bluuebunny/crossref_metadata_2025 huggingface dataset:
Spray‐n‐Sense: Sprayable Nanofibers for On‐Site Chemical Sensing
Authors: Bakshi Shrishty , Snoswell Aaron J. , Kwok Kei Yeung , Cheng Lung Hei , Altalhi Tariq A. , Santos Abel , Popat Amirali , Kumeria Tushar
Published: January 2022

A versatile “Spray‐n‐Sense” sprayable nanofiber technology for on‐site chemical detection is demonstrated. Driven by compressed gas, the “Spray‐n‐Sense” nanofibers, as the name suggests, can be directly sprayed onto any kind or shape of surfaces, while the embedded chemical reporter enables simple colorimetric/fluorometric detection. Herein, nanofibers are sprayed on several surfaces including cardboard, glass, plastic, and rubber. The sensing capabilities of the “Spray‐n‐Sense” nanofibers are established through the detection of three different analytes including two metal ions (Fe2+ and Fe3+ using 1,10‐phenanthroline and curcumin as chromogenic reporters, respectively) and ammonia (using rhodamine‐B as a fluorogenic reporter) in aqueous media. Additional to being highly portable, the “Spray‐n‐Sense” nanofibers show impressive sensor characteristics with a sub‐ppm lower limit of detection (LLOD) for Fe2+ and a wide linear working range. Whereas, the LLOD of 6.2 and 32 ppm is achieved for Fe3+ ions and ammonia, respectively. A custom‐designed smartphone application enables quantitative analysis for reliable on‐site sensing. The selectivity and specificity are imparted by the embedded reporter, and thus allow analyte detection in complex real‐life samples and simultaneous detection of multiple chemical species through co‐doping. The “Spray‐n‐Sense” nanofibers also allow for the detection of target analytes in solid samples.
Stoichiometry‐Controlled Phase Engineering of Cesium Bismuth Halides and Reversible Structure Switch
Authors: Yan Jun , Zhang Shuai , Wei Qilin , Cao Sheng , Zhao Jialong , Zou Bingsuo , Zeng Ruosheng
Published: January 2022

Perovskite metal halides have attracted extensive attention because of their excellent photoelectric properties and structural adjustability. Herein, the authors report a facile method for the controlled synthesis of cesium‐bismuth halides by controlling the stoichiometry of Cs/Bi precursors at room temperature. The 0D Cs3BiCl6 and 1D Cs3Bi2Cl9 can be obtained at the Cs/Bi feed ratio of 3:1 and 3:2, respectively. Though both metal halides exhibit a very low photoluminescence quantum yield (PLQY) due to their intrinsic nature of indirect band gaps, they exhibited bright orange broadband emission after Mn2+ doping. Combining density functional theory (DFT) calculations, it is found that an appropriate amount of Mn2+ doping does not change the crystal structures of cesium‐bismuth halides, but Mn 3d orbitals produce impurity states in the forbidden energy gaps of the host structures, resulting in efficient energy transfer from the conduction band of the host to d‐state of Mn ions. Importantly, the reversible structural switch of Mn‐doped Cs3BiCl6 and Cs3Bi2Cl9 metal halides can be flexibly adjusted through the post addition of the CsCl/BiCl3 precursors. These results tremendously enrich the synthetic chemistry of low‐dimensional metal halides and provide a beneficial reference for the regulation of crystal structure and optical properties of metal halides.
Phosphorylated and Phosphonated Low‐Complexity Protein Segments for Biomimetic Mineralization and Repair of Tooth Enamel
Authors: Chang Rong , Liu Yang‐Jia , Zhang Yun‐Lai , Zhang Shi‐Ying , Han Bei‐Bei , Chen Feng , Chen Yong‐Xiang
Published: January 2022

Biomimetic mineralization based on self‐assembly has made great progress, providing bottom‐up strategies for the construction of new organic–inorganic hybrid materials applied in the treatment of hard tissue defects. Herein, inspired by the cooperative effects of key components in biomineralization microenvironments, a new type of biocompatible peptide scaffold based on flexibly self‐assembling low‐complexity protein segments (LCPSs) containing phosphate or phosphonate groups is developed. These LCPSs can retard the transformation of amorphous calcium phosphate into hydroxyapatite (HAP), leading to merged mineralization structures. Moreover, the application of phosphonated LCPS over phosphorylated LCPS can prevent hydrolysis by phosphatases that are enriched in extracellular mineralization microenvironments. After being coated on the etched tooth enamel, these LCPSs facilitate the growth of HAP to generate new enamel layers comparable to the natural layers and mitigate the adhesion of Streptococcus mutans. In addition, they can effectively stimulate the differentiation pathways of osteoblasts. These results shed light on the potential biomedical applications of two LCPSs in hard tissue repair.
Unveiling the Emergent Traits of Chiral Spin Textures in Magnetic Multilayers
Authors: Chen Xiaoye , Lin Ming , Kong Jian Feng , Tan Hui Ru , Tan Anthony K.C. , Je Soong‐Geun , Tan Hang Khume , Khoo Khoong Hong , Im Mi‐Young , Soumyanarayanan Anjan
Published: January 2022

Magnetic skyrmions are topologically wound nanoscale textures of spins whose ambient stability and electrical manipulation in multilayer films have led to an explosion of research activities. While past efforts focused predominantly on isolated skyrmions, recently ensembles of chiral spin textures, consisting of skyrmions and magnetic stripes, are shown to possess rich interactions with potential for device applications. However, several fundamental aspects of chiral spin texture phenomenology remain to be elucidated, including their domain wall (DW) structure, thermodynamic stability, and morphological transitions. Here the evolution of these textural characteristics are unveiled on a tunable multilayer platform—wherein chiral interactions governing spin texture energetics can be widely varied—using a combination of full‐field electron and soft X‐ray microscopies with numerical simulations. With increasing chiral interactions, the emergence of Néel helicity, followed by a marked reduction in domain compressibility, and finally a transformation in the skyrmion formation mechanism are demonstrated. Together with an analytical model, these experiments establish a comprehensive microscopic framework for investigating and tailoring chiral spin texture character in multilayer films.
Sandwiching Phosphorene with Iron Porphyrin Monolayer for High Stability and Its Biomimetic Sensor to Sensitively Detect Living Cell Released NO
Authors: Zhang Chunmei , Hu Fangxin , Hao Xijuan , Rao Qianghai , Hu Tao , Sun Wei , Guo Chunxian , Li Chang Ming
Published: January 2022

Instability of 2D phosphorene material is the major obstacle for its broad applications. Herein phosphorene is sandwiched with self‐assembled iron porphyrin monolayers on both sides (I‐Phene) to significantly enhance stability. Iron porphyrin has strong interaction with phosphorene through formation of PFe bonds. The sandwich structure offers excellent stability of phosphorene by both‐sided monolayer protections for an intact phosphorene structure more than 40 days under ambient conditions. Meanwhile, the electron transfer between iron porphyrin and phosphorene result in a high oxidation state of Fe, making I‐Phene biomimetic sensitivity toward oxidation of nitric oxide (NO) for 2.5 and 4.0 times higher than phosphorene and iron‐porphyrin alone, respectively. Moreover, I‐Phene exhibits excellent selectivity, a wide detection range, and a low detection limit at a low oxidation potential of 0.82 V, which is comparable with the reported noble metal based biomimetic sensors while ranking the best among all non‐noble biomimetic ones. I‐Phene is further used for real‐time monitoring NO released from cells. This work provides effective approach against phosphorene degrading for outstanding stability, which has universal significance for its various important applications, and holds a great promise for a highly sensitive biomimetic sensor in live‐cell assays.
Agitation of yield stress fluids by gas injection
Authors: Hojeij Ali , Jossic Laurent , Séchet Philippe , Magnin Albert , Hattou Stéphane
Published: January 2022

This study is in line with two previous studies by the same authors on gas injection in yield stress fluids. Gas is injected toward the bottom wall of a prismatic tank containing a yield stress fluid. When rising toward the free surface, trains of bubbles generate fluid recirculation in the tank. Two experimental colorimetric methods are introduced and validated in order to quantify the recirculation liquid flow rate as well as the time evolution of the extent and shape of the mixed volume. The influences of the injection flow rate, fluid rheology, and reactor size have been quantified. Correlations based on the characteristic nondimensional numbers of the flow have been developed to predict the downward liquid flow rate as well as the mixed volume. A model for estimating the mixing time is also developed and compared to experimental results.
Impact of achieving a complete response to initial therapy of multiple myeloma and predictors of subsequent outcome
Authors: Kaddoura Marcella , Binder Moritz , Dingli David , Buadi Francis K. , Lacy Martha Q. , Gertz Morie A. , Dispenzieri Angela , Kapoor Prashant , Hwa Lisa , Fonder Amie , Hobbs Miriam , Hayman Suzanne , Leung Nelson , Go Ronald S. , Lin Yi , Gonsalves Wilson , Kourelis Taxiarchis , Warsame Rahma , Kyle Robert A. , Rajkumar Vincent , Kumar Shaji
Published: January 2022

Achievement of a complete response (CR) in multiple myeloma (MM) correlates with improvement in survival outcomes; however, its impact on prognostic variables at baseline outside of clinical trial settings is not well described. We sought to determine the impact of achieving a CR within 2 years from diagnosis, its effect on the prognostic value of fluorescence in situ hybridization (FISH) and International Staging System (ISS) risk, and examined additional predictors of outcome among those achieving a CR in a routine clinical setting. We evaluated 1869 newly diagnosed MM patients who had ≥ 2 monoclonal protein immunofixation studies in the serum and urine available within 24 months from diagnosis, categorizing those with ≥ 2 negative serum and urine immunofixations as achieving CR. With a landmark at 24 months, median progression‐free survival (PFS) for CR versus non‐CR patients was 29.8 versus 20.9 months (p ≤ .0002); median overall survival (OS) was 104 versus 70 months (p < .0001). The impact of achieving a CR was retained after adjusting for FISH, ISS, sex, transplant status, and involved heavy chain. Baseline FISH and ISS stage were not associated with PFS or OS among patients achieving a CR. The following variables were found as predictors of inferior OS within the CR cohort: age > 75 years, male gender, hypoalbuminemia, and non‐immunoglobulin G involved heavy chain. Our study confirms that achievement of CR within 2 years from diagnosis is associated with improvement in survival outcomes and neutralization of the impact of FISH and ISS risk, thereby confirming observations from the clinical trial setting among a clinical practice cohort.
Cytogenetic risk classification maintains its prognostic significance in transplanted FLT3‐ITD mutated acute myeloid leukemia patients: On behalf of the acute leukemia working party/European society of blood and marrow transplantation
Authors: Nagler Arnon , Labopin Myriam , Craddock Charles , Socié Gerard , Yakoub‐Agha Ibrahim , Gedde‐Dahl Tobias , Niittyvuopio Riitta , Byrne Jennifer Louise , Cornelissen Jan J. , Labussière‐Wallet Hélène , Arcese William , Milpied Noel , Esteve Jordi , Canaani Jonathan , Mohty Mohamad
Published: January 2022

FMS‐like tyrosine kinase 3 internal tandem duplication (FLT3‐ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3‐ITD patients referred for allogeneic stem cell transplantation (allo‐SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3‐ITD AML patients who underwent allo‐SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes. Median patient age was 49 years and median follow‐up duration was 36 months. Two‐year leukemia‐free survival (LFS) and incidence of relapse were 54% and 31.6%, respectively. Non‐relapse mortality was experienced by 14.4% with a 2‐year overall survival (OS) of 60.1%. On multivariate analysis, LFS was significantly lower in patients with intermediate and adverse risk cytogenetics compared with those with favorable risk cytogenetics, (hazard ratio [HR] = 1.48, 95% confidence interval [CI], 1.06–2.06; p = .02), and (HR = 01.65, 95% CI, 1.13–2.40; p = .009), respectively. OS was significantly lower in patients with adverse risk cytogenetics compared with patients with favorable risk cytogenetics (HR = 1.74, 95% CI, 1.16–2.61; p = .008) with a trend toward lower OS in patients with intermediate risk cytogenetics compared to those with favorable risk cytogenetics (HR = 1.43, 95% CI, 1.00–2.05; p = .052). In addition, adverse risk patients and intermediate risk patients experienced higher relapse rates compared with favorable risk patients (HR = 1.83, 95% CI, 1.13–2.94; p = .013 and HR = 1.82, 95% CI, 1.19–2.77; p = .005). Overall, cytogenetic studies aid in refinement of risk stratification in transplanted FLT3‐ITD AML patients.
Accumulation of high molecular weight kininogen in the brains of Alzheimer's disease patients may affect microglial function by altering phagocytosis and lysosomal cathepsin activity
Authors: Zamolodchikov Daria , Duffield Michael , Macdonald Lynn E. , Alessandri‐Haber Nicole
Published: January 2022

Increased activation of the contact system protein high molecular weight kininogen (HK) has been shown in plasma and cerebrospinal fluid of Alzheimer's disease (AD) patients, but its potential role in the brain has not been explored. We assessed HK levels in brain tissue from 20 AD patients and controls and modeled the effects of HK on microglia‐like cells in culture. We show increased levels of HK in the hippocampus of AD patients, which colocalized with amyloid beta (Aβ) deposits and activated microglia. Treatment of microglia with HK led to cell clustering and elevated levels of phagocytosed Aβ. We demonstrate that microglia internalize HK and traffic it to lysosomes, which is accompanied by reduced activity of lysosomal cathepsins L and S. Our results suggest that HK accumulation in the AD hippocampus may alter microglial uptake and degradation of Aβ fibrils, possibly contributing to microglial dysfunction in AD.
Preserving Brain LPC‐DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest
Authors: Nishikimi Mitsuaki , Shoaib Muhammad , Choudhary Rishabh C. , Aoki Tomoaki , Miyara Santiago J. , Yagi Tsukasa , Hayashida Kei , Takegawa Ryosuke , Yin Tai , Becker Lance B. , Kim Junhwan
Published: January 2022

Objective

Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC‐DHA), was significantly decreased in plasma post‐CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC‐DHA supplementation on the brain post‐CA.

Methods

We first evaluated associations between the plasma level of LPC‐DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC‐DHA supplementation.

Results

We found that decreased plasma LPC‐DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC‐DHA was associated with decreased levels of brain LPC‐DHA after CA, and supplementing plasma LPC‐DHA normalized brain levels of LPC‐DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC‐DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures.

Interpretation

The observed neuroprotection accompanied with normalized brain LPC‐DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC‐DHA post‐CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC‐DHA for brain damage after CA. ANN NEUROL 2022;91:389–403
Exceptional Manganese(II) Stability and Manganese(II)/Zinc(II) Selectivity with Rigid Polydentate Ligands**
Authors: Cieslik Patrick , Comba Peter , Dittmar Benedikt , Ndiaye Daouda , Tóth Éva , Velmurugan Gunasekaran , Wadepohl Hubert
Published: January 2022

While MnII complexes meet increasing interest in biomedical applications, ligands are lacking that enable high MnII complex stability and selectivity vs. ZnII, the most relevant biological competitor. We report here two new bispidine derivatives, which provide rigid and large coordination cavities that perfectly match the size of MnII, yielding eight‐coordinate MnII complexes with record stabilities. In contrast, the smaller ZnII ion cannot accommodate all ligand donors, resulting in highly strained and less stable six‐coordinate complexes. Combined theoretical and experimental data (X‐ray crystallography, potentiometry, relaxometry and 1H NMR spectroscopy) demonstrate unprecedented selectivity for MnII vs. ZnII (KMnL/KZnL of 108–1010), in sharp contrast to the usual Irving–Williams behavior, and record MnII complex stabilities and inertness with logKMnL close to 25.
A new slit‐radial die for simultaneously measuring steady state shear viscosity and first normal stress difference of viscoelastic liquids via capillary rheometry
Authors: Khabazian Esfahani Masood , Georgantopoulos Christos K. , Naue Ingo F. C. , Sunder Joachim , Wilhelm Manfred
Published: January 2022

A new slit‐radial die capable of simultaneously obtaining steady state shear viscosity and the average first normal stress difference coefficient via capillary rheometry has been developed. The steady state shear viscosity and average first normal stress difference coefficient are calculated in the slit part and radial part of the die, respectively. The steady state shear viscosity from the slit part of the slit‐radial die is compared to shear viscosities obtained from a capillary die and also the magnitude of the complex viscosity obtained from oscillatory shear experiment. The average value of first normal stress difference coefficient which is calculated in the radial part of the slit‐radial die is compared to first normal stress difference coefficient obtained from transient shear experiment in a cone‐plate geometry and the molecular stress function model predictions. The effect of variation of power law fitting parameters (consistency index, k and power law index, n) on average value of the first normal stress difference coefficient obtained from the radial part of the slit‐radial die is discussed. As this die has the shape of the city map of Karlsruhe it is named as Karlsruhe die.
Geophysical survey in archaeological context: A review from Cyprus
Authors: Vella Marc‐Antoine , Sarris Apostolos
Published: January 2022

Cyprus, the third largest Mediterranean island, is located at an exceptional crossroad in the eastern Mediterranean, where cultures from the Middle East, Africa and Europe have interacted for more than 10 000 years. The aim of this paper is to present an exhaustive review of the past archaeological geophysical surveys on the island. The result of our research indicates that to date, more than 30 archaeological sites spanning from the Pre‐Pottery Neolithic (ca. 10 000 BC) to the Venetian period (up to 1571 AD) have been investigated through noninvasive ground‐based techniques. The investigations concern the mapping of the extent of ancient occupation (settlements and cemeteries), the study of the internal organization of settlements (domestic architecture, palaces and fortifications), the investigation of funerary structures (tombs) and the use of space within buildings. The methods implemented are multiple and often used in combination. Emphasis has been given to ground penetrating radar (GPR), electromagnetic induction (EMI) and magnetic and electrical resistance techniques. Most surveys have been targeted towards the production of maps representing the spatial distribution of the subsurface architectural residues, and sometimes these have been accompanied by soundings, tomographies, as well as 3D reconstructions of the ancient structures. Very few sites have been subjected to the measurements of the chemical or magnetic properties of the soils in relation to the results of geophysical prospection. Further discussion concerns (i) the targets of the archaeo‐geophysical surveys in Cyprus, (ii) the limitations of the application of the specific techniques in relation to the Cypriot archaeological and geological context, (iii) the geophysical signatures of archaeological remains and (iv) the metadata accompanying the geophysical results.
Biogenesis and mechanisms of microRNA‐mediated gene regulation
Authors: Rani Varsha , Sengar Rakesh Singh
Published: January 2022

Endogenous RNAs that control posttranscriptional gene expression are microRNAs (miRNAs). These small regulatory molecules play a crucial role in certain biological processes and their expression is often strictly regulated. They are small 21–24 nucleotide molecules that act as major regulators of gene expression at the posttranscriptional level. One of the mechanisms by which miRNAs control the gene expression is to interact the interaction of the seeds with the 3ʹ‐end and and more seldom the 5ʹ‐end of mRNA transcribed by the target genes. miRNAs have been identified as important cytoplasmic regulators of gene expression. miRNAs function as posttranscriptional regulators of their messenger RNA (mRNA) targets by mRNA degradation and/or translational repression. It is becoming evident, however, that miRNAs have nuclear functions as well. About the cell type, the physiological state of the body, and various external factors, the following explanation will summarize the complex multilevel regulation of miRNA expression. A better understanding of the molecular mechanisms controlling miRNA expression will provide clarification of the variations in the expression of protein‐coding genes.
A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids
Authors: Fukushima Takeshi , Umino Maho , Sakamoto Tatsuya , Onozato Mayu
Published: January 2022

Kynurenine (KYN) is synthesized from an essential amino acid, tryptophan, by tryptophan 2,3‐dioxygenase or indoleamine 2,3‐dioxygenase via N‐formyl‐KYN in vivo. Subsequently, KYN acts as a precursor of some neuroactive metabolites such as kynurenic acid, quinolinic acid, and an important enzyme co‐factor, nicotine adenine dinucleotide. These metabolites of tryptophan are a part of the ‘kynurenine pathway.’ In addition, KYN functions as an endogenous ligand for the aryl hydrocarbon receptor, which acts as a transcription factor. The levels of tryptophan metabolites are important for the assessment of the stage of neurological disorders, and therefore have garnered significant interest for clinical diagnosis. In this review, the detection of kynurenine, kynurenic acid, quinolinic acid, and other tryptophan metabolites performed via chromatographic methods such as HPLC using UV absorbance, fluorescence, and chromatographic‐mass spectrometric detection is summarized.
Flipped classroom model applications in computing courses: Peer‐assisted groups, collaborative group and individual learning
Authors: Yildiz Durak Hatice
Published: January 2022

The Flipped Classroom (FC) provides various opportunities to ensure active learning in a student‐based learning environment. In the literature, it is pointed out that the FC model provided a positive contribution to the teaching process when it was used for learning environments in past studies. Besides this, it is seen that FC was integrated into a learning method and the results were generally associated with only FC. From this point of view, it is thought that the methodological effect of FC needs to be examined. The aim of this study is to identify whether the use of different models (peer‐assisted group: PAL‐FC, collaborative group: SGCL‐FC, and individual learning: IL‐FC) in FC for computing courses of university students has an effect on academic performances, learning motivation, academic self‐efficacy, computer anxiety of the university students, and flipped learning readiness. This study is designed with a mixed method. The working group of the study is composed of 242 university students. The application lasted for 14 weeks. In this study, data have been collected by a Personal Information Form, semi‐structured interview form, information technologies achievement test, and four different data collection tools. As a result of the research, it is found out that different applications in the FC model have a significant effect on academic success, academic self‐efficacy, e‐learning readiness in FC. FC model application with PAL‐FC has proved more successful when compared to other methods in terms of developing performance and reducing technology anxiety. Also, it is seen that motivation and academic self‐efficacy in FC has improved positively for collaborative group work.
Engineered Bacterial Flavin‐Dependent Monooxygenases for the Regiospecific Hydroxylation of Polycyclic Phenols
Authors: Herrmann Susann , Dippe Martin , Pecher Pascal , Funke Evelyn , Pietzsch Markus , Wessjohann Ludger A.
Published: January 2022

4‐Hydroxyphenylacetate 3‐hydroxylase (4HPA3H), a flavin‐dependent monooxygenase fromE. colithat catalyzes the hydroxylation of monophenols to catechols, was modified by rational redesign to convert also more bulky substrates, especially phenolic natural products like phenylpropanoids, flavones or coumarins. Selected amino acid positions in the binding pocket of 4HPA3H were exchanged with residues from the homologous protein fromPseudomonas aeruginosa, yielding variants with improved conversion of spacious substrates such as the flavonoid naringenin or the alkaloid mimetic 2‐hydroxycarbazole. Reactions were followed by an adapted Fe(III)‐catechol chromogenic assay selective for the products. Especially substitution of the residue Y301 facilitated modulation of substrate specificity: introduction of nonaromatic but hydrophobic (iso)leucine resulted in the preference of the substrate ferulic acid (having a guaiacyl (guajacyl) moiety, part of the vanilloid motif) over unsubstituted monophenols. Thein vivo(whole‐cell biocatalysts) andin vitro(three‐enzyme cascade) transformations of substrates by 4HPA3H and its optimized variants was strictly regiospecific and proceeded without generation of byproducts.
Engineering the Ligand Specificity of the Human Galectin‐1 by Incorporation of Tryptophan Analogues
Authors: Tobola Felix , Lepšík Martin , Zia Syeda Rehana , Leffler Hakon , Nilsson Ulf J. , Blixt Ola , Imberty Anne , Wiltschi Birgit
Published: January 2022

Galectin‐1 is a β‐galactoside‐binding lectin with manifold biological functions. A single tryptophan residue (W68) in its carbohydrate binding site plays a major role in ligand binding and is highly conserved among galectins. To fine tune galectin‐1 specificity, we introduced several non‐canonical tryptophan analogues at this position of human galectin‐1 and analyzed the resulting variants using glycan microarrays. Two variants containing 7‐azatryptophan and 7‐fluorotryptophan showed a reduced affinity for 3’‐sulfated oligosaccharides. Their interaction with different ligands was further analyzed by fluorescence polarization competition assay. Using molecular modeling we provide structural clues that the change in affinities comes from modulated interactions and solvation patterns. Thus, we show that the introduction of subtle atomic mutations in the ligand binding site of galectin‐1 is an attractive approach for fine‐tuning its interactions with different ligands.
Keep your eye on…
Authors: Knopf Alison
Published: January 2022

The psycho‐social context for intervention to resistance

Links between irritability, callous‐unemotional traits and threat responsenervosa
Trimetallic Catalyst Configuration for Syngas Production
Authors: Longo Alessandro , Theofanidis Stavros‐Alexandros , Poelman Hilde , Banerjee Dipanjan , Marin Guy B. , Galvita Vladimir V.
Published: January 2022

Dry reforming of methane (DRM) is a promising catalytic process for syngas production, utilizing and transforming CO2 to higher density compounds in view of circular economy. The performance of a bimetallic NiFe/MgAl2O4 strongly depends on the initial catalyst state – calcined, reduced or CO2‐reoxidized – that corresponds to different structures and is for each state significantly improved by the addition of a low Rh concentration (∼1 wt%). In the bimetallic catalyst, reduction is required to form the most active phase, a Ni3Fe alloy, showing a CH4 consumption rate of 0.9 mol s−1 kgcat−1. For the trimetallic NiFeRh, the effect of the initial state is less pronounced, yielding a CH4 consumption rate of 2.4 mol s−1 kgcat−1 after CO2‐reoxidation. Advanced characterization and modelling were used to gain insights in the trimetallic system and to systematically assess the role of each element. In NiFeRh, reduction leads to the formation of a trimetallic alloy. A subsequent CO2‐reoxidation induces partial Fe segregation from the trimetallic alloy, leading to separate Fe3O4. The latter structure represents the most active state due to the double role that the trimetallic catalyst takes up after H2‐reduction and CO2‐reoxidation: improved activity due to highly dispersed NiRh and NiFe alloy particles and carbon removal due to Fe3O4 particles.
Continuous Flow Bioconjugations of NIR‐AZA Fluorophores via Strained Alkyne Cycloadditions with Intra‐Chip Fluorogenic Monitoring**
Authors: Fitzgerald Sheila , O'Shea Donal F.
Published: January 2022

The importance of bioconjugation reactions continues to grow for cell specific targeting and dual therapeutic plus diagnostic medical applications. This necessitates the development of new bioconjugation chemistries, in‐flow synthetic and analytical methods. With this goal, continuous flow bioconjugations were readily achieved with short residence times for strained alkyne substituted carbohydrate and therapeutic peptide biomolecules in reaction with azide and tetrazine substituted fluorophores. The strained alkyne substrates included substituted 2‐amino‐2‐deoxy‐α‐D‐glucopyranose, and the linear and cyclic peptide sequences QIRQQPRDPPTETLELEVSPDPAS‐OH and c(RGDfK) respectively. The catalyst and reagent‐free inverse electron demand tetrazine cycloadditions proved more favourable than the azide 1,3‐dipolar cycloadditions. Reaction completion was achieved with residence times of 5 min at 40 °C for tetrazine versus 10 min at 80 °C for azide cycloadditions. The use of a fluorogenic tetrazine fluorophore, in a glass channelled reactor chip, allowed for intra‐chip reaction monitoring by recording fluorescence intensities at various positions throughout the chip. As the Diels‐Alder reactions proceeded through the chip, the fluorescence intensity increased accordingly in real‐time. The application of continuous flow fluorogenic bioconjugations could offer an efficient translational access to theranostic agents.
Synthesis of Chiral Hydantoins and Thiazolidinediones viaIridium‐Catalyzed Asymmetric Hydrogenation
Authors: Nie Yu , Li Jing , Yuan Qianjia , Zhang Wanbin
Published: January 2022

Comprehensive Summary

Herein, we report an iridium‐catalyzed asymmetric hydrogenation of hydantoin and thiazolidinedione derived exocyclic alkenes using our developed BiphPHOX as a ligand. The transformation shows good functional group tolerance, and gives the hydrogenated products with excellent yields (up to 99%) and enantioselectivities (up to 98% ee). A gram‐scale reaction was also carried out, and provided the hydrogenated product in excellent yield with no erosion in enantioselectivity. Finally, the transformation of the hydrogenated product provided an efficient approach for the synthesis of the intermediate of a HIV protease inhibitor.
Selective Binding of Small Molecules to Vibrio cholerae DsbA Offers a Starting Point for the Design of Novel Antibacterials
Authors: Wang Geqing , Mohanty Biswaranjan , Williams Martin L. , Doak Bradley C. , Dhouib Rabeb , Totsika Makrina , McMahon Róisín M. , Sharma Gaurav , Zheng Dan , Bentley Matthew R. , Ka‐Yan Chin Yanni , Horne James , Chalmers David K. , Heras Begoña , Scanlon Martin J.
Published: January 2022

DsbA enzymes catalyze oxidative folding of proteins that are secreted into the periplasm of Gram‐negative bacteria, and they are indispensable for the virulence of human pathogens such as Vibrio cholerae and Escherichia coli. Therefore, targeting DsbA represents an attractive approach to control bacterial virulence. X‐ray crystal structures reveal that DsbA enzymes share a similar fold, however, the hydrophobic groove adjacent to the active site, which is implicated in substrate binding, is shorter and flatter in the structure of V. cholerae DsbA (VcDsbA) compared to E. coli DsbA (EcDsbA). The flat and largely featureless nature of this hydrophobic groove is challenging for the development of small molecule inhibitors. Using fragment‐based screening approaches, we have identified a novel small molecule, based on the benzimidazole scaffold, that binds to the hydrophobic groove of oxidized VcDsbA with a KD of 446±10 μM. The same benzimidazole compound has ∼8‐fold selectivity for VcDsbA over EcDsbA and binds to oxidized EcDsbA, with KD>3.5 mM. We generated a model of the benzimidazole complex with VcDsbA using NMR data but were unable to determine the structure of the benzimidazole bound EcDsbA using either NMR or X‐ray crystallography. Therefore, a structural basis for the observed selectivity is unclear. To better understand ligand binding to these two enzymes we crystallized each of them in complex with a known ligand, the bile salt sodium taurocholate. The crystal structures show that taurocholate adopts different binding poses in complex with VcDsbA and EcDsbA, and reveal the protein‐ligand interactions that stabilize the different modes of binding. This work highlights the capacity of fragment‐based drug discovery to identify inhibitors of challenging protein targets. In addition, it provides a starting point for development of more potent and specific VcDsbA inhibitors that act through a novel anti‐virulence mechanism.
Population Pharmacokinetic Modeling and Exposure‐Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia
Authors: Wang Xiaofeng , Raoufinia Arash , Bihorel Sébastien , Passarell Julie , Mallikaarjun Suresh , Phillips Luann
Published: January 2022

An intramuscular formulation of aripiprazole monohydrate dosed once monthly (AOM) was developed to address nonadherence with the approved oral tablets. A 3‐compartment linear population pharmacokinetic model for oral and AOM doses was developed; relative bioavailability was estimated for AOM relative to oral dosing and body mass index and sex were significant predictors of AOM absorption rate constant (longer absorption half‐life for women and absorption half‐life increases with increasing body mass index). Aripiprazole apparent oral clearance for subjects with cytochrome P450 (CYP) 2D6 poor metabolizer status and in the presence of strong CYP2D6 inhibitors was approximately half that of subjects with CYP2D6 extensive metabolizer status and 24% lower in the presence of strong CYP3A4 inhibitors. Simulations of the population pharmacokinetics were conducted to evaluate the effect of different dose initiation strategies for AOM, the effects of CYP2D6 metabolizer status, coadministration of CYP2D6 and CYP3A4 inhibitors, and missed doses. An exposure‐response model with an exponential hazard function of the model‐predicted minimum concentration (Cmin) described the time to relapse. The hazard ratio (95% confidence interval) was 4.41 (2.89‐6.75). Thus, a subject with a diagnosis of schizophrenia and Cmin ≥ 95 ng/mL is 4.41 times less likely to relapse relative to a subject with Cmin < 95 ng/mL.
Pharmacokinetics and Bioequivalence Studies of Roxatidine Acetate Hydrochloride Sustained‐Release Capsule in Healthy Chinese Subjects
Authors: Li Xin , Yuan Fang , Xu Bing , Xiao Guiying , Fan Xingming , Li Yuan , Zhang Ping , Tu Shengqing
Published: January 2022

This study aimed to evaluate the bioequivalence between a generic roxatidine acetate hydrochloride (RAH) sustained‐release capsule and brand‐named formulation (ALTAT) under fasting and fed conditions. An open‐label, single‐center, randomized 2‐period crossover study with a 5‐day washout period was conducted. A single oral dose of 75‐mg generic RAH sustained‐release capsule (test drug) or a commercial capsule (reference drug) was given to healthy volunteers under fasting (n = 36) and fed conditions (n = 36). Blood samples were collected at baseline and during the 24 hours after dosing. The concentrations of roxatidine acetate (ROX) and bioactive metabolite roxatidine in plasma were detected using a validated high‐performance liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were analyzed with noncompartmental methods. As prodrug, RAH was dehydrochloric acid to ROX in body and further rapidly converted to roxatidine. Such a rapid metabolism resulted in ROX that was hardly detected in plasma. Active metabolism roxatidine was therefore used to evaluate the pharmacokinetic process. The major pharmacokinetic parameters of roxatidine including peak plasma concentration, area under the plasma concentration–time curve from time 0 to time t, and area under the plasma concentration–time curve from time 0 to infinity were similar between the 2 preparations under fasting and fed conditions. The generic RAH sustained‐release capsule is bioequivalent to the reference drug under fasting and fed conditions in healthy Chinese subjects.
The pH and Potential Dependence of Pb‐Catalyzed Electrochemical CO2 Reduction to Methyl Formate in a Dual Methanol/Water Electrolyte
Authors: Hofsommer Dillon T. , Liang Ying , Uttarwar Sandesh S. , Gautam Manu , Pishgar Sahar , Gulati Saumya , Grapperhaus Craig A. , Spurgeon Joshua M.
Published: January 2022

The conversion of waste CO2 to value‐added chemicals through electrochemical reduction is a promising technology for mitigating climate change while simultaneously providing economic opportunities. The use of non‐aqueous solvents like methanol allows for higher CO2 availability and novel products. In this work, the electrochemistry of CO2 reduction in acidic methanol catholyte at a Pb working electrode was investigated while using a separate aqueous anolyte to promote a sustainable water oxidation half‐reaction. The selectivity among methyl formate (a product unique to reduction of CO2 in methanol), formic acid, and formate was critically dependent on the catholyte pH, with higher pH conditions leading to formate and low pH favoring methyl formate. The potential dependence of the product distribution in acidic catholyte was also investigated, with a faradaic efficiency for methyl formate as high as 75 % measured at −2.0 V vs. Ag/AgCl.
Hexafluoroisopropanol‐Promoted or Brønsted Acid‐Mediated Photochemical [2+2] Cycloadditions of Alkynes with Maleimides
Authors: Triandafillidi Ierasia , Nikitas Nikolaos F. , Gkizis Petros L. , Spiliopoulou Nikoleta , Kokotos Christoforos G.
Published: January 2022

Although the use of light stimulating organic transformations has been known for more than a century, there is an increasing research interest on expanding the established knowledge. While [2+2] cycloadditions are promoted photochemically, literature precedent on the reaction between alkynes and maleimides is limited and only a handful of examples exist, focusing mainly on N‐aliphatic maleimides. Herein, the differences in reactivity between N‐alkyl and N‐aryl maleimides were identified, and the use of hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA) as viable solutions was proposed in order to achieve high yields. In the case of N‐alkyl maleimides, both HFIP‐mediated or TFA‐promoted reactions were established using LED 370 nm irradiation, without the use of an external photocatalyst. In the case of N‐aryl maleimides, thioxanthone (THX) was employed as the energy transfer photocatalyst along with LED 427 nm irradiation and HFIP. Mechanistic studies were performed, supporting the pivotal role of HFIP or TFA, in acquiring good to high yields in both classes of maleimides.
Insight into Hydrogenation Selectivity of the Electrocatalytic Nitrate‐to‐Ammonia Reduction Reaction via Enhancing the Proton Transport
Authors: Xu Yan‐Tong , Peng Zhigang , Han Ying , Zhong Huiqiong , Yang Jun , Cao Yan
Published: January 2022

The electrocatalytic nitrate‐to‐ammonia reduction reaction route (NARR) is one of the emerging routes toward green ammonia synthesis, and its conversion efficiency is controlled mainly by the hydrogenation selectivity. This study proposed a likely NARR route feasible and effective even in a neutral condition. Its high catalytic selectivity and efficiency were achieved by a switch of the sulfate solution to the phosphate buffer solution (PBS), while conditions of NO3− concentration, pH, and applied potential were maintained unchanged. Specifically, the faradaic efficiencies toward NH3 (FE
) in Na2SO4 were as low as 9.8, 19.8, and 11.4 % versus remarkably jumping to 82.8, 90.5, and 89.5 % in PBS under −0.75, −1.0, and −1.25 V, respectively. The corresponding faradaic efficiencies toward NO2− (FE
), 77.0, 69.2, and 73.7 % in Na2SO4, significantly dropped to10.8, 7.4, and 4.4 % in PBS, evidencing an unexpected selectivity reversal of the nitrate reduction from NO2− to NH3. This insight was further revealed by the visualization of the pH gradient near the electrode surface during NARR and confirmed by density functional theory calculations; PBS notably facilitated the proton transport and active mitigation over the proton transfer barrier. The use of PBS resulted in a maximal partial current density toward NH3 (J
) and NH3 formation rate (r
) up to 133.5 mA cm−2 and 1.74×10−7 mol s−1 cm−2 in 1.0 m KNO3 at −1.25 V.
Uplink performance of nonorthogonal multiple access ultradense networks with power control
Authors: Cong Lam Sinh , Pham Thanh Hiep , Tran Xuan Nam
Published: January 2022

This paper studies power control in ultradense networks which are potential network models of 5G cellular systems. The power control model that bases on stretched path loss model (SPLM) is introduced to allow each user to proactively adjust its transmission power to adapt to power loss and network status. The moment‐generating function (MGF) is utilized through the paper to analyze the uplink coverage probability (UCP) in which it is assumed that the base station (BS) of interest does not have information about fast fading of interfering channels. The analytical results indicate that the proposed power control model can reduce user power consumption while maintaining the UCP. Two interesting facts have been stated when comparing the performance of the networks in good and bad channel conditions. First, the user equipment (UE) in bad channel conditions outperforms others in good channel conditions. Second, the deployment of nonorthogonal multiple access (NOMA) technique can significantly improve the area spectral efficiency (ASE) in bad channel conditions.
The glial cell’s role in antinociceptive differential effects of oxytocin upon female and male rats
Authors: Salinas‐Abarca Ana B. , Vázquez‐Cuevas Francisco G. , González‐Gallardo Adriana , Martínez‐Lorenzana Guadalupe , González‐Hernández Abimael , Condés‐Lara Miguel
Published: January 2022

Background

Sex plays a crucial role in pain processing and response to analgesic drugs. Indeed, spinal glia seems to be significant in the sexual dimorphism observed in the above effects. Recently, studies have associated oxytocin with antinociceptive effects, but these have been mainly performed in male animals; consequently, the influence of sex has been poorly explored. Methods: Using a model of spinal nociception that produces pain through activation of the spinal glia, that is, intrathecal (i.t.) lipopolysaccharide (LPS) injection, we analysed the changes in the analgesic response to i.t. oxytocin in female and male rats by behavioural (punctate mechanical hypersensitivity), electrophysiological (unitary extracellular recordings of wide dynamic range [WDR] cells) and molecular biology (real‐time PCR of proinflammatory genes) experiments.

Results

We found that LPS‐induced hypersensitivity was longer in female (>96 h) than in male (≈4 h) rats. Besides, spinal oxytocin preferentially prevents the LPS‐induced hypersensitivity in male rather than female rats. Indeed, LPS increases the spinal neuronal‐evoked activity associated with the activation of peripheral Aδ‐ and C‐fibres and post‐discharge in males, whereas only C‐fibre discharge was enhanced in females. The electrophysiological data correlate with the fact that spinal oxytocin only prevented TNF‐α and IL‐1β synthesis in male rats.

Conclusions

Therefore, these data suggest that oxytocin‐mediated analgesia depends on a sexual dimorphism involving activation of the spinal glia. These results reinforced the idea that different strategies are required to treat pain in men and women, and that oxytocin could be used preferentially to treat pain with a significant inflammatory component in men.

Significance Statement

Oxytocin is a molecule that emerges as a potent analgesic in preclinical and clinical studies. We investigated the contribution of glia to the response of oxytocin‐induced analgesia and how sex influences in this response show that different strategies are required to treat pain in men and women, and that oxytocin could be used preferentially to treat pain with a significant inflammatory component in men.