bluuebunny/crossref_metadata_2025 huggingface dataset:
Portrayal of NLRP3 Inflammasome in Atherosclerosis: Current Knowledge and Therapeutic Targets
Authors: Tanase Daniela Maria , Valasciuc Emilia , Gosav Evelina Maria , Ouatu Anca , Buliga-Finis Oana Nicoleta , Floria Mariana , Maranduca Minela Aida , Serban Ionela Lacramioara
Published: May 2023

We are witnessing the globalization of a specific type of arteriosclerosis with rising prevalence, incidence and an overall cardiovascular disease burden. Currently, atherosclerosis increasingly affects the younger generation as compared to previous decades. While early preventive medicine has seen improvements, research advances in laboratory and clinical investigation promise to provide us with novel diagnosis tools. Given the physio-pathological complexity and epigenetic patterns of atherosclerosis and the discovery of new molecules involved, the therapeutic field of atherosclerosis has room for substantial growth. Thus, the scientific community is currently investigating the role of nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a crucial component of the innate immune system in different inflammatory disorders. NLRP3 is activated by distinct factors and numerous cellular and molecular events which trigger NLRP3 inflammasome assembly with subsequent cleavage of pro-interleukin (IL)-1β and pro-IL-18 pathways via caspase-1 activation, eliciting endothelial dysfunction, promotion of oxidative stress and the inflammation process of atherosclerosis. In this review, we introduce the basic cellular and molecular mechanisms of NLRP3 inflammasome activation and its role in atherosclerosis. We also emphasize its promising therapeutic pharmaceutical potential.
β-Secretase-1: In Silico Drug Reposition for Alzheimer’s Disease
Authors: Galeana-Ascencio Roberto A. , Mendieta Liliana , Limon Daniel I. , Gnecco Dino , Terán Joel L. , Orea María L. , Carrasco-Carballo Alan
Published: May 2023

The β-secretase-1 enzyme (BACE-1) performs a key role in the production of beta-Amyloid protein (Aβ), which is associated with the development of Alzheimer’s disease (AD). The inhibition of BACE-1 has been an important pharmacological strategy in the treatment of this neurodegenerative disease. This study aims to identify new potential candidates for the treatment of Alzheimer’s with the help of in silico studies, such as molecular docking and ADME prediction, from a broad list of candidates provided by the DrugBank database. From this analysis, 1145 drugs capable of interacting with the enzyme with a higher coupling energy than Verubecestat were obtained, subsequently only 83 presented higher coupling energy than EJ7. Applying the oral route of administration as inclusion criteria, only 41 candidates met this requirement; however, 6 of them are associated with diagnostic tests and not treatment, so 33 candidates were obtained. Finally, five candidates were identified as possible BACE-1 inhibitors drugs: Fluphenazine, Naratriptan, Bazedoxifene, Frovatriptan, and Raloxifene. These candidates exhibit pharmacophore-specific features, including the indole or thioindole group, and interactions with key amino acids in BACE-1. Overall, this study provides insights into the potential use of in silico methods for drug repurposing and identification of new candidates for the treatment of Alzheimer’s disease, especially those targeting BACE-1.
A Potential Adhesin/Invasin STM0306 Participates in Host Cell Inflammation Induced by Salmonella enterica Serovar Typhimurium
Authors: Ling Chong , Liang Shujie , Li Yan , Cao Qingyun , Ye Hui , Zhang Changming , Dong Zemin , Feng Dingyuan , Wang Weiwei , Zuo Jianjun
Published: May 2023

Salmonella enterica serovar typhimurium (S. Typhimurium) is a common Gram-negative foodborne pathogenic bacterium that causes gastrointestinal disease in humans and animals. It is well known that adhesins and invasins play crucial roles in the infection mechanism of S. Typhimurium. S. Typhimurium STM0306 has been denoted as a putative protein and its functions have rarely been reported. In this study, we constructed the STM0306 gene mutant strain of S. Typhimurium and purified the recombinant STM0306 from Escherichia coli. Deletion of the STM0306 gene resulted in reduced adhesion and invasion of S. Typhimurium to IPEC-J2, Caco-2, and RAW264.7 cells. In addition, STM0306 could bind to intestinal epithelial cells and induced F-actin modulation in IPEC-J2 cells. Furthermore, we found that STM0306 activated the nuclear factor kappa B (NF-κB) signaling pathway and increased the mRNA expression of pro-inflammatory cytokines such as IL-1β, TNF-α, as well as chemokine CXCL2, thus resulting in cellular inflammation in host cells. In vivo, the deletion of the STM0306 gene led to reduced pathogenicity of S. Typhimurium, as evidenced by lower fecal bacterial counts and reduced body weight loss in S. Typhimurium infected mice. In conclusion, the STM0306 of S. Typhimurium is an important adhesin/invasin involved in the pathogenic process and cellular inflammation of the host.
Chronic Administration of Non-Constitutive Proteasome Inhibitor Modulates Long-Term Potentiation and Glutamate Signaling-Related Gene Expression in Murine Hippocampus
Authors: Maltsev Alexander , Funikov Sergei , Rezvykh Alexander , Teterina Ekaterina , Nebogatikov Vladimir , Burov Alexander , Bal Natalia , Ustyugov Aleksey , Karpov Vadim , Morozov Alexey
Published: May 2023

Proteasomes degrade most intracellular proteins. Several different forms of proteasomes are known. Little is known about the role of specific proteasome forms in the central nervous system (CNS). Inhibitors targeting different proteasome forms are used in clinical practice and were shown to modulate long-term potentiation (LTP) in hippocampal slices of untreated animals. Here, to address the role of non-constitutive proteasomes in hippocampal synaptic plasticity and reveal the consequences of their continuous inhibition, we studied the effect of chronic administration of the non-constitutive proteasome inhibitor ONX-0914 on the LTP induced by two different protocols: tetanic stimulation and theta-burst stimulation (TBS). Both the tetanus- and TBS-evoked potentiation contribute to the different forms of hippocampal-dependent memory and learning. Field-excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from control animals and animals treated with DMSO or ONX-0914 were compared. LTP induced by the TBS was not affected by ONX-0914 administration; however, chronic injections of ONX-0914 led to a decrease in fEPSP slopes after tetanic stimulation. The observed effects correlated with differential expression of genes involved in synaptic plasticity, glutaminergic synapse, and synaptic signaling. Obtained results indicate that non-constitutive proteasomes are likely involved in the tetanus-evoked LTP, but not the LTP occurring after TBS, supporting the relevance and complexity of the role of specific proteasomes in synaptic plasticity, memory, and learning.
Intestinal Behcet’s Disease: A Review of the Immune Mechanism and Present and Potential Biological Agents
Authors: He Kun , Yan Xiaxiao , Wu Dong
Published: May 2023

Behcet’s disease (BD) is a chronic and recurrent systemic vasculitis involving almost all organs and tissues. Intestinal BD is defined as BD with predominant gastrointestinal involvement, presenting severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction in some cases. To some extent, intestinal BD is classified as a member of inflammatory bowel disease (IBD), as it has a lot in common with classical IBD including Crohn’s disease (CD) and ulcerative colitis (UC). Certainly, the underlying pathogenesis is not the same and dysregulation of immune function is believed to be one of the main pathogeneses in intestinal BD, although the etiology has not been clear up to now. Biological agents are an emerging category of pharmaceuticals for various diseases, including inflammatory diseases and cancers, in recent decades. Based on the deep understanding of the immune mechanism of intestinal BD, biological agents targeting potential pathogenic cells, cytokines and pathways are optimized options. Recently, the adoption of biological agents such as anti-tumor necrosis factor agents has allowed for the effective treatment of patients with refractory intestinal BD who show poor response to conventional medications and are faced with the risk of surgical treatment. In this review, we have tried to summarize the immune mechanism and present potential biological agents of intestinal BD.
ABCA3 Deficiency—Variant-Specific Response to Hydroxychloroquine
Authors: Yang Xiaohua , Forstner Maria , Rapp Christina K. , Rothenaigner Ina , Li Yang , Hadian Kamyar , Griese Matthias
Published: May 2023

Biallelic variants in ABCA3, the gene encoding the lipid transporter ATP-binding cassette subfamily A member 3 (ABCA3) that is predominantly expressed in alveolar type II cells, may cause interstitial lung diseases in children (chILD) and adults. Currently, there is no proven therapy, but, frequently, hydroxychloroquine (HCQ) is used empirically. We hypothesized that the in vitro responsiveness to HCQ might correlate to patients’ clinical outcomes from receiving HCQ therapy. The clinical data of the subjects with chILD due to ABCA3 deficiency and treated with HCQ were retrieved from the literature and the Kids Lung Register data base. The in vitro experiments were conducted on wild type (WT) and 16 mutant ABCA3-HA-transfected A549 cells. The responses of the functional read out were assessed as the extent of deviation from the untreated WT. With HCQ treatment, 19 patients had improved or unchanged respiratory conditions, and 20 had respiratory deteriorations, 5 of whom transiently improved then deteriorated. The in vitro ABCA3 functional assays identified two variants with complete response, five with partial response, and nine with no response to HCQ. The variant-specific HCQ effects in vivo closely correlated to the in vitro data. An ABCA3+ vesicle volume above 60% of the WT volume was linked to responsiveness to HCQ; the HCQ treatment response was concentration dependent and differed for variants in vitro. We generated evidence for an ABCA3 variant-dependent impact of the HCQ in vitro. This may also apply for HCQ treatment in vivo, as supported by the retrospective and uncontrolled data from the treatment of chILD due to ABCA3 deficiency.
The Tricky Connection between Extracellular Vesicles and Mitochondria in Inflammatory-Related Diseases
Authors: Di Mambro Tommaso , Pellielo Giulia , Agyapong Esther Densu , Carinci Marianna , Chianese Diego , Giorgi Carlotta , Morciano Giampaolo , Patergnani Simone , Pinton Paolo , Rimessi Alessandro
Published: May 2023

Mitochondria are organelles present in almost all eukaryotic cells, where they represent the main site of energy production. Mitochondria are involved in several important cell processes, such as calcium homeostasis, OXPHOS, autophagy, and apoptosis. Moreover, they play a pivotal role also in inflammation through the inter-organelle and inter-cellular communications, mediated by the release of mitochondrial damage-associated molecular patterns (mtDAMPs). It is currently well-documented that in addition to traditional endocrine and paracrine communication, the cells converse via extracellular vesicles (EVs). These small membrane-bound particles are released from cells in the extracellular milieu under physio-pathological conditions. Importantly, EVs have gained much attention for their crucial role in inter-cellular communication, translating inflammatory signals into recipient cells. EVs cargo includes plasma membrane and endosomal proteins, but EVs also contain material from other cellular compartments, including mitochondria. Studies have shown that EVs may transport mitochondrial portions, proteins, and/or mtDAMPs to modulate the metabolic and inflammatory responses of recipient cells. Overall, the relationship between EVs and mitochondria in inflammation is an active area of research, although further studies are needed to fully understand the mechanisms involved and how they may be targeted for therapeutic purposes. Here, we have reported and discussed the latest studies focused on this fascinating and recent area of research, discussing of tricky connection between mitochondria and EVs in inflammatory-related diseases.
Staphylococcus aureus Infection: Pathogenesis and Antimicrobial Resistance
Authors: Gherardi Giovanni
Published: May 2023

Staphylococcus aureus, a Gram-positive, coagulase-positive pathogen belonging to the family Staphylococcaceae with a spherical shape that forms grape-like clusters, is a commensal that is often present asymptomatically on parts of the human body [...]
Genetics and Epigenetics in Complex Diseases
Authors: Lopez-Lopez Elixabet
Published: May 2023

Many of the most common diseases are influenced by a combination of multiple factors, which include environmental effectors, as well as genetic and epigenetic variations [...]
Pathogenesis of Oral Toxicities Associated with Targeted Therapy and Immunotherapy
Authors: Villa Alessandro , Kuten-Shorrer Michal
Published: May 2023

Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as “mucositis” or “stomatitis,” oral toxicities induced by targeted therapies differ clinically and mechanistically from those associated with conventional chemotherapy. Manifesting primarily as mucosal lesions, salivary gland hypofunction, or orofacial neuropathies, these oral toxicities may nonetheless lead to significant morbidity and impact patients’ quality of life, thereby compromising clinical outcomes. We conclude that familiarity with the spectrum of associated toxicities and understanding of their pathogenesis represent important areas of clinical research and may lead to better characterization, prevention, and management of these adverse events.
A Theoretical Study of Hydrogen Abstraction Reactions in Guanosine and Uridine
Authors: Schaltz Kasper , Sauer Stephan
Published: May 2023

All the practically possible hydrogen abstraction reactions for guanosine and uridine have been investigated through quantum chemical calculations of energy barriers and rate constants. This was conducted at the level of density functional theory (DFT) with the ωB97X-D functional and the 6-311++G(2df,2pd) Pople basis set. Transition state theory with the Eckart tunneling correction was used to calculate the rate constants. The results show that the reaction involving the hydrogen labeled C4′ in the ribofuranose part has the largest rate constant for guanosine with the value 6.856 × 1010 L s−1mol−1 and the largest for uridine with the value 3.655 × 109 L s−1mol−1. Based on the results for these two nucleosides, there is a noticeable similarity between the rate constants in the ribofuranose part of the molecule, even though they are bound to two entirely different nucleobases.
Uncovering the Cryptic Gene Cluster ahb for 3-amino-4-hydroxybenzoate Derived Ahbamycins, by Searching SARP Regulator Encoding Genes in the Streptomyces argillaceus Genome
Authors: Ye Suhui , Molloy Brian , Pérez-Victoria Ignacio , Montero Ignacio , Braña Alfredo F. , Olano Carlos , Arca Sonia , Martín Jesús , Reyes Fernando , Salas José A. , Méndez Carmen
Published: May 2023

Genome mining using standard bioinformatics tools has allowed for the uncovering of hidden biosynthesis gene clusters for specialized metabolites in Streptomyces genomes. In this work, we have used an alternative approach consisting in seeking “Streptomyces Antibiotic Regulatory Proteins” (SARP) encoding genes and analyzing their surrounding DNA region to unearth cryptic gene clusters that cannot be identified using standard bioinformatics tools. This strategy has allowed the unveiling of the new ahb cluster in Streptomyces argillaceus, which had not been retrieved before using antiSMASH. The ahb cluster is highly preserved in other Streptomyces strains, which suggests a role for their encoding compounds in specific environmental conditions. By combining overexpression of three regulatory genes and generation of different mutants, we were able to activate the ahb cluster, and to identify and chemically characterize the encoded compounds that we have named ahbamycins (AHBs). These constitute a new family of metabolites derived from 3-amino-4-hydroxybenzoate (3,4-AHBA) known for having antibiotic and antitumor activity. Additionally, by overexpressing three genes of the cluster (ahbH, ahbI, and ahbL2) for the synthesis and activation of 3,4-AHBA, a new hybrid compound, AHB18, was identified which had been produced from a metabolic crosstalk between the AHB and the argimycin P pathways. The identification of this new BGC opens the possibility to generate new compounds by combinatorial biosynthesis.
Muscarinic Acetylcholine Receptor M3 Expression and Survival in Human Colorectal Carcinoma—An Unexpected Correlation to Guide Future Treatment?
Authors: Lobbes Leonard A. , Schütze Marcel A. , Droeser Raoul , Arndt Marco , Pozios Ioannis , Lauscher Johannes C. , Hering Nina A. , Weixler Benjamin
Published: May 2023

Muscarinic acetylcholine receptor M3 (M3R) has repeatedly been shown to be prominently expressed in human colorectal cancer (CRC), playing roles in proliferation and cell invasion. Its therapeutic targetability has been suggested in vitro and in animal models. We aimed to investigate the clinical role of MR3 expression in CRC for human survival. Surgical tissue samples from 754 CRC patients were analyzed for high or low immunohistochemical M3R expression on a clinically annotated tissue microarray (TMA). Immunohistochemical analysis was performed for established immune cell markers (CD8, TIA-1, FOXP3, IL 17, CD16 and OX 40). We used Kaplan–Meier curves to evaluate patients’ survival and multivariate Cox regression analysis to evaluate prognostic significance. High M3R expression was associated with increased survival in multivariate (hazard ratio (HR) = 0.52; 95% CI = 0.35–0.78; p = 0.001) analysis, as was TIA-1 expression (HR = 0.99; 95% CI = 0.94–0.99; p = 0.014). Tumors with high M3R expression were significantly more likely to be grade 2 compared to tumors with low M3R expression (85.7% vs. 67.1%, p = 0.002). The 5-year survival analysis showed a trend of a higher survival rate in patients with high M3R expression (46%) than patients with low M3R expression CRC (42%) (p = 0.073). In contrast to previous in vitro and animal model findings, this study demonstrates an increased survival for CRC patients with high M3R expression. This evidence is highly relevant for translation of basic research findings into clinically efficient treatments.
Comprehensive Characterization of a Novel Bacteriophage, vB_VhaS_MAG7 against a Fish Pathogenic Strain of Vibrio harveyi and Its In Vivo Efficacy in Phage Therapy Trials
Authors: Droubogiannis Stavros , Pavlidi Lydia , Skliros Dimitrios , Flemetakis Emmanouil , Katharios Pantelis
Published: May 2023

Vibrio harveyi, a significant opportunistic marine pathogen, has been a challenge to the aquaculture industry, leading to severe economical and production losses. Phage therapy has been an auspicious approach in controlling such bacterial infections in the era of antimicrobial resistance. In this study, we isolated and fully characterized a novel strain-specific phage, vB_VhaS_MAG7, which infects V. harveyi MM46, and tested its efficacy as a therapeutic agent in challenged gilthead seabream larvae. vB_VhaS_MAG7 is a tailed bacteriophage with a double-stranded DNA of 49,315 bp. No genes linked with virulence or antibiotic resistance were harbored in the genome. The phage had a remarkably large burst size of 1393 PFU cell−1 and showed strong lytic ability in in vitro assays. When applied in phage therapy trials in challenged gilthead seabream larvae, vB_VhaS_MAG7 was capable of improving the survival of the larvae up to 20%. Due to its distinct features and safety, vB_VhaS_MAG7 is considered a suitable candidate for applied phage therapy.
Non-Permissive Parvovirus B19 Infection: A Reservoir and Questionable Safety Concern in Mesenchymal Stem Cells
Authors: Bua Gloria , Marrazzo Pasquale , Manaresi Elisabetta , Gamberini Chiara , Bonsi Laura , Alviano Francesco , Gallinella Giorgio
Published: May 2023

Mesenchymal stromal/stem cells (MSCs) are multipotent cells with differentiation, immunoregulatory and regenerative properties. Because of these features, they represent an attractive tool for regenerative medicine and cell-based therapy. However, MSCs may act as a reservoir of persistent viruses increasing the risk of failure of MSCs-based therapies and of viral transmission, especially in immunocompromised patients. Parvovirus B19V (B19V) is a common human pathogen that infects bone marrow erythroid progenitor cells, leading to transient or persistent anemia. Characteristics of B19V include the ability to cross the placenta, infecting the fetus, and to persist in several tissues. We thus isolated MSCs from bone marrow (BM-MSCs) and fetal membrane (FM-MSCs) to investigate their permissiveness to B19V infection. The results suggest that both BM- and FM- MSCs can be infected by B19V and, while not able to support viral replication, allow persistence over time in the infected cultures. Future studies are needed to understand the potential role of MSCs in B19V transmission and the conditions that can favor a potential reactivation of the virus.
Populus euphratica GLABRA3 Binds PLDδ Promoters to Enhance Salt Tolerance
Authors: Zhang Ying , Yin Kexin , Yao Jun , Zhao Ziyan , Liu Zhe , Yan Caixia , Zhang Yanli , Liu Jian , Li Jing , Zhao Nan , Zhao Rui , Zhou Xiaoyang , Chen Shaoliang
Published: May 2023

High NaCl (200 mM) increases the transcription of phospholipase Dδ (PLDδ) in roots and leaves of the salt-resistant woody species Populus euphratica. We isolated a 1138 bp promoter fragment upstream of the translation initiation codon of PePLDδ. A promoter–reporter construct, PePLDδ-pro::GUS, was introduced into Arabidopsis plants (Arabidopsis thaliana) to demonstrate the NaCl-induced PePLDδ promoter activity in root and leaf tissues. Mass spectrometry analysis of DNA pull-down-enriched proteins in P. euphratica revealed that PeGLABRA3, a basic helix–loop–helix transcription factor, was the target transcription factor for binding the promoter region of PePLDδ. The PeGLABRA3 binding to PePLDδ-pro was further verified by virus-induced gene silencing, luciferase reporter assay (LRA), yeast one-hybrid assay, and electrophoretic mobility shift assay (EMSA). In addition, the PeGLABRA3 gene was cloned and overexpressed in Arabidopsis to determine the function of PeGLABRA3 in salt tolerance. PeGLABRA3-overexpressed Arabidopsis lines (OE1 and OE2) had a greater capacity to scavenge reactive oxygen species (ROS) and to extrude Na+ under salinity stress. Furthermore, the EMSA and LRA results confirmed that PeGLABRA3 interacted with the promoter of AtPLDδ in transgenic plants. The upregulated AtPLDδ in PeGLABRA3-transgenic lines resulted in an increase in phosphatidic acid species under no-salt and saline conditions. We conclude that PeGLABRA3 activated AtPLDδ transcription under salt stress by binding to the AtPLDδ promoter region, conferring Na+ and ROS homeostasis control via signaling pathways mediated by PLDδ and phosphatidic acid.
Mitochondrial Dysfunction in the Cardio-Renal Axis
Authors: Mendez-Barbero Nerea , Oller Jorge , Sanz Ana , Ramos Adrian , Ortiz Alberto , Ruiz-Ortega Marta , Rayego-Mateos Sandra
Published: May 2023

Cardiovascular disease (CVD) frequently complicates chronic kidney disease (CKD). The risk of all-cause mortality increases from 20% to 500% in patients who suffer both conditions; this is referred to as the so-called cardio-renal syndrome (CRS). Preclinical studies have described the key role of mitochondrial dysfunction in cardiovascular and renal diseases, suggesting that maintaining mitochondrial homeostasis is a promising therapeutic strategy for CRS. In this review, we explore the malfunction of mitochondrial homeostasis (mitochondrial biogenesis, dynamics, oxidative stress, and mitophagy) and how it contributes to the development and progression of the main vascular pathologies that could be affected by kidney injury and vice versa, and how this knowledge may guide the development of novel therapeutic strategies in CRS.
Red Ginseng Improves D-galactose-Induced Premature Ovarian Failure in Mice Based on Network Pharmacology
Authors: Shang Zijing , Fan Meiling , Zhang Jingtian , Wang Zi , Jiang Shuang , Li Wei
Published: May 2023

In this study, we evaluated the ameliorative effect and molecular mechanism of red ginseng (Panax ginseng C.A. Meyer) extract (RGE) on D-galactose (D-gal)-induced premature ovarian failure (POF) using network pharmacology analysis. Ginsenosides are important active ingredients in ginseng, which also contains some sugar and amino acid derivatives. We aimed to determine the key proteins through which RGE regulates POF. In this work, we retrieved and screened for active ingredients in ginseng and the corresponding POF disease targets in multiple databases. A PPI network of genes was constructed in the STRING database and core targets were screened using topological analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were conducted in R software. Finally, molecular docking was conducted to validate the results. Female ICR mice were used to establish a POF mouse model for in vivo experiments. Serum levels of relevant estrogens were determined using ELISA and expression levels of relevant proteins in ovarian tissues were detected using immunofluorescence and western blot analysis. Network pharmacology analysis predicted that PI3K, Akt, Bax, Bcl-2, p16, and other proteins were highly correlated with POF and RGE. The results clearly showed that RGE could increase estradiol (E2) and lower follicle-stimulating hormone (FSH) levels in D-gal-fed mice. RGE restored the expression levels of related proteins by reducing Nrf2-mediated oxidative stress, PI3K/Akt-mediated apoptosis, and senescence signaling pathways. Overall, RGE has the potential to prevent and treat POF and is likely to be a promising natural protector of the ovaries.
Ion and Molecule Transport in Membrane Systems 3.0 and 4.0
Authors: Nikonenko Victor , Pismenskaya Natalia
Published: May 2023

This book is a collection of papers published in the 3rd and 4th Special Issues of the International Journal of Molecular Sciences under the standard title, “Ion and Molecule Transport in Membrane Systems” [...]
Silencing a Chitinase Gene, PstChia1, Reduces Virulence of Puccinia striiformis f. sp. tritici
Authors: Guo Jia , Mou Ying , Li Yuanxing , Yang Qing , Wang Xue , Lin Haocheng , Kang Zhensheng , Guo Jun
Published: May 2023

Chitin is the main component of fungal cell walls, which can be recognized by pattern recognition receptors (PRRs) as pathogen-associated molecular patterns (PAMP). Chitinase in filamentous fungi has been reported to degrade immunogenic chitin oligomers, thereby preventing chitin-induced immune activation. In this study, we identified the chitinase families in 10 fungal genomes. A total of 131 chitinase genes were identified. Among the chitinase families, 16 chitinase genes from Puccinia striiformis f. sp. tritici (Pst) were identified, and the expression of PstChia1 was the highest during Pst infection. Further studies indicated that PstChia1 is highly induced during the early stages of the interaction of wheat and Pst and has chitinase enzyme activity. The silencing of PstChia1 revealed that PstChia1 limited the growth and reduced the virulence of Pst. The expression level of TaPR1 and TaPR2 was induced in PstChia1 knockdown plants, suggesting that PstChia1 is involved in regulating wheat resistance to Pst. Our data suggest that PstChia1 contributes to pathogenicity by interfering with plant immunity and regulating the growth of Pst.
Thermodynamics of Ag(I) Complex Formations with 2-Mercaptoimidazole in Water−Dimethyl Sulfoxide Solvents
Authors: Bobosaidzoda Surayo , Sodatdinova Anjuman , Akimbekova Khazon , Alister Diana , Molchanov Evgeniy , Marfin Yuriy , Usacheva Tatyana , Safarmamadzoda Safarmamad
Published: May 2023

The stability of coordination compounds of metal ions with ligands is of fundamental importance for elaborating upon practical sensors for the detection and quantification of metal ions in environmental samples. In this work, the stability constants of silver(I) complexes with 2-mercaptoimidazole (2MI) in a mixed water–dimethyl sulfoxide (DMSO) solvent were determined at 298.15 K and 308.15 K. It was found that with increasing temperature, the stability of the complexes decreases. The dependence of lgβ1 on the water−DMSO solvent compositions has its minimum at a concentration of dimethyl sulfoxide of 0.1 mol. fr. To explain the effect of the solvent, the solvation characteristics of the reagents were analyzed. In this regard, the 2MI Gibbs energy of transfer from water to aqueous dimethyl sulfoxide solvents was determined, and the influence of the aqueous DMSO solvent on the thermodynamics of 2MI protonation was analyzed. The stabilization of the silver ion and 2MI during the transition from water to a water–DMSO solvent makes a negative contribution to the change in the Gibbs energy of complexation, while the solvation of a complex particle promotes the complex formation. As a result, the Gibbs energy transfer values are slightly increased. The results of these thermodynamic studies could be useful for the development of sensor materials based on mercaptoimidazoles.
Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases
Authors: Kinoshita-Ise Misaki , Fukuyama Masahiro , Ohyama Manabu
Published: May 2023

Hair-loss diseases comprise heterogenous conditions with respective pathophysiology and clinicopathological characteristics. Major breakthroughs in hair follicle biology and immunology have led to the elucidation of etiopathogenesis of non-scarring alopecia (e.g., alopecia areata, AA) and cicatricial alopecia (e.g., lichen planopilaris, LPP). High-throughput genetic analyses revealed molecular mechanism underlying the disease susceptibility of hair loss conditions, such as androgenetic alopecia (AGA) and female pattern hair loss (FPHL). Hair loss attracted public interest during the COVID-19 pandemic. The knowledge of hair loss diseases is robustly expanding and thus requires timely updates. In this review, the diagnostic and measurement methodologies applied to hair loss diseases are updated. Of note, novel criteria and classification/scoring systems published in the last decade are reviewed, highlighting their advantages over conventional ones. Emerging diagnostic techniques are itemized with clinical pearls enabling efficient utilization. Recent advances in understanding the etiopathogenesis and management for representative hair diseases, namely AGA, FPHL, AA, and major primary cicatricial alopecia, including LPP, are comprehensively summarized, focusing on causative factors, genetic predisposition, new disease entity, and novel therapeutic options. Lastly, the association between COVID-19 and hair loss is discussed to delineate telogen effluvium as the predominating pathomechanism accounting for this sequela.
Extended Preoperative Audiometry for Outcome Prediction and Risk Analysis in Patients Receiving Cochlear Implants
Authors: Rieck Jan-Henrik , Beyer Annika , Mewes Alexander , Caliebe Amke , Hey Matthias
Published: May 2023

Background: The outcome of cochlear implantation has improved over the last decades, but there are still patients with less benefit. Despite numerous studies examining the cochlear implant (CI) outcome, variations in speech comprehension with CI remains incompletely explained. The aim of this study was therefore to examine preoperative pure-tone audiogram and speech comprehension as well as aetiology, to investigate their relationship with postoperative speech comprehension in CI recipients. Methods: A retrospective study with 664 ears of 530 adult patients was conducted. Correlations between the target variable postoperative word comprehension with the preoperative speech and sound comprehension as well as aetiology were investigated. Significant correlations were inserted into multivariate models. Speech comprehension measured as word recognition score at 70 dB with CI was analyzed as (i) a continuous and (ii) a dichotomous variable. Results: All variables that tested preoperative hearing were significantly correlated with the dichotomous target; with the continuous target, all except word comprehension at 65 dB with hearing aid. The strongest correlation with postoperative speech comprehension was seen for monosyllabic words with hearing aid at 80 dB. The preoperative maximum word comprehension was reached or surpassed by 97.3% of CI patients. Meningitis and congenital diseases were strongly negatively associated with postoperative word comprehension. The multivariate model was able to explain 40% of postoperative variability. Conclusion: Speech comprehension with hearing aid at 80 dB can be used as a supplementary preoperative indicator of CI-aided speech comprehension and should be measured regularly in the clinical routine. Combining audiological and aetiological variables provides more insights into the variability of the CI outcome, allowing for better patient counselling.
Current Debates in the Management of Visceral Artery Aneurysms: Where the Guidelines Collide
Authors: Marone Enrico Maria , Rinaldi Luigi Federico
Published: May 2023

On one hand, the main difficulties in establishing a wide, evidence-based consensus about the best approach to visceral artery aneurysms (VAAs) and pseudoaneurysms (VAPAs) are the paucity of data, due to their rarity in the general population, and the extreme heterogeneity of this group of diseases, which encompasses different aneurysm types, with different degrees of rupture risks according to their anatomical locations [...]
Impact of Financial Inclusion on India’s Economic Development under the Moderating Effect of Internet Subscribers
Authors: Pushp Aman , Gautam Rahul Singh , Tripathi Vikas , Kanoujiya Jagjeevan , Rastogi Shailesh , Bhimavarapu Venkata Mrudula , Parashar Neha
Published: May 2023

Financial inclusion is an emerging economic growth paradigm, especially in developing economies like India. It is an essential barometer for the all-encompassing growth of a country and its economy. However, there is still a debate regarding the effect of Financial Inclusion (FI) on achieving sustainable development. This study aims to determine if FI helps achieve Sustainable Development Growth (SDG) in India and if internet subscribers significantly influence the connection between FI and SDG. Secondary data from 16 states and one UT in India have been collected for 2017–2019. Therefore, the sample data is recent and covers a large country span. The data source is NITI Aayog and PMFBY (“Pradhan Mantri Fasal Bhima Yojana”) reports. The findings of this research are that FI has a positively significant relationship with sustainable development goals (SDG) in India. However, when the internet subscribers are high, the FI’s positive association with SDG gets reduced. PMFBY and SDG have been used for the first time, along with internet subscribers as moderators. The outcome has direct policy implications for improving the nation’s financial inclusion and economic growth.
Ecological Security Assessment and Warning of Cultivated Land Quality in the Black Soil Region of Northeast China
Authors: Liu Ziwei , Wang Mingchang , Liu Xingnan , Wang Fengyan , Li Xiaoyan , Wang Jianguo , Hou Guanglei , Zhao Shijun
Published: May 2023

The ecological security of cultivated land critically depends on maintaining the quality of the land under cultivation. For the security of the nation’s grain supply, the evaluation and early warning of cultivated land quality (CLQ) are essential. However, previous studies on the assessment of the ecological safety of CLQ only rigidly standardized the assessment indicators and failed to investigate the positive and negative trends and spatiotemporal driving factors of the indicators. The main objective of this study was to develop a drive–pressure–state–response (DPSR) model to identify the hierarchical structure of indicators, using an improved matter–element model to assess the CLQ in the black soil region of northeastern China from 2001 to 2020. A panel data model was employed to explore the crucial drivers of CLQ warnings. The findings reveal that socioeconomic development has a potential impact on the improvement of CLQ. CLQ is generally in a secure state, with 69.71% of cities with no warnings and only 3.46% and 0.13% of cities under serious and extreme warnings, respectively. Compared with 2001, the CLQ in 2020 effectively improved by socioeconomic development and the conservation and reasonable utilization of arable land. According to the early warning results, the cultivated land in the northern regions was of higher quality than that in the southern regions. Moreover, the CLQ was significantly positively correlated with the agricultural GDP growth rate, grain yield per unit of cultivated land area, annual precipitation, and the habitat quality index, and was significantly negatively correlated with land carrying capacity. The findings of this study can provide a scientific and targeted basis for black soil conservation and utilization.
Experimental Study on the Mechanical Properties and Microstructures of Cenosphere Concrete
Authors: Arunachalam Krishna Prakash , Avudaiappan Siva , Flores Erick I. Saavedra , Parra Pablo Fernando
Published: May 2023

The most valuable components of coal fly ash are cenospheres. Cenospheres are hollow spherical particles produced during the coal-burning processes. As a result of their excellent characteristics, such as high workability, high heat resistance, low bulk density, and high strength, cenospheres can be used in the manufacturing of lightweight cement concrete. The research efforts and outcomes are to produce long-lasting cement-based lightweight concrete (LWC) composites with good mechanical properties. The novelty of this investigation is to determine the cement concrete strength when silica fume (SF) and cenospheres (CS) were used as a replacement for cement. Throughout the experiments, a consistent substitution of 12% silica fume was incorporated into cement mass. Silica is used as a micro filler and pozzolanic reactant to strengthen concrete. The concrete mixtures were tested to ensure they met the requirements of the lightweight concrete in terms of their mechanical, physical, and durability qualities. According to the findings, lightweight concrete standards were met, and environmental sustainability was improved with the use of these mix proportions. Concrete specimen’s self-weight decreases by 35% with 30% cenosphere as a replacement. The micrograph shows the lack of portlandite is filled by mullite and other alumino silicates from the cenosphere. In order to achieve sustainability in concrete manufacturing, these mixtures can be suggested for the making of structural LWC that makes use of a large volume of industrial waste while conserving cement and natural resources.
Logarithmic Coefficients Inequality for the Family of Functions Convex in One Direction
Authors: Analouei Adegani Ebrahim , Motamednezhad Ahmad , Jafari Mostafa , Bulboacă Teodor
Published: May 2023

The logarithmic coefficients play an important role for different estimates in the theory of univalent functions. Due to the significance of the recent studies about the logarithmic coefficients, the problem of obtaining the sharp bounds for the modulus of these coefficients has received attention. In this research, we obtain sharp bounds of the inequality involving the logarithmic coefficients for the functions of the well-known class G and investigate a majorization problem for the functions belonging to this family. To prove our main results, we use the Briot–Bouquet differential subordination obtained by J.A. Antonino and S.S. Miller and the result of T.J. Suffridge connected to the Alexander integral. Combining these results, we give sharp inequalities for two types of sums involving the modules of the logarithmical coefficients of the functions of the class G indicating also the extremal function. In addition, we prove an inequality for the modulus of the derivative of two majorized functions of the class G, followed by an application.
Investigating the Relationship between Processor and Memory Reliability in Data Science: A Bivariate Model Approach
Authors: Haj Ahmad Hanan , Almetwally Ehab M. , Ramadan Dina A.
Published: May 2023

Modeling the failure times of processors and memories in computers is crucial for ensuring the reliability and robustness of data science workflows. By understanding the failure characteristics of the hardware components, data scientists can develop strategies to mitigate the impact of failures on their computations, and design systems that are more fault-tolerant and resilient. In particular, failure time modeling allows data scientists to predict the likelihood and frequency of hardware failures, which can help inform decisions about system design and resource allocation. In this paper, we aimed to model the failure times of processors and memories of computers; this was performed by formulating a new type of bivariate model using the copula function. The modified extended exponential distribution is the suggested lifetime of the experimental units. It was shown that the new bivariate model has many important properties, which are presented in this work. The inferential statistics for the distribution parameters were obtained under the assumption of a Type-II censored sampling scheme. Therefore, point and interval estimation were observed using the maximum likelihood and the Bayesian estimation methods. Additionally, bootstrap confidence intervals were calculated. Numerical analysis via the Markov Chain Monte Carlo method was performed. Finally, a real data example of processors and memories failure time was examined and the efficiency of the new bivariate distribution of fitting the data sample was observed by comparing it with other bivariate models.
Dynamics in the Reduced Mean-Field Model of Neuron–Glial Interaction
Authors: Olenin Sergey M. , Levanova Tatiana A. , Stasenko Sergey V.
Published: May 2023

The goal of this study is to propose a new reduced phenomenological model that describes the mean-field dynamics arising from neuron–glial interaction, taking into account short-term synaptic plasticity and recurrent connections in the presence of astrocytic modulation of the synaptic connection. Using computer simulation and numerical methods of nonlinear dynamics, it is shown that the proposed model reproduces a rich set of patterns of population activity, including spiking, bursting and chaotic temporal patterns. These patterns can coexist for specific regions in the parameter space of the model. The main focus of this study was on bifurcation mechanisms that lead to the occurrence of the described types of mean-field dynamics. The proposed phenomenological model can be used to reproduce various patterns of population activity of neurons in a wide range of studies of dynamic memory and information processing. One of the possible applications of such research is the development of new effective methods for the treatment of neurological diseases associated with neuron–glial interactions.
Generalized Equilibrium Problems
Authors: Balaj Mircea , Serac Dan Florin
Published: May 2023

If X is a convex subset of a topological vector space and f is a real bifunction defined on X×X, the problem of finding a point x0∈X such that f(x0,y)≥0 for all y∈X, is called an equilibrium problem. When the bifunction f is defined on the cartesian product of two distinct sets X and Y we will call it a generalized equilibrium problem. In this paper, we study the existence of the solutions, first for generalized equilibrium problems and then for equilibrium problems. In the obtained results, apart from the bifunction f, another bifunction is introduced, the two being linked by a certain compatibility condition. The particularity of the equilibrium theorems established in the last section consists of the fact that the classical equilibrium condition (f(x,x)=0, for all x∈X) is missing. The given applications refer to the Minty variational inequality problem and quasi-equilibrium problems.
Determining the Coefficients of the Thermoelastic System from Boundary Information
Authors: Tan Xiaoming
Published: May 2023

Given a compact Riemannian manifold (M,g) with smooth boundary ∂M, we give an explicit expression for the full symbol of the thermoelastic Dirichlet-to-Neumann map Λg with variable coefficients λ,μ,α,β∈C∞(M¯). We prove that Λg uniquely determines partial derivatives of all orders of these coefficients on the boundary ∂M. Moreover, for a nonempty smooth open subset Γ⊂∂M, suppose that the manifold and these coefficients are real analytic up to Γ. We show that Λg uniquely determines these coefficients on the whole manifold M¯.
The Use of Computational Fluid Dynamics for Assessing Flow-Induced Acoustics to Diagnose Lung Conditions
Authors: Makhanya Khanyisani , Connell Simon , Bhamjee Muaaz , Martinson Neil
Published: May 2023

Pulmonary diseases are a leading cause of illness and disability globally. While having access to hospitals or specialist clinics for investigations is currently the usual way to characterize the patient’s condition, access to medical services is restricted in less resourced settings. We posit that pulmonary disease may impact on vocalization which could aid in characterizing a pulmonary condition. We therefore propose a new method to diagnose pulmonary disease analyzing the vocal and cough changes of a patient. Computational fluid dynamics holds immense potential for assessing the flow-induced acoustics in the lungs. The aim of this study is to investigate the potential of flow-induced vocal-, cough-, and lung-generated acoustics to diagnose lung conditions using computational fluid dynamics methods. In this study, pneumonia is the model disease which is studied. The hypothesis is that using a computational fluid dynamics model for assessing the flow-induced acoustics will accurately represent the flow-induced acoustics for healthy and infected lungs and that possible modeled difference in fluid and acoustic behavior between these pathologies will be tested and described. Computational fluid dynamics and a lung geometry will be used to simulate the flow distribution and obtain the acoustics for the different scenarios. The results suggest that it is possible to determine the difference in vocalization between healthy lungs and those with pneumonia, using computational fluid dynamics, as the flow patterns and acoustics differ. Our results suggest there is potential for computational fluid dynamics to enhance understanding of flow-induced acoustics that could be characteristic of different lung pathologies. Such simulations could be repeated using machine learning with the final objective to use telemedicine to triage or diagnose patients with respiratory illness remotely.