Increased CD45RA+FoxP3low Regulatory T Cells with Impaired Suppressive Function in Patients with Systemic Lupus Erythematosus

BACKGROUND: The role of naturally occurring regulatory T cells (Treg) in the control of the development of systemic lupus erythematosus (SLE) has not been well defined. Therefore, we dissect the phenotypically heterogeneous CD4(+)FoxP3(+) T cells into subpopulations during the dynamic SLE development. METHODLOGY/PRINCIPAL FINDINGS: To evaluate the proliferative and suppressive capacities of different CD4(+) T cell subgroups between active SLE patients and healthy donors, we employed CD45RA and CD25 as surface markers and carboxyfluorescein diacetatesuccinimidyl ester (CFSE) dilution assay. In addition, multiplex cytokines expression in active SLE patients was assessed using Luminex assay. Here, we showed a significant increase in the frequency of CD45RA(+)FoxP3(low) naive Treg cells (nTreg cells) and CD45RA(-)FoxP3(low) (non-Treg) cells in patients with active SLE. In active SLE patients, the increased proportions of CD45RA(+)FoxP3(low) nTreg cells were positively correlated with the disease based on SLE disease activity index (SLEDAI) and the status of serum anti-dsDNA antibodies. We found that the surface marker combination of CD25(+)CD45RA(+) can be used to defined CD45RA(+)FoxP3(low) nTreg cells for functional assays, wherein nTreg cells from active SLE patients demonstrated defective suppression function. A significant correlation was observed between inflammatory cytokines, such as IL-6, IL-12 and TNFα, and the frequency of nTreg cells. Furthermore, the CD45RA(+)FoxP3(low) nTreg cell subset increased when cultured with SLE serum compared to healthy donor serum, suggesting that the elevated inflammatory cytokines of SLE serum may promote nTreg cell proliferation/expansion. CONCLUSIONS/SIGNIFICANCE: Our results indicate that impaired numbers of functional CD45RA(+)FoxP3(low) naive Treg cell and CD45RA(-)FoxP3(low) non-suppressive T cell subsets in inflammatory conditions may contribute to SLE development. Therefore, analysis of subsets of FoxP3(+) T cells, using a combination of FoxP3, CD25 and CD45RA, rather than whole FoxP3(+) T cells, will help us to better understand the pathogenesis of SLE and may lead to the development of new therapeutic strategies

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Tribology comparison of laser-cladded CrMnFeCoNi coatings reinforced by three types of ceramic (TiC/NbC/B4C)

In this study, three composite coatings were prepared by laser cladding, selecting the ceramic particles (B4C, TiC, or NbC), together with the powders of high-entropy alloy (HEA), i.e. CrMnFeCoNi. The results demonstrate that the composite coatings reinforced by varied carbides exhibited special microstructures, which lead to the features of micro-cutting wear, three-body wear, and fatigue wear, respectively. Therefore, the differences between the three composite coatings were compared, and evaluated in terms of phase structure, microstructure, chemical composition, nanoindentation, and phase interface correlation. Ultimately, the wear resistance mechanisms of selected ceramic particles reinforced HEA coatings were explained, and their applicability was estimated

Strain hardening and strengthening mechanism of laser melting deposition (LMD) additively manufactured FeCoCrNiAl0.5 high-entropy alloy

In order to develop the high-entropy alloy (HEA) with low cost and excellent mechanical properties for structural applications, the FeCoCrNiAl0.5 HEA has been fabricated by laser melting deposition, one of the advanced additive manufacturing methods. Strain hardening behaviour has been analysed and discussed using the combination of characterisation techniques. The LMD-ed FeCoCrNiAl0.5 had a true yield strength and strain of ∼463 MPa and 2.94%. Also, the true tensile strength of the LMD-ed FeCoCrNiAl0.5 reached 876 MPa, together with the ductility of 24.97% (engineering strain). The LMD-ed FeCoCrNiAl0.5 HEA exhibited a dual-phase structure of 93% face-centred cubic (FCC) phase and 6.9% ordered B2 phase. The phase boundary between the disordered FCC and ordered B2 phases played a key role in the barrier, which can block the movement of dislocations because of the lattice distortion, very large angle, and mismatch of the lattice. Dislocation pile-up and tangle caused the dislocation density near the phase boundaries to be higher than that in other areas, meanwhile, they further prevented the movement of dislocation under stress as they generated back stress, therefore LMD-ed FeCoCrNiAl0.5 HEA had a good strain hardening behaviour with a strain hardening exponent of 0.92. This study provided an innovative insight into the development of HEAs with ordered phase by laser additive manufacturing for structural applications

Strain hardening and strengthening mechanism of laser melting deposition (LMD) additively manufactured FeCoCrNiAl0.5 high-entropy alloy

In order to develop the high-entropy alloy (HEA) with low cost and excellent mechanical properties for structural applications, the FeCoCrNiAl0.5 HEA has been fabricated by laser melting deposition, one of the advanced additive manufacturing methods. Strain hardening behaviour has been analysed and discussed using the combination of characterisation techniques. The LMD-ed FeCoCrNiAl0.5 had a true yield strength and strain of ∼463 MPa and 2.94%. Also, the true tensile strength of the LMD-ed FeCoCrNiAl0.5 reached 876 MPa, together with the ductility of 24.97% (engineering strain). The LMD-ed FeCoCrNiAl0.5 HEA exhibited a dual-phase structure of 93% face-centred cubic (FCC) phase and 6.9% ordered B2 phase. The phase boundary between the disordered FCC and ordered B2 phases played a key role in the barrier, which can block the movement of dislocations because of the lattice distortion, very large angle, and mismatch of the lattice. Dislocation pile-up and tangle caused the dislocation density near the phase boundaries to be higher than that in other areas, meanwhile, they further prevented the movement of dislocation under stress as they generated back stress, therefore LMD-ed FeCoCrNiAl0.5 HEA had a good strain hardening behaviour with a strain hardening exponent of 0.92. This study provided an innovative insight into the development of HEAs with ordered phase by laser additive manufacturing for structural applications

A novel polyomavirus from the nasal cavity of a giant panda (Ailuropoda melanoleuca)

Abstract Background Polyomaviruses infect a wide variety of mammalian and avian hosts with a broad spectrum of outcomes including asymptomatic infection, acute systemic disease, and tumor induction. Methods Viral metagenomics and general PCR methods were used to detected viral nucleic acid in the samples from a diseased and healthy giant pandas. Results A novel polyomavirus, the giant panda polyomavirus 1 (GPPyV1) from the nasal cavity of a dead giant panda (Ailuropoda melanoleuca) was characterized. The GPPyV1 genome is 5144 bp in size and reveals five putative open-reading frames coding for the classic small and large T antigens in the early region, and the VP1, VP2 and VP3 capsid proteins in the late region. Phylogenetic analyses of the large T antigen of the GPPyV1 indicated GPPyV1 belonged to a putative new species within genus Deltapolyomavirus, clustering with four human polyomavirus species. The GPPyV1 VP1 and VP2 clustered with genus Alphapolyomavirus. Our epidemiologic study indicated that this novel polyomavirus was also detected in nasal swabs and fecal samples collected from captive healthy giant pandas. Conclusion A novel polyomavirus was detected in giant pandas and its complete genome was characterized, which may cause latency infection in giant pandas