Search Results (2,415)

Plant peptides, as key signaling molecules, play pivotal roles in plant growth, development, and stress responses. This review focuses on research progress in plant peptides involved in plant immunity, providing a detailed classification of immunity-related plant polypeptides, including small post-translationally modified peptides, cysteine-rich peptides, and non-cysteine-rich peptides. It discusses the mechanisms by which plant polypeptides confer disease resistance, such as their involvement in pattern-triggered immunity (PTI), effector-triggered immunity (ETI), and regulation of hormone-mediated defense pathways. Furthermore, it explores potential agricultural applications of plant polypeptides, including the development of novel biopesticides and enhancement of crop disease resistance via genetic engineering. By summarizing current research, this review aims to provide a theoretical basis for in-depth studies on peptide-mediated disease resistance and offer innovative insights for plant disease control. Full article

The retina is highly sensitive to oxygen and blood supply, and hypoxia plays a key role in retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Müller glial cells, which are essential for retinal homeostasis, respond to injury and hypoxia with reactive gliosis, characterized by the upregulation of the glial fibrillary acidic protein (GFAP) and vimentin, cellular hypertrophy, and extracellular matrix changes, which can impair retinal function and repair. The retinal pigment epithelium (RPE) supports photoreceptors, forms part of the blood–retinal barrier, and protects against oxidative stress; its dysfunction contributes to retinal degenerative diseases such as AMD, retinitis pigmentosa (RP), and Stargardt disease (SD). Extracellular vesicles (EVs) play a crucial role in intercellular communication, protein homeostasis, and immune modulation, and have emerged as promising diagnostic and therapeutic tools. Understanding the role of extracellular vesicles’ (EVs’) signaling machinery of glial cells and the retinal pigment epithelium (RPE) is critical for developing effective treatments for retinal degeneration. In this study, we investigated the bidirectional EV-mediated crosstalk between RPE and Müller cells under hypoxic conditions and its impact on cellular metabolism and retinal cell integrity. Our findings demonstrate that RPE-derived extracellular vesicles (RPE EVs) induce time-dependent metabolic reprogramming in Müller cells. Short-term exposure (24 h) promotes pathways supporting neurotransmitter cycling, calcium and mineral absorption, and glutamate metabolism, while prolonged exposure (72 h) shifts Müller cell metabolism toward enhanced mitochondrial function and ATP production. Conversely, Müller cell-derived EVs under hypoxia influenced RPE metabolic pathways, enhancing fatty acid metabolism, intracellular vesicular trafficking, and the biosynthesis of mitochondrial co-factors such as ubiquinone. Proteomic analysis revealed significant modulation of key regulatory proteins. In Müller cells, hypoxic RPE-EV exposure led to reduced expression of Dyskerin Pseudouridine Synthase 1 (DKc1), Eukaryotic Translation Termination Factor 1 (ETF1), and Protein Ser/Thr phosphatases (PPP2R1B), suggesting alterations in RNA processing, translational fidelity, and signaling. RPE cells exposed to hypoxic Müller cell EVs exhibited elevated Ribosome-binding protein 1 (RRBP1), RAC1/2, and Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 (GNAI1), supporting enhanced endoplasmic reticulum (ER) function and cytoskeletal remodeling. Functional assays also revealed the compromised barrier integrity of the outer blood–retinal barrier (oBRB) under hypoxic co-culture conditions. These results underscore the adaptive but time-sensitive nature of retinal cell communication via EVs in response to hypoxia. Targeting this crosstalk may offer novel therapeutic strategies to preserve retinal structure and function in ischemic retinopathies. Full article

Tau protein is essential for the structural stability of neurons, particularly through its role in microtubule assembly and axonal transport. However, when abnormally hyperphosphorylated or cleaved, Tau can aggregate into insoluble forms that disrupt neuronal function, contributing to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence suggests that similar Tau-related alterations may occur in individuals with chronic exposure to psychoactive substances. This review compiles experimental, clinical, and postmortem findings that collectively indicate a substance-specific influence on Tau dynamics. Alcohol and opioids, for instance, promote Tau hyperphosphorylation and fragmentation through the activation of kinases such as GSK-3β and CDK5, as well as proteases like caspase-3, leading to neuroinflammation and microglial activation. Stimulants and dissociatives disrupt insulin signaling, increase oxidative stress, and impair endosomal trafficking, all of which can exacerbate Tau pathology. In contrast, cannabinoids and psychedelics may exert protective effects by modulating kinase activity, reducing inflammation, or enhancing neuroplasticity. Psychedelic compounds such as psilocybin and harmine have been demonstrated to decrease Tau phosphorylation and facilitate cognitive restoration in animal models. Although the molecular mechanisms differ across substances, Tau consistently emerges as a convergent target altered in substance-related cognitive disorders. Understanding these pathways may provide not only mechanistic insights into drug-induced neurotoxicity but also identify Tau as a valuable biomarker and potential therapeutic target for the prevention or treatment of cognitive decline associated with substance use. Full article

Obesity, a multifactorial metabolic syndrome driven by genetic–epigenetic crosstalk and environmental determinants, manifests through pathological adipocyte hyperplasia and ectopic lipid deposition. With the limitations of conventional anti-obesity therapies, which are characterized by transient efficacy and adverse pharmacological profiles, the scientific community has intensified efforts to develop plant and fungal polysaccharide therapeutic alternatives. These polysaccharide macromolecules have emerged as promising candidates because of their diverse biological activities and often act as natural prebiotics, exerting beneficial effects through multiple pathways. Plant and fungal polysaccharides can reduce blood glucose levels, alleviate inflammation and oxidative stress, modulate metabolic signaling pathways, inhibit nutrient absorption, and reshape gut microbial composition. These effects have been shown in cellular and animal models and are associated with mechanisms underlying obesity and related metabolic disorders. This review discusses the complexity of obesity and multifaceted role of plant and fungal polysaccharides in alleviating its symptoms and complications. Current knowledge on the anti-obesity properties of plant and fungal polysaccharides is also summarized. We highlight their regulatory effects, potential intervention pathways, and structure–function relationships, thereby providing novel insights into polysaccharide-based strategies for obesity management. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Cardiopulmonary bypass (CPB) is associated with significant neurological complications, yet the mechanisms underlying brain injury remain unclear. This study investigated the role of interleukin-17A (IL-17A) in exacerbating CPB-induced neuronal apoptosis and identified vulnerable brain regions. Utilizing a rat CPB model and an oxygen–glucose deprivation/reoxygenation (OGD/R) cellular model, we demonstrated that IL-17A levels were markedly elevated in the hippocampus post-CPB, correlating with endoplasmic reticulum stress (ERS)-mediated apoptosis. Transcriptomic analysis revealed the enrichment of IL-17 signaling and apoptosis-related pathways. IL-17A-Neutralizing monoclonal antibody (mAb) and the ERS inhibitor 4-phenylbutyric acid (4-PBA) significantly attenuated neurological deficits and hippocampal neuronal damage. Mechanistically, IL-17A activated the Act1-IRE1-JNK1 axis, wherein heat shock protein 90 (Hsp90) competitively regulated Act1-IRE1 interactions. Co-immunoprecipitation confirmed the enhanced Hsp90-Act1 binding post-CPB, promoting IRE1 phosphorylation and downstream caspase-12 activation. In vitro, IL-17A exacerbated OGD/R-induced apoptosis via IRE1-JNK1 signaling, reversible by IRE1 inhibition. These findings identify the hippocampus as a key vulnerable region and delineate a novel IL-17A/Act1-IRE1-JNK1 pathway driving ERS-dependent apoptosis. Targeting IL-17A or Hsp90-mediated chaperone switching represents a promising therapeutic strategy for CPB-associated neuroprotection. This study provides critical insights into the molecular crosstalk between systemic inflammation and neuronal stress responses during cardiac surgery. Full article

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Polyvinyl chloride (PVC) is commonly employed as mulch in agriculture to boost crop yields. However, its toxicity is often overlooked. Due to its chemical stability, resistance to degradation, and the inadequacy of the recycling system, PVC tends to persist in farm environments, where it can decompose into microplastics (MPs) or nanoplastics (NPs). The radish (Raphanus sativus L.) was chosen as the model plant for this study to evaluate the underlying toxic mechanisms of PVC NPs on seedling growth through the integration of multi-omics approaches with oxidative stress evaluations. The results indicated that, compared with the control group, the shoot lengths in the 5 mg/L and 150 mg/L treatment groups decreased by 33.7% and 18.0%, respectively, and the root lengths decreased by 28.3% and 11.3%, respectively. However, there was no observable effect on seed germination rates. Except for the peroxidase (POD) activity in the 150 mg/L group, all antioxidant enzyme activities and malondialdehyde (MDA) levels were higher in the treated root tips than in the control group. Both transcriptome and metabolomic analysis profiles showed 2075 and 4635 differentially expressed genes (DEGs) in the high- and low-concentration groups, respectively, and 1961 metabolites under each treatment. PVC NPs predominantly influenced seedling growth by interfering with plant hormone signaling pathways and phenylpropanoid production. Notably, the reported toxicity was more evident at lower concentrations. This can be accounted for by the plant’s “growth-defense trade-off” strategy and the manner in which nanoparticles aggregate. By clarifying how PVC NPs coordinately regulate plant stress responses via hormone signaling and phenylpropanoid biosynthesis pathways, this research offers a scientific basis for assessing environmental concerns related to nanoplastics in agricultural systems. Full article

Background: Acute mountain sickness (AMS) is a prevalent and potentially life-threatening condition caused by rapid exposure to high-altitude hypoxia, affecting pulmonary and neurological functions. Tongqiao Jiuxin Oil (TQ), a traditional Chinese medicine formula composed of aromatic and resinous ingredients such as sandalwood, agarwood, frankincense, borneol, and musk, has been widely used in the treatment of cardiovascular and cerebrovascular disorders. Clinical observations suggest its potential efficacy against AMS, yet its pharmacological mechanisms remain poorly understood. Methods: The chemical profile of TQ was characterized using UHPLC-Q-Exactive Orbitrap HRMS. Network pharmacology was applied to predict the potential targets and pathways involved in AMS. A rat model of AMS was established by exposing animals to hypobaric hypoxia (~10% oxygen), simulating an altitude of approximately 5500 m. TQ was administered at varying doses. Physiological indices, oxidative stress markers (MDA, SOD, GSH), histopathological changes, and the expression of hypoxia- and apoptosis-related proteins (HIF-1α, VEGFA, EPO, Bax, Bcl-2, Caspase-3) in lung and brain tissues were assessed. Results: A total of 774 chemical constituents were identified from TQ. Network pharmacology predicted the involvement of multiple targets and pathways. TQ significantly improved arterial oxygenation and reduced histopathological damage in both lung and brain tissues. It enhanced antioxidant activity by elevating SOD and GSH levels and reducing MDA content. Mechanistically, TQ downregulated the expression of HIF-1α, VEGFA, EPO, and pro-apoptotic markers (Bax/Bcl-2 ratio, Caspase-3), while upregulated Bcl-2, the anti-apoptotic protein expression. Conclusions: TQ exerts protective effects against AMS-induced tissue injury by improving oxygen homeostasis, alleviating oxidative stress, and modulating hypoxia-related and apoptotic signaling pathways. This study provides pharmacological evidence supporting the potential of TQ as a promising candidate for AMS intervention, as well as the modern research method for multi-component traditional Chinese medicine. Full article

Herbivore-induced plant volatiles (HIPVs) are well known for their roles in herbivore deterrence and attraction of natural enemies, but their direct impact on insect reproduction remains largely unexplored. In this study, we provide novel evidence that two representative HIPVs, 2-heptanol and α-cedrene, exert opposing effects on the reproduction of Chilo suppressalis, a major rice pest. While both volatiles repelled adults, α-cedrene unexpectedly enhanced oviposition, whereas 2-heptanol significantly suppressed egg laying. To examine these effects, we conducted oviposition assays, preoviposition and longevity tests, combined with qPCR and transcriptome analyses to explore underlying molecular responses. Mechanistically, α-cedrene upregulated Kr-h1, a gene linked to juvenile hormone signaling and vitellogenesis, promoting reproductive investment. Transcriptomic profiling revealed divergent molecular responses: α-cedrene activated reproductive pathways, whereas 2-heptanol induced stress- and immune-related genes, suggesting a trade-off between stress defense and reproduction. These findings demonstrate that HIPVs can exert compound-specific reproductive effects beyond repellency. This work fills a key knowledge gap and highlights the potential of HIPVs as precision tools in pest management strategies that exploit behavioral and physiological vulnerabilities beyond repellency. Full article

Skeletal muscle regeneration depends on muscle stem cells, which give rise to myoblasts that drive muscle growth, repair, and maintenance. In bats—the only mammals capable of powered flight—these processes must also sustain contractile performance under extreme mechanical and metabolic stress. However, the cellular and molecular mechanisms underlying bat muscle physiology remain largely unknown. To enable mechanistic investigation of these traits, we established the first myoblast cell lines from the pectoralis muscle of Pteronotus mesoamericanus, a highly maneuverable aerial insectivore. Using both spontaneous immortalization and exogenous hTERT/CDK4 gene overexpression, we generated two stable cell lines that retain proliferative capacity and differentiate into contractile myotubes. These cells exhibit frequent spontaneous contractions, suggesting robust functional integrity at the neuromuscular junction. In parallel, we performed transcriptomic and metabolic profiling of native pectoralis tissue in the closely related Pteronotus parnellii to define molecular programs supporting muscle specialization. Gene expression analyses revealed enriched pathways for muscle metabolism, development, and regeneration, highlighting supporting roles in tissue maintenance and repair. Consistent with this profile, the flight muscle is triglyceride-rich, which serves as an important fuel source for energetically demanding processes, including muscle contraction and cellular recovery. Integration of transcriptomic and metabolic data identified three key metabolic modules—glucose utilization, lipid handling, and nutrient signaling—that likely coordinate ATP production and support metabolic flexibility. Together, these complementary tools and datasets provide the first in vitro platform for investigating bat muscle research, enabling direct exploration of muscle regeneration, metabolic resilience, and evolutionary physiology. Full article

Powdery mildew (PM), caused by Sphaerotheca phaseoli, severely threatens mungbean (Vigna radiata) productivity and quality, yet the molecular basis of resistance remains poorly defined. This study employed transcriptome profiling to compare defense responses in a resistant genotype, SUPER5, and a susceptible variety, CN84-1, following pathogen infection. A total of 1755 differentially expressed genes (DEGs) were identified, with SUPER5 exhibiting strong upregulation of genes encoding pathogenesis-related (PR) proteins, disease resistance proteins, and key transcription factors. Notably, genes involved in phenylpropanoid and flavonoid biosynthesis, pathways associated with antimicrobial compound and lignin production, were markedly induced in SUPER5. In contrast, CN84-1 showed limited activation of defense genes and downregulation of essential regulators such as MYB14. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted the involvement of plant–pathogen interaction pathways, MAPK signaling, and reactive oxygen species (ROS) detoxification in the resistant response. Quantitative real-time PCR validated 11 candidate genes, including PAL3, PR2, GSO1, MLO12, and P21, which function in pathogen recognition, signaling, the biosynthesis of antimicrobial metabolites, the production of defense proteins, defense regulation, and the reinforcement of the cell wall. Co-expression network analysis revealed three major gene modules linked to flavonoid metabolism, chitinase activity, and responses to both abiotic and biotic stresses. These findings offer valuable molecular insights for breeding PM-resistant mungbean varieties. Full article