bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative identification of human serpin PAI‐1 inhibitors from Dracaena dragon blood and molecular implications for inhibitor‐induced PAI‐1 allosterism
Authors: Xu Chong , Liu Xia , Shen Jie , Sun Quan , Guo Xiaohong , Yang Min , Leng Jing 
Published: January 2021

AbstractHuman plasminogen activator inhibitor‐1 (PAI‐1) is an important component of the coagulation system and has been recognized as a potential therapeutic target of diverse cardiovascular disorders. Previously, it was found that the extracts from the Chinese medicine Dracaena dragon blood have potent inhibitory activity against PAI‐1, but it is unclear which constituents directly participate in the inhibition and how do they regulate PAI‐1 at molecular level. Here, we describe an integrated strategy to identify the dragon blood's chemical constituents that can directly target PAI‐1. With the strategy, five compounds 1–5 are hit as promising PAI‐1 inhibitor candidates, from which three are measured to have high or moderate activity against PAI‐1. In particular, the compound 3 is determined to exhibit the highest potency; this value is roughly comparable with the widely used PAI‐1 inhibitor Tiplaxtinin. We further examine the molecular effect of compound 3 on PAI‐1 conformation at structural level. It is supposed that small‐molecule inhibitor regulates the reactive center loop (RCL) of PAI‐1 through an allosterism, that is, binding of compound 3 to PAI‐1 can allosterically stabilize RCL in latent form, thus promoting PAI‐1 conformational conversion from metastable active form to the inactive latent form. Long‐term atomistic simulations also demonstrate that removal of compound 3 can destabilize the structured β‐stranded conformation of RCL in latent form, although the current simulations are still not sufficient to characterize the full conversion dynamics trajectory.
Continued insights into virus clearance validation across continuous capture chromatography
Authors: Angelo James M. , Potter Kevin , Müller‐Späth Thomas , Xu Xuankuo , Li Zheng Jian , Ghose Sanchayita 
Published: January 2021

AbstractMulti‐column capture chromatography (MCC) has gained increased attention lately due to the significant economic and process‐related advantages it offers compared to traditional batch mode chromatography. However, for wide adoption of this technology in the clinical and commercial space, it requires scalable models for viral validation. In this study, additional viral validation studies were conducted under cGLP guidelines to assess retro‐(X‐MuLV) and parvo‐virus (minute virus of mice) clearance across twin‐column continuous capture chromatography (CaptureSMB) to supplement work previously performed. A surrogate model was validated using standard batch mode chromatography equipment based on flow path modifications to mimic the loading strategy employed in CaptureSMB. In addition, aged resin was used in this surrogate format to assess the impact of resin lifetime on viral clearance during continuous capture operation. The impact of column loading was also explored to shed light on the viral clearance mechanisms of protein A chromatography in overloading conditions. The proposed approach greatly simplifies MCC virus validation studies, and provides a robust strategy for regulatory filing of continuous biomanufacturing processes.
Development of an in vitro coculture device for the investigation of host–microbe interactions via integrative multiomics approaches
Authors: Song Won‐Suk , Shin Sung Gyu , Jo Sung‐Hyun , Lee Jae‐Seung , Jeon Hyo‐Jin , Kwon Ji‐Eun , Park Ji‐Hyeon , Cho Sungwoo , Jeong Jae Hyun , Kim Byung‐Gee , Kim Yun‐Gon 
Published: January 2021

AbstractThe commensal gut bacterium Akkermansia muciniphila is well known as a promising probiotic candidate that improves host health and prevents diseases. However, the biological interaction of A. muciniphila with human gut epithelial cells has rarely been explored for use in biotherapeutics. Here, we developed an in vitro device that simulates the gut epithelium to elucidate the biological effects of living A. muciniphila via multiomics analysis: the Mimetic Intestinal Host–Microbe Interaction Coculture System (MIMICS). We demonstrated that both human intestinal epithelial cells (Caco‐2) and the anaerobic bacterium A. muciniphila can remain viable for 12 h after coculture in the MIMICS. The transcriptomic and proteomic changes (cell–cell junctions, immune responses, and mucin secretion) in gut epithelial cells treated with A. muciniphila closely correspond with those reported in previous in vivo studies. In addition, our proteomic and metabolomic results revealed that A. muciniphila activates glucose and lipid metabolism in gut epithelial cells, leading to an increase in ATP production. This study suggests that A. muciniphila improves metabolism for ATP production in gut epithelial cells and that the MIMICS may be an effective general tool for evaluating the effects of anaerobic bacteria on gut epithelial cells.
A student centric method for calculation of fatty acid energetics: Integrated formula and web tool
Authors: Jain Paras , Singh Sneha , Arya Aditya 
Published: January 2021

AbstractMitochondrial beta‐oxidation is one of the most common modes of fatty acids' oxidation in most organisms, particularly mammals. Biochemistry undergraduate curriculum often contains the description of the process, with emphasis on ATP calculations for various types of fatty acids. During our decade long teaching experience in biochemistry, we observed the difficulty faced by students in calculating energetics of several fatty acids beyond palmitic acid. We developed a canonical formula by mathematical transformations and logical derivation to aid the calculation in a much simpler manner to ease both teaching and learning experience. ATP yield of even‐numbered fatty acids may be calculated using a formula [(7C – 6 – 1.5 D) – 2(D–2)], andadenosine triphosphate (ATP) yield for odd‐numbered fatty acids can be calculated using [(7C – 19 – 1.5 D) – 2(D–2)], where C is the number of carbon atoms in fatty acids, D is the number of double bonds. The unbold part of the formulae is limited to polyunsaturated fatty acids. Moreover, we integrated these formulae into an HTML based web‐interface for handily calculations, which is likely to augment fatty acids oxidation learning‐teaching processes easier. This tool has been recently tested in our classroom programs on biochemistry and received an excellent feedback from the learners. Also, the mathematical formula is ready for being incorporated into standard biochemistry textbooks. The webtool as an opensource biochemical calculator can be effectively used in classrooms by both instructors and students while solving comprehension based questions on lipid metabolism.
Circular business models in high value manufacturing: Five industry cases to bridge theory and practice
Authors: Okorie Okechukwu , Charnley Fiona , Russell Jennifer , Tiwari Ashutosh , Moreno Mariale 
Published: January 2021

AbstractThe transition to a circular economy (CE) requires companies to evaluate their resource flows, supply chains, and business models and to question the ways in which value is created. In the high value manufacturing (HVM) sector, this evaluation is critical, as HVM enables value in nonconventional forms, beyond profit, including unique production processes, brand recognition, rapid delivery times, and highly customized services. We investigate the role of value, cost, and other factors of influence in the selection of a circular business model (CBM) for HVM. Explored through five case studies using a qualitative evaluation of circularity, we then contribute to the emerging field of CBMs by modifying the CBM canvas that can capture the nontraditional value, traditional value, cost, and other influencing factors enabled via CBM adoption in HVM. Finally, the important role of digital technologies for incentivizing and enabling CBM adoption, is clarified.
The mediating role of brand trust in the relationship between brand personality and brand loyalty
Authors: Villagra Nuria , Monfort Abel , Sánchez Herrera Joaquín 
Published: January 2021

AbstractDespite the efforts of organisations to make their consumers loyal to their brands, numerous studies show how loyalty has been declining in recent years without apparent causes. The aim of this research is to study the relationship between personality, trust and brand loyalty, to help understand the role of each of these variables in consumers' relationships with brands. Through a structural model built from data collected from a representative sample of 1015 individuals in the Spanish market, results put forward evidence of an indirect positive influence of brand personality on consumer loyalty, mediated by brand trust. Surprisingly, the results contrast with previous studies and show that there is no direct relationship between brand personality and brand loyalty. The results of this study have implications for both researchers and managers because previous research has analysed the direct influence of brand personality on trust or loyalty but not the mediating role that trust has on the relationship between personality and loyalty.
Variation in Phytochemical, Morphological, and Ploidy Levels of Iranian Thymus Species
Authors: Tohidi Behnaz , Rahimmalek Mehdi , Arzani Ahmad 
Published: January 2021

AbstractThymus is one of the most important genera of the Lamiaceae family. This work was performed to assess inter and intra species variation, which is an indispensable prerequisite for the selection and the exploitation of the germplasm, using yield, secondary metabolites, and ploidy level criteria. Nineteen Iranian populations belonging to 11 Thymus species which includes T. vulgaris were used in this study. The results of cytological observations on the 19 populations revealed the three root‐tip chromosome numbers of 2n=2x=30, 2n=4x=56 or 60 (diploid and tetraploid). This study also presents the results of a two‐year field experiment that evaluates the agronomic and morphology of the 19 populations of Thymus spp. Cluster analysis grouped the populations into six groups and explained the relationships among ploidy levels, morphological traits, and essential oils (EOs). In general, diploid species belonged to the thymol chemotype, whilst carvacrol chemotype consistently dependent on the gene‐dosage effect. Thymus migricus, T. daenensis‐2, T. serpyllum, and T. trautvetteri populations with diverse thymol background were the best selection as the parents to improve thymol in a breeding program. Moreover, dry and fresh weight criteria can be used to improve EO content in thyme. Achieving this goal would be expected by crossing T. migricus and T. daenensis‐2. Finally, providing relevant information on the ploidy level of Thymus species, with emphasis on morphology and EO components variations, may be recommended for the selection of populations or species to improve bioactive components as well as morphological traits in future breeding programs.
The Antimicrobial Peptide Gad‐1 Clears Pseudomonas aeruginosa Biofilms under Cystic Fibrosis Conditions
Authors: Portelinha Jasmin , Angeles‐Boza Alfredo M. 
Published: January 2021

AbstractBacterial infections in cystic fibrosis (CF) patients are an emerging health issue and lead to a premature death. CF is a hereditary disease that creates a thick mucus in the lungs that is prone to bacterial biofilm formation, specifically Pseudomonas aeruginosa biofilms. These biofilms are very difficult to treat because many of them have antibiotic resistance that is worsened by the presence of extracellular DNA (eDNA). eDNA helps to stabilize biofilms and can bind antimicrobial compounds to lessen their effects. The metallo‐antimicrobial peptide Gaduscidin‐1 (Gad‐1) eradicates established P. aeruginosa biofilms through a combination of modes of action that includes nuclease activity that can cleave eDNA in biofilms. In addition, Gad‐1 exhibits synergistic activity when used with the antibiotics kanamycin and ciprofloxacin, thus making Gad‐1 a new lead compound for the potential treatment of bacterial biofilms in CF patients.
SP3‐FAIMS Chemoproteomics for High‐Coverage Profiling of the Human Cysteinome**
Authors: Yan Tianyang , Desai Heta S. , Boatner Lisa M. , Yen Stephanie L. , Cao Jian , Palafox Maria F. , Jami‐Alahmadi Yasaman , Backus Keriann M. 
Published: January 2021

AbstractChemoproteomics has enabled the rapid and proteome‐wide discovery of functional, redox‐sensitive, and ligandable cysteine residues. Despite widespread adoption and considerable advances in both sample‐preparation workflows and MS instrumentation, chemoproteomics experiments still typically only identify a small fraction of all cysteines encoded by the human genome. Here, we develop an optimized sample‐preparation workflow that combines enhanced peptide labeling with single‐pot, solid‐phase‐enhanced sample‐preparation (SP3) to improve the recovery of biotinylated peptides, even from small sample sizes. By combining this improved workflow with on‐line high‐field asymmetric waveform ion mobility spectrometry (FAIMS) separation of labeled peptides, we achieve unprecedented coverage of >14000 unique cysteines in a single‐shot 70 min experiment. Showcasing the wide utility of the SP3‐FAIMS chemoproteomic method, we find that it is also compatible with competitive small‐molecule screening by isotopic tandem orthogonal proteolysis–activity‐based protein profiling (isoTOP‐ABPP). In aggregate, our analysis of 18 samples from seven cell lines identified 34225 unique cysteines using only ∼28 h of instrument time. The comprehensive spectral library and improved coverage provided by the SP3‐FAIMS chemoproteomics method will provide the technical foundation for future studies aimed at deciphering the functions and druggability of the human cysteineome.
Personality traits and male vulnerability to commercial sexual exploitation victimisation
Authors: Reid Joan A. , Fox Bryanna , Bilali Klejdis , Diaz Jennifer 
Published: January 2021

AbstractBackgroundThere has been little research into whether personality traits increase vulnerability to serious forms of recurring victimisation, such as commercial sexual exploitation of young people.AimsTo investigate whether impulsivity, emotional dysregulation or high psychopathy scale scores indicative of personality traits increase vulnerability to commercial sexual exploitation.MethodsData were used from the longitudinalPathways to Desistance Study1170 justice‐involved men who were aged 14–19 at baseline data collection. Ninety‐eight (8%) reported having been commercially sexually exploited during adolescence or young adulthood. We investigated whether personality traits measured at baseline were related to such victimisation.ResultsResults of binomial logistic regression among the young men in this sample indicated that Factor 1 scores on the Psychopathy Checklist‐Youth Version (PCL‐YV), reflecting affective and interpersonal features, are associated with having been commercially sexually exploited, while impulsivity, emotional dysregulation and Factor 2 PCL‐YV, reflecting antisocial activities, were not. Having been a victim of other violence and being a member of a cultural or ethnic minority group were also independently related to being exploited.Conclusions and implications for practiceOur findings show that individual differences in personality, such as fearless temperament and boredom susceptibility, could differentially disadvantage young people, and put them at greater risk of commercial sexual exploitation. This knowledge could be beneficial to prevention efforts supporting male adolescents at risk for victimisation by commercial sexual exploitation, and to shed new light on the theoretical understanding of vulnerability to it.
The Influence of the Support Nature and the Metal Precursor in the Activity of Pd‐based Catalysts for the Bromate Reduction Reaction
Authors: Cerrillo Jose L. , Lopes Christian W. , Rey Fernando , Palomares Antonio E. 
Published: January 2021

AbstractPalladium catalysts supported on different materials (alumina, activated carbon and mixed oxide derived from hydrotalcite) and prepared with different metal precursors (nitrate, chloride and acetate) have been characterized and tested for the bromate reduction reaction. The catalytic behavior depends on the support nature and on the metallic precursor used for the catalyst preparation. Pd catalyst supported on a mixed oxide has a low activity due to the high affinity of the reconstructed support for the Br− formed, preventing the reactants to approximate the active Pd sites. Pd catalyst supported on activated carbon has a surface negative charge and a microporous structure, making difficult the interaction of the active sites with the reactants. The best results are obtained with the catalyst supported on alumina due to its physical‐chemical properties, i. e. mesoporosity, positive surface charge and reversible adsorption of reactants and products. These characteristics make easy bromate and H2 adsorption on the active sites and subsequent reaction, thus resulting in a better activity. The Pd precursor salt also influences the catalytic activity as it has an effect on the Pd nanocrystal size. The best results are obtained with the metal precursor that produces homogeneous and large Pd metallic crystallites.
Merging Whole‐cell Biosynthesis of Styrene and Transition‐metal Catalyzed Derivatization Reactions
Authors: Maaskant Ruben V. , Chordia Shreyans , Roelfes Gerard 
Published: January 2021

AbstractThe approach of combining enzymatic and transition‐metal catalysis has been focused almost exclusively on using purified, isolated enzymes. The use of whole‐cell biocatalysis, instead of isolated enzymes, with transition‐metal catalysis, however, has been investigated only sparsely to date. Herein we present the development of two transition‐metal catalyzed reactions used to derivatize styrene obtained from whole‐cell biosynthesis. Using a biocompatible ruthenium cross‐metathesis catalyst up to 1.5 mM stilbene could be obtained in the presence of E. coli, which simultaneously produced styrene. Using palladium catalysts and arylboronic acids, titers of up to 1 mM of several stilbene derivatives were obtained. These two transition‐metal catalyzed reactions are valuable additions to the toolbox of combined whole‐cell biocatalysis and transition‐metal catalysis, offering the possibility to supplement biosynthetic pathways with the chemical versatility of abiological transition‐metal catalysis.
A Study on the Offset Deactivation Effect of Potassium and Phosphorus on MnEuOx SCR Catalyst
Authors: Guo De‐yu , Guo Rui‐tang , Duan Chao‐peng , Liu Yuan‐zhen , Wu Gui‐lin , Pan Wei‐guo 
Published: January 2021

AbstractIn this study, a remarkable offset deactivation effect of K and P on MnEuOx SCR catalyst has been found. Experimental results showed that the NO conversion over K−P poisoned catalyst was close to 80 % at 250 °C. Several characterization techniques containing NH3‐TPD, XPS, H2‐TPR, XRD and in situ DRIFT were used to reveal the mechanism of the offset effect. The characterization of NH3‐TPD and H2‐TPR suggested that the introduction of P on MnEuOx‐K could improve its surface acidity and redox ability. Moreover, the content of chemisorbed oxygen and Mn4+ were markedly restored under the situation that the toxic elements were coexistent on catalyst surface. The strong interaction between K and P might be the major reason for the offset deactivation effect. More specifically, PO3− species were preferentially bonded with the surface potassium species and released MnO2 active sites poisoned by K. Therefore, the highly active MnO2 sites might be protected and the catalytic activity could be restored.
Three‐Dimensional Graphene Network Decorated with Highly Symmetrical Cuboid Na3V2(PO4)2F3 Particles: High Rate Capability and Cycling Stability for Sodium‐Ion Batteries
Authors: Xu Shuyuan , Li Huijun , Wang Xiaomin 
Published: January 2021

AbstractNa3V2(PO4)2F3 (NVPF) has captured significant heed for cathode materials of sodium‐ion battery (SIB), owing to its stable three‐dimensional (3D) structure channel that can accommodate Na+ diffusion. However, NVPF is still facing with a major challenge in terms of the electrochemical performance, owing to its uncontrollable morphology. Hence, it was fabricated by using a two‐step hydrothermal method, whereby NVPF cuboid particles of homogenous morphology and highly structural symmetry could anchor on the three‐dimensional graphene network (GN) structure to form NVPF@GN. The affiliation between the morphology and performance of the NVPF@GN was further probed by manipulating the morphology of the NVPF under diverse heat treatment temperatures. When the temperature reaches 480 °C, NVPF@GN manifests prolonged cyclability (the capacity fading rate of 0.01 % cycle−1 at 0.5 C during 300 cycles) and it shows outstanding rate performance (when the rate is reset to 0.5 C, the capacity is 107 mAh g−1 and capacity retention is 99 %), which can be ascribed to the high structural symmetry of NVPF@GN. These results indicate that NVPF@GN cuboids can be used as a prospective cathode material for SIBs.
Proanthocyanin‐Capped Biogenic TiO2 Nanoparticles with Enhanced Penetration, Antibacterial and ROS Mediated Inhibition of Bacteria Proliferation and Biofilm Formation: A Comparative Approach
Authors: Alomary Mohammad N. , Ansari Mohammad Azam 
Published: January 2021

AbstractBiofunctionalized TiO2 nanoparticles with a size range of 18.42±1.3 nm were synthesized in a single‐step approach employing Grape seed extract (GSE) proanthocyanin (PAC) polyphenols. The effect of PACs rich GSE corona was examined with respect to 1) the stability and dispersity of as‐synthesized GSE‐TiO2‐NPs, 2) their antiproliferative and antibiofilm efficacy, and 3) their propensity for internalization and reactive oxygen species (ROS) generation in urinary tract infections (UTIs) causing Gram‐negative Pseudomonas aeruginosa and Gram‐positive Staphylococcus saprophyticus strains. State‐of‐the‐art techniques were used to validate GSE‐TiO2‐NPs formation. Comparative Fourier transformed infrared (FTIR) spectral analysis demonstrated that PACs linked functional ‐OH groups likely play a central role in Ti4+ reduction and nucleation to GSE‐TiO2‐NPs, while forming a thin, soft corona around nascent NPs to attribute significantly enhanced stability and dispersity. Transmission electron microscopic (TEM) and inductively coupled plasma mass‐spectroscopy (ICP‐MS) analyses confirmed there was significantly (p<0.05) enhanced intracellular uptake of GSE‐TiO2‐NPs in both Gram‐negative and ‐positive test uropathogens as compared to bare TiO2‐NPs. Correspondingly, compared to bare NPs, GSE‐TiO2‐NPs induced intracellular ROS formation that corresponded well with dose‐dependent inhibitory patterns of cell proliferation and biofilm formation in both the tested strains. Overall, this study demonstrates that ‐OH rich PACs of GSE corona on biogenic TiO2‐NPs maximized the functional stability, dispersity and propensity of penetration into planktonic cells and biofilm matrices. Such unique merits warrant the use of GSE‐TiO2‐NPs as a novel, functionally stable and efficient antibacterial nano‐formulation to combat the menace of UTIs in clinical settings.