bluuebunny/crossref_metadata_2025 huggingface dataset:
The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation
Authors: Wu Qiong , Chen Jin-xian , Chen Yu , Cai Li-li , Wang Xiao-zhong , Guo Wu-hua , Zheng Jian-feng
Published: February 2018

G-protein-coupled receptor (GPCR)-related proteins are dysregulated and the GPCR CC-chemokine receptor 10 (CCR10) is significantly upregulated in inflammation-driven HCC. However, CCR10′s role in inflammation-driven hepatocarcinogenesis remains unknown. The aim of this study was to evaluate the role of CCR10 in inflammation-driven hepatocarcinogenesis. Via a targeted gene expression microarray screening alterations in GPCR family gene expression, we found CCR10 to be significantly upregulated in hepatocytes isolated from inflammation-driven human HCC tumors and matching paracancerous tissues. Tetrachloromethane (CCl4)-induced and diethylnitrosamine (DEN)-induced murine models of inflammatory hepatocarcinogenesis displayed significant hepatocellular TNF and CCR10 upregulation. Exogenous TNF applied to HepG2 and LO2 cell lines as well as wild-type (WT) mice significantly upregulated hepatocellular CCR10 expression, Akt phosphorylation, PCNA expression, and hepatocellular proliferation. Additionally, exogenous TNF significantly upregulated secretion of the natural CCR10 ligand-agonist CCL28 from both cell lines. Transgenic CCR10-knockout (CCR10 KO) in DEN-treated mice significantly increased hepatocellular apoptosis levels and significantly lowered compensatory hepatocellular proliferation but did not affect upstream TNF expression. In addition, DEN-treated CCR10 KO mice showed a significantly lower liver weight/body weight ratio, significantly lower liver tumor incidence, and significantly smaller tumors. Moreover, exogenous CCR10 expression significantly raised xenograft tumor growth in Balb/c nude mice. In vitro, CCR10 transfection or CCL28 treatment in HepG2 and LO2 cell lines significantly increased Akt phosphorylation, PCNA expression, and cell proliferation, while CCR10 silencing or Akt inhibition produced the opposite effects. In vivo, hepatocytes isolated from HCC tumor tissue and matching paracancerous tissue in DEN-treated CCR10 KO mice showed significantly lower Akt phosphorylation and PCNA expression relative to WT hepatocytes. In conclusion, inflammation-induced TNF promotes hepatocellular CCR10 expression and downstream PI3K/Akt-mediated hepatocarcinogenesis. CCR10 appears to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation and shows promise as a potential therapeutic target for inflammation-driven HCC.
Let-7c inhibits cholangiocarcinoma growth but promotes tumor cell invasion and growth at extrahepatic sites
Authors: Xie Yu , Zhang Hang , Guo Xing-Jun , Feng Ye-Chen , He Rui-Zhi , Li Xu , Yu Shuo , Zhao Yan , Shen Ming , Zhu Feng , Wang Xin , Wang Min , Balakrishnan Asha , Ott Michael , Peng Feng , Qin Ren-Yi
Published: February 2018

Cholangiocarcinoma (CCA) is a cancer type with high postoperative relapse rates and poor long-term survival largely due to tumor invasion, distant metastasis, and multidrug resistance. Deregulated microRNAs (miRNAs) are implicated in several cancer types including CCA. The specific roles of the miRNA let-7c in cholangiocarcinoma are not known and need to be further elucidated. In our translational study we show that microRNA let-7c expression was significantly downregulated in human cholangiocarcinoma tissues when compared to adjacent tissues of the same patient. Let-7c inhibited the tumorigenic properties of cholangiocarcinoma cells including their self-renewal capacity and sphere formation in vitro and subcutaneous cancer cell growth in vivo. Ectopic let-7c overexpression suppressed migration and invasion capacities of cholangiocarcinoma cell lines in vitro, however, promoted distant invasiveness in vivo. Furthermore, we found that let-7c regulated the aforementioned malignant biological properties, at least in part, through regulation of EZH2 protein expression and through the DVL3/β-catenin axis. The miRNA let-7c thus plays an important dual role in regulating tumorigenic and metastatic abilities of human cholangiocarcinoma through mechanisms involving EZH2 protein and the DVL3/β-catenin axis.
MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to an ROS augmenting agent
Authors: Wang Tingting , Liu Lingling , Chen Xuyong , Shen Yuqing , Lian Gaojian , Shah Nilay , Davidoff Andrew M , Yang Jun , Wang Ruoning
Published: February 2018

Heightened aerobic glycolysis and glutaminolysis are characteristic metabolic phenotypes in cancer cells. Neuroblastoma (NBL), a devastating pediatric cancer, is featured by frequent genomic amplification of MYCN, a member of the Myc oncogene family that is primarily expressed in the early stage of embryonic development and required for neural crest development. Here we report that an enriched glutaminolysis gene signature is associated with MYCN amplification in children with NBL. The partial knockdown of MYCN suppresses glutaminolysis in NBL cells. Conversely, forced overexpression of MYCN in neural crest progenitor cells enhances glutaminolysis. Importantly, glutaminolysis induces oxidative stress by producing reactive oxygen species (ROS), rendering NBL cells sensitive to ROS augmentation. Through a small-scale metabolic-modulator screening, we have found that dimethyl fumarate (DMF), a Food and Drug Administration-approved drug for multiple sclerosis, suppresses NBL cell proliferation in vitro and tumor growth in vivo. DMF suppresses NBL cell proliferation through inducing ROS and subsequently suppressing MYCN expression, which is rescued by an ROS scavenger. Our findings suggest that the metabolic modulation and ROS augmentation could be used as novel strategies in treating NBL and other MYC-driven cancers.
Fibroblast growth factor-21 prevents diabetic cardiomyopathy via AMPK-mediated antioxidation and lipid-lowering effects in the heart
Authors: Yang Hong , Feng Anyun , Lin Sundong , Yu Lechu , Lin Xiufei , Yan Xiaoqing , Lu Xuemian , Zhang Chi
Published: February 2018

Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice. However, the cardiac damage above was prevented by administration of FGF21. Further studies demonstrated that the metabolic regulating effect of FGF21 is not enough, contributing to FGF21-induced significant cardiac protection under diabetic conditions. Therefore, other protective mechanisms must exist. The in vivo cardiac damage was mimicked in primary neonatal or adult mouse cardiomyocytes treated with HG/Pal, which was inhibited by FGF21 treatment. Knockdown of AMPKα1/2, AKT2, or NRF2 with their siRNAs revealed that FGF21 protected cardiomyocytes from HG/Pal partially via upregulating AMPK–AKT2–NRF2-mediated antioxidative pathway. Additionally, knockdown of AMPK suppressed fatty acid β-oxidation via inhibition of ACC–CPT-1 pathway. And, inhibition of fatty acid β-oxidation partially blocked FGF21-induced protection in cardiomyocytes. Further, in vitro and in vivo studies indicated that FGF21-induced cardiac protection against type 2 diabetes was mainly attributed to lipotoxicity rather than glucose toxicity. These results demonstrate that FGF21 functions physiologically and pharmacologically to prevent type 2 diabetic lipotoxicity-induced cardiomyopathy through activation of both AMPK–AKT2–NRF2-mediated antioxidative pathway and AMPK–ACC–CPT-1-mediated lipid-lowering effect in the heart.
The carnitine system and cancer metabolic plasticity
Authors: Melone Mariarosa Anna Beatrice , Valentino Anna , Margarucci Sabrina , Galderisi Umberto , Giordano Antonio , Peluso Gianfranco
Published: February 2018

Metabolic flexibility describes the ability of cells to respond or adapt its metabolism to support and enable rapid proliferation, continuous growth, and survival in hostile conditions. This dynamic character of the cellular metabolic network appears enhanced in cancer cells, in order to increase the adaptive phenotype and to maintain both viability and uncontrolled proliferation. Cancer cells can reprogram their metabolism to satisfy the energy as well as the biosynthetic intermediate request and to preserve their integrity from the harsh and hypoxic environment. Although several studies now recognize these reprogrammed activities as hallmarks of cancer, it remains unclear which are the pathways involved in regulating metabolic plasticity. Recent findings have suggested that carnitine system (CS) could be considered as a gridlock to finely trigger the metabolic flexibility of cancer cells. Indeed, the components of this system are involved in the bi-directional transport of acyl moieties from cytosol to mitochondria and vice versa, thus playing a fundamental role in tuning the switch between the glucose and fatty acid metabolism. Therefore, the CS regulation, at both enzymatic and epigenetic levels, plays a pivotal role in tumors, suggesting new druggable pathways for prevention and treatment of human cancer.
GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion
Authors: Franco Antonietta , Sorriento Daniela , Gambardella Jessica , Pacelli Roberto , Prevete Nella , Procaccini Claudio , Matarese Giuseppe , Trimarco Bruno , Iaccarino Guido , Ciccarelli Michele
Published: February 2018

The modern understanding of the G protein-coupled receptor kinase 2 has grown towards the definition of a stress protein, for its ability to rapidly compartmentalize within the cell in response to acute stimulation. Also, mitochondria can be regulated by GRK2 localization. We show that Ionizing Radiation (IR) exposure acutely damages mitochondria regarding mass, morphology, and respiration, with recovery in a framework of hours. This phenomenon is actively regulated by GRK2, whose overexpression results to be protective, and reciprocally, deletion accelerates degenerative processes. The regulatory effects of the kinase involve a new interactome that includes binding HSP90 and binding and phosphorylation of the key molecules involved in the process of mitochondrial fusion and recovery: MFN-1 and 2.
Tools for studying growth patterns and chemical dynamics of aggregated Pseudomonas aeruginosa exposed to different electron acceptors in an alginate bead model
Authors: Sønderholm Majken , Koren Klaus , Wangpraseurt Daniel , Jensen Peter Østrup , Kolpen Mette , Kragh Kasper Nørskov , Bjarnsholt Thomas , Kühl Michael
Published: February 2018

In chronic infections, bacterial pathogens typically grow as small dense cell aggregates embedded in a matrix consisting of, e.g., wound bed sludge or lung mucus. Such biofilm growth mode exhibits extreme tolerance towards antibiotics and the immune defence system. The bacterial aggregates are exposed to physiological heterogeneity and O2 limitation due to steep chemical gradients through the matrix, which is are hypothesised to contribute to antibiotic tolerance. Using a novel combination of microsensor and bioimaging analysis, we investigated growth patterns and chemical dynamics of the pathogen Pseudomonas aeruginosa in an alginate bead model, which mimics growth in chronic infections better than traditional biofilm experiments in flow chambers. Growth patterns were strongly affected by electron acceptor availability and the presence of chemical gradients, where the combined presence of O2 and nitrate yielded highest bacterial growth by combined aerobic respiration and denitrification.
Reconstruction of kidney renal clear cell carcinoma evolution across pathological stages
Authors: Pang Shichao , Sun Yidi , Wu Leilei , Yang Liguang , Zhao Yi-Lei , Wang Zhen , Li Yixue
Published: February 2018

Although numerous studies on kidney renal clear cell carcinoma (KIRC) were carried out, the dynamic process of tumor formation was not clear yet. Inadequate attention was paid on the evolutionary paths among somatic mutations and their clinical implications. As the tumor initiation and evolution of KIRC were primarily associated with SNVs, we reconstructed an evolutionary process of KIRC using cross-sectional SNVs in different pathological stages. KIRC driver genes appeared early in the evolutionary tree, and the genes with moderate mutation frequency showed a pattern of stage-by-stage expansion. Although the individual gene mutations were not necessarily associated with survival outcome, the evolutionary paths such as VHL-PBRM1 and FMN2-PCLO could indicate stage-specific prognosis. Our results suggested that, besides mutation frequency, the evolutionary relationship among the mutated genes could facilitate to identify novel drivers and biomarkers for clinical utility.
CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism
Authors: García-Rodríguez Sonia , Rosal-Vela Antonio , Botta Davide , Cumba Garcia Luz M. , Zumaquero Esther , Prados-Maniviesa Verónica , Cerezo-Wallis Daniela , Lo Buono Nicola , Robles-Guirado José-Ángel , Guerrero Salvador , González-Paredes Elena , Andrés-León Eduardo , Corbí Ángel , Mack Matthias , Koch-Nolte Friedrich , Merino Ramón , Zubiaur Mercedes , Lund Frances E. , Sancho Jaime
Published: February 2018

In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38−/−) but not ART2-deficient (Art2−/−) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chiinflammatory monocytes, TNF-α-producing Ly6G+neutrophils and Ly6Clomonocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis.Cd38−/−pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However,Tnf-αandCxcl12gene expression inCd38−/−bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses ofCd38−/−Ly6Chimonocytes and Ly6G+neutrophils were not impaired. However,Cd38−/−Ly6Chimonocytes and Ly6Clomonocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2−/−) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chimonocytes and Ly6Clomonocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.
Mapping the dispersion of water wave channels
Authors: Apigo David J. , Kanwal Alokik , Palmieri John , Dobiszewski Kyle F. , Farrow Reginald C. , Thomas Gordon A. , Prodan Emil V. , Prodan Camelia
Published: February 2018

Large classes of electronic, photonic, and acoustic crystals and quasi-crystals have been predicted to support topological wave-modes. Some of these modes are stabilized by certain symmetries but others occur as pure wave phenomena, hence they can be observed in many other media that support wave propagation. Surface water-waves are mechanical in nature but very different from the elastic waves, hence they can provide a new platform for studying topological wave-modes. Motivated by this perspective, we report theoretical and experimental characterizations of water-wave crystals obtained by periodic patterning of the water surface. In particular, we demonstrate the band structure of the spectra and existence of spectral gaps.
Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer
Authors: Toden Shusuke , Ravindranathan Preethi , Gu Jinghua , Cardenas Jacob , Yuchang Madelaine , Goel Ajay
Published: February 2018

Proanthocyanidins are a heterogeneous group of flavan-3-ol or flavan-3,4-diol oligomers present in various fruits and vegetables. In particular, the smaller oligomeric subset of proanthocyanidins, termed the oligomeric proanthocyanidins (OPCs) appear to have potent anti-tumorigenic properties, but the underlying mechanisms for their effectiveness remain unclear. Herein, we utilized a series of in vitro, in vivo and patient-derived organoid approaches to systematically investigate the chemoprotective role of OPCs in colorectal cancer. OPCs exerted anti-tumorigenic effects through inhibition of cellular proliferation, and induced apoptosis and cell cycle arrest. Intriguingly, OPCs suppressed spheroid derived cancer stem-like cell formation and decreased the expression of intestinal cancer stem cell markers including LGR5, CD44 and CD133. Mechanistically, RNA-sequencing results confirmed that OPCs prominently interfered with developmental and self-renewal pathways and identified several self-renewal associated oncogenes targeted by OPCs. Furthermore, OPCs inhibited Hippo pathway through downregulation of its key transcriptional regulators, YAP and TAZ. Finally, we confirmed anti-tumorigenic effects of OPCs using multiple xenograft experiments and recapitulated its protective effects using patient-derived colorectal tumor organoids. Collectively, we have comprehensively assessed anti-tumorigenic properties of OPCs and our data throws light on previously unrecognized chemopreventive mechanisms of OPCs highlighting its therapeutic potential.
Nanostructured Polymer Thin Films Fabricated with Brush-based Layer-by-Layer Self-assembly for Site-selective Construction and Drug release
Authors: Park Kyungtae , Choi Daheui , Hong Jinkee
Published: February 2018

Layer-by-Layer (LbL) self-assembly has been investigated for several decades. However, the conventional LbL method has performance problems on the chair-side caused by its cumbersome and time-consuming process. Thus, we investigate a new LbL self-assembly technique for the fast and high efficient preparation process based on the brush. The multilayer films fabricated by simple sequential brushing of polyelectrolyte solutions are compared to the classical dipping method. We characterize the multilayer films by characteristics such as their morphology and thickness, and compare them against those of the classic method by profilometry, atomic force microscopy. We prepare multilayer films with biocompatible polyelectrolytes, chitosan, and alginate incorporated with a hydrophobic drug carrier. For the drug carrier, a poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) block copolymer is introduced to construct micelles containing dexamethasone, which is a well-known osteogenesis-inducing drug. The hydrogen bonding behavior between adjacent layers and micelles is investigated by Fourier transform infrared spectroscopy. Additionally, we analyze the release profiles, degradation profiles and toxicity of the multilayer films for biomedical applications. From these results, we can identify the brushing LbL method as a reliable and more efficient multilayer film-construction process compared to conventional dipping LbL, especially for practical applications in dental and clinical situations.
Delivery of exogenous mitochondria via centrifugation enhances cellular metabolic function
Authors: Kim Mi Jin , Hwang Jung Wook , Yun Chang-Koo , Lee Youngjun , Choi Yong-Soo
Published: February 2018

Mitochondria are essential organelles involved in the maintenance of cell growth and function, and have been investigated as therapeutic targets in various diseases. Recent studies have demonstrated that direct mitochondrial transfer can restore cellular functions of cells with inherited or acquired mitochondrial dysfunction. However, previous mitochondrial transfer methods are inefficient and time-consuming. Here, we developed a simple and easy mitochondrial transfer protocol using centrifugation, which can be applied to any cell type. By our simple centrifugation method, we found that the isolated mitochondria could be successfully transferred into target cells, including mitochondrial DNA-deleted Rho0 cells and dexamethasone-treated atrophic muscle cells. We found that mitochondrial transfer normalised ATP production, mitochondrial membrane potential, mitochondrial reactive oxygen species level, and the oxygen consumption rate of the target cells. Furthermore, delivery of intact mitochondria blocked the AMPK/FoxO3/Atrogene pathway underlying muscle atrophy in atrophic muscle cells. Taken together, this simple and rapid mitochondrial transfer method can be used to treat mitochondrial dysfunction-related diseases.
Machine learning for the meta-analyses of microbial pathogens’ volatile signatures
Authors: Palma Susana I. C. J. , Traguedo Ana P. , Porteira Ana R. , Frias Maria J. , Gamboa Hugo , Roque Ana C. A.
Published: February 2018

Non-invasive and fast diagnostic tools based on volatolomics hold great promise in the control of infectious diseases. However, the tools to identify microbial volatile organic compounds (VOCs) discriminating between human pathogens are still missing. Artificial intelligence is increasingly recognised as an essential tool in health sciences. Machine learning algorithms based in support vector machines and features selection tools were here applied to find sets of microbial VOCs with pathogen-discrimination power. Studies reporting VOCs emitted by human microbial pathogens published between 1977 and 2016 were used as source data. A set of 18 VOCs is sufficient to predict the identity of 11 microbial pathogens with high accuracy (77%), and precision (62–100%). There is one set of VOCs associated with each of the 11 pathogens which can predict the presence of that pathogen in a sample with high accuracy and precision (86–90%). The implemented pathogen classification methodology supports future database updates to include new pathogen-VOC data, which will enrich the classifiers. The sets of VOCs identified potentiate the improvement of the selectivity of non-invasive infection diagnostics using artificial olfaction devices.
Interleukin-33 is activated by allergen- and necrosis-associated proteolytic activities to regulate its alarmin activity during epithelial damage
Authors: Scott Ian C. , Majithiya Jayesh B. , Sanden Caroline , Thornton Peter , Sanders Philip N. , Moore Tom , Guscott Molly , Corkill Dominic J. , Erjefält Jonas S. , Cohen E. Suzanne
Published: February 2018

Interleukin (IL)-33 is an IL-1 family alarmin released from damaged epithelial and endothelial barriers to elicit immune responses and allergic inflammation via its receptor ST2. Serine proteases released from neutrophils, mast cells and cytotoxic lymphocytes have been proposed to process the N-terminus of IL-33 to enhance its activity. Here we report that processing of full length IL-33 can occur in mice deficient in these immune cell protease activities. We sought alternative mechanisms for the proteolytic activation of IL-33 and discovered that exogenous allergen proteases and endogenous calpains, from damaged airway epithelial cells, can process full length IL-33 and increase its alarmin activity up to ~60-fold. Processed forms of IL-33 of apparent molecular weights ~18, 20, 22 and 23 kDa, were detected in human lungs consistent with some, but not all, proposed processing sites. Furthermore, allergen proteases degraded processed forms of IL-33 after cysteine residue oxidation. We suggest that IL-33 can sense the proteolytic and oxidative microenvironment during tissue injury that facilitate its rapid activation and inactivation to regulate the duration of its alarmin function.
Metformin Use and Severe Dengue in Diabetic Adults
Authors: Htun Htet Lin , Yeo Tsin Wen , Tam Clarence C. , Pang Junxiong , Leo Yee Sin , Lye David C.
Published: February 2018

Diabetes mellitus is a risk factor for severe dengue in adults, but few studies have examined the association between metformin use and disease severity in dengue. In addition to its effect on glucose control, metformin has been associated with pleiotropic properties in preclinical studies. Using a cohort of laboratory-confirmed adult (≥21 years) dengue patients with diabetes mellitus admitted to Tan Tock Seng Hospital, we conducted a retrospective cohort study involving 131 (58.7%) metformin users and 92 (41.3%) non-users. Dengue severity was categorized as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS) in World Health Organization (WHO) 1997 criteria and severe dengue (SD) in WHO 2009 criteria. Multivariable Poisson regression with robust error variance was used to estimate risk ratio (RR). Compared with non-use, metformin use was associated with a decreased risk of developing severe dengue (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI]: 0.37–0.98, P = 0.04). Additionally, there was an inverse dose-response relationship (aRR = 0.69, 95% CI: 0.49–0.98, P = 0.04) with dengue severity as classified by WHO 2009 criteria. Use of metformin, however, was not associated with dengue severity based on WHO 1997 criteria; and no dose-response relationship was noted. Our results suggest metformin use could attenuate disease severity in dengue-infected diabetes mellitus individuals.
A novel heterogeneous network-based method for drug response prediction in cancer cell lines
Authors: Zhang Fei , Wang Minghui , Xi Jianing , Yang Jianghong , Li Ao
Published: February 2018

An enduring challenge in personalized medicine lies in selecting a suitable drug for each individual patient. Here we concentrate on predicting drug responses based on a cohort of genomic, chemical structure, and target information. Therefore, a recently study such as GDSC has provided an unprecedented opportunity to infer the potential relationships between cell line and drug. While existing approach rely primarily on regression, classification or multiple kernel learning to predict drug responses. Synthetic approach indicates drug target and protein-protein interaction could have the potential to improve the prediction performance of drug response. In this study, we propose a novel heterogeneous network-based method, named as HNMDRP, to accurately predict cell line-drug associations through incorporating heterogeneity relationship among cell line, drug and target. Compared to previous study, HNMDRP can make good use of above heterogeneous information to predict drug responses. The validity of our method is verified not only by plotting the ROC curve, but also by predicting novel cell line-drug sensitive associations which have dependable literature evidences. This allows us possibly to suggest potential sensitive associations among cell lines and drugs. Matlab and R codes of HNMDRP can be found at following https://github.com/USTC-HIlab/HNMDRP.
Prominent exostosis projecting from the occipital squama more substantial and prevalent in young adult than older age groups
Authors: Shahar David , Sayers Mark G. L.
Published: February 2018

Recently we reported the development of prominent exostosis young adults’ skulls (41%; 10–31 mm) emanating from the external occipital protuberance (EOP). These findings contrast existing reports that large enthesophytes are not seen in young adults. Here we show that a combination sex, the degree of forward head protraction (FHP) and age predicted the presence of enlarged EOP (EEOP) (n = 1200, age 18–86). While being a male and increased FHP had a positive effect on prominent exostosis, paradoxically, increase in age was linked to a decrease in enthesophyte size. Our latter findings provide a conundrum, as the frequency and severity of degenerative skeletal features in humans are associated typically with aging. Our findings and the literature provide evidence that mechanical load plays a vital role in the development and maintenance of the enthesis (insertion) and we suggest possible associations between aberrant loading of the EOP enthesis, sustained poor posture and EEOP formation. Accordingly, the higher numbers of individuals with EEOP in the 18-30 age group out of all cases examined raises concern about the future musculoskeletal health of this population and suggests a potential avenue for prevention intervention through posture improvement education.
Giant circular dichroism of large-area extrinsic chiral metal nanocrecents
Authors: Wang Yane , Qi Jiwei , Pan Chongpei , Wu Qiang , Yao Jianghong , Chen Zongqiang , Chen Jing , Li Yudong , Yu Xuanyi , Sun Qian , Xu Jingjun
Published: February 2018

In this work, we demonstrate the strong extrinsic chirality of the larger-area metal nanocrescents by experiments and simulations. Our results show that the metal nanocrescent exhibits giant and tunable circular dichroism (CD) effect, which is intensively dependent on the incident angle of light. We attribute the giant extrinsic chirality of the metal nanocrescent to the excitation efficiencies difference of localized surface plasmon resonance (LSPR) modes for two kinds of circularly polarized light at a non-zero incident angle. In experiment, the largest CD of 0.37 is obtained at the wavelength of 826 nm with the incident angle of 60°. Furthermore, the CD spectra can be tuned flexibly by changing the metal nanocrescent diameter. Benefitting from the simple, low-cost and mature fabrication process, the proposed large-area metal nanocrescents are propitious to application.
3D printed water-soluble scaffolds for rapid production of PDMS micro-fluidic flow chambers
Authors: Dahlberg Tobias , Stangner Tim , Zhang Hanqing , Wiklund Krister , Lundberg Petter , Edman Ludvig , Andersson Magnus
Published: February 2018

We report a novel method for fabrication of three-dimensional (3D) biocompatible micro-fluidic flow chambers in polydimethylsiloxane (PDMS) by 3D-printing water-soluble polyvinyl alcohol (PVA) filaments as master scaffolds. The scaffolds are first embedded in the PDMS and later residue-free dissolved in water leaving an inscription of the scaffolds in the hardened PDMS. We demonstrate the strength of our method using a regular, cheap 3D printer, and evaluate the inscription process and the channels micro-fluidic properties using image analysis and digital holographic microscopy. Furthermore, we provide a protocol that allows for direct printing on coverslips and we show that flow chambers with a channel cross section down to 40 μm × 300 μm can be realized within 60 min. These flow channels are perfectly transparent, biocompatible and can be used for microscopic applications without further treatment. Our proposed protocols facilitate an easy, fast and adaptable production of micro-fluidic channel designs that are cost-effective, do not require specialized training and can be used for a variety of cell and bacterial assays. To help readers reproduce our micro-fluidic devices, we provide: full preparation protocols, 3D-printing CAD files for channel scaffolds and our custom-made molding device, 3D printer build-plate leveling instructions, and G-code.
Induction of micronuclei by four cytostatic compounds in human hematopoietic stem cells and human lymphoblastoid TK6 cells
Authors: Hintzsche Henning , Montag Gracia , Stopper Helga
Published: February 2018

For mutagenicity testing, primary lymphocytes or mammalian cell lines are employed. However, the true target for carcinogenic action of mutagenic chemicals may be stem cells. Since hematopoietic cancers induced by chemical agents originate at the hematopoietic stem cell (HSC) stage and since one of the side effects of chemotherapeutic cancer treatment is the induction of secondary tumors, often leukemias, HSC may be a suitable cell system. We compared the sensitivity of HSC with the genotoxicity testing cell line TK6 for chromosomal mutations. HSC were less sensitive than TK6 cells for the genotoxic effects of the model genotoxins and chemotherapeutic agents doxorubicin, vinblastine, methyl methanesulfonate (MMS) and equally sensitive for mitomycin C (MMC). However, loss of viability after mitomycin C treatment was higher in HSC than in TK6 cells. Among the factors that may influence sensitivity for genomic damage, the generation or response to reactive oxygen species (ROS) and the effectiveness of DNA damage response can be discussed. Here we show that HSC can be used in a standard micronucleus test protocol for chromosomal mutations and that their sensitivity was not higher than that of a classical testing cell line.
DNA-based identification reveals illegal trade of threatened shark species in a global elasmobranch conservation hotspot
Authors: Feitosa Leonardo Manir , Martins Ana Paula Barbosa , Giarrizzo Tommaso , Macedo Wagner , Monteiro Iann Leonardo , Gemaque Romário , Nunes Jorge Luiz Silva , Gomes Fernanda , Schneider Horácio , Sampaio Iracilda , Souza Rosália , Sales João Bráullio , Rodrigues-Filho Luís Fernando , Tchaicka Lígia , Carvalho-Costa Luís Fernando
Published: February 2018

Here, we report trading of endangered shark species in a world hotspot for elasmobranch conservation in Brazil. Data on shark fisheries are scarce in Brazil, although the northern and northeastern regions have the highest indices of shark bycatch. Harvest is made primarily with processed carcasses lacking head and fins, which hampers reliable species identification and law enforcement on illegal catches. We used partial sequences of two mitochondrial genes (COI and/or NADH2) to identify 17 shark species from 427 samples being harvested and marketed on the northern coast of Brazil. Nine species (53%) are listed under some extinction threat category according to Brazilian law and international authorities (IUCN – International Union for Conservation of Nature; CITES – Convention on International Trade of Endangered Species of Wild Fauna and Flora). The number increases to 13 (76%) if we also consider the Near Threatened category. Hammerhead sharks are under threat worldwide, and composed 18.7% of samples, with Sphyrna mokarran being the fourth most common species among samples. As illegal trade of threatened shark species is a worldwide conservation problem, molecular identification of processed meat or specimens lacking diagnostic body parts is a highly effective tool for species identification and law enforcement.
Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice
Authors: Rabenstein Michael , Peter Franziska , Rolfs Arndt , Frech Moritz J.
Published: February 2018

Niemann-Pick disease Type C1 (NPC1) is a rare hereditary neurodegenerative disease. NPC1-patients suffer, amongst others, from ataxia, based on a loss of cerebellar Purkinje cells (PCs). Impaired expression/function of excitatory amino acid transporters (EAATs) are suspected of contributing to PC-degeneration in hereditary spinocerebellar ataxias (SCAs). Thus, we studied EAAT-expression and its impact to PC-activity in NPC1−/–mice. Western blot revealed reduced EAAT1, EAAT2, EAAT4, and βIII-spectrin levels in NPC1−/–mice. EAATs play a crucial role in synaptic transmission, thus we were interested in the impact of the reduced EAAT-expression on the function of PCs. Patch-clamp recordings of PCs showed no differences in the firing patterns of NPC1+/+and NPC1−/–mice using a low internal chloride concentration. Because EAAT4 also comprises a chloride permeable ion pore, we perturbed the chloride homeostasis using a high internal chloride concentration. We observed differences in the firing patterns of NPC1+/+and NPC1−/–mice, suggesting an impact of the altered EAAT4-expression. Additionally, the EAAT-antagonist DL-TBOA acts differently in NPC1+/+and NPC1−/–mice. Our data support the line of evidence that an altered EAAT-expression/function is involved in neurodegeneration of PCs observed in SCAs. Thus, we suggest that similar pathogenic mechanisms contribute the loss of PCs in NPC1.
Mid-infrared sensor for hydrocarbon monitoring: the influence of salinity, matrix and aging on hydrocarbon–polymer partitioning
Authors: Stach Robert , Pejcic Bobby , Heath Charles , Myers Matthew , Mizaikoff Boris
Published: February 2018

Mid-infrared sensors based on ATR spectroscopy provide a robust and reliable platform for the quantification of organic molecules dissolved in water.
Non-enzymatic portable optical sensors for microcystin-LR
Authors: Lvova Larisa , Guanais Gonçalves Carla , Prodi Luca , Lombardo Marco , Zaccheroni Nelsi , Viaggiu Emanuela , Congestri Roberta , Guzzella Licia , Pozzoni Fiorenzo , Di Natale Corrado , Paolesse Roberto
Published: February 2018

We report a selective non-enzymatic optical sensor for fast and low-cost detection of microcystin-LR and POCT estimation of water toxicity.
Gas-stimuli-responsive molecularly imprinted polymer particles with switchable affinity for target protein
Authors: Kitayama Yukiya , Isomura Manabu
Published: February 2018

Molecularly imprinted polymer particles bearing gas-responsive property was successfully prepared using functional initiator.
Surface functional DNA density control by programmable molecular defects
Authors: Chen Chong-You , Wang Chang-Ming , Chen Pai-Shan , Liao Wei-Ssu
Published: February 2018

Spatially programmable molecular-level defects via straightforward chemical lift-off manipulation leads to the direct regulation of complex surface DNA densities.
Copper-catalyzed decarboxylative regioselective synthesis of 1,5-disubstituted 1,2,3-triazoles
Authors: Kumar Navaneet , Ansari Mohd Yeshab , Kant Ruchir , Kumar Atul
Published: February 2018

A copper-catalyzed decarboxylative regioselective protocol for the synthesis of 1,5-disubstituted 1,2,3-triazoles via direct annulation of cinnamic acids with aryl azides has been developed. This is the first example of 1,5-disubstituted 1,2,3-triazoles using Cu(ii) as the catalyst, which were generally synthesized using a ruthenium(ii) catalyst.
A molecular dynamics study of the complete binding process of meropenem to New Delhi metallo-β-lactamase 1
Authors: Duan Juan , Hu Chuncai , Guo Jiafan , Guo Lianxian , Sun Jia , Zhao Zuguo
Published: February 2018

We have investigated the substrate-binding pathways of NDM-1viaunbiased molecular dynamics simulations and metadynamics.
Electrochemical nanoarchitectonics through polyaminobenzylamine–dodecyl phosphate complexes: redox activity and mesoscopic organization in self-assembled nanofilms
Authors: Lorenzo Agustín , Marmisollé Waldemar A. , Maza Eliana M. , Ceolín Marcelo , Azzaroni Omar
Published: February 2018

Hydrophobic stratified mesostructured films of amino-appended polyaniline and alkyl-phosphates present stable intrinsic electroactivity in neutral aqueous solutions.
The photolysis of α-hydroperoxycarbonyls
Authors: Liu Zhen , Nguyen Vinh Son , Harvey Jeremy , Müller Jean-François , Peeters Jozef
Published: February 2018

The atmospheric photolysis of α-hydroperoxycarbonyls is predicted to yield mainly enols and singlet O2; the atmospheric implications are discussed.
Room temperature chiral reorganization of interfacial assembly of achiral double-decker phthalocyanine
Authors: Wang Xiqian , Liu Chenxi , Jiang Yuying , Wang Chiming , Wang Tianyu , Bai Ming , Jiang Jianzhuang
Published: February 2018

Chiral reorganization with amplification of the Cotton effect is achieved at room temperature and atmospheric pressure in the solid-state.
Sub-15 nm CeO2 nanowires as an efficient non-noble metal catalyst in the room-temperature oxidation of aniline
Authors: da Silva Anderson G. M. , Batalha Daniel C. , Rodrigues Thenner S. , Candido Eduardo G. , Luz Sulusmon C. , de Freitas Isabel C. , Fonseca Fabio C. , de Oliveira Daniela C. , Taylor Jason G. , Córdoba de Torresi Susana I. , Camargo Pedro H. C. , Fajardo Humberto V.
Published: February 2018

We described the facile synthesis of sub-15 nm CeO2 nanowires for catalyzing the selective synthesis of nitrosobenzene from aniline at room temperature.
Hybrid mesoporous organosilicas with molecularly imprinted cavities: towards extended exposure of active amino groups in the framework wall
Authors: Huo Hang , Xu Xianzhu , Zhao Tingting , Li Yudong , Jiang Yanqiu , Lin Kaifeng
Published: February 2018

Towards extended exposure of active sites in the framework of ordered mesoporous materials via molecularly imprinted cavities.
Microfluidic label-free selection of mesenchymal stem cell subpopulation during culture expansion extends the chondrogenic potential in vitro
Authors: Yin Lu , Wu Yingnan , Yang Zheng , Tee Ching Ann , Denslin Vinitha , Lai Zhangxing , Lim Chwee Teck , Lee Eng Hin , Han Jongyoon
Published: February 2018

A microfluidic cell sorting based selective culture expansion method for mesenchymal stem cell improves cell yield and chondrogenic potential.
In situphoto-patterning of pressure-resistant hydrogel membranes with controlled permeabilities in PEGDA microfluidic channels
Authors: Decock Jérémy , Schlenk Mathias , Salmon Jean-Baptiste
Published: February 2018

We report the fabrication of highly permeable, pressure-resistant, hydrogel membranes in PEGDA channels, by spatially-resolved photo-polymerization.
Synthesis and green phosphorescent OLED device performance of cyanofluorene-linked phenylcarbazoles as host material
Authors: Wang Shuxin , Lee Chil Won , Lee Jun Yeob , Hwang Seok-Ho
Published: February 2018

A series of three isomeric bipolar host materials for green phosphorescent organic light-emitting diodes (PhOLEDs) was synthesized from a combination of cyanofluorene and N-phenylcarbazole moieties.
Inhibition of the expression of oncogene SRSF3 by blocking an exonic splicing suppressor with antisense oligonucleotides
Authors: Guo Jihua , Che Xiaoxuan , Wang Xiaole , Jia Rong
Published: February 2018

Inhibition of the expression of oncogene SRSF3 and cancer cell growth by blocking an exonic splicing suppressor in alternative exon 4 of SRSF3 with SR-3 antisense oligonucleotide.
Vortex-assisted low density solvent and surfactant based dispersive liquid–liquid microextraction for sensitive spectrophotometric determination of cobalt
Authors: Chaiyamate Patiwat , Seebunrueng Ketsarin , Srijaranai Supalax
Published: February 2018

The formation of a Co(II)–PV complex and the VALS-DLLME procedure.
Interaction of oxalic acid with methylamine and its atmospheric implications
Authors: Hong Yu , Liu Yi-Rong , Wen Hui , Miao Shou-Kui , Huang Teng , Peng Xiu-Qiu , Jiang Shuai , Feng Ya-Juan , Huang Wei
Published: February 2018

Oxalic acid, which is one of the most common dicarboxylic acids, is expected to be an important component of atmospheric aerosols.
Pathway complexity in the self-assembly of a zinc chlorin model system of natural bacteriochlorophyll J-aggregates
Authors: Ogi Soichiro , Grzeszkiewicz Charlotte , Würthner Frank
Published: February 2018

Self-assembly studies of a model compound of bacteriochlorophyll revealed the formation of nanoparticles as off-pathway and nanofibers as on-pathway products.
Partitioning-dependent conversion of polyelectrolyte assemblies in an aqueous two-phase system
Authors: Ma Qingming , Yuan Hao , Song Yang , Chao Youchuang , Mak Sze Yi , Shum Ho Cheung
Published: February 2018

The partitioning-dependent assembly of polyelectrolytes in an aqueous-two phase system can be converted from microcapsules to microgel particles via pH changes.
Recent advances in electrolytes for quantum dot-sensitized solar cells
Authors: Song Han , Rao Huashang , Zhong Xinhua
Published: February 2018

A comprehensive overview was shown on recent advances in electrolytes or hole-transport materials for quantum dot-sensitized solar cells (QDSCs).
Transfer of functional thermoresponsive poly(glycidyl ether) coatings for cell sheet fabrication from gold to glass surfaces
Authors: Heinen Silke , Rackow Simon , Cuellar-Camacho Jose Luis , Donskyi Ievgen S. , Unger Wolfgang E. S. , Weinhart Marie
Published: February 2018

Thermoresponsive poly(glycidyl ether) coatings prepared by self-assembly of a block-copolymer on glass facilitate cell sheet fabrication with human dermal fibroblasts.
Design and synthesis of a nonlinear optical material BaAl4S7with a wide band gap inspired from SrB4O7
Authors: Mei Dajiang , Jiang Jianqiao , Liang Fei , Zhang Shiyan , Wu Yuandong , Sun Congting , Xue Dongfeng , Lin Zheshuai
Published: February 2018

Inspired by the oxide SrB4O7with the largest known band gap among all borate crystals, the chalcogenide BaAl4S7with similar structure may possess attractive NLO properties.
A multifunctional MOF as a recyclable catalyst for the fixation of CO2 with aziridines or epoxides and as a luminescent probe of Cr(vi)
Authors: Cao Chun-Shuai , Shi Ying , Xu Hang , Zhao Bin
Published: February 2018

A multifunctional metal-organic framework (1) can serve as an efficient and recyclable catalysts for the conversion of CO2 with aziridines or epoxides. Furthermore, the material can also act as a recyclable luminescent probe for Cr(vi) species among twenty anions.
Facile synthesis of starch-based nanoparticle stabilized Pickering emulsion: its pH-responsive behavior and application for recyclable catalysis
Authors: Qi Liang , Luo Zhigang , Lu Xuanxuan
Published: February 2018

Starch-based nanoparticles participate in the stimulus-responsive Pickering emulsion for recyclable catalysis.
Direct lead isotopic analysis of bioethanol by means of multi-collector ICP-mass spectrometry with a total consumption sample introduction system
Authors: Sánchez Carlos , Bolea-Fernandez Eduardo , Costas-Rodríguez Marta , Lienemann Charles-Philippe , Todolí Jose-Luis , Vanhaecke Frank
Published: February 2018

A method has been developed for the direct (no sample pretreatment and/or isolation of the target element from the sample matrix) Pb isotopic analysis of bioethanol via multi-collector ICP-mass spectrometry (MC-ICP-MS).
Multifunctional vanadium nitride@N-doped carbon composites for kinetically enhanced lithium–sulfur batteries
Authors: Zhu Lin , Li Chuanchuan , Ren Wenjiao , Qin Mingyang , Xu Liqiang
Published: February 2018

VN@N-doped carbon composite was fabricated as sulfur host to enhance the redox kinetics of Li–S batteries, which displayed remarkable electrochemical performances.
New chiral amino alcohol ligands for catalytic enantioselective addition of diethylzincs to aldehydes
Authors: Sappino Carla , Mari Alessandra , Mantineo Agnese , Moliterno Mauro , Palagri Matteo , Tatangelo Chiara , Suber Lorenza , Bovicelli Paolo , Ricelli Alessandra , Righi Giuliana
Published: February 2018

New amino alcohol ligands suitable for immobilization on nanoparticles were successfully used in catalytic enantioselective additions of diethylzinc to aldehydes.
Planar chiral [2.2]paracyclophane-based phosphine–phenols: use in enantioselective [3 + 2] annulations of allenoates andN-tosylimines
Authors: Kitagaki Shinji , Nakamura Kento , Kawabata Chiharu , Ishikawa Asuna , Takenaga Naoko , Yoshida Keisuke
Published: February 2018

Planar chiral [2.2]paracyclophane-based phosphine–phenols efficiently catalyze the [3 + 2] annulation ofN-tosylimines and allenoate.
Nitrogen-doped hierarchical porous carbon derived from a chitosan/polyethylene glycol blend for high performance supercapacitors
Authors: Ba Yuerong , Pan Wei , Pi Shangchao , Zhao Yaomin , Mi Liwei
Published: February 2018

NHPC was prepared from a low cost chitosan/PEG blend by a facile method for high performance supercapacitors.
Discovery of N-cyclobutylaminoethoxyisoxazole derivatives as novel sigma-1 receptor ligands with neurite outgrowth efficacy in cells
Authors: Sun Hao , Wang Yun-Jie , Shi Wen-Wen , Yang Fan , Tang Jie , Pang Tao , Yu Li-Fang
Published: February 2018

Herein we reported a series of 14 novel derivatives based on the N-cyclobutylaminoethoxyisoxazole scaffold.