bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possible effects of fibroblast growth factor 21 on vascular calcification via suppressing activating transcription factor 4 mediated apoptosis and osteogenic transformation in rats
Authors: Shi Yuchen , Zheng Ze , Luo Jesse , Li Yingkai , He Songyuan , Shen Xueqian , Liu Jinghua 
Published: May 2022

AbstractVascular calcification (VC), a significant risk factor of many cardio‐cerebral vascular diseases, is a perplexing issue with no effective treatment in clinical work up to now. Endoplasmic reticulum stress (ERS) mediated apoptosis has been proved to be a significant mechanism for initiating VC process. Activating transcription factor 4 (ATF4), a key transcription factor of ERS, is most closely associated with VC. Fibroblast growth factor 21 (FGF21), an atypical member of the FGFs family, has a protective biological function in various metabolic diseases by ERS pathways. However, the possible effects of FGF21 on VC by regulating ERS, especially through the ATF4 pathway, is still unclear. Our research provides the first evidence that exogenous FGF21 treatment can alleviate the vitamin D3 plus nicotine‐induced VC at least in part via suppressing ATF4 mediated apoptosis and osteogenic transformation in rats.
Hybrid Chemoenzymatic Synthesis of C7‐Sugars for Molecular Evidence of in vivo Shikimate Pathway Inhibition
Authors: Rath Pascal , Rapp Johanna , Brilisauer Klaus , Braun Marvin , Kolukisaoglu Üner , Forchhammer Karl , Grond Stephanie 
Published: May 2022

AbstractThe design of distinctive chemical synthesis strategies aims for the most efficient routes towards versatile compounds in drug target studies. Here, we establish a powerful hybrid synthetic approach of total chemical and chemoenzymatic synthesis to efficiently obtain various 7‐deoxy‐sedoheptulose (7dSh, 1) analogues, unique C7 sugars, for structure‐activity relationship studies. 7dSh (1) is a rare microbial sugar with in planta herbicidal activity. As natural antimetabolite of 3‐dehydroquinate synthase (DHQS), 7dSh (1) inhibits the shikimate pathway, which is essential for the synthesis of aromatic amino acids in bacteria, fungi, and plants, but absent in mammals. As glyphosate, the most used chemical herbicide faces restrictions worldwide, DHQS has gained more attention as valid target of herbicides and antimicrobial agents. In vitro and in vivo analyses of the C7‐deoxysugars confirm DHQS as enzymatic target, highlight the crucial role of uptake for inhibition and add molecular aspects to target mechanism studies of C7‐sugars as our contribution to global efforts for alternative weed‐control strategies.
Second Coordination Sphere Effects on the Mechanistic Pathways for Dioxygen Activation by a Ferritin: Involvement of a Tyr Radical and the Identification of a Cation Binding Site
Authors: Yeh Chieh‐Chih George , Mokkawes Thirakorn , Bradley Justin M. , Le Brun Nick E. , de Visser Sam P. 
Published: May 2022

AbstractFerritins are ubiquitous diiron enzymes involved in iron(II) detoxification and oxidative stress responses and can act as metabolic iron stores. The overall reaction mechanisms of ferritin enzymes are still unclear, particularly concerning the role of the conserved, near catalytic center Tyr residue. Thus, we carried out a computational study of a ferritin using a large cluster model of well over 300 atoms including its first‐ and second‐coordination sphere. The calculations reveal important insight into the structure and reactivity of ferritins. Specifically, the active site Tyr residue delivers a proton and electron in the catalytic cycle prior to iron(II) oxidation. In addition, the calculations highlight a likely cation binding site at Asp65, which through long‐range electrostatic interactions, influences the electronic configuration and charge distributions of the metal center. The results are consistent with experimental observations but reveal novel detail of early mechanistic steps that lead to an unusual mixed‐valent iron(III)‐iron(II) center.
Pure white cell aplasia an exceptional condition in the immunological conundrum of thymomas: Responses to immunosuppression and literature review
Authors: Céspedes López Roberto , Amutio Díez Elena , Martín Martitegui Xabier , Balerdi Malcorra Amaia , Insunza Oleaga Lucia , Arzuaga‐Méndez Javier , Moreno Gámiz Maite , Saiz Camín Mónica , Aberasturi Plata Yoseba , García‐Ruíz Juan Carlos 
Published: May 2022

AbstractThymomas are tumours frequently associated with autoimmune manifestations or immunodeficiencies like Good syndrome. In rare cases, pure white cells aplasia (PWCA) has been described in association with thymomas. PWCA is characterized by agranulocytosis of autoimmune background primary refractory to granulocyte colony‐stimulating factor (G‐CSF). It is necessary the use of immunosuppressor to allow granulocyte recovery. Without treatment, it could be fatal.
A reliable algorithm for calculating stoichiometry parameters in the hard modeling of spectrophotometric titration data
Authors: Kazmierczak Nathanael P. , Chew Joyce A. , Vander Griend Douglas A. 
Published: May 2022

AbstractComputation of binding constants from spectrophotometric titration data is a very popular application of chemometric hard modeling. However, the calculated values are misleading if the correct binding model is not used. Given that many supramolecular systems of interest feature unknown speciation, a priori determination of binding stoichiometry constitutes an important unsolved problem in chemometrics. We present a new and reliable algorithm for accomplishing this task, implemented using a hybrid particle swarm optimization technique. Simultaneous optimization of stoichiometry ratios and binding constants allows the optimal binding model to be calculated in just a few minutes for systems with up to four reactions. Simulated data studies demonstrate that the algorithm finds the correct stoichiometry with up to nine reactions in the absence of noise, including accurately determining species with unusual stoichiometry, such as H2G5. Application to four experimental datasets shows the algorithm is robust to experimental errors for a variety of chemical systems and binding models. This algorithm will facilitate the discovery of complex binding models, increase efficiency in titration analysis, and avert incorrect stoichiometry models, thereby improving the reliability of binding constant information in spectrophotometric titrations.
Cesium‐Fluoride‐Promoted Synthesis of Stable Organocesium Reagents and Their Ambident Reactivities with Arynes
Authors: Rather Suhail A. , Athimoolam S. , Naveed Ahmed Qazi 
Published: May 2022

AbstractDescribed are the diverse reactivities of novel, stable, ambident thio‐organocesium reagents (bearing electron withdrawing groups) against benzynes. Reactions at reflux temperature predominantly led to the generation of various functionalized stable sulfonium ylides and at 40 °C the same reaction underwent direct c‐arylation. Furthermore, lack of internal hydrogen on the cesium reagent helped to produce different ortho‐bifunctional arynes in both the reactions. Interestingly, depending on the reactivities of substrates, the one‐pot tri‐component procedure generated either ylides or σ‐bond insertion products.
Para‐Fluorination of Anilides Using Electrochemically Generated Hypervalent Iodoarenes
Authors: Berger Michael , Lenhard Marola S. , Waldvogel Siegfried R. 
Published: May 2022

AbstractThe para‐selective fluorination reaction of anilides using electrochemically generated hypervalent ArIF2 is reported, with Et3N ⋅ 5HF serving as fluoride source and as supporting electrolyte. This electrochemical reaction is characterized by a simple set‐up, easy scalability and affords a broad variety of fluorinated anilides from easily accessible anilides in good yields up to 86 %.
Comprehensive molecular profiling of pancreatic ductal adenocarcinoma in FNA, biopsy, and resection specimens
Authors: Razzano Dana , Bouza Soumar J. , Hernandez Patricia V. , Wang Minhua , Robert Marie E. , Walther Zenta , Cai Guoping 
Published: May 2022

BACKGROUNDMolecular testing to identify molecular alterations in pancreatic ductal adenocarcinoma (PDAC) has been increasingly requested because of potential therapeutic implications. In this study, we compared the performance of PDAC fine‐needle aspiration (FNA), fine‐needle biopsy (FNB), and resection specimens for comprehensive molecular analysis.METHODSA next‐generation sequencing–based Oncomine Comprehensive Assay (OCA) was used to analyze molecular alterations in FNA, FNB, or resection specimens. We examined adequacy and success rates for completion of molecular testing and catalogued molecular alterations in these specimen types.RESULTSThe cohort included 23 FNA, 20 FNB, and 27 resection cases. Gene mutation or amplification analysis was successful in 18 (78%) FNA and 16 (80%) FNB specimens, whereas gene fusion assessment succeeded in 12 (52%) FNA and 12 (60%) FNB samples. All 27 (100%) resection specimens were adequate for complete OCA. There were significant differences in success rates for mutation and amplification analysis between resection and FNA or FNB specimens (P < .01) but not between FNA and FNB samples (P > .05). Manual microdissection was less likely to be performed for FNA specimens than FNB or resection specimens (P < .01). KRAS mutation was the most common mutation identified (90%), followed by mutations in TP53 (64%), CDKN2A (25%), and SMAD4 (15%) genes.CONCLUSIONSOur study demonstrated similar success rates for comprehensive molecular analysis using FNA and FNB specimens of PDAC, suggesting that FNA material could serve as an alternative source for comprehensive molecular testing. The molecular alterations identified in these specimens may have potential diagnostic and therapeutic implications.;
Retaining Hückel Aromaticity in the Triplet Excited State of Azobenzene
Authors: Swathi Krishna P. E. , Dev Vivek V. , Ramakrishnan Remya , Hariharan Mahesh 
Published: May 2022

AbstractThe implication of the potential concept of aromaticity in the relaxed lowest triplet state of azobenzene, an efficient molecular switch, using elementary aromaticity indices based on magnetic, electronic, and geometric criteria has been discussed. Azobenzene exhibits a major Hückel aromatic character retained in the diradical lowest relaxed triplet state (T1) by virtue of a twisted geometry with partial delocalization of unpaired electrons in the perpendicular p‐orbitals of two nitrogen atoms to the corresponding phenyl rings. The computational analysis has been expanded further to stilbene and N‐diphenylmethanimine for an extensive understanding of the effect of closed‐shell Hückel aromaticity in double‐bond‐linked phenyl rings. Our analysis concluded that stilbene has Hückel aromatic character in the relaxed T1 state and N‐diphenylmethanimine has a considerable Hückel aromaticity in the phenyl ring near the carbon atom while a paramount Baird aromaticity in the phenyl ring near the nitrogen atom of the C=N double bond. The results reveal the application of excited‐state aromaticity as a general tool for the design of molecular switches.
Lipids and Genes: Regulatory roles of lipids in RNA expression
Authors: Wang Xiangdong , Han Xianlin , Powell Charles A. 
Published: May 2022

AbstractNuclear lipid metabolism and metabolites play important roles in the regulation of lipid‐lipid, lipid‐gene, lipid‐chromatin, lipid‐membrane, and lipid‐protein interactions to maintain the nuclear microenvironment, three‐dimensional chromatin architecture, gene expression and transcription, and biological function. This editorial highlights the value of lipid‐gene in the identification and development of biomarkers and targets and emphasises the significance of interregulation between lipids and genes in the innovation and application of precise therapies for patients. Regulatory functions of nuclear lipid dynamics and biophysics modify transcriptomic expression, and modification (lipotranscriptome) can be a new approach for discovery and development of disease‐specific diagnoses and therapies, although there are several challenges to be overcome. A better understanding of how lipid‐based changes in nuclear functions and transcriptomic profiles modify clinical phenomes will provide new insights to understand the molecular mechanisms of diseases and to develop spatiotemporal molecular medicine diagnostics and therapeutics.
Molecular and cellular mechanisms of itch and pain in atopic dermatitis and implications for novel therapeutics
Authors: Kwatra Shawn G , Misery Laurent , Clibborn Claire , Steinhoff Martin 
Published: May 2022

AbstractAtopic dermatitis is a chronic inflammatory skin disease. Patients with atopic dermatitis experience inflammatory lesions associated with intense itch and pain, which lead to sleep disturbance and poor mental health and quality of life. We review the molecular mechanisms underlying itch and pain symptoms in atopic dermatitis and discuss the current clinical development of treatments for moderate‐to‐severe atopic dermatitis. The molecular pathology of atopic dermatitis includes aberrant immune activation involving significant cross‐talk among the skin and immune and neuronal cells. Exogenous and endogenous triggers modulate stimulation of mediators including cytokine/chemokine expression/release by the skin and immune cells, which causes inflammation, skin barrier disruption, activation and growth of sensory neurons, itch and pain. These complex interactions among cell types are mediated primarily by cytokines, but also involve chemokines, neurotransmitters, lipids, proteases, antimicrobial peptides, agonists of ion channels or various G protein–coupled receptors. Patients with atopic dermatitis have a cytokine profile characterised by abnormal levels of interleukins 4, 12, 13, 18, 22, 31 and 33; thymic stromal lymphopoietin; and interferon gamma. Cytokine receptors mainly signal through the Janus kinase/signal transducer and activator of transcription pathway. Among emerging novel therapeutics, several Janus kinase inhibitors are being developed for topical or systemic treatment of moderate‐to‐severe atopic dermatitis because of their potential to modulate cytokine expression and release. Janus kinase inhibitors lead to changes in gene expression that have favourable effects on local and systemic cytokine release, and probably other mediators, thus successfully modulating molecular mechanisms responsible for itch and pain in atopic dermatitis.
Sc(OTf)3‐Catalyzed Dearomative [3+2] Annulation of 5‐Aminoisoxazoles with Quinone Imine Ketals or Quinone Monoacetals
Authors: Yan Yingkun , Li Min , Liu Min , Huang Min , Cao Lianyi , Li Wenzhe , Zhang Xiaomei 
Published: May 2022

AbstractIsoxazolines are highly significant for the development of new synthetic methodology and pharmaceutics. Indolines and 2,3‐dihydrobenzofurans are also privileged structures in natural products and pharmaceuticals. In continuation of our ongoing research on transformations of 5‐aminoisoxazoles and quinone derivaties, herein we report Sc(OTf)3‐catalyzed dearomative [3+2] annulations of 5‐aminoisoxazoles with quinone imine ketals (QIKs) and quinone monoacetals (QMAs). A variety of indoline‐ and 2,3‐dihydrobenzofuran‐fused isoxazolines were afforded in moderate to good yields with excellent diastereoselectivities (all cases >20 : 1 dr). This method featured mild reaction conditions, wide substrate scope, and gram‐scale synthesis.
Synthesis of 1,4‐Disubstituted 1,2,3‐Triazoles from Terminal Vinyl Sulfones in Ionic Liquid: A Metal‐Free Eliminative Azide‐Olefinic Cycloaddition Route to Triazolyl Carbohydrates and Triazole‐linked Bissaccharides
Authors: Sarkar Kumares , Bose Amitabha , Pathak Tanmaya 
Published: May 2022

AbstractSeveral terminal vinyl sulfones, derived from styrene epoxide and monomesylated glycerol were reacted with benzylazide in a metal‐free condition to afford regioselectively 1,4‐disubstituted 1,2,3‐triazoles (1,4‐DTs) via Eliminative Azide‐Olefinic Cycloaddition (EAOC) reactions. The stereoelectronic repulsions between the aryl/alkyl groups attached to the azido and vinyl sulfone functionalities play a significant role in deciding the outcome of the reactions. The N, N‐dimethyl ethanolammonium formate‐water mixture consisting of a biodegradable ionic liquid turned out to be the best solvent system to reduce significantly the reaction time and increase the yield of products in almost all cases. Furthermore, a pair of exocyclic terminal vinyl sulfone‐modified carbohydrates were prepared from protected‐glucofuranoside and ‐allofuranoside. These carbohydrates were reacted under the EAOC conditions with a host of organic azides to afford the corresponding 1,4‐disubstituted 1,2,3‐triazole modified carbohydrates. Azido sugars were also reacted with terminal vinyl sulfone modified carbohydrates under similar conditions to afford 1,4‐disubstituted 1,2,3‐triazole linked bissacharides. This powerful strategy serves as a potential yet practical route for delivering two carbon unit (required for the C4‐C5 of the 1,2,3‐triazole ring) directly connected to sugar body in place of a sugar alkyne.
By all means necessary: Closed mindedness, ingroup morality, and weapon ownership
Authors: Di Santo Daniela , Pierro Antonio , Ellenberg Molly , Baldner Conrad , Kruglanski Arie W. 
Published: May 2022

AbstractThis research investigated the motivational underpinnings of attitudes towards weapon ownership. We propose that people who have a strong need for closure (NFC) would be more likely to approve of weapon ownership, but that this relationship would be serially mediated by the endorsement of binding moral foundations and fear of immigrants. Specifically, heightened NFC would promote moral concerns for the safety of one's group (i.e., the binding foundations), which, in turn, would trigger fear of immigrants, or the belief that immigrants threaten one's society. In turn, fear of immigrants would generate the approval of defensive means (i.e., weapons). We tested this serial mediation model in three studies with Italian and US samples, where NFC was both measured (Studies 1 and 3; N = 286 and N = 278) and experimentally induced (Study 2; N = 290). The results supported the proposed model. These findings suggest that a high NFC might explain individuals’ approval of weapon ownership through their moral priorities, which heighten their prejudice towards immigrants.
MHD natural convection in a corrugated enclosure with discrete isothermal heating
Authors: Choudhary Pankaj , Ray Rajendra K. 
Published: May 2022

AbstractIn this study, we numerically examine the unsteady two‐dimensional natural convective heat transfer flow problem in a corrugated enclosure containing an electrically conducting fluid whose top wall is nonuniformly heated. The vertical sidewalls of the corrugated enclosure are kept isothermally cold, while square‐shaped undulations at the bottom wall are discretely heated. Five different cases are considered depending upon the location of the heat sources. A higher‐order compact scheme is used to discretize the governing equations, and an advanced iterative solver, like the hybrid biconjugate gradient stabilized method, is used to solve the system of algebraic equations generated by the numerical discretization. We first validate our results with existing experimental and numerically computed results for the case of a square cavity with and without a heat source. Then, the computed results are analyzed over a range of key parameters, like Rayleigh number (), Hartmann number (), and Prandtl number (), to study the effect of these parameters on the characteristics of heat transfer and the flow field in the corrugated enclosure. Computed results are presented in the form of streamlines, isotherms, local and averaged Nusselt number plots, and so forth. It is found that, with the increase in the heat sources, the convection rate becomes stronger in the core region of the corrugated enclosure at higher Rayleigh numbers. Variations in the Hartmann and Prandtl numbers also have significant effects on the temperature distribution and flow field. Our simulated results show various flow features that have not been studied before.
Numerical analysis of MHD nanofluid flow and heat transfer in a circular porous medium containing a Cassini oval under the influence of the Lorentz and buoyancy forces
Authors: Jalili Bahram , Sadighi Sina , Jalili Payam , Ganji Davood D. 
Published: May 2022

AbstractThis paper reports our study on the flow characteristics and heat transfer performance of magnetohydrodynamics (MHD) nanofluid in an innovative porous, circle‐shaped enclosure incorporating a Cassini oval cavity using the Darcy law. The MHD nanofluid considered in this study is Al2O3–H2O. A two‐dimensional (2D) mathematical model is developed based on a homogeneous model. The formulation of the vorticity stream function is then used to obtain coupled equations. Finally, the coupled partial differential equations are solved numerically using the finite element method. Model predictions are then compared against results from the previously published study to verify the accuracy and validity of the developed model, and a good agreement is achieved. Figures demonstrate the effects of nanoparticle volume fraction, inclined angle, Lorentz, and buoyancy forces on the MHD nanofluid flow. The results indicate that the convection mechanism becomes weaker with an increase in solid nanoparticle volume fraction. A significant increase in the Rayleigh number will lead to a stronger and more cohesive core vortex. In addition, when magnetic force is applied horizontally, favorable Nuave occurs. Based on the numerical results, a correlation to predict the average Nusselt number within the enclosure is developed as a function of Hartmann number (Ha), Rayleigh number (Ra), and inclined angle (γ).
Native human collagen type I provides a viable physiologically relevant alternative to xenogeneic sources for tissue engineering applications: A comparative in vitro and in vivo study
Authors: Baltazar Tânia , Kajave Nilabh S. , Rodriguez Marco , Chakraborty Srija , Jiang Bo , Skardal Aleksander , Kishore Vipuil , Pober Jordan S. , Albanna Mohammad Z. 
Published: May 2022

AbstractXenogeneic sources of collagen type I remain a common choice for regenerative medicine applications due to ease of availability. Human and animal sources have some similarities, but small variations in amino acid composition can influence the physical properties of collagen, cellular response, and tissue remodeling. The goal of this work is to compare human collagen type I‐based hydrogels versus animal‐derived collagen type I‐based hydrogels, generated from commercially available products, for their physico‐chemical properties and for tissue engineering and regenerative medicine applications. Specifically, we evaluated whether the native human skin type I collagen could be used in the three most common research applications of this protein: as a substrate for attachment and proliferation of conventional 2D cell culture; as a source of matrix for a 3D cell culture; and as a source of matrix for tissue engineering. Results showed that species and tissue specific variations of collagen sources significantly impact the physical, chemical, and biological properties of collagen hydrogels including gelation kinetics, swelling ratio, collagen fiber morphology, compressive modulus, stability, and metabolic activity of hMSCs. Tumor constructs formulated with human skin collagen showed a differential response to chemotherapy agents compared to rat tail collagen. Human skin collagen performed comparably to rat tail collagen and enabled assembly of perfused human vessels in vivo. Despite differences in collagen manufacturing methods and supplied forms, the results suggest that commercially available human collagen can be used in lieu of xenogeneic sources to create functional scaffolds, but not all sources of human collagen behave similarly. These factors must be considered in the development of 3D tissues for drug screening and regenerative medicine applications.