bluuebunny/crossref_metadata_2025 huggingface dataset:
Domestication over Speciation in Allopolyploid Cotton Species: A Stronger Transcriptomic Pull
Authors: Jareczek Josef J. , Grover Corrinne E. , Hu Guanjing , Xiong Xianpeng , Arick II Mark A. , Peterson Daniel G. , Wendel Jonathan F.
Published: June 2023

Cotton has been domesticated independently four times for its fiber, but the genomic targets of selection during each domestication event are mostly unknown. Comparative analysis of the transcriptome during cotton fiber development in wild and cultivated materials holds promise for revealing how independent domestications led to the superficially similar modern cotton fiber phenotype in upland (G. hirsutum) and Pima (G. barbadense) cotton cultivars. Here we examined the fiber transcriptomes of both wild and domesticated G. hirsutum and G. barbadense to compare the effects of speciation versus domestication, performing differential gene expression analysis and coexpression network analysis at four developmental timepoints (5, 10, 15, or 20 days after flowering) spanning primary and secondary wall synthesis. These analyses revealed extensive differential expression between species, timepoints, domestication states, and particularly the intersection of domestication and species. Differential expression was higher when comparing domesticated accessions of the two species than between the wild, indicating that domestication had a greater impact on the transcriptome than speciation. Network analysis showed significant interspecific differences in coexpression network topology, module membership, and connectivity. Despite these differences, some modules or module functions were subject to parallel domestication in both species. Taken together, these results indicate that independent domestication led G. hirsutum and G. barbadense down unique pathways but that it also leveraged similar modules of coexpression to arrive at similar domesticated phenotypes.
Identification of Candidate QTLs and Genes for Ear Diameter by Multi-Parent Population in Maize
Authors: Jiang Fuyan , Liu Li , Li Ziwei , Bi Yaqi , Yin Xingfu , Guo Ruijia , Wang Jing , Zhang Yudong , Shaw Ranjan Kumar , Fan Xingming
Published: June 2023

Ear diameter (ED) is a critical component of grain yield (GY) in maize (Zea mays L.). Studying the genetic basis of ED in maize is of great significance in enhancing maize GY. Against this backdrop, this study was framed to (1) map the ED-related quantitative trait locus (QTL) and SNPs associated with ED; and (2) identify putative functional genes that may affect ED in maize. To accomplish this, an elite maize inbred line, Ye107, which belongs to the Reid heterotic group, was used as a common parent and crossed with seven elite inbred lines from three different heterotic groups (Suwan1, Reid, and nonReid) that exhibited abundant genetic variation in ED. This led to the construction of a multi-parent population consisting of 1215 F7 recombinant inbred lines (F7RILs). A genome-wide association study (GWAS) and linkage analysis were then conducted for the multi-parent population using 264,694 high-quality SNPs generated via the genotyping-by-sequencing method. Our study identified a total of 11 SNPs that were significantly associated with ED through the GWAS, and three QTLs were revealed by the linkage analysis for ED. The major QTL on chromosome 1 was co-identified in the region by the GWAS at SNP_143985532. SNP_143985532, located upstream of the Zm00001d030559 gene, encodes a callose synthase that is expressed in various tissues, with the highest expression level in the maize ear primordium. Haplotype analysis indicated that the haplotype B (allele AA) of Zm00001d030559 was positively correlated with ED. The candidate genes and SNPs identified in this study provide crucial insights for future studies on the genetic mechanism of maize ED formation, cloning of ED-related genes, and genetic improvement of ED. These results may help develop important genetic resources for enhancing maize yield through marker-assisted breeding.
Probabilistic Tsunami Hazard Analysis for Vancouver Island Coast Using Stochastic Rupture Models for the Cascadia Subduction Earthquakes
Authors: Goda Katsuichiro
Published: June 2023

Tsunami hazard analysis is an essential step for designing buildings and infrastructure and for safeguarding people and assets in coastal areas. Coastal communities on Vancouver Island are under threat from the Cascadia megathrust earthquakes and tsunamis. Due to the deterministic nature of current megathrust earthquake scenarios, probabilistic tsunami hazard analysis has not been conducted for the coast of Vancouver Island. To address this research gap, this study presents a new probabilistic tsunami hazard model for Vancouver Island from the Cascadia megathrust subduction events. To account for uncertainties of the possible rupture scenarios more comprehensively, time-dependent earthquake occurrence modeling and stochastic rupture modeling are integrated. The time-dependent earthquake model can capture a multi-modal distribution of inter-arrival time data on the Cascadia megathrust events. On the other hand, the stochastic rupture model can consider variable fault geometry, position, and earthquake slip distribution within the subduction zone. The results indicate that the consideration of different inter-arrival time distributions can result in noticeable differences in terms of site-specific tsunami hazard curves and uniform tsunami hazard curves at different return period levels. At present, the use of the one-component renewal model tends to overestimate the tsunami hazard values compared to the three-component Gaussian mixture model. With the increase in the elapsed time since the last event and the duration of tsunami hazard assessment, the differences tend to be smaller. Inspecting the regional variability of the tsunami hazards, specific segments of the Vancouver Island coast are likely to experience higher tsunami hazards due to the directed tsunami waves from the main subduction zone and due to the local underwater topography.
Itsuki Hiroyuki’s Farewell to Moscow Misfits and Entertainment Strategies: Middlebrow Novels, Jazz Novels, and Repatriates
Authors: Nakane Takayuki , Siercks Eric
Published: June 2023

This paper addresses writer Itsuki Hiroyuki’s 1966 debut novel Farewell to Moscow Misfits through the lens of middlebrow novels, jazz novels, and repatriates. This novel draws from Itsuki’s personal experience being repatriated from colonial Korea after the war and visiting the Soviet Union in the mid-1960s. Farewell was unique for its time in representing jazz, music, and youth “stilyagi” counterculture in the Soviet Union. This counterculture movement was roughly contemporaneous with the student movement of the 1960s in Japan. This period also saw the popularization of the “middlebrow novel”—an ambiguous term that was used to describe literature outside of the established pure/popular dichotomy. These amorphous “middlebrow” works allow us to read some of the cultural dynamics of the 1960s. Itsuki published many of his early works in so-called middlebrow magazines, not “pure” literary journals. Itsuki himself claimed that his works were neither pure literature nor popular literature; they were simply “entertainment”. He placed his works in relation to jazz, the circus, and enka. His unique views on cultural production and media emerged from his repatriation experiences and his encounter with Russian culture. This paper examines not only genre conventions in literature but also Itsuki’s objections to the pure/popular literary structure, as well as his place in cultural representations of the 1960s.
Preserving Sunken Military Vessels as Underwater Cultural Heritage in Colombia: Legal Challenges and Prospects for the USS Kearsarge Wreck Site
Authors: Gomez Pretel William , Jeong Moonsoo , Rodríguez-Gutiérrez Camilo Ernesto , Ortiz JR Agustin
Published: June 2023

This study examines the legal challenges related to preserving sunken military vessels as Underwater Cultural Heritage (UCH) in Colombia. These challenges include Spanish galleon shipwrecks, limited international cooperation, and the lack of legal recognition for sunken military vessels under domestic law (Law 1675 of 2013). To address these issues, this article reviews the concepts of warship and sovereign immunity as they relate to the status of sunken military vessels. The study places a particular focus on the USS Kearsarge, a military shipwreck in Colombian territorial waters protected by the Sunken Military Craft Act of 2004 (SMCA) of the United States. Additionally, it analyzes the legal frameworks and management of UCH in both Colombia and the United States, as well as providing two lists of Colombia’s sunken military vessels and foreign sunken military vessels in its waters. The research concludes by highlighting the complexities of managing UCH in Colombia and offering a prospectus on the future of the USS Kearsarge wreck site as shared heritage. Ultimately, this study underscores the need for a more comprehensive legal framework and greater international cooperation to ensure the preservation and protection of sunken military vessels in Colombia.
Silver Nano Chito Oligomer Hybrid Solution for the Treatment of Citrus Greening Disease (CGD) and Biostimulants in Citrus Horticulture
Authors: Vatcharakajon Pakpoom , Sornsaket Ampol , Choengpanya Khuanjarat , Susawaengsup Chanthana , Sornsakdanuphap Jirapong , Boonplod Nopporn , Bhuyar Prakash , Dangtungee Rapeephun
Published: June 2023

Citrus greening disease (CGD), or Huanglongbing (HLB), is principal in Citrus farming because of its severe damage, decreased yield, poor quality of fruit, and frequent disappearance before harvest. Present research blended silver nanoparticles (AgNPs) colloid with chitooligomers and monomers (COAMs) to create the composites referred to as a “hybrid solution”. The hybrid solution has been synthesized for antimicrobial effects and plant growth stimulation. The hybrid solution was applied to cure the CGD, which was then tested using the results of the iodine test kit. Study results revealed that the mechanism for antibacterial properties is efficient and leads to cell death by silver ions (positive charge) attached to the cell wall of pathogens (negative charge). COAMs increase AgNPs’ ability to adhere to negatively charged bacterial cytoplasmic membranes and amplify their electrostatic interaction. There are synergistic antibacterial effects of AgNPs–COAMs. The findings reveal a notable increase in the shoot length of leaves which may be the reason for the growth stimulation function of the hybrid solution due to the properties of COAMs as a biostimulant. The hybrid solution-treated trees yielded around 104.50 ± 4.56 kg of fruits by the trunk or foliar application. Citrus fruits did not show the presence of any silver residues, as displayed by the results of the accumulation test. Compared to conventional ampicillin, the hybrid treatment of CGD was significantly more cost-effective, increased productivity, and had minor accumulation. The acquired results may also be applied to further plant disease treatment.
Fruit Phenology of Two Hazelnut Cultivars and Incidence of Damage by Halyomorpha halys in Treated and Untreated Hazel Groves
Authors: de Benedetta Flavia , Giaccone Matteo , Pica Feliciana , Lisanti Maria Tiziana , Vinale Francesco , Turrà David , Giacca Gianpaolo Maria , Bernardo Umberto
Published: June 2023

Over the past decade, Halyomorpha halys has become one of the main threats to hazelnut production. Its trophic activity makes kernels inedible due to strongly detrimental effects on the organoleptic quality. Its management in Italy is still tricky due to the lack of effective native biocontrol agents and authorized and effective insecticides. A field test was performed on San Giovanni (SG) and Tonda Romana (TR) cultivars (early and late ripening, respectively) to assess the intensity of cimiciato damage with different pest management approaches (no insecticide and integrated pest management, IPM). Moreover, phenological analysis of fruits and the monitoring of stink bug species by traps and plant beating were carried out. In the untreated plots, the SG cv showed a higher cimiciato incidence with respect to the late TR cv (40% SG–NI vs. 23% TR–NI). This was probably due to the different phenological phases in which stink bugs injured the fruits. In fact, stink bug bites provoke different kinds of injuries (blanks, shriveled, and cimiciato) according to the fruit’s development period. Indeed, in the period of highest insect occurrence in the field, the fruits of the early cv (SG) were in kernel expansion, a phenological phase in which bug injuries are more likely in cimiciato defects. Lastly, the IPM did not provide sufficient fruit protection (19% SG–IPM vs. 11% TR–IPM). The interaction between the phenological development of hazelnuts and the brown marmorated stink bug represents a critical aspect in understanding and implementing effective strategies for controlling this key pest on hazelnut trees.
The Impact of the Built Environment and Social Environment on Physical Activity: A Scoping Review
Authors: Wang Yiyu , Steenbergen Bert , van der Krabben Erwin , Kooij Henk-Jan , Raaphorst Kevin , Hoekman Remco
Published: June 2023

This scoping review aims to provide an overview of the current state of physical activity research, focusing on the interplay between built and social environments and their respective influences on physical activity. We comprehensively searched electronic databases to identify relevant studies published between 2000 and 2022. A total of 35 articles have been reviewed based on the research question. The review found that built and social environments influence physical activity, and consideration of people’s perceptions of their surroundings can provide further insight. The literature was summarized, and recommendations were made for future research. Findings suggest that interventions targeting built and social environments can promote physical activity effectively. However, limitations in the literature exist, including a need for more standardization in research methods and consistency in measurement tools.
Health and Socioeconomic Determinants of Abuse among Women with Disabilities
Authors: Zamora Arenas Javier , Millán Jiménez Ana , Bote Marcos
Published: June 2023

The double vulnerability of women with disabilities places them at the center of this research paper. Intersectionality is key in research on gender-based violence. This study analyzes the perspective of the victims and non-victims themselves on this issue, through a comparative analysis between women with and without disabilities, at two levels of analysis: quantitative, through the adaptation of various scales (Assessment Screen-Disability/AAS-D, and the Woman Abuse Screening Tool/WAST), and qualitative, with semi-structured interviews (open scripts and different themes), and focus groups with experts from the associative network. The results obtained indicate that the most frequent type of violence is physical, followed by psychological and sexual, mainly perpetrated by partners. The higher their level of education, the more they defend themselves; receiving public aid can be a risk factor for domestic and sexual violence, and belonging to the associative movement and having paid work outside the home act as preventive measures. In conclusion, it is necessary to establish strategic protection measures and effective detection and intervention systems to make victims visible and care for them.
Persistent Maternal Mental Health Disorders and Toddler Neurodevelopment at 18 Months: Longitudinal Follow-up of a Low-Income South African Cohort
Authors: Burger Marlette , Einspieler Christa , Jordaan Esme R. , Unger Marianne , Niehaus Dana J. H.
Published: June 2023

One of the biggest threats to early childhood development in Africa is poor maternal mental health. The present study reports on the relationships between clinical diagnoses of persistent maternal mental health disorders (at 3- and/or 6- and 18-month post-term age) and toddler neurodevelopment at 18 months of age. Eighty-three mother–toddler dyads from low socio-economic status settings in Cape Town, South Africa, were included. At the 3-, 6- and 18-month postnatal visits, clinician-administered structured diagnostic assessments were carried out according to the Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) criteria. Toddler neurodevelopment at 18 months corrected age was assessed with the Bayley Scales of Infant and Toddler Development (BSID-III). No significant differences (p > 0.05) were found between toddlers with exposure to persistent mood or psychotic disorders in the different BSID-III domains compared to toddlers with no exposure. Toddlers exposed to persistent comorbid anxiety and mood disorders scored significantly higher on the cognitive (p = 0.049), motor (p = 0.013) and language (p = 0.041) domains and attained significantly higher fine motor (p = 0.043) and gross motor (p = 0.041) scaled scores compared to toddlers with no maternal mental health disorder exposure. Future investigations should focus on the role of protective factors to explain the pathways through which maternal mental health status is associated with positive toddler neurodevelopmental outcomes.
The Interplay of Formal Institutional and Cultural Distances and the Financial Performance of Foreign Subsidiaries in Latin America
Authors: Correa da Cunha Henrique , Amal Mohamed , Andersson Svante , Floriani Dinora Eliete , Farrell Carlyle
Published: June 2023

We investigate how formal institutional distance (FID) moderates the cultural distance (CD) and financial performance relationships of foreign subsidiaries of firms. Following recent research, we estimate the asymmetric effects of CD by considering its size and direction towards host countries on the opposite poles of each cultural dimension’s scale. We propose that a limited understanding of the formal institutions in the host country, as measured by the magnitude and direction of the FID, can positively moderate the CD–performance relationship. This is mainly because foreign subsidiary firms may be more reliant on their capacity to navigate the less formal (and more implicit) aspects of the host country’s institutional environment, such as their ability to cope with the CD. We use foreign subsidiary data from the Orbis database, which includes 22 developed and 22 developing home countries and over 1400 foreign subsidiaries operating in 10 of Latin America’s largest economies (host countries) from 2012 to 2015 (a period of 3 years). Findings confirm the asymmetric effects of CD; however, by considering the direction of FID, our findings reveal that the more FID is directed towards host countries that are less developed, the more significant the effects of CD on financial performance. These findings contribute to our knowledge of how formal and informal institutional distances interact by showing that the greater the FID towards less developed host countries, the more pronounced the effects of CD.
Management’s Discretionary Assessments of Goodwill Impairments—Evidence from STOXX Europe 600
Authors: Kjærland Frode , Forbord Kristian , Oust Are , Stephani Håkon
Published: June 2023

The main issues of accounting reporting regarding goodwill are whether a firm’s management reliably conveys their private information about future earnings, and whether they disclose value-relevant and useful information to accounting users. In the current International Financial Reporting Standards (IFRS) regulations, the goodwill impairment test is based on management’s discretionary assessments. This study examines how goodwill impairment is reported under IFRS considering company- and industry-specific economic factors, proxies for earnings management, and macroeconomic crisis years. We extend previous research using tobit and logit regressions by employing a fixed-effects model. This approach is possible because of a panel dataset comprising 449 of 600 active companies sampled from the STOXX Europe 600 index from 2005 to 2018. We find that goodwill impairments are largely concentrated in certain companies, industries, and years. The regression models show a significant negative correlation between companies’ return on total assets and goodwill impairments. Moreover, we discover that goodwill impairments have a significant positive correlation with goodwill intensity, debt ratio, and the proxy for reporting a one-off big bath charge. In addition, we find that the global financial crisis in 2008–2009 and the European debt crisis in 2011 differ significantly from other fiscal years.
UV-C Seed Surface Sterilization and Fe, Zn, Mg, Cr Biofortification of Wheat Sprouts as an Effective Strategy of Bioelement Supplementation
Authors: Czarnek Katarzyna , Tatarczak-Michalewska Małgorzata , Dreher Piotr , Rajput Vishnu D. , Wójcik Grzegorz , Gierut-Kot Anna , Szopa Agnieszka , Blicharska Eliza
Published: June 2023

Metalloenzymes play an important role in the regulation of many biological functions. An effective way to prevent deficiencies of essential minerals in human diets is the biofortification of plant materials. The process of enriching crop sprouts under hydroponic conditions is the easiest and cheapest to conduct and control. In this study, the sprouts of the wheat (Triticum aestivum L.) varieties Arkadia and Tonacja underwent biofortification with Fe, Zn, Mg, and Cr solutions in hydroponic media at four concentrations (0, 50, 100, and 200 µg g−1) over four and seven days. Moreover, this study is the first to combine sprout biofortification with UV-C (λ = 254 nm) radiation treatment for seed surface sterilization. The results showed that UV-C radiation was effective in suppressing seed germination contamination by microorganisms. The seed germination energy was slightly affected by UV-C radiation but remained at a high level (79–95%). The influence of this non-chemical sterilization process on seeds was tested in an innovative manner using a scanning electron microscope (SEM) and EXAKT thin-section cutting. The applied sterilization process reduced neither the growth and development of sprouts nor nutrient bioassimilation. In general, wheat sprouts easily accumulate Fe, Zn, Mg, and Cr during the applied growth period. A very strong correlation between the ion concentration in the media and microelement assimilation in the plant tissues (R2 > 0.9) was detected. The results of the quantitative ion assays performed with atomic absorption spectrometry (AAS) using the flame atomization method were correlated with the morphological evaluation of sprouts in order to determine the optimum concentration of individual elements in the hydroponic solution. The best conditions were indicated for 7-day cultivation in 100 µg g−1 of solutions with Fe (218% and 322% better nutrient accumulation in comparison to the control condition) and Zn (19 and 29 times richer in zinc concentration compared to the sprouts without supplementation). The maximum plant product biofortification with magnesium did not exceed 40% in intensity compared to the control sample. The best-developed sprouts were grown in the solution with 50 µg g−1 of Cr. In contrast, the concentration of 200 µg g−1 was clearly toxic to the wheat sprouts.
Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers
Authors: Maher Nawar , Mouhssine Samir , Matti Bassam Francis , Alwan Alaa Fadhil , Gaidano Gianluca
Published: June 2023

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Despite its indolent clinical course, therapy refractoriness and disease progression still represent an unmet clinical need. Before the advent of pathway inhibitors, chemoimmunotherapy (CIT) was the commonest option for CLL treatment and is still widely used in areas with limited access to pathway inhibitors. Several biomarkers of refractoriness to CIT have been highlighted, including the unmutated status of immunoglobulin heavy chain variable genes and genetic lesions of TP53, BIRC3 and NOTCH1. In order to overcome resistance to CIT, targeted pathway inhibitors have become the standard of care for the treatment of CLL, with practice-changing results obtained through the inhibitors of Bruton tyrosine kinase (BTK) and BCL2. However, several acquired genetic lesions causing resistance to covalent and noncovalent BTK inhibitors have been reported, including point mutations of both BTK (e.g., C481S and L528W) and PLCG2 (e.g., R665W). Multiple mechanisms are involved in resistance to the BCL2 inhibitor venetoclax, including point mutations that impair drug binding, the upregulation of BCL2-related anti-apoptotic family members, and microenvironmental alterations. Recently, immune checkpoint inhibitors and CAR-T cells have been tested for CLL treatment, obtaining conflicting results. Potential refractoriness biomarkers to immunotherapy were identified, including abnormal levels of circulating IL-10 and IL-6 and the reduced presence of CD27+CD45RO− CD8+ T cells.
The Double-Edged Sword of Erythrocytes in Health and Disease via Their Adhesiveness
Authors: Asaro Robert J. , Profumo Elisabetta , Buttari Brigitta , Cabrales Pedro
Published: June 2023

Their widespread presence throughout the vasculature, coupled with their reactivity, and thereby to their potential to release reactive oxidative species, or to utilize their anti-oxidative capacities, has promoted much discussion of the role(s) of red blood cells (RBCs) in the progression of health or, alternatively, a wide range of disease states. Moreover, these role(s) have been linked to the development of adhesiveness and, in fact, thereby to the essential pathway to their eventual clearance, e.g., by macrophages in the spleen. These disparate roles coupled with the mechanisms involved are reviewed and given. Following an analysis, novel perspectives are provided; these perspectives can lead to novel assays for identifying the potential for RBC adhesiveness as suggested herein. We describe this paradigm, that involves RBC adhesiveness, hemolysis, and ghost formation, with examples including, inter alia, the progression of atherosclerosis and the suppression of tumor growth along with other disease states.
Partner, Neighbor, Housekeeper and Dimension: 3D versus 2D Glomerular Co-Cultures Reveal Drawbacks of Currently Used Cell Culture Models
Authors: Rederer Anna , Rose Victoria , Krüger René , Schmittutz Linda , Swierzy Izabela , Fischer Lena , Thievessen Ingo , Bauer Julian , Friedrich Oliver , Schiffer Mario , Müller-Deile Janina
Published: June 2023

Signaling-pathway analyses and the investigation of gene responses to different stimuli are usually performed in 2D monocultures. However, within the glomerulus, cells grow in 3D and are involved in direct and paracrine interactions with different glomerular cell types. Thus, the results from 2D monoculture experiments must be taken with caution. We cultured glomerular endothelial cells, podocytes and mesangial cells in 2D/3D monocultures and 2D/3D co-cultures and analyzed cell survival, self-assembly, gene expression, cell–cell interaction, and gene pathways using live/dead assay, time-lapse analysis, bulk-RNA sequencing, qPCR, and immunofluorescence staining. Without any need for scaffolds, 3D glomerular co-cultures self-organized into spheroids. Podocyte- and glomerular endothelial cell-specific markers and the extracellular matrix were increased in 3D co-cultures compared to 2D co-cultures. Housekeeping genes must be chosen wisely, as many genes used for the normalization of gene expression were themselves affected in 3D culture conditions. The transport of podocyte-derived VEGFA to glomerular endothelial cells confirmed intercellular crosstalk in the 3D co-culture models. The enhanced expression of genes important for glomerular function in 3D, compared to 2D, questions the reliability of currently used 2D monocultures. Hence, glomerular 3D co-cultures might be more suitable in the study of intercellular communication, disease modelling and drug screening ex vivo.
Reasons for the Sex Bias in Osteoarthritis Research: A Review of Preclinical Studies
Authors: Franke Madeline , Mancino Chiara , Taraballi Francesca
Published: June 2023

Osteoarthritis (OA) is one of the most common degenerative diseases of articular cartilage. During OA, all the elements that contribute to the joint undergo physiological and structural changes that impair the joint function and cause joint pain and stiffness. OA can arise naturally, with the aging population witnessing an increase in diagnoses of this pathology, but the root causes of OA have yet to be identified, and increasing interest is arising towards investigating biological sex as a risk factor. Clinical studies show increased prevalence and worse clinical outcomes for female patients, yet most clinical and preclinical studies have disproportionately focused on male subjects. This review provides a critical overview of preclinical practices in the context of OA, highlighting the underlying need for taking biological sex as both a risk factor and an important component affecting treatment outcome. A unique insight into the possible reasons for female underrepresentation in preclinical studies is offered, including factors such as lack of specific guidelines requiring the analysis of sex as a biological variable (SABV), research-associated costs and animal handling, and wrongful application of the reduction principle. Additionally, a thorough investigation of sex-related variables is provided, stressing how each of them could add valuable information for the understanding of OA pathophysiology, as well as sex-dependent treatment strategies.
The Effects of 2′-Hydroxy-3,6′-Dimethoxychalcone on Melanogenesis and Inflammation
Authors: Bae Sungmin , Hyun Chang-Gu
Published: June 2023

In this study, we demonstrated that 2′-hydroxy-3,6′-dimethoxychalcone (3,6′-DMC) alleviated α-MSH-induced melanogenesis and lipopolysaccharides (LPS)-induced inflammation in mouse B16F10 and RAW 264.7 cells. In vitro analysis results showed that the melanin content and intracellular tyrosinase activity were significantly decreased by 3,6′-DMC, without cytotoxicity, via decreases in tyrosinase and the tyrosinase-related protein 1 (TRP-1) and TRP-2 melanogenic proteins, as well as the downregulation of microphthalmia-associated transcription factor (MITF) expression through the upregulation of the phosphorylation of extracellular-signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3β (GSK-3β)/catenin, and downregulation of the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and protein kinase A (PKA). Furthermore, we investigated the effect of 3,6′-DMC on macrophage RAW264.7 cells with LPS stimulation. 3,6′-DMC significantly inhibited LPS-stimulated nitric oxide production. 3,6′-DMC also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 on the protein level. In addition, 3,6′-DMC decreased the production of the tumor necrosis factor-α and interleukin-6. Successively, our mechanistic studies revealed that 3,6′-DMC also suppressed the LPS-induced phosphorylation of the inhibitor of IκBα, p38MAPK, ERK, and JNK. The Western blot assay results showed that 3,6′-DMC suppresses LPS-induced p65 translocation from cytosol to the nucleus. Finally, the topical applicability of 3,6′-DMC was tested through primary skin irritation, and it was found that 3,6′-DMC, at 5 and 10 μM concentrations, did not cause any adverse effects. Therefore, 3,6′-DMC may provide a potential candidate for preventing and treating melanogenic and inflammatory skin diseases.
Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus
Authors: Ahmad Awais , Brylid André , Dahle Charlotte , Saleh Muna , Dahlström Örjan , Enocsson Helena , Sjöwall Christopher
Published: June 2023

The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value.
Regulatory Roles of Flavonoids in Caspase-11 Non-Canonical Inflammasome-Mediated Inflammatory Responses and Diseases
Authors: Yi Young-Su
Published: June 2023

Inflammasomes are multiprotein complexes that activate inflammatory responses by inducing pyroptosis and secretion of pro-inflammatory cytokines. Along with many previous studies on inflammatory responses and diseases induced by canonical inflammasomes, an increasing number of studies have demonstrated that non-canonical inflammasomes, such as mouse caspase-11 and human caspase-4 inflammasomes, are emerging key players in inflammatory responses and various diseases. Flavonoids are natural bioactive compounds found in plants, fruits, vegetables, and teas and have pharmacological properties in a wide range of human diseases. Many studies have successfully demonstrated that flavonoids play an anti-inflammatory role and ameliorate many inflammatory diseases by inhibiting canonical inflammasomes. Others have demonstrated the anti-inflammatory roles of flavonoids in inflammatory responses and various diseases, with a new mechanism by which flavonoids inhibit non-canonical inflammasomes. This review discusses recent studies that have investigated the anti-inflammatory roles and pharmacological properties of flavonoids in inflammatory responses and diseases induced by non-canonical inflammasomes and further provides insight into developing flavonoid-based therapeutics as potential nutraceuticals against human inflammatory diseases.
Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma
Authors: Lin Li-Han , Chang Kuo-Wei , Cheng Hui-Wen , Liu Chung-Ji
Published: June 2023

The accurate diagnosis and treatment of oral squamous cell carcinoma (OSCC) requires an understanding of its genomic alterations. Liquid biopsies, especially cell-free DNA (cfDNA) analysis, are a minimally invasive technique used for genomic profiling. We conducted comprehensive whole-exome sequencing (WES) of 50 paired OSCC cell-free plasma with whole blood samples using multiple mutation calling pipelines and filtering criteria. Integrative Genomics Viewer (IGV) was used to validate somatic mutations. Mutation burden and mutant genes were correlated to clinico-pathological parameters. The plasma mutation burden of cfDNA was significantly associated with clinical staging and distant metastasis status. The genes TTN, PLEC, SYNE1, and USH2A were most frequently mutated in OSCC, and known driver genes, including KMT2D, LRP1B, TRRAP, and FLNA, were also significantly and frequently mutated. Additionally, the novel mutated genes CCDC168, HMCN2, STARD9, and CRAMP1 were significantly and frequently present in patients with OSCC. The mutated genes most frequently found in patients with metastatic OSCC were RORC, SLC49A3, and NUMBL. Further analysis revealed that branched-chain amino acid (BCAA) catabolism, extracellular matrix–receptor interaction, and the hypoxia-related pathway were associated with OSCC prognosis. Choline metabolism in cancer, O-glycan biosynthesis, and protein processing in the endoplasmic reticulum pathway were associated with distant metastatic status. About 20% of tumors carried at least one aberrant event in BCAA catabolism signaling that could possibly be targeted by an approved therapeutic agent. We identified molecular-level OSCC that were correlated with etiology and prognosis while defining the landscape of major altered events of the OSCC plasma genome. These findings will be useful in the design of clinical trials for targeted therapies and the stratification of patients with OSCC according to therapeutic efficacy.
A Rare Olive Compound Oleacein Improves Lipid and Glucose Metabolism, and Inflammatory Functions: A Comprehensive Whole-Genome Transcriptomics Analysis in Adipocytes Differentiated from Healthy and Diabetic Adipose Stem Cells
Authors: Wang Rui , Ganbold Munkhzul , Ferdousi Farhana , Tominaga Kenichi , Isoda Hiroko
Published: June 2023

Oleacein (OLE), a rare natural compound found in unfiltered extra virgin olive oil, has been shown to have anti-inflammatory and anti-obesity properties. However, little is known regarding the mechanisms by which OLE influences metabolic processes linked to disease targets, particularly in the context of lipid metabolism. In the present study, we conducted whole-genome DNA microarray analyses in adipocytes differentiated from human adipose-derived stem cells (hASCs) and diabetic hASCs (d-hASCs) to examine the effects of OLE on modulating metabolic pathways. We found that OLE significantly inhibited lipid formation in adipocytes differentiated from both sources. In addition, microarray analysis demonstrated that OLE treatment could significantly downregulate lipid-metabolism-related genes and modulate glucose metabolism in both adipocyte groups. Transcription factor enrichment and protein–protein interaction (PPI) analyses identified potential regulatory gene targets. We also found that OLE treatment enhanced the anti-inflammatory properties in adipocytes. Our study findings suggest that OLE exhibits potential benefits in improving lipid and glucose metabolism, thus holding promise for its application in the management of metabolic disorders.
A Reliability-Based Framework for Damage Accumulation Due to Multiple Earthquakes: A Case Study on Bridges
Authors: Herath Nilupa , Zhang Lihai , Mendis Priyan , Navaratnam Satheeskumar , Lokuge Weena , Setunge Sujeeva
Published: June 2023

Damage accumulation due to multiple seismic impacts over time has a significant effect on the residual service life of the bridge. A reliability-based framework was developed to make decisions in bridge maintenance activities. The feature of the framework enables quantifying the time-dependent probability of failure of bridges due to the impact of multiple earthquakes and progressive deterioration. To estimate the reliability of the bridge systems, the probability of failure of the bridge was used. Two case studies were utilised to demonstrate how the method can be applied to the real world. Results show that the accumulated damage caused by multiple earthquakes and progressive deterioration significantly impact the remaining useful life of the bridge. Furthermore, the soil conditions predominantly influence the progressive deterioration and reduce the service life of the bridge. Overall, the proposed framework enables the sustainable decision-making process for bridge maintenance activities. The results reveal the necessity of including the combined impact in the bridge maintenance system and that there is a more than 40% increase in the probability of failure, due to the combined effect of progressive deterioration and earthquake impacts, compared to the impact only due to seismic loads for the considered case study bridge.
A Boron-Containing Analogue of Acetaminophen Induces Analgesic Effect in Hot Plate Test and Limited Hepatotoxicity
Authors: Rosalez Melvin Nadir , Farfán-García Eunice D. , Badillo-Romero Jesús , Córdova-Chávez Ricardo Iván , Trujillo-Ferrara José G. , Morales-González José A. , Soriano-Ursúa Marvin A. , Martínez-Archundia Marlet
Published: June 2023

Acetaminophen is the most sold drug to treat pain. The TRPV1 channel is among its main targets. Due to its over-the-counter availability, its use is known as the main cause of acute liver failure induced by drugs. In addition, boron-containing compounds (BCC) have shown higher efficiency, potency, and affinity than their carbon counterparts. The present study explored the potential analgesic effect and hepatotoxicity of a BCC with a similar chemical structure to acetaminophen. Docking studies were carried out on the TRPV1 channel. In addition, a hot plate test was carried out with three doses of acetaminophen (APAP) and equimolar doses of 4-acetamidophenylboronic acid (4APB) in C57bl/6 mice. These same mice were submitted to a partial hepatectomy and continued compound administration, then they were sacrificed at day seven of treatment to analyze the liver histology and blood chemistry markers. From the in silico assays, it was observed that APAP and 4APB shared interactions with key residues, but 4APB showed a higher affinity on the orthosteric site. Mice administered with 4APB showed a higher latency time than those administered with their equimolar dose of APAP and the control group, with no motor pathway affected. The 4APB groups did not show an increase in hepatic enzyme activity while the APAP did show an increase in activity that was dose-dependent. Although all the experimental groups did show necrosis and inflammation, all APAP groups showed a greater cellular damage than their 4APB counterparts. In addition, the LD50 of 4APB is 409 mg/kg (against APAP-LD50 of 338 mg/kg). Thus, in the current evaluation, 4APB was a better analgesic and safer than APAP.
Stem Bark-Mediated Green Synthesis of Silver Nanoparticles from Pyrus pashia: Characterization, Antioxidant, and Antibacterial Properties
Authors: Khanal Lekha Nath , Dhakal Purna Prasad , Kandel Mani Ram , Acharya Debendra , Baral Ek Raj , Chhetri Kisan , Kalauni Surya Kant
Published: June 2023

The investigation of using medicinal plants for the production and application of silver nanoparticles (AgNPs) has attracted growing research interest. In this study, AgNPs are synthesized from the stem barks of the Pyrus pashia medicinal plant using a biosynthetic strategy. The reaction conditions were optimized under ambient conditions, including concentration, temperature, time, and pH, and various techniques were employed, such as UV-visible, FTIR, XRD, FESEM, and TEM, to characterize the synthesized AgNPs. The AgNPs produced through this biosynthesis method were found to be spherical and polydispersed, with an average size of 23.92 ± 7.04 nm. The synthesized AgNPs demonstrated an enhanced DPPH free radical scavenging capacity compared to the aqueous extract, with IC50 values of 10.67 ± 0.05 µg/mL and 13.66 ± 0.35 µg/mL, respectively. In the agar well diffusion method, the synthesized AgNPs showed higher antibacterial activity than that of the extract against Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Enterococcus faecalis (ATCC 29212), Salmonella typhi (ATCC 14028), and Shigella sonnei (ATCC 25931). Based on these findings, the study suggests that green synthesized AgNPs from P. pashia could be used for biomedical applications.
Autologous Peripheral Blood Mononuclear Cells in Patients with Small Artery Disease and Diabetic Foot Ulcers: Efficacy, Safety, and Economic Evaluation
Authors: Ragghianti Benedetta , Berardi Bianca , Mannucci Edoardo , Monami Matteo
Published: June 2023

Background: diabetic foot ulcers (DFU) represent the main cause of major amputations and hospitalisations in diabetic patients. The aim of this study was to assess the safety and cost-efficacy of intramuscular injection of peripheral blood mononuclear cells (PBMNCs) in diabetic patients with no-option chronic limb-threatening ischemia (CLTI) and small artery disease (SAD). Methods: a retrospective study was carried out on a series of type 2 diabetic patients with DFU grade Texas 3 and no-option CLTI and SAD. All patients had undergone at least a previous revascularization and were allocated to a surgery waiting list for major amputation. The principal endpoint evaluated at 90 days was a composite of TcPO2 values at the first toe ≥30 mmHg and/or TcPO2 increase of at least 50% from baseline and/or ulcer healing. Secondary endpoints were individual components of the primary endpoint, any serious and non-serious adverse events, and direct costs at one year. Results: the composite endpoint was achieved in nine patients (60.0%); one patient (6.7%) healed within ninety days and 26.7% and 46.7% showed TcPO2 ≥ 30 mmHg and a TcPO2 increase of at least 50% at ninety days, respectively. At one year, three (20.0%) patients underwent a major amputation (all diagnosed SAD grade III). One patient died after seven months, and seven patients (46.7%) healed. The overall median and mean cost per patient were EUR 8238 ± 7798 and EUR 4426 (3798; 8262), respectively. Conclusions: the use of PBMNCs implants in no-option CLTI diabetic patients with SAD seems to be of help in reducing the risk of major amputation.
The Efficacy of Probiotics, Prebiotics, and Synbiotics in Patients Who Have Undergone Abdominal Operation, in Terms of Bowel Function Post-Operatively: A Network Meta-Analysis
Authors: Ioannidis Orestis , Chatzakis Christos , Tirta Maria , Anestiadou Elissavet , Zapsalis Konstantinos , Symeonidis Savvas , Bitsianis Stefanos , Kotidis Efstathios , Pramateftakis Manousos , Mantzoros Ioannis , Angelopoulos Stamatios
Published: June 2023

Background: Abdominal operations may lead to post-operative bowel dysfunction, while administration of probiotics, prebiotics and synbiotics may limit its manifestation. Τhe study aimed to assess the efficacy of probiotics, prebiotics and synbiotics in patients who undergone abdominal operation, in terms of bowel function post-operatively. Methods: PubMed, Scopus, Cochrane Central Register of Controlled Trials (Central), Embase, US Registry of clinical trials, and sources of grey literature were searched. The relative effect sizes were estimated, and we obtained the relative ranking of the interventions using cumulative ranking curves. Results: In total, 30 studies were included in the analysis. For the outcome of post-operative ileus, probiotics was superior to placebo/no intervention (relative risk, RR: 0.38; 95%CI: 0.14–0.98) with the highest SUCRA (surface under the cumulative ranking) value (92.1%). For time to first flatus, probiotics (MD: −0.47; 95%CI: −0.78 to −0.17) and synbiotics (MD: −0.53; 95%CI: −0.96 to −0.09) were superior to placebo/no intervention. For time to first defecation and for post-operative abdominal distension probiotics were superior to placebo/no intervention. For post-operative hospitalization days, synbiotics were superior to placebo/no intervention (MD: −3.07; 95%CI: −4.80 to −1.34). Conclusions: Administration of probiotics in patients who had undergone abdominal surgery reduced the prevalence of post-operative ileus, time to first flatus, time to first defecation, and prevalence of post-operative abdominal distension. Synbiotics reduce time to first flatus and post-operative hospitalization days.