Mechanism Of Suppression Research Articles

Experience-driven suppression of irrelevant distractor locations is context dependent.

Humans can learn to attentionally suppress salient, irrelevant information when it consistently appears at a predictable location. While this ability confers behavioral benefits by reducing distraction, the full scope of its utility is unknown. As people locomote and/or shift between task contexts, known-to-be-irrelevant locations may change from moment to moment. Here we assessed a context-dependent account of learned suppression: can individuals flexibly update the locations they suppress, from trial to trial, as a function of task context? Participants searched for a shape target in displays that sometimes contained a salient, irrelevant color singleton distractor. When one scene category was presented in the background (e.g., forests), the distractor had a greater probability of appearing in one display location than the others; for another scene category (e.g., cities), we used a different high-probability location. Results in Experiments 1 and 2 (and in the Online Supplementary Material) failed to show any context-dependent suppression effects, consistent with earlier work. However, in Experiments 3 and 4, we reinforced the separation between task contexts by using distinct sets of shape and color stimuli as well as distinct kinds of reported features (line orientation vs. gap judgment). Results now showed robust task-dependent signatures of learned spatial suppression and did not appear to be tied to explicit awareness of the relationship between context and high-probability distractor location. Overall, these results reveal a mechanism of learned spatial suppression that is flexible and sensitive to task contexts, albeit one that requires sufficient processing of these contexts.

The combined immunization of cervical cancer therapeutic vaccine based on Listeria balanced lethal system has a significant therapeutic effect on tumor model mice.

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer death in women. Effective treatment of cervical cancer is urgently needed. Tumor therapeutic vaccine is a research hotspot in tumor immunotherapy, and the tumor therapeutic vaccine based on attenuated live bacteria carrier has clinical application prospect because of its clear action site and high safety. The bacterial balanced lethal system uses nutritional screening instead of antibiotic screening to avoid the risk of the spread of antibiotic resistance. So it is generally recognized as a green carrier. In our early research, we have constructed two cervical cancer therapeutic vaccine candidates (LM-HPVCW-1 and LI-HPVCW-1) based on Listeria balanced lethal system via transforming the nutrient-deficient strains with nutrition gene complementary plasmid. The complementary plasmid contained the nutrition complementary gene, LM dal gene, and its Amp gene was replaced with asd gene to delete the antibiotic resistance. Besides, it carried the shuffled HPV-16 E6E7 fusion protein gene. In vitro experiments showed that the plasmid carried by the candidate strain could be stably passaged and the target protein could be successfully expressed. In this study, we proved that the two candidate strains were safe in vivo and induced cellular immune response. At the same time, by establishing a tumor-bearing mouse model, it was proved that the two vaccine strains combined immunization could effectively inhibit mouse tumors. The mechanism of tumor suppression may be related to breaking the immunosuppression of tumor microenvironment and inducing CD8+ T cell infiltration. The therapeutic vaccine for cervical cancer constructed in this study is expected to be further applied in clinical practice.

Extracellular vesicle-associated miR-ERIA exerts the anti-angiogenic effect of macrophages in diabetic wound healing.

Many cell types are involved in the regulation of cutaneous wound healing in diabetes. Clarifying the mechanism of cell-cell interactions is important for identifying therapeutic targets for diabetic cutaneous ulcers. The function of vascular endothelial cells in the cutaneous microenvironment is critical, and a decrease in their biological function leads directly to refractory wound healing. In this study, we aimed to study the interactions of macrophages with vascular endothelial cells and elucidate the mechanism of diabetic wound angiogenesis suppression. We found that macrophages polarized to the M1 type, inhibited the migration and tube formation of human umbilical vein endothelial cells (HUVECs) by secreting extracellular vesicles after treatment with advanced glycation end products (AGEs-EVs), and contributed to wound angiogenesis and delayed wound healing in vivo. Mechanistically, we identified a novel miRNA enriched in AGEs-EVs, namely miR-ERIA, that suppress the biological function of HUVECs by targeting helicase with zinc finger 2 (HELZ2), and in vivo experiments showed that miR-ERIA suppression could promote wound angiogenesis and thus accelerate wound healing in diabetes. We found that miR-ERIA regulates diabetic wound angiogenesis by targeting HELZ2, suggesting a potential therapeutic target for diabetic foot ulcers.

Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition

BackgroundDespite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.MethodsIn this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level. The analysis was performed on breast cancer patient-derived xenograft tumors and cell lines, employing a comprehensive set of techniques, including targeted single-cell mRNA sequencing. Mechanistic insights were further gained through DNA methylation profiling and chromatin structure analysis.ResultsWe show that breast cancer tumors and cell cultures exhibit a highly heterogenous response to DNA methyltransferase inhibitors, persisting even under high drug concentrations and efficient DNA methyltransferase depletion. The observed variability in response to DNA methyltransferase inhibitors was independent of cancer-associated aberrations and clonal genetic diversity. Instead, these variations were attributed to stochastic demethylation of regulatory CpG sites and the DNA methylation-independent suppressive function of histone deacetylases.ConclusionsOur findings point to intratumoral heterogeneity as a limiting factor in the use of DNA methyltransferase inhibitors as single agents in treatment of solid cancers and highlight histone deacetylase inhibitors as essential partners to DNA methyltransferase inhibitors in the clinic.

Advances in inflammatory senescence in liver disease.

Inflammatory senescence is a process of cellular dysfunction associated with chronic inflammation, which plays a significant role in the onset and progression of liver diseases,and the research on its mechanisms becomes a hotspot currently. In viral hepatitis, the mechanisms of inflammatory senescence primarily involve oxidative stress, cell apoptosis and necrosis, as well as gut microbiota dysbiosis. In non-alcoholic fatty liver disease, the mechanisms of inflammatory senescence are more complex, involving insulin resistance, fat deposition, lipid metabolism disorders, gut microbiota dysbiosis, and NAD+ metabolism abnormalities. In liver tumors, inflammatory senescence is characterized by the weakening of tumor suppressive mechanisms, remodeling of the liver microenvironment, metabolic reprogramming, and enhanced immune evasion. Therapeutic strategies targeting inflammatory senescence have been developing recently, and antioxidant therapy, metabolic disorder improvement, and immunotherapy emerging are important interventions for liver diseases. This review focuses on the mechanisms of inflammatory secescence in liver diseases, aiming to provide novel insights for the prevention and treatment of liver diseases.

Numerical Study on the Mechanism of Gas Explosion Suppression by Different Arrangement Forms of Staggered Cylinders

ABSTRACT In order to study the suppression mechanism of porous media on gas explosion, the gas explosion behavior in a pipeline with one end closed and the other end temporarily closed by a thin film was numerically simulated in this paper, in which the porous media structure was characterized by “pseudo-porous media” composed of staggered cylinders. The RANS method is used to simulate turbulence in numerical calculation, and the coupling effect between turbulence and combustion is described by the reaction progress variable equation. The calculation results show that, compared with porosity, hole spacing is a more critical parameter affecting gas explosion. The function of pores is mainly reflected in the initial stage of explosion flame development, and the function of pore spacing is reflected after the flame reaches the maximum instantaneous displacement velocity. When the Pe number calculated based on local aperture and laminar flame velocity is less than 72, the flame cannot pass through porous media, and the influence of porous media on gas explosion can be shown. When the Pe number is greater than this value, the influence of porous media on gas explosion is not obvious; The hole spacing has a significant effect on the flame shape, bifurcation number, and flame thickness. When the hole spacing is larger, the flame front is more slender and bifurcated, while when the hole spacing is smaller, the flame presents a more blunt shape, and its expansion is delayed to a greater extent. This law provides a strong basis for the optimization of porous media in burner design, especially in adjusting the flame shape and improving combustion efficiency.

Trench MOS Schottky Diodes: A Physics-Based Analytical Model Approach to Charge Sharing.

Trench MOS Barrier Schottky (TMBS) rectifiers offer superior static and dynamic electrical characteristics when compared with planar Schottky rectifiers for a given active die size. The unique structure of TMBS devices allows for efficient manipulation of the electric field, enabling higher doping concentrations in the drift region and thus achieving a lower forward voltage drop (VF) and reduced leakage current (IR) while maintaining high breakdown voltage (BV). While the use of trenches to push electric fields away from the mesa surface is a widely employed concept for vertical power devices, a significant gap exists in the analytical modeling of this effect, with most prior studies relying heavily on computationally intensive numerical simulations. This paper introduces a new physics-based analytical model to elucidate the behavior of electric field and potential in the mesa region of a TMBS rectifier in reverse bias. Our model leverages the concept of shared charge between the Schottky and MOS junctions, capturing how electric field distribution is altered in response to trench geometry and bias conditions. This shared charge approach not only simplifies the analysis of electric field distribution but also reveals key design parameters, such as trench depth, oxide thickness, and doping concentration, that influence device performance. This model employs the concept of shared charge between the vertical Schottky and MOS junction. Additionally, it provides a detailed view of the electric field suppression mechanism in the TMBS device, highlighting the significant effects of the inversion charge on the MOS interface. By comparing our analytical results with TCAD simulations, we demonstrate strong agreement, underscoring the model's accuracy and its potential to serve as a more accessible alternative to resource-intensive simulations. This work contributes to a valuable tool for TMBS device design, offering insights into electric field management that support high-efficiency, high-voltage applications, including power supplies, automotive electronics, and renewable energy systems.

Blockade of TIPE2-Mediated Ferroptosis of Myeloid-Derived Suppressor Cells Achieves the Full Potential of Combinatory Ferroptosis and Anti-PD-L1 Cancer Immunotherapy.

Although immune checkpoint blockade (ICB) therapy has attained unprecedented clinical success, the tolerance and immune suppression mechanisms evolved by tumor cells and their tumor microenvironment (TME) hinder its maximum anti-cancer potential. Ferroptosis therapy can partially improve the efficacy of ICB, but it is still subject to immune suppression by myeloid-derived suppressor cells (MDSCs) in the TME. Recent research suggests that an MDSC blockade can unleash the full therapeutic potential of the combined therapy of ferroptosis and ICB in liver cancer treatment. However, whether blocking the intrinsic ferroptosis pathways of MDSCs can relieve imidazole ketone erastin (IKE)-initiated ferroptosis-induced immune suppression and ultimately trigger the optimal therapeutic effect of the combined ferroptosis and ICB therapy is still unknown. Here, we report that TIPE2, a phospholipid transfer protein, regulated the ferroptosis susceptibility in MDSCs through reprogramming lipid peroxidation-related phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species composition. TIPE2-deficient MDSCs resisted IKE-induced ferroptosis by up-regulating SLC7A11 and GPX4, and dissolved ferroptosis-induced immunosuppressive function by down-regulating lipid ROS whilst encouraging T cell proliferation and infiltration into tumor tissues to improve ferroptosis therapy. More importantly, TIPE2-deficient MDSCs achieved the full anti-tumor therapeutic potential of IKE-induced ferroptosis therapy and a PD-L1 blockade. These findings indicate that TIPE2 confers the ferroptosis sensitivity of MDSCs, and combining the targeting of the TIPE2 of MDSCs, ferroptosis therapy, and ICB is a novel therapeutic option for cancer treatment.

Fungal effector genes involved in the suppression of chitin signaling as novel targets for the control of powdery mildew disease via a nontransgenic RNA interference approach.

Chitin is a crucial component of fungal cell walls and an effective elicitor of plant immunity; however, phytopathogenic fungi have developed virulence mechanisms to counteract the activation of this plant defensive response. In this study, the molecular mechanism of chitin-induced suppression through effectors involved in chitin deacetylases (CDAs) and their degradation (EWCAs) was investigated with the idea of developing novel dsRNA-biofungicides to control the cucurbit powdery mildew caused by Podosphaera xanthii. The molecular mechanisms associated with the silencing effect of the PxCDA and PxEWCAs genes were first studied through dsRNA cotyledon infiltration assays, which revealed a ≈80% reduction in fungal biomass and a 50% decrease in gene expression. To assess the impact on powdery mildew disease control, in vitro and in planta assays were carried out in growth chamber and glasshouse experiments, with ≈50% reduction in disease symptoms after 8 days postinoculation (dpi) in leaf discs and 12 dpi in plants' leaves, respectively. This control was extended for 21 days when the dsRNAs were protected on the carbon dot nanocarriers. Additionally, the uptake of the dsRNAs by fungal spores was observed 12 h postapplication via confocal microscopy, and efficient processing of dsRNAs into siRNAs by the melon RNAi machinery was observed 24 h postspraying through sRNA-seq. This study highlights notable advancements in environmentally friendly disease management, and features the technological potential of RNA-based fungicides together with nanotechnology for cucurbit powdery mildew control. © 2025 Society of Chemical Industry.

Restrictor slows early transcription elongation to render RNA polymerase II susceptible to termination at non-coding RNA loci.

The eukaryotic genome is broadly transcribed by RNA polymerase II (RNAPII) to produce protein-coding messenger RNAs (mRNAs) and a repertoire of non-coding RNAs (ncRNAs). Whereas RNAPII is very processive during mRNA transcription, it terminates rapidly during synthesis of many ncRNAs, particularly those that arise opportunistically from accessible chromatin at gene promoters or enhancers. The divergent fates of mRNA versus ncRNA species raise many questions about how RNAPII and associated machineries discriminate functional from spurious transcription. The Restrictor complex, comprised of the RNA binding protein ZC3H4 and RNAPII-interacting protein WDR82, has been implicated in restraining the expression of ncRNAs. However, the determinants of Restrictor targeting and the mechanism of transcription suppression remain unclear. Here, we investigate Restrictor using unbiased sequence screens, and rapid protein degradation followed by nascent RNA sequencing. We find that Restrictor promiscuously suppresses early elongation by RNAPII, but this activity is blocked at most mRNAs by the presence of a 5' splice site. Consequently, Restrictor is a critical determinant of transcription directionality at divergent promoters and prevents transcriptional interference. Finally, our data indicate that rather than directly terminating RNAPII, Restrictor acts by reducing the rate of transcription elongation, rendering RNAPII susceptible to early termination by other machineries.

Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor outcomes due to frequent recurrence, metastasis, and resistance to treatment. A major contributor to this resistance is the tumor's ability to suppress natural killer (NK) cells, which are key players in the immune system's fight against cancer. In PDAC, the tumor microenvironment (TME) creates conditions that impair NK cell function, including reduced proliferation, weakened cytotoxicity, and limited tumor infiltration. This review examines how interactions between tumor-derived factors, NK cells, and the TME contribute to tumor progression and treatment resistance. To address these challenges, we propose a new "Triple NK Cell Biomarker Approach". This strategy focuses on identifying biomarkers from three critical areas: tumor characteristics, TME factors, and NK cell suppression mechanisms. This approach could guide personalized treatments to enhance NK cell activity. Additionally, we highlight the potential of combining NK cell-based therapies with conventional treatments and repurposed drugs to improve outcomes for PDAC patients. While progress has been made, more research is needed to better understand NK cell dysfunction and develop effective therapies to overcome these barriers.

Induction of macrophage efferocytosis in pancreatic cancer via PI3Kγ inhibition and radiotherapy promotes tumour control

BackgroundThe immune suppression mechanisms in pancreatic ductal adenocarcinoma (PDAC) remain unknown, but preclinical studies have implicated macrophage-mediated immune tolerance. Hence, pathways that regulate macrophage phenotype are of strategic interest, with...

The simulation of ELM control by the advanced divertor configuration in EAST

Abstract Edge localized modes (ELMs) are effectively suppressed in the ‘quasi-snowflake’ (QSF) divertor discharges, which has been observed in the Experimental Advanced Superconducting Tokamak (EAST). To obtain the physical mechanism of ELM suppression, the numerical simulations are carried out using the BOUT++ turbulence model. The simulations reveal that the large local magnetic shear near the outer mid-plane (OMP) induced by QSF divertor plays a key role in the ELM suppression. Using the EFIT code, a series of plasma equilibria with different 2nd X-points and nearly fixed last closed flux surfaces (LCFSs) are generated to analyze the effects of the different magnetic configurations on ELMs. Here we mainly discuss the standard single-null (SN), snowflake plus (SF+), and snowflake minus (SF-) divertors. The simulation results indicate that: (1) for linear instability, compared to SN, SF+ is more unstable, while SF- is more stable. Essentially, the local magnetic shear formed by different divertor geometries can alter the growth rate of the peeling-ballooning (P-B) mode. Through statistical analysis, there is an inverse correlation between the strength of local magnetic shear and the growth rate of P-B mode; (2) for ELM energy loss, SN is 4.60%, SF+ is 7.50%, and SF- is 0.35%. The SF+ divertor triggers a larger ELM, which is consistent with the TCV experiments; while the SF- divertor reduces the ELM amplitude, which is similar to the QSF experiments in EAST. Further analysis shows that the Reynolds stress determines the ELM size under different divertor configurations. The Reynolds stress can redistribute energy to fluctuations and cause the growth of low-n modes. What’s more, the SF- divertor not only suppresses the radial transport, but also has large magnetic flux expansion and connection length, which can reduce the target heat flux effectively. The conclusion of this paper shows that the advanced divertor configurations are promising for the future fusion.

Suppression effect on implosion of ceramic pressure hull through porous protection based on flow control

Ceramic pressure hull arrays have significant advantages for deep-sea underwater vehicles owing to their light weight and high strength. Furthermore, they are used to provide buoyancy to deep-sea underwater vehicles. However, the brittle characteristics of ceramic materials present a risk of implosion of the pressure hull in deep-sea environments. Once this occurs, a chain reaction of implosions will form in the pressure hull array, damaging the entire underwater vehicle. Therefore, effective implosion suppression strategies are required, and their suppression mechanisms must be analyzed. In this study, a numerical simulation method for porous protection based on a compressible multiphase flow is proposed from the perspective of controlling the flow with a porous protective cover, and verified through an underwater implosion protection experiment. The mechanism of implosion suppression was analyzed. It can be concluded that at the blocking and disturbing effect of the protective cover, the porous protective cover had a significant attenuating effect on the implosion shockwave. The influence of different hole parameters on the implosion suppression effect was discussed. It was found that when the porosity of the porous protective cover was fixed, more holes on the protective cover enhanced the attenuation effect on the implosion shockwave; however, after the number of holes increased to a certain extent, the implosion suppression effect remained unchanged.

Long-term suppression of Microcystis aeruginosa by tannic acid: Risks of microcystin pollution and proteomic mechanisms.

Harmful algal blooms are a critical eco-environmental issue with severe impacts on aquatic ecosystems and human health. Tannic acid (TA) has been suggested as an effective algal bloom control, but the molecular mechanisms of its interaction with algae cells and its effects on algal toxin release remain unclear. This study tracked toxin production and release in the toxigenic species Microcystis aeruginosa (M. aeruginosa) exposed to TA, revealing underlying mechanisms through proteomic analysis. High TA doses effectively inhibited M. aeruginosa growth and microcystin-leucine-arginine (MC-LR) production. However, at a specific TA concentration, M. aeruginosa produced and released more MCs, with extracellular MC-LR levels peaking at 1.91 times the control on day 15. Proteomic analysis indicated upregulation of proteins related to the tricarboxylic acid (TCA) cycle, glycolysis, and leucine and arginine biosynthesis, suggesting a compensatory response in M. aeruginosa under TA stress that enhanced cellular energy supply and MC-LR biosynthesis. In addition, TA exposure significantly downregulated proteins involved in ion and metal-cluster binding, disrupting electron transfer and photosynthesis. This study provides new insights into TA-induced MC-pollution risks and TA's mechanisms in algae suppression, offering guidance for its application in algal bloom control.

Suppressive Mechanism of Benzalkonium Chloride-Bactericidal Activity in the Presence of Oil

Suppressive Mechanism of Benzalkonium Chloride-Bactericidal Activity in the Presence of Oil

Research on the explosive characteristics and suppression mechanisms of gas generation during thermal runaway of batteries in a charged state

Research on the explosive characteristics and suppression mechanisms of gas generation during thermal runaway of batteries in a charged state

Ferroptosis: Basic Mechanisms, Key-Factors and The Role of The Diseases

Research on the explosive growth of Ferroptosis in the past decade. Ferroptosis is the way of cell death that causes lipid peroxidation, and there are a variety of inducers for Ferroptosis that can lead to a decrease in cell antioxidant capacity and the accumulation of lipid reactive oxygen species(ROS) of through multiple regulatory pathways, which leads to cell membrane damage and eventually leads to cell oxidative death. It will lead to a series of related diseases and plays a crucial role as a tumour suppressor mechanism. In this review, the relevant regulatory mechanisms of ferroptosis (especially the conventional ferroptosis pathway) are specifically summarised and the relevant diseases associated with ferroptosis are described. Fortunately, by initiating and reducing ferroptosis, there is significant potential to treat drug-resistant malignancies, ischemic organ damage, and other degenerative disorders linked to severe lipid peroxidation. Importantly, there are still a lot of obstacles to ferroptosis, and this review offers pertinent research suggestions to overcome these problems. Lastly, this article discusses the specific applicability of ferroptosis to disease; future ferroptosis research should center on these challenges.

Differential Neural Mechanisms Underlying Inhibition of Color and Dynamic Motion Distractors.

Navigating visually complex environments requires focusing on relevant information while filtering out (salient) distractions. The signal suppression hypothesis posits that salient stimuli generate an automatic saliency signal that captures attention unless overridden by learned suppression mechanisms. In support of this, ERP studies have demonstrated that salient stimuli that do not capture attention elicit a distractor positivity (PD), a putative neural index of suppression. Yet, to date, this hypothesis has been primarily tested with color singletons, leaving it unclear if the PD reflects general suppression or is specific to color singletons. This study compared lateralized ERPs elicited by color singleton and dynamic motion distractors using a variant of the additional singleton paradigm that has been shown to result in proactive suppression of colored distractors. Behavioral results showed a singleton presence benefit for both distractor types, indicating distractor suppression. However, ERP data revealed clear differences in the underlying neural mechanisms: Color singletons elicited a PD component indicative of proactive suppression, whereas motion singletons elicited a later positivity preceded by an N2pc, suggesting reactive suppression. Our findings suggest that motion singletons, unlike color singletons, are suppressed reactively after initial capture. This study highlights the importance of considering distractor feature dimensions in understanding attentional suppression mechanisms and underscores the need for caution in establishing proactive suppression based on a single metric. Further research is needed to clarify the conditions under which the early PD reliably indicates proactive suppression and to explore the neural processes underlying the suppression of various salient distractors.

MEG8 as an antagonistic pleiotropic mechanism in breast cancer

Cellular senescence connects aging and cancer. Cellular senescence is a common program activated by cells in response to various types of stress. During this process, cells lose their proliferative capacity and undergo distinct morphological and metabolic changes. Senescence itself constitutes a tumor suppression mechanism and plays a significant role in organismal aging by promoting chronic inflammation. Additionally, age is one of the major risk factors for developing breast cancer. Therefore, while senescence can suppress tumor development early in life, it can also lead to an aging process that drives the development of age-related pathologies, suggesting an antagonistic pleiotropic effect. In this work, we identified Rian/MEG8 as a potential biomarker connecting aging and breast cancer for the first time. We found that Rian/MEG8 expression decreases with age; however, it is high in mice that age prematurely. We also observed decreased MEG8 expression in breast tumors compared to normal tissue. Furthermore, MEG8 overexpression reduced the proliferative and stemness properties of breast cancer cells both in vitro and in vivo by activating apoptosis. MEG8 could exemplify the antagonistic pleiotropic theory, where senescence is beneficial early in life as a tumor suppression mechanism due to increased MEG8, resulting in fewer breast tumors at an early age. Conversely, this effect could be detrimental later in life due to aging and cancer, when MEG8 is reduced and loses its tumor-suppressive role.