Abstract:Deep brain stimulation (DBS) has been applied widely in clinic to treat movement disorders such as Parkinson’s disease. It also shows great prospects in the treatments of intractable epilepsy, refractory obsessive-compulsive disorder, and other diseases of the central nervous system in brain. Over the past three decades, the mechanisms of DBS have emerged gradually based on multiple lines of evidence in clinical applications, in animal experiments, and in simulations of computational models. Important advances in DBS mechanisms have been achieved although final conclusions are still under debate. This review analyzes and summarizes the development of DBS theories from electrophysiological perspectives: from the original theory of inhibitions or excitations to the recent prevalent theory of modulations; from focusing on neuronal activity locally at stimulation sites to discovering the decoupling of somatic and axonal responses, and further to discovering the intermittent depolarization block of axons induced by high frequency stimulations, together with de-synchronous activity presumably caused by axonal activity in population neurons in the projection brain regions. The series of advances indicate that DBS has complex mechanisms in modulating the neuronal networks. Understanding the mechanisms of DBS has significance for improving DBS therapies, for developing new stimulation modes, and for extending its clinical applications.

Abstract:Polyglutamine (polyQ) diseases are a group of neurodegenerative disorders caused by aberrant expansion of CAG trinucleotide in the coding sequence of different disease proteins. This CAG trinucleotide repeats lead to the abnormal polyQ expansion in the translated proteins, which may cause protein misfolding and aggregation. Protein aggregation or inclusion formation is a common feature shared by diverse neurodegenerative diseases. Aggregation of polyQ-expanded proteins can sequester other interacting proteins or RNA into the insoluble aggregates or inclusions, which may result in decrease in the soluble pools of both polyQ proteins and other sequestered proteins or RNA, leading to the loss of biological function. According to the interaction modes, we classified the sequestration effects of protein aggregates into four distinct types: protein (including polyQ protein) co-aggregation; specific domain/motif-mediated sequestration (including modified ubiquitin and others); RNA-mediated sequestration; and sequestration of molecular chaperones. Thus, aggregation of the polyQ-expanded proteins and sequestration of cellular essential proteins may be the major causes for cytotoxicity and neurodegeneration.

Abstract:Deep learning is the most popular research area in the field of machine learning in recent years, especially in image and speech recognition, natural language processing, and automatic driving．Biological mass spectrometry is an important research tool in the field of life sciences and plays a key role in proteomics, metabolomics, and biopharmaceuticals．In recent years, based on the development of deep learning methods, the big data analysis in proteomics centered on biological mass spectrometry will usher into a new era．This article reviews the latest applications of deep learning methods in the analysis of biological mass spectrometry data and proteomics research.

Abstract:Breast cancer is one of the most important malignant tumors affecting women’s health. Epigenetic modification and oxidative stress caused by excessive accumulation of reactive oxygen species (ROS) play a key role in the occurrence and development of breast cancer. In addition, epigenetic modification and the production and clearance of ROS interact with each other. In this paper, epigenetic modification and ROS involved in the occurrence and development of breast cancer are reviewed in order to provide possible ideas for seeking biomarkers and precise therapy for the treatment of breast cancer.

Abstract:Hepatocellular carcinoma (HCC) is a kind of cancer with extremely high mortality. Most patients have been in the advanced stage when they went to see the doctor. The enzyme methionine adenosine transferase (MAT), as the key to the survival of the cell, could promote the biosynthesis of the biological methyl donor S-adenosylmethionine (SAMe) by catalyzing the binding of methionine and adenosine triphosphate (ATP). There is a dynamic equilibrium between MAT1A and MAT2A in normal hepatocytes, which maintains the homeostasis of SAMe. The transformation of MAT1A to MAT2A will reduce the biosynthesis of SAMe and provide favorable conditions for the cell growth of HCC. Generally speaking, MAT1A expression is high but MAT2A expression is low in healthy liver tissues while MAT1A is decreased but MAT2A increased in HCC. Therefore, to accelerate the transformation of MAT2A to MAT1A, then improve the MAT1A/MAT2A ratio would be as a key to HCC treatment. This article mainly discusses the transformation of MAT1A to MAT2A in HCC, aiming to find a new way to explore the target for HCC prevention and treatment.

Abstract:Phytosterols are a type of bioactive substances widely found in plants and have broad application prospects in food, medicine, cosmetics and other fields. Phytosterols, as cholesterol analogues, can inhibit the absorption of cholesterol in the intestine and decrease serum cholesterol level and thus reduce the risk of cardiovascular diseases. In addition, phytosterols have many other functions such as cancer suppression, anti-inflammation or anti-fever, anti-oxidation and hormone-like effects. In-depth exploration of the subcellular and molecular mechanism of phytosterols’ biological functions contributes to the full development of the application value of phytosterols. Mitochondria are the most important sites for cellular energy metabolism. Cholesterol metabolism, cancer cell proliferation and apoptosis, oxidative stress, and inflammatory response are all closely related to mitochondrial function. Recent studies have suggested that phytosterols can regulate mitochondrial function in various models, which potentially may be a pivotal mechanism underlying phytosterols’ various biological functions. This article will first summarize the biological functions of phytosterols and then discuss its mitochondria-related regulatory mechanisms in detail, hoping to provide frontier insights and progress report for researchers in the field as well as to provide reference for the application of phytosterols.

Abstract:Protein phosphorylation is one of post-translational modifications (PTM), which plays a role in regulation of development, signal transduction, and processes of diseases. Because of high sensitivity, considerable throughput, and residue resolution, mass spectrometry (MS) has been the most popular tool for phosphorylation modification analysis. Common MS-centric phosphoproteomics workflow includes phosphorylation modified peptides sampling, LC-MS/MS detection, phosphorylation sites assignment and quantification. We summarized and discussed these workflow parts in this review.

Abstract:A cadmium-responsive metal ion transporter OsPDR, which was highly upregulated in the shoot of rice (Oryza sativa ssp. japonica cv. Nipponbare) at 24 h after treatment with 50 μmol/L Cd, was identified in cadmium-responsive transcriptome profiles analyzed by RNA-Seq. In this study, we isolated OsPDR from rice (Oryza sativa cv. Nipponbare) and the metal ions transport activity of OsPDR was analyzed. The results of metal tolerance experiments showed that overexpression of OsPDR can enhance yeast’s tolerance to Co, but not to Zn, Ni or Cd, and higher accumulation of Co was observed compared to the empty vector-transformed yeast as determined by inductively coupled plasma mass spectrometry (ICP-MS). The EGFP-OsPDR fusion protein was localized to the vacuolar membrane using confocal microscopy. These data suggested that OsPDR might play an important role in Co homeostasis. Additional studies are needed to understand the function of OsPDR in plants.

Abstract:Due to the relatively high lipid productivity, microalgae are promising raw material for biofuel production. The understanding for the mechanism of lipid biosynthesis is an important concern which may contribute to the increase of lipid production. Chlamydomonas reinhardtii under nitrogen depletion condition is a model system to investigate the pathway of lipid biosynthesis. Substantial amount of data have been accumulated using “omics” approaches recently, however, the identification of reference and biomarker proteins in nitrogen depletion-mediated triacylglycerol biosynthesis in C. reinhardtii is limited. In this study, C. reinhardtii CC-124 grown in control and nitrogen depleted medium were surveyed to compare the morphology, cell density, lipid content, and total protein content at multiple time points (0, 1, 2, 4 and 6 days). Under nitrogen depletion treatment, the culture turned yellow from green and the A₇₅₀ and cell number was decreased, indicated that the cell growth was retarted. Furthermore, the concentration of neutral lipid was up-regulated based on nile red staining assay, while the coomassie brilliant blue staining assay indicated that the concentration of total protein was decreased. Western blot (WB) was performed to detect the expression patterns for 20 candidate C. reinhardtii proteins at different time points. To identify the reference proteins under nitrogen depleted condition, the Pearson’s correlation coefficient (PCC) between the content of total proteins and candidate proteins was calculated. Three proteins (Histone H3, RBCL (ribulose-1, 5-bisphosphate carboxylase/oxygenase large subunit) and BCR1 (biotin carboxylase, ACCase complex 1)) were selected due to their significant positive correlations (P < 0.01) in both nitrogen depleted and control conditions. Comparison of average relative fold change (ARF) of the candidate proteins indicated that the top 3 proteins are ATPs-β (ATP synthase CF1 beta subunit), GAP2 (glyceraldehyde 3-phosphate dehydroase 2) and RMT1 (rubisco large subunit N-methyltransferase 1), their ARFs are 180.59, 52.90 and 12.48, respectively, which were then chosen as biomarkers. Futhermore, to compare the earliest time point at which biomarker band can be detectable, protein samples at early stage (0, 2, 4, 8, 12, 18, 24 and 48 h) at nitrogen depletion treatment were collected and analysed by WB, it was showed that the induction bands of ATPs-β, GAP2 and RMT1 appeared at 8, 18 and 12 h, respectively. Thus, ATPs-β was the most appreciate biomarker since it is the earliest showed and the largest degree varied among candidates proteins tested. The reference and biomarker proteins identified in this study will provide help for the mechanism investigation of nitrogen depletion responses and lipid biosynthesis in C. reinhardtii, the expression profiling acculumated for candidate proteins can be refered by the reseach community.

Abstract:Convenient, reliable detection of transmembrane protein topology, especially the orientation of the amino (N-) and carboxyl (C-) termini of a membrane-spanning segment, may aid in identifying protein-protein interactions and clarifying the important biological functions of proteins. Self-complementing split fluorescent proteins have been widely used to image protein-protein interactions, label endogenous proteins and visualize mRNA localization. Here, we expand this toolset and develop an efficient method combining a self-complementing split mNeonGreen2 with site-directed labeling (SSDL) to identify the topology of transmembrane proteins. With SSDL, for the first time, we clearly demonstrate that both the N- and C-termini of etoposide-induced protein 2.4, which localizes in the endoplasmic reticulum, have a cytosolic orientation. This method can be useful for determining the topology of other organelle-based transmembrane proteins that have insufficient structural information.