bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy
Authors: Baek Seung-Woo , Jang In-Hwan , Kim Seon-Kyu , Nam Jong-Kil , Leem Sun-Hee , Chu In-Sun
Published: March 2020

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8+ T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy.
Generation of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology
Authors: Dabrowska Magdalena , Ciolak Agata , Kozlowska Emilia , Fiszer Agnieszka , Olejniczak Marta
Published: March 2020

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by the expansion of CAG repeats in exon 1 of the huntingtin gene (HTT). Despite its monogenic nature, HD pathogenesis is still not fully understood, and no effective therapy is available to patients. The development of new techniques such as genome engineering has generated new opportunities in the field of disease modeling and enabled the generation of isogenic models with the same genetic background. These models are very valuable for studying the pathogenesis of a disease and for drug screening. Here, we report the generation of a series of homozygous HEK 293T cell lines with different numbers of CAG repeats at the HTT locus and demonstrate their usefulness for testing therapeutic reagents. In addition, using the CRISPR-Cas9 system, we corrected the mutation in HD human induced pluripotent stem cells and generated a knock-out of the HTT gene, thus providing a comprehensive set of isogenic cell lines for HD investigation.
Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery
Authors: Shuai Qi , Cai Yue , Zhao Guangkuo , Sun Xuanrong
Published: March 2020

On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7) in vitro. But when further used in vivo, TAT-NP-PTX showed an acceleration of the drug’s plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide’s positive charges may be a hot topic to overcome the present dilemma.
Rice OsHSFA3 Gene Improves Drought Tolerance by Modulating Polyamine Biosynthesis Depending on Abscisic Acid and ROS Levels
Authors: Zhu Ming-Dong , Zhang Meng , Gao Du-Juan , Zhou Kun , Tang Shan-Jun , Zhou Bin , Lv Yan-Mei
Published: March 2020

Drought is a serious problem, which causes heavy yield losses for rice. Heat-shock factors (HSFs) had been implicated in tolerance to drought and high temperature. However, there has not been much functional characterization and mechanism clarification in rice. Previously, we found an HSF gene, OsHSFA3, was highly related with drought tolerance after screening from 10,000 different samples. Herein, we cloned the OsHSFA3 from rice and overexpressed it in Arabidopsis thaliana to study its regulatory mechanism of drought tolerance. Phenotypic and physiological assays of the transgenic Arabidopsis lines showed that overexpression of OsHSFA3 confers drought tolerance by reducing water loss and reactive oxygen species (ROS) levels, whereas it increases abscisic acid (ABA) levels. However, enzymatic antioxidants such as activity levels of superoxide dismutase, peroxidase and catalase were not significantly different between wild type and transgenic lines. Instead, we observed a significant increase in polyamine content, which was correlated with increased AtADC1, AtADC2, SPDS1 and SPMS expression levels. In silico and in vivo analyses confirmed that OsHSFA3 is a nuclear-localized gene. In addition, OsHSFA3 can bind to the promoter of AtADC1 and OsADC via a yeast one-hybrid assay. Overall, this study reveals that OsHSFA3 improves drought tolerance in Arabidopsis not only by increasing ABA levels, but also by modulating polyamine levels to maintain ROS homeostasis, therefore it could be a strong candidate to develop drought-tolerant rice cultivars.
The SNP rs2298383 Reduces ADORA2A Gene Transcription and Positively Associates with Cytokine Production by Peripheral Blood Mononuclear Cells in Patients with Multiple Chemical Sensitivity
Authors: Cannata Attilio , De Luca Chiara , Korkina Liudmila G. , Ferlazzo Nadia , Ientile Riccardo , Currò Monica , Andolina Giulia , Caccamo Daniela
Published: March 2020

Systemic inflammation and immune activation are striking features of multiple chemical sensitivity (MCS). The rs2298383 SNP of ADORA2A gene, coding for adenosine receptor type 2A (A2AR), has been involved in aberrant immune activation. Here we aimed to assess the prevalence of this SNP in 279 MCS patients and 238 healthy subjects, and its influence on ADORA2A, IFNG and IL4 transcript amounts in peripheral blood mononuclear cells of randomly selected patients (n = 70) and controls (n = 66) having different ADORA2A genotypes. The ADORA2A rs2298383 TT mutated genotype, significantly more frequent in MCS patients than in controls, was associated with a three-fold increased risk for MCS (O.R. = 2.86; C.I. 95% 1.99–4.12, p < 0.0001), while the CT genotype, highly prevalent among controls, resulted to be protective (O.R. = 0.33; C.I. 95% 0.224–0.475, p < 0.0001). Notably, ADORA2A mRNA levels were significantly lower, while IFNG, but not IL4, mRNA levels were significantly higher in TT MCS patients compared with controls. A significant negative correlation was found between ADORA2A and both IFNG and IL4, while a significant positive correlation was found between IFNG and IL4. These findings suggest that A2AR defective signaling may play a relevant role in PBMC shift towards a pro-inflammatory phenotype in MCS patients.
Gene Flow Patterns among Aedes aegypti (Diptera: Culicidae) Populations in Sri Lanka
Authors: Fernando H.S.D. , Hapugoda Menaka , Perera Rushika , Black IV William C. , De Silva B.G.D.N.K.
Published: March 2020

In Sri Lanka, dengue is the most serious arboviral disease. Recent increases in dengue cases suggest a higher infection rate and spread of the disease to new areas. The present study explores gene flow patterns of Ae. aegypti, the main vector of dengue disease, among 10 collection sites including major ports and inland cities using variations at 11 microsatellite loci. Discriminant analysis of principal components (DAPC) and k-means clustering estimated eight genetic clusters. Analysis of Molecular Variance (AMOVA) estimated equal variances among cities and among collections in Colombo, Sri Lanka. Significant evidence, although weak, was detected for isolation by distance. Analysis of gene flow rates and directions using MIGRATE-n indicated that populations throughout the island served as a source of immigrants for Colombo with abundant gene flow among major commercial cities in Sri Lanka, which appear to receive migrant mosquitoes from throughout Sri Lanka. The observed patterns probably arise through human movement of Ae. aegypti during commerce from throughout Sri Lanka into Colombo increasing the risk of spread. The patterns uncovered in this study are significant for global health as Sri Lanka is situated along a key international shipping route.
Transcriptome Analyses of Diaphorina citri Midgut Responses to Candidatus Liberibacter Asiaticus Infection
Authors: Yu Hai-Zhong , Li Ning-Yan , Zeng Xiang-Dong , Song Jian-Chun , Yu Xiu-Dao , Su Hua-Nan , Chen Ci-Xiang , Yi Long , Lu Zhan-Jun
Published: March 2020

The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), is an important transmission vector of the citrus greening disease Candidatus Liberibacter asiaticus (CLas). The D. citri midgut exhibits an important tissue barrier against CLas infection. However, the molecular mechanism of the midgut response to CLas infection has not been comprehensively elucidated. In this study, we identified 778 differentially expressed genes (DEGs) in the midgut upon CLas infection, by comparative transcriptome analyses, including 499 upregulated DEGs and 279 downregulated DEGs. Functional annotation analysis showed that these DEGs were associated with ubiquitination, the immune response, the ribosome, endocytosis, the cytoskeleton and insecticide resistance. KEGG enrichment analysis revealed that most of the DEGs were primarily involved in endocytosis and the ribosome. A total of fourteen DEG functions were further validated by reverse transcription quantitative PCR (RT-qPCR). This study will contribute to our understanding of the molecular interaction between CLas and D. citri.
Bio-Inductive Materials in Direct and Indirect Pulp Capping—A Review Article
Authors: Kunert Marta , Lukomska-Szymanska Monika
Published: March 2020

The article is aimed at analyzing the available research and comparing the properties of bio-inductive materials in direct and indirect pulp capping procedures. The properties and clinical performances of four calcium-silicate cements (ProRoot MTA, MTA Angelus, RetroMTA, Biodentine), a light-cured calcium silicate-based material (TheraCal LC) and an enhanced resin-modified glass-ionomer (ACTIVA BioACTIVE) are widely discussed. A correlation of in vitro and in vivo data revealed that, currently, the most validated material for pulp capping procedures is still MTA. Despite Biodentine’s superiority in relatively easier manipulation, competitive pricing and predictable clinical outcome, more long-term clinical studies on Biodentine as a pulp capping agent are needed. According to available research, there is also insufficient evidence to support the use of TheraCal LC or ACTIVA BioACTIVE BASE/LINER in vital pulp therapy.
Long-Term Compressive Strength of Polymer Concrete-like Composites with Various Fillers
Authors: Sokołowska Joanna Julia
Published: March 2020

The durability of building composites with polymer matrix, such as polymer concretes, is considered high or excellent. However, very few studies are available that show the properties of such composites tested long after the specimens’ preparation, especially composites with fillers other than traditional rock aggregates. The paper presents the long-term compressive strength of polymer concrete containing common and alternative fine fillers, including quartz powder (ground sand) and by-products of the combustion of Polish fossil fuels (coal and lignite), tested nine or 9.5 years after preparation. The results were compiled with the data for respective specimens tested after 14 days, as well as 1.5 and 7 years. Data analysis confirmed the excellent durability of concrete-like composites with various fillers in terms of compressive strength. Density measurements of selected composites showed that the increase in strength was accompanied by an increase in volumetric density. This showed that the opinion that the development of the strength of composites with polymer matrices taking place within a few to several days was not always justified. In the case of a group of tested concrete-like composites with vinyl-ester matrices saturated with fly ashes of various origins, there was a further significant increase in strength over time.
Discrete Element Simulation and Validation of a Mixing Process of Granular Materials
Authors: Chen Jian , Furuichi Mikito , Nishiura Daisuke
Published: March 2020

The mixing processes of granular materials have gained wide interest among various fields of science and engineering. In this study, our focus is a mixing process for offshore mining. We conducted numerical simulations using the discrete element method (DEM) in comparison with experimental works on mixing color sand. Careful calibration of initial packing densities has been performed for the simulations. For validation, the steady-state torques on the mixer head, the maximal increase of surface height after mixing, and the surface mixing patterns have been compared. The effect of particle size on the simulation results has been clarified. With the particle size approaching the actual particle size, consistent torques and mixing patterns indicate the capability of the DEM code for studying the particular mixing process, while the results for the maximal increase of surface height should be interpreted with more caution.
Effect of Material and Process Variables on Characteristics of Nitridation-Induced Self-Formed Aluminum Matrix Composites—Part 2: Effect of Nitrogen Flow Rates and Processing Temperatures
Authors: Kim Dae-Young , Cha Pil-Ryung , Nam Ho-Seok , Choi Hyun-Joo , Lee Kon-Bae
Published: March 2020

The nitridation-induced self-formed aluminum matrix composite (NISFAC) process is based on the nitridation reaction, which can be significantly influenced by the characteristics of the starting materials (e.g., the chemical composition of the aluminum powder and the type, size, and volume fraction of the ceramic reinforcement) and the processing variables (e.g., process temperature and time, and flow rate of nitrogen gas). Since these variables do not independently affect the nitridation behavior, a systematic study is necessary to examine the combined effect of these variables upon nitridation. In this second part of our two-part report, we examine the effect of nitrogen flow rates and processing temperatures upon the degree of nitridation which, in turn, determines the amount of exothermic reaction and the amount of molten Al in the nitridation-induced self-formed aluminum matrix composite (NISFAC) process. When either the nitrogen flow rate or the set temperature was too low, high-quality composites were not obtained because the level of nitridation was insufficient to fill the powder voids with molten Al. Hence, since the filling of the voids in the powder bed by molten Al is essential to the NISFAC process, the conditions should be optimized by manipulating the nitrogen flow rate and processing temperature.
Acute Coronary Syndromes in Chronic Kidney Disease: Clinical and Therapeutic Characteristics
Authors: Moisi Mădălina Ioana , Rus Marius , Bungau Simona , Zaha Dana Carmen , Uivarosan Diana , Fratila Ovidiu , Tit Delia Mirela , Endres Laura , Nistor-Cseppento Delia Carmen , Popescu Mircea Ioachim
Published: March 2020

Background and Objectives: This study evaluated the clinical characteristics of the acute coronary syndromes (ACS) in chronic kidney disease (CKD) patients and established prognostic values of the biomarkers and echocardiography. Materials and Methods: 273 patients admitted to the cardiology department of the Clinical County Emergency Hospital of Oradea, Romania, with ACS diagnosis were studied. Two study groups were formed according to the presence of CKD (137 patients with ACS + CKD and 136 with ACS without CKD). Kidney Disease: Improving Global Outcomes (KDIGO) threshold was used to assess the stages of CKD. Results: Data regarding the medical history, laboratory findings, biomarkers, echocardiography, and coronary angiography were analysed for both groups. ACS parameters were represented by ST-segment elevation myocardial infarction (STEMI), which revealed a greater incidence in subjects without CKD (43.88%); non-ST-segment elevation myocardial infarction (NSTEMI), characteristic for the CKD group (28.47%, with statistically significance p = 0.04); unstable angina and myocardial infarction with nonobstructive coronary arteries (MINOCA). Diabetes mellitus, chronic heart failure, previous stroke, and chronic coronary syndrome were more prevalent in the ACS + CKD group (56.93%, p < 0.01; 41.61%, p < 0.01; 18.25%, p < 0.01; 45.26%, p < 0.01). N-terminal pro b-type natriuretic peptide (NT-proBNP) was statistically higher (p < 0.01) in patients with CKD; Killip class 3 was evidenced more frequently in the same group (p < 0.01). Single-vessel coronary artery disease (CAD) was statistically more frequent in the ACS without CKD group (29.41%, p < 0.01) and three-vessel CAD or left main coronary artery disease (LMCA) were found more often in the ACS + CKD group (27.01%, 14.6%). Conclusions: Extension of the CAD in CKD subjects revealed an increased prevalence of the proximal CAD, and the involvement of various coronary arteries is characteristic in these patients. Biomarkers and echocardiographic elements can outline the evolution and outcomes of ACS in CKD patients.
Primer for Mainstreaming Mind-Body Techniques for Extreme Climates-Insights and Future Directions
Authors: Anand Akshay , Kaur Gurkeerat , Bammidi Sridhar , Mathur Deepali , Battu Priya , Sharma Kanupriya , Tyagi Rahul , Pannu Viraaj , Bhanushali Disha , Limaye Nitin
Published: March 2020

Background: The deprivation of oxygen reaching the tissues (also termed as hypoxia) affects the normal functioning of the body. This results in development of many diseases like ischemia, glaucoma, MCI (Mild Cognitive Impairment), pulmonary and cerebral edema, stress and depression. There are no effective drugs that can treat such diseases. Despite such failure, alternative interventions such as mind-body techniques (MBTs) have not been adequately investigated. Methods: The first part of this review has been focused on philosophical aspects of various MBTs besides evolving an ayurgenomic perspective. The potential of MBTs as a preventive non-pharmacological intervention in the treatment of various general and hypoxic pathologies has been further described in this section. In the second part, molecular, physiological, and neuroprotective roles of MBTs in normal and hypoxic/ischemic conditions has been discussed. Results: In this respect, the importance of and in vivo studies has also been discussed. Conclusions: Although several studies have investigated the role of protective strategies in coping with the hypoxic environment, the efficacy of MBTs at the molecular level has been ignored.
Metabolomics to Exploit the Primed Immune System of Tomato Fruit
Authors: Luna Estrella , Flandin Amélie , Cassan Cédric , Prigent Sylvain , Chevanne Chloé , Kadiri Camélia Feyrouse , Gibon Yves , Pétriacq Pierre
Published: March 2020

Tomato is a major crop suffering substantial yield losses from diseases, as fruit decay at a postharvest level can claim up to 50% of the total production worldwide. Due to the environmental risks of fungicides, there is an increasing interest in exploiting plant immunity through priming, which is an adaptive strategy that improves plant defensive capacity by stimulating induced mechanisms. Broad-spectrum defence priming can be triggered by the compound ß-aminobutyric acid (BABA). In tomato plants, BABA induces resistance against various fungal and bacterial pathogens and different methods of application result in durable protection. Here, we demonstrate that the treatment of tomato plants with BABA resulted in a durable induced resistance in tomato fruit against Botrytis cinerea, Phytophthora infestans and Pseudomonas syringae. Targeted and untargeted metabolomics were used to investigate the metabolic regulations that underpin the priming of tomato fruit against pathogenic microbes that present different infection strategies. Metabolomic analyses revealed major changes after BABA treatment and after inoculation. Remarkably, primed responses seemed specific to the type of infection, rather than showing a common fingerprint of BABA-induced priming. Furthermore, top-down modelling from the detected metabolic markers allowed for the accurate prediction of the measured resistance to fruit pathogens and demonstrated that soluble sugars are essential to predict resistance to fruit pathogens. Altogether, our results demonstrate that metabolomics is particularly insightful for a better understanding of defence priming in fruit. Further experiments are underway in order to identify key metabolites that mediate broad-spectrum BABA-induced priming in tomato fruit.
High-Throughput White Blood Cell (Leukocyte) Enrichment from Whole Blood Using Hydrodynamic and Inertial Forces
Authors: Lombodorj Batzorig , Tseng Horas Cendana , Chang Hwan-You , Lu Yen-Wen , Tumurpurev Namnan , Lee Chun-Wei , Ganbat Batdemberel , Wu Ren-Guei , Tseng Fan-Gang
Published: March 2020

A microfluidic chip, which can separate and enrich leukocytes from whole blood, is proposed. The chip has 10 switchback curve channels, which are connected by straight channels. The straight channels are designed to permit the inertial migration effect and to concentrate the blood cells, while the curve channels allow the Dean flow to further classify the blood cells based on the cell sizes. Hydrodynamic suction is also utilized to remove smaller blood cells (e.g., red blood cell (RBC)) in the curve channels for higher separation purity. By employing the inertial migration, Dean flow force, and hydrodynamic suction in a continuous flow system, our chip successfully separates large white blood cells (WBCs) from the whole blood with the processing rates as high as 1 × 108 cells/sec at a high recovery rate at 93.2% and very few RBCs (~0.1%).
Coupled U–Pb Geochronology of Monazite and Zircon for the Bozhushan Batholith, Southeast Yunnan Province, China: Implications for Regional Metallogeny
Authors: Yan Taotao , Liu Dongsheng , Si Chen , Qiao Yu
Published: March 2020

Constraining the duration of magmatism is of vital importance to the understanding of the magmatic-hydrothermal mineral system. The Bozhushan batholith, located in the middle section of the southeastern Yunnan ore district, mainly consists of biotite monzogranite and monzogranite. Many Sn–W–polymetallic deposits are developed around the Bozhushan batholith, but their temporal and genetic relationships remain controversial. LA-ICP-MS U–Pb zircon and monazite dating were respectively conducted on the same two samples, yielding weighted mean 206Pb/238U zircon ages of 85.1 ± 0.7 and 85.6 ± 0.9 Ma, and weighted mean 206Pb/238U monazite ages of 87.1 ± 0.9 and 88.1 ± 1.1 Ma. The crystallization ages of S-type granites obtained from the zircon U–Th–Pb system and monazite U–Th–Pb system are consistent within the analytical errors. After combining the new ages obtained in this study with recently published U–Pb zircon and cassiterite ages from the giant Baniuchang Ag–Sn–Pb–Zn deposit in the north, and U–Pb zircon and Re-Os molybdenite ages from the large Guanfang W deposit in the south, a temporal framework of magmatism-mineralization in the Bozhushan region has been established. The duration of magmatic activity at Bozhushan is about 7 Ma, with W mineralization occurring at ca. 92 Ma and Sn mineralization at 88–87 Ma.
Tonalite-Dominated Magmatism in the Abitibi Subprovince, Canada, and Significance for Cu-Au Magmatic-Hydrothermal Systems
Authors: Mathieu Lucie , Crépon Alexandre , Kontak Daniel
Published: March 2020

In Archean greenstone belts, magmatism is dominated by intrusive and volcanic rocks with tholeiitic affinities, as well as tonalite- and granodiorite-dominated large-volume batholiths, i.e., tonalite–trondhjemite–granodiorite (TTG) suites. These intrusions are associated with poorly documented mineralization (Cu-Au porphyries) that, in the Neoarchean Abitibi Subprovince (>2.79 to ~2.65 Ga), Superior Province, Canada, are associated with diorite bearing plutons, i.e., tonalite–trondhjemite–diorite (TTD) suites. The importance of TTG versus TTD suites in the evolution of greenstone belts and of their magmatic-hydrothermal systems and related mineralization is unconstrained. The aim of this study was to portray the chemistry and distribution of these suites in the Abitibi Subprovince. The study used data compiled by the geological surveys of Québec and Ontario to evaluate the chemistry of TTG and TTD suites and uncovered two coeval magmas that significantly differentiated (fractional crystallization mostly): 1) a heavy rare earth elements (HREE)-depleted tonalitic magma from high pressure melting of an hydrated basalt source; and 2) a hybrid HREE-undepleted magma that may be a mixture of mantle-derived (tholeiite) and tonalitic melts. The HREE-depleted rocks (mostly tonalite and granodiorite) display chemical characteristics of TTG suites (HREE, Ti, Nb, Ta, Y, and Sr depletion, lack of mafic unit, Na-rich), while the other rocks (tonalite and diorite) formed TTD suites. Tonalite-dominated magmatism, in the Abitibi Subprovince, comprises crustal melts as well as a significant proportion of mantle-derived magmas and this may be essential for Cu-Au magmatic-hydrothermal mineralizing systems.
Chemometric Analysis of Low-field 1H NMR Spectra for Unveiling Adulteration of Slimming Dietary Supplements by Pharmaceutical Compounds
Authors: Wu Nao , Balayssac Stéphane , Danoun Saïda , Malet-Martino Myriam , Gilard Véronique
Published: March 2020

The recent introduction of compact or low-field (LF) NMR spectrometers that use permanent magnets, giving rise to proton (1H) NMR frequencies between 40 and 80 MHz, have opened up new areas of application. The two main limitations of the technique are its insensitivity and poor spectral resolution. However, this study demonstrates that the chemometric treatment of LF 1H NMR spectral data is suitable for unveiling medicines as adulterants of slimming dietary supplements (DS). To this aim, 66 DS were analyzed with LF 1H NMR after quick and easy sample preparation. A first PLS-DA model built with the LF 1H NMR spectra from forty DS belonging to two classes of weight-loss DS (non-adulterated, and sibutramine or phenolphthalein-adulterated) led to the classification of 13 newly purchased test samples as natural, adulterated or borderline. This classification was further refined when the model was made from the same 40 DS now considered as representing three classes of DS (non-adulterated, sibutramine-adulterated, and phenolphthalein-adulterated). The adulterant (sibutramine or phenolphthalein) was correctly predicted as confirmed by the examination of the 1H NMR spectra. A limitation of the chemometric approach is discussed with the example of two atypical weight-loss DS containing fluoxetine or raspberry ketone.
Structure and Aggregation Mechanisms in Amyloids
Authors: Almeida Zaida L. , Brito Rui M. M.
Published: March 2020

The aggregation of a polypeptide chain into amyloid fibrils and their accumulation and deposition into insoluble plaques and intracellular inclusions is the hallmark of several misfolding diseases known as amyloidoses. Alzheimer′s, Parkinson′s and Huntington’s diseases are some of the approximately 50 amyloid diseases described to date. The identification and characterization of the molecular species critical for amyloid formation and disease development have been the focus of intense scrutiny. Methods such as X-ray and electron diffraction, solid-state nuclear magnetic resonance spectroscopy (ssNMR) and cryo-electron microscopy (cryo-EM) have been extensively used and they have contributed to shed a new light onto the structure of amyloid, revealing a multiplicity of polymorphic structures that generally fit the cross-β amyloid motif. The development of rational therapeutic approaches against these debilitating and increasingly frequent misfolding diseases requires a thorough understanding of the molecular mechanisms underlying the amyloid cascade. Here, we review the current knowledge on amyloid fibril formation for several proteins and peptides from a kinetic and thermodynamic point of view, the structure of the molecular species involved in the amyloidogenic process, and the origin of their cytotoxicity.
The Effects of Houttuynia cordata Thunb and Piper ribesioides Wall Extracts on Breast Carcinoma Cell Proliferation, Migration, Invasion and Apoptosis
Authors: Subhawa Subhawat , Chewonarin Teera , Banjerdpongchai Ratana
Published: March 2020

Houttuynia cordata Thunb. (HCT) and Piper ribesioides Wall. (PR) are common herbs that are widely distributed throughout East Asia and possess various biological properties including anti-cancer effects. However, in breast cancer, their mechanisms responsible for anti-carcinogenic effects have not been clarified yet. In this study, the inhibitory effects of HCT and PR ethanolic extracts on breast cancer cell proliferation, migration, invasion and apoptosis were examined. In MCF-7 and MDA-MB-231 cells, HCT and PR extracts at low concentrations can inhibit colony formation and induce G1 cell cycle arrest by downregulating cyclinD1 and CDK4 expression. Additionally, HCT and PR extracts also decreased the migration and invasion of both breast cancer cell lines through inhibition of MMP-2 and MMP-9 secretion. Moreover, the induction of apoptosis was observed in breast cancer cells treated with high concentrations of HCT and PR extracts. Not only stimulated caspases activity, but HCT and PR extracts also upregulated the expression of caspases and pro-apoptotic Bcl-2 family proteins in breast cancer cells. Altogether, these findings provide the rationale to further investigate the potential actions of HCT and PR extracts against breast cancer in vivo.
Compact and Highly Sensitive NO2 Photoacoustic Sensor for Environmental Monitoring
Authors: Pan Yufeng , Dong Lei , Yin Xukun , Wu Hongpeng
Published: March 2020

A nitrogen dioxide (NO2) photoacoustic sensor for environmental monitoring was developed using a low-cost high-power laser diode emitting at 450 nm. A compact low-noise photoacoustic detection module was designed to reduce the sensor size and to suppress noise. A LabVIEW-based control system was employed for the sensor. The parameters of the sensor were studied in detail in terms of laser power and operating pressure. The linearity of the sensor response with laser power and NO2 concentration confirms that saturation does not occur. At atmospheric pressure, a 3σ detection limit of 250 ppt (part per trillion by volume) was achieved with a 1-s averaging time, which corresponds to the specific detectivity of 3.173 × 10−9 W cm−1 Hz−1/2. A 72 h outdoor continuous on-line monitoring of environmental NO2 was implemented to demonstrate the reliability and validity of the developed NO2 sensor.
Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies
Authors: Ma Liwei , Wang Haijun , Wang Jing , Liu Lei , Zhang Song , Bu Ming
Published: March 2020

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.
The Oxygen Consumption Kinetics of Commercial Oenological Tannins in Model Wine Solution and Chianti Red Wine
Authors: Jeremic Jelena , Vongluanngam Isara , Ricci Arianna , Parpinello Giuseppina Paola , Versari Andrea
Published: March 2020

One property of oenological tannins, oxygen reactivity, is commonly exploited in winemaking. The reactivity is mediated by the presence of catalysts (i.e., transition metals and sulfur dioxide) and protects wine against oxidation. This work compares the oxygen consumption rate (OCR) of four commercial oenological tannins (two procyanidins from grape skin and seed, an ellagitannin from oak wood and a gallotannin from gallnut) in a model wine solution and Chianti red wine. All samples were subjected to consecutive cycles of air saturation at 20 °C to increase the total level of oxygen provided. After each cycle, the oxygen level was measured by means of a non-invasive luminescent sensor glued to a transparent surface (sensor dots) until there was no further change in substrate reactivity. The OCR followed first-order kinetics, regardless of the tannin. As expected, the ellagitannin showed the fastest OCR, followed by the two from grape seeds and skins and finally the gallotannin. The total O2 consumption in the red wine was almost double that of the model solution, due to the oxidation of wine substrates. The measurement of OCR is helpful for setting up an advanced winemaking protocol that makes use of tannins to reduce the use of sulfur dioxide.
New Strategy to Preserve Phosphate by Ionic Liquid Matrices in Matrix-Assisted Laser Desorption/Ionization: A Case of Adenosine Nucleotides
Authors: Lin Chih-Hao , Lee Chuping , Wu Yu-Cheng , Lu I-Chung
Published: March 2020

Adenosine -5′-triphosphate (ATP) plays a valuable role in metabolic activity to produce adequate energy in a biosystem. A high ATP/AMP ratio has a correlation with diabetes that induces suppression of AMP-activated protein kinase (AMPK). Matrix-assisted laser desorption/ionization (MALDI)–mass spectrometry (MS) has outstanding potential in determining the ratio of several types of adenosine phosphates in a sample to rapidly understand the primary energy transfer in metabolism. Although MALDI is viewed as a soft ionization technique for MS analysis, excess photon energy might crack the phosphate bonds leading to misinterpretation of the ATP level. In this work, ionic liquid matrices (ILMs) were employed to reduce fragmentation and increase the detection efficiency during the MALDI process. This study demonstrated for the first time that 2,5-dihydroxybenzoic acid pyridine (DHBP) is one of the most effective matrices for further quantitative analysis of adenosine nucleotides. This systematic screening of ILMs also enhances the fundamental understanding of MALDI.
Dialysis Preparation of Smart Redox and Acidity Dual Responsive Tea Polyphenol Functionalized Calcium Phosphate Nanospheres as Anticancer Drug Carriers
Authors: Ren Xiuli , Zhang Peng , Chen Zhenhua
Published: March 2020

Large-scale preparation of biocompatible drug delivery systems with targeted recognition and controlled release properties has always been attractive. However, this strategy has been constrained by a lot of design challenges, such as complicated steps and premature drug release. Herein, in this paper, we address these problems by a facile in situ mineralization method, which synthesizes biodegradable tea polyphenol coated monodisperse calcium phosphate nanospheres using for targeted and controlled delivery of doxorubicin. Dialysis diffusion method was used to control ion release to form mineralized nanospheres. The polyphenol coatings and calcium phosphate used in this work could be biodegraded by intracellular glutathione and acidic microenvironment, respectively, resulting the release of encapsulated drug. According to confocal fluorescence microscopy, and cytotoxicity experiments, the prepared tea polyphenol functionalized, doxorubicin loaded calcium phosphate nanospheres were confirmed to have highly efficient internalization and obvious cell killing effect on target tumor cells, but not normal cells. Our results suggest that these tea polyphenols functionalized calcium phosphate nanospheres are promising vehicles for controlled release of an anticancer drug in cancer therapy.
Cytotoxic Activity of Inositol Angelates and Tirucallane-Type Alkaloids from Amoora Dasyclada
Authors: Yang Sheng-Xiang , Song Cheng-Gang , Kuang Yi , Liu Bing , Zhang Yan-Xin , Zhang Ming-Zhe , Zhang Chun-Ying , Ding Gang , Qin Jian-Chun
Published: March 2020

Three new inositol angelate compounds (1–3) and two new tirucallane-type alkaloids (4 and 5) were isolated from the Amoora dasyclada, and their structures were established mainly by means of combination of 1D and 2D nuclear magnetic resonance and HR-ESI-MS. Based on cytotoxicity testing, compounds 4 and 5 exhibited significant cytotoxic activity against human cancer cell line HepG2 with IC50 value at 8.4 and 13.2 μM. In addition, compounds 4 and 5 also showed remarkable growth inhibitory activity to Artemia salina larvae.
Bioelectronic Nose Based on Single-Stranded DNA and Single-Walled Carbon Nanotube to Identify a Major Plant Volatile Organic Compound (p-Ethylphenol) Released by Phytophthora Cactorum Infected Strawberries
Authors: Wang Hui , Wang Yue , Hou Xiaopeng , Xiong Benhai
Published: March 2020

The metabolic activity in plants or fruits is associated with volatile organic compounds (VOCs), which can help identify the different diseases. P-ethylphenol has been demonstrated as one of the most important VOCs released by the Phytophthora cactorum (P. cactorum) infected strawberries. In this study, a bioelectronic nose based on a gas biosensor array and signal processing model was developed for the noninvasive diagnostics of the P. cactorum infected strawberries, which could overcome the limitations of the traditional spectral analysis methods. The gas biosensor array was fabricated using the single-wall carbon nanotubes (SWNTs) immobilized on the surface of field-effect transistor, and then non-covalently functionalized with different single-strand DNAs (ssDNA) through π–π interaction. The characteristics of ssDNA-SWNTs were investigated using scanning electron microscope, atomic force microscopy, Raman, UV spectroscopy, and electrical measurements, indicating that ssDNA-SWNTs revealed excellent stability and repeatability. By comparing the responses of different ssDNA-SWNTs, the sensitivity to P-ethylphenol was significantly higher for the s6DNA-SWNTs than other ssDNA-SWNTs, in which the limit of detection reached 0.13% saturated vapor of P-ethylphenol. However, s6DNA-SWNTs can still be interfered with by other VOCs emitted by the strawberries in the view of poor selectivity. The bioelectronic nose took advantage of the different sensitivities of different gas biosensors to different VOCs. To improve measure precision, all ssDNA-SWNTs as a gas biosensor array were applied to monitor the different VOCs released by the strawberries, and the detecting data were processed by neural network fitting (NNF) and Gaussian process regression (GPR) with high accuracy.
New Poly(β-Cyclodextrin)/Poly(Vinyl Alcohol) Electrospun Sub-Micrometric Fibers and Their Potential Application for Wastewater Treatments
Authors: Anceschi Anastasia , Caldera Fabrizio , Bertasa Moira , Cecone Claudio , Trotta Francesco , Bracco Pierangiola , Zanetti Marco , Malandrino Mery , Mallon Peter E. , Scalarone Dominique
Published: March 2020

Cyclodextrin (CD)-based polymers are known to efficiently form molecular inclusion complexes with various organic and inorganic guest compounds. In addition, they also have a great potential as metal complexes because deprotonated hydroxyls can strongly bind metal ions under alkaline conditions. The range of environmental conditions for polycyclodextrin/metal ion complexation can be extended by the polymerization of CDs with polyacids. This article describes the preparation and characterization of a new type of poly(β-cyclodextrin) (Poly-βCD) sub-micrometric fibers and explores their potential as metal ion sorbents. A water-soluble hyper-branched β-cyclodextrin polymer was blended with poly(vinyl alcohol) (PVA) and here used to improve the mechanical and morphological features of the fibers. Solutions with a different Poly-βCD/PVA ratio were electrospun, and the fibers were cross-linked by a post-spinning thermal treatment at 160 °C to ensure non-solubility in water. The fiber morphology was analyzed by scanning electron microscopy (SEM) before and after the curing process, and physical-chemical properties were studied by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The capability of the insoluble cyclodextrin-based fibers to remove heavy metals from wastewaters was investigated by testing the adsorption of Cu2+ and Cd2+ using inductively coupled plasma-optical emission spectroscopy (ICP-OES). The results suggest that the poly(β-cyclodextrin)/poly(vinyl alcohol) sub-micrometric fibers can complex metal ions and are especially effective Cu2+ sorbents, thus opening new perspectives to the development of fibers and membranes capable of removing both metal ions and organic pollutants.
Nano/Microscale Thermal Field Distribution: Conducting Thermal Decomposition of Pyrolytic-Type Polymer by Heated AFM Probes
Authors: Li Bo , Geng Yanquan , Yan Yongda
Published: March 2020

In relevant investigations and applications of the heated atomic force microscope (AFM) probes, the determination of the actual thermal distribution between the probe and the materials under processing or testing is a core issue. Herein, the polyphthalaldehyde (PPA) film material and AFM imaging of the decomposition structures (pyrolytic region of PPA) were utilized to study the temperature distribution in the nano/microscale air gap between heated tips and materials. Different sizes of pyramid decomposition structures were formed on the surface of PPA film by the heated tip, which was hovering at the initial tip–sample contact with the preset temperature from 190 to 220 °C for a heating duration ranging from 0.3 to 120 s. According to the positions of the 188 °C isothermal surface in the steady-state probe temperature fields, precise 3D boundary conditions were obtained. We also established a simplified calculation model of the 3D steady-state thermal field based on the experimental results, and calculated the temperature distribution of the air gap under any preset tip temperature, which revealed the principle of horizontal (<700 nm) and vertical (<250 nm) heat transport. Based on our calculation, we fabricated the programmable nano-microscale pyramid structures on the PPA film, which may be a potential application in scanning thermal microscopy.
The Impact of Nutrition and Intestinal Microbiome on Elderly Depression—A Systematic Review
Authors: Klimova Blanka , Novotny Michal , Valis Martin
Published: March 2020

The aim of this review is to systematically review the evidence whether proper nutrition has a positive impact on the prevention or decline of depressive symptoms among elderly people. In addition, possible connections between nutrition, microbiome, and serotonin molecules and its tryptophan precursor are discussed. The methodology follows the PRISMA guidelines, including the PRISMA flow chart. The authors systematically reviewed peer-review, English-written articles published in Web of Science and PubMed between 2013 and 2018. The findings of six original articles, detected on the set inclusion and exclusion criteria, indicate that there is an association between nutrition and depressive symptoms in the target group, i.e., that proper nutrition has a positive impact on the prevention or reduction of depressive symptoms among elderly people. The findings also reveal that there is a considerable correlation between the intakes of vitamin B and a decrease in the prevalence of depressive symptoms. Furthermore, sufficient nutrient intake of tryptophan appears to be an important factor in terms of nutrition and serotonin levels in the body. The authors consider it important to explore associations between the overall dietary intake and depression since diets are not consumed as individual nutrients. Returning to preventive approaches seems to be a rational way to promote the mental health of seniors. Future studies thus need to include interdisciplinary collaboration: from a good diagnosis of the disease by a psychiatrist, through an analysis of the need for nutrient metabolism by a biochemist to the development of a nutritional plan by a nutritional therapist. The limitations of this review consist in a relatively small number of the studies on this topic, including just few randomized controlled trials, which are a guarantee of efficacy and objectivity in comparison with cross-sectional studies.