Search Results (9,482)

In this study, we investigated the long-term evolutionary dynamics of human norovirus GII.17[P17] using the RNA-dependent RNA polymerase (RdRp) region and the VP1 capsid gene, integrating phylogenetics, time-scaled inference, phylodynamics, and structure-based analyses. Maximum-likelihood phylogenies of both genomic regions consistently resolved four major clades (Clades 1–4). VP1 patristic-distance distributions indicated higher within-clade diversity in the phylogenetically basal Clades 1 and 3, whereas Clades 2 and 4 showed lower diversity, consistent with recent demographic expansion. Similarity-plot analysis identified pronounced variability in the VP1 P2 domain, while the S and P1 domains remained comparatively conserved, supporting P2 as the primary hotspot of diversification. Bayesian time-scaled analyses estimated the most recent common ancestor around 1993 (VP1) and 2000 (RdRp) and revealed two major lineages (Clade 1/2 and Clade 3/4), with the split between Clades 3 and 4 occurring around 2016–2017. Bayesian skyline plots showed a marked increase in effective population size after 2013, and substitution-rate estimates indicated faster evolution in VP1 than in RdRp, with higher VP1 rates in the Clade 3/4 lineage than in Clade 1/2. Capsid dimer modeling further mapped high-confidence conformational B-cell epitopes and positively selected residues predominantly to the distal surface of P2, with broadly conserved spatial patterns across clades. Compared with the Clade 1 reference (Kawasaki323), Clade 2 accumulated numerous P2 substitutions, whereas Clades 3 and 4 retained fewer changes and remained closer to Clade 1 at the amino-acid level. Together, these results suggest lineage turnover within GII.17[P17] driven by constrained diversification at the P2 surface, potentially contributing to the recent predominance of the Clade 3/4 lineage. Full article

Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical challenge, driven in part by resistance–nodulation–division (RND) efflux pumps that reduce intracellular antibiotic concentrations and limit the efficacy of many antibacterial agents, including fluoroquinolones. The aim of this study was to identify and characterize TXA11114 as a small-molecule efflux pump inhibitor (EPI) capable of restoring the activity of the fluoroquinolone levofloxacin against MDR P. aeruginosa. Methods: The antibacterial activity of the TXA11114–levofloxacin combination was evaluated using minimum inhibitory concentration (MIC) assays against panels of clinical isolates. Mechanistic studies included levofloxacin accumulation assays, ethidium bromide accumulation assays, outer-membrane permeability measurements, and whole-genome sequencing of mutants with altered potentiation phenotypes. In vivo efficacy was evaluated in murine thigh and lung infection models, while preliminary safety and drug-like properties were assessed using cytotoxicity assays and in vitro ADME profiling. Results: The TXA11114–levofloxacin combination produced > 1 log₁₀ CFU reductions in bacterial burden in murine thigh and lung infection models, exceeding the activity of levofloxacin monotherapy. TXA11114 markedly potentiated levofloxacin activity, producing substantial reductions in levofloxacin MIC values across multiple MDR clinical isolates, and also enhanced the activity of several additional efflux pump substrates, including β-lactams, tetracyclines, chloramphenicol, and trimethoprim–sulfamethoxazole. Mechanistic experiments demonstrated increased intracellular accumulation of efflux substrates without evidence of nonspecific membrane disruption, and mutations in ompH were associated with altered potentiation phenotypes. Conclusions: The TXA11114–levofloxacin combination produced significantly greater bacterial reductions than levofloxacin monotherapy in murine infection models. Levofloxacin was selected because fluoroquinolone resistance in P. aeruginosa is frequently driven by efflux-mediated mechanisms. While this study focused on levofloxacin potentiation, future work will evaluate additional efflux pump substrates and further define the molecular target of TXA11114. Full article

The limited and inconsistent efficacy of existing therapies for tuberous sclerosis complex (TSC) has driven the exploration of novel strategies, including epigenetic regulation. GSK-J4, an inducer of global H3K27me3 accumulation, shows broad anti-tumor activity. However, its therapeutic potential in TSC remains unclear. In the study, we reported that GSK-J4 inhibited cell cycle progression and induced apoptosis in primary Tsc1^+/− and Tsc2^+/− MEFs. Mechanistically, Tsc1 or Tsc2 deletion reduced global H3K27me3, correlating with increased viability, accelerated cell cycle, and suppressed apoptosis-phenotypes reversed by GSK-J4. Moreover, GSK-J4 triggered endoplasmic reticulum stress (ERS) by activating the PERK-ATF4-CHOP axis, which concurrently downregulated the proto-oncogene c-Myc, outlining a GSK-J4→p-PERK→c-Myc inhibitory pathway. Notably, GSK-J4 synergized with rapamycin to enhance cell cycle arrest and apoptosis. In vivo, this combination alleviated renal impairment in Tsc1- or Tsc2-deficient models, suggesting a promising therapeutic strategy for TSC patients with suboptimal response to mammalian target of rapamycin complex 1 (mTORC1) inhibitors. Our study elucidates a specific ERS-dependent anti-tumor mechanism of GSK-J4 in Tsc-deficient contexts and demonstrates the synergistic efficacy of combining epigenetic and mTORC1 inhibitors. Full article

Arsenic (As) is a ubiquitous and highly toxic metalloid with well-established carcinogenicity. Its accumulation and secondary release from lake sediments pose potential risks to lake ecosystem integrity and human health. Meanwhile, the ongoing intensification of lake eutrophication at the global scale has altered the sources, composition, and environmental behavior of internally derived dissolved organic matter (DOM). These changes have profoundly influenced As mobilization and transformation at the sediment-water interface (SWI). To advance understanding of the regulatory roles and underlying mechanisms of algal dissolved organic matter (ADOM) and submerged macrophyte dissolved organic matter (SMDOM) in As biogeochemical cycling under lake ecosystem regime shifts, extensive findings from the international literature were synthesized. The characteristic properties and environmental behaviors of ADOM and SMDOM were systematically compared, and their distinct regulatory pathways in lacustrine systems were further summarized. Results indicate that ADOM is typically characterized by low molecular weight, weak aromaticity, and high bioavailability. It can enhance As dissolution and mobilization from sediments through direct complexation, competition for adsorption sites, and stimulation of microbial metabolism and Fe(III) reduction. In contrast, SMDOM exhibits higher molecular weight, greater aromaticity, and a higher degree of humification. It tends to form stable complexes with mineral phases. Under the influence of radial oxygen loss (ROL) from submerged macrophyte roots during the growth phase, its capacity to promote mineral reduction is relatively limited. This process favors stable As retention in sediments. The regulatory effects of ADOM and SMDOM on As behavior are strongly modulated by environmental factors such as pH, redox potential (Eh), temperature, and light conditions, as well as by microbial communities. ADOM is more sensitive to reducing environments and photochemical processes. SMDOM, in contrast, exerts more persistent control under oxidizing conditions and at mineral-water interfaces. In addition, ADOM more readily drives microbial community shifts toward assemblages with enhanced capacities for Fe(III) reduction and As reduction or methylation. SMDOM is less likely to trigger strongly reducing processes. Based on these mechanisms, the outbreak and decay phases in algal-dominated lakes often correspond to critical periods of enhanced As mobilization and elevated ecological risk. In submerged macrophyte-dominated lakes, the decay phase may represent an important window for sedimentary As release. Finally, a conceptual framework describing the differential regulation of As biogeochemical cycling by ADOM and SMDOM is proposed. This framework provides a theoretical basis for As risk identification, the determination of critical risk periods, and the development of management strategies across lakes with different trophic states. Full article

Excessive accumulation of copper ions (Cu²⁺) in the environment and biological systems poses severe risks to ecological balance and human health, necessitating accurate detection and monitoring of Cu²⁺. Schiff base derivatives with favorable optical properties provide an efficient strategy for copper ion recognition. In this paper, fluorescent probe L (5-methyl-2-hydroxybenzaldehyde-(7-diethylaminocoumarin-3-formyl) hydrazone) was synthesized through a three-step reaction using 4-diethylaminosalicylaldehyde and diethyl malonate as starting materials. The structure of probe L was confirmed by melting point analysis, infrared spectroscopy, and nuclear magnetic resonance. Single-crystal X-ray analysis revealed that probe L crystallized into a triclinic lattice with space group $P_1^{-}$. Optical investigations, including UV–Vis spectroscopy, fluorescence spectroscopy, and aggregation-induced emission studies, demonstrated highly sensitive and selective fluorescence “turn-off” behavior of probe L towards Cu²⁺ ions in DMSO, with negligible interference from other metal ions. Job’s plot and crystallographic analysis revealed a 1:1 binding stoichiometry between probe L and Cu²⁺, forming the complex [Cu(L)]. Fluorescence titration experiments revealed a binding constant (K_b) of 5.2 × 10⁶ L/mol and a detection limit of 7.8 × 10⁻⁷ mol/L, indicating excellent sensitivity. These results suggest that probe L has considerable promise for Cu²⁺ detection in aqueous environments, with potential applications in environmental monitoring and public health protection. Full article

Background: Piperine, an alkaloid from Piper nigrum, modulates oxidative stress, proliferation, and survival pathways in several cancer models; however, its mechanistic effects in colorectal epithelial Caco-2 cells remain insufficiently defined. Objective: This study aimed to investigate the cytotoxic, antiproliferative, oxidative, autophagic, and anti-migratory effects of piperine in Caco-2 cells. Methods: Caco-2 cells were treated with piperine (0.001–0.1 mg/mL) for up to 72 h. Cell viability, proliferation, and migration were assessed using SRB and scratch assays. Oxidative stress, apoptosis, autophagy, and tight junction integrity were evaluated through ROS quantification, Western blotting, gene expression analysis, confocal microscopy, and transmission electron microscopy (TEM). NACET was used to determine the contribution of oxidative stress to piperine-induced cytotoxicity and autophagy. Results: Piperine induced a time- and dose-dependent reduction in viability, with viability decreasing to 53.0 ± 2.88% at 0.1 mg/mL after 72 h. Proliferation decreased to 51% of control levels (p < 0.001), accompanied by p21 upregulation (p < 0.05), indicating G2/M cell cycle arrest. Piperine markedly increased intracellular ROS (p < 0.001), downregulated NRF2 (p < 0.05), and suppressed GSTA1 expression (p < 0.001), while NACET co-treatment restored viability (p < 0.001). No activation of caspase-dependent apoptosis was observed. Piperine significantly enhanced autophagic flux, as shown by the increased LC3B-II/LC3B-I ratio (p < 0.01), elevated LC3B-II/LAMP-1 co-localization (p < 0.01), and chloroquine-induced accumulation of LC3B-II and p62 (p < 0.01), with preserved lysosomal function. TEM analysis confirmed a marked increase in double-membrane autophagosomes in piperine-treated cells compared with controls. NACET reduced LC3B-II/LC3B-I levels, increased p21 expression, and significantly improved cell viability, indicating that piperine-induced autophagy is cytotoxic and driven by oxidative stress. Additionally, piperine upregulated occludin (p < 0.01) and reduced cell migration independently of proliferation (p < 0.01). Conclusions: Piperine exerts antiproliferative effects in Caco-2 cells through ROS-mediated stress, p21-dependent G2/M arrest, and activation of cytotoxic autophagy. Its ability to impair migration and enhance tight junction integrity further supports its potential as a complementary therapeutic agent in colon cancer. Full article

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even when these asparagus plants are replaced with new ones, the new plants remain unproductive (asparagus replant problem). The main causes of these problems are a Fusarium infection and asparagus autotoxicity. Several reviews have been conducted on Fusarium. Despite the accumulation of evidence on asparagus autotoxicity in the literature over the past four decades, no review has focused specifically on asparagus autotoxicity. It has been reported that asparagus growth is inhibited by asparagus root residues, leachates, root exudates, and rhizosphere soils. Several phenylpropanoids, including trans-cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, have been identified as asparagus autotoxic substances in these root residues, root exudates, rhizosphere soils, growth media, and/or plant tissues. Tryptophan, 3,4-methylenedioxycinnamic acid, and iso-agatharesinol were also identified as asparagus autotoxic substances. These substances may cause autotoxicity by disrupting phytohormone levels, cellular metabolism, impairing membrane function, and by inducing oxidative stress. Although cinnamic, p-coumaric, caffeic, and ferulic acids have been reported to act as antibiotics, these compounds have also been shown to weaken the defense mechanisms of asparagus against pathogen infection, and enhance the Fusarium pathogenicity. The presence of these autotoxic substances, coupled with a Fusarium infection, may create a vicious cycle that worsens “asparagus decline” and “asparagus replant problem”. This is the first review to focus on the asparagus autotoxicity. Full article

Endometriosis affects approximately 10% of reproductive-age women and is associated with genomic instability; however, the contribution of specific DNA repair deficiencies remains poorly understood. This study investigated the expression and function of GEN1, a Holliday junction resolvase critical for homologous recombination, in patient-derived endometrial epithelial organoids (EEOs). Endometrial tissue was obtained by pipelle biopsy from women with laparoscopically confirmed endometriosis (n = 3, stage III–IV) and controls without endometriosis (n = 3). GEN1 mRNA and protein expression were reduced in primary endometrial cells from endometriosis patients compared with controls (mRNA: 0.52 ± 0.14 vs. 1.00 ± 0.19, p = 0.05; immunofluorescence intensity: 0.54 ± 0.18 vs. 1.00 ± 0.22, p = 0.05). Patient-derived EEOs from the endometriosis group showed trends toward lower formation efficiency (18.4 ± 5.6% vs. 25.2 ± 6.8%, p = 0.10) and reduced mean diameter (124.6 ± 34.2 vs. 155.8 ± 32.6 µm, p = 0.10). RNA interference (RNAi)-mediated GEN1 knockdown reduced proliferation in both groups, with a more pronounced effect in endometriosis-derived EEOs (49.7% vs. 39.5% reduction, p = 0.05). Endometriosis-derived EEOs exhibited elevated baseline γH2AX (phosphorylated histone H2AX) immunofluorescence compared with controls (2.32 ± 0.44 vs. 1.00 ± 0.28, p = 0.05), indicating increased DNA double-strand break accumulation. Furthermore, GEN1 knockdown directly increased γH2AX intensity in both groups, with endometriosis-derived EEOs showing a greater absolute increase (Δ1.26 vs. Δ0.72). To our knowledge, this study provides the first organoid-based evidence that GEN1 is downregulated in endometriosis and functionally linked to impaired proliferation and elevated DNA damage, suggesting a potential contribution of homologous recombination dysregulation to endometriosis pathogenesis. Full article

Background: The power profile is a reliable tool for monitoring performance in the cycling segment of triathlon. This study aimed to analyze the evolution of Mean Maximal Power (MMP) in international triathletes and to examine its relationship with external load-based training characteristics. Methods: Cycling training and competition data from 14 junior and U23 international triathletes (seven males: 21 ± 1 years, 69 ± 3 kg, and 181 ± 7 cm; seven females: 22 ± 3 years, 54 ± 5 kg, and 166 ± 3 cm) were analyzed longitudinally for three consecutive seasons. The MMP from the power profile was recorded, along with the training volume accumulated in each 2.0 W·kg⁻¹ power band. Results: All the MMP values, except values of 10 s, 30 s and 5 min, increased (p < 0.05) over the three seasons (Δ = 0.9% to 4.8%; ES = 0.30–0.47), as did the total time (Δ = 22.1%; ES = 0.42) and total distance (Δ = 32.8%; ES = 0.61). Specifically, the percentage of time spent in the 4–6 W·kg⁻¹ power band (ES = 0.42) and MMP values for1- 20 min durations (ES = 0.25–0.47) increased (p < 0.05) from the second to the third season. MMP values ≤ 30 s showed a very large correlation (above r = 0.74) with the percentage of time spent in power bands of 12–14 W·kg⁻¹. All the MMP values showed a negative correlation with the percentage of time spent in the 0–2 W·kg⁻¹ power band. Conclusions: Improvements in MMP ≥ 1 min values over consecutive seasons were associated with greater total training volume and time spent in moderate-intensity power bands, whereas MMP ≤ 30 s were linked to very high-intensity power outputs. Full article

Saline-alkali stress restricts crop yield by disrupting nutrient and water uptake, ionic balance, and oxidative homeostasis. Although myo-inositol enhances tolerance to abiotic stress, its role in sugar beet (Beta vulgaris L.) under saline-alkali conditions remains unclear. To investigate the effects of exogenous myo-inositol on sugar beet growth under saline-alkali soils, a pot experiment was conducted using six myo-inositol concentrations (0, 0.2, 0.4, 0.6, 0.8, and 1.0 g L⁻¹). Myo-inositol significantly influenced plant performance in a concentration-dependent manner. The 0.6 g L⁻¹ treatment produced the highest shoot and root fresh and dry weights, nearly doubling shoot biomass compared with the control. Shoot N and P contents increased markedly at 0.6 g L⁻¹, while their concentrations remained relatively stable, indicating biomass-driven nutrient accumulation. Myo-inositol reduced Na accumulation while maintaining stable K, Ca, and Mg concentrations, thereby improving ionic balance. Antioxidant capacity was enhanced, with superoxide dismutase and catalase activities significantly elevated. Root total length and surface area increased substantially, whereas specific root length and surface area decreased, suggesting improved root morphological development. Soil alkaline phosphatase activity was also stimulated at higher myo-inositol treatments. Overall, moderate myo-inositol application (with regression analysis indicating an optimum of approximately 0.56 g L⁻¹) improved sugar beet growth through enhanced nutrient acquisition, ionic balance, antioxidant capacity, and root development, offering practical insights for its use as a growth regulator in saline-alkali crop production. Full article

Background/Objectives: Staphylococcus epidermidis (RP62A) and Staphylococcus aureus (UAMS-1) are clinically relevant pathogens frequently implicated in implant-associated infections due to their ability to form biofilms. RP62A is typically linked to persistent, chronic, low-grade infections, whereas UAMS-1 is associated with acute, invasive disease. Both strains serve as representative models for chronic and acute periprosthetic joint infections (PJIs). The objective of this study was to examine and compare in vitro biofilm formation by RP62A and UAMS-1 on orthopaedic materials/disc surfaces of defined composition. Methods: In vitro biofilm formation assays were performed using orthopaedic disc surfaces composed of cobalt–chromium alloy (CoCr), titanium alloy (Ti), and polyethylene (PE) after 72 h of incubation. Biofilm biomass was quantified using crystal violet staining, with absorbance measured at OD₅₇₀. A polystyrene (PS) surface served as a control. Additionally, retrieved orthopaedic explant components were used as substrates for in vitro biofilm assays, in which RP62A was incubated for 72 h on the explanted surfaces. Supporting assays on glass slides were conducted to examine strain-specific biofilm-related architecture. Results: In vitro biofilm mass quantification assays showed strong biofilm formation by RP62A across all tested surfaces, with the highest absorbance on CoCr (OD₅₇₀ = 5.80 ± 0.19). Notably, biofilm formation on CoCr was 76% higher compared to PS (p < 0.0001). No significant differences were observed among all three surface discs (p > 0.1). Biofilm formation was highest on PE for UAMS-1 (OD₅₇₀ = 1.29 ± 0.09) and was significantly greater than on Ti (178%, p < 0.001) and CoCr (196%, p < 0.0001). In the in vitro assays performed on retrieved explant components, RP62A showed pronounced biofilm accumulation on polyethylene tibial inserts, particularly in regions of mechanical wear and friction. Supporting assays on glass slides were performed to examine strain-specific surface microstructural, revealing dense network-like structures for RP62A and thinner, discontinuous layers for UAMS-1. Conclusions: RP62A formed dense biofilms in vitro on multiple orthopaedic implant materials and retrieved explant components, consistent with its association with chronic periprosthetic joint infections. Increased biofilm accumulation was observed on mechanically worn polyethylene surfaces. In contrast, UAMS-1 showed lower biofilm formation on metallic disc surfaces, indicating strain- and material-dependent differences. These findings highlight the relevance of implant material selection and surface integrity for strategies targeting biofilm-associated implant infections. Full article

Cells rely heavily on DNA repair networks to survive genomic damage. For repairing double-strand breaks, Non-Homologous End Joining (NHEJ) remains the primary pathway, which is largely controlled by the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Researchers have long studied how phosphorylation drives this kinase. However, recent data point to an important additional layer of control. Drawing on evidence accumulated over the past two decades, we propose a “Spatiotemporal Logic Circuit” model for DNA-PKcs regulation. In this model, SUMO-associated interactions may help stabilize synaptic assembly, HUWE1-mediated neddylation may facilitate kinase activation at Lys4007, and K48-linked ubiquitination—potentially involving RNF144A—may contribute to the turnover of persistent repair complexes. Importantly, we frame these UBL-mediated events within the broader autophosphorylation-driven conformational cycle of DNA-PKcs, which remains central to NHEJ progression. Additionally, we highlight the structural interface where activation and degradation signals may converge and the extraction barrier posed by the massive DNA-PKcs scaffold. From a translational perspective, we argue that the exceptional size of DNA-PKcs (~470 kDa) and its topological entrapment on DNA render it an unusually challenging PROTAC target—one that may require p97/VCP-assisted extraction before proteolysis can proceed. We also highlight the underappreciated risk that E3 ligase loss-of-function, already documented in BET-PROTAC resistance, may similarly undermine DNA-PKcs degrader strategies. Full article

To investigate the spatiotemporal variations in particulate matter (PM) retention by common urban greening species, six tree species were studied across different functional zones in Urumqi, China, which includes traffic area (TA), residential area (RA), park area (PA), and landscape ecological forest (LA) at varying altitudes. We measured the retention of PM_0.2–3, PM_3–10, PM_>10, and PM_total for Pinus sylvestris, Picea asperata, Ulmus pumila, Ligustrum obtusifolium, Ulmus densa, and Fraxinus rhynchophylla. Results showed significant differences (p < 0.05) among functional zones, with retention capacity following the order that evergreen trees > deciduous shrubs > deciduous trees. Specifically, P. sylvestris and Picea asperata exhibited the highest overall PM retention. Temporally, PM accumulation increased over time, reaching a minimum 3 days after heavy rainfall (>20.4 mm) and a maximum after 23 days. Spatially, retention was highest in the TA and lowest in the PA. On Yamalike Mountain, PM_3–10 and PM_>10 retention by Ulmus pumila increased significantly with altitude, while other fractions showed no clear trend. These findings suggest that the spatiotemporal differences in PM retention are distinct, and the strategic selection and management of species in specific urban environments can significantly enhance the regulation of atmospheric particulate pollution. Full article

Severe browning often occurs in Multivitamin Iron Oral Solution during storage, which directly leads to the decline of product quality. To clarify the main mechanism of browning in this preparation, the contents of 5-hydroxymethylfurfural (5-HMF) and carbohydrates, as well as the relevant characteristic parameters such as color and fluorescence, were determined at different storage times in this study. Subsequently, four reaction models, namely sucrose-lysine, sucrose-citric acid, sucrose-niacin, and sucrose-folic acid, were constructed according to the formulation of the preparation to systematically investigate the effects of each system on browning. The results showed that the sucrose-lysine model was the main color-forming reaction system of the preparation. Citric acid could significantly promote the hydrolysis of sucrose to produce two reducing sugars, glucose and fructose, which not only provided sufficient substrates for the Maillard reaction (MR), but also led to the massive accumulation of 5-HMF. Further analysis revealed that heating temperature and heating time were significantly positively correlated with the contents of 5-HMF, browning index (BI), color density (CD), and reducing sugars in the solution, while significantly negatively correlated with sucrose content (p < 0.05). Two fractions, P1 and P2, were isolated by Sephadex LH-20 column chromatography. Among them, P1 with a molecular weight of 61,660 Da was identified as the key fluorescent color-forming component, whose ultraviolet and fluorescence characteristics were basically consistent with those of Multivitamin Iron Oral Solution. Ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) analysis confirmed that P1 contained characteristic fragments of conjugated unsaturated structure, which was the key chromophore responsible for its fluorescence properties. In summary, this study explored the main browning mechanism of Multivitamin Iron Oral Solution. It was found that after citric acid catalyzed the hydrolysis of sucrose, the generated reducing sugars underwent Maillard reaction with lysine to produce fluorescent color-forming substances, and heat treatment significantly aggravated the browning process. The results of this study not only provide a solid theoretical basis for optimizing the preparation process and improving the storage stability of Multivitamin Iron Oral Solution, but also offer an important reference for the research on the browning mechanism and stability of other sugar-containing liquid preparations. Full article

Clubroot caused by Plasmodiophora brassicae is a devastating soil-borne disease of oilseed rape, and physiological race differentiation of the pathogen greatly hinders disease control. The differential regulatory mechanisms of different P. brassicae races on the rhizosphere microecology remain unclear. This study aimed to reveal the race-specific effects of P. brassicae on the rhizosphere microenvironment, microbial community and nitrogen cycling of oilseed rape. A pot inoculation experiment was conducted with two typical races from Sichuan Province (race 4 CZ and race 2 KD), combined with soil physicochemical determination, high-throughput sequencing and functional prediction. The results showed that CZ exhibited a higher infection rate but a lower disease index than KD. Both races significantly decreased soil pH and reshaped soil nutrient profiles. Notably, CZ treatment caused a more pronounced pH decrease and was characterized by NH₄⁺-N accumulation, whereas KD treatment was dominated by NO₃⁻-N enrichment. Bacterial alpha diversity was increased by both races, following the order KD > CZ > CK. In contrast, fungal alpha diversity was decreased by both races, showing the pattern CK > KD > CZ. Distinct rhizosphere microbial community structures were formed under different race infections, and both races reduced the abundance of nitrogen-fixing bacteria and related functional genes. These findings indicate that distinct P. brassicae races shape race-specific rhizosphere microenvironments by differentially regulating soil acidification, nutrient availability and nitrogen-cycling functional microorganisms, thereby driving divergent pathogenic outcomes. This study is the first to reveal differential regulation of the rhizosphere microecology by distinct physiological races of P. brassicae, offering new insights for region-specific management of clubroot disease. Full article