Abstract: Kelch-like ECH associated protein 1(Keap1), a typical substrate-recognition subunit of the Cul-RING E3 ligase, plays a significant role in ubiquitination. Ubiquitination, an important post-translational modification, enables a degradation signal in both autophagy and ubiquitin-proteasome system. Recently, several substrates can be recognized and binded by wild-type Keap1, and subsequently degraded by ubiquitin proteasome system (UPS) via Keap1-Cul3-Rbx1 complex. Additionally, Keap1 has also been widely studied as a tumor suppressor protein, and mutation or abnormally deletion of Keap1 alleles contributes to different kinds of diseases. The study of Keap1 has mainly concentrated on the Keap1-Nrf2 axis, but rarely extends to downstream substrates. Given that the great importance of Keap1 in cells, this review summarizes the current research status of Keap1, including ubiquitin-proteasome system, Keap1’s structure and function, the mutation of Keap1, the substrates of Keap1, and Keap1-related diseases. It may provide a new thought for targeted therapy of Keap1-associated diseases through discussing the challenges of Keap1-related fields in clinic.
Abstract: Transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as capsaicin receptor (VR1), is a kind of ligand gated non-selective cation channel which can be activated by capsaicin, heat (>43℃) and H+ (pH<6.0). TRPV1 is highly permeable to Ca2+. Previous studies found that TRPV1 mainly distributes in nervous system and mediates pruritus and pain response. Recent studies have shown that TRPV1 also widely distributes in non-nervous cells such as mast cells, bladder epithelial cells, monocytes, skin keratinized epithelial cells, islet cells and so on. TRPV1 has a wide range of functions and can mediate beneficial or harmful biological effects on the body. In the nervous system, TRPV1 related signal pathway mainly mediates itching and pain response. Relevant studies in pancreatic cells have shown that the upregulation of TRPV1 can alleviate the process of diabetes, but studies in pulmonary epithelial cells, pulmonary vascular endothelial cells, bronchial smooth muscle cells, etc. have shown that the upregulation of TRPV1 can accelerate the development of respiratory diseases. In addition, TRPV1 has dual effects of promotion or inhibition on the disease progression in cardiovascular system, digestive system and skin system. In cancer research, it was also found that the upregulation of TRPV1 played an important antineoplastic effect, which could inhibit the proliferation, invasion and migration of tumor cells in human tongue squamous cell carcinoma, prostate cancer, breast cancer and so on, arrest the cell cycle and induce cell apoptosis. At present, many studies have been carried out on the mechanism of TRPV1, among which the mechanism of TRPV1 mediating itching and pain is relatively in depth. TRPV1 has become a promising therapeutic target due to its extensive functions. New drugs targeted to TRPV1 have been developed to ameliorate diabetes, cardiovascular diseases, and some kinds of cancers. This paper introduces the latest progress in the distribution, structural characteristics and functions of TRPV1, and focuses on the research progress of pruritus and pain related signaling pathways mediated by TRPV1. We also introduced the Chinese herbal medicine with TRPV1 as the target, looking forward to providing theoretical guidance for taking TRPV1 as a potential therapeutic target by combination of traditional Chinese medicine and modern medicine.
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: Nucleic acid aptamers are a class of single-stranded DNA or RNA molecules with specific molecular recognition capability, obtained by a process called systematic evolution of ligands by exponential enrichment (SELEX). They have the advantages of high thermal stability, ease of chemical synthesis and modification, and low immunogenicity compared to antibodies, and have attracted widespread interest in many fields such as bioanalysis, biomedicine, and biotechnology. High-quality aptamers are the basis of applications, however, the number of them that meet requirements of practical applications is very limited. How to obtain aptamers with high affinity, high specificity, and high in vivo stability is the technical bottleneck in the field of aptamers. Firstly, this review briefly introduces the basic theory of SELEX and its critical experimental steps including design of nucleic acid library, monitoring selection process, preparation of secondary library, sequencing and screening of candidate aptamers. The six main research directions of SELEX during the past thirty years are then concluded. They are respectively (1) how to improve the specificity of aptamers, (2) how to improve the stability of aptamers against nuclease degradation, (3) rapid SELEX, (4) how to isolate aptamers for complex targets, (5) how to isolate small molecule-binding aptamers, and (6) how to isolate high affinity aptamers. The development of rapid SELEX technologies has attracted tremendous attention and almost all physical separation methods have been applied to improve the SELEX efficiency. Very recently, several methods involving the highly efficient chemical reactions have been reported, providing novel strategies for the rapid isolation of aptamers. The key research progresses of SELEX technologies suitable for the isolation of small molecule-binding aptamers are subsequently reviewed and the challenges of each method are critically commented. There are three types of SELEX methods including the target-immobilized SELEX, library-immobilized SELEX (Capture-SELEX), and homogeneous SELEX (GO-SELEX). Even though the target-immobilized SELEX suffers from many issues such as steric hindrance, it is still a popularly used method due to its simplicity. In recent years, Capture-SELEX has been widely applied. The experimental conditions of Capture-SELEX (concentration of positive-SELEX target, choice of negative-SELEX targets and their concentrations) and the affinity (KD,dissociation constant) and the specificity of the isolated aptamers for the 36 targets are listed in a table. Based on the information from the table, the effect of the experimental conditions on the affinity and the specificity is discussed. The statistical data indicates that the lower concentration of the positive-SELEX targets favors the isolation of the higher affinity aptamers, while it is not a necessary condition. Negative-SELEX is currently the dominant strategy to improve the specificity of aptamers. However, the specificity of many aptamers cannot meet the requirement for practical applications. The choice of negative-SELEX targets and their concentrations in each case are quite different. In 20 out of the 36 targets, no negative-SELEX was performed for the aptamer isolation. How to obtain the aptamers with high specificity is the most difficult challenge for small molecule targets. It is in urgent need to establish novel strategies beyond negative-SELEX to improve the specificity of aptamers. The experimental conditions of GO-SELEX and the KD and the specificity of the isolated aptamers for the 13 small molecule targets are also list for comparison. The comparison data shows the less numbers of the enrichment cycles required for GO-SELEX than Capture-SELEX, while the obtained aptamers all commonly have KD in the nanomolar range. The lower enrichment efficiency of Capture-SELEX should be due to the self-dissociation of the immobilized library. The affinity evaluation is the important part of the characterization of aptamer structure and performance. More than ten affinity assays are frequently used for aptamer characterization, which are roughly divided into three categories: separation-based, immobilization-based, and homogeneous methods. All techniques could generate false-positive and false-negative results. Taking gold nanoparticle-based colorimetric assay and isothermal thermal titration as examples, we review the technical progresses and comment on the fundamental reasons resulting in the inconsistent results when the different affinity assays are conducted. The final part of this review provides an outlook on the future trends of aptamer isolation technologies, affinity characterization techniques, and the technical standardization.
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: 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: Peptide∶N-glycanase (PNGase) is a deglycosylation enzyme widely presented in fungi, plants, mammals and other eukaryotics. Only two bacterial PNGase have being isolated (PNGase F and PNGase F-II) thusfar, and both are used widely as research tools in glycomics. PNGase catalyzed the hydrolysis of the amide bond between N-acetylglucosamine and an Asn residue on an N-glycoprotein, generating a de-N-glycosylated protein and a complete N-oligosaccharide. After the reaction, the N-glycosylated Asn residue was converted to Asp. Although it is known that PNGase participates in protein degradation, organ development, individual growth and other key biological processes in organisms, its impacts on health was illustrated only recently. Human PNGase (NGLY1) deficiency could lead to a genetic disease named congenital disorder of deglycosylation-NGLY1. A nematode PNGase deficiency could reduce its life span. Its defects in mice could be embryonic lethal. This article describes the distribution, protein structure, and biological function of PNGase in different species. It can serve as an important information resource to support basic research for PNGase mechanism and innovative study for PNGase applications.
Abstract: Molecular medicine focus on understanding the diseases based on molecular level, and developing personalized medicine strategies for diagnostics and therapeutics. However, powerful molecular recognition tool is still limited for cancer diagnosis and therapy, which impeding cancer research. Aptamers are generated from systematic evolution of ligands by exponential enrichment (SELEX) also known as in vitro selection, ranging from synthetic single-stranded DNA, RNA or XNA (enhanced modified nucleotides), HNA (nucleotides of specific structures such as G quadruplex). The main advantages of aptamers including high specificity, high affinity, simple and rapid synthesis, easy chemical modification, wide target range, good tissue penetration and low immunogenicity. As a molecular recognition tool in molecular medicine, aptamer shows wide applications in developing personalized prediction, diagnosis and therapeutics for its high specificity and high affinity against target. This review discusses the applications of aptamers in disease diagnosis, including aptamer-based tumor marker discovery, liquid biopsy, and molecular imaging, Moreover, the applications of aptamer-based cancer therapy are reviewed, including aptamer-based inhibitors, aptameric drug conjugates, nanomedicines, and aptamer-mediated immunotherapy. Finally, it is promising aptamer will be extensively employed in the future including fundamental research, diagnosis and therapeutics. However, following issues are still need to be addressed. First, the application scenarios-dependent SELEX procedures lack studying which limits the clinical applications of aptamers. Second, the structure of aptamer-target complex has not been fully elucidated, which restricts the precise regulation of aptamers. Third, aptamer is easily degraded by enzymes in vivo and has a short half-life period, which hinders the applications of aptamer-drug conjugates in the development of targeted drugs. With the advancement of screening technology and the further enhancement of aptamer performance, it is expected that aptamers will find more extensive utilization in the field of molecular medicine in the future.
Abstract: With the aging population increasing worldwide, neurodegenerative diseases are becoming a major public health crisis. TAR DNA-binding protein 43 (TDP-43) is one of the major components in the inclusion bodies containing aggregated proteins in affected patients with several types of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). A large number of mutations in TDP-43 have been identified in familial cases of ALS. TDP-43 is an essential RNA/DNA binding protein critical for RNA-related metabolism, it shuttles between nucleus and cytoplasm, and undergoes phase transition to induce cytoplasmic and nucleoplasmic inclusion formation. Here, we summarized the recent advances in our understanding of protein aggregation and phase transition of TDP-43 in vitro and in vivo. Understanding the aberrant transition of TDP-43 will help identify potential therapeutic targets for neurodegenerative diseases.
Abstract: The structure of protein is determined by the sequence, and the function of protein is determined by its structure. The advent of accurate protein structure prediction tools has created new opportunities and challenges in the fields of structural biology, structural bioinformatics, drug discovery and many other fields of life sciences. The accuracy of single-chain protein structure prediction has reached a level comparable to that of experimental methods. In this review, we provide an overview of the theoretical basis, development history, and recent advances in the field of protein structure prediction. Additionally, we discuss how the large number of predicted protein structures and artificial intelligence-based methods affect experimental structural biology. Open questions and future research directions in the field of protein structure prediction are analyzed.
Abstract: As a new type of organoid model, skin organoids can reconstruct and modify different types of cells and appendages with specific functions such as umbilical cord blood stem cells, induced pluripotent stem cells, keratinocytes and fibroblasts, as well as sebaceous glands, sweat gland and hair follicles under special habitats, which can not only highly simulate the physiological structure and function of skin tissues, but also better restoring more realistic skin ecology under different in vitro environments. It can also be used in the fields of skin wound regeneration, skin tumor, immune and metabolic diseases, treatment of inflammatory diseases and drug screening. Meanwhile, skin organoids can not only make up for the deficiencies of existing in vitro skin models in terms of structure and function, but also enable high-throughput screening of drugs or raw materials, reducing the time and economic costs in the later stages of drug screening. However, due to the limitations of current technology, the types and functions of organoids cannot be fully realized to realistically simulate the physiological conditions in the body such as lipid metabolism and blood circulation. Moreover, issues such as consistency and standardization of mass-produced organoids need to be addressed, such as source cells, structure and function, which require the establishment of appropriate standards based on practical applications. Based on this, this paper details the cell sources involved in skin organoids construction and their applications in recent years and several skin appendages like organs that have been constructed and provides an outlook on the future development and optimization of skin organoids.
Abstract: The neurons can transform different spatiotemporal patterns of synaptic inputs to the action potential sequences with high temporal precision. This flexible and reliable information coding strategy plays a crucial role in the process by which the nervous system generates the specific activity patterns required by dynamical situation or specific task. The initiation of an action potential follows an all-or-none principle. When the depolarization of membrane potential exceeds a threshold value, the neuron fires an action potential. The action potential threshold is highly variable within and between cells, and its specific dynamics depends on the stimulus input and firing history. In particular, the spike threshold is sensitive to the membrane voltage changes preceding the action potential. Two primary biophysical mechanisms for such state dependence of the spike threshold are Na+ inactivation and K+ activation. In most neurons, the action potentials are initiated in the axon initial segment, and the threshold variability at this site is the crucial factor that determines how neurons transfer spatiotemporal information. However, the action potentials in electrophysiological experiments are recorded in the cell body or proximal dendrite. The threshold variability at these sites is higher than that in the axon initial segment, which mainly arises from the backpropagation of axonal action potentials. Based on somatic recordings, it is shown that the spike threshold dynamics determines the transformation principle of spatiotemporal information in the neurons, which enhances the temporal coding, feature selectivity, gain modulation, and coincidence detection. In this paper, we first introduce the conception of spike threshold and its calculation methods. Then, we present an exhaustive review on the main findings of the spike threshold variability and its origins in recent years, and mainly discuss the significance of spike threshold variability for neuronal coding. Finally, we raise several key issues on the spike threshold that need to be addressed in the future.
Abstract: Bacterial secretion systems are sophisticated nanomachines that are used by bacteria for selective transport of macromolecules across membrane. These membrane protein complexes play critical roles in bacterial pathogenicity, antibiotic resistance and ecological adaptation. Hitherto, a total of nine secretion systems have been identified and named as type I to type IX secretion systems (T1SS-T9SS) according to the chronological order of discovery. Recent advances in X-ray crystallography, nuclear magnetic resonance and cryo-electron microscopy increased the understanding of the architecture and structure of these macromolecular machineries. That provided unprecedented views to explain the mechanisms of how secretion systems release the effectors to the extracellular environment or host cells. Herein, this review summarizes the best knowledge of the progress of bacterial secretion systems (T1SS-T9SS), with a focus on their structure and function. We also highlight major advances in novel antimicrobials targeting these large protein machineries. Finally, we provide new perspectives for the future studies about structure identification and drug screening of secretion systems.
Abstract: Expansion microscopy (ExM) is a new super-resolution imaging technique. With the aid of expandable hydrogel, biological samples are uniformly physically amplified and can be imaged in super resolution by using conventional optical imaging microscopes. In ExM, after immunofluorescence staining, gel embedding, protease digestion and water swelling, the relative distance of fluorescent labeled molecules inside the biological samples was increased, so the sample can bypass the optical diffraction limit in conventional fluorescence microscope to achieve the super-resolution imaging. ExM is widely suitable for many types of biological samples such as cell and tissue sections. Proteins, nucleic acids, lipids and other biological macromolecules can also be imaged by ExM. ExM can be combined with confocal microscopy, light-sheet microscopy and super-resolution microscopy to further improve imaging resolution. In recent years, a variety of derivative technologies have been developed from base ExM, which further promotes the practical application of this technology. Protein retention expansion microscopy (proExM) can avoid complicated sample preparation process and directly image endogenous fluorescent proteins. Magnified analysis of the proteome (MAP) was suitable for super-resolution imaging in large biological samples. Iterative expansion microscopy (iExM) can increase the final expansion factor of biological samples to 16-22 times by changing the gel embedding steps. Cryo-expansion microscopy (Cryo-ExM) can provide better image fidelity. Expansion fluorescent in situ hybridization (ExFISH) and Click-ExM can achieve super-resolution imaging in nonprotein biomolecules, such as RNA, lipids, and polysaccharides. Expansion pathology (ExPath) can be used for clinicopathologic specimens imaging. The combination of ExM and light-sheet microscope can improve the image resolution to super-resolution level in the deep imaging depth. The application of ExM in super-resolution microscopy can further increase the resolution of images to 10-30 nm. In this paper, we reviewed the basic principles of ExM and its derivative technology, the research progress of combining ExM with different imaging technologies, the application progress of ExM in observing different types of biological samples, and the prospective of spreading ExM technology in the future.
Abstract: Objective Exercise has been approved as an effective anti-aging approach. However, how exercise affects the organelle-specific redox status of the endoplasmic reticulum (ER) and whether it contributes to ER function and healthy aging are still unknown.Methods We constructed an ER-specific reductive stress C. elegans model that overexpresses ctl-1, a homolog of the mammalian catalase gene, to research the effect of ER reductive stress on aging at the organismal level. We then used the HyperionER probe which responds well to hydrogen peroxide to evaluate the redox status in the ER of body wall muscle during swimming and during aging.Results Our results show that H2O2 in the ER was markedly reduced during aging and the number of body bending, the life span and the stress response ability in Pnfya-1::ctl-1ER::mCherryC. elegans was markedly decreased compared with that in Pnfya-1::ctl-1-MER::mCherry, indicating that ER reductive stress occurs during the aging process and ER reductive stress promotes aging at the organismal level. Both short-term and long-term exercise can increase the oxidative power of the ER in C. elegans, and exercise alleviates the age-related ER reductive stress and promotes healthy aging.Conclusion Our results demonstrate the effect of exercise on ER redox status at the organelle level for the first time and uncover a new mechanism for exercise in delaying aging at the organismal level from the redox point of view, suggesting that maintaining the oxidation power of the ER may be a valuable geroprotective strategy.
Abstract: With the continuous development of nanotechnology, nanoformulations show unique advantages in improving drug delivery and bioavailability. However, most nanocarriers have low drug delivery efficiency, poor therapeutic effect, potential systemic toxicity and metabolic instability. In recent years, self-assembled carrier-free nanodrugs have attracted tremendous attentions in the field of biomedicine due to their unique properties such as high drug loading capacity, low toxicity, and facile synthesis. Therefore, the self-assembled carrier-free nanodrugs exhibit broad application prospects and development potential in biomedical fields, especially in anticancer and antibacterial applications. In this review, we firstly give a brief introduction to the various intermolecular interactions of self-assembly carrier-free nanodrugs, including the hydrogen bonding, π-π stacking, hydrophobic interaction and other non-covalent forces as exemplified by electrostatic interaction and Van der Waals forces. The chemical structures of drug molecules determine the strength of non-covalent interactions. Secondly, we provide an overview of the typical methods used for self-assembly of carrier-free nanodrugs including in vitro self-assembly strategy (e.g., top-down, anti-solvent precipitation, template-assisted precipitation) and in vivo self-assembly strategy. Especially, nanodrugs prepared by in vivo self-assembly method can be targeted and self-assembled at the target location, reducing adverse reactions and achieving higher efficacy. Besides, the application of carrier-free nanodrugs in biomedical fields including anticancer, antibacterial, anti-inflammatory as well as antioxidant are comprehensively reviewed. Finally, the future challenges and development trends of carrier-free nanodrugs are also prospected, which may provide a theoretical basis for the rational design of more effective self-assembly vector free nano drugs and the feasibility of clinical application.
Abstract: Deep brain stimulation has become an effective treatment for many neurological and psychiatric conditions. However, invasive electrode implantation carries the risk of surgical complications, and the stimulation target is difficult to change after implantation. Non-invasive stimulation methods such as transcranial magnetic stimulation and transcranial electrical stimulation offer new avenues for modulating brain function. However, these non-invasive brain stimulation methods have not been shown to directly modulate deep brain activity without affecting cortical neurons. Therefore, these methods are mainly used to modulate neural activity in the superficial regions of the brain. Temporal interference (TI) stimulation is a new non-invasive deep brain stimulation method that modulates neural activity through the interaction of two high-frequency electric fields to generate a low-frequency envelope. This approach is expected to address the need for non-invasive deep brain stimulation. This paper first introduces the concept and safety of TI stimulation, and then describes the evoked field analysis methods in the existing research on TI stimulation and discusses the physiological model modeling method and simulation platform related to TI stimulation analysis. Research progress and application progress in animals and humans also were introduced. Finally, based on the current research progress, we proposed future research directions for TI stimulation, to provide new research ideas for non-invasive deep brain stimulation research.
Abstract: Cellular conversion is a process of genetic reprogramming by various methods to induce the direct transformation of one type of cell into another without going through other intermediate states. Neuronal loss is a common pathological process in a variety of neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and stroke. Neuronal loss is usually irreversible and causes motor, sensory, and psychiatric symptoms. Since the human central nervous system has limited capacity for neuronal regeneration, therapeutic strategies that use glial cells (astrocytes, microglia, and oligodendrocyte precursor cells) to transdifferentiate into functional neurons in situ of neuronal loss and integrate them into neural networks have received much attention. In recent years, successful conversion of glia-to-neuron by manipulating the gene expression of key transcription factors in neuronal fate determination in glial cells has been discovered. Nevertheless, there is still some controversy about the scientific validity of some research technologies, the rationality of judgment criteria, and the self-consistency between experimental results and conclusions. This article reviews the discovery and development of glia-to-neuron conversion and takes astrocytes, microglia, and oligodendrocyte progenitor cells as examples to summarize the important findings of glia-to-neuron conversion with discussion and perspective.
Abstract: Chitin is the second largest natural polysaccharide after cellulose, which is polymerized by N-acetyl-D-glucosamine, having important application value in agriculture, industry, medical treatment and other fields. Natural chitin exists in a highly crystalline state with complex barrier against degradation. Bacteria can secrete multiple chitinases with special functions to degrade chitin efficiently. Chitinases mainly distributed in GH18 and GH19 families in CAZy database. There are obvious phenomena of gene amplification and multi-domain combination of chitinase genes in bacteria. Chitinases with various action modes in different GH families can act synergistically to break the barrier and complete efficient degradation of crystalline chitin. Therefore, in-depth analysis of the structure and function of bacterial chitinase is of great significance for efficient degradation and high-value conversion of chitin. In this paper, the classification and structural characteristics of bacterial chitinase were introduced, which laid a foundation for further research on the functional mechanism of the enzyme. After that, the action mechanism of chitinases belong to GH18 and GH19 families, including the binding mechanism of enzyme to substrate, catalytic mechanism was summarized to further understand the characteristics of chitinase at molecular level. It is worth noting that processibility is an important characteristic of chitinase to efficiently degrade crystalline chitin, so the molecular mechanism of chitinases, including the effects of polar amino acid residues and aromatic residues on processibility was focused on. In addition, the synergistic degradation modes of extracellular chitin degradation enzymes in 3 different bacterial were summarized, which provided a theoretical basis for the design of efficient chitin degradation enzymes. Through a review of the research progress of molecular modification of chitinases, the role of protein engineering design strategy based on structural bioinformatics and big data deep learning in future modification is prospected, which provides a new perspective and ideas for the design and rational modification of chitinase. To sum up, this paper introduces the relative knowledge of chitinase from structure to mechanism and function to application, which provides a comprehensive foundation for further study of chitinase, the structural and molecular basis for the design of high-functional enzyme, and a theoretical basis for the application of chitinase.
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