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ABSTRACTLow thermal conductivity and excellent high-temperature stability make lanthanum zirconate (La2Zr2O7, LZO) a very promising material for high-temperature insulation applications. In this study, LZO porous ceramics with ultra-high porosity and an open-pore structure were prepared by the replica method using a polyurethane template. The flowability and coating quality of the ceramic slurry were optimized. When the dispersant content of the slurry was 0.6 wt% and the alcohol to water ratio was 1:1, the slurry had low surface tension and low viscosity, leading to good coating quality of the ceramic slurry on the sponge template. The pore size between hollow skeletons was 100–500 μm with the hollow structure of the skeletons forming secondary pores. LZO porous ceramics showed high porosity of 87.6%-96.0%, low thermal conductivity of 0.048–0.126 W/(m·K), and compressive strength of 0.13–0.74 MPa by adjusting the ceramic content. A high temperature insulation performance test showed that the temperature difference between the cold side and the hot side of the sample was over 1000°C, indicating the excellent thermal insulation properties of LZO porous ceramics. LZO porous ceramics had good high-temperature stability without sintering shrinkage at heat treatment temperatures below 1500°C.

Abstract E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.

α-SiAlON is a potential wave-transmittance material for radome materials, yet the comprehensive properties need to be improved. In this study, a series of SrxY0.5-xSi12-(m + n) Alm +nOnN16-n (x = 0.02, 0.04, 0.06, and 0.08) porous ceramics with porosities ranging from 44.15% to 58.62% were synthesized via tert-butanol gel-casting. The real part of the permittivity of porous ceramics was in the range of 3.13–4.18 (8.2–12.4 GHz) with over 70% wave transmittance in the thickness range of 5.5–9.5 mm. The thermal conductivity and flexural strength of porous ceramics were in the ranges of 1.063–1.703 W/(m·K) and 52.67–106.33 MPa, respectively. Compared with Y-α-SiAlON porous ceramics, the thermal insulation and mechanical properties of Sr/Y-α-SiAlON porous ceramics are improved without deteriorating wave transmittance properties. The results show that Sr/Y-α-SiAlON porous ceramics have the potential to be wave-transmittance materials by adjusting the wave transmittance, thermal insulation, and mechanical properties of α-SiAlON.

Abstract Stimulator of interferon gene (STING) is increasingly exploited for the potential in cancer immunotherapy, yet its mechanism of activation remains not fully understood. Herein, we designed a novel STING agonist, designated as HB3089 that exhibits robust and durable anti-tumor activity in tumor models across various cancer types. Cryo-EM analysis reveals that HB3089-bound human STING has structural changes similar to that of the STING mutant V147L, a constitutively activated mutant identified in patients with STING-associated vasculopathy with onset in infancy (SAVI). Both structures highlight the conformational changes of the transmembrane domain (TMD), but without the 180°-rotation of the ligand binding domain (LBD) previously shown to be required for STING activation. Further structure-based functional analysis confirmed a new STING activation mode shared by the agonist and the SAVI-related mutation, in which the connector linking the LBD and the TMD senses the activation signal and controls the conformational changes of the LBD and the TMD for STING activation. Together, our findings lead to a new working model for STING activation and open a new avenue for the rationale design of STING-targeted therapies either for cancer or autoimmune disorders.

The heat alternation and bending during the service process of the pipeline structure are the key issues affecting its residual strength. The nonuniform plastic deformation of its cross-section causes nonlinear damage to the structure, which makes it difficult to calculate the residual strength of the overall structure. This study proposed a novel variable-strength material damage model with damage accumulation, which achieved the coupling analysis of structural damage and material fatigue residual strength, making the structural strength of nonlinear damage cross-section computable. Based on this, a theoretical ultimate load model for nonlinear damage cross-section and a finite element analysis model for dynamic material strength with damage accumulation were established. The analysis was conducted on the repeated banding damage to coiled tubing. The results showed that the residual yield strength of nonlinear damaged coiled tubing showed a trend of first rapid decrease and then slow decrease with damage accumulation, and the tensile displacement showed an increasing trend with damage accumulation. The ultimate internal pressure strength of nonlinear damaged structures showed a similar downward trend to the yield strength. The nonlinear damage coupling analysis model proposed in this study has significant practical engineering application value.