Engineering topics

Ding, Wei

Publications and source records attributed to Ding, Wei.

5 records

DOE OSTI2021

The Prediction Model of Risk Factors for COVID-19 Developing into Severe Illness Based on 1046 Patients with COVID-19

This study analyzed the risk factors for patients with COVID-19 developing severe illnesses and explored the value of applying the logistic model combined with ROC curve analysis to predict the risk of severe illnesses at COVID-19 patients’ admissions. The clinical data of 1046 COVID-19 patients admitted to a designated hospital in a certain city from July to September 2020 were retrospectively analyzed, the clinical characteristics of the patients were collected, and a multivariate unconditional logistic regression analysis was used to determine the risk factors for severe illnesses in COVID-19 patients during hospitalization. Based on the analysis results, a prediction model for severe conditions and the ROC curve were constructed, and the predictive value of the model was assessed. Logistic regression analysis showed that age (OR = 3.257, 95% CI 10.466–18.584), complications with chronic obstructive pulmonary disease (OR = 7.337, 95% CI 0.227–87.021), cough (OR = 5517, 95% CI 0.258–65.024), and venous thrombosis (OR = 7322, 95% CI 0.278–95.020) were risk factors for COVID-19 patients developing severe conditions during hospitalization. When complications were not taken into consideration, COVID-19 patients’ ages, number of diseases, and underlying diseases were risk factors influencing the development of severe illnesses. The ROC curve analysis results showed that the AUC that predicted the severity of COVID-19 patients at admission was 0.943, the optimal threshold was −3.24, and the specificity was 0.824, while the sensitivity was 0.827. The changes in the condition of severe COVID-19 patients are related to many factors such as age, clinical symptoms, and underlying diseases. This study has a certain value in predicting COVID-19 patients that develop from mild to severe conditions, and this prediction model is a useful tool in the quick prediction of the changes in patients’ conditions and providing early intervention for those with risk factors.

Lian, Zhichuang↗

DOE OSTI2017

Long noncoding RNA linc00346 promotes the malignant phenotypes of bladder cancer

Background: More and more reports have demonstrated that long noncoding RNAs (lncRNAs) play an important role in the development of a variety of carcinomas, including bladder cancer. However, only a small fraction of them have been characterized. Linc00346 have been found to be upregulated in bladder cancer tissues compared to normal tissues in a microarray-based lncRNA profiling study. In this study, we would like to explore the expression pattern and functional role of linc00346 in bladder cancer. Methods: We determined the expression of linc00346 in a cohort of bladder cancer tissues with matched normal tissues as well as human bladder cancer cell lines. We investigated the biological function of linc00346 with CCK-8 assay, colony formation assay, flow cytometry analysis, transwell assay and tumor xenografts mice model. Results: We found that linc00346 was upregulated in bladder cancer tissues compared to normal tissues. Knockdown of linc00346 inhibited bladder cancer cell proliferation and migration, induced cell cycle arrest and cell apoptosis. Conclusion: Our study demonstrates that linc00346 could be a potential oncogene and a therapeutic target in bladder cancer. - Highlights: • linc00346 was upregulated in bladder cancer tissues compared to normal tissues. • linc00346 promoted bladder cancer cell proliferation and migration. • Knockdown of linc00346 induced cell cycle arrest and cell apoptosis.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2017

Increased chemo-sensitivity by knockdown coilin expression involved acceleration of premature cellular senescence in HeLa cells

Coilin is a marker protein of the Cajal body (CB). Cajal bodies, functional nuclear structure, play important roles for the maturation of telomerase mRNAs. However, whether CB participates in the process of cell senescence is unknown. Cisplatin is a frequently used drug for the chemotherapy for various cancers, which was recently reported to be able to induce premature senescence of tumor cells. In this study, we found that when HeLa cells were treated with 2 μg/ml cisplatin for 4 days, stagnant cell growth, especially in cells stained positive of SA-β-gal, was accompanied with significant changes in CB morphologies. The removal of cisplatin allowed the recovery of normal CB appearance, but was not able to restore cells from senescent states. Knocking down coilin expression by siRNA attenuated the growth and reduced the viability of treated cells, and the decreased rate of CB formation correlated with increased staining of SA-β-gal. Interestingly, when coilin knocked-down cells exposed to cisplatin, the drug sensitivity as shown by the reduction of cell viability was significantly increased compared to the control siRNA transfection groups. Overexpression of coilin phosphomutants increased SA-β-gal fluorescence following treatments with cisplatin as compared to the wild type coilin transfection. Our results indicated that coilin was an important functional player that involved in cisplatin-induced premature cell senescence. It suggested that the modulation of coilin expression could be considered as a potential anti-tumor strategy to increase the sensitivity of chemotherapy through which drug-induced cell senescence was accelerated. - Highlights: • The morphology of Cajal body change in cisplatin inducing premature cells. • The release from cisplatin treatments resulted in the recovery of CB morphology. • Knocking down coilin expression accelerated cisplatin induced senescence. • The overexpression of coilin phosphomutants induced premature senescence.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

Structural basis for DNA recognition by STAT6

STAT6 participates in classical IL-4/IL-13 signaling and stimulator of interferon genes-mediated antiviral innate immune responses. Aberrations in STAT6-mediated signaling are linked to development of asthma and diseases of the immune system. In addition, STAT6 remains constitutively active in multiple types of cancer. Therefore, targeting STAT6 is an attractive proposition for treating related diseases. Although a lot is known about the role of STAT6 in transcriptional regulation, molecular details on how STAT6 recognizes and binds specific segments of DNA to exert its function are not clearly understood. Here, we report the crystal structures of a homodimer of phosphorylated STAT6 core fragment (STAT6 CF ) alone and bound with the N3 and N4 DNA binding site. Analysis of the structures reveals that STAT6 undergoes a dramatic conformational change on DNA binding, which was further validated by performing molecular dynamics simulation studies and small angle X-ray scattering analysis. Our data show that a larger angle at the intersection where the two protomers of STAT meet and the presence of a unique residue, H415, in the DNA-binding domain play important roles in discrimination of the N4 site DNA from the N3 site by STAT6. H415N mutation of STAT6 CF decreased affinity of the protein for the N4 site DNA, but increased its affinity for N3 site DNA, both in vitro and in vivo. Results of our structure–function studies on STAT6 shed light on mechanism of DNA recognition by STATs in general and explain the reasons underlying STAT6’s preference for N4 site DNA over N3.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2016

Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.

60 APPLIED LIFE SCIENCES↗