bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the effects of thiazole compounds on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) targeted human brain glioblastoma cancer (U‐87 MG)
Authors: Korkmaz Işıl Nihan 
Published: April 2024

AbstractCancer is a fatal disease that kills thousands of people worldwide. Despite the information produced by research on cancer treatment, applications in cancer treatment are limited. Therefore, scientists’ efforts to develop more effective treatment approaches continue. In the study, we aimed to determine the anticancer potential of amino thiazole compounds on human glioblastoma (U‐87 MG) and human dermal fibroblast (HDFa) cells and their inhibition effects on enzymes that cause multidrug resistance in cancer cells. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide cell viability test was performed to understand the cytotoxic properties of thiazole derivatives. The cellular death mechanisms behind thiazole application were investigated using flow cytometry analysis. According to cell viability analysis, thiazole derivatives exhibited a greater effect on U‐87 MG than the HDFa cell line in terms of cytotoxicity. Flow cytometry showed higher apoptotic cell death in U‐87 MG cells than in the HDFa cell line. It can be concluded that thiazole compounds exert anticancer effects on U‐87 MG and HDFa as well as show apoptotic properties. Their effects on thioredoxin reductase 1 (TrxR1), glutathione S‐transferase (GST), and glutathione reductase (GR) activities, which are important in the development of chemotherapeutic methods, were also examined. From the results obtained, it was determined that the 2‐amino‐4‐(p‐tolyl)thiazole (T7) compound significantly suppressed both TrxR1 and GST activities, and the 2‐amino‐6‐methylbenzothiazole (T8) compound significantly suppressed both TrxR1 and GST activities. Compound T7 was determined to be a selective inhibitor for TrxR1 and GST targeting, and compound T8 was determined to be a selective inhibitor for TrxR1 and GR targeting glioblastoma treatment.
Hotspot Wizard‐informed engineering of a hyperthermophilic β‐glucosidase for enhanced enzyme activity at low temperatures
Authors: Erkanli Mehmet Emre , El‐Halabi Khalid , Kang Ted Keunsil , Kim Jin Ryoun 
Published: April 2024

AbstractHyperthermophilic enzymes serve as an important source of industrial enzymes due to their high thermostability. Unfortunately, most hyperthermophilic enzymes suffer from reduced activity at low temperatures (e.g., ambient temperature), limiting their applicability. In addition, evolving hyperthermophilic enzymes to increase low temperature activity without compromising other desired properties is generally difficult. In the current study, a variant of β‐glucosidase from Pyrococcus furiosus (PfBGL) was engineered to enhance enzyme activity at low temperatures through the construction of a saturation mutagenesis library guided by the HotSpot Wizard analysis, followed by its screening for activity and thermostability. From this library construction and screening, one PfBGL mutant, PfBGL‐A4 containing Q214S/A264S/F344I mutations, showed an over twofold increase in β‐glucosidase activity at 25 and 50°C compared to the wild type, without compromising high‐temperature activity, thermostability and substrate specificity. Our experimental and computational characterizations suggest that the findings with PfBGL‐A4 may be due to the elevation of local conformational flexibility around the active site, while slightly compacting the global protein structure. This study showcases the potential of HotSpot Wizard‐informed engineering of hyperthermophilic enzymes and underscores the interplays among temperature, enzyme activity, and conformational flexibility in these enzymes.
Total intracranial hemorrhage volume measurement summating all compartments best in traumatic and nontraumatic intracranial bleeding
Authors: Horn MacKenzie , Banerjee Ankur , Kasickova Linda , Volny Ondrej , Choi Hyun Seok , Letteri Federica , Ohara Tomoyuki , Tanaka Koji , Connolly Stuart , Ladenvall Per , Crowther Mark , Beyer‐Westendorf Jan , Shoamanesh Ashkan , Demchuk Andrew M. , Al Sultan Abdulaziz S. ,   for the ANNEXa‐4 Investigators
Published: April 2024

AbstractBackground and purposeThe ANNEXA‐4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume.MethodsThirty patients were randomly selected from the ANNEXA‐4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty‐eight different ANNEXA‐4 subjects were also randomly selected to assess intra‐rater reliability of total ICrH volume measurement change at baseline and 12‐h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA‐4.ResultsCompartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader.ConclusionMeasurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.
Methyl jasmonate ameliorates pain‐induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation
Authors: Mohammadinia Fatemeh , Esmaeili‐Mahani Saeed , Abbasnejad Mehdi , Dogani Manijeh , Poorrahimi Ali Mohammad 
Published: April 2024

AbstractObjectiveOrofacial pain with high prevalence is one of the substantial human health issues. The importance of this matter became more apparent when it was revealed that orofacial pain, directly and indirectly, affects cognition performances. Currently, researchers have focused on investigating pharmaceutics to alleviate pain and ameliorate its subsequent cognitive impairments.DesignIn this study, the rats were first treated with the central administration of methyl jasmonate (MeJA), which is an antioxidant and anti‐inflammatory bio‐compound. After 20 min, orofacial pain was induced in the rats by the injection of capsaicin in their dental pulp. Subsequently, the animals’ pain behaviors were analyzed, and the effects of pain and MeJA treatments on rats learning and memory were evaluated/compared using the Morris water maze (MWM) test. In addition, the expression of tumor necrosis factor‐α (TNF‐α), IL‐1β, BDNF, and COX‐2 genes in the rats’ hippocampus was evaluated using real‐time polymerase chain reaction.ResultsExperiencing orofacial pain resulted in a significant decline in the rats learning and memory. However, the central administration of 20 μg/rat of MeJA effectively mitigated these impairments. In the MWM, the performance of the MeJA‐treated rats showed a two‐ to threefold improvement compared to the nontreated ones. Moreover, in the hippocampus of pain‐induced rats, the expression of pro‐inflammatory factors TNF‐α, IL‐1β, and COX‐2 significantly increased, whereas the BDNF expression decreased. In contrast, MeJA downregulated the pro‐inflammatory factors and upregulated the BDNF by more than 50%.ConclusionsThese findings highlight the notable antinociceptive potential of MeJA and its ability to inhibit pain‐induced learning and memory dysfunction through its anti‐inflammatory effect.
Do the firm characteristics moderate the nexus between the firm's sustainable practices and financial performance?
Authors: Gartia Umakanta , Panda Ajaya Kumar 
Published: April 2024

AbstractThe paper explores the partial and integrated influence of corporate sustainability practices on the financial execution of Indian‐listed firms. The study considered a sample of 569 listed firms, and the study period spans from 2010 to 2022. Using estimates of feasible generalized least square and quintile regression, the study finds a positive association between the environmental, social, and governance (ESG) score and the financial performance of firms. All the individual dimensions of the ESG score positively affect the firm's internal and external values. Environmental practices have the highest impact on improving balance sheet values through return on asset (ROA). In contrast, social practices have the highest impact on creating market value through Tobin's Q (TQ) compared with other dimensions. However, for large firms, excess investment in ESG may not support their balance sheet through ROA but generates market value through TQ. ESG disclosers negatively impact the internal earnings of firms that are financially inflexible but, in the aggregate, support the firm's market value. In addition, the study finds a significant moderating effect of size, earnings, value, and financial flexibility on the association between ESG scores and the financial performance of the firms.
Surface plasmon resonance aptasensing and computational analysis of Staphylococcus aureusIsdA surface protein
Authors: Bruce‐Tagoe Tracy Ann , Harnish Michael T. , Soleimani Shokoufeh , Ullah Najeeb , Shen Tongye , Danquah Michael K. 
Published: April 2024

AbstractStaphylococcus aureus (S. aureus), a common foodborne pathogen, poses significant public health challenges due to its association with various infectious diseases. A key player in its pathogenicity, which is the IsdA protein, is an essential virulence factor in S. aureus infections. In this work, we present an integrated in‐silico and experimental approach using MD simulations and surface plasmon resonance (SPR)‐based aptasensing measurements to investigate S. aureus biorecognition via IsdA surface protein binding. SPR, a powerful real‐time and label‐free technique, was utilized to characterize interaction dynamics between the aptamer and IsdA protein, and MD simulations was used to characterize the stable and dynamic binding regions. By characterizing and optimizing pivotal parameters such as aptamer concentration and buffer conditions, we determined the aptamer's binding performance. Under optimal conditions of pH 7.4 and 150 mM NaCl concentration, the kinetic parameters were determined; ka = 3.789 × 104/Ms, kd = 1.798 × 103/s, and KD = 4.745 × 10−8 M. The simulations revealed regions of interest in the IsdA‐aptamer complex. Region I, which includes interactions between amino acid residues H106 and R107 and nucleotide residues 9G, 10U, 11G and 12U of the aptamer, had the strongest interaction, based on ΔG and B‐factor values, and hence contributed the most to the stability of the interaction. Region II, which covers residue 37A reflects the dynamic nature of the interaction due to frequent contacts. The approach presents a rigorous characterization of aptamer‐IsdA binding behavior, supporting the potential application of the IsdA‐binding aptamer system for S. aureus biosensing.
Benefits and risks of clofarabine in adult acute lymphoblastic leukemia investigated in depth by multi‐state modeling
Authors: Hermans Sjoerd J. F. , van Norden Yvette , Versluis Jurjen , Rijneveld Anita W. , van der Holt Bronno , de Weerdt Okke , Biemond Bart J. , van de Loosdrecht Arjan A. , van der Wagen Lotte E. , Bellido Mar , van Gelder Michel , van der Velden Walter J. F. M. , Selleslag Dominik , van Lammeren‐Venema Daniëlle , van der Velden Vincent H. J. , de Wreede Liesbeth C. , Postmus Douwe , Pignatti Francesco , Cornelissen Jan J. 
Published: April 2024

AbstractBackgroundWe recently reported results of the prospective, open‐label HOVON‐100 trial in 334 adult patients with acute lymphoblastic leukemia (ALL) randomized to first‐line treatment with or without clofarabine (CLO). No improvement of event‐free survival (EFS) was observed, while a higher proportion of patients receiving CLO obtained minimal residual disease (MRD) negativity.AimIn order to investigate the effects of CLO in more depth, two multi‐state models were developed to identify why CLO did not show a long‐term survival benefit despite more MRD‐negativity.MethodsThe first model evaluated the effect of CLO on going off‐protocol (not due to refractory disease/relapse, completion or death) as a proxy of severe treatment‐related toxicity, while the second model evaluated the effect of CLO on obtaining MRD negativity. The subsequent impact of these intermediate events on death or relapsed/refractory disease was assessed in both models.ResultsOverall, patients receiving CLO went off‐protocol more frequently than control patients (35/168 [21%] vs. 18/166 [11%], p = 0.019; HR 2.00 [1.13–3.52], p = 0.02), especially during maintenance (13/44 [30%] vs. 6/56 [11%]; HR 2.85 [95%CI 1.08–7.50], p = 0.035). Going off‐protocol was, however, not associated with more relapse or death. Patients in the CLO arm showed a trend towards an increased rate of MRD‐negativity compared with control patients (HR MRD‐negativity: 1.35 [0.95–1.91], p = 0.10), which did not translate into a significant survival benefit.ConclusionWe conclude that the intermediate states, i.e., going off‐protocol and MRD‐negativity, were affected by adding CLO, but these transitions were not associated with subsequent survival estimates, suggesting relatively modest antileukemic activity in ALL.
Synthesis, Characterization and Evaluation of the Antimicrobial and Herbicidal Activities of Some Transition Metal Ions Complexes with the Tranexamic Acid
Authors: Mohamed Amira A. , Sadeek Sadeek A. , Rashid Nihad G. , Elshafie Hazem S. , Camele Ippolito 
Published: April 2024

AbstractNew tranexamic acid (TXA) complexes of ferric(III), cobalt(II), nickel(II), copper(II) and zirconium(IV) were synthesized and characterized by elemental analysis (CHN), conductimetric (Λ), magnetic susceptibility investigations (μeff), Fourier transform infrared (FT‐IR), proton nuclear magnetic resonance (1H‐NMR), ultraviolet visible (UV‐vis.), optical band gap energy (Eg) and thermal studies (TG/DTG and DTA). TXA complexes were established in 1 : 2 (metal: ligand) stoichiometric ratio according to CHN data. Based on FT‐IR and 1H‐NMR data the disappeared of the carboxylic proton supported the deprotonating of TXA and linked to metal ions via the carboxylate group‘s oxygen atom as a bidentate ligand. UV‐visible spectra and magnetic moment demonstrated that all chelates have geometric octahedral structures. Eg values indicated that our complexes are more electro conductive. DTA revealed presence of water molecules in inner and outer spheres of the complexes. DTA results showed that endothermic and exothermic peaks were identified in the degradation mechanisms. The ligand and metal complexes were investigated for their antimicrobial and herbicidal efficacy. The Co(II) and Ni(II) complexes showed antimicrobial activity against some tested species. The obtained results showed a promising herbicidal effect of TXA ligand and its metal complexes particularly copper and zirconium against the three tested plants.
Binding and Stabilization of a Semiquinone Radical by an Artificial Metalloenzyme Containing a Binuclear Copper (II) Cofactor
Authors: Gay Rémy , Masson Yannick , Ghattas Wadih , Udry Guillermo A. Oliveira , Herrero Christian , Urvoas Agathe , Mahy Jean‐Pierre , Ricoux Rémy 
Published: April 2024

AbstractA binuclear Cu(II) cofactor was covalently bound to a lauric acid anchor. The resulting conjugate was characterized then combined with beta‐lactoglobulin (βLG) to generate a new biohybrid following the so‐called “Trojan horse” strategy. This biohybrid was examined for its effectiveness in the oxidation of a catechol derivative to the corresponding quinone. The resulting biohybrid did not exhibit the sought after catecholase activity, likely due to its ability to bind and stabilize the semiquinone radical intermediate DTB‐SQ. This semi‐quinone radical was stabilized only in the presence of the protein and was characterized using optical and magnetic spectroscopic techniques, demonstrating stability for over 16 hours. Molecular docking studies revealed that this stabilization could occur owing to interactions of the semi‐quinone with hydrophobic amino acid residues of βLG.
Mitochondrial administration alleviates lead‐ and cadmium‐induced toxicity in rat renal cells
Authors: Seydi Enayatollah , Nambani Alireza Kanani , Khorasani Ali , Kamranfar Farzaneh , Arjmand Abdollah , Pourahmad Jalal 
Published: April 2024

AbstractThe role of heavy metals such as lead (Pb) and cadmium (Cd) in the etiology of many diseases has been proven. Also, these heavy metals can affect the normal mitochondrial function. Mitochondrial administration therapy is one of the methods used by researchers to help improve mitochondrial defects and diseases. The use of isolated mitochondria as a therapeutic approach has been investigated in in vivo and in vitro studies. Accordingly, in this study, the effects of mitochondrial administration on the improvement of toxicity caused by Pb and Cd in renal proximal tubular cells (RPTC) have been investigated. The results showed that treatment to Pb and Cd caused an increase in the level of free radicals, lipid peroxidation (LPO) content, mitochondrial and lysosomal membrane damage, and also a decrease in the reduced glutathione content in RPTC. In addition, reports have shown an increase in oxidized glutathione content and changes in energy (ATP) levels. Following, the results have shown the protective role of mitochondrial administration in improving the toxicity caused by Pb and Cd in RPTC. Furthermore, the mitochondrial internalization into RPT cells is mediated through actin‐dependent endocytosis. So, it could be suggested that the treatment of Pb‐ and Cd‐induced cytotoxicity in RPTC could be carried out through mitochondria administration.
Synthesis of 1,3‐Dibromopyrene as Precursor of 1‐, 3‐, 6‐, and 8‐Substituted Long‐Axially Symmetric Pyrene Derivatives
Authors: Ruto Asuka , Seki Hitomi , Osaki Katsuki , Kaneno Daisuke , Hadano Shingo , Watanabe Shigeru , Niko Yosuke 
Published: April 2024

AbstractPyrene derivatives bearing substituents at positions 1, 3, 6, and 8 find numerous applications, as exemplified by their use in lasers, sensors, and bioimaging probes. However, these derivatives typically have point‐symmetric or short‐axially symmetric structures, whereas long‐axially symmetric derivatives remain underexplored because of the difficulty in obtaining their precursor, 1,3‐dibromopyrene. To address this problem, we herein synthesized 1,3‐dibromopyrene from 1‐methoxypyrene in an overall yield (71 % over four steps) considerably exceeding those of existing methods. 1,3‐Dibromopyrene was converted into 13OPA, a long‐axially symmetric pyrene dye with electron‐donor (alkoxy) groups at positions 1 and 3 and electron‐acceptor (formyl) groups at positions 6 and 8. 13OPA exhibited photophysical properties distinct from those of its point‐symmetric and short‐axially symmetric isomers, featuring a broad and strongly redshifted absorption, strong fluorescence with reduced sensitivity to protic solvents, and small dipole moment change upon photoexcitation. The derivatization of 13OPA into a Schiff base and its functionalization via Lewis acid‐base pairing were also demonstrated. Thus, our work expands the design scope of pyrene‐based molecules, particularly those used as emitters.
Improving therapeutic outcomes in heart failure with reduced nonvalvular ejection fraction: A clinical study of heart failure education intervention
Authors: Tian Xueli , Li Xiaozeng , Zhang Qingqing , Qiao Xiangling , Li Xin , Zhang Zijian 
Published: April 2024

AbstractObjectiveThe current study delves into the impact of heart failure education intervention on improving therapeutic outcomes for heart failure (HF) patients with reduced nonvalvular ejection fraction.MethodsThere involved a total of 60 HF patients with non‐valvular ejection fraction reduction who met the inclusion requirements. Patients enrolled were randomly distributed into an observation group and a control group. The observation group received heart failure education intervention, while the control group received conventional intervention. The therapeutic effect, changes in physical indicators, cardiac function indicators, coagulation function, self‐management scale scores, and the incidence of adverse cardiovascular events were meticulously evaluated.ResultsThe total effective proportion in the observation group was 96.67%, which was significantly higher than the control group's proportion of 76.67% (p < .05). After treatment, several parameters in the observation group showed significant improvements compared to the control group: hs‐CRP, IL‐6, LVEDV value, LVESV value, PT value, APTT value, and TT value were all evidently lower in the observation group. Additionally, the cardiac index, LVEF value, and heart failure self‐management scale fraction were significantly higher in the observation group compared to the control group (p < .05). Furthermore, the incidence of adverse cardiovascular events in the observation group was only 6.67%, which was significantly lower than the control group's incidence of 20.00% (p < .05).ConclusionHeart failure education intervention demonstrates effectiveness in improving the therapeutic outcomes for HF patients and reduced nonvalvular ejection fraction. Additionally, it enhances patients' self‐management abilities. Given these positive results, it is highly recommended to promote and implement HF education intervention in clinical practice.
Contributions of the individual domains of αIIbβ3 integrin to its extension: Insights from multiscale modeling
Authors: Joshi Onkar , Skóra Tomasz , Yarema Anna , Rabbitt Richard D. , Bidone Tamara C. 
Published: April 2024

AbstractThe platelet integrin αIIbβ3 undergoes long‐range conformational transitions between bent and extended conformations to regulate platelet aggregation during hemostasis and thrombosis. However, how exactly αIIbβ3 transitions between conformations remains largely elusive. Here, we studied how transitions across bent and extended‐closed conformations of αIIbβ3 integrin are regulated by effective interactions between its functional domains. We first carried out μs‐long equilibrium molecular dynamics (MD) simulations of full‐length αIIbβ3 integrins in bent and intermediate conformations, the latter characterized by an extended headpiece and closed legs. Then, we built heterogeneous elastic network models, perturbed inter‐domain interactions, and evaluated their relative contributions to the energy barriers between conformations. Results showed that integrin extension emerges from: (i) changes in interfaces between functional domains; (ii) allosteric coupling of the head and upper leg domains with flexible lower leg domains. Collectively, these results provide new insights into integrin conformational activation based on short‐ and long‐range interactions between its functional domains and highlight the importance of the lower legs in the regulation of integrin allostery.