bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cebulantin, a Cryptic Lanthipeptide Antibiotic Uncovered Using Bioactivity‐Coupled HiTES
Authors: Moon Kyuho , Xu Fei , Seyedsayamdost Mohammad R. 
Published: March 2019

AbstractThe majority of natural product biosynthetic gene clusters in bacteria are silent under standard laboratory growth conditions, making it challenging to uncover any antibiotics that they may encode. Herein, bioactivity assays are combined with high‐throughput elicitor screening (HiTES) to access cryptic, bioactive metabolites. Application of this strategy in Saccharopolyspora cebuensis, with inhibition of Escherichia coli growth as a read‐out, led to the identification of a novel lanthipeptide, cebulantin. Extensive NMR spectroscopic analysis allowed the elucidation of the structure of cebulantin. Subsequent bioactivity assays revealed it to be an antibiotic selective for Gram‐negative bacteria, especially against Vibrio species. This approach, referred to as bioactivity‐HiTES, has the potential to uncover cryptic metabolites with desired biological activities that are hidden in microbial genomes.
Phenology models using herbarium specimens are only slightly improved by using finer‐scale stages of reproduction
Authors: Ellwood Elizabeth R. , Primack Richard B. , Willis Charles G. , HilleRisLambers Janneke 
Published: March 2019

Premise of the StudyHerbarium specimens are increasingly used to study reproductive phenology. Here, we ask whether classifying reproduction into progressively finer‐scale stages improves our understanding of the relationship between climate and reproductive phenology.MethodsWe evaluated Acer rubrum herbarium specimens across eastern North America, classifying them into eight reproductive phenophases and four stages of leaf development. We fit models with different reproductive phenology categorization schemes (from detailed to broad) and compared model fits and coefficients describing temperature, elevation, and year effects. We fit similar models to leaf phenology data to compare reproductive to leafing phenology.ResultsFiner‐scale reproductive phenophases improved model fits and provided more precise estimates of reproductive phenology. However, models with fewer reproductive phenophases led to similar qualitative conclusions, demonstrating that A. rubrum reproduces earlier in warmer locations, lower elevations, and in recent years, as well as that leafing phenology is less strongly influenced by temperature than is reproductive phenology.DiscussionOur study suggests that detailed information on reproductive phenology provides a fuller understanding of potential climate change effects on flowering, fruiting, and leaf‐out. However, classification schemes with fewer reproductive phenophases provided many similar insights and may be preferable in cases where resources are limited.
Self‐assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer
Authors: Li Cai , Li Tianzhong , Huang Linfeng , Yang Mengsu , Zhu Guangyu 
Published: March 2019

AbstractDNA damage repair through the nucleotide excision repair (NER) pathway is one of the major reasons for the decreased antitumor efficacy of platinum‐based anticancer drugs that have been widely applied in the clinic. Inhibiting the intrinsic NER function may enhance the antitumor activity of cisplatin and conquer cisplatin resistance. Herein, we report the design, optimization, and application of a self‐assembled lipid nanoparticle (LNP) system to simultaneously deliver a cisplatin prodrug together with siRNA targeting endonuclease xeroderma pigmentosum group F (XPF), a crucial component in the NER pathway. The LNP is able to efficiently encapsulate both the platinum prodrug and siRNA molecules with a tuned ratio. Both platinum prodrug and XPF‐targeted siRNA are efficiently carried into cells and released; the former damages DNA and the latter specifically downregulates both mRNA and protein levels of XPF to potentiate the platinum drug, leading to enhanced expression levels of apoptosis markers and improved cytotoxicity in both cisplatin‐sensitive and ‐resistant human lung cancer cells. Our results demonstrate an effective approach to utilize a multi‐targeted nanoparticle system that can specifically silence an NER‐related gene to promote apoptosis induced by cisplatin, especially in cisplatin‐refractory tumors.
Synergy of Single‐ion Conductive and Thermo‐responsive Copolymer Hydrogels Achieving Anti‐Arrhenius Ionic Conductivity
Authors: Guo Shanshan , Lei Rongyuan , Liang Xinmiao , Liu Jiyan , Liu Xueqing , Gao Shuyu , Peng Xianghong , Bian Shilong , Chen Yangwei , Jin Yi , Cai Shaojun , Liu Zhihong , Feng Jiwen 
Published: March 2019

AbstractArtificial intelligence sensations have aroused scientific interest from electronic conductors to bio‐inspired ionic conductors. The conductivity of electrons decreases with increasing temperature, while the ionic conductivity agrees with an Arrhenius equation or a modified Vogel–Tammann–Fulcher (VTF) equation. Herein, thermo‐responsive poly(N‐isopropyl amide) (PNIPAm) and single‐ion‐conducting poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic lithium salt) (PAMPSLi) were copolymerized via a facile radical polymerization to demonstrate a very intriguing anti‐Arrhenius ionic conductivity behaviour during thermally induced volume‐phase transition. These smart hydrogels presented very promising scaffolds for architecting flexible, wearable or advanced functional ionic devices.
Multiple response optimization of alkaline pretreatment of sisal fiber (Agave sisalana) assisted by ultrasound
Authors: Brito Jeane Q. A. , Dias Fábio De S. , Cunha Silvio , Ramos Luiz P. , Teixeira Leonardo S. G. 
Published: March 2019

AbstractA procedure for the alkaline pretreatment of sisal fiber assisted by ultrasound was optimized to obtain a higher solubilization of hemicellulose and the removal of lignin with cellulose fraction maintenance. A full factorial design 23 was used for the evaluation of the effects of the variables (sonication time, NaOH concentration, and sonication amplitude) on the pretreatment. The optimal values for the variables using the Doehlert matrix for the sonication time, NaOH concentration, and sonication amplitude were 27 min, 4.1% (m/v), and 50%, respectively. The X‐ray diffractometry and scanning electron microscopy analyses, after pretreatment, showed changes in chemical structure and morphology due to the removal of 82% of hemicellulose and 86% of lignin from sisal fiber. The soft reaction conditions and relatively short times demonstrated the effectiveness of the combined action of ultrasound with alkaline pretreatment to improve the accessibility to cellulose in this important step of the ethanol production process from biomass.
Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK‐rearranged non‐small‐cell lung cancer
Authors: Song Peng , Zhang Fanshuang , Li Yan , Yang Guangjian , Li Wenbin , Ying Jianming , Gao Shugeng 
Published: March 2019

AbstractBackgroundTP53 mutations are the most prevalent mutations detected in non‐small‐cell lung cancer (NSCLC) and have been revealed as a negative prognostic biomarker of outcome. The impact of concomitant TP53 mutations in ALK‐rearranged NSCLC remains uncertain.MethodsTumor samples from 64 ALK‐rearranged NSCLC patients receiving crizotinib treatment were subjected to next‐generation sequencing (NGS) to identify TP53 mutational status. The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed.ResultsAmong the 64 ALK‐rearranged patients, 15 (23.4%) patients showed a TP53 mutation. Of these, six cases had disruptive mutations and nine with nondisruptive mutations. The objective response rate (ORR) and disease control rate (DCR) for TP53 mutated patients were both significantly lower compared with those for TP53 wild‐type patients (p = 0.003 and 0.023, respectively). A significantly shorter progression‐free survival (PFS) was found in TP53 mutated patients compared with TP53 wild‐type patients (p = 0.045). Nondisruptive TP53 mutations were associated with a shorter PFS in comparison with disruptive TP53 mutations in ALK‐rearranged patients (p = 0.069). When nondisruptive TP53 mutated patients were in comparison with TP53 wild‐type patients, nondisruptive TP53 mutations were associated with a significant reduced PFS (p = 0.003).ConclusionsTP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK‐rearranged NSCLC patients.
Overexpression of long non‐coding RNA NORAD promotes invasion and migration in malignant melanoma via regulating the MIR‐205‐EGLN2 pathway
Authors: Chen Yong , Cao Ke , Li Jingjing , Wang Aijun , Sun Lichun , Tang Jintian , Xiong Wei , Zhou Xiao , Chen Xiang , Zhou Jianda , Liu Yan 
Published: March 2019

AbstractGrowing evidence suggests that long non‐coding RNAs NORAD and miR‐205 play a significant role in regulating cancer progression and metastasis. In this study, high expression of NORAD was firstly observed in melanoma tissues and human malignant melanoma cell lines, our aim was to study the interaction of them in the process of invasion and migration of malignant melanoma cells. NORAD, miR‐205, and EGLN2 mRNA level in MM cells was detected by qRT‐PCR. In situ hybridization (ISH) was performed to detect NORAD expression in MM tissues specimens. Effects of NORAD and miR‐205 on Prolyl hydroxylase 2 (EGLN2) expression was explored by western blot in MM cells line. Dual‐luciferase reporter assay was performed to verify the interaction relationship between NORAD and miR‐205, as well as, miR‐205 and EGLN2. Transwell assay was conducted to explore the effects of NORAD and miR‐205 in vitro. Xenografts in nude mice experiment were used to confirm the role of NORAD and miR‐205 in vivo. In vitro, NORAD knockdown significantly inhibited migration and invasion of malignant melanoma cells and elevated the expression of miR‐205, there was an interaction between miR‐205 and NORAD in the RNA‐induced silencing complex. Upregulation of miR‐205 induced significant inhibition of migratory and invasive ability compared with the scrambled control. However, downregulating NORAD largely reversed this effect. Furthermore, the regulatory effects of miR‐205 on EGLN2 levels and the induction of endoplasmic reticulum stress were reversed by NORAD. In vivo, deletion of miR‐205 induced tumor growth in nude mice. NORAD may play critical roles in tumorigenesis and progression of malignant melanoma by regulating of the miR‐205‐EGLN2 pathway, and may serve as a new therapeutic target.
Antitumor activity of a 5T4 targeting antibody drug conjugate with a novel payload derived from MMAF via C‐Lock linker
Authors: Shi Baoying , Wu Min , Li Zhaohui , Xie Zhangming , Wei Xiaoyue , Fan Jiansheng , Xu Yingchun , Ding Ding , Akash Sajid Hamid , Chen Shuqing , Cao Sheldon 
Published: March 2019

AbstractAntibody‐drug conjugates (ADCs) belong to a promising class of biopharmaceuticals in which target‐killing of tumor cells was achieved by marrying the potency of the cytotoxic payload with the tumor specificity of the antibody. Here we developed a novel ADC (ZV0508) that targets 5T4 oncofetal antigen, which is overexpressed in many carcinomas on both bulk tumor cells and cancer stem cells. A novel cytotoxic payload called Duostatin‐5 (Duo‐5) which was derived from monomethyl auristatin F (MMAF) was attached to a 5T4 targeting antibody (ZV05) by interchain cysteine cross‐linking conjugation via a disubstituted C‐Lock linker. We have investigated the antitumor efficacy of ZV0508 by in vitro and in vivo studies, and compared its antitumor activity with ZV05‐mcMMAF (ZV0501), in which MMAF was linked via a conventional noncleavable maleimidocaproyl linker. As results, ZV0508 exhibited ideal antiproliferative effects through blocking cell cycle and inducing cell apoptosis. The in vivo studies revealed that both ZV0501 and ZV0508 exhibited excellent antitumor activities even at a single dose. Although ZV0508 was inferior to ZV0501 in vitro, it elicited more durable antitumor responses than ZV0501 in vivo. The superior in vivo activity of ZV0508 may be due to the combined use of the disubstituted C‐Lock linker and the novel payload Duo‐5, resulting in a more stable and potent ADC. Taken together, these data suggest ZV0508 is a worthy candidate for the treatment of 5T4 positive cancers.
Ectopic expression of human airway trypsin‐like protease 4 in acute myeloid leukemia promotes cancer cell invasion and tumor growth
Authors: Yan Ruhong , Liu Meng , Hu Yae , Wang Lina , Wang Can , Jiang Yizhi , Zhou Quansheng , Qi Xiaofei , Dong Ningzheng , Wu Qingyu 
Published: March 2019

AbstractTransmembrane serine proteases have been implicated in the development and progression of solid and hematological cancers. Human airway trypsin‐like protease 4 (HAT‐L4) is a transmembrane serine protease expressed in epithelial cells and exocrine glands. In the skin, HAT‐L4 is important for normal epidermal barrier function. Here, we report an unexpected finding of ectopic HAT‐L4 expression in neutrophils and monocytes from acute myeloid leukemia (AML) patients. Such expression was not detected in bone marrow cells from normal individuals or patients with chronic myeloid leukemia, acute lymphocytic leukemia and chronic lymphocytic leukemia. In AML patients who underwent chemotherapy, persistent HAT‐L4 expression in bone marrow cells was associated with minimal residual disease and poor prognostic outcomes. In culture, silencing HAT‐L4 expression in AML–derived THP‐1 cells by short hairpin RNAs inhibited matrix metalloproteinase‐2 activation and Matrigel invasion. In mouse xenograft models, inhibition of HAT‐L4 expression reduced the proliferation and growth of THP‐1 cell–derived tumors. Our results indicate that ectopic HAT‐L4 expression is a pathological mechanism in AML and that HAT‐L4 may be used as a cell surface marker for AML blast detection and targeting.
Smoking can increase nasopharyngeal carcinoma risk by repeatedly reactivating Epstein‐Barr Virus: An analysis of a prospective study in southern China
Authors: Hu Ting , Lin Chu‐Yang , Xie Shang‐Hang , Chen Geng‐Hang , Lu Yu‐Qiang , Ling Wei , Huang Qi‐Hong , Liu Qing , Cao Su‐Mei 
Published: March 2019

AbstractBackgroundThe association between smoking and nasopharyngeal carcinoma (NPC) is still uncertain. The aim of this study was to validate smoking effect on NPC and explore if smoking can induce NPC by persistently reactivating EBV in long‐term based on a prospective cohort design.MethodsA NPC screening cohort with 10 181 eligible residents in Sihui city, southern China was conducted from 2008 to 2015. The smoking habit was investigated through the trained interviewers and EBV antibodies (VCA‐IgA, EBNA1‐IgA) as screening markers were tested periodically. New NPC cases were identified through local cancer registry. Cox's regression model was used to estimate the adjusted hazard ratios (aHRs) of smoking on NPC incidence. In the non‐NPC participants, the associations between smoking and EBV seropositivity in different periods were assessed by logistic regression and generalized estimating equations (GEE).ResultsWith a median of 7.54 years, 71 NPCs were diagnosed ≥1 year after recruitment. Compared with never smokers, the aHRs of developing NPC among ever smokers were 3.00 (95%CI: 1.46‐6.16). Stratified by sex, the HRs of ever smoking were 2.59 (95%CI: 1.07‐6.23) for male and 3.75 (95%CI: 1.25‐11.20) for female, respectively. Among the non‐NPC individuals, ever smoking was not only associated with EBV seropositivity at baseline, but also in the 3‐5 years of follow up, with adjusted odds ratios (aORs) of 1.68 (95%CI: 1.29‐2.18) for VCA‐IgA and 1.92 (95%CI: 1.42‐2.59) for EBNA1‐IgA. Among the smokers who were tested EBV antibodies at least twice, the similar results were obtained using GEE.ConclusionSmoking could significantly increase the long‐term risk of NPC in southern China, partly by persistently reactivating EBV.
Modeling and Validating Fixed‐Bed Reactors: A State‐of‐the‐Art Review
Authors: Stegehake Carolin , Riese Julia , Grünewald Marcus 
Published: March 2019

AbstractModeling of heat and mass transfer in fixed‐bed reactors for heterogeneously catalyzed gas phase reactions is possible using different methods. Homogeneous and heterogeneous continuum models as well as particle resolved modeling of fixed‐bed reactors show high potential for application. Considering those approaches, advantages and disadvantages as well as underlying assumptions and boundary conditions are discussed. Additionally, methods for experimental validation are presented and discussed focusing on the two‐dimensional homogeneous models.
The sucked surgical sponge: Rare case of Gossypiboma after vaginal hysterectomy
Authors: Oehme Florian , Rühle Annika , Stickel Michael , Metzger Jürg , Gass Jörn‐Markus 
Published: March 2019

Key Clinical MessageRetained surgical material needs to be a possible differential diagnosis for patients presenting with unspecific abdominal pain after especially cavitary emergency surgery. Even though international standard checklists concerning sponge handling and counting exist, RSM could never be ruled out completely.
Nanoparticle Ripening : A Versatile Approach for the Size and Shape Control of Metallic Iron Nanoparticles
Authors: Lacroix Lise‐Marie , Meffre Anca , Gatel Christophe , Fazzini Pier‐Francesco , Lachaize Sébastien , Respaud Marc , Chaudret Bruno 
Published: March 2019

AbstractA novel approach for the synthesis of Fe(0) nanoparticles (NPs) with tunable sizes and shapes is reported. Ultrasmall Fe(0) NPs were reacted under mild conditions in the presence of a mixture of palmitic acid and amine ligands. These NPs acted not only as preformed seeds but also as an internal iron(II) source that was produced by the partial dissolution of the NPs by the acid. This fairly simple approach allows the strict separation of the nucleation and the growth steps. By changing the acid concentration, a fine tuning of the relative ratio between the remaining Fe(0) seeds and the iron(II) reservoir was achieved, giving access to both size (from 7 to 20 nm) and shape (spheres, cubes or stars) control. The partial dissolution of the ultrasmall Fe(0) NPs into iron(II) source and the successive growth was further studied by using combined TEM and Mössbauer spectroscopy. The successive corrosion, coalescence, and ripening observed could be understood in the framework of an environment‐dependent growth model.
Preparation and Measuring of Brain GABAAR‐coupled Cl‐/HCO3‐‐ Activity for Integral Assessment of Aquatic Toxicity
Authors: Menzikov Sergey A. 
Published: March 2019

AbstractThe wide use of aromatic hydrocarbons in various industries is having a negative effect on the environment and human health. Therefore, a key focus of current toxicology is the development and use of protein reporters with high sensitivity to various aromatic hydrocarbons (including phenolics and drugs). One molecular target for a wide range of pharmacology drugs and aromatic hydrocarbons (including phenol) is the neuronal GABAAR‐coupled Cl‐/HCO3‐‐ATPase. In this study, we present a protocol for isolation of the membrane‐bound Cl‐/HCO3‐‐ATPase from neuronal cells of animal brain. We then describe an uncomplicated in vitro method for measuring this ATPase activity for assessment of toxicity after interaction of this protein with an aquatic sample. This assay offers new avenues for using the Cl‐/HCO3‐‐ATPase as a biomarker of water toxicity. This biotest is efficient, requires very little of the enzyme, and retains its sensitivity at low levels of various compounds. © 2019 by John Wiley & Sons, Inc.
Selective Transformations of Triglycerides into Fatty Amines, Amides, and Nitriles by using Heterogeneous Catalysis
Authors: Jamil Md. A. R. , Siddiki S. M. A. Hakim , Touchy Abeda Sultana , Rashed Md. Nurnobi , Poly Sharmin Sultana , Jing Yuan , Ting Kah Wei , Toyao Takashi , Maeno Zen , Shimizu Ken‐ichi 
Published: March 2019

AbstractThe use of triglycerides as an important class of biomass is an effective strategy to realize a more sustainable society. Herein, three heterogeneous catalytic methods are reported for the selective one‐pot transformation of triglycerides into value‐added chemicals: i) the reductive amination of triglycerides into fatty amines with aqueous NH3 under H2 promoted by ZrO2‐supported Pt clusters; ii) the amidation of triglycerides under gaseous NH3 catalyzed by high‐silica H‐beta (Hβ) zeolite at 180 °C; iii) the Hβ‐promoted synthesis of nitriles from triglycerides and gaseous NH3 at 220 °C. These methods are widely applicable to the transformation of various triglycerides (C4–C18 skeletons) into the corresponding amines, amides, and nitriles.
Surveying pasture communities in diachronic analyses by 3D models: the diachronic canopy variation model
Authors: Passalacqua Nicodemo G. , Muzzupappa Maurizio , Lagudi Antonio , Bernardo Liliana , Schettino Aldo , Gargano Domenico 
Published: March 2019

AbstractAboveground biomass (AGB) is a parameter commonly used for assessing and monitoring primary productivity of grassland communities. Destructive AGB measurements, although accurate, are time‐consuming and do not allow for repeated measurements as required by monitoring protocols. Structure‐from‐motion (SfM) photogrammetry has been proved to be a reliable tool for rapid and not destructive AGB estimations in grass systems. Three‐dimensional (3D) models of fourteen 1 × 1 m2 pasture plots were reconstructed and AGB volume measured under several measurement settings. Volume‐based AGB measures were regressed to AGB values resulting from destructive methods to identify the measurement settings that show the best fit. Furthermore, 3D models of four mountain pasture plots were reconstructed in May, July, and August. Models relative to the same plot were aligned and their relative difference measured to produce a diachronic canopy variation model (DCVM). On the measured volume (Vd), the coefficient of density (cρ) was applied to adjust the volume values (Vadj) in relation to variation due to different DCVM point densities. The measurement setting for AGB volume estimations strongly influenced their correlation with traditional AGB scores. The best fit was obtained selecting 1 mm grid cell size and minimum point height distance. Such options were then selected to measure the DCVM. Adjusted volumes were fully correlated with the average point distance. Three plots revealed higher rates of AGB in the spring compared to summer season, as justified by the summer aridity constraints affecting vegetation productivity in Mediterranean areas. In one plot, we found an anomalous seasonal pattern, showing an AGB reduction in spring, which can be correlated with grazing, that promoted a subsequent increment in summer. Our study indicates that image‐based photogrammetric techniques allow for reliable non‐destructive measurements of surface biomass in diachronic analyses, offering a valuable tool for evaluating occurrence, magnitude, and spatial patterns of variations of community primary productivity over time. Diachronic canopy variation model produced congruent patterns of inter‐seasonal canopy variations proving to be a useful tool for analyzing local disturbance to vegetation canopy caused by grazing.
Rapid Electrochemical Detection of Vanillin in Natural Vanilla
Authors: Chen Lifu , Chaisiwamongkhol Korbua , Chen Yuqi , Compton Richard G. 
Published: March 2019

AbstractA commercially available and disposable multiwalled carbon nanotube screen‐printed electrode (CNT‐SPE) was employed to detect and determine vanillin compounds in natural vanilla. The voltammetric behaviour of vanillin at the CNT‐SPE is examined and shown to be a sensitive method for quantifying vanillin. Linear calibration for vanillin in the range of 2.5–750 μM was obtained with a detection limit of 1.03 μM and a quantification limit of 3.44 μM. The developed method comprises a simple sample preparation method and a sensitive electrochemical detection for the quantification of vanillin in vanilla pods and is an easy and simple procedure for manufacturers and consumers.