THSD7A as a Promising Biomarker for Membranous Nephrosis.

Membranous nephropathy (MN) is an autoimmune disease of the kidney glomerulus and one of the leading causes of nephrotic syndrome. The disease exhibits heterogeneous outcomes with approximately 30% of cases progressing to end-stage renal disease. Traditionally, the standard approach of diagnosing MN involves performing a kidney biopsy. Nevertheless, kidney biopsy is an invasive procedure that poses risks for the patient including bleeding and pain, and bears greater costs for the health system. The clinical management of MN has steadily advanced owing to the identification of autoantibodies to the phospholipase A2 receptor (PLA2R) in 2009 and thrombospondin domain-containing 7A (THSD7A) in 2014 on the podocyte surface. At present, serum anti-PLA2R antibody detection and glomerular PLA2R antigen staining have been used for clinical diagnosis and prognosis, but the related detection of THSD7A has not been widely used in clinical practice. Here, we summarized the emerging knowledge regarding the roles THSD7A plays in MN and its clinical implications as diagnostic, prognostic, and therapeutic response as well as Methods for detecting serum THSD7A antibodies.

Immune response of large yellow croaker Larimichthys crocea towards a recombinant vaccine candidate targeting the parasitic ciliate Cryptocaryon irritans.

Cryptocaryon irritans, a parasitic ciliate, pose a major threat to marine teleost fish aquaculture. So far, no effective and safe control method is available. In this study, the protective efficacy of a recombinant truncated surface antigen of C. irritans (rCiSA32.6t) for large yellow croaker (Larimichthys crocea) against the parasite challenge with a sub-lethal dose of the infective theronts was evaluated by comparing the relative percent survivals (RPS), the specific antibody titers in sera, and the expression levels of the immune-related genes among the negative or adjuvant control fish, fish intraperitoneally immunized with rCiSA32.6t. The results showed that a RPS of 50.1% in rCiSA32.6t-immunized fish was achieved in comparison to negative control fish against C. irritans. A significant increase was noted in the antigen-specific immunoglobulin M (IgM) and immunoglobulin T (IgT) antibody levels in the sera of the rCiSA32.6t-vaccinated fish. Compared to the negative control fish, quantitative real-time PCR analysis indicated that the interleukin-1beta, IgT, and IgM heavy chain mRNA level in the fish head kidney, spleen, gill, and skin tissue were upregulated post-rCiSA32.6t immunization. This study indicates that the rCiSA32.6t can provide a high level of immune protection against C. irritans infection in grouper and is therefore pursued as a candidate C. irritans vaccine.

Host responses against the fish parasitizing ciliate Cryptocaryon irritans.

The parasitic ciliate Cryptocaryon irritans, which infects almost all marine fish species occurring in both tropical and subtropical regions throughout the world. The disease, cryptocaryonosis, accounts for significant economic losses to the aquaculture industry. This review attempts to provide a comprehensive overview of the biology of the parasite, host-parasite interactions and both specific and non-specific host defense mechanisms are responsible for the protection of fish against challenge infections with this ciliate. Also, this article reflects the current interest in this subject area and the quest to develop an available vaccine against the disease. Due to the high frequency of clinical fish cryptocaryonosis, the study of fish immune responses to C. irritans provides an optimal experimental model for understanding immunity against extracellular protozoa.

Significantly enhancing the stereoselectivity of a regioselective nitrilase for the production of (S)-3-cyano-5-methylhexanoic acid using an MM/PBSA method.

The present investigation describes the successful molecular modification of a regio- and stereo-specific nitrilase toward rac-ISBN to (S)-CMHA, a critical intermediate in the preparation of optically pure pregabalin. Two hotspots of Trp57 and Val134 were identified based on the classical binding free energy molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) calculation method. Mutants W57F/V134M and W57Y/V134M were successfully obtained with high enantioselectivity (E >300). Furthermore, these two mutants were efficiently capable of kinetic resolution of rac-ISBN to (S)-CMHA, with both exhibiting a high e.e. (>99.9%), as well as conversion ratios of 43.8% and 40.9%, respectively. Docking and molecular dynamics simulation analysis clarified that the underlying mechanisms were related to a DC-S switch and the formation of a hydrogen bond in the active center of nitrilase. The successful utilization of the MM/PBSA method for identifying hotspots that modulate the stereoselectivity in our study could provide guidelines for the molecular modification of nitrilases, and the mutants obtained could be potentially utilized for the industrial preparation of optically pure pregabalin.

Recent research advancements on regioselective nitrilase: fundamental and applicative aspects.

Nitrilase-mediated biocatalysis reactions have been continuously arousing wide interests by scholars and entrepreneurs in organic synthesis over the past six decades. Since regioselective nitrilases could hydrolyze only one cyano group of dinitriles into corresponding cyanocarboxylic acids, which are virtually impossible by chemical hydrolysis and of interest for a variety of applications, it becomes particularly appealing to synthetic chemists. The aim of the current review is to summarize the recent advancements on regioselective nitrilases concerning their fundamental researches and applications in synthesis of a series of high-value fine chemicals and pharmaceuticals. Carbon chain lengths and substituent group positions of substrates are found to be two crucial factors in affecting regioselectivity of nitrilase. Practical applications of regioselective nitrilases in synthesis of 1,5-dimethyl-2-piperidone (1,5-DMPD), atorvastatin, gabapentin, (R)-baclofen, and (S)-pregabalin were systematically reviewed. Future perspectives clearly elucidating the mechanism of regioselectivity and further molecular modifications of regioselective nitrilases integrating within silico technology for industrial applications were discussed.

Quaternary quantum dots with gradient valence band for all-inorganic perovskite solar cells.

The severe interface charge recombination caused by the large energy difference between perovskite material and carbon electrode significantly limits the further performance improvement of the all-inorganic perovskite solar cells (PSCs). We apply innovatively multilayer of quaternary Ag-In-Ga-S (AIGS) quantum dots (QDs) with cascade-like valence bands as hole-transport materials to assemble all-inorganic PSCs, and the resultant all-inorganic PSCs exhibit a power conversion efficiency (PCE) of 8.46%, which is enhanced by 20.9% in comparison with 7% for the pristine device. The high performance of the PSCs indicates that sequential layers of AIGS QDs with cascade-like energy levels can facilitate the charge separation, reduce the barrier the holes crossing and suppress the charge recombination. Stack of QDs with cascade-like energy levels provide solution-processed PSCs with a new method to enhance device performance.

Switching the regioselectivity of two nitrilases toward succinonitrile by mutating the active center pocket key residues through a semi-rational engineering.

The 163Ala in bll6402NIT and 172Trp in blr3397NIT played a significant role in directing nitrilase regioselectivity. Amino acid mutation of two nitrilases at these two sites could alter the size of the active site pocket and further switch nitrilase regioselectivity toward succinonitrile, which lays the foundation for subsequent research on regioselective nitrilase towards several dinitriles.

[Expression of chemokine monokine induced by interferon-gama in patients with chronic hepatitis B].

OBJECTIVE: To study the expression levels of monokine induced by interferon-gama; (Mig) mRNA and its association with HBV DNA and alanine aminotransferase (ALT) in patients with chronic hepatitis B. METHODS: The level of Mig mRNA in peripheral blood mononuclear cells (PBMCs) was dynamically detected with real-time quantitative PCR, and the ratio of chemokine/GAPDH was considered to represent the final chemokine level. The plasma level of was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean level of Mig mRNA in PBMCs of the patients with chronic hepatitis B was 0.6883-/+0.0693, which was significantly higher than that in normal controls (P<0.001). The plasma Mig level in the patients was 609.6-/+73.8 pg/ml, also significantly higher than that in normal controls (P<0.05). In patients with chronic hepatitis B, the level of Mig mRNA in the PBMCs was significantly correlated with plasma Mig level (r=0.7157, P<0.001), and plasma Mig level was correlated with plasma ALT level (r=0.7220, P<0.001) and plasma HBV DNA level (r=0.7266, P<0.001). CONCLUSION: Both the expression of Mig mRNA in PBMCs and plasma Mig concentration are elevated in patients with chronic hepatitis B. Mig plays an important role in migration of the inflammatory cells to the liver and mediates the development of chronic hepatitis B.