bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury
Authors: Chase Davis H. , Bebenek Adrian M. , Nie Pengju , Jaime‐Figueroa Saul , Butrin Arseniy , Castro Danielle A. , Hines John , Linhares Brian M. , Crews Craig M. 
Published: February 2024

AbstractBrachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed “undruggable”. Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases. Recently, afatinib, an FDA‐approved kinase inhibitor, has been shown to modulate brachyury levels in multiple chordoma cell lines. Herein, we use afatinib as a lead to undertake a structure‐based drug design approach, aided by mass‐spectrometry and X‐ray crystallography, to develop DHC‐156, a small molecule that more selectively binds brachyury and downmodulates it as potently as afatinib. We eliminated kinase‐inhibition from this novel scaffold while demonstrating that DHC‐156 induces the post‐translational downmodulation of brachyury that results in an irreversible impairment of chordoma tumor cell growth. In doing so, we demonstrate the feasibility of direct brachyury modulation, which may further be developed into more potent tool compounds and therapies.
Tertiary Amides as Directing Groups for Enantioselective C−H Amination using Ion‐Paired Rhodium Complexes
Authors: Paterson Kieran J. , Dahiya Amit , Williams Benjamin D. , Phipps Robert J. 
Published: February 2024

AbstractEnantioselective C−H amination at a benzylic methylene is a vital disconnection towards chiral benzylamines. Here we disclose that butyric and valeric acid‐derived tertiary amides can undergo highly enantioselective benzylic amination using an achiral anionic Rh complex that is ion‐paired with a Cinchona alkaloid‐derived chiral cation. A broad scope of compounds can be aminated encompassing numerous arene substitutions, amides, and two different chain lengths. Excellent tolerance of ortho substituents was observed, which has not been achieved before in asymmetric intermolecular C−H amination with Rh. We speculate that the tertiary amide group of the substrate engages in hydrogen bonding interactions directly with the chiral cation, enabling a high level of organisation at the transition state for C−H amination. This is in contrast with our previous work where a substrate bearing a hydrogen bond donor was required. Control experiments led to the discovery that methyl ethers also function as proficient directing groups under the optimised conditions, potentially also acting as hydrogen bond acceptors. This finding has the promise to dramatically expand the applicability of our ion‐paired chiral catalysts.
A Ferroptosis‐Inducing Arsenene‐Iridium Nanoplatform for Synergistic Immunotherapy in Pancreatic Cancer
Authors: Zhao Xinyang , Wang Xingyun , Zhang Wei , Tian Tian , Zhang Jingyi , Wang Jing , Wei Wei , Guo Zijian , Zhao Jing , Wang Xiuxiu 
Published: February 2024

AbstractDue to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two‐dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis‐inducing effects with high drug loading capacity and, importantly, excellent anti‐cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin‐loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis‐induced chemotherapy with immunotherapy via an all‐in‐one strategy, providing new insights for future pancreatic cancer therapy.
Calcitriol restrains microglial M1 polarization and alleviates dopaminergic degeneration in hemiparkinsonian mice by boosting regulatory T‐cell expansion
Authors: Xie Yangzhi , Chen Liang , Chen Jiacheng , Chen Yongjun 
Published: February 2024

AbstractObjectiveVitamin D deficiency is a risk factor for Parkinson's disease (PD) and vitamin D supplementation robustly alleviates neurodegeneration in PD models. However, the mechanisms underlying this effect require further clarification. Current evidence suggests that harnessing regulatory T cells (Treg) may mitigate neuronal degeneration. In this study, we investigated the therapeutic effects of vitamin D receptor activation by calcitriol on PD, specifically focusing on its role in Treg.MethodsHemiparkinsonian mice model was established through the injection of 6‐OHDA into the striatum. Mice were pretreated with calcitriol before 6‐OHDA injection. The motor performance, dopaminergic neuronal survival, contents of dopamine, and dopamine metabolites were evaluated. The pro‐inflammatory cytokines levels, T‐cell infiltration, mRNA expression of indicated microglial M1/M2 phenotypic markers, and microglial marker in the midbrain were detected. Populations of Treg in the splenic tissues were assessed using a flow cytometry assay. PC61 monoclonal antibody was applied to deplete Treg in vivo.ResultsWe show that calcitriol supplementation notably improved motor performance and reduced dopaminergic degeneration in the 6‐OHDA‐induced PD model. Mechanistically, calcitriol promoted anti‐inflammatory/neuroprotective Treg and inhibited pro‐inflammatory/neurodestructive effector T‐cell generation in this model. This process significantly inhibited T‐cell infiltration in the midbrain, restrained microglial activation, microglial M1 polarization, and decreased pro‐inflammatory cytokines release. This more favorable inflammatory microenvironment rescued dopaminergic degeneration. To further verify that the anti‐inflammatory effects of calcitriol are associated with Treg expansion, we applied an antibody‐mediated Treg depletion assay. As predicted, the anti‐inflammatory effects of calcitriol in the PD model were diminished following Treg depletion.ConclusionThese findings suggest that calcitriol's anti‐inflammatory and neuroprotective effects in PD are associated with its potential to boost Treg expansion.
Causal association between systemic lupus erythematosus and the risk of migraine: A Mendelian randomization study
Authors: Ren Meixuan , Yu Hangtian , Xiao Bing , Zhao Yan , Yan Jiewei , Liu Jianghong 
Published: February 2024

AbstractBackgroundNumerous studies have found that patients with systemic lupus erythematosus (SLE) often have comorbid headache, especially migraine. However, the causal relationship between genetically determined SLE and migraine risk remains unclear. Therefore, we conducted a Mendelian randomization (MR) study to explore this causal association.MethodsGenome‐wide association studies (GWAS) provided the instrumental variables. We selected summary data from GWAS of SLE as exposure (5201 SLE patients and 9066 controls). Both outcome GWAS data were from the Finnish Gene GWAS, including migraine with aura, migraine with aura and triptan purchases, and migraine without aura. The main MR approach was inverse‐variance weighted. Pleiotropy and heterogeneity were detected using the MR pleiotropy residual sum and outlier, MR‐Egger intercept test, leave‐one‐out analysis, and Cochran's Q test.ResultsThere was a significant association between genetically predicted SLE susceptibility and increased risk of migraine with aura [odds ratio (OR) = 1.05, 95% confidence interval (CI) = 1.02–1.08, p = .001]. The result was consistent when the outcome was migraine with aura and triptan purchases [OR = 1.05, 95% CI = 1.02–1.08, p = .001]. However, we found no association between SLE and migraine without aura. Our MR study showed no pleiotropy or heterogeneity.ConclusionsOur study indicates that genetic susceptibility to SLE increases the incidence of migraine with aura but not migraine without aura. It is necessary for the routine evaluation and early recognition of migraine in patients with SLE in clinical settings.
Quality Evaluation of Asparagus officinalis by Profile of Amino Acids and Mineral Elements in Different Parts Combined with Chemometrics Methods
Authors: Liu Wei , Sun Mengyu , He Yinglong , Guo Qi , Zhang Lixia , Wang Zhihao , Zhang Guofeng 
Published: February 2024

AbstractAsparagus officinalis has a homologous value in medicine and vegetables. Its immature stem, commonly called asparagus, is a central edible part. Asparagus skin and leaf also contain rich nutrients. However, these parts are often discarded. This study investigated amino acid and mineral elements in immature stem, skinless asparagus, asparagus skin, and leaf. Their quality was further evaluated by chemometrics methods such as principal component analysis and neural network analysis. The results showed amino acid content was high in immature stem and skinless asparagus and low in leaf, whereas the mineral elements were in four parts. Quality evaluation results showed four parts were divided into three grades. Immature stem and skinless asparagus were grouped into cluster 1 with the best quality as high‐quality raw materials in food and health‐care products. Meanwhile, three AA (Cys, His, Arg) and two mineral elements (Na, Cr) were identified as quality evaluation iconic substances.
Chemical Constituents of a Marine‐derived Fungus Fusarium oxysporum F0888 and their Antibacterial Activity
Authors: Zhao ZhiYuan , Cen FuLing , Mo TuXiang , Li WanShan , Ying Chen Guang 
Published: February 2024

AbstractFive new compounds, including four hydroxyphenylacetic acid derivatives, stachylines H−K (1–4), a derivative of hydroxyphenylethanol (5), as well as seven known compounds were obtained from a marine‐derived fungus Fusarium oxysporum F0888 isolated from sediments in the South China Sea. The structures and absolute configurations of new compounds were determined by spectroscopic (IR, NMR, and HR‐ESI‐MS) analyses, comparison of optical rotations, and the modified Mosher's MTPA ester method. Antimicrobial and anti‐inflammatory activities of compounds 1–12 were tested. Unfortunately, all of isolated compounds were inactivity.
Biophysical and Biochemical Characterization of Structurally Diverse Small Molecule Hits for KRAS Inhibition
Authors: Pagba Cynthia V. , Gupta Amit K. , Dilsha Kasuni , Sadrpour Parisa , Jakubec Jacob , Prakash Priyanka , van der Hoeven Dharini , Cho Kwang‐Jin , Gilbertson Scott , Gorfe Alemayehu A. 
Published: February 2024

AbstractWe describe six compounds as early hits for the development of direct inhibitors of KRAS, an important anticancer drug target. We show that these compounds bind to KRAS with affinities in the low micromolar range and exert different effects on its interactions with binding partners. Some of the compounds exhibit selective binding to the activated form of KRAS and inhibit signal transduction through both the MAPK or the phosphatidylinositide 3‐kinase PI3K‐protein kinase B (AKT) pathway in cells expressing mutant KRAS. Most inhibit intrinsic and/or SOS‐mediated KRAS activation while others inhibit RAS‐effector interaction. We propose these compounds as starting points for the development of non‐covalent allosteric KRAS inhibitors.
Aldehyde Reductase Activity of Carboxylic Acid Reductases
Authors: Winkler Margit , Breuer Hannah G. , Schober Lukas 
Published: February 2024

AbstractCarboxylic acid reductase enzymes (CARs) are well known for the reduction of a wide range of carboxylic acids to the respective aldehydes. One of the essential CAR domains ‐ the reductase domain (R‐domain) ‐ was recently shown to catalyze the standalone reduction of carbonyls, including aldehydes, which are typically considered to be the final product of carboxylic acid reduction by CAR. We discovered that the respective full‐length CARs were equally able to reduce aldehydes. Herein we aimed to shed light on the impact of this activity on aldehyde production and acid reduction in general. Our data explains previously inexplicable results and a new CAR from Mycolicibacterium wolinskyi is presented.
Recurrent peri‐myocarditis: A rarer but unfortunate redundant presentation of thyroid storm
Authors: Nabin K. C. , Bhattarai Pratik , Zahid Erum , Pasha Muhammad Nabeel 
Published: February 2024

Key Clinical MessageThyroid storm represents a critical and life‐threatening complication from hyperthyroidism, with a notable mortality risk. Limited literature reports have explored the correlation between thyroid storm and peri‐myocarditis, although the precise pathophysiological underpinnings remain unclear. The pathophysiology of how thyroid storm and peri‐myocarditis are associated is not clearly understood; however, unfavorable prognostic factors include atrial fibrillation and recurrent thyrotoxicosis. Here, we present a case concerning recurrent peri‐myocarditis concomitant with a thyroid storm.
CO2 Photoreduction Product Selectivity with TiO2−Cu Nanocatalysts under Different Reaction Media
Authors: Nascimento Victor R. S. , Torres Juliana A. , Iga Gustavo D. , dos Santos Allef Leite , Egues Silvia M. , Filho José B. G. , Ferreira Luiz F. R. , Ribeiro Caue 
Published: February 2024

AbstractThis study explores photocatalytic conversion of CO2 using TiO2−Cu heterojunctions with different Cu contents and investigates influence of different reaction media on the process efficiency. The use of KOH favored liquid products, especially ethanol. An analysis of H2 production as the main competitive reaction was done. Sodium oxalate led to an increase in H2 evolution by approximately 600 μmol g‐1 compared to pure water, in the presence of CO2 in the reaction medium, but the blank test (without CO2) indicates a lower H2 yield (~136 μmol g−1), which suggests that the competitive reaction with CO2 also plays a role in H2 production. This role was related to the decrease of the initial pH from approximately 8.5 to 5.2, stabilizing at 5.5 at the end of the 6 h reaction. In an environment saturated with N2, the pH increases to 9 and stabilizes at 7.8 at the end of the process. In the presence of acetic acid, both CO and H2 production were suppressed, with a significant increase in the selectivity for methane via cleavage of the acid‘s carbon bond. The findings underscore the importance of optimizing reaction conditions to achieve higher yields of desired products in the photocatalytic conversion of CO2.
Hypervalent Iodine Compounds in Carbohydrate Chemistry: Glycosylation, Functionalization and Oxidation
Authors: Mahanti Mukul , Bhaskar Pal Kumar , Wallentin Carl Johan , Galan M. Carmen 
Published: February 2024

AbstractThis mini review article provides an overview on the use of hypervalent iodine compounds (HICs) in carbohydrate synthesis, focusing on their chemistry and recent applications. HICs are similar to transition metals in their reactivity but have the added benefit of being environmentally benign, and are therefore commonly used as selective oxidants and eco‐friendly reagents in organic synthesis. Herein, we summarize various synthetic uses of hypervalent iodine reagents in reactions such as glycosylation, oxidations, functionalization, and C−C bond‐forming reactions. The goal of this review is to illustrate the advantages and versatility of using HICs as an environmentally sustainable alternative to heavy metals in carbohydrate chemistry.
Chlorajaponins A—Q, Lindenane‐Related Sesquiterpenoid Dimers from Chloranthus japonicus and Their Biological Activities
Authors: Feng Wei‐Jiao , Gu Yue , Huang Pei‐Zhi , Yang Hong‐Ying , Zhang Rui , He Yi‐Lin , Lv Ting‐Hong , Li Ya , Gao Kun 
Published: February 2024

Comprehensive SummarySeventeen undescribed lindenane‐related sesquiterpenoid dimers, chlorajaponins A—Q (1—17), and 13 reported analogs (18—30) were isolated from Chloranthus japonicus Sieb. Compound 1 possesses an unprecedented 3/5/7/5/5/6/5/3 fused octacyclic scaffold, featuring a 6(5→4)‐abeo‐lindenane monomer, while 2 exhibits a 3/5/6/6/5/6/5/3 fused octacyclic scaffold. Their structures were determined through a combination of spectroscopic analyses and X‐ray crystallography. Compounds 1, 2, and 18 demonstrated significant inhibitory effects on lipid accumulation and effectively reduced the levels of triglycerides and total cholesterol, as well as the levels of aspartate aminotransferase and alanine aminotransferase in a HepG2 cell model. In addition, compounds 1, 2, and 18 significantly suppressed the protein expression of the fatty acid synthase (FASN) and the sterol regulatory element‐binding protein 1 (SREBP1). Moreover, the anti‐inflammatory assay showed that compounds 19—22 and 25 inhibited the NO production induced by lipopolysaccharide in RAW 264.7 macrophages with IC50 values of 7.89 ± 0.44, 6.25 ± 0.46, 2.98 ± 0.29, 10.77 ± 0.60, and 3.60 ± 0.28 μmol/L.
Induction of Paraquat‐Mediated Parkinsonian Phenotype in Zebrafish
Authors: Harini V. S. , Marimuthu Raghunath , Tantry M. S. Ananthakrishna , Santhakumar Kirankumar 
Published: February 2024

AbstractParaquat (PQ) is a well‐known neurotoxin closely associated with neurodegenerative Parkinson's disease (PD). Zebrafish are utilized as a model for PD research because of their well‐defined neuropathology and locomotor behavior. Here, we highlight protocols for inducing PD using PQ and analyzing locomotor activity in adult zebrafish. Basic Protocol 1 details the treatment of adult male zebrafish with 60 mg/kg PQ via intraperitoneal injection to induce a PD‐like phenotype, followed by the steps to perform a locomotor assay. Basic Protocol 2 provides step‐by‐step guidance for processing the acquired videos in ToxTrac software to understand the locomotor parameters of 0.9% saline– and 60 mg/kg PQ–injected adult zebrafish. The simplicity of the treatment strategy, low‐cost video acquisition setup, and free video processing make these protocols accessible without prior experience. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Development of Parkinson's disease features in adult zebrafishBasic Protocol 2: ToxTrac analysis for locomotor assay
The inclusion of children in divorce mediation: A continental ‘non‐directive’ approach
Authors: Brzobohatý Robin 
Published: February 2024

AbstractThis article undertakes an interdisciplinary examination of child‐inclusive mediation (CIM) in divorce and separation mediation, particularly its implementation in the Czech Republic through the Mediation and Education Centre in Brno (MEDUC). It aims to offer a comparative analysis of MEDUC's unique non‐directive mediation model, which involves children's active participation in mediation processes, in contrast to the original Australian model of Child‐Inclusive Mediation and Counseling (CIMC). This paper uses a structured theoretical methodology combining comparative and conceptual analysis. Specifically, the comparative approach contrasts Australian and Czech practices and reveals key differences and similarities in legal frameworks, philosophical theories, and the roles of mediators and child specialists. Meanwhile, the conceptual analysis draws on an extensive literature review to explore the theoretical underpinnings of Australian and Czech family mediation approaches. The study identifies considerable flexibility in adapting CIP models in different legal and cultural settings. Although Australian practices heavily influence MEDUC, it has adapted these principles to fit its legal and cultural context. The article highlights the potential of combining human rights and therapeutic approaches, augmented by developmental psychology and international child rights standards, to create a more nuanced and child‐sensitive mediation practice. The article highlights the value of a multidisciplinary, adaptive approach to practice involving children in family mediation. It suggests that integrating psychological and legal‐philosophical theories can lead to a robust model that can be adapted to different cultural and legal settings. It advocates for future research to empirically evaluate the effectiveness and sustainability of these adapted models and explore how cultural perceptions of childhood and family roles may influence the success of CIP.
Genetic diversity analysis and heterotic grouping of Indian white maize inbred lines using combining ability and SNP markers
Authors: Arora Arushi , Das Abhijit Kumar , Dixit Shubhank , KR Yathish , Singh S. B. , Sekhar J. C. , Ravikesavan R. , Sahi J. P. , Kumar I. Sudhir , Mahadevu P. , Swain Digbijaya , Kachapur R. M. , Tuinstra Mitchell R. , Venadan Sreya , Rakshit Sujay 
Published: February 2024

AbstractMaize (Zea mays L.) is a versatile crop with high genetic yield potential and various uses. While yellow maize is primarily used for animal feed, white maize is preferred as a food by rural and tribal populations in India. However, white maize landraces suffer immensely in terms of low yield. Heterotic grouping is an excellent method to develop hybrids with increased yield potential in maize. The heterotic grouping of 78 white maize inbred lines was performed using combining ability and molecular diversity analysis. The lines were crossed with two testers, and the resulting hybrids were evaluated for grain yield at three locations representing different agroecological zones in India. The combining ability analysis based on specific combining ability effects on mean grain yield was used to classify the inbred lines into heterotic groups (HG‐A: 18 inbreds; HG‐B: 33 inbreds). Additionally, marker‐based clustering using 62,470 single nucleotide polymorphisms (SNPs) generated through genotyping by sequencing was also employed to determine the genetic relationships among these lines. The combining ability information was superimposed on marker‐based clustering data to obtain the heterotic grouping information, and two distinct HGs with 7 (HG‐1) and 18 inbred lines (HG‐2) were developed. The results of this study will contribute to the development of high‐performing white maize hybrids through the efficient utilization of clear‐cut and well‐defined HGs. Hence, the use of SNP markers along with the combining ability of inbred lines is a useful method for heterotic grouping and understanding of genetic relationships of white maize.
Compact triple band notched UWB MIMO antenna with integrated GSM
Authors: Shaik Kareemulla , Kumar Vijay 
Published: February 2024

SummaryThis paper introduces an innovative four‐element Ultra‐wideband (UWB) MIMO structure featuring an integrated global system for mobile (GSM) antenna with the ability to achieve dual and triple band‐notch capabilities. The antenna's distinctiveness is achieved through the utilization of four directional meandered line shaping decoupling structures (MLSDS), an orthogonal arrangement, and multi‐slot techniques. The incorporation of orthogonal separation alongside four directional MLSDS significantly reduces the mutual interference between radiating elements. By placing MLSDS on both sides of the substrate, effective coverage of the GSM band is achieved. The development of the MIMO structure unfolds through four distinct phases. The initial stage lacks MLSDS, while the second stage incorporates MLSDS. The third and fourth stages respectively introduce MLSDS with dual and triple notch characteristics. The presence of MLSDS enhances the antenna's impedance bandwidth (IBW). The intended notches are tailored to address interference from bands like Band n41, WLAN, and X‐band. Furthermore, the proposed antenna has undergone simulation, measurement, and comparative analysis with existing models, focusing on diversity performance metrics. The results reveal its exceptional diversity performance, positioning it as a potential choice for creating a portable UWB‐MIMO system.