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Background: The vibration isolation platform (VIP) can greatly reduce the risk of damage to dynamic equipment caused by external vibration interference and provide the most stable and reliable working environment for dynamic equipment. Objective: Aiming at the problems of small vibration isolation dimension, low bearing capacity, serious motion coupling, and narrow vibration isolation bandwidth in the field of vibration isolation of dynamic load equipment, a hydraulic redundant six degrees of freedom parallel vibration isolation platform (PVIP) with active and passive composite vibration isolation support is proposed. Methods: The dynamic coupling model of active and passive hybrid vibration isolation (APHVI) of redundant PVIP is established, and the matrix diagonal decoupling control strategy and fuzzy PI control theory are combined. Analysis of passive vibration isolation performance and APHVI performance of VIP is done. Results: The simulation results show that the effect of APHVI based on fuzzy PI decoupling control is better than that of passive vibration isolation and matrix diagonal decoupling control. Conclusion: Fuzzy PI control can effectively attenuate more than 98 % of the disturbance, significantly improve the vibration isolation performance and decoupling effect of the platform, and expand the effective vibration isolation bandwidth.

On the basis of star-shaped core sandwich panel, a novel sandwich panel with petal-triangle core (SP-PSC) was proposed to improve the negative Poisson’s ratio (NPR) effect while retaining the characteristics of light weight and high strength. To study the complex structure more conveniently and quickly, a variational asymptotic method-based equivalent two-dimensional model (2D-EPM) was developed. The accuracy and efficiency of 2D-EPM were verified by the three-point bending experiment data and the 3D FE model results under different boundary and load conditions. The effects of the geometric parameters on the equivalent stiffness, buckling, natural frequency and NPR effect were also investigated. To increase the NPR of SP-PSC, the material of facesheet was changed from isotropic material to unidirectional CFPR material, and the influence of the material anisotropy on the NPR effect of SP-PSC was investigated. It is found that the NPR of SP-PSC increased first and then decreased with the increase in the fiber angle, reaching the maximum value at 40–50∘. At the same time, this law is applicable to SP-PSC with different material or geometric parameters. Finally, two improved cores, petal star-triangular core with X-shaped ligaments (PSC-X) and double-arc star-shaped core (DSC), were proposed and compared with SP-PSC in equivalent stiffness and recovered local fields to demonstrate their advantages. Compared with the original plate, the stress concentration and equivalent stiffness of the two improved PSCs significantly improved.

Due to their complex microstructures, the research on the static and dynamic behaviors of triangular honeycomb sandwich panels (triangular HSPs) is limited. In this study, the effective plate properties of triangular HSP was obtained by the homogenizing of the unit cell, and then the input to a VAM-based two-dimensional equivalent plate model (2D-EPM) to perform static and dynamic analyses. The accuracy of the proposed model for predicting the equivalent stiffness of the triangular HSP was verified by three-point bending experiments of 3D-printed specimens. Then, the static displacement, global buckling, and free vibrations predicted by 2D-EPM were verified with the results from three-dimensional finite element model simulations under various boundary conditions. The influences of structural parameters (including angle, core wall thickness, and cell side length of the unit cell) on the static and dynamic characteristics of triangular HSPs were also investigated, which can provide a useful tool for the modeling and evaluation of triangular HSPs under different conditions.

Hippo/YAP pathway plays an essential role in cell proliferation, tissue regeneration, and tumorigenesis. The emerging evidence shows that hyperactivation of the Hippo/YAP pathway induces metastasis, chemoresistance, and the attribute of cancer stem cells. Dysregulated Hippo/YAP pathway can be a dominant driver of mesothelioma, meningioma, and schwannoma. It has been reported that Hippo/YAP oncogenic activation in mesothelioma is driven by NF2 loss function. In addition, it contributes to 10% of all cancers, including lung, gastric, colon, cervical, ovarian, breast, melanoma, hepatocellular, and squamous cell carcinoma. Despite the urgent need to develop a therapeutic strategy to curb the dysregulated pathway, YAP/TAZ is difficult to be directly targeted with small molecule inhibitors because of the lack of a catalytic niche. TEADs require auto-palmitoylation to become functional. Therefore, small molecules that target palmitoylation of TEAD have been explored and VT3989 (NCT04665206) and IK-930 (NCT05228015) have success to enter the clinical trials. To target cancers with dysregulated Hippo/Yap pathway, we have discovered and are developing TY-0584, which is a potent and orally available YAP/TEAD inhibitor in the IND enabling stage. The results of PK and toxicity studies of TY-0584 showed a favorable safety profile. TY-0584 had excellent efficacy in the malignant mesothelioma H226 CDX mouse model, which is driven by NF2 deletion mutation. TY-0584 treatment also demonstrated good efficacy in the head and neck cancer PDX tumor mouse model. In previous studies, Hippo/Yap signaling promotes drug resistance to EGFR-targeted therapies in non-small cell lung cancer (NSCLC). To relax the YAP resistance mechanism in EGFR treatment, we asked if combined YAP inhibition grants an extension of responses to EGFR therapy. To this end, we treated EGFR-driven NSCLC cell models with TY-0584 and TY-9591. TY-9591 is a third-generation EGFR inhibitor developed by TYK Medicines and is currently under a pivotal Phase III clinical investigation in China (NCT05382728). The results show that the combination treatment not only offers synergistic effects, but also enhances apoptosis, compared to single drug treatment. Our in vivo data further underscores this exciting finding. Our studies showed that TY-9591 had excellent efficacy in the PC9 CDX mouse model, but tumors gradually recurred as many targeted cancer therapies did. In line with the results of the in-vitro experiments, another YAP/TEAD inhibitor TY-0536 in combination with TY-9591 significantly delay the tumor regrowth in the PC9 CDX mouse model. In summary, we identified a potent and orally available YAP/TEAD inhibitor TY-0584 which is a promising candidate for further clinical validation. [Shengli Dong and Apeng Liang contributed equally to this work. Jun Li, Shengli Dong, and Apeng Liang are the corresponding authors.] Citation Format: Apeng Liang, Shengli Dong, Guangbin Liu, Zhengfei Guo, Meihua Li, Shuaibo Han, Yundi Cao, Yian Tu, Chao Zhou, Yu Yu, Linglin Xiao, Wei Huang, Xinlong Yang, Lian Fang, Haoyun Li, Chengshan Niu, Mingyu Jiang, Feng Xing, Shaoqing Chen, Jun Li, Yusheng Wu. TY-0584: A potent, orally available small molecule YAP/TEAD inhibitor, exhibits anti-tumor effects in vitro and in vivo. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4491.

Black shale ore contains rich strategic metal resources such as vanadium, nickel, and molybdenum, but due to its complex composition, it is currently only used in the vanadium extraction industry. Metals such as nickel and molybdenum have not been effectively recovered, resulting in environmental pollution and resource waste. Using mineralogical features and a combination of beneficiation and metallurgy-based tests, the present work carried out feasibility studies of the combined beneficiation and metallurgy processes. The mineralogical features of the stone coal sample were studied using chemical analysis, an automatic mineral analyzer (BPMA), etc., and we identified the main phase composition, embedded characteristics, and particle size distribution of the associated strategic metals, vanadium, nickel, and molybdenum. The results showed that the grade of V2O5 in the stone coal was 1.29%, which was mainly present in carbonaceous clay and mica minerals. The nickel grade was 0.53%, mainly in the form of nickel–magnesium spinel and a small amount of nickel-containing magnesite. The stone coal contained 0.11% molybdenum; the mineral particles were fine, mostly in the form of molybdenite, and some were associated with carbonaceous matter and carbonaceous clay minerals. Based on the mineralogical feature, we proposed using the scrubbing–desliming and flotation process to enrich vanadium, nickel, and molybdenum. Our preliminary experiments obtained two products: vanadium–molybdenum-rich sludge and nickel-containing tailings. The V2O5 and molybdenum grades in the sludge were 4.10% and 0.44%, respectively, and the recovery was 41.31% and 51.40%, respectively. The nickel grade in the tailings was 1.49%. These products were roasted and leached. The vanadium, nickel, and molybdenum in the stone coal were effectively recovered through the beneficiation–metallurgy combination process, and the comprehensive utilization rate of the stone coal was improved.

Chalcocite-dominant secondary copper ore with a high pyrite content had a rapidly increased iron concentration in the middle and later periods of bioleaching, which increased the difficulty of separating copper and iron ions in the leaching solution. In the two aspects of microbial community succession and energy band theory, the selective dissolution mechanism of chalcocite in this type of copper ore was analyzed and illustrated using experiments and first-principles calculations. The results showed that controlling the solution potential at a lower level was beneficial to the selective leaching of chalcocite, while bacteria promoted the leaching of pyrite and chalcocite simultaneously by oxidizing Fe2+ to Fe3+ in the solution. Below 700 mV of solution potential, the bacterial community, mainly consisting of Acidithiobacillus and Sulfobacillus, had a stronger promotion on the selective dissolution of chalcocite. The solution energy level of bioleaching was higher than ideal pyrite but lower than ideal chalcocite, which resulted in the accumulation of electrons on the surface of pyrite and the formation of holes at the top of the chalcocite valence band. When bacteria assisted the oxidation of Fe2+ to Fe3+ and caused the raise of the solution potential, the difference between the solution energy level and the top of the pyrite valence band would be smaller than the width of the pyrite energy gap. Below 700 mV, the assistance of Acidithiobacillus and Sulfobacillus on the oxidation of Fe2+ was weak. Chalcocite would be selectively dissolved by oxygen and a small amount of Fe3+ in the solution. Because of the existence of Fe, Cu, and S vacancies in real minerals, the atomic activity in the Cu–S bond and the Fe–S bond enhanced, and the reaction difficulty between chalcocite, pyrite, and electron acceptors in the solution reduced. The solution potential should be controlled at 600 mV or less to ensure the selective dissolution of chalcocite.

This paper describes the performance tests for a high-viscosity asphalt mixture (HVAM) mixed with a newly developed high-viscosity asphalt (HVA) used for steel bridge deck pavement. Binder test results showed that the resistance to high-temperature rutting and low-temperature cracking of the HVA increased significantly compared to that of traditional asphalt binder and styrene-butadiene-styrene (SBS)-modified asphalt binder. Then stone mastic asphalt with this HVA was designed by Marshall Method and its engineering properties were investigated, and test results showed that HVAM has better fatigue performance and resistance against damage induced by temperature and moisture than that mixed with SBS-modified asphalt. Furthermore, dynamic modulus tests were performed on the HVAM and then master curves of the dynamic modulus and phase angle were constructed based on test results, which can be used for structure design of bridge deck paving. Application results proved the applicability of the HVAM as deck-pavi...

Asphalt rubber (AR) has been used worldwide in road engineering not only for improving the performance of asphalt mixtures but also for providing an advantage in environmental protection. Yet the application of AR is greatly restricted in China for its shortcoming of being only possible to be used in a gap or open gradation mixture to ensure stripping resistance as well as anti-rutting performance. Stabilised rubber modified asphalt (SRMA) with lower high-temperature viscosity and better store stability than traditional AR was developed in our previous research and has been widely applied in projects with good results. In this paper, to evaluate the validation of SRMA in dense mixtures, five kinds of dense mixtures commonly used in China were designed with SRMA as binder. Engineering properties, including high-temperature performance, low-temperature performance, moisture stability, fatigue performance and mechanical properties, including dynamic modulus and phase angle were laboratory evaluated and analy...

Summary Shigella species possess a type III secretion system (T3SS), which is required for human infection and that delivers effector proteins into target host cells. Here, we show that the effector, IpaH4.5 dampens the pro-inflammatory cytokine response. In both the Sereny test and a murine lung infection model, the Shigella ΔipaH4.5 mutant strain caused more severe inflammatory responses and significantly induced higher pro-inflammatory cytokine levels (MIP-2 and TNF-α) in the lung homogenates of wild type-infected mice. Moreover, there was a threefold decrease in bacterial colonization of the mutant compared with the WT and ΔipaH4.5/ipaH4.5-rescued strains. Yeast two-hybrid screening showed that IpaH4.5 specifically interacts with the p65 subunit of NF-κB. Ten truncated versions of IpaH4.5 and p65 spanning different regions were constructed and expressed to further map the IpaH binding sites with p65. The results revealed thatthe p65 region spanning amino acids 1–190 of p65 interacted with the IpaH4.5/1–293 N-terminal region. In vitro, IpaH4.5 displayed ubiquitin ligase activity towards ubiquitin and p65. Furthermore, the transcriptional activity of NF-κB was shown to be inhibited by IpaH4.5 utilizing a dual-luciferase reporter gene detection system containing NF-κB promoter response elements. Thus, we conclude that the IpaH4.5 protein is an E3 ubiquitin ligase capable of directly regulating the host inflammatory response by inhibiting the NF-κB signalling pathway.

To prevent reflective cracking of asphalt pavement in the Xinjiang Uygur Autonomous Region, stabilized rubber modified asphalt (SRMA) was developed with Karamay No. 90 petroleum asphalt and Kuqa No. 60 petroleum asphalt. Lab test results show better storage stability and workable performance than traditional asphalt rubber (AR), and similar performance with styrene butadiene styrene (SBS) modified asphalt commonly used in Xinjiang. A sand anti-fracture (SAF) mixture was designed with developed SRMA as a stress-absorbing membrane interlayer (SAMI) of asphalt pavement. Engineering properties - including high-temperature performance, low-temperature performance, moisture stability and fatigue performance, and mechanical properties - were laboratory evaluated and analyzed. Results show good performance of SAF mixture with SRMA as SAMI. SAF mixture with SRMA designed in this paper has been applied as SAMI in expressway construction engineering of Xinjiang in 2013, and the long-term performance is still been under observation.

Shigella species possess a type III secretion system (T3SS), which is required for human infection and that delivers effector proteins into target host cells. Here, we show that the effector, IpaH4.5 dampens the pro-inflammatory cytokine response. In both the Sereny test and a murine lung infection model, the Shigella ΔipaH4.5 mutant strain caused more severe inflammatory responses and significantly induced higher pro-inflammatory cytokine levels (MIP-2 and TNF-α) in the lung homogenates of wild type-infected mice. Moreover, there was a threefold decrease in bacterial colonization of the mutant compared with the WT and ΔipaH4.5/ipaH4.5-rescued strains. Yeast two-hybrid screening showed that IpaH4.5 specifically interacts with the p65 subunit of NF-κB. Ten truncated versions of IpaH4.5 and p65 spanning different regions were constructed and expressed to further map the IpaH binding sites with p65. The results revealed thatthe p65 region spanning amino acids 1-190 of p65 interacted with the IpaH4.5/1-293 N-terminal region. In vitro, IpaH4.5 displayed ubiquitin ligase activity towards ubiquitin and p65. Furthermore, the transcriptional activity of NF-κB was shown to be inhibited by IpaH4.5 utilizing a dual-luciferase reporter gene detection system containing NF-κB promoter response elements. Thus, we conclude that the IpaH4.5 protein is an E3 ubiquitin ligase capable of directly regulating the host inflammatory response by inhibiting the NF-κB signalling pathway.