Naringenin Alleviates Radiation-Induced Intestinal Injury by Inhibiting TRPV6 in Mice.

SCOPE: Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. CONCLUSION: NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.

Exploring anterion capsular contraction syndrome in cataract surgery: insights into pathogenesis, clinical course, influencing factors, and intervention approaches.

Anterior capsular contraction syndrome (ACCS) is a challenging complication that can occur following phacoemulsification cataract surgery. Characterized by capsular bag wrinkling, intraocular lens (IOL) decentration and tilt, ACCS can have negative effects on visual outcomes and patient satisfaction. This review aims to investigate the pathogenesis, clinical course, influencing factors, and intervention approaches for ACCS after cataract surgery. By understanding the underlying mechanisms and identifying factors that contribute to ACCS, surgeons can enhance their ability to predict and manage this complication. Various intervention strategies are discussed, highlighting their importance in reducing complications and improving surgical outcomes. However, further research is needed to determine optimal prevention and management strategies through long-term follow-up and comparative analyses. Advancements in this field will ultimately lead to improved visual outcomes and optimized cataract surgery for patients.

An alfalfa MYB-like transcriptional factor MsMYBH positively regulates alfalfa seedling drought resistance and undergoes MsWAV3-mediated degradation.

Drought is a major threat to alfalfa (Medicago sativa L.) production. The discovery of important alfalfa genes regulating drought response will facilitate breeding for drought-resistant alfalfa cultivars. Here, we report a genome-wide association study of drought resistance in alfalfa. We identified and functionally characterized an MYB-like transcription factor gene (MsMYBH), which increases the drought resistance in alfalfa. Compared with the wild-types, the biomass and forage quality were enhanced in MsMYBH overexpressed plants. Combined RNA-seq, proteomics and chromatin immunoprecipitation analysis showed that MsMYBH can directly bind to the promoters of MsMCP1, MsMCP2, MsPRX1A and MsCARCAB to improve their expression. The outcomes of such interactions include better water balance, high photosynthetic efficiency and scavenge excess H2O2 in response to drought. Furthermore, an E3 ubiquitin ligase (MsWAV3) was found to induce MsMYBH degradation under long-term drought, via the 26S proteasome pathway. Furthermore, variable-number tandem repeats in MsMYBH promoter were characterized among a collection of germplasms, and the variation is associated with promoter activity. Collectively, our findings shed light on the functions of MsMYBH and provide a pivotal gene that could be leveraged for breeding drought-resistant alfalfa. This discovery also offers new insights into the mechanisms of drought resistance in alfalfa.

Integrated Metabolomics and Transcriptomics Analyses Highlight the Flavonoid Compounds Response to Alkaline Salt Stress in Glycyrrhiza uralensis Leaves.

Glycyrrhiza uralensis is a saline-alkali-tolerant plant whose aerial parts are rich in flavonoids; however, the role of these flavonoids in saline-alkali tolerance remains unclear. Herein, we performed physiological, metabolomics, and transcriptomics analyses in G. uralensis leaves under alkaline salt stress for different durations. Alkaline salt stress stimulated excessive accumulation of reactive oxygen species and consequently destroyed the cell membrane, causing cell death, and G. uralensis initiated osmotic regulation and the antioxidant system to respond to stress. In total, 803 metabolites, including 244 flavonoids, were detected via metabolomics analysis. Differentially altered metabolites and differentially expressed genes were coenriched in flavonoid-related pathways. Genes such as novel.4890, Glyur001511s00039602, and Glyur000775s00025737 were highly expressed, and flavonoid metabolites such as 2'-hydroxygenistein, apigenin, and 3-O-methylquercetin were upregulated. Thus, flavonoids as nonenzymatic antioxidants play an important role in stress tolerance. These findings provide novel insights into the response of G. uralensis to alkaline salt stress.

Insights into the rotational stability of toric intraocular lens implantation: diagnostic approaches, influencing factors and intervention strategies.

Toric intraocular lenses (IOLs) have been developed to enhance visual acuity impaired by cataracts and correct corneal astigmatism. However, residual astigmatism caused by postoperative rotation of the toric IOL is an important factor affecting visual quality after implantation. To decrease the rotation of the toric IOL, significant advancements have been made in understanding the characteristics of toric IOL rotation, the factors influencing its postoperative rotation, as well as the development of various measurement techniques and interventions to address this issue. It has been established that factors such as the patient's preoperative refractive status, biological parameters, surgical techniques, postoperative care, and long-term management significantly impact the rotational stability of the toric IOL. Clinicians should adopt a personalized approach that considers these factors to minimize the risk of toric IOL rotation and ensure optimal outcomes for each patient. This article reviews the influence of various factors on toric IOL rotational stability. It discusses new challenges that may be encountered to reduce and intervene with rotation after toric IOL implantation in the foreseeable future.

Rotational stability of monofocal and diffractive multifocal toric intraocular lens with identical design and material: a propensity score based prospective comparative study.

PURPOSE: To compare the rotational stability of a monofocal and a diffractive multifocal toric intraocular lens(IOLs) with identical design and material. METHODS: This prospective study enrolled patients who underwent plate-haptic toric IOL (AT TORBI 709 M and AT LISA 909 M) implantation. Propensity score matching (PSM) was performed to balance baseline factors. Follow-up examinations were conducted at 1 h, 1 day, 3 days, 1 week, 2 weeks, 1 month, and 3 months postoperatively. A linear mixed model of repeated measures was used to investigate the changes in IOL rotation over time. A 2-week timeframe was utilized to assess differences in IOL rotation between the two groups. RESULT: After PSM, a total of 126 eyes were selected from each group for further analysis. Postoperatively, the time course of IOL rotation change in the two groups remained consistent, with the greatest rotation occurring between 1 h and 1 day postoperatively. At the 2-week postoperative mark, the monofocal toric IOL exhibited a higher degree of rotation compared to the multifocal toric IOL (5.40 ± 7.77° vs. 3.53 ± 3.54°, P = 0.015). In lens thickness(LT) ≥ 4.5 mm and white-to-white distance(WTW) ≥ 11.6 mm subgroups, the monofocal toric IOL rotated greater than the multifocal toric IOL (P = 0.026 and P = 0.011, respectively). CONCLUSION: The diffractive multifocal toric IOL exhibits superior rotational stability compared to the monofocal toric IOL, especially in subgroups LT ≥ 4.5 mm and WTW ≥ 11.6 mm. Moreover, the time course of IOL rotation change is consistent for both, with the maximum rotation occurring between 1 h and 1 day postoperatively.

Role of RNA Modifications, Especially m6A, in Aflatoxin Biosynthesis of Aspergillus flavus.

RNA modifications play key roles in eukaryotes, but the functions in Aspergillus flavus are still unknown. Temperature has been reported previously to be a critical environmental factor that regulates the aflatoxin production of A. flavus, but much remains to be learned about the molecular networks. Here, we demonstrated that 12 kinds of RNA modifications in A. flavus were significantly changed under 29 °C compared to 37 °C incubation; among them, m6A was further verified by a colorimetric method. Then, the transcriptome-wide m6A methylome and m6A-altered genes were comprehensively illuminated through methylated RNA immunoprecipitation sequencing and RNA sequencing, from which 22 differentially methylated and expressed transcripts under 29 °C were screened out. It is especially notable that AFCA_009549, an aflatoxin biosynthetic pathway gene (aflQ), and the m6A methylation of its 332nd adenine in the mRNA significantly affect aflatoxin biosynthesis in A. flavus both on media and crop kernels. The content of sterigmatocystin in both ΔaflQ and aflQA332C strains was significantly higher than that in the WT strain. Together, these findings reveal that RNA modifications are associated with secondary metabolite biosynthesis of A. flavus.

Effect of astigmatism on visual outcomes after multifocal intraocular lens implantation: a systematic review and meta-analysis.

Purpose: To investigate the effects of postoperative astigmatism on the visual outcomes following presbyopia-correcting surgery with multifocal intraocular lens implantation. Methods: A comprehensive literature search was conducted using PubMed, Embase, and Web of Science for articles published until January 2023. Additionally, we included retrospective case series and prospective comparative studies. The combined mean difference (MD) with 95% confidence intervals (CI) and odds ratio (OR) with 95% CI were used to express continuous and categorical outcomes, respectively. All statistical analyses were performed using Review Manager (version 5.4.1). Results: We included nine eligible studies that analyzed 3,088 eyes. The proportion of eyes with useful postoperative visual acuity (logMAR ≤ 0.20) and residual astigmatism significantly differed with respect to the magnitude of astigmatism and presence/absence of blurred vision (p < 0.001 for both). Additionally, the mean uncorrected distance visual acuity (MD, 0.14; 95% CI, 0.06 to 0.21; p = 0.0003) and uncorrected intermediate visual acuity (MD, 0.07; 95% CI, 0.00 to 0.13; p = 0.04), but not the uncorrected near visual acuity (MD, 0.02; 95%CI-0.01 to 0.05; p = 0.17), significantly differed according to the magnitude of astigmatism. Conclusion: Astigmatism, even at low levels (≥ 0.5D), has a significant effect on visual outcomes, especially on UDVA and UIVA, following multifocal intraocular lens implantation. Accurate preoperative and postoperative evaluation of astigmatism is important.

Regulation of Fungal Morphogenesis and Pathogenicity of Aspergillus flavus by Hexokinase AfHxk1 through Its Domain Hexokinase_2.

As a filamentous pathogenic fungus with high-yield of aflatoxin B1, Aspergillus flavus is commonly found in various agricultural products. It is crucial to develop effective strategies aimed at the prevention of the contamination of A. flavus and aflatoxin. Hexokinase AfHxk1 is a critical enzyme in fungal glucose metabolism. However, the role of AfHxk1 in A. flavus development, aflatoxin biosynthesis, and virulence has not yet been explored. In this study, afHxk1 gene deletion mutant (ΔafHxk1), complementary strain (Com-afHxk1), and the domain deletion strains (afHxk1ΔD1 and afHxk1ΔD2) were constructed by homologous recombination. Phenotype study and RT-qPCR revealed that AfHxk1 upregulates mycelium growth and spore and sclerotia formation, but downregulates AFB1 biosynthesis through related classical signaling pathways. Invading models and environmental stress analysis revealed that through involvement in carbon source utilization, conidia germination, and the sensitivity response of A. flavus to a series of environmental stresses, AfHxk1 deeply participates in the regulation of pathogenicity of A. flavus to crop kernels and Galleria mellonella larvae. The construction of domain deletion strains, afHxk1ΔD1 and afHxk1ΔD2, further revealed that AfHxk1 regulates the morphogenesis, mycotoxin biosynthesis, and the fungal pathogenicity mainly through its domain, Hexokinase_2. The results of this study revealed the biological role of AfHxk1 in Aspergillus spp., and might provide a novel potential target for the early control of the contamination of A. flavus.

Integrated analysis of microRNA expression in tears of Kazakh patients with climatic droplet keratopathy in Xinjiang, China.

Climatic droplet keratopathy (CDK) is a corneal diseases, which is characterized by increased oil-like deposits on the anterior elastic lamina and anterior stromal layer. Severe CDK can even cause blindness, with no specific available treatment. Besides. CDK is poorly understood in terms of its pathogenic mechanisms. Thus, to determine potential biomarkers for CDK, we analyzed the microRNA expression profile in tear samples from CDK patients and investigated their putative roles in the pathogenesis of CDK. Herein, miRNA sequencing and following bioinformatics analysis was performed to explore the roles of their target genes in CDK. A total of 67 differentially expressed miRNAs were identified, of which 25 were upregulated and 42 were downregulated. qPCR verification showed that among the up- and down-regulated miRNAs, expression of five and six, respectively, was most significantly different.The target genes of the differentially expressed miRNAs are involved in the FoxO signaling pathway, tumor necrosis factor (TNF) signaling pathway, and steroid hormone biosynthesis. Protein-protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. In conclusion, the panel of differentially expressed miRNAs identified may have potential utility as early diagnostic biomarkers for CDK. Moreover, the TNF signaling pathway is a new potential target in CDK for the development of treatments.

Optimization of biogas production from straw wastes by different pretreatments: Progress, challenges, and prospects.

Lignocellulosic biomass (LCB) presents a promising feedstock for carbon management due to enormous potential for achieving carbon neutrality and delivering substantial environmental and economic benefit. Bioenergy derived from LCB accounts for about 10.3 % of the global total energy supply. The generation of bioenergy through anaerobic digestion (AD) in combination with carbon capture and storage, particularly for methane production, provides a cost-effective solution to mitigate greenhouse gas emissions, while concurrently facilitating bioenergy production and the recovery of high-value products during LCB conversion. However, the inherent recalcitrant polymer crystal structure of lignocellulose impedes the accessibility of anaerobic bacteria, necessitating lignocellulosic residue pretreatment before AD or microbial chain elongation. This paper seeks to explore recent advances in pretreatment methods for LCB biogas production, including pulsed electric field (PEF), electron beam irradiation (EBI), freezing-thawing pretreatment, microaerobic pretreatment, and nanomaterials-based pretreatment, and provide a comprehensive overview of the performance, benefits, and drawbacks of the traditional and improved treatment methods. In particular, physical-chemical pretreatment emerges as a flexible and effective option for methane production from straw wastes. The burgeoning field of nanomaterials has provoked progress in the development of artificial enzyme mimetics and enzyme immobilization techniques, compensating for the intrinsic defect of natural enzyme. However, various complex factors, such as economic effectiveness, environmental impact, and operational feasibility, influence the implementation of LCB pretreatment processes. Techno-economic analysis (TEA), life cycle assessment (LCA), and artificial intelligence technologies provide efficient means for evaluating and selecting pretreatment methods. This paper addresses current issues and development priorities for the achievement of the appropriate and sustainable utilization of LCB in light of evolving economic and environmentally friendly social development demands, thereby providing theoretical basis and technical guidance for improving LCB biogas production of AD systems.

Analysis of N6-methyladenosine-modified mRNAs in diabetic cataract.

BACKGROUND: Cataracts remain a prime reason for visual disturbance and blindness all over the world, despite the capacity for successful surgical replacement with artificial lenses. Diabetic cataract (DC), a metabolic complication, usually occurs at an earlier age and progresses faster than age-related cataracts. Evidence has linked N6-methyladenosine (m6A) to DC progression. However, there exists a lack of understanding regarding RNA m6A modifications and the role of m6A in DC pathogenesis. AIM: To elucidate the role played by altered m6A and differentially expressed mRNAs (DEmRNAs) in DC. METHODS: Anterior lens capsules were collected from the control subjects and patients with DC. M6A epitranscriptomic microarray was performed to investigate the altered m6A modifications and determine the DEmRNAs. Through Gene Ontology and pathway enrichment (Kyoto Encyclopedia of Genes and Genomes) analyses, the potential role played by dysregulated m6A modification was predicted. Real-time polymerase chain reaction was further carried out to identify the dysregulated expression of RNA methyltransferases, demethylases, and readers. RESULTS: Increased m6A abundance levels were found in the total mRNA of DC samples. Bioinformatics analysis predicted that ferroptosis pathways could be associated with m6A-modified mRNAs. The levels of five methylation-related genes-RBM15, WTAP, ALKBH5, FTO, and YTHDF1-were upregulated in DC samples. Upregulation of RBM15 expression was verified in SRA01/04 cells with high-glucose medium and in samples from DC patients. CONCLUSION: M6a mRNA modifications may be involved in DC progression via the ferroptosis pathway, rendering novel insights into therapeutic strategies for DC.

Predictors of pregnancy stress and psychological birth trauma in women undergoing vaginal delivery: a cross-sectional study in China.

BACKGROUND: Psychological birth trauma exhibits a high incidence worldwide, resulting in a wide range of negative impacts on mothers, infants, couples, families and society at large through the maternal-centered ripple effect. However, there is currently limited research on psychological birth trauma in China. Social support and pregnancy stress are important influencing factors of psychological birth trauma. Consequently, this study aimed to explore predictors of pregnancy stress and psychological birth trauma in women undergoing vaginal delivery in China. METHODS: This cross-sectional study was performed at a single medical center between December 2021 and May 2022 in Hangzhou, China. Participants were selected using a convenience sampling technique. A total of 351 postpartum women within one week after vaginal delivery were included. Questionnaires were used to collect sociodemographic and obstetric characteristics and scores on the Pregnancy Stress Rating Scale (PSRS), City Birth Trauma Scale (City BiTS), Social Support Rating Scale (SSRS) and Family Adaptation Partnership Growth Affection and Resolve index (Family APGAR). Both univariate analysis and multiple linear regression analysis were conducted to assess predictors of pregnancy stress and psychological birth trauma. RESULTS: The median (IQR) of PSRS and City BiTS scores were 10.00 (14.00) and 3.00 (9.00), respectively. The incidence of postpartum posttraumatic stress disorder was 4.0% (14/351). Parity, social support, family support and level of education were predictors of pregnancy stress. Delivery complications, psychological traumatic event, pregnancy stress and family support were predictors of psychological birth trauma (P < 0.05). CONCLUSION: Pregnancy stress is related to social support, family support and some sociodemographic and obstetric characteristics. Psychological birth trauma is correlated with delivery complications, psychological traumatic event, pregnancy stress and family support. Consequently, enhancing social support, especially family support, for pregnant women as a means of reducing pregnancy stress can effectively prevent psychological birth trauma.

The epigenetic regulator Set9 harmonizes fungal development, secondary metabolism, and colonization capacity of Aspergillus flavus.

As a widely distributed food-borne pathogenic fungus, Aspergillus flavus and its secondary metabolites, mainly aflatoxin B1 (AFB1), pose a great danger to humans. It is urgent to reveal the complex regulatory network of toxigenic and virulence of this fungus. The bio-function of Set9, a SET-domain-containing histone methyltransferase, is still unknown in A. flavus. By genetic engineering means, this study revealed that, through catalyzing H4K20me2 and -me3, Set9 is involved in fungal growth, reproduction, and mycotoxin production via the orthodox regulation pathway, and regulates fungal colonization on crop kernels through adjusting fungal sensitivity reactions to oxidation stress and cell wall integrity stress. Further domain deletion and point mutation inferred that the SET domain is the core element in catalyzing H4K20 methylation, and D200 site of the domain is the key amino acid in the active center of the methyltransferase. Combined with RNA-seq analysis, this study revealed that Set9 regulates the aflatoxin gene cluster by the AflR-like protein (ALP), other than traditional AflR. This study revealed the epigenetic regulation mechanism of fungal morphogenesis, secondary metabolism, and pathogenicity of A. flavus mediated by the H4K20-methyltransferase Set9, which might provide a potential new target for early prevention of contamination of A. flavus and its deadly mycotoxins.

The Association between 24 h Movement Guidelines and Internalising and Externalising Behaviour Problems among Chinese Preschool Children.

This study examined the relationship between adherence to 24 h movement guidelines (24 h MGs) and internalising and externalising behavioural problems in Chinese children aged 3-6 years, with a specific focus on the differences between weekdays and weekends. The guidelines include recommendations for physical activity (PA), screen time (ST), and sleep duration (SD). The results indicated a stronger association between adherence to these guidelines and behavioural problems on weekends compared to weekdays. Specifically, the odds of experiencing internalising problems were 1.33 higher (95% CI: 1.05-1.69) when not satisfying all three behaviours compared to not satisfying one or two. Moreover, on weekends, when ST was not fulfilled, there was a higher likelihood of externalising behaviour problems compared to when it was fulfilled (OR, 1.18, 95% CI, 1.01-1.38), and when all three behaviours were not met, the likelihood was even higher (OR, 1.50, 95% CI, 1.04-2.18). Children who met all three guidelines had fewer internalising and externalising behavioural problems, suggesting a potential beneficial effect on mental health. The study revealed that a higher adherence to these recommendations corresponded to a lower risk of mental health problems. Additionally, higher screen time was linked to an increase in externalising behavioural issues. These findings underscore the importance of adherence to 24 h MGs for optimal mental health in children. Future interventions should consider these behavioural factors and incorporate strategies to promote adherence to these guidelines, particularly on weekends.

miR-1273h-5p protects the human corneal epithelium against UVR-induced oxidative stress and apoptosis: Role of miR-1273h-5p in climatic droplet keratopathy.

Climatic droplet keratopathy (CDK) is characterized by an increased number of oil-like deposits on the most anterior corneal layers, which affect vision and can cause blindness. Environmental ultraviolet radiation (UVR) exposure is a major risk factor, but the underlying mechanism of CDK pathogenesis is unclear. Increasing evidence has demonstrated that miRNAs participate in the cross-talk with oxidative stress. We aimed to explore whether certain miRNAs are involved in the pathogenesis of CDK. We performed miRNA sequencing of tears from patients with CDK and healthy individuals from Tacheng region of Xinjiang and conducted bioinformatic analysis of key miRNAs. We also evaluated viability, migration, and apoptosis of human corneal epithelial cells (HCECs) subjected to UVR treatment. miR-1273h-5p expression was abnormally downregulated in the tears of patients with CDK. miR-1273h-5p promoted cell proliferation and migration and inhibited UVR-induced mitochondrial apoptosis. miR-1273h-5p protected HCECs against UVR-induced oxidative damage by reducing the accumulation of reactive oxygen species and inhibiting mitochondrial apoptosis via the activation of the Nrf2 pathway. Thus, our results suggest that miR-1273h-5p protects the corneal epithelium against UVR-induced oxidative stress damage.

Comparison of visual outcomes in adult patients with different types of developmental cataracts after toric multifocal intraocular lenses implantation.

PURPOSE:  To analyze and compare the visual performance and patient satisfaction following the implantation of toric multifocal intraocular lenses (TMIOLs) in adult patients with different types of developmental cataracts (DC) accompanied by corneal astigmatism (CA). METHODS:  This is a prospective observational cohort study. Patients diagnosed with DC aged 18-30 years were divided into three groups according to the anatomic location of the lens opacity: cortical, nuclear, and posterior subcapsular (PSC) groups, and implanted with TMIOLs. Visual acuity (VA), postoperative refractive astigmatism (RA), intraocular lens (IOL) rotation, high-order aberrations (HOAs), modulation transfer function (MTF) curve, and Strehl ratio were compared. The functional vision and incidence of photic phenomena were surveyed using questionnaires. RESULTS:  Fifty-five eyes of 37 patients were enrolled and completed a 1-year follow-up. The mean CA was 2.06 ± 0.79 D preoperatively, and the mean RA was 0.29 ± 0.30 D 3-month postoperatively. The IOL rotation was 2.48° ± 1.89°, with no deviation > 10°. At 12 months, mean uncorrected distance VA improved from 0.93 ± 0.41 preoperatively to 0.08 ± 0.08 logarithm of the minimum angle of resolution (logMAR), mean uncorrected near VA increased from 0.45 ± 0.30 preoperatively to 0.12 ± 0.11 logMAR, and mean uncorrected intermediate VA was 0.14 ± 0.08 logMAR. The cortical and nuclear groups displayed better improvements in uncorrected near and intermediate VA than that in the PSC group. Similar results were observed in the 3-month defocus curves, HOAs, MTF curve, halo incidence, and near vision satisfaction. CONCLUSION: In adult patients with DC accompanied by CA, TMIOLs implantation achieved good postoperative visual outcomes and significantly reduced glasses dependency. Patients with cortical or nuclear lens opacity showed better whole-course VA and quality of vision, while patients with PSC opacity showed unsatisfactory near vision and suffered more photic phenomena.

SWD1 epigenetically chords fungal morphogenesis, aflatoxin biosynthesis, metabolism, and virulence of Aspergillus flavus.

As the main producer of aflatoxins, Aspergillus flavus is also one of the most important causes of invasive and non-invasive aspergillosis. Therefore, it is crucial to unravel the regulatory mechanisms of growth, metabolism, and pathogenicity of A. flavus. SWD1 is highly conserved across species for maintaining COMPASS methyltransferase activity, but the bio-function of SWD1 in A. flavus has not been explored. Through genetic analysis, this study revealed that SWD1 is involved in fungal morphogenesis and AFB1 biosynthesis by regulating the orthodox pathways through H3K4me1-3. Stresses sensitivity and crop models analysis revealed that SWD1 is a key regulator for the resistance of A. flavus to adapt to extreme adverse environments and to colonize crop kernels. It also revealed that the WD40 domain and 25 aa highly conserved sequence are indispensable for SWD1 in the regulation of mycotoxin bio-synthesis and fungal virulence. Metabolomic analysis inferred that SWD1 is crucial for the biosynthesis of numerous primary and secondary metabolites, regulates biological functions by reshaping the whole metabolic process, and may inhibit fungal virulence by inducing the apoptosis of mycelia through the inducer sphingosine. This study elucidates the epigenetic mechanism of SWD1 in regulating fungal pathogenicity and mycotoxin biosynthesis, and provides a potential novel target for controlling the virulence of A. flavus.