Relationships between progrosis, immune infiltration and expression of SMYD3 in pan-cancer

Objective The study focuses on the prognostic value of SMYD3 in pan cancer, and analyze the influence of SMYD3 on tumor tissue immune infiltration. Methods The gene expression and protein density data were collected from TCGA, GTEx and HPA databases. Kaplan-Meier(KM) algorithm was used to evaluate the impact of SMYD3 on the prognosis of patients with different kinds of tumor. The ESTIMATE algorithm and Timer database were applied to investigate the relationship between SMYD3 and immune microenvironment. And the results were verified in B16 cell line by knockout SMYD3. Results Higher expression of SMYD3 was observed in tumor tissue than normal tissue in both mRNA and protein level. And SMYD3 was thought to be associated with worse outcomes of patients(PPSmyd3 in B16 cell line increased the expression of antigen present genes(PConclusions Smyd3 is an important gene related to the prognosis of patients and the antigen presentation function of tumor cells. Smyd3 can inhibit the infiltration of immune cell by down-regulation of antigen-present genes, which induces the immune escape

YAP Inactivation by Soft Mechanotransduction Relieves MAFG for Tumor Cell Dedifferentiation

Solid tumor cells live in a highly dynamic mechanical microenvironment. How the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an enigma. Here, we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like cells. Mechanistically, integrin β8 was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein (YAP). YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), allowing MAFG to transactivate the stemness genes NANOG, SOX2, and NESTIN. Inactivation also restored β8 expression, thereby forming a closed mechanical loop. Importantly, MAFG expression is correlated with worse prognosis. Our findings provide mechanical insights into the regulation of tumor cell dedifferentiation, which has therapeutic implications for exploring innovative strategies to attack malignancies

Experimental study on sand production and coupling response of silty hydrate reservoir with different contents of fine clay during depressurization

To further understand the characteristics of clay and sand production (hereafter collectively referred to as sand production) and to provide optimization designs of sand control schemes are critical for gas production from clayey silt natural gas hydrate reservoirs in the South China Sea. Thus, gas-water-sand production behavoirs and coupling reservoir subsidence characteristics before, during, and after hydrate dissociation of the clayey silt hydrate reservoirs with different clay contents (5%, 10%, 15%, 20%, 25%, and 30%) have been studied through a self-developed experimental system. The results show that with the increase of clay content, the total mass of sand production first increases and then decreases, and it reaches maximum when the clayey content is 20%. The sand production is the lowest before hydrate dissociation and increases significantly during hydrate dissociation, which mainly occurs in the high-speed gas and water production stage at the beginning of hydrate dissociation. After hydrate dissociation, the sand production decreases significantly. During the whole depressurization process, the clay and free sand particles generally move to the sand outlet due to the fluid driving force and overlying stress extrusion. However, for conditions of high clay contents, those particles fail to pass through the sand control screen and gradually accumulate and block the screen by forming a mud cake, which greatly reduce the permeability of the screen and limite sand production as well as gas and water production. Our research lays a foundation for sand production prediction and sand control scheme selection during gas recovery from clayey silty hydrate reservoirs that greatly need to consider a balance between sand control and gas productivity

Cell softness renders cytotoxic T lymphocytes and T leukemic cells resistant to perforin-mediated killing

Abstract Mechanical force contributes to perforin pore formation at immune synapses, thus facilitating the cytotoxic T lymphocytes (CTL)-mediated killing of tumor cells in a unidirectional fashion. How such mechanical cues affect CTL evasion of perforin-mediated autolysis remains unclear. Here we show that activated CTLs use their softness to evade perforin-mediated autolysis, which, however, is shared by T leukemic cells to evade CTL killing. Downregulation of filamin A is identified to induce softness via ZAP70-mediated YAP Y357 phosphorylation and activation. Despite the requirements of YAP in both cell types for softness induction, CTLs are more resistant to YAP inhibitors than malignant T cells, potentially due to the higher expression of the drug-resistant transporter, MDR1, in CTLs. As a result, moderate inhibition of YAP stiffens malignant T cells but spares CTLs, thus allowing CTLs to cytolyze malignant cells without autolysis. Our findings thus hint a mechanical force-based immunotherapeutic strategy against T cell leukemia