Protein ubiquitination is one of the most important and widely exist protein post-translational modifications in eukaryotic cells, which takes the ubiquitin and ubiquitin chains as signal molecules to covalently modify other protein substrates. It plays an important roles in the control of almost all of the life processes, including gene transcription and translation, signal transduction and cell-cycle progression, besides classical 26S protesome degradation pathway. Varied modification sites in the same substrates as well as different types of ubiquitin linkages in the same modification sites contain different structural information, which conduct different signal or even determine the fate of the protein substrates in the cell. Any abnormalities in ubiquitin chain formation or its modification process may cause severe problem in maintaining the balance of intracellular environment and finally result in serious health problem of human being. In this review, we discussed the discovery, genetic characteristics and the crystal structure of the ubiquitin. We also emphasized the recent progresses of the assembly processes, structure and their biological function of ubiquitin chains. The relationship between the disregulation and related human diseases has also been discussed. These progress will shed light on the complexity of proteome, which may also provide tools in the new drug research and development processes.
Humans ; Proteome ; Ubiquitin ; chemistry ; Ubiquitination

Paraneoplastic neurological syndromes (PNS) are a rare group of immune-mediated disorders that affect the central and peripheral neuromuscular system in association with cancer.If the limbal lobe system of the brain is involved,it will show paraneoplastic limbal encephalitis(PLE).The discern of patients with PNS is challenging since tumors causing paraneoplastic neurologic disorders are often asymptomatic and sometimes occult.We report a case of PLE with double positive anti-Hu and Yo antibodies,and further analyze and discuss it in conmbination with relevant literature to improve the understanding of the disease.

Protein N-termini, as the beginning of translation, has a major impact on protein's biological functions. Its sequence and various post-translational modifications often affect protein activation, stability and cellular-localization, regulate the signal transduction, and even determine protein's final destiny. The systematic study of protein N-termini can clarify the vital function of the N-terminus, and provide in-depth knowledge of the multifunctional roles that protein has played in diverse biological processes. In addition, N-terminal research may help us to achieve high-coverage proteomics and re-annotate genomics. Combined with our own research, this review highlights recent progress of N-terminomics, especially some important enrichment strategies and technologies based on mass spectrometry.
Mass Spectrometry ; Protein Processing, Post-Translational ; Proteins ; chemistry ; Proteomics

Biliary atresia is a rare infant disease that predisposes patients to liver transplantation and death if not treated in time. However, early diagnosis is challenging because the clinical manifestations and laboratory tests of biliary atresia overlap with other cholestatic diseases. Therefore, it is very important to develop a simple, safe and reliable method for the early diagnosis of biliary atresia. Herein, a novel NIR-II fluorescence probe, HZL2, with high quantum yield, excellent biocompatibility, low cytotoxicity and rapid excretion through the liver and gallbladder was developed based on the oil/water partition coefficient and permeability. A simple fecal sample after injection of HZL2 can be used to efficiently identify the success of the mouse model of biliary atresia for the first time, allowing for an early diagnosis of the disease. This study not only developed a simple and safe method for the early diagnosis of biliary atresia with great potential in clinical translation but also provides a research tool for the development of pathogenesis and therapeutic medicines for biliary atresia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.