bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of PGRP Family in Polymorphic Worker Castes of Solenopsis invicta
Authors: Zhu Zhanpeng , Wu Hongxin , Lin Liangjie , Li Ao , Kang Zehong , Zhang Jie , Jin Fengliang , Xu Xiaoxia
Published: November 2024

Peptidoglycan recognition proteins (PGRPs) are a class of pattern recognition receptors (PRRs) that activate the innate immune system in response to microbial infection by detection of peptidoglycan, a distinct component of bacterial cell walls. Bioinformatic studies have revealed four PGRPs in the red imported fire ant Solenopsis invicta; nonetheless, the mechanism of the immune response of S. invicta induced by pathogens is still poorly understood. The peptidoglycan recognition protein full-length cDNA (designated as SiPGRP-S1/S2/S3/L) from S. invicta was used in this investigation. According to the sequencing analysis, there was a significant degree of homology between the anticipated amino acid sequence of SiPGRPs and other members of the PGRPs superfamily. Molecular docking studies demonstrated that SiPGRPs show strong binding affinity for a variety of PGN substrates. Additionally, tissue distribution analysis indicated that SiPGRPs are primarily expressed in several tissues of naïve larvae, including fat body, hemocytes, head, and thorax, as detected by quantitative real-time PCR (RT-qPCR). Microbial challenges resulted in variable changes in mRNA levels across different tissues. Furthermore, the antibacterial effects of antimicrobial peptides (AMPs) produced by major ants infected with Metarhizium anisopliae were assessed. These AMPs demonstrated inhibitory effects against M. anisopliae, Staphylococcus aureus, and Escherichia coli, with the most pronounced effect observed against E. coli. In conclusion, SiPGRPs act as pattern recognition receptors (PRRs) that identify pathogens and initiate the expression of AMPs in S. invicta, this mechanism contributes to the development of biopesticides designed for the targeted control of invasive agricultural pests.
Sulfonamide-Based Inhibition of the β-Carbonic Anhydrase from A. baumannii, a Multidrug-Resistant Bacterium
Authors: Luca Viviana De , Giovannuzzi Simone , Capasso Clemente , Supuran Claudiu T.
Published: November 2024

Acinetobacter baumannii is a Gram-negative opportunistic pathogen responsible for severe hospital-associated infections. Owing to its ability to develop resistance to a wide range of antibiotics, novel therapeutic strategies are urgently needed. One promising approach is to target bacterial carbonic anhydrases (CAs; EC 4.2.1.1), which are enzymes critical for various metabolic processes. The genome of A. baumannii encodes a β-CA (βAbauCA), which is essential for producing bicarbonate ions required in the early stages of uridine triphosphate (UTP) synthesis, a precursor for the synthesis of peptidoglycans, which are vital components of the bacterial cell wall. This study aimed to inhibit βAbauCA in vitro, with the potential to impair the vitality of the pathogen in vivo. We conducted sequence and structural analyses of βAbauCA to explore its differences from those of human CAs. Additionally, kinetic and inhibition studies were performed to investigate the catalytic efficiency of βAbauCAβ and its interactions with sulfonamides and their bioisosteres, classical CA inhibitors. Our results showed that βAbauCA has a turnover rate higher than that of hCA I but lower than that of hCA II and displays distinct inhibition profiles compared to human α-CAs. Based on the obtained data, there are notable differences between the inhibition profiles of the human isoforms CA I and CA II and bacterial βAbauCA. This could open the door to designing inhibitors that selectively target bacterial β-CAs without affecting human α-CAs, as well as offer a novel strategy to weaken A. baumannii and other multidrug-resistant pathogens.
Molecular Roles of NADPH Oxidase-Mediated Oxidative Stress in Alzheimer’s Disease: Isoform-Specific Contributions
Authors: Kim Junhyung , Moon Jong-Seok
Published: November 2024

Oxidative stress is linked to the pathogenesis of Alzheimer’s disease (AD), a neurodegenerative disorder marked by memory impairment and cognitive decline. AD is characterized by the accumulation of amyloid-beta (Aβ) plaques and the formation of neurofibrillary tangles (NFTs) of hyperphosphorylated tau. AD is associated with an imbalance in redox states and excessive reactive oxygen species (ROS). Recent studies report that NADPH oxidase (NOX) enzymes are significant contributors to ROS generation in neurodegenerative diseases, including AD. NOX-derived ROS aggravates oxidative stress and neuroinflammation during AD. In this review, we provide the potential role of all NOX isoforms in AD pathogenesis and their respective structural involvement in AD progression, highlighting NOX enzymes as a strategic therapeutic target. A comprehensive understanding of NOX isoforms and their inhibitors could provide valuable insights into AD pathology and aid in the development of targeted treatments for AD.
Functional Characterization of the 14-3-3 Gene Family in Alfalfa and the Role of MsGRF2 in Drought Response Mechanisms
Authors: Chai Lu , Liu Yuxuan , Sun Jiuding , Duan Xinhang , Yang Mei , Qian Kailin , Zhang Pan
Published: November 2024

Drought stress affects crop growth and development, significantly reducing crop yield and quality. Alfalfa (Medicago sativa L.), the most widely cultivated forage crop, is particularly susceptible to drought. The general regulatory factor (GRF) protein 14-3-3, a highly conserved family in plants, specifically recognizes and binds to phosphoserine residues in target proteins, regulating both plant development and responses to environmental stressors. In this study, 66 alfalfa 14-3-3 proteins were identified, and the full-length MsGRF2 gene was cloned and functionally analyzed. The expression of MsGRF2 was highest in alfalfa inflorescences and lowest in roots. Transgenic tobacco overexpressing MsGRF2 exhibited increased tolerance to low temperature and drought stress, evidenced by physiological indicators including low levels of active oxygen species and increased activity of antioxidant enzymes and osmoregulatory substances. Under drought stress conditions, compared to wild-type plants, MsGRF2-overexpressing tobacco plants exhibited significantly increased expression of drought stress-related genes ERD10B and TIP, while the expression of BRI1, Cu/Zn-SOD, ERF2, and KC1 was significantly reduced. Together, these results provide new insights into the roles of the 14-3-3 protein MsGRF2 in plant drought response mechanisms.
Identifying the Shared Metabolite Biomarkers and Potential Intervention Targets for Multiple Sarcopenia-Related Phenotypes
Authors: Luo Jia , Li Jingxian , Wang Weijing , Zhang Ronghui , Zhang Dongfeng
Published: November 2024

The relationship between circulating metabolites and sarcopenia-related phenotypes remains unclear. We explored the causality between circulating metabolites and sarcopenia-related phenotypes. Instrumental variables for the human metabolome were derived from the recently published GWAS, which included 690 plasma metabolites. Summary statistics for four sarcopenia phenotypes (whole-body lean mass (WBLM), usual walking pace, appendicular lean mass (ALM), and handgrip strength (HGS)) (both sexes, males and females) were obtained from relevant GWASs. We used MR to evaluate the association between circulating metabolites and sarcopenia-related phenotypes. Colocalization analysis was utilized to determine whether two associated signals were consistent with a shared causal variant rather than the confounding effect of linkage disequilibrium. Subsequently, we explored associations between modifiable risk factors and sarcopenia-related metabolites to explore which metabolites may serve as potential intervention targets through lifestyle modification. Genetically predicted plasma levels of 95 known metabolites were associated with sarcopenia-related phenotypes, and 27 metabolites were supported by robust evidence of colocalization, among which 13 metabolites had a cross-sarcopenia effect. These metabolites primarily included acyl carnitines, amino acids and their derivatives, and phospholipids. Specifically, our analyses supported causal relationships between 23, 6, and 15 metabolites and ALM, HGS, and WBLM, respectively. Seven relevant metabolites might be associated with six modifiable factors. We identified 27 metabolite biomarkers with robust causal evidence for sarcopenia-related phenotypes, highlighting 13 metabolites with a cross-sarcopenia effect, and prioritized several metabolites as the potential interventional targets of lifestyle changes. Our study provided new insight into the etiology and prevention of sarcopenia.
From Fundamentals to Innovation in Alzheimer’s Disease: Molecular Findings and Revolutionary Therapies
Authors: Sighencea Mădălina Georgeta , Popescu Ramona Ștefania , Trifu Simona Corina
Published: November 2024

Alzheimer’s disease (AD) is a global health concern and the leading cause of dementia in the elderly. The prevalence of this neurodegenerative condition is projected to increase concomitantly with increased life expectancy, resulting in a significant economic burden. With very few FDA-approved disease-modifying drugs available for AD, there is an urgent need to develop new compounds capable of impeding the progression of the disease. Given the unclear etiopathogenesis of AD, this review emphasizes the underlying mechanisms of this condition. It explores not only well-studied aspects, such as the accumulation of Aβ plaques and neurofibrillary tangles, but also novel areas, including glymphatic and lymphatic pathways, microbiota and the gut–brain axis, serotoninergic and autophagy alterations, vascular dysfunction, the metal hypothesis, the olfactory pathway, and oral health. Furthermore, the potential molecular targets arising from all these mechanisms have been reviewed, along with novel promising approaches such as nanoparticle-based therapy, neural stem cell transplantation, vaccines, and CRISPR-Cas9-mediated genome editing techniques. Taking into account the overlap of these various mechanisms, individual and combination therapies emerge as the future direction in the AD strategy.
Influence of the Nucleo-Shuttling of the ATM Protein on the Response of Skin Fibroblasts from Marfan Syndrome to Ionizing Radiation
Authors: Jakubowska Dagmara , Al-Choboq Joëlle , Sonzogni Laurène , Bourguignon Michel , Slonina Dorota , Foray Nicolas
Published: November 2024

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder affecting multiple systems, such as skeletal, cardiovascular, and ocular systems. MFS is predominantly caused by mutations in the FBN1 gene, which encodes the fibrillin-1 protein, crucial for connective-tissue integrity. FBN1 mutations lead to defective fibrillin, resulting in structurally compromised connective tissues. Additionally, these mutations cause aberrant TGF-β expression, contributing to vascular issues and increased susceptibility to radiation-induced fibrosis. Studies about the potential radiosensitivity of MFS are rare and generally limited to case reports. Here, we aimed to investigate the radiation-induced ATM nucleo-shuttling (RIANS) model to explore the molecular and cellular radiation response in fibroblasts from MFS patients. The results showed that the MFS fibroblast cell lines tested are associated with moderate but significant radiosensitivity, high yield of micronuclei, and impaired recognition of DNA double-strand breaks (DSBs) caused by a diminished RIANS. The diminished RIANS is supported by the sequestration of ATM protein in the cytoplasm not only by mutated FBN1 protein but also by overexpressed TGF-β. This report is the first molecular and cellular characterization of the radiation response of MFS fibroblasts and highlights the importance of the FBN1-TGF-β complex after irradiation.
Roscovitine, a CDK Inhibitor, Reduced Neuronal Toxicity of mHTT by Targeting HTT Phosphorylation at S1181 and S1201 In Vitro
Authors: Liu Hongshuai , McCollum Ainsley , Krishnaprakash Asvini , Ouyang Yuxiao , Shi Tianze , Ratovitski Tamara , Jiang Mali , Duan Wenzhen , Ross Christopher A. , Jin Jing
Published: November 2024

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a single mutation in the huntingtin gene (HTT). Normal HTT has a CAG trinucleotide repeat at its N-terminal within the range of 36. However, once the CAG repeats exceed 37, the mutant gene (mHTT) will encode mutant HTT protein (mHTT), which results in neurodegeneration in the brain, specifically in the striatum and other brain regions. Since the mutation was discovered, there have been many research efforts to understand the mechanism and develop therapeutic strategies to treat HD. HTT is a large protein with many post-translational modification sites (PTMs) and can be modified by phosphorylation, acetylation, methylation, sumoylation, etc. Some modifications reduced mHTT toxicity both in cell and animal models of HD. We aimed to find the known kinase inhibitors that can modulate the toxicity of mHTT. We performed an in vitro kinase assay using HTT peptides, which bear different PTM sites identified by us previously. A total of 368 kinases were screened. Among those kinases, cyclin-dependent kinases (CDKs) affected the serine phosphorylation on the peptides that contain S1181 and S1201 of HTT. We explored the effect of CDK1 and CDK5 on the phosphorylation of these PTMs of HTT and found that CDK5 modified these two serine sites, while CDK5 knockdown reduced the phosphorylation of S1181 and S1201. Modifying these two serine sites altered the neuronal toxicity induced by mHTT. Roscovitine, a CDK inhibitor, reduced the p-S1181 and p-S1201 and had a protective effect against mHTT toxicity. We further investigated the feasibility of the use of roscovitine in HD mice. We confirmed that roscovitine penetrated the mouse brain by IP injection and inhibited CDK5 activity in the brains of HD mice. It is promising to move this study to in vivo for pre-clinical HD treatment.
Identifying Herbal Candidates and Active Ingredients Against Postmenopausal Osteoporosis Using Biased Random Walk on a Multiscale Network
Authors: Jang Boyun , Kim Youngsoo , Song Jungbin , Kim Young-Woo , Lee Won-Yung
Published: November 2024

Postmenopausal osteoporosis is a major global health concern, particularly affecting aging women, and necessitates innovative treatment options. Herbal medicine, with its multi-compound, multi-target characteristics, offers a promising approach for complex diseases. In this study, we applied multiscale network and random walk-based analyses to identify candidate herbs and their active ingredients for postmenopausal osteoporosis, focusing on their underlying mechanisms. A dataset of medicinal herbs, their active ingredients, and protein targets was compiled, and diffusion profiles were calculated to assess the propagation effects. Through correlation analysis, we prioritized herbs based on their relevance to osteoporosis, identifying the top candidates like Benincasae Semen, Glehniae Radix, Corydalis Tuber, and Houttuyniae Herba. Gene Set Enrichment Analysis (GSEA) revealed that the 49 core protein targets of these herbs were significantly associated with pathways related to inflammation, osteoclast differentiation, and estrogen metabolism. Notably, compounds such as falcarindiol from Glehniae Radix and tetrahydrocoptisine from Corydalis Tuber—previously unstudied for osteoporosis—were predicted to interact with inflammation-related proteins, including IL6, IL1B, and TNF, affecting key biological processes like apoptosis and cell proliferation. This study advances the understanding of herbal therapies for osteoporosis and offers a framework for discovering novel therapeutic agents.
Genome-Wide Identification and Expression Analysis of the Alfalfa (Medicago sativa L.) U-Box Gene Family in Response to Abiotic Stresses
Authors: Li Shuaixian , Chen Xiuhua , Guo Meiyan , Zhu Xiaoyue , Huang Wangqi , Guo Changhong , Shu Yongjun
Published: November 2024

E3 ubiquitin ligases known as plant U-box (PUB) proteins regulate a variety of aspects of plant growth, development, and stress response. However, the functions and characteristics of the PUB gene family in alfalfa remain unclear. This work involved a genome-wide examination of the alfalfa U-box E3 ubiquitin ligase gene. In total, 210 members were identified and divided into five categories according to their homology with the members of the U-box gene family in Arabidopsis thaliana. The phylogenetic analysis, conserved motifs, chromosomal localization, promoters, and regulatory networks of this gene were investigated. Chromosomal localization and covariance analyses indicated that the MsPUB genes expanded MsPUB gene family members through gene duplication events during evolution. MsPUB genes may be involved in the light response, phytohormone response, growth, and development of several biological activities, according to cis-acting element analysis of promoters. In addition, transcriptome analysis and expression analysis by qRT-PCR indicated that most MsPUB genes were significantly upregulated under cold stress, drought stress, and salt stress treatments. Among them, MsPUBS106 and MsPUBS185 were significantly and positively correlated with cold resistance in alfalfa. MsPUBS110, MsPUBS067, MsPUBS111 and MsPUB155 were comprehensively involved in drought stress, low temperature, and salt stress resistance. All things considered, these discoveries offer fresh perspectives on the composition, development, and roles of the PUB gene family in alfalfa. They also provide theoretical guidance for further investigations into the mechanisms regulating the development, evolution, and stress tolerance of MsPUB.
Association of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) Genetic Variants with Risk and Outcome of Cutaneous Melanoma
Authors: Ferreira Ana Maria Castro , Carron Juliana , Gomez Gabriela Vilas Bôas , Vazquez Vinicius de Lima , Serrano Sergio Vicente , Lourenço Gustavo Jacob , Lima Carmen Silvia Passos
Published: November 2024

This study aimed to verify whether germline single nucleotide variants (SNV) in CTLA-4 gene, c.-1765C>T, c.-1661A>G, c.-1577G>A, and c.-1478G>A, influence the risk, clinicopathological aspects, and survival of patients with CM, as well as its functional consequences. A total of 432 patients with CM and 504 controls were evaluated. CTLA-4 genotypes were identified by real-time polymerase chain reaction (RT-PCR) and expression of CTLA-4 by quantitative PCR (qPCR) and luciferase assay. Cell cycle, proliferation, apoptosis/necrosis, and migration analyses were performed in SK-MEL-28 and A-375 cell lines modified to present homozygous ancestral or variant genotypes by CRISPR technique. Individuals with the CTLA-4 c.-1577 AA genotype and the combined CTLA-4 c.-1577 and c.-1478 AA + AA genotypes were at 1.60- and 3.12-fold higher risk of developing CM, respectively. The CTLA-4 c.-1577 AA genotype was seen as an independent predictor of worse event-free survival and was also associated with higher gene expression, higher cell proliferation, lower cell apoptosis, and higher cell migration. Our data present, for the first time, evidence that CTLA-4 c.-1577G>A alters the risk and clinical aspects of CM treated with conventional procedures and may be used for selecting individuals for tumor prevention and patients for distinct treatment.
De Novo RB1 Germline Variant in Retinoblastoma with Two Subsequent Independent Neoplasms: Case Report and Literature Review
Authors: Pérez-Becerra José de Jesús , Rodríguez-Machuca Víctor Ulises , González-Rodríguez María Teresa Alejandra , Brukman-Jiménez Sinhue Alejandro , Corona-Rivera Alfredo , Ramirez-Corona Juan Antonio , Cuero-Quezada Idalid , Corona-Rivera Jorge Román , Ramírez-Urenda Xóchitl Aurora , González-Pérez Graciela , Bustos-Rodríguez Felipe de Jesús , Bobadilla-Morales Lucina
Published: November 2024

Variants in the RB1 gene are associated with retinoblastoma (RB) development, and their presence in germline cells considerably increases the risk of subsequent malignant neoplasms (SMNs) in RB survivors. We report a female patient with bilateral RB who developed two SMNs in less than ten years, with a de novo pathogenic nonsense variant in RB1 [NM_000321.3:c.306T>A, p.(Cys102*)] in heterozygosity. The updated literature review of similar cases of SMN in patients with a previous diagnosis of RB reveals a wide range in both the type of subsequent malignancy and the age at which these SMNs develop. In addition, we identified only three cases with two SMNs following RB diagnosis, with at least one of these being an EWS. This case broadens the clinical and genetic landscape of RB, demonstrates the importance of a multidisciplinary approach in these patients, and highlights genetic diagnosis as a mandatory feature for management.
Molecular Mechanisms of Heterosis and Its Applications in Tree Breeding: Progress and Perspectives
Authors: Li Zeyu , Zhao Yan , Luo Keming
Published: November 2024

Heterosis, or hybrid vigor, refers to the phenomenon where hybrid progenies outperform their parents in traits such as yield and resistance. This phenomenon has been widely applied in plant breeding. Recent advances in high-throughput genomics have significantly advanced our understanding of heterosis. This review systematically summarizes the genetic, molecular, and epigenetic mechanisms underlying heterosis. Furthermore, we discuss recent advances in predictive methods for heterosis and their applications in improving growth rate, resistance to abiotic stresses, and wood yield in tree species. We also explore the role of tree genomics in unraveling the mechanisms underlying heterosis, emphasizing the potential of integrating high-resolution genomics, single-cell sequencing, and spatial transcriptomics to achieve a comprehensive understanding of heterosis from the molecular to spatial levels. Building on this, CRISPR-based gene-editing technologies can be employed to precisely edit heterotic loci, enabling the study of allele function. Additionally, molecular marker-assisted selection (MAS) can be utilized to identify heterotic loci in parental lines, facilitating the selection of optimal hybrid combinations and significantly reducing the labor and time costs of hybrid breeding. Finally, we review the utilization of heterosis in tree breeding and provide a forward-looking perspective on future research directions, highlighting the potential of integrating multi-omics approaches and emerging gene-editing tools to revolutionize tree hybrid breeding.
circARID1A Inhibits Tail Fat Cell Differentiation in Guangling Large-Tailed Sheep by Regulating the miR-493-3p/YTHDF2 Axis
Authors: Shen Yan , Liang Yu , Yuan Zikun , Qiao Liying , Liu Jianhua , Pan Yangyang , Yang Kaijie , Liu Wenzhong
Published: November 2024

The Guangling Large-Tailed sheep is renowned for its unique tail fat deposition, with a significant proportion of its total body fat being localized in the tail region. Fat deposition is a complex biological process regulated by various molecular mechanisms. Our previous studies have identified a large number of differentially expressed circular RNAs (circRNAs) in the tail adipose tissue of the Guangling Large-Tailed sheep. These circRNAs may play a pivotal role in the process of fat deposition. Given the potential regulatory functions of circRNAs in adipose metabolism, investigating their roles in tail fat deposition is of significant scientific importance. In this study, we identified novel circARID1A. Using various experimental methods, including lentivirus infection, RNase R treatment, actinomycin D assay, qPCR, western blotting, and dual-luciferase reporter assays, we determined that circARID1A inhibits the expression of miR-493-3p through competitive binding, thereby regulating adipocyte differentiation. Further research revealed that miR-493-3p promotes adipocyte differentiation by targeting YTH domain family 2 (YTHDF2), and this regulatory effect is also influenced by circARID1A. In conclusion, our findings suggest that circARID1A inhibits tail fat cell differentiation in the Guangling Large-Tailed sheep through the circARID1A/miR-493-3p/YTHDF2 axis, providing theoretical support for improving meat quality and fat deposition in sheep.
Effects of Two Decellularization Protocols on the Mechanical Behavior and Structural Properties of the Human Urethra
Authors: Kuniakova Marcela , Novakova Zuzana Varchulova , Haspinger Daniel , Niestrawska Justyna Anna , Klein Martin , Galfiova Paulina , Kovac Jan , Palkovic Michal , Danisovic Lubos , Hammer Niels , Ziaran Stanislav
Published: November 2024

This study evaluates the effects of two decellularization protocols, enzyme-detergent (ED) and detergent-detergent (DD), on the structural and biomechanical properties of human urethral tissue. Urethral samples from 18 individuals were divided into ED (n = 7) and DD (n = 11) groups, with native samples (n = 3) serving as controls. Histological and ultrastructural analyses confirmed that both protocols effectively removed cellular content while preserving essential extracellular matrix (ECM) elements, such as collagen and elastic fibers. Immunohistochemical staining for collagen IV and fibronectin revealed no significant differences between decellularized and native tissues, indicating intact ECM structure. Biomechanical testing demonstrated that DD-treated tissues had significantly lower Cauchy stress (1494.8 ± 518.4 kPa) when compared to native tissues (2439.7 ± 578.7 kPa, p = 0.013), while ED-treated tissues were similar to both groups. Both decellularized groups exhibited reduced stretch at failure and elastic modulus compared to native tissues. Cytotoxicity assays using adipose-derived stem cells demonstrated no signs of toxicity in either protocol. Overall, both ED and DD protocols effectively preserved the urethral ECM structure and mechanical properties, making them suitable for potential use in tissue-engineered grafts and for biobanking purposes. Further research is needed to refine and optimize decellularization methods to improve scaffold recellularization and ensure clinical safety and efficacy.
Convergence of Nanotechnology and Machine Learning: The State of the Art, Challenges, and Perspectives
Authors: Tripathy Arnav , Patne Akshata Y. , Mohapatra Subhra , Mohapatra Shyam S.
Published: November 2024

Nanotechnology and machine learning (ML) are rapidly emerging fields with numerous real-world applications in medicine, materials science, computer engineering, and data processing. ML enhances nanotechnology by facilitating the processing of dataset in nanomaterial synthesis, characterization, and optimization of nanoscale properties. Conversely, nanotechnology improves the speed and efficiency of computing power, which is crucial for ML algorithms. Although the capabilities of nanotechnology and ML are still in their infancy, a review of the research literature provides insights into the exciting frontiers of these fields and suggests that their integration can be transformative. Future research directions include developing tools for manipulating nanomaterials and ensuring ethical and unbiased data collection for ML models. This review emphasizes the importance of the coevolution of these technologies and their mutual reinforcement to advance scientific and societal goals.
Untargeted Urinary Volatilomics Reveals Hexadecanal as a Potential Biomarker for Preeclampsia
Authors: Pehlić Marina , Dumančić Stipe , Radan Mila , Galić Jelena , Gruica Branimir , Marijan Sandra , Vulić Marko
Published: November 2024

Preeclampsia (PE) is a severe hypertensive pregnancy disorder characterized by endothelial dysfunction, placental ischemia and oxidative stress; however, reliable non-invasive biomarkers for early detection are limited. In this study, untargeted solid-phase microextraction with gas chromatography–mass spectrometry (SPME-GC-MS) was used to analyze volatile organic compounds in the urine of 45 women with PE and 46 healthy controls. Among the 29 metabolites identified, hexadecanal—a product of lipid peroxidation and sphingolipid metabolism—was found to be the most significant, with an area under the receiver operating characteristic (ROC) curve of 0.618, highlighting its diagnostic potential. This result emphasizes the role of hexadecanal in oxidative stress and placental dysfunction, which are central to the pathophysiology of PE. The results support hexadecanal as a potential non-invasive biomarker while demonstrating the efficacy of SPME-GC-MS in identifying metabolic disorders associated with PE, paving the way for further research to confirm its clinical utility for early diagnosis and risk assessment.
Identification of a New Role of miR-199a-5p as Factor Implied in Neuronal Damage: Decreasing the Expression of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI
Authors: Muñoz-Galdeano Teresa , Reigada David , Soto Altea , Barreda-Manso María Asunción , Ruíz-Amezcua Pablo , Nieto-Díaz Manuel , Maza Rodrigo M.
Published: November 2024

Spinal cord injury (SCI) results in a cascade of primary and secondary damage, with apoptosis being a prominent cause of neuronal cell death. The X-linked inhibitor of apoptosis (XIAP) plays a critical role in inhibiting apoptosis, but its expression is reduced following SCI, contributing to increased neuronal vulnerability. This study investigates the regulatory role of miR-199a-5p on XIAP expression in the context of SCI. Using bioinformatic tools, luciferase reporter assays, and in vitro and in vivo models of SCI, we identified miR-199a-5p as a post-transcriptional regulator of XIAP. Overexpression of miR-199a-5p significantly reduced XIAP protein levels, although no changes were observed at the mRNA level, suggesting translational repression. In vivo, miR-199a-5p expression was upregulated at 3 and 7 days post-injury, while XIAP expression inversely decreased in both neurons and oligodendrocytes, being particularly significant in the latter at 7 dpi. These findings suggest that miR-199a-5p contributes to the downregulation of XIAP and may exacerbate neuronal apoptosis after SCI. Targeting miR-199a-5p could offer a potential therapeutic strategy to modulate XIAP levels and reduce apoptotic cell death in SCI.
Proposed Mechanisms of Cell Therapy for Alzheimer’s Disease
Authors: Belousova Ekaterina , Salikhova Diana , Maksimov Yaroslav , Nebogatikov Vladimir , Sudina Anastasiya , Goldshtein Dmitry , Ustyugov Aleksey
Published: November 2024

Alzheimer’s disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.
Enhancing Recovery of Structural Health Monitoring Data Using CNN Combined with GRU
Authors: Nhung Nguyen Thi Cam , Bui Hoang Nguyen , Minh Tran Quang
Published: November 2024

Structural health monitoring (SHM) plays a crucial role in ensuring the safety of infrastructure in general, especially critical infrastructure such as bridges. SHM systems allow the real-time monitoring of structural conditions and early detection of abnormalities. This enables managers to make accurate decisions during the operation of the infrastructure. However, for various reasons, data from SHM systems may be interrupted or faulty, leading to serious consequences. This study proposes using a Convolutional Neural Network (CNN) combined with Gated Recurrent Units (GRUs) to recover lost data from accelerometer sensors in SHM systems. CNNs are adept at capturing spatial patterns in data, making them highly effective for recognizing localized features in sensor signals. At the same time, GRUs are designed to model sequential dependencies over time, making the combined architecture particularly suited for time-series data. A dataset collected from a real bridge structure will be used to validate the proposed method. Different cases of data loss are considered to demonstrate the feasibility and potential of the CNN-GRU approach. The results show that the CNN-GRU hybrid network effectively recovers data in both single-channel and multi-channel data loss scenarios.
Durability of Steel-Reinforced Concrete Structures Under Effect of Climatic Temporality and Aggressive Agents (CO2, SO2) in Boca del Rio, Veracruz
Authors: González-Moreno Humberto Raymundo , Marín-Muñiz Jose Luis , López-Gonzalez Pablo Julian , Moreno-Vazquez Oscar , Zamora-Castro Sergio Aurelio , Monzón-Reyes Brenda Lizeth , Sangabriel-Lomeli Joaquin
Published: November 2024

The development of sustainable infrastructure is essential to address the challenges of climate change and reduce CO2 emissions. The use of alternative materials, such as agro-industrial ashes and silica fume, emerges as a promising option to enhance the durability of concrete and diminish its environmental impact. These materials can partially replace conventional cement, contributing to the construction of more sustainable infrastructure without compromising performance, even under adverse environmental conditions. In this study, we present an analysis of the use of sugarcane bagasse ash (SBA) and silica fume (SF) as a 15% cement replacement. The behavior of these materials was investigated under coastal conditions, analyzing climatic variables and degrading gases such as CO2, CH4, and N2O. Electrochemical techniques were employed to measure corrosion rate and potential, in addition to conducting carbonation and compressive strength tests. The mixtures with a 15% addition of SBA and SF showed improvements compared to conventional mixes. SBA reduced the corrosion rate by 25% and increased compressive strength by 12% after 150 days, while SF enhanced carbonation resistance by 20% and compressive strength by 25%. The incorporation of SBA and SF provides significant durability in coastal environments, contributing to the sustainability of infrastructure exposed to adverse weather conditions.
Properties, Production, and Recycling of Regenerated Cellulose Fibers: Special Medical Applications
Authors: Varnaitė-Žuravliova Sandra , Baltušnikaitė-Guzaitienė Julija
Published: November 2024

Regenerated cellulose fibers are a highly adaptable biomaterial with numerous medical applications owing to their inherent biocompatibility, biodegradability, and robust mechanical properties. In the domain of wound care, regenerated cellulose fibers facilitate a moist environment conducive to healing, minimize infection risk, and adapt to wound topographies, making it ideal for different types of dressings. In tissue engineering, cellulose scaffolds provide a matrix for cell attachment and proliferation, supporting the development of artificial skin, cartilage, and other tissues. Furthermore, regenerated cellulose fibers, used as absorbable sutures, degrade within the body, eliminating the need for removal and proving advantageous for internal suturing. The medical textile industry relies heavily on regenerated cellulose fibers because of their unique properties that make them suitable for various applications, including wound care, surgical garments, and diagnostic materials. Regenerated cellulose fibers are produced by dissolving cellulose from natural sources and reconstituting it into fiber form, which can be customized for specific medical uses. This paper will explore the various types, properties, and applications of regenerated cellulose fibers in medical contexts, alongside an examination of its manufacturing processes and technologies, as well as associated challenges.
Correction: Jin et al. A pH-Responsive DNA Tetrahedron/Methotrexate Drug Delivery System Used for Rheumatoid Arthritis Treatment. J. Funct. Biomater. 2023, 14, 541
Authors: Jin Yi , Ge Xingyu , Xu Yinjin , Wang Siyi , Lu Qian , Deng Aidong , Li Jingjing , Gu Zhifeng
Published: November 2024

In the original publication [...]
Spherical Shell Bioprinting to Produce Uniform Spheroids with Controlled Sizes
Authors: Son Kuk Hui , Kim Dong-Ha , Park Seunghye , Kim Hyun Jae , Park Mira , Kim Seung-Jin , Lee Sang Jin , Ahn Keunsun , Lee Jin Woo
Published: November 2024

Conventional cell spheroid production methods are largely manual, leading to variations in size and shape that compromise consistency and reliability for use in cell-based therapeutic applications. To enhance spheroid production, a spherical shell bioprinting system was implemented, enabling the high-throughput generation of uniform cell spheroids with precisely controlled sizes. The system encapsulates cells within thin alginate hydrogel shells formed through bioprinting and ion crosslinking reactions. Alginate–calcium ion crosslinking created alginate shells that contained gelatin-based bioinks with embedded cells, facilitating spontaneous cell aggregation within the shells and eliminating the need for plastic wells. By adjusting cell concentrations in the alginate–gelatin bioink, we achieved precise control over spheroid size, maintaining a sphericity above 0.94 and size deviations within ±10 µm. This method has been successfully applied to various cell types including cancer cells, fibroblasts, chondrocytes, and epithelial cells, demonstrating its versatility. This scalable approach enhances the reliability of cell therapy and drug screening, offering a robust platform for future biomedical applications.
China–ASEAN Tourism Economic Relationship Network: A Geopolitical Risk Perspective
Authors: Chen Siyue , Tan Yang , Huang Gengzhi , Zhang Hongou , Li Hang
Published: November 2024

Despite extensive research on the network structure of tourism destinations, literature on the spatial network structure of cross-border tourism–economic connections is relatively limited, specifically the complex geopolitical relationship between China and the Association of Southeast Asian Nations (ASEAN). Thus, in this study we explored the relevant characteristics and influencing factors of the spatial structure of tourism economic networks. The results first indicate that the China–ASEAN tourism economic network exhibits distinct stage characteristics, with an ‘N’-shaped fluctuating growth trend, evolving from a point-like network to a multipolar development in spatial structure. In addition, China demonstrates a distinctive personality in the network and occupies a central leadership position. Secondly, an analysis of influencing factors shows that institutional distance and geographic distance have a significant impact on the network. Geopolitical risk plays a notable indirect moderating role in the network through its association with tourism policies and regulations, tourism promotion, and cooperation. This further reveals the diverse pathways through which geopolitical risk affects the network, providing a novel perspective for research on the tourism economic network.
Study on the Interactions Between Urbanization, Tourism, and the Ecological Environment in Underdeveloped Regions: PVAR Model Analysis Based on Data from 32 Chinese Cities
Authors: Zhang Yizhu , Yan Xiaobin , Xu Jiapeng
Published: November 2024

Clarifying the dynamic relationships between urbanization, tourism development, and the ecological environment in underdeveloped regions can assist local governments in optimizing industrial upgrades and environmental management through effective policy planning, despite resource constraints, thereby promoting high-quality urban development. This study, based on data from 32 cities in northwestern China, constructs a multi-dimensional evaluation system incorporating demographic, economic, social, and environmental indicators. Using a PVAR model, the long-term dynamic interactions between urbanization, tourism, and the ecological environment are explored. The results indicate that, although in the initial stages, the three subsystems can support each other, in the long term, tourism has a positive impact on urbanization and the ecological environment, whereas both urbanization and the ecological environment negatively impact tourism. The interaction effects between urbanization, tourism, and the ecological environment are weak, with contribution rates below 20%, failing to create a synergistic development. The primary reason for this issue is that urbanization development policies lag behind the needs of tourism and ecological environment development. Policy recommendations are provided, including optimizing cross-sector collaboration strategies, enhancing urbanization quality, and prioritizing environmental protection, to foster coordinated development among the three.
Understanding the Best Nutritional Management for Creutzfeldt–Jakob Disease Patients: A Comparison Between East Asian and Western Experiences
Authors: Perna Alessia , Santoro Massimo , Colaizzo Elisa
Published: November 2024

(1) Background: Creutzfeldt–Jakob disease (CJD) is a rare and fatal neurodegenerative disorder caused by the accumulation of an altered prion protein, which usually leads to death within one year after clinical onset. CJD patients usually present with rapid cognitive impairment associated with declines in cerebellar, motor, visual, behavioral, and swallowing functions. Moreover, CJD patients lose their ability to eat and take medications orally very early on in treatment; nevertheless, there are no specific nutritional guidelines for this disease shared worldwide. (2) Methods: This review aims to describe the nutritional outcomes of CJD patients in Western countries to compare them with those described in East Asian countries and then aims to explore the most recent trends in the nutritional management of CJD patients, including some dietary compounds that present neuroprotective effects. (3) Results: In Japan’s, Taiwan’s, and China’s healthcare systems, CJD patients receive intensive life-sustaining treatment that prolongs their survival (i.e., artificial feeding); conversely, in Western countries, intensive life-sustaining treatments like tube feeding are not commonly provided to CJD patients. (4) Conclusions: It is difficult to pinpoint the reasons for these discrepancies around CJD palliative care supply, but it is clear that specific nutritional guidelines may directly improve the nutritional management of CJD patients and thus allow their families and caregivers to ensure the best end-of-life care for these patients.
Economic Justice in the Design of a Sugarcane-Derived Biofuel Supply Chain: A Fair Profit Distribution Approach
Authors: Carvajal Jimmy , Sarache William , Costa Yasel
Published: November 2024

Background: In agricultural supply chains, unequal bargaining power often leads to economic inequality, particularly for farmers. The fair profit distribution (FPD) approach offers a solution by optimizing supply chain flows (materials, information, and money) to promote economic equity among members. However, our literature review highlights a gap in applying the FPD approach to the facility location-allocation problem in supply chain network design (SCND), particularly in sugarcane-derived biofuel supply chains. Methods: Consequently, we propose a multi-period optimization model based on FPD to design a sugarcane biofuel supply chain. The methodology involves four steps: constructing a conceptual model, developing a mathematical model, designing a solution strategy, and generating insights. This model considers both investment (crop development, biorefinery construction) and operational phases over a long-term planning horizon, focusing on farm location and crop allocation. Results: By comparing the FPD model to a traditional centralized planning supply chain (CSC) approach, we examine the impact of the planning horizon, number of farms, and sugarcane prices paid by biorefineries on financial performance. While the FPD model results in lower overall system profits, it fosters a fairer economic scenario for farmers. Conclusions: This study contributes to economic justice in supply chains and offers insights to promote fair trade among stakeholders.
Semantic Categories: Uncertainty and Similarity
Authors: Fabregat-Hernández Ares , Palanca Javier , Botti Vicent
Published: November 2024

This paper addresses understanding and categorizing language by using Markov categories to establish a mathematical framework for semantic concepts. This framework enables us to measure the semantic similarity between linguistic expressions within a given text. Furthermore, this approach enables the measurement and control of uncertainty in language categorization and the creation of metrics for evaluating semantic similarity. We provide use cases to demonstrate how the proposed methods can be applied and computed, focusing on their interpretability and the universality of categorical constructions. This work contributes to the field by offering a novel perspective on semantic similarity and uncertainty metrics in language processing, generating criteria to automate their computation.
Exploring the Relationship Between Lipoprotein (a) Level and Myocardial Infarction Risk: An Observational Study
Authors: Buciu Ionut Cezar , Tieranu Eugen Nicolae , Pircalabu Andreea Stefania , Istratoaie Octavian , Zlatian Ovidiu Mircea , Cioboata Ramona , Donoiu Ionut , Militaru Constantin , Militaru Sebastian , Militaru Cristian
Published: November 2024

Background and Objectives: This observational study investigates the relationship between Lipoprotein (a) (Lp(a)) levels and the risk of acute myocardial infarction (AMI). This study aims to highlight the association of elevated Lipoprotein (a) levels with an increased atherogenic profile and the potential risk of AMI. Materials and Methods: We conducted a case–control study involving 106 individuals, including 64 AMI patients (both STEMI and NSTEMI) and 42 healthy controls. Comprehensive clinical and biochemical assessments, including Lp(a) measurements, were conducted. Results: Patients with Lp(a) levels ≥ 30 mg/dL had a threefold increased risk of AMI compared to those with lower levels, independent of traditional risk factors such as cholesterol, smoking, and body weight. Elevated Lp(a) was observed in 50% of AMI patients compared to 28.57% in controls (p = 0.028). Notably, a multivariate analysis identified high Lp(a) levels, low HDL-C levels, and obesity as significant independent predictors of AMI, indicating these factors may contribute to AMI risk more prominently than other conventional risk factors in patients with elevated Lp(a). Moreover, the association between Lp(a) and AMI risk was consistent across various patient subgroups, with low HDL-C further compounding the risk. Conclusions: Lp(a) is a significant independent risk factor for acute myocardial infarction; therefore, screening for Lp(a) levels can help identify high-risk individuals beyond traditional markers. Therapeutic approaches targeting Lp(a) may reduce AMI incidence. Future research should explore how Lp(a) promotes atherosclerosis and assess Lp(a)-lowering therapies to improve patient outcomes.