bluuebunny/crossref_metadata_2025 huggingface dataset:
The Existence of Solutions to Nonlinear Matrix Equations via Fixed Points of Multivalued F-Contractions
Authors: Hussain Nawab , Ali Ghada , Iqbal Iram , Samet Bessem
Published: February 2020

In this paper, we set up an adequate condition for the presence of a solution of the nonlinear matrix equation. To do so, we prove the existence of fixed points for multi-valued modified F-contractions in the context of complete metric spaces, which generalize, refine, and extend several existing results in the literature. An example is accompanies the obtained results to show that derived results are a proper generalization.
Deep Hybrid Model Based on EMD with Classification by Frequency Characteristics for Long-Term Air Quality Prediction
Authors: Jin Xue-Bo , Yang Nian-Xiang , Wang Xiao-Yi , Bai Yu-Ting , Su Ting-Li , Kong Jian-Lei
Published: February 2020

Air pollution (mainly PM2.5) is one of the main environmental problems about air quality. Air pollution prediction and early warning is a prerequisite for air pollution prevention and control. However, it is not easy to accurately predict the long-term trend because the collected PM2.5 data have complex nonlinearity with multiple components of different frequency characteristics. This study proposes a hybrid deep learning predictor, in which the PM2.5 data are decomposed into components by empirical mode decomposition (EMD) firstly, and a convolutional neural network (CNN) is built to classify all the components into a fixed number of groups based on the frequency characteristics. Then, a gated-recurrent-unit (GRU) network is trained for each group as the sub-predictor, and the results from the three GRUs are fused to obtain the prediction result. Experiments based on the PM2.5 data from Beijing verify the proposed model, and the prediction results show that the decomposition and classification can develop the accuracy of the proposed predictor for air pollution prediction greatly.
Background Diet Influences TMAO Concentrations Associated with Red Meat Intake without Influencing Apparent Hepatic TMAO-Related Activity in a Porcine Model
Authors: Thøgersen Rebekka , Rasmussen Martin Krøyer , Sundekilde Ulrik K. , Goethals Sophie A. , Van Hecke Thomas , Vossen Els , De Smet Stefaan , Bertram Hanne Christine
Published: February 2020

Red meat has been associated with an increased cardiovascular disease (CVD) risk, possibly through gut microbial-derived trimethylamine-N-oxide (TMAO). However, previous reports are conflicting, and influences from the background diet may modulate the impact of meat consumption. This study investigated the effect of red and white meat intake combined with two different background diets on urinary TMAO concentration and its association with the colon microbiome in addition to apparent hepatic TMAO-related activity. For 4 weeks, 32 pigs were fed chicken or red and processed meat combined with a prudent or western background diet. 1H NMR-based metabolomics analysis was conducted on urine samples and hepatic Mrna expression of TMAO-related genes determined. Lower urinary TMAO concentrations were observed after intake of red and processed meat when consumed with a prudent compared to a western background diet. In addition, correlation analyses between urinary TMAO concentrations and relative abundance of colon bacterial groups suggested an association between TMAO and specific bacterial taxa. Diet did not affect the hepatic Mrna expression of genes related to TMAO formation. The results suggest that meat-induced TMAO formation is regulated by mechanisms other than alterations at the hepatic gene expression level, possibly involving modulations of the gut microbiota.
Analysis of the Bacterial Diversity of Paipa Cheese (a Traditional Raw Cow’s Milk Cheese from Colombia) by High-Throughput Sequencing
Authors: Castellanos-Rozo José , Pérez Pulido Rubén , Grande Mª. José , Lucas Rosario , Gálvez Antonio
Published: February 2020

Background: Paipa cheese is a traditional, semi-ripened cheese made from raw cow’s milk in Colombia. The aim of this work was to gain insights on the microbiota of Paipa cheese by using a culture-independent approach. Method: two batches of Paipa cheese from three formal producers were sampled during ripening for 28 days. Total DNA from the cheese samples was used to obtain 16S rRNA gene sequences by using Illumina technology. Results: Firmicutes was the main phylum found in the cheeses (relative abundances: 59.2–82.0%), followed by Proteobacteria, Actinobacteria and Bacteroidetes. Lactococcus was the main genus, but other lactic acid bacteria (Enterococcus, Leuconostoc and Streptococcus) were also detected. Stapylococcus was also relevant in some cheese samples. The most important Proteobacteria were Enterobacteriaceae, Aeromonadaceae and Moraxellaceae. Enterobacter and Enterobacteriaceae (others) were detected in all cheese samples. Serratia and Citrobacter were detected in some samples. Aeromonas and Acinetobacter were also relevant. Other minor genera detected were Marinomonas, Corynebacterium 1 and Chryseobacterium. The principal coordinates analysis suggested that there were producer-dependent differences in the microbiota of Paipa cheeses. Conclusions: lactic acid bacteria are the main bacterial group in Paipa cheeses. However, other bacterial groups, including spoilage bacteria, potentially toxin producers, and bacteria potentially pathogenic to humans and/or prone to carry antimicrobial resistance genes are also relevant in the cheeses.
Removal of Soil Microbes Alters Interspecific Competitiveness of Epichloë Endophyte-Infected over Endophyte-Free Leymus chinensis
Authors: Liu Hui , Chen Jing , Qin Tianzi , Shi Xinjian , Gao Yubao , Ren Anzhi
Published: February 2020

Epichloë endophytes may not only affect the growth and resistances of host grasses, but may also affect soil environment including soil microbes. Can Epichloë endophyte-mediated modification of soil microbes affect the competitive ability of host grasses? In this study, we tested whether Epichloë endophytes and soil microbes alter intraspecific competition between Epichloë endophyte-colonized (EI) and endophyte-free (EF) Leymus chinensis and interspecific competition between L. chinensis and Stipa krylovii. The results demonstrated that Epichloë endophyte colonization significantly enhanced the intraspecific competitive ability of L. chinensis and that this beneficial effect was not affected by soil microbes. Under interspecific competition, however, significant interactions between Epichloë endophytes and soil microbes were observed. The effect of Epichloë endophytes on interspecific competitiveness of the host changed from positive to neutral with soil microbe removal. Here higher mycorrhizal colonization rates probably contributed to interspecific competitive advantages of EI over EF L. chinensis. Our result suggests that Epichloë endophytes can influence the competitive ability of the host through plant soil feedbacks from the currently competing plant species.
Prevalence, Population Diversity and Antimicrobial Resistance of Campylobacter coli Isolated in Italian Swine at Slaughterhouse
Authors: Di Donato Guido , Marotta Francesca , Nuvoloni Roberta , Zilli Katiuscia , Neri Diana , Di Sabatino Daria , Calistri Paolo , Di Giannatale Elisabetta
Published: February 2020

Campylobacter spp. are among the microorganisms most commonly associated with foodborne disease. Swine are known to be the main reservoir of Campylobacter coli and a possible source infection of humans as a result of carcass contamination at slaughter. The aim of this study was to evaluate the prevalence of C. coli contamination in swine carcasses, the antimicrobial resistance (AMR) patterns of isolates and the genetic diversity between strains obtained from swine and those isolated from humans. The prevalence of contamination was higher on carcasses (50.4%) than in faeces (32.9%). The 162 C. coli isolated from swine were examined by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST). The results of PFGE indicated a high genetic diversity among the isolates, with 25 different PFGE types. MLST assigned 51 sequence types (STs) to isolates. The most common genotype was ST-854 (16.04%), ST-9264 (10.49 %) and ST-1016 (6.08 %). Results of AMR showed a high resistance to quinolones and fluoroquinolones together with aminoglycosides and tetracycline. Many strains were multi-resistant with predominant R-type TeSCipNa (57%). Five resistance genes were detected along with mutation in the gyrA gene. A strong correlation between phenotypic and genotypic resistance was found for fluoroquinolone and tetracycline. Genetic profiles obtained in swine isolates were compared to those of 11 human strains. All human strains and 64.19% of animal strains (104/162) were assigned to the ST-828 clonal complex.
Enhanced Cypermethrin Degradation Kinetics and Metabolic Pathway in Bacillus thuringiensis Strain SG4
Authors: Bhatt Pankaj , Huang Yaohua , Zhang Wenping , Sharma Anita , Chen Shaohua
Published: February 2020

Cypermethrin is popularly used as an insecticide in households and agricultural fields, resulting in serious environmental contamination. Rapid and effective techniques that minimize or remove insecticidal residues from the environment are urgently required. However, the currently available cypermethrin-degrading bacterial strains are suboptimal. We aimed to characterize the kinetics and metabolic pathway of highly efficient cypermethrin-degrading Bacillus thuringiensis strain SG4. Strain SG4 effectively degraded cypermethrin under different conditions. The maximum degradation was observed at 32 °C, pH 7.0, and a shaking speed of 110 rpm, and about 80% of the initial dose of cypermethrin (50 mg·L−1) was degraded in minimal salt medium within 15 days. SG4 cells immobilized with sodium alginate provided a higher degradation rate (85.0%) and lower half-life (t1/2) of 5.3 days compared to the 52.9 days of the control. Bioaugmentation of cypermethrin-contaminated soil slurry with strain SG4 significantly enhanced its biodegradation (83.3%). Analysis of the degradation products led to identification of nine metabolites of cypermethrin, which revealed that cypermethrin could be degraded first by cleavage of its ester bond, followed by degradation of the benzene ring, and subsequent metabolism. A new degradation pathway for cypermethrin was proposed based on analysis of the metabolites. We investigated the active role of B. thuringiensis strain SG4 in cypermethrin degradation under various conditions that could be applied in large-scale pollutant treatment.
Host Innate Immune Response of Geese Infected with Clade 2.3.4.4 H5N6 Highly Pathogenic Avian Influenza Viruses
Authors: Wu Siyu , Huang Jianni , Huang Qiwen , Zhang Junsheng , Liu Jing , Xue Qian , Li Weiqiang , Liao Ming , Jiao Peirong
Published: February 2020

Since 2014, highly pathogenic avian influenza (HPAI) H5N6 viruses have circulated in waterfowls and caused human infections in China, posing significant threats to the poultry industry and the public health. However, the genetics, pathogenicity and innate immune response of H5N6 HPAIVs in geese remain largely unknown. In this study, we analyzed the genetic characteristic of the two H5N6 viruses (GS38 and DK09) isolated from apparently healthy domestic goose and duck in live poultry markets (LPMs) of Southern China in 2016. Phylogenetic analysis showed that the HA genes of the two H5N6 viruses belonged to clade 2.3.4.4 and were clustered into the MIX-like group. The MIX-like group viruses have circulated in regions such as China, Japan, Korea, and Vietnam. The NA genes of the two H5N6 viruses were classified into the Eurasian sublineage. The internal genes including PB2, PB1, PA, NP, M, and NS of the two H5N6 viruses derived from the MIX-like. Therefore, our results suggested that the two H5N6 viruses were reassortants of the H5N1 and H6N6 viruses and likely derived from the same ancestor. Additionally, we evaluated the pathogenicity and transmission of the two H5N6 viruses in domestic geese. Results showed that both the two viruses caused serious clinical symptoms in all inoculated geese and led to high mortality in these birds. Both the two viruses were transmitted efficiently to contact geese and caused lethal infection in these birds. Furthermore, we found that mRNA of pattern recognition receptors (PRRs), interferons (IFNs), and stimulated genes (ISGs) exhibited different levels of activation in the lungs and spleens of the two H5N6 viruses-inoculated geese though did not protect these birds from H5N6 HPAIVs infection. Our results suggested that the clade 2.3.4.4 waterfowl-origin H5N6 HPAIVs isolated from LPMs of Southern China could cause high mortality in geese and innate immune-related genes were involved in the geese innate immune response to H5N6 HPAIVs infection. Therefore, we should pay more attention to the evolution, pathogenic variations of these viruses and enhance virological surveillance of clade 2.3.4.4 H5N6 HPAIVs in waterfowls in China.
Diversity and Bioactive Potential of Actinobacteria from Unexplored Regions of Western Ghats, India
Authors: Siddharth Saket , Vittal Ravishankar Rai , Wink Joachim , Steinert Michael
Published: February 2020

The search for novel bioactive metabolites continues to be of much importance around the world for pharmaceutical, agricultural, and industrial applications. Actinobacteria constitute one of the extremely interesting groups of microorganisms widely used as important biological contributors for a wide range of novel secondary metabolites. This study focused on the assessment of antimicrobial and antioxidant activity of crude extracts of actinobacterial strains. Western Ghats of India represents unique regions of biologically diverse areas called “hot spots”. A total of 32 isolates were obtained from soil samples of different forest locations of Bisle Ghat and Virjapet situated in Western Ghats of Karnataka, India. The isolates were identified as species of Streptomyces, Nocardiopsis, and Nocardioides by cultural, morphological, and molecular studies. Based on preliminary screening, seven isolates were chosen for metabolites extraction and to determine antimicrobial activity qualitatively (disc diffusion method) and quantitatively (micro dilution method) and scavenging activity against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. Crude extracts of all seven isolates exhibited fairly strong antibacterial activity towards MRSA strains (MRSA ATCC 33591, MRSA ATCC NR-46071, and MRSA ATCC 46171) with MIC varying from 15.62 to 125 μg/mL, whereas showed less inhibition potential towards Gram-negative bacteria Salmonella typhi (ATCC 25241) and Escherichia coli (ATCC 11775) with MIC of 125–500 μg/mL. The isolates namely S1A, SS5, SCA35, and SCA 11 inhibited Fusarium moniliforme (MTCC 6576) to a maximum extent with MIC ranging from 62.5 to 250 μg/mL. Crude extract of SCA 11 and SCA 13 exhibited potent scavenging activities against DPPH and ABTS radicals. The results from this study suggest that actinobacterial strains of Western Ghats are an excellent source of natural antimicrobial and antioxidant compounds. Further research investigations on purification, recovery, and structural characterization of the active compounds are to be carried out.
A Novel Eye Drop Candidate for Age-Related Macular Degeneration Treatment: Studies on its Pharmacokinetics and Distribution in Rats and Rabbits
Authors: Choi Eun-Jeong , Choi Go-Wun , Kim Ju Hee , Jang Hee-Woon , Lee Ju-Hee , Bae Hyun Ju , Kim Young Gwan , Lee Yong-Bok , Cho Hea-Young
Published: February 2020

Age-related macular degeneration (AMD) is wearing down of macula of retina, causing a blur or loss of vision in the center of the visual field. It can be categorized into dry or wet AMD. Until now, medical treatments for dry AMD have not been developed yet. The aim of this study was to evaluate pharmacokinetics (PKs) and tissue distribution of CK41016, a novel candidate for dry AMD, after intravenous (IV) or eye drop administration in rats and rabbits. In addition, a simple and sensitive bioanalytical method for CK41016 using ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was developed. PK parameters were estimated by compartmental analysis using a WinNonlin® software version 8.1 (a Certara™ company). A PK model of CK41016 was well-described by the two-compartment model. The tissue-to-plasma partition coefficient (Kp) of CK41016 was the highest in the vitreous humor of rats and the cornea of rabbits after eye drop administration. In addition, the Caco-2 cell transporter assay confirmed that CK41016 was not an active substrate for the efflux transporter. In summary, the PKs and tissue distribution of CK41016 were successfully evaluated and investigated whether this drug was a substrate of efflux transporters.
Comprehensive Investigation of Moringa oleifera from Different Regions by Simultaneous Determination of 11 Polyphenols Using UPLC-ESI-MS/MS
Authors: Zhu Yanqin , Yin Qinhong , Yang Yaling
Published: February 2020

In this study, we develop and validate a simultaneous quantification of polyphenols method based on an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to adequately understand how different habitats influence the quality and profile of Moringa oleifera polyphenol. Furthermore, principal component analysis (PCA) and hierarchical cluster analysis (HCA) were used to compare and discriminate 25 samples collected from different areas. A significant correlation was found between the polyphenol profile and the collection area. Significant differences in the polyphenol content of Moringa oleifera from different regions indicate that the genetic diversity of Moringa oleifera was relatively rich, possibly due to differences in cultivation conditions, climate, or soil environment resulting in the accumulation of different polyphenols. These observations provide a theoretical basis for subsequent Moringa oleifera germplasm selection and development research. Furthermore, the quantitative analysis methodology used to characterize the polyphenols may be used toward developing quality assessment and future pharmacodynamic investigations of Moringa oleifera.
Sucupira Oil-Loaded Nanostructured Lipid Carriers (NLC): Lipid Screening, Factorial Design, Release Profile, and Cytotoxicity
Authors: Vieira Raquel , Severino Patricia , Nalone Luciana A. , Souto Selma B. , Silva Amélia M. , Lucarini Massimo , Durazzo Alessandra , Santini Antonello , Souto Eliana B.
Published: February 2020

Essential oils are odorant liquid oily products consisting of a complex mixture of volatile compounds obtained from a plant raw material. They have been increasingly proven to act as potential natural agents in the treatment of several human conditions, including diabetes mellitus (DM). DM is a metabolic disorder characterized by chronic hyperglycemia closely related to carbohydrate, protein and fat metabolism disturbances. In order to explore novel approaches for the management of DM our group proposes the encapsulation of sucupira essential oil, obtained from the fruits of the Brazilian plants of the genus Pterodon, in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS). Encapsulation was performed by hot high-pressure homogenization (HPH) technique and the samples were then analyzed by dynamic light scattering (DLS) for mean average size and polydispersity index (PI) and by electrophoretic light scattering (ELS) for zeta potential (ZP), immediately after production and after 24 h of storage at 4 °C. An optimal sucupira-loaded NLC was found to consist of 0.5% (m/V) sucupira oil, 4.5% (m/V) of Kollivax® GMS II and 1.425% (m/V) of TPGS (formulation no. 6) characterized by a mean particle size ranging from 148.1 ± 0.9815 nm (0 h) to 159.3 ± 9.539 nm (at 24 h), a PI from 0.274 ± 0.029 (0 h) to 0.305 ± 0.028 (24 h) and a ZP from −0.00236 ± 0.147 mV (at 0 h) to 0.125 ± 0.162 (at 24 h). The encapsulation efficiency and loading capacity were 99.98% and 9.6%, respectively. The optimized formulation followed a modified release profile fitting the first order kinetics, over a period of 8 h. In vitro cytotoxicity studies were performed against Caco-2 cell lines, for which the cell viability above 90% confirmed the non-cytotoxic profile of both blank and sucupira oil-loaded NLC.
Novozym 435-Catalyzed Synthesis of Well-Defined Hyperbranched Aliphatic Poly(β-thioether ester)
Authors: Wu Wan-Xia , Liu Zi
Published: February 2020

A series of new hyperbranched aliphatic poly(β-thioether ester)s were prepared by the enzymatic ring-opening polycondensation of 1,4-oxathiepan-7-one (OTO) and AB2/ABB’ comonomer with acid-labile β-thiopropionate groups. Two kinds of comonomers, methyl 3-((3-hydroxy-2-(hydroxymethyl)propyl)thio)propanoate (HHTP) and methyl 3-((2,3-dihydroxypropyl)thio)propanoate (DHTP), with different primary alcohols and secondary alcohols, were synthesized by thiol–ene click chemistry and thiol-ene Michael addition, respectively. Immobilized lipase B from Candida antarctica (CALB), Novozym 435, was used as the catalyst. The random copolymers were characterized by 1H-NMR, 13C-NMR, GPC, TGA, and DSC. All branched copolyesters had high molecular weights over 15,000 Da with narrow polydispersities in the range of 1.75–2.01 and were amorphous polymers. Their degradation properties under acidic conditions were also studied in vitro. The polymeric nanoparticles of hyperbranched poly(β-thioether ester)s were successfully obtained and showed good oxidation-responsive properties, indicating their potential for biomedical applications.
Parallel Strategy Increases the Thermostability and Activity of Glutamate Decarboxylase
Authors: Zhang Qing-Fei , Hu Sheng , Zhao Wei-Rui , Huang Jun , Mei Jia-Qi , Mei Le-He
Published: February 2020

Glutamate decarboxylase (GAD; EC 4.1.1.15) is a unique pyridoxal 5-phosphate (PLP)-dependent enzyme that specifically catalyzes the decarboxylation of L-glutamic acid to produce γ-aminobutyric acid (GABA), which exhibits several well-known physiological functions. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, a parallel strategy comprising sequential analysis and free energy calculation was applied to identify critical amino acid sites affecting thermostability of GAD and select proper mutation contributing to improve structure rigidity of the enzyme. Two mutant enzymes, D203E and S325A, with higher thermostability were obtained, and their semi-inactivation temperature (T5015) values were 2.3 °C and 1.4 °C higher than the corresponding value of the wild-type enzyme (WT), respectively. Moreover, the mutant, S325A, exhibited enhanced activity compared to the wild type, with a 1.67-fold increase. The parallel strategy presented in this work proved to be an efficient tool for the reinforcement of protein thermostability.
Amyloid-Beta1-42 -Induced Increase in GABAergic Tonic Conductance in Mouse Hippocampal CA1 Pyramidal Cells
Authors: Calvo-Flores Guzmán Beatriz , Kim SooHyun , Chawdhary Bhavya , Peppercorn Katie , Tate Warren P , Waldvogel Henry J , Faull Richard LM , Montgomery Johanna , Kwakowsky Andrea
Published: February 2020

Alzheimer’s disease (AD) is a complex and chronic neurodegenerative disorder that involves a progressive and severe decline in cognition and memory. During the last few decades a considerable amount of research has been done in order to better understand tau-pathology, inflammatory activity and neuronal synapse loss in AD, all of them contributing to cognitive decline. Early hippocampal network dysfunction is one of the main factors associated with cognitive decline in AD. Much has been published about amyloid-beta1-42 (Aβ1-42)-mediated excitotoxicity in AD. However, increasing evidence demonstrates that the remodeling of the inhibitory gamma-aminobutyric acid (GABAergic) system contributes to the excitatory/inhibitory (E/I) disruption in the AD hippocampus, but the underlying mechanisms are not well understood. In the present study, we show that hippocampal injection of Aβ1-42 is sufficient to induce cognitive deficits 7 days post-injection. We demonstrate using in vitro whole-cell patch-clamping an increased inhibitory GABAergic tonic conductance mediated by extrasynaptic type A GABA receptors (GABAARs), recorded in the CA1 region of the mouse hippocampus following Aβ1-42 micro injection. Such alterations in GABA neurotransmission and/or inhibitory GABAARs could have a significant impact on both hippocampal structure and function, causing E/I balance disruption and potentially contributing to cognitive deficits in AD.
Hydrogen-Bonding Linkers Yield a Large-Pore, Non-Catenated, Metal-Organic Framework with pcu Topology
Authors: Yazdanparast Mohammad S. , Day Victor W. , Gadzikwa Tendai
Published: February 2020

Pillared paddle-wheel-based metal-organic framework (MOF) materials are an attractive target as they offer a reliable method for constructing well-defined, multifunctional materials. A drawback of these materials, which has limited their application, is their tendency to form catenated frameworks with little accessible volume. To eliminate this disadvantage, it is necessary to investigate strategies for constructing non-catenated pillared paddle-wheel MOFs. Hydrogen-bonding substituents on linkers have been postulated to prevent catenation in certain frameworks and, in this work, we present a new MOF to further bolster this theory. Using 2,2′-diamino-[1,1′-biphenyl]-4,4′-dicarboxylic acid, BPDC-(NH2)2, linkers and dipyridyl glycol, DPG, pillars, we assembled a MOF with pcu topology. The new material is non-catenated, exhibiting large accessible pores and low density. To the best of our knowledge, this material constitutes the pcu framework with the largest pore volume and lowest density. We attribute the lack of catenation to the presence of H-bonding substituents on both linkers.
A Review of Small Molecule Inhibitors and Functional Probes of Human Cathepsin L
Authors: Dana Dibyendu , Pathak Sanjai K.
Published: February 2020

Human cathepsin L belongs to the cathepsin family of proteolytic enzymes with primarily an endopeptidase activity. Although its primary functions were originally thought to be only of a housekeeping enzyme that degraded intracellular and endocytosed proteins in lysosome, numerous recent studies suggest that it plays many critical and specific roles in diverse cellular settings. Not surprisingly, the dysregulated function of cathepsin L has manifested itself in several human diseases, making it an attractive target for drug development. Unfortunately, several redundant and isoform-specific functions have recently emerged, adding complexities to the drug discovery process. To address this, a series of chemical biology tools have been developed that helped define cathepsin L biology with exquisite precision in specific cellular contexts. This review elaborates on the recently developed small molecule inhibitors and probes of human cathepsin L, outlining their mechanisms of action, and describing their potential utilities in dissecting unknown function.
Thermodynamic Driving Forces and Chemical Reaction Fluxes; Reflections on the Steady State
Authors: Pekař Miloslav
Published: February 2020

Molar balances of continuous and batch reacting systems with a simple reaction are analyzed from the point of view of finding relationships between the thermodynamic driving force and the chemical reaction rate. Special attention is focused on the steady state, which has been the core subject of previous similar work. It is argued that such relationships should also contain, besides the thermodynamic driving force, a kinetic factor, and are of a specific form for a specific reacting system. More general analysis is provided by means of the non-equilibrium thermodynamics of linear fluid mixtures. Then, the driving force can be expressed either in the Gibbs energy (affinity) form or on the basis of chemical potentials. The relationships can be generally interpreted in terms of force, resistance and flux.
The Tomato Metallocarboxypeptidase Inhibitor I, which Interacts with a Heavy Metal-Associated Isoprenylated Protein, Is Implicated in Plant Response to Cadmium
Authors: Manara Anna , Fasani Elisa , Molesini Barbara , DalCorso Giovanni , Pennisi Federica , Pandolfini Tiziana , Furini Antonella
Published: February 2020

Metallocarboxypeptidases are metal-dependent enzymes, whose biological activity is regulated by inhibitors directed on the metal-containing active site. Some metallocarboxypeptidase inhibitors are induced under stress conditions and have a role in defense against pests. This paper is aimed at investigating the response of the tomato metallocarboxypeptidase inhibitor (TCMP)-1 to Cd and other abiotic stresses. To this aim, the tomato TCMP-1 was ectopically expressed in the model species Arabidopsis thaliana, and a yeast two-hybrid analysis was performed to identify interacting proteins. We demonstrate that TCMP-1 is responsive to Cd, NaCl, and abscisic acid (ABA) and interacts with the tomato heavy metal-associated isoprenylated plant protein (HIPP)26. A. thaliana plants overexpressing TCMP-1 accumulate lower amount of Cd in shoots, display an increased expression of AtHIPP26 in comparison with wild-type plants, and are characterized by a modulation in the expression of antioxidant enzymes. Overall, these results suggest a possible role for the TCMP-1/HIPP26 complex in Cd response and compartmentalization.
Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides)
Authors: Cavaliere Alessandra , Probst Katrin C. , Paisey Stephen J. , Marshall Christopher , Dheere Abdul K. H. , Aigbirhio Franklin , McGuigan Christopher , Westwell Andrew D.
Published: February 2020

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15–30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1–5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min).
Trityl-Containing Alcohols—An Efficient Chirality Transmission Process from Inductor to the Stereodynamic Propeller and their Solid-State Structural Diversity
Authors: Górczyńska Sylwia , Brzdonkiewicz Aleksandra , Jelecki Maciej , Czapik Agnieszka , Stasiak Bartosz , Kwit Marcin
Published: February 2020

The cascade process of a dynamic chirality transmission from the permanent chirality center to the stereodynamic triphenylmethyl group has been studied for series of optically active trityl derivatives. The structural analysis, carried out with the use of complementary methods, enabled us to determine the mechanism of chirality transfer. The process of chirality transmission involves a set of weak but complementary electrostatic interactions. The induction of helicity in a trityl propeller is revealed by rising non-zero cotton effects in the area of trityl UV-absorption. The presence of an additional stereogenic center in close proximity to the trityl-containing stereogenic center significantly affects the sign and, to a lesser extent, magnitude of the respective cotton effects. Despite the bulkiness of the trityl, in the crystalline phase, the molecules under study strictly fill the space. In the crystal, molecules form aggregates stabilized by OH•••O hydrogen bonds. However, the presence of two trityl groups precludes formation of OH•••O hydrogen bonding. Additionally, the trityl group seems to be responsible for the formation of the solid solutions by e.g., racemates of trans- and cis-2-tritylcyclohexanol. Therefore, the trityl group acts as a supramolecular protective group, which in turn can be used in the crystal engineering.
How do the Hückel and Baird Rules Fade away in Annulenes?
Authors: Casademont-Reig Irene , Ramos-Cordoba Eloy , Torrent-Sucarrat Miquel , Matito Eduard
Published: February 2020

Two of the most popular rules to characterize the aromaticity of molecules are those due to Hückel and Baird, which govern the aromaticity of singlet and triplet states. In this work, we study how these rules fade away as the ring structure increases and an optimal overlap between p orbitals is no longer possible due to geometrical restrictions. To this end, we study the lowest-lying singlet and triplet states of neutral annulenes with an even number of carbon atoms between four and eighteen. First of all, we analyze these rules from the Hückel molecular orbital method and, afterwards, we perform a geometry optimization of the annulenes with several density functional approximations in order to analyze the effect that the distortions from planarity produce on the aromaticity of annulenes. Finally, we analyze the performance of three density functional approximations that employ different percentages of Hartree-Fock exchange (B3LYP, CAM-B3LYP and M06-2X) and Hartree-Fock. Our results reveal that functionals with a low percentage of Hartree-Fock exchange at long ranges suffer from severe delocalization errors that result in wrong geometrical structures and the overestimation of the aromatic character of annulenes.
Continuous Flow Esterification of a H-Phosphinic Acid, and Transesterification of H-Phosphinates and H-Phosphonates under Microwave Conditions
Authors: Kiss Nóra Zsuzsa , Henyecz Réka , Keglevich György
Published: February 2020

The microwave (MW)-assisted direct esterification of phenyl-H-phosphinic acid, transesterification of the alkyl phenyl-H-phosphinates so obtained, and the similar reaction of dibenzyl phosphite (DBP) were investigated in detail, and the batch accomplishments were translated into a continuous flow operation that, after optimization of the parameters, such as temperature and flow rate, proved to be more productive. Alcoholysis of DBP is a two-step process involving an intermediate phosphite with two different alkoxy groups. The latter species are of synthetic interest, as precursors for optically active reagents.
Quality Enhancement Mechanism of Alkali-Free Chinese Northern Steamed Bread by Sourdough Acidification
Authors: Yan Bowen , Yang Huayu , Wu Yejun , Lian Huizhang , Zhang Hao , Chen Wei , Fan Daming , Zhao Jianxin
Published: February 2020

Alkali was used to adjust the pH and neutralize the excess acids of dough in the processing of Chinese northern steamed bread (CNSB). However, extra alkali addition generally resulted in alkalic flavor and poor appearance. The aim of this work was to investigate the role of proofed dough pH on the texture of CNSB. Correlation analysis demonstrated that the pH value of proofed dough has a significant effect on the textural properties of CNSB. The mechanism studies found that gradual acidification of dough by lactic acid bacteria is a critical factor affecting the process. Conversely, chemical acidification weakened the texture property of products and reduced the dough rheology. Scanning electron microscope (SEM) analysis showed that fermentation with starter for 12 h produced a continuous and extensional protein network in the proofed dough. Furthermore, the decreasing pH of proofed dough increased the extractability of protein in a sodium dodecyl sulfate (SDS)-containing medium and the content of free sulfhydryl (SH). The structure and content of gluten, especially influenced by gradual acidification level, change the quality of the final product. It is a novel approach to obtain an alkali-free CNSB with excellent quality by moderate gluten adjustment.
Value-Added Lager Beer Enriched with Eggplant (Solanum melongena L.) Peel Extract
Authors: Horincar Georgiana , Enachi Elena , Bolea Carmen , Râpeanu Gabriela , Aprodu Iuliana
Published: February 2020

Manufacturing beer with a high biological value requires identifying new methods for increasing the health-enhancing compounds level. The aim of this study was to increase the biological value of beer by adding antioxidant-rich eggplant (Solanum melongena L.) peel extract (EPE). The total phenolic content (TPC), total flavonoid content (TFC), and total monomeric anthocyanin content (TMA) were determined. Moreover, the antioxidant activity was evaluated by different radical scavenging assays. The addition of different levels of EPE resulted in a significant increase of TPC and TFC of beer samples from 0.426 to 0.631 mg GAE/mL, and from 0.065 to 0.171 mg CE/mL, respectively. The EPE-supplemented beer samples developed a reddish color because of the presence of anthocyanin pigments. The TMA content of beer varied from 0.011 to 0.083 mg D3G/mL with the level of added EPE. The HPLC analysis indicated that the anthocyanins prevailing in the eggplant peels were delphinidin-3-rutinoside, delphininidin-3-glucoside and delphinidin-3-rutinoside-5-glucoside. The radical scavenging assays indicated a linear increase of the antioxidant activity following EPE addition, without altering the physicochemical parameters of the beer. These results are promising for using the EPE as a functional ingredient for beer production.
Effect and Analysis of Bacterial Lysates for the Treatment of Recurrent Urinary Tract Infections in Adults
Authors: Ahumada-Cota Ricardo E. , Hernandez-Chiñas Ulises , Milián-Suazo Feliciano , Chávez-Berrocal María E. , Navarro-Ocaña Armando , Martínez-Gómez Daniel , Patiño-López Genaro , Salazar-Jiménez Erika P. , Eslava Carlos A.
Published: February 2020

Urinary tract infection (UTI) is a relevant public health problem, economically and socially affecting the lives of patients. The increase of antimicrobial bacterial resistance significantly hinders the treatment of UTIs, raising the need to search for alternative therapies. Bacterial lysates (BL) obtained from Escherichia coli and other pathogens have been used to treat different infectious diseases with promising results. This work aims to evaluate the effect and composition of an autologous BL for the treatment and control of recurrent UTIs in adults. The results show remission in 70% of the patients within the first three months after the administration of BL, while the infection is maintained under control for 6–12 months. The analysis by liquid chromatography–mass spectrometry (LC-MS) of the BL fractions recognized by the sera of patients shows the presence of cytosolic proteins, fimbriae, OMPs, and LPS. Our study demonstrates that the autologous BL contributed to the treatment and control of recurrent UTIs in adults, and its composition shows that different surface components of E. coli are potential immunogens that could be used to create a polyvalent protective vaccine.
Physicians’, Nurses’ and Pharmacists’ Perceptions of Determinants to Deprescribing in Nursing Homes Considering Three Levels of Action: A Qualitative Study
Authors: Foley Rose-Anna , Hurard Lucie Lechevalier , Cateau Damien , Koutaissoff Daria , Bugnon Olivier , Niquille Anne
Published: February 2020

Background: Polypharmacy and the use of potentially inappropriate medications are frequent safety issues among nursing home (NH) residents. Deprescribing can significantly reduce the number of drugs used, medication costs, and mortality. This qualitative study sought to understand and compare the perceptions and practices of nurses, pharmacists, and physicians regarding deprescribing in Swiss NHs, referring to an implementation approach on three levels of action: the individual, the institution, and the healthcare system. Methods: Two focus groups were held with 21 participants: one focus group with 11 pharmacists, another with 10 nurses and six semi-structured interviews with physicians were conducted and focused on their individual experience and practices. They were audiotaped and fully transcribed, and a content analysis was performed using to MAXQDA (Ver 12) software. Results: (1) At an individual level, physicians were concerned by consequences of deprescribing in terms of safety. Nurses were closest to residents and stressed the importance of finding the right time, creating a bond of trust before deprescribing and considering the purpose of the stay in the NH. Pharmacists relied on structured guides for deprescribing, which led their reflection and practice. All professionals saw the complexity of the clinical situations, as well as residents’ and relatives’ fears of interruption of care. (2) At an institutional level, the professionals stressed the lack of time to discuss patients’ health and treatment, while pre-existing interprofessional collaboration, specifically, quality circles, seemed useful tools to create common knowledge. In order to reduce prescriptions, better coordination between physicians, nurses, pharmacists and specialists seemed crucial. (3) At the health system level, funding still needs to be provided to consolidate the process, go beyond organisational constraints and ensure deprescribing serves the patient’s wellbeing above all. Conclusions: At the individual level of implementation, the different healthcare professionals expressed specific concerns about deprescribing, depending on their defined role in NHs. Their perspective about the different levers to promote deprescribing at institutional and healthcare system levels converge towards interprofessional collaboration supported by the healthcare system. Specific funding and incentives are therefore needed to support a sustainable interprofessional team.
Effect of Shading on Red Colour and Fruit Quality in Blush Pears “ANP-0118” and “ANP-0131”
Authors: Peavey Madeleine , Goodwin Ian , McClymont Lexie , Chandra Subhash
Published: February 2020

Some cultivars of Pyrus communis develop mature fruit with a distinctive red blush. Investigating the patterns of pear colour development in response to sunlight has implications for orchard management of these pears. The objectives of these experiments are to study the seasonal patterns of colour development and investigate the influence of shade and sunlight exposure on the red colour and harvest quality of blush pears “ANP-0118” and “ANP-0131”. Several long, medium and short shading treatments were applied at different stages of fruit development from 28 (“ANP-0131”) and 29 (“ANP-0118”) days after full bloom (DAFB) until harvests at 119 DAFB (“ANP-0118”) and 175 DAFB (“ANP-0131”). Fruits were measured every three weeks for colour parameters (a*, hue angle, chroma) and at harvest for quality parameters (fresh weight, visual assessments of percentage blush coverage and blush intensity, flesh firmness and soluble solids concentration). In the unshaded control, red colour increased during the growing season (increase in a* value and decrease in hue angle), as well as increasing in chroma value. Periods of shading during the season negatively affected red colour in both cultivars, as evidenced by significant decreases in a* value and increases in hue angle. Shaded fruits that were subsequently re-exposed to sunlight reacted with a dynamic increase in a* value and decrease in hue angle. Fruit shaded for the length of the experiment or prior to harvest had significantly lower a* values than the control at harvest. Visual assessment at harvest of percentage blush coverage and blush intensity were significantly affected by shading in both cultivars. Shading treatments applied early in the experiment had a negative effect on the fresh fruit weight of “ANP-0118”.
Variability in the Capacity to Produce Damage-Induced Aldehyde Green Leaf Volatiles among Different Plant Species Provides Novel Insights into Biosynthetic Diversity
Authors: Engelberth Jurgen , Engelberth Marie
Published: February 2020

Green leaf volatiles (GLVs) are commonly released by plants upon damage, thereby providing volatile signals for other plants to prepare against the major causes of damage, herbivory, pathogen infection, and cold stress. However, while the biosynthesis of these compounds is generally well understood, little is known about the qualities and quantities that are released by different plant species, nor is it known if release patterns can be associated with different clades of plants. Here, we provide a first study describing the damage-induced release of major GLVs by more than 50 plant species. We found major differences in the quantity and quality of those compounds between different plant species ranging from undetectable levels to almost 100 µg per gram fresh weight. We also found major shifts in the composition that correlate directly to the quantity of emitted GLV. However, we did not find any major patterns that would associate specific GLV release with distinct clades of plants.
Energy-Economizing Optimization of Magnesium Alloy Hot Stamping Process
Authors: Gao Mengdi , Wang Qingyang , Li Lei , Ma Zhilin
Published: February 2020

Reducing the mass of vehicles is an effective way to improve energy efficiency and mileage. Therefore, hot stamping is developed to manufacture lightweight materials used for vehicle production, such as magnesium and aluminum alloys. However, in comparison with traditional cold stamping, hot stamping is a high-energy-consumption process, because it requires heating sheet materials to a certain temperature before forming. Moreover, the process parameters of hot stamping considerably influence the product forming quality and energy consumption. In this work, the energy-economizing indices of hot stamping are established with multiobjective consideration of energy consumption and product forming quality to find a pathway by which to obtain optimal hot stamping process parameters. An energy consumption index is quantified by the developed models, and forming quality indices are calculated using a finite element model. Response surface models between the process parameters and energy-economizing indices are established by combining the Latin hypercube design and response surface methodology. The multiobjective problem is solved using a multiobjective genetic algorithm (NSGA-II) to obtain the Pareto frontier. ZK60 magnesium alloy hot stamping is applied as a case study to obtain an optimal combination of parameters, and compromise solutions are compared through stamping trials and numerical simulations. The obtained results may be used for guiding process optimization regarding energy saving and the method of manufacturing parameters selection.