Navigating the Landscape of Coronary Microvascular Research: Trends, Triumphs, and Challenges Ahead.

Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.

Adulteration detection of multi-species vegetable oils in camellia oil using Raman spectroscopy: Comparison of chemometrics and deep learning methods.

Oil adulteration is a global challenge in the production of high value-added natural oils. Raman spectroscopy combined with mathematical modeling can be used for adulteration detection of camellia oil (CAO). In this study, the advantages of traditional chemometrics and deep learning methods in identifying and quantifying adulterated CAO were compared from a statistical perspective, and no significant difference were founded in the identification of CAO at different levels of adulteration. The recognition rate of pure and adulterated CAO was 100 %, but there were misclassifications among different adulterated CAOs. The deep learning models outperformed chemometrics methods in quantitative prediction of adulteration level, with RP2, RMSEP, and RPD of the optimal ConvLSTM model achieved 0.999, 0.9 % and 31.5, respectively. The classifiers and models developed in this study based on deep learning have wide applicability and reliability, and provide a fast and accurate method for adulteration detection in CAO.

Strain- and sex-specific differences in intestinal microhemodynamics and gut microbiota composition.

Background: Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer, and is essential for maintaining physiological integrity. Our study aimed to elucidate the relationships among intestinal microhemodynamics, genetic background, sex, and microbial composition. Methods: To dissect the microhemodynamic landscape of the BALB/c, C57BL/6J, and KM mouse strains, laser Doppler flowmetry paired with wavelet transform analysis was utilized to determine the amplitude of characteristic oscillatory patterns. Microbial consortia were profiled using 16S rRNA gene sequencing. To augment our investigation, a broad-spectrum antibiotic regimen was administered to these strains to evaluate the impact of gut microbiota depletion on intestinal microhemodynamics. Immunohistochemical analyses were used to quantify platelet endothelial cell adhesion molecule-1 (PECAM-1), estrogen receptor α (ESR1), and estrogen receptor ß (ESR2) expression. Results: Our findings revealed strain-dependent and sex-related disparities in microhemodynamic profiles and characteristic oscillatory behaviors. Significant differences in the gut microbiota contingent upon sex and genetic lineage were observed, with correlational analyses indicating an influence of the microbiota on microhemodynamic parameters. Following antibiotic treatment, distinct changes in blood perfusion levels and velocities were observed, including a reduction in female C57BL/6J mice and a general decrease in perfusion velocity. Enhanced erythrocyte aggregation and modulated endothelial function post-antibiotic treatment indicated that a systemic response to microbiota depletion impacted cardiac amplitude. Immunohistochemical data revealed strain-specific and sex-specific PECAM-1 and ESR1 expression patterns that aligned with observed intestinal microhemodynamic changes. Conclusions: This study highlights the influence of both genetic and sex-specific factors on intestinal microhemodynamics and the gut microbiota in mice. These findings also emphasize a substantial correlation between intestinal microhemodynamics and the compositional dynamics of the gut bacterial community.

Comprehensive investigation on the flavor difference in five types of tea from JMD (Camellia sinensis 'Jinmudan').

BACKGROUND: Jinmudan (JMD) is a high-aroma variety widely cultivated in China. The current study primarily focuses on the key volatile metabolites in JMD black and oolong teas, and investigates the impact of processing technologies on the aroma quality of JMD tea. However, few studies have explored the suitability of JMD for producing a certain type of tea or the characteristic quality differences among various JMD teas using multivariate statistical analysis methods. RESULTS: The principal volatile metabolites contributing to the floral quality of JMD tea are linalool, geraniol, indole and phenethyl alcohol. In JMD black tea (BT), the key volatile metabolites include methyl salicylate, geraniol, (E)-ß-ocimene and phenethyl alcohol. In JMD oolong tea (OT), the key volatile metabolites include indole, linalyl valerate and phenethyl alcohol. In JMD yellow tea (YT), the key volatile metabolites include methyl salicylate, geraniol and terpinolene. In JMD white tea (WT), the key volatile metabolites include methyl salicylate, geraniol and terpinolene. In JMD green tea (GT), the key volatile metabolites include (E)-ß-ocimene, indole and geraniol. Comparative analysis and KEGG pathway enrichment analysis revealed that flavonoid biosynthesis is the primary metabolic pathway responsible for the taste differences among various tea types. GT exhibited higher levels of phloretin, dihydromyricetin and galangin. The contents of vitexin, tricetin in YT were relatively higher. The contents of aromadendrin and naringenin in BT were higher, while OT contained higher levels of kaempferol. Additionally, WT showed higher contents of 3-O-acetylpinobanksin and 3,5,7-pinobanksin. CONCLUSION: This study explained the reasons for the quality differences of different JMD tea and provided a reliable theoretical basis for the adaptability of JMD tea. © 2024 Society of Chemical Industry.

Olaparib combined with CDK12-IN-3 to promote genomic instability and cell death in ovarian cancer.

Large-scale phase III clinical trials of Olaparib have revealed benefits for ovarian cancer patients with BRCA gene mutations or homologous recombination deficiency (HRD). However, fewer than 50% of ovarian cancer patients have both BRCA mutations and HRD. Therefore, improving the effect of Olaparib in HR-proficient patients is of great clinical value. Here, a combination strategy comprising Olaparib and CDK12-IN-3 effectively inhibited the growth of HR-proficient ovarian cancer in cell line, patient-derived organoid (PDO), and mouse xenograft models. Furthermore, the combination strategy induced severe DNA double-strand break (DSB) formation, increased NHEJ activity in the G2 phase, and reduced HR activity in cancer cells. Mechanistically, the combination treatment impaired Ku80 poly(ADP-ribosyl)ation (PARylation) and phosphorylation, resulting in PARP1-Ku80 complex dissociation. After dissociation, Ku80 occupancy at DSBs and the resulting Ku80-primed NHEJ activity were increased. Owing to Ku80-mediated DNA end protection, MRE11 and Rad51 foci formation was inhibited after the combination treatment, suggesting that this treatment suppressed HR activity. Intriguingly, the combination strategy expedited cGAS nuclear relocalization, further suppressing HR and, conversely, increasing genomic instability. Moreover, the inhibitory effect on cell survival persisted after drug withdrawal. These findings provide a rationale for the clinical application of CDK12-IN-3 in combination with Olaparib.

Role of oxylipins in ovarian function and disease: A comprehensive review.

Ovaries are essential for healthy female reproduction, with the follicles as their fundamental functional units, which consist of an oocyte and surrounding granulosa cells. The development and formation of follicles in the ovaries are closely linked to reproductive health. Oxylipins refer to oxidative metabolites produced from the oxidation of polyunsaturated fatty acids, either through automatic oxidation or with the help of specific enzymes. They play crucial regulatory roles in the immune system, oxidative stress, and inflammatory reactions and are intimately linked to the development of numerous illnesses, such as diabetes, heart disease, asthma, and Alzheimer's disease. Furthermore, oxylipins have a complex relationship with ovarian function, and both prostaglandins and leukotrienes produced by arachidonic acid affect processes such as follicle growth and development, ovulation, and hormone regulation. The synthesis and metabolism of oxylipins in the ovaries are finely regulated. Oxylipin dysregulation has been linked to various ovarian diseases, including endometriosis, polycystic ovary syndrome, ovarian cancer, and premature ovarian insufficiency. In addition, potential therapeutic targets and interventions targeting the oxylipin pathway for the treatment of ovarian diseases have become a prominent research focus, including regulating the enzymes responsible for oxylipin synthesis, using anti-inflammatory agents, and regulating lipid metabolism. Recent research has been directed towards improving the reproductive outcomes of women with ovarian diseases through this series of interventions. An overview of the role of oxylipins in ovarian function and disease is provided in this article, which will aid researchers in understanding the current state of the field and in identifying future directions.

A repressive H3K36me2 reader mediates Polycomb silencing.

In animals, evolutionarily conserved Polycomb repressive complex 2 (PRC2) catalyzes histone H3 lysine 27 trimethylation (H3K27me3) and PRC1 functions in recruitment and transcriptional repression. However, the mechanisms underlying H3K27me3-mediated stable transcriptional silencing are largely unknown, as PRC1 subunits are poorly characterized in fungi. Here, we report that in the filamentous fungus Magnaporthe oryzae, the N-terminal chromodomain and C-terminal MRG domain of Eaf3 play key roles in facultative heterochromatin formation and transcriptional silencing. Eaf3 physically interacts with Ash1, Eed, and Sin3, encoding an H3K36 methyltransferase, the core subunit of PRC2, and a histone deacetylation co-suppressor, respectively. Eaf3 co-localizes with a set of repressive Ash1-H3K36me2 and H3K27me3 loci and mediates their transcriptional silencing. Furthermore, Eaf3 acts as a histone reader for the repressive H3K36me2 and H3K27me3 marks. Eaf3-occupied regions are associated with increased nucleosome occupancy, contributing to transcriptional silencing in M. oryzae. Together, these findings reveal that Eaf3 is a repressive H3K36me2 reader and plays a vital role in Polycomb gene silencing and the formation of facultative heterochromatin in fungi.

Chloride intracellular channel 4 blockade improves cognition in mice with Alzheimer's disease: CLIC4 protein expression and tau protein hyperphosphorylation.

Numerous academic literature suggests that amyloid-ß (Aß) deposition, tau protein phosphorylation, and irreversible neuronal death are the three major causes of AD. The chloride intracellular channel (CLIC) protein family not only regulates the polarisation of neurons, but also has important implications for neuronal survival. Chloride intracellular channel 4 (CLIC4) can be pathologically activated by cyclin-dependent kinase 5 (Cdk5), which causes a significant increase in the expression of CLIC4 and mediates neuronal apoptosis. CLIC4 knockdown inhibits H2O2-induced neuronal apoptosis; however, the relationship between CLIC4 and AD remains unknown. In the present study, we showed that CLIC4 expression was elevated in the hippocampus of AD mice; knockdown of hippocampal CLIC4 alleviated Aß25-35-induced cognitive impairment in mice; overexpression of hippocampal CLIC4 accelerated Aß deposition and tau protein hyperphosphorylation in young AD mice (APP/PS1 mice at three months of age). CLIC4 overexpressing mice had a longer escape latency compared to controls in behavioural testing (Morris water maze and T-maze tests). By Co-immunoprecipitation/mass spectrometry (Co-IP/MS) of HT22 cells to identify proteins that specifically bind to CLIC4, we found interactions with CCAAT enhancer binding protein (C/EBPß); a critical pathway involved in the development of various neurodegenerative diseases. In addition, the knockdown of hippocampal CLIC4 alleviated AD-like pathology by inhibiting the C/EBPß/AEP signaling pathway. These data suggest an essential role for high CLIC4 expression in the pathophysiology of AD and reveal that inhibition of CLIC4 expression may provide an opportunity for treatment.

Ancient genomes illuminate the demographic history of Shandong over the past two millennia.

Shandong province, located in the Lower Yellow River, is one of the birthplaces of ancient Chinese civilization. However, the comprehensive genetic histories of this region have remained largely unknown until now due to a lack of ancient human genomes. Here, we present 21 ancient genomes from Shandong dating from the Warring States period to the Jin-Yuan Dynasties. Unlike the early Neolithic samples from Shandong, the historical samples are most closely related to post-Late Neolithic populations of the Middle Yellow River Basin, suggesting a population turnover in Shandong from the Neolithic Age to the Historical era. In addition, we detect a close genetic affinity between the historical samples in Shandong and present-day Han Chinese, showing long-term genetic stability in Han Chinese at least since the Warring States period.

Urinary enterolignans and enterolignan-predicting microbial species are favourably associated with liver fat and other obesity markers.

Aims: Plant-derived lignans may protect against obesity, while their bioactivity needs gut microbial conversion to enterolignans. We used repeated measures to identify enterolignan-predicting microbial species and investigate whether enterolignans and enterolignan-predicting microbial species are associated with obesity. Methods: Urinary enterolignans, fecal microbiota, body weight, height, and circumferences of the waist (WC) and hips (HC) were repeatedly measured at the baseline and after 1 year in 305 community-dwelling adults in Huoshan, China. Body composition and liver fat [indicated by the controlled attenuation parameter (CAP)] were measured after 1 year. Multivariate-adjusted linear models and linear mixed-effects models were used to analyze single and repeated measurements, respectively. Results: Enterolactone and enterodiol levels were both inversely associated with the waist-to-hip ratio, body fat mass (BFM), visceral fat level (VFL), and liver fat accumulation (all P < 0.05). Enterolactone levels were also associated with lower WC (ß = -0.0035 and P = 0.013) and HC (ß = -0.0028 and P = 0.044). We identified multiple bacterial genera whose relative abundance was positively associated with the levels of enterolactone (26 genera) and enterodiol (22 genera, all P false discovery rate < 0.05), and constructed the enterolactone-predicting microbial score and enterodiol-predicting microbial score to reflect the overall enterolignan-producing potential of the host gut microbiota. Both these scores were associated with lower body weight and CAP (all P < 0.05). The enterolactone-predicting microbial score was also inversely associated with the BFM (ß = -0.1128 and P = 0.027) and VFL (ß = -0.1265 and P = 0.044). Conclusion: Our findings support that modulating the host gut microbiome could be a potential strategy to prevent obesity by enhancing the production of enterolignans.

Posttranslational regulatory mechanism of PD-L1 in cancers and associated opportunities for novel small-molecule therapeutics.

Despite the tremendous progress in cancer research over the past few decades, effective therapeutic strategies are still urgently needed. Accumulating evidence suggests that immune checkpoints are the cause of tumor immune escape. PD-1/PD-L1 are among them. Posttranslational modification is the most critical step for protein function, and the regulation of PD-L1 by small molecules through posttranslational modification is highly valuable. In this review, we discuss the mechanisms of tumor cell immune escape and several posttranslational modifications associated with PD-L1 and describe examples in which small molecules can regulate PD-L1 through posttranslational modifications. Herein, we propose that the use of small molecule compounds that act by inhibiting PD-L1 through posttranslational modifications is a promising therapeutic approach with the potential to improve clinical outcomes for cancer patients.

Research on the generation and annotation method of thin section images of tight oil reservoir based on deep learning.

The cast thin sections of tight oil reservoirs contain important parameters such as rock mineral composition and content, porosity, permeability and stratigraphic characteristics, which are of great significance for reservoir evaluation. The use of deep learning technology for intelligent identification of thin section images is a development trend of mineral identification. However, the difficulty of making cast thin sections, the complexity of the making process and the high cost of thin section annotation have led to a lack of cast thin section images, which cannot meet the training requirements of deep learning image recognition models. In order to increase the sample size and improve the training effect of deep learning model, we proposed a generation and annotation method of thin section images of tight oil reservoir based on deep learning, by taking Fuyu reservoir in Sanzhao Sag as the target area. Firstly, the Augmentor strategy space was used to preliminarily augment the original images while preserving the original image features to meet the requirements of the model. Secondly, the category attention mechanism was added to the original StyleGAN network to avoid the influence of the uneven number of components in thin sections on the quality of the generated images. Then, the SALM annotation module was designed to achieve semi-automatic annotation of the generated images. Finally, experiments on image sharpness, distortion, standard accuracy and annotation efficiency were designed to verify the advantages of the method in image quality and annotation efficiency.

Analysis of Coding Gain Due to In-Loop Reshaping.

Reshaping, a point operation that alters the characteristics of signals, has been shown capable of improving the compression ratio in video coding practices. Out-of-loop reshaping that directly modifies the input video signal was first adopted as the supplemental enhancement information (SEI) for the HEVC/H.265 without the need to alter the core design of the video codec. VVC/H.266 further improves the coding efficiency by adopting in-loop reshaping that modifies the residual signal being processed in the hybrid coding loop. In this paper, we theoretically analyze the rate-distortion performance of the in-loop reshaping and use experiments to verify the theoretical result. We prove that the in-loop reshaping can improve coding efficiency when the entropy coder adopted in the coding pipeline is suboptimal, which is in line with the practical scenarios that video codecs operate in. We derive the PSNR gain in a closed form and show that the theoretically predicted gain is consistent with that measured from experiments using standard testing video sequences.

Effect of dural puncture epidural block technique on fetal heart rate variability during labor analgesia.

PURPOSE: To explore the effect of dural puncture epidural (DPE) block technique on fetal heart rate variability (HRV) during labor analgesia. METHODS: Sixty full-term primiparas who were in our hospital from April 2021 to October 2021 were selected and randomized into epidural analgesia (CEA) and dural puncture epidural analgesia (DPEA) groups (n = 30). After a successful epidural puncture, routine epidural catheter (EC) was performed in CEA group, and spinal anesthesia needle (as an EC) was used to puncture the dura mater to subarachnoid space in DPE group. Anesthetics were injected through EC. The time when the temperature sensation plane reached T10 (W1) and visual analog pain score (VAS), baseline heart rate score, amplitude variation score, cycle variation score, acceleration score, deceleration score, and total score of the first contraction after W1 were recorded. Apgar scores at 1 min, 5 min, and 10 min of neonates after delivery were recorded. RESULTS: The onset time of anesthesia in CEA group was significantly longer than that in DPEA group (p < .05). However, there are no significant differences in W1, VAS, baseline heart rate score, amplitude variation score, cycle variation score, acceleration score, deceleration score, and total score of the first contraction after W1 between the two groups (p > .05). Moreover, the Apgar scores at 1 min, 5 min and 10 min of neonates after delivery were not notably different between the two groups (p > .05). CONCLUSION: Compared with CEA, DPE block technique in labor analgesia relieves maternal pain without adverse effects on fetal HRV and newborns.

5,7,4'-Trimethoxyflavone triggers cancer cell PD-L1 ubiquitin-proteasome degradation and facilitates antitumor immunity by targeting HRD1.

Targeting the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway has been identified as a successful approach for tumor immunotherapy. Here, we identified that the small molecule 5,7,4'-trimethoxyflavone (TF) from Kaempferia parviflora Wall reduces PD-L1 expression in colorectal cancer cells and enhances the killing of tumor cells by T cells. Mechanistically, TF targets and stabilizes the ubiquitin ligase HMG-CoA reductase degradation protein 1 (HRD1), thereby increasing the ubiquitination of PD-L1 and promoting its degradation through the proteasome pathway. In mouse MC38 xenograft tumors, TF can activate tumor-infiltrating T-cell immunity and reduce the immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells, thus exerting antitumor effects. Moreover, TF synergistically exerts antitumor immunity with CTLA-4 antibody. This study provides new insights into the antitumor mechanism of TF and suggests that it may be a promising small molecule immune checkpoint modulator for cancer therapy.

Simultaneous and multiplexed phenotyping of circulating exosomes with the orthogonal CRISPR-Cas platform.

Simultaneous and multiplexed exosome protein profiling via an orthogonal CRISPR-Cas platform was achieved in this work. Aptamers were recruited to translate exosome surface protein information into Cas12a/Cas13a cleavage activity. The established multiplexed platform performed robustly with biological matrixes and could profile exosome proteins in clinical serum samples.

Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor ß among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

Profiling of the Proteins Interacting with Amyloid Beta Peptides in Clinical Samples by PACTS-TPP.

The accumulation of amyloid beta (Aß1-42) results in neurotoxicity and is strongly related to neurodegenerative disorders, especially Alzheimer's disease (AD), but the underlying molecular mechanism is still poorly understood. Therefore, there is an urgent need for researchers to discover the proteins that interact with Aß1-42 to determine the molecular basis. Previously, we developed peptide-ligand-induced changes in the abundance of proTeinS (PACTS)-assisted thermal proteome profiling (TPP) to identify proteins that interact with peptide ligands. In the present study, we applied this technique to analyze clinical samples to identify Aß1-42-interacting proteins. We detected 115 proteins that interact with Aß1-42 in human frontal lobe tissue. Pathway enrichment analysis revealed that the differentially expressed proteins were involved mainly in neurodegenerative diseases. Further orthogonal validation revealed that Aß1-42 interacted with the AD-associated protein mitogen-activated protein kinase 3 (MAPK3), and knockdown of the Aß1-42 amyloid precursor protein (APP) inhibited the MAPK signaling pathway, suggesting potential functional roles for Aß1-42 in interacting with MAPK3. Overall, this study demonstrated the application of the PACTS-TPP in clinical samples and provided a valuable data source for research on neurodegenerative diseases.

Dataset on cardiac structural and functional parameters in TMAO-challenged mouse.

Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite formed from dietary choline and l-carnitine, known to impede cholesterol metabolism and is implicated in the pathogenesis of thrombosis and atherosclerosis, contributing to the etiology of cardiovascular diseases. We present a dataset derived from an experimental study designed to elucidate the cardiotoxic effects of TMAO. This dataset encompasses echocardiographic assessments from two cohorts of mice: one subjected to a 6-week regimen of 20 mg/kg/day TMAO injections (n = 16) and a control group (n = 18). Each subject's echocardiographic dataset comprises six high-resolution TIFF images, capturing both B-type and M-mode views in standard echocardiographic planes, along with two additional M-mode images enriched with analysed cardiac functional data. Complementing these images, a CSV-formatted report details critical cardiac parameters, including heart rate, ejection fraction, and fractional shortening, among others. In a novel approach to enhance data integrity and permit tailored analyses, we provide the original output files from the echocardiography apparatus, which researchers can reprocess using dedicated analysis software. This dataset is anticipated to be instrumental in advancing our understanding of the mechanistic links between TMAO exposure and cardiac dysfunction.

Two H3K36 methyltransferases differentially associate with transcriptional activity and enrichment of facultative heterochromatin in rice blast fungus.

Di- and tri-methylation of lysine 36 on histone H3 (H3K36me2/3) is catalysed by histone methyltransferase Set2, which plays an essential role in transcriptional regulation. Although there is a single H3K36 methyltransferase in yeast and higher eukaryotes, two H3K36 methyltransferases, Ash1 and Set2, were present in many filamentous fungi. However, their roles in H3K36 methylation and transcriptional regulation remained unclear. Combined with methods of RNA-seq and ChIP-seq, we revealed that both Ash1 and Set2 are redundantly required for the full H3K36me2/3 activity in Magnaporthe oryzae, which causes the devastating worldwide rice blast disease. Ash1 and Set2 distinguish genomic H3K36me2/3-marked regions and are differentially associated with repressed and activated transcription, respectively. Furthermore, Ash1-catalysed H3K36me2 was co-localized with H3K27me3 at the chromatin, and Ash1 was required for the enrichment and transcriptional silencing of H3K27me3-occupied genes. With the different roles of Ash1 and Set2, in H3K36me2/3 enrichment and transcriptional regulation on the stress-responsive genes, they differentially respond to various stresses in M. oryzae. Overall, we reveal a novel mechanism by which two H3K36 methyltransferases catalyze H3K36me2/3 that differentially associate with transcriptional activities and contribute to enrichment of facultative heterochromatin in eukaryotes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00127-3.