Search Results (11,476)

Allelopathy means that one plant produces chemical substances to affect the growth of other plants. Crop rotation is considered as a potential strategy to alleviate the allelopathic inhibition. So, it is important to identify rotation crops with wide availability and low inhibitory effects. In this study, the allelopathic potential of soil extracts was investigated on the germination, seedling growth, biomass, and biochemical parameters (malondialdehyde, photosynthetic pigments, and antioxidant enzyme activities) of five crops, by a series of laboratory experiments. Firstly, both soil water extracts (SWE) and soil ethanol extracts (SEE) exhibited allelopathic inhibition on the seed germination and the root length of all seedlings in a dose-dependent relationship. The SWE significantly promoted the shoot length of bok choy and Chinese lettuce, while the SEE had no significant effect in bok choy. The application of SEE resulted in a significant increase in the dry weight of bok choy and rocket. In contrast, SWE had a negligible effect on bok choy and lettuce. Both of them caused decrease in the dry weight of the other seedlings. Then, the allelopathic synthetic effect index of water/ethanol extracts was chemo-inhibitory, and the inhibitory effect increased with increasing extract concentration. The SWE had the strongest inhibition on rocket and the SEE on lettuce. Both of them had the weakest effect on bok choy. The extracts significantly inhibited the photosynthetic capacity in five crops, manifested as decrease in photosynthetic pigments and dose-dependent effects. The malondialdehyde (MDA) content in all crops increased in a dose-dependent manner, confirming that the extracts caused lipid peroxidation. However, the defense strategies of different crops vary significantly. There is crop with active defense, such as bok choy treated with SWE. It delayed oxidative damage by continuously upregulating the activities of superoxide dismutase (SOD) and catalase (CAT). This is the key physiological mechanism for tolerance. There is also the oxidative stress failure type, as follows: CAT activity of rocket and cabbage increased, but the SOD activity did not increase by SEE. This reveals the physiological essence of their sensitivity—the lack of persistent scavenging ability for reactive oxygen species. Based on the inhibition of peroxidase (POD) and ascorbic acid peroxidase (APX), it is speculated that the extracts may inhibit the hydrogen peroxide scavenging pathway, which centered on the ascorbate–glutathione cycle. It is the fundamental reason why the continuous accumulation of MDA though SOD/CAT is up. This study confirmed the allelopathic effects of the water and ethanol extracts on five vegetable crops, and found that bok choy was less affected by them. The soil extracts affected the growth and development of seedlings by regulating their oxidative metabolism and photosynthetic capacity. These results support recommending pak choi as a rotation crop. This provides crops for subsequent field experiments and a new direction for next-step research on continuous cropping obstacles. Full article

For the first time, a regulatory network linking melanin, genes, pathways, and edible quality was constructed for 138 Auricularia cornea strains sourced domestically and internationally. This marks the inaugural study of A. cornea spanning from cellular to physical-mechanical properties. Correlation analysis between melanin and edible quality traits (hardness, springiness, cohesiveness, gumminess, chewiness, and resilience) revealed that hardness, cohesiveness, and gumminess increased with rising melanin content, while springiness correspondingly decreased. Genome-wide association analysis identified 15,597,589 SNP loci. A total of 39 genes related to food quality were annotated, including one melanin-related lacquer enzyme gene, ACW004924. Real-time quantitative PCR validation of key genes identified for melanin and edible quality traits revealed results consistent with those from correlation analysis. The lacquer enzyme genes ACW004736, ACW006232, which regulate melanin synthesis, and the tyrosinase genes ACW001451, ACW002443, and ACW001003 were also identified in edible quality traits. These genes perform similar functions in GO-enriched metabolic processes, catalytic activity, and cellular structural complexes, as well as in KEGG-enriched pathways such as carbon metabolism and polysaccharide synthesis. They catalyze melanin synthesis and promote interactions between melanin and cell wall polysaccharides, chitin, and structural proteins, thereby stabilizing the cellular scaffold structure, jointly mediating the effect of melanin on the edible quality of A. cornea. The results supplement the downstream regulatory chain of catalytic enzymes and edible quality in the γ-L-glutaminyl-3,4-dihydroxybenzene (GDHB) pigment synthesis pathway, and form an information network of melanin synthesis, cell wall structure optimization, and edible quality regulation. Full article

Verticillium wilt (VW), caused by the soil-borne phytopathogen Verticillium dahliae, is a devastating vascular disease that severely threatens global cotton production and causes substantial economic losses. Jasmonic acid (JA) signaling plays a crucial role in plant innate immunity; however, the molecular mechanisms governing JA biosynthesis during cotton defense responses to V. dahliae infection remain largely elusive. In this study, we identified that GhAOS1 (allene oxide synthase 1), a key rate-limiting enzyme-encoding gene in the JA biosynthetic pathway, was rapidly and significantly induced by V. dahliae infection and exclusively localized in chloroplasts. Functional analysis in GhAOS1-silenced cotton and overexpressing Arabidopsis plants demonstrated that GhAOS1 positively regulates resistance to V. dahliae. Transcriptome analysis of GhAOS1-silenced cotton plants showed that DEGs are significantly enriched in phenylpropanoid biosynthesis, flavonoid biosynthesis, and α-linolenic acid metabolism pathways. Consistent with these findings, silencing GhAOS1 significantly reduced endogenous JA levels and suppressed the expression of defense-related genes and JA biosynthetic genes in cotton. Furthermore, we identified that the transcription factor GhWRKY70 directly binds to the W-box cis-acting element in the GhAOS1 promoter through Y1H, LUC, and EMSA, which activated GhAOS1 transcription. Silencing GhWRKY70 in cotton significantly enhanced plant susceptibility to V. dahliae and suppressed the expression of JA signaling pathway-related genes. Collectively, our results elucidate that GhWRKY70 positively regulates cotton resistance to VW by activating GhAOS1-mediated JA biosynthesis, revealing a novel GhWRKY70-GhAOS1 regulatory module that integrates JA signaling to coordinate cotton immune responses against V. dahliae. This study provides new insights into the molecular mechanism of JA-mediated defense and offers potential targets for molecular breeding of VW-resistant cotton. Full article

Objective: Posaconazole, a second-generation triazole antifungal used for the prevention or treatment of invasive fungal infections, has been shown to markedly increase tacrolimus exposure in vivo when co-administered, potentially leading to clinically significant adverse events. A physiologically based pharmacokinetic (PBPK) model was developed to predict tacrolimus–posaconazole interactions in renal transplant recipients with different CYP3A5 genotypes, to inform tacrolimus dose adjustment in clinical practice. Methods: First, to obtain the critical inhibition parameters, in vitro enzyme kinetic studies were conducted. Based on these data, a whole-body physiologically based pharmacokinetic (PBPK) model for TAC was developed and validated in PK-Sim. A published, validated posaconazole PBPK model was applied concurrently. Model performance was evaluated against published pharmacokinetic data in healthy volunteers receiving tacrolimus with posaconazole. A virtual Chinese renal transplant recipient was generated by incorporating population-specific physiological parameters, including CYP3A5 genotype-dependent enzyme expression. Results: In vitro experimental results demonstrated that POSA acts as a potent reversible competitive inhibitor of CYP3A4/5-mediated TAC metabolism. The tacrolimus PBPK model adequately captured pharmacokinetics across CYP3A5 genotypes, and tacrolimus pharmacokinetics during co-administration with posaconazole were also predicted. Compared with CYP3A5 expressers, nonexpressers showed greater variability in tacrolimus whole-blood concentrations and greater susceptibility to posaconazole-mediated interactions. The CYP3A5*3*3 genotype was associated with higher C_max and AUC. Dose optimization simulations predicted that after 6–7 days of posaconazole co-administration, nonexpressers would require the reduction of tacrolimus dosing frequency from every 12 h to every 24 h to maintain trough concentrations within 8–15 ng/mL, whereas a 50% dose reduction was predicted to be optimal for expressers. Conclusions: A tacrolimus–posaconazole PBPK drug–drug interaction model was developed for the population of renal transplant recipients and used to simulate tacrolimus trough concentrations across CYP3A5 genotypes and dosing regimens, supporting genotype-informed co-administration in clinical practice. Full article

Elicitation is a powerful strategy for increasing bioactive metabolites in plant systems. This study is among the first to integrate growth responses, antioxidant enzyme activities, and metabolite profiling in G. paniculata adventitious roots (ARs). The study aims to evaluate the effects of yeast extract (YE) and salicylic acid (SA) on biomass traits, antioxidant enzymes (peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase), and phenolic metabolite profiles. ARs were exposed to YE (0.25–2 g L⁻¹) and SA (50–400 µM) for 28 days. Yeast extract significantly enhanced antioxidant capacity by promoting enzyme activities, phenolics, and flavonoids. In contrast, SA exhibited concentration-dependent effects. Moderate concentrations improved antioxidant activity, while higher concentrations promoted the accumulation of specific flavonoids. Maximum biomass production was achieved with 1 g L⁻¹ YE, which also resulted in the highest metabolite productivity. Conversely, SA treatments caused a progressive reduction in biomass with increasing concentration, although they enhanced the accumulation of selected bioactive compounds. Notably, 100 µM SA resulted in the highest phenolic content and antioxidant activity, whereas 400 µM SA markedly increased flavonoids such as rutin and quercetin. HPLC analysis identified seventeen phenolic compounds, demonstrating that YE acts as a broad-spectrum elicitor, whereas SA functions as a selective metabolic modulator. The differential enzymatic responses further highlight elicitor-specific regulatory patterns in antioxidant defense and secondary metabolism. Overall, these findings demonstrate that elicitor type and concentration differentially influence the balance between growth and secondary metabolism, providing a framework for optimizing metabolite production in controlled in-vitro systems. Full article

Biological control fungi play an important role in the management of plant-parasitic nematodes; however, the molecular basis underlying their diverse biocontrol strategies remains incompletely understood. In this study, a comparative genomic analysis was performed on four representative biocontrol fungi: Purpureocillium lilacinum PLFJ-1, Trichoderma harzianum CBS 226.95, Pochonia chlamydosporia 170, and Aspergillus niger CBS 513.88. Genome comparison revealed substantial variation: genome size ranged from 34.0 Mb (A. niger) to 44.2 Mb (P. chlamydosporia), GC content from 47.5% (T. harzianum) to 58.5% (P. lilacinum), and predicted gene models also differed markedly among the four fungi. Phylogenetic analysis based on the Internal Transcribed Spacer divided these fungi into two major clades corresponding to distinct evolutionary lineages. Orthogroup analysis identified both a conserved core gene set and species-specific gene repertoires. Functional annotation using KEGG, KOG, and GO indicated a high degree of conservation across core metabolic processes, catalytic activities, and cellular components, with distinct differences within specific functional categories. Further comparative analyses demonstrated pronounced variation in the composition and abundance of carbohydrate-active enzymes (CAZymes) and peptidases, as well as a notable expansion and enrichment of S8 subtilisin-like serine peptidases in the nematode-parasitic fungi P. lilacinum and P. chlamydosporia. Secondary metabolite analysis revealed lineage-specific biosynthetic gene clusters (BGCs). Notably, P. lilacinum and P. chlamydosporia carried PKS/NRPS clusters potentially linked to nematicidal activity, while A. niger and T. harzianum displayed broader but less infection-specific metabolic profiles. Together, these findings suggest that distinct enzymatic and metabolic gene repertoires, particularly expansions of S8 serine peptidases and specific CAZyme families, may contribute to the biocontrol potential of these fungi. Full article

Background/Objectives: Cytochrome P450 enzymes (CYP2D6, CYP2C19, CYP3A4) play a key role in interindividual variability in cardiovascular drug metabolism. This study aimed to describe metabolizer phenotype distributions in a Turkish emergency cardiac cohort and across diagnostic categories. Methods: This retrospective descriptive pharmacogenomic study included 250 patients. Genotyping was performed using TaqMan assays for CYP2D6 (*2, *4, *10, *41), CYP2C19 (*2, *17), and CYP3A4 (*22, *1B). Phenotypes were assigned according to CPIC guidelines. CYP2D6 copy-number variation was not assessed. Results: Non-normal metabolizer phenotypes were observed in 55.6% (CYP2D6), 84.4% (CYP2C19), and 30.4% (CYP3A4) of patients. For CYP2D6, normal (44.4%) and intermediate (42.0%) metabolizers predominated. For CYP2C19, intermediate metabolizers were most frequent (36.0%), followed by normal (22.8%), rapid (17.2%), poor (14.8%), and ultra-rapid metabolizers (9.2%). CYP3A4 showed predominantly normal activity (69.6%). Phenotype distributions varied across diagnoses without clear clustering. Conclusions: A high prevalence of CYP2D6 and CYP2C19 variability with predicted functional relevance based on CPIC was observed, whereas CYP3A4 activity was more stable. These findings provide descriptive pharmacogenomic data to support future genotype-guided cardiovascular therapy studies. Full article

Thyroid hormones (THs) are essential regulators of human brain development, and disrupted TH availability during pregnancy or early life is linked to adverse neurodevelopmental outcomes. Concerns that environmental chemicals interfere with TH signalling have increased the need for human-relevant in vitro systems to identify thyroid hormone system-disrupting chemicals (THSDCs) for risk assessment. Here, we compared two human-induced pluripotent stem cell (hiPSC)-derived brain organoid models for THSDC assessment: (i) human cortical organoids (COs) generated by unguided differentiation, offering higher architectural complexity but lower throughput; and (ii) neural stem cell-derived organoids (NSCOs), designed for scalability with reduced cellular diversity. Both models expressed key TH handling components, including the transporter SLC16A2 (MCT8) and the inactivating enzyme DIO3. Using LC–MS/MS, we show that exogenous T3 is depleted from culture media and metabolized to 3,3′-T2 and 3′-T1 in both models, alongside upregulation of T3-responsive genes (HR, KLF9, DIO3, SEMA3C). Pulse and chronic co-exposures to reference disruptors iopanoic acid (IA, deiodinase inhibitor) and silychristin (SC, MCT8 inhibitor) altered T3 metabolism and modulated T3-responsive transcriptional endpoints. In NSCOs, high-content imaging revealed treatment-associated changes in cell composition, with chronic T3 reducing the SOX2-positive progenitor pool and THSDCs blocking this effect. Together, these findings provide a framework for organoid qualification—linking TH handling, transcriptomic responsiveness, and scalable phenotypic readouts—as a necessary step toward model validation and implementation of brain organoids in THSDC risk assessment pipelines. Full article

Plant-parasitic nematodes (PPNs) rank among the most economically destructive soilborne pathogens worldwide, causing annual crop losses estimated at USD 125–175 billion. Traditional management of plant parasitic nematodes has depended significantly on synthetic nematicides; however, increasing regulatory constraints, environmental pollution, and the rise of resistant nematode populations have generated an urgent need for sustainable alternatives. Humic substances (HS), comprising humic acids, fulvic acids, and humins derived primarily from leonardite and lignite, represent biologically active components of soil organic matter. Their different functional groups, like carboxylic, phenolic, and carbonyl groups, have direct nematicidal and nematostatic effects by stopping eggs from hatching, slowing down juvenile development, and lowering infectivity. They also indirectly improve soil structure, nutrient bioavailability, and the composition of the rhizosphere microbiome. Plant growth-promoting rhizobacteria (PGPR), particularly Bacillus spp. and Pseudomonas spp., suppress PPN populations through antibiotic biosynthesis, cuticle-degrading hydrolytic enzymes, nematostatic volatile organic compounds, and elicitation of induced systemic resistance (ISR). This review methodically analyzes the individual and synergistic processes by which HS and PGPR inhibit PPNs and enhance plant growth. Humic compounds strongly promote PGPR rhizosphere colonization, augmenting microbial metabolic activity and bioinoculant stability, hence producing combinatorial suppressive effects unattainable by either input independently. The combined HS-PGPR approach is reliable and environmentally sustainable for comprehensive nematode control, requiring multidisciplinary research to achieve global sustainable agriculture. Full article

In recent years, the pivotal role of the gut microbiota and its metabolites in host health and disease has garnered increasing attention. Dietary phosphatidylcholine and choline are metabolized by gut bacteria to generate trimethylamine (TMA). Upon entering the bloodstream, TMA is oxidized by host liver enzymes to trimethylamine N-oxide (TMAO), a known independent risk factor for various systemic diseases, including atherosclerosis, thrombosis, and chronic kidney disease. Within this complex “diet–gut–host” metabolic axis, the microbial choline TMA-lyase (CutC) acts as the key rate-limiting enzyme that catalyzes the cleavage of choline to produce TMA. This review systematically summarizes the discovery history, enzymatic structural characteristics, and catalytic mechanism of CutC, highlighting its potential as a microbial metabolic target for treating associated diseases. By specifically analyzing existing inhibitor strategies and interventions, this article emphasizes the extensive potential of specific targeting of the CutC enzyme in precisely regulating the functions of the microecology. Full article

Geroprotective molecules are currently being actively investigated for the prevention of skin aging. An overview of geroprotectors in dermatology encompasses agents such as antioxidants, ultraviolet (UV) photoprotective agents, chemical peels, and carbon dioxide (CO₂) lasers, each with inherent limitations, including poor tolerability in individuals with sensitive skin. Regarding biostimulators, high-molecular-weight peptides (exceeding 500 kDa) exhibit limited cutaneous bioavailability, underscoring the need for low-molecular-weight geroprotective compounds. One such candidate is dehydroepiandrosterone DHEA, a neurosteroid with anti-aging and anti-stress properties, which also serves as a precursor to sex steroids. Although topical hormone replacement therapy with estrogens and androgens is being utilized, it remains confined to formal hormone replacement regimens and is associated with a significant adverse effect profile. The aim of this review was to analyze the key molecular mechanisms underlying the effects of DHEA on the skin, with particular emphasis on its metabolism and sex- and age-dependent mechanisms of action. Additionally, this review seeks to elucidate the factors contributing to the absence of approved topical DHEA formulations and to outline the potential of DHEA as an anti-aging agent in dermatological applications. DHEA has demonstrated significant skin-improving effects in several studies; its investigation has been predominantly confined to postmenopausal women. Furthermore, the outcome measures employed in these studies lacked specificity. DHEA is not permitted for use in cosmetic products within the European Union due to its hormonal activity. Its use is only allowed as an extemporaneous formulation under the established regulatory frameworks of individual countries. The indications for its use and the appropriate dosage for men and women must be clearly defined based on the results of future clinical studies. Promising research directions include the pharmacogenetic characterization of steroidogenic enzymes and sex hormone receptors, as well as the evaluation of DHEA in both sexes, specifically in premenopausal women and in men presenting with late-onset hypogonadism. Additionally, the biological effects of the primary metabolites of DHEA, androstenedione, and 5-androstenediol, on the cutaneous function remain unexplored, including their potential anti-aging activity mediated through retinoid receptor activation. Full article

In recent times, the importance given to versatile functional nutrition has increased, escalating interest in fermented foods and their potential health benefits. Fermentation is an ancient method frequently used to develop functional and bioactive products. Fermented microalgae and their biomass are important sustainable biotechnological resources for increasing the nutritional value, healthiness, and functionality of foods and for producing high-value-added bioactive compounds. The fermentation of microalgae encompasses the conversion of carbohydrates into sugar or organic substances by a range of microorganisms, particularly lactic acid bacteria (LAB). The fermentation process can activate numerous beneficial mechanisms by enhancing the bioavailability of bioactive compounds in microalgae. Lactic acid bacteria are widely used in food fermentation due to their safety and metabolic versatility. Their ability to produce organic acids, enzymes, and bioactive metabolites makes them suitable for modifying microalgal biomass. This review aims to provide a detailed and critical evaluation of fermented microalgae, including health effects, functional enhancements, bioactivities, and industrial applications. Full article

Global warming and associated environmental changes are reducing arable land and intensifying salinization risks, posing growing threats to food security. Soil salinity is an increasing threat to agricultural productivity worldwide, particularly in arid and semi-arid areas. Wheat (Triticum aestivum L.) is one of the most important and widely cultivated cereal crops for human consumption and livestock feed. However, with increasing water scarcity and the incidence of salt-affected lands, wheat productivity is increasingly affected by salinity. Previous studies have investigated salinity tolerance mechanisms mainly at the seedling and reproductive stages of wheat; however, comparatively fewer studies integrate rapid biochemical and physiological responses during the first hours of germination stress exposure together with transcriptional analyses during early seedling establishment, even though this stage is critical for stand establishment. Here, we evaluated early physiological and transcriptional responses of salt-tolerant, moderate, and sensitive wheat cultivars exposed to 0 or 150 mM NaCl during germination and the early seedling stage. Tolerant and sensitive cultivars showed contrasting germination performance under salinity. Physiological analysis showed that salt-tolerant cultivars exhibited higher proline accumulation and higher antioxidant enzyme activities (CAT, SOD, and GR), while maintaining lower MDA levels under salinity compared with sensitive cultivars. Notably, tolerant cultivars showed marked upregulation of TaHKT1;4, TaP5CS, TaMYB, and TaDHN genes associated with ion homeostasis, osmoprotectant metabolism, and stress-responsive regulation. These responses represent integrated early-stage biochemical, physiological, and transcriptional indicators of salinity responsiveness rather than direct predictors of final yield performance. Full article

Drug exposure during pregnancy and early life is typically considered a short-term clinical intervention rather than a determinant of long-term pharmacological outcomes. Consequently, the developmental context is largely absent from drug discovery and drug development paradigms, where efficacy, safety and target engagement are evaluated predominantly in adult, steady-state systems. This disconnect may contribute to unexplained variability in drug response and toxicity later in life. Pregnancy is accompanied by dynamic remodeling of the maternal gut microbiota and its metabolic output, generating bioactive microbial metabolites that regulate immune tone, metabolic homeostasis and the expression of drug-metabolizing enzymes and transporters. These microbial signals intersect with pharmacological interventions across gestation, shaping maternal pharmacokinetics, placental regulation and fetal drug exposure during developmentally sensitive windows. Importantly, microbiota–drug interactions initiated during pregnancy do not terminate at birth. Instead, they extend into infancy through vertical microbial transmission, breast milk-mediated metabolic signaling, and the immaturity of neonatal drug-handling systems, collectively contributing to developmental programming of drug responsiveness beyond early life. In this review, we propose a microbiota-informed framework that reframes perinatal drug exposure as a developmentally embedded signal operating across a maternal–placental–infant continuum. This perspective introduces a missing developmental dimension into drug discovery and highlights new opportunities to improve translational predictability and precision pharmacotherapy across the life course. Full article

This study examined the effects of dietary crude protein (CP) level and starch: fat ratio (SFR) on glucose and lipid metabolism in geese. A total of 360 male Jiangnan White geese were allocated to a 3 × 2 factorial arrangement with two CP levels (14.5% and 16.5%) and three SFRs (SFR_20:1, SFR_11:1, and SFR_5:1) from 28 to 63 days of age. Under the low-protein condition, Both the SFR_11:1 and SFR_5:1 group enhanced body weight of geese at 63 d, but SFR _5:1 increased subcutaneous and abdominal fat deposition. Dietary SFR changed liver cholesterol metabolism and glycogen content, while CP levels mainly affected the activity of enzymes related to liver glucose and lipid metabolism: 14.5% CP increased AMPK and ACC activity, but decreased FAS, CS and G6PC activity. Both CP level and SFR altered muscle fatty acid composition, but the effect of SFR was usually more significant. An SFR of 11:1 was beneficial for improving the muscle fatty acid profile. Gene expression analysis further revealed that low protein compensatorily regulated liver energy metabolism, while excessive fat in low SFR diets led to lipid metabolism disorders. In conclusion, optimizing the energy structure of low-protein diets, especially by maintaining a medium SFR (11:1), could improve glucose and lipid metabolism in geese while increasing body weight. Full article