Abstract:Protein acylation is a type of protein post-translational modification. Novel acylations except for acetylation, have been expanded successively in recent years. Histone acylation can directly modulate the packaging of chromatin either by altering the net charge of histone molecules or by altering inter-nucleosomal interactions, thereby promoting the regulation of transcription in the nucleus and the gene expression; besides, acylation can regulate the structure and function of non-histone protein, which changes in protein interactions between its binding partners, widely participating in a variety of cellular and molecular biological regulation. Exercise is one of the most critical factors that affect protein acylation, it not only enhances histone acylation level and involves in the regulation of gene expression, but also maintains tissue and cell metabolic homeostasis by regulating the histone acetyl transferases/histone deacetylases. Exercise modulates protein acylation through two pathways. On one hand, exercise regulates substance metabolism to change the level of metabolite in the human body, which provides abundant acyl-donors for acylation, such as acetyl-coenzyme A, succinyl-coenzyme A and lactoyl-coenzyme A. The acyl-coenzyme A comes from the intermediate products of glucose, fatty acids and amino acids metabolism in the body. Exercise-induced enhanced metabolism, increased tricarboxylic acid cycle rate, changes in energy content and enzyme activity all affect the concentration of acyl-CoA, thereby affecting the overall acylation level in a more three-dimensional and multi-dimensional manner. On the other hand, dramatic redox reactions and changes in kinase activity during exercise can also change the expression and activity of deacetylases such as the sirtuins family, regulating the balance of acylation/deacylation. Redox reactions in the intracellular surge during exercise cause an increase in the NAD⁺/NADH ratio, and can clearly activate sirtuins. In addition, altered levels of active factors and kinases can also promote gene and protein expression of enzymes and regulate deacylation. Briefly, the regulation of exercise on protein acylation is a new mechanism for exercise that improves metabolism, promotes health and prevents chronic diseases, relevant research work is still in its infancy and deserves special focus.

Abstract:Brain and muscle arnt-like protein 1 (Bmal1) is the core gene of biological clock, which belongs to the transcription factor family of bHLH-PAS (basic helix-loop-helix-per-arnt-sim) domain. It can regulate the circadian rhythm through its own expression and the transcription-translation feedback regulation of the biological clock, which plays an important role in the life activities of organism. The disorder of biological clock induces a series of chronic metabolic diseases, such as cardiovascular diseases, hepatopathy and neurodegenerative diseases, usually accompanied by abnormal expression of Bmal1. Exercise may up-regulate Bmal1 expression in peripheral tissues and organs to improve chronic metabolic diseases. Different exercise loads and types of exercise, such as aerobic exercise, resistance exercise, will lead to the differential expression of Bmal1. There are many potential mechanisms of Bmal1 in improving chronic metabolic diseases by exercise intervention, such as reducing inflammation and oxidative stress, regulating autophagy, maintaining mitochondrial quality and function, interacting with exerkines and microRNA. This article reviews the physiological function of Bmal1 in multiple tissues and organs and the relationship between corresponding chronic metabolic diseases, discussing the influence of exercise intervention on Bmal1 expression deeply and putting forward the potential mechanism of Bmal1 in improving chronic metabolic diseases by exercise, in order to provide a new perspective for exercise as a non-drug treatment to prevent and treat chronic metabolic diseases.

Abstract:Exercise with adequate intensity and duration or specialized exercise therapy have been widely proven to be effective in enhancing pain thresholds or increasing pain tolerance in healthy subjects or chronic pain patients. Exercise induced hypoalgesia (EIH) may involve various central structures in the endogenous pain modulation; motor stimulation with different types can activate either spinal cord induced local inhibition or supraspinal structures induced descending pain inhibition influencing the nociception at the spinal cord level. At the spinal level, continued exercise can down-regulate the expression of IL-1β, IL-6 and TNF-α, while the transient hypoalgesia effect of voluntary movement could be elicited by gate control of the dorsal horn; at supraspinal and subcortical levels, endogenous opioids, cannabinoids, and 5-HT-related descending inhibition of PAG and RVM can be modulated by exercise with different intensity, while the nociceptive discrimination of the thalamus and cognitive processing of the basal amygdala might also be affected by the somatosensory input of exercise, respectively; at cortical level, M1 can be activated by voluntary movement, rTMS or tDCS showed a significant antinociceptive effect in patients with chronic pain, while the DLPFC, MOPFC and insula associated with exercise have also been proven to participate in the EIH effect. In pathological pain state, the EIH is affected with the limited activity of motor cortex and the impaired function of descending pain inhibition, while the active treatment with exercise at non-affected body parts can still partially reverse the pain sensitization and induce the EIH effect. The investigation of EIH effect at spinal, subcortical and cortical levels will assist one to better understand EIH mechanisms, and help to provide the prevention of chronic pain via non-pharmacological exercise therapy.

Abstract:Sarcopenia is an aging syndrome characterized by progressive decline of skeletal muscle mass and strength. It is a great significance to explore its pathogenesis for the treatment and prevention of sarcopenia. Studies have shown that exosomes are closely related to sarcopenia, and may be a useful means of weakening/preventing sarcopenia, but its underlying mechanism remains unclear. Recent studies have shown that exosomes are rich in exerkines/cytokines, which not only participate in the “cross talk” between cells and tissues, but also mediate many pathophysiological processes including the proliferation and differentiation of skeletal muscle cells. Moreover, exercise can effectively improve sarcopenia by promoting the release of exosomes and regulating the expression of miRNAs and/or proteins carried by exosomes. In this paper, we summarized the exosomes and their biological characteristics, as well as the relationship between exosomes and sarcopenia. Firstly, exosomes themselves or the carried mRNA are involved in the aging, promoting the secretion of inflammatory factors and weakening the muscle protein breakdown (MPB) pathway, indicating the exosomes is important to improve the pathology of sarcopenia. There is a strategy for delaying MPB in sarcopenia by increasing the concentration and number of exosomes in skeletal muscle cells. Secondly, exosomes are closely associated with exercise. Both acute and long-term endurance exercise may promote the release of exosomes and induce a “qualitative” change in exosomes. Moreover, we also analyzed the influence of exercise on exosomes and its underlying mechanism. The underlying mechanism is that exercise would improve skeletal muscle homeostasis through activation of exosomes/exosomes-derived miRNAs or mediate protein degradation through activation of the PI3K/PKB/mTOR pathway, ultimately weakening sarcopenia.

Abstract:Plasma membrane disruptions have been documented under physiological conditions in lots of mechanically active tissues, such as in skeletal muscle, the stratified epithelium that covers our body, the endothelia that line our blood vessels, the epithelial barrier of our gastrointestinal tract. Timely and effective plasma membrane repair (PMR) mechanisms have evolved to rapidly reseal a membrane breach to ensure cell survival. Otherwise, these membrane disruption events initiate a “death cascade”. PMR is coordinated by many “tinkerers”, which have a clear division of labor and show certain timing characteristics. The endosomal sorting complexes required for transport (ESCRT) is the “tinkerer” found recently who plays a key role in the repair of plasma membrane disruptions. It is composed of ESCRT-0, ESCRT-I, ESCRT-II, ESCRT-III, VPS4-VTA1 and ALIX, which take part in the budding and the formation of multivesicular body (MVB). This paper reviews two repair methods mediated by ESCRT system with budding and the formation of MVB. The function of ESCRT complex in plasma membrane repair can improve membrane disruptions, which is able to be used as an effective prevention and treatment strategy for cancer, Alzheimer’s disease, muscle injury and muscular dystrophy.

Abstract:The bone formation metabolism dominated by osteoblasts (OB) has been restrained and the bone resorption metabolism dominated by osteoclasts (OC) is abnormally elevated, leading to bone metabolism disorders. As the key seven-transmembrane proteins that sense external signal stimuli in OBs, chondrocytes and OCs, G protein-coupled receptors (GPCRs) have been widely recognized by bone in their key regulatory roles in the differentiation and function of OBs, chondrocytes and OCs. Thus, those research results have got more attention in metabolism field. Loss of GPCRs function or abnormal increase in the homeostasis of the osteocyte homeostasis leads to the differentiation and dysfunction of OB, chondrocytes and OC, which results in bone loss and degeneration of the microstructure of bone tissue. Studies have shown that exercise is an important way to improve bone metabolism disorders by promoting bone formation and inhibiting bone resorption. The analysis found that the molecular regulation mechanism of this process is related to the key signaling pathways (cAMP/PKA/Atf4, JNK/AP-1, ERK1/2, etc.) and cytokines (T-PINP, Nkx3.2, Sox9 and Cleaved-caspase-3, etc.) are closely related to the differentiation and function of OB, chondrocytes and OC. Except from the confirmed GPR48, this review tested out the molecular mechanism of GPCRs regulating bone formation and bone resorption and their role in the effect of exercise on bone metabolism. The mechanism of other GPCRs in the improvement of bone metabolism by exercise has yet to be revealed on what kind of exercise mode and intensity can effectively regulate GPCR and improve bone metabolism and so on. The results help to screen out sensitive GPCRs on membranes as “effectors” for drug development of bone metabolic diseases and “star proteins” for mechanical stimulation in exercise intervention and provide more targets or perspectives for the research and prevention of osteoporosis.

Abstract:Malignant tumors had always been one of the main diseases endangering human life and health. The development of nano-drugs had the huge potential to ameliorate the prognosis of malignant tumors, particularly by modifying the surface of nanoparticles with cell membranes, it was possible to obtain effective malignant tumor treatment. Biomimetic modification of cell membrane was an emerging way that enabled nanoparticles new biological functions by coating different cell membranes on the surface of the nanoparticles. Many studies had shown that cell membrane biomimetic modified nanoparticles retained the complex biological functions of natural cell membrane while displayed physicochemical properties that were suitable for effective drug delivery. They prolonged blood circulation time and exhibited lower immunogenicity compared to traditional synthetic nano-drug delivery systems. Modified nanoparticles cross various biological barriers and even posessed specific tumor targeting as well. Based on these properties, cell membrane biomimetic modified nanoparticles emerged an ideal drug delivery system for tumor therapy. In this paper, we summarized the recent progress of cell membrane biomimetic modified nanoparticles for tumor therapy and discussed their characteristics which included: excellent immune escaping property; high drug-loading capacity; specifity of tumor targeting; outstanding penetrability for blood brain barrier. Then, the protocols of preparing cell membrane biomimetic modified nanoparticles and characterization analysis were briefly introduced. At last, we demonstrated the positive roles of cell membrane biomimetic modified nanoparticles on tumor-targeting therapy, tumor photothermal therapy, and tumor immunotherapy. This review provided guiding rules of methodology and theoretical basis for studying cell membrane biomimetic modified nanoparticles in tumor therapy.

Abstract:The coronaviruses (CoVs), which are a family of positive-strand RNA viruses, infect the mammals and birds. Seven CoVs are responsible for human-to-human transmission, especially the SARS-CoV-2, thereby posing a daunting challenge to global public health security. As the most common modification in viral glycoproteins, glycosylation plays the crucial role in host recognition, immunity avoidance, virus replication, assembly and transmission. In this review, we summarized and discussed the latest studies about glycosylation in coronaviridae members. Focused on the spike protein, nearly one hundred of N/O-glycosyltion sites have been reported. The N-glycans from spike protein are dominated by the high-mannose and complex-type, while the O-glycosylation is rather complicated. Significantly, it is known that the viral glycosylation depend on host cells, thus the glycan pattern of the produced recombinant viral glycoproteins might be different from that of native viral proteins, which represent a crucial determinant for vaccine design. The latest results based on bioinformatics, biochip, mass spectrography and genetic technology facilitate the overall perspective for glycosylation researching in CoVs. By summarizing the distribution of glycosylation sites, the structure of glycans, the biological functions and the research technologies, this review will help promote diagnosis, treatment and vaccine development related to coronaviruses.

Abstract:PARP16 is a momo-ADP ribotransferase belonging to the members of the poly(ADP-ribose) poiyerases (PARPs) family, unlike other family members, it is an anchored transmembrane protein located in the endoplasmic reticulum. During the unfolding protein reaction of the endoplasmic reticulum, the two pressure sensors PERK and IRE1α of the endoplasmic reticulum will be activated, and PARP16 plays an important role in this process.Through their single ADP-ribosylation and activating biological activity, PARP16 can regulate cancer, cardiovascular diseases and cystic fibrosis, which make it become a great potential drug target for major human diseases such as cancer and cardiovascular disease. This article mainly describes the structures and function of PARP16, related diseases mediated, and small molecule inhibitors.

Abstract:Spatial transcriptome technologies aim to quantitatively measure the gene expression of cells and provide information on the specific location of cells in tissue space. Compared with traditional transcriptome technologies, the spatial transcriptome technologies can obtain the true gene expression characteristics of cells in the tissue in physiological environment and its relationship with the microenvironment, further advancing the understanding of cell characteristics in normal and pathological states. In recent years, significant progress has been made in the development of spatial transcriptome technologies. The cell throughput, detected quantity and quality of transcripts have been continuously improved, and the spatial location information has become more accurate and comprehensive. This paper reviews the development and applications of spatial transcriptome technologies, which were classified into 4 major categories based on in situ hybridization, high-throughput sequencing, in situ sequencing, and live cell barcodes, respectively. Each of them has its advantages and disadvantages so that should be applied in different situations, and it is foreseeable that these spatial transcriptome technologies will continue to be improved, including preventing RNA degradation, improving detection throughput and efficiency, reducing costs, and obtaining complete spatial single-cell transcriptomes. At the same time, based on the acquisition of cell spatial information, future spatial transcriptome technologies will be combined with the dimension of time, further improve the level of transcriptome research from the perspective of spatiotemporal transcriptome, and continuously deepen the understanding of the true characteristics of tissue cells, so as to advance the understanding of developmental processes, cancer and other malignant diseases and the development of new treatments.

Abstract:Bio-derived materials, such as collagen, gelatin, fibrinogen, cellulose, starch and chitosan etc, are attracting more and more attention for being used as hemostatic materials due to their excellent biocompatibility, biodegradability and procoagulant activity. This review discusses several types of hemostatic materials and the corresponding hemostatic mechanisms. Our focus is tailored towards the basic structure, hemostatic mechanism, commercial products and the latest scientific research progress of the above-mentioned bio-derived hemostatic materials. Finally, the tendencies of their development are prospected.

Abstract:Objective Social cues such as eye gaze, head direction, and walking direction of biological motion are critical for human survival and social interaction. Since social and peripheral cues both have reflexive characteristics of attentional orientation, social attention is often regarded as one kind of exogenous attention. However, empirical evidence suggests that this explanation cannot fully account for all phenomena of social attention. Whether social attention and exogenous attention possess the same mechanism remains unclear.Methods Here, we used a typical spatial cueing paradigm to systematically examine the effects of cue validity on social attention and exogenous attention, triggered by eye gaze and peripheral cues, respectively.Results The results showed that both kinds of attention were affected by cue validity. With the increase of cue validity, the attention effects of eye gaze and peripheral cues increased. When the cue validity was noninformative (0.5) or strongly predictive (0.8), there was no significant difference in the attentional effects between social attention and exogenous attention. More importantly, however, when the cue validity was 0.2 (i.e., counterpredictive), the attentional effects of both cues were significantly different. While the facilitation effects of the eye gaze cue were weakened, the attentional effects of the peripheral cue were reversed and showed an inhibition pattern, suggesting that gaze-triggered attention is more strongly reflexive than exogenous attention orienting.Conclusion Our finding thus provides new evidence supporting the theoretical hypothesis that there exist significant differences between social attention and classical exogenous attention, at least in certain stages of their processing. Our study also offers a new method to distinguish social attention and exogenous attention through voluntary attentional control.

Abstract:Objective To evaluate the accuracy of predicting the kinship relationship between individuals based on the identity-by-state (IBS) algorithm.Methods The Illumina GSA chip was used to perform whole-genome detection on 253 samples. Based on high-density single nucleotide polymorphism (SNP) data, the IBS sharing statistics between two individuals was calculated to predict the kinship relationship. Filtering SNP by different conditional parameters to evaluate the influence of the number of sites on the accuracy of the algorithm’s prediction.Results The prediction accuracy rate of 1st-4th degree of relatives proved to be as high as 99%, with a paired difference of 1st degree and no false positive. Decrease in the number of SNPs has no significant impact on the accuracy of prediction, and the algorithm still achieves a higher accuracy rate even in the lower density of SNP markers.Conclusion The IBS algorithm provides an effective method for forensic genealogy inference, which has good application value for forensic on-site inspection materials with trace degradation.

Abstract:Objective This study opens a new direction for photoacoustic tomography (PAT) to image human cervical trachea.Methods A multi-wavelength PAT experiment was performed on the cervical trachea of seven volunteers. The characteristics of high resolution (up to 150 μm) images of the respiratory cycle and different layers of tracheal wall were studied by PAT, and the imaging advantages and defects of this technique were evaluated.Results Our study demonstrated the ability of PAT to image human cervical trachea, and delineate the structural characteristics of it and its surrounding tissues. Variation of tracheal lumen at different phases of a respiratory cycle by PAT indicated its high time resolution. Collagen, as an endogenous contrast of PAT, was abundant in tracheal cartilage, which has a wavelength of absorption coefficient ranging from 900 nm to 1 300 nm. This study shows that the wavelength of 910 nm is best for tracheal cartilage imaging.Conclusion It can be considered as a non-invasive, convenient and non-ionizing radiation imaging method for real-time evaluation of human trachea. Given the high spatial resolution and real-time capabilities, PAT has the potential to become a useful tool for non-invasive airway imaging in future. We believe this study sets the ground work for the analysis of the human trachea using PAT in vivo.

Abstract:Objective Protein flexibility plays important roles in various biochemical processes in the living organisms, such as enzyme catalysis, signal transduction, substance transport and storage, etc. Prediction of the intrinsic flexible motions based on the tertiary structure of proteins is helpful for our better understanding of the mechanism of protein functions, which is an important scientific problem in the research field of protein structure-function relationship. Convolutional neural network (CNN), one of the mainstream algorithms in deep learning, has been successfully applied in the study of protein structure-function relationship.Methods In the present work, based on the idea of PointNet method developed in the computer vision research, a CNN model was proposed to predict the protein flexibility. In this model, protein structures were treated as three-dimensional point clouds, where the atomic coordinates of proteins were directly inputted into the model, and the permutation invariance and global rotation invariance of the point cloud were delt with by using the pooling operations and a spatial transformation network, respectively. In addition, considering the varied sizes of different proteins, a new mini-batch optimization strategy was proposed, where the model was trained by using the mini-batches of protein structures with different sizes as input. The Pearson correlation coefficient was used as the evaluation function for the training of the model. Besides that, in order to further enhance the performance of the network, an improved model was constructed based on the PointNet-based CNN model, in which the max-pooling and the average-pooling were concatenated to better extract the global features of protein structures. Then the PointNet-based CNN model and the improved model were trained and tested by using the temperature factors (B-factors) of 243 non-redundant proteins.Results The results show that the average Pearson correlation coefficient between the predicted and the experimental temperature factors predicted by the PointNet-based model and the improved model were 0.64 and 0.65, respectively. The prediction accuracy of our models is better than that of the Gaussian network model that has been widely used in investigating protein flexibility. Especially, for the 74 relatively loose natural disordered proteins from the Disbind website, the average Pearson correlation coefficient predicted by our models were 0.62 and 0.64, respectively, which were significantly better than GNM.Conclusion Our studies provide an effective model for the effective prediction of the intrinsic flexibility encoded in protein structures.