Background The outbreak of the coronavirus disease 2019 (Covid‐19) has shown a global spreading trend. Early and effective predictors of clinical outcomes are urgently needed to improve management of Covid‐19 patients. Objective The aim of the present study was to evaluate whether elevated D‐dimer levels could predict mortality in patients with Covid‐19. Methods Patients with laboratory confirmed Covid‐19 were retrospective enrolled in Wuhan Asia General Hospital from January 12, 2020, to March 15, 2020. D‐dimer levels on admission and death events were collected to calculate the optimum cutoff using receiver operating characteristic curves. According to the cutoff, the subjects were divided into two groups. Then the in‐hospital mortality between two groups were compared to assess the predictive value of D‐dimer level. Results A total of 343 eligible patients were enrolled in the study. The optimum cutoff value of D‐dimer to predict in‐hospital mortality was 2.0 µg/mL with a sensitivity of 92.3% and a specificity of 83.3%. There were 67 patients with D‐dimer ≥2.0 µg/mL, and 267 patients with D‐dimer <2.0 µg/mL on admission. 13 deaths occurred during hospitalization. Patients with D‐dimer levels ≥2.0 µg/mL had a higher incidence of mortality when comparing with those who with D‐dimer levels <2.0 µg/mL (12/67 vs 1/267, P < .001; hazard ratio, 51.5; 95% confidence interval, 12.9‐206.7). Conclusions D‐dimer on admission greater than 2.0 µg/mL (fourfold increase) could effectively predict in‐hospital mortality in patients with Covid‐19, which indicated D‐dimer could be an early and helpful marker to improve management of Covid‐19 patients. (Chinese Clinical Trial Registry: ChiCTR2000031428).

GATA3 expression has been reported in urothelial and breast carcinomas; however, the published data on GATA3 expression in tumors from other organs are limited. Immunohistochemical evaluation of GATA3 expression in 1,110 carcinomas and 310 cases of normal tissue using tissue microarray sections, 48 breast and bladder biopsy specimens, and 53 breast fine-needle aspiration biopsy specimens was performed. Sixty-two of 72 urothelial carcinomas (86%) and 138 of 147 breast carcinomas (94%) tested positive for GATA3. All other cases, except for 2 of 96 endometrial carcinomas, tested negative for GATA3. On fine-needle aspiration biopsy samples, 88% of primary breast carcinomas and 82% of metastatic breast carcinomas tested positive for GATA3. Our study revealed that GATA3 is a sensitive and specific marker for the diagnosis of breast and urothelial carcinomas. When working on a tumor of unknown origin, GATA3 should be routinely included in the initial screening panel if either a breast or urothelial primary tumor is suspected.

SUMMARY Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is essential for for biosynthetic reactions and antioxidant functions; however, detection of NADPH metabolism in living cells remains technically challenging. We develop and characterize ratiometric, pH-resistant, genetically encoded fluorescent indicators for NADPH (iNap sensors) with various affinities and wide dynamic range. The iNap sensors permitted quantification of cytosolic and mitochondrial NADPH pools that were controlled by cytosolic NAD+ kinase levels, and revealed cellular NADPH dynamics under oxidative stress depending on glucose availability. We find that mammalian cells have a strong tendency to maintain physiological NADPH homeostasis, which is regulated by glucose-6-phosphate dehydrogenase (G6PD) and AMP kinase (AMPK). Moreover, using the iNap sensors we monitor NADPH fluctuations during the activation of macrophage cells or wound response in vivo. These data demonstrate that the iNap sensors will be valuable tools for monitoring NADPH dynamics in live-cells, and gaining new insights into cell metabolism.

GlcNAcylation, a dynamic posttranslational modification, is involved in a wide range of biological processes and some human diseases. Although there is emerging evidence that some tumor-associated proteins are modified by GlcNAcylation, the role of GlcNAcylation in tumor progression remains unclear. Here, we show that GlcNAcylation enhances the migration/invasion of breast cancer cells in vitro and lung metastasis in vivo. The decrease of cell surface E-cadherin is the molecular mechanism underlying GlcNAcylation-induced breast cancer metastasis. p120 and β-catenin, but not E-cadherin, are GlcNAcylated; the GlcNAcylation of p120 and β-catenin might play roles in the decrease of cell surface E-cadherin. Moreover, immunohistochemistry analysis indicated that the global GlcNAcylation level in breast tumor tissues is elevated significantly as compared with that in the corresponding adjacent tissues; further, GlcNAcylation was significantly enhanced in metastatic lymph nodes compared with their corresponding primary tumor tissues. This is the first report to clearly elucidate the roles and mechanisms whereby GlcNAcylation influences the malignant properties of breast cancer cells. These results also suggest that GlcNAcylation might be a potential target for the diagnosis and therapy of breast cancer. Cancer Res; 70(15);