RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation

Numerical Simulation of Dense Solid-Liquid Mixing in Stirred Vessel with Improved Dual Axial Impeller

Computational fluid dynamics (CFDs) were adopted in order to investigate the solid suspending process in a dense solid–liquid system (with a solid volume fraction of 30%), agitated by a traditional dual axial impeller and a modified dual axial impeller, otherwise known as a dual triple blade impeller (DTBI) and a dual rigid-flexible triple blade impeller (DRFTBI), respectively. The effects of rotational speed, connection strap length/width, and off-bottom clearance on the solid distribution were investigated. The results show that the proportion of solid concentration larger than 0.4 in the DTBI system was 26.56 times of that in the DRFTBI system. This indicates that the DRFTBI system can strengthen the solid suspension and decrease the solid accumulation in the bottom of the tank. Furthermore, the velocity and turbulent kinetic energy in the DRFTBI system were promoted. In addition, for an optimal selection, the optimum length of connection strap was 1.2 H1, the optimum range of connection strap width was D/7–D/8, and the off-bottom clearance selected as T/4 was better

Numerical Simulation of Dense Solid-Liquid Mixing in Stirred Vessel with Improved Dual Axial Impeller

Computational fluid dynamics (CFDs) were adopted in order to investigate the solid suspending process in a dense solid–liquid system (with a solid volume fraction of 30%), agitated by a traditional dual axial impeller and a modified dual axial impeller, otherwise known as a dual triple blade impeller (DTBI) and a dual rigid-flexible triple blade impeller (DRFTBI), respectively. The effects of rotational speed, connection strap length/width, and off-bottom clearance on the solid distribution were investigated. The results show that the proportion of solid concentration larger than 0.4 in the DTBI system was 26.56 times of that in the DRFTBI system. This indicates that the DRFTBI system can strengthen the solid suspension and decrease the solid accumulation in the bottom of the tank. Furthermore, the velocity and turbulent kinetic energy in the DRFTBI system were promoted. In addition, for an optimal selection, the optimum length of connection strap was 1.2 H1, the optimum range of connection strap width was D/7–D/8, and the off-bottom clearance selected as T/4 was better

High-Entropy Design Toward Ultrahigh Energy Storage Density Under Moderate Electric Field in Bulk Lead-Free Ceramics

Electrostatic capacitors with ultrahigh energy-storage density are crucial for the miniaturization of pulsed power devices. A long-standing challenge is developing dielectric materials that achieve ultrahigh recoverable energy density Wrec ≥ 10 J cm−3 under moderate electric fields (30 ≤ E ≤ 50 kV mm−1). Herein, a specific high-entropy strategy is proposed to modulate the phase structure and interfacial polarization of medium-entropy base materials using linear dielectrics. This strategy ensures a sufficient polar phase and a high enough electric field for complete polarization, thereby achieving ultrahigh Wrec by enhancing polarization strength. The validity of this strategy is demonstrated in the (Na0.282Bi0.282Ba0.036Sr0.28Nd0.08)TiO3-xCa0.7Bi0.2TiO3 (NBBSNT-xCBT) (x = 0–0.15) system. The CBT-modulated samples exhibit a polyphase structure of R3c, P4bm, and Pm-3m with reduced remnant polarization (Pr). Additionally, the addition of CBT effectively suppresses interfacial polarization, enhancing the maximum polarization (Pmax). These factors significantly improve the value of ∆P = Pmax − Pr. As a result, an ultrahigh Wrec of 10.5 J cm−3 with a high-efficiency η of 80.3% is obtained in the x = 0.1 sample under a moderate electric field of 45 kV mm−1 for the first time. This work paves the way for achieving superior energy-storage performance under moderate electric fields

Geological, geochemical and sulfur isotopic characteristics of critical metal-enriched pyritic ore in the Puyi area, northwest Guizhou Province: Constraints on the genesis of the deposit

The study of the isotopic and elemental geochemical characteristics and genesis of critical metal-enriched pyritic ore in the Puyi area of Northwest Guizhou provides more abundant information for the exploitation of pyritic ore resources, comprehensive utilization and evaluation of associated beneficial elements, and understanding the mechanism of critical metal-enriched pyritic ore. Based on the comprehensive collection of existing geological and mineral data, combined with field investigation, the geochemical characteristics and genesis of pyrite in this area are studied by using element geochemistry and sulfur isotope analysis, and the metallogenic model is preliminarily established. The study shows that the critical metal-enriched pyritic ore mainly occurs in the crystalline tuff at the bottom of the Longtan Formation of the middle Permian(P2l), and the ore body is simple in shape and distributed in layers. The beneficial elements, such as REEs, Li, Nb, Zr, Li, Nb, Zr, Ga, can be comprehensively utilized. The results show that ΣREE usually ranges from 180×10-6 to 1 630×10-6, with an average of 431.24×10-6 and up to 1 634.57×10-6; Ga usually ranges from 25×10-6 to 120×10-6, with an average of 32.51×10-6 and up to 120.00×10-6; Nd generally ranges from 40×10-6 to 380×10-6, with an average of 103.29×10-6 and up to 380.00×10-6; and the maximum values of Li and Al2O3 are 1 366.00×10-6 and 42.17%. The REE distribution pattern of pyritic ore is characterized by enrichment in LREEs and relative depletion in HREEs. The ore-forming elements Ga, Li, Zr, Ti, Se, Cd, Nb, V and Hg are relatively enriched, while Ba, Sr, Zn and Te are relatively depleted. The δ34S of pyrite in pyritic ore mainly range from -33.90‰ to -18.60‰(on average of -16.04‰), which shows the characteristics of the enrichment of light sulfur. The sulfur source of critical metal-enriched pyritic ore was greatly affected by the reduction of biological bacteria. Pyritic ore is mainly formed in the sedimentary stage by microbial iron reduction, microbial sulfate reduction and chemical iron reduction. It is suggested that REEs in pyritic ore mainly occur in clay minerals in the form of similar isomorphic substitution, and the formation process can be divided into the weathering transportation stage, sedimentary mineralization stage and diagenetic epigenetic stage