bluuebunny/crossref_metadata_2025_split huggingface dataset:
A stability‐indicating, reversed‐phase HPLC method for quantification of assay and organic impurities in doxycycline hyclate bulk and parenteral dosage forms
Authors: Pippalla Sreenivas , Nekkalapudi Arjuna Rao , Jillellamudi Suresh Babu , Reddy Mukkala Prasada , Kumar Cholleti Vijay 
Published: March 2023

AbstractThe aim of this study is to develop a stability‐indicating, reversed‐phase HPLC method for the quantification of assay and organic impurities (process and degradation) of doxycycline hyclate in a doxycycline injectable formulation. Both the active and dosage forms are officially present in the USP monograph, and assay and impurity methods are provided by separate UPLC techniques, which are highly sensitive to the flow rate and temperature, considering the quality control requirements and user‐friendliness. A simple stability‐indicating HPLC method with a shorter run time was developed for the simultaneous quantification of assay and impurity. The method was developed using HPLC with a gradient program and a reversed‐phase Waters XBridge BEH C8 column (150 × 4.6 mm, 3.5 μm i.d.). Mobile phase A consisted of phosphate buffer (pH 8.5, 25 mM potassium phosphate, 2 mM ethylenediaminetetraacetic acid, and 0.5 ml of triethylamine). Mobile phase B consisted of methanol with a flow rate of 1.7 ml/min, a column temperature of 55°C, a UV wavelength of 270 nm, and an injection volume of 25 μl. Modern research represents a concomitant method for quantifying assay and organic impurities of doxycycline hyclate (active form) and doxycycline for injection (dosage form). The assay and impurity method were validated per United States Pharmacopeia (USP) 1225 and International Conference on Harmonization (ICH) guidelines. The retention time of doxycycline and degradation impurity, 4‐epidoxycycline, was about 9.8 and 6.4 min, respectively. The linearity range of doxycycline and 4‐epidoxycycline was 0.5–150 and 0.5–18 μg/ml, respectively. The percentage of recovery of doxycycline and 4‐epidoxycycline was 98.7–100.6% and 88.0–112.0%. Validation of the analytical method demonstrated that the method is suitable, specific, linear, accurate, precise, rugged, and stability indicating for estimating the assay, known and degraded impurities of doxycycline, and doxycycline for injection.
‘On Water’‐Promoted Three‐Component Tandem Michael Addition/D−A Cycloaddition Reaction to Construct Polycyclic N‐Heterocycles Derivatives
Authors: Dong Yu , Luo Liang‐Xian , Hua Chen , He Ze‐Jing , Chen Yong , Shi Zhi‐Chuan , Li Zhong‐Hui , He Bing 
Published: March 2023

Abstract‘On Water’‐promoted the three‐component tandem Michael addition/D−A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N‐heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction.
Differential Chemoproteomics Reveals MARK2/3 as Cell Migration‐Relevant Targets of the ALK Inhibitor Brigatinib
Authors: Hu Qianqian , Liao Yi , Cao Jessica , Fang Bin , Yun Sang Y. , Kinose Fumi , Haura Eric B. , Lawrence Harshani R. , Doebele Robert C. , Koomen John M. , Rix Uwe 
Published: March 2023

AbstractMetastasis poses a major challenge in cancer management, including EML4‐ALK‐rearranged non‐small cell lung cancer (NSCLC). As cell migration is a critical step during metastasis, we assessed the anti‐migratory activities of several clinical ALK inhibitors in NSCLC cells and observed differential anti‐migratory capabilities despite similar ALK inhibition, with brigatinib displaying superior anti‐migratory effects over other ALK inhibitors. Applying an unbiased in situ mass spectrometry‐based chemoproteomics approach, we determined the proteome‐wide target profile of brigatinib in EML4‐ALK+ NSCLC cells. Dose‐dependent and cross‐competitive chemoproteomics suggested MARK2 and MARK3 as relevant brigatinib kinase targets. Functional validation showed that combined pharmacological inhibition or genetic modulation of MARK2/3 inhibited cell migration. Consistently, brigatinib treatment induced inhibitory YAP1 phosphorylation downstream of MARK2/3. Collectively, our data suggest that brigatinib exhibits unusual cross‐phenotype polypharmacology as, despite similar efficacy for inhibiting EML4‐ALK‐dependent cell proliferation as other ALK inhibitors, it more effectively prevented migration of NSCLC cells due to co‐targeting of MARK2/3.
Promotional Effect of Zirconium Doping on the NH3‐SCR Activity of CeO2 and CeO2‐TA Modified by Thiourea: A Comparative Study
Authors: Li Jun , Zhou Fei , Xiong Zhibo , Du Yanping , Yang Qiguo , Wang Wei , Lu Wei 
Published: March 2023

AbstractZirconium (Zr) was doped to optimize the NH3‐SCR activity of both CeO2 and thiourea modified CeO2‐TA catalysts for comparison. Different from the promotional influence of thiourea modification on the agglomeration of CeO2, the transformation from nanoparticles to nanocubes and the formation of highly crystallized CeOSO4, Zr doping lowers the agglomeration of nanoparticles, loosens the surface morphology of catalyst and promotes the formation of Ce‐Zr solid solution. Furthermore, Zr doping exhibits a synergistic promotional effect of thiourea modification on the dispersion of Ce3+ and S6+ species on the surface of CeO2, and increases the concentrations of the surface total oxygen and chemisorbed oxygen of CeO2‐TA. Interestingly, Zr doping instead decreases the promotional effect of thiourea modification on the high‐temperature or medium/low‐temperature reducibility of catalyst, but increases both Brønsted and Lewis acid sites of CeO2‐TA by inducing the highly dispersive sulfate species rather than the CeOSO4 crystal, which might be crucial to the NH3‐SCR activity of Ce‐based catalyst.
Artificial neural network (ANN) modeling for simultaneous removal of a binary mixture of Pb(II) and Cu(II) by cobalt hydroxide nano‐flakes
Authors: Zolgharnein Javad , Shariatmanesh Tahere , Farahani Saeideh Dermanaki 
Published: March 2023

AbstractA three‐layer artificial neural network (ANN) model was developed to predict the efficiency of Cu(II) and Pb(II) ion removal from aqueous solution by cobalt hydroxide nano‐flakes. It is based on experimental sets obtained from a D‐optimal design. The input variables to the neural network were as follows: the initial concentration of Pb(II) and Cu (II) ions (mg L−1), initial pH, and sorbent mass (g). The configuration of the backpropagation neural network for both Cu(II) and Pb (II) ions was a tangent sigmoid transfer function (tansig) at the hidden layer, linear transfer function (purelin) at the output layer, and Levenberg–Marquardt training algorithm (LMA). ANN‐predicted results were very close to the experimental results with a coefficient of determination (R2) of 0.9970 and mean square error (MSE) 0.000376. Analysis based on the ANN model indicated that sorbent mass appeared to be the most influential factor in the adsorption process of Cu(II) and Pb(II). Characterization of the cobalt hydroxide nano‐flakes and possible metal ions‐adsorbent interactions were confirmed by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), and scanning electron microscopy (SEM).
Caffeine Biodegradation by Cytochrome P450 1A2. What Determines the Product Distributions?
Authors: Mokkawes Thirakorn , de Visser Sam P. 
Published: March 2023

AbstractCaffeine is a natural compound found in plant seeds that after consumption by humans effects the central nervous system as well as the cardiovascular system. In general, the cytochrome P450 enzymes in the liver are involved in the biodegradation of caffeine, which gives paraxanthine, theobromine and theophylline products. There has been debate for many years why multiple products are obtained and how their distributions are determined. To this end we performed a high‐level computational study using a combination of molecular dynamics and quantum mechanical approaches. A series of quantum chemical cluster models on the mechanism of caffeine activation by P450 model complexes give hydrogen atom abstraction barriers that predicts the correct ordering and statistical distribution of products. Our studies highlight that second‐coordination sphere effects and thermochemical properties of the substrate determine the product distributions.
Ionic Liquid‐Mediated Approach for the Synthesis of Site‐Specific Thioether Conjugates
Authors: Abujubara Helal , Yang Jie , Birsen Otyakmaz A. , Noisier Anaïs F. M. , Czechtizky Werngard , Lemurell Malin , Tietze Alesia A. 
Published: March 2023

AbstractSite‐specific conjugation approaches are of great importance in drug discovery, notably for the synthesis of biochemical probes or molecular conjugates for targeted delivery. Herein, we report a mild ionic liquid (IL)‐mediated thiolation technique that relies on the use of 1,3‐ethyl‐methyl imidazolium acetate, [C2mim][OAc] as a solvent and precursor to generate activated IL, as well as a solvent for the conjugation reaction. First, a focused library of active ILs was prepared for functionalizing/conjugating cysteine‐containing small molecules and unprotected peptides. Interestingly, a bifunctional active IL could also be successfully employed as a linker for the conjugation of peptides lacking Cys. This study sets the ground for further investigation of the use of active ILs for modifying, labeling or conjugating larger and more complex therapeutic modalities such as proteins and antibodies.
λ3‐ and λ5‐Iodanes: Substituent Effects and Pseudorotation/Hypervalent Twisting
Authors: Parida Keshaba N. , Moorthy J. Narasimha 
Published: March 2023

AbstractHypervalent iodine (III and V) compounds exhibit positional isomerization through pseudorotation or twisting; the latter have been invoked for the stability as well as the reactivity of λ3‐ and λ5‐iodanes. By judicious exploitation of sterics, the twisting process in iodanes can be facilitated to promote reactivity. For example, ortho‐substitution in λ3‐ and λ5‐iodanes accelerates α‐tosyloxylation of ketones and oxidation of alcohols. The enhancement of reactivity arises from sterically‐induced non‐planarity and the resultant weakening of the 3c–4e bonds involving the hypervalent iodine atom. The ortho‐substitution constitutes an important strategy to maneuver reactivity, control selectivity, and develop new catalysts, including chiral, for diverse reactions. This review entails coverage of the literature developments in regard to the effect of substituents and twisting/pseudorotation on the stability as well as the reactivity of hypervalent λ3‐ and λ5‐iodanes, and the application of the latter for synthetic transformations.
Residue‐Selective C−H Sulfenylation Enabled by Acid‐Activated S‐Acetamidomethyl Cysteine Sulfoxide with Application to One‐Pot Stapling and Lipidation Sequence
Authors: Ohkawachi Kento , Anzaki Kaito , Kobayashi Daishiro , Kyan Ryuji , Yasuda Takuma , Denda Masaya , Harada Norio , Shigenaga Akira , Inagaki Nobuya , Otaka Akira 
Published: March 2023

AbstractA tyrosine (Tyr)‐ or tryptophan (Trp)‐selective metal‐free C−H sulfenylation reaction using an acid‐activated S‐acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from Cys(Acm)(O) under acidic conditions allows the sulfenylation of Tyr. Significantly, the reaction in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys‐Tyr‐linked peptide even in the presence of Trp residues. In contrast, a Cys‐Trp‐linked peptide was selectively obtained from the reaction in the presence of guanidine hydrochloride (Gn ⋅ HCl) under acidic conditions. Established Tyr‐ and Trp‐selective sulfenylation methods were used in the Cys‐Tyr stapling and Trp lipidation of glucagon‐like peptides 1 in a one‐pot/stepwise manner. Investigation of the mechanism showed that orbital‐ and charge‐controlled reactions are responsible for the Trp and Tyr selectivity, respectively.
Hierarchical Self‐assembly of G‐Quadruplexes Based Hydrogel Consisting of Guanine and Peptide Epitope†
Authors: Zhang Hongyue , Yang Xuejiao , Liang Juan , Chen Kaihua , Wang Huaimin 
Published: March 2023

Comprehensive SummaryGuanosine‐based hydrogels have attracted considerable attention because of their simplicity and easy preparation. However, the sugar moiety limits its further applications because of the necessity of sugar in the hydrogel formation. This work reports a G‐quadruplexes‐based hydrogel consisting of guanine and peptide epitope to form a supramolecular hydrogel in the presence of metal cations. Using the metal ion‐responsive peptide epitope from the ion channel to replace sugar motif at N9 position of guanosine results in a novel nucleopeptide. The results show that the gelation time, the diameter of nanofibers, the anisotropic property, and the mechanical property of the hydrogel can be simply controlled using metal cations. The magnesium and calcium ions direct the alignment of nanofibers to form anisotropic nano‐bundles. The mechanistic studies indicate the formation of G‐quadruplexes in the hydrogel. Compared to the storage modulus of nucleopeptide without the metal cation, adding zinc ions results in an over three‐order increase in mechanical properties. Cytotoxicity experiment indicates the good biocompatibility of our hydrogel. Moreover, we demonstrate that the guanine‐capped peptide could release STING agonist in a controlled manner. This work illustrates a simple way to modulate the property of the nucleopeptide hydrogel to develop soft materials.
Zirconium‐2‐Imidazolidinethione Functionalized Reduced Graphene Oxide Aerogel for Efficient Removal of Fluoride Ions and Anionic Dyes from Aqueous Solutions: Multivariate Process Optimization
Authors: Islam Aminul , Fatima Sana 
Published: March 2023

AbstractA multifunctional aerogel (zirconium‐2‐imidizalodinethione‐reduced graphene oxide aerogel, Zr‐IMDT/rGOA) is synthesized by functionalizing graphene oxide with ZrCl4 and 2‐imidazolidinethione through one‐pot hydrothermal reduction and subsequent freeze drying. The aerogel is employed for the removal of anionic pollutants. Zr‐IMDT/rGOA shows good removal performance for both fluoride ions (F−) and anionic dyes (Alizarin Red S (ARS) and Eosin Y (EY)). The removal efficiency of F− is 97.96% at pH 4.6, time 30 min, an initial concentration of 10 mg L−1, and an adsorbent dosage of 0.01 g as optimized by the Box Behnken Design in response surface methodology. . Brouers‐Sotolongo isotherm model fits well with the equilibrium sorption data and maximum sorption capacity (Qmax) of 328.28, 694.00, and 1449.28 mg g−1 is obtained for F−, ARS, and EY, respectively. Fractal‐like pseudo‐second‐order kinetic model is best suited to the kinetic data and >50% removal is attained for all analytes within 5 min indicating fairly fast kinetics. Zr‐IMDT/rGOA shows good selectivity for F− in the presence of counter ions (Cl−, NO3−, SO42−, HCO3−, and H2PO4−) and could be regenerated up to five cycles with >90% removal. The synthesized aerogel is successfully applied to remove F− from groundwater, river water, and tea infusion.
Restorative validity and healing through inquiry: A visual ethnographic case study in Guatemala
Authors: Dazzo Giovanni P. , Cúmez Carmencita , Henderson Erica , Peccerelli Fredy 
Published: March 2023

AbstractThis case study is an exploration of the potential restorative and healing qualities of inquiry. The co‐authors—a university‐affiliated researcher, a Kaqchikel Maya community leader, and forensic anthropologists—document their stories navigating a participatory action research project as co‐researchers. Using visual ethnography, we illustrate how we approached inquiry from a place ofrestorative validity, which challenges inquirers to reclaim and restore the humanity of researcher, researched, and the research process itself. Through a culturally sustaining frame, we grounded our interpretations in the Maya cultural elements of land, community, and attachment to place. We demonstrate how we intertwined our various ways of knowing and methods, from Indigenous oral tradition to interactive techniques such as ripples of change, to co‐create a form of inquiry rooted in relationships, justice, and liberation. As peace, conflict, and justice researchers and practitioners work with those who have been subjected to and witnessed atrocities, we problematize whether our methodological practices are in line with our values as a community of care. In moving toward restorative validity, we ask: If the outside world robs people of their humanity, identities, and memories, do we simply observe and document these injustices; or can our inquiry work toward reclamation and restoration?
Granulocyte development, tissue recruitment, and function during allergic inflammation
Authors: Radtke Daniel , Voehringer David 
Published: March 2023

AbstractGranulocytes provide a fast innate response to pathogens and allergens. In allergy and anti‐helminth immunity, epithelial cells of damaged barriers release alarmins like IL‐25, IL‐33, and thymic stromal lymphopoietin (TSLP) but also chemokines like CXCL1 or CCL11 to promote cell recruitment and inflammation. In addition, mast cells positioned at barrier tissue sites also quickly release mediators upon specifically sensing antigens through IgE bound to FcεR1 on their surface. Released mediators induce the recruitment of different granulocytes in a timely ordered manner. First, neutrophils extravasate from the blood vasculature to the side of alarmin release and promote a potent inflammatory response. Alarmins and activated mast cells further promote activation of ILC2s and recruitment of basophils and eosinophils, which inhibit neutrophil recruitment and enhance tissue type 2 immunity. In addition to their potent pro‐inflammatory effector functions, granulocytes can also contribute to termination and resolution of inflammation. Here, we summarize the development and tissue recruitment of granulocyte subsets, and describe general effector functions and aspects of their increasingly appreciated role in limiting tissue damage. We further discuss targeting approaches for therapeutic interventions in allergic disorders.
Treatment of status epilepticus: Physiology, pharmacology, and future directions
Authors: Sankar Raman 
Published: March 2023

AbstractThe review presents retrospective, present views and future perspectives on the treatment of status epilepticus (SE). First, presynaptic, postsynaptic, and extrasynaptic mechanisms underlying sustaining ongoing seizure activity are highlighted. Next, mechanism‐based choices of antiseizure medications capable of promptly arresting SE are introduced. Finally, challenges associated with translating the advances in laboratory research in clinical practice are discussed.
Study on the nonuniform mechanical degradation of membranes considering temperature and relative humidity distribution in proton exchange membrane fuel cells
Authors: Liu Wenqing , Qiu Diankai , Peng Linfa , Lai Xinmin 
Published: March 2023

AbstractThe membrane usually breaks down at a specific local position due to the mechanical degradation caused by nonuniform hygrothermal conditions in proton exchange membrane fuel cells. Many studies have been carried out analyzing the stress and strain on membrane along thickness direction, but few of them considered the stress along the surface. By imposing uneven temperature and water profiles according to experiments and simulation, this study systematically investigated effects of varying temperatures, relative humidity, and gas flow directions on the membrane stress/strain in a comprehensive 3D model. The results proved that nonuniform temperature and water content affect the response of the membrane a lot. Although the membrane at the inlet of the flow field suffers higher stress, the membrane at the outlet is easier to fail because higher humidity leads to lower yield stress. For the operating condition, the stress range of cells under the counter‐flow reactant gas is 0.2 MPa less than those under co‐flow direction. And increasing humidity to near‐saturated condition would reduce the stress range from 1.2 to 0.49 MPa. The study contributes to achieving better fatigue resistance for membranes in terms of controlling anisotropic heat and relative humidity for fuel cells.
Microglial IL‐1RA ameliorates brain injury after ischemic stroke by inhibiting astrocytic CXCL1‐mediated neutrophil recruitment and microvessel occlusion
Authors: Huang Xiaoyan , Guo Mingyan , Zhang Yangfan , Xie Jiatian , Huang Rong , Zuo Zhiyi , Saw Phei Er , Cao Minghui 
Published: March 2023

AbstractAcute ischemic stroke (AIS), one of the leading causes of mortality worldwide, is characterized by a rapid inflammatory cascade resulting in exacerbation of ischemic brain injury. Microglia are the first immune responders. However, the role of postischemic microglial activity in ischemic brain injury remains far from being fully understood. Here, using the transgenic mouse line CX3CR1creER:R26iDTR to genetically ablate microglia, we showed that microglial deletion exaggerated ischemic brain injury. Associated with this worse outcome, there were increased neutrophil recruitment, microvessel blockade and blood flow stagnation in the acute phase, accompanied by transcriptional upregulation of chemokine (C‐X‐C motif) ligand 1 (CXCL1). Our study showed that microglial interleukin‐1 receptor antagonist (IL‐1RA) suppressed astrocytic CXCL1 expression induced by oxygen and glucose deprivation and inhibited neutrophil migration. Furthermore, neutralizing antibody therapy against CXCL1 or the administration of recombinant IL‐1RA protein reduced brain infarct volume and improved motor coordination performance of mice after ischemic stroke. Our study suggests that microglia protect against acute ischemic brain injury by secreting IL‐1RA to inhibit astrocytic CXCL1 expression, which reduces neutrophil recruitment and neutrophil‐derived microvessel occlusion.
The potential role of SARS‐CoV‐2 infection in acute coronary syndrome and type 2 myocardial infarction (T2MI): Intertwining spread
Authors: Alsaidan Aseel Awad , Al‐Kuraishy Hayder M. , Al‐Gareeb Ali I. , Alexiou Athanasios , Papadakis Marios , Alsayed Khalid Adel , Saad Hebatallah M. , Batiha Gaber El‐Saber 
Published: March 2023

AbstractCoronavirus disease 2019 (COVID‐19) is a novel pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It has been shown that SARS‐CoV‐2 infection‐induced inflammatory and oxidative stress and associated endothelial dysfunction may lead to the development of acute coronary syndrome (ACS). Therefore, this review aimed to ascertain the link between severe SARS‐CoV‐2 infection and ACS. ACS is a spectrum of acute myocardial ischemia due to a sudden decrease in coronary blood flow, ranging from unstable angina to myocardial infarction (MI). Primary or type 1 MI (T1MI) is mainly caused by coronary plaque rupture and/or erosion with subsequent occlusive thrombosis. Secondary or type 2 MI (T2MI) is due to cardiac and systemic disorders without acute coronary atherothrombotic disruption. Acute SARS‐CoV‐2 infection is linked with the development of nonobstructive coronary disorders such as coronary vasospasm, dilated cardiomyopathy, myocardial fibrosis, and myocarditis. Furthermore, SARS‐CoV‐2 infection is associated with systemic inflammation that might affect coronary atherosclerotic plaque stability through augmentation of cardiac preload and afterload. Nevertheless, major coronary vessels with atherosclerotic plaques develop minor inflammation during COVID‐19 since coronary arteries are not initially and primarily targeted by SARS‐CoV‐2 due to low expression of angiotensin‐converting enzyme 2 in coronary vessels. In conclusion, SARS‐CoV‐2 infection through hypercytokinemia, direct cardiomyocyte injury, and dysregulation of the renin‐angiotensin system may aggravate underlying ACS or cause new‐onset T2MI. As well, arrhythmias induced by anti‐COVID‐19 medications could worsen underlying ACS.