bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying Magnetic‐Responsive Nanocatalyst‐Liquid Interface for Active Molecule Manipulation to Boost Catalysis Beyond Diffusion Limit
Authors: Mohamed‐Ibrahim Nur Amalina binte , Kheng Boong Siew , Zhong Ang Zhi , Shiuan Ng Li , Tan Jia Ying Charlene , Chong Carice , Kwee Lee Hiang 
Published: April 2022

AbstractEfficient nanocatalysis requires swift delivery of reactants to catalytic sites, but the presence of diffusion‐dominated, hydrodynamic boundary layers on all heterogeneous catalysts impedes fast chemical transformation. Here, efficient nanocatalysis is achieved by applying a magnetic‐responsive nanocatalyst‐liquid interface to create a vortex‐like flow that rapidly pulls reactants from bulk solution to the catalyst, beyond the diffusion limit. Consequently, our design attains a >90 % degradation efficiency in <5 min with reaction kinetics tunable via the nanocatalyst spin rate. The spinning nanocatalyst notably exhibits reaction kinetics and molecule transfer rates >10‐fold and 30‐fold faster than traditional homogenization methods, respectively. This unique molecule delivery design will complement recent advances in active catalytic nanomaterials to realize ideal nanocatalysis in emerging chemical, energy, and environmental applications.
Towards a Generalized ORR Mechanism in M2+‐Containing DMSO: Oxygen Reduction and Evolution in Ca2+‐Containing DMSO on Atomically Smooth and Rough Pt
Authors: Koellisch‐Mirbach Andreas , Bawol Pawel Peter , Park Inhee , Baltruschat Helmut 
Published: April 2022

AbstractThe oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) in Ca2+ containing dimethyl sulfoxide (DMSO) on atomically smooth Pt(111) and Pt(100) and rough Pt surfaces is reported. As demonstrated by cyclic voltammetry and XPS, the bromine adlayer used to protect Pt single crystals against ambient air and solvent vapor is desorbed in DMSO and does not affect the following measurements. Cyclic voltammetry, differential electrochemical mass spectrometry (DEMS), and rotating ring disk electrode (RRDE) investigations with variation of the electrode surface roughness and atomically surface structure show, that on Pt electrodes the CaO2 adsorbate layer formation determines the ORR product distribution. On Pt electrodes, calcium peroxide is formed on the clean electrode, whereas calcium superoxide is formed at the adsorbate covered electrode. We furthermore identified four key parameters, which strongly affect the ORR product distribution: 1) The electrode oxide interaction: A strong interaction increases superoxide contribution; 2) The alkaline earth metal oxide interaction: A strong interaction increases peroxide contribution; 3) The electrode surface area: A large electrode surface area increases peroxide contribution; 4) Electrode surface defects: Defects increase superoxide contribution. Finally, reviewing earlier results of our group, we provide a more general mechanism for the oxygen reduction alkaline earth metal cation containing DMSO, for a variety of electrode materials.
Peroxynitrite‐Promoted Persulfide Prodrugs with Protective Potential against Paracetamol Poisoning
Authors: Xu Ya‐Wen , Xu Bi‐Xin , Wang Jiankun , Jin Hao‐Wen , Xu Si‐Tao , Wang Guangji , Zhen Le 
Published: April 2022

AbstractThe newly emerging persulfide prodrugs provide additional options for the profound study of persulfide, a fascinating molecule expected to intervene in biological functions and even diseases. Peroxynitrite is often the culprit in pathological processes characterized by oxidative stress, while the persulfide prodrug responsive to it is still pending. To enrich the family of redox‐activated prodrugs, we designed prodrugs with a 2‐oxo‐2‐phenylacetamide trigger, which achieved the release of persulfide via 1, 6‐N,S‐relay. The degradation of prodrugs and the formation of persulfides were confirmed to be peroxynitrite‐responsible by the qualitative and quantitative studies based on LC‐MS/MS methods and a spectrophotometry‐based tag‐switch strategy. Furthermore, these prodrugs showed potent peroxynitrite scavenging activity, cellular therapeutic potential against paracetamol poisoning in HepG2 and oxidative stress in H9c2, as well as desirable in vitro metabolic properties.
Boron‐Locked Starazine – A Soluble and Fluorescent Analogue of Starphene
Authors: Feng Yi , Zhou Jiadong , Qiu Honglin , Schnitzlein Matthias , Hu Jingtao , Liu Linlin , Würthner Frank , Xie Zengqi 
Published: April 2022

AbstractA starlike heterocyclic molecule containing an electron‐deficient nonaaza‐core structure and three peripheral isoquinolines locked by three tetracoordinate borons, namely isoquinoline‐nona‐starazine (QNSA), is synthesized by using readily available reactants through a rather straightforward approach. This new heteroatom‐rich QNSA possesses a quasi‐planar π‐backbone structure, and bears phenyl substituents on borons which protrude on both sides of the π‐backbones endowing it with good solubility in common organic solvents. Contrasting to its starphene analogue, QNSA shows intense fluorescence with a quantum yield (PLQY) of up to 62 % in dilute solution.
Reactivity of Diphenylberyllium as a Brønsted Base and Its Synthetic Application
Authors: Thomas‐Hargreaves Lewis R. , Berthold Chantsalmaa , Augustinov William , Müller Matthias , Ivlev Sergei I. , Buchner Magnus R. 
Published: April 2022

AbstractDiphenylberyllium [Be3Ph6] is shown here to react cleanly as a Brønsted base with a vast variety of protic compounds. Through the addition of the simple molecules tBuOH, HNPh2 and HPPh2, as well as the more complex 1,3‐bis‐(2,6‐diisopropylphenyl)imidazolinium chloride, one or two phenyl groups in diphenylberyllium were protonated. As a result, the long‐postulated structures of [Be3(OtBu)6] and [Be(μ‐NPh2)Ph]2 have finally been verified and shown to be static in solution. Additionally [Be(μ‐PPh2)(HPPh2)Ph]2 was generated, which is only the second beryllium‐phospanide to be prepared; the stark differences between its behaviour and that of the analogous amide were also examined. The first crystalline example of a beryllium Grignard reagent with a non‐bulky aryl group has also been prepared; it is stabilised with an N‐heterocyclic carbene.
A Mesoionic Diselenolene Anion and the Corresponding Radical Dianion
Authors: Dong Zhaowen , Sienkiewicz Andrzej , Suleymanov Abdusalom A. , Berton Cesare , Fadaei‐Tirani Farzaneh , Scopelliti Rosario , Severin Kay 
Published: April 2022

AbstractDichalcogenolenes are archetypal redox non‐innocent ligands with numerous applications. Herein, a diselenolene ligand with fundamentally different electronic properties is described. A mesoionic diselenolene was prepared by selenation of a C2‐protected imidazolium salt. This ligand is diamagnetic, which is in contrast to the paramagnetic nature of standard dichalcogenolene monoanions. The new ligand is also redox‐active, as demonstrated by isolation of a stable diselenolene radical dianion. The unique electronic properties of the new ligand give rise to unusual coordination chemistry. Thus, preparation of a hexacoordinate aluminum tris(diselenolene) complex and a Lewis acidic aluminate complex with two ligand‐centered unpaired electrons was achieved.
New enantioselective liquid chromatography method development and validation of dipeptidyl peptidase IV inhibitors using a macrocyclic glycopeptide (vancomycin) chiral stationary phase under polar ionic mode condition
Authors: Arnipalli Manikanta Swamy , Nimmu Narendra varma , Boddapati S. N. Murthy , Challa Gangu Naidu , Jaweria Syed , Kola A. Emmanuel 
Published: April 2022

AbstractThe direct separation of dipeptidyl peptidase IV (DPP‐4) inhibitors such as Sitagliptin (STG), Linagliptin (LIG), and Saxagliptin (SAG) enantiomers in normal phase conditions have been achieved on immobilized polysaccharide‐based chiral stationary phases (CSPs), as well as on the macrocyclic glycopeptide vancomycin chiral stationary phase (Chirobiotic V2) under polar ionic mode. The enantiomers of these targets could be separated completely (resolution factor Rs > 2) using the Chirobiotic V2 column in polar ionic mode with the mobile phase (MeOH/AcOH/TEA 100/0.3/0.1 v/v/v) in an isocratic elution at 1.0 ml min−1. The effect of the mobile phase composition on separation, including buffer salts, acid–base modifiers, and analyte structures, was evaluated. The developed technique was validated in the polar ionic mode according to the International Conference on Harmonization (ICH) Q2R1 guidelines in terms of accuracy, precision, selectivity, linearity, limit of detection (LOD), and limit of quantification (LOQ). The calibration curve was linear in a concentration range from LOQ to 3.75 μg/ml. The LOD and LOQ of STG, LIG, and SAG were 0.15 and 0.45, 0.15 and 0.50, 0.16 and 0.50, respectively. The proposed method is said to be selective, accurate, and precise. Finally, the validated method was used successfully for the quantitative determination of DPP‐4 enantiomers in pharmaceutical analytes.
Synthesis, in vitro Antileishmanial Efficacy and Hit/Lead Identification of Nitrofurantoin‐Triazole Hybrids
Authors: Zuma Nonkululeko H. , Aucamp Janine , Viljoen Maryna , N'Da David D. 
Published: April 2022

AbstractLeishmaniasis is a vector‐borne neglected parasitic infection affecting thousands of individuals, mostly among populations in low‐ to moderate‐income developing countries. In the absence of protective vaccines, the management of the disease banks solely on chemotherapy. However, the clinical usefulness of current antileishmanial drugs is threatened by their toxicity and the emergence of multidrug‐resistant strains of the causative pathogens. This emphasizes the imperative for the development of new and effective antileishmanial agents. In this regard, we synthesized and evaluated in vitro the antileishmanial activity and cytotoxicity profile of a series of nitrofurantoin‐triazole hybrids. The nitrofurantoin derivative 1 featuring propargyl moiety was distinctively the most active of all, was nontoxic to human cells and possessed submicromolar cellular activity selectively directed towards the pathogens of the life threatening visceral leishmaniasis. Hence it was identified as potential antileishmanial lead for further investigation into its prospective to act as alternative to therapies.
Estimation of coefficient of variation using linear moments and calibration approach for nonsensitive and sensitive variables
Authors: Shahzad Usman , Ahmad Ishfaq , Hanif Muhammad , Al‐Noor Nadia H. 
Published: April 2022

AbstractAssessment of coefficient of variation (CV) is of major importance in numerous examinations. However, the appearance of extreme observations raises concerns about the outcomes of CV estimates based on conventional moments. So, motivated by some recent developments in finite sampling theory, we propose some new estimators of CV based on the properties of linear moments (L‐moments and Trimmed L‐moments), which are highly robust whenever outliers or extreme observations appear in a dataset. The proposed estimators are initially established on the premise that the variable of interest is nonsensitive which deals with the subjects that do not embarrass respondents when asked about them explicitly. These estimators are also applied to situations where the variable of interest is associated with sensitive issues that cause measurement errors resulting from nonresponse or unreliable reporting where such issues can be mitigated by increasing respondent participation by scrambled response models which obscure the true value of the sensitive variable. Four models are considered for this article: additive, multiplicative, mixed, and combined additive‐multiplicative models. Finally, in both nonsensitive and sensitive settings, real‐life data sets are employed to undertake simulation‐based analysis. In all cases, the proposed estimators considerably increased efficiency.
Introducing Alternative Algorithms for the Determination of the Distribution of Relaxation Times
Authors: Bergmann Tobias G. , Schlüter Nicolas 
Published: April 2022

AbstractImpedance spectroscopy is a powerful characterization method to evaluate the performance of electrochemical systems. However, overlapping signals in the resulting impedance spectra oftentimes cause misinterpretation of the data. The distribution of relaxation times (DRT) method overcomes this problem by transferring the impedance data from the frequency domain into the time domain, which yields DRT spectra with an increased resolution. Unfortunately, the determination of the DRT is an ill‐posed problem, and appropriate mathematical regularizations become inevitable to find suitable solutions. The Tikhonov algorithm is a widespread method for computing DRT data, but it leads to unlikely spectra due to necessary boundaries. Therefore, we introduce the application of three alternative algorithms (Gold, Richardson Lucy, Sparse Spike) for the determination of stable DRT solutions and compare their performances. As the promising Sparse Spike deconvolution has a limited scope when using one single regularization parameter, we furthermore replaced the scalar regularization parameter with a vector. The resulting method is able to calculate well‐resolved DRT spectra.
Impact of Obesity on Postprandial Triglyceride Contribution to Glucose Homeostasis, Assessed with a Semimechanistic Model
Authors: Leohr Jennifer , Kjellsson Maria C. 
Published: April 2022

The integrated glucose‐insulin model is a semimechanistic model describing glucose and insulin after a glucose challenge. Similarly, a semiphysiologic model of the postprandial triglyceride (TG) response in chylomicrons and VLDL‐V6 was recently published. We have developed the triglyceride‐insulin‐glucose‐GLP‐1 (TIGG) model by integrating these models and active GLP‐1. The aim was to characterize, using the TIGG model, the postprandial response over 13 hours following a high‐fat meal in 3 study populations based on body mass index categories: lean, obese, and very obese. Differential glucose and lipid regulation were observed between the lean population and obese or very obese populations. A population comparison revealed further that fasting glucose and insulin were elevated in obese and very obese when compared with lean; and euglycemia was achieved at different times postmeal between the obese and very obese populations. Postprandial insulin was incrementally elevated in the obese and very obese populations compared with lean. Postprandial chylomicrons TGs were similar across populations, whereas the postprandial TGs in VLDL‐V6 were increased in the obese and very obese populations compared with lean. Postprandial active GLP‐1 was diminished in the very obese population compared with lean or obese. The TIGG model described the response following a high‐fat meal in individuals who are lean, obese, and very obese and provided insight into the possible regulation of glucose homeostasis in the extended period after the meal by utilizing lipids. The TIGG‐model is the first model to integrate glucose and insulin regulation, incretin effect, and postprandial TGs response in chylomicrons and VLDL‐V6.
A Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Novel Insulin Dimer
Authors: Walford Geoffrey A. , Duncan Kelly E. , Hernandez Moises , Vaddady Pavan , Hompesch Marcus , Morrow Linda , Stoch S. Aubrey 
Published: April 2022

Insulin molecules of size much greater than natural insulin have been synthesized and studied with the intention of widening the therapeutic window between adequate glycemic control and hypoglycemia as compared with conventional insulins. MK‐1092 is a synthetic insulin dimer with favorable properties demonstrated in preclinical studies. Here, we report the results of the first‐in‐human, randomized, double‐blind, active‐control, single ascending dose trial of MK‐1092, conducted in healthy adults, adults with type 1 diabetes (T1D), and adults with type 2 diabetes (T2D). MK‐1092 was well tolerated in all study populations, and no dose‐related adverse events were identified across the evaluated dose range (4–64 nmol/kg). Circulating concentrations of MK‐1092 were approximately dose‐proportional. Maximum glucose infusion rate (GIR) and 24‐hour time‐weighted average GIR were evaluated under euglycemic clamp conditions. These pharmacodynamic measurements were approximately dose‐proportional in all study populations; at similar doses, the GIR parameters were lower in adults with T2D than in healthy adults or adults with T1D, likely due to the influence of insulin resistance. At doses ≥ 16 nmol/kg, MK‐1092 had similar or greater effects than glargine 3 nmol/kg (0.5 units/kg) on increasing GIR in each study population and on suppressing free fatty acids and ketone generation in adults with T1D. MK‐1092 did not prevent a subsequent high dose of lispro from increasing the GIR in healthy adults. Additional studies in adults with T1D and T2D are needed to further evaluate the safety, tolerability, and efficacy profile of MK‐1092 and its potential for differentiation from more conventional insulins. (ClinicalTrials.gov: NCT03170544)
A novel reduced switch single‐phase five‐level inverter
Authors: Bogineni Jayachandra , Nakka Jayaram 
Published: April 2022

AbstractConventional multilevel inverters (MLI) incorporate many independent dc sources and switches, which adds to the overall system's cost and complexity. This article presents a detailed analysis of a reduced switch single‐phase five‐level inverter for medium‐ and high‐power applications. The comparison of the proposed topology with traditional and recently developed MLI topologies shows that the topology proposed has a smaller number of circuit elements, isolated dc sources, and voltage stress of half of the supply voltage on 50% of switches. Reducing the number of components and sources reduces the complexity and total cost of the inverter. These reduced switches voltage stresses increase the overall system reliability. The MATLAB/SIMULINK simulations for different load changes were carried out for analysis in software mode. The scaled‐down prototype is used for the validation of simulation analysis. The components comparison was also carried out to list the advantages of this topology over other MLI configurations.
Posttranslational modification of Aurora A‐NSD2 loop contributes to drug resistance in t(4;14) multiple myeloma
Authors: Jiang Hongmei , Wang Yixuan , Wang Jingjing , Wang Yafei , Wang Sheng , He Enyang , Guo Jing , Xie Ying , Wang Jingya , Li Xin , Peng Ziyi , Wang Mengqi , Hou Jian , Liu Zhiqiang 
Published: April 2022

AbstractBackgroundt(4;14)(p16;q32) cytogenetic abnormality renders high level of histone methyltransferase NSD2 in multiple myeloma (MM) patients, and predicts poor clinical prognosis, but mechanisms of NSD2 in promoting chemoresistance have not been well elucidated.MethodsAn epigenetics compound library containing 181 compounds was used to screen inhibitors possessing a prior synergistic effect with bortezomib (BTZ) in vitro. Molecular biology techniques were applied to uncover underlying mechanisms. Transcriptome profile assay was performed by RNA‐seq. NSG mouse‐based xenograft model and intra‐bone model were applied to qualify the synergistic effect in vivo.ResultsWe identified an Aurora kinase A inhibitor (MLN8237) possessed a significant synergistic effect with BTZ on t(4;14) positive MM cells. Aurora A protein level positively correlated with NSD2 level, and gain‐ and loss‐of‐functions of Aurora A correspondingly altered NSD2 protein and H3K36me2 levels. Mechanistically, Aurora A phosphorylated NSD2 at S56 residue to protect the protein from cleavage and degradation, thus methylation of Aurora A and phosphorylation of NSD2 bilaterally formed a positive regulating loop. Transcriptome profile assay of MM cells with AURKA depletion identified IL6R, STC2 and TCEA2 as the downstream target genes responsible for BTZ‐resistance (BR). Clinically, higher expressions of these genes correlated with poorer outcomes of MM patients. Combined administration of MLN8237 and BTZ significantly suppressed tumour growth in LP‐1 cells derived xenografts, and remarkably alleviated bone lesion in femurs of NSG mice.ConclusionsAurora A phosphorylates NSD2 at S56 residue to enhance NSD2 methyltransferase activity and form a positive regulating loop in promoting MM chemoresistance, thus pharmacologically targeting Aurora A sensitizes t(4;14) positive MM to the proteasome inhibitors treatment. Our study uncovers a previously unknown reason of MM patients with t(4;14) engendering chemoresistance, and provides a theoretical basis for developing new treatment strategy for MM patients with different genomic backgrounds.
Relevance of polyclonal plasma cells and post‐therapy immunomodulation in measurable residual disease assessment in multiple myeloma
Authors: Das Nupur , Dahiya Meetu , Gupta Ritu , Kumar Lalit , Sharma Atul , Rai Sandeep , Singh Saroj , Prajapati Vijay K. , Sahoo Ranjit K. , Gogia Ajay 
Published: April 2022

AbstractBackgroundImmunophenotypic profile and post‐therapy alteration in antigenic expression were evaluated in normal, reactive, and aberrant plasma cells (NPC, RPC, and APC) for impact on measurable residual disease (MRD) assessment in multiple myeloma (MM).MethodsSamples from non‐MM staging marrow (n = 30), Hodgkin's lymphoma (n = 30) and MM (n = 724) were prospectively evaluated for expression profiles of NPC, RPC, and APC using antigens recommended in consensus guidelines.ResultsPolyclonal NPC‐RPC demonstrated aberrations for all antigens evaluated with a higher frequency of aberrancies in post‐therapy samples compared to treatment naïve samples (p < 0.001%). Immunomodulation in APC was observed in 79% of post‐therapy samples with a change in expression of 1, 2, and ≥3 antigens in 19.9%, 15.6%, and 43.5% samples, respectively. In 13.4% of samples, APC showed no aberrancy and aberrant status was assigned based on cytoplasmic light chain restriction (cyLCR) alone. 9% samples with an admixture of NPC and APC displayed normal cytoplasmic kappa to lambda ratio (cyKLR) when the percentage of APC of total PC (neoplastic plasma cell index, NPCI), was below 25% and 50% for kappa and lambda restricted cases, respectively.ConclusionThe panorama and high frequency of antigenic aberrations on polyclonal PC signify the importance of MRD assay validation on a large cohort under normal and reactive conditions. Frequent Immunophenotypic shifts in APC re‐confirm the redundancy of baseline immunophenotype for MRD evaluation. Small clones of APC may be missed by assessment of cyKLR alone and therefore, surface marker aberrancy supported by cyLCR is required for definitive assignment of residual APC.