Research Progress in Iron-Based Nanozymes: Catalytic Mechanisms, Classification, and Biomedical Applications.

Natural enzymes are crucial in biological systems and widely used in biology and medicine, but their disadvantages, such as insufficient stability and high-cost, have limited their wide application. Since Fe3O4 nanoparticles were found to show peroxidase-like activity, researchers have designed and developed a growing number of nanozymes that mimic the activity of natural enzymes. Nanozymes can compensate for the defects of natural enzymes and show higher stability with lower cost. Iron, a nontoxic and low-cost transition metal, has been used to synthesize a variety of iron-based nanozymes with unique structural and physicochemical properties to obtain different enzymes mimicking catalytic properties. In this perspective, catalytic mechanisms, activity modulation, and their recent research progress in sensing, tumor therapy, and antibacterial and anti-inflammatory applications are systematically presented. The challenges and perspectives on the development of iron-based nanozymes are also analyzed and discussed.

Cascade Reaction Regulated Electrochemiluminescence via Dual-Atomic-Site Catalysts.

Single-atom catalysts (SACs), a novel kind of electrocatalysts with full metal utilization, have been developed as unique signal amplifiers in several sensing platforms. Herein, based on theoretical prediction of the oxygen reduction reaction (ORR) mechanism on different atom sites, we constructed dual-atomic-site catalysts (DACs), Fe/Mn-N-C, to catalyze luminol-dissolved oxygen electrochemiluminescence (ECL). Computational simulation indicated that the weak adsorption of OH* on a single Fe site was overcome by introducing Mn as the secondary metallic active site, resulting in a synergic dual-site cascade mechanism. The superior catalytic activity of Fe/Mn-N-C DACs for the ORR was proven by the highly efficient cathodic luminol ECL, surpassing the performance of single-site catalysts (SACs), Fe-N-C and Mn-N-C. Furthermore, the ECL system, enhanced by a cascade reaction, exhibited remarkable sensitivity to ascorbic acid, with a detection limit of 0.02 nM. This research opens up opportunities for enhancing both the ECL efficiency and sensing performance by employing a rational atomic-scale design for DACs.

Perspective for Single Atom Nanozymes Based Sensors: Advanced Materials, Sensing Mechanism, Selectivity Regulation, and Applications.

Nanozymes are a kind of nanomaterial mimicking enzyme catalytic activity, which has aroused extensive interest in the fields of biosensors, biomedicine, and climate and ecosystems management. However, due to the complexity of structures and composition of nanozymes, atomic scale active centers have been extensively investigated, which helps with in-depth understanding of the nature of the biocatalysis. Single atom nanozymes (SANs) cannot only significantly enhance the activity of nanozymes but also effectively improve the selectivity of nanozymes owing to the characteristics of simple and adjustable coordination environment and have been becoming the brightest star in the nanozyme spectrum. The SANs based sensors have also been widely investigated due to their definite structural features, which can be helpful to study the catalytic mechanism and provide ways to improve catalytic activity. This perspective presents a comprehensive understanding on the advances and challenges on SANs based sensors. The catalytic mechanisms of SANs and then the sensing application from the perspectives of sensing technology and sensor construction are thoroughly analyzed. Finally, the major challenges, potential future research directions, and prospects for further research on SANs based sensors are also proposed.

Recipient-derived IL-22 alleviates murine acute graft-versus-host disease in association with reduced activation of antigen presenting cells.

Acute graft-versus-host disease (aGVHD) remains a major challenging complication of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). CD4+ effector T cells and their related cytokines mediate pathogenesis of aGVHD, in which donor-T-cell derived interleukin-22 (IL-22) was recently indicated to play a role. The role of recipient-derived IL-22 in aGVHD remains to be elucidated. By applying IL-22 knock out (IL-22KO) mice as recipients of allotransplant, we found recipient derived IL-22 alleviated aGVHD and improved survival of allotransplant recipients. Knock out of IL-22 in recipient increased levels of T-helper (Th1) 1 cells but decreased levels of regulatory T cells (Tregs) in target tissues of aGVHD. Levels of IL-22 increased in aGVHD mice. Recipient antigen presenting cells (APCs) are important sources of IL-22. IL-22 reduced activation of APCs in vitro. Defect of IL-22 in APCs resulted in increased polarization of Th1 cells but decreased level of Tregs in an in vitro co-culture system. Our data highlight an immunoregulatory function of recipient-derived IL-22 in aGVHD.

The polymorphism of chicken-type lysozyme gene in Japanese flounder (Paralichthys olivaceus) and its association with resistance/susceptibility to Listonella anguillarum.

Lysozyme is a crucially spread hydrolase in organisms that can defend against bacterial infection in innate immunity. In this study, we successfully sequenced the coding region of chicken-type lysozyme gene (PoLysC) in Paralichthys olivaceus and identified nine single nucleotide polymorphisms (SNPs). We then amplified the 2500 bp promoter region of lysozyme and identified the eight sites of polymorphisms. All SNPs were genotyped between susceptible and resistance groups after Listonella anguillarum challenge. One of these SNP sites in the codon of PoLysC was genotyped and determined to be a significant marker by analyzing its distribution in the susceptible and resistant groups. As a nonsynonymous mutation, the frequency of 140G/C genotype in the resistant group was higher (67.74%) than that in the susceptible group (32.26%). The linkage between SNP140 and polymorphisms in the promoter region was also studied. Results revealed that the frequency of haplotype CC-536/CC-1200/GG140 in the resistance group was significantly higher than that in the susceptible group. The quantitative expression of lysozyme gene in the resistant group was also higher than that in the susceptible group. This finding indicated that the linkage between polymorphism -536 and -1200 sites in promoter and SNP140 in codon sequence was associated with the resistance of P. olivaceus to L. anguillarum. All these results suggest that the mutations in promoter and coding region were related to changes in PoLysC for resisting L. anguillarum. The haplotype CC-536/CC-1200/GG140 was a potential marker and can thus be applied to selective breeding for the disease resistance of P. olivaceus.

Donor T-cell-derived interleukin-22 promotes thymus regeneration and alleviates chronic graft-versus-host disease in murine allogeneic hematopoietic cell transplant.

Defect of thymus results in poor posttransplant immune recovery and dysfunction of immune tolerance after allogeneic hematopoietic cell transplants (allo-HCT). Improving thymus regeneration represents a potential strategy to accelerate recovery of T-cell immunity. IL-22 was reported to mediate thymus regeneration after injury. In this study, we found donor T-cell is a major source of IL-22 in allotransplant recipient. Through applying IL-22 knock out (IL-22KO) mice in allo-HCT, we found donor T-cell derived IL-22 promotes thymus regeneration in association with increased level of intra-thymic IL-22. IL-22KO T-cell-transplanted recipients show deficient thymus recovery which is reversed by injection of exogenous IL-22. T-cell derived IL-22 promotes proliferation of thymic epithelial cells (TECs) in vitro. In addition, donor T-cell derived IL-22 increases expression level of Aire in the thymus and decreases skin chronic graft-versus-host disease (GVHD). Furthermore, short-term use of exogenous IL-22 posttransplant accelerates recovery of thymus without increasing severity of acute GVHD. Our data indicate that cross-talk between T-cell and TECs is an important mechanism to mediate reconstitution of T-cell immunity after allo-HCT.

[Correlation of Serum Albumin with Renal Function in Patients with Acute Leukemia].

OBJECTIVE: To investigate the relationship between serum albumin and renal function in patients with acute leukemia (AL) and its clinical significance. METHODS: The clinical data and related test results of 267 newly diagnosed patients with acute leukemia from April 2015 to April 2017 were collected for retrospective cross-sectional analysis. Multivariate regression model was used for statistical analysis. RESULTS: The creatinine level in serum of newly diagnosed acute leukemia patients decreased with the increase of albumin level (the first quartile-the fourth quartile had an average creatinine level of 72.0 µmol/L, 65.2 µmol/L, 62.8 µmol/L, 58.6 µmol/L); Multiple regression model results showed that each elevated albumin 1 g/L, the serum creatinine level decreased 0.89 µmol/L. The serum albumin was grouped into the model by quartile, and the first quartile was used as the reference group. With the increase of albunin, the ß value decreased steply (the second and fourth quartile ß values were -12.7, -14.81, -15.98), the trend line test p value was <0.05. CONCLUSION: Serum albumin negatively correlats with creatinine level in newly diagnosed acute leukemia patients, and its elevation shows protective effect on renal function.

[Statins Regulate the Proliferation and Apoptosis of T-ALL Cells through the Inhibition of Akt Pathway].

OBJECTIVE: To investigate the effect of Statins on proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cells and its possible mechanism. METHODS: Jurkat and CCRF-CEM cells were cultured in different concentrations of Fluvastatin and Simvastatin for 24 h respectively. Then, the cell growth inhibition level was defected by CCK-8; the DNA replication was analyzed by EdU; the cell apoptosis was analyzed by Annexin V/7-AAD double labeling; the cell cycle changes were analyzed by flow cytometry; the expressions of Cyclin D1, p21, p27, BAX, BCL-2 and p-Akt were determined by Western blot. RESULTS: Fluvastatin and Simvastatin both significantly inhibited the growth of Jurkat and CCRF-CEM cells in a dose-dependent manner. The inhibitory rate of Jurkat and CCRF-CEM cells at 0.2 mmol/L Fluvastatin was 41.14% and 57.08% respectively, while the 0.2 mmol/L Simvastatin could supress 68.42% of Jurkat and 77.10% of CCRF-CEM cells. Half or more than half of cell inhibition were observed in Statins-treated groups with significantly statistical differences, compared with the control groups (P<0.05). After the Jurkat and CCRF-CEM cells were treated with Fluvastation and Simvastation of different concentrations for 24 hours, the proportion of early and later apoptotic cells both increased; moreover, the total apoptotic rate increased significantly(P<0.05) at 0.2 mmol/L and 0.3 mmol/L concentration of Fluvastatin and Simvastatin. The detection of cell cycle showed that both of Jurkat and CCRF-CEM cells were arrested in G1 phase. Western blot revealed that, in comparison with the control group, the expressions of BAX, p21 and p27 in cells treated with Statins were up-regulated, while Cyclin D1, BCL-2 and p-Akt expressions were down-regulated. CONCLUSION: Statins can suppress T-ALL cell proliferation and induce cell apoptosis through the inhibition of Akt pathway.