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Psoriasis, an immune-mediated inflammatory skin disorder characterized by a chronically relapsing-remitting course, continues to be primarily managed through topical therapy. While oral administration of tyrosine kinase 2 inhibitors (TYK2i) stands as an effective approach for psoriasis treatment, the potential efficacy of topical application of TYK2i remains unexplored. Herein, the carbomer/alginic acid hydrogel is embedded with borneol (BO) as a new topical carrier of TYK2i for achieving enhanced transdermal permeation and anti-psoriasis efficacy. The hydrogel system, i.e., TYK2i-BO-gel, exhibits significantly improved preventative and therapeutic effects in mice models of psoriasiform dermatitis, as evidenced by phenotypical images, psoriasis severity score index (PSI), histology, immunohistochemical staining, and PCR analysis. Remarkably, TYK2i-BO-gel outperforms conventional topical corticosteroid therapy by significantly preventing psoriatic lesion recurrence as measured by a nearly 50 % reduction in ear thickness changes (p

BackgroundNatural killer (NK) cells are key effector cells of antitumor immunity. However, tumors can acquire resistance programs to escape NK cell-mediated immunosurveillance. Identifying mechanisms that mediate this resistance enables us to define approaches to improve immune-mediate antitumor activity. In previous studies from our group, a genome-wide CRISPR-Cas9 screen identified Charged Multivesicular Body Protein 2A (CHMP2A) as a novel mechanism that mediates tumor intrinsic resistance to NK cell activity.MethodsHere, we use an immunocompetent mouse model to demonstrate that CHMP2A serves as a targetable regulator of not only NK cell-mediated immunity but also other immune cell populations. Using the recently characterized murine 4MOSC model system, a syngeneic, tobacco-signature murine head and neck squamous cell carcinoma model, we deleted mCHMP2A using CRISPR/Cas9-mediated knock-out (KO), following orthotopic transplantation into immunocompetent hosts.ResultsWe found that mCHMP2A KO in 4MOSC1 cells leads to more potent NK-mediated tumor cell killing in vitro in these tumor cells. Moreover, following orthotopic transplantation, KO of mCHMP2A in 4MOSC1 cells, but not the more immune-resistant 4MOSC2 cells enables both T cells and NK cells to better mediate antitumor activity compared with wild type (WT) tumors. However, there was no difference in tumor development between WT and mCHMP2A KO 4MOSC1 or 4MOSC2 tumors when implanted in immunodeficient mice. Mechanistically, we find that mCHMP2A KO 4MOSC1 tumors transplanted into the immunocompetent mice had significantly increased CD4+T cells, CD8+T cells. NK cell, as well as fewer myeloid-derived suppressor cells (MDSC).ConclusionsTogether, these studies demonstrate that CHMP2A is a targetable inhibitor of cellular antitumor immunity.

Previous studies have shown that paricalcitol (PA) has a protective effect on the kidneys. However, the exact molecular mechanism by which PA affects diabetic nephropathy (DN) progression remains uncertain. PBMCs of patients with DN were isolated, and CYP2J2 and VDR levels were detected by qPCR. Pearson correlation analysis was utilized to detect the relationship between uACR and CYP2J2 and VDR and between CYP2J2 and VDR. The protective effects of PA on DN have been examined by TUNEL, HE staining, ELISA, and Flow cytometry assays in STZ‐induced mice. Moreover, THP‐1 cells were stimulated with HG/LPS for in vitro studies. ELISA, qPCR, western blot, and Flow cytometry assays were utilized to assess the effects of PA on DN progression by regulating CYP2J2. The interaction between CYP2J2 and VDR was analyzed by CHIP‐qPCR and luciferase experiments. CYP2J2 and VDR levels were downregulated and uACR level was upregulated in DN patients. CYP2J2 and VDR were positively correlated in PBMCs. Both CYP2J2 and VDR are inversely correlated with uACR. Moreover, after PA treatment, 11, 12‐EET levels increased, inflammatory factor levels decreased, and M2 macrophage polarization was promoted in STZ‐induced mice and HG/LPS‐triggered THP‐1 cells. Depletion of CYP2J2 and VDR decreased 11, 12‐EET level, enhanced inflammatory factor levels, and inhibited M2 macrophage polarization, which were reversed by CYP2J2 overexpression in HG/LPS‐treated cells. Furthermore, VDR bound to the CYP2J2 promoter and promoted CYP2J2 transcriptional expression. The present work pointed out a new use for PA to inhibit DN progression by increasing EET level, inhibiting inflammatory response, and inducing M2 macrophage polarization via regulating the VDR/CYP2J2 axis. [ABSTRACT FROM AUTHOR]

In order to evaluate the safety of tebuconazole as a fungicide in bananas, after a simple and rapid pre-treatment, the residues of tebuconazole in different parts of banana were detected by high-performance liquid chromatography (HPLC) within 35 days. The mean recoveries and relative standard deviations in banana samples were 87.17 ~ 96.68% and 2.85 ~ 8.49%, respectively. The half-lives of tebuconazole in whole banana, banana pulp, and banana peel were 7.31 ~ 8.68 days, 11.12 ~ 13.39 days, and 4.06 ~ 5.74 days, respectively. It can be seen that tebuconazole dissipated fastest in the peel and slowest in the pulp. And the contents of tebuconazole in banana pulp and banana peel were 3 ~ 35% and 65 ~ 97%, respectively, which can be seen that tebuconazole was mainly distributed in the peel, and only a small part was transmitted to the pulp. Results also showed that the residual amounts of tebuconazole in banana pulp were increased at the first three days and then gradually dissipated, and were below the maximum residue limit (MRL) in China. The results of dietary intake risk assessment showed that the HQ (hazard quotient) were 0.45 ~ 2.69%, which were within the acceptable range. Overall, our research results show that tebuconazole in the field control of banana freckle disease has high security and low risk with the application dose of 133 g/L and diluted 1000 times in water, and can provide an important reference for the rational use of tebuconazole as a systemic fungicide in the field. [ABSTRACT FROM AUTHOR]

Estimating the population of defects is a key reference for completion evaluation in crowdsourced testing. Current studies commonly use the biological capture–recapture model (CRC model) to estimate the population of defects in crowdsourced tests with good results. However, the lack of consideration of false negatives for defects in existing studies leads to imprecise estimation of completion in crowdsourced testing, which in turn influences decision support during crowdsourced testing. This study analyzes the basic assumptions of the CRC model in biology and maps them to the field of crowdsourced testing, improves the Lincoln–Peterson estimator and sample coverage estimator utilizing false negative assumptions, and compares them with original estimators in 29 real crowdsourced testing projects. The experimental results show that our improved estimators can effectively reduce the estimation relative error of the population of defects caused by false negatives. [ABSTRACT FROM AUTHOR]

Located in the southwest of Jiangxi Province, Dayu County has the most abundant tungsten resources in China. In this paper, 2969 agricultural soil samples were collected downstream of the tungsten mining area in Dayu, and all samples were tested for the contents of potentially toxic elements (PTEs) such as Cd, Pb, Zn, Cr, Cu, Ni, Hg, as well as the mining-related elements W, Sn, Mo and pH. In addition, 135 soil samples were measured for chemical morphology of Cd. The results show that the distribution patterns of Cd, Pb, Zn, Cu and W, Sn, Mo are relatively consistent, which are considered to be affected by upstream mining activities. Hg is possibly overlaying the effects of human production and living activities. Cr and Ni are considered as a natural source. From the perspective of total concentration, the ecological risk of PTEs in the study area was low, with over 80% of the samples being evaluated as safe. However, based on chemical fraction of Cd, more than 75% of the samples were assessed as moderately or severely contaminated. The serious acidification of soil in the study area is the main reason for the increase activity of Cd and its ecological risk. [ABSTRACT FROM AUTHOR]

Summary: The Moringa seed protein (MOS) is a new protein resource, the development and utilisation of MOS is still in its early stages due to the late introduction of its varieties. To improve the range of available MOS protein, this study investigated the effects of different pH levels on the ultrasonic modification of MOS protein (UMOWP), exploring the feasibility of UMOWP emulsion systems in food. The zeta potential analysis revealed that the isoelectric point (pI) of UMOWP was 5.8. The secondary structures of UMOWP could be regulated by pH. Moreover, different secondary structures led to different tertiary structures and chemical bonds in UMOWP. Compared with pH values near pI, surface hydrophobicity significantly increased but the total S–S group and particle size decreased away from pI. Furthermore, UMOWP partially dissociated at pH 3, and the degree of dissociation was weaker at pH 9 and pH 11. These structural changes led to significant improvements in the emulsification properties of UMOWP at pH 11, resulting in better environmental stability of the emulsion. These findings provide a foundation for the potential application of MOS proteins in the food industry. [ABSTRACT FROM AUTHOR]