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Previous studies have revealed that the infectious scrapie isoform of prion protein (PrPSc) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrPSc-seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Here we report that in transgenic (Tg) mice expressing hamster cellular prion protein (PrPC) infected with the 263K prion, the prion-seeding activity becomes undetectable in the skin tissues of TC-5RW-treated Tg mice by both sPMCA and RT-QuIC assays, whereas such prion-seeding activity is readily detectable in the skin of untreated mice. Notably, TC-5RW exhibits an inhibitory effect on the in vitro amplification of PrPSc in both skin and brain tissues by sPMCA and RT-QuIC. Moreover, we reveal that TC-5RW is able to directly decrease protease-resistant PrPSc and inhibit the seeding activity of PrPSc from chronic wasting disease and various human prion diseases. Our results suggest that the level of prion-seeding activity in the skin may serve as a useful biomarker for assessing the therapeutic efficacy of compounds in a clinical trial of prion diseases and that TC-5RW may have the potential for the prevention/treatment of human prion diseases.

Solid-state diffusion bonding (DB) of TiAl alloy and Ti2AlNb alloy was carried out using pure Ti as an interlayer at 1000 °C under 20 MPa for 60–120 min. The effects of bonding times on the interfacial microstructure and mechanical performance of the TiAl/Ti/Ti2AlNb bonded joints at room temperature (RT) were investigated detailly. The results demonstrated that the diffusion layers (DLs) mainly consisted of four characteristic layers, (I) single coarse α2 phase adjacent TiAl alloy, (II) single refined α2 phase at the bonding interface, (III) equiaxed/acicular α2 phase embedded in β phase adjacent Ti2AlNb alloy and (IV) both equiaxed α2 phase and acicular O phase embedded in β phase adjacent Ti2AlNb alloy, respectively. The thickness of the four layers increased with the increasing of the bonding time. The growth of DLs is controlled by diffusion and the reaction rate constant k for region I, II, III and IV are 1.22 × 10−6, 1.27 × 10−6, 2.6 × 10−7 and 7.7 × 10−7 m·s−1/2, respectively. Meanwhile, the interface α2 grain grows up without texture. The maximum tensile strength of 281 MPa was maintained at 1000 °C for 90 min under the pressure of 20 MPa. Consequently, the phase transformation and dynamic recrystallization behavior of the DLs were discussed.

Genetic Creutzfeldt-Jakob disease (gCJD) accounts for approximately 10–15% of human prion diseases. It is an autosomal dominant disease caused by missense or insertion mutations of the gene that encodes prion protein (PRNP). In general, the manifestations and neuropathological changes of gCJD are similar to those of sporadic CJD (sCJD), and the diagnostic sensitivities of cerebrospinal fluid (CSF) markers, electroencephalography (EEG), and magnetic resonance imaging (MRI) are generally lower in gCJD than sCJD. Here we report on a 56-year-old Chinese woman who was diagnosed with gCJD and suspected to have thyroid cancer. The patient carried the glutamate to alanine substitution at codon 196 (E196A) of PRNP, which is quite a rare mutation and has only been reported in China. To our knowledge, this is the fourth case of E196A gCJD in the world. Here, we compared the manifestations and assistant examinations of the current patient with those of three previously reported Chinese patients with E196A gCJD in order to illustrate the common features of E196A gCJD.

Alteration in cellular prion protein (PrPC) localization on the cell surface through mediation of the glycosylphosphatidylinositol (GPI) anchor has been reported to dramatically affect the formation and infectivity of its pathological isoform (PrPSc). A patient with Gerstmann-Sträussler-Scheinker (GSS) syndrome was previously found to have a nonsense heterozygous PrP-Q227X mutation resulting in an anchorless PrP. However, the allelic origin of this anchorless PrPSc and cellular trafficking of PrPQ227X remain to be determined. Here, we show that PrPSc in the brain of this GSS patient is mainly composed of the mutant but not wild-type PrP (PrPWt), suggesting pathological PrPQ227X is incapable of recruiting PrPWt in vivo. This mutant anchorless protein, however, is able to recruit PrPWt from humanized transgenic mouse brain but not from autopsied human brain homogenates to produce a protease-resistant PrPSc-like form in vitro by protein misfolding cyclic amplification (PMCA). To further investigate the characteristics of this mutation, constructs expressing human PrPQ227X or PrPWt were transfected into neuroblastoma cells (M17). Fractionation of the M17 cells demonstrated that most PrPWt is recovered in the cell lysate fraction, while most of the mutant PrPQ227X is recovered in the medium fraction, consistent with the results obtained by immunofluorescence microscopy. Two-dimensional gel-electrophoresis and Western blotting showed that cellular PrPQ227X spots clustered at molecular weights of 22–25 kDa with an isoelectric point (pI) of 3.5–5.5, whereas protein spots from the medium are at 18–26 kDa with a pI of 7–10. Our findings suggest that the role of GPI anchor in prion propagation between the anchorless mutant PrP and wild-type PrP relies on the cellular distribution of the protein.

Post-bonded compression of TiAl/Ti2AlNb joint was conducted between deformation temperatures 950 °C and 1050 °C, with the strain rate range of 0.001 s−1–0.0001 s−1 and the height reduction of 50% in the present work. And the hot deformation behavior of the joint was investigated based on an analysis of the strain-stress curve, Arrhenius constitutive equation and processing map. The Arrhenius relationship (AR) and the parallel Arrhenius relationship (PAR) were established to describe the flow stress as a function of the strain rates and deformation temperatures. As a consequence, the average error between the AR and the PAR was only 1.1%, showing that the bonding interface has a feeble influence on the hot compression process of the joint. Moreover, an optimized processing map of the joint was constructed by overlaying the macro-instability map on the interfacial microstructure control region. The stability region of the joint was defined to this domain with the deformation temperature higher than 1050 °C and the strain rate lower than 0.0005 s−1. On balance, this work can be used to not only improve the hot working ability of the joint but also develop the interfacial microstructure of the joint.

Prion diseases are fatal neurodegenerative processes caused by the accumulation of the pathological prion protein, PrPSc . While pathological lesions are limited to the central nervous system (CNS), disease-specific proteins accumulate and replicate in secondary lymphoid organs prior to neuroinvasion, and their replication there depends on the abundance of cellular prion protein (PrPC ). PrPC is expressed in both central and peripheral lymphoid tissues, and up- or downregulates innate and adaptive immune responses. In addition to prion diseases, PrPC is also immunologically involved in other neurological disorders and infectious diseases, including Alzheimer's disease and human immunodeficiency virus infection. Herein, we summarize the expression and functions of PrPC in various immunocytes, as well as its immunological and pathological roles in neurodegeneration and infection.

Brittle compounds and large residual stresses are easily formed at the diffusion bonding (DB) joints of dissimilar intermetallic compounds, which will deteriorate the performance of the joints. In this study, in order to conduct an in-depth study of the strengthening mechanisms, the post-bonded heat treatment (PBHT) and post-bonded hot deformation (PBHD) were applied to the TiAl/Ti2AlNb DB joint. Comparative studies were implemented aiming to reveal the strengthening mechanisms and their influence on interfacial microstructure and mechanical properties. The experimental results indicated that the harmful intermetallic compound AlNb2 phase in the DB joint was eliminated by PBHT and PBHD. Meanwhile, the diffusion layers were changed from O + (AlNb2+α2) + (α2+β/B2+γ) three layers of DB joints to (α2+β/B2+O + Ti3NbAl2) + (α2+β/B2+γ) two layers of PBHD joint. Interestingly, the Ti3NbAl2 phase was first found in the DB joint after PBHD. After testing, the tensile strength and the relative tensile strength (defined as the tensile strength ratio of the joint and the TiAl alloy) of samples increased by 272.54 MPa and 39.2% after PBHD, respectively. In comparison, the tensile strength and the relative tensile strength of samples increased by 75.96 MPa and 10.96% after PBHT. This demonstrated that PBHD could induce the formation and uniform dispersion of the Ti3NbAl2 phase, which is indispensable to improve the tensile strength of the TiAl/Ti2AlNb DB joint.