Over 4100 protein identifications from a Xenopus laevis fertilized egg digest using reversed‐phase chromatographic prefractionation followed by capillary zone electrophoresis–electrospray ionization–tandem mass spectrometry analysis

A tryptic digest generated from Xenopus laevis fertilized embryos was fractionated by RPLC. One set of 30 fractions was analyzed by 100‐min CZE‐ESI‐MS/MS separations (50 h total instrument time), and a second set of 15 fractions was analyzed by 3‐h UPLC‐ESI‐MS/MS separations (45 h total instrument time). CZE‐MS/MS produced 70% as many protein IDs (4134 versus 5787) and 60% as many peptide IDs (22 535 versus 36 848) as UPLC‐MS/MS with similar instrument time (50 h versus 45 h) but with 50 times smaller total consumed sample amount (1.5 μg versus 75 μg). Surprisingly, CZE generated peaks that were 25% more intense than UPLC for peptides that were identified by both techniques, despite the 50‐fold lower loading amount; this high sensitivity reflects the efficient ionization produced by the electrokinetically pumped nanospray interface used in CZE. This report is the first comparison of CZE‐MS/MS and UPLC‐MS/MS for large‐scale eukaryotic proteomic analysis. The numbers of protein and peptide identifications produced by CZE‐ESI‐MS/MS approach those produced by UPLC‐MS/MS, but with nearly two orders of magnitude lower sample amounts.     

Photothermal Catalytic Gel Featuring Spectral and Thermal Management for Parallel Freshwater and Hydrogen Production

Desalination processes often require large amounts of energy to create clean water, and vice versa for the generation of energy. This interdependence creates a tension between the two essential resources. Current research focuses on one or the other, which exacerbates water‐energy stress, while few tackle both issues jointly. Herein, a low‐carbon technology, H₂O–H₂ co‐generation system that enables concurrent steady freshwater and clean energy output is reported. The water‐energy coupled technology features a spectrally and thermally managed solar harvesting gel for photoredox and photoheating effects. This photothermal catalytic gel exploits interfacial solar heating for heat confinement, and localized plasmonic heating at the catalyst active sites to remarkably improve water and hydrogen production, thus maximizing energy value per area. To this end, a stand‐alone renewable solar desalination system is successfully demonstrated for parallel production of freshwater and hydrogen under natural sunlight. By doing so, the water–energy nexus is transformed into a synergistic bond that offers opportunities to better meet expected demand rather than acting in competition.     

DNA Methylation-Mediated Low Expression of CFTR Stimulates the Progression of Lung Adenocarcinoma

Biochemical Genetics - In recent years, the mortality rate of lung adenocarcinoma (LUAD) is persistently increasing, which has already caused a huge impact on human living standards. Hence, there...     

Discovery of potential anti-SARS-CoV-2 drugs based on large-scale screening in vitro and effect evaluation in vivo

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis. Clinical candidates with high efficacy, ready availability, and that do not develop resistance are in urgent need. Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture, there are few confirmed antiviral candidates in vivo. In this study, 94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs. Among them, 24 compounds with low cytotoxicity were selected, and of these, 17 compounds also effectively suppressed SARS-CoV-2 infection in HeLa cells transduced with human ACE2. Six compounds disturb multiple processes of the SARS-CoV-2 life cycle. Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2 infection. Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant. Except for cisatracurium, six compounds reduced hamster pulmonary viral load, and IL-6 and TNF-α mRNA when assayed at 4 d postinfection. In particular, sertraline, salinomycin, and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro, suggesting promising application for COVID-19 treatment.

     

A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo

Sorting nexins (SNXs) are phosphoinositide-binding proteins implicated in the sorting of various membrane proteins in vitro, but the in vivo functions of them remain largely unknown. We reported previously that SNX10 is a unique member of the SNX family genes in that it has vacuolation activity in cells. We investigate the biological function of SNX10 by loss-of-function assay in this study and demonstrate that SNX10 is required for the formation of primary cilia in cultured cells. In zebrafish, SNX10 is involved in ciliogenesis in the Kupffer's vesicle and essential for left-right patterning of visceral organs. Mechanistically, SNX10 interacts with V-ATPase complex and targets it to the centrosome where ciliogenesis is initiated. Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo and does so synergistically with SNX10. We further discover that SNX10 and V-ATPase regulate the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. These results identify an SNX10/V-ATPase-regulated vesicular trafficking pathway that is crucial for ciliogenesis, and reveal that SNX10/V-ATPase, through the regulation of cilia formation in various organs, play an essential role during early embryonic development.