Abstract:Previous studies suggest that TLR4 is the membrane receptor for recognizing LPS. Recent studies have shown that Caspase-11 may play an important role in recognizing cytoplasmic LPS. Upon cytoplasmic LPS binding with Casp-11, Casp-11 activation is observed. Activated Casp-11 directly cleaves gasdermin D, inducing Casp-11-dependent pyroptosis and activates NLRP3/ASC-Casp-1 dependent IL-1β and IL-18 secretion. Besides, it also increases the elimination of Gram-negative bacteria by promoting the fusion of phagosomes and lysosomes. In the process of severe endotoxemia, due to excessive activation of Casp-11, a large number of cells undergo pyroptosis, which lead to intracellular proinflammatory mediators released, induce an uncontrollable inflammatory response, and ultimately lead to the occurrence of endotoxin shock. Casp-11 is a key molecule in endotoxin shock. In this paper, we review the latest progress of Casp-11 in LPS identification, activation and effect in endotoxin.

Abstract:Mitochondrion are one of the most important organelles in eukaryotic cells, the main function of which is to provide energy for the survival of cells. The abnormal mitochondrial can cause lesions in cells and even organs, and a growing number of diseases have been linked to mitochondrial defects. Mitochondrial transplantation, an intrusive therapy, which isolated the mitochondria from the normal parts of the patient and then inject it into the damaged or absent areas, so that the injured cells can be treated and the organ functions return to normal. As a novel therapeutic strategy, the manner has emerged in the basic research of some diseases, especially in the field of acute myocardial ischemia reperfusion injury, which has been developed to the clinical trial stage. Based on the origin of mitochondria, several feasible methods of mitochondrial transplantation in the experimental phase were summarized. In addition, the protection of cerebral ischemia/induced neuronal injury and tumor therapy by mitochondria transplantation were also introduced. Moreover, the molecular mechanisms of mitochondrial damage and mitochondrial transplantation were discussed, and put forward the research ideas for developing targeted therapeutic biological agents for mitochondrial transplantation. The paper aims to provide a new perspective for curing of mitochondrial deficiency diseases.

Abstract:Autophagy is widely found in eukaryotic cells, and closely related to the physiological and pathological processes in the body. Autophagy-lysosomal pathway is a process of self-degradation of cells, mainly involved in the degradation of long-lived proteins to remove damaged or excessive protein and organelles. Autophagy is usually categorized into three groups: macroautophagy, chaperone-mediated autophagy, and microautophagy.Deficits in the ALP lead to protein aggregation, resulting in the accumulation of abnormal proteins and ineffective organelles, which are hallmarks of Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD) and so on. The process of autophagy is regulated by a series of complex signaling molecules. One of them is TFEB, a member of the MiT family of transcription factors. Studies have shown that transcription factor EB (TFEB) can coordinate autophagy through positively regulating autophagosome formation and autophagosome- lysosome fusion. In addition, it enhances cellular clearance through lysosomal exocytosis. Therefore, as a major regulator of autophagosomal biogenesis, TFEB has been a key factor in the pathogenesis of related diseases. We reviewed the regulation of ALP and TFEB and their effects on neurodegenerative diseases, and looked forward to the complex effects of ALP and TFEB on pathology and their therapeutic significance.

Abstract:Ribosome is a protein translation machine and the target of a variety of clinical antimicrobial drugs. Therefore, in-depth understanding of bacterial protein translation mechanism is of great significance. Translation consists of initiation, elongation, termination, and recycling, coordinating to achieve high fidelity and precise regulation. Translocation is one of the most important events in the process of translation, which requires large conformational changes of the ribosome as well as the precise movement of tRNA2-mRNA through ribosome. In bacteria, translocation is driven by elongation factor G that catalyzes the hydrolysis of GTP. The recent development in single molecule fluorescence resonance energy transfer (smFRET) makes it possible to study tRNA movements and observe the conformational dynamics of the ribosome in real time. Here, we review the recent smFRET study progress in the dynamics of ribosome translocation. These advances will provide much insights into the molecular details and dynamics of the ribosome complexes, shedding new light on the process of translocation.

Abstract:In recent years, it has been proposed that sensory-motor experiences are often used to access concrete concepts，and the sensory-motor system is tightly related to the language system. Metaphors, which convey abstract concepts via concrete concepts, are common rhetoric in daily life. Exploring the role of the sensory-motor system in metaphor comprehension will lead to an improved understanding of the form and process of abstract concepts, and further elucidate the relationship between the sensory-motor system and the language system. In this paper, we summarize the experimental paradigm，cognitive features of sensory-motor metaphor comprehension, the mechanism of brain regions involved in sensory channels, action control and action performance during metaphor processing. We propose that the sensory-motor system selectively functions in metaphor comprehension, and the comprehension process relies on activities of sensory-motor regions, and the simulation of sensory-motor experience is not immediate and rapid but rather is influenced by language comprehension strategies. In the “Embodied abstraction” frame, “Simulated sensorimotor metaphor theory” further explains the interaction between the sensory-motor system and metaphor comprehension. Future studies are needed to verify and supplement these theories by adopting other analysis methods, and from other study perspectives like grammar, language acquisition and motion dysfunction.

Abstract:A method of focusing strongly scattered light through turbid media based on spatial light wavefront modulation was proposed in the field of biophysical imaging. The content and procedure of this new method was detailed described. The strict optical theory indicates that the focusing result is better if the effect of interference is considered more intensely. The experiment also indicates this phenomenon. In addition, the experiment reveals that under the same conditions, the more the number of pixels controlled on spatial light modulator, the better the focusing result is. This new method has higher signal-to-noise ratio than other methods. The result of focusing and the phase board uploaded on spatial light modulator are displayed in the paper. At the same time, the convergence rate of focusing is much faster than other methods. That is mainly because our method has considered interference and the focusing result is the superposition of all pixels modulated on spatial light modulator. Therefore, we think that it will provide a new idea for the research of biophysics imaging.

Abstract:Antimicrobial peptides have broad spectrum of antibacterial properties and are expected to become the better alternatives of antibiotics. Studies on the antibacterial mechanism can provide guidance for the design of new antibacterial peptides. No matter what kind of antibacterial mechanism, antibacterial peptides adsorb on the cell membrane firstly. In this manuscript, the molecular dynamic simulations were used to study the interaction between antimicrobial peptide BLFcin6 and five different membranes. For five kinds of cell membranes, the peptide combined with the surface of DPPC-CHOL membrane and POPG membrane rapidly, and tend to entered the hydrophobic interior of DPPC membrane. However, the peptide have little contact with POPC-CHOL membrane and POPC membrane. In terms of interaction energy, the peptide and POPG membrane have the strongest interaction, which mainly arise through the electrostatic interaction between the pepetide and the hydrophilic head of POPG membrane. For peptide and DPPC membrane, the interaction are mainly arise between the peptide and the hydrophobic tail of DPPC membrane. However, the peptide only combined with the surface of DPPC-CHOL membrane because of the effects of cholesterol. In the process of combination, the N-terminal Argnine residues contact with the cell membrane firstly, electrostatic interaction plays a key role in the process of peptide anchor in the cell membrane. The research explain why BLFcin6 peptide have antibacterial effect at the atomic level, which are the key residues, and also provide help for the further study of BLFcin6 peptide and its derivatives.

Abstract:Recent studies have suggested that the deformability of cells can be an effective biomarker to indicate the progression of diseases. Because of the obstacle of cellular heterogeneity, it was very difficult to make new cells stretch under the reported experimental conditions. In this paper, a cell electro-stretching method based on dielectrophoresis-coupled microfluidic chip was optimized and the effect of doxorubicin (DOX) on stiffness of leukemia NB4 cells was investigated using the established method. Firstly, positive dielectrophoresis (pDEP) method for cell capturing was optimized and validated, and the results demonstrated that it was easy to obtain pDEP effect of cells if the conductivity of cell suspension (σ_e) was so low as to make “cross-over” frequencies appear, meanwhile the frequency of the E-field f was adjusted in the range of the “cross-over” frequencies from Low-f₀ to High-f₀. Subsequently, three parameters affecting cell stretching were systemically discussed, and the results suggested that it was a prerequisite for cell electro-stretching that the conductivity of cell suspension (σ_e) was lower than that of cell cytoplasm (σ_c). In addition, increased voltage or decreased frequency of the E-field can also prompt cell stretching. Finally, the correlation between cell mechanical behavior and cell functional variation of NB4 cells was investigated via the optimized cell electro-stretching method, and the results showed that DOX treatment could make NB4 cells produce apoptosis and stiffen. Taken together, this study provides a novel cell electro-stretching method for the simple and efficient detection of cell deformability.

Abstract:One of the feature of the pathogenesis of type 2 diabetes is lipotoxicity-induced reduction in pancreatic β-cell mass. To study the mechanism by which free fatty acids cause β-cell death, we studied the contribution of different cell death pathways induced by palmitate in the β-cell line INS1. In addition to previously reported apoptosis, we propose pyroptosis as a novel pathway that partially contributes to the pancreatic β-cell death induced by free fatty acids using the real-time lapse image. We provide evidence that the mechanism of pyroptosis could involve DFNA5.