bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Integrated Approach to Identify the Q‐Markers of Banxia‐Houpo Decoction Based on Nontargeted Multicomponent Profiling, Network Pharmacology, and Chemometrics
Authors: Wang Long , Wu Weigang , Li Guoxiang , Chen Haiyang , Fan Yinyin , Chen Wei , Zhou Guifang , Li Wenlong 
Published: November 2024

ABSTRACTIntroductionThe inherent complexity of traditional Chinese medicine (TCM) poses significant challenges in directly correlating quality evaluation with clinical efficacy. Banxia‐Houpo Decoction (BHD), a classical TCM formula, has demonstrated efficacy in treating globus hystericus. However, the intricate composition of BHD, which contains both volatile and non‐volatile active components, complicates efforts to ensure its consistent quality and clinical effectiveness.ObjectiveThe aim of this study was to introduce an integrated approach that combines non‐targeted multicomponent analysis, network pharmacology, and multivariate chemometrics to identify quality markers for the effective quality control of BHD.Materials and MethodsFirst, a nontargeted high‐definition MSE method based on ultraperformance liquid chromatography–quadrupole time‐of‐flight–mass spectrometry (UHPLC‐QTOF‐MS) was developed for the comprehensive multi‐component characterization of BHD. Next, the quality markers of nonvolatile compounds in BHD were identified through network pharmacology analysis. Subsequently, volatile organic compounds (VOCs) in BHD samples were analyzed via headspace solid‐phase microextraction–gas chromatography–mass spectrometry (HS‐SPME‐GC‐MS) and headspace gas chromatography–ion mobility spectrometry (HS‐GC‐IMS). Finally, the orthogonal partial least squares discriminant analysis (OPLS‐DA) model was applied to screen for potential markers.ResultsBased on in‐house library‐driven automated peak annotation and comparison with 25 reference compounds, 128 components were identified for the first time. Additionally, honokiol, magnolol, magnoflorine, 6‐gingerol, rosmarinic acid, and adenosine were preliminarily identified as potential quality markers for BHD through network pharmacology analysis. By employing two complementary techniques, HS‐SPME‐GC‐MS and HS‐GC‐IMS, a total of 145 volatile compounds was identified in the BHD samples. Four potential differential VOCs in the BHD samples were further identified based on the variable importance in projection (VIP ≥ 1.5) using HS‐GC‐IMS combined with chemometric analysis.ConclusionIn conclusion, this study not only contributes to establishing quality standards for BHD but also offers new insights into quality assessment and identification in the development of classical formulations enriched with volatile components.
Diverse reactivity of maleimides in polymer science and beyond
Authors: Kirkpatrick Bruce E , Anseth Kristi S , Hebner Tayler S 
Published: November 2024

AbstractMaleimides are remarkably versatile functional groups, capable of participating in homo‐ and copolymerizations, Diels–Alder and (photo)cycloadditions, Michael additions, and other reactions. Their reactivity has afforded materials ranging from polyimides with high upper service temperatures to hydrogels for regenerative medicine applications. Moreover, maleimides have proven to be an enabling chemistry for pharmaceutical development and bioconjugation via straightforward modification of cysteine residues. To exert spatiotemporal control over reactions with maleimides, multiple approaches have been developed to photocage nucleophiles, dienes, and dipoles. Additionally, further substitution of the maleimide alkene (e.g. monohalo‐, dihalo‐, thio‐, amino‐ and methyl‐maleimides, among other substituents) confers tunable reactivity and dynamicity, as well as responsive mechanical and optical properties. In this mini‐review, we highlight the diverse functionality of maleimides, underscoring their notable impact in polymer science. This moiety and related heterocycles will play an important role in future innovations in chemistry, biomedical, and materials research. © 2024 The Author(s). Polymer International published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Rapid Synthesis of Self‐Healing, pH‐Responsive IA‐Based Hydrogels via Frontal Polymerization
Authors: Irfan Muhammad , Zhai Jiang , Li Qing , Chen Su , Li Guo‐Xing , Xiao Ji Jun 
Published: November 2024

ABSTRACTSelf‐healing polymeric gels have emerged as a promising class of materials due to their ability to repair damage autonomously, offering significant advantages for various applications. Nevertheless, a major hurdle to their widespread practical use lies in their often‐compromised mechanical strength and long reaction time. Herein, we present the synthesis of a new type of self‐healing hydrogels using poly(itaconic acid‐co‐hydroxypropyl alcohol‐co‐acrylic acid), also known as poly(IA‐co‐HPA‐co‐AAc), by a frontal polymerization (FP) method. The rapid reaction rate of FP facilitates the swift and energy‐efficient synthesis of the hydrogels within 10 min, eliminating the need for prolonged reaction times. Additionally, the results revealed that the synthesized hydrogels exhibited pH‐dependent responsiveness, robust mechanical integrity, and autonomous self‐healing capabilities, obviating the requirement for external stimuli. The exceptional self‐healing properties can be attributed to the extensive hydrogen bonding network between the polymer chains, enabling them to recover up to 80% of their original mechanical strength. Rheological analysis confirmed the presence of a robust and stable gel network, evidenced by high storage modulus (G′) values across the entire frequency and strain sweep tests. This research addresses a significant knowledge gap in IA‐based hydrogels by introducing a rapid, optimized method for constructing self‐healing materials through hydrogen bonding interactions.
Informing pregnancy dose via target‐mediated drug disposition modeling and simulations for a recombinant human monoclonal antibody
Authors: Moc Willeford Courtney , Shetty Krithika , Sheridan Douglas , Engler Frank 
Published: November 2024

AbstractRLYB212 is a human monoclonal anti‐human platelet antigen (HPA)‐1a immunoglobulin gamma 1 in clinical development as a subcutaneous injection for the prevention of maternal alloimmunization to fetal HPA‐1a leading to fetal and neonatal alloimmune thrombocytopenia (FNAIT). This analysis developed a target‐mediated drug disposition (TMDD) model to simultaneously characterize RLYB212 pharmacokinetics (PK) and HPA‐1a‐positive platelet dynamics in HPA‐1b/b (HPA‐1a‐negative) volunteers. The model was then used to perform simulations to inform a dosing regimen in a phase II clinical study in pregnant women, where simulations accounted for physiological changes throughout pregnancy. Allometric scaling (0.75) for clearance and intercompartment transfer rate and volume (1) was included in the base model to account for variations in body weight. A 0.06 mg RLYB212 dose with a loading dose of 0.12 mg was identified as the optimal dosing regimen of RLYB212, which maintained exposures below the target upper boundary of ~10 ng/mL throughout pregnancy. This work presents an application of the TMDD model that advances the quantitative clinical pharmacology toolkit to understand monoclonal antibody PK in pregnancy.
Pharmacokinetic/pharmacodynamic analysis of geographic atrophy lesion area in patients receiving pegcetacoplan treatment or sham
Authors: Crass Ryan L. , Prem Komal , Gaudreault Francois , Lusk Elizabeth , Ribeiro Ramiro , Chapel Sunny , Baumal Caroline R. 
Published: November 2024

AbstractPegcetacoplan is a complement C3/C3b inhibitor indicated for the treatment of geographic atrophy (GA). A population pharmacokinetic (PK)/pharmacodynamic (PD) analysis of pegcetacoplan used GA lesion area measurements from three clinical studies to determine the effect of pegcetacoplan exposure on GA progression. A base disease progression model was developed using data from sham‐treated eyes and untreated fellow eyes, followed by treatment effect assessment in dose–response and PK/PD models. In total, 1501 patients from FILLY (NCT02503332), OAKS (NCT03525613), and DERBY (NCT03525600) received intravitreal pegcetacoplan 15 mg monthly or every other month (EOM) or sham treatment monthly or EOM and were included in the population analysis of lesion area. Disease progression over time was adequately described as linear‐with‐time over the 24‐month maximal study duration. Disease‐specific covariates associated with slower lesion growth were unilateral, unifocal, and subfoveal GA lesions and >20 intermediate or large drusen groups (≥63 μm) at baseline. The dose–response model estimated 0.80‐fold (95% CI: 0.75, 0.84) and 0.83‐fold (95% CI: 0.78, 0.87) reductions in GA lesion growth rate with pegcetacoplan monthly and EOM, respectively, versus sham. A relationship between vitreous humor concentration and GA lesion growth rate was quantified as 2.6% per unit of log‐transformed vitreous pegcetacoplan concentration in the PK/PD model. PK/PD predictions of treatment effect based on exposure (pegcetacoplan monthly: 0.80 [90% CI: 0.77, 0.84]; pegcetacoplan EOM: 0.83 [90% CI: 0.80, 0.86]) were consistent with predictions based on dose response. These results support the benefit of pegcetacoplan administered monthly or EOM in slowing GA lesion growth.
Concentration–QT modeling demonstrates that the selective mineralocorticoid receptor modulator, balcinrenone (AZD9977), does not prolong QT interval
Authors: Sundell Jesper , Rekic Dinko , Melin Johanna , Johansson Susanne , Ebrahimi Ahmad , Dota Corina , Parkinson Joanna 
Published: November 2024

AbstractBalcinrenone (AZD9977) is a selective mineralocorticoid receptor modulator in development in combination with dapagliflozin for treatment of heart failure with impaired kidney function and chronic kidney disease. A prespecified concentration–QT analysis was performed based on data from a phase I single ascending dose study prospectively designed as a thorough QT study substitute. Oral single doses of balcinrenone of 5–800 mg, plus fractionated doses of 800 and 1200 mg, were evaluated in 62 healthy male participants. Time‐matched 12‐lead digital electrocardiogram and plasma concentrations were measured pre‐dose and up to 48 h postdose in the participants. Analysis was performed using a linear mixed‐effect model, where baseline‐adjusted Fridericia‐corrected QT interval (ΔQTcF) was a dependent variable and time‐matched balcinrenone concentration an independent variable. The model fit was deemed adequate by evaluation of goodness‐of‐fit plots, and the slope of the concentration–ΔQTcF relationship was nonsignificant (−0.003 ms/μmol/L; 95% confidence interval [CI]: −0.181, 0.176). The high clinical exposure scenario was defined as the maximum concentration (2.156 μmol/L) following the highest expected therapeutic dose (40 mg once daily) under fed conditions and in presence of a strong cytochrome P450 3A4 inhibitor. Estimated baseline‐adjusted and placebo‐corrected QTcF interval (ΔΔQTcF) at this concentration was 0.35 ms (90% CI: −1.29, 2.00). Furthermore, the upper 90% ΔΔQTcF CI was estimated to be below the threshold of regulatory concern of 10 ms at all observed concentrations (up to 16.7 μmol/L). Hence, it can be concluded that balcinrenone does not induce QTcF prolongation at the high clinical exposure scenario.
Therapeutic Potential of Ocimum basilicum L. Extract in Alleviating Autistic‐Like Behaviors Induced by Maternal Separation Stress in Mice: Role of Neuroinflammation and Oxidative Stress
Authors: Amini‐Khoei Hossein , Taei Nafiseh , Dehkordi Hossein Tahmasebi , Lorigooini Zahra , bijad Elham , Farahzad Anahita , Madiseh Mohammad Rahimi 
Published: November 2024

ABSTRACTA confluence of genetic, environmental, and epigenetic factors shapes autism spectrum disorder (ASD). Early‐life stressors like MS play a contributing role in this multifaceted neurodevelopmental disorder. This research was to explore the efficacy of Ocimum basilicum L. (O.B.) extract in mitigating behaviors reminiscent of autism prompted by maternal separation (MS) stress in male mice, focusing on its impact on neuroinflammation and oxidative stress. MS mice were treated with O.B. extract at varying dosages (20, 40, and 60 mg/kg) from postnatal days (PND) 51–53 to PND 58–60. Behavioral experiments, including the Morris water maze, three‐chamber test, shuttle box, and resident‐intruder test, were conducted post‐treatment. The method of maternal separation involved separating the pups from their mothers for 3 h daily, from PND 2 to PND 14. Molecular analysis of hippocampal tissue was performed to assess gene expression of Toll‐like receptor 4 (TLR4), tumor necrosis factor‐α (TNF‐α), and interleukin‐1β (IL‐1β). Hippocampal and serum malondialdehyde (MDA) levels and total antioxidant capacity (TAC) were measured. O.B. extract administration resulted in the amelioration of autistic‐like behaviors in MS mice, as evidenced by improved spatial and passive avoidance memories and social interactions, as well as reduced aggression in behavioral tests. O.B. extract attenuated oxidative stress and neuroinflammation, as indicated by decreased MDA and increased TAC levels, as well as downregulation of TLR4, TNF‐α, and IL‐1β expression in the hippocampus. O.B. extract may offer a novel therapeutic avenue for ASD, potentially mediated through its anti‐inflammatory and antioxidant properties.
A Comprehensive Review of Antimicrobial Agents Against Clinically Important Bacterial Pathogens: Prospects for Phytochemicals
Authors: Ghosh Soumyadip , Basu Soumya , Anbarasu Anand , Ramaiah Sudha 
Published: November 2024

ABSTRACTAntimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes. Therefore, in this review, we have addressed the challenges and focused on various phytochemicals as antimicrobial agents acting on the membranes of clinically important bacterial pathogens. Antibacterial phytochemicals comprise diverse group of agents found in a wide range of plants. These compounds have been found to disrupt cell membranes, inhibit enzymes, interfere with protein synthesis, generate reactive oxygen species, modulate quorum sensing, and inhibit bacterial adhesion, making them promising candidates for the development of novel antibacterial therapies. Recently, polyphenolic compounds have been reported to have proven efficacy against nosocomial multidrug‐resistant pathogens. However, more high‐quality studies, improved standards, and the adoption of rules and regulations are required to firmly confirm the clinical efficacy of phytochemicals derived from plants. Identifying potential challenges, thrust areas of research, and considering viable approaches is essential for the successful clinical translation of these compounds.
Wavelength Stabilization of Entangled Biphotons Using Dynamic Temperature Compensation for Quantum Interference Applications
Authors: Liu Yuting , Hong Huibo , Xiang Xiao , Quan Runai , Li Xinghua , Liu Tao , Cao Mingtao , Zhang Shougang , Dong Ruifang 
Published: November 2024

AbstractIn this paper, a dynamic temperature compensation method is presented to stabilize the wavelength of the entangled biphoton source, which is generated on spontaneous parametric down‐conversion from a magnesium oxide doped periodically poled lithium niobate waveguide. Utilizing the dispersive Fourier transformation technique, the photon wavelength variation is monitored in case of conventional static temperature control, revealing a long‐term wavelength drift up to 556.8 pm over a 14‐h measurement period. A Hong‐Ou‐Mandel (HOM) interferometer is constructed to assess the impact on quantum applications, showing a decrease in visibility from 95.5% to 69.4%. To address this issue, a digital proportional‐integral‐differential algorithm is implemented to dynamically compensate the working temperature variation of the waveguide, thereby instantly stabilizing the wavelength to a peak‐to‐peak fluctuation of +138.05 pm/‐127.61 pm with the standard deviation being 30.49 pm. The wavelength stability shows more than a hundredfold enhancement in terms of Allan deviation, reaching at an averaging time of 10000 s. With the dynamic control in operation, the HOM interference visibility turns to stable at 96.1% ± 0.6%. The method provides a simple and accessible solution for precisely controlling and stabilizing the wavelength of entangled biphotons, thus improving performance in various quantum information processing applications.
Optimization of protein identifications through the use of different chromatographic approaches and bioinformatic pipelines
Authors: Castaño Jesus D. , Beaudry Francis 
Published: November 2024

RationaleSelection of proteomic workflows for a given project can be a daunting task. This research provides a guide outlining the impact on protein identification of different steps such as chromatographic separation, data acquisition strategies, and bioinformatic pipelines. The data presented here will help experts and nonexpert proteomic users to increase proteome coverage and peptide identification.MethodsHeLa protein digests were analyzed through different C18 chromatographic columns (15 and 50 cm in length), using top 12 data‐dependent acquisition (DDA), top 20 DDA, and data‐independent acquisition (DIA) with a nanospray source in positive mode in a Thermo Q Exactive instrument. The raw data were analyzed using different search engines, rescoring approaches, and multi‐engine searches. The results were analyzed in the context of peptide and protein identifications, precursor properties, and computation requirements to understand the differences between methods.ResultsOur results showed that higher column lengths and top N DDA approaches were able to significantly increase protein identifications. The use of multiple search engines yielded limited gains, whereas the use of rescoring methods clearly outperformed other strategies. Finally, DIA approaches, although successful at generating new identifications, had a limited performance influenced by the previous collection of DDA data, which could prohibitively increase instrument time. Nonetheless, the use of library‐free methods showed promising results.ConclusionsOur results highlight the impact of different experimental approaches on proteome coverage. Changes in chromatographic columns, data acquisition, or bioinformatic analysis can significantly increase the number of protein identifications (>400%). Thus, this research provides a reference upon which to build a successful proteomic workflow with different considerations at every step.
Mechanical and Tribological Properties of Carbon Fiber Reinforced POM Composite Filled With Maleamidic Acid Treated Carbon Nanotube
Authors: Jian Li , Xiaodong Tang 
Published: November 2024

ABSTRACTIn order to attain improved mechanical properties of the carbon fiber (CF) reinforced polyoxymethylene (POM) composite, maleamidic acid treated carbon nanotube (CNT) was deposited on carbon fiber. The mechanical properties of composites have been investigated. The tensile strength values of the treated CF/POM composites at all CNT mixing ratios are found to be higher than that of untreated one. The surface morphologies of the fractured surfaces of the composites were recorded using scanning electron microscopy (SEM) to gain information about the fiber–matrix interfacial adhesion in the composites. The friction coefficient of all the CF/POM/CNT composites decrease as the load increases from 10 to 20 N under the same sliding speed of 1000 r/min. XPS results showed that the formation of C–O, C=O, and O–C=O based species give rise to chemical bonds of the CF and the POM.
Computational Insight into Warfarin Blockage by Silymarin Components via DFT and Molecular Docking
Authors: Bardak Fehmi 
Published: November 2024

AbstractSilymarin has been utilized as a traditional, complementary, and integrative medicine for centuries, despite a poor molecular‐level understanding of its interactions with other medicinal compounds and enzyme structures. However, recent studies indicate that this supplement, as with many others, should be considered with caution because it has the potential to interact with many drugs, medical plants, and foods. Silymarin is composed of several compounds that are either enantiomeric or have similar structures. Thus, this study presents the electronic structure properties and reactivity characteristics of silymarin components and warfarin through density functional theory modeling at the M06‐2X/6–311 + G(d,p) level of theory. The ligand‐protein interactions of the compounds with human serum albumin, cytochrome P450 (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) enzymes, and alanine transaminase were presented using molecular docking. The critical residue‐based interactions of silymarin components and warfarin were fingerprinted. Furthermore, their drug‐likeness and toxicity characteristics were compared to those of warfarin and the well‐known flavonoids, taxifolin, and quercetin. The possibility of inhibiting the target enzymes to reduce the effectiveness of warfarin has been highlighted.
Advancement in Heterogeneous Catalysts for the Synthesis of Benzothiazole Derivatives
Authors: Kohli Sahil , Rawat Srishti , Rathee Garima , Nagar Shailly , Rawat Manish , Saraswat Vandana 
Published: November 2024

AbstractBenzothiazole derivatives, a class of heterocyclic compounds, hold significant relevance in medicinal chemistry, materials science, and agrochemicals due to their diverse biological activities and applications. The conventional synthetic routes often involve harsh conditions and generate significant waste, prompting the exploration of more sustainable approaches. This work offers a comprehensive analysis of the developments in the use of heterogeneous catalysts for the production of benzothiazole derivatives, covering research from 2013 onward. Compared to traditional techniques, heterogeneous catalysts provide improved sustainability, efficiency, and recyclability. The review covers many heterogeneous catalysts and discusses their selectivity, recyclability, and catalytic activity. The utilization of heterogeneous catalysts is noteworthy as it facilitates the synthesis process's overall sustainability by allowing for milder reaction conditions, less environmental effect, and easier catalyst separation and recovery. The potential of heterogeneous catalysis in promoting the production of benzothiazole derivatives and satisfying the increasing need for these substances in various industrial applications is also highlighted.
Synthesis of Paracetamol‐Appended Bis 1,2,3‐Triazole Analogues as Anti‐Inflammatory Agents
Authors: Bathini Vineesha , Thumma Vishnu , Mallikanti Veerabhadraiah , Angajala Kishore Kumar , Pochampally Jalapathi 
Published: November 2024

AbstractParacetamol‐based bis 1,2,3‐triazole analogues were synthesized involving copper‐catalyzed click chemistry protocol. The new compounds were characterized by 1H NMR, 13C NMR, and mass spectral techniques. All the compounds were evaluated for their in vitro anti‐inflammatory properties using diclofenac as standard reference. The compound 6b with chlorine and fluorine functions displayed outstanding activity with IC50 values of 7.34 ± 0.45 µM and 7.84 ± 0.47 µM, respectively. Compound 6g with methyl and fluorine functions displayed best activity with IC50 values of 9.34 ± 0.22 µM and 9.40 ± 0.35 µM, respectively. Compound 6i, 6k, 6f, 6a, 6e, 6h, 6j, and 6l exhibited promising activity with respect to diclofenac. Using PyRx tool, the molecular docking study against crystal structure of COX‐2 proved the binding efficacies with notable binding interactions.