Tafenoquine and its derivatives as inhibitors for the severe acute respiratory syndrome coronavirus 2.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely affected human lives around the world as well as the global economy. Therefore, effective treatments against COVID-19 are urgently needed. Here, we screened a library containing Food and Drug Administration (FDA)-approved compounds to identify drugs that could target the SARS-CoV-2 main protease (Mpro), which is indispensable for viral protein maturation and regard as an important therapeutic target. We identified antimalarial drug tafenoquine (TFQ), which is approved for radical cure of Plasmodium vivax and malaria prophylaxis, as a top candidate to inhibit Mpro protease activity. The crystal structure of SARS-CoV-2 Mpro in complex with TFQ revealed that TFQ noncovalently bound to and reshaped the substrate-binding pocket of Mpro by altering the loop region (residues 139-144) near the catalytic Cys145, which could block the catalysis of its peptide substrates. We also found that TFQ inhibited human transmembrane protease serine 2 (TMPRSS2). Furthermore, one TFQ derivative, compound 7, showed a better therapeutic index than TFQ on TMPRSS2 and may therefore inhibit the infectibility of SARS-CoV-2, including that of several mutant variants. These results suggest new potential strategies to block infection of SARS-CoV-2 and rising variants.

Development of novel green methods for preparation of lead-free preserved pidan (duck egg).

Pidan, a pickled duck egg, is a traditional Chinese cuisine and generally produced by soaking in metal ion containing strong alkaline solution such as NaOH solution. However, nowadays consumers possess negative perception for using strong alkali in food processing. Therefore, the objective of the current study was to determine the potential of incinerated eggshell powder and alkaline electrolyzed oxidized (EO) water for pidan production rather than harmful NaOH use. This study aims to obtain the optimal physicochemical and sensory qualities of pidan. Various dosing (1-5%) of the incinerated eggshell powder solution or alkaline EO water was used as a basic pickling solution. Duck eggs were pickled at 25-27 °C for 15-30 days with 3 days of an observation interval. Actual commercial process commonly undergoes for 14 days of ripening, after 25 days of picking process with incinerated eggshell powder or EO water. Results showed that physicochemical and sensory attributes of pidan obtained by incinerated eggshell powder solution and alkaline EO water were not significantly different (P < 0.05) from the commercial product. This study reports a cost-effective and green alternative method for pidan processing by replacing costly NaOH without compromising their physico-chemical and sensory attributes.

PCDH10 exerts tumor-suppressor functions through modulation of EGFR/AKT axis in colorectal cancer.

Protocadherin 10 (PCDH10) is identified as a tumor suppressor in multiple cancers. The molecular mechanisms that mediate the functions of PCDH10 have yet to be fully elucidated. Here, we demonstrated that ectopic expression of PCDH10 in colorectal cancer (CRC) cells induced cell cycle retardation and increased apoptosis through regulation of the p53/p21/Rb axis and Bcl-2 expression. Overexpression of PCDH10 reversed the epithelial-mesenchymal transition (EMT) process with morphological changes and EMT marker alterations. Mechanistic study revealed that PCDH10 inhibited AKT/GSK3ß signaling pathway which in turn reduced ß-catenin activity and thus attenuated Snail and Twist1 expression. Furthermore, PCDH10 inhibited the stemness of CRC cells, including spheroid formation and stem cell markers. A proteomics approach revealed that PCDH10 could interact with EGFR, which was further verified by co-immunoprecipitation. Moreover, restoration of PCDH10 expression reduced EGFR phosphorylation. Accordingly, our work proposes a novel pathway by which PCDH10 directly engages in the negative regulation of EGFR/AKT/ß-catenin signaling pathway, resulting in tumor suppression.

Structural changes of Er:YAG laser-irradiated human dentin.

OBJECTIVE: The aim of this study was to investigate the phase, compositional, and morphological changes of Er:YAG laser-irradiated dentin. BACKGROUND DATA: To date, nothing comprehensive has been reported about the phase and compositional changes of human dentin after Er:YAG laser irradiation. METHODS: The human dentin was irradiated by Er:YAG laser with irradiation energies from 300 mJ/pulse-10 pps-10 sec to 700 mJ/pulse-10 pps-10 sec with and without water spray. After irradiation, the specimens were analyzed by means of x-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). RESULTS: After exposure to Er:YAG laser, dentin showed no phase changes on the x-ray diffractometer. In Fourier transform infrared analysis, two absorption bands at 2200 and 2015 cm(-1) could be traced on dentin treated by Er:YAG laser with irradiation energies beyond 300 mJ/pulse-10 pps-10 sec and without water spray. The OH(-) band disappeared at 1630 cm(-1). Scanning electron micrographs revealed that laser energy of 500 mJ/pulse-10 pps-10 sec was sufficient to prompt melting and recrystallization of dentin crystals. CONCLUSIONS: Our study demonstrated that Er:YAG laser irradiation on dentin with water spray would not significantly change the structure and composition. Therefore, water cooling is important for reducing the thermal effect of Er:YAG laser.