bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton Occupancies in Histidine Side Chains of Carbonic Anhydrase II by Neutron Crystallography and NMR – Differences, Similarities and Opportunities
Authors: Zoë Fisher Suzanne , Raum Heiner N. , Weininger Ulrich 
Published: December 2024

AbstractHistidine is a key amino‐acid residues in proteins that can exist in three different protonation states: two different neutral tautomeric forms and a protonated, positively charged one. It can act as both donor and acceptor of hydrogen bonds, coordinate metal ions, and engage in acid/base catalysis. Human Carbonic Anhydrase II (HCA II) is a pivotal enzyme catalyzing the reversible hydration of carbon dioxide. It contains 12 histidine residues: six are surface exposed, two buried, three are active site zinc ion ligands, and one is a proton shuttle. Comparing results from NMR spectroscopy with previously determined neutron protein crystal structures enabled a side‐by‐side investigation of the proton occupancies and preferred tautomeric states of the histidine residues in HCA II. Buried and zinc coordinating histidines remain in one neutral tautomeric state across the entire pH range studied, as validated by both methods. In contrast, solvent‐exposed histidines display high variability in proton occupancies. While the data were overall remarkably consistent between methods, some discrepancies were observed, shedding light on the limitations of each technique. Therefore, combining these methods with full awareness of the advantages and drawbacks of each, provides insights into the dynamic protonation landscape of HCA II histidines, crucial for elucidating enzyme catalytic mechanisms.
Impact of Mild Hypothermia As Adjunctive Therapy in Patients With ST‐Elevation Myocardial Infarction: A Meta‐Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Laborante Renzo , Paglianiti Donato Antonio , Galli Mattia , Patti Giuseppe , D'Amario Domenico 
Published: December 2024

ABSTRACTBackgroundThe prevention of reperfusion injury remains an unmet need in ST‐elevation myocardial infarction (STEMI) patients. Several randomized controlled trials (RCTs) evaluated mild hypothermia as adjunctive therapy during STEMI, with conflicting results.AimsTo summarize the evidence about the efficacy and safety of mild hypothermia in patients with STEMI, as well as its conclusiveness through a trial sequential analysis (TSA).MethodsPubMed and Scopus electronic databases were screened for eligible studies until August 12, 2024. Efficacy endpoints were all‐cause death, infarct size (IS), left ventricular ejection fraction (LVEF), the occurrence of microvascular obstruction (MVO), thrombolysis in myocardial infarction (TIMI) flow grade 3, and the resolution of ST‐segment elevation (i.e., > 50−70% from baseline) after the procedure. Safety endpoints included: the incidence of atrial fibrillation (AF), infections, any bleeding, major bleeding, acute and subacute stent thrombosis (STh), cardiogenic shock/pulmonary oedema, and ventricular fibrillation/tachycardia. “Door‐to‐balloon time” was indicated as the procedural endpoint. Two pre‐specified subgroup analyses were planned according to the mean ischemic time and the site of hypothermia induction (intra‐coronary vs. extra‐coronary). A TSA was run to explore whether the effect estimate of each efficacy outcome could be influenced by further studies.ResultsTen RCTs were included. Hypothermia did not provide a benefit for any of the specified efficacy endpoints. Furthermore, it enhanced the risk of infection, the risk of STh in patients with a mean ischemic time of less than 4 h, and the risk of AF in patients undergoing extra‐coronary hypothermia. Finally, it was also associated with an increased “door‐to‐balloon time”, and a trend toward an increased risk of any bleeding. No significant difference was found for the other endpoints. TSA showed conclusive evidence of an absence of benefit of hypothermia on IS, MVO, LVEF, and TIMI three flow.ConclusionsMild hypothermia is not beneficial and causes relevant delays in clinical management of STEMI patients, raising safety issues mainly related to the occurrence of STh, AF, and infections.
Graphene Acid: A Potent Carbocatalyst for the Friedel–Crafts Arylation of Aldehydes with Indoles
Authors: Galathri Eirini M. , Hrubý Vítězslav , Mountanea Olga G. , Mantzourani Christiana , Chronopoulos Demetrios D. , Otyepka Michal , Kokotos Christoforos G. 
Published: December 2024

AbstractCarbocatalysis represents a highly attractive and effective field within the realm of metal‐free nanocatalysis, significantly advancing sustainability in synthetic chemistry. Graphene acid (GA) emerges as a well‐defined graphene derivative, characterized by a high density of homogeneously distributed carboxylic groups over graphene lattice. This unique and uniform structure positions GA as an elegant alternative to other 2D carbocatalysts, namely graphene oxide. GA was successfully employed as the catalyst in a Friedel–Crafts‐type reaction between indoles and aldehydes, facilitating the synthesis of bis(indolyl)methanes, organic compounds exhibiting interesting biological properties and significant pharmaceutical potential. The metal‐free nature of GA, combined with the performance of the reaction “on water” under mild conditions, highlight the green credentials of the developed protocol. Comprehensive substrate screening, including a plethora of aliphatic or aromatic aldehydes and various 1‐ or 2‐substituted indoles, resulted in moderate to high yields of variously functionalized bis(indolyl)methanes. Mechanistic and recovering studies showed that GA acts catalytically as a Brønsted acid, maintaining its catalytic activity at a high rate for six subsequent cycles.
Fisetin as a Blueprint for Senotherapeutic Agents — Elucidating Geroprotective and Senolytic Properties with Molecular Modeling
Authors: Spiegel Maciej 
Published: December 2024

Targeting senescent cells and the factors that accelerate this pathological state has recently emerged as a novel field in medicinal chemistry. As attention shifts to synthetic substances, studies on natural agents are often overlooked. In this paper, we present a detailed computational modeling study that encompasses quantum mechanics and molecular dynamics to elucidate the senotherapeutic activity of fisetin. The mitochondrial environment, serving as a proxy for senescence, received special attention. Throughout the study, fisetin’s outstanding geroprotective properties—exhibiting significant potential against •OOH, O2•–, and •OH radicals, surpassing those of Trolox or ascorbate—were identified. Furthermore, fisetin demonstrated a high capacity to restore oxidatively damaged biomolecules to their pristine forms, thereby renewing the functionality of proteins and amino acids. The senolytic properties were examined in terms of Bcl–2 and Bcl–xL inhibition. The results indicated that fisetin not only binds effectively to these proteins but also, with appropriate modifications, may exhibit specific selectivity toward either target. This study highlights fisetin’s remarkable activity in these areas and provides a molecular description of the underlying processes, paving the way for future research.
Structural Characteristics of a Partially Planarized Triarylmethyl Cation with Unsymmetrical Push–Pull Structure
Authors: Ito Masato , Endoh Naoki , Kyoya Moe , Shimajiri Takuya , Kubo Yuji 
Published: December 2024

AbstractWe report the physical properties of a new class of triarylmethyl‐based carbocations containing both an electron‐donating diphenyl ether moiety and an electron‐accepting carbonyl group with a helical plane framework. Their unique packing patterns were clarified by X‐ray crystallographic analysis, which depend on the counter anions to influence their photophysical properties in the solid states. Notably, the interactions between π‐cation species and planar anion species lead to a unique panchromatic property, accompanying a near‐infrared absorption with a λonset value of 1030 nm, which can be assigned to intermolecular charge transfer transition. We found that the π‐cation species with planar anion formed cation dimers, being stacked in opposite directions. The two cation molecules are flanked by two anions on both the top and bottom side. Pair interaction energy decomposition analysis (PIEDA) calculations imply that the origins of the unique packing patterns of the π‐cations originate from the electrostatic forces of four neighbouring π‐anion species.
Defluorinative Diazolation‐Cyclization Relay for Synthesis of Furan‐Bridged Triheterocycles and Colorimetric Sensor Application
Authors: Feng Man‐Hang , Chen Da‐Qing , Gao Shu‐Ji , Ge Danhua , Chen Xiaojun , Ma Mengtao , Shen Zhi‐Liang , Chu Xue‐Qiang 
Published: December 2024

AbstractPolyaromatics, as the assembly of diverse cyclic π‐systems, exhibit unique physicochemical properties when compared to their individual constituents. In this study, we developed a strategic connection of two azacycles via a furan bridge through a defluorinative diazolation‐cyclization reaction of trifluoromethyl enones and N‐heterocycles. A range of modular 2,4‐furan‐bridged triheterocycles (FBTHs), featuring a C3‐trifluoromethyl group, was synthesized with broad substrate scope and good regioselectivity under transition metal‐free conditions. This three‐component protocol was achieved through successive C(sp3)‐F bond functionalization of one trifluoromethyl group, which is recognized for its stability and durability. Moreover, the synthetically useful functionalities such as bromide and formyl group could be easily installed on the resulting products, and the imidazole‐containing FBTH could serve as a valuable ligand in the preparation of an advanced colorimetric sensor, thereby underscoring their potential applications.
Health‐Risk Assessment of Groundwater Arsenic Levels in Bhagalpur, India, and Development of a Cost‐Effective Paper‐Based Arsenic Testing‐Kit
Authors: Maity Sourav , Dokania Puja , Goenka Manav , Patil Pritam Bajirao , Sarkar Angana 
Published: December 2024

ABSTRACTArsenic is considered one of the most hazardous trace metals in groundwater researched to date because of the hazardous impacts like cancer, skin irritation, and other skin‐related diseases. The present study involved collecting 60 water samples from Bhagalpur district, Bihar, India, to estimate the arsenic concentration. The human health risk assessment of the samples concerning children and adults was also performed, and the maximum concentration of arsenic was found to be relatively high in some sample sites. Prolonged exposure to arsenic could be fatal to the local population. The current study also focuses on developing a low‐cost paper‐based arsenic detection kit. The paper‐based test kit was tested for parameters like color development for different forms and concentrations of arsenic, storage conditions for the test strips, the effect of different interfering agents on color development, and optimization of the AgNO3 solution. The cost analysis was carried out, and it was found that the kit would cost 0.046 USD per sample, which is 70–100 times lower than the cost of current methods.
Investigating the C2 Modulation of the Imidazo[1,2‐a]pyrazine‐Based Hit Compound CTN1122: Synthesis, in vitro Antileishmanial Activity, Cytotoxicity and Casein Kinase 1 Inhibition
Authors: Tisseur Lhana , Cojean Sandrine , Gassama Khadidiatou , Logé Cédric , Pagniez Fabrice , Cavé Christian , Bernadat Guillaume , Loiseau Philippe M. , Bach Stéphane , Thiéfaine Jérôme , Picot Carine , Tomasoni Christophe , Leclercq Olivier , Baratte Blandine , Robert Thomas , Le Pape Patrice , Rachidi Najma , Bazin Marc‐Antoine , Marchand Pascal 
Published: December 2024

AbstractOur research group previously discovered CTN1122, an imidazo[1,2‐a]pyrazine compound with promising antileishmanial activity against intramacrophage amastigotes of Leishmania major and L. donovani strains. CTN1122 effectively targets Leishmania casein kinase 1 (L–CK1.2) and exhibits a favorable safety profile. To further explore its chemical space, we developed a convergent strategy to modify the C2 position of the imidazo[1,2‐a]pyrazine core using Suzuki‐Miyaura coupling of the corresponding triflate intermediate. Among 15 newly synthesized analogs, seven derivatives featuring variously substituted phenyl rings at C2 demonstrated L–CK1.2 inhibition within micromolar to submicromolar ranges and antileishmanial activity in vitro with low cytotoxicity in macrophages. Compounds 7 d and 7 l were particularly potent, with IC50 values of 1.25 μM and 0.92 μM against L. major, and 1.44 μM and 2.34 μM against L. donovani, respectively. They showed IC50 L–CK1.2=0.30 μM and 0.57 μM with enhanced selectivity indices (SI=3.8 and 1.6) over the human CK1ϵ ortholog. Additionally, four C2 analogs and two C5 isomers exhibited notable antiparasitic effects without strongly inhibiting L–CK1.2, indicating a possible alternative mechanism of action. Compound 7 k displayed the highest general activity, with IC50 values of 0.31 μM on L. major and 0.27 μM on L. donovani, coupled with favorable selectivity indexes.
Association Between Self‐Reported Oral Health and Dental Fear Among Illicit Drug Users in Northern Finland
Authors: Vainionpää Raija , Tiisanoja Antti , Kokkola Outi , Riipinen Pirkko , Anttonen Vuokko 
Published: December 2024

ABSTRACTObjectivesAbout 10% of adults in northern Finland have severe dental fear, but there is a lack of detailed knowledge about dental fear among illicit drug users. The aim of the study was to evaluate the prevalence of dental fear and its association with self‐reported oral health and health behavior as well as background factors of the customers of substance abuse services living in the region of Oulu, Northern Ostrobothnia, Finland.Materials and MethodsOne hundred seventeen volunteers, either active or former illicit drug users, were interviewed face‐to‐face about their background factors, health and health behaviors, and use of illicit drugs. The Modified Dental Anxiety Scale (MDAS) was used to assess a situation‐specific level of dental anxiety. For analyses, Pearson's χ2 test, Fisher's exact test, ANOVA, and logistic regression analysis were performed.ResultsThree out of four participants had at least moderate dental fear (MDAS ≥ 10) and 24% had severe dental fear (MDAS ≥ 19), with the average MDAS being 14.0 (SD 5.7). Participants in drug rehabilitation reported significantly more dental fear than the rest of the participants. Severe dental fear was associated (adjusted) with previous painful experiences OR 10.8 (2.3–52.0) and poor behavior by dental personnel OR 4.1 (1.2–13.9).ConclusionsDental fear is common among illicit drug users, and it is, particularly, associated with previous painful experiences and poor behavior by dental personnel.
Exploring the role of environmental regulations in green marketing success
Authors: David Lemuel Kenneth , Wang Jianling , Cisse Idrissa I. , Angel Vanessa 
Published: December 2024

AbstractIn response to growing consumer demand for sustainability, this study examines the impact of green marketing on brand perception and consumer purchase intent across 80 countries from 2006 to 2023. Drawing on data from Bloomberg, Thomson Reuters Eikon, and Sustainalytics, this research employs structural equation modeling and hierarchical linear modeling to analyze the relationships between green marketing expenditure, brand perception, and consumer behavior. The findings reveal that increased investment in green marketing significantly enhances brand perception and purchase intent, with outcomes varying across different economic, cultural, and regulatory contexts. These results highlight the importance of tailoring green marketing strategies to specific regions, providing actionable insights for advertisers aiming to foster brand loyalty through sustainability. Implications suggest that both advertisers and policymakers can strengthen consumer trust and brand loyalty by aligning sustainable marketing efforts with local cultural and regulatory expectations.
Sulfur‐Bridged Iron and Molybdenum Catalysts for Electrocatalytic Ammonia Synthesis
Authors: Yuan Xiaojiao , Galán‐Mascarós J. R. 
Published: December 2024

AbstractCarbon zero electrocatalytic nitrogen reduction reaction (NRR), converting N2 to NH3 under ambient temperature and pressure, offers a sustainable alternative to the energy‐intensive Haber‐Bosch process. Nevertheless, NRR still faces major challenges due to direct dissociation of the strong N≡N triple bond, poor selectivity, as well as other issues related to the inadequate adsorption, activation and protonation of N2. In nature's nitrogen fixation, microorganisms are able to convert N2 to ammonia at ambient temperature and pressure, and in aqueous environment, thanks to the nitrogenase enzymes. The core NRR performance is achieved with sulfur‐rich Fe transition metal clusters as active site cofactors to capture and reduce N2, with optimum performance found for Fe−Mo clusters. Because of this reason, artificial analogs in Fe−Mo coordination chemistry have been explored. However, the studies of sulfur coordinated Fe, Mo catalysts for electrocatalytic ammonia synthesis are scarce. In this review, the recent progress of Fe−Mo sulfur‐bridged catalysts (including sulfur‐coordinated single‐site catalysts in carbon frameworks and MoS2‐based catalysts) and their activities for the ammonia synthesis from nitrate reduction reaction (NO3–RR) and nitrogen reduction reaction (NRR) are summarized. Further existing challenges and future perspectives are also discussed.
Unique MIMO System Using Gaussian Signals and the Advantage of These Signals in Sensing CSI and Multipath Fading
Authors: Alyassri Salam , Ilyas Muhammad , Aljumaily Mustafa S. , Al‐jumaili Saif , Duru Adil Deniz 
Published: December 2024

ABSTRACTTo improve communication network efficiency, researchers must look at all aspects of transmission and the mechanisms that regulate their evolution as a whole. These features include solutions for dealing with the channel's noise and interference. To decrease interference and increase spectrum efficiency, orthogonal frequency division multiple access (OFDMA) systems employ orthogonal signals. While transmitting and receiving signals, noise and numerous feeds can be done in diverse ways. It has become increasingly common to use 256 quadratic modulation (QAM), which is more vulnerable to noise and has a higher bit error rate (BER). BERs in OFDM systems were high when multiple feeds and noise were present, as demonstrated in this article. Starting with the transmission and reception of Gaussian subband signals, an improved system has been designed that includes numerous stages of development. Thus, the need for “orthogonally” of transmitted signals to increase spectrum efficiency has been eliminated, as has the effect of surrounding channels. We have created a header for every frame that has been transmitted. Several transmitters and numerous receivers send these frames in parallel so that the channel state information (CSI) attributes may be evaluated using parallel processing. Using the identical transmission conditions for both OFDM systems and the proposed system, the simulation results reveal a significant reduction in BER values. This results in BER values of fewer than 10−1 when there are two tabs and 10−1 when there are three tabs for multiple feeding in the OFDM system. This corresponds to BER values of 10−11 in a suggested system when there are three tabs. Some improvements have been made to the proposed design to make it distinctive and qualified to be regarded as a multiaccess system in today's contemporary communication infrastructures.
Fluorinated Sulfonamides: Synthesis, Characterization, In Silico, Molecular Docking, ADME, DFT Predictions, and Structure‐Activity Relationships, as Well as Assessments of Antimicrobial and Antioxidant Activities
Authors: Reheim Mohamed A. M. Abdel , Ghazal Basma , Abdelhamid Sayeda Abdelrazek , Elhagali Gameel A. M. , El‐Gaby Mohamed S. A. 
Published: December 2024

ABSTRACTThe design and synthesis of unique two series of fluorinated sulfonamides 3a‐f and 5a‐g utilizing nucleophilic aromatic substitution reactions of tetrafluorophthalonitrile 1 with various sulfonamides 2 under a variety of different reactions conditions were the key goals of the current research. The chemical composition of the generated products has been investigated via mass spectroscopy, 1HNMR, 13CNMR, infrared, and elemental analyzes. Antimicrobial studies were conducted in vitro to evaluate the activity of all new synthesized compounds against resistant strains. The first series showed high potency in very low concentrations. All compounds were studied against DPPH Radical Scavenging Activity and the other series showed high activity even in low molar ratio. In silico molecular docking was used to investigate the potential binding pathways for different receptors: dihydroprotien synthase protein (ID Code: 1AJ0) as an antibacterial and EGFRWT co‐crystallized with erlotinib [PDB ID code 1m17]. Furthermore, synthesized compounds with good ADME predictions to the Lipinski rule of five demonstrated that the recently synthesized compounds had high drug‐likeness qualities when the physicochemical parameter for the most powerful novel candidates was determined. Moreover, the DFT/B3LYP method functionalized with a 6‐31G (d, p) basis set was employed to calculate quantum parameters, MEP analysis, HUMO, and LUMO.
Novel Transgenic Zebrafish Lines to Study the CHRNA3‐B4‐A5 Gene Cluster
Authors: Hua Yuanqi , Habicher Judith , Carl Matthias , Manuel Remy , Boije Henrik 
Published: December 2024

ABSTRACTAcetylcholine (ACh), a vital neurotransmitter for both the peripheral (PNS) and central nervous systems (CNS), signals through nicotinic ACh receptors (nAChRs) and muscarinic ACh receptors (mAChR). Here, we explore the expression patterns of three nAChR subunits, chrna3, chrnb4, and chrna5, which are located in an evolutionary conserved cluster. This close genomic positioning, in a range of vertebrates, may indicate co‐functionality and/or co‐expression. Through novel transgenic zebrafish lines, we observe widespread expression within both the PNS and CNS. In the PNS, we observed expression of chrna3tdTomato, chrnb4eGFP, and chrna5tdTomato in the intestinal enteric nervous system; chrna5tdTomato and chrnb4eGFP in sensory ganglia of the lateral line; and chrnb4eGFP in the ear. In the CNS, the expression of chrnb4eGFP and chrna5tdTomato was found in the retina, all three expressed in diverse regions of the brain, where a portion of chrna3tdTomato and chrnb4eGFP cells were found to be inhibitory efferent neurons projecting to the lateral line. Within the spinal cord, we identify distinct populations of chrna3tdTomato‐, chrnb4eGFP‐, and chrna5tdTomato‐expressing neurons within the locomotor network, including dmrt3a‐expressing interneurons and mnx1‐expressing motor neurons. Notably, three to four primary motor neurons per hemisegment were labeled by both chrna3tdTomato and chrnb4eGFP. Interestingly, we identified an sl‐type secondary motor neuron per hemisegement that strongly expressed chrna5tdTomato and co‐expressed chrnb4eGFP. These transgenic lines provide insights into the potential roles of nAChRs within the locomotor network and open avenues for exploring their role in nicotine exposure and addiction in a range of tissues throughout the nervous system.