bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond the Endosomal Bottleneck: Understanding the Efficiency of mRNA/LNP Delivery
Authors: Liu Haiyin , Chen Moore Z. , Payne Thomas , Porter Christopher J.H. , Pouton Colin W. , Johnston Angus P.R. 
Published: July 2024

AbstractThe development of lipid nanoparticles (LNP) holds great promise for vaccine and therapeutic applications. However, ineffective transport of nucleic acid cargo from endosomes to the cytosol, termed “endosomal escape,” has remained a bottleneck to achieving greater LNP efficacy. Poor understanding of the mechanisms of endosomal escape and a lack of suitable techniques to assess the efficiency of escape have also impeded progress in this field. To address this gap, a modified SNAPSwitch/SNAP‐tag assay is developed to compare the cytosolic delivery capabilities of various LNP formulations, comparing ionizable lipids used in major commercial LNP products. The results show that all the LNP formulations tested exhibited low (<10%) endosomal escape efficiency. Interestingly, a limited correlation is found between the amount of mRNA delivery to the cytosol and protein expression. While endosomal escape of mRNA LNP cargo is necessary for protein expression, subcellular processes after delivery to the cytosol play a critical role in maximising protein expression. These findings challenge existing paradigms and reveal critical parameters for optimizing nucleic acid delivery and therapeutic effectiveness of next‐generation LNP.
Unleashing 2D MXene's Plasmonic Effect for Advanced Photonic Device Applications
Authors: Jang Moonjeong , Kim Seoung Hyun , Kim Shinho , Chae Kwanbyung , Choi Sodam , Ha Hwi Heon , Song Jungchul , Bak Min Jun , Cho Su‐Ho , Kim Eunji , Song Wooseok , Han Hee , Jang Min Seok , Ahn Chi Won , Lee Yonghee 
Published: July 2024

AbstractMXenes, the largest family of 2D transition metal carbides/nitrides, have emerged as promising materials for various applications due to their exceptionally fascinating properties. In this study, the potential of MXenes is investigated in plasmonic applications, particularly focusing on surface‐enhanced Raman scattering (SERS) and broadband photodetection. The study explored a broader range of light‐matter interactions based on edge plasmons that emerge at sub‐monolayer coverage of MXene, while existing studies have primarily focused on thicknesses exceeding tens of nanometers. Additionally, by incorporating MXenes onto 3D trench nanostructures, To maximize their plasmonic properties is aimed by enhancing the manifestation of edge plasmons, leading to intensified light amplification. The fabricated opto‐electronic devices exhibit remarkable sensitivity in SERS detection, achieving a detection limit as low as ≈0.1 nm for the target dye molecule, significantly surpassing typical thresholds for non‐metal‐based detection. Additionally, the enhancement factor exceeds that of commercially available Au‐based SERS substrates. Furthermore, MXene‐based photodetectors demonstrate competitive photoresponsivity and response time, particularly toward the near‐infrared (NIR) wavelength bands, which are challenging to achieve with MXene‐based photodetectors. Through a comprehensive analysis, including electric field calculations, the mechanisms driving the observed enhancements are unveiled, primarily attributing them to edge plasmons.
Wearable Photoferroelectric Perovskite X‐Ray Detectors
Authors: Li Haojin , Wang Chang‐feng , Luo Qing‐feng , Ma Chuang , Zhang Jing , Zhao Ri , Yang Tinghuan , Du Yachao , Chen Xin , Li Telun , Liu Xinmei , Song Xin , Yang Ye , Yang Zhou , Liu Shengzhong (Frank) , Zhang Yi , Zhao Kui 
Published: July 2024

AbstractHigh‐sensitivity wearable radiation detectors are essential for personnel protection in radiation environments such as defense, nuclear facilities, and medical fields. Traditional detectors using bulk crystals lack flexibility, and emerging perovskite films suffer from lead toxicity and poor charge transport. Herein, lead‐free photoferroelectric hybrid metal halide perovskite flexible membranes for wearable detectors are presented, offering superior X‐ray response with sensitivities up to 7872 ± 517 µC Gyair−1 cm−2 at 50 V bias and 394 ± 67 µC Gyair−1 cm−2 in a self‐driven mode, detection limit of lower than 77 nGyair s−1, and excellent imaging capabilities. This exceptional performance is attributed to the spontaneous polarization that promotes efficient charge transport. Additionally, they show remarkable radiation stability, long‐term air stability, mechanical fatigue resistance, and water stability. They also exhibit efficient energy response under the Compton effect and meet the angle response requirements of the International Electrotechnical Commission standard for direct‐reading personal dose equivalent meters, paving the way for their integration into flexible, wearable dosimeters. These advancements have the potential to drive the realization of the next generation of flexible wearable radiation detectors.
Deconstructing the High Voltage Degradation Mechanisms in Na2/3Ni1/3Mn2/3O2 with Single Crystals and Advanced Electrolyte
Authors: Darga Joe , Manthiram Arumugam 
Published: July 2024

AbstractSodium layered oxide cathodes can uniquely benefit from the existing lithium‐ion battery industry as sodium‐ion batteries gain traction as a potential low‐cost, drop‐in replacement. However, achieving relevant energy density with a suitable cycle life remains a challenge for sodium layered oxides. At high operating potentials, several competing degradation mechanisms prevent P2‐type Na2/3Ni1/3Mn2/3O2 (≈550 Wh kg−1) from achieving meaningful cycle life—with bulk structural instability and surface reactivity being the primary retractors. Herein, the issue of particle cracking is addressed through detailed synthesis methods of “single‐crystal” materials. By comparison to a polycrystalline baseline, the single‐crystal materials quantify the capacity loss due to isolation of active material caused by intergranular particle cracking. The single crystal materials are then employed in cells with an advanced, “localized saturated electrolyte” (LSE) to demonstrate the magnitude of capacity loss due to electrolyte decomposition at the cathode surface. Mitigation of the surface reactivity through the LSE electrolyte effectively demonstrates the elevated importance of surface reactivity at high voltages despite the onset of egregious particle cracking. This work aims to guide future research into understanding molten‐salt assisted syntheses and advance the debate on surface versus bulk degradation.
Biomimetic Mechanical Robust Cement‐Resin Composites with Machine Learning‐Assisted Gradient Hierarchical Structures
Authors: Wu Zhangyu , Pan Hao , Huang Peng , Tang Jinhui , She Wei 
Published: July 2024

AbstractBiological materials relying on hierarchically ordered architectures inspire the emergence of advanced composites with mutually exclusive mechanical properties, but the efficient topology optimization and large‐scale manufacturing remain challenging. Herein, this work proposes a scalable bottom‐up approach to fabricate a novel nacre‐like cement‐resin composite with gradient brick‐and‐mortar (BM) structure, and demonstrates a machine learning‐assisted method to optimize the gradient structure. The fabricated gradient composite exhibits an extraordinary combination of high flexural strength, toughness, and impact resistance. Particularly, the toughness and impact resistance of such composite attractively surpass the cement counterparts by factors of approximately 700 and 600 times, and even outperform natural rocks, fiber‐reinforced cement‐based materials and even some alloys. The strengthening and toughening mechanisms are clarified as the regional‐matrix densifying and crack‐tip shielding effects caused by the gradient BM structure. The developed gradient composite not only endows a promising structural material for protective applications in harsh scenarios, but also paves a new way for biomimetic metamaterials designing.
Lung function in relation to brain aging and cognitive transitions in older adults: A population‐based cohort study
Authors: Grande Giulia , Li Yuanjing , Trevisan Caterina , Rizzuto Debora , Kalpouzos Grégoria , Ding Mozhu , Laukka Erika J , Bellander Tom , Fratiglioni Laura , Qiu Chengxuan 
Published: July 2024

AbstractBACKGROUNDWe investigated the association of peak expiratory flow (PEF) with dementia; cognitive impairment, no dementia (CIND); and transition from CIND to dementia, and possible underlying neuropathological mechanisms.METHODSA population‐based cohort of adults aged 60+ was followed over 15 years to detect dementia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria), CIND (assessed through a cognitive battery), and progression from CIND to dementia, in relation to baseline PEF observations. A subsample (n = 462) had 6‐year follow‐up data on brain magnetic resonance imaging markers of neurodegeneration and small vessel disease.RESULTSIn fully adjusted models, poor PEF performance (< 10th vs. ≥ 80th percentile) was associated with increased hazards for dementia (hazard ratio [HR] = 1.89; 95% confidence interval [CI] = 1.23–2.92) and CIND (HR = 1.55; 95% CI = 1.01–2.38) and CIND progression to dementia, although not statistically significantly (HR = 2.44; 95% CI = 0.78–6.88). People with poor PEF also experienced the fastest ventricular enlargement (β coefficient = 0.67 mL/year; 95% CI = 0.13–1.21) and had the highest likelihood of developing lacunes (odds ratio = 5.05; 95% CI = 1.01–25.23).DISCUSSIONPoor lung function contributes to cognitive deterioration possibly through accelerated brain atrophy and microvascular damage.Highlights
Poor lung function increased the risk of dementia and mild cognitive impairment (MCI).
Poor lung function accelerated the progression from MCI to dementia.
Poor lung function was linked to brain microvascular damage and global brain atrophy.
Gold‐Catalyzed Diyne‐Ene Annulation for the Synthesis of Polysubstituted Benzenes through Formal [3+3] Approach with Amide as the Critical Co‐Catalyst
Authors: Wei Jingwen , Pham Thong , Attah Emmanuel Ifeanyi , Liu Mengjia , Yaroshuk Timothy , Chen Hao , Wojtas Lukasz , Shi Xiaodong 
Published: July 2024

AbstractThe one‐step synthesis of tetra‐substituted benzenes was accomplished via gold‐catalyzed diyne‐ene annulation. Distinguished from prior modification methods, this novel strategy undergoes formal [3+3] cyclization, producing polysubstituted benzenes with exceptional efficiency. The critical factor enabling this transformation was the introduction of amides, which were reported for the first time in gold catalysis as covalent nucleophilic co‐catalysts. This interesting protocol not only offers a new strategy to achieve functional benzenes with high efficiency, but also enlightens potential new reaction pathways within gold‐catalyzed alkyne activation processes.
A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Imaging/Photoacoustic Imaging‐Guided Phototherapy
Authors: Wang Ben , Zhou Hui , Chen Lu , Ding Yancheng , Zhang Xinyue , Chen Huiyu , Liu Hanyu , Li Ping , Chen Ying , Yin Chao , Fan Quli 
Published: July 2024

AbstractOvercoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near‐infrared‐II (NIR‐II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria‐targeting abilities, and a large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type‐I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs‐mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.
Hocheffizienter Niedrigbeladener PdOx/AlSiOx‐Katalysator für die Ethylen‐Dimerisierung
Authors: Otroshchenko Tatiana , Sharapa Dmitry I. , Fedorova Elizaveta A. , Zhao Dan , Kondratenko Evgenii V. 
Published: July 2024

AbstractDie Ethylen‐Dimerisierung ist ein industrieller Prozess, der derzeit mit homogenen Katalysatoren durchgeführt wird. Hier stellen wir einen hochaktiven heterogenen Katalysator vor, der winzige Mengen von atomar dispergiertem Pd enthält. Er erfordert keine Cokatalysatoren oder Aktivatoren und übertrifft die Leistung früherer Katalysatoren, die unter ähnlichen Reaktionsbedingungen getestet wurden. Die Selektivität für C4‐ und C6‐Kohlenwasserstoffe betrug bei 200 °C etwa 80 % bzw. 10 % bei 42 % C2H4‐Umsatz unter Verwendung eines industriell relevanten Reaktionsgemisches mit 50 Vol.‐% Ethylen. Unsere Experimente zur Kinetik und Katalysatorcharakterisierung, ergänzt durch Dichtefunktionaltheorie‐Berechnungen, liefern molekulare Einblicke in die lokale Umgebung isolierter Pd(II)Ox‐Spezies und ihre Rolle bei der Erzielung einer hohen Aktivität in der Zielreaktion. Als der entwickelte Katalysator rationell mit einem Mo‐haltigen Olefinmetathesekatalysator im gleichen Reaktor integriert wurde, reagierten die gebildeten Butene mit Ethylen zu Propylen mit einer Selektivität von 98 % bei etwa 24 % C2H4‐Umsatz.
Investigation of the ageing behaviour of multiple reused polypropylene binding twines
Authors: du Maire Philippe , Gärtner Felix , Deckert Matthias H. , Johlitz Michael , Öchsner Andreas 
Published: July 2024

AbstractClimate change is one of the significant challenges of the 21st century. To achieve climate goals a change in plastic waste management needs to be implemented. This research examines the potential of thermo‐mechanical recycling of plastic waste, focusing on agricultural binding twines made from polypropylene. Old binding twines from agriculture were collected and recycled with a twin screw extruder. The ageing behaviour of the recyclate in terms of multiple recycling is examined in detail with tensile tests and melt volume rate measurements. The findings indicate a general degradation in mechanical properties and a decrease in viscosity due to molecular chain scission. Despite these degradations, the material remains processable, indicating the potential for continued recycling loops.
A Genome‐Wide Association Study Suggests New Susceptibility Loci for Primary Antiphospholipid Syndrome
Authors: Casares‐Marfil Desiré , Martínez‐Bueno Manuel , Borghi Maria Orietta , Pons‐Estel Guillermo ,   PRECISESADS Clinical Consortium, Reales Guillermo , Zuo Yu , Espinosa Gerard , Radstake Timothy , van den Hoogen Lucas L. , Wallace Chris , Guthridge Joel , James Judith A , Cervera Ricard , Meroni Pier Luigi , Martin Javier , Knight Jason S. , Alarcón‐Riquelme Marta E. , Sawalha Amr H. 
Published: July 2024

ObjectivePrimary antiphospholipid syndrome (PAPS) is a rare autoimmune disease characterized by the presence of antiphospholipid antibodies and the occurrence of thrombotic events and pregnancy complications. Our study aimed to identify novel genetic susceptibility loci associated with PAPS.MethodsWe performed a genome‐wide association study comprising 5,485 individuals (482 affected individuals) of European ancestry. Significant and suggestive independent variants from a meta‐analysis of approximately 7 million variants were evaluated for functional and biological process enrichment. The genetic risk variability for PAPS in different populations was also assessed. Hierarchical clustering, Mahalanobis distance, and Dirichlet Process Mixtures with uncertainty clustering methods were used to assess genetic similarities between PAPS and other immune‐mediated diseases.ResultsWe revealed genetic associations with PAPS in a regulatory locus within the HLA class II region near HLA‐DRA and in STAT1‐STAT4 with a genome‐wide level of significance; 34 additional suggestive genetic susceptibility loci for PAPS were also identified. The disease risk allele near HLA‐DRA is associated with overexpression of HLA‐DRB6, HLA‐DRB9, HLA‐DQA2, and HLA‐DQB2 in immune cells, vascular tissue, and nervous tissue. This association is independent of the association between PAPS and HLA‐DRB1*1302. Functional analyses highlighted immune‐related pathways in PAPS‐associated loci. The comparison with other immune‐mediated diseases revealed a close genetic relatedness to neuromyelitis optica, systemic sclerosis, and Sjögren syndrome, suggesting co‐localized causal variations close to STAT1‐STAT4, TNPO3, and BLK.ConclusionThis study represents a comprehensive large‐scale genetic analysis for PAPS and provides new insights into the genetic basis and pathophysiology of this rare disease.image
Substantive Similarities Between Synovial Fluid and Synovial Tissue T cells in Inflammatory Arthritis Via Single‐Cell RNA and T Cell Receptor Sequencing
Authors: Durham Lucy E. , Humby Frances C. , Ng Nora , Ryan Sarah , Nuamah Rosamond , Fung Kathy , Kallayil Athul Menon , Dhami Pawan , Kirkham Bruce W. , Taams Leonie S. 
Published: July 2024

ObjectiveSynovial fluid (SF)–derived T cells are frequently studied as a proxy for investigating the synovial tissue (ST) T cell infiltrate in inflammatory arthritis. However, because ST is the primary site of inflammatory activity, there is debate as to whether SF provides a true reflection of the ST T cell population.MethodsIn this study, we used single‐cell RNA sequencing paired with single‐cell T cell receptor (TCR) sequencing to directly compare memory T cells from paired samples of SF and ST from six patients with inflammatory arthritis to investigate their similarity in terms of TCR repertoire and T cell subset composition.ResultsThe TCR repertoires of SF and ST T cells were strikingly similar, particularly for CD8+ T cells. A median of 49% of the total CD8+ TCR repertoire in SF was shared with ST, compared with 20% shared with blood. Similarly, 47% of the ST CD8+ TCR repertoire was shared with SF compared to 25% with blood. Furthermore, once the effect of collagenase digestion on gene expression by ST T cells had been accounted for, the frequencies of specific CD8+ and CD4+ T cell subsets were, in general, similar in SF and ST and were distinct from blood.ConclusionOur results suggest that T cells migrate and equilibrate between the SF and ST and maintain similar phenotypes in both sites. We conclude that SF is an appropriate proxy for investigating the T cell infiltrate in inflamed synovium, particularly in terms of investigating the TCR repertoire.image
High‐throughput G protein‐coupled receptor‐based autocrine screening for secondary metabolite production in yeast
Authors: Saleski Tatyana E. , Peng Huadong , Lengger Bettina , Wang Jinglin , Jensen Michael Krogh , Jensen Emil D. 
Published: July 2024

AbstractBiosensors are valuable tools in accelerating the test phase of the design‐build‐test‐learn cycle of cell factory development, as well as in bioprocess monitoring and control. G protein‐coupled receptor (GPCR)‐based biosensors enable cells to sense a wide array of molecules and environmental conditions in a specific manner. Due to the extracellular nature of their sensing, GPCR‐based biosensors require compartmentalization of distinct genotypes when screening production levels of a strain library to ensure that detected levels originate exclusively from the strain under assessment. Here, we explore the integration of production and sensing modalities into a single Saccharomyces cerevisiae strain and compartmentalization using three different methods: (1) cultivation in microtiter plates, (2) spatial separation on agar plates, and (3) encapsulation in water‐in‐oil‐in‐water double emulsion droplets, combined with analysis and sorting via a fluorescence‐activated cell sorting machine. Employing tryptamine and serotonin as proof‐of‐concept target molecules, we optimize biosensing conditions and demonstrate the ability of the autocrine screening method to enrich for high producers, showing the enrichment of a serotonin‐producing strain over a nonproducing strain. These findings illustrate a workflow that can be adapted to screening for a wide range of complex chemistry at high throughput using commercially available microfluidic systems.
Spectrum–effect relationship between HPLC fingerprint and hypoglycemic of litchi leaves (Litchi chinensis Sonn) in vitro
Authors: Liang Yanli , Xie Jingjing , Huang Dongfang , Cao Yupin , Zheng Piaoxue , Lu Chunlian , Ma Yuming , Peng Jiawen , Qin Zujie , Liang Jie 
Published: July 2024

AbstractLitchi chinensis Sonn (Litchi) has been listed in the Chinese Pharmacopeia, and is an economically and medicinally valuable species within the family Sapindaceae. However, the material basis of its pharmacological action and the pharmacodynamic substances associated with its hypoglycemic effect are still unclear. The predominant objective of this study was to establish the fingerprint profile of litchi leaves and to evaluate the relationship between the components of the high‐performance liquid chromatography (HPLC) fingerprint of litchi leaves, assess its hypoglycemic effect by measuring α‐glucosidase and α‐amylase inhibition, and find the spectrum–effect relationship of litchi leaves by bivariate correlation analysis, Grey relational analysis and partial least squares regression analysis. In this study, the fingerprint of litchi leaves was established by HPLC, and a total of 15 common peaks were identified that clearly calibrated eight components, with P1 being gallic acid, P2 being protocatechuic acid, P3 being catechin, P6 being epicatechin, P12 being rutin, P13 being astragalin, P14 being quercetin and P15 being kaempferol. The similarities between the fingerprints of 11 batches of litchi leaves were 0.766–0.979. Simultaneously, the results of the spectrum–effect relationship showed that the chemical constituents represented by peaks P8, P3, P12, P14, P2, P13, and P11 were relevant to the hypoglycemic effect.
Mentalizing self mind but not others: Self‐reported mentalization difficulties in multiple sclerosis
Authors: Kuzu Kumcu Müge , Törenli Kaya Zulal , Hoşgören Alıcı Yasemin 
Published: July 2024

AbstractBackgroundMentalization can be defined as a mental process by which an individual directly or indirectly perceives and interprets one's own and others' behavior, emotions, beliefs, and needs based on designed mental states. Mentalization problems may be linked to remove associative white matter fiber disconnection. Multiple sclerosis (MS) is one of the diseases with white matter lesions. By comparing MS patients with healthy controls, it was aimed to assess whether MS patients' mentalization skills are affected.MethodThis study involved 243 participants (170 healthy controls and 73 patients with MS). All the participants completed a sociodemographic questionnaire and the Mentalization Scale (MentS).ResultsWhile it was discovered that MentS scores for the dimension of others‐based mentalization (MentS‐O) were statistically lower in MS group, there was no statistically significant difference between the groups in terms of the dimensions of motivation to mentalize (MentS‐M) and self‐based mentalization (MentS‐S) scores.ConclusionWe may conclude that MS patients have trouble comprehending other people's thoughts. This effect can be one of the causes of MS patients' issues with social cognition.