bluuebunny/crossref_metadata_2025 huggingface dataset:
The Restorative Effects of Unique Green Space Design: Comparing the Restorative Quality of Classical Chinese Gardens and Modern Urban Parks
Authors: Zhang Zhenyu , Jiang Mu , Zhao Jingwei
Published: September 2024

The purpose of this paper is to explore the restorative effects of two unique Urban Green Spaces (UGSs): modern urban parks (MUPs) and classical Chinese gardens (CCGs). Compared to MUPs, little research has been conducted on the potential restorative effects of CCGs. To fill this gap, we collected video clips of various scenes in Suzhou, Jiangsu Province, ‘the city of gardens’ in China, and produced video images of CCGs and MUPs representing UGSs. Public ratings of these videos were collected using the Short-Version Revision Repair Scale (SRRS) to analyze the perceived restorative effects and drivers of CCGs and MUPs in combination with landscape elements, which were deeply parsed using computer vision techniques (semantic segmentation techniques) and expert scoring methods. The aim is to enhance the therapeutic effects of CCGs and MUPs. The results indicate that the differences between the two landscape types in terms of their restorative effects are not significant. The videos representing CCGs had a greater standard deviation of restorative effects (a lower level of consensus) compared to the videos depicting MUPs. Deep learning techniques for semantic segmentation combined with expert scoring methods can effectively help us to understand the drivers influencing restorative effects, and we combined our findings to conclude that improved waterscape design is an essential driver for enhancing the perceived restorative effects of CCGs and that decreasing specific artificial modern structures, enhancing vegetation cover, and increasing public exposure to nature are critical to strengthening the restorative effects of both. Hopefully, these findings will improve visitors’ recovery in UGS environments and guide landscape architects to more effectively design healing UGSs.
A Task Offloading and Resource Allocation Strategy Based on Multi-Agent Reinforcement Learning in Mobile Edge Computing
Authors: Jiang Guiwen , Huang Rongxi , Bao Zhiming , Wang Gaocai
Published: September 2024

Task offloading and resource allocation is a research hotspot in cloud-edge collaborative computing. Many existing pieces of research adopted single-agent reinforcement learning to solve this problem, which has some defects such as low robustness, large decision space, and ignoring delayed rewards. In view of the above deficiencies, this paper constructs a cloud-edge collaborative computing model, and related task queue, delay, and energy consumption model, and gives joint optimization problem modeling for task offloading and resource allocation with multiple constraints. Then, in order to solve the joint optimization problem, this paper designs a decentralized offloading and scheduling scheme based on “task-oriented” multi-agent reinforcement learning. In this scheme, we present information synchronization protocols and offloading scheduling rules and use edge servers as agents to construct a multi-agent system based on the Actor–Critic framework. In order to solve delayed rewards, this paper models the offloading and scheduling problem as a “task-oriented” Markov decision process. This process abandons the commonly used equidistant time slot model but uses dynamic and parallel slots in the step of task processing time. Finally, an offloading decision algorithm TOMAC-PPO is proposed. The algorithm applies the proximal policy optimization to the multi-agent system and combines the Transformer neural network model to realize the memory and prediction of network state information. Experimental results show that this algorithm has better convergence speed and can effectively reduce the service cost, energy consumption, and task drop rate under high load and high failure rates. For example, the proposed TOMAC-PPO can reduce the average cost by from 19.4% to 66.6% compared to other offloading schemes under the same network load. In addition, the drop rate of some baseline algorithms with 50 users can achieve 62.5% for critical tasks, while the proposed TOMAC-PPO only has 5.5%.
Molecular Characterization of Listeria monocytogenes in the Food Chain of the Republic of Kosovo from 2016 to 2022
Authors: Jashari Besart , Capitaine Karine , Bisha Bledar , Stessl Beatrix , Blagoevska Katerina , Cana Armend , Jankuloski Dean , Félix Benjamin
Published: September 2024

The present study describes the genetic characterization of L. monocytogenes strains found in the Republic of Kosovo’s food chain. From 2016 to 2022, 995 samples were collected. Overall, 648 samples were from ready-to-eat (RTE) food products, 281 from food products consumed cooked (FPCC), 60 from raw materials, and 6 from environmental samples. Overall, 11.76% (117 out of 995) of the samples were contaminated by L. monocytogenes, comprising 6.33% (41 out of 648) from RTE products, 14.95% (42 out of 281) from FPCC, 55.00% (33 out of 60) from raw materials, and 16.66% (1 out of 6) from environmental samples. All isolates were subjected to molecular serotyping and clonal complex (CC) identification by using real-time PCR, as well as multilocus sequence typing. All isolates were grouped into four molecular serotypes, IIa (34.19%), IIb (3.48%), IIc (32.48%), and IVb (29.91%), as well as Lineage I (33.33%) and Lineage II (66.66%). In total, 14 CCs were identified from 41 RTE isolates; however, CC29 (7), CC2 (6), and CC6 (6) were the most dominant. By contrast, CC9 was by far the most represented CC in both FPCC (21) and RM (14). Moreover, 30 isolates expressed CC1, CC2, CC4, or CC6, which are particularly associated with severe human infections.
Dynamic Changes of Active Components and Volatile Organic Compounds in Rosa roxburghii Fruit during the Process of Maturity
Authors: Xu Su , Deng Junyi , Wu Siyao , Fei Qiang , Lin Dong , Chen Haijiang , Tao Guangcan , Meng Lingshuai , Hu Yan , Ma Fengwei
Published: September 2024

Rosa roxburghii (R. roxburghii), native to the southwest provinces of China, is a fruit crop of important economic value in Guizhou Province. However, the changes in fruit quality and flavor during R. roxburghii fruit ripening have remained unknown. Here, this study investigated the changes of seven active components and volatile organic compounds (VOCs) during the ripening of the R. roxburghii fruit at five different ripening stages including 45, 65, 75, 90, and 105 days after anthesis. The results indicated that during the ripening process, the levels of total acid, vitamin C, and soluble sugar significantly increased (p < 0.05), while the levels of total flavonoids, superoxide dismutase (SOD), and soluble tannin significantly decreased (p < 0.05). Additionally, the content of total phenol exhibited a trend of first decreasing significantly and then increasing significantly (p < 0.05). A total of 145 VOCs were detected by HS-SPME-GC-MS at five mature stages, primarily consisting of aldehydes, alcohols, esters, and alkenes. As R. roxburghii matured, both the diversity and total quantity of VOCs in the fruit increased, with a notable rise in the contents of acids, ketones, and alkenes. By calculating the ROAV values of these VOCs, 53 key substances were identified, which included aromas such as fruit, citrus, green, caramel, grass, flower, sweet, soap, wood, and fat notes. The aromas of citrus, caramel, sweet, and wood were predominantly concentrated in the later stages of R. roxburghii fruit ripening. Cluster heatmap analysis revealed distinct distribution patterns of VOCs across five different maturity stages, serving as characteristic chemical fingerprints for each stage. Notably, stages IV and V were primarily characterized by a dominance of alkenes. OPLS-DA analysis categorized the ripening process of R. roxburghii fruit into three segments: the first segment encompassed the initial three stages (I, II, and III), the second segment corresponded to the fourth stage (IV), and the third segment pertained to the fifth stage (V). Following the variable importance in projection (VIP) > 1 criterion, a total of 30 key differential VOCs were identified across the five stages, predominantly comprising ester compounds, which significantly influenced the aroma profiles of R. roxburghii fruit. By integrating the VIP > 1 and ROAV > 1 criteria, 21 differential VOCs were further identified as key contributors to the aroma changes in R. roxburghii fruit during the ripening process. This study provided data on the changes in quality and aroma of R. roxburghii fruit during ripening and laid the foundation for the investigation of the mechanism of compound accumulation during ripening.
Developing an Acceptable Nixtamalised Maize Product for South African Consumers: Sensory, Survey and Nutrient Analysis
Authors: Colbert Taylon , Bothma Carina , Pretorius Wilben , du Toit Alba
Published: September 2024

South Africa produces high-quality maize, yet food insecurity and malnutrition are prevalent. Maize is a staple for most South Africans and is often eaten as pap, gruel cooked from maize meal (corn flour) and water without diet diversification. Considering the reliance on maize in low-income communities, could nixtamalised maize products be developed that are nutritious, homemade and consumer-acceptable? Nixtamalisation could offer a solution. However, its acceptability and nutritional benefits remain in question. We aimed to develop a product using consumer-led methods. Consumer panels evaluated and selected products using overall acceptability (9-point hedonic scale), Just-About-Right (JAR) and penalty analysis. Consumer-acceptable nixtamalised chutney-flavoured maize chips were moderately liked (7.35) and reached acceptable JAR scores (74.2%). The nixtamalised products were liked and liked very much (56%), 61% of panel members agreed and strongly agreed to purchase and prepare, and 50% to consume nixtamalised products. Nutrient analysis of the chutney chips showed high energy (2302 kJ/100 g) and total fats (23.72), of which saturated fats were 11.47%. Total fibre (17.19 g/100 g), protein (6.64 g/100 g), calcium (163.3) and magnesium (53.67 g/100 g) were promising, while high phosphorous (566.00 mg/100 g) may indicate anti-nutrients present. Nixtamalisation can alleviate food insecurity and malnutrition in countries such as South Africa.
Evaluation of AV Deadheading Strategies
Authors: Mantri Sruthi , Bergman David , Lownes Nicholas
Published: September 2024

The transition of the vehicle fleet to incorporate AV will be a long and complex process. AVs will gradually form a larger and larger share of the fleet mix, offering opportunities and challenges for improved efficiency and safety. At any given point during this transition a portion of the AV fleet will be consuming roadway capacity while deadheading, which means operating without passengers. Should these unoccupied vehicles simply utilize the shortest paths to their next destination, they will contribute to congestion for the rest of the roadway users without providing any benefit to human passengers. There is an opportunity to develop routing strategies for deadheading AVs that mitigate or eliminate their contribution to congestion while still serving the mobility needs of AV owners or passengers. Some of the AV fleet will be privately owned, while some will be part of a shared AV fleet. In the former, some AVs will be owned by households that are lower-income and benefit from the ability to have fewer vehicles to serve the mobility needs of the household. In these cases, it is especially important that deadheading AVs can meet household mobility needs while also limiting the contribution to roadway congestion. The aim of this study is to develop and evaluate routing strategies for deadheading autonomous vehicles (AVs) that balance the reduction of roadway congestion and the mobility needs of households. By proposing and testing a bi-objective program, this study seeks to identify effective methodologies for routing unoccupied AVs in a manner that mitigates their negative impact on traffic while still fulfilling essential transportation requirements of the household. Three strategies are proposed to deploy AV deadheading methodology to route deadheading vehicles on longer paths, reducing congestion for occupied vehicles, while still meeting the trip-making needs of households. Case studies on two transportation networks are presented alongside their practical implications and computational requirements.
Gels for Water Remediation: Current Research and Perspectives
Authors: Buema Gabriela , Segneanu Adina-Elena , Herea Dumitru-Daniel , Grozescu Ioan
Published: September 2024

The development of cost-effective and high-performance technologies for wastewater treatment is essential for achieving a sustainable economy. Among the various methods available for water remediation, adsorption is widely recognized as an effective and straightforward approach for removing a range of pollutants. Gel materials, particularly hydrogels and aerogels, have attracted significant research interest due to their unique properties. Hydrogels, for instance, are noted for their ability to be regenerated and reused, ease of separation and handling, and suitability for large-scale applications. Additionally, their low cost, high water absorption capacity, and contribution to environmental protection are important advantages. Aerogels, on the other hand, are distinguished by their low thermal conductivity, transparency, flexibility, high porosity, mechanical strength, light weight, large surface area, and ultralow dielectric constant. This review provides a comprehensive analysis of the current literature, highlighting gaps in knowledge regarding the classification, preparation, characterization, and key properties of these materials. The potential application of hydrogels and aerogels in water remediation, particularly in removing contaminants such as dyes, heavy metals, and various organic and inorganic pollutants, is also discussed.
Phylo-Epigenetics in Phylogeny Analyses and Evolution
Authors: Santourlidis Simeon
Published: September 2024

Long-standing, continuous blurring and controversies in the field of phylogenetic interspecies relations, associated with insufficient explanations for dynamics and variability of speeds of evolution in mammals, hint at a crucial missing link. It has been suggested that transgenerational epigenetic inheritance and the concealed mechanisms behind play a distinct role in mammalian evolution. Here, a comprehensive sequence alignment approach in hominid species, i.e., Homo sapiens, Homo neanderthalensis, Denisovan human, Pan troglodytes, Pan paniscus, Gorilla gorilla, and Pongo pygmaeus, comprising conserved CpG islands of housekeeping genes, uncover evidence for a distinct variability of CpG dinucleotides. Applying solely these evolutionary consistent and inconsistent CpG sites in a classic phylogenetic analysis, calibrated by the divergence time point of the common chimpanzee (P. troglodytes) and the bonobo or pygmy chimpanzee (P. paniscus), a “phylo-epigenetic” tree has been generated, which precisely recapitulates branch points and branch lengths, i.e., divergence events and relations, as they have been broadly suggested in the current literature, based on comprehensive molecular phylogenomics and fossil records of many decades. It is suggested here that CpG dinucleotide changes at CpG islands are of superior importance for evolutionary developments. These changes are successfully inherited through the germ line, determining emerging methylation profiles, and they are a central component of transgenerational epigenetic inheritance. It is hidden in the DNA, what will happen on it later.
The Phylogenomic Characterization of Planotetraspora Species and Their Cellulases for Biotechnological Applications
Authors: Bouras Noureddine , Bakli Mahfoud , Dif Guendouz , Smaoui Slim , Șmuleac Laura , Paşcalău Raul , Menendez Esther , Nouioui Imen
Published: September 2024

This study aims to evaluate the in silico genomic characteristics of five species of the genus Planotetraspora: P. kaengkrachanensis, P. mira, P. phitsanulokensis, P. silvatica, and P. thailandica, with a view to their application in therapeutic research. The 16S rRNA comparison indicated that these species were phylogenetically distinct. Pairwise comparisons of digital DNA-DNA hybridization (dDDH) and OrthoANI values between these studied type strains indicated that dDDH values were below 62.5%, while OrthoANI values were lower than 95.3%, suggesting that the five species represent distinct genomospecies. These results were consistent with the phylogenomic study based on core genes and the pangenome analysis of these five species within the genus Planotetraspora. However, the genome annotation showed some differences between these species, such as variations in the number of subsystem category distributions across whole genomes (ranging between 1979 and 2024). Additionally, the number of CAZYme (Carbohydrate-Active enZYme) genes ranged between 298 and 325, highlighting the potential of these bacteria for therapeutic research applications. The in silico physico-chemical characteristics of cellulases from Planotetraspora species were analyzed. Their 3D structure was modeled, refined, and validated. A molecular docking analysis of this cellulase protein structural model was conducted with cellobiose, cellotetraose, laminaribiose, carboxymethyl cellulose, glucose, and xylose ligand. Our study revealed significant interaction between the Planotetraspora cellulase and cellotetraose substrate, evidenced by stable binding energies. This suggests that this bacterial enzyme holds great potential for utilizing cellotetraose as a substrate in various applications. This study enriches our understanding of the potential applications of Planotetraspora species in therapeutic research.
Modified R-GLIM Score Is a Good Prognostic Tool to Predict a Long-Term Prognosis in Poor Conditioned Elderly Patients with Aspiration Pneumonia, a Pilot Study
Authors: Wakita Yoshinori , Asai Nobuhiro , Ohashi Wataru , Mori Naoharu , Maekawa Masato , Mikamo Hiroshige
Published: September 2024

Background. While prognostic guidelines for pneumonia have widely allowed clinicians to treat patients, poor prognostic factors for 1- or 2-year survival times have never been mentioned to our knowledge. Patients and methods. We conducted this retrospective study to evaluate whether malnutrition according to the GLIM criteria is a poor prognostic factor for 1- or 2-year survival among patients with aspiration pneumonia. All patients with community-onset aspiration pneumonia who were admitted to Aichi Medical University and had intervention from our nutrition support team (NST) in 2019 and 2020 were enrolled in this study. Results. A total of 56 patients were enrolled in the study. The mean age was 86 ± 6.5 and 25 (45%) were male. Thirty-one patients died during this observational period. Comparing the survival and death group, higher respiratory rate (RR) and malnutrition were seen more frequently in the death group than in the survival group. Then, the patients were divided into the following three groups: those with an RR ≥ 22 and malnutrition, those with malnutrition, and a control group [patients who were not malnourished and had a low RR (<22)]. Comparing the three groups, patients with an RR ≥ 22 and malnutrition had significantly shorter overall survival times (OSs) than those in the other groups (p = 0.009 by Log-Rank test) for 1-year prognosis. The result of 2-year prognosis displayed a statistical significance that was the same as that for 1-year prognosis (p = 0.004 by Log-Rank test). The Cox hazard regression model showed that a higher RR was an independent poor prognostic factor for 1- and 2-year survival among aspiration pneumonia patients. Conclusions. This pilot study showed that combined scores of higher RR and malnutrition according to the GLIM criteria (modified R-GLIM score) was an independent poor prognostic factor for 1 or 2-year survival among super-elderly patients (aged over 80 years) with aspiration pneumonia.
Investigating Changes in the Soil Fungal Community Structure, Functions, and Network Stability with Prolonged Grafted Watermelon Cultivation
Authors: Zhou Xing , Guo Bingyu , Zhang Ruyi , Zhou Linfei , Huang Xinqi , Liu Liangliang
Published: September 2024

Grafting is a commonly employed technique for enhancing the yield and improving resistance to biotic and abiotic stress of cultivated plants. However, whether and how continuous cropping of grafted plants affects the composition, function, and stability of the soil fungal community remain poorly understood. In this study, we investigated the effects of planting years (including 0 years (Y0), 2 years (Y2), 10 years (Y10), and 18 years (Y18)) of grafted watermelon on the structure and functional composition of the soil fungal community under field conditions. Compared with the Y0 soil, the Y2, Y10, and Y18 soils exhibited a significant (p < 0.05) decrease in the richness, Shannon index, and evenness (56.8–65.7%, 22.4–46.3%, and 3.8–38.1%, respectively) in the alpha diversity of the fungal community, but a significant (p < 0.05) increase (0.4–1.3 times) in the fungal population. The structure, core and unique microbiomes, and functional composition of the soil fungal community differed significantly across different planting years. The Y2, Y10, and Y18 soils exhibited significant increases (p < 0.05) in relative abundances of Ascomycota and saprophytic fungi and the proportion of core OTUs, but significantly decreased abundances of Basidiomycota, Chytridiomycota, Rozellomycota, pathogenic and symbiotic fungi, and the proportion of unique OTUs when compared with the Y0 soil. The types of potential plant pathogens and their relative abundance were also significantly increased alongside the planting years (among Y2, Y10, and Y18 soils). Furthermore, the results indicated that the continuous cropping of grafted watermelon altered the co-occurrence networks, leading to a reduction in the complexity and stability of the fungal community networks. Overall, our findings suggest that continuous cropping of grafted watermelon may adversely affect the structure and functioning of soil microbial community, eventually decreasing the effectiveness of grafting technology disease control.
The Natural Habitats, Nutrients, and Heavy Metal Status of Wild Steppe Peony Populations in Serbia
Authors: Marković Tatjana , Tanasić Bojana , Gordanić Stefan , Prijić Željana , Mrđan Snežana , Dragumilo Ana , Lukić Milan , Radanović Dragoja
Published: September 2024

Steppe peony (Paeonia tenuifolia L.) is a strictly protected herbaceous species in Serbia, yet its growing conditions, nutrient needs, and heavy metal status are under-researched. This research is vital for conservation, as it supports sustainable cultivation, genetic diversity, and habitat restoration. This study addresses the gap in understanding how climate and soil characteristics affect P. tenuifolia, particularly regarding nutrient availability and heavy metal accumulation. Despite its recognized medicinal value, insufficient data on environmental impacts limit effective conservation and cultivation strategies. Addressing this gap will help determine optimal growth conditions and ensure the species’ survival and medicinal use. Data on P. tenuifolia natural habitats in Serbia were collected following the Descriptor List for medicinal plants. Field and laboratory analyses assessed climatic and soil characteristics, as well as macro- and microelement contents and heavy metals in soil and plant organs. In Serbia, P. tenuifolia thrives in a semi-arid steppe climate on light, sandy loam soils with a pH of 6.9–7.4. The soils are rich in humus (4.36–5.76%) and nitrogen (0.34–0.37%), but low in phosphorus (1.16–3.50 mg/100 g) and variable in potassium (12.5–52.4 mg/100 g). Soil microelements are abundant, and harmful heavy metals are below critical levels. Plant organs, including flowers, seeds, leaves, and stems, show high phosphorus and magnesium levels, while potassium, manganese, and copper are generally low. The levels of potentially harmful elements like cadmium and chromium are near the maximum-allowed limits, suggesting avoidance of highly acidic soils for the cultivation of P. tenuifolia. Among the examined soils, Arenic chernozem is recommended for preserving the species’ natural resources.
Obesity Parameters as Predictor of Poor Outcomes in Hospitalized Patients with Confirmed Mild-to-Moderate COVID-19
Authors: Barus Nadya R. V. , Tahapary Dicky Levenus , Kurniawan Farid , Sinto Robert , Wafa Syahidatul , Wisnu Wismandari , Mansjoer Arif , Wijaya Calysta Nadya , Felix Immanuel , Tarigan Tri Juli Edi , Harbuwono Dante Saksono , Soewondo Pradana
Published: September 2024

(1) Background: This study aims to assess visceral fat values, waist circumference (WC), body mass index (BMI), and body fat percentage for their ability to predict poor outcomes during COVID-19 patients’ hospitalization; (2) Methods: This study was a prospective cohort of mild–moderate COVID-19 patients hospitalized at Dr. Cipto Mangunkusumo National General Hospital from December 2020 to March 2021. This study includes hospitalized patients over 18 diagnosed with COVID-19 using RT-PCR. Patients who do not have chest radiography, waist circumference, a bioimpedance analyzer (BIA) error, or are unable to stand or mobilize during the examination are excluded from this study. Cox regression was used for multivariate analysis; (3) Results: The study included two hundred sixty-one patients. The median visceral fat value was 10 (equivalent to 100 cm2), the WC was 93.4 cm, the BMI was 26.1 kg/m2, and the body fat percentage was 31.5%. Based on multivariate Cox regression, WC was statistically significant as an independent factor influencing poor outcomes in COVID-19 patients (RR 1.037 [95% CI 1.011–1.064]) along with COVID-19 degree of severity (RR 3.063 [95% CI 1.537–6.104]) and comorbidities (RR 2.123 [95% CI 1.017–4.435]); (4) Conclusions: Waist circumference can influence poor outcomes in confirmed COVID-19 patients during hospitalization.
How to Reduce Physical Inactivity in School Context? A Systematic Review of the Concept of Body Practices
Authors: Soto-Lagos Rodrigo , Castillo-Parada Tatiana , Pozo-Gómez Luiz , Romero-Álvarez Pablo , Urzúa Gabriel
Published: September 2024

(1) Background: Physical inactivity is a recognized global problem, with schools identified by UNESCO and WHO as critical settings for intervention. Despite existing efforts, the prevalence of physical inactivity remains high. This study aims to explore the potential of the concept of body practices as a novel framework to address physical inactivity within school contexts, potentially offering an alternative to traditional intervention models. (2) Methods: This study carried out a systematic review of the concept of body practices to understand its use in the scientific literature. (3) Results: The results indicate that (a) the definition of the concept that the authors used is broad; (b) the problems they face are varied, such as the life cycle, negative emotions, gender, physical inactivity, well-being, and social problems; (c) the research methodologies are predominantly quantitative; (d) and the intervention in schools focuses on students, but not on the entire school community. (4) Conclusions: this concept has great potential for use in initiatives and/or policies that seek to address physical inactivity in the school context.
Network Analysis of Enhancer–Promoter Interactions Highlights Cell-Type-Specific Mechanisms of Transcriptional Regulation Variation
Authors: Koesterich Justin , Liu Jiayi , Williams Sarah E. , Yang Nan , Kreimer Anat
Published: September 2024

Gene expression is orchestrated by a complex array of gene regulatory elements that govern transcription in a cell-type-specific manner. Though previously studied, the ability to utilize regulatory elements to identify disrupting variants remains largely elusive. To identify important factors within these regions, we generated enhancer–promoter interaction (EPI) networks and investigated the presence of disease-associated variants that fall within these regions. Our study analyzed six neuronal cell types across neural differentiation, allowing us to examine closely related cell types and across differentiation stages. Our results expand upon previous findings of cell-type specificity of enhancer, promoter, and transcription factor binding sites. Notably, we find that regulatory regions within EPI networks can identify the enrichment of variants associated with neuropsychiatric disorders within specific cell types and network sub-structures. This enrichment within sub-structures can allow for a better understanding of potential mechanisms by which variants may disrupt transcription. Together, our findings suggest that EPIs can be leveraged to better understand cell-type-specific regulatory architecture and used as a selection method for disease-associated variants to be tested in future functional assays. Combined with these future functional characterization assays, EPIs can be used to better identify and characterize regulatory variants’ effects on such networks and model their mechanisms of gene regulation disruption across different disorders. Such findings can be applied in practical settings, such as diagnostic tools and drug development.
One-Pot, Multi-Component Green Microwave-Assisted Synthesis of Bridgehead Bicyclo[4.4.0]boron Heterocycles and DNA Affinity Studies
Authors: Paisidis Polinikis , Kokotou Maroula G. , Kotali Antigoni , Psomas George , Fylaktakidou Konstantina C.
Published: September 2024

Anthranilic acids, salicylaldehydes and arylboronic acids reacted in EtOH/H2O (1/3) at 150 °C under microwave irradiation for 1 h to give, in excellent yields and purity, twenty-three bridgehead bicyclo[4.4.0]boron heterocycles via one-pot, three-component green synthesis. The scope and the limitations of the reactions are discussed in terms of the substitution of ten different anthranilic acids, three salicylaldehydes and three arylboronic acids. The replacement of salicylaldehyde with o-hydroxyacetophenone demanded a lipophilic solvent for the reaction to occur. Eight novel derivatives were isolated following crystallization in a toluene-containing mixture that included molecular sieves. The above one-pot, three-component reactions were completed under microwave irradiation at 180 °C within 1.5 h, thus avoiding the conventional prolonged heating reaction times and the use of a Dean–Stark apparatus. All derivatives were studied for their affinity to calf thymus DNA using proper techniques like viscosity and UV–vis spectroscopy, where DNA-binding constants were found in the range 2.83 × 104–8.41 × 106 M−1. Ethidium bromide replacement studies using fluorescence spectroscopy indicated Stern–Volmer constants between 1.49 × 104 and 5.36 × 104 M−1, whereas the corresponding quenching constants were calculated to be between 6.46 × 1011 and 2.33 × 1012 M−1 s−1. All the above initial experiments show that these compounds may have possible medical applications for DNA-related diseases.
Post-Translational Modifications to Cysteine Residues in Plant Proteins and Their Impact on the Regulation of Metabolism and Signal Transduction
Authors: Boutin Charlie , Clément Camille , Rivoal Jean
Published: September 2024

Cys is one of the least abundant amino acids in proteins. However, it is often highly conserved and is usually found in important structural and functional regions of proteins. Its unique chemical properties allow it to undergo several post-translational modifications, many of which are mediated by reactive oxygen, nitrogen, sulfur, or carbonyl species. Thus, in addition to their role in catalysis, protein stability, and metal binding, Cys residues are crucial for the redox regulation of metabolism and signal transduction. In this review, we discuss Cys post-translational modifications (PTMs) and their role in plant metabolism and signal transduction. These modifications include the oxidation of the thiol group (S-sulfenylation, S-sulfinylation and S-sulfonylation), the formation of disulfide bridges, S-glutathionylation, persulfidation, S-cyanylation S-nitrosation, S-carbonylation, S-acylation, prenylation, CoAlation, and the formation of thiohemiacetal. For each of these PTMs, we discuss the origin of the modifier, the mechanisms involved in PTM, and their reversibility. Examples of the involvement of Cys PTMs in the modulation of protein structure, function, stability, and localization are presented to highlight their importance in the regulation of plant metabolic and signaling pathways.
Identification of VvAGL Genes Reveals Their Network’s Involvement in the Modulation of Seed Abortion via Responding Multi-Hormone Signals in Grapevines
Authors: Liu Fei , Aziz Rana Badar , Wang Yumiao , Xuan Xuxian , Yu Mucheng , Qi Ziyang , Chen Xinpeng , Wu Qiqi , Qu Ziyang , Dong Tianyu , Li Shaonan , Fang Jinggui , Wang Chen
Published: September 2024

The formation of seedless traits is regulated by multiple factors. AGLs, which belong to the MADS-box family, were reported to be important regulators in this process; however, the underlying mechanism remains elusive. Here, we identified the VvAGL sub-family genes during the seed abortion process in seedless grapevine cv. ‘JingkeJing’ and found 40 differentially expressed VvAGL members and 1069 interacting proteins in this process. Interestingly, almost all members and their interacting proteins involved in the tryptophan metabolic pathway (K14486) and participated in the phytohormone signalling (KO04075) pathway, including the growth hormone (IAA), salicylic acid (SA), abscisic acid (ABA), cytokinin (CTK), and ethylene signalling pathways. The promoters of AGL sub-family genes contain cis-elements in response to hormones such as IAA, ABA, CTK, SA, and ETH, implying that they might respond to multi-hormone signals and involve in hormone signal transductions. Further expression analysis revealed VvAGL6-2, VvAGL11, VvAGL62-11, and VvAGL15 had the highest expression at the critical period of seed abortion, and there were positive correlations between ETH-VvAGL15-VvAGL6-2, ABA-VvAGL80, and SA-VvAGL62 in promoting seed abortion but negative feedback between IAA-VvAGL15-VvAGL6-2 and CTK-VvAGL11. Furthermore, many genes in the IAA, ABA, SA, CTK, and ETH pathways had a special expressional pattern in the seed, whereby we developed a regulatory network mediated by VvAGLs by responding to multihormonal crosstalk during grape seed abortion. Our findings provide new insights into the regulatory network of VvAGLs in multi-hormone signalling to regulate grape seed abortion, which could be helpful in the molecular breeding of high-quality seedless grapes.
Genome-Wide Identification, Characterization, and Expression Analysis of the MYB-R2R3 Gene Family in Black Pepper (Piper nigrum L.)
Authors: Fan Rui , Huang Kai , Zhao Zhican , Hao Yupeng , Guan Xueying , Luo Haiyan , Hao Chaoyun
Published: September 2024

Black pepper (Piper nigrum L.), a prominent spice crop, known as the “king of spices”, originated from India. The growth and development of black pepper are influenced by various environmental conditions. MYB transcription factors play a crucial role in controlling metabolic processes, abiotic stress management, and plant growth and development. In this study, we identified 160 PnMYB transcription factors in the black pepper genome. Phylogenetic analysis was performed using 125 R2R3-MYB proteins from black pepper and Arabidopsis thaliana, resulting in the mapping of 20 groups on the phylogenetic tree, each containing members from both species. Most members of the PnMYB family possess two introns, and motif 3 and motif 4 are conserved in all members. The number of genes on each chromosome ranges from 1 to 10. Collinear analysis indicated the creation of new members through gene fragments and tandem replication. The Ka/Ks ratio indicated that purifying selection and positive selection acted on PnMYB of pepper. The majority of pepper PnMYB family members were in the nucleus. Significant differences in gene expression levels were observed between different species and infection periods when Piper nigrum L. and Piper flaviflorum were infected with Phytophthora capsici. These findings are valuable for future studies on the biological role and molecular mechanism of the PnMYB gene.
Towards Targeting Endothelial Rap1B to Overcome Vascular Immunosuppression in Cancer
Authors: Ghadrdoost Nakhchi Behshid , Kosuru Ramoji , Chrzanowska Magdalena
Published: September 2024

The vascular endothelium, a specialized monolayer of endothelial cells (ECs), is crucial for maintaining vascular homeostasis by controlling the passage of substances and cells. In the tumor microenvironment, Vascular Endothelial Growth Factor A (VEGF-A) drives tumor angiogenesis, leading to endothelial anergy and vascular immunosuppression—a state where ECs resist cytotoxic CD8+ T cell infiltration, hindering immune surveillance. Immunotherapies have shown clinical promise. However, their effectiveness is significantly reduced by tumor EC anergy. Anti-angiogenic treatments aim to normalize tumor vessels and improve immune cell infiltration. Despite their potential, these therapies often cause significant systemic toxicities, necessitating new treatments. The small GTPase Rap1B emerges as a critical regulator of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) signaling in ECs. Our studies using EC-specific Rap1B knockout mice show that the absence of Rap1B impairs tumor growth, alters vessel morphology, and increases CD8+ T cell infiltration and activation. This indicates that Rap1B mediates VEGF-A’s immunosuppressive effects, making it a promising target for overcoming vascular immunosuppression in cancer. Rap1B shares structural and functional similarities with RAS oncogenes. We propose that targeting Rap1B could enhance therapies’ efficacy while minimizing adverse effects by reversing endothelial anergy. We briefly discuss strategies successfully developed for targeting RAS as a model for developing anti-Rap1 therapies.
Cell-Type-Specific Expression of Leptin Receptors in the Mouse Forebrain
Authors: Canepa Cade R. , Kara John A. , Lee Charles C.
Published: September 2024

Leptin is a hormone produced by the small intestines and adipose tissue that promotes feelings of satiety. Leptin receptors (LepRs) are highly expressed in the hypothalamus, enabling central neural control of hunger. Interestingly, LepRs are also expressed in several other regions of the body and brain, notably in the cerebral cortex and hippocampus. These brain regions mediate higher-order sensory, motor, cognitive, and memory functions, which can be profoundly altered during periods of hunger and satiety. However, LepR expression in these regions has not been fully characterized on a cell-type-specific basis, which is necessary to begin assessing their potential functional impact. Consequently, we examined LepR expression on neurons and glia in the forebrain using a LepR-Cre transgenic mouse model. LepR-positive cells were identified using a ‘floxed’ viral cell-filling approach and co-labeling immunohistochemically for cell-type-specific markers, i.e., NeuN, VGlut2, GAD67, parvalbumin, somatostatin, 5-HT3R, WFA, S100β, and GFAP. In the cortex, LepR-positive cells were localized to lower layers (primarily layer 6) and exhibited non-pyramidal cellular morphologies. The majority of cortical LepR-positive cells were neurons, while the remainder were identified primarily as astrocytes or other glial cells. The majority of cortical LepR-positive neurons co-expressed parvalbumin, while none expressed somatostatin or 5-HT3R. In contrast, all hippocampal LepR-positive cells were neuronal, with none co-expressing GFAP. These data suggest that leptin can potentially influence neural processing in forebrain regions associated with sensation and limbic-related functions.
Impact of Extremely Low-Frequency Electromagnetic Fields on Skeletal Muscle of Sedentary Adult Mice: A Pilot Study
Authors: Morabito Caterina , Di Sinno Noemi , Mariggiò Maria A. , Guarnieri Simone
Published: September 2024

Extremely low-frequency electromagnetic fields (ELF-EMFs) are ubiquitous in industrialized environments due to the continuous use of electrical devices. Our previous studies demonstrated that ELF-EMFs affect muscle cells by modulating oxidative stress and enhancing myogenesis. This pilot study investigated these effects on the skeletal muscles of sedentary adult mice, assessing physiological responses to ELF-EMF exposure and potential modulation by antioxidant supplementation. Male C57BL/6 mice were exposed to ELF-EMFs (0.1 or 1.0 mT) for 1 h/day for up to 5 weeks and fed a standard diet without or with N-acetyl-cysteine (NAC). The results showed transient increases in muscle strength (after 2 weeks of exposure at 1.0 mT), potentially linked to muscle fiber recruitment and activation, revealed by higher PAX7 and myosin heavy chain (MyH) expression levels. After ELF-EMF exposure, oxidative status assessment revealed transient increases in the expression levels of SOD1 and catalase enzymes, in total antioxidant capacity, and in protein carbonyl levels, markers of oxidative damage. These effects were partially reduced by NAC. In conclusion, ELF-EMF exposure affects skeletal muscle physiology and NAC supplementation partially mitigates these effects, highlighting the complex interactions between ELF-EMFs and antioxidant pathways in vivo. Further investigations on ELF-EMFs as a therapeutic modality for muscle health are necessary.
Comparative Analysis of Casparian Strip Membrane Domain Protein Family in Oryza sativa (L.) and Arabidopsis thaliana (L.)
Authors: Xue Baoping , Liang Zicong , Liu Yue , Li Dongyang , Cao Peng , Liu Chang
Published: September 2024

The Casparian strip membrane domain proteins (CASPs) are pivotal for the formation of the Casparian strip (CS) in endodermal cells and play a crucial role in a plant’s response to environmental stresses. However, existing research on the CASP gene family in rice and Arabidopsis lacks a comprehensive bioinformatics analysis and necessitates further exploration. In this study, we identified 41 OsCASP and 39 AtCASP genes, which were grouped into six distinct subgroups. Collinearity analysis underscored the pivotal roles of WGD and TD events in driving the evolution of CASPs, with WGDs being the dominant force. On the one hand, the analysis of cis-elements indicated that most OsCASP and AtCASP genes contain MYB binding motifs. On the other hand, RNA-seq revealed that the majority of OsCASP and AtCASP genes are highly expressed in roots, particularly in endodermal cells, where OsCASP_like11/9 and AtCASP_like1/31 demonstrated the most pronounced expression. These results suggest that OsCASP_like11/9 and AtCASP_like1/31 might be candidate genes involved in the formation of the endodermis CS. RT-qPCR results demonstrated that OsCASP_like2/3/13/17/21/30 may be candidate genes for the ion defect process. Collectively, this study offers a theoretical foundation for unraveling the biological functions of CASP genes in rice and Arabidopsis.
Development of Novel Alaninamide Derivatives with Anticonvulsant Activity and Favorable Safety Profiles in Animal Models
Authors: Abram Michał , Jakubiec Marcin , Koczurkiewicz-Adamczyk Paulina , Doroz-Płonka Agata , Rapacz Anna , Kamiński Krzysztof
Published: September 2024

In our current study, we developed a focused series of original ((benzyloxy)benzyl)propanamide derivatives that demonstrated potent activity across in vivo mouse seizure models, specifically, maximal electroshock (MES) and 6 Hz (32 mA) seizures. Among these derivatives, compound 5 emerged as a lead molecule, exhibiting robust protection following intraperitoneal (i.p.) injection, as follows: ED50 = 48.0 mg/kg in the MES test, ED50 = 45.2 mg/kg in the 6 Hz (32 mA) test, and ED50 = 201.3 mg/kg in the 6 Hz (44 mA) model. Additionally, compound 5 displayed low potential for inducing motor impairment in the rotarod test (TD50 > 300 mg/kg), indicating a potentially favorable therapeutic window. In vitro toxicity assays further supported its promising safety profile. We also attempted to identify a plausible mechanism of action of compound 5 by applying both binding and functional in vitro studies. Overall, the data obtained for this lead molecule justifies the more comprehensive preclinical development of compound 5 as a candidate for a potentially broad-spectrum and safe anticonvulsant.
Identification of a Novel Subset of Human Airway Epithelial Basal Stem Cells
Authors: Cheng Christopher , Katoch Parul , Zhong Yong-Ping , Higgins Claire T. , Moredock Maria , Chang Matthew E. K. , Flory Mark R. , Randell Scott H. , Streeter Philip R.
Published: September 2024

The basal cell maintains the airway’s respiratory epithelium as the putative resident stem cell. Basal cells are known to self-renew and differentiate into airway ciliated and secretory cells. However, it is not clear if every basal cell functions as a stem cell. To address functional heterogeneity amongst the basal cell population, we developed a novel monoclonal antibody, HLO1-6H5, that identifies a subset of KRT5+ (cytokeratin 5) basal cells. We used HLO1-6H5 and other known basal cell-reactive reagents to isolate viable airway subsets from primary human airway epithelium by Fluorescence Activated Cell Sorting. Isolated primary cell subsets were assessed for the stem cell capabilities of self-renewal and differentiation in the bronchosphere assay, which revealed that bipotent stem cells were, at minimum 3-fold enriched in the HLO1-6H5+ cell subset. Crosslinking-mass spectrometry identified the HLO1-6H5 target as a glycosylated TFRC/CD71 (transferrin receptor) proteoform. The HLO1-6H5 antibody provides a valuable new tool for identifying and isolating a subset of primary human airway basal cells that are substantially enriched for bipotent stem/progenitor cells and reveals TFRC as a defining surface marker for this novel cell subset.
The Regulatory Roles of Inflammation and Inflammasomes in Liver Diseases
Authors: Yi Young-Su
Published: September 2024

Inflammation is an innate immune response that protects our body from various pathogens and cellular dangers [...]