bluuebunny/crossref_metadata_2025_split huggingface dataset:
A modulatory role of CG methylation on gene expression in soybean implicates its potential utility in breeding
Authors: Wang Ying , Xun Hongwei , Lv Jiameng , Ju Wanting , Jiang Yuhui , Wang Meng , Guo Ruihong , Zhang Mengru , Ding Xiaoyang , Liu Bao , Xu Chunming 
Published: January 2025

SummaryCytosine methylation (mCG) is an important heritable epigenetic modification, yet its functions remain to be fully defined in important crops. This study investigates mCG in soybean following the loss‐of‐function mutation of two GmMET1 genes. We generated knockout mutants of GmMET1s by CRISPR‐Cas9 and conducted comprehensive methylome and transcriptome analyses. Our findings unravel the functional redundancy of the two GmMET1s, with GmMET1b being more critically involved in maintaining mCG levels, and complete knockout of both copies is lethal. We establish that genome‐wide mCG levels scale with aggregated expression of GmMET1s. We identify a set of mCG‐regulated genes whose expression levels were quantitatively modulated by upstream, body, or downstream mCG. Moreover, we find genes that were negatively regulated by upstream or body mCG are enriched in specific biological processes such as that of jasmonic acid metabolism. Notably, >80% of the differentially methylated genes (DMGs) in the mutants also exist as DMGs in natural soybean populations. Phenotypically, mutants that are heterozygous for GmMET1a and homozygous for GmMET1b knockouts (GmMET1a+/−GmMET1b−/−) exhibited early flowering, which was inherited by their selfed progeny (GmMET1a+/+GmMET1b−/−) with otherwise normal growth and development. Moreover, mutation of either GmMET1s, with slight reduction of mCG levels and similar phenotypes compared to the wild type under normal conditions, showed enhanced tolerance to cold and drought stresses. Together, our results underscore highly orchestrated regulatory effects of mCG on gene expression in soybean, which dictates growth, development and stress responses, implicating its utility in the improvement of soybean for better adaptability and higher yield.
The ZmAHL25‐ZmPUB19‐ZmMPK5 Module Positively Regulates Resistance to Rhizoctonia solani in Maize
Authors: Liang Guanyu , Liu Chenxu , Liu Jiazong , Wan Kun , Sun Haonan , Liu Baoshen , Zhang Yongzhong , Wang Xiaojing , Li Ning 
Published: January 2025

ABSTRACTUbiquitin‐mediated proteolysis is a crucial mechanism in plant defenses against pathogens. However, the role of E3 ubiquitin ligases in the maize (Zea mays) defense response against Rhizoctonia solani, a major soil‐borne fungal pathogen that causes banded leaf and sheath blight, remains unclear. We previously identified the maize ZmPUB19 gene, which encodes a U‐box E3 ubiquitin ligase and is upregulated upon R. solani infection, suggesting its potential involvement in maize defense responses. In this study, we established that ZmPUB19 positively influences the maize defense response to R. solani. In vitro and in vivo experiments revealed that ZmPUB19 interacts with and ubiquitinates the mitogen‐activated protein kinase ZmMPK5, resulting in ZmMPK5 degradation in response to R. solani infection. The Zmmpk5 mutant demonstrated superior resistance to R. solani compared to the wild type. Additionally, we identified an AT‐Hook Motif Nuclear Localized (AHL) transcription factor, ZmAHL25, which binds to the AT‐rich cis‐element in the ZmPUB19 promoter and activates its expression under R. solani attack. Notably, decreased expression of ZmAHL25 increased maize susceptibility to R. solani. Collectively, our findings show that the ZmAHL25‐ZmPUB19‐ZmMPK5 module plays a positive role in regulating maize defense responses to R. solani infection.
Biocontrol Effect Induced by Streptomyces anulatusZAM4‐4 on Phytophthora capsici Causing Pepper Blight in Capsicum annuum
Authors: Long Meimei , Li Shanshan , Liu Changyun , Luo Yaqi , Huang Liguo , Wang Qiuyue , Cheng Qiangyi , Sun Xianchao , Fan Guangjin , Ma Guanhua 
Published: January 2025

ABSTRACTPepper blight, caused by the soilborne pathogen Phytophthora capsici, poses a formidable threat to pepper (Capsicum annuum) production. The prevalent use of chemical fungicides for pepper blight management has been associated with adverse environmental consequences. To address the drawbacks of chemical fungicides in agriculture, the exploration of biological control agents has emerged as a promising alternative. Here, we identified strain ZAM4‐4 as Streptomyces anulatus, which demonstrated potent inhibitory effects against P. capsici by impeding spore germination and zoospore release, while significantly enhancing the activities of superoxide dismutase (SOD), peroxidases (POD) and phenylalanine ammonia‐lyase (PAL). Moreover, the application of ZAM4‐4 fermentation resulted in notably increased height and fresh weight of pepper plants compared to the control group. Interestingly, ZAM4‐4 exhibited compatibility with a variety of conventional fungicides (metalaxyl, dimethomorph and fluopicolide), encouraging us to explore its combined use with fungicides to enhance control effectiveness. Both laboratory and pot experiments provided compelling evidence that the combined application of ZAM4‐4 and dimethomorph achieved a control efficacy comparable to that of high concentrations of dimethomorph alone in combatting pepper blight. Overall, our investigation demonstrated that ZAM4‐4 not only bolstered the resistance of pepper against Phytophthora blight by inhibiting P. capsici reproduction and elevating enzymatic activities, consequently stimulating plant growth, but also displayed improved and sustained control of pepper blight when used in combination with dimethomorph. These findings highlight the promising potential of ZAM4‐4 for future applications in the field of biological control for sustainable pepper blight management.
The Public's Premium: George W. Bush's Symbiosis of the Rhetorical Presidency and the Unitary Executive
Authors: Venterink Stef Lage , Olthof Jelte 
Published: January 2025

ABSTRACTPresident George W. Bush has become synonymous with ever‐expanding executive power. Both scholars of the rhetorical presidency as well as the unitary executive theory have come this conclusion on the basis of studying only either part of the administration's dual use of its powers. This article offers a different perspective by showing that a president's public and private powers are not antithetical but compatible. It suggests that presidents are free to move between both modes of power and that, if used symbiotically, a president's power grows even greater than the sum of its parts. The article connects this to recent scholarship about the role of public opinion in keeping unitary presidents in check and discusses both the role of presidential rhetoric in this, as well as the public's suitability as the final safeguard. The article builds on Vanessa Beasley's suggestions for a case‐driven approach by looking at the Bush Administration's unrelenting efforts to secure the public's approval in going to war with Saddam Hussein's Iraq in 2003 as well as the 2004 prison abuse scandal, in which the administration exclusively relied its executive powers in an attempt to circumvent public's approval for an unpopular policy.
Drainage Pattern Recognition Method Using Graph Convolutional Networks Combined With Three‐Dimensional Elevation Features
Authors: Qiang Bo , Liu Tao , Du Ping , Li Pengpeng , Wang Wenning , Xu Shenglu 
Published: January 2025

ABSTRACTDrainage pattern recognition plays a crucial role in flood management, hydraulic engineering site selection, and biodiversity maintenance. Although deep learning methods have been widely employed in drainage pattern recognition in recent years, most research has focused on two‐dimensional features, with limited attention given to the impact of three‐dimensional elevation features. This study, therefore, introduces a graph convolutional network (GCN) approach that incorporates three‐dimensional elevation features. This method integrates three‐dimensional elevation features into the feature system of deep learning‐based drainage pattern recognition for the first time, combining two‐dimensional geometric and topological features to comprehensively capture variations in both vertical and planar morphology of drainage patterns. Specifically, this study extracts representative drainage pattern samples (e.g., dendritic, skeleton, parallel, and fan) from OSM and HydroSHEDS river vector data. Six features are designed based on the micro‐to‐macro processes involved in drainage pattern development, and a novel drainage pattern feature description index is proposed. A GCN model architecture based on the first‐order Chebyshev polynomial is then developed to extract both global and local information of drainage patterns under three‐dimensional elevation features. Experimental results demonstrate that the recognition accuracy of this method achieves 90% on the test dataset, with precision, recall, and F1 scores improving by at least 3% compared to methods such as support vector machines (SVM) and GraphSAGE. This suggests that the feature description index incorporating three‐dimensional elevation features more comprehensively reflects the development process of drainage patterns, thereby improving recognition accuracy and offering new methods and perspectives for drainage pattern research.
Unexpected pathway for intercontinental movement into the Nearctic revealed by phylogenetic analyses
Authors: Tomoyasu Kye , Cannizzaro Andrew G. , Berg David J. 
Published: January 2025

AbstractMuch of North America's freshwater biodiversity is derived from Palearctic lineages. Isopods of the Holarctic family Asellidae are among the most widespread and diverse freshwater crustaceans, but Nearctic species are poorly studied. We examined the evolutionary history of the family, utilizing Sanger sequencing of mitochondrial and nuclear DNA, and both maximum likelihood and Bayesian inference. The genera Calasellus and Salmasellus from the western United States are shown to be basally derived, suggesting they have only distant affinity to other Nearctic taxa and represent relictual lineages that likely diverged in the Jurassic. Remaining Nearctic asellids formed a monophyletic group sister to the Lake Baikal endemic genus Baicalasellus, which diverged during the Early Cretaceous. Our results show a close connection between Nearctic and eastern Palearctic asellids, with an Early Cretaceous divergence consistent with limited connections between Asia and North America. We propose that asellids used a Beringian route to colonize the Nearctic from west to east, in contrast to Europe to North America routes hypothesized for other freshwater crustaceans. Many of the genera we analysed were non‐monophyletic; taxonomic revision may shed further light on the route and timing of asellid diversification in the Nearctic and on the processes by which freshwater taxa colonized this realm.
Antibiotics synergize the toxicity of acaricides against the bulb mite, Rhizoglyphus robini
Authors: Samadieh Hosein , Talebi Majid , Izadi Hamzeh , Khajehali Jahangir 
Published: January 2025

As the world’s most valuable spice, saffron holds significant economic importance in Iran. Rhizoglyphus robini Claparede (Acari: Astigmata: Acaridae) is one of the most critical and damaging pests affecting corm plants globally, including saffron fields in Iran. The repeated use of acaricides has led to the development of resistance in pest populations. Bacterial communities play a crucial role in the various physiological processes of their insect hosts, including the metabolism involved in detoxification. Bioassays against R. robini were performed with two acaricides, abamectin, and propargite, using a filter paper method. Based on the results, the LC50 values of 2.3 and 25 mg a.i./L were estimated for abamectin and propargite, respectively. The impact of antibiotic pretreatment on acaricide toxicity was assessed using six antibiotics: tetracycline, azithromycin, penicillin, cefalexin, cefixime, and streptomycin. The antibiotics (1.5 mL of 100 mg/L) were added to Petri dishes with a layer of filter paper. Mortality was significantly increased in the tetracycline pretreatment group, whereas the other antibiotics showed negligible effects. A bioassay comparing tetracycline pretreatment with a mixture of the other five antibiotics revealed that the antibiotic mixture also significantly enhanced toxicity. Pretreatment with the antibiotic mixture led to a 5.6-fold increase in abamectin toxicity and a 10.2-fold increase in propargite toxicity. To estimate the density of bacterial community in different treatments, total DNA was extracted, and 16S rRNA gene amplification was performed using a general bacterial primer pair. The semi-quantitative PCR results indicated reduced bacterial density in mites treated with tetracycline or an antibiotic mixture compared with the control. Enzymatic assays showed that the activities of detoxification enzymes, including glutathione S-transferases, carboxyl/cholinesterases, and cytochrome P450 monooxygenases, were significantly reduced in mites pretreated with tetracycline or antibiotic mixture. These findings suggest that bacterial community may influence acaricide metabolism by modulating detoxification enzyme activities in their hosts. This study provides a basis for further research into the mechanisms of symbiont-mediated detoxification in pest management.
Combining two predatory mite species (Phytoseiidae) to control two-spotted spider mites in greenhouse strawberry production
Authors: Wang Endong , Hou Zhengrong , Yan Hong , Dong Jie , Jiang Xiaohuan , Zhang Bo , Xu Xuenong 
Published: January 2025

Strawberry is an important economic crop worldwide, whereas two-spotted spider mites (TSSM, Tetranychus urticae) is the major pest in fruit production. To produce the organic and safe fruits in greenhouses, we selected two strawberry varieties that are most widely planted in northern China with popular taste to study the TSSM control efficiency by two predatory mites of Phytoseiulus persimilis and Neoseiulus californicus. We comprehensively evaluated the control methods by analyzing TSSM population dynamics, predatory mite numbers, leaf chlorophyll content, fruit weight, sugar content, and the cost of investing in predatory mites. We found that the mite-resistant variety Miaoxiang can largely maintain TSSM at a relative low-density, and N. californicus can provide sufficient control against TSSM during the whole growth season. When TSSM density was high in Suizhu, the combined use of predatory mites led to a substantial reduction of 85.99% in pest numbers, all at reasonable prices. Our fieldwork has demonstrated the crucial importance of pest monitoring and early warning systems in determining the application of biocontrol agents, taking into account factors such as TSSM population size and rate of expansion. These findings strongly suggest that utilizing suitable biocontrol agents represents a promising approach for effectively managing TSSM infestations in greenhouse strawberry production.
Single- and multiple-dose pharmacokinetics and safety of the SARS-CoV-2 3CL protease inhibitor RAY1216: a phase 1 study in healthy participants
Authors: Hu Yue , Li Haijun , Wang Kun , Wu Dandan , Zhang Hong , Ding Yanhua , Wu Junyan , Ye Suiwen , Peng Yun , Liu Li 
Published: January 2025

ABSTRACT

Coronavirus disease 2019, which leads to pneumonia, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RAY1216 is a 3C-like protease inhibitor that targets SARS-CoV-2. The aim of our study was to assess the pharmacokinetics (PK) and safety of RAY1216 in healthy volunteers. This was a randomized, placebo-controlled, double-blind study consisting of four components: a single ascending dose study, a drug-drug interaction study, a multiple ascending dose study, and a food-effect study. All participants were randomly assigned to receive either a single dose or multiple doses of RAY1216 or placebo. A total of 88 healthy adult participants (male-to-female ratio of 1:1) aged 18–50 years were enrolled. A total of 37 participants (42%) experienced at least one adverse event (AE). All AEs were mild or moderate and were resolved without additional treatment. The most commonly reported adverse drug reactions were hypertriglyceridemia, hyperuricemia, and elevated serum creatinine levels. RAY1216 was well-absorbed after administration with exposure increasing in a dose-dependent manner. Food appeared to increase exposure and delay the absorption of RAY1216. Ritonavir significantly inhibited drug metabolism, and increased drug exposure increased the associated safety risks. RAY1216 was found to be well tolerated and safe in healthy participants. On the basis of preclinical results, PK characteristics, and the safety profile of RAY1216, a dosage of 400 mg three times daily was selected, thereby establishing a foundation for future research and for the clinical application of RAY1216.

CLINICAL TRIALS

This study is registered with ClinicalTrials.gov as
NCT05829551
.
Metastable Nanoprecipitates in Alloys: Phenomenology and Atomistic Simulation
Authors: Razumov I. K. , Gornostyrev Yu. N. 
Published: January 2025

Abstract
Metastable disperse states arising from decomposition in alloys are of considerable interest and have an important practice-related significance, providing high strength properties. Recently, the stabilization mechanism of disperse states through the formation of a shell enriched in alloying elements has attracted special attention. The paper presents a concise overview of the theoretical concepts pertaining to the formation and stabilization of disperse states in alloys, along with recent findings from first-principles atomistic simulations of Al–Cu–X, Fe–Cu–X, and Al–Sc–Zr alloys, wherein precipitates with a core–shell structure have been observed. Furthermore, the paper addresses the conditions of kinetic and thermodynamic stabilization of precipitates in relation to coalescence processes during annealing.
Role of biosimilar introduction on insulin glargine prices: a retrospective analysis in 28 European countries
Authors: Morolla Davide , Beran David , Ewen Margaret , Raviglione Mario , von Schoen-Angerer Tido 
Published: January 2025

ObjectiveQuantify insulin glargine prices following the market introduction of biosimilars. Examine price levels and price changes for originator and biosimilars, by country.MethodsRetrospective quantitative analysis using insulin glargine pricing data, both of the originator product and its biosimilars. Segmented regression analysis using a dual-model approach: pooled and country-specific.Setting28 European countries using data from the European Medicine Price Database for the period 2013–2023.Main outcome measuresPrice variations between countries were analysed to assess trends and correlations before and after biosimilar market entry.ResultsIn the 28 countries studied, cost of insulin glargine underwent a median 21.6% decrease overall in the last decade (p<0.001). In 2022, the median price was €9.0 for the originator (first to market) Lantus (IQR €8.1–€10.4), €8.9 for the biosimilar Abasaglar (IQR €7.6–€10.1) and €7.0 for the biosimilar Semglee (median €7.0; IQR €6.8–€7.5). The originator price was higher than biosimilars (p=0.009). Biosimilar market entry was associated with an overall significant price reduction of the originator, both immediately after entry (p<0.001) and in the long-term postentry (p<0.001). No significant correlation was observed between the price of insulin and the countries’ economic indicators.ConclusionThis is the first study to show the price trend of insulin glargine and its correlation with the introduction of biosimilars, in Europe. A significant price reduction of the originator was observed after biosimilars entered the market. The median cost of biosimilars was lower than the originator, although with substantial differences between individual countries and producers.
What about physician wellness? Impact of a quality improvement intervention
Authors: Mathura Pamela , Pascheto Isabella , Ringrose Jennifer , Ramsay Gillian 
Published: January 2025

BackgroundEmergency department (ED) consultations with general internal medicine (GIM) are required when patients need admission, assistance with safe disposition or evaluation and management of complex or acute medical needs. GIM physicians often balance responsibilities between hospital wards and the ED, which can lead to delayed ED consultations, difficulty balancing workload and potential burn-out. To address this issue, a quality improvement (QI) initiative was trialled, establishing a dedicated GIM ED consultation service to manage these duties independently. This study aimed to evaluate the impact of this intervention on physician wellness.MethodsA pre–post design was used, with two questionnaires adapted from the validated Mini Z version 2.0 (Zero Burnout Program) Worklife measure for clinicians. These were distributed via Google Forms to collect feedback from participating GIM physicians before and after the intervention. Data were analysed using descriptive statistics and the Mini Z outcome measurement scale.Results13 physicians completed the surveys. Applying the Mini Z scale, the GIM ED consultation service had no impact on physician well-being or burn-out. There was a minor increase in satisfaction (1 point) and stress levels (2 points), and the working environment worsened slightly (1 point). Comparing preintervention and postintervention survey responses, job satisfaction improved (36%), while reports of ‘burn-out’ (23%) and ‘beginning to burn out’ (8%) decreased. Postintervention, physicians reported decreased time for documentation (23%), a perception of a more chaotic work environment (23%) and an increase in work encroaching on personal time (15%) when on the ED consultation service. Additionally, there was a 23% reduction in the likelihood of needing to reduce clinical teaching unit service weeks.ConclusionWhen conducting QI initiatives, consider measuring the wellness of physicians and other healthcare providers. Proactively integrating wellness strategies into interventions requires further exploration which may enhance participant experience and initiative sustainability.
Impact of preoperative opioid exposure on cost of care and workplace productivity loss after elective surgery
Authors: Shabet Christina Lynn , Alessio Dominic , Kenney Brooke , Bicket Mark C , Brummett Chad M , Waljee Jennifer F 
Published: January 2025

IntroductionA high proportion of surgical patients has previous opioid exposure, which is associated with poorer recovery and increased morbidity. However, much less is known regarding the direct and indirect costs that are associated with healthcare utilization among individuals on preoperative opioid therapy.MethodsWe analyzed The Merative MarketScan Commercial Database linked with the Merative MarketScan Health and Productivity Management Database to include all adult patients admitted and discharged from common elective surgeries between January 1, 2018 and June 30, 2021. Patients were clustered by preoperative opioid exposure and estimates for total direct payments (in USD) generated and workplace absenteeism were assessed for a 6-month period.Results10 737 patients were included in our cohort; 17.0% classified as ‘low’ preoperative opioid use (median oral morphine equivalents (IQR)=126 (75–225)), 5.0% as ‘medium’ (370 (225–640)) and 3.0% as ‘high’ (4500 (2120–10 908)). Compared with opioid naive or low preoperative use, individuals with high preoperative use had significantly higher estimated payments for care at 6 months ($4212 for high vs $2706 for naive (p=0.007) and $3059 for low (p=0.045)), while utilizing increased ambulatory care including clinic and outpatient visits after surgery. There was no significant difference in workplace absenteeism between groups.ConclusionHigh preoperative opioid use is associated with increased healthcare utilization and costs following common elective surgery. Future efforts should focus on this patient population to explore interventions that could optimize value-based care by improving outcomes and reducing costs.