Search Results (4,580)

Exogenous gibberellin (GA₃) significantly improves sugar accumulation in longan (Dimocarpus longan) fruit, yet its molecular mechanism remains unclear. This study demonstrates that 50 mg/L GA₃ optimally enhances sucrose, glucose, fructose, total sugar, and sweetness in longan. Transcriptomic analysis revealed 1345 differentially expressed genes (DEGs), including the sugar transporter gene DlSWEET3a, which was upregulated by GA₃. Subcellular localization confirmed DlSWEET3a resides on the plasma membrane. Functional assays in yeast demonstrated its ability to transport glucose, fructose, mannose, and galactose. Critically, transient overexpression of DlSWEET3a in longan fruit and stable overexpression in tobacco leaves significantly increased soluble sugar content. These results establish that GA₃ promotes sugar accumulation in longan fruit partly through the upregulation of the plasma membrane hexose transporter DlSWEET3a, providing a mechanistic insight into gibberellin-mediated fruit quality improvement. Full article

Type 2 diabetes mellitus (T2DM) can be traditionally treated by edible and medicinal species rich in flavonoids and triterpenoids known for their metabolic benefits. Cucumis prophetarum L. has shown antioxidant and antidiabetic properties in decoction extracts. Since solvent polarity strongly influences the extraction of secondary metabolites, this study investigated the hydroalcoholic extracts of C. prophetarum L. to explore their chemical composition and insulin-sensitizing potential. Hydroalcoholic extracts from the leaf, stem, and root of C. prophetarum L. were analyzed by UV-Vis spectroscopy, ATR-FTIR, and UHPLC-ESI-QqTOF–MS/MS to profile their secondary metabolites. The insulin-sensitizing potential of each extract was assessed using an in vitro model of palmitic-acid-induced insulin resistance in L6 skeletal muscle cells, followed by Western blot analysis of key insulin-signaling proteins. Flavonoid glycosides such as apigenin-C,O-dihexoside, apigenin-malonylhexoside, and luteolin-C,O-dihexoside were abundant in leaf and stem extracts, while cucurbitacins predominated in the root. MTT assay confirmed that hydroalcoholic stem and root extracts of C. prophetarum L. were non-cytotoxic to L6 myotubes, whereas the leaf extract reduced viability only at higher concentrations. Oil Red O staining revealed a pronounced decrease in lipid accumulation following stem and root extract treatment. Consistently, the stem extract enhanced insulin signaling through the activation of the IRS-1/PI3K/Akt pathway, while the root extract primarily modulated the AMPK–mTOR pathway. Importantly, both extracts promoted GLUT4 translocation to the plasma membrane, highlighting their complementary mechanisms in restoring insulin sensitivity. Hydroalcoholic extracts of C. prophetarum L. alleviate insulin resistance through multiple molecular mechanisms, with bioactivity and composition differing markedly from previously reported in the decoctions, which highlight a promising source of insulin-sensitizing phytochemicals and underscore the importance of solvent selection in maximizing therapeutic potential. Full article

Signaling mediated by CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) peptides and their receptors is essential for plants to adapt to abiotic stress. To address the global issue of drought-induced growth inhibition and mortality in poplar (Populus spp.), this study investigated the function of the PtrCLE1A gene from Populus trichocarpa Torr. et Gray in drought tolerance regulation. We employed gene cloning, expression vector construction, and genetic transformation of poplar, combined with bioinformatics analysis, subcellular localization, phenotypic observation, physiological index measurement, and gene expression analysis. The results demonstrated that both PtrCLE1A and PtrCLE1B encode pre-propeptides containing a signal peptide, with an identical mature peptide sequence (RLSPGGPDPRHH), and their putative receptors are PtrCLV1/2. Furthermore, the PtrCLE1A pre-propeptide was localized around the plasma membrane in tobacco (Nicotiana benthamiana Domin) mesophyll cells, consistent with its predicted function. PtrCLE1A and PtrCLE1B are primarily expressed in the roots and xylem of P. trichocarpa. Additionally, only the PtrCLE1A promoter contained drought-responsive cis-elements, and its expression was induced by drought stress in root, xylem, and leaf tissues of P. trichocarpa. Overexpression of the PtrCLE1A gene in Populus tomentosa Carrière (triploid) significantly increased adventitious root length under osmotic stress. Overexpression lines exhibited 22.00% to 22.92% longer adventitious roots than EV lines at 50/100 mM mannitol, and 65.12% to 73.17% longer at 150 mM mannitol. The OE lines also exhibited higher photosynthetic capacity and instantaneous water use efficiency (iWUE), along with reduced membrane damage under drought conditions, indicating enhanced drought resistance. This study provides new genetic resources and a theoretical foundation for molecular breeding of drought-tolerant poplar. Full article

In mammals, CD22 is a member of the Siglec family and plays essential roles in B-cell activation, signal transduction, and immune regulation. However, its functions in teleost fish remain largely unclear. In this study, a CD22 homolog designated On-CD22 was identified and cloned from Nile tilapia (Oreochromis niloticus). On-CD22 transcripts were highly expressed in the head kidney and peripheral blood of healthy fish and showed significant expression changes following infection with Streptococcus agalactiae, Aeromonas hydrophila, or stimulation with poly(I:C). Subcellular localization analysis indicated that On-CD22 is predominantly localized to the plasma membrane. Luciferase reporter assays performed in heterologous cell systems showed that overexpression of On-CD22 was associated with changes in the basal transcriptional activities of NF-κB, IFN1, IFN3, and STAT1 responsive promoters under unstimulated conditions. Furthermore, single-cell transcriptomic analysis revealed that On-CD22 expression was mainly confined to the B-cell population within head-kidney leukocytes. Collectively, these findings suggest that On-CD22 may be involved in immune regulatory processes in Nile tilapia. Full article

Serotonergic signaling is traditionally conceived as a transient, vesicle-mediated process restricted to the synaptic cleft. Here, we propose an expanded model in which serotonin can also be inserted into the plasma membrane of neurons and glial cells, forming a stable, membrane-associated reservoir that prolongs its availability beyond classical synaptic timescales. In this framework, the synapse emerges not as a simple neurotransmitter–receptor interface but as a dynamic, multiscale medium where membrane order, hydration, and quantum-level processes jointly govern information flow. Two temporal “tunnels” appear to regulate serotonin bioavailability: its aggregation in synaptic vesicles during exocytosis, and its cholesterol-dependent insertion into neuronal and glial membranes at the tripartite synapse. Lipid raft microdomains enriched in cholesterol and gangliosides thus act as active regulators of a continuum between transient and constitutive serotonin signaling. This extended serotonergic persistence prompts a reconsideration of current pharmacological models and the action of antidepressants such as fluoxetine, which not only inhibits the serotonin transporter (SERT) but also accumulates in lipid rafts, perturbs raft organization, and alters serotonin–cholesterol equilibria, contributing to SERT-independent effects. Grounded in the recently established fundamental parameters of biological systems, this model invites a broader, quantum-informed rethinking of synaptic transmission. Full article

This study investigated the metabolic mechanisms driving physiological functional remodeling in RFM by analyzing plasma biochemical parameters and metabolomic profiles at key peripartum timepoints (21 and 7 d prepartum and 4 h postpartum), integrated with placental and fetal membrane metabolic characteristics. The results revealed that RFM cows exhibited significant negative energy balance (NEB) as early as 21 days before parturition, characterized by elevated plasma levels of non-esterified fatty acids, β-hydroxybutyrate, and malondialdehyde, alongside reduced activity of antioxidant enzymes (GSH-Px, CAT) (p ≤ 0.05). Metabolomic analysis demonstrated persistent lipid metabolism dysregulation, amino acid imbalance, and nucleotide metabolism disturbances in RFM cows from 21 days prepartum to 4 h postpartum, indicating premature mobilization of adipose and muscle tissues. Further metabolomic analyses of the placenta and fetal membranes confirmed that metabolic dysfunction compromises energy supply during parturition, adversely affecting immune homeostasis and extracellular matrix degradation in the placenta and fetal membranes of RFM dairy cows. These physiological dysfunctions have the potential to impede the timely expulsion of fetal membranes after calving. In conclusion, RFM is closely associated with early-onset metabolic dysfunction during the periparturient period, where insufficient energy supply due to NEB, oxidative stress, and immune-endocrine disruptions collectively impair normal fetal membrane detachment. Full article

Filoviruses, including Ebola (EBOV) and Marburg (MARV) viruses, are zoonotic pathogens that cause severe hemorrhagic fever in humans, with mortality rates reaching up to 90%. Filovirus egress and spread are driven by the viral matrix protein VP40 and regulated both positively and negatively by a growing number of specific host interactors. Here, we identify tetraspanin protein CD9, a plasma membrane organizing and scaffolding protein, as playing a role in facilitating efficient egress of EBOV and MARV. Indeed, we observed a significant decrease in viral egress of VLPs and live filoviruses from CD9-KD cells as compared to that from WT cells. Moreover, exogenous expression of CD9 rescued egress of VP40 VLPs close to WT levels in the CD9-KD cells. These findings identify tetraspanin CD9 as a positive regulator of filovirus egress, and thus CD9 may represent a potential new target for antiviral therapies targeting the late stage of the filovirus lifecycle. Full article

Background/Objectives: Silicosis remains a major occupational health concern worldwide and is characterized by notable clinical heterogeneity in terms of disease progression and complications. However, the underlying metabolic mechanisms contributing to this heterogeneity remain poorly understood. Methods: We conducted a case–control study involving 156 silicosis patients and 132 silica-exposed controls. The plasma samples were analyzed via untargeted metabolomics based on liquid chromatography–mass spectrometry (LC-MS/MS). To explore disease subtypes and potential biomarkers, we applied non-negative matrix factorization (NMF) clustering, weighted gene co-expression network analysis (WGCNA), and machine learning approaches. Results: A total of 860 differentially abundant metabolites, including elevated pathogen-associated compounds, were identified in silicosis patients. Unsupervised NMF clustering revealed two distinct metabolic subtypes with different clinical features. Patients in the NMF2 subgroup had a 5.3-fold greater risk of pulmonary infections (p = 0.026) than those in the NMF1 subgroup. Metabolomic analysis revealed that NMF2 was enriched in arachidonic acid and unsaturated fatty acid metabolism pathways, with prominent LysoPC accumulation, suggesting inflammation-related lipid peroxidation. In contrast, NMF1 was characterized by increased spermidine biosynthesis and urea cycle activity, along with suppressed saturated fatty acid metabolism and reduced LysoPC processing, potentially affecting membrane integrity and promoting fibrosis. A machine learning-derived dual-metabolite panel, tyrosocholic acid and PI (20:4/0:0), achieved AUC values above 0.85 for both silicosis detection and subtype classification. Conclusions: These findings highlight metabolic heterogeneity in silicosis and suggest clinically relevant subtypes, providing a foundation for improved stratification, early detection, and targeted interventions. Full article

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), poses a severe threat to global wheat production. The adaptor protein complex AP-1 plays a crucial role in vesicular trafficking, yet its function in rust fungi remains poorly understood. In this study, a gene encoding an AP-1 σ subunit, designated PsAP1, was identified in Pst. The expression of PsAP1 was highly induced during the early infection stage. Heterologous expression of PsAP1 in a Fusarium graminearum mutant partially restored its pathogenic defects. Subcellular localization analysis revealed that PsAP1 localizes to the plasma membrane, cytoplasm, and nucleus. Silencing PsAP1 in wheat using Barley stripe mosaic virus-mediated host-induced gene silencing (BSMV-HIGS) significantly attenuated Pst pathogenicity, reducing hyphal growth by 6.7% (colony diameter), sporulation by 61.6% (lesion length), and pathogen biomass by 66%, along with enhanced accumulation of host reactive oxygen species. Transcriptomic analysis further demonstrated that silencing PsAP1 disrupted multiple pathways, including MAPK signaling, glutathione metabolism, and carbohydrate metabolism. These findings indicate that PsAP1 facilitates Pst infection by modulating vesicular trafficking, suppressing host immunity, and reprogramming host metabolism. This study provides novel insights into the pathogenic mechanisms of rust fungi and suggests a potential target for disease control. Full article

Invariant chain, also known as CD74 when expressed on the plasma membrane, is classically recognized for its role in Major Histocompatibility Complex class II molecule assembly, trafficking, and peptide loading in professional antigen presenting cells. However, recent studies implicate CD74 as a broader regulator of tumor–immune interactions, modulating antigen presentation, cytokine signaling, and immune evasion across diverse cancers. This review synthesizes emerging evidence that CD74 functions as a “master regulator” of antigen presentation in cancer, integrating its canonical chaperone role with its noncanonical role in transcription regulation and in signaling via macrophage migration inhibitory factor. We explore how tumor microenvironmental contexts redefine CD74 biology, influencing antitumor immunity and therapeutic outcomes. Full article

Background/Objectives: Toxoplasma gondii (T. gondii) dense granule antigen 14 (GRA14) is a parasitophorous vacuole membrane protein that plays a critical role in the development of chronic-stage cysts. However, its potential as a vaccine antigen and long-term immunity have not been evaluated using a virus-like particle (VLP) platform. Methods: influenza matrix protein (M1)-based VLPs displaying GRA14 were generated. Female BALB/c mice were intranasally immunized with the VLP vaccine and orally challenged with lethal ME49 cysts either 10 weeks or 32 weeks after prime vaccination for short-term and long-term immunity evaluation, respectively. Results: GRA14 VLP vaccination elicited higher levels of T. gondii-specific IgG, IgG1, and IgG2a antibody responses in sera compared to non-immunized controls. Upon challenge infection, elevated IgG- and IgA-secreting plasma cells, germinal center B cells, and memory B cells were observed, and CD4⁺, CD8⁺ T-cells, as well as both Th1 (IFN-γ) and Th2 (IL-4, IL-5) cytokines, were also increased. For the short-term immunity study, vaccinated mice exhibited suppressed cerebral inflammation, significantly reduced brain cyst burdens, maintained stable body weight, and achieved 100% survival. For the long-term study, GRA14 VLPs sustained elevated IgG and IgG1 levels as well as conferred partial yet significant protection, with lower cyst loads and 83% survival. Conclusions: GRA14 VLPs induce durable, balanced humoral and cellular immunity and provide both short-term and long-term protection against lethal chronic toxoplasmosis, supporting their potential as promising vaccine candidates. Full article

The anti-aging gene/protein Klotho (Kl), most present in kidneys, has been well studied in mice (mKl), but not in rats (rKl). This study investigated the renal rKl expression in male and female rats. Sex-related measurement of rKl-controlled electrolytes was performed in plasma/urine samples, as were tests on species differences in renal Kl expression (rats vs. mice). rKl mRNA/protein expression was studied by qRT-PCR/Western-blotting in renal total RNA/cell membranes and its localization by immunofluorescence microscopy. Urine/plasma ions (phosphate/total calcium) and macroelements (phosphorus/calcium) were measured biochemically and by ICP-MS, respectively. In rat kidneys, the rKl mRNA/protein was detected in the cortex, outer and inner stripe but not in the papilla, and was immunolocalized in the basolateral membrane of proximal tubules in the cortex and outer stripe, but not in the intercalating cells of the cortical distal tubules, whereas mKl was observed in the mouse kidney cortex but not the outer stripe. Female-dominant expression of renal rKl, affected by androgen’s inhibitory effect, may have contributed to the sex-related level of urine electrolytes, particularly phosphates. Renal mKl expression was male-dominant. Sex- and species-related differences in renal Kl expression may be relevant for the selection of the sex and/or the model organism in studies addressing aging/mineral homeostasis. Full article

Considering the challenges associated with implementing emerging technologies and bacterial-derived antimicrobial metabolites at an industrial scale in the meat industry, this comprehensive review investigates the interactions between lactic acid bacteria-producing antimicrobial metabolites and emerging food preservation technologies applied to meat systems. By integrating evidence from microbiology, food engineering, and molecular physiology, the review characterizes how metabolites-derived compounds exert inhibitory activity through pH modulation, membrane permeabilization, disruption of proton motive force, and interference with cell wall biosynthesis. These biochemical actions are evaluated in parallel with the mechanistic effects of high-pressure processing, pulsed electric fields, cold plasma, irradiation, pulsed light, ultrasound, ohmic heating and nanotechnology. Across the literature, consistent patterns of synergy emerge: many emerging technologies induce structural and metabolic vulnerabilities in microbial cells, thereby amplifying the efficacy of antimicrobial metabolites while enabling reductions in process intensity. The review consolidates these findings to elucidate multi-hurdle strategies capable of improving microbial safety, extending shelf life, and preserving the physicochemical integrity of meat products. Remaining challenges include optimizing combinational parameters, ensuring metabolite stability within complex matrices, and aligning integrated preservation strategies with regulatory and industrial constraints. Full article

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

Membrane rupture, induced by lipid peroxidation, is a severe threat to osmotic balance, as membrane pores contribute to ferroptosis, an iron-dependent cell death. To alleviate osmotic stress, membrane constituents dynamically reconstruct the membrane and interact with intracellular molecules. Tumor-derived acidosis shift glycolysis-dependent metabolism toward lipid metabolism, increasing polyunsaturated fatty acids (PUFAs). PUFAs enhance membrane fluidity but make cancer susceptible to lipid peroxidation. Also, the ionization of phospholipids under low pH can accelerate membrane rupture. This stress can be mitigated by the redistribution of cholesterol, which maintains tension–compression balance and acts as antioxidants. When excessive reactive aldehydes—byproducts of lipid peroxidation—overwhelm cholesterol’s protective role, lipid peroxides promote membrane cracks. Moreover, a deficiency in glutathione can alter cholesterol’s function, turning it into a pro-oxidant. In contrast, ceramide, derived from membrane lipids, indirectly prevents ferroptosis by facilitating cytochrome c release. This review integrates recent findings on how membrane components and environmental stressors influence ferroptosis. It also suggests potential therapeutic strategies. This could advance our understanding of ferroptosis in cancer. Full article