Search Results (4,449)

Sugarcane smut is a fungal disease caused by Sporisorium scitamineum. To explore its biological control strategies, this study collected rhizosphere soil of sugarcane, isolated and identified biocontrol bacteria from it, and conducted multi-level control efficacy evaluations. The results showed that five bacterial strains with effective antagonistic activity against the sexual mating and teliospore germination of S. scitamineum were isolated and identified: 2143-2 (Pseudomonas baetica), 2143-4 (Bacillus subtilis), 2143-6 (Burkholderia diffusa), Y8-2 (Pseudomonas reinekei), and Y8-3 (Bacillus amyloliquefaciens). The results of the pot inoculation experiments showed that all five strains could prolong the incubation period of sugarcane smut and significantly reduce the disease incidence, demonstrating marked control effects, with strains 2143-4 and Y8-2 being the most effective. The results of the field inoculation experiments and natural field infection experiments indicated that strain Y8-2 exhibited the best biocontrol efficacy against sugarcane smut, with control efficacies of 68.40% and 73.99% in the field inoculation experiments, and 65.73% under natural field infection conditions. In addition, the biocontrol strains could improve the physiological stress-tolerance characteristics of sugarcane plants, which was conducive to enhancing the resistance of sugarcane plants to sugarcane smut. Full article

Southern corn leaf blight (SCLB), caused by Bipolaris maydis, poses a serious threat to maize production worldwide. In our previous study, Bacillus velezensis BV3 was isolated and demonstrated strong antagonistic activity against maize leaf spot pathogens and effective disease control in greenhouse experiments. In this study, we evaluated the plant growth-promoting effects of BV3 on two maize cultivars through root application in pot experiments, and investigated the underlying molecular mechanisms using transcriptomic and metabolomic analyses. Inoculation with BV3 significantly promoted maize growth. Moreover, BV3 treatment induced extensive transcriptional and metabolic reprogramming in maize. Transcriptomic analysis identified numerous differentially expressed genes (DEGs) mainly enriched in plant–pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, and phenylpropanoid biosynthesis pathways. Metabolomic analysis revealed substantial changes in metabolite accumulation, particularly in lipids, amino acids, sugars, organic acids, and polyphenols, with enriched pathways including secondary metabolite biosynthesis, phenylpropanoid biosynthesis, and flavonoid biosynthesis. LC/MS and GC/MS analyses further revealed that BV3 produced diverse bioactive compounds. 2,4-DTBP and surfactin exhibited strong antifungal activities, particularly against B. maydis and Exserohilum turcicum. Overall, Bacillus sp. BV3 exhibits strong biocontrol efficacy against maize leaf spot pathogens and significant plant growth-promoting activity, highlighting its potential as an eco-friendly biocontrol agent for the management of southern corn leaf blight. Full article

Petiveria alliacea L. (commonly known as “anamu,” “guiné,” “hierba de zorro,” and “tipi”) has been widely used in Mesoamerican traditional medicine to treat pain and inflammation. However, scientific evidence supporting its efficacy in diabetic neuropathy remains limited. This study evaluated the antinociceptive potential of a methanolic leaf extract of P. alliacea in a murine model of alloxan-induced diabetic neuropathy and investigated its possible mechanisms of action. Diabetic CD-1 mice were evaluated for mechanical allodynia and hyperalgesia using the Von Frey test and for tonic pain using the formalin test. Pharmacological antagonists were administered to assess the involvement of opioid, nitric oxide, serotonergic, and GABAergic pathways. Phytochemical profiling was performed by LC-ESI-MS/MS, and potential pharmacological and pharmacokinetic properties of the identified metabolites were predicted using in silico tools (PASS online, SwissTargetPrediction, SwissADME, and pkCSM). The methanolic extract significantly reduced mechanical allodynia and hyperalgesia in diabetic mice and attenuated nociceptive responses in both phases of the formalin test, showing an effect comparable to gabapentin. Antinociceptive activity was not altered by naloxone or L-NAME but was significantly attenuated by methiothepin and bicuculline, suggesting that serotonergic and GABAergic pathways contribute, at least in part, to the observed antinociceptive effects. LC-ESI-MS/MS analysis identified 38 metabolites, including flavonoids, alkaloids, and terpenes, with in silico predictions supporting their potential analgesic and anti-inflammatory activities. The methanolic leaf extract of P. alliacea exhibits significant antinociceptive activity in diabetic neuropathy, partially likely to involve serotonergic and GABAergic mechanisms, supporting its ethnomedicinal use and its potential as a source of novel analgesic agents. Full article

The aim of this study was to isolate and molecularly identify lactic acid bacteria (LAB) associated with the epiphytic microflora and silage of wheatgrass (Agropyron spp.), as well as to evaluate their biotechnological potential as starter cultures for the ensiling of difficult-to-ensile forage crops under the climatic conditions of northern Kazakhstan. A total of 63 bacterial isolates were obtained and grown on MRS medium under different temperature conditions. Based on growth characteristics, pH values, and titratable acidity, 15 highly active strains were selected, demonstrating stable acidification (pH 3.99–4.75) and high metabolic activity. All isolates were catalase negative and capable of fermenting a wide range of carbohydrates and polyols, although pronounced strain-specific differences were observed. The selected strains exhibited proteolytic and antagonistic activity against test microorganisms and showed high tolerance to osmotic stress, maintaining growth at NaCl concentrations of up to 8–10%. Molecular identification based on 16S rRNA gene sequencing revealed that nine technologically significant strains belonged to the species Lactococcus garvieae, Pediococcus acidilactici, Lactiplantibacillus plantarum, Enterococcus faecalis and Enterococcus faecium. The results obtained in this study demonstrate the high environmental adaptability of the isolated strains and confirm their potential for the development of effective microbial inoculants aimed at improving fermentation processes and enhancing the preservation of difficult-to-ensile forage crops under cold-climate conditions. Full article

Treatment-induced neuroendocrine prostate cancer (t-NEPC) is the major form of resistance to androgen receptor signaling inhibitors (ARSI) in advanced prostate cancer, characterized by pronounced invasiveness and lineage plasticity. Through in-depth analysis of prostate cancer cohorts, we found that glutamate ionotropic receptor kainate (GRIK) family members, specifically GRIK2 and GRIK5, are highly expressed in neural lineage plastic prostate cancer cells, NEPC patient-derived xenografts (PDX), and NEPC patient samples. Their expression positively correlates with neuroendocrine markers and inversely correlates with androgen receptor (AR) activity. Additionally, functional analyses indicated that AR has a direct transcriptional inhibitory effect on GRIK2 and GRIK5, and the absence of AR signaling leads to the upregulation of GRIK2 and GRIK5. Further RNA sequencing analysis revealed that GRIK5 silencing reprograms the cellular transcriptome, resulting in significant downregulation of AR signaling and fatty acid metabolism, while simultaneously activating immune and inflammatory responses in enzalutamide-resistant prostate cancer cells. In both cell line and NEPC PDX organoid models, loss of GRIK5 impaired proliferation and clonogenic growth. Notably, GRIK5 also contributes to enzalutamide resistance. Pharmacological evaluation revealed that Pan-GRIK antagonists exhibit anti-tumor activity, although the required relatively high concentrations suggest that more potent therapeutic strategies should be developed. Collectively, this study establishes that GRIK family members play critical roles in enzalutamide resistance and NEPC progression, highlighting GRIK signaling as a potential therapeutic target for overcoming lineage plasticity in prostate cancer. Full article

Polygonatum cyrtonema (P. cyrtonema) Hua is an important economic crop with both edible and medicinal value. However, frequent root rot severely restricts its industrial development, resulting in sharp yield reduction and quality deterioration. To clarify the primary pathogenic fungi causing root rot of P. cyrtonema Hua, 58 fungal strains from naturally diseased P. cyrtonema Hua plants in different habitats were isolated in this study. By combining morphological observation and molecular identification based on 18S rDNA and ITS rDNA sequences, the species of 22 pathogenic fungi were identified, among which 10 strains belonged to the genus Fusarium, accounting for 45.45% of the identified isolates. The pathogenicity of 21 pathogenic fungi was verified according to Koch’s postulates, with findings indicating that Fusarium species exhibited significant pathogenic potential. Meanwhile, six previously identified endophytic Paenibacillus strains isolated from P. cyrtonema Hua were employed to perform dual culture assays and antifungal evaluations of their fermentation supernatants against representative strains including F. concentricum F2, Neopestalotiopsis sp. F3 and F. oxysporum F8. The results indicated that the antagonistic activity exhibited by the six strains exceeded 50%, with the inhibition rates of their fermentation supernatants against strains F2, F3 and F8 surpassing 73%. This study confirmed that Fusarium is the dominant pathogenic fungal group causing root rot of P. cyrtonema Hua. Furthermore, highly effective antagonistic endophytes were preliminarily identified, offering candidate strains and a theoretical foundation for the green management of root rot in P. cyrtonema Hua. Full article

Background: Obesity is associated with aggressive prostate cancer, but the links between metabolic dysregulation, inflammation, adipocyte-associated signaling, and tumor growth remain incompletely defined. This study examined whether high-fat diet (HFD)-associated systemic changes and adipocyte-derived paracrine interactions are linked to prostate cancer growth in preclinical models. Methods: An HFD xenograft model and adipocyte co-culture systems were used to evaluate systemic and local tumor-supportive features. Pharmacologic/nutritional modulation was tested using green tea or EGCG, arctigenin, and the CCR2 antagonist RS 504393, alone or in combination. Tumor growth, cell proliferation, angiogenesis-related features, circulating metabolic and cytokine levels, and selected tumor-associated signaling proteins were analyzed. Results: HFD feeding was associated with increased circulating free fatty acids, IGF-1, MCP-1, IL-6, and VEGF, together with increased tumor growth, Ki67 staining, and CD31-positive microvessel density. Adipocyte co-culture systems were used to evaluate treatment-associated changes in prostate cancer cell proliferation under adipocyte-associated conditions. Combined modulation with green tea/EGCG, arctigenin, and RS 504393 was associated with greater reductions in adipocyte-associated proliferation, tumor growth, Ki67 staining, and CD31-positive microvessel density than single or dual interventions. Antibody array analysis showed treatment-associated changes in selected stress- and apoptosis-related proteins, including cleaved caspase-7 and phosphorylated Chk1. Conclusions: HFD-associated metabolic and inflammatory alterations, adipocyte-associated interactions, proliferative activity, angiogenesis-related features, and stress/apoptosis-related signaling changes were linked within a tumor-supportive framework in preclinical prostate cancer models. Combined pharmacologic/nutritional modulation was associated with reduced tumor-supportive features under HFD conditions. Further mechanistic and translational validation is needed. Full article

The study investigates the impact of molecular iodine (I₂) supplementation on the viability, invasiveness, and angiogenic potential of high-risk neuroblastoma (NB). In vitro assays were performed using NB cell lines SK-N-AS (non-MYCN-amplified) and SK-N-BE(2) (MYCN-amplified). The role of peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated using the antagonist GW9662, gene expression (RT-qPCR), and protein levels (Western blot). In vivo, zebrafish xenografts were used to evaluate tumor size, angiogenesis, and caudal cell dissemination. I₂ supplementation significantly decreased cell viability in both cell lines, independent of PPARγ activation. In SK-N-BE(2), I₂ impaired cell migration, as measured by a wound-healing assay, in apparent independence of PPARγ activation. However, gene expression indicates that I₂ acts in complex ways, including direct antioxidant effects and PPARγ-mediated effects. The significant decrease in reactive oxygen species levels (DCFDA staining) and the silencing of the long noncoding RNA myocardial infarction-associated transcript (MIAT) by I₂ were directly associated with decreased MYCN and TrkB expression. In contrast, PPARγ activation was accompanied by overexpression of FasN and TrkA and a significant decrease in Aurka, a MYCN-stabilizing protein. In zebrafish, I₂-pretreated SK-N-BE(2) xenografts exhibited a clear reduction in angiogenesis (vascular density) and a decrease in invasive capacity. In conclusion, I₂ supplementation decreases cell viability and attenuates invasion and angiogenesis in NB cells, highlighting its potential as an adjuvant to conventional therapy for high-risk NB. Full article

Background/Objectives: Cytokinin and auxin are essential for vascular development in plants. This study aims to explore whether these two hormones exhibit crosstalk in the cambium, analogous to that observed in the apical meristem. Methods: Using the hybrid poplar (Populus alba × Purshia glandulosa clone ‘84K’), we integrated gravitropic induction with transcriptomic analysis and identified the cytokinin biosynthesis gene PagIPT5 as differentially expressed in a tension wood induction system. PagIPT5 overexpression lines were generated and assessed for growth-related phenotypes. The interaction between cytokinin and auxin was investigated via anatomical observation, cell proliferation assays, in situ PCR, and immunofluorescence detection of auxin and cytokinin. Results: Compared with the wild type, PagIPT5 overexpression lines showed growth inhibition and an auxin-deficient phenotype. High PagIPT5 expression in the vascular cambium elevated cytokinin levels while reducing auxin levels, leading to decreased cambial cell proliferation and suppressed xylem development. However, in the tension wood induction system, both auxin and cytokinin levels increased in the vascular cambium of tension wood relative to opposite wood. Treatment with a superoxide anion activator promotes the accumulation of both auxin and cytokinin in 84K plants. Conclusions: These results revealed an antagonistic interaction between the two hormones in the cambium zone. However, this antagonism is attenuated in tension wood, which may be induced by the accumulation of superoxide anion in tension wood. Full article

Piezo1 mechanosensitive ion channels convert mechanical stimuli into biochemical signals across diverse tissues, yet their role in the contractile function of adult skeletal muscle remains unclear. Here, we demonstrate that Piezo1 regulates skeletal muscle mechanics through a channel-independent mechanism that tunes the length-tension relationship. We examined the effects of pharmacological modulation using the Piezo1 agonist Yoda1 and antagonist Dooku1 in individual muscle fibers from wild-type mice and from muscles with reduced Piezo1 expression (anti-Piezo1 shRNA) using calcium influx and electrophysiological assays. Ex vivo force measurements were performed on these muscles and compared with the dystrophic mdx model. Piezo1 activation had no effect on force at resting length, whereas its inhibition significantly reduced contractile force at stretched lengths, indicating a selective role in length-dependent force regulation. This effect was independent of extracellular calcium and diminished by Piezo1 knockdown. This reduction was absent in mdx muscle, demonstrating dependence on an intact dystrophin-associated cytoskeleton. These findings identify Piezo1 as a previously unrecognized regulator of muscle mechanical performance that operates independently of ion conduction. Our results uncover a mechanobiological interface between Piezo1 and cytoskeletal integrity, expanding current concepts of muscle mechanoregulation and highlighting Piezo1 as a potential therapeutic target for improving muscle function. Full article

Ryanodine receptor-like (RyR-like) is a key endoplasmic reticulum (ER) Ca²⁺ release channel governing intracellular Ca²⁺ homeostasis and cellular stress responses in invertebrates. However, its function in bivalves under high-temperature stress remains unclear. In the present study, one RyR-like was identified from Yesso scallop Patinopecten yessoensis (PyRyR-like). Its function in regulating intracellular Ca²⁺, IRE1α-mediated unfolded protein response (UPR) and apoptosis in the mantle after high-temperature (25 °C) treatment was investigated using molecular cloning, qRT-PCR, Western blot, pull-down assay, cellular calcium imaging, TUNEL and histology assays; High temperature treatment significantly increased intracellular Ca²⁺ content at 1 and 6 h (p < 0.05), but decreased it at 3, 12 and 24 h (p < 0.05); meanwhile, the cAMP level, PyPKA activity, mRNA expression level of PyRyR-like, and protein expression levels of PyFKBP12 and PyGRP78 were significantly increased at different times. However, high temperature did not affect the expression level of PyNVL and PyXBP1(S). The SPRY and RYR domains of PyRyR-like separately interacted with PyFKBP12 and PyPKA. Moreover, RyR antagonist Dantrolene reversed high-temperature-induced alterations in Ca concentration, PKA activity, and core UPR- and apoptosis-related molecules, and suppressed Caspase-3 activity. These findings suggest that PyRyR-like plays an important role in the high-temperature response of scallops by regulating intracellular Ca²⁺ homeostasis and mediating UPR activation and apoptosis, providing new insight into the molecular mechanism underlying scallop adaptation to high temperature. Full article

Background: Breast cancer is the most common malignancy among women and a leading cause of cancer-related deaths globally. Its development involves hormonal, genetic, environmental and inflammatory factors. Among environmental contributors, cadmium (Cd²⁺), a metalloestrogen known to induce redox imbalance, as well as estrogen metabolites, may exert divergent biological effects. Methods: This study investigated the effects of 17β-estradiol (E2) and its metabolites—2-methoxyestradiol (2-MeOE2) and 4-hydroxyestradiol (4-OHE2)—administered alone or in combination with CdCl₂, on estrogen receptor–-positive MCF-7 breast cancer cells and their doxorubicin-resistant cells (MCF-7/DOX). We evaluated cytotoxicity, interaction profiles (synergism/antagonism), and redox-related enzymes associated with drug resistance, including superoxide dismutase 1 (SOD1) and glutathione S-transferase pi (GST-pi). There are no known examples of these types of interactions, especially those involving estrogen metabolites with opposing biological activities—anticancer 2-MeOE2 and procarcinogenic—4-OHE2 in combination with cadmium. Cell viability was assessed after 48 h exposure to individual and combined treatments of CdCl₂. Interaction types (synergism/antagonism) were determined via the combination index method. Antioxidative enzymes were evaluated by quantitative and immunocytochemical analysis of SOD1, GST and GST-pi expression. Results: All tested compounds reduced cell viability in a concentration-dependent manner, with CdCl₂ showing the highest cytotoxicity. MCF-7 cell lines were generally more sensitive to CdCl₂, E2, and 2-MeOE2, whereas MCF-7/DOX cell lines exhibited greater sensitivity to 4-OHE2. Combination studies revealed predominantly antagonistic interactions, particularly for CdCl₂ + 2-MeOE2, suggesting a protective redox-modulating effect of this metabolite. Resistant cells consistently displayed higher SOD1 activity and GST-pi expression, indicating enhanced adaptive responses to oxidative stress. Conclusions: Our study underscores the importance of concentration-dependent interactions between environmental Cd²⁺ and pathways regulated by 17β-estradiol and its metabolites, particularly in the context of cytotoxicity and redox imbalance relevant to breast cancer progression and therapy resistance. Full article

Progression to fibrosis is a major complication of chronic kidney disease (CKD) in obesity, type 2 diabetes, hypertension, and metabolic syndrome, yet effective antifibrotic therapies remain limited. Here, we review how disordered renal energy metabolism—ectopic lipid accumulation, impaired fatty acid oxidation (FAO), and a compensatory shift toward glycolysis—drives tubulointerstitial fibrosis in fatty kidney disease. Lipid overload in tubular, glomerular, and vascular cells arises from increased uptake via scavenger and lipoprotein receptors, enhanced lipogenesis, and reduced lipid catabolism and clearance. Spatial lipidomic studies further reveal nephron-segment-specific lipid signatures and obesity-associated oxidized phospholipids linked to glomerular inflammation. Lipotoxicity, mitochondrial damage, and associated innate-immune signaling, ferroptosis, cellular senescence, and adipose-derived mediators (including leptin, adiponectin, and a locally active renin–angiotensin system) converge on myofibroblast activation from pericytes, fibroblasts, and other resident cells. We discuss established and emerging therapies targeting this metabolic axis—peroxisome proliferator-activated receptor-α (PPARα) modulators, sodium–glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and the mineralocorticoid receptor antagonist finerenone—and propose that restoring metabolic flexibility, by rescuing FAO while limiting maladaptive glycolysis, offers a promising disease-modifying strategy for fatty kidney disease. Full article

The aim of this study is to develop and comprehensively evaluate the efficacy of an innovative formulation of a biological preparation consisting of a bacterial consortium (Serratia proteamaculans B5, Pseudomonas putida D7 and Lysinibacillus sp. S1), embedded in a pullulan polysaccharide matrix, as an agent for inducing systemic resistance in barley (Hordeum vulgare L.) to phytopathogenic stress caused by Fusarium graminearum. To optimize the product’s protective efficacy and minimize the pesticide load on the agroecosystem, a reduced dose of Fundazol (50% of the standard rate) was incorporated into the formulation. The constituent strains exhibited high indole-3-acetic acid production (53.29–69.2 μg·mL⁻¹) and strong antagonistic activity against phytopathogenic fungi, with inhibition zones reaching up to 32.5 mm. Pot and field trials were conducted to comprehensively assess the effect of the biological product on the stress tolerance of barley plants. Pre-sowing seed treatment reduced proline accumulation (by up to 2.3-fold), maintained photosynthetic pigment levels, and increased field germination to 79%. Under infectious field conditions, treatment with the biopreparation contributed to the stabilization of yield structure parameters (treated plants exhibited increases in height and biomass of 9–21%) and the improvement of grain quality indicators. Overall, the results obtained demonstrate the potential of the developed biopreparation as a component of comprehensive protection strategies and as an inducer of plant priming mechanisms. Full article

Biological control is one of the most effective strategies for managing crop fungal diseases such as rice blast, which severely threatens global food security. However, the limited availability of microbial biocontrol resources and incomplete understanding of their mechanisms hinder the development of practical biocontrol technologies for rice blast. In this study, a Bacillus stercoris strain, JK-6, isolated from the rhizosphere soil of rice, was identified as a promising biocontrol agent with strong antagonistic activity against multiple fungal pathogens. The fermentation broth of JK-6 yielded inhibition rates of 94.96% against Magnaporthe oryzae (rice blast), 75.83% against Bipolaris maydis (maize southern leaf blight), and 70.46% against Fusarium graminearum (wheat head blight). Whole-genome sequencing of JK-6 revealed 12 biosynthetic gene clusters, one of which was responsible for the biosynthesis of the lipopeptide surfactin. Further assays showed that 200 μM surfactin exhibited broad-spectrum antifungal activity, with inhibition rates of 82.90%, 66.76%, and 52.54% against M. oryzae, B. maydis, and F. graminearum, respectively. Mechanistically, surfactin suppresses fungal growth by downregulating genes involved in integral and intrinsic membrane components and oxygen transport, as validated by transcriptomic analysis. Our discoveries not only advance the conceptual understanding of the surfactin-mediated JK-6 antagonistic activity against fungal diseases but also offer an effective new approach for the practical control of crop fungal diseases. Full article