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DOAJ Open Access 2025
Bridging the Gap: The State of Global Transplant Research Collaboration

Isabella Faria, MD, Stalin Canizares, MD, Adriana Montalvan, MD, MPH et al.

Background. The field of transplant research has long been recognized for its innovative approaches and international collaborations. This study aims to dissect the landscape of global collaborations within transplant research during a past decade. Methods. Through a comprehensive bibliometric and network analysis of 5 high-impact factor transplantation journals from 2012 to 2021, we evaluated scientific production and collaboration patterns in 9 250 articles. International, national, and single-institution collaboration types were analyzed, using coauthorship as a measure of scientific collaboration. Results. The data set revealed 40 622 authors from 2 094 institutions across 94 countries, with a marked increase in international collaborations during the past decade. The United States and Western European countries emerged as central nodes in the global network, facilitating the majority of collaborative efforts. Only 2.2% of potential institutional collaborations were explored during the decade. We found a lower chance of citations for single-institution research over time. Low- and middle-income countries were underrepresented in high-impact transplant research. Conclusions. The findings underscore the necessity of fostering inclusive, equitable research collaborations that bridge the gap between high-income countries and low- and middle-income countries, limiting their contributions to advancing global patient care. Practical recommendations for enhancing global collaboration in transplant research include facilitating academic exchanges, equitable collaboration practices, and increased funding opportunities. This study calls for a strategic shift toward a more inclusive and integrated global research landscape, aiming to advance transplant research and patient care universally. Addressing these disparities could lead to a more integrated global research landscape, benefiting transplant research and patient care universally.

DOAJ Open Access 2025
E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production

Chenxi Li, Chenyang Tang, Xiqian Liu et al.

ABSTRACT Membrane-associated RING-CH-type finger (MARCH) proteins, a class of E3 ubiquitin ligases, have been reported to be involved in the infection of multiple viruses and the regulation of type I interferon (IFN) production. However, the specific role and mechanisms by which MARCH proteins influence Japanese encephalitis virus (JEV) infection remain poorly understood. Here, we systematically investigate the functional relevance of MARCH proteins in JEV replication by examining the effects of siRNA-mediated knockdown of MARCHs on viral infection. We identified MARCH5 as a positive regulator of JEV replication. The knockout of MARCH5 dramatically reduced viral yields, whereas its overexpression significantly enhanced JEV replication. Mechanistically, MARCH5 specifically interacts with the JEV envelope (E) protein and promotes its K27-linked polyubiquitination at the lysine (K) residues 136 and 166. This ubiquitination enhances viral attachment to permissive cells. Substituting these lysine residues with arginine (R) attenuated JEV replication in vitro and reduced viral virulence in vivo. Furthermore, JEV infection upregulated the expression of MARCH5. We also discovered that MARCH5 degrades mitochondrial antiviral-signaling protein (MAVS) through the ubiquitin-proteasome pathway by catalyzing its K48-linked ubiquitination, thereby inhibiting type I IFN production in JEV-infected cells. This suppression of type I IFN further facilitates JEV infection. In conclusion, these findings disclosed a novel role of MARCH5 in positively regulating JEV infection and revealed an important mechanism employed by MARCH5 to regulate the innate immune response.IMPORTANCEJEV is the leading cause of viral encephalitis in many countries of Asia with an estimated 100,000 clinical human cases and causes economic loss to the swine industry. Until now, there is no clinically approved antiviral for the treatment of JEV infection. Although vaccination prophylaxis is widely regarded as the most effective strategy for preventing Japanese encephalitis (JE), the incidence of JE cases continues to rise. Thus, a deeper understanding of virus-host interaction will enrich our knowledge of the mechanisms underlying JEV infection and identify novel targets for the development of next-generation live-attenuated vaccines and antiviral therapies. To the best of our knowledge, this study is the first to identify MARCH5 as a pro-viral host factor that facilitates JEV infection. We elucidated two distinct mechanisms by which MARCH5 promotes JEV infection. First, MARCH5 interacts with viral E protein and mediates the K27-linked ubiquitination of E protein at the K136 and K166 residues to facilitate efficient viral attachment. Furthermore, double mutations of K136R-K166R attenuated JEV infection in vitro and reduced viral virulence in mice. Second, the upregulated expression of MARCH5 induced by JEV infection further suppresses the RIG-I-like receptor (RLR) signaling pathway to benefit viral infection. MARCH5 downregulates type I IFN production by conjugating the K48-linked polyubiquitin at the K286 of MAVS, which leads to MAVS degradation through the ubiquitin-proteasome pathway. In summary, this study provides novel insights into the role played by MARCH proteins in JEV infection and identifies specific ubiquitination sites on JEV E protein that could be targeted for viral attenuation and the development of antiviral therapeutics.

DOAJ Open Access 2024
The N-terminal region of DNMT3A engages the nucleosome surface to aid chromatin recruitment

Hannah Wapenaar, Gillian Clifford, Willow Rolls et al.

Abstract DNA methyltransferase 3A (DNMT3A) plays a critical role in establishing and maintaining DNA methylation patterns in vertebrates. Here we structurally and biochemically explore the interaction of DNMT3A1 with diverse modified nucleosomes indicative of different chromatin environments. A cryo-EM structure of the full-length DNMT3A1-DNMT3L complex with a H2AK119ub nucleosome reveals that the DNMT3A1 ubiquitin-dependent recruitment (UDR) motif interacts specifically with H2AK119ub and makes extensive contacts with the core nucleosome histone surface. This interaction facilitates robust DNMT3A1 binding to nucleosomes, and previously unexplained DNMT3A disease-associated mutations disrupt this interface. Furthermore, the UDR-nucleosome interaction synergises with other DNMT3A chromatin reading elements in the absence of histone ubiquitylation. H2AK119ub does not stimulate DNMT3A DNA methylation activity, as observed for the previously described H3K36me2 mark, which may explain low levels of DNA methylation on H2AK119ub marked facultative heterochromatin. This study highlights the importance of multivalent binding of DNMT3A to histone modifications and the nucleosome surface and increases our understanding of how DNMT3A1 chromatin recruitment occurs.

Biology (General)
DOAJ Open Access 2024
Unleashing the Potential of CRISPR/Cas9 Genome Editing for Yield-Related Traits in Rice

Archana Thiruppathi, Shubham Rajaram Salunkhe, Shobica Priya Ramasamy et al.

Strategies to enhance rice productivity in response to global demand have been the paramount focus of breeders worldwide. Multiple factors, including agronomical traits such as plant architecture and grain formation and physiological traits such as photosynthetic efficiency and NUE (nitrogen use efficiency), as well as factors such as phytohormone perception and homeostasis and transcriptional regulation, indirectly influence rice grain yield. Advances in genetic analysis methodologies and functional genomics, numerous genes, QTLs (Quantitative Trait Loci), and SNPs (Single-Nucleotide Polymorphisms), linked to yield traits, have been identified and analyzed in rice. Genome editing allows for the targeted modification of identified genes to create novel mutations in rice, avoiding the unintended mutations often caused by random mutagenesis. Genome editing technologies, notably the CRISPR/Cas9 system, present a promising tool to generate precise and rapid modifications in the plant genome. Advancements in CRISPR have further enabled researchers to modify a larger number of genes with higher efficiency. This paper reviews recent research on genome editing of yield-related genes in rice, discusses available gene editing tools, and highlights their potential to expedite rice breeding programs.

DOAJ Open Access 2024
Electron Transfer in the Biogeochemical Sulfur Cycle

Xuliang Zhuang, Shijie Wang, Shanghua Wu

Microorganisms are key players in the global biogeochemical sulfur cycle. Among them, some have garnered particular attention due to their electrical activity and ability to perform extracellular electron transfer. A growing body of research has highlighted their extensive phylogenetic and metabolic diversity, revealing their crucial roles in ecological processes. In this review, we delve into the electron transfer process between sulfate-reducing bacteria and anaerobic alkane-oxidizing archaea, which facilitates growth within syntrophic communities. Furthermore, we review the phenomenon of long-distance electron transfer and potential extracellular electron transfer in multicellular filamentous sulfur-oxidizing bacteria. These bacteria, with their vast application prospects and ecological significance, play a pivotal role in various ecological processes. Subsequently, we discuss the important role of the pili/cytochrome for electron transfer and presented cutting-edge approaches for exploring and studying electroactive microorganisms. This review provides a comprehensive overview of electroactive microorganisms participating in the biogeochemical sulfur cycle. By examining their electron transfer mechanisms, and the potential ecological and applied implications, we offer novel insights into microbial sulfur metabolism, thereby advancing applications in the development of sustainable bioelectronics materials and bioremediation technologies.

DOAJ Open Access 2023
Non-enzymatic electrochemical sensor for wearable monitoring of sweat biomarkers: A mini-review

Yu Liu, Tao Liu, Danfeng Jiang

Sweat contains a wealth of health-related biomarkers, which has been a promising resource for personalized real-time monitoring at molecular level. Emergence of non-enzymatic electrochemical sensor that simulates the enzyme catalysis utilizing the functional material further promotes the development of wearable sweat sensor, successfully addressing the limitations of enzyme sensing in sensitivity and stability. Thus, there is an urgent need for centering on the regulation of the nanostructure, combination and preparation method of functional materials to enhance the catalytic activity for enzyme-free detection of sweat biomarkers. This review aims to present the superiors of enzyme-free sensing on wearable sweat sensor, and provides guidance for material innovation, sensor design and system integration. Firstly, we primarily focus on the recent advances of novel functional nanomaterials in wearable non-enzymatic electrochemical sensor, and briefly describe the sensing principles for detecting biomarkers in sweat. Subsequently, the correlation between the electrochemical strategy and functional material is elaborately interpreted by coupling with the diverse molecular structures of the biomarkers and the pH changes of test environments. Finally, challenges and opportunities for wearable non-enzymatic electrochemical sensor in sweat sensing are delineated in the development of future personalized healthcare.

DOAJ Open Access 2023
A Potentially Practicable Halotolerant Yeast <i>Meyerozyma guilliermondii</i> A4 for Decolorizing and Detoxifying Azo Dyes and Its Possible Halotolerance Mechanisms

Yue Feng, Jingru Cui, Bingwen Xu et al.

In this study, a halotolerant yeast that is capable of efficiently decolorizing and detoxifying azo dyes was isolated, identified and characterized for coping with the treatment of azo-dye-containing wastewaters. A characterization of the yeast, including the optimization of its metabolism and growth conditions, its detoxification effectiveness and the degradation pathway of the target azo dye, as well as a determination of the key activities of the enzyme, was performed. Finally, the possible halotolerance mechanisms of the yeast were proposed through a comparative transcriptome analysis. The results show that a halotolerant yeast, A4, which could decolorize various azo dyes, was isolated from a marine environment and was identified as <i>Meyerozyma guilliermondii</i>. Its optimal conditions for dye decolorization were ≥1.0 g/L of sucrose, ≥0.2 g/L of (NH<sub>4</sub>)<sub>2</sub>SO<sub>4</sub>, 0.06 g/L of yeast extract, pH 6.0, a temperature of 35 °C and a rotation speed of ≥160 rpm. The yeast, A4, degraded and detoxified ARB through a series of steps, relying on the key enzymes that might be involved in the degradation of azo dye and aromatic compounds. The halotolerance of the yeast, A4, was mainly related to the regulation of the cell wall components and the excessive uptake of Na<sup>+</sup>/K<sup>+</sup> and/or compatible organic solutes into the cells under different salinity conditions. The up-regulation of genes encoding Ca<sup>2+</sup>-ATPase and casein kinase II as well as the enrichment of KEGG pathways associated with proteasome and ribosome might also be responsible for its halotolerance.

Biology (General)
DOAJ Open Access 2023
Structure prediction of novel isoforms from uveal melanoma by AlphaFold

Zhe Zhang, Chen Li, Qian Li et al.

Abstract Alternative splicing is an important mechanism that enhances protein functional diversity. To date, our understanding of alternative splicing variants has been based on mRNA transcript data, but due to the difficulty in predicting protein structures, protein tertiary structures have been largely unexplored. However, with the release of AlphaFold, which predicts three-dimensional models of proteins, this challenge is rapidly being overcome. Here, we present a dataset of 315 predicted structures of abnormal isoforms in 18 uveal melanoma patients based on second- and third-generation transcriptome-sequencing data. This information comprises a high-quality set of structural data on recurrent aberrant isoforms that can be used in multiple types of studies, from those aimed at revealing potential therapeutic targets to those aimed at recognizing of cancer neoantigens at the atomic level.

DOAJ Open Access 2023
Impact of Plasma Rich in Growth Factors (PRGF) Eye Drops on Ocular Redness and Symptomatology in Patients with Dry Eye Disease

Javier Lozano-Sanroma, Alberto Barros, Ignacio Alcalde et al.

<i>Background and Objectives</i>: Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). <i>Materials and Methods</i>: Patients were divided into two groups of treatment: standard treatment group (<i>n</i> = 43 eyes) and PRGF group (<i>n</i> = 59). Patients’ symptomatology (inferred from OSDI and SANDE questionnaires), ocular inflammation, tear stability, and ocular surface damage were analyzed at baseline and after 3 months of treatment. <i>Results</i>: OSDI test scores were significantly lower in both groups (<i>p</i> < 0.001). SANDE frequency test scores also improved statistically, with differences between groups (<i>p</i> = 0.0089 SANDE frequency and <i>p</i> < 0.0119 SANDE severity). There was a greater reduction in ocular redness (ocular inflammation) in the PRGF group (<i>p</i> < 0.0001) and fluorescein tear break-up time was significantly improved in the PRGF group (<i>p</i> = 0.0006). No significant changes were found in terms of ocular surface damage. No adverse events were obtained in either group. <i>Conclusions</i>: The addition of PRGF to the standard treatment of DED, according to the results obtained, proved to be safe and produced an improvement in ocular symptomatology and signs of inflammation, particularly in moderate and severe cases, when compared to standard treatment.

Medicine (General)
DOAJ Open Access 2023
Essential Oil Composition, Antioxidant Activity and Leaf Micromorphology of Five Tunisian <i>Eucalyptus</i> Species

Flavio Polito, Florinda Fratianni, Filomena Nazzaro et al.

<i>Eucalyptus</i> species have been widely employed in the projects of reforestation in Tunisia. Although their ecological functions are controversial, these plants are indeed important to counteract soil erosion, and represent a fast-growing source of fuelwood and charcoal wood. In the present study, we considered five <i>Eucalyptus</i> species, namely <i>Eucalyptus alba</i>, <i>E. eugenioides</i>, <i>E. fasciculosa</i>, <i>E. robusta</i>, and <i>E. stoatei</i> cultivated in the Tunisian <i>Arboreta</i>. The aim was to carry out the micromorphological and anatomical characterization of the leaves, the extraction and phytochemical profile of the essential oils (EOs), and the evaluation of their biological properties. Four of the EOs showed the prevalence of eucalyptol (1,8-cineole) varying from 64.4 to 95.9%, whereas <i>a</i>-pinene predominated in <i>E. alba</i> EO (54.1%). These EOs showed in vitro antioxidant activity, and reduced the oxidative cellular stress as shown by their activity on reactive oxygen species (ROS) production, and modulation of the expression of antioxidant enzymes, such as glutamate-cysteine ligase (GCL) and heme oxygenase-1 (Hmox-1). Moreover, the EOs inhibited the production of nitric oxide (NO), showing anti-inflammatory activity. The data collected suggest that these EOs may be considered a promising therapeutic strategy for inflammation-based diseases and may represent an additional value for the economy of Tunisia.

Therapeutics. Pharmacology
DOAJ Open Access 2022
Mussaenda macrophylla Wall. exhibit anticancer activity against Dalton’s lymphoma ascites (DLA) bearing mice via alterations of redox-homeostasis and apoptotic genes expression

Marina Lalremruati, C. Lalmuansangi, Mary Zosangzuali et al.

Abstract Background Mussaenda macrophylla is a shrub widely used in Mizo traditional practice for treatment of cancer, fever, cough, ulcer and dysentery. We have previously shown the antioxidant nature of the plant. In this study, we explore the anticancer activity of the aqueous extract of M. macrophylla (MMAE) using Dalton’s lymphoma ascites (DLA) bearing mice as our model. Results MMAE significantly inhibited the tumor growth and increased the survival time of the tumor bearing DLA mice. MMAE significantly increased the glutathione (GSH) levels; and glutathione-s-transferase (GST) and superoxide dismutase (SOD) activities. Consistently, MMAE decreased lipid peroxidation levels in DLA mice. Reduced RBC and hemoglobin levels were significantly reversed by MMAE treatment. MMAE also lowers the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (CRE) levels that were otherwise elevated in the DLA control animals. Induction of DNA damage, up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes in DLA bearing mice following MMAE treatment provide an insight into apoptosis based anticancer activities of M. macrophylla. Conclusion Our findings demonstrate the role of the aqueous extract of M. macrophylla as a potential anticancer agent possibly targeting the apoptotic pathway. Graphical Abstract

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