T-cell infiltration in the central nervous system and their association with brain calcification in Slc20a2-deficient mice

Primary familial brain calcification (PFBC) is a rare neurodegenerative and neuropsychiatric disorder characterized by bilateral symmetric intracranial calcification along the microvessels or inside neuronal cells in the basal ganglia, thalamus, and cerebellum. Slc20a2 homozygous (HO) knockout mice are the most commonly used model to simulate the brain calcification phenotype observed in human patients. However, the cellular and molecular mechanisms related to brain calcification, particularly at the early stage much prior to the emergence of brain calcification, remain largely unknown. In this study, we quantified the central nervous system (CNS)-infiltrating T-cells of different age groups of Slc20a2-HO and matched wild type mice and found CD45+CD3+ T-cells to be significantly increased in the brain parenchyma, even in the pre-calcification stage of 1-month-old -HO mice. The accumulation of the CD3+ T-cells appeared to be associated with the severity of brain calcification. Further immunophenotyping revealed that the two main subtypes that had increased in the brain were CD3+ CD4− CD8– and CD3+ CD4+ T-cells. The expression of endothelial cell (EC) adhesion molecules increased, while that of tight and adherents junction proteins decreased, providing the molecular precondition for T-cell recruitment to ECs and paracellular migration into the brain. The fusion of lymphocytes and EC membranes and transcellular migration of CD3-related gold particles were captured, suggesting enhancement of transcytosis in the brain ECs. Exogenous fluorescent tracers and endogenous IgG and albumin leakage also revealed an impairment of transcellular pathway in the ECs. FTY720 significantly alleviated brain calcification, probably by reducing T-cell infiltration, modulating neuroinflammation and ossification process, and enhancing the autophagy and phagocytosis of CNS-resident immune cells. This study clearly demonstrated CNS-infiltrating T-cells to be associated with the progression of brain calcification. Impairment of blood–brain barrier (BBB) permeability, which was closely related to T-cell invasion into the CNS, could be explained by the BBB alterations of an increase in the paracellular and transcellular pathways of brain ECs. FTY720 was found to be a potential drug to protect patients from PFBC-related lesions in the future

A heterozygous moth genome provides insights into herbivory and detoxification

How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al

Unravelling the 2e⁻ ORR Activity Induced by Distance Effect on Main-Group Metal InN₄ Surface Based on First Principles

The p-electron-dominated main-group metals (Sb, Se, In, etc.) have recently been reported to possess excellent oxygen reduction reaction (ORR) activity by means of heteroatom doping into graphene. However, on these main group metal surfaces, other approaches especially the distance effect to modulate catalytic activity are rarely involved. In this work, the origin of excellent 2e− ORR catalytic activity of graphene-supported InN4 moiety by tuning the distance between metallic In atoms is thoroughly investigated by employing the first-principles calculations. Our DFT calculations show that the 2e− ORR catalytic activity strongly depends on the crystal orbital Hamilton population (COHP) between In and O atoms. This work is useful for the rational design of main group metal single atom electrocatalysts

Influences of high aspect ratio carbon nanotube network on normal stress difference measurements and extrusion behaviors for isotactic polypropylene nanocomposite melts

We have investigated the role that representative nonequilibrium carbon nanotube (CNT) network structures play in the flow-induced property changes of relatively high aspect ratio CNT/isotactic polypropylene (iPP) nanocomposites. Stable CNT network can form in CNT/iPP nanocomposites at relatively low CNT contents due to the employment of high aspect ratio CNTs. As experimentally demonstrated and theoretically predicted by Kharchenko et al. (Nat. Mater., 2004), large apparent negative normal stress differences (Delta N) might occur in long CNT systems under some particular conditions, for example, which satisfy the condition that the CNT network is strong enough to accommodate appreciable rotational distortion. In this study, we focused on the measurements of normal stress differences to explore the particular conditions for appearance of negative Delta N. We find that the values of Delta N are immensely influenced by initial normal stresses induced by squeezing deformation during the sample loading. Large negative Delta N can be observed under the subsequent shear flow with zeroing the initial normal stresses in our high aspect ratio CNT/iPP nanocomposites only if the CNT content is above the CNT gelation concentration, which is consistent with the previous studies of Kharchenko et al. This interesting result about the measurements of Delta N is further confirmed by a die-shrinkage extrusion behavior and at the same time the effect of shape-distortion instability in the extrusion of neat iPP can be diminished in the CNT/iPP nanocomposites

Effects of Nanoparticles on the Antipullout Strength between the Reinforcement and Cement Mortar

Recently, the use of nanomaterials (i.e., Nano-Silica (NS) and Nano-SiC(NC)) to improve the mechanical properties and durability performances of cement-based materials has received considerable attention. This work presents the effects of nanoparticles (NS), the specimen size, and the water-reducing agent on the antipullout strength between the reinforcement and cement mortar on the basis of the laboratory antipullout tests. The mechanism is, then, validated by the microscopic analysis with Scanning Electron Microscopy (SEM). Results show that NS can accelerate the hydration reaction of cement, produce more Calcium Silicate Hydrate (CSH) gel, and increase the density of the cement mortar, thereby improving the microstructure and antipullout strength. The moderate NS (1.0%) is recommended to improve antipullout between the reinforcement and cement mortar. Besides, the specimen size and water-reducing agent have an obvious influence on the antipullout strength. These results would provide guidance on the design or construction of the cement mortar with reinforcement

Metabolomic variation in wild and cultured cordyceps and mycelia of Isaria cicadae

The article of record as published may be found at https://doi.org/10.1002/bmc.4478Isaria cicadae is one of the fungi used in traditional Chinese medicine with the longest tradition. It is used not only as a herbal medicine but also as a health food in Asia, together with cultured cordyceps and mycelia of the fungus used as substitute. However, the differences in their metabolite are unknown. Using a high‐performance liquid chromatography–mass spectrometry (HPLC–MS)‐based metabolomic method, we found that the fungus varies in its metabolism during growth on wild insects, artificially raised insects and artificial medium. There were 109 discriminatory metabolites detected in the samples by orthogonal projection to latent structure discriminant analysis and one‐way ANOVA. High level of nonribosomal peptides (NRPs) only existed in the insect portions of the wild cordyceps (WI) and cultured cordyceps (CI), revealing that immunostimulation of the host insects enhanced the synthesis of NRPs in the fungus. The finding of a signifi- cantly higher level of sphingolipids in both the insect portions (WI, CI) and the coremia of the wild cordyceps (WC) and cultured cordyceps (CC) but not in cultured mycelia (CM) of I. cicadae implies that the immunostimulation of the live insects can induce the fungus to produce more sphingolipids, and this enhanced ability is probably heritable. Apart from NRPs and sphingolipids, the insect portions also contained higher levels of bioactive compounds such as lateritin, anisomycin, streptimidone and ustiloxins. In contrast, the coremium groups (WC, CC) and CM contained 10‐fold less NRP but much higher levels of sanative metabolites such as tocotrienol, 3′‐deoxy‐ hanasanagin, γ‐aminobutyric acid and phospholipids than the insect portions. The significantly higher content of antioxidants in WC, CC and CM than in WI and CI suggests that environmental oxygen has a significant effect on the metabolites. The temperature stress which the wild cordyceps encounters during growth is responsible for the relatively high content of trehalose. These findings indicate that the immunity of the host insect and growth environment have a strong impact on the metabolomic variation in Isaria cicadae. The variation in metabolites suggests differential utilization value for the insect portions, coremia and mycelia of the fungus.National Natural Science Foundation of China, Grant/Award Numbers: 31471821 and 31570024; Natural Science Foundation of Anhui Province, Grant/Award Numbers: 1808085MC89 and KJ2015ZD21National Natural Science Foundation of China, Grant/Award Numbers: 31471821 and 31570024; Natural Science Foundation of Anhui Province, Grant/Award Numbers: 1808085MC89 and KJ2015ZD2