bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and Derivatization of a Carbene‐Sulfinate Palladacycle
Authors: Teng Qiaoqiao , Zhang Lina , Liu Wei , Huang Guangqing , Arachchige Dinuk Thulsan Munasinghe , Yang Sen , Meng Qi 
Published: February 2025

ABSTRACTAn unprecedented C‐SO oxidative‐cleavage reaction was disclosed for fused thiazoline‐1‐oxide‐azolium salts with Ag2O to afford Ccarbene^SO2 palladacyclic complexes. The complex could undergo reversible redox reactions with Br2 to afford an intermediary N‐heterocyclic carbene (NHC) complex with a sulfonyl bromide dangling group. This complex allowed divergent hydrolysis, alcoholysis, and aminolysis to prepare a series of sulfonate and sulfonamide functionalized NHC complexes and a Ccarbene^NSO2 palladacycle via further deprotonation. Selected complexes were employed in catalysis to show excellent activities in the aqueous Suzuki‐Miyaura coupling reactions and hydroamination reactions of aryl alkynes.
Combining 16S rRNA Gene Sequencing and Metabolomics to Study the Therapeutic Effects of Sangge Jiangzhi Pill on Hyperlipidemia Rats
Authors: Pan Xuan , Wang Jianhai , Liu Shuo , Yu Ruonan , Li Ziyu , Zhang Yumeng , Wang Miao , Zhao Chunjie , Zhao Min 
Published: February 2025

ABSTRACTSangge Jiangzhi pill, as a traditional Chinese medicine compound preparation, can be used to treat hyperlipidemia. However, the specific material basis and mechanism of action of the Sangge Jiangzhi pill are not clear. In this study, gut microbiota and host metabolism were investigated using 16S rRNA sequencing and metabolomics techniques. The changes in body weight, organ index, serum biochemical levels, and liver pathology demonstrated that the Sangge Jiangzhi pill reduced body weight and attenuated fat accumulation in hyperlipidemic rats. The results of gut microbiota analysis demonstrated that the Sangge Jiangzhi pill significantly enhanced the richness and diversity of gut microbiota in hyperlipidemia rats. Moreover, it regulated the relative abundance of Ligilactobacillus, Limosilactobacillus, Lactobacillus, Blautia, Parabacteroides, Helicobacter, Colidextribacter, Desulfovibrio, Rikenella, and Tuzzerella to protect the intestinal barrier and relieve the oxidative stress reaction. Metabonomics analysis showed that a total of 32 differential metabolites were identified in feces. The results of the correlation analysis revealed a significant association between intestinal microbiota and fecal metabolites. These results suggested that the Sangge Jiangzhi pill could achieve the purpose of treating hyperlipidemia by regulating gut microbiota imbalance and metabolic activity disorder.
Characterization and Identification of the Metabolites of Tuxobertinib in Rat, Dog, Monkey, and Human Liver Microsomes by Liquid Chromatography Combined With High Resolution Mass Spectrometry
Authors: Liu Pei , Huang Jing , Zhao Yao , Zhang Jing , Xue Qianrong , Zhang Shuqin 
Published: February 2025

ABSTRACTTuxobertinib is an EGFR tyrosine kinase inhibitor, which was undergoing clinical development for the treatment of non‐small cell lung cancer (NSCLC). The aim of this study was to characterize the metabolites of tuxobertinib in liver microsomes and recombinant cytochrome P450 enzymes and to propose the metabolic pathways. The metabolites were generated by individually incubating tuxobertinib (5 μM) with rat, dog, monkey, and human liver microsomes, NADPH, and at 37°C for 60 min. The samples were analyzed by ultra‐high‐performance liquid chromatography‐quadrupole/orbitrap mass spectrometry (UPLC‐Q/Orbitrap‐MS) using electrospray ionization in positive ion mode. The metabolites were characterized and identified by their accurate MS and MS/MS data. Totally, 18 metabolites were detected, and their structure was characterized. All these metabolites were ‐NADPH‐dependent. The metabolic pathways of tuxobertinib included O‐dealkylation, hydroxylation, oxidative deamination, dehydrogenation, and the opening of morpholine. M4 (O‐dealkylation) was the major metabolite in all species. No human specific metabolite was observed. In human recombinant CYP3A4, 13 metabolites were detected, and CYP3A4 was the primary enzyme responsible for tuxobertinib metabolism. This is the first report on the metabolism of tuxobertinib, which provided an overview of the metabolism profiles of tuxobertinib in vitro, which is helpful in understanding its safety and action.
Quantitative Comparison of Different Parts of Tribulus terrestris L. at Different Harvest Times and Comparison of Antihypertensive Effects at the Same Harvest Time
Authors: Li Fei , DU De‐Feng , Chen Ming‐Yue , Gong Xiao‐Meng , Su Hui‐Min , Wang Yi‐Fan , Shi Lei , Zhang Chao , Guo Fei 
Published: February 2025

ABSTRACTThe whole plant of Tribulus terrestris (TT) is used to treat hypertension and cardio‐cerebrovascular diseases. The harvest time has an important influence on the quality of medicinal plants. Therefore, it is necessary to study the effect of harvest time on the content of components in different parts of TT and compare the antihypertensive effect of different parts of TT at harvest time with a relatively high content of 14 components. Ultraviolet–visible spectrometry (UV–Vis spectrometry) was used to determine the total saponin content in T. terrestris fruit (TTF), T. terrestris stems (TTS), and T. terrestris leaves (TTL) at different harvest times. Within the studied harvest times, the total saponin content was higher in TTL than in TTF or TTS. Ultra‐high performance liquid chromatography‐triple quadrupole tandem mass spectrometry analysis revealed significant differences in the spatial and temporal differences in the content of 14 components in the three plant parts. The multivariate statistical analysis identified six components as markers of different TT content in the different parts. The suitable TTF harvest period was from August 11 to September 1, while TTS and TTL were suitable for harvesting from July 21 to September 11. The treatment effects on blood pressure, serum indexes, and thoracic aorta morphology confirmed that the antihypertensive effects of TTL were better than those of TTF or TTS. The study emphasized the effect of harvest time on the content of components in different parts of TT and confirmed that TTS and TTL also had medicinal value.
Unique Liquid Chromatography Technique for Determining a New Selective PPARα Modulator Drug (Pemafibrate) in the Tablet Dosage Form, Robustness by Design Expert in the Light of Quality by Design
Authors: Han Fei , Yang Yankun , Bai Zhonghu , Nathi Rathnakar , Konduru Naresh 
Published: February 2025

ABSTRACTThis research study presents a precise, accurate, and linear liquid‐chromatography method for the determination of pemafibrate in tablet dosage forms, despite the presence of a high volume of excipients. Various challenges were addressed through experimental approaches and evidence‐based solutions. The method employs a suitable stationary phase, X‐Bridge C18 (150 × 4.6 mm, 3.5 μm), and an appropriate isocratic program. Key parameters include a flow rate of 1.0 mL/min, a column temperature of 40°C, an injection volume of 10 μL, and a runtime of 15 min. The wavelength was set at 210 nm because of its high response. Mobile phase optimization, based on experimental results, consists of 0.1% H3PO4 buffer and acetonitrile in a 40:60 v/v ratio. The method has been validated according to ICH Q2 (R2) and Ch. P <9101> guidelines, achieving a recovery rate of 99.1% to 100.5% at levels of 50%, 100%, and 150%. Linearity was demonstrated from 25% to 300% concentration levels, with a correlation coefficient (r2) value of 1.000. Precision results showed %RSD values of 1.0 and 1.1. Forced degradation studies indicated sensitivity to acid hydrolysis stress conditions and stability under physical stress conditions.
Taguchi L9 Optimization of Microwave‐Assisted Solid–Liquid Duo Heating for Berberine Extraction With HPTLC Analysis
Authors: Satija Saurabh , Vyas Manish , Pandey Parijat , Garg Munish 
Published: February 2025

ABSTRACTWe present an optimized approach for the extraction of berberine using microwave‐assisted solid–liquid duo heating. The conventional procedure relies on the simultaneous heating of the sample matrix and the dissolving solvent under microwave energy. To improve the efficiency of this process, we employed the Taguchi L9 orthogonal design methodology, focusing on key extraction parameters, including microwave power, irradiation time, solute‐solvent ratio, and temperature. Berberine content was quantified using high‐performance thin‐layer chromatography (HPTLC). Our findings revealed that the most influential parameters in the berberine extraction process were microwave power (ranked as the most critical factor), followed by irradiation time (second in importance), and temperature (third in significance). Utilizing the dual heating approach in microwave‐assisted extraction (MAE) led to a more precise and efficient determination of extraction parameters, resulting in enhanced accuracy and higher yield. Additionally, this optimized method significantly reduced the overall extraction time, making it an ideal choice for berberine extraction under optimal conditions.
Comparative Chromatographic Analysis of Amino Acids in the Seeds of Three Nigella L. Representatives
Authors: Shanaida Mariia , Korablova Olha , Rakhmetov Dzhamal , Serafyn Oksana , Lashch Neonila , Shanaida Volodymyr 
Published: February 2025

ABSTRACTAmino acids are an important class of primary metabolites that can exhibit various pharmacological activities. In this study, the comparative gas chromatography–mass spectrometry (GC/MS) analysis of free and total amino acids in the seeds of three representatives of the Nigella L. genus (Nigella arvensis L., Nigella damascena L. [cultivar “Rizdvyana zirochka”], and Nigella sativa L. [cultivar “Faraon”]) was conducted under their cultivation in Ukraine. Regarding the free state of amino acids, 11 were detected in the raw material of N. damascena, and 9 were found in both N. sativa and N. arvensis. It was found the highest content of L‐aspartic acid, specifically 50.359 mg/g in N. damascena (cultivar “Rizdvyana zirochka”), 33.816 mg/g in N. sativa (cultivar “Faraon”), and 31.028 mg/g in N. arvensis. It was revealed that L‐leucine, L‐valine, and L‐tyrosine dominated among the essential amino acids detected in the free state in the seeds of all studied samples. L‐glycine and L‐proline had the highest amounts among the semiessential amino acids, while L‐aspartic acid, L‐glutamic acid, and L‐phenylalanine are predominant in the nonessential group. Some of the detected in the Nigella sp. amino acids possess significant therapeutic potential.
Metabolomic Analysis of Serum Reveals a Unique Metabolomic Profile in Patients With Myositis and Identified Several Potential Biomarkers in Polymyositis Versus Dermatomyositis Patients
Authors: Xie Shuoshan , Li Caiyan , Lu Congyu , Liu Yanjuan 
Published: February 2025

ABSTRACTDM and PM were the two major subtypes in myositis; among which, a unique metabolomic and biomarker profile remains lacking. Serum from 36 diagnosed myositis patients (28 DM and 8 PM) and 29 healthy controls was analyzed using HPLC‐Q‐TOF‐MS/MS. PLS‐DA was conducted through MetaboAnalyst 5.0 to identify the differential metabolites. The KEGG analysis was utilized to observe the related metabolic pathways. The potential biomarker value was assessed using ROC analysis. The relationship between the clinical characteristics and the levels of identified differential metabolites was analyzed using R language. PLS‐DA showed a clear separation between healthy controls and myositis patients, and 131 differential metabolites were identified. KEGG analysis uncovered multiple disturbed metabolic pathways. Besides, nine differential metabolites were identified between PM and DM patients, which were involved in pentose and glucuronate interconversions. ROC curve analysis revealed the AUC of these identified metabolites is above 0.7. Among them, indoxyl sulfate, oleamide, and palmitoylethanolamide presented moderate or strong correlation with clinical characteristics. Metabolomics presents a different spectrum between myositis patients and healthy controls, PM and DM patients. Besides, indoxyl sulfate, oleamide, and palmitoylethanolamide may be potential biomarkers in distinguishing PM from DM.
A Simple Rapid HPLC‐UV Method for Assessing C‐Terminal Arginine Content in Darbepoetin Alfa
Authors: Zybin Dmitry I. , Klishin Anatoly A. , Orlova Natalia V. , Seregin Yuri A. , Sorokina Tatiana S. , Kapustin Dmitry V. 
Published: February 2025

ABSTRACTUpon the development of biosimilar drugs, the structural, physical–chemical, and functional similarity to the original drug should be ensured. We have proposed a simple and rapid HPLC‐UV method for assessing the content of C‐terminal Arg166 in darbepoetin alfa samples, in particular after their isolation from the culture fluid. All the stages of the described method (from the sample extraction to obtaining a chromatographic profile) take about 5 h. The proposed approach will be useful for laboratories developing a technology for producing recombinant darbepoetin alfa, to assess the quality of the product, and for subsequent optimization of the production process.
A Dual Diagnosis of Okur–Chung Neurodevelopmental Syndrome and Becker Muscular Dystrophy: Inquiry Into the Lower Limits of Neurodevelopmental Functioning Attributable to Muscular Dystrophy
Authors: Liu Victoria , Hanson Eva , Owens Joshua W , Hopkin Robert J. , Shillington Amelle 
Published: February 2025

ABSTRACTPurpose:This case discusses the limits of neurodevelopmental functioning attributable to Duchenne's Muscular Dystrophy (DMD) dysfunction.MethodA 3‐year‐old male presented with global developmental delay, growth failure, and dysmorphic facial features. An SNP microarray revealed an interstitial duplication in exon 55 of DMD suggestive of Becker Muscular Dystrophy (BMD), but his degree of delays led to follow‐up exome sequencing revealing a pathogenic CSNK2A1 variant diagnostic for Okur–Chung Neurodevelopmental Syndrome.FindingsLarge cohorts predict a full‐scale IQ (FSIQ) of 88.3 ± 13.9 among all patients with BMD and 86.1 ± 15.0 among all patients with DMD, while variants impacting the brain dystrophin isoform Dp140 are associated with FSIQ of 77.7 ± 10.8 in BMD and 78.8 ± 18.6 in DMD.ConclusionAn FSIQ one standard deviation below these expected ranges should prompt screening for alternative causes of neurodevelopmental delays, and an FSIQ two standard deviations below these ranges should prompt broad‐spectrum genetic testing.
Identification of Genetic Variants in Status Epilepticus Associated With Fever
Authors: Hanafusa Hiroaki , Yamaguchi Hiroshi , Morisada Naoya , Ye Ming Juan , Oikawa Shizuka , Tokumoto Shoichi , Nishiyama Masahiro , Nozu Kandai , Nagase Hiroaki 
Published: February 2025

AbstractPurposeStatus epilepticus associated with fever (SEF) is often encountered in pediatric emergency departments, and some patients develop neurological emergencies, such as acute encephalopathy (AE). Although numerous genetic variants of developmental and epileptic encephalopathy (DEE) have been reported, the frequency of these disease‐associated variants of SEF is unknown. The first aim of this study was to investigate the associated genetic variants of SEF. The second aim was to compare the variations in genes between SEF and DEE.MethodThis retrospective, clinical observational study included patients with SEF or DEE who visited Kobe University Hospital or Kobe University affiliated hospitals and provided consent for a genetic diagnosis of SEF or DEE between January 1, 2021, and December 31, 2022.FindingFifteen patients with SEF and 27 patients with DEE consented to a genetic diagnosis and were included in the study. The detection rate of genetic variants was lower in patients with SEF (26.7%) than in those with DEE (63.0%), although there is no statistically significant difference (p = 0.05, Fisher's exact test). Analysis of patients with DEE revealed a wide variety of causative genes for DEE (16 different genes), whereas in SEF cases, only SCN1A variants were detected.ConclusionOur study is the first to clarify the detection rates of different genetic variants in SEF. Patients with SEF may have less genetic involvement in the onset of epileptic seizures, compared to those with DEE.
Pachysandra Species: Phytochemistry, Pharmacology, and Synthetic Advance—A Mini‐Review
Authors: Ha Nguyen Manh , Hoai Le The , Son Ninh The 
Published: February 2025

ABSTRACTPachysandra (the family Buxaceae) is a small genus containing medicinal plants. This brief communication first describes its phytochemistry and pharmacological activities. More than 140 metabolites were separated, and steroidal alkaloids‐based pregnane skeletons were the main compounds obtained. (+)‐Axillaridine A, epipachysamines B and D–E, pachysandrines B–D, pachysamines A–B, pachystermine A, and (+)‐spiropachysine are likely primary metabolites. Various compounds were identified as previously undescribed compounds. Non‐alkaloids, such as sterols, triterpenoids, mono‐phenols, coumarins, megastigmanes, and lignans, were also identified. Pachysandra steroidal alkaloids showed potential for drug development as they exhibited anticancer, antimicrobial, antiestrogenic, and gastric protective activities. The amine substituents at carbons C‐3 and C‐20 might cause differences in pharmacological results. The underlying mechanisms, such as the PI3K/Akt/mTOR signaling pathway, were proposed to explain pharmacological activities. Pachysandra phytotoxins exhibited antioxidative and antidiabetic activities. Synthetic products of Pachysandra steroidal alkaloids had higher cytotoxic effects than the natural compounds.
Luminescence and Electroanalytical Properties of Carbon Quantum Dots in the Context of Immunosensor Design
Authors: Alemu Yemataw Addis , Louw Clementine J , Paolucci Francesco , Valenti Giovanni , Baker Priscilla G L 
Published: February 2025

AbstractElectroanalytical techniques are powerful tools in biological sensing because of their sensitivity and versatility. In recent decades, great attention has been given to the fabrication of electroactive nanomaterial‐based biosensors. In this context, carbon quantum dots (CQDs) have received special attention and have been used to develop many sensors because of their remarkable advantages such as high photostability, high solubility and stability in water, biocompatibility, high photoluminescence emission intensities, and simple methods of synthesis. Since they are very small in size, they have high surface area to volume ratios which in turn can allow good catalytic activities of the working electrodes in electrochemical reactions. Being motivated by these advantages, in this work we prepared two types of carbon quantum dots (CQD‐COOH and CQD‐NH2) and used them to modify screen printed carbon electrodes (SPCEs) for detection of Troponin I (cTnI). These carbon quantum dot – modified SPCE immunosensors have offered promising results for the determination of cTnI with a limit of detection 62 pg/mL and 171 pg/mL, respectively. This simple approach to sensor design further offers valuable insights into the construction of paper based printed electrodes modified with new carbon‐based nanomaterials as immunosensors for detection of other biomarkers of various diseases.
ESI‐MS‐Visualization of Cyanoarene Photocatalysts by Specific Supramolecular Interaction with Br‐Anion
Authors: Shlapakov Nikita S. , Burykina Julia V. , Kobelev Andrey D. , Kostyukovich Alexander Yu. , Minyaev Mikhail E. , Ananikov Valentine P. 
Published: February 2025

AbstractIsophthalonitrile derivatives (IPNs) have emerged as promising organic photocatalysts due to their efficiency and accessibility; however, their inherent lability under light‐induced conditions poses significant challenges in monitoring their transformation pathways. Understanding these pathways is crucial for optimizing photocatalytic processes and enhancing reaction efficiency. In this study, we present a novel approach utilizing electrospray ionization mass spectrometry (ESI‐MS) to visualize cyanoarene photocatalysts by taking advantage of their specific supramolecular interaction with bromide anions. Our findings reveal that bromide ions facilitate the detection of IPNs and their transformation products with high sensitivity and selectivity, even in complex reaction environments. The interaction predominantly occurs in the gas phase, minimizing interference in solution‐based transformations. The developed anion‐enhanced detection (AED‐ESI‐MS) not only provides real‐time insights into photocatalyst behavior but also opens new possibilities for the detailed mechanistic investigation of light‐driven reactions. The proposed AED‐ESI‐MS approach using other anions may offer broad applicability and may be worth studying further across various photocatalytic systems.
A Comprehensive Analysis of the Radiographic Characteristics and Bilateral Symmetry of the Mental Foramen
Authors: Algabri Radhwan , Abulohoom Faisal , Fadag Abdelrahman , Al‐Sharani Hesham , Al‐Aqab Sami , Al‐Hutbany Nassr , Alryashi Emad , Keshk Ahmed , Alqutaibi Ahmed Yaseen 
Published: February 2025

ABSTRACTObjectivesThere is currently a scarcity of data on the frequency and bilateral symmetry of the position and other characteristics of the mental foramen (MF) and accessory mental foramina in Yemen. The objective of this study was to analyze the position and other characteristics, as well as the symmetry of the MF, in a sample of the Yemeni population.Materials and MethodsA retrospective analysis was conducted on a sample of 500 digital panoramic radiographs (1000 sides). The study examined various characteristics of the MF, including horizontal and vertical positions, shapes, appearances, and the presence of accessory mental foramina. Additionally, the study explored potential associations between these characteristics and variables such as the subject's gender, sides, and symmetry. Data analysis was performed using SPSS, and statistical significance was evaluated using chi‐square tests; the p value was set at 0.05.ResultsThe horizontal position of the MF was most frequently observed between the first and second lower premolars (63.2%). The vertical position of the MF was predominantly below the apices of the lower premolars (66.2%). The majority of MFs had a round shape (46.3%). In 72% and 75.6% of cases, there was a continuous and descending relationship between the MF and the mandibular canal, respectively. Accessory mental foramina was present in 3.8% of cases. Gender differences were significant for the shape of the MF and the pattern of the canal on the right side. The symmetry rates for various features included horizontal positions (87.4%), vertical positions (82.6%), and shapes (80.4%).ConclusionThe MF is most commonly situated horizontally between the lower premolars and vertically below the apices of these teeth. The majority of MFs showed a round shape and a continuous and descending relationship with the mandibular canal. In most instances, characteristics of the MF were symmetrical on both sides.