bluuebunny/crossref_metadata_2025_split huggingface dataset:
How many Mutations are needed to Evolve the Chemical Makeup of a Synthetic Cell?
Authors: Lefèvre‐Morand Rodrigue Yves Louis , Nikel Pablo Iván , Acevedo‐Rocha Carlos G. 
Published: January 2024

AbstractThe chemical evolution of a synthetic cell endowed with a synthetic amino acid as building block, analog to tryptophan, required the emergence of key mutations in genes involved in, inter alia, the general stress response, amino acid metabolism, stringent response, and chemotaxis. Understanding adaptation mechanisms to non‐canonical biomass components will inform strategies for engineering synthetic metabolic pathways and cells.
Ginsenoside Rg3 overcomes tamoxifen resistance through inhibiting glycolysis in breast cancer cells
Authors: Zhao Wenhui , Ma Jianli , Zhang Qingyuan , Zhang Han , Ma Wenjie , Li Shuo , piao Ying , Zhao Shu , Dai Shaochun , Tang Dabei 
Published: January 2024

AbstractTamoxifen (TAM) resistance poses a significant clinical challenge in human breast cancer and exhibits high heterogeneity among different patients. Rg3, an original ginsenoside known to inhibit tumor growth, has shown potential for enhancing TAM sensitivity in breast cancer cells. However, the specific role and underlying mechanisms of Rg3 in this context remain unclear. Aerobic glycolysis, a metabolic process, has been implicated in chemotherapeutic resistance. In this study, we demonstrate that elevated glycolysis plays a central role in TAM resistance and can be effectively targeted and overcome by Rg3. Mechanistically, we observed upregulation of 6‐phosphofructo‐2‐kinase/fructose‐2,6‐bisphosphatase 3 (PFKFB3), a key mediator of glycolysis, in TAM‐resistant MCF‐7/TamR and T‐47D/TamR cells. Crucially, PFKFB3 is indispensable for the synergistic effect of TAM and Rg3 combination therapy, which suppresses cell proliferation and glycolysis in MCF‐7/TamR and T‐47D/TamR cells, both in vitro and in vivo. Moreover, overexpression of PFKFB3 in MCF‐7 cells mimicked the TAM resistance phenotype. Importantly, combination treatment significantly reduced TAM‐resistant MCF‐7 cell proliferation in an in vivo model. In conclusion, this study highlights the contribution of Rg3 in enhancing the therapeutic efficacy of TAM in breast cancer, and suggests that targeting TAM‐resistant PFKFB3 overexpression may represent a promising strategy to improve the response to combination therapy in breast cancer.
The use of silicon in the membrane electrode assembly of fuel cells
Authors: Antolini Ermete 
Published: January 2024

AbstractSilicon, silicon‐based and Si‐containing materials are widely used and play different roles in fuel cells. These materials have been used overall in polymer electrolyte membrane fuel cells, but also in solid oxide fuel cells and phosphoric acid fuel cells. The most used Si compounds in fuel cells are SiO2 and SiC. In this work an overview of the use of Si‐based and Si‐containing materials in the membrane electrode assembly of fuel cells is presented.
From Small‐Area Observations to Insight: Surface‐Feature‐Extrapolation of Anodes for Alkaline Oxygen Evolution Reaction
Authors: Jain Adarsh , Vinayakumar Vineetha , Olean‐Oliveira André , Marcks Christian , Chatwani Mohit , Mechler Anna K. , Andronescu Corina , Segets Doris 
Published: January 2024

AbstractIn this study, we developed a statistical framework, named multistage data quantification (MSDQ), to evaluate representative surface characteristics such as surface roughness, surface area, and homogeneity score of cobalt oxide‐based anodes, and contributing to a deeper insight into the quality of the anode surface. Atomic force microscopy (AFM) was employed to capture the surface morphology of two anodes that have a comparable loading of cobalt oxide but exhibit distinct morphological features. Application of MSDQ exposed notable disparities in surface characteristics across these anodes, underlining the critical importance of MSDQ in precise surface characterization. Specifically, surface roughness, surface area and homogeneity score effectively elucidated the disparities in electrocatalytic activity for the oxygen evolution reaction (OER), as quantified through scanning droplet cell (SDC) measurements. By conducting a systematic comparative analysis, the respective contributions of the extrinsic surface characteristics of the anodes to the intrinsic electrocatalytic material property could be differentiated and quantified. Applications of our findings range from benchmarking of anodes to optimization of anode manufacturing processes.
Mechanistic Insights into the electron‐transfer driven substrate activation by [4Fe‐4S]‐dependent Enzymes
Authors: Wei Wen‐Jie , Liao Rong‐Zhen 
Published: January 2024

Abstract[4Fe‐4S]‐dependent enzymes catalyze many different types of biological reactions. The quantum chemical cluster approach and the combined quantum mechanics/molecular mechanics approach, with the broken symmetry approach, are powerful tools for understanding the reaction mechanism in enzymes. This review discusses examples of the computational studies on [4Fe‐4S]‐dependent enzymes, focusing on the electron‐transfer driven substrate activation.
A Rational Design of Electrochemically and Photophysically Tunable Triarylamine Luminophores by Consecutive (Pseudo‐)Four‐Component Syntheses
Authors: Kohlbecher Regina , Müller Thomas J. J. 
Published: January 2024

AbstractThe concatenation of Suzuki coupling and two‐fold Buchwald‐Hartwig amination in sequentially palladium‐catalyzed consecutive multicomponent syntheses paves a concise, convergent route to diversely functionalized para‐biaryl‐substituted triarylamines (p‐bTAAs) from simple, readily available starting materials. An extensive library of p‐bTAAs permits comprehensive investigations of their electronic properties by absorption and emission spectroscopy, cyclic voltammetry, and quantum chemical calculations, which contribute to a deep understanding of their electronic structure. The synthesized p‐bTAAs exhibit tunable fluorescence from blue to yellow upon photonic excitation with quantum yields up to 98 % in solution and 92 % in the solid state. Furthermore, a pronounced bathochromic shift of the emission maxima by increasing solvent polarity indicates positive emission solvatochromism. Aggregation‐induced enhanced emission (AIEE) in dimethyl sulfoxide (DMSO)/water mixtures causes the formation of intensely blue fluorescent aggregates. Cyclic voltammetry shows reversible first and second oxidations of p‐bTAAs at low potentials, which are tunable by variation of the introduced para substituents. 3D Hammett plots resulting from the correlation of oxidation potentials and emission maxima with electronic substituent parameters emphasize the rational design of tailored p‐bTAAs with predictable electrochemical and photophysical properties.
Versatile Spectroscopic Cell for Operando Studies in Heterogeneous Catalysis Using Tender X‐ray Spectroscopy in Fluorescence Mode
Authors: Suarez Orduz H. A. , Heck S.‐L. , Dolcet P. , Watier Y. , Casapu M. , Grunwaldt J.‐D. , Glatzel P. 
Published: January 2024

AbstractThe design and commissioning of a cell suitable for operando studies using high‐energy‐resolution fluorescence‐detected X‐ray absorption near‐edge structure (HERFD‐XANES) spectroscopy in the tender X‐ray regime is reported. The cell is optimized for measurements within the energy range of 1.5 keV to 4.5 keV. It has a plug‐flow geometry and can be used for sieved powder samples, analogous to reactors employed for laboratory tests. The functionality of the spectroscopic cell is demonstrated in the area of emission control using CO oxidation as target reaction over 1 wt.% Rh/γ‐Al2O3 as catalyst. We show how HERFD‐XANES at the Rh L3‐edge captures variations in the noble metal structure resulting from the interaction with the support material and reactant molecules. Moreover, distinct structural changes were identified along the catalyst bed as a function of temperature and local gas mixture.
Pharmacokinetics, Bioequivalence, and Safety Evaluation of Two Oral Formulations of Calcium Dobesilate Capsules in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Wang Yanrong , Liu Ying , Tang Liyuan , Gao Jie , LI Hongmin , Dai Xinya , Chen Ran , Wang Fengqin 
Published: January 2024

AbstractTo determine the pharmacokinetics (PK), safety, and bioequivalence profiles of 0.5‐g calcium dobesilate capsules in both fasting and fed states for the test drug and reference drug. A randomized‐sequence, single‐dose, open‐label, 2‐period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR202000268‐01). The fasting and fed studies, both involving 24 subjects, were conducted. A single dosage of either the reference or the test preparation was given to each eligible subject in a 1:1 ratio, followed by a 7‐day rest interval before the administration of the alternative formulation. After taking the capsules, plasma samples were taken for 48 hours, and using liquid chromatography‐tandem mass spectrometry, the calcium dobesilate level was determined. The PK parameters evaluated in the study included the maximum serum concentration (Cmax), area under the plasma concentration‐time curve (AUC) from time 0 to the last quantifiable concentration, AUC from time 0 to infinity, half‐life, time to Cmax, and terminal elimination rate constant. In addition, the safety evaluation encompassed monitoring fluctuations in vitals (temperature, pulse, and blood pressure) and laboratory tests (urinalysis, hepatic function, blood biochemistry, and hematology), as well as recording the emergence of adverse events (AEs). The geometric mean ratio (GMR) of the test/reference medications was used to assess bioequivalence by determining if the 90% confidence intervals of the GMR fell within the predefined range of 80%‐125%. AEs were assessed as safety end points. The study included 48 healthy Chinese volunteers (with n = 24 each for the fasting and the fed conditions), and no subjects dropped out for any reason. The differences in the PK metrics for the test and reference drugs for both conditions were insignificant (P > .05). For bioequivalence, irrespective of whether the food was consumed or not, the range of the 90% confidence intervals of the GMR for Cmax, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity was between 80% and 125%. In the experiment, no serious AEs were recorded. Our findings revealed that the calcium dobesilate capsules used as the reference and the test drugs were both bioequivalent. Irrespective of whether the healthy Chinese volunteers consumed food or not, the PK and safety profiles were comparable.
Prediction of M3B4‐type MBenes as Promising Catalysts for CO2 Capture and Reduction
Authors: Li Mingxia , Zhang Yaoyu , Gao Dongyue , Li Ying , Yu Chao , Fang Yi , Huang Yang , Tang Chengchun , Guo Zhonglu 
Published: January 2024

AbstractThe rational design of novel catalysts with high activity and selectivity for carbon dioxide reduction reaction (CO2RR) is highly desired. In this work, we have extensive investigations on the properties of two‐dimensional transition metal borides (MBenes) to achieve efficient CO2 capture and reduction through first‐principles calculations. The results show that all the investigated M3B4‐type MBene exhibit remarkable CO2 capture and activation abilities, which proved to be derived from the lone pair of electrons on the MBene surface. Then, we emphasize that the investigated MBenes can further selectively reduce activated CO2 to CH4. Moreover, a new linear scaling relationship of the adsorption energies of potential‐determining intermediates (*OCH2O and *HOCH2O) versus ΔG(*OCHO) has been established, where the CO2RR limiting potentials on MBenes are determined by the different fitting slopes of ΔG(*OCH2O) and ΔG(*HOCHO), allowing significantly lower limiting potentials to be achieved compared to transition metals. Especially, two promising CO2RR catalysts (Mo3B4 and Cr3B4 MBene) exist quite low limiting potentials of −0.48 V and −0.66 V, as well as competitive selectivity concerning hydrogen evolution reactions have been identified. Our research results make future advances in CO2 capture by MBenes easier and exploit the applications of Mo3B4 and Cr3B4 MBenes as novel CO2RR catalysts.
Charge‐Transfer Modulation of Emissivity in Polarized Diketopyrrolopyrroles
Authors: Kumar G. Dinesh , Banasiewicz Marzena , Hu Wei‐Hsu , Hany Roland , Vakuliuk Olena , Nüesch Frank , Deperasińska Irena , Gryko Daniel T. 
Published: January 2024

AbstractStrongly polarized donor‐acceptor‐donor′ diketopyrrolopyrroles, differing in the type of key donor moiety, were designed and synthesized to examine how this affects the non‐radiative decay. Dyes possessing less electron‐rich N‐carbazolyl substituents are characterized by strong yellow emission from a locally excited (LE) state, whereas replacing this donor with more electron‐rich N‐phenothiazinyl substituent changes the relative position of charge‐transfer (CT) and LE states, leading to weaker, reddish‐orange fluorescence. As a result, there is solvent‐dependent charge‐transfer emission shifted to as far as 700 nm. The opening of the intersystem crossing channel to the triplet state possessing CT character is the most likely cause of the fluorescence quantum yield variation in some cases. These results reveal that the fate of molecules in their excited state can be fine‐tuned by very small structural changes.
Setting‐zero analysis for multistage amplifier design
Authors: Lei Junqing , Wu Chenjian 
Published: January 2024

SummaryA setting‐zero analysis method is presented to facilitate the prediction of zeros in multistage amplifiers. The main objective of this method is to simplify the analysis process of such amplifiers while improving the overall performance, and the feasibility is confirmed by various examples presented in this paper. By proposing a single‐capacitor cascode Miller compensation three‐stage amplifier using setting‐zero analysis, this paper has theoretically verified that the addition of a grounding second‐stage compensation capacitor is unnecessary. Measurement results show that this amplifier consumes a current of 38 μA at a 1.2 V supply voltage, with a 103 dB open‐loop gain. When driving a 1 nF load capacitor, this design achieves 1.88 MHz gain bandwidth and 73° phase margin, with a 3.33 V/μs average slew rate and an average 1% settling time of 0.40 μs under the unity‐gain configuration.
ICH Q14‐inspired novel approach to establish an SFC‐based purity method for carbamazepine
Authors: Schmidt Alexander H. , Stanic Mijo , Parr Maria Kristina 
Published: January 2024

AbstractThe proposed ICH Q14 guideline “Analytical procedure development” describes science and risk‐based approaches for development and maintenance of analytical procedures suitable for the assessment of the quality of drug substances and drug products. As a case study, the systematic development and validation of a supercritical fluid chromatography (SFC)‐based purity method for carbamazepine is presented. Systematic analytical quality by design (AQbD) principles were applied using the software package Fusion QbD to the method development approach. The relationship between chromatographic parameters and the responses of interest were examined to improve the reliability of the method by understanding, reducing, and controlling sources of variability. Method performance qualification in terms of method robustness was finally carried out with the parameters that were classified as critical after method development and a validation study met previously set acceptance criteria. The developed SFC purity method for carbamazepine demonstrated readiness as a viable alternative to the official HPLC method published in the Ph.Eur. with improved peak resolution, improved peak symmetry, and faster analysis times (3 min vs. 80 min for the official method). Its inherent reliability illustrates the superiority of AQbD in method development and application for drug quality assurance.
Capillary electrokinetic chromatography for chiral separation of potential SARS‐CoV‐2 3CL protease inhibitors
Authors: Brier Lucile , Furman Christophe , Charton Julie , Deprez Benoit , Lipka Emmanuelle 
Published: January 2024

AbstractIn this work, a capillary electrophoresis method was developed as a quality control tool to determine the enantiomeric purity of a series of five chiral compounds evaluated as potential severe acute respiratory syndrome coronavirus 2 3CL protease inhibitors. The first cyclodextrin tested, that is, highly sulfated‐β‐cyclodextrin, at 6% (m/v) in a 25 mM phosphate buffer, using a capillary dynamically coated with polyethylene oxide, at an applied voltage of 15 kV and a temperature of 25°C, was found to successfully separate the five derivatives. The limits of detection and quantification were calculated together with the greenness score of the method in order to evaluate the method in terms of analytical and environmental performance. In addition, it is noteworthy that simultaneously high‐performance liquid chromatography separation of the enantiomers of the same compounds with two different columns, the amylose tris(3,5‐dimethylphenylcarbamate)‐coated and the cellulose tris(3,5‐dichlorophenylcarbamate)‐immobilized on silica stationary phases, was studied. Neither the former stationary phase nor the latter was able to separate all derivatives in a mobile phase consisting of n‐heptane/propan‐2‐ol 80/20 (v/v).
Achieving dynamic efficiency in pharmaceutical innovation: Identifying the optimal share of value and payments required
Authors: Woods Beth , Lomas James , Sculpher Mark , Weatherly Helen , Claxton Karl 
Published: January 2024

AbstractIt has been argued that cost‐effectiveness analysis of branded pharmaceuticals only considers static efficiency, neglects dynamic effects and undermines incentives for socially valuable innovation. We present a framework for designing pharmaceutical pricing policy to achieve dynamic efficiency. We develop a coherent framework that identifies the long‐term static and dynamic benefits and costs of offering manufacturers different levels of reward. The share of value that would maximise long‐term population health depends on how the quantity and quality of innovation responds to payment. Using evidence of the response of innovation to payment, the optimal share of value of new pharmaceuticals to offer to manufacturers is roughly 20% (range: 6%–51%). Reanalysis of a sample of NICE technology appraisals suggests that, in most cases, the share of value offered to manufacturers and the price premium paid by the English NHS were too high. In the UK, application of optimal shares would offer considerable benefits under both a public health objective and a broader view of social welfare. We illustrate how an optimal share of value can be delivered through a range of payment mechanisms including indirect price regulation via the use of different approval norms by an HTA body.
Effect of Dufour and chemical reaction on an unsteady magneto hydrodynamics flow past an exponentially moving plate
Authors: Mangamma Ch. , Pramod Kumar P. , Malga Bala Siddulu , Appidi Lakshmi , Matta Sweta 
Published: January 2024

AbstractThe aim of the study is to measure the Dufour number effects on the flow patterns and heat transfer in an exponentially accelerated infinite vertical plate embedded in a porous medium in the presence of heat source and chemical reaction. Time‐dependent variations in temperature, velocity, and other factors should be taken into consideration due to the flow's unsteadiness. The fluid considered is a gray, absorbing/emitting radiation but nonscattering medium. Using the finite element method, a set of nondimensionless equations is solved analytically. Results are discussed graphically for concentration, temperature, and velocity profiles. Skin friction, Sherwood number, and Nusselt number are also explained for flow parameters through graphs.
The Lnc‐ENST00000602558/IGF1 axis as a predictor of response to treatment with tripterygium glycosides in rheumatoid arthritis patients
Authors: Gao Yang , Wang Xiaoyue , Gao Yanfeng , Bai Jian , Zhao Yanpeng , Wang Renyi , Wang Hanzhou , Zhu Guangzhao , Wang Xixi , Han Xiaochen , Zhang Yanqiong , Wang Hailong 
Published: January 2024

AbstractAimsGrowing clinical evidence suggests that not all patients with rheumatoid arthritis (RA) benefit to the same extent by treatment with tripterygium glycoside (TG), which highlights the need to identify RA‐related genes that can be used to predict drug responses. In addition, single genes as markers of RA are not sufficiently accurate for use as predictors. Therefore, there is a need to identify paired expression genes that can serve as biomarkers for predicting the therapeutic effects of TG tablets in RA.MethodsA total of 17 pairs of co‐expressed genes were identified as candidates for predicting an RA patient's response to TG therapy, and genes involved in the Lnc‐ENST00000602558/GF1 axis were selected for that purpose. A partial‐least‐squares (PLS)‐based model was constructed based on the expression levels of Lnc‐ENST00000602558/IGF1 in peripheral blood. The model showed high efficiency for predicting an RA patient's response to TG tablets.ResultsOur data confirmed that genes co‐expressed in the Lnc‐ENST00000602558/IGF1 axis mediate the efficacy of TG in RA treatment, reduce tumor necrosis factor‐α induced IGF1 expression, and decrease the inflammatory response of MH7a cells.ConclusionWe found that genes expressed in the Lnc‐ENST00000602558/IGF1 axis may be useful for identifying RA patients who will not respond to TG treatment. Our findings provide a rationale for the individualized treatment of RA in clinical settings.