Search Results (4,296)

Snakebite envenoming is a neglected tropical disease contributing to a significant number of morbidities and mortalities globally. Reports indicate that venom variation influences antivenom efficacy, which might affect treatment outcomes. The venom composition of Daboia russelii (Russell’s viper), one of the big four snakes in India, has been extensively studied from different geographical regions of India. Nonetheless, the Russell’s viper venom proteome from Kerala (Western Ghats region), together with its study in comparison with the same species’ venom from Tamil Nadu, has not been explored yet. In the current study, Daboia russelii venom from Irula (RVi) and the Western Ghats region in Kerala (RVwg) was characterized through mass spectrometry-based proteomics and few functional assays. The proteomics study identified 52 proteins from 14 snake protein families in RVi and 61 proteins from 17 snake venom protein families in RVwg. Some of the protein families, including DNase and hyaluronidase, as well as vascular endothelial growth factor, were exclusively identified in RVwg venom. Comparative functional analysis indicated that RVwg exhibited higher fibrinogenolytic and hyaluronidase activities, while RVi venom showed higher phospholipase A₂ and L-amino acid oxidase activities. Through ELISA, RVi venom showed an end-point titration value of 1:24,300 for all the antivenoms used in this study, whereas for RVwg, compared to PSAV (Premium serums and vaccines) (1:2700), Virchow and VINS (both 1:8100) antivenoms showed better immunological cross-reactivity. Immunoblotting experiments indicated differential binding and recognition of antigenic epitopes present in both venoms by the polyvalent antivenoms used in the current study. All these findings highlight that the venom proteome varies according to the geographical location, and this significantly influences antivenom efficacy. Full article

Blue fescue (Festuca glauca) is a widely used ornamental grass worldwide. Drought is an important limiting factor for the growth and development of blue fescue; therefore, cultivating new strains of blue fescue with a strong drought tolerance is of great significance for its production practice. To investigate the drought tolerance mechanism of ds-1, this study subjected both ds-1 and “Festina” to a natural drought treatment and measured their physiological and biochemical indicators. A transcriptomic analysis was also conducted to explore the underlying molecular mechanisms. The results showed that, after the drought treatment, the relative water content (RWC), water use efficiency (WUE), and photosynthetic rate (Pn) of ds-1 leaves were significantly higher than those of “Festina”; in addition, the contents of H₂O₂ and O₂⁻, the relative electrical conductivity (REC), the malondialdehyde (MDA) content, the gas conductance (Gs), and the transpiration rate (Tr) were significantly lower than those of “Festina”. The peroxidase (POD) activity of ds-1 was significantly higher than that of “Festina”, while the superoxide dismutase (SOD) activity of ds-1 was significantly lower than that of “Festina”. The transcriptome data analysis showed that there were a total of 9475 differentially expressed genes (DEGs) between ds-1 and “Festina”. A Venn plot analysis showed 692 DEGs between ds-1—8d vs. “Festina”—8d and ds-1—16d vs. “Festina”—16d. A KEGG enrichment analysis showed that these 692 genes were mainly enriched in 86 pathways, including those related to the photosynthesis antenna protein, plant hormone signal transduction, MAPK signaling, starch and sucrose metabolism, and arginine and proline metabolism. Further screening identified genes that may be associated with drought stress, including PYL, PP2C, SnRK2, ABF, BRI1, JAZ, MYC2, Lhc, and MPK6. The qRT-PCR results indicated that the expression trends of the DEGs were consistent with the transcriptome sequencing results. Our research results can provide a basis for exploring candidate genes for drought tolerance in blue fescue. In addition, our research results provide valuable genetic resources for the development of drought-resistant ornamental grass varieties, which can help reduce water consumption in cities and decrease labor and capital investment. Full article

Background: Glioblastomas (GBMs) are the most aggressive and common neoplasms that affect glial cells, presenting rapid growth, invasion, and resistance to treatments. Studies have demonstrated the potentially inhibitory effect of flavonoids on glioblastoma cells’ stemness and viability. However, further research is needed to explore sensitivity and the mechanism of action in chemoresistant cells. Methods: In this study, we characterized the impact of apigenin treatment on the viability and differentiation of human GBM cells in vitro and its effects on tumorigenesis and regulation of the inflammatory response in vivo. Results: The flavonoid apigenin reduced the viability of U-251 cells, patient-derived cells TG-1 and OB-1 stem cells in a dose-dependent manner, associated with the induction of acidic vesicle organelles formation and apoptosis. Treatment with apigenin also inhibited migration and induced neural differentiation in the remaining viable cells, characterized by a decrease in the expression of the precursor marker nestin and an increase in the expression of astrocyte and neuron markers, GFAP and β-III tubulin, respectively. The xenotransplantation of apigenin-pretreated U251 cells into rat brains did not lead to tumor formation, unlike untreated cells. The surrounding area of transplanted untreated U251 cells exhibited reactive microglia and astrocytes, along with increased VEGF expression, which was absent in implant sites of apigenin-pretreated GBM cells. Moreover, in this implant area, we observed a significant decrease in the expression of mRNA for inflammatory factors IL-1β, TNF, and NOS2, and the downregulation of IL-10 and IL-4. Conclusions: These results demonstrate that apigenin inhibits the growth of tumoral cells, affecting the viability of tumor stem cells and impairing tumorigenicity, while altering the regulatory profile of immunomodulatory proteins. Therefore, this flavonoid can be considered for further studies to determine its use as an adjuvant to the treatment of human GBMs. Full article

Survival rates for those with metastatic osteosarcoma (OS) have not improved over the last four decades. It is imperative that novel approaches to treating and curing OS be sought. We, therefore, turned our attention to Brusatol (Bru), a naturally occurring Nrf2 inhibitor reported to elicit anti-cancer effects in a multitude of tumour models. Importantly there is emerging evidence that Nrf2 is implicated in chemoradiotherapy resistance in OS and that inhibiting Nrf2 may represent a desirable route to treating OS. Surprisingly, using the human OS cell line, MG63, we actually found that Bru promoted cell growth. Compared to control, normoxic cultures, the application of Bru (50 nM) over 3 days led to an increase in cell number by approximately 1.7-fold. A similar outcome occurred for cells under hypoxic conditions, although the extent of cell growth was significantly less at around 1.3-fold. Furthermore, Bru prevented MG63 differentiation in response to co-treatment with the calcitriol analogue, EB1089, and the lipid growth factor, lysophosphatidic acid. The extent of inhibition was profound at approximately 2.8-fold. The application of the Nrf2 activator, dimethyl fumarate, did not rescue these phenotypes. Whilst Bru has shown promise in other cancer models, it would appear, from our findings, that this agent may not be suitable for the treatment of OS. Full article

The MADS-box transcription factors play essential roles in various processes of plant growth and development. Here, we identified 107 MADS-box genes in Osmanthus fragrans Lour. genome (OfMADS), encoding proteins ranging from 61 to 608 amino acids. Phylogenetic analysis classified these genes into five subfamilies: MIKC*, MIKCC, Mα, Mβ, and Mγ, with conserved motif architectures within subfamilies. Tandem and whole-genome duplications were identified as key drivers of OfMADS expansion. Cis-regulatory element analysis revealed enrichment for hormone response and developmental regulatory motifs, implicating roles in growth and flowering processes. Transcriptome dynamics across six floral developmental stages (bolting to petal shedding) uncovered 78 differentially expressed OfMADS genes, including 16 exhibiting flower-specific expressions. Integrated metabolome profiling demonstrated robust correlations between critical OfMADS regulators and scent metabolites. This nexus suggests a potential role of these OfMADS in regulating specialized metabolite biosynthesis pathways. Our multi-omics study provides insights into the regulatory hierarchy of OfMADS in coordinating floral morphogenesis and the accumulation of economically significant metabolites in O. fragrans. These findings establish a foundation for subsequent functional validation and molecular breeding of horticultural traits. Full article

The Nile tilapia (Oreochromis niloticus), a key aquaculture species, displays marked sexual growth dimorphism, with males growing faster than females. This process is governed by intricate interactions between antagonistic regulators, including transcription factors, growth factors, and steroid hormones, operating through sex-specific developmental pathways. While circular RNAs (circRNAs) are known to modulate gene expression by sponging microRNAs (miRNAs), their role in teleost sex differentiation remains poorly understood. To address this gap, we profiled circRNA expression in tilapia gonads by constructing six circRNA libraries from testes and ovaries of 180 days after hatching (dah) fish, followed by high-throughput sequencing. We identified 6564 gonadal circRNAs distributed across all 22 linkage groups, including 226 differentially expressed circRNAs (DECs; 108 testis-biased, 118 ovary-biased). Functional enrichment analysis linked their host genes to critical pathways such as cAMP signaling, cell adhesion molecules, and—notably—sexual differentiation processes (e.g., estrogen signaling, oocyte meiosis, and steroid hormone biosynthesis). Furthermore, we deciphered competing endogenous RNA (ceRNA) networks, uncovering circRNA–miRNA–mRNA interactions targeting germ cell determinants, sex-specific transcription factors, and steroidogenic enzymes. This study provides the first systematic exploration of circRNA involvement in tilapia sex differentiation and gonadal differentiation, offering novel insights into the post-transcriptional regulation of sexual dimorphism. Our findings advance the understanding of circRNA biology in fish and establish a framework for future studies on aquaculture species with similar reproductive strategies. Full article

Bulbine species (Asphodelaceae) are routinely used in many African communities to treat various dermatological disorders, including wounds, due to their relative accessibility, affordability, safety records, and reported efficacies. However, these reported biological activities lack robust empirical evidence and well-validated cellular mechanisms for plausible applications. Hence, this review was aimed at investigating the bioactive compounds of Bulbine species linked to their cellular wound healing attributes, their toxicity, and cytotoxicity. A detailed literature search was conducted using Web of Science, Google scholar, and PubMed, followed by Scopus and VOSviewer (version 1.6.20) bibliographic analyses. Bulbine frutescens (L.) Willd. and Bulbine natalensis Baker safely mediate tissue healing and coagulation cascade as adaptogens and cytotoxic agents. The wound healing activities of the Bulbine species were linked to the synergistic wound healing or tissue repair properties of bioactive compounds (such as saponins, terpenoids, luteolin, and apigenin) via the expression of collagen type-I, alpha-2 (COL1A2) gene, collagen III, increase in the wound tensile strength, and anti-cytokine interleukin-10 (IL-10) mRNA. Bulbine species were also reported to contain specialised biomarker compounds (such as naphthoquinones, bulbine-emodin, and aloe-emodin) which mediate the activation of hydroxyproline, Aryl Hydrocarbon Receptor, transforming growth factor beta—β1 (TGFβ1), and the suppressor of mothers against decapentaplegic proteins (SMAD), which ultimately induce tissue granulation, myofibroblast differentiation, re-epithelialization, higher protein complexes, and scar tissue formations. These findings give credence to the wound healing therapeutic potential of Bulbine species. However, additional clinical studies are necessary to further ascertain the reported efficacies of Bulbine species’ bioactive principles, their overall safety, and the underlying cellular mechanisms involved in the wound healing process and carcinogenesis. Full article

To explore strategies for the safe utilization of farmland co-contaminated with cadmium (Cd) and lead (Pb), this field study systematically evaluated the impacts of humic acid (HA) and potassium fulvate (PF) at different application rates (0, 1500, 3000, and 4500 kg·ha⁻¹) on the growth, yield, and translocation of Cd and Pb within the soil–plant system of maize (Zea mays L.). The results showed that while HA and PF did not significantly alter total soil Cd and Pb concentrations, they markedly reduced their bioavailable fractions. This mitigation of heavy metal phytotoxicity significantly promoted maize growth and yield, with the high-dose HA treatment increasing yield by a maximum of 32.9%. Both amendments dose-dependently decreased Cd and Pb concentrations, bioconcentration factors (BCF), and translocation factors (TF) in all maize tissues, particularly in the grains. At equivalent application rates, PF was slightly more effective than HA in reducing heavy metal concentrations in the grains. Notably, a significant positive correlation was observed between Cd and Pb concentrations across all plant parts, confirming a synergistic accumulation and translocation mechanism. This synergy provides a physiological explanation for the broad-spectrum immobilization efficacy of these humic substances. In conclusion, applying HA and PF presents a dual-benefit strategy for increasing yield and reducing risks in Cd- and Pb-contaminated farmlands. This study proposes a differentiated application approach: PF is the preferred option when ensuring food-grade safety is the primary goal, whereas high-dose HA is more advantageous for maximizing yield in soils with low-to-moderate contamination risk. Full article

The digital economy is significantly transforming the global economic environment and has emerged as the primary driver behind China’s high-quality development. The comprehensive melding of the cultural and tourism sectors (CTI) serves as a strategic approach to boost regional competitiveness and enhance public welfare. This study investigates the mechanisms and boundary conditions through which the growth of the digital economy across China’s 31 provinces from 2011 to 2023 impacts CTI, aiming to address existing research gaps related to micro-level transmission mechanisms and the analysis of contextual variables. Utilizing a two-way fixed-effects moderated mediation model complemented by instrumental variable (IV-2SLS) regression for testing endogeneity, the research uncovers intricate interactions among the digital economy, CTI, and significant influencing factors. The results strongly suggest that advancements in the digital economy substantially facilitate the integration of cultural and tourism sectors. This beneficial effect is partially mediated through two primary channels: the construction of new infrastructure and enhancements in employment quality, underscoring the critical role of both material and human capital in digital empowerment. Significantly, this research uniquely identifies that new quality productive forces (NQP) have a notable negative moderating impact on the link between the digital economy and cultural–tourism integration. This indicates that in provinces exhibiting high levels of NQP, the positive influence of the digital economy on cultural–tourism integration is considerably diminished. This unexpected finding can be interpreted through mechanisms such as resource dilution, varied integration pathways or maturity effects, along with differences in developmental stages and priorities. Furthermore, it resonates well with the resource-based view, innovation ecosystem theory, and dynamic capability theory. Instrumental variable regression further substantiates the notable positive influence of the digital economy on the integration of cultural tourism. This approach effectively tackles potential endogeneity concerns and reveals the upward bias that may exist in fixed-effects models. The findings contribute significantly to theoretical frameworks by enhancing the understanding of the intricate mechanisms facilitating the digital economy and, for the first time, innovatively designating NQP as a surprising key boundary condition. This enriches theories related to industrial advancement and resource allocation in the digital age. On a practical note, the research provides nuanced and differentiated policy guidance aimed at optimizing pathways for integration across various Chinese provinces at different stages of development. Additionally, it underscores significant implications for other developing nations engaged in digital tourism growth, thereby improving its global relevance. Full article

In the Red List of Threatened Species, released by International Union for Conservation of Nature (IUCN), Paphiopedilum helenae has been classified as an endangered species. It exhibits exceptional decorative value and germplasm resource potential. To elucidate the ecological adaptation of this species and the characteristics of its rhizosphere microbiome, bacterial 16S rRNA and fungal ITS sequences of three wild populations of P. helenae were investigated using Illumina high-throughput sequencing technology and the microbial community structures and diversities were systematically compared. These three populations were spanned across distinct geographical locations in Longzhou County, Guangxi. The results showed that the bacterial community in the rhizosphere soil of P. helenae comprised 31 phyla, primarily including Actinobacteriota, Proteobacteria, Chloroflexi and Acidobacteriota. On the other hand, the fungal community consisted of 10 phyla, dominated by Ascomycota and Basidiomycota. There were significant differences in the diversity of rhizosphere microbes across different populations of P. helenae. The LG population had the highest bacterial richness (Chao index: 2912.71 ± 131.73; p < 0.05) and diversity (Shannon index: 6.40 ± 0.06; p < 0.01), while the MQ population had the lowest diversity (Shannon index: 3.47 ± 0.24; p < 0.01) of fungi. The degree of variation in fungal β-diversity was significantly higher than that of bacteria. Soil organic matter (SOM) and available nitrogen (AN) contents were the core factors shaping the microbial communities in the rhizosphere soil of P. helenae, which jointly explained 49.87% and 16.39% of variations in the bacterial and fungal communities. Furthermore, population-specific enrichment of functionally significant microorganisms was evident. Population MQ was enriched with plant growth-promoting and stress-resistant fungi, such as Geminibasidium, Trichoderma, etc. Population LG was enriched with oligotrophic bacteria (e.g., Patescibacteria), while population SL exhibited an overwhelming dominance of Ascomycota (93.25%) and enrichment of pathogenic fungal genus Nigrospora. This research revealed the variations in the functional adaptation strategy of P. helenae and the microbial communities in the rhizosphere soils across different geographical locations. This suggests that microbial community imbalance in rhizosphere soil may be one of the factors leading to the endangerment of this plant species. The study proposed a differentiated protection strategy for endangered plant species based on microbial resources. The results provide a theoretical basis for development of a “microorganism-assisted protection” strategy for ecological restoration and sustainable utilization of endangered orchid plants. Full article

Objective: This study examines the effects of non-standard (lactose-reduced, hydrolyzed), cow-milk-based infant formulas on early childhood growth outcomes compared to standard formulas and breastfeeding. Methods: This retrospective cohort study included full-term infants with a birth weight >2500 g. Exposure and control data, including the type of infant formula [non-standard vs. standard] and breastfeeding status, were obtained at 2-month well visits. Growth outcomes (weight-for-age, length-for-age, BMI (Body Mass Index), and weight-for-length z-scores] were calculated using WHO (World Health Organization) growth standards at 1- and 2-year well visits. Generalized linear mixed models were used to evaluate associations between formula type and growth outcomes, adjusting for maternal, infant, and socioeconomic factors. Results: A total of 5515 infants were included in the final analysis. Feeding practices included exclusive breastfeeding (35%), standard formula (42%), and non-standard formula (23%). Infants fed non-standard formulas had significantly higher weight-for-age, BMI, and weight-for-length z-scores at 12 months than those fed standard formulas, and after controlling for other covariates, weight-for-age and BMI z-scores remained significantly higher in the non-standard formula infants. At 24 months, only weight-for-age z-scores remained significantly higher for non-standard formula users compared to standard formula users. Both non-standard and standard formula groups showed significantly higher weight-for-age, BMI, weight-for-length, and length-for-age z-scores compared to breastfed infants at 12 and 24 months. Conclusions: Non-standard infant formula may have a differential effect on growth during the first year of life compared to standard infant formula and breastfeeding. Future research should explore the long-term health effects of non-standard infant formula use and the risk of obesity. Full article

In many cancers, tumorigenesis is determined in part by the cell type in the tissue that transforms, which has been called the cell of origin. In intestinal cancer, previous observations suggested that transformation can occur from both stem cells and more differentiated cells; in the latter case, this is provided that NF-kB is activated and apoptosis is blocked. However, whether these distinct transformation trajectories yield similar types of cancer remains unresolved. In this study the effect of APC loss within different cellular backgrounds was analyzed. Transformation of either stem-like cells or secretory-like cells, as defined by CD24 or c-KIT expression, by deleting the APC function in organoids in vitro, led to WNT-independent growth of organoids in both cellular populations. Importantly, transformed cultures derived from secretory-like cells had significantly distinct gene expression profiles as compared to the more stem cell-derived (CD44^high cells) APC mutant cultures and in fact preserved a level of gene expression that relates back to their original cell lineage. Our data highlights the influence of different cellular backgrounds on the initiation of intestinal cancer and suggests that the cell of origin could be a defining factor in colorectal cancer heterogeneity. Full article

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone, is a significant modulator of energy homeostasis. We evaluated serum FGF21 levels in patients with a deficiency of mitochondrial aminoacyl-tRNA synthetase (mt-aARSs). Six patients with mitochondrial aminoacyl tRNA synthetase deficiency and twelve healthy volunteers were included in this study. Whole-exome sequencing was used for molecular diagnosis. Serum FGF21 levels in the case group and healthy volunteers were analyzed using the enzyme-linked immunosorbent assay. Exome sequencing test revealed nine different pathogenic variants in the AARS2, EARS2, DARS2, SARS2, and WARS2 genes. A statistically significant difference was found between the serum FGF21 levels of the case and control groups: case group (n = 6), 882.49 ± 923.60 pg/mL; control group (n = 12), 20.89 ± 2.63 pg/mL (p < 0.001). The area under the ROC curve for FGF21 in the differential diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiency was 1.000 (0.813–1.000). Sensitivity and specificity were 100%, and positive and negative predictive values were also 100% for an FGF21 cut-off value > 27.4 pg/mL. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARSs deficiency may provide insight into the level of damage. Investigation of the biochemical mechanisms underlying the different levels of damage caused by different aminoacyl tRNA synthetases will be important in terms of elucidating clinical heterogeneity. Full article

Mechanistic cancer models can encapsulate beliefs about the main factors influencing tumour growth. In recent decades, many different types of dynamic models have been used for this purpose. The integration of a model’s differential equations yields a simulation of the behaviour of the system over time, thus enabling tumour progression to be predicted. A requisite for the reliability of these quantitative predictions is that the model is structurally identifiable and observable, i.e., that it is theoretically possible to infer the correct values of its parameters and state variables from time course data. In this paper, we show how to analyse these properties of tumour growth models using a well-established methodology, which we implemented previously in an open-source software tool. To this end, we provide an account of 20 published models described by ordinary differential equations, some of which incorporate the effect of interventions including chemotherapy, radiotherapy, and immunotherapy. For each model, we describe its equations and analyse their structural identifiability and observability, discussing how they are affected by the experimental design. We provide computational implementations of these models, which enable readily reproducing results. Our results inform about the possibility of inferring the parameters and state variables of a given model using a specific measurement setup, and, together with the corresponding methodology and implementation, they can be used as a blueprint for analysing other models not included here. Thus, this paper serves as a guide to select the most appropriate model for each application. Full article

Dental caries, a prevalent biofilm-mediated chronic disease, causes enamel demineralization, pulp infection, and systemic complications. Dental plaque biofilm is the initiating factor for the occurrence and development of caries. Streptococcus mutans is an opportunistic pathogen linked to the structure and ecology of dental plaque biofilms. The molecular mechanism of S. mutans during biofilm ontogeny in driving cariogenesis has been extensively elucidated. Here, we observed that asiatic acid is a potent biofilm disruptor that selectively dismantles S. mutans biofilm architectures, prompting us to investigate its mechanism. The minimum biofilm inhibition concentration (MBIC) of asiatic acid on S. mutans was 62.5 μM, but the MBIC level did not substantially impede planktonic growth. Using the static active-attachment model, it was demonstrated that asiatic acid significantly reduced biofilm biomass (p < 0.001) and extracellular polysaccharides (EPS) content (p < 0.001), while concurrently diminishing acid production (p = 0.017) and metabolic activity (p = 0.014). Confocal and scanning electron microscopy further confirmed structural disintegration, including bacterial detachment and reduced biofilm thickness. Transcriptome analysis of S. mutans biofilm treated with asiatic acid revealed 454 differentially expressed genes (adjusted p < 0.05, |log₂FC| ≥ 1). Notably, genes related to the CiaRH two-component system (ciaR, ciaH), a central regulatory hub for biofilm maturation and acid tolerance. This disruption initiates a downstream cascade, causing a coordinated downregulation of critical gene clusters essential for virulence and pathogenesis, including stress response (htrA, clpP, groEL, dnaK), and the glucan-binding protein gene (gbpC) essential for biofilm structural integrity. These findings provide the first mechanistic evidence linking asiatic acid to transcriptional reprogramming in S. mutans biofilm, offering a novel ecological strategy for caries prevention by targeting key regulatory pathways. Full article