bluuebunny/crossref_metadata_2025 huggingface dataset:
Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo
Authors: Wei Xiaoyu , Chen Yatang , Huang Wenxiang
Published: May 2018

Liver fibrosis remains a major cause of morbidity and mortality with a complicated etiology and notorious complications, but there is a lack of efficacious therapeutics. Epithelial to mesenchymal transition (EMT) has a central role in the course of liver fibrosis, and thus, prevention of the development of EMT may control and even reverse liver fibrosis. This study aimed to examine the beneficial effect of ginsenoside Rg1, a phrenological active component isolated from Ginseng, and interrogate the mechanism in vitro and in vivo, with a focus on transforming growth factor‐β (TGF‐β)/Smad and Nrf2‐mediated signaling pathways. We employed a TGF‐β‐induced EMT model in HSC‐T6 cells and CCl4‐induced liver fibrosis in animal. We found that ginsenoside Rg1 significantly reduced cell proliferation and reversed transforming growth factor‐β (TGF‐β)‐induced EMT in HSC‐T6 cells; and ginsenoside Rg1 induced cell apoptosis, Ginsenoside Rg1 decreased the cellular level of collagen I and III in HSC‐T6 cells, indicating the amelioration of fibrosis. We showed that ginsenoside Rg1 reduced cellular reactive oxygen species (ROS). We also observed similar beneficial effects of ginsenoside Rg1 in vivo. The data showed that ginsenoside Rg1 decreased the level of alanine aminotransferase and aspartate aminotransferase, and collage type IV (IV‐C), hyaluronic acid, and laminin in carbon tetrachloride (CCl4)‐induced liver fibrotic model. Mechanistically, we showed that ginsenoside Rg1 tuned down the TGF‐β/Smad and stimulated Nrf‐2 nuclear translocation, which could explain the beneficial effects. In aggregate, our results demonstrate that ginsenoside Rg1 exhibits a protective effect on liver fibrosis via suppressing EMT and cellular ROS level. © 2018 BioFactors, 44(4):327–335, 2018
Predictive impact of the inflammation‐based indices in colorectal cancer patients with adjuvant chemotherapy
Authors: Tao Yong , Ding Lei , Yang Guan Gen , Qiu Jian Ming , Wang Dong , Wang Hongtao , Fu Chao
Published: May 2018

Increasing evidences reported that cancer‐triggered inflammation was associated with survival prognosis from colorectal cancer (CRC). However, the comprehensive effects of inflammatory‐based coNLR‐PLR that combines neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) rarely remain to be determined during chemotherapy. We retrospectively analyzed clinical data and baseline laboratory parameters from 153 colorectal cancer patients who underwent palliative adjuvant chemotherapy between January 2009 to January 2012. Receiver operating characteristic (ROC) curves and linear regression analyzed the predictive ability of NLR, and PLR for calculating the score of coNLR‐PLR. Overall survival (OS) and recurrence‐free survival (RFS) rates were estimated using the Kaplan‐Meier method and analyzed by the Cox proportional hazards model in univariate and multivariate analysis. The optimal cut‐off value of NLR and PLR was 2.24 and 186 by the ROC analysis. Kaplan‐Meier method showed that patients with high coNLR‐PLR score was associated with poorer OS and RFS (all P < .05). In univariate and multivariate analysis, it obtained that the coNLR‐PLR severed as a strong independent prognostic factor for OS and RFS (all P < .05). These results highlight that coNLR‐PLR index severed as a strong predictor of prognosis biomarker in CRC patients receiving adjuvant chemotherapy. Furthermore, its assessment could contribute to accurately predicting prognosis after chemotherapy in clinical practice.
The Use of Cyclometalated NHCs and Pyrazoles for the Development of Fully Efficient Blue PtII Emitters and Pt/Ag Clusters
Authors: Arnal Lorenzo , Fuertes Sara , Martín Antonio , Sicilia Violeta
Published: May 2018

New bis‐pyrazole complexes [Pt(C^C*)(RpzH)2]X, containing a cyclometalated N‐heterocyclic carbene ligand (HC^C*=1‐(4‐(ethoxycarbonyl)phenyl)‐3‐methyl‐1H‐imidazol‐2‐ylidene) were prepared as chloride (X=Cl−, RpzH: 3,5‐Me2pzH 1 a, 4‐MepzH 2 a, pzH 3 a), perchlorate (X=ClO4−, 1 b–3 b), or hexafluorophosphate (X=PF6−, RpzH: 3,5‐Me2pzH 1 c) salts. The X‐ray structure of 1 a showed that the Cl− anion is trapped by the cation through two N−H⋅⋅⋅Cl bonds. In solution of methanol, acetone and THF at RT, 1 a–3 a coexist in equilibrium with the corresponding [PtCl(C^C*)(RpzH)] (B) and RpzH species. In CH2Cl2, this equilibrium takes place just for 2 a and 3 a, but it is completely shifted to the left at 243 and 223 K for 2 a and 3 a, respectively. The low‐lying absorption and emission bands were assigned to intraligand (ILCT) charge transfer on the NHC group. Quantum yield measurements in PMMA films revealed that 1 b, 2 b and 1 c are amongst the most efficient blue‐light emitters, with values up to 100 %. Proton abstraction from the coordinated 3,5‐Me2pzH in 1 b by NEt3 and replacement by Ag+ afforded a neutral [Pt2Ag2] cluster containing Pt→Ag dative bonds.
Different Selectivities in the Insertions into C(sp2)−H Bonds: Benzofulvenes by Dual Gold Catalysis Competition Experiments
Authors: Plajer Alex J. , Ahrens Lukas , Wieteck Marcel , Lustosa Danilo M. , Babaahmadi Rasool , Yates Brian , Ariafard Alireza , Rudolph Matthias , Rominger Frank , Hashmi A. Stephen K.
Published: May 2018

An unprecedented, often almost quantitative access to tricyclic aromatic compounds by dual gold catalysis was developed. This synthetic route expands the scope of benzofulvene derivatives through a C(sp2)−H bond insertion in easily available starting materials. The insertion takes place with an exclusive chemoselectivity with respect to the competing aromatic C−H positions. A bidirectional synthesis with two competing ortho‐aryl C−H bonds in the selectivity‐determining step also shows perfect selectivity; this result is explained by a computational investigation of the two conceivable intermediates. The intramolecular competition of two non‐equivalent aryl C−H bonds with a benzylic methyl group also showed perfect selectivity.
Synthesis and Characterization of 4‐(1,2,4‐Triazole‐5‐yl)furazan Derivatives as High‐Performance Insensitive Energetic Materials
Authors: Xu Zhen , Cheng Guangbin , Yang Hongwei , Zhang Jiaheng , Shreeve Jean'ne M.
Published: May 2018

3‐Nitro‐4‐(5‐nitro‐1,2,4‐triazol‐3‐yl)furazan (2), N,N′‐bis(trinitroethyl)‐3,5′‐diamino‐4‐(1,2,4‐triazol‐3‐yl)furazan (3), N,N′‐bis(trinitroethyl)‐3,5′‐dinitramino‐4‐(1,2,4‐triazol‐3‐yl)furazan (4) and eighteen nitrogen‐rich salts (5 a, 5 b, 5 d–5 i, 5 g‐1, 6 a–6 i) were designed and synthesized. These 4‐(1,2,4‐triazole‐5‐yl)furazan derivatives were fully characterized by IR and NMR spectra, elemental analysis, and differential scanning calorimetry (DSC). The solid‐state structures of 2, 5 d, 5 e, 5 h, 5 g‐1, 6 g, and 6 i were confirmed via single crystal X‐ray analysis. Detonation performance (detonation velocities and pressures) of these energetic compounds was evaluated and the impact and friction sensitivities were measured using standard BAM technology. Some of the compounds, for example, 2 (D: 9152 m s−1, P=37.1 GPa) and 4 (D: 9355 m s−1, P=40.1 GPa) exhibit excellent detonation performance, which are comparable to the highly explosive benchmarks such as RDX (D: 8795 m s−1, P=34.9 GPa) and HMX (D: 9144 m s−1, P=39.2 GPa).
N‐Arylamines Coupled with Aldehydes, Ketones, and Imines by Means of Photocatalytic Proton‐Coupled Electron Transfer
Authors: Xia Qing , Tian Hao , Dong Jianyang , Qu Yi , Li Lili , Song Hongjian , Liu Yuxiu , Wang Qingmin
Published: May 2018

A photoredox‐catalyzed umpolung strategy for coupling reactions between aldehydes, ketones, imines, and N‐arylamines is reported. These reactions proceed by a Brønsted acid‐activated proton‐coupled electron transfer pathway, and the protocol was used to synthesize a broad scope of 1,2‐amino alcohols and vicinal diamines, both of which are common motifs in biologically active natural products, pharmaceutically active molecules, and ligands.
Recurrence rate of atrial fibrillation after the first clinical episode: A prospective evaluation using continuous cardiac rhythm monitoring
Authors: Simantirakis Emmanuel N. , Papakonstantinou Panteleimon E. , Kanoupakis Emmanuel , Chlouverakis Gregory I. , Tzeis Stylianos , Vardas Panos E.
Published: May 2018

Background

Decision making regarding a patient who has experienced a first clinical episode of atrial fibrillation (AF) is challenging, and the AF recurrences should be a significant consideration. Continuous long‐term rhythm monitoring via implantable loop recorders (ILRs) has enabled us to evaluate the AF recurrence profile after the first clinical episode and to investigate clinical parameters associated with the course of the arrhythmia.

Hypothesis

Continuous rhythm monitoring via ILRs in AF patients after the first clinical episode is of clinical significance and precisely evaluate the AF recurrence profile.

Methods

Thirty consecutive patients with paroxysmal AF received an ILR after their first symptomatic episode. We evaluated the maximum duration of episodes and the recurrence rate of the arrhythmia during a follow‐up period of 3 years.

Results

Three patients (10%) had no AF recurrence, whereas 4 patients (13.3%) presented only 1 episode. Almost half of the patients (46.7%) had a low recurrence rate (<5 episodes/year), whereas the majority of patients (19/30) suffered from episodes with maximum duration ≤24 hours. Eleven patients (36.7%) presented either no episode or a low recurrence rate with episodes lasting ≤24 hours. The use of statins was greater in patients with a low recurrence rate (P = 0.025).

Conclusions

A significant percentage of patients either suffer no AF recurrence after their first symptomatic episode or show a low recurrence rate. Most patients present episodes of short duration. If these findings are confirmed in larger studies, they could have clinical implications ensuring individualized management of the arrhythmia in the future.
Distinct timing of neurogenesis of ipsilateral and contralateral retinal ganglion cells
Authors: Marcucci Florencia , Soares Célia A. , Mason Carol
Published: May 2018

In higher vertebrates, the circuit formed by retinal ganglion cells (RGCs) projecting ipsilaterally (iRGCs) or contralaterally (cRGCs) to the brain permits binocular vision and depth perception. iRGCs and cRGCs differ in their position within the retina and in expression of transcription, guidance and activity‐related factors. To parse whether these two populations also differ in the timing of their genesis, a feature of distinct neural subtypes and associated projections, we used newer birthdating methods and cell subtype specific markers to determine birthdate and cell cycle exit more precisely than previously. In the ventrotemporal (VT) retina, i‐ and cRGCs intermingle and neurogenesis in this zone lags behind RGC production in the rest of the retina where only cRGCs are positioned. In addition, within the VT retina, i‐ and cRGC populations are born at distinct times: neurogenesis of iRGCs surges at E13, and cRGCs arise as early as E14, not later in embryogenesis as reported. Moreover, in the ventral ciliary margin zone (CMZ), which contains progenitors that give rise to some iRGCs in ventral neural retina (Marcucci et al., 2016), cell cycle exit is slower than in other retinal regions in which progenitors give rise only to cRGCs. Further, when the cell cycle regulator Cyclin D2 is missing, cell cycle length in the CMZ is further reduced, mirroring the reduction of both i‐ and cRGCs in the Cyclin D2 mutant. These results strengthen the view that differential regulation of cell cycle dynamics at the progenitor level is associated with specific RGC fates and laterality of axonal projection.
Supramolecular Gluing of Polymeric Hydrogels
Authors: Lovrak Matija , Picken Stephen J. , Eelkema Rienk , van Esch Jan H.
Published: May 2018

We report a simple method for gluing polymer hydrogels together, based on supramolecular chemistry. The gluing is achieved by reactive self‐assembly of a low molecular weight gelator at the interface of the two polymer hydrogels. Formation and assembly of the hydrazine‐based gelator into fibers at the polymer gel interface leads to a greatly increased detachment stress.
Self‐Assembled Organic Crystalline Microring Cavities with High Q‐Factors
Authors: Bando Kazuki , Fujii Honami , Mizuno Kei , Narushima Kaishi , Miyazaki Akihito , Sasaki Fumio , Hotta Shu , Yanagi Hisao
Published: May 2018

Organic crystalline microstructures are recently a target of intense research from the point of view of photonic devices such as microcavities and optical waveguides. A bottom‐up method based upon self‐assembly produces organic microstructures including oriented needles. A top‐down approach, in turn, enabled the fabrication of microstructures of different morphologies and configurations such as microrings and microdisks. In the present study, by using a bottom‐up technique we have developed organic microrings of high crystallinity with minimized crystal imperfections. We have found out that the said microrings function as resonators with high quality (Q) factors. We observe a series of sharply resolved peaks in their photoluminescence spectra and assign those peaks to whispering gallery modes formed in the microrings. Their mode numbers are precisely determined from their mode spacings with the maximum of Q‐factor being ∼2000. The number is extremely high compared with those of other organic microrings of the same size.
Separating Extreme pH Gradients Using Amphiphilic Copolymer Membranes
Authors: Ruiz‐Pérez Lorena , Hurley Claire , Tomas Salvador , Battaglia Giuseppe
Published: May 2018

Polymeric vesicles, also called polymersomes, are highly efficient biomimetic systems. They can generate compartmentalized volumes at the nanoscale supported by synthetic amphiphilic membranes that closely mimic their biological counterparts. Membrane permeability and the ability to separate extreme pH gradients is a crucial condition a successful biomimetic system must meet. We show that polymersomes formed by non‐ionic polybutadiene‐b‐polyethylene oxide (PBd‐b‐PEO) amphiphilic block copolymers engineer robust and stable membranes that are able to sustain pH gradients of 10 for a minimum of eight days. The cells′ endo‐lysomal compartments separate gradients between three and one, while we generated a pH gradient of threefold as great. This feature clearly is of great importance for applications as nanoreactors and drug‐delivery systems where separating different aqueous volumes at the nanoscale level is an essential requirement.
Lipids, Apolipoproteins, and Inflammatory Biomarkers of Cardiovascular Risk: What Have We Learned?
Authors: Rhainds David , Brodeur Mathieu R. , Tardif Jean‐Claude
Published: May 2018

Cardiovascular diseases (CVD) are the first cause of death in the world. CVD risk is influenced by multiple factors, some nonmodifiable such as age, sex, and genetic background, and others modifiable. Great progress has been made over the last decades in the identification of biomarkers of incident or recurrent CV risk and surrogate endpoints of CV outcomes. We present the current state of knowledge for CV biomarkers in plasma including lipids, apolipoproteins, inflammation‐related, and emerging omics‐based biomarkers. Clinically validated surrogate endpoints for CV outcomes include plasma low‐density lipoprotein‐cholesterol reduction, and plasma triglyceride reduction is a likely relevant surrogate endpoint. High‐density lipoprotein‐cholesterol is not a validated surrogate endpoint, but is a useful biomarker of CV risk. CV risk biomarkers of interest include apolipoprotein B and non‐HDL‐cholesterol, lipoprotein (a), C‐reactive protein, and recently, genetic and protein‐based risk scores and gut microbiota‐derived trimethylamine oxide levels.
Genetic differences between type 1 diabetes with and without other autoimmune diseases
Authors: Shimura Kanako , Miura Junnosuke , Kawamoto Manabu , Kawaguchi Yasushi , Yamanaka Hisashi , Uchigata Yasuko
Published: May 2018

Background

Clusters of autoimmune diseases (ADs) are present in some people with type 1 diabetes. This clustering suggests the existence of common genetic backgrounds for abnormal autoimmunity in these individuals. However, the genetic differences between type 1 diabetes patients with and without other ADs are not well known.

Methods

To investigate the clinical background and genetic differences between type 1 diabetes patients with and without other ADs, single nucleotide polymorphisms (SNPs) in the CTLA4, SUMO4, PTPN22, IRF5, STAT4, and BLK genes were analysed by using either a TaqMan assay or direct sequencing. The frequencies of alleles, genotypes of each gene, and the human leukocyte antigen (HLA) haplotype were analysed to investigate differences among 3 groups: type 1 diabetes with systemic ADs (group A), type 1 diabetes with other organ‐specific ADs (group B), and type 1 diabetes without other ADs (group C).

Results

The frequency of the C allele in the ‐1123G > C SNP in the PTPN22 gene promoter was significantly higher in groups A and B than in group C (P = .0258 and .0207, respectively). The allele frequencies of the other SNPs were comparable.

The frequency of HLA DRB1*0405‐DQB1*0401 was significantly higher in groups A and B than in group C (P = .021 and .0395, respectively).

Conclusions

The ‐1123G > C SNP in the PTPN22 gene promoter and HLA DRB1*0405‐DQB1*0401 might influence the concurrence of systemic and organ‐specific ADs in patients with type 1 diabetes.
Supramolecular Pt and Pd Complexes of 4,4′‐Dipyridylditelluride/Diselenide Ligands through Self‐Assembly
Authors: Dey Sandip , Vivekananda Kotipalli V. , Bhuvanesh Nattamai
Published: May 2018

The self‐assembly of 4,4′‐dipyridylditelluride/diselenide and M(OTf)2 {M = cis‐[Pt(PEt3)2]2+ or cis‐[Pd(dppe)]2+; dppe = 1,2‐bis(diphenylphosphino)ethane} yields [M(µ2‐4,4′‐py2E2)]n(OTf)2n (E = Se, Te). The major and minor products, indistinguishable by simple proton NMR and phosphorus NMR spectroscopy, can be detected by heteronuclear (77Se, 125Te, and 195Pt) NMR spectroscopy. The respective dimeric and trimeric structures are assigned by ESI and MALDI‐TOF mass spectrometry, and for the first time, their equilibria have been established. The rhomboid shape of the dimeric complex containing the Pt–N bond is confirmed by its X‐ray diffraction structure. The formation of the cluster‐type minor product [Pd3(µ‐E)2(dppe)3](OTf)2 has also been identified in the reactions of the Pd complexes.
Electroanalysis of an Iron@Graphene‐Carbon Nanotube Hybrid Material
Authors: Soto Dayana , Alzate Manuela , Gallego Jaime , Orozco Jahir
Published: May 2018

Hybrid nanomaterials have outstanding properties that are superior to the corresponding constituents working alone. This work reports on the electroanalysis of a hybrid material‐decorated screen‐printed carbon electrode (SPCE) that consists of iron nanoparticles supported at multi‐wall carbon nanotubes (MWCNT), coated with graphene layers, named Fe@G‐MWCNT. Electrochemical and morphological characterizations were carried out by cyclic voltammetry, electrochemical impedance spectroscopy and high‐resolution transmission electron microscopy, respectively. After optimizing the amount of hybrid material to be drop casted at the SPCE, its electrochemical activation in sulphuric acid produced an enhanced response. The resultant electrochemically reduced Fe@G‐MWCNT‐e‐modified electrode exhibited a diffusion‐controlled redox process with an enhanced heterogeneous electron‐transfer rate constant of 3.21×10−2 cm⋅s−1, which was superior to that from the MWCNT counterpart. However, it was slightly lower than that from a Fe‐MWCNT‐decorated electrode. The graphene coating limited slightly the electron‐transfer process, but works as a protective layer that prevent the loss of Fe catalytic activity. The electrochemical response of the hybrid with graphene coated Fe decreased only a 24.3 % after one week, respect to 51.9 % of the uncoated one. In addition, the hybrid material‐modified electrode exhibited electrocatalytic activity towards the reduction of H2O2 in a linear range of 0.5 mM to 9.8 mM, with sensitivity of 7.97 μA⋅mM−1 and LOD of 0.65 mM, thereby opening an avenue for the development of more specific and highly sensitive Fe@G‐MWCNT hybrid‐based (bio) sensors.
A Graphene‐based Electrochemical Sensor for the Individual, Selective and Simultaneous Determination of Total Chlorogenic Acids, Vanillin and Caffeine in Food and Beverage Samples
Authors: Yiğit Aydın , Alpar Nurcan , Yardım Yavuz , Çelebi Metin , Şentürk Zühre
Published: May 2018

An electrochemical sensor based on the electrocatalytic activity of graphene (GR) was prepared, and used for the individual, selective and simultaneous determination of 5‐O‐Caffeoylquinic acid (5‐CQA) that is major compound of chlorogenic acids in coffee, vanillin (VAN) and caffeine (CAF). The electrochemical behaviors of these compounds on GR modified glassy carbon electrode (GR/GCE) were investigated by cyclic voltammetry and square‐wave adsorptive stripping voltammetry. By using stripping conditions after 30 s accumulation under open‐circuit voltage, the electrochemical oxidation peaks appeared at +0.53, 0.83 and 1.39 V in phosphate buffer pH 2.5, and good linear current responses were obtained with detection limits of 4.4×10−9, 5.0×10−7, and 3.0×10−7 M for 5‐CQA, VAN and CAF, respectively. The potential applicability of the proposed method was illustrated in commercial food and beverage samples.
HPLC−EC Analysis of Estrogenic Compounds: A Comparison of Diamond and Tetrahedral Amorphous Carbon Electrode Performance
Authors: Aigaje Espinosa Elizabeth K. , Qiu Joy , Jarošová Romana , Castiaux Andre , Swain Greg M.
Published: May 2018

High pressure liquid chromatography (HPLC) with amperometric detection was used to quantify estrogenic compounds in water samples. The main goal was to compare the detection figures of merit for boron‐doped diamond thin‐film (BDD) and nitrogen‐incorporated tetrahedral amorphous carbon (ta‐C : N) thin‐film electrodes. The target analytes were estrone, estradiol, and estriol. The BDD and ta‐C : N electrodes were investigated because of their excellent properties, which include a wide potential window, low background current, microstructural stability at high potentials, low limits of detection, weak molecular adsorption, fouling resistance and response reproducibility. ta‐C : N electrodes have not yet been investigated extensively in electroanalysis and are receiving increasing interest because they exhibit many of the excellent electrochemical properties of BDD electrodes and they can be deposited at room temperature by physical vapor deposition. The results reveal as low or lower background current and noise for the ta‐C : N electrode, as compared to the BDD electrode, and comparable or superior analytical detection figures of merit for all three emerging pollutants. The linear dynamic range for both electrodes was from 0.2 to 100 μmol L−1 for estriol, and 0.4 to 100 μmol L−1 for estradiol and estrone, and the sensitivity ranged from 9.1 to 11.2 mA mol L−1. For all three analytes, the limit of detection (S/N=3) ranged from 0.16–0.35 μmol L−1 (45‐95 ppb) for BDD and 0.20–0.34 μmol L−1 (58‐95 ppb) for ta‐C : N.
Hypermethylation of CpG islands is associated with increasing chromosomal damage in chinese lead‐exposed workers
Authors: Yu Li‐bo , Tu Yu‐ting , Huang Jing‐wen , Zhang Ya‐nan , Zheng Guo‐qiao , Xu Xiao‐wen , Wang Jin‐wei , Xiao Jean Qin , Christiani David C. , Xia Zhao‐lin
Published: May 2018

Lead is a widely existing environmental pollutant with potential carcinogenicity. To investigate the association of blood lead level (B‐Pb) with potential chromosomal damage and cancer, we analyzed micronucleus (MN) frequency of peripheral blood lymphocytes (PBLs) and the methylation status of six human tumor suppressor genes (TSGs) post lead exposure. In the study, 147 lead‐exposed workers were divided into two groups according to their B‐Pb P50 value, with other 50 lead‐unexposed workers as a control group. The cytokinesis‐blocked micronucleus (CBMN) assay was performed to detect chromosomal damage of PBLs of both lead‐exposed and ‐unexposed workers. The methylation‐specific polymerase chain reaction (MSP‐PCR) was further used to examine the methylation status of six TSGs (GSTP1, hMLH1, MGMT, p14, p15, and p16). Results showed that MN frequencies of high B‐Pb workers 8.1 ± 3.1‰ and low B‐Pb workers 5.7 ± 2.3‰ were significantly higher than that of control group 2.8 ± 1.9‰ (P < 0.01), while the MN frequency of high B‐Pb workers was also higher than that of the low B‐Pb workers (P < 0.01). The MN frequency in PBLs of lead‐exposed group with the methylated TSGs was significantly higher than that in PBLs with the unmethylated TSGs (P < 0.05). Notably, the CpG island methylator phenotype (CIMP) correlated with chromosome damage (P < 0.05). Additionally, workers with high B‐Pb had higher chromosome damage than those with low B‐Pb (P < 0.05). Taken altogether, the results suggest that lead‐exposed workers with CIMP positive and high B‐Pb have a higher risk of being vulnerable to tumorigenesis. Environ. Mol. Mutagen. 59:549–556, 2018. © 2018 Wiley Periodicals, Inc.
Impact of Polarization Dynamics and Charged Defects on the Electrocaloric Response of Ferroelectric Pb(Zr,Ti)O3 Ceramics
Authors: Weyland Florian , Bradeško Andraž , Ma Yang‐Bin , Koruza Jurij , Xu Bai‐Xiang , Albe Karsten , Rojac Tadej , Novak Nikola
Published: May 2018

The impact of charged point defects on the electrocaloric response of morphotropic Pb(Zr,Ti)O3 (PZT) ceramics is investigated using direct electrocaloric and polarization hysteresis measurements. The electrocaloric response determined for undoped, hard‐, and soft‐doped PZT is rationalized by considering the dipolar entropy change over polarization change and hysteresis losses. The highest electrocaloric effect is observed in poled hard PZT with the field applied along the poling direction, which is related to the reduced hysteresis losses caused by internal electric fields associated with defect complexes. The weak hysteretic dependency of polarization as function of the electric field in hard PZT also allows inducing an inverse electrocaloric effect. The experimental results are compared with model calculations that provide a physical interpretation. The results reveal how the electrocaloric response of ferroelectrics can be optimized by defect engineering.
Discontinuation of carbamazepine due to concerns of long‐term consequences of enzyme induction
Authors: Mäkinen Jussi , Rainesalo Sirpa , Raitanen Jani , Saarinen Jukka , Sandell Satu , Peltola Jukka
Published: May 2018

Objective

Treatment with carbamazepine (CBZ), a potent enzyme inducer, is known to affect the lipid profile, steroid, and vitamin D metabolism. Consequently, it has been postulated that patients on CBZ should be switched to noninducing antiepileptic drugs (AEDs). However, little is known about the seizure outcome following a CBZ switch in seizure‐free patients. We aimed to address this issue using a controlled observational study design.

Methods

Fifty‐eight patients taking CBZ for focal epilepsy were assessed for discontinuing CBZ treatment due to concerns of long‐term adverse‐effects; 34 discontinued its therapy and 24 continued with CBZ. Six‐month seizure freedom was the primary end point. Furthermore, serum samples (total cholesterol (TC), low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), triglycerides, sex hormone–binding globulin (SHBG), free testosterone, and 25‐hydroxyvitamin D levels from before and at least 3 months after discontinuation or continuation were obtained from all patients.

Results

Seizure‐free patients had a 5‐fold elevated odds of seizure recurrence if CBZ was discontinued (95% confidence interval [CI 0.51–49.3; p = 0.17). A significant decrease in serum levels of TC, LDL, HDL, and SHBG as well as a significant increase in that of free testosterone were found in the discontinuation group compared with those who continued CBZ. Nonsignificant changes in triglycerides and vitamin D levels were detected.

Significance

Discontinuation of CBZ in seizure‐free patients seems to carry a moderate, but legitimate, risk of relapse. Conversely, our results indicate that CBZ might have unfavorable effects on serum levels of TC, LDL, HDL, SHBG, and free testosterone.
Dynamic behavior of a smart device on a surface subjected to earthquake motion
Authors: Na Yunsu , El-Tawil Sherif , Ibrahim Ahmed , Eltawil Ahmed
Published: May 2018

This paper leverages concepts from an existing model to simulate the planar response of a smart device subjected to friction forces induced by an underlying moving plane. An interpolation technique is used to enhance detection of transition points (between sticking and sliding states), which must be accurately identified because of the frequency of their occurrence during seismic motion. The behavior of a smart device on an unconstrained table or desk, which is itself on a moving floor, is introduced and discussed. After validation of the results using experimental data, the revised model is used to study the sliding potential of smart devices on a surface during strong seismic events. Sliding spectra associated with selected ground motions are presented and extended to incorporate the effect of vertical accelerations with the purpose of assessing their influence. It is shown that vertical accelerations have a minimal effect on the sliding behavior of smart devices and that a “probability of exceeding the slip limit” curve can be developed to relate the probability of sticking to a demand parameter that represents the ground motion.
Analysis of the exome aggregation consortium (ExAC) database suggests that the BAP1‐tumor predisposition syndrome is underreported in cancer patients
Authors: Massengill James B. , Sample Klarke M. , Pilarski Robert , McElroy Joseph , Davidorf Frederick H. , Cebulla Colleen M. , Abdel‐Rahman Mohamed H.
Published: May 2018

The BAP1‐tumor predisposition syndrome (BAP1‐TPDS) has been recently identified to predispose patients to a variety of cancers and preneoplastic lesions. About 130 unrelated probands have been identified worldwide; however, the impact of the syndrome is suspected to be much larger given the diversity of the cancer phenotype. To evaluate the frequency of germline BAP1 mutations in the general and cancer populations, we analyzed the Exome Aggregation Consortium (ExAC), a database that contains 53105 exomes of unrelated individuals unaffected by cancer (general population) and exomes of 7601 unrelated individuals affected by cancer provided by the Cancer Genome Atlas (TCGA, cancer subjects). BAP1 null variants were seen at much higher frequency in the cancer subjects (0.0526%) compared to the general population (0.00188%) with a relative risk of 27.93 and (P = 0.0011, [95% CI: 3.122‐249.883], Fisher's exact test). We also studied a reported BAP1 null variant, c.1203T > G, p.T401* (rs200156887), observed commonly in the general population. Sequencing and restriction fragment polymorphism of the RT‐4 cell line that contains this variant revealed that it is in fact a 3bp deletion/insertion, c.1201_1203delinsGAG, a likely benign missense alteration p.Y401E explaining the relative high frequency of this variant in the general population. In conclusion, germline null mutations in BAP1 have a significantly higher frequency in cancer patients than the general population. Given the low frequency of reported families with BAP1‐TPDS, our results suggest that the syndrome is underreported especially in patients with cancer.
Conditional depletion of GSK3b protects oligodendrocytes from apoptosis and lessens demyelination in the acute cuprizone model
Authors: Xing Bin , Brink Lauren E. , Maers Kelly , Sullivan Mara L. , Bodnar Richard J. , Stolz Donna B. , Cambi Franca
Published: May 2018

Apoptosis is recognized as the main mechanism of oligodendrocyte loss in Multiple Sclerosis caused either by immune mediated injury (Barnett & Prineas, ) or a direct degenerative process (oligodendrogliapathy; Lucchinetti et al., ). Cuprizone induced demyelination is the result of non‐immune mediated apoptosis of oligodendrocytes (OL) and represents a model of oligodendrogliapathy (Simmons, Pierson, Lee, & Goverman, ). Glycogen Synthase Kinase (GSK) 3b has been shown to be pro‐apoptotic for cells other than OL. Here, we sought to investigate whether GSK3b plays a role in cuprizone‐induced apoptosis of OL by using a novel inducible conditional knockout (cKO) of GSK3b in mature OL. While depletion of GSK3b has no effect on survival of uninjured OL, it increases survival of mature OL exposed to cuprizone. We show that GSK3b‐deficient OLs are protected against caspase‐dependent, but not against caspase‐independent apoptosis. Active GSK3b is present in the nuclei of OL at peak of caspase‐dependent apoptosis. Significant preservation of myelinated axons is associated with GSK3b depletion and glial cell activation is markedly reduced. Collectively, the data show that GSK3b is pro‐apoptotic for caspase‐dependent cell death, likely through activation of nuclear GSK3b and its depletion promotes survival of oligodendrocytes and attenuates myelin loss.
Neutrophil‐to‐lymphocyte ratio as a prognostic indicator in head and neck cancer: A systematic review and meta‐analysis
Authors: Tham Tristan , Bardash Yonatan , Herman Saori Wendy , Costantino Peter David
Published: May 2018

Background

The purposes of this systematic review and meta‐analysis were to investigate the relationship between the neutrophil‐to‐lymphocyte ratio (NLR) and prognosis in head and neck cancer.

Methods

A systematic review and meta‐analysis were done to investigate the role of NLR in overall survival (OS), disease‐specific survival (DSS), disease‐free survival (DFS), and progression‐free survival (PFS).

Results

For qualitative analysis, 33 cohorts with over 10 072 patients were included. For quantitative analysis, 15 studies were included with 5562 patients. The pooled data demonstrated that an elevated NLR significantly predicted poorer OS and DSS.

Conclusion

An elevated pretreatment NLR is a prognostic marker for head and neck cancer. It represents a simple and easily obtained marker that could be used to stratify groups of high‐risk patients who might benefit from adjuvant therapy.
Quantification of the seasonal hillslope water storage that does not drive streamflow
Authors: Dralle David N. , Hahm W. Jesse , Rempe Daniella M. , Karst Nathaniel J. , Thompson Sally E. , Dietrich William E.
Published: May 2018

The relationship between seasonal catchment water storage and discharge is typically nonunique due to water storage that is not directly hydraulically connected to streams. Hydraulically disconnected water volumes are often ecologically and hydrologically important but cannot be explicitly estimated using current storage–discharge techniques. Here, we propose that discharge is explicitly sensitive to changes in only some fraction of seasonally dynamic storage that we call “direct storage,” whereas the remaining storage (“indirect storage”) varies without directly influencing discharge. We use a coupled mass balance and storage–discharge function approach to partition seasonally dynamic storage between these 2 pools in the Northern California Coast Ranges. We find that indirect storage constitutes the vast majority of dynamic catchment storage, even at the wettest times of the year. Indirect storage exhibits lower variability over the course of the wet season (and in successive winter periods) than does direct storage. Predicted indirect storage volumes and dynamics match field observations. Comparison of 2 neighbouring field sites reveals that indirect storage volumes can occur as unsaturated storage held under tension in soils and weathered bedrock and as near‐surface saturated storage that remains on hillslopes (and is eventually evapotranspired). Indirect storage volumes (including moisture in the weathered bedrock) may support plant transpiration, and our method indicates that this important water source could be quantified from precipitation and stream discharge records.
Effects of differential hillslope‐scale water retention characteristics on rainfall–runoff response at the Landscape Evolution Observatory
Authors: van den Heuvel Daniël B. , Troch Peter A. , Booij Martijn J. , Niu Guo‐Yue , Volkmann Till H.M. , Pangle Luke A.
Published: May 2018

Hillslopes turn precipitation into runoff and thus exert important controls on various Earth system processes. It remains difficult to collect reliable data necessary for understanding and modeling these Earth system processes in real catchments. To overcome this problem, controlled experiments are being conducted at the Landscape Evolution Observatory at Biosphere 2, The University of Arizona. Previous experiments have revealed differences in hydrological response between 2 landscapes within Landscape Evolution Observatory, even though both landscapes were designed to be identical. In an attempt to discover where the observed differences stem from, we use a fully 3‐dimensional hydrological model (CATchment HYdrology) to show the effect of soil water retention characteristics and saturated hydraulic conductivity on the hydrological response of these 2 hillslopes. We also show that soil water retention characteristics can be derived at hillslope scale from experimental observations of soil moisture and matric potential. It is found that differences in soil packing between the 2 landscapes may be responsible for the observed differences in hydrological response. This modeling study also suggests that soil water retention characteristics and saturated hydraulic conductivity have a profound effect on rainfall–runoff processes at hillslope scale and that parametrization of a single hillslope may be a promising step in modeling rainfall–runoff response in real catchments.
Exhaled breath analysis in evaluation of psychological stress: A short literature review
Authors: Tonacci Alessandro , Sansone Francesco , Pala Anna Paola , Conte Raffaele
Published: May 2018

Physiological stress is pervasive in today's society. Its detection is normally performed through several unobtrusive methods, driving both caregivers and patients to take measures to reduce the burden of this condition on human health. Among the methods for assessing stress, exhaled breath analysis represents a non‐invasive, real‐time alternative to classic laboratory tests. Therefore, a literature review was performed to assess the presence of altered parameters, related to psychological stress, in exhaled breath. Most studies in our review measured nitric oxide (NO), whose concentration was often correlated, either positively or negatively, with psychological stress, with reasonable scientific support. Other compounds (isoprene, terpene and so on) were rarely studied and with mixed evidence. Further investigations are needed to elucidate the involvement and the pathophysiological role of NO in stress, possibly including a greater number of individuals, as sample size actually represents the main limitation of the work published to date.
Recent advances for identification of new scaffolds and drug targets for Mycobacterium tuberculosis
Authors: Dhiman Rohan , Singh Ramandeep
Published: May 2018

Tuberculosis (TB) is a leading cause of mortality and morbidity with an estimated 1.7 billion people latently infected with the pathogen worldwide. Clinically, TB infection presents itself as an asymptomatic infection, which gradually manifests to life threatening disease. The emergence of various drug resistant strains of Mycobacterium tuberculosis and lengthy duration of chemotherapy are major challenges in the field of TB drug development. Hence, there is an urgent need to develop scaffolds that possess a novel mechanism of action, can shorten the duration of therapy, and are active against both drug resistant and susceptible strains. In this review, we will discuss recent progress made in the field of TB drug development with emphasis on screening methods and drug targets from M. tuberculosis. The current review provides insights into mechanism of action of new scaffolds that are being evaluated in various stages of clinical trials. © 2018 IUBMB Life, 70(9):905–916, 2018
Redox‐guided small molecule antimycobacterials
Authors: Kulkarni Amogh , Sharma Ajay Kumar , Chakrapani Harinath
Published: May 2018

The emergence of drug resistance has posed a major challenge to treatment of tuberculosis worldwide. The new drug candidates in the pipeline are few and therefore there is an urgent need to develop antimycobacterials with novel mechanisms of action. Maintenance of redox homeostasis is integral to mycobacterial survival and growth. Therefore, perturbation of this equilibrium can result in irreversible stress induction and inhibition of growth. Herein, we review a number of small molecules that have either been designed to induce redox stress or were found to do so after their discovery. A number of these small molecules are quite effective against drug‐resistant mycobacterial strains and thus offer scope for exploration of potentially new mechanism of action. The progress in redox‐guided antimycobacterial compounds and the challenges towards clinical applications are reviewed. © 2018 IUBMB Life, 70(9):826–835, 2018
Effects of fucoxanthin on autophagy and apoptosis in SGC‐7901cells and the mechanism
Authors: Zhu Yue , Cheng Jing , Min Zhenli , Yin Tingzi , Zhang Rong , Zhang Wei , Hu Ling , Cui Zhiwen , Gao Chengzhi , Xu Shiqiang , Zhang Chunxiang , Hu Xiamin
Published: May 2018

Autophagy and apoptosis are involved in the development of a variety of cancers. Fucoxanthin is a natural compound known to have antitumor effects, so we aimed to explore its effects on autophagy and apoptosis in gastric cancer SGC7901 cells. Specifically, we performed methyl thiazolyl tetrazolium assay, transmission electron microscopy, real‐time polymerase chain reaction, Western blot analysis, immunofluorescence assay, and cell apoptosis analysis to clarify the role of fucoxanthin in SGC‐7901 cells. Our results indicate that fucoxanthin significantly inhibits the viability of SGC‐7901 cells, effectively inducing both autophagy and apoptosis by up‐regulating the expressions of beclin‐1, LC3, and cleaved caspase‐3 (CC3), and by down regulating Bcl‐2. Fucoxanthin‐induced autophagy also seems to occur before, and may promote apoptosis.
Functional variants in the LC3B gene promoter in acute myocardial infarction
Authors: Gao Feng , Su Qiang , Yang Wentao , Pang Shuchao , Wang Shuai , Cui Yinghua , Zhang Jinguo , Yan Bo
Published: May 2018

Acute myocardial infarction (AMI) is a common disease mainly caused by atherosclerosis, for which genetic causes remain largely unknown. Recently, low frequency and rare genetic variants have been proposed as risk factors. Autophagy has been involved in many cellular processes, such as lipid metabolism and inflammation, and implicated in human diseases, including cardiovascular diseases. In previous studies, we have reported reduced levels of LC3B, a core protein and a marker for autophagy, in AMI patients. In this study, the LC3B gene promoter was genetically and functionally analyzed in large cohorts of AMI patients (n = 383) and healthy controls (n = 390). A total of 25 DNA sequence variants (DSVs) including SNPs were found. Seven DSVs and three SNPs were only identified in AMI patients. All the DSVs and SNPs (except one) significantly decreased the transcriptional activity of the LC3B gene promoter in both HEK‐293 and H9c2 cells (P < 0.05). Further electrophoretic mobility shift assay suggested that the DSVs affected the binding of transcription factors. In contrast, the DSVs and SNPs found only in controls or in both AMI patients and controls did not significantly affected LC3B gene promoter activity (P > 0.05). Therefore, our data suggested that the DSVs identified in AMI patients may change LC3B level by affecting the transcriptional activity of LC3B gene promoter, contributing to the AMI development. Upregulation of the LC3B gene expression may provide a novel and potential therapy for AMI patients.
Differential GIP/GLP‐1 intestinal cell distribution in diabetics’ yields distinctive rearrangements depending on Roux‐en‐Y biliopancreatic limb length
Authors: Palha António M. , Pereira Sofia S. , Costa Madalena M. , Morais Tiago , Maia André F. , Guimarães Marta , Nora Mário , Monteiro Mariana P.
Published: May 2018

As incretins are known to play an important role in type 2 diabetics (T2D) improvement observed after Roux‐en‐Y gastric bypass (RYGB), our aim was to assess whether increasing the length of RYGB biliopancreatic limb in T2D would modify the incretin staining cell density found after the gastric outlet. Small intestine biopsies (n = 38) were harvested during RYGB at two different distances from the duodenal angle; either 60‐90 cm (n = 28), from non‐diabetic (n = 18) patients, and T2D (n = 10), or 200 cm (n = 10) from T2D. GIP and GLP‐1 staining cells were identified by immunohistochemistry and GLP‐1/GIP co‐staining cells by immunofluorescence. Incretin staining cell density at the proximal small intestine of T2D and non‐diabetic individuals was similar. At 200 cm, T2D patients depicted a significantly lower GIP staining cell density (0.181 ± 0.016 vs 0.266 ± 0.033, P = 0.038) with a similar GLP‐1 staining cell density when compared to the proximal gut. GIP/GLP‐1 co‐staining cells was similar in all studied groups. In T2D patients, the incretin staining cells density in the distal intestine is significantly different from the proximal gut. Thus, a longer RYGB biliopancreatic limb produces a distinctive incretin cell pattern at the gastro‐enteric anastomosis that can result in different endocrine profiles.
Multiple phosphorylation sites on γ‐tubulin are essential and contribute to the biogenesis of basal bodies in Tetrahymena
Authors: Joachimiak Ewa , Jerka‐Dziadosz Maria , Krzemień‐Ojak Łucja , Wacławek Ewa , Jedynak Katarzyna , Urbanska Paulina , Brutkowski Wojciech , Sas‐Nowosielska Hanna , Fabczak Hanna , Gaertig Jacek , Wloga Dorota
Published: May 2018

The mechanisms that regulate γ‐tubulin, including its post‐translational modifications, are poorly understood. γ‐Tubulin is important for the duplication of centrioles and structurally similar basal bodies (BBs), organelles which contain a ring of nine triplet microtubules. The ciliate Tetrahymena thermophila carries hundreds of cilia in a single cell and provides an excellent model to specifically address the role of γ‐tubulin in the BBs assembly and maintenance. The genome of Tetrahymena contains a single γ‐tubulin gene. We show here that there are multiple isoforms of γ‐tubulin that are likely generated by post‐translational modifications. We identified evolutionarily conserved serine and threonine residues as potential phosphosites of γ‐tubulin, including S80, S129, S131, T283, and S360. Several mutations that either prevent (S80A, S131A, T283A, S360A) or mimic (T283D) phosphorylation were conditionally lethal and at a higher temperature phenocopied a loss of γ‐tubulin. Cells that overproduced S360D γ‐tubulin displayed phenotypes consistent with defects in the microtubule‐dependent functions, including an asymmetric division of the macronucleus and abnormalities in the pattern of BB rows, including gaps, fragmentation, and misalignment. In contrast, overexpression of S129D γ‐tubulin affected the orientation, docking, and structure of the BBs, including a loss of either the B‐ or C‐subfibers or the entire triplets. We conclude that conserved potentially phosphorylated amino acids of γ‐tubulin are important for either the assembly or stability of BBs.