bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aliphatic Amines Unlocked for Selective Transformations through Diazotization
Authors: Durka Jakub , Zielińska Barbara , Gryko Dorota 
Published: December 2024

AbstractWhile aromatic diazonium salts are important reagents in organic synthesis, ‘Diazonium ions generated from ordinary aliphatic primary amines are usually useless for preparative purposes, since they lead to a mixture of products giving not only substitution by any nucleophile present, but also elimination and rearrangements if the substrate permits.’1 In this work, we report that this statement is no longer valid, and it is now possible to control diazotization of aliphatic amines by utilizing isopentyl nitrite in HFIP. This transformation enabled electrophilic aromatic substitution with these highly abundant and commercially available alkyl reagents, as well as transforming them into building blocks typically employed in organic synthesis. The methodology opens an avenue for reactions involving aliphatic amines, even such demanding substrates as amino acids, as a source of carbocations thus expanding the degree of chemical space.
Asymmetric S‐Arylation of Sulfenamides to Access Axially Chiral Sulfilimines Enabled by Anionic Stereogenic‐at‐Cobalt(III) Complexes
Authors: Fang Wei , Meng Yan‐Dong , Ding Shu‐Ying , Wang Ju‐Yan , Pei Zheng‐Hao , Shen Meng‐Lan , Yao Chuan‐Zhi , Li Qiankun , Gu Zhenhua , Yu Jie , Jiang Hua‐Jie 
Published: December 2024

AbstractAn efficient enantioselective coupling reaction between sulfenamides and cyclic diaryliodonium salts is established via adaptive Cu/anionic stereogenic‐at‐Co(III) complex combined catalysis, precisely synthesizing a broad range of axially chiral sulfilimines with excellent enantioselectivities, diastereoselectivities, regioselectivities, and chemoselectivities (67 examples under same conditions, up to 98 % ee). The following thermodynamically controlled pyramidal inversion enables efficient stereodivegent synthesis of all four stereoisomers. Mechanistic studies suggest that anionic stereogenic‐at‐cobalt(III) complexes serve as counteranions of diaryliodonium and anionic ligand of Cu(I) catalyst simultaneously, which could be regarded as an explanation for outstanding selectivities.
The Role of Electron Transfer in Copper‐Mediated C(sp2)−H Trifluoromethylation
Authors: Ball Margaret A. P. , Myers Preston J. , Ritch Grayson D. , Bower Jamey K. , Moore Curtis E. , Szymczak Nathaniel K. , Zhang Shiyu 
Published: December 2024

AbstractWe report copper(II) and copper(III) trifluoromethyl complexes supported by a pyridinedicarboxamide ligand (L) as a platform for investigating the role of electron transfer in C(sp2)−H trifluoromethylation. While the copper(II) trifluoromethyl complex is unreactive towards (hetero)arenes, the formal copper(III) trifluoromethyl complex performs C(sp2)−H trifluoromethylation of a wide range of (hetero)arenes. Mechanistic studies using the copper(III) trifluoromethyl complex suggest that the mechanism of arene trifluoromethylation is substrate‐dependent. When the thermodynamic driving force for electron transfer is high, the reaction proceeds through a previously unidentified single electron transfer (SET) mechanism, where an initial electron transfer occurs between the substrate and oxidant prior to CF3 group transfer. Otherwise, a CF3 radical release/electrophilic aromatic substitution (SEAr) mechanism is followed. These studies provide valuable insights into the role of strong oxidants and potential mechanistic dichotomy in Cu‐mediated C(sp2)−H trifluoromethylation.
Self‐assembled free nanocarrier prodrugs based on camptothecin and dihydroartemisinin exhibit accumulation and improved anticancer efficacy
Authors: Garg Mohan , Rangaswamy Roopashree , Mishra Rahul , Giri Shivangi , Chinnathambi Arunachalam , Alahmadi Tahani Awad , Arulselvan Palanisamy , Thangavelu Indumathi 
Published: December 2024

AbstractSmall molecule targeted inhibitor therapies often have several drawbacks, including limited oral bioavailability, quick metabolism, toxic effects that limit dosage, and poor water solubility. This study aims to develop a nanodrug self‐delivery system that does not require a carrier by utilizing the self‐assembly of camptothecin (CPT) and dihydroartemisinin (DHA). CPT/DHA nanoparticles (NPs) with varying diameters can be synthesized without requiring further carrier materials or chemical modifications by changing the CPT‐to‐DHA ratio (10:1, 5:1, 2:1, 1:1). Even more crucially, CPT/DHA NPs generate an AIE impact when they self‐assemble. CPT/DHA NPs are used for cell tracking and bioimaging fluorescent probes. We chose CPT/DHA NPs (2:1) with a size of approximately 140 nm for the anticancer examinations. The A549 cells were used to assess the cytotoxicity, morphological changes by biochemical staining methods and apoptosis by flow cytometric techniques of CPT/DHA NPs. Finally, in vitro anticancer research proved that CPT/DHA NPs are biocompatible and have strong synergistic anticancer properties.
The Multiscale Wisdom of the Body: Collective Intelligence as a Tractable Interface for Next‐Generation Biomedicine
Authors: Levin Michael 
Published: December 2024

ABSTRACTThe dominant paradigm in biomedicine focuses on genetically‐specified components of cells and their biochemical dynamics, emphasizing bottom‐up emergence of complexity. Here, I explore the biomedical implications of a complementary emerging field: diverse intelligence. Using tools from behavioral science and multiscale neuroscience, we can study development, regenerative repair, and cancer suppression as behaviors of a collective intelligence of cells navigating the spaces of possible morphologies and transcriptional and physiological states. A focus on the competencies of living material—from molecular to organismal scales—reveals a new landscape for interventions. Such top‐down approaches take advantage of the memories and homeodynamic goal‐seeking behavior of cells and tissues, offering the same massive advantages in biomedicine and bioengineering that reprogrammable hardware has provided information technologies. The bioelectric networks that bind individual cells toward large‐scale anatomical goals are an especially tractable interface to organ‐level plasticity, and tools to modulate them already exist. This suggests a research program to understand and tame the software of life for therapeutic gain by understanding the many examples of basal cognition that operate throughout living bodies.
Lasia spinosa Stem Aqueous Extract Potentiates Antidiabetic Effects Exhibiting Antioxidant Genes Upregulation and DNA‐Damage Protection
Authors: Sharmen Farjana , Abu Ahmed A. M. , Rahman Md. Atiar 
Published: December 2024

ABSTRACTThis research elucidated the hypoglycemic effect correlated with DNA‐protective and antioxidative activity of Lasia spinosa stem aqueous extract (LSSAE) using streptozotocin‐induced type 2 diabetic rat models. LSSAE, characterized by phytochemical screening, gas chromatography–mass spectroscopy (GC–MS), and FTIR analyses, was investigated for its DNA‐protective activity by exposing PBR322 plasmid DNA to Fenton's reagents. Long Evans rats, treated by LSSAE, were found to be improved for body weight, fasting blood glucose level, and oral glucose load. A 30‐day supplement of LSSAE significantly recovered serum biochemical markers, including hepatic (i.e., ALP, AST, ALT, and TB); renal (i.e., creatinine and uric acid); and lipid profiles (i.e., TC, TG, HDLc, LDLc, and VLDLc). An increased level of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH), and a decreased level of malondialdehyde (MDA) were observed in LSSAE‐treated rat liver. Antioxidant enzyme activities were evaluated by mRNA expression level of antioxidant genes (CAT, SOD2, GPX1, PON1, PFK1, GAPDH, using the 2−ΔΔCT method, normalized with housekeeping gene, ß‐ACTIN) using qRT‐PCR. Additionally, histological examination confirmed the restoration of morphology, and function of pancreatic β‐cell, kidney, liver, and spleen. Results reveal that LSSAE exerts an antidiabetic effect through upregulation of antioxidant genes, DNA protection and modulation of biochemical and histological parameters.
How Does Cloning Change Phenolics, Minerals and Antioxidant Activity in Helichrysum arenarium (L.) Moench (Clone A, Clone B)?
Authors: Saygi Kadriye Ozlem , Erenler Ramazan , Telci Isa 
Published: December 2024

ABSTRACTTissue culture and cloning are valuable techniques in plant biology research as they enable the production of genetically identical plants, which may be utilized for many purposes, such as crop enhancement, plant breeding, and genetic manipulation. Helichrysum arenarium (L.) Moench, also known as immortelle or strawflower (Asteraceae), is a species of flowering plant in the sunflower family. In this study, the aerial part of two Clones (Clone A, Clone B) of H. arenarium were used to consider the effect of Clones on the phenolics, minerals, and antioxidant activities. The methanol extracts were analyzed and compared for phenolic compounds and antioxidant activities. Inductively coupled plasma‐optical emission spectroscopy is a widely used method for the determination of a wide range of elements in plant materials, including macro and microelements. Calcium and potassium are the major mineral elements. The phenolics were identified and quantified using high‐performance liquid chromatography combined with tandem mass spectrometry. The highest caffeic acid was determined in the methanolic extract, followed by protocatechuic aldehyde and protocatechuic acid.
Diverse Multinuclear Alkali Metallated (Li, Na, K, Rb, Cs) Family of the 1,3,5‐tris‐2‐aminopyridyl‐2,4,6‐triethylbenzene Framework
Authors: Lynch Jennifer R. , Navarro Marta , Kennedy Alan R. , Robertson Stuart D. , Mulvey Robert E. , Hernán‐Gómez Alberto 
Published: December 2024

AbstractLiterature on Group One organoelement chemistry is dominated by lithium, though sodium and potassium also feature prominently, whereas rubidium and caesium are rarely mentioned. With recent breakthroughs hinting that organoelement compounds of these two heavier metals can perform better than their lighter congeners in particular applications, important advantages could be missed unless complete sets of alkali metals are included in studies. Here, we report the synthesis and characterisation of a complete set of multi‐alkali‐metallated molecular compounds of the 1,3,5‐tris[(4,6‐dimethylpyridin‐2‐yl)aminomethyl]‐2,4,6‐triethylbenzene framework. Made by deprotonating the framework N−H bonds by a suitable base, the set comprises six THF‐solvated compounds, four of which are homometallic, either containing Li in a trinuclear structure or Na, K, and Rb in hexanuclear structures. Since deprotonation was incomplete with Cs, its homometallic compound is tetranuclear containing two un‐metallated N−H bonds. A heterobimetallic trilithium‐tricaesium hexanuclear compound was also obtained by using a bimetallic Li−Cs base for deprotonation. Such alkali‐metallated frameworks are often precursors to other multimetallic frameworks with unique properties across different fields of science.
Probing TCR Specificity Using Artificial In Vivo Diversification of CDR3 Regions
Authors: Giorgetti Orlando B. , Haas‐Assenbaum Annette , Boehm Thomas 
Published: December 2024

ABSTRACTThe T‐cell receptor sequences expressed on cells recognizing a specific peptide in the context of a given MHC molecule can be explored for common features that might explain their antigen specificity. However, despite the development of numerous experimental and bioinformatic strategies, the specificity problem remains unresolved. To address the need for additional experimental paradigms, we report here on an in vivo experimental strategy designed to artificially diversify a transgenic TCR by CRISPR/Cas9‐mediated mutagenesis of Tcra and Tcrb chain genes. In this system, an initially monoclonal repertoire of known specificity is converted into an oligoclonal pool of TCRs of altered antigen reactivity. Tracking the fate of individual clonotypes during the intrathymic differentiation process illuminates the strong selective pressures that shape the repertoire of naïve T cells. Sequence analyses of the artificially diversified repertoires identify key amino acid residues in the CDR3 regions required for antigen recognition, indicating that artificial diversification of well‐characterized TCR transgene sequences helps to reduce the complexities of learning the rules of antigen recognition.
Understanding Structural Dynamics in Flexible Rare‐Earth Metal‐Organic Frameworks
Authors: Loukopoulos Edward , Trikalitis Pantelis N. 
Published: December 2024

AbstractFlexible Metal‐Organic Frameworks (FL‐MOFs) are emerging advanced materials with the ability to respond to various stimuli by adapting their structure and pore. In particular, FL‐MOFs based on rare‐earth (RE) elements offer a unique and sophisticated approach towards truly novel responsive materials and properties. This Concept article provides an overview of the main principles and factors that affect structural features in RE‐FL‐MOFs, identifying trends and exploring potential rational design strategies. Common challenges and possible future research directions are also discussed.
Systemic hypoxia has a larger effect on reducing the external load at lower exercise intensity during heart rate clamped cycling
Authors: Li Siu Nam , Peeling Peter , Scott Brendan R. , Peiffer Jeremiah J. , Shaykevich Alex , Girard Olivier 
Published: December 2024

AbstractThe effects of acute hypoxic exposure on mechanical output and internal responses during cycling with heart rate (HR) clamped at lactate thresholds 1 and 2 (LT1 and LT2, respectively) were investigated. On separate days, 12 trained males cycled for 15 min at a clamped HR corresponding to LT1 and LT2 under normoxic or hypoxic conditions (simulated altitude of ∼3500 m and inspired oxygen fraction of 13.6%). Power output (PO), arterial oxygen saturation, ventilatory and perceptual responses were measured every 3 min, with metabolic response assessed pre‐ and post‐exercise. At LT1, PO was consistently lower in hypoxia compared to normoxia (p < 0.01). At LT2, PO was not different between normoxia and hypoxia at 3 and 6 min (both p > 0.42) but was significantly lower in hypoxia at 9, 12 and 15 min (all p < 0.04). Overall, hypoxia induced a greater decrease in PO at LT1 (−33.3% ± 11.3%) than at LT2 (−18.0 ± 14.7%) compared to normoxia. Ventilatory, perceptual and metabolic responses were influenced by exercise intensity (all p < 0.01) but not environmental conditions (all p > 0.17). A simulated altitude of ∼3500 m is more effective in reducing cycling PO at LT1 than LT2 during HR clamped cycling while maintaining other internal loads. Therefore, normobaric hypoxia provides a greater benefit via a larger decrease in the mechanical constraints of exercise at lower exercise intensities.
Germanic Rampart or Roman Encampment?—New Geoarchaeological Evidence at the Roman Conflict Site at Kalkriese (NW‐Germany)
Authors: Härtling Joachim W. , Stele Andreas , Ortisi Salvatore , Jepsen Andre , Rappe Marc , Bussmann Jens , Fülling Alexander 
Published: December 2024

ABSTRACTKalkriese, near Osnabrueck (NW Germany), is considered the location of the ‘Battle of Varus’, where a coalition of Germanic tribes, under the leadership of Arminius, defeated three Legions under the command of Varus in 9 ad. Roman coinage and remains of military equipment prove that the Oberesch site at Kalkriese saw military operations between Germanic tribes and the Roman legions during Early Imperial times, but the sequence and magnitude of the military operations still remain unclear. In this study, we present for the first time absolute dates from the Oberesch site to decipher the general sequence of the Holocene landscape development at Kalkriese, identify the antique surface, and evaluate the ‘Germanic Rampart Theory’ and the ‘Roman Encampment Theory’. The geoprofile encompasses the entire stratigraphic sequence from the Pleistocene base, indicating intensive agricultural use of the area since the Early Neolithic. A fossil topsoil of late Pre‐Roman Iron Age to Roman Imperial Age was identified, which probably represents the antique surface of the Roman conflict site. Our results do not support either the ‘Germanic Rampart Theory’ or the ‘Roman Encampment Theory’, as both linear structures seem to be of High Middle Age origin.
Magnetohydrodynamic Natural Convection in a Circular Dome‐Shaped Enclosure
Authors: Venkatadri K. 
Published: December 2024

ABSTRACTThe design of flow structures plays a crucial role in enhancing natural convective heat transfer within enclosures. By optimizing the geometry of enclosures to influence flow structures, we can significantly improve their natural convective heat transfer performance. Specifically, the dome‐shaped wall can alter flow direction, improving flow circulation and natural convection. The current study conducts a numerical investigation of the laminar flow and natural convective heat transfer of air within a dome‐shaped enclosure, while also considering the impact of a magnetic field. The analysis encompasses the interaction between magnetic field and buoyancy‐driven flow. Governing equations for momentum, energy, and angular momentum are formulated, integrating the influence of the Lorentz force. The working fluid Pr = 0.71 is considered in this study. The equations are transformed into dimensionless form using key parameters, such as the buoyancy number (Ra) and Hartmann number (Ha). The modeled partial differential equations were carried out with a vorticity‐stream function algorithm to explore the influence of magnetic field strength on the flow and thermal characteristics. Results indicate significant alterations in flow patterns and temperature distribution behavior under varying magnetic field and Rayleigh number. The interaction between buoyancy and magnetic fields plays a critical role in determining the heat transfer characteristics of an incompressible fluid, with Ra enhancing, and Ha suppressing, convective efficiency. Heat transfer enhancement of 82.84% is noticed for a Rayleigh number ranging from 103 to 104, while a 48.316% decrement is found for a Hartmann number ranging from 0 to 10 with Ra = 105. The transition from a magnetically dominated regime (high Ha) to a thermally driven regime (low Ha) leads to a shift from a uniform temperature field to one with more complex thermal layering and mixing, which is reflected in the varying shapes and amplitudes of the Nusselt number distributions. At higher Ha values, magnetic forces dominate, significantly suppressing buoyancy‐driven convection, and reducing the intensity of thermal mixing.
Nonpuerperal uterine inversion complicating a huge prolapsed submucous myoma: A case report
Authors: Abasiattai Aniekan Monday , James Robert , Atat Bless , Edemekong Victor , Etuknwa Utibe 
Published: December 2024

SynopsisNonpuerperal uterine inversion complicating a huge submucous fundal myoma.
Skin Sensitization Potency Prediction Based on Read‐Across (RAx) Incorporating RhE‐Based Testing Strategy (RTSv1)–Defined Approach: RTSv1‐Based RAx
Authors: Suzuki Sho , Mizumachi Hideyuki , Miyazawa Masaaki 
Published: December 2024

ABSTRACTIn recent years, nonanimal approaches for skin sensitization have been developed in response to political, regulatory, and ethical demands. The reconstructed human epidermis (RhE)–based testing strategy (RTS)v1–defined approach (DA) is used to categorize skin sensitization potency. However, the RTSv1 DA alone cannot be used to predict potency based on EC3 values [the estimated concentration that produces a stimulation index of 3 in the local lymph node assay (LLNA)], and underpredictions have been reported. Read‐across (RAx) can complement DA data and improve prediction confidence. Although case studies combining new approach methodology/DA data with RAx have been reported, they focus on a single target chemical and lack a comprehensive and robust strategy with well‐examined reliability. This study developed a strategy incorporating the RTSv1 DA into RAx (RTSv1‐based RAx) to predict skin sensitization potency, applying it to 43 chemicals. The predictive performance of RTSv1‐based RAx was evaluated by comparing its predicted potency category and EC3 outcomes with those of RTSv1 DA and the LLNA. RTSv1‐based RAx accurately predicted the Globally Harmonized System of Classification (GHS) subcategorization for 38 chemicals and determined the predicted EC3 values for 17 sensitizers within a fourfold range of LLNA‐derived EC3 values. This study demonstrates that RTSv1‐based RAx offers robust predictivity for both GHS subcategorization and predicted EC3 values, making it useful for quantitative risk assessment.
The effect of early weaning on feeding behavior parameters in rodents: A systematic review
Authors: Alves Swane Miranda , de Oliveira Elifrances Galdino , Araújo Eulália Rebeca Da Silva , Silva Paula Brielle Pontes , de Castro Raul Manhães , de Souza Sandra Lopes 
Published: December 2024

AbstractBreastfeeding is essential for somatic development, especially neurodevelopment. The abrupt termination of the mother–child bond, early weaning, is a stressful event during the neonatal period. This has lifelong consequences. The impact on neural plasticity will be reflected in behavioral expression, including feeding behavior. This behavior is modulated by encephalic and peripheral structures, such as the serotonergic and dopaminergic neurotransmission systems, as well as hormonal signaling, leptin, and ghrelin. The central nervous system, particularly the hypothalamus, receives information from the gastrointestinal tract to regulate hunger and satiety. Early weaning alters these mechanisms that control feeding behavior. The alterations most commonly reported in the literature are hyperphagia, increased body mass, and molecular alterations related to the control of feeding behavior. Studies have attempted to identify the factors involved in the changes in feeding behavior control caused by early weaning. Furthermore, pharmacological interventions, herbal medicines, calcium supplementation, and physical activity have been investigated as potential means of reversing these changes. Consequently, the objective of this literature review was to analyze the effects of early weaning on the modulation of parameters that act to control feeding behavior.