bluuebunny/crossref_metadata_2025 huggingface dataset:
ARTP/NTG Compound Mutagenesis Improved the Spinosad Production and the Insecticidal Virulence of Saccharopolyspora Spinosa
Authors: Zhu Zirong , Chen Wangqiong , Cao Li , Xia Ziyuan , Rang Jie , Hu Shengbiao , Xia Liqiu
Published: November 2024

Spinosad is an efficient and broad-spectrum environmentally friendly biopesticide, but its low yield in wild-type Saccharopolyspora spinosa limits its further application. ARTP/NTG compound mutagenesis was used in this study to improve the spinosad titer of S. spinosa and obtain a high-yield mutant—NT24. Compared with the wild-type strain, the fermentation cycle of NT24 was shortened by 2 days and its maximum titer of spinosad reached 858.3 ± 27.7 mg/L, which is 5.12 times more than for the same-period titer of the wild-type strain. In addition, RT-qPCR, resequencing, and targeted metabolomics showed that the upregulation of the key differential genes accD6, fadD, sdhB, oadA, and gntZ caused increased metabolic flux in the tricarboxylic acid cycle and pentose phosphate pathway, suggesting that the accumulation of pyruvate and short-chain acyl-CoA was the primary cause of spinosad accumulation in NT24. This study demonstrates the effectiveness of ARTP mutagenesis in S. spinosa, and provides new insights for the mechanism of spinosad biosynthesis and metabolic engineering in S. spinosa.
Genome-Wide Identification of the ClpB Gene Family in Tomato and Expression Analysis Under Heat Stress
Authors: Zhang Yuemei , Yang Tailai , Han Jiaxi , Su Xiao , Cong Yanqing , Zhou Ming , Wang Yan , Lin Tao
Published: November 2024

Tomato is a widely grown horticultural crop, and its growth process is often affected by high temperatures. Caseinolytic Protease B (ClpB), a homologous protein to heat shock protein 101 (HSP101), plays a vital role in plant heat adaptation and development. In this study, we identified six SlClpB genes in tomatoes, distributed across four chromosomes. Collinearity analysis revealed that the gene pairs SlClpB-2 and SlClpB-3A, as well as SlClpB-3C and SlClpB-12, resulted from segmental duplication events. Phylogenetic and motif analyses showed that ClpB proteins possess highly conserved domains across different species. We used RNA-seq data to analyze the expression patterns of the ClpB family. Among them, SlClpB-3A and SlClpB-12 exhibited increased expression in multiple tissues under heat stress. Specifically, SlClpB-2, SlClpB-3A, and SlClpB-3C were highly expressed in the fruit orange stage and in flower buds under heat treatment, while in seedlings, SlClpB-2 and SlClpB-3A exhibited heat-induced expression. Real-time quantitative fluorescent PCR (qRT-PCR) results showed that the expression of SlClpB-2 and SlClpB-3A was significantly increased under heat stress in the leaves and buds of Ailsa Craig, Micro-Tom, and M82. Overall, our findings provide valuable insights into the regulatory mechanisms of SlClpB genes in response to heat stress.
Anticholinesterase and Anti-Inflammatory Activities of the Essential Oils of Sawdust and Resin-Rich Bark from Azorean Cryptomeria japonica (Cupressaceae): In Vitro and In Silico Studies
Authors: Lima Ana , Arruda Filipe , Frias Jorge , Wortham Tanner , Janeiro Alexandre , Rodrigues Tânia , Baptista José , Lima Elisabete
Published: November 2024

Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder characterized by severe cognitive impairment, affects millions of people worldwide. However, AD therapy remains limited and mainly symptomatic-focused, with acetylcholinesterase (AChE) inhibitors being the major available drugs. Thus, AD is considered by the WHO as a disorder of public health priority. Among several strategies that have been identified to combat AD, the use of natural multi-target drug ligands (MTDLs) appears to be a promising approach. In this context, we previously found that the essential oils (EOs), obtained via hydrodistillation, from Azorean Cryptomeria japonica sawdust (CJS) and resin-rich bark (CJRRB) were able to exert antioxidant activity via different mechanisms of action. Therefore, in the present work, these EOs were screened for their (i) in vitro anti-AChE and anti-butyrylcholinesterase (BChE) activities, evaluated by a modified Ellman’s assay; (ii) in vitro anti-inflammatory potential, using the albumin denaturation method; and (iii) toxicity against Artemia salina. The CJRRB–EO exhibited both anti-AChE and anti-BChE activities (IC50: 1935 and 600 µg/mL, respectively), whereas the CJS–EO only displayed anti-BChE activity, but it was 3.77-fold higher than that of the CJRRB–EO. Molecular docking suggested that α-pinene and ferruginol compounds contributed to the anti-AChE and anti-BChE activities, respectively. Moreover, the anti-inflammatory activity of the CJS–EO, the CJRRB–EO, and diclofenac was 51%, 70%, and 59% (at a concentration of only 2.21 μg/mL), respectively, with the latter two presenting comparable activity. Concerning the EOs’ potential toxicity, the CJRRB–EO exhibited a lower effect than the CJS–EO (LC50: 313 and 73 µg/mL, respectively). Overall, the EOs from C. japonica biomass residues, chiefly the CJRRB–EO, displayed antioxidant, anticholinesterase, and anti-inflammatory activities in a concentration-dependent manner. These properties demonstrate that these residues may be suitable natural MTDLs for AD complementary therapy when administered through aromatherapy, or, alternatively, could serve as low-cost sources of valuable ingredients, such as α-pinene.
Genome-Wide Identification and Analysis of WD40 Family and Its Expression in F. vesca at Different Coloring Stages
Authors: Yang Hongyu , Yao Wenxia , Fan Xiangjun , Lu Yang , Wang Yan , Ma Zonghuan
Published: November 2024

WD40 proteins play important roles in the synthesis and regulation of anthocyanin, the regulation of plant morphology and development, and the response to various abiotic stresses. However, the role of WD40 in Fragaria vesca (F. vesca) has not been studied. In this study, a total of 216 FvWD40 family members were identified, which were divided into four subfamilies based on evolutionary tree analysis. Subcellular localization predictions show that FvWD40 family members are mainly localized in chloroplasts, nuclei, and cytoplasm. An analysis of collinearity revealed a total of eight pairs of intraspecific collinearity of the FvWD40 gene family, and interspecific collinearity showed that the FvWD40 gene family covaried more gene pairs with Arabidopsis thaliana (Arabidopsis) than with rice (Oryza sativa). Promoter cis-acting elements revealed that the FvWD40 gene family contains predominantly light, hormone, and abiotic stress response elements. Tissue-specific expression analysis showed that a number of members including FvWD40-111 and FvWD40-137 were highly expressed in all tissues, and a number or members including FvWD40-97 and FvWD40-102 were lowly expressed in all tissues. The FvWD40 gene family was found to be expressed at all four different coloring stages of F. vesca by qRT-PCR, with lower expression at the 50% coloring stage (S3). FvWD40-24, FvWD40-50, and FvWD40-60 showed the highest expression during the white fruit stage (S1) period, suggesting that these genes play a potential regulatory role in the pre-fruit coloring stage. FvWD40-62, FvWD40-88 and FvWD40-103 had the highest expression at the 20% coloration stage (S2), and FvWD40-115, FvWD40-170, FvWD40-184 and FvWD40-195 had the highest expression at the full coloration stage (S4). These results suggest a potential role for these genes during fruit coloration. This study lays a foundation for further research on the function of the WD40 gene family.
The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer’s Disease
Authors: Tangavelou Karthikeyan , Bhaskar Kiran
Published: November 2024

In Alzheimer’s disease (AD), tau dissociates from microtubules (MTs) due to hyperphosphorylation and misfolding. It is degraded by various mechanisms, including the 20S proteasome, chaperone-mediated autophagy (CMA), 26S proteasome, macroautophagy, and aggrephagy. Neurofibrillary tangles (NFTs) form upon the impairment of aggrephagy, and eventually, the ubiquitin chaperone valosin-containing protein (VCP) and heat shock 70 kDa protein (HSP70) are recruited to the sites of NFTs for the extraction of tau for the ubiquitin–proteasome system (UPS)-mediated degradation. However, the impairment of tau degradation in neurons allows tau to be secreted into the extracellular space. Secreted tau can be monomers, oligomers, and paired helical filaments (PHFs), which are seeding competent pathological tau that can be endocytosed/phagocytosed by healthy neurons, microglia, astrocytes, oligodendrocyte progenitor cells (OPCs), and oligodendrocytes, often causing proteotoxic stress and eventually triggers senescence. Senescent cells secrete various senescence-associated secretory phenotype (SASP) factors, which trigger cellular atrophy, causing decreased brain volume in human AD. However, the molecular mechanisms of proteotoxic stress and cellular senescence are not entirely understood and are an emerging area of research. Therefore, this comprehensive review summarizes pertinent studies that provided evidence for the sequential tau degradation, failure, and the mechanistic link between tau-driven proteotoxic stress and cellular senescence in AD.
Studies on the Oxidative Damage of the Wobble 5-Methylcarboxymethyl-2-Thiouridine in the tRNA of Eukaryotic Cells with Disturbed Homeostasis of the Antioxidant System
Authors: Sierant Malgorzata , Szewczyk Rafal , Dziergowska Agnieszka , Krolewska-Golinska Karolina , Szczupak Patrycja , Bernat Przemyslaw , Nawrot Barbara
Published: November 2024

We have previously shown that 2-thiouridine (S2U), either as a single nucleoside or as an element of RNA chain, is effectively desulfurized under applied in vitro oxidative conditions. The chemically induced desulfuration of S2U resulted in two products: 4-pyrimidinone nucleoside (H2U) and uridine (U). Recently, we investigated whether the desulfuration of S2U is a natural process that also occurs in the cells exposed to oxidative stress or whether it only occurs in the test tube during chemical reactions with oxidants at high concentrations. Using different types of eukaryotic cells, such as baker’s yeast, human cancer cells, or modified HEK293 cells with an impaired antioxidant system, we confirmed that 5-substituted 2-thiouridines are oxidatively desulfurized in the wobble position of the anticodon of some tRNAs. The quantitative LC-MS/MS-MRMhr analysis of the nucleoside mixtures obtained from the hydrolyzed tRNA revealed the presence of the desulfuration products of mcm5S2U: mcm5H2U and mcm5U modifications. We also observed some amounts of immature cm5S2U, cm5H2U and cm5U products, which may have indicated a disruption of the enzymatic modification pathway at the C5 position of 2-thiouridine. The observed process, which was triggered by oxidative stress in the living cells, could impair the function of 2-thiouridine-containing tRNAs and alter the translation of genetic information.
The Oral Microbiota, Microbial Metabolites, and Immuno-Inflammatory Mechanisms in Cardiovascular Disease
Authors: Wang Zheng , Kaplan Robert C. , Burk Robert D. , Qi Qibin
Published: November 2024

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Recent advancements in high-throughput omics techniques have enhanced our understanding of the human microbiome’s role in the development of CVDs. Although the relationship between the gut microbiome and CVDs has attracted considerable research attention and has been rapidly evolving in recent years, the role of the oral microbiome remains less understood, with most prior studies focusing on periodontitis-related pathogens. In this review, we summarized previously reported associations between the oral microbiome and CVD, highlighting known CVD-associated taxa such as Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans. We also discussed the interactions between the oral and gut microbes. The potential mechanisms by which the oral microbiota can influence CVD development include oral and systemic inflammation, immune responses, cytokine release, translocation of oral bacteria into the bloodstream, and the impact of microbial-related products such as microbial metabolites (e.g., short-chain fatty acids [SCFAs], trimethylamine oxide [TMAO], hydrogen sulfide [H2S], nitric oxide [NO]) and specific toxins (e.g., lipopolysaccharide [LPS], leukotoxin [LtxA]). The processes driven by these mechanisms may contribute to atherosclerosis, endothelial dysfunction, and other cardiovascular pathologies. Integrated multi-omics methodologies, along with large-scale longitudinal population studies and intervention studies, will facilitate a deeper understanding of the metabolic and functional roles of the oral microbiome in cardiovascular health. This fundamental knowledge will support the development of targeted interventions and effective therapies to prevent or reduce the progression from cardiovascular risk to clinical CVD events.
Special Issue “Advances in the Physiology of Primary and Secondary Plant Metabolism Under Abiotic and Biotic Stress”
Authors: Zagoskina Natalia
Published: November 2024

One of the most relevant areas of biology is the study of plant adaptation processes to the action of various stress factors of abiotic and biotic nature, which is reflected in the works of molecular biologists, geneticists, microbiologists, plant physiologists, and biochemists, as well as biotechnologists [...]
The T2T Genome of the Domesticated Silkworm Bombyx mori
Authors: Li Wan-Shun , Xiao Ying-Dan , Liu Jian-Qiu , Li Sheng-Long , Chen Yue , Xu Ya-Jing , Yang Xue , Wang Yan-Jue , Li Zhi-Qing , Xia Qing-You , Mita Kazuei
Published: November 2024

Genome sequences contain the fundamental genetic information that largely determines the biology of a species. Over the past 20 years, advancements in high-throughput sequencing technologies and bioinformatics tools have matured, facilitating genome assembly and ushering in the telomere-to-telomere (T2T) era. Bombyx mori is renowned as a silk-producing insect and serves as an important model organism extensively studied across various fields of biology. In this study, we present the first assembled T2T genome by integrating HiFi, ultra-long ONT, NGS, and Hi-C data. This assembly comprises 450,267,439 base pairs from 28 chromosomes and includes annotations for a total of 18,253 protein-coding genes. A completeness evaluation revealed that 99.1% of conserved single-copy genes were included, as determined by a BUSCO analysis. Furthermore, the consensus quality (QV) assessed through Merqury was recorded at 59.88. The proportion of repeat sequence achieved 60.77%, marking it as the highest reported value for B. mori to date. In comparison to previously published genomes, our assembly offers a more complete and higher quality representation, particularly concerning highly homologous tandem regions such as telomeres, rDNA clusters, and Gr family regions. Furthermore, our extensive experience in genome assembly, including sample preparation experience and assembly strategies to reduce complexity, will provide valuable references for other species aiming to achieve their own T2T genome assemblies.
Impact of Hyaluronic Acid and Other Re-Epithelializing Agents in Periodontal Regeneration: A Molecular Perspective
Authors: Polizzi Alessandro , Leanza Ylenia , Belmonte Antonio , Grippaudo Cristina , Leonardi Rosalia , Isola Gaetano
Published: November 2024

This narrative review delves into the molecular mechanisms of hyaluronic acid (HA) and re-epithelializing agents in the context of periodontal regeneration. Periodontitis, characterized by chronic inflammation and the destruction of tooth-supporting tissues, presents a significant challenge in restorative dentistry. Traditional non-surgical therapies (NSPTs) sometimes fail to fully manage subgingival biofilms and could benefit from adjunctive treatments. HA, with its antibacterial, antifungal, anti-inflammatory, angiogenic, and osteoinductive properties, offers promising therapeutic potential. This review synthesizes the current literature on the bioactive effects of HA and re-epithelializing agents, such as growth factors and biomaterials, in promoting cell migration, proliferation, and extracellular matrix (ECM) synthesis. By modulating signaling pathways like the Wnt/β-catenin, TGF-β, and CD44 interaction pathways, HA enhances wound healing processes and tissue regeneration. Additionally, the role of HA in facilitating cellular crosstalk between epithelial and connective tissues is highlighted, as it impacts the inflammatory response and ECM remodeling. This review also explores the combined use of HA with growth factors and cytokines in wound healing, revealing how these agents interact synergistically to optimize periodontal regeneration. Future perspectives emphasize the need for further clinical trials to evaluate the long-term outcomes of these therapies and their potential integration into periodontal treatment paradigms.
Overexpression Analysis of PtrLBD41 Suggests Its Involvement in Salt Tolerance and Flavonoid Pathway in Populus trichocarpa
Authors: Wang Jiewan , Liu Yi , Song Xingshun
Published: November 2024

Soil salinization is a significant environmental stress factor, threatening global agricultural yield and ecological security. Plants must effectively cope with the adverse effects of salt stress on survival and successful reproduction. Lateral Organ Boundaries (LOB) Domain (LBD) genes, a gene family encoding plant-specific transcription factors (TFs), play important roles in plant growth and development. Here, we identified and functionally characterized the LBD family TF PtrLBD41 from Populus trichocarpa, which can be induced by various abiotic stresses, including salt, dehydration, low temperature, and Abscisic Acid (ABA). Meanwhile, transgenic plants overexpressing PtrLBD41 showed a better phenotype and higher tolerance than the wild-type (WT) plants under salt stress treatment. Transcriptome analysis found that the differentially expressed genes (DEGs) between the WT and overexpression (OE) line were enriched in the flavonoid biosynthetic process, in which chalcone synthases (CHS), naringenin 3-dioxygenase (F3H), and chalcone isomerase (CHI) were significantly up-regulated under salt stress conditions through qRT-PCR analysis. Therefore, we demonstrate that PtrLBD41 plays an important role in the tolerance to salt stress in P. trichocarpa.
vScreenML v2.0: Improved Machine Learning Classification for Reducing False Positives in Structure-Based Virtual Screening
Authors: Andrianov Grigorii V. , Haroldsen Emeline , Karanicolas John
Published: November 2024

The enthusiastic adoption of make-on-demand chemical libraries for virtual screening has highlighted the need for methods that deliver improved hit-finding discovery rates. Traditional virtual screening methods are often inaccurate, with most compounds nominated in a virtual screen not engaging the intended target protein to any detectable extent. Emerging machine learning approaches have made significant progress in this regard, including our previously described tool vScreenML. The broad adoption of vScreenML was hindered by its challenging usability and dependencies on certain obsolete or proprietary software packages. Here, we introduce vScreenML 2.0 to address each of these limitations with a streamlined Python implementation. Through careful benchmarks, we show that vScreenML 2.0 outperforms other widely used tools for virtual screening hit discovery.
Gene Co-Expression Network Analysis Associated with Endometrial Cancer Tumorigenesis and Survival Outcomes
Authors: Clark Alexis J. , Singh Rajesh , Leonis Regina L. , Stahlberg Eric A. , Clark Zachary S. , Lillard James W.
Published: November 2024

Endometrial cancer (EC) presents a substantial health challenge, with increasing incidence and mortality rates. Despite advances in diagnosis and treatment, understanding the molecular underpinnings of EC progression remains unknown. In this study, we conducted a comprehensive investigation utilizing The Cancer Genome Atlas (TCGA-UCEC n = 588) data to analyze gene co-expression patterns, elucidate biological process pathways, and identify potential prognostic and diagnostic biomarkers for EC, using weighted gene co-expression network analysis (WGCNA), differential gene expression, survival analysis, and functional analysis, respectively. We determined that the Green module (M5) was significantly correlated with patient survival. Functional analysis of the genes in module M5 indicates involvement in cell cycle regulation, mitotic spindle assembly, and intercellular signaling. TPX2, BUB1, and ESPL1 were among the top differentially expressed genes in the Green module, suggesting their involvement in critical pathways that contribute to disease progression and patient survival outcomes. The biological and clinical assessments of our findings provide an understanding of the molecular landscape of EC and identified several potential prognostic markers for patient risk stratification and treatment selection.
Molecular Insights into the Reproductive Patterns and Genetic Structure of Wheat Stripe Rust in Ili, Xinjiang
Authors: Lai Hanlin , Li Yue , Deng Feifei , Yang Hong , Li Jin , Chen Jianghua , Sun Jingjing , Li Guangkuo , Fernando W. G. Dilantha , Gao Haifeng
Published: November 2024

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a globally significant fungal disease that seriously threatens wheat yield, particularly in China. This study investigates the genetic structure and reproductive patterns of Pst populations in Ili, Xinjiang, using 12 pairs of Simple Sequence Repeat (SSR) molecular markers. Analyses of 79 Pst isolates from either spring or winter wheat areas in Ili revealed three primary genetic clusters, indicating notable differences between populations associated with spring and winter wheat. The STRUCTURE results, complemented by UPGMA and PCoA analyses, highlight significant genetic diversity within these populations, with evidence of genetic recombination and sexual reproduction in certain areas. Pst populations in Ili exhibit a mixed mode of reproduction, predominantly sexual in Qapqal and Xinyuan D and primarily asexual within the spring wheat populations. The gene flow analysis underscores extensive inter-population communication, which facilitates the spread and adaptation of the pathogen across diverse wheat-growing environments. This study marks the first documentation of sexual reproduction in Pst within Xinjiang, providing new insights into its spread and genetic variation. These findings suggest that sexual reproduction may play a role in the regional adaptation and evolution of Pst, impacting future management strategies for wheat stripe rust in Xinjiang and potentially in broader Central Asian contexts.
L-Arginine and Intermittent Hypoxia Are Stress-Limiting Factors in Male Wistar Rat Models
Authors: Kurhaluk Natalia , Lukash Oleksandr , Kamiński Piotr , Tkaczenko Halina
Published: November 2024

The aim of this study was to evaluate the combined effects of L-arginine, intermittent hypoxia training (IHT), and acute stress on oxygen-dependent processes in rats, including mitochondrial oxidative phosphorylation, microsomal oxidation, and the intensity of lipoperoxidation processes. In addition, our study investigated how the modulatory effect of the NO synthase mechanism on the concentration of catecholamines (CA), such as adrenaline and noradrenaline, and their biosynthetic precursors (DOPA, dopamine) varies depending on the cholinergic (acetylcholine, Ach-acetylcholinesterase, AChE) status in rats. This study investigated the protective stress-limiting effects of L-arginine impact and IHT in the blood and liver of rats. The results showed that L-arginine promoted the maintenance of NAD-dependent oxidation in mitochondria, which was detrimental compared to succinate oxidation, and was accompanied by depletion of respiratory activity reserves under stress induced by high concentrations of CA. The interdependence of SC-dependent oxidation and the functional role of NAD-dependent substrate oxidation in the mitochondrial respiratory chain in stress conditions induced using inhibitors revealed the importance of the NO system. Administration of L-arginine during the IHT course prior to stress exposure increased the compensatory capacity of the organism. L-arginine increased the compensatory capacity of the sympathoadrenal system in stress-exposed rats. In the early stages of IHT, modulation of the CA concentration was observed with a concomitant increase in lipoperoxidation processes, and in the final stages of IHT, the CA concentrations increased, but there was also an inhibition of lipoperoxidation, which was particularly enhanced by the administration of L-arginine. The increase in blood concentrations of CA and ACh was accompanied by a decrease in AChE activity at different stages of adaptation to hypoxia induced by IHT (days 5, 10, and 14). Thus, the IHT method significantly mobilises the reserve capacity of oxygen-dependent processes through the system of CA, ACh-AChE mediated by nitric oxide.
NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models
Authors: Tumdam Roshan , Hussein Yara , Garin-Shkolnik Tali , Stern Shani
Published: November 2024

N-methyl-D-aspartate receptors (NMDARs) are critical components of the mammalian central nervous system, involved in synaptic transmission, plasticity, and neurodevelopment. This review focuses on the structural and functional characteristics of NMDARs, with a particular emphasis on the GRIN2 subunits (GluN2A-D). The diversity of GRIN2 subunits, driven by alternative splicing and genetic variants, significantly impacts receptor function, synaptic localization, and disease manifestation. The temporal and spatial expression of these subunits is essential for typical neural development, with each subunit supporting distinct phases of synaptic formation and plasticity. Disruptions in their developmental regulation are linked to neurodevelopmental disorders, underscoring the importance of understanding these dynamics in NDD pathophysiology. We explore the physiological properties and developmental regulation of these subunits, highlighting their roles in the pathophysiology of various NDDs, including ASD, epilepsy, and schizophrenia. By reviewing current knowledge and experimental models, including mouse models and human-induced pluripotent stem cells (hiPSCs), this article aims to elucidate different approaches through which the intricacies of NMDAR dysfunction in NDDs are currently being explored. The comprehensive understanding of NMDAR subunit composition and their mutations provides a foundation for developing targeted therapeutic strategies to address these complex disorders.
Doxorubicin-Induced Cardiotoxicity Through SIRT1 Loss Potentiates Overproduction of Exosomes in Cardiomyocytes
Authors: Zhang Shuai , Yang Yu , Lv Xinchen , Zhou Xue , Zhao Wangqian , Meng Linfeng , Xu Hongfei , Zhu Shaohua , Wang Ying
Published: November 2024

Mutual interaction between doxorubicin (DOX) and cardiomyocytes is crucial for cardiotoxicity progression. Cardiomyocyte injury is an important pathological feature of DOX-induced cardiomyopathy, and its molecular pathogenesis is multifaceted. In addition to the direct toxic effects of DOX on cardiomyocytes, DOX-induced exosomes in the extracellular microenvironment also regulate the pathophysiological states of cardiomyocytes. However, the mechanisms by which DOX regulates exosome secretion and subsequent pathogenesis remain incompletely understood. Here, we found that DOX significantly increased exosome secretion from cardiomyocytes, and inhibiting this release could alleviate cardiomyocyte injury. DOX promoted exosome secretion by reducing cardiomyocyte silencing information regulator 1 (SIRT1) expression, exacerbating cardiotoxicity. DOX impaired lysosomal acidification in cardiomyocytes, reducing the degradation of intracellular multivesicular bodies (MVBs), resulting in an increase in MVB volume before fusing with the plasma membrane to release their contents. Mechanistically, SIRT1 loss inhibited lysosomal acidification by reducing the expression of the ATP6V1A subunit of the lysosomal vacuolar-type H+ ATPase (V-ATPase) proton pump. Overexpressing SIRT1 increased ATP6V1A expression, improved lysosomal acidification, inhibited exosome secretion, and thereby alleviated DOX-induced cardiotoxicity. Interestingly, DOX also induced mitochondrial-derived vesicle formation in cardiomyocytes, which may further increase the abundance of MVBs and promote exosome release. Collectively, this study identified SIRT1-mediated impairment of lysosomal acidification as a key mechanism underlying the increased exosome secretion from cardiomyocytes induced by DOX, providing new insights into DOX-induced cardiotoxicity pathogenesis.
Silk Foams with Metallic Nanoparticles as Scaffolds for Soft Tissue Regeneration
Authors: de Lartigue Claire , Belda Marín Cristina , Fitzpatrick Vincent , Esposito Antonella , Casale Sandra , Landoulsi Jessem , Guénin Erwan , Egles Christophe
Published: November 2024

Tissue regeneration can be achieved by providing endogenous cells with a biomaterial scaffold that supports their adhesion and proliferation, as well as the synthesis and deposition of an extracellular matrix (ECM). In this work, silk fibroin protein foams were formed by lyophilization to generate tissue engineering scaffolds. Three types of medically relevant nanoparticles (NPs) (iron oxide, gold and silver) were added to this biomaterial to assess the ability of silk foams to be functionalized with these NPs. The structural and mechanical properties of the foams with and without the NPs were suitable for tissue support. The in vitro cytocompatibility of the scaffolds was confirmed according to the ISO 10993 guidelines. The biocompatibility of the scaffolds was investigated by assessing inflammation and endogenous cell colonization in a mouse subcutaneous model These in vivo experiments demonstrated a loss of acute inflammation and the absence of chronic inflammation in the grafted animals. The obtained results show that silk foams are good candidates for supporting soft tissue regeneration with the additional possibility of functionalization with NPs.
Parkinson’s Disease: Biomarkers for Diagnosis and Disease Progression
Authors: Arya Rakesh , Haque A. K. M. Ariful , Shakya Hemlata , Billah Md. Masum , Parvin Anzana , Rahman Md-Mafizur , Sakib Khan Mohammad , Faruquee Hossain Md. , Kumar Vijay , Kim Jong-Joo
Published: November 2024

Parkinson’s disease (PD) is a progressive neurological disease that causes both motor and nonmotor symptoms. While our understanding of putative mechanisms has advanced significantly, it remains challenging to verify biomarkers with sufficient evidence for regular clinical use. Clinical symptoms are the primary basis for diagnosing the disease, which can be mild in the early stages and overlap with other neurological disorders. As a result, clinical testing and medical records are mostly relied upon for diagnosis, posing substantial challenges during both the initial diagnosis and the continuous disease monitoring. Recent biochemical, neuroimaging, and genetic biomarkers have helped us understand the pathophysiology of Parkinson’s disease. This comprehensive study focuses on these biomarkers, which were chosen based on their relevance, methodological excellence, and contribution to the field. Biochemical biomarkers, including α-synuclein and glial fibrillary acidic protein (GFAP), can predict disease severity and progression. The dopaminergic system is widely used as a neuroimaging biomarker to diagnose PD. Numerous genes and genome wide association study (GWAS) sites have been related to the development of PD. Recent research on the SNCA gene and leucine-rich repeat protein kinase 2 (LRRK2) has shown promising results. By evaluating current studies, this review intends to uncover gaps in biomarker validation and use, while also highlighting promising improvements. It emphasizes the need for dependable and reproducible indicators in improving PD diagnosis and prognosis. These biomarkers may open up new avenues for early diagnosis, disease progression tracking, and the development of personalized treatment programs.
A Novel Gene, OsRLCK191, Involved in Culm Strength Improving Lodging Resistance in Rice
Authors: Chang Huilin , Sha Hanjing , Gao Shiwei , Liu Qing , Liu Yuqiang , Ma Cheng , Shi Bowen , Nie Shoujun
Published: November 2024

Lodging is one of the major problems in rice production. However, few genes that can explain the culm strength within the temperate japonica subspecies have been identified. In this study, we identified OsRLCK191, which encodes receptor-like cytoplasmic kinase and plays critical roles in culm strength. OsRLCK191 mutants were produced by the CRISPR-Cas9 DNA-editing system. Compared with wild types (WTs), the bending moment of the whole plant (WP), the bending moment at breaking (BM), and the section modulus (SM) were decreased in rlck191 significantly. Although there is no significant decrease in the culm length of rlck191 compared with the WT; in the mutant, except the length of the fourth internode being significantly increased, the lengths of other internodes are significantly shortened. In addition, the yield traits of panicle length, thousand-seed weight, and seed setting rate decreased significantly in rlck191. Moreover, RNA-seq experiments were performed at an early stage of rice panicle differentiation in shoot apex. The differentially expressed genes (DEGs) are mainly involved in cell wall biogenesis, cell wall polysaccharide metabolic processes, cellar component biogenesis, and DNA-binding transcription factors. Transcriptome analysis of the cell wall biological process pathways showed that major genes that participated in the cytokinin oxidase/dehydrogenase family, cellulose synthase catalytic subunit genes, and ethylene response factor family transcription factor were related to culm strength. Our research provides an important theoretical basis for analyzing the lodging resistance mechanism and lodging resistance breeding of temperate japonica.
Development of LAT1-Selective Nuclear Medicine Therapeutics Using Astatine-211
Authors: Kaneda-Nakashima Kazuko , Shirakami Yoshifumi , Hisada Kentaro , Feng Sifan , Kadonaga Yuichiro , Ooe Kazuhiro , Watabe Tadashi , Manabe Yoshiyuki , Shimoyama Atsushi , Murakami Masashi , Toyoshima Atsushi , Haba Hiromitsu , Kanai Yoshikatsu , Fukase Koichi
Published: November 2024

We investigated nuclear medicine therapeutics targeting the L-type amino acid transporter 1 (LAT1). We previously reported that a nuclear medicine therapeutic drug using astatine 211 (211At), an alpha-emitting nuclide that can be produced in an accelerator and targets LAT1 as a molecular target, is effective. The seed compound was 3-[211At] Astato-α-methyl-L-tyrosine (211At-AAMT-OH-L). We used a unique labeling method. By changing the OH group of phenol to a methyl group, retention was successfully increased. It was also found that the amount of the L-isomer taken up by the D-isomer and L-isomer was clearly higher, and the L-isomer was superior as a therapeutic drug. Compounds in which the methyl group was replaced with an ethyl or propyl group were also examined, but their retention did not increase significantly. In fact, we observed increased non-specific accumulation and dynamics, suggesting that labeling may be off. In addition, 211At-AAMT-O-Me-L, which has a simple structure, was clearly superior in terms of uptake speed for several candidate compounds. As a result, we were able to develop a compound that can be easily labeled, has high specific radioactivity, is stable, and has a strong therapeutic effect.
Oxidative Stress and Cancer Therapy: Controlling Cancer Cells Using Reactive Oxygen Species
Authors: Ju Songhyun , Singh Manish Kumar , Han Sunhee , Ranbhise Jyotsna , Ha Joohun , Choe Wonchae , Yoon Kyung-Sik , Yeo Seung Geun , Kim Sung Soo , Kang Insug
Published: November 2024

Cancer is a multifaceted disease influenced by various mechanisms, including the generation of reactive oxygen species (ROS), which have a paradoxical role in both promoting cancer progression and serving as targets for therapeutic interventions. At low concentrations, ROS serve as signaling agents that enhance cancer cell proliferation, migration, and resistance to drugs. However, at elevated levels, ROS induce oxidative stress, causing damage to biomolecules and leading to cell death. Cancer cells have developed mechanisms to manage ROS levels, including activating pathways such as NRF2, NF-κB, and PI3K/Akt. This review explores the relationship between ROS and cancer, focusing on cell death mechanisms like apoptosis, ferroptosis, and autophagy, highlighting the potential therapeutic strategies that exploit ROS to target cancer cells.
Uranium-Mediated Thiourea/Urea Conversion on Chelating Ligands
Authors: Noufele Christelle Njiki , Roca Jungfer Maximilian , Hagenbach Adelheid , Nguyen Hung Huy , Abram Ulrich
Published: November 2024

2,6-Dipicolinoylbis(N,N-dialkylthioureas) and H2LR2 react with uranyl salts and a supporting base (e.g., NEt3) under formation of monomeric or oligomeric complexes of the compositions [UO2(LR2)(solv)] (solv = donor solvents) or [{UO2(LR2)(µ2-OMe)}2]2–. In such complexes, the uranyl ions are commonly coordinated by the “hard” O,N,O or N,N,N donor atom sets of the central ligand unit and the lateral sulfur donor atoms remain uncoordinated. Their individual structures, however, depend on the reaction conditions, particularly on the equivalents of NEt3 used. An unprecedented, selective hydrolysis of the uranium-coordinating bis(thioureato) ligands results in an S/O donor atom exchange at exclusively one thiourea side-arm, when an excess of NEt3 is used. The resulting trimeric uranyl complexes are isolated in fair yields and have a composition of [(UO2)3(L2Et2)2(µ2–OR)(µ3-O)]–. H2L2Et2 represents the newly formed 2,6-dipicolinoyl(N,N-diethylthiourea)(N,N-diethylurea) and R = H, Me, or Et. {L2Et2}2– binds to the uranyl units via the pyridine ring, the dialkylurea arm, and the central carbonyl groups, while the thiourea unit remains uncoordinated. The central cores of the products consist of oxido-centered triangular {(UO2)3O}4+ units. The observed reactivity is metal-driven and corresponds mechanistically most probably to a classical metal-catalyzed hydrodesulfurization. The hydrolytic thiourea/urea conversion is only observed in the presence of uranyl ions. The products were isolated in crystalline form and studied spectroscopically and by X-ray diffraction. The experimental findings are accompanied by DFT calculations, which help to understand the energetic implications in such systems.
Standard Descriptors and Selected Biomarkers in Assessment of Posidonia oceanica (L.) Delile Environmental Response
Authors: Vidaković-Cifrek Željka , Tkalec Mirta , Bakran-Petricioli Tatjana , Dolenc Koce Jasna , Bobetić Jelena , Cvrtila Adam , Grbčić Ana , Maroević Janja , Mikec Nina , Samac Jelena , Smiljanec Mateja
Published: November 2024

Endemic Mediterranean seagrass Posidonia oceanica is highly endangered today as it lives in a narrow infralittoral zone intensely exposed to human impact. P. oceanica beds are especially endangered in the Adriatic Sea as the central and northern Adriatic could be considered as a naturally suboptimal area for P. oceanica growth. In this research, we used some standard descriptors of Posidonia meadows at different locations and depths and determined the biochemical parameters (phenolic compounds, photosynthetic pigments, and enzyme activities) in its leaves in order to find possible correlations among the measured parameters and environmental conditions. Photosynthetic pigments were shown to be sensitive biomarkers in the assessment of P. oceanica response to different light conditions, but more research is needed to elucidate the impact of other environmental factors. Overall, the results of this research show that the studied parameters are good bioindicators of a meadow’s environmental state, but it is necessary to analyze a number of diverse indicators together to properly characterize the state of a particular P. oceanica meadow. This approach would be very useful in the determination of P. oceanica conservation status, which is the first step towards improving monitoring protocols and implementing appropriate conservation measures.
Condition Monitoring in Marine Oil Separation Systems Using Wavelet Packet Transform and Genetic Technique
Authors: Hernández Ángela , Castejón Cristina , Ávila Deivis , Gómez-García María Jesús , Marichal Graciliano Nicolás
Published: November 2024

Condition Monitoring is key to predictive maintenance and especially in the operational efficiency of the Marine Oil Separation System. These systems are crucial for environmental protection and compliance with international maritime regulations. Therefore, it is necessary to design a technique capable of analyzing the signals from sensors and estimating the remaining useful life in order to avoid breakage or unnecessary replacement. This work presents an intelligent method with signal processing based on Wavelet Packets Transform that provides energy data from vibration measurements as characteristic parameters. These values can be related to its RUL, and they are used as inputs for the training process. In particular, a Genetic Neuro-Fuzzy system is proposed as an intelligent classification technique. Once the training process is completed, it can be concluded that a good classifier has been built, since it relates the energy state of the oil separation system with its remaining useful life, and therefore, the necessary information for efficient predictive maintenance is achieved. Furthermore, a mechanism to obtain the final set of fuzzy rules has been developed, showing the correspondence between these fuzzy rules and the neural network structure.
Two-Dimensional Prediction of Transient Cavitating Flow Around Hydrofoils Using a DeepCFD Model
Authors: Liu Bohan , Park Sunho
Published: November 2024

Cavitation is a common phenomenon in naval and ocean engineering, typically occurring in the wakes of high-speed rotating propellers and on the surfaces of fast-moving underwater vehicles. To investigate cavitation phenomena, computational fluid dynamics (CFD) simulations are indispensable. Nevertheless, the inherently complex nature of cavitation, which involves phase transitions, heat transfer, and significant pressure fluctuations, often results in high computational costs for these simulations. To address the computational challenges associated with cavitation simulations, a DeepCFD model, which leverages convolutional neural networks (CNNs), was employed to accurately predict cavitation around hydrofoils. Through specific modifications, the DeepCFD model was trained on 400 hydrofoil configurations, learned from CFD simulations. The numerical methods were validated against a modified NACA66 hydrofoil. It was found that the model could accurately predict cavitation shapes under various flow conditions, although it showed some discrepancies in velocity predictions, especially for detached cavitating flows. The significance of this study lies in its potential to simply predict cavitating flows and expedite marine vehicle design through the application of CNNs in cavitation prediction, offering a novel and impactful approach to computational fluid dynamics in the field.
Optimal Control of Nonlinear, Nonautonomous, Energy Harvesting Systems Applied to Point Absorber Wave Energy Converters
Authors: Yassin Houssein , Demonte Gonzalez Tania , Nelson Kevin , Parker Gordon , Weaver Wayne
Published: November 2024

Pursuing sustainable energy solutions has prompted researchers to focus on optimizing energy extraction from renewable sources. Control laws that optimize energy extraction require accurate modeling, often resulting in time-varying, nonlinear differential equations. An energy-maximizing optimal control law is derived for time-varying, nonlinear, second-order, energy harvesting systems. We demonstrate that sustaining periodic motion under this control law when subjected to periodic disturbances necessitates identifying appropriate initial conditions, inducing the system to follow a limit cycle. The general optimal solution is applied to two point absorber wave energy converter models: a linear model where the analytical derivation of initial conditions suffices and a nonlinear model demanding a numerical approach. A stable limit cycle is obtained for the latter when the initial conditions lie within an ellipse centered at the origin of the phase plane. This work advances energy-maximizing optimal control solutions for nonautonomous nonlinear systems with application to point absorbers. The results also shed light on the significance of initial conditions in achieving physically realizable periodic motion for periodic energy harvesting systems.
A Quasi Time-Domain Method for Fatigue Analysis of Reactor Pressure Vessels in Floating Nuclear Power Plants in Marine Environments
Authors: Ma Fuxuan , Li Huanming , Zhang Meng , Qu Xiangiang
Published: November 2024

The reactor pressure vessel (RPV) in onshore nuclear power plants is typically analysed for fatigue life by considering the temperature, internal pressure, and seismic effects using a simplified time-domain fatigue analysis. In contrast, the frequency-domain fatigue analysis method is commonly employed to assess the fatigue life of ship structures. The RPV of a floating nuclear power plant (FNPP) is subjected to a combination of temperature, internal pressure, and wave loads in the marine environment. Consequently, it is essential to effectively integrate the frequency-domain fatigue analysis method used for hull structures with the time-domain fatigue analysis method for RPVs in FNPPs or, alternatively, to develop a suitable method that effectively accounts for the temperature, internal pressure, and wave loads. In this study, a quasi-time-domain method is proposed for the fatigue analysis of RPVs in FNPPs. In this method, secondary components of marine environmental loads are filtered out using principal component analysis. Subsequently, the stress spectrum induced by waves is transformed into a stress time history. Fatigue stress under the combined influence of temperature, internal pressure, and wave loads is then obtained through a stress component superposition method. Finally, the accuracy of the quasi-time-domain method was validated through three numerical examples. The results indicate that the calculated values obtained by the quasi-time-domain method are slightly higher than those obtained by the traditional time-domain method, with a maximum deviation of no more than 24%. Additionally, the computation time of the quasi-time-domain method is reduced by 98.67% compared to the traditional time-domain method.