bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐fibrosis attributes: UHPLC‐MS/MS‐based pharmacokinetics profiling of a novel autotaxin inhibitor with excellent in vivo efficacy in rat
Authors: Wang Hongjin , Long Tengfei , Zhang Hao , Li Meng , Sun Qi , Zhai Xin , Sun Lixin 
Published: December 2021

Abstract3,4‐Difluorobenzyl(1‐ethyl‐5‐(4‐((4‐hydroxypiperidin‐1‐yl)‐methyl)thiazol‐2‐yl)‐1H‐indol‐3‐yl)carbamate (NAI59), a small molecule with outstanding therapeutic effectiveness to anti‐pulmonary fibrosis, was developed as an autotaxin inhibitor candidate compound. To evaluate the pharmacokinetics and plasma protein binding of NAI59, a UPLC–MS/MS method was developed to quantify NAI59 in plasma and phosphate‐buffered saline. The calibration curve linearity ranged from 9.95 to 1990.00 ng/mL in plasma. The accuracy was −6.8 to 5.9%, and the intra‐ and inter‐day precision was within 15%. The matrix effect and recovery, as well as dilution integrity, were within the criteria. The chromatographic and mass spectrometric conditions were also feasible to determine phosphate‐buffered saline samples, and it has been proved that this method exhibits good precision and accuracy in the range of 9.95–497.50 ng/mL in phosphate‐buffered saline. This study is the first to determine the pharmacokinetics, absolute bioavailability, and plasma protein binding of NAI59 in rats using this established method. Therefore, the pharmacokinetic profiles of NAI59 showed a dose‐dependent relationship after oral administration, and the absolute bioavailability in rats was 6.3%. In addition, the results of protein binding showed that the combining capacity of NAI59 with plasma protein attained 90% and increased with the increase in drug concentration.
Semi‐rational Engineering of a Promiscuous Fatty Acid Hydratase for Alteration of Regioselectivity
Authors: Zhang Yan , Breum Niels Mikkel Dyrby , Schubert Sune , Hashemi Negin , Kyhnau Rikke , Knauf Marius Sandholt , Mathialakan Masuthan , Takeuchi Michiki , Kishino Shigenobu , Ogawa Jun , Kristensen Peter , Guo Zheng , Eser Bekir Engin 
Published: December 2021

AbstractFatty acid hydratases (FAHs) catalyze regio‐ and stereo‐selective hydration of unsaturated fatty acids to produce hydroxy fatty acids. Fatty acid hydratase‐1 (FA‐HY1) from Lactobacillus Acidophilus is the most promiscuous and regiodiverse FAH identified so far. Here, we engineered binding site residues of FA‐HY1 (S393, S395, S218 and P380) by semi‐rational protein engineering to alter regioselectivity. Although it was not possible to obtain a completely new type of regioselectivity with our mutant libraries, a significant shift of regioselectivity was observed towards cis‐5, cis‐8, cis‐11, cis‐14, cis‐17‐eicosapentaenoic acid (EPA). We identified mutants (S393/S395 mutants) with excellent regioselectivity, generating a single hydroxy fatty acid product from EPA (15‐OH product), which is advantageous from application perspective. This result is impressive given that wild‐type FA‐HY1 produces a mixture of 12‐OH and 15‐OH products at 63 : 37 ratio (12‐OH : 15‐OH). Moreover, our results indicate that native FA‐HY1 is at its limit in terms of promiscuity and regiospecificity, thus it may not be possible to diversify its product portfolio with active site engineering. This behavior of FA‐HY1 is unlike its orthologue, fatty acid hydratase‐2 (FA‐HY2; 58 % sequence identity to FA‐HY1), which has been shown earlier to exhibit significant promiscuity and regioselectivity changes by a few active site mutations. Our reverse engineering from FA‐HY1 to FA‐HY2 further demonstrates this conclusion.
Pt3Fe Nanoparticles Triggered High Catalytic Performance for Oxygen Reduction Reaction in Both Alkaline and Acidic Media
Authors: Zhang Shuaihui , Jiang Kaiyue , Jiang Haitao , Zhu Jinhui , Ji Huiping , Lu Chenbao , Zhang Longhai , Li Jin , Chen Zhenying , Ke Changchun , Zhuang Xiaodong 
Published: December 2021

AbstractPt‐based nanomaterials are now the most reliable catalysts for oxygen reduction reaction (ORR). However, the low atomic utilization efficiency and poor stability severely limit their widespread application. Herein, a facile molten salt approach for synthesizing N‐doped porous carbon embedded with Pt3Fe intermetallic nanoparticles is presented. The Pt loading of the as‐prepared materials is as low at 5.91 wt. %, while exhibiting a half‐wave potential of 0.85 V and diffusion limiting current density of −5.68 mA cm−2 in alkaline condition, which is superior to commercial Pt/C (0.83 V, −5.48 mA cm−2). As cathode for Zn‐air battery, the power density and specific capacity up to 130.0 mW cm−2 and 833 mAh g−1, respectively, are outperforming Pt/C batteries (85.8 mW cm−2, 632 mAh g−1). The theoretical calculations identify the origin of activity on Pt3Fe; the Pt3Fe (111) plane exhibits more positive activity than (200) plane.
Parahydrogen‐Induced Polarization in Hydrogenation Reactions Mediated by a Metal‐Free Catalyst
Authors: Zakharov Danila O. , Chernichenko Konstantin , Sorochkina Kristina , Yang Shengjun , Telkki Ville‐Veikko , Repo Timo , Zhivonitko Vladimir V. 
Published: December 2021

AbstractWe report nuclear spin hyperpolarization of various alkenes achieved in alkyne hydrogenations with parahydrogen over a metal‐free hydroborane catalyst (HCAT). Being an intramolecular frustrated Lewis pair aminoborane, HCAT utilizes a non‐pairwise mechanism of H2 transfer to alkynes that normally prevents parahydrogen‐induced polarization (PHIP) from being observed. Nevertheless, the specific spin dynamics in catalytic intermediates leads to the hyperpolarization of predominantly one hydrogen in alkene. PHIP enabled the detection of important HCAT‐alkyne‐H2 intermediates through substantial 1H, 11B and 15N signal enhancement and allowed advanced characterization of the catalytic process.
Synthesis, Structure, and Dynamics of Chiral Eight‐Membered Cyclic Molecules with Thienylene and Cyclopropylene Units Alternately Connected
Authors: Miura Tomoya , Ishihara Yumi , Nakamuro Takayuki , Moritani Shunsuke , Nagata Yuuya , Murakami Masahiro 
Published: December 2021

AbstractA rhodium(II)‐catalyzed asymmetric cyclooligomerization of bifunctional monomers possessing triazolyl and vinyl groups at 2,3‐ and 3,4‐positions on the thiophene ring is studied. Structurally interesting cyclic dimers in which thienylene and cyclopropylene units are alternately connected are obtained as the major components. The eight‐membered rings in the center are non‐planar and adopt a tub‐shaped conformation. We also observe the phenomenon of racemization caused by a tub‐to‐tub ring‐flipping, the activation energy of which is determined as 108 kJ mol−1 by electronic circular dichroism spectra measurement.
Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma
Authors: Suzuki Masaru , Cole John J. , Konno Satoshi , Makita Hironi , Kimura Hiroki , Nishimura Masaharu , Maciewicz Rose A. 
Published: December 2021

AbstractBackgroundChronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases.MethodsThe plasma proteome was evaluated using an aptamer‐based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics.ResultsSubjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under‐explored.ConclusionThis investigational study evaluating the plasma proteome in clinically‐phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.
Lignin‐First Monomers to Catechol: Rational Cleavage of C−O and C−C Bonds over Zeolites
Authors: Wu Xian , Liao Yuhe , Bomon Jeroen , Tian Guilong , Bai Shao‐Tao , Van Aelst Korneel , Zhang Qiang , Vermandel Walter , Wambacq Ben , Maes Bert U. W. , Yu Jihong , Sels Bert F. 
Published: December 2021

AbstractA catalytic route is developed to synthesize bio‐renewable catechol from softwood‐derived lignin‐first monomers. This process concept consists of two steps: 1) O‐demethylation of 4‐n‐propylguaiacol (4‐PG) over acidic beta zeolites in hot pressurized liquid water delivering 4‐n‐propylcatechol (4‐PC); 2) gas‐phase C‐dealkylation of 4‐PC providing catechol and propylene over acidic ZSM‐5 zeolites in the presence of water. With large pore sized beta‐19 zeolite as catalyst, 4‐PC is formed with more than 93 % selectivity at nearly full conversion of 4‐PG. The acid‐catalyzed C‐dealkylation over ZSM‐5 zeolite with medium pore size gives a catechol yield of 75 %. Overall, around 70 % catechol yield is obtained from pure 4‐PG, or 56 % when starting from crude 4‐PG monomers obtained from softwood by lignin‐first RCF biorefinery. The selective cleavage of functional groups from biobased platform molecules through a green and sustainable process highlights the potential to shift feedstock from fossil oil to biomass, providing drop ins for the chemicals industry.
Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions
Authors: Yan Bing , Shi Changxia , Beckham Gregg T. , Chen Eugene Y.‐X. , Román‐Leshkov Yuriy 
Published: December 2021

AbstractActivating inert sp3–sp3 carbon‐carbon (C−C) bonds remains a major bottleneck in the chemical upcycling of recalcitrant polyolefin waste. In this study, redox mediators are used to activate the inert C−C bonds. Specifically, N‐hydroxyphthalimide (NHPI) is used as the redox mediator, which is oxidized to phthalimide‐N‐oxyl (PINO) radical to initiate hydrogen atom transfer (HAT) reactions with benzylic C−H bonds. The resulting carbon radical is readily captured by molecular oxygen to form a peroxide that decomposes into oxygenated C−C bond‐scission fragments. This indirect approach reduces the oxidation potential by >1.2 V compared to the direct oxidation of the substrate. Studies with model compounds reveal that the selectivity of C−C bond cleavage increases with decreasing C−C bond dissociation energy. With NHPI‐mediated oxidation, oligomeric styrene (OS510; Mn=510 Da) and polystyrene (PS; Mn≈10 000 Da) are converted into oxygenated monomers, dimers, and oligomers.
Selective Electrosynthesis of 2,5‐Diformylfuran in a Continuous‐Flow System
Authors: Zhang Yuchi , Li Wenjing , Cao Yucai , Chen Ming , Li Wenqian , Zai Jiantao , Iqbal Asma , Qi Rongrong , Qian Xuefeng 
Published: December 2021

AbstractThe gram‐scale selective oxidation of biomass‐based chemicals, in particular 5‐hydroxymethylfurfural (HMF), into value‐added 2,5‐diformylfuran (DFF) has a high application potential but suffers from high cost, low selectivity, and harsh reaction conditions. Besides, the electrooxidation strategy requires the usage of expensive electrodes and struggles with low selectivity and efficiency, which restricts its further scaled‐up application. In this regard, a continuous‐flow system was developed through redox mediator I−/I2 for the efficient synthesis of DFF, which could accelerate the mass transfer of I− (I2) to aqueous (organic) phase and avoid over‐oxidation to achieve high selectivity. After the solvent system, iodine concentration, and reaction time were optimized, highly efficient DFF synthesis (selectivity >99 %) could be achieved in the electrochemical flow system using inexpensive graphite felt (GF) as electrode. Moreover, selective HMF oxidation was paired with the hydrogen evolution reaction with increased efficiency after using in‐situ‐loaded GF‐CoS2/CoS and GF‐Pt electrodes. As a result, the required energy to achieve the gram‐scale synthesis of DFF was significantly reduced, demonstrating outstanding potential for large‐scale production of the target product.
Comparative development of limb musculature in phylogenetically and ecologically divergent lizards
Authors: Diaz Raul E. , Taylor‐Diaz Elizabeth A. , Trainor Paul A. , Diogo Rui , Molnar Julia L. 
Published: December 2021

AbstractBackgroundSquamate reptiles (lizards, snakes, and amphisbaenians) exhibit incredible diversity in their locomotion, behavior, morphology, and ecological breadth. Although they often are used as models of locomotor diversity, surprisingly little attention has been given to muscle development in squamate reptiles. In fact, the most detailed examination was conducted almost 80 years ago and solely focused on the proximal limb regions. Herein, we present forelimb and hindlimb muscle morphogenesis data for three lizard species with different locomotion and feeding strategies: the desert grassland whiptail lizard, the central bearded dragon, and the veiled chameleon. This study fills critical gaps in our understanding of muscle morphogenesis in squamate reptiles and presents a comparative and temporospatial analysis of muscle development.ResultsOur results reveal a conserved pattern of early muscle development among lizards with different adult morphologies and ecologies. The variations that exist are concentrated in distal regions, particularly the specialized autopodia of chameleons, where differentiation of muscles associated with the digits is delayed.ConclusionsThe chameleon autopod provides an example of major evolutionary modifications to the skeleton with only minor disruption of the conserved order and pattern of limb muscle development. This robustness of muscle patterning facilitates the evolution of extreme yet functional phenotypes.
Practice makes perfect: Commentary on Burnette et al. (2021)
Authors: De Young Kyle P. , Kambanis Paraskevi Evelyna 
Published: December 2021

AbstractUnderrepresented identities have been overlooked in the development of measures assessing eating disorders; therefore, limited normative data exist for these identities. To address this, Burnette et al. sought to provide Eating Disorder Examination‐Questionnaire and Eating Attitudes Test‐26 norms for transgender adults using Amazon's MTurk. However, they were unable to achieve this goal due to what they perceived as high rates of invalid responses. Instead, they provided recommendations for conducting MTurk research. However, little or no evidence supports the validity of several recommendations, partly because their study was not designed to derive or validate recommendations. By their own admission, their strategies failed to address what they identified as the central problem. We express concern about Burnette et al.'s recommendations because (a) the recommendations are built on assumptions about the problem that may not be true; and (b) the recommendations are not provided within the context of limitations of self‐report/online data collection writ large. We detail these concerns and propose that strategies for mitigating inattentive/invalid responding be subjected to validation prior to being recommended to prevent the implementation of procedures that result in the exclusion of the target population, individuals who we historically, and perhaps still, unjustly exclude from research.
The dynamics of social cohesion in response to simulated intergroup conflict in banded mongooses
Authors: Preston Elizabeth F. R. , Thompson Faye J. , Kyabulima Solomon , Croft Darren P. , Cant Michael A. 
Published: December 2021

AbstractIntergroup conflict is widespread in nature and is proposed to have strong impacts on the evolution of social behavior. The conflict–cohesion hypothesis predicts that exposure to intergroup conflict should lead to increased social cohesion to improve group success or resilience in future conflicts. There is evidence to support this prediction from studies of affiliative responses to outgroup threats in some animal societies. However, most of these studies have focused on behavioral changes over short time periods (minutes and hours after exposure to an outgroup), and hence very little is known about the dynamics and durability of responses to intergroup conflict over the longer term. We investigated this question by simulating intergroup encounters in wild banded mongooses (Mungos mungo) and measuring social behavior before, during, and after these encounters over a 5‐day period. We also ran control trials with non‐threatening stimuli. Banded mongooses reacted immediately to intrusion stimuli by vocalizing, grouping together, and advancing on the stimulus. In the first 5 min after simulated intrusions, we saw an elevation in grooming levels, but in the hour after exposure grooming rates declined sharply, contrary to our expectation. In the two subsequent days, grooming rates remained at this depressed rate. In control trials, the initial increase in grooming was not seen, but grooming declined compared to the longer‐term time periods. Grooming changed across time, but not in the same pattern as during intrusions, suggesting that intrusions had an impact above and beyond that of the experimental setup. The dynamics of grooming responses were short lived and more complex than we initially expected. We suggest this unexpected result may be linked to the frequency of aggressive intergroup encounters in this system. As control and experimental trials were run at different times of year, future work would be needed to confirm that these relative patterns are replicable. Our results indicate short‐lived impacts of outgroup threat on measures of social cohesion in this species, but cannot confirm longer‐term changes.
Tuning Material Properties of Porous Organic Cage CC3 with Postsynthetic Dynamic Covalent Chemistry
Authors: Rivera Matthew P. , Liu Ming , He Donglin , Lively Ryan P. 
Published: December 2021

AbstractPorous organic cages (POCs) represent a new class of microporous materials with an impressive breadth of potential applications. One of their many advantages is the degree of tunability of cage properties, similar to that seen in more established microporous materials like metal‐organic frameworks. In this work, a prototypical POC, CC3, is used to explore the potential to tune cage properties via post‐synthetic dynamic covalent chemistry. Ethylenediamine, the linker used in another POC, CC1, was partially substituted into the CC3 cage structure to varying degrees based on the starting relative molar ratios. The resulting products were investigated for the relative distribution of the two linkers, crystallinity, and surface area. It was found that even when small amounts of other compatible diamine linkers are introduced, they substitute into the existing cages, although some structural products are apparently favored over others within the reactant ratios investigated.
Non‐traditional encryption methods: Moving toward electrochemical cryptography
Authors: Biddle Giana , McGoldrick Leif , Halamek Jan 
Published: December 2021

AbstractCybersecurity and encryption are critical in diverse applications from simple emails to high‐priority government secrets. It is best accomplished by an “unbreakable” cipher or one which is only decrypted by those with a matching cipher key to the initial encryption. Recent advances have incorporated quantitative data as an asymmetric encryption key. With this method, the sender and receiver each run the same experiment to encode and decode the message of interest. Experimental asymmetric keys can come from DNA, enzymatic assays, and most recently, electrochemical data. This manuscript summarizes recent advances in cryptography and outlines new electrochemical techniques.
Optimal tuning of fractional‐order proportional, integral, derivative and tilt‐integral‐derivative based power system stabilizers using Runge Kutta optimizer
Authors: El‐Dabah Mahmoud Abbas , Kamel Salah , Abido Mohammad Ali Yousef , Khan Baseem 
Published: December 2021

AbstractLow‐frequency power system oscillation is of great concern as it may lead to power system instability. Moreover, this action will lead to the abate capability of electric power transfer. By introducing a stabilizing signal into the excitation system, it was possible to improve the damping in the system. The power system stabilizer (PSS) provides this signal. This manuscript aims to find the optimal tuning of three different PSS controllers using a recent optimization algorithm called Runge Kutta optimizer (RUN). Based on the obtained results, the RUN shows superiority and fast convergence over competitive algorithms. In addition, the fractional‐order proportional, integral, derivative (FOPID) and tilt‐integral‐derivative (TID) based PSS shows great damping capability over the lead–lag, PI, and FOPID‐based PSS. Also, the TID‐based PSS achieves better performance indices in terms of the lowest maximum overshoot and minimum settling time. Hence, it is recommended for PSS based controller.
A longitudinal examination of the relation between academic stress and anxiety symptoms among adolescents in India: The role of physiological hyperarousal and social acceptance
Authors: Trevethan Mackenzie , Jain Anjali T. , Shatiyaseelan Anuradha , Luebbe Aaron M. , Raval Vaishali V. 
Published: December 2021

Academic stress is a critical aspect of adolescent experience around the world, but particularly in countries with dense populations that lead to highly competitive college admissions. With a population of over one billion people, the competition for higher education in India is significantly high. Although research has shown that academic pressures are associated with anxiety in adolescents, this work is primarily cross‐sectional. The current study examined academic stress and anxiety symptoms over time and assessed physiological hyperarousal as a mediator and social acceptance as a moderator of this relation in a sample of adolescents from India (N = 282, 13–18 years, 84% female). Adolescents completed measures of academic stress, physiological hyperarousal, social acceptance and anxiety symptoms at two‐time points, 5 months apart. Findings demonstrate direct effects of academic stress on changes in symptoms of generalised anxiety and panic, as well as indirect effects through physiological hyperarousal. Social acceptance did not moderate the relation, although it uniquely predicted changes in panic disorder symptoms over time. The findings of this study contribute to the scientific understanding of a potential mechanism through which academic stress leads to anxiety among adolescents in India.