bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Antiobesity Effects of Rosehip (Rosa canina) Flesh by Antagonizing the PPAR Gamma Activity in High‐Fat Diet‐Fed Mice
Authors: Sanz‐Lamora Hèctor , Nicola‐Llorente Mariano , Torres‐Oteros Daniel , Pérez‐Martí Albert , Aghziel Inass , Lozano‐Castellón Julián , Vallverdú‐Queralt Anna , Canudas Sílvia , Marrero Pedro F. , Haro Diego , Relat Joana 
Published: February 2024

ScopeThe rosehip (Rosa canina) is a perennial shrub with a reddish pseudofruit that has demonstrated antidiabetic, antiatherosclerotic, and antiobesogenic effects in rodent models but there is low information about the molecular mechanisms underlying these effects on the onset and progression of diet‐induced obesity.Methods and resultsFour‐week‐old C57BL/6J male mice are subjected to a high‐fat diet (HFD)‐supplemented or not with R. canina flesh for 18 weeks. The results indicated that the R. canina flesh exerts a preventive effect on HFD‐induced obesity with a significant reduction in body‐weight gain and an improvement of hyperglycemia and insulin resistance caused by a HFD. At the tissue level, subcutaneous white adipose tissue exhibits a higher number of smaller adipocytes, with decreased lipogenesis. On its side, the liver shows a significant decrease in lipid droplet content and in the expression of genes related to lipogenesis, fatty acid oxidation, and glucose metabolism. Finally, the data suggest that most of these effects agree with the presence of a putative Perosxisome proliferator‐activated receptor gamma (PPARγ) antagonist in the R. canina flesh.ConclusionsR. canina flesh dietary supplementation slows down the steatotic effect of a HFD at least in part through the regulation of the transcriptional activity of PPARγ.
Comprehensive splicing analysis of the alternatively spliced CHEK2 exons 8 and 10 reveals three enhancer/silencer‐rich regions and 38 spliceogenic variants
Authors: Sanoguera‐Miralles Lara , Llinares‐Burguet Inés , Bueno‐Martínez Elena , Ramadane‐Morchadi Lobna , Stuani Cristiana , Valenzuela‐Palomo Alberto , García‐Álvarez Alicia , Pérez‐Segura Pedro , Buratti Emanuele , de la Hoya Miguel , Velasco‐Sampedro Eladio A 
Published: February 2024

AbstractSplicing is controlled by a large set of regulatory elements (SREs) including splicing enhancers and silencers, which are involved in exon recognition. Variants at these motifs may dysregulate splicing and trigger loss‐of‐function transcripts associated with disease. Our goal here was to study the alternatively spliced exons 8 and 10 of the breast cancer susceptibility gene CHEK2. For this purpose, we used a previously published minigene with exons 6–10 that produced the expected minigene full‐length transcript and replicated the naturally occurring events of exon 8 [Δ(E8)] and exon 10 [Δ(E10)] skipping. We then introduced 12 internal microdeletions of exons 8 and 10 by mutagenesis in order to map SRE‐rich intervals by splicing assays in MCF‐7 cells. We identified three minimal (10‐, 11‐, 15‐nt) regions essential for exon recognition: c.863_877del [ex8, Δ(E8): 75%] and c.1073_1083del and c.1083_1092del [ex10, Δ(E10): 97% and 62%, respectively]. Then 87 variants found within these intervals were introduced into the wild‐type minigene and tested functionally. Thirty‐eight of them (44%) impaired splicing, four of which (c.883G>A, c.883G>T, c.884A>T, and c.1080G>T) induced negligible amounts (<5%) of the minigene full‐length transcript. Another six variants (c.886G>A, c.886G>T, c.1075G>A, c.1075G>T, c.1076A>T, and c.1078G>T) showed significantly strong impacts (20–50% of the minigene full‐length transcript). Thirty‐three of the 38 spliceogenic variants were annotated as missense, three as nonsense, and two as synonymous, underlying the fact that any exonic change is capable of disrupting splicing. Moreover, c.883G>A, c.883G>T, and c.884A>T were classified as pathogenic/likely pathogenic variants according to ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)‐based criteria. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Ultra‐high molecular weight polyethylene micro‐ribbon fibers gel spun using orange terpenes
Authors: Brown Kenneth R. , Love‐Baker Cole , Xue ZhiJing , Li Xiaodong 
Published: February 2024

AbstractToxic, hazardous petrochemical solvents are commonly used for industrial‐scale ultra‐high molecular weight polyethylene (UHMWPE) fiber production, but orange terpenes, a byproduct of orange fruit production, present a bio‐derived, sustainable alternative. In this work, fine UHMWPE fibers were spun using orange terpenes as the spin solvent, hot‐drawn at a draw ratio of 5:1, investigated for their morphology, microstructure, and thermal and mechanical properties. The resulting fibers exhibited a flat, micro‐ribbon cross‐section, which is highly desirable for achieving high fiber volume fractions in UHMWPE‐fiber reinforced composites. After drawing, the fibers possessed 4× greater breaking tenacity than any previously published studies on UHMWPE fibers spun using orange terpenes with a tenacity of 8.6 cN/dtex and tensile modulus of 229.2 cN/dtex. Microstructural analysis via differential scanning calorimetry and X‐ray diffraction revealed that the hot drawing process significantly increased molecular orientation, but crystallinity decreased due to crystallite melting during drawing. Therefore, the mechanical properties of these fibers may be significantly improved with optimization of the fiber drawing process. This work establishes the strong potential of orange terpenes as an environmentally‐friendly alternative solvent for UHMWPE gel spinning and sets a foundation for future parametric optimization of the spinning and drawing of these fibers.Highlights
Micro‐ribbon ultra‐high molecular weight polyethylene fibers were prepared using bio‐solvent orange terpenes.
Flat profile enables tight packing, aspect ratio maintained after drawing.
Drawn fibers were 4× stronger than any previous work with orange terpenes.
Near‐melt drawing reduced crystallinity, improved molecular alignment.
Pharmaco‐phosphoproteomic analysis of cancer‐associated KIT mutations D816V and V560G
Authors: Murray Heather C. , Miller Kasey , Dun Matthew D. , Verrills Nicole M. 
Published: February 2024

AbstractThe CD117 mast/stem cell growth factor receptor tyrosine kinase (KIT) is critical for haematopoiesis, melanogenesis and stem cell maintenance. KIT is commonly activated by mutation in cancers including acute myeloid leukaemia, melanoma and gastrointestinal stromal tumours (GISTs). The kinase and the juxtamembrane domains of KIT are mutation hotspots; with the kinase domain mutation D816V common in leukaemia and the juxtamembrane domain mutation V560G common in GISTs. Given the importance of mutant KIT signalling in cancer, we have conducted a proteomic and phosphoproteomic analysis of myeloid progenitor cells expressing D816V‐ and V560G‐KIT mutants, using an FDCP1 isogenic cell line model. Proteomic analysis revealed increased abundance of proteases and growth signalling proteins in KIT‐mutant cells compared to empty vector (EV) controls. Pathway analysis identified increased oxidative phosphorylation in D816V‐ and V560G‐mutant KIT cells, which was targetable using the inhibitor IACS010759. Dysregulation of RNA metabolism and cytoskeleton/adhesion pathways was identified in both the proteome and phosphoproteome of KIT‐mutant cells. Phosphoproteome analysis further revealed active kinases such as EGFR, ERK and PKC, which were targetable using pharmacological inhibitors. This study provides a pharmaco‐phosphoproteomic profile of D816V‐ and V560G‐mutant KIT cells, which reveals novel therapeutic strategies that may be applicable to a range of cancers.
Ternary complexes of isopentenyl phosphate kinase from Thermococcus paralvinellae reveal molecular determinants of non‐natural substrate specificity
Authors: Johnson Bryce P. , Mandal Prashant S. , Brown Sara M. , Thomas Leonard M. , Singh Shanteri 
Published: February 2024

AbstractIsopentenyl phosphate kinases (IPKs) have recently garnered attention for their central role in biocatalytic “isoprenol pathways,” which seek to reduce the synthesis of the isoprenoid precursors to two enzymatic steps. Furthermore, the natural promiscuity of IPKs toward non‐natural alkyl‐monophosphates (alkyl‐Ps) as substrates has hinted at the isoprenol pathways' potential to access novel isoprenoids with potentially useful activities. However, only a handful of IPK crystal structures have been solved to date, and even fewer of these contain non‐natural substrates bound in the active site. The current study sought to elucidate additional ternary complexes bound to non‐natural substrates using the IPK homolog from Thermococcus paralvinellae (TcpIPK). Four such structures were solved, each bound to a different non‐natural alkyl‐P and the phosphoryl donor substrate/product adenosine triphosphate (ATP)/adenosine diphosphate (ADP). As expected, the quaternary, tertiary, and secondary structures of TcpIPK closely resembled those of IPKs published previously, and kinetic analysis of a novel alkyl‐P substrate highlighted the potentially dramatic effects of altering the core scaffold of the natural substrate. Even more interesting, though, was the discovery of a trend correlating the position of two α helices in the active site with the magnitude of an IPK homolog's reaction rate for the natural reaction. Overall, the current structures of TcpIPK highlight the importance of continued structural analysis of the IPKs to better understand and optimize their activity with both natural and non‐natural substrates.
Discovery and optimization of spirocyclic lactams that inhibit acyl‐ACP thioesterase
Authors: Asmus Elisabeth , Barber David M. , Bojack Guido , Bollenbach‐Wahl Birgit , Brown Ronald W. , Döller Uwe , Freigang Jörg , Gatzweiler Elmar , Getachew Rahel , Heinemann Ines , Hohmann Sabine , Ko Kwang‐Yoon , Laber Bernd , Lange Gudrun , Mattison Rebecca L. , Minn Klemens , Müller Thomas , Petry Thomas , Reingruber Anna M. , Schmutzler Dirk , Svejda Andrea , Frackenpohl Jens 
Published: February 2024

AbstractBACKGROUNDThere are various methods to control weeds, that represent considerable challenges for farmers around the globe, although applying small molecular compounds is still the most effective and versatile technology to date. In the search for novel chemical entities with new modes‐of‐action that can control weeds displaying resistance, we have investigated two spirocyclic classes of acyl‐ACP thioesterase inhibitors based on X‐ray co‐crystal structures and subsequent modelling studies.RESULTSBy exploiting scaffold‐hopping and isostere concepts, we were able to identify new spirolactam‐based lead structures showing promising activity in vivo against commercially important grass weeds in line with strong target affinity.CONCLUSIONThe present work covers a series of novel herbicidal lead structures that contain a spirocyclic lactam as a structural key feature carrying ortho‐substituted benzyl or heteroarylmethylene side chains. These new compounds show good acyl‐ACP thioesterase inhibition in line with strong herbicidal activity. Glasshouse trials showed that the spirolactams outlined herein display promising control of grass‐weed species in pre‐emergence application combined with dose–response windows that enable partial selectivity in wheat and corn. Remarkably, some of the novel acyl‐ACP thioesterase‐inhibitors showed efficacy against resistant grass weeds such as Alopecurus myosuroides and Lolium spp. on competitive levels compared with commercial standards. © 2024 Society of Chemical Industry.
Influence of Metal Ions and Organic Solutions on Activity and Stability of Beta‐Glucosidase Nanoflowers
Authors: Altinkaynak Cevahir , Samsa Canan Gulmez , Ekremoglu Murat , Turk Merve , Ozturkler Melek , Özdemir Nalan , Atakisi Onur 
Published: February 2024

Abstractβ‐Glucosidase, a pivotal enzyme in the synthesis of various glycosides with wide applications in industries such as food, cosmetics, beverages, bioenergy, nutraceuticals, pharmaceuticals, and detergents, undergoes immobilization to enhance its utility in industrial processes and improve enzymatic properties. In this study, the conventional hybrid nanoflower synthesis method was used for β‐glucosidase‐inorganic hybrid nanoflowers. Following a comprehensive pH and temperature scanning of the nanoflowers, the influence of metallic ions and various organic solvents on hybrid nanoflowers to enhance the activity and stability of the biocatalyst were investigated. The optimal morphology for β‐Glu/NFs was determined to be 0.01 mg/mL. To obtain the optimum activity conditions, we explored pH values ranging from 3 to 8 and temperatures between 30 and 80 °C. Both the free form and β‐Glu/NFs exhibited higher activity in acidic conditions, with a significant decrease in activity observed at pH 7 and 8. β‐Glu/NFs demonstrated superior activity compared to the free enzyme in the presence of metal ions, exhibiting a remarkable 3.6‐fold increase in activity in chloroform, and approximately 2.8 and 2.7 times increase in benzene and glycerol, respectively. Moreover, it displayed over a 2‐fold increase in activity in methanol, ethanol, isopropanol, n‐butanol, acetone, and DMSO.
Mechanical properties of poly(N‐acryloyl‐glycinamide) hydrogels dependent on initiation number of the polymerization reaction
Authors: Osawa Shigehito , Akiyama Yoshikatsu 
Published: February 2024

AbstractHydrogels with polymer networks formed through physical interactions have received attention because of their post‐moldability and self‐healing properties upon physicochemical stimulation. Although hydrogels become fragile without covalent crosslinking, poly(N‐acryloyl‐glycinamide) (PNAGA) hydrogels, which are formed through hydrogen bonding among PNAGA molecules, have recently demonstrated exceptional strain. In this study, we prepared a series of PNAGA hydrogels with different molecular weights and constant weight concentrations of PNAGA. Stress–strain tests demonstrated that higher molecular weights of PNAGA promote extensibility. The swelling ability of the hydrogel also increased with higher molecular weights of PNAGA, suggesting that high molecular weights of PNAGA significantly increase the tolerability of hydrogels to shape change, which opens up new possibilities for developing robust hydrogels without the requirement for cross‐linking. Although different behaviors were not observed with changes in the molecular weight, we achieved hydrogel re‐construction using the PNAGA powder obtained from hydrogels, which demonstrates an advantage of such polymer networks based on hydrogen bonding. Regarding the healing ability of the cut surfaces, hydrogels with a lower molecular weight exhibited higher recoveries, probably owing to the high PNAGA mobility in the hydrogels. Finally, this study elucidates the importance of controlling the molecular weight when developing functional hydrogels.
Recent Advances of Engineered Cell Membrane‐Based Nanotherapeutics to Combat Inflammatory Diseases
Authors: Ma Jiaxin , Ding Linyu , Peng Xuqi , Jiang Lai , Liu Gang 
Published: February 2024

AbstractAn immune reaction known as inflammation serves as a shield from external danger signals, but an overactive immune system may additionally lead to tissue damage and even a variety of inflammatory disorders. By inheriting biological functionalities and serving as both a therapeutic medication and a drug carrier, cell membrane‐based nanotherapeutics offer the potential to treat inflammatory disorders. To further strengthen the anti‐inflammatory benefits of natural cell membranes, researchers alter and optimize the membranes using engineering methods. This review focuses on engineered cell membrane‐based nanotherapeutics (ECMNs) and their application in treating inflammation‐related diseases. Specifically, this article discusses the methods of engineering cell membranes for inflammatory diseases and examines the progress of ECMNs in inflammation‐targeted therapy, inflammation‐neutralizing therapy, and inflammation‐immunomodulatory therapy. Additionally, the article looks into the perspectives and challenges of ECMNs in inflammatory treatment and offers suggestions as well as guidance to encourage further investigations and implementations in this area.
Strategies to Improve the Output Performance of Triboelectric Nanogenerators
Authors: Li Cong , Bai Yuan , Shao Jiajia , Meng Hongyu , Li Zhou 
Published: February 2024

AbstractTriboelectric nanogenerators (TENGs) can collect and convert random mechanical energy into electric energy, with remarkable advantages including broadly available materials, straightforward preparation, and multiple applications. Over the years, researchers have made substantial advancements in the theoretical and practical aspects of TENG. Nevertheless, the pivotal challenge in realizing full applications of TENG lies in ensuring that the generated output meets the specific application requirements. Consequently, substantial research is dedicated to exploring methods and mechanisms for enhancing the output performance of TENG devices. This review aims to comprehensively examine the influencing factors and corresponding improvement strategies of the output performance based on the contact electrification mechanism and operational principles that underlie TENG technology. This review primarily delves into five key areas of improvement: materials selection, surface modification, component adjustments, structural optimization, and electrode enhancements. These aspects are crucial in tailoring TENG devices to meet the desired performance metrics for various applications.
Branes in JT (super)gravity from group theory
Authors: Belaey Andreas , Mariani Francesca , Mertens Thomas G. 
Published: February 2024

Abstract
In this work, we revisit the end-of-the-world (EOW) brane amplitudes in JT gravity from a BF gauge theoretic perspective. Observing and identifying the correct group theoretic ingredient for a closed EOW brane as a discrete series character, we use the group theory framework as a guide towards formulating the analogous supersymmetric problem. We compute these amplitudes explicitly in the supersymmetric generalizations of JT gravity ($$ \mathcal{N} $$
N
= 1, 2, 4), motivated by the prospective of possibly finite amplitudes. In the process, we develop some of the representation theory of OSp(2|2, ℝ) and PSU(1, 1|2), relevant for the $$ \mathcal{N} $$
N
= 2 and $$ \mathcal{N} $$
N
= 4 cases.
Celestial two-point functions and rectified dictionary
Authors: Furugori Hideo , Ogawa Naoki , Sugishita Sotaro , Waki Takahiro 
Published: February 2024

Abstract
A naive celestial dictionary causes massless two-point functions to take the delta-function forms in the celestial conformal field theory (CCFT). We rectify the dictionary, involving the shadow transformation so that the two-point functions follow the standard power-law. In this new definition, we can smoothly take the massless limit of the massive dictionary. We also compute a three-point function using the new dictionary and discuss the OPE in CCFT.
Anomaly enforced gaplessness and symmetry fractionalization for SpinG symmetries
Authors: Brennan T. Daniel 
Published: February 2024

Abstract
Symmetries and their anomalies give strong constraints on renormalization group (RG) flows of quantum field theories. Recently, the identification of a theory’s global symmetries with its topological sector has provided additional constraints on RG flows to symmetry preserving gapped phases due to mathematical results in category and topological quantum field theory. In this paper, we derive constraints on RG flows from ℤ2-valued pure- and mixed-gravitational anomalies that can only be activated on non-spin manifolds. We show that such anomalies cannot be matched by a unitary, symmetry preserving gapped phase without symmetry fractionalization. In particular, we discuss examples that commonly arise in 4d gauge theories with fermions.
Wnt/β-catenin-driven EMT regulation in human cancers
Authors: Xue Wenhua , Yang Lin , Chen Chengxin , Ashrafizadeh Milad , Tian Yu , Sun Ranran 
Published: February 2024

AbstractMetastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial–mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/β-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3β that destructs β-catenin, while ligand–receptor interaction impairs GSK-3β function to increase β-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/β-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance β-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/β-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/β-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression.
Graphical abstract
The human OPA1delTTAG mutation induces adult onset and progressive auditory neuropathy in mice
Authors: Affortit Corentin , Coyat Carolanne , Saidia Anissa Rym , Ceccato Jean-Charles , Charif Majida , Sarzi Emmanuelle , Flamant Frédéric , Guyot Romain , Cazevieille Chantal , Puel Jean-Luc , Lenaers Guy , Wang Jing 
Published: February 2024

AbstractDominant optic atrophy (DOA) is one of the most prevalent forms of hereditary optic neuropathies and is mainly caused by heterozygous variants in OPA1, encoding a mitochondrial dynamin-related large GTPase. The clinical spectrum of DOA has been extended to a wide variety of syndromic presentations, called DOAplus, including deafness as the main secondary symptom associated to vision impairment. To date, the pathophysiological mechanisms underlying the deafness in DOA remain unknown. To gain insights into the process leading to hearing impairment, we have analyzed the Opa1delTTAG mouse model that recapitulates the DOAplus syndrome through complementary approaches combining morpho-physiology, biochemistry, and cellular and molecular biology. We found that Opa1delTTAG mutation leads an adult-onset progressive auditory neuropathy in mice, as attested by the auditory brainstem response threshold shift over time. However, the mutant mice harbored larger otoacoustic emissions in comparison to wild-type littermates, whereas the endocochlear potential, which is a proxy for the functional state of the stria vascularis, was comparable between both genotypes. Ultrastructural examination of the mutant mice revealed a selective loss of sensory inner hair cells, together with a progressive degeneration of the axons and myelin sheaths of the afferent terminals of the spiral ganglion neurons, supporting an auditory neuropathy spectrum disorder (ANSD). Molecular assessment of cochlea demonstrated a reduction of Opa1 mRNA level by greater than 40%, supporting haploinsufficiency as the disease mechanism. In addition, we evidenced an early increase in Sirtuin 3 level and in Beclin1 activity, and subsequently an age-related mtDNA depletion, increased oxidative stress, mitophagy as well as an impaired autophagic flux. Together, these results support a novel role for OPA1 in the maintenance of inner hair cells and auditory neural structures, addressing new challenges for the exploration and treatment of OPA1-linked ANSD in patients.