The search for new two-dimensional monolayers with diverse electronic properties has attracted growing interest in recent years. Here, we present an approach to construct MA2Z4 monolayers with a septuple-atomic-layer structure, that is, intercalating a MoS2-type monolayer MZ2 into an InSe-type monolayer A2Z2. We illustrate this unique strategy by means of first-principles calculations, which not only reproduce the structures of MoSi2N4 and MnBi2Te4 that were already experimentally synthesized, but also predict 72 compounds that are thermodynamically and dynamically stable. Such an intercalated architecture significantly reconstructs the band structures of the constituents MZ2 and A2Z2, leading to diverse electronic properties for MA2Z4, which can be classified according to the total number of valence electrons. The systems with 32 and 34 valence electrons are mostly semiconductors. Whereas, those with 33 valence electrons can be nonmagnetic metals or ferromagnetic semiconductors. In particular, we find that, among the predicted compounds, (Ca,Sr)Ga2Te4 are topologically nontrivial by both the standard density functional theory and hybrid functional calculations. While VSi2P4 is a ferromagnetic semiconductor and TaSi2N4 is a type-I Ising superconductor. Moreover, WSi2P4 is a direct gap semiconductor with peculiar spin-valley properties, which are robust against interlayer interactions. Our study thus provides an effective way of designing septuple-atomic-layer MA2Z4 with unusual electronic properties to draw immediate experimental interest.

This study aimed to investigate the protective effects of dietary glutamate and aspartate supplementations on diquat-induced oxidative stress in piglets. Diquat injection significantly reduced growth performance, including body weight, average daily weight gain, and feed intake (P<0.05). Meanwhile, diquat administration induced oxidative stress evidenced by the decreased serum nitric oxide (NO) and elevated malondialdeyhde (MDA) concentration (P<0.05). Furthermore, diquat-induced oxidative stress disrupted intestinal absorption system and decreased serum threonine, serine, and glycine levels. Dietary supplementation with glutamate improved final body weight, antioxidant system, and expressions of amino acids transporters and enhanced serum glutamate concentration compared with diquat group (P<0.05). While aspartate failed to alleviate diquat-induced oxidative stress, growth depression, and dysfunction of nutrients absorption except for liver relative weight. In conclusion, dietary supplementation with glutamate confers beneficial effects on diquat-induced oxidative stress in piglets, while aspartate exhibits little effects.

In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a fulllength cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis. The majority of individuals who develop acute viral hepatitis recover completely, and only a small fraction, less than one tenth of 1%, develop fulminant hepatic failure; why this occurs is not known.1 The fulminant form of the disease occurs at all ages of life and is not specific for any one viral type. The hallmark of the condition is the extreme rapidity of the necroinflammatory process resulting in widespread or total hepatocellular necrosis in weeks or even days; any satisfactory explanation must explain this rapid progression.A novel murine cDNA fgl2, encoding a protein with prothrombinase-like activity, was previously cloned in our laboratory.2 The sequence of the cDNA was essentially identical to a previously described sequence corresponding to a gene encoding a mouse fibrinogen-like protein, originally described as a cytotoxic T-cell-specific gene. When the cDNA containing the entire coding region was expressed in RAW 264.7 cells, a prothrombinase activity was detected by both a one-stage clotting assay and cleavage of 125 I-labeled prothrombin. Using a model of fulminant viral hepatitis, we demonstrated a causal relationship between the induction of fgl2 prothrombinase and the mortality of murine hepatitis virus infection (MHV-3). 3 We demonstrated that after MHV-3 infection in susceptible mice, mRNA transcripts of fgl2 were seen in macrophages and endothelial cells in the liver followed by fibrin deposition and liver necrosis. 4 The infusion of high-titered monoclonal antibodies to fgl2 prevented the coagulation disturbance, the hepatic necrosis, and mortality associated with MHV-3 infection. 5H...

Thrombosis is a prominent feature of acute vascular rejection (AVR), the current barrier to survival of pig-to-primate xenografts. Fibrinogen-like protein 2 (fgl2/fibroleukin) is an inducible prothrombinase that plays an important role in the pathogenesis of fibrin deposition during viral hepatitis and cytokine-induced fetal loss. We hypothesized that induction of fgl2 on the vascular endothelium of xenografts contributes to thrombosis associated with AVR. We first examined fgl2 as a source of procoagulant activity in the pig-to-primate combination. The porcine fgl2 (pfgl2) was cloned and its chromosomal locus was identified. Recombinant pfgl2 protein expressed in vitro was detected on the cell surface and generated thrombin from human prothrombin. Studies of pig-to-baboon kidney xenografts undergoing AVR in vivo revealed induction of pfgl2 expression on graft vascular endothelial cells (ECs). Cultured porcine ECs activated by human TNF-α in vitro demonstrated induction of pfgl2 expression and enhanced activation of human prothrombin. The availability of gene-targeted fgl2-deficient mice allowed the contribution of fgl2 to the pathogenesis of AVR to be directly examined in vivo. Hearts heterotopically transplanted from fgl2+/+ and fgl2+/− mice into Lewis rats developed AVR with intravascular thrombosis associated with induction of fgl2 in graft vascular ECs. In contrast, xenografts from fgl2−/− mice were devoid of thrombosis. These observations collectively suggest that induction of fgl2 on the vascular endothelium plays a role in the pathogenesis of AVR-associated thrombosis. Manipulation of fgl2, in combination with other interventions, may yield novel strategies by which to overcome AVR and extend xenograft survival.

Fine differences in the phosphorylation and acylation of lipooligosaccharide (LOS) from Neisseria species are thought to profoundly influence the virulence of the organisms and the innate immune responses of the host, such as signaling through toll-like receptor 4 (TLR4) and triggering receptor expressed on myeloid cells (TREM). MALDI time-of-flight (TOF) mass spectrometry was used to characterize heterogeneity in the native LOS from Neisseria gonorrheae and N. meningitidis. A sample preparation methodology previously reported for Escherichia coli lipopolysaccharide (LPS) employing deposition of untreated LOS on a thin layer of a film composed of 2,4,6-trihydroxyacetophenone and nitrocellulose was used. Prominent peaks were observed corresponding to molecular ions and to fragment ions primarily formed by cleavage between the 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) and the lipid A (LA). Analyses of these data and comparison with spectra of the corresponding Odeacylated or hydrogen fluoride-treated LOS enabled the detection of novel species that apparently differed by the expression of up to three phosphates with one or more phosphoethanolamine (PEA) groups on the LA. We found that the heterogeneity profile of acylation and phosphorylation correlates with the induction of proinflammatory cytokines in THP-1 monocytic cells. This methodology enabled us to rapidly profile components of structural variants of native LOS that are of importance biologically.-John, C. M., M. Liu, and G. A. Jarvis. Profiles of structural heterogeneity in native lipooligosaccharides of Neisseria and cytokine induction. J. Lipid Res. 2009. 50: 424-438. Supplementary key words lipooligosaccharideThe lipooligosaccharide (LOS) of Neisseria gonorrheae and N. meningitidis is structurally related to the lipopolysaccharide (LPS) of enteric Gram-negative bacteria but does not have repeating O-antigens (1). LOS and LPS have conserved inner cores composed of L-glycero-D-manno-heptose (Hep) and 3-deoxy-D -manno-oct-2-ulosonic acid (Kdo), which are anchored in the outer membrane by lipid A (LA). The structure of the LA of gonococci and meningococci, although based on a limited number of studies, generally differs from that of Escherichia coli in the acylation and the chain length of the fatty acid residues. With regard to phosphorylation, a limited number of studies have shown that gonococci and meningococci elaborate LOS containing a LA, which is phosphorylated with variable numbers of phosphate (P) and phosphoethanolamine (PEA) residues. The recent report of a PEA transferase specific for the LA on meningococcal LOS creates the possibility of phase variation in phosphorylation (2). Thus, the LA expressed by these organisms exhibit heterogeneity in acylation and phosphorylation, both of which have been shown to influence the endotoxicity in E. coli LPS (3).The innate immune response to bacterial pathogens relies on the detection of pathogen-associated molecular patterns by pattern recognition molecules. Toll-like receptor 4 (TLR4) is one of...

The discovery of topological quantum states marks a new chapter in both condensed matter physics and materials sciences. By analogy to spin electronic system, topological concepts have been extended into phonons, boosting the birth of topological phononics (TPs). Here, we present a high-throughput screening and data-driven approach to compute and evaluate TPs among over 10,000 real materials. We have discovered 5014 TP materials and grouped them into two main classes of Weyl and nodal-line (ring) TPs. We have clarified the physical mechanism for the occurrence of single Weyl, high degenerate Weyl, individual nodal-line (ring), nodal-link, nodal-chain, and nodal-net TPs in various materials and their mutual correlations. Among the phononic systems, we have predicted the hourglass nodal net TPs in TeO3, as well as the clean and single type-I Weyl TPs between the acoustic and optical branches in half-Heusler LiCaAs. In addition, we found that different types of TPs can coexist in many materials (such as ScZn). Their potential applications and experimental detections have been discussed. This work substantially increases the amount of TP materials, which enables an in-depth investigation of their structure-property relations and opens new avenues for future device design related to TPs.

We have previously shown that the lipooligosaccharide (LOS) from Neisseria meningitidis and N. gonorrhoeae engages the TLR4–MD-2 complex. In this study, we report that LOS from different meningococcal and gonococcal strains have different potencies to activate NF-κB through TLR4–MD-2 and that the relative activation can be correlated with ion abundances in MALDI-TOF mass spectrometry that are indicative of the number of phosphoryl substituents on the lipid A (LA) component of the LOS. The LOSs from three of the strains, meningococcal strain 89I and gonococcal strains 1291 and GC56, representing high, intermediate, and low potency on NF-κB activation, respectively, differently activated cytokine expression through the TLR4–MD-2 pathway in monocytes. In addition to induction of typical inflammatory cytokines such as TNF-α, IL-1β, and IL-6, MIP-1α and MIP-1β also were significantly higher in cells treated with 89I LOS, which had the most phosphoryl substitutions on the LA compared with 1291 LOS and GC56 LOS. We found that LOS activated both the MyD88- and TRIF-dependent pathways through NF-κB and IFN regulatory factor 3 transcription factors, respectively. Moreover, LOS induced the expression of costimulatory molecule CD80 on the surfaces of monocytes via upregulation of IFN regulatory factor 1. These results suggest that phosphoryl moieties of LA from N. meningitidis and N. gonorrhoeae LOSs play an important role in activation of both the MyD88- and TRIF-dependent pathways. Our findings are consistent with the concept that bacteria modulate pathogen-associated molecular patterns by expression of phosphoryl moieties on the LA to optimize interactions with the host.

Using a set of parental and recombinant murine hepatitis virus strains, we demonstrate that the nucleocapsid protein induces transcription of the novel fgl2 prothrombinase gene and elevated procoagulant activity in those strains that produce fulminant hepatitis. Chinese hamster ovary cells cotransfected with a construct expressing nucleocapsid protein from susceptible strains and with a luciferase reporter construct containing the fgl2 promoter showed a 6-fold increase in luciferase activity compared with nontransfected cells or cells cotransfected with a construct expressing nucleocapsid protein from resistant strains. Two deletions found at coding sites 111-123 and 1143-1145 of structural domains I and III, respectively, of the nucleocapsid gene may account for the differences between pathogenic and nonpathogenic strains. Preliminary mapping of the fgl2 promoter has defined a region from ؊372 to ؊306 upstream from the ATG translation initiation site to be responsive to nucleocapsid protein. Hence, mapping of genetic determinants in parental and recombinant strains demonstrates that the nucleocapsid protein of strains that induce fulminant hepatitis is responsible for transcription of the fgl2 prothrombinase gene. These studies provide new insights into the role of the nucleocapsid gene in the pathogenesis of viral hepatitis.