bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline
Authors: Nguyen Vi , Taine Elaine G. , Meng Dehao , Cui Taixing , Tan Wenbin
Published: March 2024

Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-β peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.
Indole-3-Propionic Acid, a Gut Microbiota-Derived Tryptophan Metabolite, Promotes Endothelial Dysfunction Impairing Purinergic-Induced Nitric Oxide Release in Endothelial Cells
Authors: Geddo Federica , Antoniotti Susanna , Gallo Maria Pia , Querio Giulia
Published: March 2024

Different gut microbiota-derived metabolites influence cardiovascular function, and, among all, the role of indole-3-propionic acid (IPA), from tryptophan metabolism, shows controversial effects. The aim of this study was to evaluate its role in endothelial dysfunction. IPA effects were studied on bovine aortic endothelial cells (BAE-1). First, IPA cytotoxicity was evaluated by an MTS assay. Then, the levels of intracellular reactive oxygen species (ROS) were evaluated by a microplate reader or fluorescence microscopy with the CellROX® Green probe, and nitric oxide (NO) production was studied by fluorescence microscopy with the DAR4M-AM probe after acute or chronic treatment. Finally, immunoblotting analysis for endothelial nitric oxide synthase (eNOS) phosphorylation (p-eNOS) was performed. In BAE-1, IPA was not cytotoxic, except for the highest concentration (5 mM) after 48 h of treatment, and it showed neither oxidant nor antioxidant activity. However, the physiological concentration of IPA (1 μM) significantly reduced NO released by adenosine triphosphate (ATP)-stimulated BAE-1. These last data were confirmed by Western blot analysis, where IPA induced a significant reduction in p-eNOS in purinergic-stimulated BAE-1. Given these data, we can speculate that IPA negatively affects the physiological control of vascular tone by impairing the endothelial NO release induced by purinergic stimulation. These results represent a starting point for understanding the mechanisms underlying the relationship between gut microbiota metabolites and cardiometabolic health.
A Precision Therapy Approach for Retinitis Pigmentosa 11 Using Splice-Switching Antisense Oligonucleotides to Restore the Open Reading Frame of PRPF31
Authors: Grainok Janya , Pitout Ianthe L. , Chen Fred K. , McLenachan Samuel , Heath Jeffery Rachael C. , Mitrpant Chalermchai , Fletcher Sue
Published: March 2024

Retinitis pigmentosa 11 is an untreatable, dominantly inherited retinal disease caused by heterozygous mutations in pre-mRNA processing factor 31 PRPF31. The expression level of PRPF31 is linked to incomplete penetrance in affected families; mutation carriers with higher PRPF31 expression can remain asymptomatic. The current study explores an antisense oligonucleotide exon skipping strategy to treat RP11 caused by truncating mutations within PRPF31 exon 12 since it does not appear to encode any domains essential for PRPF31 protein function. Cells derived from a patient carrying a PRPF31 1205C>A nonsense mutation were investigated; PRPF31 transcripts encoded by the 1205C>A allele were undetectable due to nonsense-mediated mRNA decay, resulting in a 46% reduction in PRPF31 mRNA, relative to healthy donor cells. Antisense oligonucleotide-induced skipping of exon 12 rescued the open reading frame with consequent 1.7-fold PRPF31 mRNA upregulation in the RP11 patient fibroblasts. The level of PRPF31 upregulation met the predicted therapeutic threshold of expression inferred in a non-penetrant carrier family member harbouring the same mutation. This study demonstrated increased PRPF31 expression and retention of the nuclear translocation capability for the induced PRPF31 isoform. Future studies should evaluate the function of the induced PRPF31 protein on pre-mRNA splicing in retinal cells to validate the therapeutic approach for amenable RP11-causing mutations.
Toward a Mechanism-Driven Integrated Framework to Link Human Exposure to Multiple Toxic Metal(loid) Species with Environmental Diseases
Authors: Gailer Jürgen
Published: March 2024

The ongoing anthropogenic pollution of the biosphere with As, Cd, Hg and Pb will inevitably result in an increased influx of their corresponding toxic metal(loid) species into the bloodstream of human populations, including children and pregnant women. To delineate whether the measurable concentrations of these inorganic pollutants in the bloodstream are tolerable or implicated in the onset of environmental diseases urgently requires new insight into their dynamic bioinorganic chemistry in the bloodstream–organ system. Owing to the human exposure to multiple toxic metal(loid) species, the mechanism of chronic toxicity of each of these needs to be integrated into a framework to better define the underlying exposure–disease relationship. Accordingly, this review highlights some recent advances into the bioinorganic chemistry of the Cd2+, Hg2+ and CH3Hg+ in blood plasma, red blood cells and target organs and provides a first glimpse of their emerging mechanisms of chronic toxicity. Although many important knowledge gaps remain, it is essential to design experiments with the intent of refining these mechanisms to eventually establish a framework that may allow us to causally link the cumulative exposure of human populations to multiple toxic metal(loid) species with environmental diseases of unknown etiology that do not appear to have a genetic origin. Thus, researchers from a variety of scientific disciplines need to contribute to this interdisciplinary effort to rationally address this public health threat which may require the implementation of stronger regulatory requirements to improve planetary and human health, which are fundamentally intertwined.
Histamine H1 Receptor-Mediated JNK Phosphorylation Is Regulated by Gq Protein-Dependent but Arrestin-Independent Pathways
Authors: Michinaga Shotaro , Nagata Ayaka , Ogami Ryosuke , Ogawa Yasuhiro , Hishinuma Shigeru
Published: March 2024

Arrestins are known to be involved not only in the desensitization and internalization of G protein-coupled receptors but also in the G protein-independent activation of mitogen-activated protein (MAP) kinases, such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), to regulate cell proliferation and inflammation. Our previous study revealed that the histamine H1 receptor-mediated activation of ERK is dually regulated by Gq proteins and arrestins. In this study, we investigated the roles of Gq proteins and arrestins in the H1 receptor-mediated activation of JNK in Chinese hamster ovary (CHO) cells expressing wild-type (WT) human H1 receptors, the Gq protein-biased mutant S487TR, and the arrestin-biased mutant S487A. In these mutants, the Ser487 residue in the C-terminus region of the WT was truncated (S487TR) or mutated to alanine (S487A). Histamine significantly stimulated JNK phosphorylation in CHO cells expressing WT and S487TR but not S487A. Histamine-induced JNK phosphorylation in CHO cells expressing WT and S487TR was suppressed by inhibitors against H1 receptors (ketotifen and diphenhydramine), Gq proteins (YM-254890), and protein kinase C (PKC) (GF109203X) as well as an intracellular Ca2+ chelator (BAPTA-AM) but not by inhibitors against G protein-coupled receptor kinases (GRK2/3) (cmpd101), β-arrestin2 (β-arrestin2 siRNA), and clathrin (hypertonic sucrose). These results suggest that the H1 receptor-mediated phosphorylation of JNK is regulated by Gq-protein/Ca2+/PKC-dependent but GRK/arrestin/clathrin-independent pathways.
Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry
Authors: Hur Young-Min , Kwon Eun-Jin , You Young-Ah , Park Sunwha , Kim Soo-Min , Lee Gain , Go Yoon-Young , Kim Young-Ju
Published: March 2024

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.
Mapping of Prion Structures in the Yeast Rnq1
Authors: Galliamov Arthur A. , Malukhina Alena D. , Kushnirov Vitaly V.
Published: March 2024

The Rnq1 protein is one of the best-studied yeast prions. It has a large potentially prionogenic C-terminal region of about 250 residues. However, a previous study indicated that only 40 C-terminal residues form a prion structure. Here, we mapped the actual and potential prion structures formed by Rnq1 and its variants truncated from the C-terminus in two [RNQ+] strains using partial proteinase K digestion. The location of these structures differed in most cases from previous predictions by several computer algorithms. Some aggregation patterns observed microscopically for the Rnq1 hybrid proteins differed significantly from those previously observed for Sup35 prion aggregates. The transfer of a prion from the full-sized Rnq1 to its truncated versions caused substantial alteration of prion structures. In contrast to the Sup35 and Swi1, the terminal prionogenic region of 72 residues was not able to efficiently co-aggregate with the full-sized Rnq1 prion. GFP fusion to the Rnq1 C-terminus blocked formation of the prion structure at the Rnq1 C-terminus. Thus, the Rnq1-GFP fusion mostly used in previous studies cannot be considered a faithful tool for studying Rnq1 prion properties.
Chaperones—A New Class of Potential Therapeutic Targets in Alzheimer’s Disease
Authors: Batko Joanna , Antosz Katarzyna , Miśków Weronika , Pszczołowska Magdalena , Walczak Kamil , Leszek Jerzy
Published: March 2024

The review describes correlations between impaired functioning of chaperones and co-chaperones in Alzheimer’s disease (AD) pathogenesis. The study aims to highlight significant lines of research in this field. Chaperones like Hsp90 or Hsp70 are critical agents in regulating cell homeostasis. Due to some conditions, like aging, their activity is damaged, resulting in β-amyloid and tau aggregation. This leads to the development of neurocognitive impairment. Dysregulation of co-chaperones is one of the causes of this condition. Disorders in the functioning of molecules like PP5, Cdc37, CacyBP/SIPTRAP1, CHIP protein, FKBP52, or STIP1 play a key role in AD pathogenesis. PP5, Cdc37, CacyBP/SIPTRAP1, and FKBP52 are Hsp90 co-chaperones. CHIP protein is a co-chaperone that switches Hsp70/Hsp90 complexes, and STIP1 binds to Hsp70. Recognition of precise processes allows for the invention of effective treatment methods. Potential drugs may either reduce tau levels or inhibit tau accumulation and aggregation. Some substances neuroprotect from Aβ toxicity. Further studies on chaperones and co-chaperones are required to understand the fundamental tenets of this topic more entirely and improve the prevention and treatment of AD.
Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model
Authors: Houtak Ghais , Nepal Roshan , Bouras George , Shaghayegh Gohar , Bennett Catherine , Finnie John , Fenix Kevin , Psaltis Alkis James , Wormald Peter-John , Vreugde Sarah
Published: March 2024

Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 μL (200 μg/μL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.
A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-RNAs in Pancreatic Cancer: A Forward-Looking Plan for Diagnosis and Treatment
Authors: Trifylli Eleni Myrto , Kriebardis Anastasios G. , Koustas Evangelos , Papadopoulos Nikolaos , Fortis Sotirios P. , Tzounakas Vassilis L. , Anastasiadi Alkmini T. , Sarantis Panagiotis , Vasileiadi Sofia , Tsagarakis Ariadne , Aloizos Georgios , Manolakopoulos Spilios , Deutsch Melanie
Published: March 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide, while it persists as the fourth most prevalent cause of cancer-related death in the United States of America. Although there are several novel therapeutic strategies for the approach of this intensely aggressive tumor, it remains a clinical challenge, as it is hard to identify in early stages, due to its asymptomatic course. A diagnosis is usually established when the disease is already in its late stages, while its chemoresistance constitutes an obstacle to the optimal management of this malignancy. The discovery of novel diagnostic and therapeutic tools is considered a necessity for this tumor, due to its low survival rates and treatment failures. One of the most extensively investigated potential diagnostic and therapeutic modalities is extracellular vesicles (EVs). These vesicles constitute nanosized double-lipid membraned particles that are characterized by a high heterogeneity that emerges from their distinct biogenesis route, their multi-variable sizes, and the particular cargoes that are embedded into these particles. Their pivotal role in cell-to-cell communication via their cargo and their implication in the pathophysiology of several diseases, including pancreatic cancer, opens new horizons in the management of this malignancy. Meanwhile, the interplay between pancreatic carcinogenesis and short non-coding RNA molecules (micro-RNAs or miRs) is in the spotlight of current studies, as they can have either a role as tumor suppressors or promoters. The deregulation of both of the aforementioned molecules leads to several aberrations in the function of pancreatic cells, leading to carcinogenesis. In this review, we will explore the role of extracellular vesicles and miRNAs in pancreatic cancer, as well as their potent utilization as diagnostic and therapeutic tools.
Chicoric Acid Ameliorated Beta-Amyloid Pathology and Enhanced Expression of Synaptic-Function-Related Markers via L1CAM in Alzheimer’s Disease Models
Authors: Wang Ruonan , Kang Shijia , Zhao Zirui , Jin Lingling , Cui Xiaolin , Chen Lili , Schachner Melitta , Li Sheng , Guo Yanjie , Zhao Jie
Published: March 2024

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease. The accumulation of amyloid-beta (Aβ) plaques is a distinctive pathological feature of AD patients. The aims of this study were to evaluate the therapeutic effect of chicoric acid (CA) on AD models and to explore its underlying mechanisms. APPswe/Ind SH-SY5Y cells and 5xFAD mice were treated with CA. Soluble Aβ1–42 and Aβ plaque levels were analyzed by ELISA and immunohistochemistry, respectively. Transcriptome sequencing was used to compare the changes in hippocampal gene expression profiles among the 5xFAD mouse groups. The specific gene expression levels were quantified by qRT-PCR and Western blot analysis. It was found that CA treatment reduced the Aβ1–42 levels in the APPswe/Ind cells and 5xFAD mice. It also reduced the Aβ plaque levels as well as the APP and BACE1 levels. Transcriptome analysis showed that CA affected the synaptic-plasticity-related genes in the 5xFAD mice. The levels of L1CAM, PSD-95 and synaptophysin were increased in the APPswe/Ind SH-SY5Y cells and 5xFAD mice treated with CA, which could be inhibited by administering siRNA-L1CAM to the CA-treated APPswe/Ind SH-SY5Y cells. In summary, CA reduced Aβ levels and increased the expression levels of synaptic-function-related markers via L1CAM in AD models.
Hsp70 and Calcitonin Receptor Protein in Extracellular Vesicles from Glioblastoma Multiforme: Biomarkers with Putative Roles in Carcinogenesis and Potential for Differentiating Tumor Types
Authors: Alberti Giusi , Sánchez-López Christian M. , Marcilla Antonio , Barone Rosario , Caruso Bavisotto Celeste , Graziano Francesca , Conway de Macario Everly , Macario Alberto J. L. , Bucchieri Fabio , Cappello Francesco , Campanella Claudia , Rappa Francesca
Published: March 2024

Glioblastoma multiforme (GBM) is a malignancy of bad prognosis, and advances in early detection and treatment are needed. GBM is heterogenous, with varieties differing in malignancy within a tumor of a patient and between patients. Means are needed to distinguish these GMB forms, so that specific strategies can be deployed for patient management. We study the participation of the chaperone system (CS) in carcinogenesis. The CS is dynamic, with its members moving around the body in extracellular vesicles (EVs) and interacting with components of other physiological systems in health and disease, including GBM. Here, we describe the finding of high amounts of Hsp70 (HSPA1A) and the calcitonin receptor protein (CTR) in EVs in patients with GBM. We present a standardized protocol for collecting, purifying, and characterizing EVs carrying Hsp70 and CTR in plasma-derived EVs from patients with GBM. EVs from GBM patients were obtained just before tumor ablative surgery (T0) and 7 days afterwards (T1); Hsp70 was highly elevated at T0 and less so at T1, and CTR was greatly increased at T0 and reduced to below normal values at T1. Our results encourage further research to assess Hsp70 and CTR as biomarkers for differentiating tumor forms and to determine their roles in GBM carcinogenesis.
Autumn Olive (Elaeagnus umbellata Thunb.) Berries Improve Lipid Metabolism and Delay Aging in Middle-Aged Caenorhabditis elegans
Authors: Kim Yebin , Nam Seonghyeon , Lim Jongbin , Jang Miran
Published: March 2024

This study evaluated the positive effects of autumn olive berries (AOBs) extract on delaying aging by improving lipid metabolism in middle-aged Caenorhabditis elegans that had become obese due to a high-glucose (GLU) diet. The total phenolic content and DPPH radical scavenging abilities of freeze-dried AOBs (FAOBs) or spray-dried AOBs (SAOBs) were examined, and FAOBs exhibited better antioxidant activity. HPLC analysis confirmed that catechin is the main phenolic compound of AOBs; its content was 5.95 times higher in FAOBs than in SAOBs. Therefore, FAOBs were used in subsequent in vivo experiments. FAOBs inhibited lipid accumulation in both the young adult and middle-aged groups in a concentration-dependent manner under both normal and 2% GLU conditions. Additionally, FAOBs inhibited ROS accumulation in a concentration-dependent manner under normal and 2% GLU conditions in the middle-aged worms. In particular, FAOB also increased body bending and egg production in middle-aged worms. To confirm the intervention of genetic factors related to lipid metabolism from the effects of FAOB, body lipid accumulation was confirmed using worms deficient in the daf-16, atgl-1, aak-1, and akt-1 genes. Regarding the effect of FAOB on reducing lipid accumulation, the impact was nullified in daf-16-deficient worms under the 2% GLU condition, and nullified in both the daf-16- and atgl-1-deficient worms under fasting conditions. In conclusion, FAOB mediated daf-16 and atgl-1 to regulate lipogenesis and lipolysis in middle-aged worms. Our findings suggest that FAOB improves lipid metabolism in metabolically impaired middle-aged worms, contributing to its age-delaying effect.
Landscape of FLT3 Variations Associated with Structural and Functional Impact on Acute Myeloid Leukemia: A Computational Study
Authors: Mirza Zeenat , Al-Saedi Dalal A. , Alganmi Nofe , Karim Sajjad
Published: March 2024

Acute myeloid leukemia (AML) is hallmarked by the clonal proliferation of myeloid blasts. Mutations that result in the constitutive activation of the fms-like tyrosine kinase 3 (FLT3) gene, coding for a class III receptor tyrosine kinase, are significantly associated with this heterogeneous hematologic malignancy. The fms-related tyrosine kinase 3 ligand binds to the extracellular domain of the FLT3 receptor, inducing homodimer formation in the plasma membrane, leading to autophosphorylation and activation of apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. In the present study, we evaluated the association of FLT3 as a significant biomarker for AML and tried to comprehend the effects of specific variations on the FLT3 protein’s structure and function. We also examined the effects of I836 variants on binding affinity to sorafenib using molecular docking. We integrated multiple bioinformatics tools, databases, and resources such as OncoDB, UniProt, COSMIC, UALCAN, PyMOL, ProSA, Missense3D, InterProScan, SIFT, PolyPhen, and PredictSNP to annotate the structural, functional, and phenotypic impact of the known variations associated with FLT3. Twenty-nine FLT3 variants were analyzed using in silico approaches such as DynaMut, CUPSAT, AutoDock, and Discovery Studio for their impact on protein stability, flexibility, function, and binding affinity. The OncoDB and UALCAN portals confirmed the association of FLT3 gene expression and its mutational status with AML. A computational structural analysis of the deleterious variants of FLT3 revealed I863F mutants as destabilizers of the protein structure, possibly leading to functional changes. Many single-nucleotide variations in FLT3 have an impact on its structure and function. Thus, the annotation of FLT3 SNVs and the prediction of their deleterious pathogenic impact will facilitate an insight into the tumorigenesis process and guide experimental studies and clinical implications.
MaSMG7-Mediated Degradation of MaERF12 Facilitates Fusarium oxysporum f. sp. cubense Tropical Race 4 Infection in Musa acuminata
Authors: Huang Huoqing , Liu Siwen , Huo Yile , Tian Yuzhen , Liu Yushan , Yi Ganjun , Li Chunyu
Published: March 2024

Modern plant breeding relies heavily on the deployment of susceptibility and resistance genes to defend crops against diseases. The expression of these genes is usually regulated by transcription factors including members of the AP2/ERF family. While these factors are a vital component of the plant immune response, little is known of their specific roles in defense against Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) in banana plants. In this study, we discovered that MaERF12, a pathogen-induced ERF in bananas, acts as a resistance gene against Foc TR4. The yeast two-hybrid assays and protein-protein docking analyses verified the interaction between this gene and MaSMG7, which plays a role in nonsense-mediated RNA decay. The transient expression of MaERF12 in Nicotiana benthamiana was found to induce strong cell death, which could be inhibited by MaSMG7 during co-expression. Furthermore, the immunoblot analyses have revealed the potential degradation of MaERF12 by MaSMG7 through the 26S proteasome pathway. These findings demonstrate that MaSMG7 acts as a susceptibility factor and interferes with MaERF12 to facilitate Foc TR4 infection in banana plants. Our study provides novel insights into the biological functions of the MaERF12 as a resistance gene and MaSMG7 as a susceptibility gene in banana plants. Furthermore, the first discovery of interactions between MaERF12 and MaSMG7 could facilitate future research on disease resistance or susceptibility genes for the genetic improvement of bananas.
Mitochondrial Dysfunction Causes Cell Death in Patients Affected by Fragile-X-Associated Disorders
Authors: Grandi Martina , Galber Chiara , Gatto Cristina , Nobile Veronica , Pucci Cecilia , Schaldemose Nielsen Ida , Boldrin Francesco , Neri Giovanni , Chiurazzi Pietro , Solaini Giancarlo , Baracca Alessandra , Giorgio Valentina , Tabolacci Elisabetta
Published: March 2024

Mitochondria are involved in multiple aspects of neurodevelopmental processes and play a major role in the pathogenetic mechanisms leading to neuro-degenerative diseases. Fragile-X-related disorders (FXDs) are genetic conditions that occur due to the dynamic expansion of CGG repeats of the FMR1 gene encoding for the RNA-binding protein FMRP, particularly expressed in the brain. This gene expansion can lead to premutation (PM, 56–200 CGGs), full mutation (FM, >200 CGGs), or unmethylated FM (UFM), resulting in neurodegeneration, neurodevelopmental disorders, or no apparent intellectual disability, respectively. To investigate the mitochondrial mechanisms that are involved in the FXD patients, we analyzed mitochondrial morphology and bioenergetics in fibroblasts derived from patients. Donut-shaped mitochondrial morphology and excessive synthesis of critical mitochondrial proteins were detected in FM, PM, and UFM cells. Analysis of mitochondrial oxidative phosphorylation in situ reveals lower respiration in PM fibroblasts. Importantly, mitochondrial permeability transition-dependent apoptosis is sensitized to reactive oxygen species in FM, PM, and UFM models. This study elucidated the mitochondrial mechanisms that are involved in the FXD phenotypes, and indicated altered mitochondrial function and morphology. Importantly, a sensitization to permeability transition and apoptosis was revealed in FXD cells. Overall, our data suggest that mitochondria are novel drug targets to relieve the FXD symptoms.
Transcriptome Sequencing Reveals the Mechanism of Auxin Regulation during Root Expansion in Carrot
Authors: Li Xuan , Yan Xuemin , Wu Zhe , Hou Leiping , Li Meilan
Published: March 2024

Carrot is an important vegetable with roots as the edible organ. A complex regulatory network controls root growth, in which auxin is one of the key players. To clarify the molecular mechanism on auxin regulating carrot root expansion, the growth process and the indole-3-acetic acid (IAA) content in the roots were measured in this experiment. It was found that the rapid expansion period of the root was from 34 to 41 days after sowing and the IAA content was the highest during this period. The root growth then slowed down and the IAA levels decreased. Using the transcriptome sequencing database, we analyzed the expression of IAA-metabolism-related genes and found that the expression of most of the IAA synthesis genes, catabolism genes, and genes related to signal transduction was consistent with the changes in IAA content during root expansion. Among them, a total of 31 differentially expressed genes (DEGs) were identified, including 10 IAA synthesis genes, 8 degradation genes, and 13 genes related to signal transduction. Analysis of the correlations between the DEGs and IAA levels showed that the following genes were closely related to root development: three synthesis genes, YUCCA10 (DCAR_012429), TAR2 (DCAR_026162), and AMI1 (DCAR_003244); two degradation genes, LPD1 (DCAR_023341) and AACT1 (DCAR_010070); and five genes related to signal transduction, IAA22 (DCAR_012516), IAA13 (DCAR_012591), IAA27 (DCAR_023070), IAA14 (DCAR_027269), and IAA7 (DCAR_030713). These results provide a reference for future studies on the mechanism of root expansion in carrots.
Mesenchymal Stromal Cells Derived from Canine Adipose Tissue: Evaluation of the Effect of Different Shipping Vehicles Used for Clinical Administration
Authors: Andreoli Valentina , Berni Priscilla , Conti Virna , Ramoni Roberto , Basini Giuseppina , Grolli Stefano
Published: March 2024

Mesenchymal Stromal Cells (MSCs)-based therapies are rapidly gaining interest in veterinary medicine. Cellular therapy represents a new challenge for practitioners and requires precise coordination between the cell processing laboratory and the veterinary clinic. Cryopreservation is the best method to provide fast, in-time, and long-distance delivery of cells for therapeutic applications. However, potentially toxic cryoprotectants and xenobiotic products make the direct administration of cells impracticable for patients. Alternatively, the cells may be resuspended in a ready-to-use vehicle and shipped to the veterinary clinic. In this study, two nutrient-poor vehicles (physiologic saline and ringer lactate solutions) and two nutrient-rich vehicles (the releasate derived from autologous Platelet Poor Plasma and Platelet Rich Plasma) were tested on adipose tissue-derived canine MSCs (AD-MSCs). AD-MSCs stored for 2, 4, or 24 h in the different media were compared regarding mortality, metabolic activity, and replicative capacity. Furthermore, antioxidant activity and the pattern of expression of genes related to AD-MSCs function were performed following 24 h of storage. The results showed that all the different vehicles preserve cell vitality and replication following short-term storage. In long-term storage, the vehicle and cell density affect cell vitality, proliferation, and gene expression (CCL-2, CXCR-4, and TSG-6). Nutrient-rich vehicles seem better suited to preserve cell functionalities in this contest.
Insect Diversity in Pinus sylvestris Forest Stands Damaged by Lymantria monacha
Authors: Čėsna Vytautas , Gedminas Artūras , Lynikienė Jūratė , Marčiulynienė Diana
Published: March 2024

Outbreaks of Lymantria monacha are of great concern, as their occurrence is predicted to become more intense and frequent due to a warming climate. A frequent treatment to control mass outbreaks of the pest is with the bioinsecticide Foray 76B. However, knowledge of how this treatment affects non-target insect species is limited. We surveyed the assemblages of non-target epigeal and arboreal insects in Pinus sylvestris forests in the year following bioinsecticide application. A collection of insects using sweep nets and pitfall traps was carried out in L. monacha-infested pine stands, (i) treated with Foray 76B and (ii) untreated, in three regions of Lithuania from May to October 2021. The results revealed that, in Neringa forests, species richness of the epigeal insects was lower in treated than in untreated sampling plots, with 36 and 41 different insect species, respectively. The relative abundance of epigeal Coleoptera in treated plots was 3.6%, while in untreated it was 53.2%. There was a significant decrease in the relative abundance of Carabus arcencis in Kapčiamiestis (by 7.4%) and Marcinkonys (by 16.7%). Treated plots were distinguished by lower relative abundance of arboreal Hymenoptera at all three study locations.
RETRACTED: De Vecchis et al. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice? J. Clin. Med. 2016, 5, 86
Authors: De Vecchis Renato , Cantatrione Claudio , Mazzei Damiana , Baldi Cesare
Published: March 2024

The Journal of Clinical Medicine retracts the article “Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice [...]
How Cognitive Ability Shapes Personality Differentiation in Real Job Candidates: Insights from a Large-Scale Study
Authors: Stamate Alina , Denis Pascale , Sauvé Geneviève
Published: March 2024

The differentiation of personality by the cognitive ability hypothesis proposes that individuals with higher cognitive ability have more variability in their personality structure than those with lower cognitive ability. A large sample of actual job candidates (n = 14,462) who participated in an online proctored test session, providing socio-demographic information and completing cognitive ability, personality, and language proficiency assessments, was used to test this hypothesis. The total sample was divided into three equal groups (low, average, high) using percentiles as the cutoff point to investigate the effects of cognitive ability. An ANCOVA demonstrated the significant effect of cognitive ability on personality traits, controlling for language proficiency. Principal component analyses showed that the personality structure differed between the cognitive ability groups, with the high-cognitive-ability group having an additional personality component. Similarly, analyses across job complexity levels indicated more personality components for high-job-complexity positions. The implications, limitations, and future directions of this study are discussed.
Unlocking the Potential of Artificial Intelligence in Fashion Design and E-Commerce Applications: The Case of Midjourney
Authors: Zhang Yanbo , Liu Chuanlan
Published: March 2024

The fashion industry has shown increasing interest in applying artificial intelligence (AI), yet there is a significant gap in exploring the potential of emerging diffusion-modeling-based AI image-generation systems for fashion design and commerce. Therefore, this study aims to assess the effectiveness of Midjourney, one such AI system, in both fashion design and related commerce applications. We employed the action research approach with the Functional, Expressive, and Aesthetic (FEA) Consumer Needs Model as the theoretical framework. Our research comprised three stages: refining an initial idea into well-defined textual design concepts, facilitating concept development, and validating the preceding observations and reflections by creating a new line of hemp-based products that were evaluated by targeted consumers through an online survey. Findings reveal that this AI tool can assist fashion designers in creating both visually expressive attire and ready-to-wear products, meeting defined design criteria and consumer needs. Midjourney shows promise in streamlining the fashion design process by enhancing ideation and optimizing design details. Potential e-commercial applications of such AI systems were proposed, benefiting physical and digital fashion businesses. It is noted that, to date, the major limitations of using Midjourney encompass its restriction to only facilitating early fashion design stages and necessitating substantial involvement from designers.
Emerging Multilingual Children’s School Language Socialization: A Three-Year Longitudinal Case Study of a Korean Middle School
Authors: Jang Jinsil
Published: March 2024

This qualitative case study reports the impact of schooling on migrant children’s language socialization, particularly focusing on the role of language ideologies and practices within Korean schools. Despite an increasing population of migrant multilingual children in Korean schools, the education system predominantly follows a monolingual orientation with Korean as the primary medium of instruction. The research aims to address this gap by investigating the influence of Korean teachers’ and emergent multilingual youths’ language ideologies on bi- and multilingual language education. Additionally, this study explores how emerging multilingual children comply with or exhibit ambivalence/resistance toward instructed practices. Data were collected over three years from a regional middle school in South Korea and inductively analyzed using constant comparative methods. The findings underscore the significance of creating a multilingual space in classrooms where teachers value diverse linguistic and other semiotic resources, fostering more active engagement and negotiation of meaning among multilingual students. In contrast, monolingual-oriented classrooms result in the students’ passive behavior and hinder socialization into the Korean school environment. This study advocates for a more inclusive learning environment that recognizes and embraces multilingual values, facilitating meaningful language practices among emerging multilingual youth.
Removal of Plastics from Micron Size to Nanoscale Using Wood Filter
Authors: Li Min , Liu Gonggang , Wang Chongqing , Chang Shanshan , Hu Jinbo
Published: March 2024

Plastic pollution, particularly microplastic (MP) and nanoplastic (NP) pollution, has become a significant concern. This study explores the use of porous wood for filtration to remove MPs and NPs and investigates their removal mechanisms. Undecorated fir wood with a thickness of 4 mm achieves a 91% removal rate for model polystyrene (PS) MPs (2.6 μm) at a water flux of 198 L/m2h. However, its separation performance for NPs (255.8 and 50.9 nm) is poor. It also shows that fir wood (coniferous wood) has a higher PS removal rate than poplar wood (hard wood). With poly dimethyl diallyl ammonium chloride (PDDA) modification, both MPs and NPs are effectively removed, with NPs’ removal rate increasing from <10% to 90% for PDDA/wood. Characterization results reveal that size-exclusive interception dominates for micron-sized particles, and electrostatic interaction is crucial for nanosized particles. Additionally, intercepted NPs have been used as a strong binder for hot-pressed wood to remarkably enhance the mechanical properties of wood, suggesting a novel recycle utilization of discarded wood filters. Overall, this renewable wood material offers a simple solution for tackling MP/NP pollution.
Evaluation of Adhesive Joints Using Ultrasonic Rayleigh Waves
Authors: Kowalczyk Jakub , Ulbrich Dariusz
Published: March 2024

Adhesive joints are non-separable connections that are used in numerous ways in vehicle construction, particularly in buses. The widespread use of adhesive joints makes it necessary to assess their quality, especially under production conditions. The main goal of this study was to develop a mathematical model to estimate the width of the adhesive path in a plywood-adhesive-closed-profile joint based on selected parameters of the ultrasonic surface wave. A digital ultrasonic flaw detector and Rayleigh wave probes were applied. The test involved evaluating different widths of hybrid adhesive and two-component epoxy adhesive. The tests were conducted on a steel profile from a bus construction. The attenuation of the ultrasonic waves on the steel profile (0.026 db/mm) and the adhesive (0.264 dB/mm) was determined. A one-size-fits-all model for estimating adhesive path width for specific conditions is proposed.
Effect of Mn/Ag Ratio on Microstructure and Mechanical Properties of Heat-Resistant Al-Cu Alloys
Authors: Fu Xiangzhou , Yang Hailong , Wang Hanzhang , Huang Chifu , Chen Yongbin , Huang Qiangang , Li Anmin , Pan Liwen
Published: March 2024

This paper mainly investigated the effect of the Mn/Ag ratio on the microstructure and room temperature and high-temperature (350 °C) tensile mechanical properties of the as-cast and heat-treated Al-6Cu-xMn-yAg (x + y = 0.8, wt.%) alloys. The as-cast alloy has α-Al, Al2Cu, and a small amount of Al7Cu2 (Fe, Mn) and Al20Cu2 (Mn, Fe)3 phases. After T6 heat treatment, a massive dispersive and fine θ′-Al2Cu phase (100~400 nm) is precipitated from the matrix. The Mn/Ag ratio influences the quantity and size of the precipitates; when the Mn/Ag ratio is 1:1, the θ′-Al2Cu precipitation quantity reaches the highest and smallest. Compared with the as-cast alloy, the tensile strength of the heat-treated alloy at room temperature and high temperature is greatly improved. The strengthening effect of the alloy is mainly attributed to the nanoparticles precipitated from the matrix. The Mn/Ag ratio also affects the high-temperature tensile mechanical properties of the alloy. The high-temperature tensile strength of the alloy with a 1:1 Mn/Ag ratio is the highest, reaching 135.89 MPa, 42.95% higher than that of the as-cast alloy. The analysis shows that a synergistic effect between Mn and Ag elements can promote the precipitation and refinement of the θ′-Al2Cu phase, and there is an optimal ratio (1:1) that obtains the lowest interfacial energy for co-segregation of Mn and Ag at the θ′/Al interface that makes θ′-Al2Cu have the best resistance to coarsening.
Simultaneous Pore Detection and Morphological Features Extraction in Laser Powder Bed Fusion with Image Processing
Authors: Li Jiaming , Zhang Xiaoxun , Ma Fang , Wang Shuxian , Huang Yuanyou
Published: March 2024

Internal pore defects are inevitable during laser powder bed fusion (LPBF), which have a significant impact on the mechanical properties of the parts. Therefore, detecting pores and obtaining their morphology will contribute to the quality of LPBF parts. Currently, supervised models are used for defect image detection, which requires a large amount of LPBF sample data, image labeling, and computing power equipment during the training process, resulting in high detection costs. This study extensively collected LPBF sample data and proposed a method for pore defect classification by obtaining its morphological features while detecting pore defects in optical microscopy (OM) images under various conditions. Compared with other advanced models, the proposed method achieves better detection accuracy on pore defect datasets with limited data. In addition, quickly detecting pore defects in a large number of labeling ground truth images will also contribute to the development of deep learning. In terms of image segmentation, the average accuracy scores of this method in the test images exceed 85%. The research results indicate that the algorithm proposed in this paper is suitable for quickly and accurately identifying pore defects from optical microscopy images.
Improved Thermal and Electrical Properties of P-I-N-Structured Perovskite Solar Cells Using ZnO-Added PCBM as Electron Transport Layer
Authors: Jeong Younghun , Han Dongwoon , Kim Seongtak , Mo Chan Bin
Published: March 2024

Not only can perovskite solar cells be exposed to high temperatures, up to 80 °C, depending on the operating environment, but absorbed energy is lost as heat, so it is important to have thermal stability for commercialization. However, in the case of the recently reported p-i-n structure solar cell, most of the electron and hole transport layers are composed of organic materials vulnerable to heat transfer, so the light absorption layer may be continuously exposed to high temperatures when the solar cell is operated. In this study, we attempted to improve the thermal conductivity of the electron transport layer using phenyl-C61-butyric acid methyl ester (PCBM) containing zinc oxide (ZnO). As a result, the thermal conductivity was improved by more than 7.4% and 23.5% by adding 6.57vol% and 22.38vol% of ZnO to PCBM, respectively. In addition, the insertion of ZnO resulted in changes in the electron transport behavior and energy level of the electron transport layer. As a result, it was confirmed that not only could the temperature stability of the perovskite thin film be improved, but the efficiency of the solar cell could also be improved from 14.12% to 17.97%.