Human primary epidermal organoids enable modeling of dermatophyte infections

Technology of generating human epidermal derivatives with physiological relevance to in vivo epidermis is continuously investigated for improving their effects on modeling of human natural dermatological status in basic and clinical studies. Here, we report a method of robust establishment and expansion of human primary epidermal organoids (hPEOs) under a chemically defined condition. hPEOs reconstruct morphological, molecular, and functional features of human epidermis and can expand for 6 weeks. Remarkably, hPEOs are permissive for dermatophyte infections caused by Trichophyton Rubrum (T. rubrum). The T. rubrum infections on hPEOs reflect many aspects of known clinical pathological reactions and reveal that the repression on IL-1 signaling may contribute to chronic and recurrent infections with the slight inflammation caused by T. rubrum in human skin. Thus, our present study provides a new insight into the pathogenesis of T. rubrum infections and indicates that hPEOs are a potential ex vivo model for both basic studies of skin diseases and clinical studies of testing potential antifungal drugs.Subject terms: Skin stem cells, Infection     

Meta-analysis of the prevalence of Echinococcus in dogs in China from 2010 to 2019

BackgroundEchinococcosis (canine Echinococcus disease) is a neglected tropical disease that causes serious public harm. Dogs, as a terminal host of Echinococcus spp., are a key part of the Echinococcus epidemic. Echinococcosis spreads easily in humans and animals in some areas of China and it is therefore necessary to fully understand the prevalence of Echinococcus spp. in dogs.Methodology/Principal findingsPubMed, ScienceDirect, Chongqing VIP, China National Knowledge Infrastructure (CNKI), and WanFang databases were searched for relevant articles published in the past 10 years. A final total of 108 studies were included. The overall prevalence of Echinococcus spp. in dogs in China was 7.3%, with the highest point estimate found in sampling year 2015 (8.2%) and publication year 2015 (16.5%). Northwestern China (7.9%) had the highest infection rate in China. Qinghai Province (13.5%) showed the highest prevalence among the 11 provinces we included. We also found that geographical and climatic factors are related to the incidence of canine echinococcosis. We further investigated the source of heterogeneity by analysis of subgroups (sampling district, detection method, dog type, season, parasite species, medication, and study quality level).Conclusions/SignificanceOur research indicated that Echinococcus spp. were still prevalent in some areas in China. More localized prevention and control policies should be formulated, including improving drinking water hygiene and strengthening hygiene promotion. We recommend the rational use of anti-Echinococcus drugs. In addition, treatment of livestock offal and feces and improving the welfare of stray dogs may play an important role in reducing canine Echinococcus infections.     

Internalization of ferromagnetic nanowires by different living cells

The ability of living cells, either adherent or suspended, to internalize nickel nanowires is demonstrated for MC3T3-E1, UMR106-tumour and Marrow-Stromal cells. Nanowires were produced by electrodeposition, 20 μm long and 200 nm in diameter. Cell separation and manipulation was achieved for the three cell types. Applied magnetic field successfully oriented the internalized nanowires but no clear anisotropy is induced on the adherent cells. Nanowires tend to bind to cytoplasm metalloproteins and trigger lysosome reorganization around the nucleus. This work demonstrates the applications of nanowires in adherent and suspended cells for cell separation and manipulation, and further explore into their role in nanobiotechnology.     

Plant‐derived recombinant human serum transferrin demonstrates multiple functions

Human serum transferrin (hTf) is the major iron‐binding protein in human plasma, having a vital role in iron transport. Additionally, hTf has many other uses including antimicrobial functions and growth factor effects on mammalian cell proliferation and differentiation. The multitask nature of hTf makes it highly valuable for different therapeutic and commercial applications. However, the success of hTf in these applications is critically dependent on the availability of high‐quality hTf in large amounts. In this study, we have developed plants as a novel platform for the production of recombinant (r)hTf. We show here that transgenic plants are an efficient system for rhTf production, with a maximum accumulation of 0.25% total soluble protein (TSP) (or up to 33.5 μg/g fresh leaf weight). Furthermore, plant‐derived rhTf retains many of the biological activities synonymous with native hTf. In particular, rhTf reversibly binds iron in vitro, exhibits bacteriostatic activity, supports cell proliferation in serum‐free medium and can be internalized into mammalian cells in vitro. The success of this study validates the future application of plant rhTf in a variety of fields. Of particular interest is the use of plant rhTf as a novel carrier for cell‐specific or oral delivery of protein/peptide drugs for the treatment of human diseases such as diabetes. To demonstrate this hypothesis, we have additionally expressed an hTf fusion protein containing glucagon‐like peptide 1 (GLP‐1) or its derivative in plants. Here, we show that plant‐derived hTf‐GLP‐1 fusion proteins retain the ability to be internalized by mammalian cells when added to culture medium in vitro.     

Assessing Genome-Wide Statistical Significance for Large p Small n Problems

Assessing genome-wide statistical significance is an important issue in genetic studies. We describe a new resampling approach for determining the appropriate thresholds for statistical significance. Our simulation results demonstrate that the proposed approach accurately controls the genome-wide type I error rate even under the large p small n situations.     

Host sunflower-induced silencing of parasitism-related genes confers resistance to invading Orobanche cumana

Orobanche cumana is a holoparasitic plant that attaches to host–plant roots and seriously reduces the yield of sunflower (Helianthus annuus L.). Effective control methods are lacking with only a few known sources of genetic resistance. In this study, a seed-soak agroinoculation (SSA) method was established, and recombinant tobacco rattle virus vectors were constructed to express RNA interference (RNAi) inducers to cause virus-induced gene silencing (VIGS) in sunflower. A host target gene HaTubulin was systemically silenced in both leaf and root tissues by the SSA–VIGS approach. Trans-species silencing of O. cumana genes were confirmed for 10 out of 11 target genes with silencing efficiency of 23.43%–92.67%. Knockdown of target OcQR1, OcCKX5, and OcWRI1 genes reduced the haustoria number, and silencing of OcEXPA6 caused further phenotypic abnormalities such as shorter tubercles and necrosis. Overexpression of OcEXPA6 caused retarded root growth in alfalfa (Medicago sativa). The results demonstrate that these genes play an important role in the processes of O. cumana parasitism. High-throughput small RNA (sRNA) sequencing and bioinformatics analyses unveiled the distinct features of target gene-derived siRNAs in O. cumana such as siRNA transitivity, strand polarity, hotspot region, and 21/22-nt siRNA predominance, the latter of which was confirmed by Northern blot experiments. The possible RNAi mechanism is also discussed by analyzing RNAi machinery genes in O. cumana. Taken together, we established an efficient host-induced gene silencing technology for both functional genetics studies and potential control of O. cumana. The ease and effectiveness of this strategy could potentially be useful for other species provided they are amenable to SSA.

Knockdown of several parasitism-related genes endows sunflower with resistance to invading broomrape.