Biology subjects

Zheng, X.

Publications and source records attributed to Zheng, X..

39 records · Page 3Linked to original sources

bioRxiv2017

Murine Glomerular Transcriptome Links Endothelial Cell-Specific Molecule-1 Deficiency With Susceptibility To Diabetic Nephropathy

Diabetic nephropathy (DN) is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms which govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1), as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

immunology↗

bioRxiv2017

Detecting Drug-Target Binding In Cells Using Fluorescence Activated Cell Sorting Coupled With Mass Spectrometry Analysis

The assessment of drug-target engagement for determining the efficacy of a compound inside cells remains challenging, particularly for difficult target proteins. Existing techniques are more suited to soluble protein targets. Difficult target proteins include those with challenging in vitro solubility, stability or purification properties that preclude target isolation. Here, we report a novel technique that measures intracellular compound-target complex formation, as well as cellular permeability, specificity and cytotoxicity - the Toxicity-Affinity-Permeability-Selectivity (TAPS) technique. The TAPS assay is exemplified here using human kynurenine 3-monooxygenase (KMO), a challenging intracellular membrane protein target of significant current interest. TAPS confirmed target binding of known KMO inhibitors inside cells. We conclude that the TAPS assay can be used to facilitate intracellular hit validation on most, if not all intracellular drug targets.

pharmacology and toxicology↗

bioRxiv2017

Assessment of the World Largest Afforestation Program: Success, Failure, and Future Directions

The Three-North Afforestation Program (TNAP), initiated in 1978 and scheduled to be completed in 2050, is the worlds largest afforestation project and covers 4.07 x 106 km2 (42.4%) of China. We systematically assessed goals and outcomes of the first 30 years of the TNAP using high-resolution remote sensing and ground survey data. With almost 23 billion dollars invested between 1978 and 2008, the forested area within the TNAP region increased by 1.20 x 107 ha, but the proportion of high quality forests declined by 15.8%. The establishment of shelterbelts improved crop yield by 1.7%, much lower than the 5.9% expected once all crop fields are fully protected by shelterbelts. The area subjected to soil erosion by water decreased by 36.0% from 6.72 x 107 to 4.27 x 107 ha; the largest reductions occurred in areas where soil erosion had been most severe and forests contributed more than half of this improvement. Desertification area increased from 1978 to 2000 but decreased from 2000 to 2008; the 30-year net reduction was 13.0% (4.05x106 ha), with 8.0% being accounted for by afforestation in areas with only slight, prior desertification. In addition to its direct impacts, the TNAP has enhanced peoples awareness of environmental protection and attracted consistent attention and long-term commitment from the Chinese government to the restoration and protection of fragile ecosystems in the vast Three-North region. The significant decline in forest quality, limited success in reducing desertification, and low coverage of shelterbelts are aspects of the TNAP in need of re-assessment, and additional ca. 34 billion dollars will be needed to ensure the completion of the TNAP.

ecology↗