDBT) was removed within 50h or 56h, respectively. Diphenylsulfide (DPS) possessed the lowest desulfurization efficiencies with 60% being transformed within 50h and 80% at 90h. The desulfurization activities of five substrates by resting cells are in order of TH>BTH>DPS>DBT>4,6-DMDBT. In addition, when DBT and 4,6-DMDBT were mixed, they could be simultaneously desulfurized by strain ZD-19. However, DBT appeared to be attacked prior to 4,6-DMDBT. The desulfurization rate of DBT or 4,6-DMDBT in mixture is lower than they are desulfurized separately, indicating that the substrate competitive inhibition is existent when DBT and 4,6-DMDBT are mixed. [Copyright &y& Elsevier]

Abstract: The present study was designed to investigate the effect of sinomenine (SIN), an alkaloid extracted from sinomenium acutum, on the antigen-induced activation of RBL-2H3. For this investigation, the RBL-2H3 cells were sensitized with dinitrophenyl (DNP)-specific IgE overnight in 1.0 ml of Eagle''s MEM (EMEM), and varying doses of SIN were added to the culture medium for 30 min and challenged with dinitrophenyl-human serum albumin (DNP-HSA) to induce mast cell degranulation before supernatants were collected. The effects of SIN on antigen-induced release of β-hexosaminidase were measured by enzymatic assay, calcium influx by FACS, cytokines by ELISA, and signaling events by immunoblotting. The results showed that treatment with SIN was followed by a decrease in FcεRI-mediated mast cell release of β-hexosaminidase, production of IL-4 and TNF-α, phosphorylation of Gab2 (Scaffolding adapter Grb2-associated binder 2), Akt and p38 mitogen-activated protein kinase (MAPK). In addition, SIN had no effect on the phosphorylation of LAT and no significant difference on calcium mobilization was observed between control and SIN treated group. These results suggested that SIN might suppress the antigen-induced activation of RBL-2H3 cells via a Ca2+ independent pathway. [Copyright &y& Elsevier]

Abstract: The operon is a specific functional organization of genes found in bacterial genomes. Most genes within operons share common features. The support vector machine (SVM) approach is here used to predict operons at the genomic level. Four features were chosen as SVM input vectors: the intergenic distances, the number of common pathways, the number of conserved gene pairs and the mutual information of phylogenetic profiles. The analysis reveals that these common properties are indeed characteristic of the genes within operons and are different from that of non-operonic genes. Jackknife testing indicates that these input feature vectors, employed with RBF kernel SVM, achieve high accuracy. To validate the method, Escherichia coli K12 and Bacillus subtilis were taken as benchmark genomes of known operon structure, and the prediction results in both show that the SVM can detect operon genes in target genomes efficiently and offers a satisfactory balance between sensitivity and specificity. [Copyright &y& Elsevier]

Asymmetric cell division generates cell diversity in bacteria, yeast, and higher eukaryotes . In Drosophila, both neural and muscle progenitors divide asymmetrically . In these cells the Inscuteable (Insc) protein complex coordinates cell polarity and spindle orientation. Abstrakt (Abs) is a DEAD-box protein that regulates aspects of cell polarity in oocytes and embryos . We use a conditional allele of abs to investigate its role in neural and muscle progenitor cell polarity. In neuroblasts we observe loss of apical Insc crescents, failure in basal protein targeting, and defects in spindle orientation. In the GMC4-2a cell we observe loss of apical Insc crescents, defects in basal protein targeting, and equalization of sibling neuron fates; muscle precursors show a similar equalization of sibling cell fates. These phenotypes resemble those of insc mutants; indeed, abs mutants show a striking loss of Insc protein levels but no change of insc RNA levels. Furthermore, we find that the Abs protein physically interacts with insc RNA. Our results demonstrate a novel role for Abs in the posttranscriptional regulation of insc expression, which is essential for proper cell polarity, spindle orientation, and the establishment of distinct sibling cell fates within embryonic neural and muscle progenitors. [Copyright &y& Elsevier]

Protein–protein interactions (PPIs) describe the direct physical contact of two proteins that usually results in specific biological functions or regulatory processes. The characterization and study of PPIs through the investigation of their pattern and principle have remained a question in biological studies. Various experimental and computational methods have been used for PPI studies, but most of them are based on the sequence similarity with current validated PPI participators or cellular localization patterns. Most methods ignore the fact that PPIs are defined by their specific biological functions. In this study, we constructed a novel rule-based computational method using gene ontology and KEGG pathway annotation of PPI participators that correspond to the complicated biological effects of PPIs. Our newly presented computational method identified a group of biological functions that are tightly associated with PPIs and provided a new function-based tool for PPI studies in a rule manner. • An explainable rule-based machine learning model of protein-protein interaction was built. • Each protein was represented by a binary GO and KEGG annotation vector. • We used the sum and the absolute difference of two protein vectors to represent a protein-protein pair. • The key GO and KEGG function features were identified using feature selection method. • The prediction rules of protein-protein interactions were learned using decision tree. [ABSTRACT FROM AUTHOR]

Antifreeze protein (AFP) is a proteinaceous compound with improved antifreeze ability and binding ability to ice to prevent its growth. As a surface-active material, a small number of AFPs have a tremendous influence on the growth of ice. Therefore, identifying novel AFPs is important to understand protein–ice interactions and create novel ice-binding domains. To date, predicting AFPs is difficult due to their low sequence similarity for the ice-binding domain and the lack of common features among different AFPs. Here, a computational engine was developed to predict the features of AFPs and reveal the most important 39 features for AFP identification, such as antifreeze-like/N-acetylneuraminic acid synthase C-terminal, insect AFP motif, C-type lectin-like, and EGF-like domain. With this newly presented computational method, a group of previously confirmed functional AFP motifs was screened out. This study has identified some potential new AFP motifs and contributes to understanding biological antifreeze mechanisms. [ABSTRACT FROM AUTHOR]

In this work, a series of WS 2 , ZnO base films and ZnO&WS 2 (ZnO@WS 2 and WS 2 @ZnO) heterojunction composite films were synthesized by the single/two-step Radio Frequency Magnetron Sputtering. Interestingly, it is found that structure, morphology and growth mechanism of the samples depends on the regulation different experimental parameters. The result of morphology characterization demonstrated that the standing WS 2 with different morphology depend on growth time and the multi-directional growth of the ZnO based film. And using the WS 2 base films promoted the growth of ZnO sheet-like morphology. The result of X-ray diffraction characterization showed that the location and the shape of the characteristic peaks existed in the ZnO&WS 2 heterojunction composite films are analogous to ZnO (002) and WS 2 (002)/(101) alone. Furthermore, the ultrafast nonlinear optical behavior and dynamics of the samples were studied. The "W" and "M" type image of open-aperture Z-scan curve were analyzed. From the results, the samples showed multiphoton absorption induced the ground state or excited state saturated absorption or reverse saturated absorption behavior. And the two-photon absorption and three-photon absorption coefficients of ZnO@WS 2 heterojunction composite films reached 1.93 × 10−9 m/W, −2.22 × 10−23 m3/W2, respectively. The bi-exponential decay of the positive signal assigned to the pump-induced deep-level or excited state absorption. Moreover, these findings indicate that the excitation wavelength increases and the detection wave band widen. The study shows that the carrier lifetime of ZnO@WS 2 heterojunction composite films is significantly higher than that of the WS 2 base films. ZnO&WS 2 heterojunction composite films will be promising candidates in nonlinear optical material. • The standing WS 2 , ZnO films and ZnO＆WS 2 heterojunction composite films have been synthesized. • Growth mechanism and morphology of semiconducting ZnO＆WS 2 is investigated. • The optical properties and mechanism of samples with different conditions is investigated. • The sputtering conditions and laser parameters dependent on the ultrafast NLA and dynamics properties of samples are analyzed. [ABSTRACT FROM AUTHOR]

The degradation of a pinned photodiode (PPD) 8T CMOS image sensor (8T-CIS) due to total ionizing dose (TID) and displacement damage dose (DDD) have been investigated with γ-ray and proton irradiation. The dark current and its distributions were studied. We observed a significant increase in the dark current after the proton irradiation than that after the γ-ray irradiation. We observed that the peak values in the Gaussian distribution shift to higher values as a result of TID effects while comparing the dark current distribution results of the γ-ray and proton irradiation. In contrast, the hot pixel tailing increases with the DDD effect. At the same time, the degradation of the light response of the device was investigated by observing the quantum efficiency in the wavelength range of 420–800 nm. A comparison of the results obtained from the γ-ray and proton irradiations showed that the short-wavelength degradation was caused by the TID whereas the DDD caused the degradation in the full spectral range. • Performance of the 8T pinned CMOS image sensors degraded after irradiation. • Dark current increased significantly after proton and γ-ray irradiation. • SRIM simulated the proton trajectories and the vacancy density. • Distribution of dark current was different after γ-ray and proton irradiation. • Light response within 420–800 nm degraded after irradiation. [ABSTRACT FROM AUTHOR]

The aim of the study was to explore the diagnostic value of T2 mapping in an experimental rat model of chronic liver disease. Chronic hepatitis was induced in Sprague-Dawley male rats (n=88) by intraperitoneal and abdominal subcutaneous injection of carbon tetrachloride in olive oil. The normal control rats (n=12) were similarly injected with the same dose of normal saline. All rats were randomly selected and subjected to T2-weighted/spectral adiabatic inversion recovery and multiple gradient- and spin-echo sequence. After scanning, rats were sacrificed immediately and livers removed for staining with hematoxylin and eosin, as well as Masson's trichrome, to determine the pathological stage of hepatic fibrosis, necroinflammatory activity and steatosis. The T2 values were measured and associated with histopathological findings. The T2 values were significantly associated with hepatic fibrosis (P<0.05), but not with hepatitis (P>0.05) or steatosis (P>0.05). By partial correlation analysis, a significant positive correlation was observed between the T2 values and stages of liver fibrosis (r=0.820; P<0.05). T2 values increased with progressive hepatic fibrosis. The differences between T2 values and stages of liver fibrosis were statistically significant. Statistically significant differences were observed between different stages of liver fibrosis (P<0.05), with an area under the curve value of 0.944 for predicting stage F1 or greater, 0.942 for stage F2 or greater, 0.958 for stage F3 or greater, and 0.948 for F4. Thus, the T2 value is one of the quantitative indices of imaging and accurately reflects the stages of liver fibrosis. [ABSTRACT FROM AUTHOR]

Deletion mutation has been proved as the important factor for occurrence and development of disease, especially those with cancer. With the popularity of precision medicine, the individual cancer therapeutic strategy has highlighted the requirement to develop a straightforward and competent strategy for deletion mutation determination. Hence, the present study is dedicated to develop a one-step assay to identify deletion mutation with sequence specificity for clinical practice. Taking advantage of loop-mediated isothermal amplification, an ultrasensitive and rapid deletion mutation determination method is established, which allow as low as 30 copies or 0.1% target variants under strong interferential background can be accurately distinguished in 30 min dispensing with professional operation and complex data interpretation. As a demonstration, the epidermal growth factor receptor p.E746-A750del, a crucial factor for the susceptibility of tyrosine kinase inhibitor in non-small-cell lung cancer treatment, has been accurately identified by this method with both cell lines and real clinical samples. By tailor-made primer set, this method can be extended for other deletion mutants, making it a molecular diagnostic tool and could be readily adapted for cancer diagnosis, therapy and prognosis in point of care diagnostic test scenario. Image 1 • One-step determination of deletion mutant within 30 min. • Accurate detection of 0.1% target variants under strong interferential background. • This genotyping platform can be extended for any desired deletion mutants. [ABSTRACT FROM AUTHOR]

Nanoparticles (NPs) have been widely used as anticancer and antibacterial agents. However, before their use in biomedical applications, some in vitro assays should be carried out to investigate their interaction with biological systems. The copper oxide NPs (CuO NPs) were synthesized by hydrothermal method and their interaction with human serum albumin (HSA), leukemia K562 cells and three strains of bacteria was explored by spectroscopic, docking, cellular, and antibacterial investigations. The TEM, DLS, XRD, FTIR, Raman, and UV–visible techniques revealed that synthesized CuO NPs provide a crystalline structure corresponding to CuO nanoclusters with good colloidal stability. Biothermodynamic studies showed that CuO NPs formed a static complex with HSA molecules through hydrogen bonds which was further confirmed by docking analysis. UV–Vis spectroscopy results exhibited that the melting temperature (Tm) of HSA was slightly changed in the presence of CuO NPs. Cellular studies displayed that CuO NPs selectively resulted in the mortality of K562 cells through cell membrane leakage, caspase-9 and -3 activation, and apoptosis. Finally, antibacterial assays depicted that CuO NPs can induce an inhibitory effect in the case of both Gram-negative and Gram-positive bacteria. In conclusion, this study may provide useful data regarding the protein binding and biomedical applications of NPs. • CuO NPs were synthesized by hydrothermal method. • CuO NPs formed a static complex with HSA molecules through hydrogen bonds. • Tm of HSA was slightly changed in the presence of CuO NPs. • CuO NPs selectively result in the mortality of K562 cells. • CuO NPs induced antibacterial effects aganist both Gram-negative and Gram-positive bacteria. [ABSTRACT FROM AUTHOR]

• We identify a natural Ser-Leu substitution in the HA cleavage site of EA H1N2 virus. • Ser-Leu substitution at the P2 position reduces viral replication and HA cleavage. • Ser-Leu also affects survival rates in mice infected with reassortant viruses. • This amino acid change may be valuable for influenza vaccine development. Swine influenza viruses not only constitute a potential economic problem for livestock, but also pose a substantial threat to human health. Mutation in the proteolytic cleavage site of hemagglutinin (HA) is recognized as an essential factor of tissue tropism and viral pathogenicity. However, the molecular properties of the cleavage site of Eurasian avian-like swine (EA) H1N2 virus remain largely unknown. In this study, we found a serine-leucine (Ser-Leu) substitution at the P2 position of the HA cleavage site (S328 L) in naturally occurring EA H1N2 virus. To study the effect of this substitution, we used reverse genetics to generate recombinant wild-type and mutant viruses containing a single amino acid mutation at the P2 position in A/swine/Guangdong/YJ28/2014 (YJ28) or A/swine/Guangdong/DG2/2015 (DG2) background. In vitro experiments showed that the Ser-Leu substitution at the P2 position attenuated the viral replication and HA cleavage efficiency. In vivo analyses revealed that, while all mice inoculated with r/DG2-S328 L or r/YJ28 viruses survived, the survival rates of r/DG2- and r/YJ28-L328S-inoculated animals were 20 % and 40 %, respectively. Furthermore, the Ser-Leu substitution at the P2 position attenuated the replication in nasal turbinate and lungs. In summary, this amino acid change may be useful to understand the molecular properties of the cleavage site and be valuable for vaccine development. [ABSTRACT FROM AUTHOR]

The interaction of nanoparticles with protein and cells may provide important information regarding their biomedical implementations. Herein, after synthesis of tin oxide (SnO 2) nanoparticles by hydrothermal method, their interaction with human serum albumin (HSA) was evaluated by multispectroscopic and molecular docking (MD) approaches. Furthermore, the selective antiproliferative impact of SnO 2 nanoparticles against leukemia K562 cells was assessed by different cellular assays, whereas lymphocytes were used as control cells. TEM, DLS, zeta potential and XRD techniques showed that crystalline SnO 2 nanoparticles have a size of less than 50 nm with a good colloidal stability. Fluorescence and CD spectroscopy analysis indicated that the HSA undergoes some slight conformational changes after interaction with SnO 2 nanoparticles, whereas the secondary structure of HSA remains intact. Moreover, MD outcomes revealed that the charged residues of HSA preferentially bind to SnO 2 nanoclusters in the binding pocket. Antiproliferative examinations displayed that SnO 2 nanoparticles can selectively cause the mortality of K562 cells through induction of cell membrane leakage, activation of caspase-9, -8, -3, down regulation of Bcl-2 mRNA, the elevation of ROS level, S phase arrest, and apoptosis. In conclusion, this data may indicate that SnO 2 nanoparticles can be used as promising particles to be integrated into therapeutic platforms. • Investigation of HSA structural changes in the presence of tin oxide NPs. • Selective anticancer effect of tin oxide NPs against K562 cells [ABSTRACT FROM AUTHOR]

In this paper, ZnO, MoS 2 and ZnO-time/MoS 2 films with excellent nonlinear absorption (NA) properties were successfully prepared by single/two-step magnetron sputtering. The morphology, structure and NA property of the samples were studied. The scanning electron microscope results show that cluster-like MoS 2 have different morphology. This phenomenon can be attributed to the fact that the multi-directional growth of the ZnO base films causes the original growth orientation of MoS 2 to be changed. The NA characteristics under different excitation intensities are studied by Z-Scan technology. The material exhibits the reverse saturation absorption characteristic caused by two-photon absorption. Furthermore, the order of magnitude of NA coefficient for samples was determined to be 10−6 cm/W. The ZnO-time/MoS 2 films display excellent NA characteristics, which are desirable for field of optical switch, optical limiting, optical communication and integrated optics. Image 1 • The ZnO-time/MoS 2 films with different conditions have been synthesized. • The ultrafast nonlinear optical properties of ZnO-time/MoS 2 films were analyzed. • The mechanism of growth and nonlinear absorption for ZnO-time/MoS 2 films is analyzed. [ABSTRACT FROM AUTHOR]

Background: Helicobacter himalayensis was isolated from Marmota himalayana in the Qinghai-Tibet Plateau, China, and is a new non-H. pylori species, with unclear taxonomy, phylogeny, and pathogenicity. Results: A comparative genomic analysis was performed between the H. himalayensis type strain 80(YS1)T and other the genomes of Helicobacter species present in the National Center for Biotechnology Information (NCBI) database to explore the molecular evolution and potential pathogenicity of H. himalayensis. H. himalayensis 80(YS1)T formed a clade with H. cinaedi and H. hepaticus that was phylogenetically distant from H. pylori. The H. himalayensis genome showed extensive collinearity with H. hepaticus and H. cinaedi. However, it also revealed a low degree of genome collinearity with H. pylori. The genome of 80(YS1)T comprised 1,829,936 bp, with a 39.89% GC content, a predicted genomic island, and 1769 genes. Comparatively, H. himalayensis has more genes for functions in "cell wall/membrane/envelope biogenesis" and "coenzyme transport and metabolism" sub-branches than the other compared helicobacters, and its genome contained 42 virulence factors genes, including that encoding cytolethal distending toxin (CDT). Conclusions: We characterized the H. himalayensis 80(YS1)T genome, its phylogenetic position, and its potential pathogenicity. However, further understanding of the pathogenesis of this potentially pathogenic bacterium is required, which might help to manage H. himalayensis-induced diseases. [ABSTRACT FROM AUTHOR]

DNA sequencing-based measurable residual disease (MRD) detection has shown to be clinically relevant in AML. However, the same methodology cannot be applied to fusion gene-driven subtypes of AML such as core-binding factor AML (CBF-AML). Here in this study, we evaluated the effectiveness of using DNA and RNA sequencing in MRD detection and in tracking clonal dynamics in CBF-AML. Using RNA-seq, we were able to quantify expression levels of RUNX1-RUNX1T1 and CBFB-MYH11 at diagnosis and their levels of reduction during remission (P < 6.3e−05 and P < 2.2e−13). The level of reduction of RUNX1-RUNX1T1 as measured by RNA-seq and qPCR were highly correlated (R2 = 0.74, P < 5.4e−05). A decision tree analysis, based on 3-log reduction of RUNX1-RUNX1T1 and cKIT-D816mut at diagnosis, stratified RUNX1-RUNX1T1 AML patients into three subgroups. These three subgroups had 2-year overall survival rates at 87%, 74%, and 33% (P < 0.08) and 2-year relapse incidence rates at 13%, 42%, and 67% (P < 0.05). On the other hand, although low residual allelic burden was common, it was not associated with long-term outcome, indicating that mutation clearance alone cannot be interpreted as MRD-negative. Overall, our study demonstrates that the clinical utility of RNA sequencing as a potential tool for MRD monitoring in fusion gene-driven AML such as RUNX1-RUNX1T1 AML. [ABSTRACT FROM AUTHOR]

As a trace heavy metal, lead (Pb) has many anthropogenic applications but also produces many environmental pollution problems because of its high toxicity. In this study, we combined two in situ high-resolution sampling techniques – high-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) – with the DGT-induced fluxes in sediment (DIFS) model to explore the mechanism of Pb release and resupply between sediments and pore water in the lower reaches and estuary of the Jiuxi River and the adjacent coast. An analysis of the chemical forms of Pb in the sediments showed that the content of the acid-extractable fraction (F1) was higher at the coastal site than at the other sampling sites, which indicates that Pb in the coastal sediments had greater activity and was more likely to cause Pb pollution. The apparent diffusion fluxes of Pb across the sediment-water interface (SWI) in the lower reaches, estuary and coastal zone are negative, and the absolute value of Pb flux in the estuary is several times higher than that in the other two stations, indicating a strong downward Pb diffusion trend, which may be due to water pollution caused by the nearby sewage outlet. As an insensitive element to redox, Pb did not exhibit an obvious correlation with Fe. In particular, the high Pb concentration and strong downward diffusion trend of the overlying water in the estuary caused the significant negative correlation between Pb and Fe. The calculated results of the DIFS model show that the reduced layer in the intertidal zone along the coast has the highest R value, the highest desorption rate (k − 1) and the shortest response time (T c), indicating that sediment particles in the coastal intertidal zone supply Pb to the pore water at the fastest rate; consequently, Pb pollution in the coastal zone is worthy of further attention. • Two high-resolution sampling techniques were combined to explore the sediment-water interface microenvironment. • Downward diffusion of overlying water Pb leads to a negative correlation between Fe and Pb and a negative flux of Pb. • The complexation of Pb with DOM is the main reason for higher dissolved Pb concentration compared with DGT-labile Pb. • The resupply of Pb in coastal sediments is much higher and likely produces a potential risk of Pb pollution. [ABSTRACT FROM AUTHOR]

Chronic inflammation and immune responses are two core element that characterize the tumor microenvironment. A large number of immune/inflammatory cells (including tumor associated macrophages, neutrophils and myeloid derived suppressor cells) as well as cytokines (such as IL-6, IL-10, TGF-β) are present in the tumor microenvironment, which results in both a chronic inflammatory state and immunosuppression. As a consequence tumor cell migration, invasion, metastasis and anticancer drug sensitivity are modulated. On the one hand, secreted cytokines change the function of cytotoxic T lymphocytes and antigen presenting cells, thereby inhibiting tumor specific immune responses and consequently inducing a special immunosuppressive microenvironment for tumor cells. On the other hand, tumor cells change the differentiation and function of immune/inflammatory cells in the tumor microenvironment especially via the NF-κB and STAT3 signaling pathways. This may promote proliferation of tumor cells. Here we review these double edged effects of immune/inflammatory cells and cytokines on tumor cells, and explored their interactions with inflammation, hypoxia, and immune responses in the tumor microenvironment. The tumor inflammatory or immunosuppressive reactions mediated by the high activity of NF-κB or STAT3 can occur alone or simultaneously, and there is a certain connection between them. Inhibiting the NF-κB or STAT3 signaling pathway is likely to curb the growth of tumor cells, reduce the secretion of pro-inflammatory factors, and enhance the anti-tumor immune response. [ABSTRACT FROM AUTHOR]

• A differential coulometric dual-strips system based on screen-printed electrode technology. • Extract levodopa signal from complex samples through differential method. • The system demonstrates a high sensitivity and low detection limit for the determination of levodopa. • A widely adaptable strategy for interference-free electrochemical biosensors. As a vital therapeutic agent for Parkinson's disease, dosage control of levodopa has always been a major obstacle in ensuring efficacy and curbing side effects. Simple and fast electrochemical detection methods are the main force in this field. Here, we presented a differential dual-strip method based on the coulometry for high accuracy determination of levodopa. The difference between the two strip signals with or without the tyrosinase extracted the levodopa signal from the samples. The Prussian Blue modified carbon screen-printed electrode was used to convert and amplify the electrochemical signal upon the presence of levodopa. The system exhibited a linear behavior in the 0–10 μM concentration range and a detection limit of 0.25 μM. Furthermore, it was proved to be stable in effectively distinguishing levodopa from complex samples through anti-interference experiments and serum tests. We demonstrated the superiority of dual-strip differential coulometry for the determination of levodopa towards Parkinson's disease clinical management. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), characterized by a rapid decline in renal function, is triggered by an acute inflammatory response that leads to kidney damage. An effective treatment for AKI is lacking. Using in vitro and in vivo AKI models, our laboratory has identified a series of anti-inflammatory molecules and their derivatives. In the current study, we identified the protective role of rutaecarpine (Ru) on renal tubules. We obtained a series of 3-aromatic sulphonamide-substituted Ru derivatives exhibiting enhanced renoprotective and anti-inflammatory function. We identified Compound-6c(Cpd-6c) as having the best activity and examined its protective effect against cisplatin nephropathy both in vivo and in vitro in cisplatin-stimulated tubular epithelial cells (TECs). Our results showed that Cpd-6c restored renal function more effectively than Ru, as evidenced by reduced blood urea nitrogen and serum creatinine levels in mice. Cpd-6c alleviated tubular injury, as shown by PAS staining and molecular analysis of kidney injury molecule-1 (KIM-1), with both prevention and treatment protocols in cisplatin-treated mice. Moreover, Cpd-6c decreased kidney inflammation, oxidative stress and programmed cell death. These results have also been confirmed in cisplatin-treated TECs. Using web-prediction algorithms, molecular docking, and cellular thermal shift assay (CETSA), we identified phosphodiesterase 4B (PDE4B) as a Cpd-6c target. In addition, we firstly found that PDE4B was up-regulated significantly in the serum of AKI patients. After identifying the function of PDE4B in cisplatin-treated tubular epithelial cells by siRNA transfection or PDE4 inhibitor rolipram, we showed that Cpd-6c treatment did not protect against cisplatin-induced injury in PDE4B knockdown TECs, thus indicating that Cpd-6c exerts its renoprotective and anti-oxidative effects via the PDE4B-dependent pathway. Collectively, Cpd-6c might serve as a potential therapeutic agent for AKI and PDE4B may be highly involved in the initiation and progression of AKI. [ABSTRACT FROM AUTHOR]