Search Results (585)

TasA gene, encoding a functional amyloid protein critical for biofilm formation and antimicrobial activity, was cloned from the endophytic strain Bacillus amyloliquefaciens BS-3, isolated from rubber tree roots. This study identified the shortest functional TasA variant (483 bp, 160 aa) reported to date, featuring unique amino acid substitutions in conserved domains. Bioinformatics analysis predicted a signal peptide (1–27 aa) and transmembrane domain (7–29 aa), which were truncated to optimize heterologous expression. Two prokaryotic vectors (pET28a and pCZN1) were constructed, with pCZN1-TasA expressed solubly in Escherichia coli Arctic Express at 15 °C, while pET28a-TasA formed inclusion bodies at 37 °C. Purified recombinant TasA exhibited potent antifungal activity, achieving 98.6% ± 1.09 inhibition against Colletotrichum acutatum, 64.77% ± 1.34 against Alternaria heveae. Notably, TasA completely suppressed spore germination in C. acutatum and Oidium heveae Steinmannat 60 μg/mL. Structural analysis via AlphaFold3 revealed that truncation enhanced protein stability. These findings highlight BS-3-derived TasA as a promising biocontrol agent, providing molecular insights for developing protein-based biopesticides against rubber tree pathogens. Full article

Background: A precise drug delivery system enables the optimization of treatments with minimal side effects if it can deliver medication only when activated by a specific light source. This study presents a controlled drug delivery system based on poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) designed for the sustained release of vancomycin hydrochloride. Methods: The MPs were co-loaded with indocyanine green (ICG), a near-infrared (NIR) responsive agent, and fabricated via the double emulsion method.They were characterized for stability, surface modification, biocompatibility, and antibacterial efficacy. Results: Dynamic light scattering and zeta potential analyses confirmed significant increases in particle size and surface charge reversal following chitosan coating. Scanning electron microscopy revealed uniform morphology in uncoated MPs (1–10 $\mathsf{\mu }$m) and irregular surfaces post-coating. Stability tests demonstrated drug retention for up to 180 days. Among formulations, PVI1 exhibited the highest yield (76.67 ± 1.3%) and encapsulation efficiency (56.2 ± 1.95%). NIR irradiation (808 nm) enhanced drug release kinetics, with formulation PVI4 achieving over 48.9% release, resulting in improved antibacterial activity. Chitosan-coated MPs (e.g., PVI4-C) effectively suppressed drug release without NIR light for up to 8 h, with cumulative release reaching only 10.89%. Without NIR light, bacterial colonies exceeded 1000 CFU; NIR-triggered release reduced them below 120 CFU. Drug release data fitted best with the zero-order and Korsmeyer–Peppas models, suggesting a combination of diffusion-controlled and constant-rate release behavior. Conclusions: These results demonstrate the promise of chitosan-coated NIR-responsive PLGA MPs for precise, on-demand antibiotic delivery and improved antibacterial performance. Full article

Soil degradation resulting from intensive agricultural practices, the excessive use of agrochemicals, and climate-induced stresses has significantly impaired soil fertility, disrupted microbial diversity, and reduced crop productivity. Plant growth-promoting bacteria (PGPB) represent a sustainable biological approach to restoring degraded soils by modulating plant physiology and soil function through diverse molecular mechanisms. PGPB synthesizes indole-3-acetic acid (IAA) to stimulate root development and nutrient uptake and produce ACC deaminase, which lowers ethylene accumulation under stress, mitigating growth inhibition. They also enhance nutrient availability by releasing phosphate-solubilizing enzymes and siderophores that improve iron acquisition. In parallel, PGPB activates jasmonate and salicylate pathways, priming a systemic resistance to biotic and abiotic stress. Through quorum sensing, biofilm formation, and biosynthetic gene clusters encoding antibiotics, lipopeptides, and VOCs, PGPB strengthen rhizosphere colonization and suppress pathogens. These interactions contribute to microbial community recovery, an improved soil structure, and enhanced nutrient cycling. This review synthesizes current evidence on the molecular and physiological mechanisms by which PGPB enhance soil restoration in degraded agroecosystems, highlighting their role beyond biofertilization as key agents in ecological rehabilitation. It examines advances in nutrient mobilization, stress mitigation, and signaling pathways, based on the literature retrieved from major scientific databases, focusing on studies published in the last decade. Full article

A simple and rapid precipitation process was successfully employed to prepare silver phosphate (SP, Ag₃PO₄). Two different phosphate sources: diammonium hydrogen phosphate ((NH₄)₂HPO₄) and dipotassium hydrogen phosphate (K₂HPO₄) were applied separately as the precursor, obtaining ((NH₄)₂HPO₄)⁻ and K₂HPO₄⁻ derived SP powders, named SP-A or SP-P, respectively. Fourier transform infrared (FTIR) spectra pointed out the vibrational characteristics of P–O and O–P–O interactions, confirming the presence of the PO43– functional group for SP. X-ray diffraction (XRD) patterns revealed that the SP crystallized in a cubic crystal structure. Whereas the field emission scanning electron microscope (FESEM) exposed spherical SP particles. The potentially antibacterial activity of SP-A and SP-P against bacterial Bacillus stratosphericus, yeast Meyerozyma guilliermondii, and fungal Phanerodontia chrysosporium was subsequently investigated. All studied microorganisms were recovered and isolated from the aquatic plant during the tissue culture process. The preliminary result of the antimicrobial test revealed that SP-A has higher antimicrobial activity than SP-P. The superior antimicrobial efficiency of SP-A compared to SP-P may be attributed to its purity and crystallite size, which provide a higher surface area and more active sites. In addition, the presence of potassium-related impurities in SP-P could have negatively affected its antimicrobial performance. These findings suggest that SP holds potential as an antimicrobial agent for maintaining sterility in tissue cultures, particularly in aquatic plant systems. The growth of both B. stratosphericus and M. guilliermondii was suppressed effectively at 30 ppm SP-A, whereas 10 ppm of SP-A can suppress P. chrysosporium development. This present work also highlights the potential of SP at very low concentrations (10–30 ppm) for utilization as an effective antimicrobial agent in tissue culture, compared to a commercial antimicrobial agent, viz., acetic acid, at the same concentration. Full article

Burkholderia gladioli is a multifaceted bacterium with both pathogenic and beneficial strains, and nonpathogenic Burkholderia species have shown potential as plant growth-promoting rhizobacteria (PGPRs) and biocontrol agents. However, the molecular mechanisms underlying their beneficial functions remain poorly characterized. This study systematically investigated the antimicrobial mechanisms and plant growth-promoting properties of B. gladioli strain ZBSF BH07, isolated from the grape rhizosphere, by combining genomic and functional analyses, including whole-genome sequencing, gene annotation, phylogenetic and comparative genomics, in vitro antifungal assays, and plant growth promotion evaluations. The results showed that ZBSF BH07 exhibited broad-spectrum antifungal activity, inhibiting 14 grape pathogens with an average inhibition rate of 56.58% and showing dual preventive/curative effects against grape white rot, while also significantly promoting grape seedling growth with increases of 54.9% in plant height, 172.9% in root fresh weight, and 231.34% in root dry weight. Genomic analysis revealed an 8.56-Mb genome (two chromosomes and one plasmid) encoding 7431 genes and 26 secondary metabolite biosynthesis clusters (predominantly nonribosomal peptide synthetases), supporting its capacity for antifungal metabolite secretion, and functional analysis confirmed genes for indole-3-acetic acid (IAA) synthesis, phosphate solubilization, and siderophore production. These results demonstrate that ZBSF BH07 suppresses pathogens via antifungal metabolites and enhances grape growth through phytohormone regulation and nutrient acquisition, providing novel insights into the dual mechanisms of B. gladioli as a biocontrol and growth-promoting agent and laying a scientific foundation for developing sustainable grapevine disease management strategies. Full article

Sclerotinia sclerotiorum (S. sclerotiorum), a necrotrophic phytopathogen, causes sclerotinia stem rot (SSR) in many crops like oilseed rape, resulting in severe economic losses. Developing eco-friendly compound fungicides has become a critical research priority. This study explored the combination of sodium selenite and cuminic acid to screen for the optimal mixing ratio and investigate its inhibitory effects and mechanisms against S. sclerotiorum. The results demonstrated that synergistic effects were observed with a 1:3 combination ratio of sodium selenite to cuminic acid. After treatment with the selenium compound agent, ultrastructural observations revealed that the hyphae of S. sclerotiorum became severely shriveled, deformed, and twisted. The agent significantly reduced oxalic acid production and the activities of polymethylgalacturonide (PMG) and carboxymethylcellulose enzymes (Cx), while increasing the exocytosis of nucleic acids and proteins from the mycelium. Foliar application of the selenium compound agent significantly reduced lesion areas in rapeseed. Combined with the results of transcriptome sequencing, this study suggests that the compound agent effectively inhibits the growth of S. sclerotiorum by disrupting its membrane system, reducing the activity of cell wall-degrading enzymes, and suppressing protein synthesis, etc. This research provides a foundation for developing environmentally friendly and effective fungicides to control S. sclerotiorum. Full article

Seed germination is recognized for enhancing the accumulation of bioactive compounds. Perilla frutescens (L.) Britt., commonly known as perilla seed, is rich in fatty acids that may be beneficial for anti-hair loss. This study investigated the hair regeneration potential of perilla seed extracts—non-germinated (NG-PS) and germinated in distilled water (0 ppm selenium; G0-PS), and germinated with 80 ppm selenium (G80-PS)—obtained from supercritical fluid extraction (SFE) and screw compression (SC). SFE extracts exhibited significantly higher levels of polyphenols, tocopherols, and fatty acids compared to SC extracts. Among the germinated groups, G0-PS showed the highest bioactive compound content and antioxidant capacity. Remarkably, treatment with SFE-G0-PS led to a significant increase in the proliferation and migration of hair follicle cells, reaching 147.21 ± 2.11% (p < 0.05), and resulted in complete wound closure. In addition, its antioxidant and anti-inflammatory properties were reflected by a marked scavenging effect on TBARS (59.62 ± 0.66% of control) and suppressed nitrite amounts (0.44 ± 0.01 µM). Moreover, SFE-G0-PS markedly suppressed SRD5A1-3 gene expression—key regulators in androgenetic alopecia—in both DU-145 and HFDPCs, with approximately 2-fold and 1.5-fold greater inhibition compared to finasteride and minoxidil, respectively. Simultaneously, it upregulated the expression of hair growth-related genes, including CTNNB1, SHH, SMO, GLI1, and VEGF, by approximately 1.5-fold, demonstrating stronger activation than minoxidil. These findings suggest the potential of SFE-G0-PS as a natural therapeutic agent for promoting hair growth and preventing hair loss. Full article

Metastases are the leading cause of cancer-related deaths. The spread of neoplasms involves multiple mechanisms, with metastatic tumors exhibiting molecular behaviors distinct from their primary counterparts. The key hallmarks of metastatic lesions include chromosomal instability, copy number alterations (CNAs), and a reduced degree of subclonality. Furthermore, metabolic adaptations such as enhanced glycogen synthesis and storage, as well as increased fatty acid oxidation (FAO), play a critical role in sustaining energy supply in metastases and contributing to chemoresistance. FAO promotes the infiltration of macrophages into the tumor, where they polarize to the M2 phenotype, which is associated with immune suppression and tissue remodeling. Additionally, the tumor microbiome and the action of cytotoxic drugs trigger neutrophil extravasation through inflammatory pathways. Chemoresistant neutrophils in the tumor microenvironment can suppress effector lymphocyte activation and facilitate the formation of neutrophil extracellular traps (NETs), which are linked to drug resistance. This article examines the genomic features of metastatic tumors, along with the metabolic and immunological dynamics within the metastatic tumor microenvironment, and their contribution to drug resistance. It also discusses the molecular mechanisms underlying resistance to chemotherapeutic agents commonly used in the treatment of metastatic cancer. Full article

Background: The spleen is the primary reservoir of immune cells in mammals. Diverse stimuli can disrupt spleen homeostasis, resulting in spleen injury and immune dysfunction. This study employed a porcine model to assess the therapeutic potential of salvianolic acid B (SAB) against lipopolysaccharide (LPS)-induced splenic injury. Methods: Seventy-two male weanling piglets were randomly assigned to one of four groups: CON-SS, SAB-SS, CON-LPS, and SAB-LPS. The CON-SS and CON-LPS groups received a basal diet, while SAB-SS and SAB-LPS groups received a SAB-supplemented diet. After 14 d, the CON-SS and SAB-SS groups received an intraperitoneal injection of sterile saline, whereas the CON-LPS and SAB-LPS groups were injected with LPS. Blood and spleen tissues were harvested 6 h post-injection for biochemical analysis. Results: LPS induced systemic immune disorders in piglets, as evidenced by increased immune organ indices and decreased white blood cell, lymphocyte, and basophil counts in blood (p < 0.05). LPS also caused histoarchitectural disruption, cell apoptosis, oxidative stress, and inflammation in the spleen (p < 0.05). Conversely, SAB improved splenic histopathology and reduced splenic apoptosis and pro-inflammatory mediators in piglets (p < 0.05). SAB significantly mitigated peroxidation accumulation by facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 and strengthening the antioxidant system, and inhibited nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activation (p < 0.05). Mechanistically, SAB attenuated LPS-induced splenic oxidative stress and NLRP3 inflammasome activation by restoring mitochondrial structure and function (p < 0.05). Conclusions: This research unveils that SAB alleviates LPS-induced spleen disorder by reinforcing antioxidant system and suppressing NLRP3 inflammasome, highlighting SAB’s potential as a prospective therapeutic agent for spleen disorders. Full article

Downy mildew, caused by Plasmopara viticola, is a major threat to grapevine (Vitis vinifera) cultivation in humid climates. Restrictions on synthetic pesticides and inconsistent efficacy of current biocontrol agents, especially under rainy conditions, complicate disease management. This study evaluated the potential of compost tea to suppress downy mildew in a two-year field experiment (2023 and 2024), combined with reduced synthetic fungicide applications. The study design compared two phytosanitary management strategies on a commercial vineyard: a conventional fungicide against a compost tea strategy supplemented with two cymoxanil applications. The experiment set up had three replicated blocks, each consisting of 100 plants for a total of 600 plants. Mechanistic insights were provided through controlled laboratory experiments involving pre- and post-infection leaf assays, vineyard bacteriome profiling, via 16S rRNA gene sequencing for bacterial communities, across vineyard compartments, i.e., bulk soil, rhizosphere, and phyllosphere, and grapevine metabolomic analysis by GC-MS analysis. Field trials demonstrated that compost tea combined with two fungicide applications effectively reduced disease severity, notably outperforming the fungicide alone in the particularly rainy year of 2023. Bacteriome analysis revealed that compost tea treatment enriched beneficial bacterial genera, including Pseudomonas, Sphingomonas, Enterobacter, Massilia, and Bacillus, known for their growth-promoting and biocontrol activity in the rhizosphere and phyllosphere. Laboratory assays on detached leaves further showed that compost tea alone could suppress both infection and sporulation of P. viticola. Metabolomic analysis highlighted the accumulation of compounds such as tartaric and shikimic acids in compost tea treated leaves, suggesting a potential role in induced resistance. The findings indicate that applying compost tea with reduced fungicide treatments represents a promising and sustainable strategy for managing grapevine downy mildew, even in challenging climates. Full article

Clubroot, caused by Plasmodiophora brassicae Woronin, poses a major threat to Chinese cabbage (Brassica rapa subsp. pekinensis) production worldwide, significantly impacting crop yield, quality, and economic value. Biological control represents a promising approach since it is non-toxic and eco-friendly, and it reduces the risk of pathogen resistance development. In this study, our objective was to screen for actinomycetes that can effectively inhibit clubroot. We screened 13 actinomycete strains, identifying 2, XDS3-6 and CD1-1, with substantial in vivo inhibitory effects, achieving infection suppression rates above 64% against P. brassicae. Phylogenetic analysis classified XDS3-6 and CD1-1 as Streptomyces virginiae and Streptomyces cinnamonensis, respectively. Both strains exhibited protease and glucanase production capabilities, essential for pathogenic suppression. Additionally, these strains induced host defense responses, as evidenced by increased jasmonic acid (JA) and salicylic acid (SA) accumulation and elevated activities of defense-related enzymes. Colonization studies of XDS3-6 and CD1-1 mutant strains in cabbage roots indicated sustained root colonization, with peak colony-forming units (CFUs) at 20 days post-inoculation, reaching 11.0 × 10⁴ CFU/g and 8.5 × 10⁴ CFU/g, respectively, and persisting for at least 30 days. Overall, these findings underscore the potential of Streptomyces strains XDS3-6 and CD1-1 as effective biocontrol agents, providing a theoretical foundation for their application in managing clubroot in Chinese cabbage. Full article

Vitamin C, also known as L-ascorbic acid (AA), functions as a pro-oxidant in cancer at high doses and exerts anticancer effects by generating reactive oxygen species (ROS) and selectively inducing damage to cancer cells. However, AA at low doses promotes cancer cell proliferation. The efficacy of high-dose AA therapy is frequently restricted by inadequate intracellular AA uptake, resulting from low expression of sodium-dependent vitamin C transporter 2 (SVCT2). In this study, we investigated whether valproic acid (VPA), a histone deacetylase inhibitor, could circumvent this constraint by increasing the expression of SVCT2 in colorectal cancer cells, including HCT-116 and DLD-1 with low SVCT2 levels. We found that VPA increased SVCT2 expression in both cell lines. Co-treatment with AA and VPA increased the number of apoptotic cells and enhanced intracellular AA uptake via VPA-upregulated SVCT2, followed by increased ROS production in both cell lines. Furthermore, the combination increased the synergistic anticancer effects and suppressed the hormetic dose response of AA in both cell lines. In a xenograft mouse model, co-treatment decreased tumor size and increased the tumor growth inhibition ratio compared to treatment with AA or VPA alone. Accordingly, VPA treatment enhanced SVCT2 expression in colorectal cancer cells, suppressed the hormetic dose-response effect of AA, and improved the potential of high-dose AA therapy as an anticancer agent. Full article

L-asparaginase (L-ASNase) remains a vital chemotherapeutic agent for acute lymphoblastic leukemia (ALL), primarily due to its mechanism of depleting circulating asparagine essential for leukemic cell proliferation. However, existing ASNases (including pegylated ones) face limitations including immunogenicity, rapid clearance, and off-target toxicities. Earlier, we have shown that the conjugation of L-ASNase with the polyamines and their copolymers results in significant enhancement of the antiproliferative activity due to accumulation in tumor cells. We suggested that this effect is probably mediated by polyamine transport system (PTS) receptors that are overexpressed in ALL cells. Here, we investigated the effect of competitive inhibitors of PTS receptors to the L-ASNase interaction with cancer cells (L5178Y, K562 and A549). L-ASNase from Rhodospirillum rubrum (RrA), Erwinia carotovora (EwA), and Escherichia coli (EcA) were conjugated with natural polyamines (spermine—spm, spermidine—spd, putrescine—put) and a synthetic branched polymer, polyethyleneimine 2 kDa (PEI2 ), using carbodiimide chemistry. Polyamine conjugation with L-ASNase significantly increased enzyme binding and cellular uptake, as quantified by fluorimetry and confocal microscopy. This increased cellular uptake translated into increased cytotoxicity of L-ASNase conjugates. The presence of competitive ligands to PTS receptors decreased the uptake of polyamine-conjugated enzymes-fatty acid derivatives of polyamines produced the strongest suppression. Simultaneously with this suppression, in some cases, competitive ligands to PTS significantly promoted the uptake of the native unconjugated enzymes, “equalizing” the cellular access for native vs conjugated ASNase. The screening for competing inhibitors of PTS receptor-mediated endocytosis revealed spermine and caproate/lipoate derivatives as the most potent inhibitors or antagonists, significantly reducing the cytostatic efficacy of polyamine-conjugated ASNases. The results obtained emphasize the complex, cell-type-dependent and inhibitor-specific nature of these interactions, which highlights the profound involvement of PTS in L-ASNase internalization and cytotoxic activity. These findings support the viability of polyamine conjugation as a strategy to enhance L-ASNase delivery and therapeutic efficacy by targeting the PTS. Full article

Liver injury caused by the irrational use of acetaminophen (APAP) represents a significant challenge in the field of public health. In clinical treatment, apart from N—acetylcysteine (NAC), the only approved antidote, there are extremely limited effective intervention measures for APAP-induced hepatotoxicity. Therefore, exploring novel liver-protecting drugs and elucidating their mechanisms of action is of great scientific significance and clinical value. Rosmarinic acid (RA), as a natural polyphenolic compound, has been proven to have significant antioxidant activity. Previous studies have shown that it has a protective effect against drug-induced liver injury. Nevertheless, the precise protective mechanism of RA in APAP-induced acute liver injury (AILI) has not been fully defined. This study was based on an AILI mouse model to systematically explore the liver-protecting effect of RA and its underlying molecular mechanisms. The research results showed that pretreatment with RA could notably mitigate liver pathological injury. It could decrease the activities of ALT and AST in the serum, suppress the liver inflammatory reaction, and reverse the decline in the levels of CAT, T-AOC, SOD, and GSH caused by APAP. Meanwhile, RA could enhance antioxidant defense capabilities by activating the Keap1/Nrf2/HO-1 signaling pathway, regulate the xCT/GPX4 axis to inhibit lipid peroxidation, and thus block the process of ferroptosis. In conclusion, this study confirmed that RA exerts a protective effect against AILI by regulating the Keap1/Nrf2/HO-1 axis to enhance antioxidant capacity and inhibit ferroptosis through the xCT/GPX4 pathway. Our research provides a theoretical basis for RA as a potential therapeutic agent for APAP-induced liver injury. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to fibrosis and hepatocellular carcinoma (HCC). Gut-derived lipopolysaccharide (LPS) promotes hepatic inflammation, fibrosis, and angiogenesis through toll-like receptor 4 (TLR4) signaling. This study examined the effects of rifaximin, a non-absorbable, gut-targeted antibiotic, on MASH-related liver fibrosis and early hepatocarcinogenesis, with a focus on the LPS–epiregulin–IL-8–angiogenesis axis.MASH was induced in Fischer 344 rats using a choline-deficient, L-amino acid-defined high-fat diet (CDAHFD). Rifaximin (30 mg/kg/day) was orally administered for 12 weeks. Liver histology, gene expression, intestinal permeability, LPS levels, and angiogenic markers were evaluated. Rifaximin reduced hepatic inflammation, fibrosis, hydroxyproline content, and fibrogenic gene expression. The number and size of GST-P-positive preneoplastic lesions and proliferation-related genes were decreased. Portal LPS levels and Kupffer cell activation declined, with downregulation of Lbp, Cd14, Tlr4, and inflammatory cytokines. Rifaximin decreased hepatic epiregulin and IL-8 expression, attenuated CD34-positive neovascularization, and suppressed proangiogenic gene expression, accompanied by improved intestinal barrier function and reduced gut permeability. Rifaximin mitigates MASH progression by restoring gut barrier integrity, limiting LPS translocation, and inhibiting fibrogenic and angiogenic pathways. These results suggest its potential as a chemopreventive agent in MASH-related hepatocarcinogenesis. Full article