Abstract:Biomembranes play fundamental roles in all living systems to partition cells into subcellular compartments. However, these typically flat membranes may also fold into 3D periodic nanostructures, termed cubic membranes (CM), under certain physiological or pathological conditions. Three types of CM arrangements—gyroid (G), double diamond (D) and primitive (P)—have been identified in multiple cell types, yet their biological function is still obscure. The surfaces describing CM are triply periodic minimal or level surfaces and of great technological potential in crystalline and liquid crystalline materials at various length scales. This review briefly introduces: (1) the characterization of CM nanostructures by transmission electron microscope (TEM), scanning electron microscope (SEM) and EM tomography in biological systems; (2) an update on experimental data describing the role of lipids, proteins and Ca²⁺ on CM formation; (3) the proposed optical and antioxidant properties of CM; (4) the potential applications as a diagnostic biomarker for various human diseases, use of CM-derived lipids as gene delivery vehicles, use of CM as structural antioxidant, and CM-based photonic crystals as versatile light-modulators.

Abstract:Ferroptosis is a new form of cell death which is identified in recent years. It is an oxidative cell death induced by small molecules in certain circumstance, which is dependent on iron ion. Ferroptosis is caused by the imbalance of generation and degradation of intracellular reactive oxygen species(ROS). Ferroptosis inducer inhibits glutathione peroxidases(GPX) directly or indirectly through different pathway, resulting in the decrease of cellular antioxidant capacity and accumulation of ROS, which ultimately leads to ferroptosis. In this paper, we summarized the identification, characteristics and mechanism of ferroptosis. Besides, ferroptosis is involved in the development of many diseases, such as Parkinson disease, pancreatic cancer. And ferroptosis activated or inhibited can interfere with the progress of disease. Therefore, we believe that drugs based on ferroptosis will be used for treatment of disease in the future.

Abstract:Metaproteomics is a new frontier of microbiological science that collects the proteomic data from microbes in nature using mass spectrometry and explores the corresponding genetic and biochemical mechanisms with systematical bioinformatics. In contrast to the traditional approach, metaproteomic informatics adopts new strategies, including algorithms, databases and searches. As the metaproteomic samples generally contain very complicated protein components, a large dataset with all the potential microbe genomes is basically required for searching peptides based on the signals of mass spectrometry, while such searching process is real time-consuming. Several considerable factors such as dataset capacity, searching strategy and false positive control, therefore, have to be carefully evaluated to achieve the better results of protein identification with an acceptable accuracy and efficiency. Meanwhile, except a common sequence merger in proteomic informatics, metaproteomics has to deal with the issues of vast sequence homologous and species grouping. Solving these problems relies on effective utilization to the public information gained from NCBI for species classification, and filtration treatment from sequence to species using LCA algorithm. Herein, we briefly introduce this field, including which is the basic informatics strategy of metaproteomics, what are the tough challenges in metaproteomic informatics, and how the technique difficulties are being solved in future.

Abstract:Large conductance Ca²⁺ activated potassium channels are regulated by both intracellular Ca²⁺ and membrane potential. BK channel couples membrane voltage with the intracellular signal system, that plays important roles for cellular functions. BK channel is widely and densely expressed in various tissues of many species. Recent studies have demonstrated that BK channel was expressed in cardiomyocytes and involved in the regulation of cardiac systolic and diastolic. In this work, we present some progress in the study of coupling between BK channel and L-type Ca²⁺ channel gating and the function of cardiomyocyte BK channels as well as the response to substrate stiffness. These reports will help to understand the pathophysiology of mechano-sensitive ion channel-associated heart diseases.

Abstract:This study focused on the changes of network topological efficiency under the condition of maximizing the intrinsic functional connectivity, and explored the relationships between altered topological efficiency and depressive psychopathology. For this purpose, we collected the resting-state functional MRI data from 20 major depressive disorder (MDD) patients and 20 healthy control (HC) individuals with matching of age, gender and education level. Graph theory analysis showed that the patients with MDD exhibited significantly reduced nodal efficiency in the left parahippocampal gyrus, right amygdala, left heschl and left temporal pole (middle temporal gyrus) compared with the HC group. The reduced nodal efficiency indicated that the function of transmitting information to other regions was weakened in MDD patients. The local efficiency of the left medial superior frontal gyrus, left orbital superior frontal gyrus, right rectus, left amygdala, right superior parietal gyrus, left thalamus, and left temporal pole (middle temporal gyrus) were also significantly reduced. And the local efficiency of the left medial superior frontal gyrus, left amygdala, left thalamus had negative correlation with PHQ-9. The reduced local efficiency implied that the ability of information transmission at the local level was damaged in the depressed brain network. These results suggested that the prefrontal-thalamo-limbic system involving affective processing was damaged in MDD patients. Our findings might provide a potential biomarker for the clinical diagnosis of depressed patients.

Abstract:The vasculotropic pathogenic bacteria Bartonella henselae secretes 7 Bep effector proteins (BepA-G) and injects these proteins into host cells using a type Ⅳ secretion system. Among these effector proteins, BepD-F contain multiple copies of Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs in their N-terminal regions. After injection into host cells, the tyrosine residues in these EPIYA motifs will be phosphorylated by SFK, and the tyrosine-phosphorylated EPIYA motifs can subsequently interact with various SH2 domain-containing proteins from host cell and interfere with the SH2 signaling pathways of the host cells. In addition to B. henselae Bep effector proteins, numerous pathogenic bacteria effector proteins had been identified previously to contain EPIYA motifs. They were also found to utilize their EPIYA motifs to disrupt the SH2-signaling pathways of respective host cells, although they share no obvious overall sequence similarities. In contrast, only 6 proteins containing EPIYA motifs were found in human proteome, much lower than random occurrences, probably due to its toxicity in human cells. JAM-A is one of EPIYA motif containing proteins occurring in blood platelet, which can recruit Csk to avoid thrombus formation. BepE was reported to interact with Csk and disturb Csk-related signaling pathways. Here we reported the crystal structures of complexes between Csk and the phosphorylated EPIYA motifs from BepE and JAM-A, and biophysical measurements of their binding affinities. The complex structures show that Csk binds with two phosphopeptides in a similar way. The Csk SH2 domain binds with phosphotyrosine. Phosphopeptides are perpendicular to β-sheets in SH2 domain. Results of SPR show that the affinity of BepE with Csk is much higher than that of JAM-A. These results suggest that the EPIYA motif of toxic proteins binds with the SH2 domain of human Csk by a higher affinity, then disturb the SH2 domain proteins involved signaling pathways. The results reported here laid a solid foundation for our understanding of the structural basis of how toxic EPIYA motifs interrupt the SH2 signaling pathways of host cells.

Abstract:Whether encoding protein is the golden standard for distinguishing protein coding genes and non-coding RNA (ncRNA), while recent detected peptide coding small open reading frames (sORFs) from lncRNA challenged this standard. Now, more and more studies have shown that peptide coding sORFs exist in different regions of eukaryotic genomes universally, which play important roles in biological activities. Because of the low expression level as well as low abundance and the short sequence length, there are few computational and experimental methods or data resources exploited for peptide coding sORFs, then study of peptide coding sORFs is in its early phase. At present, most studies of peptide coding sORFs are concentrated on several model eukaryotes，people know little about its intrinsic features, therefore the peptide coding sORFs bring more challenges for genome annotation under the precision medicine era. In this work, comprehensive sequence and function analysis of the peptide coding sORFs were firstly performed based on more than 80 prokaryotic genomes. The results show that peptide coding sORFs also exist in prokaryotic genomes universally and many peptide coding sORFs sequences are conserved among different genomes. Further analysis indicates that the sequence complexity decreases and their functions are relatively centered with the decrease of sequence length of peptide coding sORFs. Finally, we summarized the problems and challenges psoposed by peptide coding sORFs, which will provide solid theoretical basis for future sORFs related studies.

Abstract:Abstract　In order to construct a bone tissue engineering scaffold that could sequentially release multiple growth factors, the released system combining of PLLA microspheres and nHA/PLGA porous scaffolds was prepared in this study. Firstly, BMP-2 was encapsulated into PLLA microspheres to prepare the BMP-2-PLLA microspheres, then BMP-2-PLLA microspheres, nHA/PLGA and FGF-2 freeze-dried powder were mixed according to a certain proportion to prepare the BMP-2-PLLAms/FGF-2-nHA/PLGA scaffolds by supercritical fluid foaming technique. The results indicated that the BMP-2-PLLA microspheres were spherical, and the particle size of BMP-2-PLLA microspheres ranged from 6 to 10 μm. The drug loading and encapsulation efficiency of BMP-2-PLLA microspheres was 1.45×10^-3% and 61.9%, respectively. BMP-2-PLLAms/FGF-2-nHA/PLGA composite scaffolds were obtained with the pore size of 100-200 μm, the porosity of 75.8%, the compressive strength of 6.8 MPa, and the degradation rate of 19.9% at 8 weeks. The cumulative releases of FGF-2 and BMP-2 from the scaffolds were respectively about 77.1% and 44.2% after 7 days, 84.9% and 61.5% after 14 days. The results of BMSCs proliferation and differentiation showed that FGF-2 and BMP-2 released from the composite scaffolds could significantly promote cell proliferation and differentiation, and present a high bioactivity. BMP-2-PLLAms/FGF-2-nHA/PLGA scaffolds realized the sequential delivery of BMP-2 and FGF-2, and could induce BMSCs proliferation and differentiation effectively.

Abstract:To investigate the role of histone deacetylase3(HDAC3) in T cell homeostasis, we deleted hdac3 in CD4⁺CD8⁺ double positive(DP) stage of thymocytes using the cd4-cre transgene .The CD4Cre-mediated hdac3 deletion did not impact T cell development in the thymus but resulted in a dramatic loss of peripheral T cells. In addition, peripheral T cells in hdac3 knock-out mice showed a dominant activation/effector/memory phenotype. Mechanism analysis revealed an increased cell apoptosis which was accompanied by an accelerated cell proliferation in the peripheral T cells of hdac3 knock-out mice. Moreover, Fas and FasL positive cells and FasL expression increased significantly in the peripheral T cells of hdac3 knock-out mice. In vitro TCR activation did not affect the apoptosis of normal peripheral T cells, but dramatically increased apoptosis of peripheral T cells from hdac3 knock-out mice. Our results presented here indicate an important role of HDAC3 in maintaining homeostasis of peripheral T cells by refraining them from activation- induced cell death.