Abstract:Programmed cell death is critical for maintenance cellular organisms homeostasis. Necroptosis is a recently identified mode of programmed cell death that morphologically similar to necrosis. Necroptosis is mediated by Receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and its substrate Mixed lineage kinase domain-like protein（MLKL）. It has been shown that necroptosis is related to several human diseases, such as inflammatory diseases, autoimmune diseases, tumors and degenerative diseases. In this review, we will discuss the molecular mechanisms of necroptosis and its associated diseases.

Abstract:Calcification of atherosclerotic plaque, which mainly observed in the intima of arterial vessels, is one of the clinical signs of atherosclerosis in cardiovascular diseases. Calcification in atheroma dose not increase the vulnerability of plaque, while microcalcification (μCalcs) located within the fibrous cap could intensify the background circumferential stress in the cap, resulting in increased vulnerability of plaque. The mechanisms of calcification in atherosclerotic plaques include passive calcification and active calcification. Passive calcification is regulated by hormones and local signals. The mechanisms of active calcification are a cell-mediated process, participated by matrix vesicles, cell apoptosis, exosomes, oxidative stress response and autophagy. This paper reviews the calcification mechanisms of atherosclerotic plaque.

Abstract:The transmembrane-bound Nrf1 transcription factor, a key member of the CNC-bZIP (cap’n’collar -basic leucine zipper) family, plays a vital role in maintaining intracellular redox balance, proteostasis, endoplasmic reticulum and mitochondrial stability, and so on. Deficiency of Nrf1 in different tissues and organs resulted in a series of diseases in mouse model, including nonalcoholic steatohepatitis, neurodegenerative diseases, diabetes and others. In recent years, new functions of Nrf1 have been gradually revealed in various animal models and clinical findings, especially involving in the process of brown fat tissue thermogenic adaptation (cold adaptation), cholesterol metabolism, glucose metabolism, endoplasmic reticulum stress, and congenital disorder of deglycosylation. Therefore, to gain a better understanding of Nrf1, a briefly review focused on its biological functions was demonstrated in this work.

Abstract:Protein disulfide isomerase (PDI) can catalyze the formation, breakage and rearrangement of disulfide bonds, and promote protein folding, which is essential to stabilize the three-dimensional structure of proteins. The dysregulation of PDI expression or enzyme activity is closely related to a series of diseases, such as cancer, neurodegenerative diseases, and thrombosis. In this review, we summarized the structure of PDI, its relationship with diseases and the research progress of its inhibitors. We also pointed out the current problems and the development direction of PDI inhibitors, which will provide references for its further research.

Abstract:The human gut microbiota is a metabolic organ that plays an essential role in human health and disease. The molecular mechanisms of its involvement in processes such as host food digestion, immunity and brain function are the synergistic coupling of specific metabolic pathways between microorganism and human. Enzymes are the basic functional units that involved in the transformation of substances in the metabolic pathways. An in-depth look into the catalytic mechanisms of the enzymes encoded by human gut microbiota will provide a theoretical framework for exploring the interventions of precision nutrition and medicine targeting the human gut microbiota (or intestinal enzymes). Studies on enzymatic hydrolysis of specific substrates have shown that the human gut microbiota not only encodes all known families of carbohydrate active enzymes (CAZYmes), but also contains plenty of the potentially novel CAZYmes. This paper describes the principles of classification and catalytic properties of CAZYmes, and mainly reviews the research progresses on the crystal structures of novel CAZYmes derived from the human gut microbiota.

Abstract:Syntaxin-1, known as a multi-domain protein, regulates vesicle fusion by forming SNARE complex with synaptobrevin-2 and SNAP-25. However, the role of syntaxin-1 in synapse formation remains uncovered. Here we demonstrated that the expression level of syntaxin-1 was highly associated with the process of synaptogenesis. The R151A and I155A mutations but not Habc or transmembrane domain truncations of syntaxin-1 impaired its facilitation in synapse formation. Our results suggested that syntaxin-1 accelerated synapse formation via activating synaptic vesicle release.

Abstract:We constructed a non-redundant non-ribosomal protein-RNA interface dataset (including 694 structures) from the Protein Data Bank (PDB). The interface preferences of amino acids, nucleotides and the secondary structure elements of protein and RNA were computed based on the dataset. The results show that β-ladder, β-bridge and 310-helix of proteins and the unpaired nucleotides of RNA, especially those irregularly arranged nucleotides have remarkably high interface propensities. Based on these, we classified the secondary structure elements, constructed the 60×12 amino acid-nucleotide pairwise potential, and used it as a scoring function in protein-RNA docking to select the near native structures. The results show the 60×12 pairwise potential has a scoring success rate of 65.77%, better than those of the pairwise potentials with secondary structure information of protein or RNA considered, as well as better than that of our previously constructed 60×8* potential based on the 251 protein-RNA complex structures. This work is helpful for strengthening the understanding of protein-RNA specific interactions and can advance the progress of protein-RNA complex structure prediction.