Search Results (5,732)

Rhododendron fortunei Lindl is known for its unique aroma, but the molecular mechanism behind plant hormone-mediated aroma biosynthesis remains unclear. To explore how brassinosteroids (BRs) and methyl jasmonate (MeJA) regulate its aroma, this study analyzed R. fortunei petal samples via physiological assays, volatile metabolome analysis, and transcriptome sequencing. Physiologically, BR/MeJA significantly increased the superoxide dismutase (SOD) and catalase (CAT) activity and decreased the malondialdehyde (MDA) content. Metabolome analysis identified 1268 volatile organic compounds (VOCs), with 265/70 VOCs up-/downregulated in the BR group and 248/181 VOCs up-/downregulated in the MeJA group compared to the controls. Transcriptome sequencing identified 19,333 differentially expressed genes (DEGs), which were enriched in pathways such as terpenoid and polyketide metabolism. Multi-omics screening revealed the candidate gene RfCYP92C6, whose transient overexpression in Nicotiana benthamiana increased the terpenoid content 2.2-fold. These findings clarify the aroma regulation mechanism of BRs/MeJA in R. fortunei and support the improvement of its aroma traits via genetic engineering. Full article

Brassica napus is a key oilseed crop with potential for cultivation in contaminated soils. However, the molecular mechanisms underlying chromium (Cr) toxicity and tolerance are not well-defined. This study aimed to elucidate these mechanisms by analyzing two contrasting cultivars, ZS758 and ZD622, under 50 μM Cr stress using a hydroponic experiment for physiological assessments, transcriptomics, and metabolomics. Cr exposure significantly increased tissue Cr content and severely inhibited plant growth, photosynthesis, and mineral nutrient uptake. Multi-omics analysis revealed extensive transcriptional and metabolic reprogramming. Specifically, we identified 15,882 and 13,371 differentially expressed genes (DEGs) and 256 and 136 differentially expressed metabolites (DEMs) identified in ZS758 and ZD622, respectively. These changes were primarily enriched in carbohydrate and amino acid metabolism pathways. The tolerant cultivar ZS758 exhibited more robust activation of defense-related pathways, including cell wall biosynthesis, hormone signaling, and transporter activity. Our integrative analysis reveals that Cr tolerance in rapeseed associated with cultivar-specific physiological and molecular adaptations. These insights provide potential targets and pathways for developing Cr-resistant varieties for sustainable agriculture in contaminated environments. Full article

Objective: CDK4/6 inhibitors constitute standard first-line therapy for hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). We investigated real-world predictors of overall survival (OS), with particular focus on high ER expression (≥90%). Methods: In this multicenter, retrospective study, we analyzed 603 HR-positive/HER2-negative MBC patients treated with CDK4/6 inhibitors (ribociclib or palbociclib) between May 2020 and June 2024. We evaluated demographic, clinical, and pathological factors for their impact on OS using univariate and multivariate Cox regression analyses. Results: In univariate analysis, significantly longer OS was observed in endocrine therapy-naive patients (median OS: 51.0 vs. 33.3 months; p < 0.001), those without liver metastases (50.0 vs. 34.0 months; p = 0.019), bone-only metastases (57.7 vs. 40.5 months; p = 0.022), and PR-positive patients (50.0 vs. 36.0 months; p = 0.037). Patients with ER expression ≥90% showed a strong trend toward longer OS (49.0 vs. 41.0 months; p = 0.072). In multivariate analysis, endocrine therapy naivety (p = 0.045) and high ER expression (≥90%) (p = 0.031) emerged as independent predictors of superior OS. Conclusions: Our study identifies treatment naivety and exceptionally high ER expression (≥90%) as key independent predictors of prolonged OS in CDK4/6 inhibitor-treated MBC patients. These findings underscore the importance of early CDK4/6 inhibitor implementation and suggest that quantitative ER assessment may refine patient selection beyond conventional positivity thresholds. Full article

The pine wood nematode (PWN) Bursaphelenchus xylophilus is a highly destructive forest quarantine pest and causal agent of pine wilt disease. The molecular response mechanism of Larix kaempferi (Japanese larch) to B. xylophilus infection remains unclear. This study aims to reveal the dynamic patterns of its defense response and screen key genes through time series transcriptomics. We found larch trees can proactively adjust their defense strategies to deal with the invasion of B. xylophilus. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, plant hormone signal transduction, MAPK signal pathway, and genes related to phenylpropane biosynthesis were more important. Through weighted gene coexpression network analysis (WGCNA), we identified two core modules that were rich in terpenoids, genes related to phenylpropane metabolism and cell wall strengthening, hormone signaling and defense regulation, and cytoskeleton and transport. Ultimately, we identified 20 core genes that were associated with several resistance-related processes, including the biosynthesis of resistance metabolites, post-translational regulation of protein homeostasis and defense signals, and transcriptional and translational reprogramming of gene expression. This study systematically depicted for the first time the continuous transcriptional regulatory network of L. kaempferi in response to pine wood nematodes. The key genes discovered provide important targets for subsequent functional verification and resistance breeding. Full article

Huanghuai sheep, a newly developed meat-specialized breed in China, are valued for their rapid growth and high meat quality, but the optimal slaughter age and the molecular basis of these traits remain poorly understood. Gaining insight into these mechanisms is vital for improving production efficiency and guiding molecular breeding in this economically important breed. Although previous studies have described the phenotypic characteristics of Huanghuai sheep, the genetic regulatory networks controlling muscle growth and meat quality at different developmental stages remain unclear. No thorough analysis of growth traits and transcriptomic variations across key age points has been conducted. Therefore, in this study, we aimed to evaluate how growth stage influences muscle development, carcass characteristics, and meat quality in Huanghuai sheep by integrating phenotypic characterization with transcriptomic profiling to identify key genes and molecular pathways underlying these economically important traits throughout development. Sixty Huanghuai sheep were assigned to three groups (twenty per group) representing key developmental stages (3, 9, and 18 months of age). Carcass traits and meat quality were evaluated. RNA sequencing of the longissimus dorsi muscle was performed to identify differentially expressed genes (DEGs), followed by bioinformatics analysis and experimental validation. The results indicated that the 9-month-old sheep presented a favorable balance of dressing percentage and intramuscular unsaturated fatty acid content, while those aged 18 months old exhibited the highest dressing percentage (61.23%). Transcriptome analysis identified 1395 DEGs (p < 0.05 and |log2FC| > 1) and enrichment analysis revealed key pathways involved in thyroid hormone synthesis, skeletal muscle satellite cell proliferation, and skeletal muscle tissue growth. Several candidate genes for muscle development (e.g., ACTC1, SIX2, HK2) and meat quality (e.g., TLR2, CHI3L1, ACOT7) were identified and validated. Their expression patterns showed significant correlations between critical growth performance and fatty acid composition metrics. These findings provide novel insights into the molecular networks regulating economically important traits in Huanghuai sheep, offering valuable targets for future molecular breeding programs aimed at enhancing productivity and meat quality. Full article

The AGC kinase family is crucial for regulating plant disease resistance, integrating hormone signals, managing reactive oxygen species (ROS) metabolism, and maintaining redox balance. However, research on AGC kinases in Solanaceae plants is limited, and the functions of most AGC kinases remain unidentified. Using the tetraploid potato (Solanum tuberosum L.) cultivar ‘Tingsha No. 9’, we conducted a genome-wide identification of the AGC gene family and profiled transcript responses to late-blight (Phytophthora infestans) stress. Additionally, we examined the subcellular localization and characterized the phenotypic responses of overexpression lines of the late-blight–responsive kinase StD6PK under late-blight stress. A total of 141 AGC family members were identified in ‘Qingshu No. 9’, categorized into eight subfamilies. This classification includes one cultivar-specific subfamily that was previously unrecognized, as well as 50 AGC family members within subfamily 1. AGC family members had significant differences in physicochemical characteristics and most of which were located in the nucleus. AGC family members are distributed on 46 chromosomes, with the largest number of chromosome 11 and the least number of chromosome 7. Gene duplication is dominated by whole-genome duplication (WGD) and segmental duplication. Ka/Ks values of all collinear pairs are less than 1. Purification selection drives family evolution in a long evolutionary process. Its promoter is rich in light-responsive, hormone-responsive, and stress-responsive elements, and its expression varies significantly in tissues; and some genes are highly expressed in specific organs. RNA-seq analysis revealed that 78.1% of the members responded to late-blight stress, and the expression levels of the selected eight subfamily members all showed significant increases or decreases after inoculation with late blight. StD6PK (Soltu.Q9.Chr04_A40011450.g) was strongly induced at 48~72 h, and its expression level at 72 h was 5.7 times higher than that at 0 h. Stable transformation of potato demonstrated that overexpression of StD6PK could enhance the resistance of potato to late blight, with subcellular localization revealing its nuclear localization characteristic. This study was the first time to complete the identification of AGC family genome of tetraploid potato ‘Qingshu No. 9’, reveal its evolution and expression characteristics, clarify the response characteristics of StD6PK to late blight, and provide insights into the evolutionary and functional basis of the AGC kinase gene family in potato late blight resistance mechanisms, while supplying genetic resources to accelerate the development of late blight-resistant germplasm. Full article

The AP2/ERF (APETALA2/ethylene-responsive factor) superfamily is one of the largest transcription factor families in plants and is not only vital for plant growth and development but also participates in responding to various abiotic stresses. However, few studies have investigated the function of the AP2/ERF gene family in natural rubber (NR) biosynthesis in Hevea brasiliensis. Here, 174 HbAP2/ERF genes were identified genome-wide and classified into 18 subclades based on gene-conserved structure and phylogenetic analysis. Gene duplication analysis revealed that 7 tandem and 100 segmental duplication events were major drivers of this gene family. Cis-element analysis in HbAP2/ERF promoters identified light-, hormone-, stress-, and development-associated cis-elements. Tissue-specific expression profiles revealed that 160 HbAP2/ERFs were expressed in at least one tissue. The protein–protein interaction network identified 59 potential interactions among the HbAP2/ERFs. Critically, dual-luciferase reporter assays confirmed that two key regulators exhibit distinct regulatory modes on NR biosynthesis-related genes: HbAP2/ERF25 significantly repressed the transcriptional activities of HbMVD1, HbCPT7, and HbSRPP1, whereas HbAP2/ERF46 repressed HbMVD1 but activated HbHMGR1, HbFPS1, and HbSRPP1. These findings reveal the complex regulatory network of HbAP2/ERFs in NR biosynthesis, establish a comprehensive framework for understanding their evolution and functional diversification, and provide novel molecular targets for genetic improvement of NR yield in rubber tree breeding and metabolic engineering. Full article

Objective: The Italian Drug Agency (AIFA) Determination n. 589 of 2015 (Note 79) establishes that the use of bisphosphonates or denosumab is necessary for the primary prevention of bone fractures in postmenopausal patients with early breast cancer (EBC) undergoing adjuvant endocrine therapy (ET). Since adherence to the 2015 AIFA recommendation was still very low in 2019, a new bone health management model was identified to improve adherence to this recommendation. Methods: The aim of this project (Predict & Prevent) was to increase the percentage of patients with early breast cancer (EBC) with hormone receptor-positive (HR+) tumors treated. The project identified a new bone health model of management including the following: training of breast multidisciplinary teams and bone health specialists; presentation and implementation of this model in cancer centers; evaluation, at baseline and 12 months after the implementation of the project, of two key performance indicators (KPIs): rate of HR+ EBC patients assessed for bone health within 30 days from the start of adjuvant ET (KPI-1) and rate of HR+ breast cancer patients receiving bisphosphonates or denosumab within 90 days from the start of adjuvant ET (KPI-2). The primary endpoints of this study were the assessment of the rates of the two key performance indicators (KPIs) 12 months after the start of the project (T3) in comparison with the rates recorded at time 0 (T0) in each participating cancer center and the bone fracture rates at 5 years. In this first analysis, we reported the rates of two KPIs 12 months after the start of the new model (T3) and the comparison with the rates recorded at time 0 (T0) in each participating cancer center, to assess whether these percentages had increased after the implementation of the new organizational model. The rates of bone fractures will be evaluated after five years from implementation of this project in every cancer center. Results: From 2020 to 2022, 10 Italian cancer centers were involved in this project. As of September 2023, 9 cancer centers reported rates relative to two KPIs assessed in each hospital. In 6 hospitals (Negrar, Brescia, Bergamo, Aviano, Turin, Rome), the rates relative to KPI-1 and to KPI-2 increased progressively from time T0 (at baseline) to time T3 (after 12 months from the start of the project), due to training of multidisciplinary teams and implementation of a new bone health management model. In the other three cancer centers (Ancona, Genoa, Naples), where the rate of evaluation of bone health (KPI-1) and the indication for bisphosphonates/denosumab (KPI-2) in HR+ EBC patients were already high at time T0, the rates remained high even after 12 months from the start of this project. Conclusions: After 12 months from the implementation of this new organizational model of bone health management, an increase in the rate of postmenopausal HR+ EBC patients on adjuvant ET assessed for bone health and the rate of patients treated with bisphosphonate/denosumab were reported in six out of nine cancer centers. In the other three cancer centers, where the rates were high at baseline, the rates also remained high after 12 months from the new model implementation. This new model should be adopted in all cancer centers to allow adequate management of bone health in all postmenopausal HR+ EBC patients undergoing adjuvant ET, with the ultimate goal of reducing the rate of bone fractures in these patients in subsequent years. Full article

Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract from Bombyx batryticatus (FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine. Full article

Objective: The purpose of the study was to conduct a systematic review assessing the impact of pharmacological and non-pharmacological interventions on Relative Energy Deficiency in Sport (REDs). The study design follows a systematic review and meta-analysis. The data sources are CINAHL, MEDLINE, SportDiscus, ERIC, and Embase from inception until July 2025. Eligibility criteria for selecting the studies include the experimental, quasi-experimental, and pre-experimental literature that investigated interventions designed to support the symptoms of REDs. Results: A total of nineteen studies (fifteen non-pharmacological interventions, four pharmacological interventions), with a total of 759 females, were included in the review. Non-pharmacological interventions demonstrated positive benefits on menstrual function recovery, energy availability, fat mass, and body fat percentage. Meta-analyses quantified nutrition intervention benefits on an individual’s fat mass (kg), 1.36 (95% CI 0.68, 2.04), and body percentage fat (%), 2.21 (95% CI 1.34, 3.08). It was also possible to identify the impact of non-pharmacological interventions on total triiodothyronine (T3) biomarkers (nmol/L), −2.37 (95% CI −5.57, 0.83). It should be noted, however, that non-pharmacological interventions were limited by quality and certainty assessment, identifying included evidence as low to moderate. Pharmacological interventions demonstrated some positive (at times very strong effect sizes) results for impact on bone mineral density, but conclusions are currently limited by well-powered experimental studies. Conclusions: The current evidence base favors non-pharmacological management as an initial response for managing REDs. Initial pharmacological management appears to identify limited but potentially (depending on the drug) promising evidence for the impact on bone mineral density; further evidence is required to be more certain about the impact on hormonal profiling and menstrual recovery function. Further research is needed to help develop a greater understanding. Full article

Yeast culture (YC) is a microbial product that enhances ruminal fiber breakdown and improves nutrient digestion and utilization. Our previous research showed that oxalic acid (OA) is a crucial metabolite in YC that enhances rumen function. This study aimed to investigate the effects of YC, OA, and their combination (YO) on rumen function, growth, and fattening in sheep. Twenty lambs were divided into 4 groups (ctrl, YC, OA, and YO; n = 5 each) and fed a diet supplemented with 2 levels of YC and 2 doses of OA for 60 days in a 2 × 2 factorial design. Growth and fattening performance, rumen microbiome analysis, serum indices and anti-oxidant levels, and metabolomic profiling were performed. Individual supplementation with YC and OA significantly increased the digestibility of dry matter (DM), organic matter (OM), and crude protein (CP) (p < 0.001); neutral detergent fiber (NDF) (p < 0.05); and acid detergent fiber (ADF) (p < 0.001) and their interaction significantly increased dry matter intake (DMI) (p = 0.05). Serum IgA and IgM levels were higher in the supplemented groups (p < 0.05). Serum calcium levels were higher in the OA and YO groups (p < 0.001). The supplemented groups showed significantly higher growth hormone and superoxide dismutase levels (p < 0.05). The longissimus dorsi muscle had higher levels of iron in the OA and YO groups; zinc in the OA, YO, and YC groups (p < 0.01); and selenium in the YC group (p < 0.05). The OA group had a higher total antioxidant capacity. All supplemented groups showed higher bacterial richness and diversity. Ruminococcus, Succinivibrio, and Fibrobacter were positively correlated with the fermentation and digestibility parameters. The supplementation also altered metabolite levels and types in key physiological pathways. In conclusion, this supplementation improved bacterial composition, nutrient digestibility, weight gain, carcass weight and quality, serum indices, antioxidant levels and metabolomic profiles. This suggests potential for the development of dietary supplements for ruminants. Full article

Soil salinization severely constrains agricultural productivity and ecosystem sustainability. Suaeda salsa L. is a representative halophyte and demonstrates strong adaptability and potential for saline–alkali land restoration. To elucidate its physiological responses to salt stress, pot experiments were conducted under four salinity levels, namely CK (0 mM NaCl), LS (800 mM NaCl), MS (1600 mM NaCl), and HS (2400 mM NaCl), with 20 replicates per treatment, and the dynamics of endogenous hormone were analyzed using targeted metabolomics. The soil salinity levels were prepared by adding NaCl solutions of different molarities to achieve the desired salinity treatments. Results showed that low to moderate salinity (CK-LS: 0–800 mM) promoted growth performance, whereas higher salinity (HS: 2400 mM) significantly inhibited biomass accumulation, plant height, and stem diameter (p < 0.01). Salinity markedly affected nutrient accumulation in Suaeda salsa, with Na increasing up to 222%, K decreasing by 17–33%, Ca by 7–21%, Mg by 35–46%, and S by 45–56% across growth stages, while Fe remained unchanged. Under increasing salinity, stress-related hormones such as abscisic acid, jasmonic acid, salicylic acid, and indole derivatives were upregulated, while gibberellins decreased markedly. Zeatin and its derivatives showed significant increases under MS (p < 0.01). Correlation analysis indicated positive associations of abscisic acid and zeatin with growth traits, and negative correlations for gibberellins (R > 0.6). These findings suggest that Suaeda salsa adapts to saline conditions by modulating hormone-mediated ion balance, osmotic regulation, and defense metabolism, thereby optimizing growth and biomass allocation under salt stress. Full article

Background: Family planning is essential for improving maternal and child health. However, misconceptions and cultural beliefs remain significant barriers to contraceptive use in many conservative societies. Purpose: This study aimed to assess the prevalence of contraceptive misconceptions and examine their impact on contraceptive use among married women in Al-Ahsa, Saudi Arabia. Methods: A cross-sectional study was conducted from January to April 2023, enrolling 379 married women aged 18–49 years from primary healthcare centers in Al-Ahsa. A structured, validated questionnaire was used to collect data on sociodemographic characteristics, contraceptive practices, and the prevalence of common misconceptions. Statistical tests were performed for data analysis using SPSS version 26. Results: Misconceptions were highly prevalent, with 94.7% believing contraceptives affect mood, 92.3% linking them to hormonal disorders, and 63.3% to impaired future pregnancies. Conclusions: The findings indicate that widespread misconceptions about contraceptives persist among married women in Al-Ahsa. These beliefs significantly limit the optimal use of family planning methods, despite relatively high educational attainment in the population. The study highlights an urgent need for targeted, culturally sensitive interventions to correct misinformation and improve women’s reproductive health outcomes. Full article

Auxin response factors (ARFs) are crucial components of auxin signaling, playing a vital role in plant growth, development, hormone regulation, and stress responses. Salinity influences plant growth and development; however, Avicennia marina exhibits remarkable salt tolerance. This study analyzed Avicennia marina ARF genes (AmARFs) and their roles in responding to salt and indole-3-acetic acid (IAA) stress. The results indicated that across 5–15 days, endogenous IAA and abscisic acid (ABA) levels in A. marina leaves showed significant, time-dependent changes under salt and IAA treatments, with IAA fluctuating around 2.0–3.3 µg g⁻¹ FW and ABA rising sharply under combined high-salt + IAA conditions (AS25), reaching up to ~25 µg g⁻¹ FW (p < 0.05). This is the first genome-wide identification of 41 ARF genes in Avicennia marina with expression responses to combined salt and auxin treatments. We identified 41 AmARF genes spread across 23 chromosomes. These genes are divided into four groups according to their phylogenetic relationships. Their coding regions encode amino acids from 361 to 1264, and the number of exons varies from 2 to an unspecified upper limit of 25. Examining these gene promoters revealed various hormone- and stress-response elements, with each gene containing distinct response elements. Sixteen miRNAs can inhibit various ARF genes, while protein–protein interactions and 3D structures offered valuable insights into AmARF proteins. GO enrichment analysis revealed that all 41 AmARFs are involved in the auxin-activated signaling pathway and are also involved in cell division. According to the expression experiments, 11 randomly selected genes showed predominantly upregulation in response to salt and IAA stressors compared with controls. These findings extend our understanding of the functional roles of AmARFs in stress responses. The systematic annotation of AmARF family genes offers candidate genes for future functional validation, which may help elucidate the precise roles of AmARFs in stress responses. Full article

Sodium butyrate (NaBu), a common feed additive, has been shown to enhance reproductive performance in livestock and poultry. However, whether NaBu exerts this effect by directly regulating follicular development remains unclear. In this study, a three-dimensional (3D) in vitro culture system of mouse preantral follicles was used to investigate the effects of NaBu on follicular growth, hormone secretion, maturation of oocytes, and subsequent embryonic development. Preantral follicles were treated with different doses of NaBu on the fourth day of culture. Subsequently, the mature oocytes (MII stage) were released from the follicles on the ninth day and subjected to parthenogenetic activation for developmental assessment. The results showed that 0.10 mM NaBu treatment could significantly promote follicular growth, antral formation, and oocyte maturation. Furthermore, NaBu also significantly increased estradiol (E₂) secretion, improved follicular structure, and maintained cellular viability. qPCR analysis revealed that NaBu significantly increased the mRNA levels of STAR, CYP11A1, and CYP1B1. In addition, it significantly enhanced the distribution and organization of F-actin, with increases in the mRNA levels of GDF9, BMP15, and CX37. NaBu treatment significantly reduced intracellular ROS levels and increased the mRNA levels of NRF2 and SOD1, while SOD2 and GSR showed increasing trends without significant differences. NaBu significantly improved oocyte cytoskeletal organization and the morphology of the spindle, but it did not lead to a significant increase in the rates of cleavage and blastocyst formation after parthenogenetic activation. Collectively, these findings indicate that NaBu promotes follicular development and improves oocyte quality, at least partly, by enhancing steroidogenesis, alleviating oxidative stress, and maintaining cytoskeletal integrity, providing insight into its potential application for improving reproductive performance in livestock and poultry. Full article