International Journal of Molecular Sciences最新文献

Abiotic stresses including drought, salinity, heat, cold, and heavy metal toxicity severely constrain plant productivity worldwide. Nitrogen (N), beyond its fundamental nutritional role, has emerged as a central regulator of plant stress responses through its involvement in metabolic reprogramming, osmotic adjustment, antioxidant defense, and hormonal signaling. This review synthesizes current advances in understanding how nitrogen availability and form influence plant tolerance to major abiotic stresses. Particular emphasis is placed on nitrogen-mediated modulation of reactive oxygen species (ROS) scavenging systems, nitrogen-carbon metabolic coordination, phytohormonal crosstalk, osmoprotectant biosynthesis, and regulation of stress-responsive gene expression. Recent molecular insights highlight the role of nitrogen transporters, nitrate signaling pathways, and nitrogen-use efficiency in stress adaptation mechanisms. Furthermore, agronomic and biotechnological strategies aimed at optimizing nitrogen management to enhance stress resilience are discussed, including precision fertilization, integrated nutrient management, and genetic approaches targeting nitrogen-responsive regulatory networks. By integrating physiological, biochemical, and molecular perspectives, this review provides a comprehensive framework for understanding nitrogen-driven mitigation strategies under abiotic stress conditions and outlines future research directions for sustainable crop production in changing environments.

N,N-Dimethyl-1,3-propanediamine (DMAPA) is an important aliphatic diamine widely used in fine chemical manufacturing. Its industrial production traditionally relies on Raney nickel catalysts, which suffer from pyrophoric hazards and limited selectivity due to imine condensation side reactions. To address these challenges, we report an Al₂O₃-supported Ni-Cu alloy catalyst as an efficient alternative for the selective hydrogenation of N,N-dimethylaminopropionitrile (DMAPN). The optimized Ni₃₀Cu₅/Al₂O₃ catalyst achieves complete DMAPN conversion and over 90% DMAPA selectivity under industrially relevant conditions (120 °C, 2.5 MPa H₂). X-ray diffraction, X-ray photoelectron spectroscopy, and transmission electron microscopy analyses confirm the formation of substitutional Ni-Cu alloy nanoparticles, where Cu incorporation induces both geometric isolation of Ni ensembles and electronic modulation of surface active sites, thereby suppressing condensation-derived by-products. In addition, an NH₃/ethanol-assisted process further improves selectivity while reducing autogenous operating pressure. Overall, this work demonstrates a safe and highly selective catalytic system for primary diamine synthesis, providing a practical alternative to conventional Raney Ni-based processes.

Artificial optical radiation, spanning from 100 nm to 1 mm, encompasses ultraviolet (UV) and infrared (IR) light. UV light is well known for its risks on the skin and eyes. Recently, there has been growing interest in light at 405 nm (violet-blue light, VBL) due to its antimicrobial properties and perceived safety for mammalian cells when administered in controlled amounts. This research delved into the impact of 405 nm VBL on corneal and retinal pigment epithelial cell cultures. ARPE-19 and corneal BCE C/D 1b cells were exposed to VBL for varying doses, according at different exposure times, to evaluate cell viability, oxidative stress levels and apoptotic indicators. A 3D printed prototype with 14 LEDs centred at 405 nm wavelength was used to ensure uniform distribution of light during exposure. Cell viability was assessed using the MTT assay, measurement of oxygen species (ROS) production was carried out, and Western blot analysis was employed to study catalase and SOD-1 expression and apoptotic marker activation. Exposure to 405 nm VBL for both term (3 h) and prolonged durations (9 h) led to a weak decrease in cell viability in ARPE-19 cells, whereas the effect on BCE C/D 1b cells was negligible. There was no increase in ROS production, with catalase and SOD-1 expression remaining stable, suggesting no pro-oxidative stress effects in these models. Moreover, no activation of caspase-3 and accumulation of cytochrome C were found. Based on our results, exposure to 405 nm light at regulated levels does not pose a threat to the viability of the tested cell lines and does not lead to oxidative stress and apoptosis under these conditions. These results suggest a favourable cytocompatibility profile for these specific ocular cell models, laying a foundation for further investigations into its ocular safety.

Nervonic acid (NA), a very-long-chain monounsaturated fatty acid, is known for its benefits in treating neurological diseases and promoting brain health. In this study, we utilized two different receptors, Brassica juncea (B. juncea, rich in erucic acid, C22:1) and Brassica napus (B. napus, high in oleic acid, C18:1), to overproduce NA through systematic metabolic engineering. Two multi-gene vector constructs, Napin-3 and Napin-5 (CgKCS::SLC1-1::DGAT1; CgKCS::SLC1-1::BnFAE1::LdLPAAT::DGAT1), are driven by seed-specific napin promoters. In B. juncea, Napin-3 and Napin-5 expression elevated NA levels to 48.7% and 46.3% in seed oil, respectively, compared to 2.5% in wild types. In B. napus, Napin-3 and Napin-5 expression achieved NA levels of 45% and 39.6%, respectively, while NA is absent in wild types. To our knowledge, this represents the highest NA production in plants to date, with stable oil content and yield, enabling cost-effective NA production. In B. juncea, a significant increase in NA is observed alongside a decrease in C18:1, C20:1, and C22:1 levels; in B. napus, the rise in NA is accompanied by a decrease in C18:1, and an increase in C20:1 and C22:1. These patterns reflect the dynamic equilibrium of fatty acids following NA conversion, influenced by the Dynamic Substrate Tugging (DST) Mechanism, in the form of either an EA-tugging mode or C18:1-tugging mode mechanism, depending on the cellular context. NA is an elongation product derived from C18:1, catalyzed by CgKCS with broad substrate specificity, indicating that plants with high levels of C18:1, similarly to those rich in C22:1, serve as excellent candidates for NA production. This "green factory" for NA production provides strong support for its pharmaceutical, nutraceutical, and industrial applications. The exogenous and the endogenous enzymes coordinate function remodeling of the intra-seed fatty acid elongation flux through the DST strategy, thereby systematically enhancing the synthesis and accumulation efficiency of the target fatty acid.

Atherosclerosis, the leading cause of death worldwide, is a chronic inflammatory disease leading to the accumulation of lipid-rich plaques within the artery wall. Accumulating evidence indicates that intestinal microbiota plays an important regulatory role in atherosclerosis at all stages of the disease. Through numerous metabolites, the intestinal microbiota can regulate immune and inflammatory cells and their mediators, as well as lipid metabolism, thereby contributing to the development and progression of atherosclerosis. With these assumptions in mind, we investigated the possibility of using Limosilactobacillus fermentum MC1 (L. fermentum MC1) and its exopolysaccharides (EPSs) in the reduction of lipid and atherogenic parameters as a preventive strategy in preventing the occurrence of cardiovascular diseases (CVD). We investigated the effect of L. fermentum MC1 and its EPSs on the health status of mice by monitoring the following parameters: body weight, colon length and weight, relative weight of organs, hematological (Hgb, WBC, number of erythrocytes, MCHC, MCV, MCH), and biochemical blood parameters including glucose, serum enzymes (ALT, ALP, amylase), urea, creatinine and lipid profile (total cholesterol, triglycerides, HDL, VLDL, LDL), different atherogenic parameters, blood biomarkers such as lymphocyte-to-monocyte (LMR) and neutrophil-to-lymphocyte (NLR) ratios, molecular inflammatory markers (IL1β, IL6, MCP1, IL1α, TLR4, TNFα, CD68, TGFβ), apoptosis markers (BCL2, AIFM1, IGF-1R), and endoplasmic reticulum stress markers (CHOP and GRP94) as well as oxidative stress (NOX2) markers in the colon. Furthermore, the level of lipid peroxidation, nitric oxide and glutathione concentrations in the liver, kidneys and spleen were measured. L. fermentum MC1 and its EPSs may prevent the development of atherosclerosis and the progression of CVD through antioxidant, anti-inflammatory, immunomodulatory activities, and regulation of the gut microbiome and lipid metabolism. The observed reduction in lipid and atherogenic determinants suggests that L. fermentum MC1 and its EPSs may contribute to atheroprotection and confer multiple health benefits.

Magnolia kobus (M. kobus) has long been used to treat nasal congestion, allergic rhinitis, and sinusitis. In the current study, we demonstrate the effects and underlying mechanisms of M. kobus flower water extract (ME) and ME-derived constituent magnolin on in vitro osteoblastogenic and anti-osteoclastogenic responses. Treatment with ME or magnolin markedly enhanced the osteoblast differentiation and mineralization in MC3T3-E1 pre-osteoblasts. This osteoblastogenic activity of ME or magnolin was closely associated with upregulation of osteoblast-specific molecules, including RUNX2, DLX5, OSX, alkaline phosphatase, collagen type I, and osteopontin, as well as the activation of mitogen-activated protein kinase (MAPK) signaling pathways. Concurrently, magnolin inhibited osteoclast differentiation through inactivating MAPK pathways and downregulating NFATc1, c-Fos, tartrate-resistant acid phosphatase, and cathepsin K in RANKL-treated RAW264.7 cells. These observations suggest that ME and magnolin have pharmacological potential for the treatment and prevention of metabolic bone disorders, including osteoporosis.

Acute coronary syndrome (ACS), driven by inflammation and thrombosis, remains a leading cause of morbidity globally. While traditional risk scores are useful, the prognostic value of combining inflammatory and autoimmune biomarkers remains understudied. This study aimed to evaluate the predictive role of high-sensitivity C-reactive protein (hs-CRP), platelet factor 4 (PF4), D-dimer, and antiphospholipid antibodies (anticardiolipin and anti-β2-glycoprotein I) for the development of major adverse cardiovascular events (MACE) in patients with ACS. We conducted a prospective cohort study at a tertiary referral center in Mexico. A total of 103 patients admitted with confirmed ACS were included. Blood samples were collected upon admission to measure biomarker levels. Participants were followed for 30 days. The primary outcome was the occurrence of MACE, defined as reinfarction, death, percutaneous coronary intervention, or bypass surgery. Multivariate logistic regression analysis was performed to identify independent predictors, adjusting for age, smoking, and comorbidities. MACE occurred in 51.4% of participants. Patients with adverse outcomes were significantly older and had longer hospital stays (p < 0.05). In the biomarker analysis, PF4 and hs-CRP demonstrated high sensitivity (98%) but low specificity. In the multivariate analysis, IgG anti-β2-glycoprotein I (p < 0.001) and D-dimer (p = 0.024) emerged as significant independent predictors of MACE. Conversely, IgM isotypes did not show independent predictive value. Beyond traditional risk factors, markers of coagulation (D-dimer) and autoimmunity (IgG anti-β2-glycoprotein I) are independent predictors of short-term adverse events in ACS patients. Integrating these multidomain biomarkers into clinical assessment may enhance risk stratification and prognostic accuracy.

Salinity stress severely limits barley production by disrupting physiological and biochemical processes critical for growth and yield. Although numerous studies have examined individual physiological or antioxidant responses to salinity, an integrated multivariate understanding of how these mechanisms collectively contribute to yield stability at the flowering stage remains limited. This study aimed to elucidate the integrated antioxidant and physiological mechanisms underlying salinity tolerance in barley genotypes during flowering. Barley plants were subjected to controlled salinity treatments, and a comprehensive set of phenolic compounds, antioxidant capacity indices, physiological traits, and yield components were measured. Multivariate analyses, including redundancy analysis (RDA) and partial least squares regression (PLSR), identified key traits contributing to yield stability under salinity. Multivariate analyses revealed also genotype-specific physiological strategies underlying contrasting salinity tolerance levels. Antioxidant defenses, such as total phenolics, DPPH and ABTS radical scavenging activities, and α-tocopherol, along with osmotic regulators like proline and soluble sugars, were closely associated with improved water status and reduced oxidative damage. These coordinated responses correlated strongly with yield components, including thousand-grain weight and main spike seed number. Notably, this study provides new insights into the predictive relevance of selected biochemical and physiological markers for yield performance under salt stress using PLSR at the flowering stage. PLSR further demonstrated the high predictive power of a limited subset of biochemical and physiological markers for yield traits under salt stress. Collectively, these findings reveal that the interplay between antioxidant machinery and osmotic adjustment at flowering is critical for barley resilience to salinity, providing valuable physiological markers to inform breeding strategies aimed at improving salt tolerance.

Cardiovascular-kidney-metabolic syndrome is a novel concept defined by the American Heart Association, highlighting the complex interactions between the cardiovascular system, kidney function and metabolic risk factors. Poor cardiovascular-kidney-metabolic health is increasingly prevalent worldwide, giving rise to a need to optimize early detection of cardiovascular dysfunction. Heart failure is one of the most prevalent forms of cardiovascular disease in patients with chronic kidney disease and metabolic risk factors, but screening and diagnostic strategies remain challenging. Current guidelines endorse the use of prediction scores, as well as a biomarker-based strategy in patients at increased risk. Despite evidence supporting the use of biomarkers such as natriuretic peptides, there are considerable limitations to their use in the setting of cardiovascular-kidney-metabolic syndrome. Moreover, there is mounting evidence supporting the use of other biomarkers reflecting underlying mechanisms leading to heart failure. The aim of this review is to assess current approaches to screening for and diagnosing heart failure in cardiovascular-kidney-metabolic syndrome, highlighting the strengths and pitfalls of gold-standard and emerging biomarkers, while also addressing gaps in evidence and future research directions. Validation of screening biomarkers and development of multimarker prediction scores could impact clinical practice and reduce the growing morbidity and mortality in cardiovascular-kidney-metabolic syndrome.

Ovarian cancer is the most lethal gynecologic malignancy, with chemoresistance and recurrence driven by cancer stem cells (CSCs). Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) mediate tumor-stroma communication, but their role in ovarian cancer progression and therapy remains unclear. Here, we investigated bone marrow (BM)-MSC-EVs, their effects on ovarian cancer cells, and the underlying molecular mechanisms. BM-MSCs were isolated, confirmed using flow cytometry and trilineage differentiation, and their EVs characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Kuramochi cells were treated with BM-MSC-EVs and assessed for proliferation, colony formation, migration, invasion, apoptosis, and chemosensitivity. Aldehyde dehydrogenase (ALDH⁺) Kuramochi cells, with or without EV exposure, were transplanted into non-obese diabetic severe combined immunodeficiency mice for xenograft studies, followed by histology, immunohistochemistry, Western blotting, and EV miRNA profiling. BM-MSC-EVs increased cancer cell proliferation but reduced colony formation, migration, and invasion in vitro. They sensitized ALDH⁺ CSC-like cells to carboplatin, while paclitaxel response remained unchanged. In vivo, EVs accelerated tumor growth and activated prosurvival (p-AKT, BCL-2), angiogenic (VEGFA, CD31), and epithelial-mesenchymal transition-associated (vimentin) pathways. EVs were found to be enriched in hsa-miR-100-5p, hsa-miR-122-5p, and hsa-let-7i-5p based on miRNA array analysis, and these findings were further validated by qRT-PCR. These findings reveal the dual roles of BM-MSC-EVs: enhancing carboplatin sensitivity while promoting tumor progression and angiogenesis.