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Background Eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) display distinct patterns of inflammation. However, the pathogenic mechanisms underlying the heterogeneity of CRSwNP need further investigation. Objective To investigate local immunoglobulin E (IgE) production and phenotype of mast cells in eosinophilic and non-eosinophilic CRSwNP in Chinese. Methods Total and specific IgE levels were analyzed by means of the ImmunoCAP system. The molecular steps involved in class switch recombination to IgE were investigated using RT-PCR assays. Mast cell phenotypes, IgE- and high affinity IgE receptor (FcεRI)-positive cells, and allergen binding to specific IgE in sinonasal mucosa were determined by means of immunohistochemistry. Results Compared with controls and non-eosinophilic CRSwNP, local total IgE levels were increased, and local specific IgE to common aeroallergens was more frequently found, in Chinese eosinophilic CRSwNP independent of atopy and without significant association with Staphylococcus aureus enterotoxins. The ε germline gene transcript was also more frequently detected in eosinophilic CRSwNP. The number of IgE- and FcεRI-positive cells was increased in eosinophilic CRSwNP. Most IgE- and FcεRI-positive cells were mast cells. Dust mite antigens could bind to IgE on mast cells in situ. The number of mast cells positive for both tryptase and chymase and activated mast cells was increased in eosinophilic CRSwNP and the number of activated mast cells positively correlated with local IgE level, eotaxin-1 level, and eosinophil count in CRSwNP. Conclusions and Clinical Relevance The local IgE induced by common aeroallergens may mediate mast cell activation and contribute to subsequent eosinophilic inflammation in Chinese CRSwNP. This study offers a rationale for considering intervention strategies designed to target “local allergy” in eosinophilic CRSwNP.

Regulatory T cells (Tregs) are required to control immune responses and maintain homeostasis, but are a significant barrier to anti-tumor immunity 1 . Conversely, Treg instability, characterized by loss of the master transcription factor Foxp3 and acquisition of pro-inflammatory properties 2 , can promote autoimmunity and/or facilitate more effective tumor immunity 3 , 4 . A comprehensive understanding of the pathways that regulate Foxp3 could lead to more effective Treg therapies for autoimmune disease and cancer. Despite improved functional genetic tools that now allow for systematic interrogation, dissection of the gene regulatory programs that modulate Foxp3 expression has not yet been reported. In this study, we developed a CRISPR-based pooled screening platform for phenotypes in primary mouse Tregs and applied this technology to perform a targeted loss-of-function screen of ~490 nuclear factors to identify gene regulatory programs that promote or disrupt Foxp3 expression. We discovered several novel modulators including ubiquitin-specific peptidase 22 (Usp22) and ring finger protein 20 (Rnf20). Usp22, a member of the deubiquitination module of the SAGA chromatin modifying complex, was discovered to be a positive regulator that stabilized Foxp3 expression; whereas the screen suggested Rnf20, an E3 ubiquitin ligase, can serve as a negative regulator of Foxp3. Treg-specific ablation of Usp22 in mice reduced Foxp3 protein and created defects in their suppressive function that led to spontaneous autoimmunity but protected against tumor growth in multiple cancer models. Foxp3 destabilization in Usp22-deficient Tregs could be rescued by ablation of Rnf20, revealing a reciprocal ubiquitin switch in Tregs. These results reveal novel modulators of Foxp3 and demonstrate a screening method that can be broadly applied to discover new targets for Treg immunotherapies for cancer and autoimmune disease.

Nasal IL-4(+) TFH cells might be involved in local IgE production in eosinophilic nasal polyps.

Summary. AL (primary or immunoglobulin light chain) amyloidosis (AL) differs from myeloma per se in that tissue deposits of amyloid are found, typically in association with small numbers of clonal plasma cells producing l light chains, and also in that AL patients typically present with a predominantly dysfunctional organ-system. This constellation of features ± ®brillar deposits comprised of light chains, l light chain predominance, and organ-system tropism and dysfunction ± remains unexplained. Select patients with AL respond to haemopoietic stem cell transplantation (SCT) with clinical improvement and extended survival, particularly those who do not have cardiac involvement. In order to ascertain whether the organ-system tropism of AL was associated with immunoglublin light chain variable region (Ig V L ) germline gene utilization, we attempted to clone, sequence and assign germline donors to the clonal Ig V L genes of 62 AL patients, all of whom were treated with SCT. We succeeded in 39 cases, identifying clonal AL genes derived from donors of the lI (n 10), lII (n 5), lIII (n 6), lVI (n 11) and KI (n 7) subtypes. The majority of the donors (IGLV6S1, DPL5, DPL2, DPL23 and LFVK431) were genes that appear in the expressed repertoire <5% of the time, suggesting an intrinsic propensity to form amyloid under certain conditions. Patients whose clones derived from the lVI IGLV6S1 donor uniformly presented with dominant renal involvement while those with other V l or unknown donors often had dominant cardiac or other organ involvement, particularly patients whose clones derived from the lI DPL2 donor. In addition, both early (<3 months) and overall post-SCT survival were signi®cantly better in lVI IGLV6S1 patients compared to patients with other V l donors. These ®ndings indicate that there are important associations in AL amyloidosis among Ig V L gene utilization, organ-system tropism and post-SCT survival.

Recent studies in tumor immunology indicate that malignant cells frequently express normal testicular-specific proteins. Because these proteins show restricted normal tissue distribution, they are usually highly immunogenic and may be potential targets for immunotherapy. In the present study, we have used a pair of sequence-specific primers in reverse transcription-polymerase chain reaction (

Frequent oil spill accidents and leakage of organic solvent destroy aquatic ecosystems and threaten marine lives. Separation of the oily pollutant from water with material has long been treated as an effective and environmentally friendly solution. As a result, great efforts have been made to construct a material with high oil adsorption capacity, high oil−water separation efficiency, high oil−water selectivity, and superior recyclability. Surface chemical composition and surface topography are two key factors that determine the surface wettability and oil−water separation efficiency of a material. In this review, we summarize the popular oil−water separation materials during the past five years, including adsorption material, filtration material, and smart controllable special wettable separation material. Before that, a basic theory of surface specific wettability is introduced. The perspectives and challenges of each material are also highlighted.

Summary Graphdiyne (GDY) as an emerging 2D carbon-network nanomaterial possesses many fascinating properties that lead to numerous exciting applications, but the use of GDY and its derivatives in the antibacterial field has not yet been discovered. In this study, we first report on the use and evaluation of GDY and graphdiyne oxide (GDYO) as antibacterial agents and propose the antibacterial mechanisms of GDY-based nanomaterials. GDYO has been synthesized via the surface oxidation of GDY, and the antibacterial activity of GDYO has been compared with that of GDY through a series of antibacterial tests. Surprisingly, surface oxidation endowed inert GDY with superior antibacterial capability against two representative bacterial models: Escherichia coli and Staphylococcus aureus . Antibacterial mechanism experiments disclose that the antibacterial function of GDYO is a result of reactive oxygen species-dependent oxidation stress when a dispersed GDYO suspension has a direct contact with bacteria especially under visible light irradiation.