bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Deep Learning to the Discovery of Promising VEGFR‐2 Inhibitors
Authors: Yucel Mehmet Ali , Adal Ercan , Aktekin Mine Buga , Hepokur Ceylan , Gambacorta Nicola , Nicolotti Orazio , Algul Oztekin 
Published: May 2024

AbstractVascular endothelial growth factor receptor 2 (VEGFR‐2) stands as a prominent therapeutic target in oncology, playing a critical role in angiogenesis, tumor growth, and metastasis. FDA‐approved VEGFR‐2 inhibitors are associated with diverse side effects. Thus, finding novel and more effective inhibitors is of utmost importance. In this study, a deep learning (DL) classification model was first developed and then employed to select putative active VEGFR‐2 inhibitors from an in‐house chemical library including 187 druglike compounds. A pool of 18 promising candidates was shortlisted and screened against VEGFR‐2 by using molecular docking. Finally, two compounds, RHE‐334 and EA‐11, were prioritized as promising VEGFR‐2 inhibitors by employing PLATO, our target fishing and bioactivity prediction platform. Based on this rationale, we prepared RHE‐334 and EA‐11 and successfully tested their anti‐proliferative potential against MCF‐7 human breast cancer cells with IC50 values of 26.78±4.02 and 38.73±3.84 μM, respectively. Their toxicities were instead challenged against the WI‐38. Interestingly, expression studies indicated that, in the presence of RHE‐334, VEGFR‐2 was equal to 0.52±0.03, thus comparable to imatinib equal to 0.63±0.03. In conclusion, this workflow based on theoretical and experimental approaches demonstrates effective in identifying VEGFR‐2 inhibitors and can be easily adapted to other medicinal chemistry goals.
Towards the Targeted Protein Degradation of PRMT1
Authors: Martin Poppy L. , Pérez‐Areales Francisco Javier , Rao Shalini V. , Walsh Stephen J. , Carroll Jason S. , Spring David R. 
Published: May 2024

AbstractTargeting the protein arginine methyltransferase 1 (PRMT1) has emerged as a promising therapeutic strategy in cancer treatment. The phase 1 clinical trial for GSK3368715, the first PRMT1 inhibitor to enter the clinic, was terminated early due to a lack of clinical efficacy, extensive treatment‐emergent effects, and dose‐limiting toxicities. The incidence of the latter two events may be associated with inhibition‐driven pharmacology as a high and sustained concentration of inhibitor is required for therapeutic effect. The degradation of PRMT1 using a proteolysis targeting chimera (PROTAC) may be superior to inhibition as proceeds via event‐driven pharmacology where a PROTAC acts catalytically at a low dose. PROTACs containing the same pharmacophore as GSK3368715, combined with a motif that recruits the VHL or CRBN E3‐ligase, were synthesised. Suitable cell permeability and target engagement were shown for selected candidates by the detection of downstream effects of PRMT1 inhibition and by a NanoBRET assay for E3‐ligase binding, however the candidates did not induce PRMT1 degradation. This paper is the first reported investigation of PRMT1 for targeted protein degradation and provides hypotheses and insights to assist the design of PROTACs for PRMT1 and other novel target proteins.
Revealing the Roles of Guanidine Hydrochloride Ionic Liquid in Ion Inhibition and Defects Passivation for Efficient and Stable Perovskite Solar Cells
Authors: Saeed Aamir , Wang Liang , Chen Zhaoyang , Fang Junhui , Hussain Iqbal , Yuan Lin , Wang Shuai , Zhao Jianwei , Zhang Haitao , Miao Qingqing 
Published: May 2024

AbstractAs a result of full‐scale ongoing global efforts, the power conversion efficiency (PCE) of the organic‐inorganic metal halide perovskite has skyrocketed. Unfortunately, the long‐term operational stability for commercialization standards is still lagging owing to intrinsic defects such as ion migration‐induced degradation, undercoordinated Pb2+, and shallow defects initiated by disordered crystal growth. Herein, we employed multifunctional, non‐volatile tetra‐methyl guanidine hydrochloride [TMGHCL] ionic liquid (IL) as an additive to elucidate defects’ passivation effects on organic‐inorganic metal halide perovskite. More specifically, the formation of hydrogen bonds between H+ in GA+ and I− and coordinate bonding between Cl− and undercoordinated Pb2+ could significantly passivate these defects. The hypothesis was confirmed by both experimental and DFT simulations displaying that the optimized ratio of IL integration restrains ion migration, improving grains’ size, and significantly elongating the carrier lifetime. Remarkably, the modified cell achieved a peak efficiency of 22.00 % with negligible hysteresis, compared to the control device‘s PCE of 20.12 %. In addition, the TMGHCL‐based device retains its 93.29 % efficiency after 16 days of continuous exposure to air with a relative humidity of 35±5% and temperature of 25±5 °C. This efficient approach of adding IL to perovskites absorber can produce high PCE and has strong commercialization potential.
Enhancement of Li/S Battery Performance by a Modified Reduced Graphene Oxide Carbon Host Decorated with MoO3
Authors: Piñuela‐Noval Juan , Fernández‐González Daniel , Suárez Marta , Verdeja Luis Felipe , Celeste Arcangelo , Pierini Adriano , Mazzei Franco , Navarra Maria Assunta , Brutti Sergio , Fernández Adolfo , Agostini Marco 
Published: May 2024

AbstractElectrochemical energy storage systems based on sulfur and lithium can theoretically deliver high energy with the further benefit of low cost. However, the working mechanism of this device involves the dissolution of sulfur to high‐molecular weight lithium polysulfides (LiPs with general formula Li2Sn, n≥4) in the electrolyte during the discharge process. Therefore, the resulting migration of partially dissociated LiPs by diffusion or under the effect of the electric field to the lithium anode, activates an internal shuttle mechanism, reduces the active material and in general leads to loss of performance and cycling stability. These drawbacks poses challenges to the commercialization of Li/S cells in the short term. In this study, we report on the decoration of reduced graphene oxide with MoO3 particles to enhance interactions with LiPs and retain sulfur at the cathode side. The combination of experiments and density functional theory calculations demonstrated improvements in binding interactions between the cathode and sulfur species, enhancing the cycling stability of the Li/S cells.
Anchoring Single‐Atomic Metal Sites in Metalloporphyrin‐Based Covalent Organic Frameworks for Enhanced Photocatalytic Hydrogen Evolution
Authors: Zhang Yue , Chen Zi‐Ao , Xu Zi‐Jian , Li Jun‐Yu , Li Xi‐Ya , Fang Zhi‐Bin , Zhang Teng 
Published: May 2024

AbstractA photoactive covalent organic framework (COF) was built from metalloporphyrin and bipyridine monomers and single‐atomic Pt sites were subsequently installed. Integrating photosensitizing metalloporphyrin and substrate‐activating Pt(bpy) moieties in a single solid facilitates multielectron transfer and accelerates photocatalytic hydrogen evolution with a maximum production rate of 80.4 mmol h−1 gPt−1 and turnover frequency (TOF) of 15.7 h−1 observed. This work demonstrates that incorporation of single‐atomic metal sites with photoactive COFs greatly enhances photocatalytic activity and provides an effective strategy for the design and construction of novel photocatalysts.
Susceptibility of Leishmania to novel pentavalent organometallics: Investigating impact on DNA and membrane integrity in antimony(III)‐sensitive and ‐resistant strains
Authors: Islam Arshad , do Prado Bruno Rodrigues , Dittz Dalton , Rodrigues Bernardo Lages , Silva Sydnei Magno da , do Monte‐Neto Rubens L. , Shabeer Muhammad , Frézard Frédéric , Demicheli Cynthia 
Published: May 2024

AbstractThe aim the present study was to investigate the impact of novel pentavalent organobismuth and organoantimony complexes on membrane integrity and their interaction with DNA, activity against Sb(III)‐sensitive and ‐resistant Leishmania strains and toxicity in mammalian peritoneal macrophages. Ph3M(L)2 type complexes were synthesized, where M = Sb(V) or Bi(V) and L = deprotonated 3‐(dimethylamino)benzoic acid or 2‐acetylbenzoic acid. Both organobismuth(V) and organoantimony(V) complexes exhibited efficacy at micromolar concentrations against Leishmania amazonensis and L. infantum but only the later ones demonstrated biocompatibility. Ph3Sb(L1)2 and Ph3Bi(L1)2 demonstrated distinct susceptibility profiles compared to inorganic Sb(III)‐resistant strains of MRPA‐overexpressing L. amazonensis and AQP1‐mutated L. guyanensis. These complexes were able to permeate the cell membrane and interact with the Leishmania DNA, suggesting that this effect may contribute to the parasite growth inhibition via apoptosis. Taken altogether, our data substantiate the notion of a distinct mechanism of uptake pathway and action in Leishmania for these organometallic complexes, distinguishing them from the conventional inorganic antimonial drugs.
The use of sequential window acquisition of all theoretical fragment ion spectra (SWATH), a data‐independent acquisition high‐resolution mass spectrometry approach, in forensic toxicological regimes: A review
Authors: Sarkisian Maria , Rodda Luke N. 
Published: May 2024

AbstractSequential window acquisition of all theoretical fragment ion spectra (SWATH) is a type of high‐resolution mass spectrometry that uses data‐independent acquisition. Compared with more targeted acquisition schemes, the power behind this data‐independent acquisition technique comes from its ability to mitigate interferences via the use of SWATH acquisition windows (Q1 quadrupole isolation windows) while still obtaining all accurate mass information. However, consistent with high‐resolution mass spectrometry techniques, its routine and high throughput implementation in forensic toxicology is limited due to the complex processing power required to effectively manage the large amount of acquired data. It is therefore pivotal to create an efficient and validated identification criterion that confidently reports suspected positive detections as a confirmational technique for final reporting. This review examines all publications that implemented SWATH in a forensic toxicological framework with suggestive best practices and commonly used criteria. Seventeen publications were reviewed for extraction, liquid chromatography and mass spectrometry parameters, and more specifically for all SWATH applicable characteristics including spray voltages, collision energies and spreads, mass error, isotopic ratio difference, retention time error, and library score thresholds. Notwithstanding the challenges SWATH implementation faces for a laboratory, the technique demonstrates its potential to be utilized in routine forensic toxicology testing regimes and aids in the detection of both common and emerging novel drugs simultaneously.
Secondary production of the central rangeland region of the United States
Authors: Raynor Edward J. , Derner Justin D. , Hartman Melannie D. , Dorich Christopher D. , Parton William J. , Hendrickson John R. , Harmoney Keith R. , Brennan Jameson R. , Owensby Clenton E. , Kaplan Nicole E. , Lutz Susan M. , Hoover David L. , Augustine David J. 
Published: May 2024

AbstractRangelands are the dominant land use across a broad swath of central North America where they span a wide gradient, from <350 to >900 mm, in mean annual precipitation. Substantial efforts have examined temporal and spatial variation in aboveground net primary production (ANPP) to precipitation (PPT) across this gradient. In contrast, net secondary productivity (NSP, e.g., primary consumer production) has not been evaluated analogously. However, livestock production, which is a form of NSP or primary consumer production supported by primary production, is the dominant non‐cultivated land use and an integral economic driver in these regions. Here, we used long‐term (mean length = 19 years) ANPP and NSP data from six research sites across the Central Great Plains with a history of a conservative stocking to determine resource (i.e., PPT)–productivity relationships, NSP sensitivities to dry‐year precipitation, and regional trophic efficiencies (e.g., NSP:ANPP ratio). PPT–ANPP relationships were linear for both temporal (site‐based) and spatial (among site) gradients. The spatial PPT–NSP model revealed that PPT mediated a saturating relationship for NSP as sites became more mesic, a finding that contrasts with many plant‐based PPT–ANPP relationships. A saturating response to high growing‐season precipitation suggests biogeochemical rather than vegetation growth constraints may govern NSP (i.e., large herbivore production). Differential sensitivity in NSP to dry years demonstrated that the primary consumer production response heightened as sites became more xeric. Although sensitivity generally decreased with increasing precipitation as predicted from known PPT–ANPP relationships, evidence suggests that the dominant species' identity and traits influenced secondary production efficiency. Non‐native northern mixed‐grass prairie was outperformed by native Central Great Plains rangeland in sensitivity to dry years and efficiency in converting ANPP to NSP. A more comprehensive understanding of the mechanisms leading to differences in producer and consumer responses will require multisite experiments to assess biotic and abiotic determinants of multi‐trophic level efficiency and sensitivity.
Anthropogenic and climatic factors interact to influence reproductive timing and effort
Authors: Smith Geoffrey D. , Wilcoxen Travis E. , Hudson Spencer B. , Virgin Emily E. , Durso Andrew M. , Van der Walt Marilize , Spence Austin R. , Neuman‐Lee Lorin A. , Webb Alison C. , Terletzky Patricia A. , French Susannah S. 
Published: May 2024

AbstractReproduction, although absolutely essential to a species’ persistence, is in itself challenging. As anthropogenic change increasingly affects every landscape on Earth, it is critical to understand how specific pressures impact the reproductive efforts of individuals, which directly contribute to the success or failure of populations. However, organisms rarely encounter a single burden at a time, and the interactions of environmental challenges can have compounding effects. Understanding environmental and physiological pressures is difficult because they are often context‐dependent and not generalizable, but long‐term monitoring across variable landscapes and weather patterns can improve our understanding of these complex interactions. We tested the effects of urbanization, climate, and individual condition on the reproductive investment of wild side‐blotched lizards (Uta stansburiana) by measuring physiological/reproductive metrics from six populations in urban and rural areas over six consecutive years of variable precipitation. We observed that reproductive stage affected body condition, corticosterone concentration, and oxidative stress. We also observed that reproductive patterns differed between urban and rural populations depending on rainfall, with rural animals increasing reproductive investment during rainier years compared to urban conspecifics, and that reproductive decisions appeared to occur early in the reproductive process. These results demonstrate the plastic nature of a generalist species optimizing lifetime fitness under varying conditions.
Impact of heart failure hospitalizations on clinical outcomes after mitral transcatheter edge‐to‐edge repair: Results from the EXPAND study
Authors: Kessler Mirjam , Rottbauer Wolfgang , von Bardeleben Ralph Stephan , Grasso Carmelo , Lurz Philipp , Mahoney Paul , Price Matthew , Williams Mathew , Denti Paolo , Estevez‐Loureiro Rodrigo , Kar Saibal , Maisano Francesco 
Published: May 2024

AbstractAimThis analysis aimed to compare the clinical outcomes associated with heart failure (HF) readmissions and to identify associations with HF hospitalizations (HFH) in patients treated with the MitraClip™ NTR/XTR System in the EXPAND study.Methods and resultsThe global, real‐world EXPAND study enrolled 1041 patients with primary or secondary mitral regurgitation (MR) treated with the MitraClip NTR/XTR System. Echocardiograms were analysed by an independent echocardiographic core laboratory. The study population was stratified into HFH and No‐HFH groups based on the occurrence of HFH 1 year post‐index procedure. Clinical outcomes including MR severity, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and all‐cause mortality were compared (HFH: n = 181; No‐HFH: n = 860). Both groups achieved consistent 1‐year MR reduction to ≤1+ (HFH vs. No‐HFH: 87.3% vs. 89.5%, p = 0.6) and significant 1‐year improvement in KCCQ scores (+16.5 vs. +22.3, p = 0.09) and NYHA functional class. However, more patients in the No‐HFH group had 1‐year NYHA class ≤II (HFH vs. No‐HFH: 67.9% vs. 81.9%, p < 0.01). All‐cause mortality at 1 year was 36.8% in the HFH group versus 10.4% in the No‐HFH group (p < 0.001). The HFH rate decreased by 63% at 1 year post‐M‐TEER versus 1 year pre‐treatment (relative risk 0.4, p < 0.001). Independent HFH associations were MR ≥2+ at discharge, HFH 1 year prior to treatment, baseline NYHA class ≥III, baseline tricuspid regurgitation ≥2+, and baseline left ventricular ejection fraction ≤40%.ConclusionsThis study reports the impact of HFH on clinical outcomes post‐treatment in the EXPAND study. Results demonstrate that the occurrence of HFH was associated with worse 1‐year survival, and treatment with the MitraClip system substantially reduced HFH and improved patient symptoms and quality of life.
Visible‐Light‐Driven Formyl Group Migration Triggered Remote Desaturation
Authors: Hong Yuwei , Qin Yizhou , Yang Xiong , Zhou Lanxi , Yuan Yao , Zhu Gangguo 
Published: May 2024

AbstractDehydrogenation of unactivated alkanes to form versatile alkenes is an important but challenging task in synthetic chemistry. Enabled by a radical‐mediated formyl group migration, a novel visible light‐induced remote desaturation of aldehydes is developed, delivering a panel of trifluoromethylated δ,ϵ‐ or γ,δ‐unsaturated aldehydes in moderate to excellent yields with good functional group tolerance at room temperature. Mechanistic studies indicate a reaction pathway comprising the cascade trifluoromethylation of C−C double bonds, intramolecular addition to aldehydes, β‐fragmentation of alkoxy radicals, single electron transfer oxidation, and deprotonation. It provides a good complementary approach to the existing desaturation protocols.
Three years of morphological dune development after planting marram grass on a beach
Authors: Strypsteen Glenn , Bonte Dries , Taelman Charlotte , Derijckere Jennifer , Rauwoens Pieter 
Published: May 2024

AbstractCoastal regions globally face escalating challenges from climate change, including rising sea levels and intensified storm events. To address these threats, coastal resilience emerges as a critical paradigm advocating the integration of nature‐based solutions with traditional engineering approaches. Coastal dunes, acting as protective barriers, offer a promising avenue. This three‐year study assesses the efficacy of an artificial dune system to address local sand‐related nuisances on the adjacent seawall featuring planted marram grass in Oosteroever, Belgium. The focus is on understanding sediment accumulation, dune morphology and vegetation development. The results demonstrate a significant increase in dune height, reaching up to 2 m in the zones planted with marram grass, surpassing the height of the adjacent seawall. Comprehensive profiles and drone surveys revealed consistent dune growth of 27 m3/m, which contrasted with the substantial erosion in the adjacent unvegetated beach areas of up to 30 m3/m. One storm event caused dune toe erosion of 1.5 m3/m, but the dune demonstrated rapid recovery through natural aeolian processes. Marram grass development was not impacted by the initial planting configuration and density and was more pronounced at the perimeter edges of the dune. This study highlights the success of the ‘dune‐in‐front‐of‐a‐dike’ approach, offering insights for sustainable coastal resilience strategies.
Combining hillslope erosion and river connectivity models to assess large scale fine sediment transfers: Application over the Rhône River (France)
Authors: Fabre Clément , Fressard Mathieu , Bizzi Simone , Branger Flora , Piegay Hervé 
Published: May 2024

AbstractSediment connectivity at the catchment scale includes the processes linking sediment sources, sinks and the river outlet. Soil erosion models usually estimate yields without considering riverine processes or human infrastructure that may affect sediment connectivity. Quantifying these processes at a large scale is a determinant of understanding sediment transfers from continental lands to marine ecosystems. This study tries to fill this gap by coupling the soil erosion model WaTEM/SEDEM (WS) with the riverine connectivity tool CASCADE to quantify sediment fluxes in the Rhône watershed. The coupling returned a good fit, with deviations of −51.7%. WS alone predicts the exported fluxes better with a deviation of −34.9%. Nevertheless, this paper shows the importance of considering connectivity and transport capacity to develop a more realistic representation of fine sediment dynamics at a large scale. However, connectivity tools depend on the quality of the models (soil erosion and hydrology) and the geomorphological data on which they depend, which is a limiting factor in large‐scale studies.
A critical review of distributed fiber optic sensing applied to geologic carbon dioxide storage
Authors: Liu Tianxiang , Li Qi , Li Xiaying , Tan Yongsheng , Cao Xiaomin 
Published: May 2024

AbstractIn the context of global climate change, carbon capture and storage (CCS) has become a direct and effective measure for reducing greenhouse gases emission. However, injecting CO2 into the subsurface reservoirs may pose risks related to geological hazards. Therefore, monitoring the variations in underground temperature fields, strain fields, and vibration fields induced by CO2 injection is essential for predicting and controlling geological hazards. Distributed fiber optic sensing (DFOS) technology, with its unique features, enables real‐time monitoring of temperature, strain, and vibration. By deploying fiber optic (FO) cables inside wellbores, a DFOS can be used to effectively capture multiple underground response parameters. This paper reviews the applications of DFOS technology in CO2 geological sequestration. The chapter covers aspects such as the literature review, principles and applications of fiber optics, and representative monitoring projects. Finally, the paper discusses the challenges and proposed solutions for DFOS technology in this context. © 2024 Society of Chemical Industry and John Wiley & Sons, Ltd.