bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-Dimensional Quantitative Structure–Activity Relationship Study of Transient Receptor Potential Vanilloid 1 Channel Antagonists Reveals Potential for Drug Design Purposes
Authors: Gianibbi Beatrice , Visibelli Anna , Spinsanti Giacomo , Spiga Ottavia
Published: July 2024

Transient receptor potential vanilloid 1 (TRPV1) was reported to be a putative target for recovery from chronic pain, producing analgesic effects after its inhibition. A series of drug candidates were previously developed, without the ability to ameliorate the therapeutic outcome. Starting from previously designed compounds, derived from the hybridization of antagonist SB-705498 and partial agonist MDR-652, we performed a virtual screening on a pharmacophore model built by exploiting the Cryo-EM 3D structure of a nanomolar antagonist in complex with the human TRPV1 channel. The pharmacophore model was described by three pharmacophoric features, taking advantage of both the bioactive pose of the antagonist and the receptor exclusion spheres. The results of the screening were implemented inside a 3D-QSAR model, correlating with the negative decadic logarithm of the inhibition rate of the ligands. After the validation of the obtained 3D-QSAR model, we designed a new series of compounds by introducing key modifications on the original scaffold. Again, we determined the compounds’ binding poses after alignment to the pharmacophoric model, and we predicted their inhibition rates with the validated 3D-QSAR model. The obtained values resulted in being even more promising than parent compounds, demonstrating that ongoing research still leaves much room for improvement.
Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment
Authors: Choi Eui-Hwan , Kim Mi-Hye , Park Sun-Ji
Published: July 2024

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common neurodegenerative diseases, and they affect millions of people worldwide, particularly older individuals. Therefore, there is a clear need to develop novel drug targets for the treatment of age-related neurodegenerative diseases. Emerging evidence suggests that mitochondrial dysfunction and reactive oxygen species (ROS) generation play central roles in the onset and progression of neurodegenerative diseases. Mitochondria are key regulators of respiratory function, cellular energy adenosine triphosphate production, and the maintenance of cellular redox homeostasis, which are essential for cell survival. Mitochondrial morphology and function are tightly regulated by maintaining a balance among mitochondrial fission, fusion, biogenesis, and mitophagy. In this review, we provide an overview of the main functions of mitochondria, with a focus on recent progress highlighting the critical role of ROS−induced oxidative stress, dysregulated mitochondrial dynamics, mitochondrial apoptosis, mitochondria-associated inflammation, and impaired mitochondrial function in the pathogenesis of age-related neurodegenerative diseases, such as AD and PD. We also discuss the potential of mitochondrial fusion and biogenesis enhancers, mitochondrial fission inhibitors, and mitochondria-targeted antioxidants as novel drugs for the treatment of these diseases.
Obesity and Obesity-Related Disorders—Editorial
Authors: Nowicka Grażyna
Published: July 2024

Obesity and obesity-related complications, including various metabolic diseases and cancers, are significant health problems in developed and developing countries [...]
The Biological Effect of Platelet-Rich Plasma on Rotator Cuff Tears: A Prospective Randomized In Vivo Study
Authors: Pitsilos Charalampos , Karachrysafi Sofia , Fragou Aikaterini , Gigis Ioannis , Papadopoulos Pericles , Chalidis Byron
Published: July 2024

The positive effect of platelet-rich plasma (PRP) on tendon metabolism has been extensively investigated and proven in vitro. Additionally, in vivo animal studies have correlated the application of PRP with the enhancement of tenocyte anabolic activity in the setting of tendon degeneration. However, less is known about its in vivo effect on human tendon biology. The purpose of the current prospective randomized comparative study was to evaluate the effect of PRP on torn human supraspinatus tendon. Twenty consecutive eligible patients with painful and magnetic resonance imaging (MRI)-confirmed degenerative supraspinatus tendon tears were randomized in a one-to-one ratio into two groups. The patients in the experimental group (n = 10) underwent an ultrasound-guided autologous PRP injection in the subacromial space 6 weeks before the scheduled operation. In the control group (n = 10), no injection was made prior to surgery. Supraspinatus tendon specimens were harvested from the lateral end of the torn tendon during shoulder arthroscopy and were evaluated under optical and electron microscopy. In the control group, a mixed cell population of oval and rounded tenocytes within disorganized collagen and sites of accumulated inflammatory cells was detected. In contrast, the experimental group yielded abundant oval-shaped cells with multiple cytoplasmic processes within mainly parallel collagen fibers and less marked inflammation, simulating the intact tendon structure. These findings indicate that PRP can induce microscopic changes in the ruptured tendon by stimulating the healing process and can facilitate a more effective recovery.
The Role of Gamma Delta T Lymphocytes in Physiological and Pathological Condition—Focus on Psoriasis, Atopic Dermatitis, Autoimmune Disorders, Cancer and Lymphomas
Authors: Chojnacka-Purpurowicz Joanna , Owczarczyk-Saczonek Agnieszka , Nedoszytko Bogusław
Published: July 2024

Gamma delta (γδ) T cells are a heterogeneous population of cells that play roles in inflammation, host tissue repair, clearance of viral and bacterial pathogens, regulation of immune processes, and tumor surveillance. Recent research suggests that these are the main skin cells that produce interleukin-17 (I-17). Furthermore, γδ T cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. γδ T cells are found in epithelial tissues, where many cancers develop. There, they participate in antitumor immunity as cytotoxic cells or as immune coordinators. γδ T cells also participate in host defense, immune surveillance, and immune homeostasis. The aim of this review is to present the importance of γδ T cells in physiological and pathological diseases, such as psoriasis, atopic dermatitis, autoimmune diseases, cancer, and lymphoma.
Plastic Fly: What Drosophila melanogaster Can Tell Us about the Biological Effects and the Carcinogenic Potential of Nanopolystyrene
Authors: Aloisi Massimo , Grifoni Daniela , Zarivi Osvaldo , Colafarina Sabrina , Morciano Patrizia , Poma Anna Maria Giuseppina
Published: July 2024

Today, plastic pollution is one of the biggest threats to the environment and public health. In the tissues of exposed species, micro- and nano-fragments accumulate, leading to genotoxicity, altered metabolism, and decreased lifespan. A model to investigate the genotoxic and tumor-promoting potential of nanoplastics (NPs) is Drosophila melanogaster. Here we tested polystyrene, which is commonly used in food packaging, is not well recycled, and makes up at least 30% of landfills. In order to investigate the biological effects and carcinogenic potential of 100 µm polystyrene nanoparticles (PSNPs), we raised Oregon [R] wild-type flies on contaminated food. After prolonged exposure, fluorescent PSNPs accumulated in the gut and fat bodies. Furthermore, PSNP-fed flies showed considerable alterations in weight, developmental time, and lifespan, as well as a compromised ability to recover from starvation. Additionally, we noticed a decrease in motor activity in DNAlig4 mutants fed with PSNPs, which are known to be susceptible to dietary stressors. A qPCR molecular investigation of the larval intestines revealed a markedly elevated expression of the genes drice and p53, suggesting a response to cell damage. Lastly, we used warts-defective mutants to assess the carcinogenic potential of PSNPs and discovered that exposed flies had more aberrant masses than untreated ones. In summary, our findings support the notion that ingested nanopolystyrene triggers metabolic and genetic modifications in the exposed organisms, eventually delaying development and accelerating death and disease.
Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges
Authors: Seyhan Attila A.
Published: July 2024

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of the central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis of GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans and postoperative confirmation via histopathological and molecular analysis. Imaging techniques struggle to differentiate between tumor progression and treatment-related changes, leading to potential misinterpretation and treatment delays. Similarly, tissue biopsies, while informative, are invasive and not suitable for monitoring ongoing treatments. These challenges have led to the emergence of liquid biopsy, particularly through blood samples, as a promising alternative for GBM diagnosis and monitoring. Presently, blood and cerebrospinal fluid (CSF) sampling offers a minimally invasive means of obtaining tumor-related information to guide therapy. The idea that blood or any biofluid tests can be used to screen many cancer types has huge potential. Tumors release various components into the bloodstream or other biofluids, including cell-free nucleic acids such as microRNAs (miRNAs), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), proteins, extracellular vesicles (EVs) or exosomes, metabolites, and other factors. These factors have been shown to cross the blood-brain barrier (BBB), presenting an opportunity for the minimally invasive monitoring of GBM as well as for the real-time assessment of distinct genetic, epigenetic, transcriptomic, proteomic, and metabolomic changes associated with brain tumors. Despite their potential, the clinical utility of liquid biopsy-based circulating biomarkers is somewhat constrained by limitations such as the absence of standardized methodologies for blood or CSF collection, analyte extraction, analysis methods, and small cohort sizes. Additionally, tissue biopsies offer more precise insights into tumor morphology and the microenvironment. Therefore, the objective of a liquid biopsy should be to complement and enhance the diagnostic accuracy and monitoring of GBM patients by providing additional information alongside traditional tissue biopsies. Moreover, utilizing a combination of diverse biomarker types may enhance clinical effectiveness compared to solely relying on one biomarker category, potentially improving diagnostic sensitivity and specificity and addressing some of the existing limitations associated with liquid biomarkers for GBM. This review presents an overview of the latest research on circulating biomarkers found in GBM blood or CSF samples, discusses their potential as diagnostic, predictive, and prognostic indicators, and discusses associated challenges and future perspectives.
Exploring the Effects of an Alfalfa Leaf-Derived Adsorbent on Microbial Community, Ileal Morphology, Barrier Function, and Immunity in Turkey Poults during Chronic Aflatoxin B1 Exposure
Authors: Nava-Ramírez María de Jesús , Liu Jing , Hernández-Ramírez Juan Omar , Hernandez-Velasco Xochitl , Latorre Juan D. , Vázquez-Durán Alma , Zhang Guolong , Senas-Cuesta Roberto , Gómez-Rosales Sergio , Stein Andressa , Hargis Billy M. , Téllez-Isaías Guillermo , Méndez-Albores Abraham , Maguey-González Jesús A.
Published: July 2024

This article follows-up on our recently published work, which evaluated the impact of the addition of an alfalfa leaf-derived adsorbent in the aflatoxin B1 (AFB1)-contaminated diet in regard to the production parameters, blood cell count, serum biochemistry, liver enzymes, and liver histology of turkey poults. This paper presents complementary results on microbial community, ileal morphology, barrier function, and immunity. For this purpose, 350 1-day-old female turkey poults were randomly distributed into five groups: (1) Control, AFB1-free diet; (2) AF, AFB1-contaminated diet at 250 ng/g; (3) alfalfa, AFB1-free diet + 0.5% (w/w) adsorbent; (4) alfalfa + AF, AFB1-contaminated diet at 250 ng/g + 0.5% (w/w) adsorbent; and (5) YCW + AF, AFB1-contaminated diet at 250 ng/g + 0.5% (w/w) commercial yeast cell wall-based adsorbent (reference group). In general, in the AF group, the growth of opportunistic pathogens was promoted, which lead to gut dysbacteriosis, mainly influenced by Streptococcus lutetiensis. Conversely, a significant increase in beneficial bacteria (Faecalibacterium and Coprococcus catus) was promoted by the addition of the plant-based adsorbent. Moreover, the AF group had the lowest villus height and a compromised barrier function, as evidenced by a significant (p < 0.05) increase in fluorescein isothiocyanate dextran (FITC-d), but these negative effects were almost reversed by the addition of the alfalfa adsorbent. Furthermore, the AF + YCW and alfalfa + AF groups exhibited a significant increase in the cutaneous basophil hypersensitivity response compared to the rest of the experimental groups. Taken together, these results pointed out that the alfalfa counteracts the adverse effects of AFB1 in poults, facilitating the colonization of beneficial bacteria and improving the barrier function of the turkey poults.
Mouse Model of Parkinson’s Disease with Bilateral Dorsal Striatum Lesion with 6-Hydroxydopamine Exhibits Cognitive Apathy-like Behavior
Authors: Okitsu Masato , Fujita Masayo , Moriya Yuki , Kotajima-Murakami Hiroko , Ide Soichiro , Kojima Rika , Sekiyama Kazunari , Takahashi Kazushi , Ikeda Kazutaka
Published: July 2024

Among the symptoms of Parkinson’s disease (PD), apathy comprises a set of behavioral, affective, and cognitive features that can be classified into several subtypes. However, the pathophysiology and brain regions that are involved in these different apathy subtypes are still poorly characterized. We examined which subtype of apathy is elicited in a mouse model of PD with 6-hydroxydopamine (6-OHDA) lesions and the behavioral symptoms that are exhibited. Male C57/BL6J mice were allocated to sham (n = 8) and 6-OHDA (n = 13) groups and locally injected with saline or 4 µg 6-OHDA bilaterally in the dorsal striatum. We then conducted motor performance tests and apathy-related behavioral experiments. We then pathologically evaluated tyrosine hydroxylase (TH) immunostaining. The 6-OHDA group exhibited significant impairments in motor function. In the behavioral tests of apathy, significant differences were observed between the sham and 6-OHDA groups in the hole-board test and novelty-suppressed feeding test. The 6-OHDA group exhibited impairments in inanimate novel object preference, whereas social preference was maintained in the three-chamber test. The number of TH+ pixels in the caudate putamen and substantia nigra compacta was significantly reduced in the 6-OHDA group. The present mouse model of PD predominantly showed dorsal striatum dopaminergic neuronal loss and a decrease in novelty seeking as a symptom that is related to the cognitive apathy component.
Transcriptomic Analyses Reveal That Coffea arabica and Coffea canephora Have More Complex Responses under Combined Heat and Drought than under Individual Stressors
Authors: Marques Isabel , Fernandes Isabel , Paulo Octávio S. , Batista Dora , Lidon Fernando C. , Rodrigues Ana P. , Partelli Fábio L. , DaMatta Fábio M. , Ribeiro-Barros Ana I. , Ramalho José C.
Published: July 2024

Increasing exposure to unfavorable temperatures and water deficit imposes major constraints on most crops worldwide. Despite several studies regarding coffee responses to abiotic stresses, transcriptome modulation due to simultaneous stresses remains poorly understood. This study unravels transcriptomic responses under the combined action of drought and temperature in leaves from the two most traded species: Coffea canephora cv. Conilon Clone 153 (CL153) and C. arabica cv. Icatu. Substantial transcriptomic changes were found, especially in response to the combination of stresses that cannot be explained by an additive effect. A large number of genes were involved in stress responses, with photosynthesis and other physiologically related genes usually being negatively affected. In both genotypes, genes encoding for protective proteins, such as dehydrins and heat shock proteins, were positively regulated. Transcription factors (TFs), including MADS-box genes, were down-regulated, although responses were genotype-dependent. In contrast to Icatu, only a few drought- and heat-responsive DEGs were recorded in CL153, which also reacted more significantly in terms of the number of DEGs and enriched GO terms, suggesting a high ability to cope with stresses. This research provides novel insights into the molecular mechanisms underlying leaf Coffea responses to drought and heat, revealing their influence on gene expression.
Functional Activity of Isoform 2 of Human eRF1
Authors: Shuvalov Alexey , Klishin Alexandr , Biziaev Nikita , Shuvalova Ekaterina , Alkalaeva Elena
Published: July 2024

Eukaryotic release factor eRF1, encoded by the ETF1 gene, recognizes stop codons and induces peptide release during translation termination. ETF1 produces several different transcripts as a result of alternative splicing, from which two eRF1 isoforms can be formed. Isoform 1 codes well-studied canonical eRF1, and isoform 2 is 33 amino acid residues shorter than isoform 1 and completely unstudied. Using a reconstituted mammalian in vitro translation system, we showed that the isoform 2 of human eRF1 is also involved in translation. We showed that eRF1iso2 can interact with the ribosomal subunits and pre-termination complex. However, its codon recognition and peptide release activities have decreased. Additionally, eRF1 isoform 2 exhibits unipotency to UGA. We found that eRF1 isoform 2 interacts with eRF3a but stimulated its GTPase activity significantly worse than the main isoform eRF1. Additionally, we studied the eRF1 isoform 2 effect on stop codon readthrough and translation in a cell-free translation system. We observed that eRF1 isoform 2 suppressed stop codon readthrough of the uORFs and decreased the efficiency of translation of long coding sequences. Based on these data, we assumed that human eRF1 isoform 2 can be involved in the regulation of translation termination. Moreover, our data support previously stated hypotheses that the GTS loop is important for the multipotency of eRF1 to all stop codons. Whereas helix α1 of the N-domain eRF1 is proposed to be involved in conformational rearrangements of eRF1 in the A-site of the ribosome that occur after GTP hydrolysis by eRF3, which ensure hydrolysis of peptidyl-tRNA at the P site of the ribosome.
A Systematic Hierarchical Virtual Screening Model for RhlR Inhibitors Based on PCA, Pharmacophore, Docking, and Molecular Dynamics
Authors: Du Jiarui , Li Jiahao , Wen Juqi , Liu Jun , Xiao Haichuan , Zhang Antian , Yang Dongdong , Sun Pinghua , Zhou Haibo , Xu Jun
Published: July 2024

RhlR plays a key role in the quorum sensing of Pseudomonas aeruginosa. The current structure–activity relationship (SAR) studies of RhlR inhibitors mainly focus on elucidating the functional groups. Based on a systematic review of previous research on RhlR inhibitors, this study aims to establish a systematic, hierarchical screening model for RhlR inhibitors. We initially established a database and utilized principal component analysis (PCA) to categorize the inhibitors into two classes. Based on the training set, pharmacophore models were established to elucidate the structural characteristics of ligands. Subsequently, molecular docking, molecular dynamics simulations, and the calculation of binding free energy and strain energy were performed to validate the crucial interactions between ligands and receptors. Then, the screening criteria for RhlR inhibitors were established hierarchically based on ligand structure characteristics, ligand–receptor interaction, and receptor affinity. Test sets were finally employed to validate the hierarchical virtual screening model by comparing it with the current SAR studies of RhlR inhibitors. The hierarchical screening model was confirmed to possess higher accuracy and a true positive rate, which holds promise for subsequent screening and the discovery of active RhlR inhibitors.
Potential Transcriptional Enhancers in Coronaviruses: From Infectious Bronchitis Virus to SARS-CoV-2
Authors: Patarca Roberto , Haseltine William A.
Published: July 2024

Coronaviruses constitute a global threat to human and animal health. It is essential to investigate the long-distance RNA-RNA interactions that approximate remote regulatory elements in strategies, including genome circularization, discontinuous transcription, and transcriptional enhancers, aimed at the rapid replication of their large genomes, pathogenicity, and immune evasion. Based on the primary sequences and modeled RNA-RNA interactions of two experimentally defined coronaviral enhancers, we detected via an in silico primary and secondary structural analysis potential enhancers in various coronaviruses, from the phylogenetically ancient avian infectious bronchitis virus (IBV) to the recently emerged SARS-CoV-2. These potential enhancers possess a core duplex-forming region that could transition between closed and open states, as molecular switches directed by viral or host factors. The duplex open state would pair with remote sequences in the viral genome and modulate the expression of downstream crucial genes involved in viral replication and host immune evasion. Consistently, variations in the predicted IBV enhancer region or its distant targets coincide with cases of viral attenuation, possibly driven by decreased open reading frame (ORF)3a immune evasion protein expression. If validated experimentally, the annotated enhancer sequences could inform structural prediction tools and antiviral interventions.
Molecular Adaptations of BDNF/NT-4 Neurotrophic and Muscarinic Pathways in Ageing Neuromuscular Synapses
Authors: Balanyà-Segura Marta , Polishchuk Aleksandra , Just-Borràs Laia , Cilleros-Mañé Víctor , Silvera Carolina , Ardévol Anna , Tomàs Marta , Lanuza Maria A. , Hurtado Erica , Tomàs Josep
Published: July 2024

Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. Similarly, presynaptic muscarinic signalling plays a fundamental modulatory function in this synapse. However, whether or not these signalling pathways are compromised in ageing neuromuscular system has not yet been analysed. The present study analyses, through Western blotting, the differences in expression and activation of the main key proteins of the BDNF/NT-4 and muscarinic pathways related to neurotransmission in young versus ageing Extensor digitorum longus (EDL) rat muscles. The main results show an imbalance in several sections of these pathways: (i) a change in the stoichiometry of BDNF/NT-4, (ii) an imbalance of Tropomyosin-related kinase B receptor (TrkB)-FL/TrkB-T1 and neurotrophic receptor p 75 (p75NTR), (iii) no changes in the cytosol/membrane distribution of phosphorylated downstream protein kinase C (PKC)βI and PKCε, (iv) a reduction in the M2-subtype muscarinic receptor and P/Q-subtype voltage-gated calcium channel, (v) an imbalance of phosphorylated mammalian uncoordinated-18-1 (Munc18-1) (S313) and synaptosomal-associated protein 25 (SNAP-25) (S187), and (vi) normal levels of molecules related to the management of acetylcholine (Ach). Based on this descriptive analysis, we hypothesise that these pathways can be adjusted to ensure neurotransmission rather than undergoing negative alterations caused by ageing. However, further studies are needed to assess this hypothetical suggestion. Our results contribute to the understanding of some previously described neuromuscular functional age-related impairments. Strategies to promote these signalling pathways could improve the neuromuscular physiology and quality of life of older people.
Navigating Lipodystrophy: Insights from Laminopathies and Beyond
Authors: Krüger Peter , Hartinger Ramona , Djabali Karima
Published: July 2024

Recent research into laminopathic lipodystrophies—rare genetic disorders caused by mutations in the LMNA gene—has greatly expanded our knowledge of their complex pathology and metabolic implications. These disorders, including Hutchinson-Gilford progeria syndrome (HGPS), Mandibuloacral Dysplasia (MAD), and Familial Partial Lipodystrophy (FPLD), serve as crucial models for studying accelerated aging and metabolic dysfunction, enhancing our understanding of the cellular and molecular mechanisms involved. Research on laminopathies has highlighted how LMNA mutations disrupt adipose tissue function and metabolic regulation, leading to altered fat distribution and metabolic pathway dysfunctions. Such insights improve our understanding of the pathophysiological interactions between genetic anomalies and metabolic processes. This review merges current knowledge on the phenotypic classifications of these diseases and their associated metabolic complications, such as insulin resistance, hypertriglyceridemia, hepatic steatosis, and metabolic syndrome, all of which elevate the risk of cardiovascular disease, stroke, and diabetes. Additionally, a range of published therapeutic strategies, including gene editing, antisense oligonucleotides, and novel pharmacological interventions aimed at addressing defective adipocyte differentiation and lipid metabolism, will be explored. These therapies target the core dysfunctional lamin A protein, aiming to mitigate symptoms and provide a foundation for addressing similar metabolic and genetic disorders.
Arabidopsis thaliana MYC2 and MYC3 Are Involved in Ethylene-Regulated Hypocotyl Growth as Negative Regulators
Authors: Li Yuke , Cheng Ying , Wei Fan , Liu Yingxiao , Zhu Ruojia , Zhao Pingxia , Zhang Jing , Xiang Chengbin , Kang Erfang , Shang Zhonglin
Published: July 2024

The ethylene-regulated hypocotyl elongation of Arabidopsis thaliana involves many transcription factors. The specific role of MYC transcription factors in ethylene signal transduction is not completely understood. The results here revealed that two MYCs, MYC2 and MYC3, act as negative regulators in ethylene-suppressed hypocotyl elongation. Etiolated seedlings of the loss-of-function mutant of MYC2 or MYC3 were significantly longer than wild-type seedlings. Single- or double-null mutants of MYC2 and MYC3 displayed remarkably enhanced response to ACC(1-aminocyclopropane-1-carboxylate), the ethylene precursor, compared to wild-type seedlings. MYC2 and MYC3 directly bind to the promoter zone of ERF1, strongly suppressing its expression. Additionally, EIN3, a key component in ethylene signaling, interacts with MYC2 or MYC3 and significantly suppresses their binding to ERF1’s promoter. MYC2 and MYC3 play crucial roles in the ethylene-regulated expression of functional genes. The results revealed the novel role and functional mechanism of these transcription factors in ethylene signal transduction. The findings provide valuable information for deepening our understanding of their role in regulating plant growth and responding to stress.
Microbial and Metabolic Gut Profiling across Seven Malignancies Identifies Fecal Faecalibacillus intestinalis and Formic Acid as Commonly Altered in Cancer Patients
Authors: Kulecka Maria , Czarnowski Paweł , Bałabas Aneta , Turkot Maryla , Kruczkowska-Tarantowicz Kamila , Żeber-Lubecka Natalia , Dąbrowska Michalina , Paszkiewicz-Kozik Ewa , Walewski Jan , Ługowska Iwona , Koseła-Paterczyk Hanna , Rutkowski Piotr , Kluska Anna , Piątkowska Magdalena , Jagiełło-Gruszfeld Agnieszka , Tenderenda Michał , Gawiński Cieszymierz , Wyrwicz Lucjan , Borucka Magdalena , Krzakowski Maciej , Zając Leszek , Kamiński Michał , Mikula Michał , Ostrowski Jerzy
Published: July 2024

The key association between gut dysbiosis and cancer is already known. Here, we used whole-genome shotgun sequencing (WGS) and gas chromatography/mass spectrometry (GC/MS) to conduct metagenomic and metabolomic analyses to identify common and distinct taxonomic configurations among 40, 45, 71, 34, 50, 60, and 40 patients with colorectal cancer, stomach cancer, breast cancer, lung cancer, melanoma, lymphoid neoplasms and acute myeloid leukemia (AML), respectively, and compared the data with those from sex- and age-matched healthy controls (HC). α-diversity differed only between the lymphoid neoplasm and AML groups and their respective HC, while β-diversity differed between all groups and their HC. Of 203 unique species, 179 and 24 were under- and over-represented, respectively, in the case groups compared with HC. Of these, Faecalibacillus intestinalis was under-represented in each of the seven groups studied, Anaerostipes hadrus was under-represented in all but the stomach cancer group, and 22 species were under-represented in the remaining five case groups. There was a marked reduction in the gut microbiome cancer index in all case groups except the AML group. Of the short-chain fatty acids and amino acids tested, the relative concentration of formic acid was significantly higher in each of the case groups than in HC, and the abundance of seven species of Faecalibacterium correlated negatively with most amino acids and formic acid, and positively with the levels of acetic, propanoic, and butanoic acid. We found more differences than similarities between the studied malignancy groups, with large variations in diversity, taxonomic/metabolomic profiles, and functional assignments. While the results obtained may demonstrate trends rather than objective differences that correlate with different types of malignancy, the newly developed gut microbiota cancer index did distinguish most of the cancer cases from HC. We believe that these data are a promising step forward in the search for new diagnostic and predictive tests to assess intestinal dysbiosis among cancer patients.
FILO: Automated FIx-LOcus Identification for Android Framework Compatibility Issues
Authors: Mobilio Marco , Riganelli Oliviero , Micucci Daniela , Mariani Leonardo
Published: July 2024

Keeping up with the fast evolution of mobile operating systems is challenging for developers, who have to frequently adapt their apps to the upgrades and behavioral changes of the underlying API framework. Those changes often break backward compatibility. The consequence is that apps, if not updated, may misbehave and suffer unexpected crashes if executed within an evolved environment. Being able to quickly identify the portion of the app that should be modified to provide compatibility with new API versions can be challenging. To facilitate the debugging activities of problems caused by backward incompatible upgrades of the operating system, this paper presents FILO, a technique that is able to recommend the method that should be modified to implement the fix by analyzing a single failing execution. FILO can also provide additional information and key symptomatic anomalous events that can help developers understand the reason for the failure, therefore facilitating the implementation of the fix. We evaluated FILO against 18 real compatibility problems related to Android upgrades and compared it with Spectrum-Based Localization approaches. Results show that FILO is able to efficiently and effectively identify the fix-locus in the apps.
Predicting the Distribution of Neoceratitis asiatica (Diptera: Tephritidae), a Primary Pest of Goji Berry in China, under Climate Change
Authors: Song Zhongkang , Fan Guanghui , Deng Changrong , Duan Guozhen , Li Jianling
Published: July 2024

Climate warming affects the growth and development of pests, resulting in changes in their geographical distribution, which increases the difficulty in terms of prevention and control. The fruit fly, Neoceratitis asiatica (Becker), is a predominant frugivorous pest that causes serious yield loss in the goji berry, Lycium barbarum L. In recent years, with the expansion of cultivation area, the damage induced by the pest has become increasingly severe, significantly impeding the production of the goji berry. In this study, the potential suitable habitats of N. asiatica under current and future climate scenarios were simulated and predicted using the optimal MaxEnt model, based on the screening distribution records and environmental factors. The changes in the pest distribution under climate change were determined using ArcGIS. The results showed that the best combination of parameters for MaxEnt were feature combination (FC) = LQPT and regularization multiplier (RM) = 1. The dominant environmental factors influencing pest distribution were mean temperature of driest quarter, mean temperature of coldest quarter and precipitation of coldest quarter. Under different climate conditions, the suitable habitats of the pest primarily ranged between 27°–47° N and 73°–115° E. Under current climate conditions, the area of moderately and highly suitable habitats was 42.18 × 104 km2, and mainly distributed in Inner Mongolia (13.68 × 104 km2), Gansu (9.40 × 104 km2), Ningxia (5.07 × 104 km2), Qinghai (4.10 × 104 km2), and Xinjiang (3.97 × 104 km2) Provinces. Under future climate scenarios, the suitable area was projected to be lower than the current ones, except SSP245–2050s and SSP370–2070s, and the centroids of suitable habitats were mainly shifted to the northeast, except SSP370–2050s and SSP585–2070s. Our results provide valuable guidance for the monitoring and management of N. asiatica, as well as the selection of pest-free goji berry cultivation sites.
Mechanical Thrombectomy in Ischemic Stroke with a Large Infarct Core: A Meta-Analysis of Randomized Controlled Trials
Authors: Romoli Michele , Princiotta Cariddi Lucia , Longoni Marco , Stufano Gianluca , Giacomozzi Sebastiano , Pompei Luca , Diana Francesco , D’Anna Lucio , Sacco Simona , Vidale Simone
Published: July 2024

Background/Objectives: Endovascular treatment (EVT) is recommended for acute ischemic stroke due to large-vessel occlusion (LVO) and an Alberta Stroke Program Early CT Score (ASPECTS) ≥ 6. Randomized controlled trials (RCTs) have recently become available on EVT effects in people with LVO-related large core stroke (ASPECTS 0–5). Here, we provide an updated meta-analysis of the EVT effect on functional neurological status in people with large-core stroke. Methods: The study followed the PRISMA guidelines. PubMed, EMBASE and Cochrane Central were searched for RCTs comparing EVT vs. best medical treatment (BMT) in large-core LVO stroke. The primary outcome was functional independence at 90 days (modified Rankin Scale; mRS 0–2). The secondary outcomes were symptomatic intracranial hemorrhage (sICH), good functional outcome (mRS 0–3) and excellent functional outcome (mRS 0–1). EVT vs. BMT was compared through random effect meta-analysis. Heterogeneity was assessed with the I2 and Q test and risk of bias reported according to the RoB2 tool. Results: Six RCTs were included (n = 1656 patients). All studies had a moderate risk of bias, with blinding bias due to the nature of the intervention, potential allocation bias and incomplete outcome reporting. Functional independence was significantly more frequent in the EVT vs. BMT group (OR = 2.47, 95% CI = 1.52–4.03, p < 0.001). sICH rates (OR = 1.77, 95% CI = 1.01–3.11, p = 0.04) and good functional outcome (OR = 2.20; 95% CI = 1.72–2.81, p < 0.001) were more frequent in the EVT vs. BMT group, while the rates of mRS 0–1 did not differ. Conclusions: In patients with large-core stroke and LVO, EVT plus BMT as compared to BMT alone carries a significant increase in independent ambulation and good functional outcome at 3 months despite the marginal increase in sICH.
Brain Responses Difference between Sexes for Strong Desire to Void: A Functional Magnetic Resonance Imaging Study in Adults Based on Graph Theory
Authors: Ying Xiaoqian , Gao Yi , Liao Limin
Published: July 2024

Background: The alternations of brain responses to a strong desire to void were unclear, and the gender differences under the strong desire to void remain controversial. The present study aims to identify the functional brain network’s topologic property changes evoked by a strong desire to void in healthy male and female adults with synchronous urodynamics using a graph theory analysis. Methods: The bladders of eleven healthy males and eleven females were filled via a catheter using a specific infusion and withdrawal pattern. A resting-state functional magnetic resonance imaging (fMRI) was performed on the enrolled subjects, scanning under both the empty bladder and strong desire to void states. An automated anatomical labeling (AAL) atlas was used to identify the ninety cortical and subcortical regions. Pearson’s correlation calculations were performed to establish a brain connection matrix. A paired t-test (p < 0.05) and Bonferroni correction were applied to identify the significant statistical differences in topological properties between the two states, including small-world network property parameters [gamma (γ) and lambda (λ)], characteristic path length (Lp), clustering coefficient (Cp), global efficiency (Eglob), local efficiency (Eloc), and regional nodal efficiency (Enodal). Results: The final data suggested that females and males had different brain response patterns to a strong desire to void, compared with an empty bladder state. Conclusions: More brain regions involving emotion, cognition, and social work were active in females, and males might obtain a better urinary continence via a compensatory mechanism.
Assessment of ELR, PLR, NLR and BLR Ratios during Omalizumab Treatment of Chronic Spontaneous Urticaria
Authors: Branicka Olga , Rymarczyk Barbara , Gawlik Radosław , Glück Joanna
Published: July 2024

Background: There is a need for searching for biomarkers indicating patients who will benefit the most from treatment with omalizumab for chronic spontaneous urticaria (CSU). The aim of this study was to assess whether the eosinophil/neutrophil/platelet/basophil-to-lymphocyte ratio (ELR, NLR, PLR, BLR) may predict the response to omalizumab treatment of chronic spontaneous urticaria. Methods: A retrospective data analysis of CSU patients treated s-c with 300 mg of omalizumab every four weeks under the drug program was carried out. NLR, ELR, PLR and BLR, DLQI, UAS-7, CRP, anti-TPO and tIgE were assessed before (V0) and after three (V3) and six months (V6) of treatment. Results: Among 52 patients with CSU, 21 were responders, 24 were partially responders and 6 were non-responders to treatment with 300 mg omalizumab every four weeks. An amount of 18 patients had features of type I autoallergic CSU (CSUaiTI) and 34 patients had autoimmunity type IIb CSU with mast cell-directed activating autoantibodies (CSUaiTIIb). NLR, ELR, PLR and BLR indices did not change during a six-month-course of biological treatment. Initial values of ELR and BLR were significantly correlated with the initial tIgE level and anti-TPO/IgE ratio. Initial values of NLR, ELR and BLR were significantly correlated with initial CRP. Comparisons between type I autoallergic CSU (CSUaiTI) and autoimmunity type IIb CSU (CSUaiTIIb) revealed that the absolute number and percentage of eosinophils, basophils, BLR and tIgE were significantly higher in type CSUaiTI and anti-TPO and anti-TPO/IgE were significantly lower in type CSUaiTI. Conclusions: NLR, ELR, PLR and BLR do not change significantly during six months of omalizumab treatment and do not appear to be useful in predicting its efficacy.
Clinical Significance and Patterns of Potential Drug–Drug Interactions in Cardiovascular Patients: Focus on Low-Dose Aspirin and Angiotensin-Converting Enzyme Inhibitors
Authors: Anfinogenova Nina D. , Stepanov Vadim A. , Chernyavsky Alexander M. , Karpov Rostislav S. , Efimova Elena V. , Novikova Oksana M. , Trubacheva Irina A. , Falkovskaya Alla Y. , Maksimova Aleksandra S. , Ryumshina Nadezhda I. , Shelkovnikova Tatiana A. , Ussov Wladimir Y. , Vaizova Olga E. , Popov Sergey V. , Repin Alexei N.
Published: July 2024

Objective: This study assessed the patterns and clinical significance of potential drug–drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018–2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann–Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to ‘aspirin + captopril’ combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to ‘aspirin + enalapril’ and ‘aspirin + lisinopril’ combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to ‘aspirin + enalapril’ and ‘aspirin + lisinopril’ combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information.
Current Trends in the Use of Biomass in the Manufacture of Rigid Polyurethane Foams: A Review
Authors: Dukarska Dorota , Mirski Radosław
Published: July 2024

This paper discusses methods of using biomass from the agriculture, forestry, food and aquaculture industries as potential raw materials for bio-polyols and as fillers in the production of rigid polyurethane (RPUR) foams. Various aspects of obtaining bio-polyols are discussed, as well as the impact of replacing petrochemical polyols with bio-polyols on the properties of foams. Special attention is paid to the conversion of vegetable oils and lignin. Another important aspect of the research is the use of biomass as foam fillers. Chemical and physical modifications are discussed, and important factors, such as the type and origin of biomass, particle size and amount, affecting the foaming process, microstructure and properties of RPUR foams are identified. The advantages and disadvantages of using biomass in foam production are described. It is found that bio-polyols can replace (at least partially) petrochemical polyols while maintaining the high insulation and strength of foams. In the case of the use of biomass as fillers, it is found that the shaping of their properties is largely dependent on the specific characteristics of the filler particles. This requires further research into process optimization but allows for the fine-tuning of RPUR foam properties to meet specific requirements.
Evaluating Large Language Models’ Ability Using a Psychiatric Screening Tool Based on Metaphor and Sarcasm Scenarios
Authors: Yakura Hiromu
Published: July 2024

Metaphors and sarcasm are precious fruits of our highly evolved social communication skills. However, children with the condition then known as Asperger syndrome are known to have difficulties in comprehending sarcasm, even if they possess adequate verbal IQs for understanding metaphors. Accordingly, researchers had employed a screening test that assesses metaphor and sarcasm comprehension to distinguish Asperger syndrome from other conditions with similar external behaviors (e.g., attention-deficit/hyperactivity disorder). This study employs a standardized test to evaluate recent large language models’ (LLMs) understanding of nuanced human communication. The results indicate improved metaphor comprehension with increased model parameters; however, no similar improvement was observed for sarcasm comprehension. Considering that a human’s ability to grasp sarcasm has been associated with the amygdala, a pivotal cerebral region for emotional learning, a distinctive strategy for training LLMs would be imperative to imbue them with the ability in a cognitively grounded manner.
The Relationship between Trait Emotional Intelligence and Creative Self-Efficacy in Gifted Children: A Cross-Lagged and Cross-Temporal Mediation Analysis
Authors: Cheng Li , Liu Xinmei , Liu Yujuan , Wu Yilin
Published: July 2024

The present study aimed to investigate the causal relationship between trait emotional intelligence and creative self-efficacy in gifted children and to explore the cross-temporal mediating role of self-concept between these two variables. A total of 177 gifted children aged 10–13 years (M = 11.29, SD = 0.68) were selected from an experimental class of gifted children in a middle school. The results showed that (1) the trait emotional intelligence and creative self-efficacy of gifted children decreased with age and that (2) trait emotional intelligence at time 1 (T1) positively and significantly predicted creative self-efficacy at time 2 (T2). The Self-Description Questionnaire was added at the second follow-up, which revealed that (3) T2 non-academic self-concept fully mediated the relationship between T1 trait emotional intelligence and T2 creative self-efficacy. This study revealed a lasting positive effect of trait emotional intelligence on the development of creative self-efficacy in gifted children. Additionally, trait emotional intelligence was found to indirectly influence creative self-efficacy through non-academic self-concept.
The Impact of Chromosomal Mosaicisms on Prenatal Diagnosis and Genetic Counseling—A Narrative Review
Authors: Militaru Mariela Sanda , Babliuc Ioana-Mădălina , Bloaje-Florică Vanesa-Larisa , Danci Valentin-Adrian , Filip-Deac Iulia , Kutasi Enikő , Simon Vasile , Militaru Mihai , Cătană Andreea
Published: July 2024

Genetic disorders represent a high-impact diagnosis for both patients and their families. Prenatal screening methods and, when recommended, genetic testing allow parents to make informed decisions about the course a pregnancy is going to take. Although offering certainty about the potential evolution and prognosis of the pregnancy, and then the newborn, is usually not possible, genetic counseling can offer valuable insights into genetic disorders. Chromosomal mosaicisms are genetic anomalies that affect only some cell lines in either the fetus or the placenta or both. They can affect autosomal or heterosomal chromosomes, and they can be either numerical or structural. The prognosis seems to be more severe if the genetic alterations are accompanied by malformations visible in ultrasounds. Several genetic techniques can be used to diagnose certain mosaicisms, depending on their nature. A novel approach in prenatal care is non-invasive prenatal screening (NIPS), also known as non-invasive prenatal testing (NIPT), which, although it does not always have diagnostic value, can provide valuable information about potential genetic anomalies, especially numerical, with high sensitivity (Se).