bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal-Free, PPA-Mediated Fisher Indole Synthesis via Tandem Hydroamination–Cyclization Reaction between Simple Alkynes and Arylhydrazines
Authors: Aksenov Alexander V. , Makieva Dinara C. , Arestov Rodion A. , Arutiunov Nikolai A. , Aksenov Dmitrii A. , Aksenov Nicolai A. , Leontiev Alexander V. , Aksenova Inna V.
Published: August 2024

A new variant of Fisher indole synthesis involving Bronsted acid-catalyzed hydrohydrazination of unactivated terminal and internal acetylenes with arylhydrazines is reported. The use of polyphosphoric acid alone either as the reaction medium or in the presence of a co-solvent appears to provide the required balance for activating the C–C triple bond towards the nucleophilic attack of the hydrazine moiety without unrepairable reactivity loss of the latter due to competing amino group protonation. Additionally, the formal hydration of acetylenes to the corresponding ketones occurs under the same conditions, making it an alternative approach for generating carbonyl groups from alkynes.
The Mitochondrial Genome of Ylistrum japonicum (Bivalvia, Pectinidae) and Its Phylogenetic Analysis
Authors: Han Yida , Xie Yaoyu , Hao Zhenlin , Mao Junxia , Wang Xubo , Chang Yaqing , Tian Ying
Published: August 2024

The Ylistrum japonicum is a commercially valuable scallop known for its long-distance swimming abilities. Despite its economic importance, genetic and genomic research on this species is limited. This study presents the first complete mitochondrial genome of Y. japonicum. The mitochondrial genome is 19,475 bp long and encompasses 13 protein-coding genes, three ribosomal RNA genes, and 23 transfer RNA genes. Two distinct phylogenetic analyses were used to explore the phylogenetic position of the Y. japonicum within the family Pectinidae. Based on one mitochondrial phylogenetic analysis by selecting 15 Pectinidae species and additional outgroup taxa and one single gene phylogenetic analysis by 16S rRNA, two phylogenetic trees were constructed to provide clearer insights into the evolutionary placement of Y. japonicum within the family Pectinidae. Our analysis reveals that Ylistrum is a basal lineage to the Pectininae clade, distinct from its previously assigned tribe, Amusiini. This study offers critical insights into the genetic makeup and evolutionary history of Y. japonicum, enhancing our knowledge of this economically vital species.
Sodium Acetate Enhances Neutrophil Extracellular Trap Formation via Histone Acetylation Pathway in Neutrophil-like HL-60 Cells
Authors: Yasuda Hiroyuki , Takishita Yutaka , Morita Akihiro , Tsutsumi Tomonari , Nakagawa Naoya , Sato Eisuke F.
Published: August 2024

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis, as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, and H3K14ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.
Assessment of Dried Serum Spots (DSS) and Volumetric-Absorptive Microsampling (VAMS) Techniques in Therapeutic Drug Monitoring of (Val)Ganciclovir—Comparative Study in Analytical and Clinical Practice
Authors: Kocur Arkadiusz , Czajkowska Agnieszka , Moczulski Mateusz , Kot Bartłomiej , Rubik Jacek , Pawiński Tomasz
Published: August 2024

Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are antiviral medications primarily used to treat infections caused by cytomegalovirus (CMV), particularly in immunocompromised individuals such as solid organ transplant (SOT) recipients. Therapy with GCV is associated with significant side effects, including bone marrow suppression. Therefore, therapeutic drug monitoring (TDM) is mandatory for an appropriate balance between subtherapeutic and toxic drug levels. This study aimed to develop and validate three novel methods based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for GCV determination in serum (reference methodology), dried serum spots (DSS), and VAMS-Mitra™ devices. The methods were optimized and validated in the 0.1–25 mg/L calibration range. The obtained results fulfilled the EMA acceptance criteria for bioanalytical method validation. Assessment of DSS and VAMS techniques extended GCV stability to serum for up to a minimum of 49 days (at room temperature, with desiccant). Developed methods were effectively evaluated using 80 clinical serum samples from pediatric renal transplant recipients. Obtained samples were used for DSS, and dried serum VAMS samples were manually generated in the laboratory. The results of GCV determination using serum-, DSS- and VAMS-LC-MS/MS methods were compared using regression analysis and bias evaluation. The conducted statistical analysis confirmed the interchangeability between developed assays. The DSS and VAMS samples are more accessible and stable during storage, transport and shipment than classic serum samples.
Enhanced Efficacy of Gastric Cancer Treatment through Targeted Exosome Delivery of 17-DMAG Anticancer Agent
Authors: Park Jung Hyun , Kim Say-June , Kim Ok-Hee , Kim Dong Jin
Published: August 2024

In this study, we explored the potential of genetically engineered exosomes as vehicles for precise drug delivery in gastric cancer therapy. A novel antitumor strategy using biocompatible exosomes (Ex) was devised by genetically engineering adipose-derived stem cells to express an MKN45-binding peptide (DE532) on their surfaces. 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) was encapsulated in engineered exosomes, resulting in 17-DMAG-loaded DE532 exosomes. In both in vitro and in vivo experiments using mouse gastric cancer xenograft models, we demonstrated that 17-DMAG-loaded DE532 Ex exhibited superior targetability over DE532 Ex, 17-DMAG-loaded Ex, and Ex. Administration of the 17-DMAG-loaded DE532 Ex yielded remarkable antitumor effects, as evidenced by the smallest tumor size, lowest tumor growth rate, and lowest excised tumor weight. Further mechanistic examinations revealed that the 17-DMAG-loaded DE532 Ex induced the highest upregulation of the pro-apoptotic marker B-cell lymphoma-2-like protein 11 and the lowest downregulation of the anti-apoptotic marker B-cell lymphoma-extra large. Concurrently, the 17-DMAG-loaded DE532 Ex demonstrated the lowest suppression of antioxidant enzymes, such as superoxide dismutase 2 and catalase, within tumor tissues. These findings underscore the potential of 17-DMAG-loaded DE532 exosomes as a potent therapeutic strategy for gastric cancer, characterized by precise targetability and the potential to minimize adverse effects.
Serum Splicing Factor Proline- and Glutamine-Rich Is a Diagnostic Marker for Non-Small-Cell Lung Cancer and Other Solid Cancers
Authors: Yang Libang , Gilbertsen Adam , Jacobson Blake , Kratzke Robert , Henke Craig A.
Published: August 2024

Cancer markers are measurable molecules in blood or tissues that are produced by tumor cells or immune cells in response to cancer progression. They play an important role in clinical diagnosis, prognosis, and therapy monitoring. Splicing factor proline- and glutamine-rich (SFPQ) plays an important role in cancer growth and metastasis. SFPQ is not only more highly expressed in non-small-cell lung cancer (NSCLC) cells than it is in controls, but also highly expressed in cancer cells in patients with other solid cancers. Thus, a new enzyme-linked immunosorbent assay (ELISA) for detecting SFPQ was developed, in which the SFPQ protein is trapped by the first specific mAb coated on a microplate, and then recognized by a second specific mAb. This assay allows for the specific detection of SFPQ in the serum of patients with solid cancer. Regarding NSCLC, the serum SFPQ levels distinguished the non-cancer controls from the patients with NSCLC, with an area under the curve of 0.876, a sensitivity of 87%, and a specificity of 94%. The serum SFPQ levels were significantly elevated in the patients with NSCLC or other solid cancers. In conclusion, serum SFPQ could be a promising novel diagnostic biomarker for NSCLC and other malignancies.
Effect of Mifepristone on Migration and Proliferation of Oral Cancer Cells
Authors: Iftikhar Anem , Shepherd Simon , Jones Sarah , Ellis Ian
Published: August 2024

Glucocorticoid receptor (GR) overexpression has been linked to increased tumour aggressiveness and treatment resistance. GR antagonists have been shown to enhance treatment effectiveness. Emerging research has investigated mifepristone, a GR antagonist, as an anticancer agent with limited research in the context of oral cancer. This study investigated the effect of mifepristone at micromolar (µM) concentrations of 1, 5, 10 and 20 on the proliferation and migration of oral cancer cells, at 24 and 48 h. Scratch and scatter assays were utilised to assess cell migration, MTT assays were used to measure cell proliferation, Western blotting was used to investigate the expression of GR and the activation of underlying Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signalling pathways, and immunofluorescence (IF) was used to determine the localisation of proteins in HaCaT (immortalised human skin keratinocytes), TYS (oral adeno squamous cell carcinoma), and SAS-H1 cells (squamous cell carcinoma of human tongue). Mifepristone resulted in a dose-dependent reduction in the proliferation of HaCaT, TYS, and SAS-H1 cells. Mifepristone at a concentration of 20 µM effectively reduced collective migration and scattering of oral cancer cells, consistent with the suppression of the PI3K-Akt and MAPK signalling pathways, and reduced expression of N-Cadherin. An elongated cell morphology was, however, observed, which may be linked to the localisation pattern of E-Cadherin in response to mifepristone. Overall, this study found that a high concentration of mifepristone was effective in the suppression of migration and proliferation of oral cancer cells via the inhibition of PI3K-Akt and MAPK signalling pathways. Further investigation is needed to define its impact on epithelial–mesenchymal transition (EMT) markers.
Phase Separation of SARS-CoV-2 Nucleocapsid Protein with TDP-43 Is Dependent on C-Terminus Domains
Authors: Strong Michael J. , McLellan Crystal , Kaplanis Brianna , Droppelmann Cristian A. , Junop Murray
Published: August 2024

The SARS-CoV-2 nucleocapsid protein (N protein) is critical in viral replication by undergoing liquid–liquid phase separation to seed the formation of a ribonucleoprotein (RNP) complex to drive viral genomic RNA (gRNA) translation and in suppressing both stress granules and processing bodies, which is postulated to increase uncoated gRNA availability. The N protein can also form biomolecular condensates with a broad range of host endogenous proteins including RNA binding proteins (RBPs). Amongst these RBPs are proteins that are associated with pathological, neuronal, and glial cytoplasmic inclusions across several adult-onset neurodegenerative disorders, including TAR DNA binding protein 43 kDa (TDP-43) which forms pathological inclusions in over 95% of amyotrophic lateral sclerosis cases. In this study, we demonstrate that the N protein can form biomolecular condensates with TDP-43 and that this is dependent on the N protein C-terminus domain (N-CTD) and the intrinsically disordered C-terminus domain of TDP-43. This process is markedly accelerated in the presence of RNA. In silico modeling suggests that the biomolecular condensate that forms in the presence of RNA is composed of an N protein quadriplex in which the intrinsically disordered TDP-43 C terminus domain is incorporated.
Clinical Significance of B-Type Natriuretic Peptide and N-Terminal Pro-B-Type Natriuretic Peptide in Pediatric Patients: Insights into Their Utility in the Presence or Absence of Pre-Existing Heart Conditions
Authors: Ludwikowska Kamila Maria , Tokarczyk Monika , Paleczny Bartłomiej , Tracewski Paweł , Szenborn Leszek , Kusa Jacek
Published: August 2024

The clinical significance of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in pediatric patients remains an area of evolving understanding, particularly regarding their utility in the presence or absence of pre-existing heart conditions. While clear cutoff values and established roles in heart failure are understood in adult patients, pediatric norms vary with age, complicating interpretation. Notably, the emergence of multi-system inflammatory syndrome in children (MIS-C) has highlighted the importance of these markers not only in the detection of acute heart failure but also as a marker of disease severity and even as a differential diagnosis tool. This review summarizes current knowledge on the utility of BNP and NT-proBNP in pediatric patients. Their unique physiology, including circulation and compensation mechanisms, likely influence BNP and NT-proBNP release, potentially even in non-heart failure states. Factors such as dynamic volemic changes accompanying inflammatory diseases in children may contribute. Thus, understanding the nuanced roles of BNP and NT-proBNP in pediatric populations is crucial for the accurate diagnosis, management, and differentiation of cardiac and non-cardiac conditions.
Anti-Neuroinflammatory Effect of Ombuin from Rhamnus erythroxylon Pall. Leaves in LPS-Induced BV-2 Microglia by Targeting Src and Suppressing the PI3K-AKT/NF-κB Signaling Pathway
Authors: Bian Yanjie , Qiao Nan , Han Suyun , Gao Jixiang , Lv Xiaofang , Yuan Lihuan , Zhang Linjing , Wei Zuofu
Published: August 2024

The leaves of Rhamnus erythroxylon Pall. are widely used as tea substitutes in northwest China for their fragrant aroma, anti-irritability, and digestion-enhancing properties. Ombuin, a main flavonoid compound found in the leaves, exhibited notable anti-inflammatory and antioxidant effects. However, its potential role in treating neuroinflammatory-related diseases remains unexplored. Thus, this study aims to evaluate the anti-neuroinflammatory effects of ombuin and to explore the underlying molecular mechanisms. According to our findings, ombuin dramatically reduced the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1β, nitric oxide (NO), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated BV-2 microglia. Further analysis, including transcriptomics, network pharmacology, molecular docking, and cellular heat transfer assays, revealed that Src was a direct target of ombuin. Western blot analysis showed that ombuin effectively suppressed Src phosphorylation and inhibited the downstream expressions of p-PI3K p85, p-AKT1, p-IKKα/β, p-IκBα, and nuclear factor κB (NF-κB). Meanwhile, the repression of Src significantly reversed the anti-neuroinflammatory activity of ombuin. Our results identified Src as a direct target of ombuin and implied that ombuin exerted an anti-neuroinflammatory effect by inhibiting Src phosphorylation and suppressing the activation of the PI3K-AKT and NF-κB pathways, which might provide an alternative therapeutic strategy for neurodegenerative diseases.
Precision Medicine in Childhood Cancer: The Influence of Genetic Polymorphisms on Vincristine-Induced Peripheral Neuropathy
Authors: Marangoni-Iglecias Luciana , Rojo-Tolosa Susana , Márquez-Pete Noelia , Cura Yasmín , Moreno-Toro Noelia , Membrive-Jiménez Cristina , Sánchez-Martin Almudena , Pérez-Ramírez Cristina , Jiménez-Morales Alberto
Published: August 2024

Cancer is the leading cause of disease-related death among children. Vincristine (VCR), a key component of childhood cancer treatment protocols, is associated with the risk of peripheral neuropathy (PN), a condition that may be reversible upon drug discontinuation but can also leave lasting sequelae. Single nucleotide polymorphism (SNP) in genes involved in VCR pharmacokinetics and pharmacodynamics have been investigated in relation to an increased risk of PN. However, the results of these studies have been inconsistent. A retrospective cohort study was conducted to investigate the potential association of drug transporter genes from the ATP-binding cassette (ABC) family and the centrosomal protein 72 (CEP72) gene with the development of PN in 88 Caucasian children diagnosed with cancer and treated with VCR. Genotyping was performed using real-time PCR techniques for the following SNPs: ABCB1 rs1128503, ABCC1 rs246240, ABCC2 rs717620, and CEP72 rs924607. The results indicated that age at diagnosis (OR = 1.33; 95% CI = 1.07–1.75) and the ABCC1 rs246240 G allele (OR = 12.48; 95% CI = 2.26–100.42) were associated with vincristine-induced peripheral neuropathy (VIPN). No association was found between this toxicity and CEP72 rs924607. Our study provides insights that may contribute to optimizing childhood cancer therapy in the future by predicting the risk of VIPN
Comparison of Peptidomes Extracted from Healthy Tissue and Tumor Tissue of the Parotid Glands and Saliva Samples
Authors: Puchalski Michał , Tretiakow Dmitry , Skorek Andrzej , Szydłowski Konrad , Stodulski Dominik , Mikaszewski Bogusław , Odroniec Amadeusz , Musiał Natalia , Thiel Marcel , Czaplewska Paulina , Ołdziej Stanisław
Published: August 2024

Salivary gland tumors are highly variable in clinical presentation and histology. The World Health Organization (WHO) classifies 22 types of malignant and 11 types of benign tumors of the salivary glands. Diagnosis of salivary gland tumors is based on imaging (ultrasound, magnetic resonance imaging) and fine-needle aspiration biopsy, but the final diagnosis is based on histopathological examination of the removed tumor tissue. In this pilot study, we are testing a new approach to identifying peptide biomarkers in saliva that can be used to diagnose salivary gland tumors. The research material for the peptidomic studies was extracts from washings of neoplastic tissues and healthy tissues (control samples). At the same time, saliva samples from patients and healthy individuals were analyzed. The comparison of the peptidome composition of tissue extracts and saliva samples may allow the identification of potential peptide markers of salivary gland tumors in patients’ saliva. The peptidome compositions extracted from 18 tumor and 18 healthy tissue samples, patients’ saliva samples (11 samples), and healthy saliva samples (8 samples) were analyzed by LC-MS tandem mass spectrometry. A group of 109 peptides was identified that were present only in the tumor tissue extracts and in the patients’ saliva samples. Some of the identified peptides were derived from proteins previously suggested as potential biomarkers of salivary gland tumors (ANXA1, BPIFA2, FGB, GAPDH, HSPB1, IGHG1, VIM) or tumors of other tissues or organs (SERPINA1, APOA2, CSTB, GSTP1, S100A8, S100A9, TPI1). Unfortunately, none of the identified peptides were present in all samples analyzed. This may be due to the high heterogeneity of this type of cancer. The surprising result was that extracts from tumor tissue did not contain peptides derived from salivary gland-specific proteins (STATH, SMR3B, HTN1, HTN3). These results could suggest that the developing tumor suppresses the production of proteins that are essential components of saliva.
A Potential Link between Myeloperoxidase Modified LDL, Atherosclerosis and Depression
Authors: Daher Jalil
Published: August 2024

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide.
High-Fat Feeding Alters Circulating Triglyceride Composition: Roles of FFA Desaturation and ω-3 Fatty Acid Availability
Authors: Shen Tong , Oh Youngtaek , Jeong Shinwu , Cho Suengmok , Fiehn Oliver , Youn Jang H.
Published: August 2024

Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD). Plasma triglycerides (TGs) are a key factor for assessing the risk of diabetes or CVD. However, previous lipidomics studies have demonstrated that not all TG molecules behave the same way. Individual TGs with different fatty acid compositions are regulated differentially under various conditions. In addition, distinct groups of TGs were identified to be associated with increased diabetes risk (TGs with lower carbon number [C#] and double-bond number [DB#]), or with decreased risk (TGs with higher C# and DB#). In this study, we examined the effects of high-fat feeding in rats on plasma lipid profiles with special attention to TG profiles. Wistar rats were maintained on either a low-fat (control) or high-fat diet (HFD) for 2 weeks. Plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to lipidomics analyses. High-fat feeding significantly impacted circulating lipid profiles, with the most significant effects observed on TG profile. The effects of an HFD on individual TG species depended on DB# in their fatty acid chains; an HFD increased TGs with low DB#, associated with increased diabetes risk, but decreased TGs with high DB#, associated with decreased risk. These changes in TGs with an HFD were associated with decreased indices of hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profiles. Decreased SCD activity would reduce the conversion of saturated to monounsaturated fatty acids, contributing to the increases in saturated TGs or TGs with low DB#. In addition, an HFD selectively depleted ω-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#. Thus, an HFD had profound impacts on circulating TG profiles. Some of these changes were at least partly explained by decreased hepatic SCD activity and depleted ω-3 PUFA.
Contribution of Keratinocytes in Skin Cancer Initiation and Progression
Authors: Dainese-Marque Océane , Garcia Virginie , Andrieu-Abadie Nathalie , Riond Joëlle
Published: August 2024

Keratinocytes are major cellular components of the skin and are strongly involved in its homeostasis. Oncogenic events, starting mainly from excessive sun exposure, lead to the dysregulation of their proliferation and differentiation programs and promote the initiation and progression of non-melanoma skin cancers (NMSCs). Primary melanomas, which originate from melanocytes, initiate and develop in close interaction with keratinocytes, whose role in melanoma initiation, progression, and immune escape is currently being explored. Recent studies highlighted, in particular, unexpected modes of communication between melanocytic cells and keratinocytes, which may be of interest as sources of new biomarkers in melanomagenesis or potential therapeutic targets. This review aims at reporting the various contributions of keratinocytes in skin basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and melanoma, with a greater focus on the latter in order to highlight some recent breakthrough findings. The readers are referred to recent reviews when contextual information is needed.
Investigating Genetic Overlap between Alzheimer’s Disease, Lipids, and Coronary Artery Disease: A Large-Scale Genome-Wide Cross Trait Analysis
Authors: Kirby Artika , Porter Tenielle , Adewuyi Emmanuel O. , Laws Simon M.
Published: August 2024

There is evidence to support a link between abnormal lipid metabolism and Alzheimer’s disease (AD) risk. Similarly, observational studies suggest a comorbid relationship between AD and coronary artery disease (CAD). However, the intricate biological mechanisms of AD are poorly understood, and its relationship with lipids and CAD traits remains unresolved. Conflicting evidence further underscores the ongoing investigation into this research area. Here, we systematically assess the cross-trait genetic overlap of AD with 13 representative lipids (from eight classes) and seven CAD traits, leveraging robust analytical methods, well-powered large-scale genetic data, and rigorous replication testing. Our main analysis demonstrates a significant positive global genetic correlation of AD with triglycerides and all seven CAD traits assessed—angina pectoris, cardiac dysrhythmias, coronary arteriosclerosis, ischemic heart disease, myocardial infarction, non-specific chest pain, and coronary artery disease. Gene-level analyses largely reinforce these findings and highlight the genetic overlap between AD and three additional lipids: high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), and total cholesterol. Moreover, we identify genome-wide significant genes (Fisher’s combined p value [FCPgene] < 2.60 × 10−6) shared across AD, several lipids, and CAD traits, including WDR12, BAG6, HLA-DRA, PHB, ZNF652, APOE, APOC4, PVRL2, and TOMM40. Mendelian randomisation analysis found no evidence of a significant causal relationship between AD, lipids, and CAD traits. However, local genetic correlation analysis identifies several local pleiotropic hotspots contributing to the relationship of AD with lipids and CAD traits across chromosomes 6, 8, 17, and 19. Completing a three-way analysis, we confirm a strong genetic correlation between lipids and CAD traits—HDL and sphingomyelin demonstrate negative correlations, while LDL, triglycerides, and total cholesterol show positive correlations. These findings support genetic overlap between AD, specific lipids, and CAD traits, implicating shared but non-causal genetic susceptibility. The identified shared genes and pleiotropic hotspots are valuable targets for further investigation into AD and, potentially, its comorbidity with CAD traits.
Development of a Bmi1+ Cardiac Mouse Progenitor Immortalized Model to Unravel the Relationship with Its Protective Vascular Endothelial Niche
Authors: Albericio Guillermo , Higuera Marina , Araque Paula , Sánchez Cristina , Herrero Diego , García-Brenes Miguel A. , Formentini Laura , Torán José Luis , Mora Carmen , Bernad Antonio
Published: August 2024

The adult mammalian heart has been demonstrated to be endowed with low but real turnover capacity, especially for cardiomyocytes, the key functional cell type. The source, however, of that turnover capacity remains controversial. In this regard, we have defined and characterized a resident multipotent cardiac mouse progenitor population, Bmi1+DR (for Bmi1+ Damage-Responsive cells). Bmi1+DR is one of the cell types with the lowest ROS (Reactive Oxygen Species) levels in the adult heart, being particularly characterized by their close relationship with cardiac vessels, most probably involved in the regulation of proliferation/maintenance of Bmi1+DR. This was proposed to work as their endothelial niche. Due to the scarcity of Bmi1+DR cells in the adult mouse heart, we have generated an immortalization/dis-immortalization model using Simian Vacuolating Virus 40-Large Antigen T (SV40-T) to facilitate their in vitro characterization. We have obtained a heterogeneous population of immortalized Bmi1+DR cells (Bmi1+DRIMM) that was validated attending to different criteria, also showing a comparable sensitivity to strong oxidative damage. Then, we concluded that the Bmi1-DRIMM population is an appropriate model for primary Bmi1+DR in vitro studies. The co-culture of Bmi1+DRIMM cells with endothelial cells protects them against oxidative damage, showing a moderate depletion in non-canonical autophagy and also contributing with a modest metabolic regulation.
Fibrosis-Related microRNAs in Crohn’s Disease with Fibrostenosis and Inflammatory Stenosis
Authors: Jerala Miha , Remic Tinkara , Hauptman Nina , Zidar Nina
Published: August 2024

Crohn’s disease (CD) is frequently complicated by strictures that can be either inflammatory or fibrostenotic. This distinction is important for deciding the best treatment course, but it can be difficult to determine clinically, sometimes even by advanced imaging techniques. We performed miRNA PCR panel screening on pooled samples of ileum with CD fibrostenosis or inflammatory stenosis. Eight miRNAs with profibrotic (miR-93-5p, miR-376c-3p and miR-424-5p), or fibroprotective (miR-133a-3p, miR-133b, miR-193a-5p, miR-335-5p and miR-378a-3p) functions described in the literature were selected for validation on 20 samples each of CD with fibrostenosis or inflammatory stenosis, with a separate sampling of the submucosa and subserosa. The results showed significant differences between the groups in subserosal samples, with upregulation of profibrotic miRNAs and downregulation of fibroprotective miRNAs in fibrostenosis compared to inflammatory stenosis. Only miR-424-5p showed a significant difference in the submucosa. There were significant differences in miRNA expression between subserosa and submucosa. Our results provide further evidence that the major differences between fibrostenosis and inflammatory stenosis are located in the subserosa, which is inaccessible to endoscopic sampling, highlighting the need for cross-sectional imaging or serological markers. We identify several miRNAs previously not connected to fibrosis in CD, which could potentially serve as biomarkers of fibrostenosis.
Infestation of Rice Striped Stem Borer (Chilo suppressalis) Larvae Induces Emission of Volatile Organic Compounds in Rice and Repels Female Adult Oviposition
Authors: Shen Chen , Yu Shan , Tan Xinyang , Luo Guanghua , Yu Zhengping , Ju Jiafei , Yang Lei , Huang Yuxuan , Li Shuai , Ji Rui , Zhao Chunqing , Fang Jichao
Published: August 2024

Plants regulate the biosynthesis and emission of metabolic compounds to manage herbivorous stresses. In this study, as a destructive pest, the pre-infestation of rice striped stem borer (SSB, Chilo suppressalis) larvae on rice (Oryza sativa) reduced the subsequent SSB female adult oviposition preference. Widely targeted volatilomics and transcriptome sequencing were used to identify released volatile metabolic profiles and differentially expressed genes in SSB-infested and uninfested rice plants. SSB infestation significantly altered the accumulation of 71 volatile organic compounds (VOCs), including 13 terpenoids. A total of 7897 significantly differentially expressed genes were identified, and genes involved in the terpenoid and phenylpropanoid metabolic pathways were highly enriched. Correlation analysis revealed that DEGs in terpenoid metabolism-related pathways were likely involved in the regulation of VOC biosynthesis in SSB-infested rice plants. Furthermore, two terpenoids, (−)-carvone and cedrol, were selected to analyse the behaviour of SSB and predators. Y-tube olfactometer tests demonstrated that both (−)-carvone and cedrol could repel SSB adults at higher concentrations; (−)-carvone could simultaneously attract the natural enemies of SSB, Cotesia chilonis and Trichogramma japonicum, and cedrol could only attract T. japonicum at lower concentrations. These findings provide a better understanding of the response of rice plants to SSB and contribute to the development of new strategies to control herbivorous pests.
Obesity-Associated Colorectal Cancer
Authors: Gonzalez-Gutierrez Lucia , Motiño Omar , Barriuso Daniel , de la Puente-Aldea Juan , Alvarez-Frutos Lucia , Kroemer Guido , Palacios-Ramirez Roberto , Senovilla Laura
Published: August 2024

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies.
Engineering of g-C3N4 for Photocatalytic Hydrogen Production: A Review
Authors: Yan Yachao , Meng Qing , Tian Long , Cai Yulong , Zhang Yujuan , Chen Yingzhi
Published: August 2024

Graphitic carbon nitride (g-C3N4)-based photocatalysts have garnered significant interest as a promising photocatalyst for hydrogen generation under visible light, to address energy and environmental challenges owing to their favorable electronic structure, affordability, and stability. In spite of that, issues such as high charge carrier recombination rates and low quantum efficiency impede its broader application. To overcome these limitations, structural and morphological modification of the g-C3N4-based photocatalysts is a novel frontline to improve the photocatalytic performance. Therefore, we briefly summarize the current preparation methods of g-C3N4. Importantly, this review highlights recent advancements in crafting high-performance g-C3N4-based photocatalysts, focusing on strategies like elemental doping, nanostructure design, bandgap engineering, and heterostructure construction. Notably, sophisticated doping techniques have propelled hydrogen production rates to a 104-fold increase. Ingenious nanostructure designs have expanded the surface area by a factor of 26, concurrently extending the fluorescence lifetime of charge carriers by 50%. Moreover, the strategic assembly of heterojunctions has not only elevated charge carrier separation efficiency but also preserved formidable redox properties, culminating in a dramatic hundredfold surge in hydrogen generation performance. This work provides a reliable and brief overview of the controlled modification engineering of g-C3N4-based photocatalyst systems, paving the way for more efficient hydrogen production.
Protein Language Models and Machine Learning Facilitate the Identification of Antimicrobial Peptides
Authors: Medina-Ortiz David , Contreras Seba , Fernández Diego , Soto-García Nicole , Moya Iván , Cabas-Mora Gabriel , Olivera-Nappa Álvaro
Published: August 2024

Peptides are bioactive molecules whose functional versatility in living organisms has led to successful applications in diverse fields. In recent years, the amount of data describing peptide sequences and function collected in open repositories has substantially increased, allowing the application of more complex computational models to study the relations between the peptide composition and function. This work introduces AMP-Detector, a sequence-based classification model for the detection of peptides’ functional biological activity, focusing on accelerating the discovery and de novo design of potential antimicrobial peptides (AMPs). AMP-Detector introduces a novel sequence-based pipeline to train binary classification models, integrating protein language models and machine learning algorithms. This pipeline produced 21 models targeting antimicrobial, antiviral, and antibacterial activity, achieving average precision exceeding 83%. Benchmark analyses revealed that our models outperformed existing methods for AMPs and delivered comparable results for other biological activity types. Utilizing the Peptide Atlas, we applied AMP-Detector to discover over 190,000 potential AMPs and demonstrated that it is an integrative approach with generative learning to aid in de novo design, resulting in over 500 novel AMPs. The combination of our methodology, robust models, and a generative design strategy offers a significant advancement in peptide-based drug discovery and represents a pivotal tool for therapeutic applications.
Which Signal-to-Noise Ratio Is Used in Simulations? Transmitter Side versus Receiver Side: A Study Based on Long Term Evolution Downlink Transmission
Authors: Liu Yu-Sun , You Shingchern D. , Jhan Zong-Ru , Li Meng-Fan
Published: August 2024

The bit error rate (BER) in relation to the signal-to-noise ratio (SNR) serves as a widely recognized metric for assessing the performance of communication systems. The concept of SNR is so integral that many existing studies presume its definition to be understood, often omitting the specifics of its calculation in their simulations. Notably, the computation of SNR from the perspective of the transmitter yields distinct behaviors and outcomes compared to that from the receiver’s side, particularly when the channel encompasses more than mere noise. Typically, research papers utilize the transmitter-side (or ensemble-average) SNR to benchmark the BER performance across various methodologies. Conversely, the receiver-side (or short-term) SNR becomes pertinent when prioritizing the receiver’s performance. In the context of simulating the long-term evolution (LTE) downlink, applying both SNR calculation approaches reveals that the receiver-side SNR not only produces a significantly lower BER compared to the transmitter-side SNR but also alters the relative BER performance rankings among the channel models tested. It is deduced that while the transmitter-side SNR is apt for broad performance comparisons, it falls short in thoroughly examining the BER behavior of a receiver across varying SNR scenarios. Therefore, the transmitter-side SNR is useful when comparing the performance of the simulated system with other studies. Conversely, if the primary concern is the actual BER performance of the receiver, the receiver-side SNR could provide a more accurate performance assessment.
AI-Driven QoS-Aware Scheduling for Serverless Video Analytics at the Edge
Authors: Giagkos Dimitrios , Tzenetopoulos Achilleas , Masouros Dimosthenis , Xydis Sotirios , Catthoor Francky , Soudris Dimitrios
Published: August 2024

Today, video analytics are becoming extremely popular due to the increasing need for extracting valuable information from videos available in public sharing services through camera-driven streams in IoT environments. To avoid data communication overheads, a common practice is to have computation close to the data source rather than Cloud offloading. Typically, video analytics are organized as separate tasks, each with different resource requirements (e.g., computational- vs. memory-intensive tasks). The serverless computing paradigm forms a promising approach for mapping such types of applications, enabling fine-grained deployment and management in a per-function, and per-device manner. However, there is a tradeoff between QoS adherence and resource efficiency. Performance variability due to function co-location and prevalent resource heterogeneity make maintaining QoS challenging. At the same time, resource efficiency is essential to avoid waste, such as unnecessary power consumption and CPU reservation. In this paper, we present Darly, a QoS-, interference- and heterogeneity-aware Deep Reinforcement Learning-based Scheduler for serverless video analytics deployments on top of distributed Edge nodes. The proposed framework incorporates a DRL agent that exploits performance counters to identify the levels of interference and the degree of heterogeneity in the underlying Edge infrastructure. It combines this information along with user-defined QoS requirements to improve resource allocations by deciding the placement, migration, or horizontal scaling of serverless functions. We evaluate Darly on a typical Edge cluster with a real-world workflow composed of commonly used serverless video analytics functions and show that our approach achieves efficient scheduling of the deployed functions by satisfying multiple QoS requirements for up to 91.6% (Profile-based) of the total requests under dynamic conditions.
Boosting the Performance of Lithium-Sulfur Batteries with PY−DHBD−COF-Enhanced Separators
Authors: He Hong , Wang Wei , Guo Xiaobei
Published: August 2024

Lithium–sulfur batteries (LSBs) hold promise for use in next-generation high-energy-density energy storage systems. However, the commercial application of LSBs is hindered by the shuttle effect of polysulfides. In this study, we synthesized a covalent organic framework material (PY−DHBD−COF) and employed it to modify the separators of LSBs in order to buffer the shuttle effect of polysulfides. A modified separator, involving PY−DHBD−COF coating of the commercial Celgard 2500 PP separator, is prepared via a vacuum-assisted self-assembly method. The PY−DHBD−COF features hydroxyl and imine bonds, which can adsorb lithium polysulfides (LiPSs) and buffer the shuttle effect. The PY−DHBD−COF coating exhibits a thin thickness and oriented nanochannels, facilitating electrolyte wetting and Li+ transport. As a result, the LSBs with PY−DHBD−COF-modified separators exhibit a high specific capacity of 373 mAh g−1 at 4 C with only 0.005% capacity decay per cycle after 450 cycles at 2 C, demonstrating an excellent cycling performance.
Investigating the Influence of Anthropogenic Activities on Behavioral Changes of an Orb Web Spider (Neoscona vigilans)
Authors: Bilal Ahmad , Butt Abida , Kazam Adeel , Ali Shakir , Isha  , Chang Young-Cheol
Published: August 2024

Orb web spiders are common and highly diversified animals found in almost all habitats. They have remarkable plasticity against biotic and abiotic factors, making them excellent indicators of environmental health. The web creation behavior of spiders is influenced by disturbances in the environment. The aim of this research was to observe the alteration in the web-building behavior of Neoscona vigilans caused by human activities, specifically traffic disturbances. Spider webs were located and photographed at nighttime along the roadside, and their web characteristics were calculated. Spiders were captured from webs for their body measurements. Spider fourth leg length, carapace width, and body length had a significant association with web size and diameter, CTL, capture area, and mesh size. The quantity of trapped prey, the height of the plant, and the foliage radius increased with the distance from the road. Conversely, anchor points and web elevation from the ground dropped. The highest and lowest proportions of anomalies (modifications/defects) were recorded as holes (52.7%) in 105 webs (100%) and supernumerary (0.7%) in 55 webs (52.4%), respectively. Road disturbance had a negative influence on the spider’s behavior as the webs formed in close proximity to the road had a higher frequency of anomalies, with a gradual decrease distantly. We can gain further insight into how different environmental changes, disruptions, and pollutants lead to this imperfection in the otherwise flawless perfect structure of spider webs.
Microorganism Contribution to Mass-Reared Edible Insects: Opportunities and Challenges
Authors: Carpentier Joachim , Abenaim Linda , Luttenschlager Hugo , Dessauvages Kenza , Liu Yangyang , Samoah Prince , Francis Frédéric , Caparros Megido Rudy
Published: August 2024

The interest in edible insects’ mass rearing has grown considerably in recent years, thereby highlighting the challenges of domesticating new animal species. Insects are being considered for use in the management of organic by-products from the agro-industry, synthetic by-products from the plastics industry including particular detoxification processes. The processes depend on the insect’s digestive system which is based on two components: an enzymatic intrinsic cargo to the insect species and another extrinsic cargo provided by the microbial community colonizing—associated with the insect host. Advances have been made in the identification of the origin of the digestive functions observed in the midgut. It is now evident that the community of microorganisms can adapt, improve, and extend the insect’s ability to digest and detoxify its food. Nevertheless, edible insect species such as Hermetia illucens and Tenebrio molitor are surprisingly autonomous, and no obligatory symbiosis with a microorganism has yet been uncovered for digestion. Conversely, the intestinal microbiota of a given species can take on different forms, which are largely influenced by the host’s environment and diet. This flexibility offers the potential for the development of novel associations between insects and microorganisms, which could result in the creation of synergies that would optimize or expand value chains for agro-industrial by-products, as well as for contaminants.