Search Results (86)

Smart nucleic acid hydrogels (SNAHs), endowed with stimulus responsiveness, function as programmable molecular switches that can perceive diverse external stimuli and undergo rapid, reversible, and highly specific conformational or performance changes. These dynamic properties have enabled the rational design of biosensors with bionic behaviors, facilitating cascaded “recognition–decision–execution” processes that support advanced biological analysis. Consequently, SNAHs are recognized as a core breakthrough for the next generation of intelligent biosensing units. However, a systematic mapping between SNAH design strategies, specific stimuli, and application fields remains lacking. This review mainly analyzes advances in SNAH-based biosensors over the past five years, proposing flexible and feasible design strategies and key trends in customization. Firstly, we systematically summarize molecular recognition modules involved in the construction of SNAHs, including aptamers, DNAzymes, antibodies, and specific binding peptides. Subsequently, we elaborate on the responses of these modules to external stimuli, so as to further facilitate the signal transduction of signals derived from physical, chemical, and biological sources involving temperature, light, magnetic fields, pH, nucleic acids, proteins, other biomolecules, and pathogens. Additionally, the review outlines the research progress of SNAHs in environmental monitoring, food safety, and medical diagnostics. Finally, we provide an integrated perspective on future opportunities and challenges, highlighting the innovative framework for designing SNAH-based biosensors and offering a practical roadmap for next-generation intelligent sensing applications. Full article

Research into muscle tissue pathologies offers great opportunities for new pharmaceutical agents. Current therapies, including corticosteroids and immunosuppressants, have limited efficacy and significant adverse effects. In this context, steroidal hydrazone compound 4d was investigated for its ability to promote muscle growth and regeneration as a potential anabolic and regenerative modulator. Flow cytometry analysis showed that 4d significantly increases cell populations in S phase, indicating a strong proliferative stimulus in pathways regulated by TNF-α, AKT, MAFbX, and SMAD2/3. Molecular docking studies showed that 4d shares strong interactions with the known MasR agonist (EP-2825), exhibiting a higher predicted binding affinity. Furthermore, 4d demonstrated the ability to interact with ACVR1/2A receptors, mimicking the binding profiles of known antagonists and potentially inhibiting myostatin/SMAD signaling. Taken together, experimental and computational evidence supports a dual-mechanistic model in which 4d promotes muscle proliferation and regeneration by (1) activating the MasR–PI3K/AKT/mTOR axis and (2) inhibiting the ACVR1/2A–SMAD pathway, counteracting the action of myostatin. These findings position compound 4d as a promising therapeutic candidate against muscle wasting disorders, including cancer-related cachexia, by inducing a robust and multifactorial anabolic response. Full article

Understanding the molecular crosstalk between drought and iron (Fe) homeostasis is crucial for developing drought-tolerant wheat cultivars with enhanced nutrient quality. In this study, transcriptomic data mining identified 23,271 and 5933 differentially expressed genes (DEGs) under drought and Fe deficiency, respectively, with 2479 DEGs in response to both stresses. Notably, this overlapping set included significant numbers of genes encoding transcription factors (TFs) (149 genes), Fe homeostasis components (274 genes), and those involved in phytohormones pathways (245 genes), particularly the abscisic acid (ABA) pathway. Gene Ontology (GO) analysis revealed specific and commonly affected biological processes, such as response to abiotic stimulus and heme binding. Furthermore, co-expression network analysis revealed modules highly enriched with genes involved in transcriptional regulation and Fe uptake, enabling the identification of key hub regulatory genes, belonging to the MYB, NAC, BHLH, and AP2/ERF families, involved in the shared stress response. Finaly, the expression of a set of candidate TF-encoding genes was validated using qRT-PCR in durum wheat under drought and Fe starvation, providing a detailed overview of the possible shared regulatory mechanisms linking drought and Fe deficiency responses. Full article

MicroRNAs (miRNAs) play a critical role in gene regulation in plants. Several members of the pentatricopeptide repeat (PPR) family have been identified as predicted targets of Ahyp-miR0005, a miRNA specific to amaranth. PPR proteins are essential for mitochondrial and chloroplast biogenesis, as well as plastid-to-nucleus communication, processes fundamental for retrograde signaling between the plastid and nucleus (RSBPN). In this study, we identified the target of Ahyp-miR0005 and its association with the PPR protein family across Amaranthus hypochondriacus, Arabidopsis thaliana, Nicotiana tabacum, and Solanum lycopersicum. Cleavage inhibition by Ahyp-miR0005 was predicted, and the distribution of miRNA binding sites per target gene was analyzed, including their localization within coding PPR domains. Among the main Ahyp-miR0005 target genes, we identified GUN-1, ABO5, and MORF1. Interaction network analysis revealed that different target genes are co-expressed in response to the same stimulus. Gene expression profiling with the Arabidopsis eFP Browser revealed substantial transcriptional changes in predicted targets under six abiotic stress conditions. We further show that abiotic stresses alter the expression of Ahyp-miR0005 amaranth target genes. We anticipate that the expression of Ahyp-miR0005 in non-amaranth plants could replicate the reorganization and coordination of gene expression through RSBPN, thereby improving plant tolerance to various abiotic stresses. Full article

This study investigated the molecular mechanisms by which phthalates induce depression, utilizing network toxicology and molecular docking techniques. By integrating the TargetNet, GeneCards, and PharmMapper databases, 658 potential target genes of phthalates were identified. Additionally, 5433 depression-related targets were retrieved from the GeneCards and OMIM databases. Comparative analysis revealed 360 common targets implicated in both phthalate action and depression. A Protein-Protein Interaction (PPI) network was constructed using the STRING database. Subsequently, the CytoHubba plugin (employing the MCC algorithm) within Cytoscape was used to screen the network, identifying the top 20 hub genes. These core genes include AKT1, CASP3, TNF, TP53, BCL2, and IL6, among others. Validation on the GEO dataset (GSE23848) revealed that the expression of multiple core genes was significantly upregulated in patients with depression (p < 0.05). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that phthalates mainly regulate biological processes such as extracellular stimulus response, lipopolysaccharide metabolism, and chemical synaptic transmission. Depression is mediated by the AGE-RAGE signaling pathway (a complication of diabetes), lipids and atherosclerosis, Endocrine resistance, and the PI3K-Akt signaling pathway. Molecular docking confirmed that phthalates have strong binding activity with key targets (CASP3, TNF, TP53, BCL2, IL6). These findings present a novel paradigm for evaluating the health risks posed by environmental pollutants. Full article

Background/Objectives: A common approach to investigating visual form processing is through studying responses to visual stimuli that comprise illusory contours. Such stimuli induce contours where none exist physically and thus reveal the constructive nature of visual perception and the conditions that engender it. The present work used IC stimuli to study the development of visual form detection and extraction in infants and adults. Methods: Infant and adult participants viewed square stimulus forms with either real or illusory contours, while their looking behavior was measured with an eye tracker. Fixations of the stimuli were coded by region, distinguishing between the contours of the forms and within the forms themselves. Fixations were summed by region, and fixations on forms were interpreted to index the detection of coherent, whole forms. Fixations on contours (real and illusory) were interpreted to index the extraction of form edges. Results: Total form fixations differed by age. For real contours, fixations by infants exceeded those by adults; when contours were illusory, adult fixations were greater than those of infants. Contour fixations were similar between ages. Infants and adults both looked more at contours when illusory than when real. Conclusions: Together, the results provide new conclusions about change and continuity in the visual analysis of form and contour. The results suggest that the visual detection and binding of simple form structure appears to develop between infancy and adulthood. However, the exploration of contours that support the extraction of form contours from backgrounds appears to change little between infancy and adulthood. Full article

Background: Lysophosphatidic acid (LPA) receptor 3 (LPA₃) is involved in many physiological and pathophysiological actions of this bioactive lipid, particularly in cancer. The actions of LPA and oleoyl-methoxy glycerophosphothionate (OMPT) were compared in LPA₃-transfected HEK 293 cells. Methods: Receptor phosphorylation, ERK 1/2 activation, LPA₃-β-arrestin 2 interaction, and changes in intracellular calcium were analyzed. Results: Our data indicate that LPA and OMPT increased LPA₃ phosphorylation, OMPT being considerably more potent than LPA. OMPT was also more potent than LPA to activate ERK 1/2. In contrast, OMPT was less effective in increasing intracellular calcium than LPA. The LPA-induced LPA₃-β-arrestin 2 interaction was fast and robust, whereas that induced by OMPT was only detected at 60 min of incubation. LPA- and OMPT-induced receptor internalization was fast, but that induced by OMPT was more marked. LPA-induced internalization was blocked by Pitstop 2, whereas OMPT-induced receptor internalization was partially inhibited by Pitstop 2 and Filipin and entirely by the combination of both. When LPA-stimulated cells were rechallenged with 1 µM LPA, hardly any response was detected, i.e., a “refractory” state was induced. However, a conspicuous and robust response was observed if OMPT was used as the second stimulus. Conclusions: The differences in these agents’ actions suggest that OMPT is a biased agonist. These findings suggest that two binding sites for these agonists might exist in the LPA₃ receptor, one showing a very high affinity for OMPT and another likely shared by LPA and OMPT (structural analogs) with lower affinity. Full article

Turbot and brill are two congeneric commercial flatfish species with striking differences in skin organization. The calcified appendages in turbot skin are conical tubercles, while in brill, they are elasmoid scales. A skin injury involving epidermal and dermal levels was evaluated 72 h post-injury to compare the skin regeneration processes between both species. An immune-enriched 4x44k turbot oligo-microarray was used to characterize the skin transcriptome and gene expression profiles in both species. RNA-seq was also performed on the brill samples to improve transcriptome characterization and validate the microarray results. A total of 15,854 and 12,447 expressed genes were identified, respectively, in the turbot and brill skin (10,101 shared) using the oligo-microarray (11,953 and 9629 annotated). RNA-seq enabled the identification of 11,838 genes in brill skin (11,339 annotated). Functional annotation of skin transcriptomes was similar in both species, but in turbot, it was enriched on mechanisms related to maintenance of epithelial structure, mannosidase activity, phospholipid binding, and cell membranes, while in brill, it was enriched on biological and gene regulation mechanisms, tissue development, and transferase and catalytic activities. The number of DEGs identified after skin damage in brill and turbot was 439 and 143, respectively (only 14 shared). Functions related to catabolic and metabolic processes, visual and sensorial perception, response to wounding, and wound healing were enriched in turbot DEGs, while metabolism, immune response, oxidative stress, phospholipid binding, and response to stimulus were enriched in brill. The results indicate that differences may be related to the stage of wound repair due to their different skin architecture. This work provides a foundation for future studies directed at skin defense mechanisms, with practical implications in flatfish aquaculture. Full article

The risk of Aspergillus flavus contamination is expanding with global warming. Targeting the pathogenicity of A. flavus at its source and diminishing its colonization within the host may be a potential control strategy. Oxidative stress transcription factor AtfA plays a pivotal role in A. flavus pathogenicity by combating reactive oxygen species (ROS) generated by host immune cells. This study employed chromatin immunoprecipitation sequencing to elucidate the binding sites and epigenetic mechanisms of AtfA under oxidative stress. Among the total 1022 identified potential AtfA-binding peaks, a 10-bp region predominated by 5′-DRTGTTGCAA-3′, which is highly similar to the AP-1 binding motif was predicted. The significantly regulated genes exhibited a variety of biological functions, including regulation of filamentous growth, response to extracellular stimulus, and regulation of gene expression. Moreover, AtfA indirectly influenced these processes via the MAPK signaling pathway, carbon metabolism, and fatty acid metabolism in response to oxidative stress. The absence of atfA contributed to the decrease in the growth and development, sporulation, AFB₁ biosynthesis, and invasion ability of A. flavus under oxidative stress. These findings suggest that AtfA is critical to overcome oxidative stress induced by the host immune cells during the infection, providing a novel target for early prevention of A. flavus contamination. Full article

Skin mast cells (MCs) mediate acute allergic reactions in the cutaneous environment and contribute to chronic dermatoses, including urticaria, and atopic or contact dermatitis. The cAMP response element binding protein (CREB), an evolutionarily well conserved transcription factor (TF) with over 4,000 binding sites in the genome, was recently found to form a feedforward loop with KIT, maintaining MC survival. The most selective MC function is degranulation with its acute release of prestored mediators. Herein, we asked whether CREB contributes to the expression and function of the degranulation-competent receptors FcεRI and MRGPRX2. Interference with CREB by pharmacological inhibition (CREBi, 666-15) or RNA interference only slightly affected the expression of these receptors, while KIT was strongly attenuated. Interestingly, MRGPRX2 surface expression moderately increased following CREB-knockdown, whereas MRGPRX2-dependent exocytosis simultaneously decreased. FcεRI expression and function were regulated consistently, although the effect was stronger at the functional level. Preformed MC mediators (tryptase, histamine, β-hexosaminidase) remained comparable following CREB attenuation, suggesting that granule synthesis did not rely on CREB function. Collectively, in contrast to KIT, FcεRI and MRGPRX2 moderately depend on unperturbed CREB function. Nevertheless, CREB is required to maintain MC releasability irrespective of stimulus, insinuating that CREB may operate by safeguarding the degranulation machinery. To our knowledge, CREB is the first factor identified to regulate MRGPRX2 expression and function in opposite direction. Overall, the ancient TF is an indispensable component of skin MCs, orchestrating not only survival and proliferation but also their secretory competence. Full article

The abdominal testes of Asian elephants show normal spermatogenesis. Heat shock in cryptorchid testes elevates heat shock factor (HSF) expression, leading to germ cell apoptosis, while increased heat shock proteins (HSPs) levels provide protection. To investigate how heat shock affects elephant spermatogenic cells, focusing on heat shock-related molecules and the cell death mechanism, immunohistochemistry and TUNEL staining were employed to assess the immunoexpression of several heat shock-related molecules and the status of apoptosis in elephant fibroblasts (EF) induced by heat shock stimulus. Additionally, the immunoexpression of heat shock-related molecules and cell proliferation status in the elephant spermatogenic cells. Our finding indicated that heat shock-induced HSF1 immunoexpression in EF leads to apoptosis mediated by T-cell death-associated gene 51 (TDAG51) while also upregulating HSP70 to protect damaged cells. In elephant spermatogenic cells, immunostaining revealed a predominance of proliferating cell nuclear antigen (PCNA)-positive cells with minimal TDAG51- and TUNEL-positive cells, suggesting active proliferation and apoptosis suppression during normal spermatogenesis in the abdominal testis. Interestingly, spermatogonia co-immunoexpressed HSF1 and HSP90, potentially reducing apoptosis through protective mechanisms different from those observed in other mammals. Spermatogenic cells did not show immunolocalisation of HSP70, and hence, it may not contribute to protecting the spermatogonia from heat shock because the transcriptional activity of HSF1 is suppressed by HSP90A binding. This study provides insight into the specific heat shock response and defence mechanisms in elephant spermatogenic cells and may contribute to our understanding of species-specific adaptation to environmental stresses of the testis. Full article

Salinity is a common abiotic stress that limits crop productivity. Although there is a wealth of evidence suggesting that miRNA and lncRNA play important roles in the response to salinity in rice seedlings and reproductive stages, the mechanism by which competing endogenous RNAs (ceRNAs) influence salt tolerance and yield in rice has been rarely reported. In this study, we conducted full whole-transcriptome sequencing of rice panicles during the reproductive period to clarify the role of ceRNAs in the salt stress response and yield. A total of 214 lncRNAs, 79 miRNAs, and 584 mRNAs were identified as differentially expressed RNAs under salt stress. Functional analysis indicates that they play important roles in GO terms such as response to stress, biosynthesis processes, abiotic stimuli, endogenous stimulus, and response to stimulus, as well as in KEGG pathways such as secondary metabolite biosynthesis, carotenoid biosynthesis, metabolic pathways, and phenylpropanoid biosynthesis. A ceRNA network comprising 95 lncRNA–miRNA–mRNA triplets was constructed. Two lncRNAs, MSTRG.51634.2 and MSTRG.48576.1, were predicted to bind to osa-miR172d-5p to regulate the expression of OsMYB2 and OsMADS63, which have been reported to affect salt tolerance and yield, respectively. Three lncRNAs, MSTRG.30876.1, MSTRG.44567.1, and MSTRG.49308.1, may bind to osa-miR5487 to further regulate the expression of a stress protein (LOC_Os07g48460) and an aquaporin protein (LOC_Os02g51110) to regulate the salt stress response. This study is helpful for understanding the underlying molecular mechanisms of ceRNA that drive the response of rice to salt stress and provide new genetic resources for salt-resistant rice breeding. Full article

Litter size is a crucial quantitative trait in animals, closely linked to follicular development. Circular RNA (circRNA), a type of single-stranded closed-loop endogenous RNA with stable expression, plays pivotal roles in various biological processes, yet its function in goat follicular development remains unclear. In this study, we collected large (follicle diameter > 3 mm) and small (1 mm < follicle diameter < 3 mm) follicles from black goats in the Chuanzhong region for circRNA sequencing, with the aim of elucidating the functional circRNAs that influence follicle development in goats. Differential analysis revealed that 17 circRNAs were upregulated in large follicles, and 28 circRNAs were upregulated in small follicles. Functional enrichment analysis revealed significant enrichment of pathways related to reproduction, including cellular response to follicle-stimulating hormone stimulus, the PI3K-Akt signaling pathway, the MAPK signaling pathway, and the Notch signaling pathway. Based on the ceRNA mechanism, 45 differentially expressed circRNAs were found to target and bind a total of 418 miRNAs, and an intercalation network including miR-324-3p (circRNA2497, circRNA5650), miR-202-5p (circRNA3333, circRNA5501), and miR-493-3p (circRNA4995, circRNA5508) was constructed. In addition, conservation analysis revealed that 2,239 circRNAs were conserved between goats and humans. Prediction of translation potential revealed that 154 circRNAs may potentially utilize both N6-methyladenosine (m6A) and internal ribosome entry site (IRES) translation mechanisms. Furthermore, the differential expression and circularization cleavage sites of five circRNAs were validated through RT-qPCR and DNA sequencing. Our study constructed a circRNA map in goat follicle development, offering a theoretical foundation for enhancing goat reproductive performance. Full article

The sperm-specific phospholipase C zeta (PLCζ) protein is widely considered as the predominant physiological stimulus for initiating the Ca²⁺ release responsible for oocyte activation during mammalian fertilization. The increasing number of genetic and clinical reports that directly link PLCζ defects and/or deficiencies with oocyte activation failure (OAF) necessitates the use of a powerful therapeutic intervention to overcome such cases of male factor infertility. Currently, in vitro fertilization (IVF) clinics treat OAF cases after intracytoplasmic sperm injection (ICSI) with Ca²⁺ ionophores. Despite their successful use, such chemical agents are unable to trigger the physiological pattern of Ca²⁺ oscillations. Moreover, the safety of these ionophores is not yet fully established. We have previously demonstrated that recombinant PLCζ protein can be successfully used to rescue failed oocyte activation, resulting in efficient blastocyst formation. Herein, we produced a maltose binding protein (MBP)-tagged recombinant human PLCζ protein capable of inducing Ca²⁺ oscillations in mouse oocytes similar to those observed at fertilization. Circular dichroism (CD) experiments revealed a stable, well-folded protein with a high helical content. Moreover, the recombinant protein could retain its enzymatic properties for at least up to 90 days after storage at −80 °C. Finally, a chick embryo model was employed and revealed that exposure of fertilized chicken eggs to MBP-PLCζ did not alter the embryonic viability when compared to the control, giving a first indication of its safety. Our data support the potential use of the MBP-PLCζ recombinant protein as an effective therapeutic tool but further studies are required prior to its use in a clinical setting. Full article

Compounds of natural or synthetic origin present in personal care products, food additives, and packaging may interfere with hormonal regulation and are called endocrine-disrupting chemicals (EDCs). The thyroid gland is an important target of these compounds. The objective of this study was to analyze public data on the human thyroid transcriptome and investigate potential new targets of EDCs in the embryonic and adult thyroid glands. We compared the public transcriptome data of adult and embryonic human thyroid glands and selected 100 up- or downregulated genes that were subsequently subjected to functional enrichment analysis. In the embryonic thyroid, the most highly expressed gene was PRMT6, which methylates arginine-4 of histone H2A (86.21%), and the downregulated clusters included plasma lipoprotein particles (39.24%) and endopeptidase inhibitory activity (24.05%). For the adult thyroid gland, the most highly expressed genes were related to the following categories: metallothionein-binding metals (56.67%), steroid hormone biosynthetic process (16.67%), and cellular response to vascular endothelial growth factor stimulus (6.67%). Several compounds ranging from antihypertensive drugs to enzyme inhibitors were identified as potentially harmful to thyroid gland development and adult function. Full article