bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome Analysis of Mesenchymal Progenitor Cells Revealed Molecular Insights into Metabolic Dysfunction and Inflammation in Polycystic Ovary Syndrome
Authors: Huang Mei-Chi , Chen Pei-Lung , Hsu Chia-Lang
Published: July 2024

Polycystic ovary syndrome (PCOS) is a female endocrine disorder with metabolic issues. Hyperandrogenism combined with hyperinsulinemia exacerbates the reproductive, metabolic, and inflammatory problems in PCOS patients. The etiology of PCOS is unclear. Patient-specific induced pluripotent stem cells (iPSCs) offer a promising model for studying disease mechanisms and conducting drug screening. Here, we aim to use mesenchymal progenitor cells (MPCs) derived from PCOS iPSCs to explore the mechanism of PCOS. We compared the transcriptome profiles of PCOS and healthy control (HC) iPSC-derived MPCs (iPSCMs). Moreover, we assess the impact of androgens on iPSCMs. In the comparison between PCOS and HC, the expression levels of 1026 genes were significantly different. A gene set enrichment analysis (GSEA) revealed that adipogenesis- and metabolism-related genes were downregulated, whereas inflammation-related genes were upregulated in the PCOS iPSCMs. Dysregulation of the TGF-β1 and Wnt signaling pathways was observed in the PCOS iPSCMs. Furthermore, there was impaired adipogenesis and decreased lipolysis in the PCOS iPSCMs-derived adipocytes. With testosterone treatment, genes related to metabolism were upregulated in the HC iPSCMs but downregulated in the PCOS iPSCMs. The impact of testosterone varied among HCs and PCOS iPSCMs, possibly because of a genetic predisposition toward PCOS. This study found specific signaling pathways that could serve as therapeutic targets for PCOS.
Role of IL-27 in COVID-19: A Thin Line between Protection and Disease Promotion
Authors: Korobova Zoia R. , Arsentieva Natalia A. , Santoni Angela , Totolian Areg A.
Published: July 2024

Cytokine storm is usually described as one of the main reasons behind COVID-associated mortality. Cytokines are essential protein molecules engaged in immune responses; they play a critical role in protection against infections. However, they also contribute to inflammatory reactions and tissue damage, becoming a double-edged sword in the context of COVID-19. Recent studies have suggested various cytokines and chemokines that play a crucial role in the immune response to SARS-CoV-2 infection. One such cytokine is interleukin 27 (IL-27), which has been found to be elevated in the blood plasma of patients with COVID-19. Within this study, we will explore the role of IL-27 in immune responses and analyze both the existing literature and our own prior research findings on this cytokine in the context of COVID-19. It affects a wide variety of immune cells. Regardless of the pathological process it is involved in, IL-27 is critical for upholding the necessary balance between tissue damage and cytotoxicity against infectious agents and/or tumors. In COVID-19, it is involved in multiple processes, including antiviral cytotoxicity via CD8+ cells, IgG subclass switching, and even the activation of Tregs.
IgLON5-IgG: Innocent Bystander or Perpetrator?
Authors: Andersen Jane , Jeffrey Bronte , Varikatt Winny , Rodriguez Michael , Lin Ming-Wei , Brown David A.
Published: July 2024

Anti-IgLON5 (IgLON5-IgG)-associated disease is a newly defined clinical entity. This literature review aims to evaluate its pathogenesis, which remains a pivotal question. Features that favour a primary neurodegenerative mechanism include the non-inflammatory tauopathy neuropathological signature and overrepresentation of microtubule-associated protein tau (MAPT) H1/H1 genotype as seen in other sporadic tauopathies. In contrast, the cell-surface localisation of IgLON5, capability of anti-IgLON5 antibodies to exert direct in vitro pathogenicity and disrupt IgLON5 interactions with its binding partners, human leukocyte antigen (HLA)-DRB1*10:01 and HLA-DQB1*05:01 allele preponderance with high affinity binding of IgLON5 peptides, and responsiveness to immunotherapy favour a primary autoimmune process. The presentation and course of anti-IgLON5-associated disease is heterogenous; hence, we hypothesise that a multitude of immune mechanisms are likely simultaneously operational in this disease cohort.
Development of Bivalent Aptamer-DNA Carrier-Doxorubicin Conjugates for Targeted Killing of Esophageal Squamous Cell Carcinoma Cells
Authors: Zhang Tianlu , Yin Kai , Niu Xidong , Bai Xue , Wang Zhaoting , Ji Mengmeng , Yuan Baoyin
Published: July 2024

Esophageal cancer ranks the seventh in cancer incidence and the sixth in cancer death. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of the total cases of esophageal cancer. Chemotherapy is the most effective drug-based method for treatment of esophageal cancer. However, severe side effects of traditional chemotherapy limit its treatment efficacy. Targeted chemotherapy can deliver chemotherapeutic drugs to cancer cells and specifically kill these cells with reduced side effects. In the work, the bivalent aptamer-DNA carrier (BAD) was designed by using an ESCC cell-specific aptamer as the recognition molecule and a GC base-rich DNA sequence as the drug carrier. With doxorubicin (Dox) as chemotherapeutic drugs, the bivalent aptamer-DNA-Dox conjugate (BADD) was constructed for targeted killing of ESCC cells. Firstly, the truncated A2(35) aptamer with a retained binding ability was obtained through optimization of an intact A2(80) aptamer and was used to fuse with DNA carrier sequences for constructing the BAD through simple DNA hybridization. The results of gel electrophoresis and flow cytometry analysis showed that the BAD was successfully constructed and had a stronger binding affinity than monovalent A2(35). Then, the BAD was loaded with Dox drugs to construct the BADD through noncovalent intercalation. The results of fluorescence spectra and flow cytometry assays showed that the BADD was successfully constructed and can bind to target cells strongly. Confocal imaging further displayed that the BADD can be specifically internalized into target cells and release Dox. The results of CCK-8 assays, Calcein AM/PI staining, and wound healing assays demonstrated that the BADD can specifically kill target cells, but not control cells. Our results demonstrate that the developed BADD can specifically deliver doxorubicin to target ESCC cells and selectively kill these cells, offering a potentially effective strategy for targeted chemotherapy of ESCC.
Exogenous GA3 Enhances Nitrogen Uptake and Metabolism under Low Nitrate Conditions in ‘Duli’ (Pyrus betulifolia Bunge) Seedlings
Authors: Zhang Weilong , Cheng Xiaohua , Jing Zhaotian , Cao Ying , Yuan Shuai , Zhang Haixia , Zhang Yuxing
Published: July 2024

‘Duli’ (Pyrus betulifolia Bunge) is one of the main rootstocks of pear trees in China. Gibberellin (GA) is a key plant hormone and the roles of GA in nitrate (NO3−) uptake and metabolism in plants remain unclear. In this study, we investigated the effects of exogenous GA3 on the N metabolism of ‘Duli’ seedlings under NO3− deficiency. The results showed that exogenous GA3 significantly improves ‘Duli’ growth under NO3− deficiency. On the one hand, GA3 altered the root architecture, increased the content of endogenous hormones (GA3, IAA, and ZR), and enhanced photosynthesis; on the other hand, it enhanced the activities of N−metabolizing enzymes and the accumulation of N, and increased the expression levels of N absorption (PbNRT2) and the metabolism genes (PbNR, PbGILE, PbGS, and PbGOGAT). However, GA3 did not delay the degradation of chlorophyll. Paclobutrazol had the opposite effect on growth. Overall, GA3 can increase NO3− uptake and metabolism and relieve the growth inhibition of ‘Duli’ seedlings under NO3− deficiency.
Mass Spectrometry Imaging Combined with Sparse Autoencoder Method Reveals Altered Phosphorylcholine Distribution in Imipramine Treated Wild-Type Mice Brains
Authors: Rahman Md Foyzur , Islam Ariful , Islam Md. Monirul , Mamun Md. Al , Xu Lili , Sakamoto Takumi , Sato Tomohito , Takahashi Yutaka , Kahyo Tomoaki , Aoyagi Satoka , Kaibuchi Kozo , Setou Mitsutoshi
Published: July 2024

Mass spectrometry imaging (MSI) is essential for visualizing drug distribution, metabolites, and significant biomolecules in pharmacokinetic studies. This study mainly focuses on imipramine, a tricyclic antidepressant that affects endogenous metabolite concentrations. The aim was to use atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI)-MSI combined with different dimensionality reduction methods to examine the distribution and impact of imipramine on endogenous metabolites in the brains of treated wild-type mice. Brain sections from both control and imipramine-treated mice underwent AP-MALDI-MSI. Dimensionality reduction methods, including principal component analysis, multivariate curve resolution, and sparse autoencoder (SAE), were employed to extract valuable information from the MSI data. Only the SAE method identified phosphorylcholine (ChoP) as a potential marker distinguishing between the control and treated mice brains. Additionally, a significant decrease in ChoP accumulation was observed in the cerebellum, hypothalamus, thalamus, midbrain, caudate putamen, and striatum ventral regions of the treated mice brains. The application of dimensionality reduction methods, particularly the SAE method, to the AP-MALDI-MSI data is a novel approach for peak selection in AP-MALDI-MSI data analysis. This study revealed a significant decrease in ChoP in imipramine-treated mice brains.
Discovery of the Natural Bibenzyl Compound Erianin in Dendrobium Inhibiting the Growth and EMT of Gastric Cancer through Downregulating the LKB1-SIK2/3-PARD3 Pathway
Authors: Wei Xin , Liu Qunshan , Liu Liu , Wang Dan , Liu Jiajia , Zhu Qizhi , Xu Ziming , Chen Qi , Xu Weiping
Published: July 2024

Erianin, a bibenzyl compound found in dendrobium extract, has demonstrated broad anticancer activity. However, its mechanism of action in gastric cancer (GC) remains poorly understood. LKB1 is a tumor-suppressor gene, and its mutation is an important driver of various cancers. Yet some studies have reported contradictory findings. In this study, we combined bioinformatics and in vitro and in vivo experiments to investigate the effect and potential mechanism of Erianin in the treatment of GC. The results show that LKB1 was highly expressed in patients’ tumor tissues and GC cells, and it was associated with poor patient prognosis. Erianin could promote GC cell apoptosis and inhibit the scratch repair, migration, invasion, and epithelial–mesenchymal transition (EMT) characteristics. Erianin dose-dependently inhibited the expression of LKB1, SIK2, SIK3, and PARD3 but had no significant effect on SIK1. Erianin also inhibited tumor growth in CDX mice model. Unexpectedly, 5-FU also exhibited a certain inhibitory effect on LKB1. The combination of Erianin and 5-FU significantly improved the anti-tumor efficacy of 5-FU in the growth of GC cells and xenograft mouse models. In summary, Erianin is a potential anti-GC compound that can inhibit GC growth and EMT properties by targeting the LKB1-SIK2/3-PARD3-signaling axis. The synergistic effect of Erianin and 5-FU suggests a promising therapeutic strategy for GC treatment.
Evaluation of SARS-CoV-2-Specific IgY Antibodies: Production, Reactivity, and Neutralizing Capability against Virus Variants
Authors: Schön Jacob , Aebischer Andrea , Halwe Nico Joël , Ulrich Lorenz , Hoffmann Donata , Reiche Sven , Beer Martin , Grund Christian
Published: July 2024

The emergence of SARS-CoV-2 in late 2019 initiated a global pandemic, which led to a need for effective therapeutics and diagnostic tools, including virus-specific antibodies. Here, we investigate different antigen preparations to produce SARS-CoV-2-specific and virus-neutralizing antibodies in chickens (n = 3/antigen) and rabbits (n = 2/antigen), exploring, in particular, egg yolk for large-scale production of immunoglobulin Y (IgY). Reactivity profiles of IgY preparations from chicken sera and yolk and rabbit sera were tested in parallel. We compared three types of antigens based on ancestral SARS-CoV-2: an inactivated whole-virus preparation, an S1 spike-protein subunit (S1 antigen) and a receptor-binding domain (RBD antigen, amino acids 319–519) coated on lumazine synthase (LS) particles using SpyCather/SpyTag technology. The RBD antigen proved to be the most efficient immunogen, and the resulting chicken IgY antibodies derived from serum or yolk, displayed strong reactivity with ELISA and indirect immunofluorescence and broad neutralizing activity against SARS-CoV-2 variants, including Omicron BA.1 and BA.5. Preliminary in vivo studies using RBD–lumazine synthase yolk preparations in a hamster model showed that local application was well tolerated and not harmful. However, despite the in vitro neutralizing capacity, this antibody preparation did not show protective effect. Further studies on galenic properties seem to be necessary. The RBD–lumazine antigen proved to be suitable for producing SARS-CoV-2 specific antibodies that can be applied to such therapeutic approaches and as reference reagents for SARS-CoV-2 diagnostics, including virus neutralization assays.
Transcriptome-Wide Identification of m6A Writers, Erasers and Readers and Their Expression Profiles under Various Biotic and Abiotic Stresses in Pinus massoniana Lamb.
Authors: Yao Sheng , Song Yidan , Cheng Xiang , Wang Dengbao , Li Qianzi , Zhang Jingjing , Chen Qingyang , Yu Qiong , Ji Kongshu
Published: July 2024

N6-methyladenosine (m6A) RNA modification is the most prevalent form of RNA methylation and plays a crucial role in plant development. However, our understanding of m6A modification in Masson pine (Pinus massoniana Lamb.) remains limited. In this study, a complete analysis of m6A writers, erasers, and readers in Masson pine was performed, and 22 m6A regulatory genes were identified in total, including 7 m6A writers, 7 m6A erases, and 8 readers. Phylogenetic analysis revealed that all m6A regulators involved in Masson pine could be classified into three distinct groups based on their domains and motifs. The tissue expression analysis revealed that the m6A regulatory gene may exert a significant influence on the development of reproductive organs and leaves in Masson pine. Moreover, the results from stress and hormone expression analysis indicated that the m6A regulatory gene in Masson pine might be involved in drought stress response, ABA-signaling-pathway activation, as well as resistance to Monochamus alternatus. This study provided valuable and anticipated insights into the regulatory genes of m6A modification and their potential epigenetic regulatory mechanisms in Masson pine.
Glioma and Peptidergic Systems: Oncogenic and Anticancer Peptides
Authors: Sánchez Manuel Lisardo , Mangas Arturo , Coveñas Rafael
Published: July 2024

Glioma cells overexpress different peptide receptors that are useful for research, diagnosis, management, and treatment of the disease. Oncogenic peptides favor the proliferation, migration, and invasion of glioma cells, as well as angiogenesis, whereas anticancer peptides exert antiproliferative, antimigration, and anti-angiogenic effects against gliomas. Other peptides exert a dual effect on gliomas, that is, both proliferative and antiproliferative actions. Peptidergic systems are therapeutic targets, as peptide receptor antagonists/peptides or peptide receptor agonists can be administered to treat gliomas. Other anticancer strategies exerting beneficial effects against gliomas are discussed herein, and future research lines to be developed for gliomas are also suggested. Despite the large amount of data supporting the involvement of peptides in glioma progression, no anticancer drugs targeting peptidergic systems are currently available in clinical practice to treat gliomas.
Theoretical and Experimental Study on Carbodiimide Formation
Authors: Csécsi Marcell Dániel , Kondor Virág , Reizer Edina , Boros Renáta Zsanett , Tóth Péter , Farkas László , Fiser Béla , Mucsi Zoltán , Nagy Miklós , Viskolcz Béla
Published: July 2024

Carbodiimides are important crosslinkers in organic synthesis and are used in the isocyanate industry as modifier additives. Therefore, the understanding of their formation is of high importance. In this work, we present a theoretical B3LYP/6-31G(d) and SMD solvent model and experimental investigation of the formation of diphenylcarbodiimide (CDI) from phenyl isocyanate using a phosphorus-based catalyst (MPPO) in ortho-dichlorobenzene (ODCB) solvent. Kinetic experiments were based on the volumetric quantitation of CO2 evolved, at different temperatures between 40 and 80 °C. Based on DFT calculations, we managed to construct a more detailed reaction mechanism compared to previous studies which is supported by experimental results. DFT calculations revealed that the mechanism is composed of two main parts, and the rate determining step of the first part, controlling the CO2 formation, is the first transition state with a 52.9 kJ mol−1 enthalpy barrier. The experimental activation energy was obtained from the Arrhenius plot (ln k vs. 1/T) using the observed second-order kinetics, and the obtained 55.8 ± 2.1 kJ mol−1 was in excellent agreement with the computational one, validating the complete mechanism, giving a better understanding of carbodiimide production from isocyanates.
AdNAC20 Regulates Lignin and Coumarin Biosynthesis in the Roots of Angelica dahurica var. formosana
Authors: Qu Wenjie , Huang Wenjuan , Chen Chen , Chen Jinsong , Zhao Lin , Jiang Yijie , Du Xuan , Liu Renlang , Chen Yinyin , Hou Kai , Xu Dongbei , Wu Wei
Published: July 2024

Angelica dahurica var. formosana (ADF), which belongs to the Umbelliferae family, is one of the original plants of herbal raw material Angelicae Dahuricae Radix. ADF roots represent an enormous biomass resource convertible for disease treatment and bioproducts. But, early bolting of ADF resulted in lignification and a decrease in the coumarin content in the root, and roots lignification restricts its coumarin for commercial utility. Although there have been attempts to regulate the synthesis ratio of lignin and coumarin through biotechnology to increase the coumarin content in ADF and further enhance its commercial value, optimizing the biosynthesis of lignin and coumarin remains challenging. Based on gene expression analysis and phylogenetic tree profiling, AdNAC20 as the target for genetic engineering of lignin and coumarin biosynthesis in ADF was selected in this study. Early-bolting ADF had significantly greater degrees of root lignification and lower coumarin contents than that of the normal plants. In this study, overexpression of AdNAC20 gene plants were created using transgenic technology, while independent homozygous transgenic lines with precise site mutation of AdNAC20 were created using CRISPR/Cas9 technology. The overexpressing transgenic ADF plants showed a 9.28% decrease in total coumarin content and a significant 12.28% increase in lignin content, while knockout mutant plants showed a 16.3% increase in total coumarin content and a 33.48% decrease in lignin content. Furthermore, 29,671 differentially expressed genes (DEGs) were obtained by comparative transcriptomics of OE-NAC20, KO-NAC20, and WT of ADF. A schematic diagram of the gene network interacting with AdNAC20 during the early-bolting process of ADF was constructed by DEG analysis. AdNAC20 was predicted to directly regulate the transcription of several genes with SNBE-like motifs in their promoter, such as MYB46, C3H, and CCoAOMT. In this study, AdNAC20 was shown to play a dual pathway function that positively enhanced lignin formation but negatively controlled coumarin formation. And the heterologous expression of the AdNAC20 gene at Arabidopsis thaliana proved that the AdNAC20 gene also plays an important role in the process of bolting and flowering.
The REPLUMLESS Transcription Factor Controls the Expression of the RECEPTOR-LIKE CYTOPLASMIC KINASE VI_A2 Gene Involved in Shoot and Fruit Patterning of Arabidopsis thaliana
Authors: Kenesi Erzsébet , Beöthy-Fehér Orsolya , Szőllősi Réka , Domonkos Ildikó , Valkai Ildikó , Fehér Attila
Published: July 2024

The promoter of the RECEPTOR-LIKE CYTOPLASMIC KINASE VI_A2 (RLCK VI_A2) gene contains nine binding sites for the REPLUMLESS (RPL) transcription factor. In agreement, the expression of the kinase gene was strongly downregulated in the rpl-4 mutant. Comparing phenotypes of loss-of-function mutants, it was revealed that both genes are involved in stem growth, phyllotaxis, organization of the vascular tissues, and the replum, highlighting potential functional interactions. The expression of the RLCKVI_A2 gene from the constitutive 35S promoter could not complement the rpl-4 phenotypes but exhibited a dominant positive effect on stem growth and affected vascular differentiation and organization. The results also indicated that the number of vascular bundles is regulated independently from stem thickness. Although our study cannot demonstrate a direct link between the RPL and RLVKVI_A2 genes, it highlights the significance of the proper developmental regulation of the RLCKVI_A2 promoter for balanced stem development.
Proteomic Analysis of Rap1A GTPase Signaling-Deficient C57BL/6 Mouse Pancreas and Functional Studies Identify an Essential Role of Rap1A in Pancreas Physiology
Authors: Shahwar Durrey , Baqai Sadaf , Khan Faisal , Khan M. Israr , Javaid Shafaq , Hameed Abdul , Raza Aisha , Saleem Uddin Sadaf , Hazrat Hina , Rahman M. Hafizur , Musharraf Syed Ghulam , Chotani Maqsood A.
Published: July 2024

Ras-related Rap1A GTPase is implicated in pancreas β-cell insulin secretion and is stimulated by the cAMP sensor Epac2, a guanine exchange factor and activator of Rap1 GTPase. In this study, we examined the differential proteomic profiles of pancreata from C57BL/6 Rap1A-deficient (Null) and control wild-type (WT) mice with nanoLC-ESI-MS/MS to assess targets of Rap1A potentially involved in insulin regulation. We identified 77 overlapping identifier proteins in both groups, with 8 distinct identifier proteins in Null versus 56 distinct identifier proteins in WT mice pancreata. Functional enrichment analysis showed four of the eight Null unique proteins, ERO1-like protein β (Ero1lβ), triosephosphate isomerase (TP1), 14-3-3 protein γ, and kallikrein-1, were exclusively involved in insulin biogenesis, with roles in insulin metabolism. Specifically, the mRNA expression of Ero1lβ and TP1 was significantly (p < 0.05) increased in Null versus WT pancreata. Rap1A deficiency significantly affected glucose tolerance during the first 15–30 min of glucose challenge but showed no impact on insulin sensitivity. Ex vivo glucose-stimulated insulin secretion (GSIS) studies on isolated Null islets showed significantly impaired GSIS. Furthermore, in GSIS-impaired islets, the cAMP-Epac2-Rap1A pathway was significantly compromised compared to the WT. Altogether, these studies underscore an essential role of Rap1A GTPase in pancreas physiological function.
Correction: Scimeca et al. Microcalcifications Drive Breast Cancer Occurrence and Development by Macrophage-Mediated Epithelial to Mesenchymal Transition. Int. J. Mol. Sci. 2019, 20, 5633
Authors: Scimeca Manuel , Bonfiglio Rita , Menichini Erika , Albonici Loredana , Urbano Nicoletta , De Caro Maria Teresa , Mauriello Alessandro , Schillaci Orazio , Gambacurta Alessandra , Bonanno Elena
Published: July 2024

In the original publication [...]
Antimicrobial Evaluation of Two Polycyclic Polyprenylated Acylphloroglucinol Compounds: PPAP23 and PPAP53
Authors: Ammanath Aparna Viswanathan , Matsuo Miki , Wang Huanhuan , Kraus Frank , Bleisch Anton , Peslalz Philipp , Mohammad Majd , Deshmukh Meghshree , Grießhammer Anne , Purkayastha Moushumi , Vorbach Andreas , Macek Boris , Brötz-Oesterhelt Heike , Maier Lisa , Kretschmer Dorothee , Peschel Andreas , Jin Tao , Plietker Bernd , Götz Friedrich
Published: July 2024

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John’s wort with its antidepressant, antitumor and antimicrobial properties. The chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here, we studied the antimicrobial activity of two synthetic PPAP-derivatives, the water-insoluble PPAP23 and the water-soluble sodium salt PPAP53. In vitro, both compounds exhibited good activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar effect was also seen with serum albumin. In silico docking studies with PPAP53 revealed that it binds to the F1 pocket of human serum albumin with a binding energy of −7.5 kcal/mol. In an infection model of septic arthritis, PPAP23 decreased the formation of abscesses and S. aureus load in kidneys; in a mouse skin abscess model, topical treatment with PPAP53 reduced S. aureus counts. Both PPAPs were active against anaerobic Gram-positive gut bacteria such as neurotransmitter-producing Clostridium, Enterococcus or Ruminococcus species. Based on these results, we foresee possible applications in the decolonization of pathogens.
Analysis of the Aging-Related AP2/ERF Transcription Factor Gene Family in Osmanthus fragrans
Authors: Chen Gongwei , Shao Tianqi , Zhou Yixiao , Chen Fengyuan , Zhang Dandan , Gu Heng , Yue Yuanzheng , Wang Lianggui , Yang Xiulian
Published: July 2024

Ethylene-Responsive Factor (ERF) is a key element found in the middle and lower reaches of the ethylene signal transduction pathway. It is widely distributed in plants and plays important roles in plant growth and development, hormone signal transduction, and various stress processes. Although there is research on AP/ERF family members, research on AP2/ERF in Osmanthus fragrans is lacking. Thus, in this work, AP2/ERF in O. fragrans was extensively and comprehensively analyzed. A total of 298 genes encoding OfAP2/ERF proteins with complete AP2/ERF domains were identified. Based on the number of AP2/ERF domains and the similarity among amino acid sequences between AP2/ERF proteins from A. thaliana and O. fragrans, the 298 putative OfAP2/ERF proteins were divided into four different families, including AP2 (45), ERF (247), RAV (5), and SOLOIST (1). In addition, the exon–intron structure characteristics of these putative OfAP2/ERF genes and the conserved protein motifs of their encoded OfAP2/ERF proteins were analyzed, and the results were found to be consistent with those of the population classification. A tissue-specific analysis showed the spatiotemporal expression of OfAP2/ERF in the stems and leaves of O. fragrans at different developmental stages. Specifically, 21 genes were not expressed in any tissue, while high levels of expression were found for 25 OfAP2/ERF genes in several tissues, 60 genes in the roots, 34 genes in the stems, 37 genes in young leaves, 34 genes in old leaves, 32 genes in the early flowering stage, 18 genes in the full flowering stage, and 37 genes in the late flowering stage. Quantitative RT-PCR experiments showed that OfERF110a and OfERF110b had the highest expression levels at the full-bloom stage (S4), and this gradually decreased with the senescence of petals. The expression of OfERF119c decreased first and then increased, while the expression levels of OfERF4c and OfERF5a increased constantly. This indicated that these genes may play roles in flower senescence and the ethylene response. In the subsequent subcellular localization experiments, we found that ERF1-4 was localized in the nucleus, indicating that it was expressed in the nucleus. In yeast self-activation experiments, we found that OfERF112, OfERF228, and OfERF23 had self-activation activity. Overall, these results suggest that OfERFs may have the function of regulating petal senescence in O. fragrans.
From Proteome to Potential Drugs: Integration of Subtractive Proteomics and Ensemble Docking for Drug Repurposing against Pseudomonas aeruginosa RND Superfamily Proteins
Authors: Urra Gabriela , Valdés-Muñoz Elizabeth , Suardiaz Reynier , Hernández-Rodríguez Erix W. , Palma Jonathan M. , Ríos-Rozas Sofía E. , Flores-Morales Camila A. , Alegría-Arcos Melissa , Yáñez Osvaldo , Morales-Quintana Luis , D’Afonseca Vívian , Bustos Daniel
Published: July 2024

Pseudomonas aeruginosa (P. aeruginosa) poses a significant threat as a nosocomial pathogen due to its robust resistance mechanisms and virulence factors. This study integrates subtractive proteomics and ensemble docking to identify and characterize essential proteins in P. aeruginosa, aiming to discover therapeutic targets and repurpose commercial existing drugs. Using subtractive proteomics, we refined the dataset to discard redundant proteins and minimize potential cross-interactions with human proteins and the microbiome proteins. We identified 12 key proteins, including a histidine kinase and members of the RND efflux pump family, known for their roles in antibiotic resistance, virulence, and antigenicity. Predictive modeling of the three-dimensional structures of these RND proteins and subsequent molecular ensemble-docking simulations led to the identification of MK-3207, R-428, and Suramin as promising inhibitor candidates. These compounds demonstrated high binding affinities and effective inhibition across multiple metrics. Further refinement using non-covalent interaction index methods provided deeper insights into the electronic effects in protein–ligand interactions, with Suramin exhibiting superior binding energies, suggesting its broad-spectrum inhibitory potential. Our findings confirm the critical role of RND efflux pumps in antibiotic resistance and suggest that MK-3207, R-428, and Suramin could be effectively repurposed to target these proteins. This approach highlights the potential of drug repurposing as a viable strategy to combat P. aeruginosa infections.
Rate of Free Flap Failure and Return to the Operating Room in Lower Limb Reconstruction: A Systematic Review
Authors: Serra Pietro Luciano , Boriani Filippo , Khan Umraz , Atzeni Matteo , Figus Andrea
Published: July 2024

Background: Soft tissue defects of the lower limbs pose significant challenges in reconstructive surgery, accounting for approximately 10% of all reconstructive free flaps performed. These reconstructions often encounter higher complication rates due to various factors such as inflammation, infection, impaired blood flow, and nerve injuries. Methods: A systematic review was conducted following PRISMA guidelines, reviewing literature from 2017 to 2024. Eligible studies included those on free flap reconstruction of lower limb defects in living human subjects, with more than three cases and reported rates of flap failure and return to the operating room. Systematic reviews and metanalysis were excluded. Results: A total of 17 studies comprising 5061 patients and 5133 free flap reconstructions were included. The most common defects were in the lower leg (52.19%) due to trauma (79.40%). The total flap necrosis rate was 7.78%, the partial necrosis rate was 9.15%, and the rate of return to the operating room for suspected vascular compromise was 13.79%. Discussion: Lower limb reconstruction presents challenges due to diverse etiologies and variable tissue requirements. Factors such as recipient vessel availability, flap selection, and multidisciplinary approaches influence outcomes. Muscle and fasciocutaneous flaps remain common choices, each with advantages and limitations. This systematic review underscores the importance of individualized treatment planning. Conclusions: Microsurgical reconstruction of lower limb defects demonstrates safety and reliability, with overall favorable outcomes. Flap selection should be tailored to specific patient needs and defect characteristics, emphasizing meticulous surgical techniques and multidisciplinary collaboration. This systematic review provides valuable insights into current standards and encourages adherence to best practices in lower limb reconstruction.
Yeast Particle Encapsulation of Azole Fungicides for Enhanced Treatment of Azole-Resistant Candida albicans
Authors: Soto Ernesto R. , Rus Florentina , Ostroff Gary R.
Published: July 2024

Addressing the growing problem of antifungal resistance in medicine and agriculture requires the development of new drugs and strategies to preserve the efficacy of existing fungicides. One approach is to utilize delivery technologies. Yeast particles (YPs) are 3–5 µm porous, hollow microspheres, a byproduct of food-grade Saccharomyces cerevisiae yeast extract manufacturing processes and an efficient and flexible drug delivery platform. Here, we report the use of YPs for encapsulation of tetraconazole (TET) and prothioconazole (PRO) with high payload capacity and stability. The YP PRO samples were active against both sensitive and azole-resistant strains of Candida albicans. The higher efficacy of YP PRO versus free PRO is due to interactions between PRO and saponifiable lipids in the YPs. Encapsulation of PRO in glucan lipid particles (GLPs), a highly purified form of YPs that do not contain saponifiable lipids, did not result in enhanced PRO activity. We evaluated the co-encapsulation of PRO with a mixture of the terpenes: geraniol, eugenol, and thymol. Samples co-encapsulating PRO and terpenes in YPs or GLPs were active on both sensitive and azole-resistant C. albicans. These approaches could lead to the development of more effective drug combinations co-encapsulated in YPs for agricultural or GLPs for pharmaceutical applications.
Acne Detection Based on Reconstructed Hyperspectral Images
Authors: Mohammed Ridha Ali , Isa Nor Ashidi Mat , Tawfik Ayman
Published: July 2024

Acne Vulgaris is a common type of skin disease that affects more than 85% of teenagers and frequently continues even in adulthood. While it is not a dangerous skin disease, it can significantly impact the quality of life. Hyperspectral imaging (HSI), which captures a wide spectrum of light, has emerged as a tool for the detection and diagnosis of various skin conditions. However, due to the high cost of specialised HS cameras, it is limited in its use in clinical settings. In this research, a novel acne detection system that will utilise reconstructed hyperspectral (HS) images from RGB images is proposed. A dataset of reconstructed HS images is created using the best-performing HS reconstruction model from our previous research. A new acne detection algorithm that is based on reconstructed HS images and RetinaNet algorithm is introduced. The results indicate that the proposed algorithm surpasses other techniques based on RGB images. Additionally, reconstructed HS images offer a promising and cost-effective alternative to using expensive HSI equipment for detecting conditions like acne or other medical issues.
Deep Learning for Pneumonia Detection in Chest X-ray Images: A Comprehensive Survey
Authors: Siddiqi Raheel , Javaid Sameena
Published: July 2024

This paper addresses the significant problem of identifying the relevant background and contextual literature related to deep learning (DL) as an evolving technology in order to provide a comprehensive analysis of the application of DL to the specific problem of pneumonia detection via chest X-ray (CXR) imaging, which is the most common and cost-effective imaging technique available worldwide for pneumonia diagnosis. This paper in particular addresses the key period associated with COVID-19, 2020–2023, to explain, analyze, and systematically evaluate the limitations of approaches and determine their relative levels of effectiveness. The context in which DL is applied as both an aid to and an automated substitute for existing expert radiography professionals, who often have limited availability, is elaborated in detail. The rationale for the undertaken research is provided, along with a justification of the resources adopted and their relevance. This explanatory text and the subsequent analyses are intended to provide sufficient detail of the problem being addressed, existing solutions, and the limitations of these, ranging in detail from the specific to the more general. Indeed, our analysis and evaluation agree with the generally held view that the use of transformers, specifically, vision transformers (ViTs), is the most promising technique for obtaining further effective results in the area of pneumonia detection using CXR images. However, ViTs require extensive further research to address several limitations, specifically the following: biased CXR datasets, data and code availability, the ease with which a model can be explained, systematic methods of accurate model comparison, the notion of class imbalance in CXR datasets, and the possibility of adversarial attacks, the latter of which remains an area of fundamental research.
A Novel Technical Framework for the Evaluation of Node Significance and Edge Connectivity in Global Shipping Network
Authors: Duan Wei , Li Zhenfu , Zhou Yutao , Deng Zhao
Published: July 2024

Marine transportation is pivotal in the rapid development of global trade, significantly enhancing international economic and trade connectivity and impacting the sustainable development of the global economy. In this study, we developed a novel technical framework based on the Laplacian matrix to evaluate the node significance and edge connectivity of the global shipping network using 2019 vessel schedule data from the top 30 liner shipping companies, as ranked by Alphaliner. Our analyses were conducted in both L-space, characterizing the connectivity function, and P-space, characterizing the transfer function. The findings indicate the following. (1) There is no consistent relationship between node significance and centrality for most ports. Ports with high node significance are mainly located in the Asia–Pacific region, with Singapore Port being the port with the highest node significance in L-space and Shanghai Port being the port with the highest node significance in P-space. (2) In L-space, the structures with significant improvements in edge connectivity in the shipping network have at least one port node that exhibits both low degree centrality and low betweenness centrality; these are primarily found on East African routes. (3) In P-space, the structures with significant improvements in edge connectivity in the shipping network are more complex but are notably linked to the ports of Assaluyeh and Bandar Abbas in Iran. The proposed node evaluation and edge addition strategy effectively analyze port significance and edge connectivity, providing decision-making support for optimizing port layouts, supporting container route planning, and enhancing the overall performance of the shipping network.
Magnaporthe-Unique Gene MUG1 Is Important for Fungal Appressorial Penetration, Invasive Hyphal Extension, and Virulence in Rice Blast Fungi
Authors: Zhang Huixia , Chen Zhiyi , Yu Zechen , Tang Liu , Gao Wenqiang , Lu Xunli , Yang Jun
Published: July 2024

Species-unique genes that encode specific proteins and have no homologs in other species play certain roles in the evolution of species and adaptations to external environments. Nevertheless, the biological roles of unique genes in plant pathogenic fungi remain largely unknown. Here, four Magnaporthe-unique genes (MUG1–MUG4), which were highly expressed during the early infection stages, were functionally characterized in the rice blast fungus Magnaporthe oryzae. Subcellular localization assays revealed that Mug1, Mug2, and Mug4 were localized to the cytoplasm and that Mug3 was localized into the nuclei. Furthermore, through gene knockout and phenotypic analysis, only MUG1 was found to be indispensable for fungal virulence and conidiation. Detailed microscopic analysis revealed that the deletion mutants of MUG1 clearly exhibited reduced appressorial turgor pressure and invasive hyphal development. Taken together, our findings indicate that the Magnaporthe-unique gene MUG1 plays a vital role in infection-related morphogenesis and virulence in rice blast fungi and suggest the specific and important roles of species-unique genes.
Developing and Validating a Nomogram Model for Predicting Ischemic Stroke Risk
Authors: Zhou Li , Wu Youlin , Wang Jiani , Wu Haiyun , Tan Yongjun , Chen Xia , Song Xiaosong , Wang Yilin , Yang Qin
Published: July 2024

Background and purpose: Clinically, the ability to identify individuals at risk of ischemic stroke remains limited. This study aimed to develop a nomogram model for predicting the risk of acute ischemic stroke. Methods: In this study, we conducted a retrospective analysis on patients who visited the Department of Neurology, collecting important information including clinical records, demographic characteristics, and complete hematological tests. Participants were randomly divided into training and internal validation sets in a 7:3 ratio. Based on their diagnosis, patients were categorized as having or not having ischemic stroke (ischemic and non-ischemic stroke groups). Subsequently, in the training set, key predictive variables were identified through multivariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods, and a nomogram model was constructed accordingly. The model was then evaluated on the internal validation set and an independent external validation set through area under the receiver operating characteristic curve (AUC-ROC) analysis, a Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA) to verify its predictive efficacy and clinical applicability. Results: Eight predictors were identified: age, smoking status, hypertension, diabetes, atrial fibrillation, stroke history, white blood cell count, and vitamin B12 levels. Based on these factors, a nomogram with high predictive accuracy was constructed. The model demonstrated good predictive performance, with an AUC-ROC of 0.760 (95% confidence interval [CI]: 0.736–0.784). The AUC-ROC values for internal and external validation were 0.768 (95% CI: 0.732–0.804) and 0.732 (95% CI: 0.688–0.777), respectively, proving the model’s capability to predict the risk of ischemic stroke effectively. Calibration and DCA confirmed its clinical value. Conclusions: We constructed a nomogram based on eight variables, effectively quantifying the risk of ischemic stroke.
“How Often Do You Encounter the Verb Obnaruzhit’?” Subjective Frequency of Russian Verbs in Heritage Speakers and Other Types of Russian–German Bilinguals
Authors: Clasmeier Christina , Anstatt Tanja
Published: July 2024

The literature shows that word frequency data obtained from corpora (corpus frequency, CF) and L1 speaker estimation (subjective frequency, SF) are substantially correlated. However, little is known about languages other than English and the frequency estimation of different types of bilingual speakers. We address both issues and compare the correlation coefficients of the CF and SF for 49 Russian verbs as well as SF data between four groups of Russian speakers: monolinguals (MOs), late bilinguals (LBs), heritage speakers (HSs), and foreign language learners (FLs). We gained SF data from a frequency estimation study with 447 participants and found that despite the reduced exposure to Russian in the three bilingual groups, their SF data were correlated with the CF at the same level (moderately) as the monolinguals’ SF. Interestingly, the correlations between the SF of the MOs, LBs, and HSs were very high, indicating that the SF is extremely stable over different speaker groups and that HSs do not differ from other L1 speakers in this respect. Furthermore, in absolute terms, HSs judged the verbs consistently lower than LBs and MOs, demonstrating that speakers have a finely adjusted ability to estimate the frequency with which they encounter words. The learners, on the other hand, were a clearly distinguished group, with only moderate correlations with all groups of L1 speakers.
Understanding Galectin-3’s Role in Diastolic Dysfunction: A Contemporary Perspective
Authors: Hao Wen-Rui , Cheng Chun-Han , Liu Ju-Chi , Chen Huan-Yuan , Chen Jin-Jer , Cheng Tzu-Hurng
Published: July 2024

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3’s role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3’s role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.
Effect of Countersample Coatings on the Friction Behaviour of DC01 Steel Sheets in Bending-under-Tension Friction Tests
Authors: Trzepieciński Tomasz , Szwajka Krzysztof , Szewczyk Marek , Barlak Marek , Zielińska-Szwajka Joanna
Published: July 2024

The aim of this article is to provide an analysis of the influence of the type of hard anti-wear coatings on the friction behaviour of DC01 deep-drawing steel sheets. DC01 steel sheets exhibit high formability, and they are widely used in sheet metal forming operations. The tribological properties of the tool surface, especially the coating used, determine the friction conditions in sheet metal forming. In order to carry out the research, this study developed and manufactured a special bending-under-tension (BUT) friction tribometer that models the friction phenomenon on the rounded edges of tools in the deep-drawing process. The rationale for building the tribotester was that there are no commercial tribotesters available that can be used to model the phenomenon of friction on the rounded edges of tools in sheet forming processes. The influence of the type of coating and sheet deformation on the coefficient of friction (CoF) and the change in the topography of the sheet surface were analysed. Countersamples with surfaces prepared using titanium + nitrogen ion implantation, nitrogen ion implantation and electron beam remelting were tested. The tests were carried out in conditions of dry friction and lubrication with oils with different kinematic viscosities. Under dry friction conditions, a clear increase in the CoF value, with the elongation of the samples for all analysed types of countersamples, was observed. Under lubricated conditions, the uncoated countersample showed the most favourable friction conditions. Furthermore, oil with a lower viscosity provided more favourable conditions for reducing the coefficient of friction. Within the entire range of sample elongation, the most favourable conditions for reducing the CoF were provided by uncoated samples and lubrication with S100+ oil. During the friction process, the average roughness decreased as a result of flattening the phenomenon. Under dry friction conditions, the value of the Sa parameter during the BUT test decreased by 20.3–30.2%, depending on the type of countersample. As a result of the friction process, the kurtosis and skewness increased and decreased, respectively, compared to as-received sheet metal.