Epigenetic activation of the TUSC3 gene as a potential therapy for XMEN disease.

BACKGROUND: X-linked MAGT1 deficiency with increased susceptibility to Epstein-Barr virus infection and N-linked glycosylation defect (XMEN) disease is a rare combined immunodeficiency caused by loss-of-function mutations in the magnesium transporter 1 (MAGT1) gene. MAGT1 deficiency impairs magnesium transport and the N-linked glycosylation of a panel of proteins, which subsequently abolishes the expression of key immune receptors such as natural killer group 2, member D (aka NKG2D). These effects induce immune system abnormalities, chronic Epstein-Barr virus infection, and neoplasia. Recent research shows that MAGT1 and tumor candidate suppressor 3 (TUSC3) share high sequence and functional similarity. OBJECTIVE: We sought to investigate the feasibility of activating TUSC3 expression to provide a potential therapeutic strategy for XMEN disease. METHODS: The expression profiles of MAGT1 and TUSC3 were analyzed using multiple databases, real-time quantitative PCR, and Western blot. The effects of decitabine and panobinostat on the regulation of TUSC3 expression were explored in both MAGT1 knockout (KO)/patient-derived lymphocytes and MAGT1 KO hepatocytes. RESULTS: Although TUSC3 is widely expressed, it is undetectable specifically in the immune system and liver, consistent with the main diseased tissues in patients with XMEN disease. CRISPR/Cas9-mediated KO of MAGT1 in the NKL cell line successfully mimicked the phenotypes of XMEN patient-derived lymphocytes, and exogenous expression of TUSC3 rescued the deficiencies in KO NKL cells. Using this in vitro model, we identified 2 epigenetic drugs, decitabine and panobinostat, by screening. Combination treatment using these 2 drugs significantly upregulated TUSC3 expression and rescued the immune and liver abnormalities. CONCLUSIONS: Epigenetic activation of TUSC3 expression constitutes an effective therapeutic strategy for XMEN disease.

A review on removal of organophosphorus pesticides in constructed wetland: Performance, mechanism and influencing factors.

The residues of organophosphorus pesticides (OPPs) have been widely detected in rivers, the gulf, and even groundwater and drinking water, which may pose a serious threat to aquatic ecosystems and human health. Compared to other treatments, constructed wetlands (CWs) have been demonstrated to be a cost-effective alternative risk mitigation strategy for non-point-source pesticide pollution. This review summarizes 32 studies related to the remediation of OPPs in 117 CWs during 2001-2017 worldwide. The performances, mechanisms and influencing factors in the studies are comprehensively and critically reviewed in this paper. Overall, the OPPs were efficiently removed with an efficiency up to 87.22 ±â€¯16.61%. The removal efficiency, differences and related reasons among different types of CWs in developed and developing countries and the different types of OPPs in CWs are well-evaluated in detail. In addition, the main processes for OPPs removal in CWs involve phytoremediation (plant uptake, phytoaccumulation, phytovolatilization and phytodegradation), substrate adsorption or sedimentation, and biodegradation. Based on the quantitative analysis by mass balance, for water-soluble pesticides, the dominant removal process was via microbiological degradation. This result was in contrast to findings obtained with hydrophobic OPPs, for which the dominant processes were biodegradation and sorption by substrate. Therefore, the behavior of microbial transformation prevails. Additionally, the presence of plants can facilitate the elimination of OPPs in CWs, promoting the process by an average percentage of approximately 6.19 ±â€¯9.46%. Statistical analysis shows that loading of inlet OPPs is the largest limiting factor and that the HRT and T are the most significant parameters that influence the efficiency of trapping OPPs in CWs. Simultaneously, we can also obtain suitable parameters for the design and operation of CWs. This review promotes further research on plant-microbe joint combined remediation and examines the different behaviors of water-soluble and hydrophobic OPPs in CWs.

Development of a novel, sensitive amperometric-FIA glucose biosensor by packing up the amperometric cell with glucose oxidase modified anion exchange resin.

In this work, the anion exchange resin (AER) was modified with a layer of glucose oxidase (GOD) and poly(diallyldimethylammonium chloride) (PDDA), respectively, via layer-by-layer electrostatic self-assembling strategy. The PDDA and GOD modified AER (PDDA/GOD/AER) was then packed into a home-made amperometric cell for flow injection analysis (FIA) of glucose. This design simplified the setup by integrating the enzyme reactor into the amperometric cell. And the AER in the cell behaved bifunctional, it was not only the support of enzymes, but also an anti-interference tool due to its retention effect toward ascorbic acid (AA) and uric acid (UA). A platinum modified porous titanium (Pt/PTi) electrode was utilized in the cell as the working electrode (WE), due to its large effective surface area it could increase the response by 8.3 times as compared with the planar pure platinum electrode. The proposed biosensor was very sensitive (22.4 microA cm(-2) mM(-1)) in glucose quantification, and the linear range was from 1 micromol L(-1) to 2 mmol L(-1) with the detection limit of 0.8 micromol L(-1). The biosensor was used for serum glucose determination, and the result obtained was satisfying. This work may have provided a reference design of the amperometric cell which could be adopted in other enzymatic-FIA biosensors.