Engineering topics

Zhang, Shijie

Publications and source records attributed to Zhang, Shijie.

3 records

DOE OSTI2018

Role of capsaicin sensitive sensory nerves in ischemia reperfusion-induced acute kidney injury in rats

Highlights: • The sensory neuropeptides of CGRP and SP significantly increased after renal IR injury in kidney. • The large dose of capsaicin treatment in neonatal rats resulted in degeneration of capsaicin sensitive sensory nerves. • The degeneration of capsaicin sensitive sensory nerves and the reduction of CGRP and SP aggravated IR-induced AKI in rats. • The degeneration of capsaicin sensitive sensory nerves activated the ERK signal pathway of spinal cord and kidney. Acute kidney injury (AKI) is a common kidney disorder which is associated with a high risk of mortality. Extensive evidence revealed the participation of renal afferent sensory nerves in the pathophysiology of renal ischemia reperfusion (IR) injury, however the role of these nerves in renal IR injury is controversial and remains to be further explored. Here, we report that capsaicin sensitive sensory nerves and neuropeptides prevented renal damage in AKI induced by IR injury. The sensory afferent degeneration model was established by injecting 50 mg/kg of capsaicin to male neonatal rats and verified by the tail flick test and reduced sensory neuropeptide of substance P and calcitonin gene related peptide in spinal cord, dorsal root ganglion and kidney after 12 weeks. Then, a model of renal IR injury was established. The sensory afferent degeneration in the AKI group increased the level of serum creatinine, NGAL and KIM-1, aggravated to some extent renal pathological damage, and enhanced the proinflammatory cytokines expressions and tubular cell apoptosis. In addition, it was also discovered that the level of phospho-ERK/ERK (p-ERK/ERK) showed an increase in spinal cord and kidney after degeneration of capsaicin sensitive sensory nerves. In conclusion, the degeneration of sensory nerves aggravated IR-induced AKI in rats, and the activated ERK signaling in spinal cord and kidney after sensory afferent degeneration might be the possible mechanism in the aggravated renal injury.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions

Second harmonic generation (SHG) was integrated with Raman spectroscopy for the analysis of pharmaceutical materials. Particulate formulations of clopidogrel bisulfate were prepared in two crystal forms (Form I and Form II). Image analysis approaches enable automated identification of particles by bright field imaging, followed by classification by SHG. Quantitative SHG microscopy enabled discrimination of crystal form on a per particle basis with 99.95% confidence in a total measurement time of ~10 ms per particle. Complementary measurements by Raman and synchrotron XRD are in excellent agreement with the classifications made by SHG, with measurement times of ~1 min and several seconds per particle, respectively. In conclusion, coupling these capabilities with at-line monitoring may enable real-time feedback for reaction monitoring during pharmaceutical production to favor the more bioavailable but metastable Form I with limits of detection in the ppm regime.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2017

Dynamic X-ray diffraction sampling for protein crystal positioning

A sparse supervised learning approach for dynamic sampling (SLADS) is described for dose reduction in diffraction-based protein crystal positioning. Crystal centering is typically a prerequisite for macromolecular diffraction at synchrotron facilities, with X-ray diffraction mapping growing in popularity as a mechanism for localization. In X-ray raster scanning, diffraction is used to identify the crystal positions based on the detection of Bragg-like peaks in the scattering patterns; however, this additional X-ray exposure may result in detectable damage to the crystal prior to data collection. Dynamic sampling, in which preceding measurements inform the next most information-rich location to probe for image reconstruction, significantly reduced the X-ray dose experienced by protein crystals during positioning by diffraction raster scanning. The SLADS algorithm implemented herein is designed for single-pixel measurements and can select a new location to measure. In each step of SLADS, the algorithm selects the pixel, which, when measured, maximizes the expected reduction in distortion given previous measurements. Ground-truth diffraction data were obtained for a 5 µm-diameter beam and SLADS reconstructed the image sampling 31% of the total volume and only 9% of the interior of the crystal greatly reducing the X-ray dosage on the crystal. Furthermore, by using in situ two-photon-excited fluorescence microscopy measurements as a surrogate for diffraction imaging with a 1 µm-diameter beam, the SLADS algorithm enabled image reconstruction from a 7% sampling of the total volume and 12% sampling of the interior of the crystal. When implemented into the beamline at Argonne National Laboratory, without ground-truth images, an acceptable reconstruction was obtained with 3% of the image sampled and approximately 5% of the crystal. The incorporation of SLADS into X-ray diffraction acquisitions has the potential to significantly minimize the impact of X-ray exposure on the crystal by limiting the dose and area exposed for image reconstruction and crystal positioning using data collection hardware present in most macromolecular crystallography end-stations.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗