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Group B Streptococcus (GBS) remains the leading cause of neonatal meningitis, a disease associated with high rates of adverse neurological sequelae. The in vivo relationship between GBS and brain tissues remains poorly characterized, partly because past studies had focused on microbial rather than host processes. Additionally, the field has not capitalized on systems-level technologies to probe the host-pathogen relationship. Here, we use multiplexed quantitative proteomics to investigate the effect of GBS infection in the murine brain at various levels of tissue complexity, beginning with the whole organ and moving to brain vascular substructures. Infected whole brains showed classical signatures associated with the acute-phase response. In isolated brain microvessels, classical blood-brain barrier proteins were unaltered, but interferon signaling and leukocyte recruitment proteins were upregulated. The choroid plexus showed increases in peripheral immune cell proteins. Proteins that increased in abundance in the vasculature during GBS invasion were associated with major histocompatibility complex (MHC) class I antigen processing and endoplasmic reticulum dysfunction, a finding which correlated with altered host protein glycosylation profiles. Globally, there was low concordance between the infection proteome of whole brains and isolated vascular tissues. This report underscores the utility of unbiased, systems-scale analyses of functional tissue substructures for understanding disease.IMPORTANCE Group B Streptococcus (GBS) meningitis remains a major cause of poor health outcomes very early in life. Both the host-pathogen relationship leading to disease and the massive host response to infection contributing to these poor outcomes are orchestrated at the tissue and cell type levels. GBS meningitis is thought to result when bacteria present in the blood circumvent the selectively permeable vascular barriers that feed the brain. Additionally, tissue damage subsequent to bacterial invasion is mediated by inflammation and by immune cells from the periphery crossing the blood-brain barrier. Indeed, the vasculature plays a central role in disease processes occurring during GBS infection of the brain. Here, we employed quantitative proteomic analysis of brain vascular substructures during invasive GBS disease. We used the generated data to map molecular alterations associated with tissue perturbation, finding widespread intracellular dysfunction and punctuating the importance of investigations relegated to tissue type over the whole organ.

The commercialization of deep-sea mining has put forward strict requirements for ore collection output, ore collection efficiency, and environmental disturbance. However, the research of seafloor massive sulfide collection is in the initial stage. The influence of ore-collecting working parameters on the ore-collecting performance is not clear. In order to realize the commercial exploitation of deep-sea minerals, it is urgent to carry out the analysis and research on the influence of ore-collecting parameters on ore-collecting characteristics. The computational fluid dynamics-discrete element method is adopted in this paper to carry out numerical simulation research. Through the qualitative and quantitative analysis method, the influence law of six ore collecting parameters on ore collecting characteristics was analyzed. On this basis, the prediction model of ore-collecting characteristics and the optimal selection of ore-collecting parameters are proposed. Through the research, it is suggested to select 133.2 kg/s flow suction for ore collecting hard pipe; 60 rpm rotation speed is recommended for the mining head. It is recommended to select mining areas with the mineral density of 3000 kg/m3 for collection. The collection stage should be broken as far as possible to the 25 mm chip size. The recommended cutting depth is 224 mm if the strength and system metrics are met. The research of this paper provides a theoretical basis for the practice of deep-sea ore collection and has guiding significance for the selection of ore collection parameters, structural optimization design, and other engineering problems. [ABSTRACT FROM AUTHOR]

Humans can incorporate the xenoglycan N-glycolylneuraminic acid (Neu5Gc) from the diet into reproductive tissues and secretions. Most humans also have circulating antibodies specific for this dietary xenoglycan. The potential for inflammation induced by incorporated Neu5Gc and circulating anti-Neu5Gc antibodies, termed xenosialitis, has been discussed as a factor influencing several human diseases. Potential effects of xenosialitis on human fertility remain unknown. Here, we investigate possible adverse effects of the presence of Neu5Gc on sperm or endometrium combined with anti-Neu5Gc antibodies in semen or uterine secretions in a mouse model. We use Cmah(-/-) mice, humanized for Neu5Gc deficiency. We find that the viability, migration, and capacitation of sperm with incorporated Neu5Gc are negatively affected when these are exposed to anti-Neu5Gc antibodies. In addition, we find that after copulation, activated uterine neutrophils and macrophages show increased phagocytosis of sperm in the presence of anti-Neu5Gc antibodies via the complement receptor 3 (C3R) and Fcγ I/II/III (Fc receptor). Furthermore, Neu5Gc in endometrial cells combined with the presence of anti-Neu5Gc antibodies alters the receptivity and decidualization of endometrial explants. These studies provide mechanistic insights on how Neu5Gc on sperm and/or endometrium combined with anti-Neu5Gc antibodies in semen and uterine fluid might contribute to unexplained human infertility.

The intracellular chaperone heat-shock protein 70 (Hsp70) can be secreted from cells, but its extracellular role is unclear, as the protein has been reported to both activate and suppress the innate immune response. Potential immunomodulatory receptors on myelomonocytic lineage cells that bind extracellular Hsp70 are not well defined. Siglecs are Ig-superfamily lectins on mammalian leukocytes that recognize sialic acid-bearing glycans and thereby modulate immune responses. Siglec-5 and Siglec-14, expressed on monocytes and neutrophils, share identical ligand-binding domains but have opposing signaling functions. Based on phylogenetic analyses of these receptors, we predicted that endogenous sialic acid-independent ligands should exist. An unbiased screen revealed Hsp70 as a ligand for Siglec-5 and Siglec-14. Hsp70 stimulation through Siglec-5 delivers an anti-inflammatory signal, while stimulation through Siglec-14 is pro-inflammatory. The functional consequences of this interaction are also addressed in relation to a SIGLEC14 polymorphism found in humans. Our results demonstrate that an endogenous non-sialic acid-bearing molecule can be either a danger-associated or self-associated signal through paired Siglecs, and may explain seemingly contradictory prior reports on extracellular Hsp70 action.

Heparan sulfate proteoglycans (HSPGs) are an important constituent of the macrophage glycocalyx and extracellular microenvironment. To examine their role in atherogenesis, we inactivated the biosynthetic gene N-acetylglucosamine N-deacetylase-N-sulfotransferase 1 (Ndst1) in macrophages and crossbred the strain to Ldlr(-/-) mice. When placed on an atherogenic diet, Ldlr(-/-)Ndst1(f/f)LysMCre(+) mice had increased atherosclerotic plaque area and volume compared to Ldlr(-/-) mice. Diminished sulfation of heparan sulfate resulted in enhanced chemokine expression; increased macrophages in plaques; increased expression of ACAT2, a key enzyme in cholesterol ester storage; and increased foam cell conversion. Motif analysis of promoters of upregulated genes suggested increased type I interferon signaling, which was confirmed by elevation of STAT1 phosphorylation induced by IFN-β. The proinflammatory macrophages derived from Ndst1(f/f)LysMCre(+) mice also sensitized the animals to diet-induced obesity. We propose that macrophage HSPGs control basal activation of macrophages by maintaining type I interferon reception in a quiescent state through sequestration of IFN-β.

The deep‐sea six‐stage centrifugal pump is an essential power source of the lifting system that conveys slurry containing coarse particles. Emergency failure of the electric system can easily lead to pump blockage because of slurry reflux. The reflux movement of particles in a six‐stage pump under emergency power failure is investigated using the verified computation fluid dynamics and discrete element method (CFD‐DEM) simulation. The JKR contact model is used to perform particle simulation. Simultaneously, shaped particles are added to realistically simulate the reflux characteristics under deep‐sea mining conditions. The effect of particle size, shape, and size distribution in the reflux is investigated. The blockage behavior of the particles during reflux and the blockage mechanism is clarified. Particles with less shape and size below 30 mm are more conducive to safe slurry transportation. The experimental results verify the credibility of the CFD‐DEM simulation results. [ABSTRACT FROM AUTHOR]

This paper proposes a method that considers the bus net Fuzzy control strategy quickly and accurately for power. Due to the intermittent and fluctuating characteristics of distributed generation units in microgrid, the power quality will be reduced and the normal operation of microgrid will be affected. In this paper, empirical modal analysis fused with convolutional neural network algorithm is applied to the power control strategy of microgrid energy storage system to improve the economy and reliability of microgrid. The design process of the controller is analyzed, and fuzzy rules and membership functions are designed according to the effect requirements of the controller. Then, the center of gravity method is used to obtain the output power of the energy storage system. The simulation results show that the configuration scheme based on the optimization of the hybrid energy storage system in the whole life cycle in this paper not only ensures the stability of the energy storage system but also effectively avoids power fluctuations and stabilizes the peak shaving and valley filling rate. While improving the economy of the energy storage system, it also increases the service life of the energy storage system. [ABSTRACT FROM AUTHOR]