bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metalloradical Catalysis: General Approach for Controlling Reactivity and Selectivity of Homolytic Radical Reactions
Authors: Lee Wan‐Chen Cindy , Zhang X. Peter 
Published: March 2024

AbstractSince Friedrich Wöhler's groundbreaking synthesis of urea in 1828, organic synthesis over the past two centuries has predominantly relied on the exploration and utilization of chemical reactions rooted in two‐electron heterolytic ionic chemistry. While one‐electron homolytic radical chemistry is both rich in fundamental reactivities and attractive with practical advantages, the synthetic application of radical reactions has been long hampered by the formidable challenges associated with the control over reactivity and selectivity of high‐energy radical intermediates. To fully harness the untapped potential of radical chemistry for organic synthesis, there is a pressing need to formulate radically different concepts and broadly applicable strategies to address these outstanding issues. In pursuit of this objective, researchers have been actively developing metalloradical catalysis (MRC) as a comprehensive framework to guide the design of general approaches for controlling over reactivity and stereoselectivity of homolytic radical reactions. Essentially, MRC exploits the metal‐centered radicals present in open‐shell metal complexes as one‐electron catalysts for homolytic activation of substrates to generate metal‐entangled organic radicals as the key intermediates to govern the reaction pathway and stereochemical course of subsequent catalytic radical processes. Different from the conventional two‐electron catalysis by transition metal complexes, MRC operates through one‐electron chemistry utilizing stepwise radical mechanisms.
Nuclear Magnetic Resonance Chemical Shift as a Probe for Single‐Molecule Charge Transport
Authors: Qiao X. , Sil A. , Sangtarash S. , Smith S. M. , Wu C. , Robertson C. M. , Nichols R. J. , Higgins S. J. , Sadeghi H. , Vezzoli A. 
Published: March 2024

AbstractExisting modelling tools, developed to aid the design of efficient molecular wires and to better understand their charge‐transport behaviour and mechanism, have limitations in accuracy and computational cost. Further research is required to develop faster and more precise methods that can yield information on how charge transport properties are impacted by changes in the chemical structure of a molecular wire. In this study, we report a clear semilogarithmic correlation between charge transport efficiency and nuclear magnetic resonance chemical shifts in multiple series of molecular wires, also accounting for the presence of chemical substituents. The NMR data was used to inform a simple tight‐binding model that accurately captures the experimental single‐molecule conductance values, especially useful in this case as more sophisticated density functional theory calculations fail due to inherent limitations. Our study demonstrates the potential of NMR spectroscopy as a valuable tool for characterising, rationalising, and gaining additional insights on the charge transport properties of single‐molecule junctions.
Kinetics of microwave carbothermal reduction of Sb2O3: Isothermal and non‐isothermal microwave thermogravimetric analysis
Authors: Yang Qinsheng , Liu Chenhui , Zhu Xiongjin , Srinivasakannan Chandrasekhar , Li Yingwei , Dai Ying 
Published: March 2024

AbstractKinetics of antimony production via carbothermal reduction of Sb2O3–carbon powder–NaCl mixture using microwave and conventional heating was investigated to identify the dominant controlling mechanism. Results of conventional heating revealed the temperature range of conventional carbothermal reduction reaction is 500°C to 800°C, with the average activation energy of each stage being 81.97 kJ/mol (α = 0.1–0.5), 65.17 kJ/mol (α = 0.5–0.75), and 69.86 kJ/mol (α = 0.75–1.0), respectively. In the microwave field, the carbothermal reduction reaction of raw materials can be completed at 600°C to obtain antimony, and the weight loss data of the carbothermal reduction process were recorded for the first time. The above results show that the microwave field enhanced the interfacial chemical effect, accelerated the interfacial diffusion from the metal phase to the oxide phase, and reduced the activation energy of the carbon thermal reduction process to 6.85 kJ/mol. The growth index of antimony grain growth process is estimated to be 4.33, controlled by the surface diffusion. These data provide a reliable theoretical basis for studying the reduction reactions of minerals in microwave fields.
Novel polyurethane foam with low released heat for application in bone binder
Authors: Jiao Gangwei , Cao Yang , Liu Xiaodong , Fu Qiang , Gu Ning , Ren Ying , Sun Youyi 
Published: March 2024

AbstractBecause of the significant advantages of bone adhesives compared with traditional mechanical fixation, many scholars have studied polyurethane bone adhesives. However, polyurethane will release a lot of heat in the reaction process, producing high temperature. The high temperature does not only easily cause a human discomfort but also will destroy the tissue structure of human. In this paper, a new polyurethane composite based on phase transition materials and hydroxyapatite is prepared to reduce released heat for application in bone binder. The mechanical properties, adhesive strength, and released heat‐induced temperature of polyurethane composite are investigated in detail. It exhibits good viscoelastic performance with a large elastic deformation (>30%) and good adhesive strength (>0.2 MPa). Furthermore, the released heat of polyurethane composite is effectively reduced, in which the temperature drastically decreases from 110.4 to 41.8°C. The work does not only confirm formation of high‐performance bone binder but also provides a new method to reduce released heat of polyurethane for various applications.
Tarsals from the Sima de los Huesos Middle Pleistocene site (Atapuerca, Burgos, Spain)
Authors: Pablos Adrián , Arsuaga Juan Luis 
Published: March 2024

AbstractHere, we provide a complete, updated, and illustrated inventory, as well as a comprehensive study, of the tarsals (rearfoot) recovered from the Middle Pleistocene site of Sima de los Huesos (SH, Atapuerca, Spain) in comparison to other Homo comparative samples, both extant and fossil. The minimum number of individuals (MNI) estimated from the tarsals has been established as 15, which represents 51.7% of the 29 dental individuals identified within the SH sample. Within the SH hominin foot sample, an exclusive combination of primitive or plesiomorphic and derived or autapomorphic traits can be observed when compared with other Homo individuals/populations. Other characters are shared among SH hominins and Neandertals that might represent shared derived or autapomorphic traits for this evolutionary line, and most are likely related to robusticity (e.g., rectangular‐like trochlea of the talus, broad calcanei, broad naviculars, and short lateral cuneiforms). Additionally, we observed some exclusive autapomorphic traits in the SH tarsal sample (e.g., narrow head of the talus and short intermediate cuneiforms). A few exclusive traits in SH tarsal remains are even more robust than in Neandertals (e.g., broad lateral malleolar facet in talus, more projected sustentaculum tali, and broad medial cuneiform). These traits could suggest a slightly higher level of gracilization in the tarsal bones of Neandertals compared to the SH sample that is also supported by other anatomical postcranial skeleton elements. Additionally, some paleobiological inferences are made in relation to body size (stature and body mass) and some associations are proposed within the SH sample. In conclusion, the morphology of the SH tarsi confirms an evolutionary relationship of sister groups between this population and Neandertals, probably representing a morphotype similar to the Neandertal ancestors.
N1‐Benzoylated 5‐(4‐pyridinyl)indazole‐based kinase inhibitors: Attaining haspin and Clk4 selectivity via modulation of the benzoyl substituents
Authors: Aboelfotouh Habiba G. , Abdallah Mennatallah , Khalifa Hend , Aboushady Youssef , Abadi Ashraf H. , Engel Matthias , Abdel‐Halim Mohammad 
Published: March 2024

AbstractHaspin and Clk4 are both understudied protein kinases (PKs), offering potential targets for the development of new anticancer agents. Thus, the identification of new inhibitors targeting these PKs is of high interest. However, the inhibitors targeting haspin or Clk4 developed to date show a poor selectivity profile over other closely related PKs, increasing the risk of side effects. Herein, we present two newly developed N1‐benzyolated 5‐(4‐pyridinyl)indazole‐based inhibitors (18 and 19), derived from a newly identified indazole hit. These inhibitors exhibit an exceptional inhibitory profile toward haspin and/or Clk4. Compound 18 (2‐acetyl benzoyl) showed a preference to inhibit Clk4 and haspin over a panel of closely related kinases, with sixfold selectivity for Clk4 (IC50 = 0.088 and 0.542 μM, respectively). Compound 19 (4‐acetyl benzoyl) showed high selectivity against haspin over the common off‐target kinases (Dyrks and Clks) with an IC50 of 0.155 μM for haspin. Molecular docking studies explained the remarkable selectivity of 18 and 19, elucidating how the new scaffold can be modified to toggle between inhibition of haspin or Clk4, despite the high homology of the ATP‐binding sites. Their distinguished profile allows these compounds to be marked as interesting chemical probes to assess the selective inhibition of haspin and/or Clk4.
Early executive functioning predicts externalizing problems in neurodiverse preschoolers
Authors: All Katherine , Chawarska Katarzyna , Macari Suzanne L. 
Published: March 2024

AbstractChildren with autism spectrum disorder (ASD) often exhibit externalizing problems, which have been linked with increased anxiety and depression, peer rejection, and parental stress. Identification of early predictors of externalizing behaviors in autism will facilitate identification of vulnerable children and implementation of early preventative interventions. There is ample evidence that executive functioning, social functioning, and temperament are predictive of later externalizing problems in general populations, but less is known about these relations in ASD and other neurodiverse populations, particularly in the early preschool years. To address this gap, we assessed the relations between executive functioning, social functioning, and temperament at age 3 and externalizing problems at age 5 in a sample of neurodiverse children with ASD and other neurodevelopmental disorders and delays. Analyses revealed that severity of early executive functioning impairment predicted increased externalizing problems. Severity of social autism symptoms moderated this relationship such that the effect of executive functioning on externalizing problems decreased as autism symptoms increased. These findings suggest that executive functioning is an important target for identifying and developing interventions for vulnerable children and underscore the necessity of considering severity of autism symptoms when researching the development of externalizing problems in children with neurodevelopmental disorders.
Computer‐aided design to enhance the stability of aldo‐keto reductase KdAKR
Authors: Dai Chen , Tian Jia‐Xin , Chen Yu‐Feng , Ni Yue‐Han , Cui Lei , Cao Hai‐Xing , Song Lin‐Lin , Xu Shen‐Yuan , Wang Ya‐Jun , Zheng Yu‐Guo 
Published: March 2024

AbstractThe aldo‐keto reductase (AKR) KdAKR from Kluyvermyces dobzhanskii can reduce t‐butyl 6‐chloro‐(5S)‐hydroxy‐3‐oxohexanoate ((5S)‐CHOH) to t‐butyl 6‐chloro‐(3R,5S)‐dihydroxyhexanoate ((3R,5S)‐CDHH), which is the key chiral intermediate of rosuvastatin. Herein, a computer‐aided design that combined the use of PROSS platform and consensus design was employed to improve the stability of a previously constructed mutant KdAKRM6. Experimental verification revealed that S196C, T232A, V264I and V45L produced improved thermostability and activity. The “best” mutant KdAKRM10 (KdAKRM6‐S196C/T232A/V264I/V45L) was constructed by combining the four beneficial mutations, which displayed enhanced thermostability. Its T5015 and Tm values were increased by 10.2 and 10.0°C, respectively, and half‐life (t1/2) at 40°C was increased by 17.6 h. Additionally, KdAKRM10 demonstrated improved resistance to organic solvents compared to that of KdAKRM6. Structural analysis revealed that the increased number of hydrogen bonds and stabilized hydrophobic core contributed to the rigidity of KdAKRM10, thus improving its stability. The results validated the feasibility of the computer‐aided design strategy in improving the stability of AKRs.
Renewable energy use, slack financial resources, and board attributes: Does energy efficiency policy matter?
Authors: Uyar Ali , Gerged Ali Meftah , Kuzey Cemil , Karaman Abdullah S. 
Published: March 2024

AbstractThis study examined the impact of slack financial resources, board characteristics (such as gender diversity, tenure, and skill/expertise), and energy efficiency policies on firms' consumption of renewable energy. Using a dataset of 17,753 observations from 2002 to 2019, we primarily utilized fixed‐effects regression, among other methods, for robustness analysis. We find that while slack financial resources, board gender diversity, and energy efficiency policies are positively associated with more renewable energy consumption, board skill is negatively associated with it. Interaction effects showed that firms with more female and tenured directors effectively utilize slack financial resources for increased renewable energy consumption, unlike firms with more expert directors. Energy efficiency policies enhanced the positive impact of female directors on renewable energy consumption but mitigated the influence of expert directors, weakening their association.
Host cell proteins in monoclonal antibody processing: Control, detection, and removal
Authors: Ito Takao , Lutz Herb , Tan Lihan , Wang Bin , Tan Janice , Patel Masum , Chen Lance , Tsunakawa Yuki , Park Byunghyun , Banerjee Subhasis 
Published: March 2024

AbstractHost cell proteins (HCPs) are process‐related impurities in a therapeutic protein expressed using cell culture technology. This review presents biopharmaceutical industry trends in terms of both HCPs in the bioprocessing of monoclonal antibodies (mAbs) and the capabilities for HCP clearance by downstream unit operations. A comprehensive assessment of currently implemented and emerging technologies in the manufacturing processes with extensive references was performed. Meta‐analyses of published downstream data were conducted to identify trends. Improved analytical methods and understanding of “high‐risk” HCPs lead to more robust manufacturing processes and higher‐quality therapeutics. The trend of higher cell density cultures leads to both higher mAb expression and higher HCP levels. However, HCP levels can be significantly reduced with improvements in operations, resulting in similar concentrations of approx. 10 ppm HCPs. There are no differences in the performance of HCP clearance between recent enhanced downstream operations and traditional batch processing. This review includes best practices for developing improved processes.
When will we have a clone? An industry perspective on the typical CLD timeline
Authors: Clarke Howard , Mayer‐Bartschmid Anke , Zheng Chenxing , Masterjohn Elizabeth , Patel Falguni , Moffat Mark , Wei Qingxiang , Liu Ren , Emmins Robyn , Fischer Simon , Rieder Stephanie , Kelly Thomas 
Published: March 2024

AbstractCell line development (CLD) represents a complex but highly critical process during the development of a biological drug. To shed light on this crucial workflow, a team of BioPhorum members (authors) has developed and executed surveys focused on the activities and effort involved in a typical CLD campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering three distinguishable stages of a standard CLD process: (1) Pre‐transfection, including vector design and construction; (2) Transfection, spanning the initial introduction of vector into cells and subsequent selection and analysis of the pools; and (3) Single Cell Cloning and Lead Clone Selection, comprising methods of isolating single cells and confirming clonal origin, subsequent expansion and screening processes, and methods for identifying and banking lead clones. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. In this survey review, the authors interpret and highlight responses for antibody development and, where relevant, contrast complex molecule development challenges to provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line.
Myofascial junction: Emerging insights into the connection between deep/muscular fascia and muscle
Authors: Pirri Carmelo , Petrelli Lucia , Guidolin Diego , Porzionato Andrea , Fede Caterina , Macchi Veronica , De Caro Raffaele , Stecco Carla 
Published: March 2024

AbstractMuscles and fasciae are mutually connected and are influenced by force transmission. However, the anatomical connectivity and histological features of these structures remain unclear. The aim of this study was to assess the evidence for connection between muscles and deep/muscular fasciae. We assessed this relationship in different topographical regions of human cadavers and in mice. The results showed that myofascial junctions (MFJ) were made up of collagen I immune‐positive structures occupying an average area of 5.11 ± 0.81 μm2, distributed in discrete regions at the interface between muscle and fascia with an average density of 9.7 ± 2.51 MFJ/mm and an average inclination angle of 35.25 ± 1.52°. These specialized structures also showed collagen III and HA immunopositivity and the presence of elastic fibers. The human myofascial junction can be visualized, opening emerging insights into the connection between deep/muscular fascia and muscle.
Helping college students with autism spectrum disorder: Exploring factors affecting use of counselling
Authors: Noble Nicole , Bueno Nicholas , Zatopek Audrey , Hernandez Jeremias 
Published: March 2024

AbstractIntroductionIndividuals with autism spectrum disorder (ASD) experience mental health concerns at a higher prevalence rate than the general population, yet mental health professionals have limited education, training and experience in counselling individuals with ASD.MethodsTo better understand the unique mental health concerns this population encounters, this qualitative study explored the experiences of 102 college students with ASD as they considered, attended and stopped counselling.ResultsSpecifically, this study investigated the motives the participants reported for attending counselling, the reasons professionals indicated that the participants should attend counselling, the barriers the participants were confronted with in seeking counselling and the causes for terminating counselling.ConclusionBased on these findings, implications for counselling this population and future research are provided.
Investigating the Effects and Mechanisms of Cyclomorusin on Osteoclasts in a High Glucose Environment
Authors: Guo Dong‐Gui , Zhu Jun , Wang Hui‐Juan , Pan Bo‐Wen 
Published: March 2024

AbstractDiabetes mellitus is an endocrine disease characterized by prolonged hyperglycemia. Prolonged high blood sugar levels interfere with the differentiation and maturation process of OBs and OCs, leading to the onset of osteoporosis. However, OCs differentiation and maturation is a complex regulatory process. In this study, we used a co‐culture system of RAW264.7 and MC3T3‐E1 cells under HG concentration to explore the effect of CYM on OCs in a HG environment. The effects of CYM on the formation and function of OCs were observed using TRAP‐positive cell counts and bone resorption pits. Then, mRNA and protein expression levels of OCs‐related genes were detected by real‐time qPCR and western blotting. The results showed that CYM had an inhibitory effect on OCs differentiation and bone resorption, reduced mRNAs expression of OCs‐associated genes, and downregulated RANKL/RANK/TRAF6 pathway that mediates OCs differentiation. CYM could be a promising natural compound against diabetic osteoporosis.
Synthesis, Theoretical Study, and Anticonvulsant Evaluation of N‐Arylenaminones
Authors: Jiménez‐Vázquez Hugo A. , Guevara‐Salazar J. Alberto , Quintana‐Zavala Delia 
Published: March 2024

AbstractN‐Arylenaminones are highly versatile compounds which can be synthesized in relatively simple ways. In this work we explored the synthesis of the four monosubstituted N‐(4‐R‐phenyl)enaminones 3 a (R=NO2), 3 b (R=F), 3 c (R=H), and 3 d (R=OMe) with the goal of determining the influence of the substituents′ electronic effects on tautomer stability and biological activity. These compounds were analyzed by means of Density Functional Theory calculations (DFT), to evaluate the relative stability of the possible tautomers. We found that the enaminone structure is the most stable with respect to the ketoimine and iminoenol forms. In addition, all four compounds display anticonvulsant activity, with 3 d being the one that mostly increased latency and mostly decreased the number of convulsions with respect to the control group. The suggested mechanism of action involves blockage of the voltage‐dependent Na+ channels, considering that these molecules meet the structural characteristics needed to block the receptor, as is the case of the positive control molecules phenytoin (PHT) and valproic acid (VPA).
Novel Triazole‐Containing “Dipeptides”: Synthesis, Molecular Docking and Analgesic Activity Studies
Authors: Ghochikyan Tariel V. , Zhamharyan Arusyak G. , Afrikyan Shushanik G. , Frangyan Vardges R. , Galstyan Armen S. 
Published: March 2024

AbstractDipeptides of a new structure based on β‐triazolalanines and (L)‐α‐amino acids were synthesized and optimal conditions were developed that ensure both chemical and optical purity of the final products. Molecular docking was carried out and possible intermolecular interactions of dipeptides with potential targets were established. Based on these studies, the analgesic property of chosen dipeptides was studied and it was found that some compounds possess revealed antinociceptive activity in the tail‐flick test.
Efficient Transferase Engineering for SAM Analog Synthesis from Iodoalkanes
Authors: Schülke Kai H. , Fröse Jana S. , Klein Alina , Garcia‐Borràs Marc , Hammer Stephan C. 
Published: March 2024

AbstractS‐Adenosyl‐l‐methionine (SAM) is an important cosubstrate in various biochemical processes, including selective methyl transfer reactions. Simple methods for the (re)generation of SAM analogs could expand the chemistry accessible with SAM‐dependent transferases and go beyond methylation reactions. Here we present an efficient enzyme engineering strategy to synthesize different SAM analogs from “off‐the‐shelf” iodoalkanes through enzymatic alkylation of S‐adenosyl‐l‐homocysteine (SAH). This was achieved by mutating multiple hydrophobic and structurally dynamic amino acids simultaneously. Combinatorial mutagenesis was guided by the natural amino acid diversity and generated a highly functional mutant library. This approach increased the speed as well as the scale of enzyme engineering by providing a panel of optimized enzymes with orders of magnitude higher activities for multiple substrates in just one round of enzyme engineering. The optimized enzymes exhibit catalytic efficiencies up to 31 M−1 s−1, convert various iodoalkanes, including substrates bearing cyclopropyl or aromatic moieties, and catalyze S‐alkylation of SAH with very high stereoselectivities (>99 % de). We further report a high throughput chromatographic screening system for reliable and rapid SAM analog analysis. We believe that the methods and enzymes described herein will further advance the field of selective biocatalytic alkylation chemistry by enabling SAM analog regeneration with “off‐the‐shelf” reagents.