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A large number of SARS-related coronaviruses (SARSr-CoV) have been detected in horseshoe bats since 2005 in different areas of China. However, these bat SARSr-CoVs show sequence differences from SARS coronavirus (SARS-CoV) in different genes (S, ORF8, ORF3, etc) and are considered unlikely to represent the direct progenitor of SARS-CoV. Herein, we report the findings of our 5-year surveillance of SARSr-CoVs in a cave inhabited by multiple species of horseshoe bats in Yunnan Province, China. The full-length genomes of 11 newly discovered SARSr-CoV strains, together with our previous findings, reveals that the SARSr-CoVs circulating in this single location are highly diverse in the S gene, ORF3 and ORF8. Importantly, strains with high genetic similarity to SARS-CoV in the hypervariable N-terminal domain (NTD) and receptor-binding domain (RBD) of the S1 gene, the ORF3 and ORF8 region, respectively, were all discovered in this cave. In addition, we report the first discovery of bat SARSr-CoVs highly similar to human SARS-CoV in ORF3b and in the split ORF8a and 8b. Moreover, SARSr-CoV strains from this cave were more closely related to SARS-CoV in the non-structural protein genes ORF1a and 1b compared with those detected elsewhere. Recombination analysis shows evidence of frequent recombination events within the S gene and around the ORF8 between these SARSr-CoVs. We hypothesize that the direct progenitor of SARS-CoV may have originated after sequential recombination events between the precursors of these SARSr-CoVs. Cell entry studies demonstrated that three newly identified SARSr-CoVs with different S protein sequences are all able to use human ACE2 as the receptor, further exhibiting the close relationship between strains in this cave and SARS-CoV. This work provides new insights into the origin and evolution of SARS-CoV and highlights the necessity of preparedness for future emergence of SARS-like diseases.

The association between physical activity, sedentary behavior and health-related quality of life in children and adolescents has been mostly investigated in those young people with chronic disease conditions. No systematic review to date has synthesized the relationship between physical activity, sedentary behavior and health-related quality of life in the general healthy population of children and adolescents. The purpose of this study was to review systematically the existing literature that evaluated the relations between physical activity, sedentary behavior and health-related quality of life in the general population of children and adolescents. We conducted a computer search for English language literature from databases of MEDLINE, EMBASE, PSYCINFO and PubMed-related articles as well as the reference lists of existing literature between 1946 and the second week of January 2017 to retrieve eligible studies. We included the studies that assessed associations between physical activity and/or sedentary behavior and health-related quality of life among the general population of children and adolescents aged between 3-18 years. The study design included cross-sectional, longitudinal and health intervention studies. We excluded the studies that examined associations between physical activity, sedentary behavior and health-related quality of life among children and adolescents with specific chronic diseases, and other studies and reports including reviews, meta-analyses, study protocols, comments, letters, case reports and guidelines. We followed up the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement in the reporting of this review. The risk of bias of the primary studies was assessed by the Newcastle-Ottawa Scale. We synthesized the difference in health-related quality of life scores between different levels of physical activity and sedentary time. In total, 31 studies met the inclusion criteria and were synthesized in the review. Most of the included studies used a cross-sectional design (n = 21). There were six longitudinal studies and three school-based physical activity intervention studies. One study used both cross-sectional and longitudinal designs. We found that higher levels of physical activity were associated with better health-related quality of life and increased time of sedentary behavior was linked to lower health-related quality of life among children and adolescents. A dose-response relation between physical activity, sedentary behavior and health-related quality of life was observed in several studies suggesting that the higher frequency of physical activity or the less time being sedentary, the better the health-related quality of life. The findings in this study suggest that school health programs promoting active lifestyles among children and adolescents may contribute to the improvement of health-related quality of life. Future research is needed to extend studies on longitudinal relationships between physical activity, sedentary behavior and health-related quality of life, and on effects of physical activity interventions on health-related quality of life among children and youth.

The development of infrared photodetectors is mainly limited by the choice of available materials and the intricate crystal growth process. Moreover, thermally activated carriers in traditional III–V and II–VI semiconductors enforce low operating temperatures in the infrared photodetectors. Here we demonstrate infrared photodetection enabled by interlayer excitons (ILEs) generated between tungsten and hafnium disulfide, WS2/HfS2. The photodetector operates at room temperature and shows an even higher performance at higher temperatures owing to the large exciton binding energy and phonon-assisted optical transition. The unique band alignment in the WS2/HfS2 heterostructure allows interlayer bandgap tuning from the mid- to long-wave infrared spectrum. We postulate that the sizeable charge delocalization and ILE accumulation at the interface result in a greatly enhanced oscillator strength of the ILEs and a high responsivity of the photodetector. The sensitivity of ILEs to the thickness of two-dimensional materials and the external field provides an excellent platform to realize robust tunable room temperature infrared photodetectors.Formation of interlayer excitons with high oscillator strength in a WS2/HfS2 heterostructure enables the realization of high-responsivity room-temperature mid- and long-wavelength infrared photodetectors.

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.

Low-density compressible materials enable various applications but are often hindered by structure-derived fatigue failure, weak elasticity with slow recovery speed and large energy dissipation. Here we demonstrate a carbon material with microstructure-derived super-elasticity and high fatigue resistance achieved by designing a hierarchical lamellar architecture composed of thousands of microscale arches that serve as elastic units. The obtained monolithic carbon material can rebound a steel ball in spring-like fashion with fast recovery speed (∼580 mm s −1 ), and demonstrates complete recovery and small energy dissipation (∼0.2) in each compress-release cycle, even under 90% strain. Particularly, the material can maintain structural integrity after more than 10 6 cycles at 20% strain and 2.5 × 10 5 cycles at 50% strain. This structural material, although constructed using an intrinsically brittle carbon constituent, is simultaneously super-elastic, highly compressible and fatigue resistant to a degree even greater than that of previously reported compressible foams mainly made from more robust constituents. Low-density compressible materials often suffer from fatigue-induced failure or limited elasticity. Here, the authors create a hierarchical multi-arch carbon material that achieves high compressibility, superior elasticity and fatigue resistance simultaneously, inspired by properties of arches in daily life.

Circ-ITCH, a novel circRNA, was generated from several exons of itchy E3 ubiquitin protein ligase (ITCH). Recently, circ-ITCH has been demonstrated to be involved in cancer development. However, there have been few investigations on the specific role of circ-ITCH in glioma. In this study, we performed quantitative real-time polymerase chain reaction analysis and identified that circ-ITCH was significantly downregulated in glioma tissues and cell lines. The function assays showed that upregulation of circ-ITCH inhibited glioma cell proliferation and invasion in vitro as well as reduced cell growth in vivo. Moreover, miR-106a-5p was found serving as a target of circ-ITCH and miR-106a-5p mimics could reverse the inhibitory effect of circ-ITCH on glioma cell proliferation and invasion. We also revealed that circ-ITCH increased SASH1 expression by sponging miR-106a-5p in glioma cells. In addition, SASH1 downregulation could abrogate the suppressive effect of circ-ITCH on glioma progression. Taken together, our results suggested that circ-ITCH could suppress glioma cell proliferation and invasion via regulating the miR-106a-5p/SASH1 axis, elucidating a novel molecular target for glioma treatment.

Heat shock protein 60 (HSP60) is a chaperonin with essential functions for cell physiology and survival, and its expression correlates with prognosis in a number of malignancies. The aim of this study is to determine the relationship of HSP60 status with clinicopathological parameters and prognosis in gastric cancer. The levels of HSP60 and matrix metallopeptidase 9 (MMP-9) antigen was evaluated by immunohistochemistry in 223 gastric carcinoma samples. The association between HSP60 and MMP-9, clinicopathological parameters, and prognosis of gastric cancer was examined. The level of HSP60 protein was significantly associated with depth invasion, lymph node metastasis and stage of disease (all P<0.05). Both univariate and multivariate analyses revealed that HSP60 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (both P<0.05). Furthermore, HSP60 overexpression was associated with a poor prognosis in patients with advanced gastric cancer in different risk groups. Moreover, HSP60 was significantly correlated with MMP-9 among 223 gastric cancer tissues (P<0.001). Patients who had HSP60 overexpression, in which tumor cells displayed high invasiveness, had poor OS and shorter RFS. HSP60 plays an important role on tumor aggressiveness and prognosis, and may act as a promising target for prognostic prediction.

Plasticity is ubiquitous and plays a critical role in material deformation and damage; it inherently involves the atomistic length scale and picosecond time scale. A fundamental understanding of the elastic-plastic deformation transition, in particular, incipient plasticity, has been a grand challenge in high-pressure and high-strain-rate environments, impeded largely by experimental limitations on spatial and temporal resolution. Here, we report femtosecond MeV electron diffraction measurements visualizing the three-dimensional (3D) response of single-crystal aluminum to the ultrafast laser-induced compression. We capture lattice transitioning from a purely elastic to a plastically relaxed state within 5 ps, after reaching an elastic limit of ~25 GPa. Our results allow the direct determination of dislocation nucleation and transport that constitute the underlying defect kinetics of incipient plasticity. Large-scale molecular dynamics simulations show good agreement with the experiment and provide an atomic-level description of the dislocation-mediated plasticity. Understanding incipient plasticity has been experimentally limited by spatial and temporal resolution. Here the authors report ultra-fast, in situ electron diffraction measurement of dislocation defect dynamics in the early stage of plastic deformation in Al under laser-driven compression.

The survival of farmed fish can be threatened by incidence of Aeromonas hydrophila infection. In addition, gut infection may promote dysbiosis of gut flora and dysregulate immune response in gut-liver axis in teleost fish. The current study aimed to evaluate the pathogenesis of A. hydrophila on gut barrier breach and synchronized immune response in gut-liver axis of RCCs. RCCs were subjected to continuous anal-intubation with A. hydrophila . Midgut sections were stained with periodic acid-Schiff (PAS) and immune-related gene expressions and biochemical indices in gut-liver axis were investigated. The severe midgut injury was detected in RCC anal-intubated with A. hydrophila , along with atrophy of the midgut villi, and the expression levels of tight junction (TJ) genes were consistently lower than those of the control ( P < 0.05). Moreover, RCC receiving anal intubation with A. hydrophila showed the upregulation of pathological indices and immure genes in the midgut and liver. These findings demonstrated that gut infection with A. hydrophila can significantly disrupt epithelial permeability to exacerbate gut barrier breach and increase bacterial burdens in tissues as well as dysregulate immune response in gut-liver axis of RCC.

In this work, an innovative design model aimed at enhancing the efficacy of ground-state probabilistic logic with a binary energy landscape (GSPL-BEL) is presented. This model enables the direct conversion of conventional CMOS-based logic circuits into corresponding probabilistic graphical representations based on a given truth table. Compared to the conventional approach of solving the configuration of Ising model-basic probabilistic gates through linear programming, our model directly provides configuration parameters with embedded many-body interactions. For larger-scale probabilistic logic circuits, the GSPL-BEL model can fully utilize the dimensions of many-body interactions, achieving minimal node overhead while ensuring the simplest binary energy landscape and circumventing additional logic synthesis steps. To validate its effectiveness, hardware implementations of probabilistic logic gates were conducted. Probabilistic bits were introduced as Ising cells, and cascaded conventional XNOR gates along with passive resistor networks were precisely designed to realize many-body interactions. HSPICE circuit simulation results demonstrate that the probabilistic logic circuits designed based on this model can successfully operate in free, forward, and reverse modes, exhibiting the simplest binary probability distributions. For a 2-bit × 2-bit integer factorizer involving many-body interactions, compared to the logic synthesis approach, the GSPL-BEL model significantly reduces the number of consumed nodes, the solution space (in the free-run mode), and the number of energy levels from 12, 4096, and 9–8, 256, and 2, respectively. Our findings demonstrate the significant potential of the GSPL-BEL model in optimizing the structure and performance of probabilistic logic circuits, offering a new robust tool for the design and implementation of future probabilistic computing systems.