The mechanism of RGS5 regulating gastric cancer mismatch repair protein.

The incidence and mortality rates of gastric cancer (GC) remain alarmingly high worldwide, imposing a substantial healthcare burden. In this study, we utilized data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A 4-gene prognostic model was developed to predict patient prognosis, and its accuracy was validated across multiple datasets. Patients with a low-risk score exhibited improved prognosis, elevated tumor mutation burden, heightened sensitivity to both immunotherapy and conventional chemotherapy. Notably, our investigation revealed that the key gene RGS5 positively modulates the expression of mismatch repair proteins via c-Myc. Furthermore, co-immunoprecipitation (COIP) assays demonstrated the interaction between RGS5 and c-Myc. Additionally, we confirmed that RGS5 regulates c-Myc through the ubiquitin-proteasome pathway. Moreover, RGS5 was identified as a positive regulator of PD-L1 expression and exhibited a negative correlation with the majority of immune cells. These findings underscore the potential of RGS5 as a novel biomarker and therapeutic target in the context of GC.

Guanine-Rich RNA Sequence Binding Factor 1 Deficiency Promotes Colorectal Cancer Progression by Regulating PI3K/AKT Signaling Pathway.

Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified. Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells. Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities. Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

First report of multidrug-resistant carbapenemase-producing Aeromonas caviae co-harboring mcr-3.43 and mcr-7.2.

Hospital sewage serves as a crucial reservoir for antibiotic resistance genes. As colistin and carbapenems are the last-resort antibiotics, the emergence of their resistance genes has become a significant concern in clinical settings. In this study, we found that two novel mcr alleles (mcr-3.43 and mcr-7.2) with two carbapenemase genes (blaNDM-1 and blaKPC-2) were encoded in a single Aeromonas caviae strain isolated from hospital sewage. Our phylogenetic analysis revealed that the mcr-3.43 gene clustered with mcr-3.17 (with 95.55% amino acid identity), while the mcr-7.2 gene clustered with mcr-7.1 (with 68.68% amino acid identity). BLAST search against GenBank showed that mcr-7.2 was exclusively detected in Aeromonas spp. Mobile genetic elements were not found in the genetic context of mcr-7.2, suggesting that the dissemination of mcr-7.2 in Aeromonas spp. may be dependent on vertical transfer or recombination. The blaNDM-1 was adjacent to a recombinase gene and flanked by two IS91 elements, indicating a potential mobilization mechanism mediated by recombination and/or ISs. The blaKPC-2 gene was located on an IncU plasmid and adjacent to an ISKpn6. In summary, our study provides evidence for Aeromonas spp. as one of the potential reservoirs of colistin and carbapenem resistance genes.IMPORTANCEThe study discovered two novel mcr genes (mcr-3.43 and mcr-7.2) and two carbapenemase genes (blaNDM-1 and blaKPC-2) in a single Aeromonas caviae strain retrieved from hospital sewage. Using phylogenetic analysis and comparative data evaluation, the study revealed the genetic relatedness and dissemination potential of the detected resistance genes. With the exclusive discovery that mcr-7.2 is only present in Aeromonas spp. and the lack of mobile genetic elements in its genetic context, there is a strong indication of limited dissemination. The identification of these four resistance genes in a single strain of Aeromonas provided valuable insights into their potential presence in this genus. This study revealed that hospital sewage functions as a significant reservoir for antibiotic resistance genes, including colistin and carbapenem resistance genes.

The research progress and research trends in acute coronary syndrome nursing: A review of visual analysis based on the Web of Science database.

Acute coronary syndrome (ACS) is one of the most common and severe forms of cardiovascular disease and has attracted worldwide attention with increased morbidity and mortality in recent years. There are few review studies in the field of its care in the form of bibliometric studies. We searched the Web of Science Core Collection database for articles and reviews in the area of ACS nursing for visual mapping analysis. Our objectives are to explore the hot topics and frontiers of research in the field of ACS nursing and to identify collaborative relationships between countries, institutions, and authors. This study will provide researchers with intuitive reference data for future in-depth studies of ACSs.

GR5 acts in the G protein pathway to regulate grain size in rice.

Grain size is an important determinant of grain yield in rice. Although dozens of grain size genes have been reported, the molecular mechanisms that control grain size remain to be fully clarified. Here, we report the cloning and characterization of GR5 (GRAIN ROUND 5), which is allelic to SMOS1/SHB/RLA1/NGR5 and encodes an AP2 transcription factor. GR5 acts as a transcriptional activator and determines grain size by influencing cell proliferation and expansion. We demonstrated that GR5 physically interacts with five Gγ subunit proteins (RGG1, RGG2, DEP1, GS3, and GGC2) and acts downstream of the G protein complex. Four downstream target genes of GR5 in grain development (DEP2, DEP3, DRW1, and CyCD5;2) were revealed and their core T/CGCAC motif identified by yeast one-hybrid, EMSA, and ChIP-PCR experiments. Our results revealed that GR5 interacts with Gγ subunits and cooperatively determines grain size by regulating the expression of downstream target genes. These findings provide new insight into the genetic regulatory network of the G protein signaling pathway in the control of grain size and provide a potential target for high-yield rice breeding.

Controllable Spin-Orbit Torque Induced by Interfacial Ion Absorption in Ta/CoFeB/MgO Multilayers with Canted Magnetizations.

Electrically generated spin-orbit torque (SOT) has emerged as a powerful pathway to control magnetization for spintronic applications including memory, logic, and neurocomputing. However, the requirement of external magnetic fields, together with the ultrahigh current density, is the main obstacle for practical SOT devices. In this paper, we report that the field-free SOT-driven magnetization switching can be successfully realized by interfacial ion absorption in perpendicular Ta/CoFeB/MgO multilayers. Besides, the tunable SOT efficiency exhibits a strong dependence on interfacial Ti insertion thicknesses. Polarized neutron reflection measurements demonstrate the existence of canted magnetization with Ti inserted, which leads to deterministic magnetization switching. In addition, interfacial characterization and first-principles calculations reveal that B absorption by the Ti layer is the main cause behind the enhanced interfacial transparency, which determines the tunable SOT efficiency. Our findings highlight an attractive scheme to a purely electric control spin configuration, enabling innovative designs for SOT-based spintronics via interfacial engineering.

Multi-Scale FPGA-Based Infrared Image Enhancement by Using RGF and CLAHE.

Infrared sensors capture thermal radiation emitted by objects. They can operate in all weather conditions and are thus employed in fields such as military surveillance, autonomous driving, and medical diagnostics. However, infrared imagery poses challenges such as low contrast and indistinct textures due to the long wavelength of infrared radiation and susceptibility to interference. In addition, complex enhancement algorithms make real-time processing challenging. To address these problems and improve visual quality, in this paper, we propose a multi-scale FPGA-based method for real-time enhancement of infrared images by using rolling guidance filter (RGF) and contrast-limited adaptive histogram equalization (CLAHE). Specifically, the original image is first decomposed into various scales of detail layers and a base layer using RGF. Secondly, we fuse detail layers of diverse scales, then enhance the detail information by using gain coefficients and employ CLAHE to improve the contrast of the base layer. Thirdly, we fuse the detail layers and base layer to obtain the image with global details of the input image. Finally, the proposed algorithm is implemented on an FPGA using advanced high-level synthesis tools. Comprehensive testing of our proposed method on the AXU15EG board demonstrates its effectiveness in significantly improving image contrast and enhancing detail information. At the same time, real-time enhancement at a speed of 147 FPS is achieved for infrared images with a resolution of 640 × 480.

RIG-I promotes immune evasion of colon cancer by modulating PD-L1 ubiquitination.

Colon cancer is one of the most prevalent cancers and exhibits high mortality worldwide. Despite the certain success in the immunotherapy of many tumor types, the limited response of colon cancer to immunotherapy remains a difficult problem. Retinoic acid-inducible gene-I (RIG-I) is a crucial component in innate antiviral immunity, but its role in antitumor immunity remains unclear. Here, in this report, we found that silencing RIG-I decreased resistance to tumor cells killed by T cells and attenuated colon tumor growth in immunocompetent mice. Meanwhile, overexpressing RIG-I promoted tumor progression, and high expression of RIG-I sensitized cells to anti-programmed cell death protein-1 (PD-1) therapy in vivo. Interestingly, we found that RIG-I influenced programmed cell death ligand 1 (PD-L1) expression to promote colon cancer immune evasion without relying on type I interferon stimulation. Mechanistically, RIG-I could compete with Speckle Type POZ protein (SPOP) to bind PD-L1, leading to attenuation of the polyubiquitination and proteasomal degradation of PD-L1. Collectively, our work reveals new insights into the contribution of RIG-I to driving immune evasion by maintaining the stability of PD-L1 through post-translational modification and provides a promising biomarker of the efficacy of immunotherapy in colon cancer.

RIG-I promotes cell proliferation in esophageal squamous cell carcinoma by facilitating p21 degradation.

Retinoic acid-inducible gene-I (RIG-I) is considered a key sensor for host recognition of RNA virus infections. Recent studies have shown that RIG-I also regulates carcinogenesis. However, the role of RIG-I in esophageal squamous cell carcinoma (ESCC) remains unclear. We investigated the RIG-I expression in ESCC cells using a public database, immunohistochemistry, and Western blotting. We evaluated the proliferative activity of ESCC cells using CCK-8, colony formation, and EdU staining assays. Further, we determined the ESCC cell-cycle changes using flow cytometry and the ubiquitination of p21 in the cells using cycloheximide chase and ubiquitination assays. Finally, we verified the in vivo effects of RIG-I on ESCC cells by constructing xenograft models. RIG-I was highly expressed in ESCC cells and significantly promoted their proliferation and cell-cycle. Moreover, RIG-I knockdown inhibited xenograft growth in nude mice. Furthermore, RIG-I accelerated the cell-cycle by promoting the ubiquitination and degradation of p21. Overall, this study revealed that the increased expression of RIG-I due to ESCC accelerated the progression of esophageal cancer by promoting the ubiquitination and degradation of p21, which is related to the prognosis of ESCC. Thus, RIG-I may be a novel therapeutic target for ESCC treatment.

Monopolar spindle 1 contributes to tamoxifen resistance in breast cancer through phosphorylation of estrogen receptor α.

PURPOSE: The overexpression of mitotic kinase monopolar spindle 1 (Mps1) has been identified in many tumor types, and targeting Mps1 for tumor therapy has shown great promise in multiple preclinical cancer models. However, the role played by Mps1 in tamoxifen (TAM) resistance in breast cancer has never been reported. METHODS: The sensitivity of breast cancer cells to tamoxifen was analysed in colony formation assays and wound healing assays. Enhanced transactivational activity of estrogen receptor α (ERα) led by Mps1 overexpression was determined by luciferase assays. The interaction between Mps1 and ERα was verified by co-immunoprecipitation and proximity ligation assay. Phosphorylation of ERα by Mps1 was detected by in vitro kinase assay and such phosphorylation process in vivo was proven by co-immunoprecipitation. The potential phosphorylation site(s) of ERα were analyzed by mass spectrometry. RESULTS: Mps1 determines the sensitivity of breast cancer cells to tamoxifen treatment. Mps1 overexpression rendered breast cancer cells more resistant to tamoxifen, while an Mps1 inhibitor or siMps1 oligos enabled cancer cells to overcome tamoxifen resistance. Mechanistically, Mps1 interacted with estrogen receptor α and stimulated its transactivational activity in a kinase activity-dependent manner. Mps1 was critical for ERα phosphorylation at Thr224 amino acid site. Importantly, Mps1 failed to enhance the transactivational activity of the ERα-T224A mutant. CONCLUSION: Mps1 contributes to tamoxifen resistance in breast cancer and is a potential therapeutic that can overcome tamoxifen resistance in breast cancer.

Effectiveness of sleep interventions to reduce delirium in critically ill patients: A systematic review and meta-analysis.

PURPOSE: To analyze the effectiveness of sleep interventions in reducing the incidence and duration of delirium in the ICU. MATERIALS AND METHODS: We searched the PubMed, Embase, CINAHL, Web of Science, Scopus, and Cochrane databases for relevant randomized controlled trials from inception to August 2022. Literature screening, data extraction, and quality assessment were performed independently by two investigators. Data from the included studies were analyzed using Stata and TSA software. RESULTS: Fifteen randomized controlled trials were eligible. Meta-analysis showed that the sleep intervention was associated with a reduced incidence of delirium in the ICU (RR = 0.73, 95% CI = 0.58 to 0.93, p < 0.001) compared to the control group. The results of the trial sequence analysis further confirm that sleep interventions are effective in reducing the occurrence of delirium. Pooled data from the three dexmedetomidine trials showed significant differences in the incidence of ICU delirium between groups (RR = 0.43, 95% CI = 0.32 to 0.59, p < 0.001). The respective pooled results of other sleep interventions (e.g., light therapy, earplugs, melatonin, and multicomponent nonpharmacologic treatments) did not find a significant effect on reducing the incidence and duration of ICU delirium (p > 0.05). CONCLUSIONS: The current evidence suggests that non-pharmacological sleep interventions are not effective in preventing delirium in ICU patients. However, limited by the number and quality of included studies, future well-designed multicenter randomized controlled trials are still needed to validate the results of this study.

VOC transport in an occupied residence: Measurements and predictions via deep learning.

Monitoring and prediction of volatile organic compounds (VOCs) in realistic indoor settings are essential for source characterization, apportionment, and exposure assessment, while it has seldom been examined previously. In this study, we conducted a field campaign on ten typical VOCs in an occupied residence, and obtained the time-resolved VOC dynamics. Feature importance analysis illustrated that air change rate (ACR) has the greatest impact on the VOC concentration levels. We applied three multi-feature (temperature, relative humidity, ACR) deep learning models to predict the VOC concentrations over ten days in the residence, indicating that the long short-term memory (LSTM) model owns the best performance, with predictions the closest to the observed data, compared with the other two models, i.e., recurrent neural network (RNN) model and gated recurrent unit (GRU) model. We also found that human activities could significantly affect VOC emissions in some observed erupted peaks. Our study provides a promising pathway of estimating long-term transport characteristics and exposures of VOCs under varied conditions in realistic indoor environments via deep learning.

Machine learning approach for estimating the human-related VOC emissions in a university classroom.

Indoor air quality becomes increasingly important, partly because the COVID-19 pandemic increases the time people spend indoors. Research into the prediction of indoor volatile organic compounds (VOCs) is traditionally confined to building materials and furniture. Relatively little research focuses on estimation of human-related VOCs, which have been shown to contribute significantly to indoor air quality, especially in densely-occupied environments. This study applies a machine learning approach to accurately estimate the human-related VOC emissions in a university classroom. The time-resolved concentrations of two typical human-related (ozone-related) VOCs in the classroom over a five-day period were analyzed, i.e., 6-methyl-5-hepten-2-one (6-MHO), 4-oxopentanal (4-OPA). By comparing the results for 6-MHO concentration predicted via five machine learning approaches including the random forest regression (RFR), adaptive boosting (Adaboost), gradient boosting regression tree (GBRT), extreme gradient boosting (XGboost), and least squares support vector machine (LSSVM), we find that the LSSVM approach achieves the best performance, by using multi-feature parameters (number of occupants, ozone concentration, temperature, relative humidity) as the input. The LSSVM approach is then used to predict the 4-OPA concentration, with mean absolute percentage error (MAPE) less than 5%, indicating high accuracy. By combining the LSSVM with a kernel density estimation (KDE) method, we further establish an interval prediction model, which can provide uncertainty information and viable option for decision-makers. The machine learning approach in this study can easily incorporate the impact of various factors on VOC emission behaviors, making it especially suitable for concentration prediction and exposure assessment in realistic indoor settings.

Current genetic strategies to investigate gene functions in Trichoderma reesei.

The filamentous fungus Trichoderma reesei (teleomorph Hypocrea jecorina, Ascomycota) is a well-known lignocellulolytic enzymes-producing strain in industry. To increase the fermentation titer of lignocellulolytic enzymes, random mutagenesis and rational genetic engineering in T. reesei were carried out since it was initially found in the Solomon Islands during the Second World War. Especially the continuous exploration of the underlying regulatory network during (hemi)cellulase gene expression in the post-genome era provided various strategies to develop an efficient fungal cell factory for these enzymes' production. Meanwhile, T. reesei emerges competitiveness potential as a filamentous fungal chassis to produce proteins from other species (e.g., human albumin and interferon α-2b, SARS-CoV-2 N antigen) in virtue of the excellent expression and secretion system acquired during the studies about (hemi)cellulase production. However, all the achievements in high yield of (hemi)cellulases are impossible to finish without high-efficiency genetic strategies to analyze the proper functions of those genes involved in (hemi)cellulase gene expression or secretion. Here, we in detail summarize the current strategies employed to investigate gene functions in T. reesei. These strategies are supposed to be beneficial for extending the potential of T. reesei in prospective strain engineering.

A low-frequency acceleration sensor inspired by saccule in human vestibule.

A human vestibular system is a group of devices in the inner ear that govern the balancing movement of the head, in which the saccule is responsible for sensing gravity accelerations. Imitating the sensing principle and structure of the Sensory Hair (SH) cell in the saccule, a Bionic Sensory Hair (BSH) was developed, and 9 BSH arrays were arranged in the bionic macular at the bottom of the spherical shell to prepare a Bionic Saccule (BS). Based on the piezoelectric equation, the electromechanical theoretical models of the BSH cantilever and BS were deduced. They were subjected to impact oscillations using an exciter, and their output charges were analyzed to check their sensing ability. The results showed that BSH could sense its bending deflection, and the BS could sense its position change in the sagittal plane and in space. They exhibited a sensitivity of 1.6104 Pc s2/m and a fast response and similar sensing principles and low resonance frequency to those of the human saccule. The BS is expected to be used in the field of robotics and clinical disease diagnosis as a part of the artificial vestibular system in the future.

In situ synthesis of g-C3N4/TiO2 heterojunction by a concentrated absorption process for efficient photocatalytic degradation of tetracycline hydrochloride.

The construction of heterojunctions between semiconductors is a preferred route to improve overall photocatalytic activity. In this work, a facile and feasible method was innovatively developed to one-step prepare g-C3N4/TiO2 heterojunctions via an absorption-calcination process using nitrogen and titanium precursors directly. This method can effectively avoid interfacial defects and establish a tight interfacial connection between g-C3N4 and TiO2. The resultant g-C3N4/TiO2 composites exhibited prominent photodegradation efficiency for tetracycline hydrochloride (TC-HCl) under visible light and simulated-sunlight irradiation. The optimal g-C3N4/TiO2 composite (urea content of 4 g) showed the highest photocatalytic efficiency, which can degrade 90.1% TC-HCl under simulated-sunlight irradiation within 30 min, achieving 3.9 and 2 times increases compared to pure g-C3N4 and TiO2, respectively. Besides, photodegradation pathways based on the role of active species ·O2- and ·OH were identified, indicating that a direct Z-scheme heterojunction was formed over the g-C3N4/TiO2 photocatalyst. The enhanced photocatalytic performance can be attributed to the close-knit interface contact and the formation of Z-scheme heterojunction between g-C3N4 and TiO2, which can accelerate the photo-induced charge carrier separation, broaden the spectra absorption range, and retain a higher redox potential. This one-step synthesis method may provide a new strategy for the construction of Z-scheme heterojunction photocatalysts consisting of g-C3N4 and TiO2 for environmental remediation and solar energy utilization.

PD-L1 expression downregulation by RNF43 in gastric carcinoma enhances antitumour activity of T cells.

Ring finger protein 43 (RNF43), a transmembrane E3 ubiquitin ligase, has been indicated to be a potential biomarker for gastric cancer treatment, as this protein increases tumour cell apoptosis and suppresses cellular proliferation. The role of RNF43 in cellular immunotherapy remains unclear. Herein, we aimed to explore the expression level of RNF43 in gastric cancer cell lines and its role in cellular immunotherapy. The expression level of RNF43 and PD-L1 and their correlation in gastric cancer cell lines were analysed. The expression of PD-L1 was negatively correlated with that of RNF43 in gastric cancer cell lines. RNF43 interacted with PD-L1 to augment both K48- and K63-linked ubiquitination of PD-L1 in gastric cancer cell lines. In addition, RNF43 expression in gastric cancer cell lines could enhance the antitumour activity of T cells. In conclusion, this study reveals that RNF43 can inhibit PD-L1 expression to enhance the antitumour activity of cellular immunotherapy.

Mixed-Dimensional van der Waals Heterostructure for High-Performance and Air-Stable Perovskite Nanowire Photodetectors.

An organic-inorganic hybrid perovskite nanowire (NW), CH3NH3PbI3, shows great potential for high-performance photodetectors due to its excellent photoresponse. However, the inefficient carrier collection between the one-dimensional (1D) NWs and metallic electrodes, as well as degradation of the perovskite, limits the viability of the CH3NH3PbI3 NWs for commercial production. Here, we demonstrate a photodetector with a mixed-dimensional van der Waals heterostructure of hexagonal boron nitride (hBN)/graphene (Gr)/1D CH3NH3PbI3, which exhibits excellent responsivity and specific detectivity of up to 558 A/W and 2.3 × 1012 Jones, owing to the improved carrier extraction at the electrical contact between Gr and the NW. As for the atomic encapsulation of hBN, the device is extremely robust and maintains its outstanding performance for more than 2 months when exposed to air. Moreover, benefitting from the 1D geometry of the CH3NH3PbI3 NW, our device is highly sensitive to polarized light. The mixed-dimensional van der Waals heterostructure, hBN/Gr/1D CH3NH3PbI3, would provide a novel idea and protocol for fabricating high-performance and air-stable photoelectronic devices based on organic-inorganic hybrid perovskite NWs.

Rice microtubule-associated protein OsMAP65-3.1, but not OsMAP65-3.2, plays a critical role in phragmoplast microtubule organization in cytokinesis.

In plants, MAP65 preferentially cross-links the anti-parallel microtubules (MTs) and plays an important role for cytokinesis. However, the functions of MAP65 isoforms in rice (Oryza sativa. L) are largely unknown. Here, we identified two MAP65-3 homologs in rice, OsMAP65-3.1 and OsMAP65-3.2. We found that both OsMAP65-3.1 and OsMAP65-3.2 were similar in dimerization and location to AtMAP65-3, and the expression of either rice genes driven by the AtMAP65-3 promoter suppressed the cytokinesis failure and growth defect of atmap65-3. However, OsMAP65-3.1 with native promoter also recovered the atmap65-3, but OsMAP65-3.2 with its own promoter had no effects. OsMAP65-3.1 but not OsMAP65-3.2 was actively expressed in tissues enriched with dividing cells. R1R2R3-Myb (MYB3R) transcription factors directly bound to the OsMAP65-3.1 promoter but not that of OsMAP65-3.2. Furthermore, osmap65-3.2 had no obvious phenotype, while either osmap65-3.1 or osmap65-3.1(+/-) was lethal. The eminent MTs around the daughter nuclei and cytokinesis defects were frequently observed in OsMAP65-3.1-defective plants. Taken together, our findings suggest that OsMAP65-3.1, rather than OsMAP65-3.2, plays essential roles in rice cytokinesis resulting from their differential expression which were passably directly regulated by OsMYB3Rs.

A histone H3K9 methyltransferase Dim5 mediates repression of sorbicillinoid biosynthesis in Trichoderma reesei.

Sorbicillinoids (also termed yellow pigment) are derived from either marine or terrestrial fungi, exhibit various biological activities and therefore show potential as commercial products for human or animal health. The cellulolytic filamentous fungus Trichoderma reesei is capable to biosynthesize sorbicillinoids, but the underlying regulatory mechanism is not yet completely clear. Herein, we identified a histone H3 lysine 9 (H3K9) methyltransferase, Dim5, in T. reesei. TrDIM5 deletion caused an impaired vegetative growth as well as conidiation, whereas the ∆Trdim5 strain displayed a remarkable increase in sorbicillinoid production. Post TrDIM5 deletion, the transcription of sorbicillinoid biosynthesis-related (SOR) genes was significantly upregulated with a more open chromatin structure. Intriguingly, hardly any expression changes occurred amongst those genes located on both flanks of the SOR gene cluster. In addition, the assays provided evidence that H3K9 triple methylation (H3K9me3) modification acted as a repressive marker at the SOR gene cluster and thus directly mediated the repression of sorbicillinoid biosynthesis. Transcription factor Ypr1 activated the SOR gene cluster by antagonizing TrDim5-mediated repression and therefore contributed to forming a relatively more open local chromatin environment, which further facilitated its binding and SOR gene expression. The results of this study will contribute to understanding the intricate regulatory network in sorbicillinoid biosynthesis and facilitate the endowment of T. reesei with preferred features for sorbicillinoid production by genetic engineering.