Search Results (15,170)

Dehydration response element binding proteins (DREBs) have been identified as major regulators of cold acclimatization in many angiosperms. Cold stress is one of the primary abiotic stresses affecting kiwifruit growth and development. However, kiwifruit is currently one of the most widely consumed fruits worldwide because of its high nutritional value. 5-Aminolevulinic acid (5-ALA) is a nonprotein amino acid known for its distinct promotional effects on plant resistance, growth, and development. However, studies on the function of the kiwifruit DREB gene in alleviating low-temperature stress in its seedlings via exogenous 5-ALA have not been reported. Therefore, in this study, we performed a genome-wide identification of DREB gene family members in kiwifruit and analyzed the regulatory effects of exogenous 5-ALA on kiwifruit DREB genes under low-temperature stress. A total of 193 DREB genes were identified on 29 chromosomes. Phylogenetic analysis classified these genes into six subfamilies. Although there were some differences in cis-elements among subfamilies, all of them contained more biotic or abiotic stresses and hormone-related cis-acting elements. GO and KEGG enrichment analyses revealed that AcDREB plays an essential role in hormone signaling, metabolic processes, and the response to adverse stress. Under low-temperature stress, the application of exogenous 5-ALA inhibited the accumulation of APX and DHAR, promoted an increase in chlorophyll, and increased the accumulation of enzymes and substances such as 5-ALA, MDHAR, GR, ASA, GAH, and GSSH, thereby accelerating ROS scavenging and increasing the cold hardiness of kiwifruits. Functional analysis revealed that 46 differentially expressed DREB genes, especially those encoding AcDREB69, AcDREB92, and AcDREB148, which are involved in ethylene signaling and defense signaling, and, after the transcription of downstream target genes is activated, are involved in the regulation of low-temperature-stressed kiwifruits by exogenous 5-ALA, thus improving the cold tolerance of kiwifruits. Notably, AcDREB69, AcDREB92, and AcDREB148 could serve as key genes for cold tolerance. This study is the first to investigate the function of AcDREB genes involved in the role of exogenous 5-ALA in regulating low-temperature stress, revealing the regulatory mechanism by which DREB is involved in the ability of exogenous 5-ALA to alleviate low-temperature stress. Full article

Diverse realities challenge the management capacity of public and private systems to ensure equitable quality and efficient access to resources, in line with the 2030 Agenda and the Sustainable Development Goals, which aim to close gaps in essential services and ensure quality of life. The reality in Spain, and more specifically in the Principality of Asturias, is that most resources are concentrated in urban areas rather than rural ones, partly due to the region’s geography. Background/Objectives: This study aimed to explore the perspectives of various stakeholders on the early childhood care system in the Principality of Asturias (Spain), with the purpose of analyzing the mechanisms and determinants involved in its functioning and identifying opportunities for improvement. Methods: A qualitative study was conducted using the theoretical framework of the National Institute on Minority Health and Health Disparities (NIMHD) as a conceptual basis. Semi-structured interviews were carried out with 24 participants selected based on their relationship with early childhood care systems, encompassing different levels of responsibility and operational roles. Data were analyzed using a phenomenological approach, employing inductive and deductive coding to identify recurring patterns and code co-occurrences within ATLAS.ti software. Conclusions: This study reveals major barriers to equitable early childhood intervention (ECI) in rural areas, such as geographic isolation, lack of specialists, long waiting times, and poor transport. Six key themes emerged, including the need for standardized system management, better family support, and digital tools like centralized electronic health records. Rural areas are directly limited regarding their access to services, highlighting the need for fair territorial planning and a holistic, inclusive care model. Improving coordination, accessibility, and technology is vital. Full article

Colostrum is a nutrient-rich fluid secreted by mammals shortly after birth, primarily to provide passive immunity and support early immune development in newborns. Among its various sources, bovine colostrum is the most widely used supplement due to its high bioavailability, safety profile, and clinically supported health benefits. Rich in immunoglobulins, lactoferrin, growth factors, and antimicrobial peptides, bovine colostrum exhibits diverse biological activities that extend beyond neonatal health. Recently, the rising prevalence of cancer—driven by environmental stressors such as radiation, processed foods, and chronic inflammation, as well as non-environmental hereditary factors including germline mutations, family history, and epigenetic inheritance—has fueled interest in natural adjunctive therapies. Scientific studies have explored the anticancer potential of bovine colostrum, highlighting its ability to modulate immune responses, inhibit tumor growth, induce apoptosis in cancer cells, and reduce inflammation. Key components including lactoferrin and proline-rich peptides have been identified as contributors to these effects. Additionally, bovine colostrum may help reduce the side effects of standard cancer treatments, such as mouth sores from chemotherapy or weakened immune systems, by helping to heal tissues and boost the body’s defenses. While large-scale clinical studies are still needed, current findings suggest that bovine colostrum holds promise as a supportive element in integrative cancer care. In conclusion, bovine colostrum represents a safe, bioactive-rich natural supplement with multifaceted therapeutic potential, particularly in oncology, owing to its key components such as lactoferrin, immunoglobulins, growth factors (e.g., IGF-1, TGF-β), and proline-rich polypeptides (PRPs), which contribute to its immunomodulatory, anti-inflammatory, and potential anticancer effects. Ongoing and future research will be crucial to fully understand its mechanisms of action and establish its role in evidence-based cancer prevention and treatment strategies. Full article

The TIFY gene family participates in crucial processes including plant development, stress adaptation, and hormonal signaling cascades. While the TIFY gene family has been extensively characterized in model plant systems and agricultural crops, its functional role in Eucalyptus grandis, a commercially valuable tree species of significant ecological and economic importance, remains largely unexplored. In the present investigation, systematic identification and characterization of the TIFY gene family were performed in E. grandis using a combination of genome-wide bioinformatics approaches and RNA-seq-based expression profiling. Nineteen EgTIFY genes were identified in total and further grouped into four distinct subfamilies, TIFY, JAZ (subdivided into JAZ I and JAZ II), PPD, and ZML, based on phylogenetic relationships. These genes exhibited considerable variation in gene structure, chromosomal localization, and evolutionary divergence. Promoter analysis identified a multitude of cis-acting motifs involved in mediating hormone responsiveness and regulating abiotic stress responses. Transcriptomic profiling indicated that EgJAZ9 was strongly upregulated under methyl jasmonate (JA) treatment, suggesting its involvement in JA signaling pathways. Taken together, these results offer valuable perspectives on the evolutionary traits and putative functional roles of EgTIFY genes. Full article

Cellular senescence is a fundamental contributor to numerous dysfunctions and degenerative diseases, including osteoporosis. In genetically modified and preclinical animal models, therapeutic strategies targeting persistent senescent cells have been shown to delay and prevent osteoporosis. Senolytics are a class of drugs or compounds designed to selectively eliminate senescent cells without adversely affecting normal cells. In this review, we focus on the role of senolytic agents in regulating bone metabolism and their potential in the treatment of osteoporosis. We discussed major types of senolytics, such as natural compounds, kinase inhibitors, Bcl-2 family inhibitors, inhibitors of the mouse double minute 2/p53 interaction, heat shock protein 90 inhibitors, p53-binding inhibitors, and histone deacetylase inhibitors. This review also highlights the progress of senolytics in clinical trials. However, clinical results diverge from preclinical evidence. Therefore, senolytics should be critically evaluated as a potential therapeutic strategy for osteoporosis, with further validation required. Full article

Lactoferrin (Lf) is a multifunctional iron-binding glycoprotein of the transferrin family that plays a central role in host defense, particularly in protection against infection and tissue injury. Abundantly present in colostrum, secretory fluids, and neutrophil granules, Lf exerts broad-spectrum antimicrobial activity against bacteria, viruses, fungi, and parasites. These effects are mediated by iron sequestration, disruption of microbial membranes, inhibition of microbial adhesion, and interference with host–pathogen interactions. Beyond its antimicrobial functions, Lf regulates pro- and anti-inflammatory mediators and mitigates excessive inflammation. Additionally, Lf alleviates oxidative stress by scavenging reactive oxygen species and enhancing antioxidant enzyme activity. This review summarizes the current understanding of Lf’s biological functions, with a particular focus on its roles in microbial infections, immune modulation, oxidative stress regulation, and inflammation. These insights underscore the therapeutic promise of Lf as a natural, multifunctional agent for managing infectious and inflammatory diseases and lay the groundwork for its clinical application in immune-related disorders. Full article

Cyclophilins (Cyps), a family of peptidyl-prolyl isomerases, play essential roles in the life cycle of coronaviruses by interacting with viral proteins and modulating host immune responses. In this systematic review, we examined cell culture, animal model, and clinical studies assessing the anti-viral efficacy of cyclosporine A (CsA, PubChem CID: 5284373) and its non-immunosuppressive derivatives against coronaviruses. CsA demonstrated robust anti-viral activity in vitro across a broad range of coronaviruses, including but not limited to HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2, with potent EC₅₀ values in the low micromolar range. Non-immunosuppressive analogs such as Alisporivir and NIM811 exhibited similar inhibitory effects. In vivo, CsA treatment significantly reduced viral load, ameliorated lung pathology, and improved survival in coronavirus-infected animals. Clinical studies further indicated that CsA administration was associated with improved outcomes in COVID-19 patients, including reduced mortality and shorter hospital stays. Mechanistic studies revealed that CsA disrupts the formation of viral replication complexes, interferes with critical Cyp–viral protein interactions, and modulates innate immune signaling. These findings collectively demonstrate the therapeutic potential of cyclophilin inhibitors as broad-spectrum anti-virals against current and emerging coronaviruses. Full article

Atherosclerosis is a multifactorial, chronic inflammatory disorder characterized by the progressive accumulation of plaque within the arterial wall. Recent research has highlighted the pivotal role of bioactive peptides in modulating vascular homeostasis and inflammation. Among these, salusin-α and salusin-β have emerged as critical regulators of atherogenesis. These peptides are generated via differential proteolytic processing of preprosalusin: an amino acid precursor encoded by the torsin family 2 member A gene. Despite their common origin, salusin-α and salusin-β exhibit divergent biological activities. Salusin-β promotes vascular inflammation by enhancing oxidative stress, activating the nuclear factor kappa B signaling pathway, and upregulating proinflammatory cytokines as well as adhesion molecules, and it also facilitates foam cell formation by increasing the expression of acyl-CoA/cholesterol acyltransferase 1 and scavenger receptors, thereby contributing to plaque progression. In contrast, salusin-α appears to exert protective, anti-inflammatory, and anti-atherogenic effects by increasing the expression of the interleukin-1 receptor antagonist and inhibiting key proinflammatory mediators. Additionally, these peptides modulate the proliferation of vascular smooth muscle cells and fibroblasts, with salusin-β promoting cellular proliferation and fibrosis via calcium and 3′,5′-cyclic adenosine monophosphate-mediated pathways, while the role of salusin-α in these processes is less well defined. Altered plasma levels of salusins have been correlated with the presence and severity of atherosclerotic lesions, suggesting their potential as diagnostic biomarkers and therapeutic targets. This review provides a comprehensive overview of biosynthesis, tissue distribution, and dual roles of salusins in vascular inflammation and remodeling, emphasizing their significance in the pathogenesis and early detection of atherosclerotic cardiovascular disease. Full article

Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition. Full article

The GLABROUS1 Enhancer Binding Protein (GeBP) gene family plays a crucial role in plant growth, development, and stress responses. In this study, 28 GeBP genes were identified in Brassica oleracea using HMMER and validated through multiple conserved domain databases. A phylogenetic tree was constructed based on the GeBP protein sequences from B. oleracea, Arabidopsis thaliana, Brassica rapa, and Brassica napus, dividing them into four evolutionary clades (A–D), which revealed a close evolutionary relationship within the genus Brassica. Conserved motif and gene structure analyses showed clade-specific features, while physicochemical property analysis indicated that most BoGeBP proteins are hydrophilic, nuclear-localized, and structurally diverse. Gene duplication and chromosomal localization analyses suggested that both segmental and tandem duplication events have contributed to the expansion of this gene family. Promoter cis-element analysis revealed a dominance of light-responsive and hormone-responsive elements, implying potential roles in photomorphogenesis and stress signaling pathways. Notably, the protein encoded by BolC01g019630.2J possesses both a transmembrane domain and characteristics of the Major Facilitator Superfamily (MFS) transporter family, and it is predicted to localize to the plasma membrane. This suggests that it may act as a molecular bridge between environmental signal perception and transcriptional regulation, potentially representing a novel signaling mechanism within the GeBP family. This unique feature implies its involvement in transmembrane signal perception and downstream transcriptional regulation under environmental stimuli, providing valuable insights for further investigation of its role in stress responses and metabolic regulation. Overall, this study provides a theoretical foundation for understanding the evolutionary patterns and functional diversity of the GeBP gene family in B. oleracea and lays a basis for future functional validation and breeding applications. Full article

Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington’s disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology. Full article

Abscisic acid (ABA) is a key phytohormone involved in regulating plant growth and responses to environmental stress. As receptors of ABA, pyrabactin resistance 1 (PYR)/PYR1-like (PYL) proteins play a central role in initiating ABA signal transduction. In this study, a total of 30 PopPYL genes were identified and classified into three sub-families (PYL I–III) in the pan-genome of 17 Populus species, through phylogenetic analysis. Among these subfamilies, the PYL I subfamily was the largest, comprising 21 members, whereas PYL III was the smallest, with only four members. To elucidate the evolutionary dynamics of these genes, we conducted synteny and Ka/Ks analyses. Results indicated that most PopPYL genes had undergone purifying selection (Ka/Ks < 1), while a few were subject to positive selection (Ka/Ks > 1). Promoter analysis revealed 258 cis-regulatory elements in the PYL genes of Populus euphratica (EUP) and Populus pruinosa (PRU), including 127 elements responsive to abiotic stress and 33 ABA-related elements. Furthermore, six structural variations (SVs) were detected in PYL_EUP genes and significantly influenced gene expression levels (p < 0.05). To further explore the functional roles of PYL genes, we analyzed tissue-specific expression profiles of 17 PYL_EUP genes under drought stress conditions. PYL6_EUP was predominantly expressed in roots, PYL17_EUP exhibited leaf-specific expression, and PYL1_EUP showed elevated expression in stems. These findings suggest that the drought response of PYL_EUP genes is tissue-specific. Overall, this study highlights the utility of pan-genomics in elucidating gene family evolution and suggests that PYL_EUP genes contribute to the regulation of drought stress responses in EUP, offering valuable genetic resources for functional characterization of PYL genes. Full article

Work–life balance (WLB) is central to sustainable social and economic development, as reflected in the UN Sustainable Development Goals 3, 5, and 8. The purpose of this article is to identify and examine the key organisational and personal factors influencing the perceived work–life balance of employees in rural areas. The theoretical framework is grounded in three complementary approaches: the job demands–resources (JD-R) model, spillover theory, and boundary theory. Together, they offer a comprehensive perspective on role dynamics in the context of limited resources, technostress, and family-related tensions. The study was conducted on a sample of 700 rural employees in Poland, predominantly women (60.6%), with the majority aged 35–55 years (53.0%). Data were collected via a structured questionnaire and analysed using an exploratory approach based on regression trees (CART), which are effective in identifying latent and multidimensional relationships. The findings highlight the mechanisms underlying WLB disruptions in rural contexts and pinpoint areas for intervention through public and organisational policies aimed at supporting employee well-being. The most influential factors were workplace comfort, work flexibility, time autonomy, and employee age. Notably, younger employees require better working conditions than older ones to achieve similar WLB levels. The CART analysis also indicates that some disadvantages, such as low workplace comfort, can be mitigated by more flexible work schedules. Employers should therefore provide multidimensional support through complementary measures, monitor job demands, and educate employees on the effective use of available resources. Full article

PR/SET domain 2 (PRDM2)/RIZ is a member of the histone/protein methyltransferases (PRDMs) superfamily. Discovered to have the ability to bind retinoblastoma in the mid-1990s, PRDM2 was assumed to play a role in neuronal development. Like other family members characterized by a conserved N-terminal PR structural domain and a classical C2H2 zinc-finger array at the C-terminus, PRDM2 encodes two major protein types, the RIZ1 and RIZ2 isoforms. The two subtypes differ in the presence or absence of the PR domain: the RIZ1 subtype has the PR domain, whereas the RIZ2 subtype lacks it. The PR domain exhibits varying conservation levels across species and shares structural and functional similarities with the catalytic SET domain, defining histone methyltransferases. Functioning as an SET domain, the PR domain possesses protein-binding interfaces and acts as a lysine methyltransferase. The variable number of classic C2H2 zinc fingers at the C-terminus may mediate protein–protein, protein–RNA, or protein–DNA interactions. An imbalance in the RIZ1/RIZ2 mechanism may be an essential cause of malignant tumors, where PR-positive isoforms are usually lost or downregulated. Conversely, PR-negative isoforms are always present at higher levels in cancer cells. RIZ1 isoforms are also important targets for estradiol interaction with hormone receptors. PRDM2 can regulate gene transcription and expression combined with transcription factors and plays a role in the development of several systemic diseases through mRNA expression deletion, code-shift mutation, chromosomal deletion, and missense mutation occurrence. Thus, PRDM2 is a key indicator for disease diagnosis, but it lacks systematic summaries to serve as a reference for study. Therefore, this paper describes the structure and biological function of PRDM2 from the perspective of its role in various systemic diseases. It also organizes and categorizes its latest research progress to provide a systematic theoretical basis for a more in-depth investigation of the molecular mechanism of PRDM2’s involvement in disease progression and clinical practice. Full article

The understanding of hidden emotions—situations in which individuals deliberately express an emotion different from what they genuinely feel—is a key skill in theory of mind (ToM) development. This ability allows children to reason about discrepancies between internal emotional states and external expressions and is closely tied to linguistic development, particularly vocabulary related to mental states, which supports complex emotional reasoning. Children who are deaf or hard of hearing (DHH), especially those born to hearing non-signing families and raised in oral language environments, may face challenges in early language exposure. This can impact the development of social and emotional skills, including the ability to understand hidden emotions. This study compares the understanding of hidden emotions in hearing children (n = 59) and DHH children (n = 44) aged 7–12 years. All children were educated in spoken language environments; none of the DHH participants had native exposure to sign language. Participants completed a hidden emotions task involving illustrated stories where a character showed a certain emotion in front of two observers, only one of whom was aware of the character’s true emotional state. The task assessed children’s understanding of the character’s emotional state as well as their ability to reason about the impact of hiding emotions on the beliefs of the observers. The results showed that the hearing children outperformed their DHH peers in understanding hidden emotions. This difference was not attributed to hearing status per se but to language use. Specifically, children’s spontaneous use of cognitive verbs (e.g., think or know) in their explanations predicted task performance across the groups, emphasizing the role of mental state language in emotional reasoning. These findings underscore the importance of early and accessible language exposure in supporting the emotional and social cognitive development of DHH children. Full article