A strategy to reconstitute immunity without GVHD via adoptive allogeneic Tscm therapy

IntroductionAdoption of allogeneic T cells directly supplements the number of T cells and rapidly induces T-cell immunity, which has good efficacy for treating some tumors and immunodeficiency diseases. However, poor adoptive T-cell engraftment and graft-versus-host disease (GVHD) limit the application of these methods. Alloreactive T-cell clones were eliminated from the donor T-cell repertoire, and the remaining T-cell clones were prepared as Tscm for T-cell adoptive treatment to reconstruct recipient T-cell immunity without GVHD.MethodsThe subjects in this study included three different strains of mice. Lymphocytes from mice (C57BL/6) were used as the donor T-cell repertoire, from which the Tscm allo-reactive T cell clone was depleted (ATD-Tscm). This was confirmed by showing that the Tscm was not responsive to the alloantigen of the recipient (BALB/c). To prepare ATD-Tscm cells, we used recipient lymphocytes as a simulator, and coculture of mouse and recipient lymphocytes was carried out for 7 days. Sorting of non-proliferative cells ensured that the prepared Tscm cells were nonresponsive. The sorted lymphocytes underwent further expansion by treatment with TWS119 and cytokines for an additional 10 days, after which the number of ATD-Tscm cells increased. The prepared Tscm cells were transferred into recipient mice to observe immune reconstitution and GVHD incidence.ResultsOur protocol began with the use of 1×107 donor lymphocytes and resulted in 1 ×107 ATD-Tscm cells after 17 days of preparation. The prepared ATD-Tscm cells exhibited a nonresponse upon restimulation of the recipient lymphocytes. Importantly, the prepared ATD-Tscm cells were able to bind long and reconstitute other T-cell subsets in vivo, effectively recognizing and answering the “foreign” antigen without causing GVHD after they were transferred into the recipients.DiscussionOur strategy was succeeded to prepare ATD-Tscm cells from the donor T-cell repertoire. The prepared ATD-Tscm cells were able to reconstitute the immune system and prevent GVHD after transferred to the recipients. This study provides a good reference for generating ATD-Tscm for T-cell adoptive immunotherapy

The Vigabatrin Induced Retinal Toxicity is Associated with Photopic Exposure and Taurine Deficiency: An In Vivo Study

Background/Aims: Retinal toxicity is one of the most commonly discussed and concerning adverse effects of vigabatrin (VGB). The present study explored the relationship between the VGB elicited retinal toxicity, photopic exposure, and taurine deficiency, aiming at screening for risk factors to minimize the adverse effects of VGB. Methods: The effects of VGB on function and morphology of mouse retinas were examined via a series of in vivo tests, including electroretinography (ERG), Spectral domain optical coherence tomography (SD-OCT), and optokinetic testing. Moreover, VGB-treated mice were in addition treated with taurine to verify possible protective effects against retinal toxicity. Results: A close relationship between VGB induced retinal toxicity and light exposure was observed. The VGB-treated mice which were reared in darkness preserved better visual function and retinal architectures as verified by the optokinetic tests, OCT and ERG examinations. The retinal taurine level of the VBG-treated mice which were exposed to light were significantly lower than that of the VBG mice reared in darkness. Furthermore, several in vivo evidence provided by our research confirmed that the VGB induced morphological and functional impairments could be partially alleviated by taurine treatment. The present study showed the retinal toxicity of VGB by in vivo measurements. Conclusion: The VGB induced retinal toxicity is closely associated with photopic exposure and taurine deficiency. Patients who are taking VGB might benefit from minimization of light exposure and dietetic taurine supplements

Additional file 1: Table S1. of QTL variations for growth-related traits in eight distinct families of common carp (Cyprinus carpio)

Phenotypic correlations between growth-related traits in eight common. Table S2. List of suggestive (P < 0.05) and significant (P < 0.01) QTLs for body weight (BW) in eight common carp families based on half-sib analysis. Table S3. List of suggestive (P < 0.05) and significant (P < 0.01) QTLs for total length (TL) in eight common carp families based on half-sib analysis. Table S4. List of suggestive (P < 0.05) and significant (P < 0.01) QTLs for body thickness (BT) in eight common carp families based on half-sib analysis. (DOCX 123 kb

Assessment of Bone Metabolism in Male Patients With Benign Paroxysmal Positional Vertigo

Objective: Several studies have suggested a probable association between benign paroxysmal positional vertigo (BPPV) and both reduction of bone mineral density (BMD) and serum vitamin D levels, but none of these studies have explored their findings by examining bone turnover markers (BTM) in male idiopathic BPPV patients. This study aimed to evaluate the relationship between BMD and serum 25-hydroxyvitamin D (25(OH) D), with the occurrence of BPPV along with the characteristics of bone metabolism in male idiopathic BPPV patients.Methods: This retrospective study comprised 60 male idiopathic BPPV patients and 92 age-matched healthy controls referred to Ningbo No.2 Hospital during the period of February 2016 to February 2018. All subjects' serum levels of 25(OH) D, bone formation marker amino-terminal propeptide of type I procollagen (PINP), and bone resorption marker β-isomerized carboxy-terminal telopeptide of type I collagen (β-CTX) were measured. BMD was determined by dual energy X-ray absorption at the lumbar spine and hip.Results: Among male patients with BPPV, the prevalence of BMD reduction was 35.0%, which was similar to that of 27.2% in healthy controls. There were significant differences in the mean serum 25(OH) D level and prevalence of vitamin D deficiency between the two groups, with p-values of 0.049 and 0.009, respectively. The bone turnover markers of PINP and β-CTX in BPPV patients were lower than those in healthy controls. Logistic regression showed that vitamin D deficiency were associated with BPPV with an odds ratio of 3.8 (95% confidence interval = 1.25–11.73).Conclusion: Our study found that decreased serum vitamin D may be a risk factor for BPPV in male patients. The level of bone turnover among male patients with BPPV was lower than that among healthy controls

Highly Efficient Microwave Absorption of Magnetic Nanospindle–Conductive Polymer Hybrids by Molecular Layer Deposition

Oxidative molecular layer deposition (oMLD) was applied to fabricate conductive polymer–magnetic material core–shell microwave absorbers in this work. One dimensional Fe₃O₄–poly­(3,4-ethylenedioxythiophene) (PEDOT) nanospindles with controllable PEDOT thickness were successfully synthesized. Their absorption performance was evaluated in the 2–18 GHz frequency range. With the advantage of oMLD, PEDOT shell thicknesses can be controlled precisely. Because the permittivity of Fe₃O₄–PEDOT nanospindles obviously increases while their permeability decreases slightly with the PEDOT cycles, the properties can be tuned effectively by only adjusting the PEDOT cycle number. With a proper PEDOT shell thickness, excellent reflection characteristics can be obtained. Remarkably high absorption strength (−55.0 dB at 16.2 GHz) and good absorption bandwidth (4.34 GHz less than −10 dB) were realized. Such excellent performance is better than that reported previously for most magnetic material-based absorbers. Considering the precise controllability and excellent absorption performance of the prepared microwave absorbers, we believe that oMLD is a facile synthetic route for microwave absorbers