Case Report: A Nasopharyngeal Cancer Patient Got COVID-19 During Radiochemotherapy in Wuhan.

The coronavirus disease (COVID-19) infection, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Reports of COVID-19 among cancer patients are limited and most studies focus mainly on its epidemiological and clinical features. In this study, we report the case of a nasopharyngeal cancer patient from Wuhan who contracted COVID-19 during radiochemotherapy and has since recovered from the infection. We hope that this report will provide valuable insight into the treatment of SARS-CoV-2-infected cancer patients through an account of our experience.

A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients.

In this study, we aimed to evaluate the diagnostic value of serological assay for SARS-CoV-2. A newly-developed ELISA assay for IgM and IgG antibodies against N protein of SARS-CoV-2 was used to screen the serums of 238 admitted hospital patients between February 6 and February 14, 2020 with confirmed or suspected SARS-CoV-2. SARS-CoV-2 RNA was detected on pharyngeal swab specimens using real time RT-PCR. 194 (81.5%) of the serums were detected to be antibody (IgM and/or IgG) positive, significantly higher than the positive rate of viral RNA (64.3%). There was no difference in the positive rate of antibodies between the confirmed patients (83.0%, 127/153) and the suspected patients (78.8%, 67/85), whose nucleic acid tests were negative. The antibody positive rates were very low in the first five days after initial onset of symptoms, and then rapidly increased as the disease progressed. After 10 days, the antibody positive rates jumped from below 50% to over 80%. However, the positive rates of viral RNA maintained above 60% in the first 11 days after initial onset of symptoms, and then rapidly decreased. Overall, the suspected patients were most likely infected by SARS-CoV-2. Before the 11th day after initial onset of symptoms, nucleic acid test is key for confirmation of viral infection. The combination of serological assay can greatly improve the diagnostic efficacy. After the 11th day post-disease onset, the diagnosis for viral infection should be majorly dependent on serological assay.

Chlorine dioxide-induced and Congo red-inhibited Marangoni effect on the chlorite-trithionate reaction front.

Hydrodynamic flows can exert multiple effects on an exothermal autocatalytic reaction, such as buoyancy and the Marangoni convection, which can change the structure and velocity of chemical waves. Here we report that in the chlorite-trithionate reaction, the production and consumption of chlorine dioxide can induce and inhibit Marangoni flow, respectively, leading to different chemo-hydrodynamic patterns. The horizontal propagation of a reaction-diffusion-convection front was investigated with the upper surface open to the air. The Marangoni convection, induced by gaseous chlorine dioxide on the surface, produced from chlorite disproportionation after the proton autocatalysis, has the same effect as the heat convection. When the Marangoni effect is removed by the reaction of chlorine dioxide with the Congo red (CR) indicator, an oscillatory propagation of the front tip is observed under suitable conditions. Replacing CR with bromophenol blue (BPB) distinctly enhanced the floating, resulting in multiple vortexes, owing to the coexistence between BPB and chlorine dioxide. Using the incompressible Navier-Stokes equations coupled with reaction-diffusion and heat conduction equations, we numerically obtain various experimental scenarios of front instability for the exothermic autocatalytic reaction coupled with buoyancy-driven convection and Marangoni convection.

lncRNA uc009yby.1 promotes renal cell proliferation and is associated with poor survival in patients with clear cell renal cell carcinomas.

The expression and function of long non-coding RNAs (lncRNAs) in clear cell renal cell carcinoma (ccRCC) remains unclear. The present study measured the expression profiles of three lncRNAs (uc009yby.1, ENST00000514034, and ENST00000450687) using reverse transcription-quantitative polymerase chain reaction, and assessed their signatures in distinguishing ccRCC from matched normal tissues via analysis of receiver operating characteristic (ROC) curves. The expression of uc009yby.1 was inhibited by transfection of renal cells with small interfering RNA, and then the cell proliferation was evaluated by using a Cell Counting Kit-8. The results showed that the expressions of uc009yby.1 and ENST00000514034 were markedly increased in ccRCC compared with the matched normal tissues (P<0.0001 and P=0.0008, respectively), whereas the ENST00000450687 expression was not significantly altered. ROC curves yielded an area under the curve (AUC) value of 0.7000 for uc009yby.1, with sensitivity of 54.29% and specificity of 82.86%; and an AUC value of 0.6627 for ENST00000514034, with sensitivity of 60.00% and specificity of 67.14%. Furthermore, knockdown of uc009yby.1 suppressed renal cell proliferation (Day 0, P=0.7844; Day 1, P=0.0018; Day 2, P=0.0001; Day 3, P<0.000; Day 4, P<0.0001). Taken together, these findings suggest that the expression profiles of uc009yby.1 and ENST00000514034 may serve as novel biomarkers for ccRCC detection, and that uc009yby.1 is strongly associated with renal cell proliferation.

Renoprotective effects of ursolic acid on ischemia/reperfusion­induced acute kidney injury through oxidative stress, inflammation and the inhibition of STAT3 and NF­κB activities.

Ursolic acid, a pentacyclic triterpene compound with low toxicity and easy availability, has a variety of biological activities, including antitumor, antioxidant, antihepatitis, anti­inflammatory and antibacterial effects. The present study aimed to investigate the renoprotective effects of ursolic acid on ischemia/reperfusion­induced acute kidney injury (I/R­IAKI) in rats associated with its antioxidant and anti­inflammatory effects, as well as interference with the signal transducer and activator of transcription (STAT)3/nuclear factor (NF)­κB signaling pathway. The present study demonstrated that pre­treatment with ursolic acid significantly increased renal functioning and attenuated increases of serum angiotensin II levels in rats subjected to I/R­IAKI. In addition, I/R­IAKI­induced inflammation and oxidative stress were significantly reduced by pre­treatment with ursolic acid. Furthermore, ursolic acid significantly suppressed the upregulation of STAT3, NF­κB and caspase­3 activities in rats following I/R­IAKI. These results indicated that ursolic acid may be a potential drug for reducing I/R­IAKI through suppression of inflammation and oxidative stress damage, as well as modulation of STAT3 and NF­κB activities.

Highly selective aza-nitrile inhibitors for cathepsin K, structural optimization and molecular modeling.

As a new type of cathepsin K inhibitor, azadipeptide nitriles have the characteristics of proteolytic stability and excellent inhibitory activity, but they exhibit barely any satisfactory selectivity. Great efforts have focused on improving their selectivity toward cathepsin K. In this sequential study, we report the further structural optimization, synthesis, molecular modeling, and in vitro enzymatic assays of a new series of potent and selective inhibitors of cathepsin K without the P2-P3 amide linker. Significant selective improvements were achieved for cathepsin K over L, S and B, and a triaryl meta-product possessed the favorable balance between potency (Ki = 0.29 nM) and selectivity of cathepsin K over cathepsin L (320-fold), S (1784-fold) and B (8566-fold). We undertook a covalent protein-ligand docking study to explain the improved selectivity of several representative compounds. Such a selectivity improvement would be useful to avoid harmful side effects in practical applications of these compounds.

Highly selective azadipeptide nitrile inhibitors for cathepsin K: design, synthesis and activity assays.

We have developed a series of azadipeptide nitriles with different P3 groups. A triaryl meta-phenyl derivative, compound 13, was not only a potent inhibitor for cathepsin K (K(i) = 0.0031 nM), but also highly selective over both cathepsins B and S (~1000-fold). A protein-ligand docking study performed on the series provided a possible explanation why compound 13 could be significantly more potent than the others, especially compound 12 in the same series.