bluuebunny/crossref_metadata_2025 huggingface dataset:
Newly Established Blueberry Plants: The Role of Inorganic Nitrogen Forms in Nitrogen and Calcium Absorption
Authors: Arias María Ignacia , Nario Adriana , Rojas Krystel , Blanc Poulette , Bonomelli Claudia
Published: November 2024

Efficient nitrogen (N) management is crucial for maximizing the growth of young blueberry plants (Vaccinium corymbosum). This study evaluates the effects of the N fertilization form (ammonium, NH4+; nitrate, or NO3−) and application timing on the blueberries’ establishment, N and Ca absorption, and N distribution. The experiment was conducted in the southern hemisphere, in Chile, from October 2023 to January 2024. Six-month-old blueberry cv. Blue Ribbon plants were cultivated in pots. NH4+ and NO3− were used as full or split-dose applications using the 15N isotopic dilution technique. Plant leaves, stems, root growth, and biomass, as well as their N and Ca contents, were measured. Our results showed that 90 days after nitrogen application, blueberry plants obtained the lowest biomass in their leaves, stems, and roots when NO3− was applied in T1 or T1T2. The same pattern was observed for N and Ca contents, hence for N recovery. During the first period (T1) of application, heavy rain (100 mm) was registered over the course of a few days and caused leaching. Therefore, applying nitrate to young blueberry plants cultivated in areas with spring rainfall and low temperatures would not be recommended because the leaching losses and lower growth conditions, such as low temperatures and high precipitation, led to reduced transpiration, resulting in lower calcium and nitrogen contents. These confirm that N fertilization management (form and timing) can ensure a better establishment for young blueberry plants, optimizing their growth and sustainable production by minimizing nitrogen losses.
Exploring Self-Care, Anxiety, Depression, and the Gender Gap in the Software Engineering Pipeline
Authors: Takaoka Alicia Julia Wilson , Jaccheri Letizia , Sharma Kshitij
Published: November 2024

Software engineers may experience burnout, which is often caused by the anxieties and stresses of the workplace. Understanding the well-being and resilience practices of software engineers and evaluating their knowledge of mental health is one factor to understand our current, diverse, multi-generational workplaces. Here, we present preliminary results of a study examining the self-care practices of software engineers, a general overview of the state of mental health of software engineers, and correlations between expressions of mental health and demographic factors. Among 224 respondents, positive correlations between imposter syndrome and happiness, anxiety, and depression were identified. We also identified negative correlations between mental health literacy and imposter syndrome, happiness, anxiety, and depression. Well-being had a positive correlation with self-efficacy, as well as with happiness. We also present the Gender Gap in mental health and our findings in relation to that construct. Our findings suggest increasing mental health support services.
5-Hydroxymethylcytosine: Far Beyond the Intermediate of DNA Demethylation
Authors: Zheng Kaixi , Lyu Zhengbing , Chen Jianqing , Chen Guodong
Published: November 2024

Epigenetics plays a pivotal role in regulating gene expression and cellular differentiation. DNA methylation, involving the addition of methyl groups to specific cytosine bases, is a well-known epigenetic modification. The recent discovery of 5-hydroxymethylcytosine (5hmC) has provided new insights into cytosine modifications. 5hmC, derived from the oxidation of 5-methylcytosine (5mC), serves as both an intermediate in demethylation and a stable chemical modification in the genome. In this comprehensive review, we summarize the recent research advancements regarding the functions of 5hmC in development and disease. We discuss its implications in gene expression regulation, cellular differentiation, and its potential role as a diagnostic and prognostic marker in various diseases. Additionally, we highlight the challenges associated with accurately detecting and quantifying 5hmC and present the latest methodologies employed for its detection. Understanding the functional role of 5hmC in epigenetic regulation and further advancing our understanding of gene expression dynamics and cellular processes hold immense promise for the development of novel therapeutic strategies and precision medicine approaches.
Relationships Among Origin, Genotype, and Oenological Traits of Brettanomyces Yeasts
Authors: Canonico Laura , Agarbati Alice , Comitini Francesca , Ciani Maurizio
Published: November 2024

Brettanomyces yeasts play a relevant role in the fermentation industry, showing controversial behavior. There is growing interest in these yeasts in the fermentation industry as beer and bioethanol production, while in winemaking, they are considered spoilage microorganisms mainly used to produce ethyl phenols. These compounds may alter wine’s organoleptic characteristics, leading to significant economic loss. In this work, 45 Brettanomyces strains from seven different environments were genotyped and assayed for some oenological characters to investigate the possible relationship among sources of isolation, genotype characterization, and oenological characters. The results of biotyping showed four main clusters which were also distinguished according to the oenological characters. The oenological characters also distinguished the strains based on the isolation source, suggesting an overall relation between origin and biotypes. The negative correlation between fermentation rate and ethyl phenols production in the Brettanomyces population may indicate the adaptation to hostile environments differently from crop strains that showed the opposite behavior. The overall results contribute to clarifying some features of Brettanomyces yeasts, even if further investigations into the ability of these yeasts to colonize winemaking environments are needed.
A Systems Biology Approach Towards a Comprehensive Understanding of Ferroptosis
Authors: Arbatskiy Mikhail , Balandin Dmitriy , Akberdin Ilya , Churov Alexey
Published: November 2024

Ferroptosis is a regulated cell death process characterized by iron ion catalysis and reactive oxygen species, leading to lipid peroxidation. This mechanism plays a crucial role in age-related diseases, including cancer and cardiovascular and neurological disorders. To better mimic iron-induced cell death, predict the effects of various elements, and identify drugs capable of regulating ferroptosis, it is essential to develop precise models of this process. Such drugs can be tested on cellular models. Systems biology offers a powerful approach to studying biological processes through modeling, which involves accumulating and analyzing comprehensive research data. Once a model is created, it allows for examining the system’s response to various stimuli. Our goal is to develop a modular framework for ferroptosis, enabling the prediction and screening of compounds with geroprotective and antiferroptotic effects. For modeling and analysis, we utilized BioUML (Biological Universal Modeling Language), which supports key standards in systems biology, modular and visual modeling, rapid simulation, parameter estimation, and a variety of numerical methods. This combination fulfills the requirements for modeling complex biological systems. The integrated modular model was validated on diverse datasets, including original experimental data. This framework encompasses essential molecular genetic processes such as the Fenton reaction, iron metabolism, lipid synthesis, and the antioxidant system. We identified structural relationships between molecular agents within each module and compared them to our proposed system for regulating the initiation and progression of ferroptosis. Our research highlights that no current models comprehensively cover all regulatory mechanisms of ferroptosis. By integrating data on ferroptosis modules into an integrated modular model, we can enhance our understanding of its mechanisms and assist in the discovery of new treatment targets for age-related diseases. A computational model of ferroptosis was developed based on a modular modeling approach and included 73 differential equations and 93 species.
Identification of Laccase Family of Auricularia auricula-judae and Structural Prediction Using Alphafold
Authors: Kim Jeong-Heon , Park Youn-Jin , Jang Myoung-Jun
Published: November 2024

Laccase is an enzyme that plays an important role in fungi, including lignin degradation, stress defense, and formation of fruiting bodies. Auricularia auricula-judae is a white-rot fungus in the Basidiomycota phylum, capable of delignifying wood. In this study, seven genes belonging to the laccase family were identified through de novo sequencing, containing Cu-Oxidase, Cu-Oxidase_2, and Cu-Oxidase_3 domains. Subsequently, the physical characteristics, phylogenetic relationships, protein secondary structure, and tertiary structure of the laccase family (AaLac1–AaLac7) were analyzed. Prediction of N-glycosylation sites identified 2 to 10 sites in the laccase family, with AaLac7 having the highest number of sites at 10. Sequence alignment and analysis of the laccase family showed high consistency in signature sequences. Phylogenetic analysis confirmed the relationship among laccases within the family, with AaLac3–AaLac4 and AaLac5–AaLac6 being closely positioned on the tree, exhibiting high similarity in tertiary structure predictions. This study identified and analyzed laccase family genes in Auricularia auricula-judae using de novo sequencing, offering a simple method for identifying and analyzing the laccase family in organisms with unknown genetic information.
Elucidation of the Role of SHMT2 in L-Serine Homeostasis in Hypoxic Hepa1-6 Cells
Authors: Zhang Shuo , He Ruoxu , Zhang Mingsi , Zhang Jingcheng , Wu Mengting , Zhang Guangji , Jiang Tao
Published: November 2024

Hypoxia is a characteristic feature of malignancy; however, its effect on metabolism remains unclear. In this study, Hepa1-6 cells were cultured under hypoxic conditions and their metabolites were analyzed. Elevated levels of L-serine along with increased glycolytic activity are prominent features of hypoxia. Transcriptome sequencing revealed the downregulation of genes involved in L-serine synthesis and metabolism, which was confirmed by PCR analysis and comparison with public databases. Further experimental evidence indicates that the accumulation of L-serine under hypoxic conditions is attributable not only to enhanced glycolysis but also to a reduction in the catabolism of L-serine mediated by serine hydroxymethyltransferase 2 (SHMT2).
Neuroinflammatory Proteins in Huntington’s Disease: Insights into Mechanisms, Diagnosis, and Therapeutic Implications
Authors: Li Xinhui , Tong Huichun , Xu Shuying , Zhou Gongke , Yang Tianqi , Yin Shurui , Yang Sitong , Li Xiaojiang , Li Shihua
Published: November 2024

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by a CAG tract expansion in the huntingtin gene (HTT). HD is characterized by involuntary movements, cognitive decline, and behavioral changes. Pathologically, patients with HD show selective striatal neuronal vulnerability at the early disease stage, although the mutant protein is ubiquitously expressed. Activation of the immune system and glial cell-mediated neuroinflammatory responses are early pathological features and have been found in all neurodegenerative diseases (NDDs), including HD. However, the role of inflammation in HD, as well as its therapeutic significance, has been less extensively studied compared to other NDDs. This review highlights the significantly elevated levels of inflammatory proteins and cellular markers observed in various HD animal models and HD patient tissues, emphasizing the critical roles of microglia, astrocytes, and oligodendrocytes in mediating neuroinflammation in HD. Moreover, it expands on recent discoveries related to the peripheral immune system’s involvement in HD. Although current immunomodulatory treatments and inflammatory biomarkers for adjunctive diagnosis in HD are limited, targeting inflammation in combination with other therapies, along with comprehensive personalized treatment approaches, shows promising therapeutic potential.
Ruta graveolens, but Not Rutin, Inhibits Survival, Migration, Invasion, and Vasculogenic Mimicry of Glioblastoma Cells
Authors: Camerino Iolanda , Franco Paola , Bajetto Adriana , Thellung Stefano , Florio Tullio , Stoppelli Maria Patrizia , Colucci-D’Amato Luca
Published: November 2024

Glioblastoma (GBM) is the most aggressive type of brain tumor, characterized by poor outcome and limited therapeutic options. During tumor progression, GBM may undergo the process of vasculogenic mimicry (VM), consisting of the formation of vascular-like structures which further promote tumor aggressiveness and malignancy. The resulting resistance to anti-angiogenetic therapies urges the identification of new compounds targeting VM. Extracts of natural plants may represent potential therapeutic tools. Among these, components of Ruta graveolens water extract (RGWE) display a wide range of biological activities. To test the effect of RGWE on human GBM and rat glioma cell line VM, tube formation on a gelled matrix was monitored. Quantitative assessment of VM formation shows the clear-cut inhibitory activity of RGWE. Unlike rutin, one of the most abundant extract components, the whole RGWE strongly reduced the migration and invasion of GBM tumor cells. Moreover, RGWE induced cell death of GBM patient-derived cancer stem cells and impaired VM at sub-lethal doses. Overall, our data reveal a marked RGWE-dependent inhibition of GBM cell survival, migration, invasion, and VM formation. Thus, the clear-cut ability of RGWE to counteract GBM malignancy deserves attention, holding the promise to bring natural products to clinical use, thus uncovering new therapeutic opportunities.
Neutrophil Elastase, Neuron-Specific Enolase, and S100B Protein as Potential Markers of Long-Term Complications Caused by COVID-19 in Patients with Type 2 Diabetes Mellitus (T2DM) and Advanced Stage of Diabetic Nephropathy (NfT2DM)—Observational Studies
Authors: Rabczyński Maciej , Chwałek Sandra , Adamiec-Mroczek Joanna , Lewandowski Łukasz , Trocha Małgorzata , Nowak Beata , Misiuk-Hojło Marta , Bednarska-Chabowska Dorota , Kuźnik Edwin , Lubieniecki Paweł , Kluz Joanna , Kaszubowska Zofia , Kondracki Mikołaj , Grodzki Wojciech , Federowicz Jakub , Mierzchała-Pasierb Magdalena , Gamian Andrzej , Bronowicka-Szydełko Agnieszka , Madziarska Katarzyna
Published: November 2024

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions. The aim of this study was to assess the value of measuring and attempt a quantitative evaluation using Enzyme-Linked Immunosorbent Assay (ELISA) tests of three non-serum proteins, whose presence in the blood during COVID-19 was associated with severe disease progression: neutrophil elastase (NE), calcium-binding protein S100B, and neuron-specific enolase (NSE). The concentrations of these proteins were measured in blood serum samples collected before the COVID-19 pandemic from (1) patients with type 2 diabetes (T2DM); (2) advanced stage diabetic nephropathy (NfT2DM); (3) a healthy group; and in blood serum samples collected two years after recovering from COVID-19 from patients with (4) T2DM and (5) NfT2DM. It was found that elevated levels of NE and NSE were significantly more common (p < 0.05) in patients with NfT2DM after recovering from COVID-19 compared to the other groups, while elevated levels of S100B were significantly more frequently observed in patients with T2DM after recovering from COVID-19 (p < 0.05). Demonstrating differences in the prevalence of NE, NSE, and S100B in individuals who recovered from COVID-19 with T2DM and NfT2DM makes these proteins important components of the developing predictive model for early detection of PCS. To our knowledge, this is the first study showing the significance of NE, NSE, and S100B in PCS in the context of T2DM and NfT2DM.
Applications of CRISPR Technologies in Forestry and Molecular Wood Biotechnology
Authors: Cao Hieu Xuan , Michels David , Vu Giang Thi Ha , Gailing Oliver
Published: November 2024

Forests worldwide are under increasing pressure from climate change and emerging diseases, threatening their vital ecological and economic roles. Traditional breeding approaches, while valuable, are inherently slow and limited by the long generation times and existing genetic variation of trees. CRISPR technologies offer a transformative solution, enabling precise and efficient genome editing to accelerate the development of climate-resilient and productive forests. This review provides a comprehensive overview of CRISPR applications in forestry, exploring its potential for enhancing disease resistance, improving abiotic stress tolerance, modifying wood properties, and accelerating growth. We discuss the mechanisms and applications of various CRISPR systems, including base editing, prime editing, and multiplexing strategies. Additionally, we highlight recent advances in overcoming key challenges such as reagent delivery and plant regeneration, which are crucial for successful implementation of CRISPR in trees. We also delve into the potential and ethical considerations of using CRISPR gene drive for population-level genetic alterations, as well as the importance of genetic containment strategies for mitigating risks. This review emphasizes the need for continued research, technological advancements, extensive long-term field trials, public engagement, and responsible innovation to fully harness the power of CRISPR for shaping a sustainable future for forests.
Characteristics of Pulmonary Inflammation in Patients with Different Forms of Active Tuberculosis
Authors: Shepelkova Galina S. , Evstifeev Vladimir V. , Berezovskiy Yuriy S. , Ergeshova Anush E. , Tarasov Ruslan V. , Bagirov Mamed A. , Yeremeev Vladimir V.
Published: November 2024

Targeted treatment of tuberculosis-associated lung damage requires an understanding of the precise mechanisms of immunopathology. A major obstacle to the longitudinal study of tuberculosis (TB) immunopathogenesis in humans is the lack of serial lung biopsies during disease progression and treatment, which could be used to characterize local immune pathways involved in tissue damage. Understanding of the immunobiology of lung tissue damage in tuberculosis has largely been based on animal models. Our study looked for signs of inflammation in TB patients’ lung biopsies. Results were compared between a site of infection and relatively healthy tissue outside the site. The most significant differences in the expression of microRNAs (miRs) and cytokine/chemokines were observed between the non-decayed tuberculoma and the surrounding parenchyma. In addition, these parameters showed almost no differences between the cavitary wall and surrounding tissue. This is an indication that the inflammatory process is more prevalent in fibrotic cavitary tuberculosis (FCT). In FCT subjects, no difference was observed between the cavity wall and the parenchyma in the production of key inflammatory factors such as IL-6, IL-11, IL-17, and IFNγ. This is an indication that the limits of the inflammatory response are broader in FCT. The expression levels of miR-191, miR-193a, miR-222, miR-223, miR-18, miR-155, miR-376c, miR-26a, miR-150, and miR-124 were not significantly different between the cavernous wall and lung tissue in patients with FCT, further confirming the spread of inflammatory and destructive processes beyond the focus of infection.
The Role of Dicer Phosphorylation in Gemcitabine Resistance of Pancreatic Cancer
Authors: Chiu Ching-Feng , Lin Hui-Ru , Su Yen-Hao , Chen Hsin-An , Hung Shao-Wen , Huang Shih-Yi
Published: November 2024

Dicer, a cytoplasmic type III RNase, is essential for the maturation of microRNAs (miRNAs) and is implicated in cancer progression and chemoresistance. Our previous research demonstrated that phosphorylation of Dicer at S1016 alters miRNA maturation and glutamine metabolism, contributing to gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we focused on the role of Dicer phosphorylation at S1728/S1852 in GEM-resistant PDAC cells. Using shRNA to knock down Dicer in GEM-resistant PANC-1 (PANC-1 GR) cells, we examined cell viability through MTT and clonogenic assays. We also expressed phosphomimetic Dicer 2E (S1728E/S1852E) and phosphomutant Dicer 2A (S1728A/S1852A) to evaluate their effects on GEM resistance and metabolism. Our results show that phosphorylation at S1728/S1852 promotes GEM resistance by reprogramming glutamine metabolism. Specifically, phosphomimetic Dicer 2E increased intracellular glutamine, driving pyrimidine synthesis and raising dCTP levels, which compete with gemcitabine’s metabolites. This metabolic shift enhanced drug resistance. In contrast, phosphomutant Dicer 2A reduced GEM resistance. These findings highlight the importance of Dicer phosphorylation in regulating metabolism and drug sensitivity, offering insights into potential therapeutic strategies for overcoming GEM resistance in pancreatic cancer.
Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment
Authors: Ye Qianwen , Zhang Mingshuo , Li Shuyue , Liu Wenyue , Xu Chunming , Li Yumei , Xie Renjian
Published: November 2024

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized.
Impact of Reductive Stress on Human Infertility: Underlying Mechanisms and Perspectives
Authors: Moustakli Efthalia , Zikopoulos Athanasios , Skentou Charikleia , Katopodis Periklis , Domali Ekaterini , Potiris Anastasios , Stavros Sofoklis , Zachariou Athanasios
Published: November 2024

Antioxidants have a well-established effect on general health and are essential in preventing oxidative damage to cells by scavenging free radicals. Free radicals are thought to be neutralized by these substances, which include polyphenols, β-carotene, and vitamins C and E, reducing cellular damage. On the other hand, recent data indicates that consuming excessive amounts of antioxidants may have side effects. Apoptosis and cell signaling are two beneficial physiological processes that are affected by excessive supplementation. Other negative effects include paradoxical enhancement of oxidative stress and unbalanced cellular redox potential. Overdosing on particular antioxidants has been associated with increased medication interactions, cancer progression, and fatality risks. Additionally, the complex impacts they may have on fertility might be both useful and adverse, depending on the quantity and duration of usage. This review delves into the dual role of antioxidants and emphasizes the importance of employing antioxidants in moderation. Antioxidant overconsumption may disrupt the oxidative balance necessary for normal sperm and oocyte function, which is one of the potential negative effects of antioxidants on fertility in both males and females that are also investigated. Although modest usage of antioxidants is generally safe and useful, high levels of antioxidants can upset hormonal balance, impair sperm motility, and negatively impact the outcomes of assisted reproductive technologies (ART). The findings emphasize the need to use antioxidant supplements in a balanced way, the importance of further research to optimize their use in fertility treatments, and the importance of supporting reproductive health to avoid adverse effects.
The Role of the Bone Morphogenetic Protein Antagonist Noggin in Nucleus Pulposus Intervertebral Disc Cells
Authors: Chen Shuimu , Bigdon Sebastian , Riether Carsten , Ma Xiaochi , Niu Xiaoyi , Häckel Sonja , Li Zhen , Gantenbein Benjamin
Published: November 2024

Low back pain (LBP) is a significant global health issue, contributing to disability and socioeconomic burdens worldwide. The degeneration of the human intervertebral disc (IVD) is a critical factor in the pathogenesis of LBP. Recent studies have emphasized the significance of a specific set of genes and extracellular matrix (ECM) in IVD health. In particular, Noggin has emerged as a critical gene due to its high expression levels in healthy nucleus pulposus cells (NPCs) observed in our previous research. In this study, it was hypothesized that decreased Noggin expression in NPCs is associated with IVD degeneration and contributes to LBP development. A lentivirus-mediated RNAi was applied to knock down Noggin expression in primary NPCs from six human donors. The NPCs after transduction were evaluated through cell viability analysis, XTT assay, and cell apoptosis analyses. After two weeks, a colony formation assay was used to examine the anchor-independent growth ability of transduced cells. At the transcript level, anabolic and catabolic markers were quantified using RT-qPCR. The results demonstrated that lentivirus-mediated downregulation of Noggin significantly inhibited cell proliferation, reduced cell viability, and suppressed colony formation, while inducing apoptosis in human NPCs in vitro. Notably, it disrupted cellular anabolic processes and promoted catabolic activity in human NPCs post-transduction. Our findings indicated that the degeneration of human IVD is possibly related to decreased Noggin expression in NPCs. This research provides valuable insights into the role of Noggin in IVD homeostasis and its implications in LBP treatment.
The Effects of Lead and Cross-Talk Between Lead and Pea Aphids on Defence Responses of Pea Seedlings
Authors: Morkunas Iwona , Woźniak Agnieszka , Bednarski Waldemar , Ostrowski Adam , Kęsy Jacek , Glazińska Paulina , Wojciechowska Julia , Bocianowski Jan , Rucińska-Sobkowiak Renata , Mai Van Chung , Karolewski Zbigniew , Labudda Mateusz , Batista Anielkis , Jeandet Philippe
Published: November 2024

The main goal of this study was to investigate the effect of lead (Pb) at various concentrations, as an abiotic factor, and the cross-talk between Pb and pea aphid (Acyrthosiphon pisum (Harris)) (Hemiptera: Aphididae), as a biotic factor, on the defence responses of pea seedlings (Pisum sativum L. cv. Cysterski). The analysis of growth parameters for pea seedlings demonstrated that Pb at a low concentration, i.e., 0.025–0.0625 mM Pb(NO3)2, caused a hormesis effect, i.e., stimulation of seedling growth, whereas Pb at higher concentrations, i.e., 0.01–0.325 mM Pb(NO3)2, inhibited growth, which manifested as the inhibition of length and fresh biomass. The differences in the level of the main defence-related phytohormones, such as abscisic acid (ABA), jasmonic acid (JA) and salicylic acid (SA), and indole-3-acetic acid (IAA)—an auxin stimulating plant cell growth—depended on the dose of Pb, aphid infestation and direct contact of the stress factor with the organ. A high accumulation of soluble sugars in the organs of pea seedlings both at sublethal doses and hormetic doses at early experimental time points was observed. At 0 h and 24 h of the experiment, the hormetic doses of Pb significantly stimulated invertase activities, especially in the roots. Moreover, an increase was observed in the pisatin concentration in pea seedlings growing in the presence of different concentrations of Pb and in the case of cross-talk between Pb and A. pisum in relation to the control. Additionally, a significant induction of the expressions of isoflavone synthase (IFS) and 6α-hydroxymaackiain 3-O-methyltransferase (HMM) genes, which participate in the regulation of the pisatin biosynthesis pathway, in pea seedlings growing under the influence of sublethal 0.5 mM Pb(NO3)2 and hormetic 0.075 mM Pb(NO3)2 doses of Pb was noted. The obtained results showed that the response of P. sativum seedlings depends on the Pb dose applied, direct contact of the stress factor with the organ and the duration of contact.
Antibacterial and Photocatalytic Applications of Silver Nanoparticles Synthesized from Lacticaseibacillus rhamnosus
Authors: Lavecchia Roberto , García-Martínez Janet B. , Contreras-Ropero Jefferson E. , Barajas-Solano Andrés F. , Zuorro Antonio
Published: November 2024

The biosynthesis of silver nanoparticles (AgNPs) presents an innovative and sustainable approach in nanotechnology with promising applications in fields such as medicine, food safety, and pharmacology. In this study, AgNPs were successfully synthesized using the probiotic strain Lacticaseibacillus rhamnosus (BCRC16000), addressing challenges related to stability, biocompatibility, and scalability that are common in conventional nanoparticle production methods. The formation of AgNPs was indicated by a color change from yellow to brown, and UV–visible spectrophotometry confirmed their presence with a characteristic absorption peak at 443 nm. Furthermore, Fourier transform infrared (FTIR) spectroscopy revealed the involvement of biomolecules in reducing silver ions, which suggests their role in stabilizing the nanoparticles. In addition, field emission scanning electron microscopy (FE-SEM) showed significant morphological and structural changes. At the same time, dynamic light scattering (DLS) and zeta potential analyses provided valuable insights such as average size (199.7 nm), distribution, and stability, reporting a polydispersity index of 0.239 and a surface charge of −36.3 mV. Notably, the AgNPs demonstrated strong antibacterial activity and photocatalytic efficiency, underscoring their potential for environmental and biomedical applications. Therefore, this study highlights the effectiveness of Lacticaseibacillus rhamnosus in the biosynthesis of AgNPs, offering valuable antibacterial and photocatalytic properties with significant industrial and scientific implications.
Functional Evaluation of a Novel Homozygous ADCY3 Variant Causing Childhood Obesity
Authors: Mohammed Idris , Selvaraj Senthil , Ahmed Wesam S. , Al-Barazenji Tara , Dauleh Hajar , Love Donald R. , Saraiva Luis R. , Hussain Khalid
Published: November 2024

Adenylate cyclase 3 (ADCY3) is a transmembrane protein predominantly expressed in the primary cilia of neurons. It plays a vital role in converting ATP to cAMP, a secondary messenger that regulates various downstream signaling pathways such as carbohydrates and lipids metabolism. Homozygous loss-of-function variants in the ADCY3 gene lead to severe early-onset obesity and insulin resistance whereas gain-of-function variants protect against obesity. To describe a novel pathogenic ADCY3 variant implicated in early-onset obesity and functionally characterize this variant via in vitro and in silico validation, we identified a novel homozygous nonsense variant c.2520C>G, p.Thr840X in the ADCY3 gene using gene panel sequencing in a four-year-old girl. She was born to first-cousin consanguineous parents. The patient presented with severe obesity, and exhibited hepatomegaly and insulin resistance, with other biochemical and hormonal tests being normal. In vitro and in silico functional analyses showed downregulation and impaired activation of the ADCY3 protein. Our findings contribute to existing research that supports the role of ADCY3 in the genetic pathogenesis of early-onset obesity. In vitro and in silico functional characterization of the novel p.Thr840X variant showed impaired enzymatic activity leading to receptor loss of function, consistent with the patient’s phenotype. Genetic testing is essential in severe early-onset obesity and early diagnosis could benefit patients with personalized treatment strategies.
Non-HLA Autoantibodies Against Angiotensin II Receptor 1 (AT1R) and Endothelin A Receptor (ETAR) in Pediatric Kidney Transplantation
Authors: Antoniello Benedetta , Negrisolo Susanna , Marzenta Diana , Vadori Marta , De Gaspari Piera , Cozzi Emanuele , Benetti Elisa
Published: November 2024

Antibody-mediated rejection (AMR) is the leading cause of premature kidney transplant failure. The role of alloantibodies against Human Leukocyte Antigens (HLA) has been a primary focus in AMR. More recently autoantibodies and alloantibodies against the angiotensin II receptor type 1 (AT1R) and the endothelin A receptor (ETAR) have been linked to poor allograft outcomes in kidney transplantation. Nevertheless, evidence supporting routine testing remains insufficient. ELISA testing for anti-AT1R and anti-ETAR antibodies was performed in a pediatric renal transplant cohort. We selected 12 pediatric recipients who had undergone protocol biopsies and antibody measurements at 6 and 24 months post-transplant. Immunohistochemistry was performed on biopsies for AT1R and ETAR as well as the adhesion molecules ICAM-1 and VCAM-1. The analysis showed that ICAM-1 and VCAM-1 expression was significantly increased, along with the presence of circulating antibodies, in patients at 24 months post-transplant compared to patients without circulating antibodies. The presence of anti-AT1R and anti-ETAR antibodies does not seem to influence the expression of their receptors in the transplanted organ. Instead, the increase in adhesion molecules may precede the development of histological damage. Therefore, enlarging the cohort and extending long-term observation would help to understand the impact of anti-AT1R and anti-ETAR antibodies after transplantation.
MIMR: Development of a Web-Based System for miRNA and mRNA Integrated Analysis
Authors: Kim Dayeon , Ko Younhee
Published: November 2024

The human body is a complex network of systems that is harmonized with multiple biological components. To understand these interactions is very challenging. With rapid development of advanced sequencing technologies, massive amounts of data such as mRNA, miRNA are rapidly accumulated. The integrated analysis of mRNA–miRNA has brought an extensive understanding of complex biological systems and pathological mechanisms. MicroRNAs (miRNAs) are small non-coding RNAs that intricately regulate target gene products, resulting in the inhibition of gene expression. While these miRNAs play crucial roles in essential biological processes—ranging from immunity and metabolism to cell death—their specific impacts on diseases remain unknown. Recent studies have been focused on the integration of miRNA and mRNA expression to reveal the underlying biological pathways and mechanisms responsible for disease manifestation. We proposed a novel approach for integrative analysis of miRNA and mRNA expression data and developed MIMR (Integrative Analysis of miRNA and mRNA), a web-based application that leverages the Random Walk with Restart (RWR) algorithm. MIMR incorporates both direct and indirect interactions by utilizing protein–protein interaction (PPI) networks and experimentally validated mRNA–miRNA target interactions. MIMR provides comprehensive results, including novel pathological pathways associated with a specific disease and interactive network diagrams representing the mRNAs and miRNAs. We applied it to Alzheimer and breast cancer data and successfully identified the novel biological pathways related to these diseases. In summary, MIMR will offer a deeper insight into the hidden mechanisms of diseases and identify potential therapeutic strategies through integrated analysis of miRNAs and mRNAs.
Impact of Dietary Patterns and Serum Amino Acid Profile on Metabolic Syndrome Development in Mexican Women with Polycystic Ovary Syndrome
Authors: Rentería Midory Sánchez , Montoya Jorge Arturo Parra , Romero Geraldine Sosa , de Jesús González Piñuelas Lizbeth , López-Barradas Adriana M. , Granados-Portillo Omar , Chagollán Mariel García , Suárez Ana Laura Pereira , Gillevet Patrick M. , Magaña Natali Vega , Peña Rodríguez Marcela
Published: November 2024

Polycystic ovary syndrome (PCOS) is the main endocrine disorder in women of reproductive age worldwide. This condition is often associated with various metabolic alterations that contribute to the development of metabolic syndrome (MetS). Recent research suggests that branched-chain amino acid (BCAA) dysregulation is observed in PCOS. This study aims to investigate the relationship between dietary patterns, body composition, metabolic analytes, and serum amino acid levels in Mexican women with PCOS. Utilizing a cross-sectional design, we found that both study groups, PCOS (n = 24) and PCOS + MetS (n = 21), exhibited increased relative fat mass and dietary habits characterized by high simple sugar intake and low protein consumption, correlating with levels of relative fat mass and leptin. Notably, serum concentrations of BCAAs and glutamic acid were significantly elevated in the PCOS + MetS group. Our findings suggest that a metabolic approach may enhance the prediction and management of MetS in women with PCOS, highlighting the importance of dietary interventions in this population.
Combined Analysis of Metabolomics and Transcriptome Revealed the Effect of Bacillus thuringiensis on the 5th Instar Larvae of Dendrolimus kikuchii Matsumura
Authors: Li Jinyan , Guo Qiang , Yang Bin , Zhou Jielong
Published: November 2024

Dendrolimus kikuchii Matsumura (D. kikuchii) is a serious pest of coniferous trees. Bacillus thuringiensis (Bt) has been widely studied and applied as a biological control agent for a variety of pests. Here, we found that the mortality rate of D. kikuchii larvae after being fed Bt reached 95.33% at 24 h; the midgut membrane tissue was ulcerated and liquefied, the MDA content in the midgut tissue decreased and the SOD, CAT and GPx enzyme activities increased, indicating that Bt has toxic effects on D. kikuchii larvae. In addition, transmission electron microscopy showed that Bt infection caused severe deformation of the nucleus of the midgut tissue of D. kikuchii larvae, vacuoles in the nucleolus, swelling and shedding of microvilli, severe degradation of mitochondria and endoplasmic reticulum and decreased number. Surprisingly, metabolomics and transcriptome association analysis revealed that four metabolic-related signaling pathways, Nicotinate and nicotinamide metabolism, Longevity regulating pathway—worm, Vitamin digestion and absorption and Lysine degradation, were co-annotated in larvae. More surprisingly, Niacinamide was a common differential metabolite in the first three signaling pathways, and both Niacinamide and L-2-Aminoadipic acid were reduced. The differentially expressed genes involved in the four signaling pathways, including NNT, ALDH, PNLIP, SETMAR, GST and RNASEK, were significantly down-regulated, but only SLC23A1 gene expression was up-regulated. Our results illustrate the effects of Bt on the 5th instar larvae of D. kikuchii at the tissue, cell and molecular levels, and provide theoretical support for the study of Bt as a new biological control agent for D. kikuchii.
Angiopoietin 1 Attenuates Dysregulated Angiogenesis in the Gastrocnemius of DMD Mice
Authors: McClennan Andrew , Hoffman Lisa
Published: November 2024

Duchenne muscular dystrophy (DMD) is a degenerative neuromuscular disease caused by a lack of functional dystrophin. Ang 1 paracrine signalling maintains the endothelial barrier of blood vessels, preventing plasma leakage. Chronic inflammation, a consequence of DMD, causes endothelial barrier dysfunction in skeletal muscle. We aim to elucidate changes in the DMD mouse’s gastrocnemius microvascular niche following local administration of Ang 1. Gastrocnemii were collected from eight-week-old mdx/utrn+/− and healthy mice. Additional DMD cohort received an intramuscular injection of Ang 1 to gastrocnemius and contralateral control. Gastrocnemii were collected for analysis after two weeks. Using immunohistochemistry and real-time quantitative reverse transcription, we demonstrated an abundance of endothelial cells in DMD mouse’s gastrocnemius, but morphology and gene expression were altered. Myofiber perimeters were shorter in DMD mice. Following Ang 1 treatment, fewer endothelial cells were present, and microvessels were more circular. Vegfr1, Vegfr2, and Vegfa expression in Ang 1-treated gastronemii increased, while myofiber size distribution was consistent with vehicle-only gastrocnemii. These results suggest robust angiogenesis in DMD mice, but essential genes were underexpressed—furthermore, exogenous Ang 1 attenuated angiogenesis. Consequentially, gene expression increased. The impact must be investigated further, as Ang 1 therapy may be pivotal in restoring the skeletal muscle microvascular niche.
Anti-Pruritic and Immunomodulatory Effects of Coix [Coix lacryma-jobi L. var. ma-yuen (Rom. Caill.) Stapf.] Sprouts Extract
Authors: Lee Eun-Song , Kim Yong-Il , Lee Jeong-Hoon , Kim Jang-Hoon , Kim Yong-Goo , Han Kyung-Sook , Yoon Young-Ho , Cho Byoung-Ok , Cho Ju-Sung
Published: November 2024

This study explored the anti-pruritic and immunomodulatory effects of Coix sprouts extract, focusing on histamine release and IL-31 cytokine production in HMC-1 cells. The extract significantly inhibited both factors, indicating its potential for pruritus relief. In a pruritus induction mouse model, Coix sprouts extract outperformed prednisolone in anti-pruritus effectiveness, also improving skin lesions and inhibiting mast cell infiltration. The extract suppressed tryptase expression, reduced release, inhibited mast cell proliferation, and lowered nitric oxide production, suggesting anti-inflammatory properties. Coix sprouts extract shows promise in suppressing inflammation and pruritus, making it a valuable candidate for clinical use. Additionally, the analysis of coixol content in Coix sprouts revealed variations in growth time, indicating their potential as functional materials with anti-pruritus and immune-enhancing applications.
Nrf2 Deficiency Exacerbates the Decline in Swallowing and Respiratory Muscle Mass and Function in Mice with Aspiration Pneumonia
Authors: Hashimoto Hikaru , Okazaki Tatsuma , Honkura Yohei , Ren Yuzhuo , Ngamsnae Peerada , Hisaoka Takuma , Koshiba Yasutoshi , Suzuki Jun , Ebihara Satoru , Katori Yukio
Published: November 2024

Aspiration pneumonia exacerbates swallowing and respiratory muscle atrophy. It induces respiratory muscle atrophy through three steps: proinflammatory cytokine production, caspase-3 and calpain, and then ubiquitin–proteasome activations. In addition, autophagy induces swallowing muscle atrophy. Nrf2 is the central detoxifying and antioxidant gene whose function in aspiration pneumonia is unclear. We explored the role of Nrf2 in aspiration pneumonia by examining swallowing and respiratory muscle mass and function using wild-type and Nrf2-knockout mice. Pepsin and lipopolysaccharide aspiration challenges caused aspiration pneumonia. The swallowing (digastric muscles) and respiratory (diaphragm) muscles were isolated. Quantitative RT-PCR and Western blotting were used to assess their proteolysis cascade. Pathological and videofluoroscopic examinations evaluated atrophy and swallowing function, respectively. Nrf2-knockouts showed exacerbated aspiration pneumonia compared with wild-types. Nrf2-knockouts exhibited more persistent and intense proinflammatory cytokine elevation than wild-types. In both mice, the challenge activated calpains and caspase-3 in the diaphragm but not in the digastric muscles. The digastric muscles showed extended autophagy activation in Nrf2-knockouts compared to wild-types. The diaphragms exhibited autophagy activation only in Nrf2-knockouts. Nrf2-knockouts showed worsened muscle atrophies and swallowing function compared with wild-types. Thus, activation of Nrf2 may alleviate inflammation, muscle atrophy, and function in aspiration pneumonia, a major health problem for the aging population, and may become a therapeutic target.
Comprehensive Analysis and Verification of the Prognostic Significance of Cuproptosis-Related Genes in Colon Adenocarcinoma
Authors: Gu Yixiao , Li Chengze , Yan Yinan , Ming Jingmei , Li Yuanhua , Chao Xiang , Wang Tieshan
Published: November 2024

Colon adenocarcinoma (COAD) is a frequently occurring and lethal cancer. Cuproptosis is an emerging type of cell death, and the underlying pathways involved in this process in COAD remain poorly understood. Transcriptomic and clinical data for COAD patients were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We investigated alterations in DNA and chromatin of cuproptosis-related genes (CRGs) in COAD. In order to identify predictive differentially expressed genes (DEGs) and various molecular subtypes, we used consensus cluster analysis. Through univariate, multivariate, and Lasso Cox regression analyses, four CRGs were identified. A risk prognostic model for cuproptosis characteristics was constructed based on four CRGs. This study also examined the association between the risk score and the tumor microenvironment (TME), the immune landscape, and drug sensitivity. We distinguished two unique molecular subtypes using consensus clustering analysis. We discovered that the clinical characteristics, prognosis, and TME cell infiltration characteristics of patients with multilayer CRG subtypes were all connected. The internal and external evaluations of the predicted accuracy of the prognostic model built using data derived from a cuproptosis risk score were completed at the same time. A nomogram and a clinical pathological analysis make it more useful in the field of medicine. A significant rise in immunosuppressive cells was observed in the high cuproptosis risk score group, with a correlation identified between the cuproptosis risk score and immune cell infiltration. Despite generally poor prognoses, the patients with a high cuproptosis risk but low tumor mutation burden (TMB), cancer stem cell (CSC) index, or microsatellite instability (MSI) may still benefit from immunotherapy. Furthermore, the cuproptosis risk score positively correlated with immune checkpoint gene expression. Analyzing the potential sensitivity to medications could aid in the development of clinical chemotherapy regimens and decision-making. CRGs are the subject of our in-depth study, which exposed an array of regulatory mechanisms impacting TME. In addition, we performed additional data mining into clinical features, prognosis effectiveness, and possible treatment medications. COAD’s molecular pathways will be better understood, leading to more precise treatment options.