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Evolutionarily constrained regions (ECRs) are a hallmark for sites of critical importance for a protein’s structure or function. ECRs can be inferred by comparing the amino acid sequences from multiple protein homologs in the context of the evolutionary relationships that link the analyzed proteins. The compilation and analysis of the datasets required to infer ECRs, however, are time consuming and require skills in coding and bioinformatics, which can limit the use of ECR analysis in the biomedical community. Here, we developed Aminode, a user-friendly webtool for the routine and rapid inference of ECRs. Aminode is pre-loaded with the results of the analysis of the whole human proteome compared with proteomes from 62 additional vertebrate species. Profiles of the relative rates of amino acid substitution and ECR maps of human proteins are available for immediate search and download on the Aminode website. Aminode can also be used for custom analyses of protein families of interest. Interestingly, mapping of known missense variants shows great enrichment of pathogenic variants and depletion of non-pathogenic variants in Aminode-generated ECRs, suggesting that ECR analysis may help evaluate the potential pathogenicity of variants of unknown significance. Aminode is freely available at http://www.aminode.org.

We have performed three-dimensional dynamic simulations to study strain-driven morphological evolution and the formation of quantum structures on heteroepitaxial core--shell nanowire surfaces. Our simulations show that depending on geometric and material parameters, such as the radius of the wire, the thickness of the shell, and the mismatch strain, various surface morphologies including smooth core--shell nanowire surfaces, nanoring arrays, nanowire arrays, and ordered quantum dot arrays can be obtained by controlling initial surface configurations through prepatterning. It is also shown that these quantum structures may be trapped in a metastable state and may undergo a series of metastable state transitions during subsequent dynamic evolution. Our results identify possible pathways for fabrication of ordered quantum structures on the epitaxial core--shell nanowire surfaces and provide guidelines for achieving smooth core--shell structures.

Polydopamine (PDA), which is derived from marine mussels, has excellent potential in early diagnosis of diseases and targeted drug delivery owing to its good biocompatibility, biodegradability, and photothermal conversion. However, when used as a solid nanoparticle, the application of traditional PDA is restricted because of the low drug-loading and encapsulation efficiencies of hydrophobic drugs. Nevertheless, the emergence of mesoporous materials broaden our horizon. Mesoporous polydopamine (MPDA) has the characteristics of a porous structure, simple preparation process, low cost, high specific surface area, high light-to-heat conversion efficiency, and excellent biocompatibility, and therefore has gained considerable interest. This review provides an overview of the preparation methods and the latest applications of MPDA-based nanodrug delivery systems (chemotherapy combined with radiotherapy, photothermal therapy combined with chemotherapy, photothermal therapy combined with immunotherapy, photothermal therapy combined with photodynamic/chemodynamic therapy, and cancer theranostics). This review is expected to shed light on the multi-strategy antitumor therapy applications of MPDA-based nanodrug delivery systems. Graphical Abstract

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The toxicity of deoxynivalenol (DON) in healthy humans and animals has been extensively studied. However, whether the natural-low-dose DON is scatheless under unhealthy conditions, especially intestinal injury, is unknown. Infection of enterotoxigenic Escherichia coli (ETEC) is a classical intestinal injury model. In this study, we explored the effects of low-dose DON on intestinal injury induced by the ETEC infection and the underlying mechanism in piglets, mice, and IPEC-J2 monolayer cells. Results showed that significant growth slowdown, severe diarrhea, and intestinal damage, bacterial multiplication, and translocation were observed in the experimental group (low-dose DON, 0.75 mg/kg in feed for piglets, and 1 mg/kg body weight for mice, combined with the ETEC infection). Meanwhile, more aggressive intestinal inflammation and barrier dysfunction were observed in animals and IPEC-J2 monolayer cells. Higher expression levels of NLRP3 inflammasome and LC3B were observed in jejunum and IPEC-J2 in the experimental group. After treatment with NLRP3 or caspase1 inhibitors, excessive intestinal inflammation rather than barrier dysfunction in the experimental group was limited. CRISPR-Cas9-mediated knockout of LC3B alleviated intestinal inflammation and barrier dysfunction and also inhibited NLRP3 inflammasome. In conclusion, a low dose of DON aggravates intestinal inflammation and barrier dysfunction induced by the ETEC infection by activating macroautophagy and NLRP3 inflammasome.

As a large heterogeneous information infrastructure, space terrestrial coinformation network provides a reliable and effective services for all types of space-based users, aviation users, marine users and land-based users through satellite networks. However, the precious computing and storage resources of satellite nodes during the service life is not fully exploited, and the enormous potential of the space information network (SIN) needs to be tapped to provide personalized services to end users. In this paper, to improve the utilization of satellite node resources and better meet the real-time requirements of compute-intensive and delay-sensitive users, we propose the SIN fog service. SIN fog service is an extension of fog service paradigm. The visionary concept is to integrate the computing power of satellite network edge nodes, enabling a wide range of benefits, including enhanced computing power, decreased bandwidth, reduced latency and without the need to lay complex and expensive ground networks, which can be widely developed in location navigation, environmental detection, traffic management, anti-terrorism, etc. We present the architecture and a potential use case of the SIN fog service. Then we discuss several related key security and challenges and finally the anti-quantum and efficient mutual-authentication protocol is introduced.INDEX TERMS Space information network, fog service, architecture, security. I. INTRODUCTIONSpace information network (SIN) is a globally heterogeneous network that includes satellite backbones, high-altitude platforms, aircraft, terrestrial control stations, and ground communications equipment. With the rapid development of satellite communication and computing power in recent years, SIN has been able to provide a globally reliable communication network for communication equipment via satellite networks [1]. Currently, the delay from terrestrial communication equipment to its visible Low earth orbit (LEO) satellites can be reduced to 1 to 4 ms [2], which can meet the user's quality of service (QoS) requirement. Compared with the traditional communication network, SIN has the natural advantage and is not restricted by the region. Even if the communication equipment is not connected to the traditional mode of communication in the ocean, desert or mountain areas, reliable communication can be established through visible satellites. During the operation of the SIN, the built-in computing and storage modules of satellites canThe associate editor coordinating the review of this manuscript and approving it for publication was Jiafeng Xie.