bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells
Authors: Lu Xiaodan , Liu Fuyao , Chen Hongming , Cai Haojie , Zhang Lei , Li Jing 
Published: October 2024

ABSTRACTHyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK‐MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG), tumor necrosis factor (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐8 (IL‐8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate‐lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8‐OHdG and inflammatory factor TNF‐α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFβ and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.
Fragment and torsion biasing algorithms for construction of small organic molecules in proteins using DOCK
Authors: Bickel John D. , Boysan Brock T. , Rizzo Robert C. 
Published: October 2024

AbstractThe computational construction of small organic molecules (de novo design), directly in a protein binding site, is an effective means for generating novel ligands tailored to fit the pocket environment. In this work, we present two new methods, which aim to improve de novo design outcomes using (1) biasing algorithms to prioritize selection and/or acceptance of fragments and torsions during growth, and (2) parallel‐based clustering and pruning algorithms to remove duplicate molecules as candidate fragment are added. Large‐scale testing encompassing thousands of simulations were employed to interrogate the methods in terms of multiple metrics which include numbers of duplicate molecules generated, pairwise‐similarity, focused library reconstruction rates, fragment and torsion frequencies, fragment and torsion rank scores, interaction energy and drug‐likeness scores, and 3D pose comparisons. The biasing algorithms, particularly those that include fragment and torsion components simultaneously, led to molecules that more closely mimicked the distributions of fragments and torsions found in drug‐like libraries. The new parallel‐based clustering and pruning algorithms, compared with the existing serial approach, also led to larger ensembles comprised of topologically unique molecules with much greater efficiency by removing redundant growth paths.
Pre‐training strategy for antiviral drug screening with low‐data graph neural network: A case study in HIV‐1 K103N reverse transcriptase
Authors: Boonpalit Kajjana , Chuntakaruk Hathaichanok , Kinchagawat Jiramet , Wolschann Peter , Hannongbua Supot , Rungrotmongkol Thanyada , Nutanong Sarana 
Published: October 2024

AbstractGraph neural networks (GNN) offer an alternative approach to boost the screening effectiveness in drug discovery. However, their efficacy is often hindered by limited datasets. To address this limitation, we introduced a robust GNN training framework, applied to various chemical databases to identify potent non‐nucleoside reverse transcriptase inhibitors (NNRTIs) against the challenging K103N‐mutated HIV‐1 RT. Leveraging self‐supervised learning (SSL) pre‐training to tackle data scarcity, we screened 1,824,367 compounds, using multi‐step approach that incorporated machine learning (ML)‐based screening, analysis of absorption, distribution, metabolism, and excretion (ADME) prediction, drug‐likeness properties, and molecular docking. Ultimately, 45 compounds were left as potential candidates with 17 of the compounds were previously identified as NNRTIs, exemplifying the model's efficacy. The remaining 28 compounds are anticipated to be repurposed for new uses. Molecular dynamics (MD) simulations on repurposed candidates unveiled two promising preclinical drugs: one designed against Plasmodium falciparum and the other serving as an antibacterial agent. Both have superior binding affinity compared to anti‐HIV drugs. This conceptual framework could be adapted for other disease‐specific therapeutics, facilitating the identification of potent compounds effective against both WT and mutants while revealing novel scaffolds for drug design and discovery.
Choice of blood collection methods influences extracellular vesicles counts and miRNA profiling
Authors: Tran Vivian , Oliveira‐Jr Getulio Pereira de , Chidester Stephanie , Lu Shulin , Pleet Michelle L. , Ivanov Alexander R. , Tigges John , Yang Moua , Jacobson Steven , Gonçalves Maria C. B. , Schmaier Alec A. , Jones Jennifer , Ghiran Ionita C. 
Published: October 2024

AbstractCirculating RNAs have been investigated systematically for over 20 years, both as constituents of circulating extracellular vesicles (EVs) or, more recently, non‐EV RNA carriers, such as exomeres and supermeres. The high level of variability and low reproducibility rate of EV/extracellular RNA (exRNA) results generated even on the same biofluids promoted several efforts to limit pre‐analytical variability by standardizing sample collection and sample preparation, along with instrument validation, setup and calibration. Anticoagulants (ACs) are often chosen based on the initial goal of the study and not necessarily for the later EV and/or exRNA analyses. We show the effects of blood collection on EV size, abundance, and antigenic composition, as well on the miRNAs. Our focus of this work was on the effect of ACs on the number and antigenic composition of circulating EVs and on a set of circulating miRNA species, which were shown to be relevant as disease markers in several cancers and Alzheimer's disease. Results show that while the number of plasma EVs, their relative size, and post‐fluorescence labeling profile varied with each AC, their overall antigenic composition, with few exceptions, did not change significantly. However, the number of EVs expressing platelet and platelet‐activation markers increased in serum samples. For overall miRNA expression levels, EDTA was a better AC, although this may have been associated with stimulation of cells in the blood collection tube. Citrate and serum rendered better results for a set of miRNAs that were described as circulating markers for Alzheimer's disease, colon, and papillary thyroid cancers.
A Novel Rhodamine‐Tetraphenylporphyrin Fluorescence Probe for Imaging Mercury In Vitro and In Vivo
Authors: Li Ling , Yao Yinuo , Wang Xiaowan , Yu Yaoqi , Ji Tailong , Li Han , Li Yi , Liu Yuanyuan 
Published: October 2024

ABSTRACTA highly selective fluorescent sensor Por‐RBO for determination of Hg2+ was designed and synthesized with Rhodamine B and Tetraphenylporphyrin. The sensor can determine the Hg2+ of a solution within the pH 5.0–8.0, free from interference of other metal ions. When detected in buffer solution, the fluorescence was the strongest when five times the concentration of Hg2+ ion was added. Calculated by fluorescence titration method, the detection limit of sensor Por‐RBO for Hg2+ ion was as low as 0.12 μmol/L. The geometries of Por‐RBO and Por‐RBO‐Hg2+ were optimized at the B3LYP/6‐31G** level by density functional theory. The charge distribution, orbital interactions, and bonding characteristics were analyzed and compared in detail to discuss the recognition mechanism and structure–fluorescence property relationships. The results of cell fluorescence imaging and CCK‐8 experiments indicate that the sensor Por‐RBO exhibits lower cytotoxicity. Por‐RBO can be used for fluorescence distribution imaging of Hg2+ in living cells.
A Global Analysis of Historical and Future Changes in Mediterranean Climate‐Type Regions
Authors: Urdiales‐Flores Diego , Zittis George , Hadjinicolaou Panos , Cherchi Annalisa , Alessandri Andrea , Peleg Nadav , Lelieveld Jos 
Published: October 2024

ABSTRACTMediterranean climate‐type regions (MCRs) are characterised by warm‐to‐hot dry summers and mild‐wet winters. These regions are typically found on the western or southern edges of continents, for example, in the Mediterranean Basin, the west coast of North and South America, southern Africa and southwest Australia. The MCRs are vulnerable to climate variability and change related to their unique characteristics, such as pronounced rainfall seasonality and prolonged hot and dry summers. Based on historical observations and CMIP6 climate projections, we apply an empirical bio‐climatic assessment of how the geographic distribution of MCRs has changed during the last century and how these zones will be further impacted under continued warming. Results indicate a poleward and eastward expansion of MCRs in the Mediterranean Basin, North America‐California and South America‐Central Chile regions. For parts of Southern Africa and Southern Australia, a retreat of the MCR margins and an expansion of more arid climate zones are projected. These shifts are particularly profound according to high emission and radiative forcing pathways and future scenarios. The warming in MCRs is projected to accelerate (e.g., mean regional warming of up to 5.5°C under a 4°C global warming scenario), and precipitation will decrease by about 5%–10% for every additional degree of global warming. One exception is the California MCR, where rainfall will likely increase. Such changes can challenge water resources, food security and other aspects of human livelihood and ecosystems in these unique geographical zones.
The synergistic immunomodulatory activity of Lycium barbarum glycopeptide and isochlorogenic acid A on RAW264.7 cells
Authors: Xu Ge , Yu Zhipeng , Zhao Wenzhu 
Published: October 2024

AbstractBACKGROUNDRegulation of the immune system to maintain homeostasis in the organism has become a focus of research, and the synergistic effect of multi‐component complexes will effectively improve the immunomodulatory activity. The present study aimed to investigate the interaction and synergistic immunomodulatory activity of isochlorogenic acid A (IAA) and Lycium barbarum glycopeptide (LbGp).RESULTSThe results obtained indicated that non‐covalent intermolecular interactions were employed to form the LbGp–IAA complex, with a binding ratio of 135.15 mg g−1. The formation of LbGp–IAA complex altered the conformation of LbGp, and IAA was mainly bound to LbGp by van der Waals forces and hydrogen bonds. In addition, LbGp–IAA promoted the proliferation of RAW264.7 cells. The IAA and LbGp interaction had a synergistic effect on the promotion of phagocytosis and the expression of nitric oxide, tumor necrosis faction‐α and interleukin‐1β, which improved the immunomodulatory effect of LbGp. Furthermore, the combination of LbGp and IAA synergistically inhibited lipopolysaccharide‐induced inflammatory response.CONCLUSIONIn summary, the binding of IAA enhanced the immunomodulatory activity of LbGp and coordinated the immune response, and did not trigger an inflammatory response, which was potentially attributed to the alteration of spatial structure of LbGp through the binding of IAA. The results provide new perspectives for the study of glycopeptide–polyphenol interactions. © 2024 Society of Chemical Industry.
Accelerated oxygenation for the production of fortified (mystelle‐type) sweet wines: effects on the chemical and flavor profile
Authors: Bianchi Alessandro , Pettinelli Stefano , Pittari Elisabetta , Paoli Leonardo , Sanmartin Chiara , Pons Alexandre , Mencarelli Fabio , Piombino Paola 
Published: October 2024

AbstractBACKGROUNDFortified wine is an important category in the wine world with very famous wines such as Porto or Jerez‐wine type. The quality of fortified wines increased significantly with barrel aging not only because of a long oxidation process, but also because, in Porto wines such as Ruby or Vintage styles, the long period in bottle permits their fining. Reducing the time of oxidation can favor the development of this technique even for less known sweet wines, making them good quality and less expensive. In the present study, we have used Gamay red variety subjected to postharvest controlled dehydration at 20–22 °C and 70–75% relative humidity with an airflow of 1 m s−1. Then the grapes were pressed, and alcohol was added to the must up to an alcohol content of 15.85% (mystelle‐type wine). The mass was split into six glass jars, three were oxygenated (OX) and three not (Control), and the oxygenation lasted 62 days.RESULTSWine that was oxygenated had a slightly higher volatile acidity, lower alcohol content (13.00%), and lower anthocyanins and polyphenols content. In term of volatile organic compounds (VOCs), the Control wine had a higher content of alcohols, whereas the OX sample had a higher content of lactones, furans and esters. Sensory evaluation confirmed the VOCs analysis; the two wines had a statistically different profile depending on the oxidation treatment. In general, OX wine was more appreciated in terms of visual attractiveness, taste and olfactory pleasantness.CONCLUSIONIn conclusion, the technique described in the present study could be a valid alternative to traditional aging of fortified sweet wines, reducing time and costs. © 2024 Society of Chemical Industry.
Assessment and Multiscenario Simulation of Land Use and Ecosystem Services Interactions in Inner Mongolia
Authors: Dai Zhen‐Zhong , Chang Sen , Zhu Zhi‐Yuan , Duan Jia‐Jia , Jiang Tian‐Yu , Wu Wen‐Qiang , Feng Yong‐Zhong , Yang Gai‐He , Wang Xing 
Published: October 2024

ABSTRACTBalancing land development and ecological protection poses significant challenges for sustainable development in arid and semi‐arid regions like Inner Mongolia. This study uses the integrated valuation of ecosystem services (ESs) trade‐offs model and patch‐generated land‐use simulation model to analyze the impacts of land‐use/cover (LULC) changes on ESs from 2005 to 2020 and simulate scenarios for 2035. The results show that (1) ecological governance efforts improved the comprehensive ecological index (CEI), habitat quality, and soil conservation capacity but led to a decrease in the annual water yield (AWY) in the eastern region. Additionally, the conversion of grassland and forest land to construction land and farmland caused slight declines in carbon sequestration and increased nitrogen export. (2) The external driving factors of different ESs vary, and the internal relationships within ESs have also changed. Notably, changes in LULC transformed the synergy between AWY and habitat quality into a trade‐off relationship after 2010 due to increased forest and grassland. (3) Among the five land‐use scenarios, the comprehensive development scenario combined with zonal management strategies can achieve the sustainable development goals of economic growth, ecological protection, and food security. This study clarifies the internal and external factors affecting ESs in Inner Mongolia and provides a scientific basis for future LULC management and ecological governance policies. It fills a gap in the spatiotemporal simulation of ESs under multiple scenarios in this region. These findings offer valuable references for promoting sustainable development in similar arid and semi‐arid regions, highlighting the importance of integrating multi‐objective strategies and adaptive management practices to balance ecological and economic objectives.
Innovative and Cost‐Effective Approaches to the Measurement of Sediment Levels in Small Water Reservoirs
Authors: Paseka Stanislav 
Published: October 2024

ABSTRACTSedimentation in small water reservoirs poses a critical challenge with significant environmental, economic, and social implications. To address this issue, this study will employ three measurement techniques—GNSS RTK Trimble R8s, Echolot HDS LIVE 7 with Active Imaging 3‐in‐1, and the Mivardi Carp Scout bait boat—to assess sediment levels in Žebětínský Pond in Brno, Czech Republic. The research reveals that each method offers distinct advantages and limitations. Through measurement and triangulated networks, the study creates a digital terrain model that facilitates the determination of reservoir volume and sediment levels. The comparison shows that the cost‐effective alternatives, Echolot HDS LIVE 7 and Mivardi Carp Scout, provide sufficiently accurate results. The evaluation shows that while the GNSS RTK Trimble R8s has the highest level of accuracy and is unique in its ability to measure both along the shoreline of the reservoir and the hard bottom, it comes with increased costs and logistical challenges. The Echolot HDS LIVE 7 and Mivardi Carp Scout offer efficient, cost‐effective solutions that are suitable for a quick estimate of sediment thickness. This research contributes to the use of reliable mathematical models and water management strategies, advocating for a pragmatic approach to the selection of methods based on the project characteristics. The study provides valuable insights into sediment measurement techniques, guiding future endeavors in reservoir management and environmental conservation. It is also used to easily indicate the loss of arable land in the catchment upstream of the reservoir.
Artificial Grassland Revegetation Improves Soil Water Retention and Storage Capacity of the Degraded Hillside Alpine Meadow
Authors: Ma Yulei , Meng Lingchao , Liu Yifan , Pinos Juan , Shi Zhihua , Wu Gao‐Lin 
Published: October 2024

ABSTRACTThe crucial role of soil water retention and storage in soil hydrology and the water cycle is well established. However, in sensitive and degraded ecosystems like alpine meadows, the effectiveness of revegetation in enhancing these critical functions remains understudied. This study investigates the effects of revegetating severely degraded hillside meadows with artificial grasslands on soil water retention and storage capacity in the Qinghai‐Tibetan Plateau. Soil analyses at a depth of 0–20 cm revealed significant improvements in soil properties after revegetation, with increases in soil organic matter content (86.8%), total porosity (11.9%), capillary porosity (31.6%), and clay content (13.5%). Both the saturated hydraulic conductivity (Ks) and field capacity (FC) increased markedly, by 9.7% and 63.7% in the upper layer (0–10 cm) and 21.7% and 69.6% in the lower layer (10–20 cm), respectively. Structural equation modeling identified bulk density, root mass density, FC, capillary porosity, and clay content as the dominant direct factors influencing Ks with path coefficients of −0.56, 0.30, −0.53, 0.57, and −0.12, respectively, while vegetation cover and aboveground biomass were found to have indirect influences. These findings demonstrate that revegetation with artificial grasslands effectively improves soil water retention and storage capacity in degraded hillside alpine meadows by regulating key soil hydraulic and physical properties. This enhanced water‐holding capacity has significant implications for understanding the dynamics of revegetation by artificial grassland establishment in improving ecosystem health and eco‐hydrological functions in these vulnerable environments. Furthermore, the study provides valuable insights and a theoretical basis for developing ecological restoration solutions for degraded hillside meadows in other alpine regions.
Soil Erosion Under Climate and Land Use Changes in China: Incorporating Ecological Policy Constraints
Authors: Zhang Yi , Zeng Yi , Zong Renjie , Fang Nufang 
Published: October 2024

ABSTRACTProjections of soil erosion under climate and land use changes are pivotal for optimizing soil conservation strategies. Ecological policies are thought to influence future land‐use changes and associated soil erosion dynamics. However, these policies are inadequately incorporated into projections, leaving the future trajectory of soil erosion still unclear. China's ecological redline policy (ERP) is among the first national policies to integrate multiple ecosystem services into land use planning, preventing anthropogenic soil erosion on over 25% of the territory. Therefore, focusing on China, three alternative Shared Socioeconomic Pathway and Representative Concentration Pathway scenarios (SSP1‐2.6, SSP3‐7.0, and SSP5‐8.5) were coupled with future‐oriented ERP to reflect future soil erosion patterns by the late‐21st century. Projections rely on an integrated multi‐model approach. The conducted analysis suggests that climate change is projected to exacerbate soil erosion by 12.06%–36.90% due to increased precipitation, characterized by high‐intensity events. Land use change is projected to mitigate or even reverse the climate‐induced increase in soil erosion. The combined climate and land use simulations showed that the annual average soil erosion rate will increase by 26.36% under the SSP5‐8.5 scenario, while it will decrease by 8.08% and 14.94% under the SSP1‐2.6 and SSP3‐7.0 scenarios, respectively. The implementation of ERP reduces potential soil erosion by 4.08%–14.89% (equal to 0.31–0.86 Gt year−1 soil loss) in the late‐21st century, particularly in scenarios with intensive conflicts between population and land sources. This study provides a valuable reference for the formulation of national strategies aimed at controlling soil loss accelerated by climate change.