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Various methods have been exploited to replicate nacre features into artificial structural materials with impressive structural and mechanical similarity. However, it is still very challenging to produce nacre-mimetics in three-dimensional bulk form, especially for further scale-up. Herein, we demonstrate that large-sized, three-dimensional bulk artificial nacre with comprehensive mimicry of the hierarchical structures and the toughening mechanisms of natural nacre can be facilely fabricated via a bottom-up assembly process based on laminating pre-fabricated two-dimensional nacre-mimetic films. By optimizing the hierarchical architecture from molecular level to macroscopic level, the mechanical performance of the artificial nacre is superior to that of natural nacre and many engineering materials. This bottom-up strategy has no size restriction or fundamental barrier for further scale-up, and can be easily extended to other material systems, opening an avenue for mass production of high-performance bulk nacre-mimetic structural materials in an efficient and cost-effective way for practical applications. Artificial materials that replicate the mechanical properties of nacre represent important structural materials, but are difficult to produce in bulk. Here, the authors exploit the bottom-up assembly of 2D nacre-mimetic films to fabricate 3D bulk artificial nacre with an optimized architecture and excellent mechanical properties.

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. The kinase exists in the forms of two complexes, mTORC1 and mTORC2, and it participates in cell growth, proliferation, metabolism, and survival. The kinase activity is closely related to the occurrence and development of multiple human diseases. Inhibitors of mTOR block critical pathways to produce antiviral, anti-inflammatory, antiproliferative and other effects, and they have been applied to research in cancer, inflammation, central nervous system diseases and viral infections. Existing mTOR inhibitors are commonly divided into mTOR allosteric inhibitors, ATP-competitive inhibitors and dual binding site inhibitors, according to their sites of action. In addition, there exist several dual-target mTOR inhibitors that target PI3K, histone deacetylases (HDAC) or ataxia telangiectasia mutated and Rad-3 related (ATR) kinases. This review focuses on the structure of mTOR protein and related signaling pathways as well as the structure and characteristics of various mTOR inhibitors. Non-rapalog allosteric inhibitors will open new directions for the development of new therapeutics specifically targeting mTORC1. The applications of ATP-competitive inhibitors in central nervous system diseases, viral infections and inflammation have laid the foundation for expanding the indications of mTOR inhibitors. Both dual-binding site inhibitors and dual-target inhibitors are beneficial in overcoming mTOR inhibitor resistance.

Extreme cavitation scenarios, such as water column separations in hydraulic systems during transient processes caused by large cavitation bubbles, can lead to catastrophic destruction. In the present paper, we study the onset criteria and dynamics of large cavitation bubbles in a tube. A new cavitation number $Ca_2 = {l^*}^{-1} Ca_0$ is proposed to describe the maximum length $L_{max}$ of the cavitation bubble, where $l^*$ is a non-dimensional length of the water column indicating its slenderness, and $Ca_0$ is the classic cavitation number. Combined with the onset criteria for acceleration-induced cavitation ($Ca_1<1$, Pan et al., Proc. Natl Acad. Sci. USA, vol. 114, 2017, pp. 8470–8474), we show that the occurrence of large cylindrical cavitation bubbles requires both $Ca_2<1$ and $Ca_1<1$ simultaneously. We also establish a Rayleigh-type model for the dynamics of large cavitation bubbles in a tube. The bubbles collapse at a finite end speed, and the time from the maximum bubble size to collapse is $T_c=\\sqrt {2}\\sqrt {lL_{max}}\\sqrt {{\\rho }/{p_\\infty }}$, where $l$ is the length of the water column, $L_{max}$ is the maximum bubble length, $\\rho$ is the liquid density and $p_{\\infty }$ is the reference pressure in the far field. The analytical results are validated against systematic experiments using a modified ‘tube-arrest’ apparatus, which can decouple acceleration and velocity. The results in the current work can guide design and operation of hydraulic systems encountering transient processes.

Watchman Nee (Ni Tuosheng, 1903–1972), one of the most prominent theologians in Republican China (1911–1949), developed a “spiritual theology” that is concentrated on the work of the Holy Spirit. This theological perspective shares parallels with Pentecostal-Charismatic theology. This paper examines Nee’s attitude toward Pentecostalism and the charismatic experience. First, based on his teaching of the three-stage work of the Holy Spirit, Nee argued that the inner guidance of the Holy Spirit was more important than any external manifestation and that the “baptism of the Holy Spirit” in the Pentecostal-Charismatic movement was not a personal experience that Christians should pursue. Second, in terms of subjective experience, Nee’s trichotomous view of human nature as consisting of spirit, soul, and body suggested that many charismatic experiences originate in the soul and need to be overcome. Third, concerning the spiritual world, Nee regarded as the work of evil spirits those charismatic experiences that occur in irrational and unconscious situations. Nee’s negative stance towards Pentecostalism and the charismatic experience serves as a means of distinguishing his spiritual theology from Pentecostalist-Charismatic movements. Both Nee’s theology and his church practices reveal a strong elitist element, in stark contrast to Pentecostalism.

Dormancy is a common survival strategy in plants to temporarily suspend visible growth under unsuitable conditions. The elaborate mechanism underlying bud break in perennial woody plants is gradually illustrated. Here, we identified a grape vine WRKY transcription factor, VvWRKY37 , which was highly expressed in dormant buds. It was particularly induced by the application of exogenous abscisic acid, and depressed on exposure to gibberellin and low temperature (4°C) stress at the transcript level. The yeast one-hybrid assay confirmed that VvWRKY37 had a transcriptional activity. Ectopic over-expression of VvWRKY37 significantly delayed bud break of transgenic poplar plants. As an ABA-inducible gene, VvWRKY37 also depressed the expression of ABA catabolic gene CYP707A s and enhanced the accumulation of endogenous ABA in transgenic poplar plants. The molecular pieces of evidence showed that VvWRKY37 preferentially recognized and bound W-box 5′-G/CATTGACT/C/G-3′ cis -element in vitro . Additionally, VvABI5 and VvABF2 acted as the upstream transcriptional activators of VvWRKY37 via protein-DNA interactions. Taken together, our findings provided valuable insights into a new regulatory mechanism of WRKY TF by which it modulates bud break through ABA-mediated signaling pathways.

Strain can have a dramatic effect on the properties of materials. Zhang et al. introduced a large strain in the material PbTiO 3 by growing it epitaxially in a composite with PbO. On the boundaries between the two materials, their normally different lattice constants were matched, giving rise to the strain. As a consequence, the films exhibited a very large electric polarization even in the absence of an electric field. The method may be applicable to generating other functional materials. Scence , this issue p. 494 Epitaxial growth of PbTiO 3 /PbO composite thin films gives rise to strain and a very large spontaneous polarization. Strain engineering has emerged as a powerful tool to enhance the performance of known functional materials. Here we demonstrate a general and practical method to obtain super-tetragonality and giant polarization using interphase strain. We use this method to create an out-of-plane–to–in-plane lattice parameter ratio of 1.238 in epitaxial composite thin films of tetragonal lead titanate (PbTiO 3 ), compared to 1.065 in bulk. These thin films with super-tetragonal structure possess a giant remanent polarization, 236.3 microcoulombs per square centimeter, which is almost twice the value of known ferroelectrics. The super-tetragonal phase is stable up to 725°C, compared to the bulk transition temperature of 490°C. The interphase-strain approach could enhance the physical properties of other functional materials.

Exploring the subsurface structure and stratification of Mars advances our understanding of Martian geology, hydrological evolution and palaeoclimatic changes, and has been a main task for past and continuing Mars exploration missions 1 – 10 . Utopia Planitia, the smooth plains of volcanic and sedimentary strata that infilled the Utopia impact crater, has been a prime target for such exploration as it is inferred to have hosted an ancient ocean on Mars 11 – 13 . However, 45 years have passed since Viking-2 provided ground-based detection results. Here we report an in situ ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia conducted by the Zhurong rover of the Tianwen-1 mission. A detailed subsurface image profile is constructed along the roughly 1,171 m traverse of the rover, showing an approximately 70-m-thick, multi-layered structure below a less than 10-m-thick regolith. Although alternative models deserve further scrutiny, the new radar image suggests the occurrence of episodic hydraulic flooding sedimentation that is interpreted to represent the basin infilling of Utopia Planitia during the Late Hesperian to Amazonian. While no direct evidence for the existence of liquid water was found within the radar detection depth range, we cannot rule out the presence of saline ice in the subsurface of the landing area. A ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia constructed a detailed subsurface image profile showing a roughly 70-m-thick, multi-layered structure below regolith.

Design concept evaluation is a huge challenge in the R&D stage of new product development. The information in the assessments often depends on the decision-makers’ individual preferences. However, sometimes the decision-makers cannot give precise and complete information because it is very difficult for them to be familiar with all the criteria. In this situation, an incomplete information decision-making matrix is established. In this paper, decision-making methods based on incomplete information are compared in the literature review. Incomplete information determination method using trust mechanism is proved as a proper way to solve this problem, and the missing information are computed based on the alternatives However, in design concept evaluation, experts commonly provide their preferences using linguistic words according to the different attributes. Hence, we propose a three-step Multiple Attributes Group Decision-making (MAGDM) method where the missing value are determined by attributes. In step one, a data repairing method is proposed based on trust theory. After that, in step two, a comprehensive weight determination method combining AHP and entropy is proposed to obtain the weight of index attributes. Finally, the Rough-TOPSIS method is applied in the design scheme ranking step. In the case study, the proposed method is implemented in a tourism product design process to show its effectiveness.

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe , Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.

Traditional methods for hydrochemical analyses are effective but less diversified, and are constrained to limited objects and conditions. Given their poor accuracy and reliability, they are often used in complement or combined with other methods to solve practical problems. Cluster analysis is a multivariate statistical technique that extracts useful information from complex data. It provides new ideas and approaches to hydrogeochemical analysis, especially for groundwater hydrochemical classification. Hierarchical cluster analysis is the most widely used method in cluster analysis. This study compared the advantages and disadvantages of six hierarchical cluster analysis methods and analyzed their objects, conditions, and scope of application. The six methods are: The single linkage, complete linkage, median linkage, centroid linkage, average linkage (including between-group linkage and within-group linkage), and Ward’s minimum-variance. Results showed that single linkage and complete linkage are unsuitable for complex practical conditions. Median and centroid linkages likely cause reversals in dendrograms. Average linkage is generally suitable for classification tasks with multiple samples and big data. However, Ward’s minimum-variance achieved better results for fewer samples and variables.