Abstract: Small ubiquitin-related modifier protein (SUMO) modification is a kind of widespread form of post-translational modification. It exists in multiple physiological and pathological processes, and is involved in a number of signal transduction pathways. Sumoylation is one of the important regulating mechanism in the cellular response to stress, and a growing body of research suggests that the SUMO play an important role in the process of embryonic development and organogenesis in mammals. Sumoylation plays an important role in the formation and development of organs in fetal development. The components of the sumoylation pathway (UBC9, SUMO1-3, PIAS, SENP1-7) play important roles in the coordination of the dialogue between the blastocyst and the uterus, the development of the heart, and craniofacial development. When these developmental dysfunctions occur, they can lead to preimplantation defects, developmental defects, and fetal death. In this review, we will focus on recent advances in this field, summarizing the important roles in early embryonic development and organogenesis of SUMO, UBC9, PIAS, and SENPs, which have been linked to the SUMO pathway, and the consequences of aberrant SUMOylation, to provide a reference for future research.
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: Mitochondrial membrane integrity is so pivotal to cell survival that its damage can lead to apoptosis, pyroptosis or inflammation. The damage includes mitochondrial outer membrane permeabilization (MOMP), mitochondrial inner membrane permeabilization (MIMP), and mitochondrial permeability transition (MPT), which regulate different signaling pathways and thus lead to different cell fate outcomes. These signaling pathways are intersecting, which makes the involved mechanisms intricate and poorly understood. In this review, we firstly analysis the role of distinct degrees of MOMP in cell survival, tumorigenesis, and apoptosis, which may operate as a tristable switch. Then we discuss the molecular mechanism of MIMP in triggering inflammation through the release of mtDNA and envision that low order oligomers of Bak/Bax induce MOMP and promote apoptosis, while high order oligomers induce MIMP and cause inflammatory response. Furthermore, we clarify the working mechanisms of MOMP-induced apoptosis and MPT-driven pyroptosis under different stimulus intensities. Finally, we outline the intrinsic connection underlying cell-fate decision influenced by mitochondrial membrane integrity. Therefore, a deep understanding of the dynamical mechanisms of how mitochondrial membrane integrity regulates cell fate should give insight into the diagnosis and treatment of cancer and neurodegenerative diseases.
Abstract: The intracellular protein constantly remains in the dynamic process of synthesis and degradation, and its homeostasis appears to be closely related to the cellular function. A variety of protein quality control (PQC) mechanisms exist to monitor abnormalities occurred during protein synthesis and degradation, thereby ensuring proteome integrity and cellular fitness. The ribosome is the most abundant organelle in cells, and it is the major site for protein synthesis, for which each stage from biosynthesis to degradation is tightly controlled by various quality control mechanisms. Ribosome-associated quality control (RQC) and ribophagy are identified as two major ribosome-associated PQC mechanisms that synergistically involve in the maintenance of translational function and protein homeostasis. Also, they represent key players in adjusting ribosome content and translational activity for the changing environment, in turn facilitating cell survival under stress conditions. The dysregulation of RQC and ribophagy malfunction can substantially alter cellular fate and render cell death, resulting in the onset and development of various ribosomopathies, including congenital diseases, neurological diseases, and malignant tumors. Targeting ribosomal dysfunction by restoring effective ribosome-associated PQC may serve as potential remedy in treating ribosomopathies. The current review focuses on ribosomal-associated PQC with in-depth discussion regarding to the key roles of these pathways for the maintenance of protein homeostasis as well as their potential effects on the development of various human diseases.
Abstract: The vast majority of bacteria require iron for growth. Iron is an essential element required for key biological processes including amino acid synthesis, oxygen transport, respiration, nitrogen fixation, methanogenesis, the citric acid cycle, photosynthesis, and DNA biosynthesis. However, obtaining iron presents challenges for the majority of microorganisms. In the ocean, the distribution of iron in the marine environment is spatially heterogeneous, which is one of the main limiting factors affecting marine primary productivity. Dissolved iron is a scarce resource for marine creatures because it is mainly present as a less soluble trivalent state (Fe3+), which makes it prone to settling and being “removed”. Marine microorganisms are presented with unique challenges to obtain essential iron ions required to survive and thrive in the ocean. To obtain enough iron source for life metabolism, microorganisms have evolved many ways to meet the demand for iron intake, among which siderophores is the most representative one. Siderophores are low molecular mass iron-binding ligands produced by marine bacteria. Microbial siderophores are multidentate Fe3+ chelators used by microbes during siderophore-mediated assimilation. They possess high affinity and selectivity for Fe3+. Among them, marine siderophore-mediated microbial iron uptake allows marine microbes to proliferate and survive in the iron-deficient marine environments. Being an important metabolic cofactor, siderophores also strongly influences the circulation of other elements. In order to better understand the role of siderophores in marine microbial ecology and deepen our understanding of marine iron cycle dynamics, this paper summarizes the types of siderophores such as hydroxamates, catecholates and carboxylates, two main siderophores synthesis pathways of microorganism and the mechanism of regulating siderophores synthesis, describes the transmembrane transport process of siderophores and several functional protein elements, the functions of siderophores such as anti-oxidative stress, regulation of pathogen virulence, formation of multifunctional iron and sulfur polymers, and anti-pathogens and so on. Although siderophores have been studied and discussed, further research can be carried out in the following aspects, such as the interaction mechanism between siderophores and marine microorganisms, the application of synthetic biology, and the coupling ability of siderophores behavior with other elements.
Abstract: Music is an auditory art, which may play an important role in education and psychological development of children. Phonological awareness describes the ability to perceive, recognize, analyze, and manipulate phonological units, which is an important indicator to predict children’s literacy skills. This review summarized experimental studies on the effect of musical training on children’s phonological awareness in the last decade, and discussed the relevant neural basis and hypotheses. It has been demonstrated that musical training could not only promote children’s phonological awareness at the behavioral level, but also affect children’s phonological auditory processing ability at the pre-attention level. Music training may affect the neural basis of phonological processing from two aspects: on the one hand, it may affect children’s speech perception ability at the pre-attention level by strengthening the basic auditory neural pathway and the auditory cortex; on the other hand, it may affect the phonological coding and auditory-motor integration by enhancing the functional connectivity among regions related to phonological processing. The related neural mechanisms provide the biological basis for music training to promote children’s phonological awareness. Based on the existing researches and theoretical hypotheses, the review proposed a hierarchical model to explain the cognitive mechanism of the effect of music training on phonological awareness, which presents that there are three levels of the cognitive neural mechanisms of phonological awareness effected by musical training. The first level, musical training may promote the basic auditory processing of speech by strengthening the basic auditory neural pathways, in which training in rhythm may strengthen the perception of speech duration, and training in pitch may strengthen the perception of speech frequency. The second level, musical training may further promote speech coding by enhancing the neural networks for speech processing, in which training in rhythm promotes the recognition of consonant, rhyme, and syllable, training in pitch promotes the recognition of vowel, rhyme, and syllable. The third level, musical training may promote the speech motoric representation and auditory-motor integration by enhancing the interaction between auditory and motor cortex, further improve the quality of phonological representation. The potential theoretical significance of the effects of musical training on children’s phonological awareness was discussed in the context of revealing the cognitive neural mechanism and rules of human’s language development, and the potential application in the field of children’s education was also discussed.
Abstract: Cancer has a high incidence and mortality and is a major threat to human health. Cancer prognosis analysis can effectively avoid excessive treatment and waste of medical resources and provide a scientific basis for medical staff and their families to make medical decisions. It has become a necessary condition for cancer research. With the rapid development of artificial intelligence technology and medical informatization in recent years, smart medicine has received widespread attention. It has become possible to analyze the prognosis of cancer patients automatically. As an essential part of smart medicine, cancer patients need to conduct effective intelligent prognostic analysis. This article reviews the existing machine learning-based cancer prognosis methods. Firstly, it provides an overview of machine learning and cancer prognosis, introduces cancer prognosis and related machine learning methods, and analyzes the application of machine learning in cancer prognosis. Then, it summarizes cancer prognosis methods based on machine learning, including cancer susceptibility prediction, cancer recurrence prediction, and cancer survival prediction, and sorts out their research status, cancer types and data sets involved, and machine learning methods used and prediction performance. Finally, the cancer prognosis methods are summarized and prospected, and the aspects that should be explored and improved are proposed: (1) include other high-fatal cancers in the prognostic analysis; (2) comprehensive analysis of cancer expression data and image data to improve prognostic performance; (3) optimize the prognostic model to improve prognostic performance.
Abstract: With the development of synchrotron radiation photon sources (especially the fourth generation of synchrotron radiation light sources), the radiation flux available for experiments is getting higher and higher, and the radiation damage of experimental samples (especially biological macromolecules such as proteins) is getting more and more serious. In the existing synchrotron radiation facilities around the world, the photon flux of SAXS experimental station for protein and other biological macromolecule solutions is basically in the order of 1013 cps. At such a high flux, the radiation damage of protein and other biological macromolecule solution samples is very serious in experimental measurement. If there is no effective radiation protection measures, protein solution samples will be damaged by irradiation within the millisecond irradiation time, resulting in the inability to obtain effective experimental data. Radiation damage severely restricts the application of SAXS in protein solution samples. Therefore, it is of great guiding significance for the scattering experiments of protein and other biomolecular solutions to understand the generation mechanism, influencing factors and judgment criteria of radiation damage of protein solution samples, and to effectively reduce the degree of radiation damage or delay the generation time of radiation damage. On the basis of a brief introduction to the basic concepts of irradiation damage mechanism, influencing factors, and irradiation dose of biomolecular solution samples, this paper summarizes the criteria and protective measures of radiation damage in synchrotron radiation SAXS experiments. In addition, this paper also compares the advantages and disadvantages of various protective measures, discusses the available acquisition time of SAXS-beamline scattering data on the high energy photon source (HEPS) under construction, and points out that the protective agents of irradiation damage are a valuable research direction.
Abstract: For the urgent need to develop a point-of-care test (POCT) method for coagulation detection that is rapid, sensitive, accurate, real-time, and environment-independent, the sensing principles and models of acoustic sensors used in coagulation detection were analyzed and summarized following the introduction of the main physical and chemical changes and corresponding parameters in the process of coagulation. The coagulation process consists of a series of enzyme-linked reactions promoted by coagulation factors triggered by endogenous or exogenous activators and the physical parameters such as blood viscosity, shear resistance, and density change accordingly. Acoustic sensors were adopted to detect the physical parameters in the coagulation process. The relationship between the samples and the coagulation time, thrombus dynamics, protein content, and so on was elaborated and provided information for the patient’s clotting state. In this paper, the sensing principle and mathematical model of quartz crystal microbalance (QCM), surface acoustic wave (SAW) sensor, thin-film bulk acoustic resonator (FBAR), and Lamb wave sensor were introduced. The design idea and hot points of the acoustic sensors were discussed in terms of structure, piezoelectric material, sensitive film, and processing technology. Combined with the characteristics of blood samples, the relationship between acoustic signals and the coagulation process was analyzed, and the application of acoustic sensors in coagulation detection was summarized and prospected. In addition, the application and research hotspots of microfluidic chips integrated with acoustic sensors for coagulation detection have been included, because the integration of the acoustic sensors into the microfluidic chip can help to control the environment and operation conditions for coagulation testing, which can better meet the needs of POC coagulation testing. Finally, the challenges and future development for coagulation detection of acoustic sensors were discussed and prospected.
Abstract: Objective Rheotaxis, namely to orient and swim against the water flow, is a conserved behavior across most fish and amphibians. While the study of rheotaxis behavior has a relatively long history, and in recent years the behavioral algorithm of rheotaxis has been described, how distributed neural circuits integrate multisensory information, make decisions, and generate counterflow motor sequences remain largely unknown. Whole brain calcium imaging of larval zebrafish during rheotaxis would provide a unique opportunity to tackle this difficult problem.Methods To this end, we developed a microfluidic device that can precisely control the water flow and elicit rheotaxis behavior. By integrating the chip with a customized light field tracking microscope, we built a system to record whole brain neural activity in freely behaving larval zebrafish during rheotaxis.Results Larval zebrafish showed reliable rheotaxis behavior in the setup, represented by prominent positional holding and counterflow swimming bouts in water flow. In the meanwhile, we successfully recorded zebrafish whole brain neural activity, from which a few brain regions were identified whose calcium signals strongly correlated with rheotaxis behavior.Conclusion Our study, for the first time, demonstrates a method for imaging whole brain neural activity in larval zebrafish while the animal is performing rheotaxis. Future analysis and modelling of the neural activity and behavioral data will deepen our understanding of sensorimotor transformation in this important naturalistic behavior.
Abstract: Objective To investigate the effect and mechanism of Zuogui pill-containing serum (ZGP-containing serum) on chemotherapy-damaged granular cells (GCs) and theca cells (TCs).Methods GCs and TCs were cultured respectively, the model group was established with phosphoramide mustard (PM), then treated by ZGP-containing serum. The survival rates of GCs and TCs was determined by CCK-8. Real-time fluorescent quantitative PCR (RT-PCR) and Western blot methods were used to detect the expression of Beclin-1, light chain 3 (LC3B), p62, Bax and Caspase3.Results 10% ZGP-containing serum had the best effect on the recovery of cell survival rate. Compared with the blank control group, Beclin-1, LC3B, Bax and Caspase3 have higher expression in the model group (P<0.05), and 10% ZGP-containing serum can down-regulate the expression of them (P<0.05). Moreover, the expression of p62 is lower in the model group than the blank control group (P<0.05), and 10% ZGP-containing serum can up-regulate it (P<0.05). In addition, in the groups of GCs, after activating or inhibiting the autophagy pathway, the expression of autophagy-related proteins and apoptosis-related proteins both changed correspondingly.Conclusion PM can damage GCs and TCs by promoting apoptosis and activating autophagy/lysosomal degradation pathways, 10% ZGP-containing serum can alleviate the damage. There is a cross-talk between autophagy and apoptosis in the process of PM damaging GCs which can be alleviated by 10% ZGP containing serum.
Abstract: ObjectiveDendrobium officinale has long been used as an important medicinal herb in oriental medicine. Polysaccharide, flavonoid, and alkaloid are the major active ingredients, the production and accumulation of which are frequently affected by numerous environmental cues. Phytohormone supplemented in culture medium has facilitated the mass production of orchids. However, their mechanism of action on the production of active components in Dendrobium officinale is far from clear.Methods Here, major medicinal metabolites were comparatively analyzed in Dendrobium officinale seedlings exposed to the most commonly used phytohormones (NAA and/or 6-BA), and transcriptomes corresponding to the treatments were generated.Results Results showed that phytohormones greatly affected the accumulation of polysaccharide, alkaloid, and flavonoid, and triggered tremendous transcriptional changes. It was demonstrated that 6-BA induced more transcripts than NAA and that β-glucosidase (BGLU) expression was closely related to polysaccharide production. Further functional analysis revealed that factors including phytohormone category, concentration, treating duration, and seedling growth stages, can drastically affect the BGLU expression and the corresponding polysaccharide production, thus partially answered the key question at molecular level why the medicinal constituents are unstable in tissue culture derived Dendrobium plants.Conclusion Altogether, the present study clearly demonstrated that BGLU is a key regulator for polysaccharide production in Dendrobium officinale in response to phytohormone treatments.
Abstract: ObjectiveTP53 is an important tumor suppressor gene, however, mutations of p53 occur in over 50% of all cancers and are indicative of highly aggressive cancers that are hard to treat. Targeting mutant p53 (mutp53) is one of the effective strategies in cancer therapy.Methods We constructed a high throughput screen system which contains the p53 targeted puma, H1299-p53R273H-PUMA-luciferase, and H1299-p53R175H-PUMA-luciferase to screen compounds targeting mutp53. Using immunofluorescence assay to detect the effect of andrographolide on the expression of mutp53 in HT29 (R273H) and SK-BR-3 (R175H) cells. Western blotting experiment and qRT-PCR analysis were used to further observe the protein and mRNA expressions of andrographolide on p53 downstream target genes PUMA, p21, and Noxa in mutp53 tumor cells. Then MTT and flow cytometry were used to detect andrographis paniculata The effect of lactone on tumor cell proliferation and apoptosis. In addition, after knocking down Hsp70 expression by siRNA, the reactivation effect of andrographolide on mutp53 downstream genes was also studied.Results Andrographolide enhanced PUMA-luciferase expressions in both cell lines. Andrographolide could reduce the expressions of mutp53 in HT29 (R273H) and SK-BR-3 (R175H) cells, while the expressions of wild-type p53 increased by immunofluorescence assay. Andrographolide can inhibit the cancer cell proliferation and induce apotposis in mutant p53 cancer cells. Andrographolide can enhance the p53 downstream target protein and mRNA expressions of PUMA, p21, and Noxa. Andrographolide increased the expression of molecular chaperone Hsp70 in HT29 and SK-BR-3 cells, as the chaperones play important role in p53 structure function, we knocked down Hsp70 by siRNA and found that the upregulation of p53 targeted genes was reversed.Conclusion Andrographolide restores the wild-type-like p53 function dependent on Hsp70.
Abstract: Objective Hair shaft is one kind of common biological evidences at the crime scene. However, it fails to play an important role in the crime investigation due to lack of effective method of individual identification. The single amino acid polymorphisms (SAPs) in the hair shaft proteome contain information of individual genetic differences.Methods In order to study SAPs in the hair shaft, the proteome of single 2 cm hair shaft samples (6 people, 2 hairs per person) were extracted using ionic liquid following with LC-MS/MS detecting. The protein composition of the hair shaft was analyzed. A custom SAP protein sequence database was built for East Asian population as the searching database. Based on the custom SAP and SNP corresponding annotation table information, the nsSNP profiles were imputed corresponding to SAP. The accuracy of SAP was verified by comparing the imputed nsSNP profiles from SAP with nsSNP profiles obtained from the whole exome sequencing. The validated SAPs were used to calculate the random matching probability.Results In 12 samples, 321 SAPs were obtained, with an average of (131±17) for each sample. The value of random matching probability for 6 people ranged from 1.4×10-4 to 1.0×10-9.Conclusion In this paper, a method for detecting SAP in hair shaft proteins of East Asian populations was established, and the ability of individual identification application was verified, which provided a powerful tool and new ideas for individual identification of hair shaft in forensic science.
Abstract: Objective As for the unique properties of good biocompatibility and excellent optical performance, silica nanotubes have shown potential applications in different fields. The properties of the silica nanotubes were well correlated with their size and morphologies. In order to prepare silica nanotubes with much larger size and expand their applications in different fields, this study selected wide peptide nanotubes as templates for biomimetic synthesis of silica materials.Methods In order to obtain silica nanotubes with relative large size, here we prepared silica nanotubes by using wide nanotubes (with diameters of approximately 40 nm) self-assembled by the bola peptide Ac-KI3VK-CONH2 as templates through a biomimetic mineralization route. The stability of the peptide nanotubes was firstly investigated and the results demonstrated that these nanotubes can be easily destroyed by dilution, addition of organic solvents, or changing the solution pH value, showing poor stability. Then, we chose methyl n-silicate (TMOS) with fast reaction rate as the precursor to prepare silica nanomaterials and systemically explored the influence of different factors on the size and morphology of the silica nanotubes.Results The results demonstrated that the ideal condition for preparing silica nanotubes with uniform shape and size was using TMOS as precursor and keeping its concentration at 1.11%-3.33% (v/v) under neutral or weak alkaline conditions.Conclusion This work successfully prepared silica nanotubes with relative large diameter by using self-assemblies formed by a bola peptide as templates and silicon source with fast reaction rate, which is of great significance and may expand the applications of wide silica nanotubes in different fields.
Abstract: Objective Based on chemical structural characteristics, the bioactivity of polyoxypregnane glycosides from Dregea sinensis, and the molecular interaction between compounds and targeted proteins were investigated.Methods The bioactive screening of 191 polyoxypregnane glycosides (>800 u) , and the kinetic evaluation on human immune-related proteins was carried out by molecular docking and SPR experiment.Results Seven compounds (6, 18, 23, 30, 78, 79, and 80) and 3 immune-related proteins (IL-2Rα, TLR4, and TNF-α) were selected through virtual screening. Compounds 30 and 78 showed the significant binding tendency with IL-2Rα and TLR4 in SPR experiment, and KD values with IL-2Rα were 2.41×10-6 and 2.14×10-6 mol/L, meanwhile KD values with TLR4 were 1.96×10-5 and 5.60×10-6 mol/L, respectively. The interactions between targeted proteins and compounds were further characterized by discovery studio. The analysis of molecular docking revealed the binding pocket residues for SPR-positive molecules 6, 18, 30, 78, and 80.Conclusion The result indicated these glycosides could bind to targeted proteins through forming hydrogen bonds and Pi-Pi interactions. The study is meaningful for bioactive evaluation of polyoxypregnane glycosides, and provides valuable exploration to the underlying mechanisms of effective compounds with low abundance.
Abstract: Objective Serum anti-phospholipase A2 receptor antibody IgG (PLA2R-IgG) is an important basis for the diagnosis and treatment of idiopathic membranous nephropathy. By now, its conventional detection method is ELISA. To improve the reaction convenience, and obtain the assay sensitivity and wide detecting range, a novel immunoassay was established for PLA2R-IgG detection.Methods Here, based on europium fluorescent microspheres an indirect immunochromatographic assay (ICA) for PLA2R-IgG was developed and evaluated. The reaction process was firstly chosen, and the method parameters were assessed like pH of activating buffer for microspheres, the ratio of europium microspheres to antibodies, and reaction time.Results The performance metrics of the newly proposed assay were analyzed that the sensitivity was 0.7 RU/ml of PLA2R-IgG, the standard curve equation was y=0.771x－1.437 with 0.995 of R, the linear working range was 0.7-1 500 RU/ml, the recoveries were 86.27%-98.98%, the average variable coefficient of intra assay was 8.13%, the cross reaction ratio were above 0.1% and PLA2R-IgG-ICA reagents were stable for 10 d at 37℃. The correlation was 0.953 between developed method and commercial ELISA kits, the consistency was also high. The positive detection rate was 76.9%.Conclusion The established PLA2R-IgG-ICA using two-step dosing was rapid, sensitive, quantitative and accurate with potential clinical application.
Abstract: Objective The axial length (AL) and the corneal curvature radius (CR) in the optical biological parameters of the eye can be used as two important parameters for the prevention and monitoring of ocular myopia. In order to improve the speed and accuracy of measuring the length of eye axis and to achieve high precision of corneal curvature simultaneously dynamic measurement, This paper proposes a system for measuring optical biological parameters of the eye based on low-coherence light interference technology.Methods The system uses a rotating optical delay line to quickly change the optical path of the reference light, and uses a standard part with a curvature radius of 8 mm to calibrate the vertex of the human cornea to the distance between the target ring and the interference signal of the cornea trigger the camera and the data acquisition card to achieve synchronous acquisition, thereby realizing rapid measurement of the axial length and precise positioning of the distance between the target ring and the corneal vertex, while ensuring the magnification of the imaging system constant and real-time data collection.Results Experimental results show that this low-coherence optical interferometry system can measure the axial length and corneal curvature radius in real time. The axial length error is less than 40 μm, and the human corneal curvature radius variance is 2.082 36×10-2 μm.Conclusion The system measures AL and CR quickly and accurately, which may play an important role in the prevention and monitoring of myopia.
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