Abstract:In recent years, nanomaterials have provided a new research approach for biosensor technology and greatly improved the performance of biosensor. Molybdenum disulfide (MoS₂) nanomaterials have been widely used in biosensors due to their unique properties such as large specific surface area, adjustable band gap and high electron mobility. This paper introduces electrochemical, field effect transistor (FET), surface-enhanced Raman scattering (SERS), colorimetric method and dual-mode biosensor based on MoS₂ nanomaterials. Among them, MoS₂ electrochemical biosensor uses the redox reaction between target and biological probe to analyze the concentration of target. It has the advantages of high sensitivity, fast response speed and simple operation, but its experimental cost is high, so low-cost experimental methods need to be developed in the future. When MoS₂ acts on FET, it is used as the channel material to contact the analyte, and the gate applies bias voltage to realize the current change. It is small in size and high in sensitivity, but there are few reports on the detection of biomolecules in actual human samples. Therefore, it is necessary to focus on solving the problem of compatibility between sensor and biological solution in the future. MoS₂ nanocomposite SERS biosensor can be combined with chemical enhancement and electromagnetic enhancement to achieve singlemolecule detection. Its sample consumption is small and no special treatment is required, but the large-scale optical analysis system of its detection process is complex and expensive. Therefore, the simplification of optical analysis equipment and detection system is a problem to be further studied. MoS₂ nanocomposite colorimetric biosensor utilizes its peroxidase activity to catalyze the color change of the chromogenic substrate. It has the advantages of easy operation and low cost, but its sensitivity is not high and the reaction time is long. Therefore, in the future, it is necessary to find high-performance MoS₂ nanomaterials to achieve fast and highly sensitive detection. MoS₂ nanocomposite dual-mode biosensor is based on one material to form two detection signals, combining two analytical methods for substance detection, with strong specificity and high accuracy. At present, how to extract a variety of information and apply it to dual-mode detection is still the focus of research, and the integration of detection instruments in dual-mode sensing will also be the trend of future development. Based on the analysis and conclusion of this paper, which provides ideas for the further application and future research directions of MoS₂ biosensors in the field of biological detection.

Abstract:DNA nanotechnology is a technique for generating programmable nucleic acid structures based on the Watson Crick base pairing principle. Nanostructures synthesized by DNA nanotechnology can not only interact with small molecules, nucleic acids, proteins, viruses and cancer cells, but also serve as nanocarriers to deliver different therapeutic drugs due to their high precision engineering design, unprecedented programmability and inherent biocompatibility. DNA origami, as an effective and multifunctional method to construct 2D and 3D programmable nanostructures, is a milestone in the development of DNA nanotechnology. Due to its highly controllable geometric shape space address-ability and easy chemical modification, DNA origami has great application potential in many fields. This review first introduces the basic principle of DNA origami, summarizes the development process of DNA origami according to the time sequence, introduces the software development process used to design DNA origami and compares its advantages and disadvantages. Drug loading of DNA nanostructures is described by category of drug loading, and drug release is described by release mode. Ideally, drug delivery carriers should be able to carry one or more drugs for collaborative treatment and penetrate the cell membrane and barrier to avoid harmful chemical and enzymatic degradation drugs, as well as adverse toxicity and immunogenicity, and show targeted and controlled drug release. Although drug delivery schemes based on DNA origami technology have not been applied in clinic, they are currently developing rapidly and show great potential in cancer treatment. This paper introduces the origin of DNA origami, starting with the basic principles and current progress, the methods of drug loading and releasing using DNA origami were summarized. Based on this technology, the future development trend, opportunities and challenges were prospected.

Abstract:Molecular recognition and drug delivery are crucial for diseases’ early diagnosis and targeted therapy. DNA, a natural nanoparticle, has good biocompatibility, molecular recognition characteristic, and sequence programmability, it has been widely concerned in biomedical researches. However, DNA nanomaterials depend on the photoresponsive systems and hard to penetrate the cytomembrane, these series of troubles make them difficult to meet the needs of complex experiments. Since DNA was identified to an excellent nanostructured building block, more and more new material systems assembled with DNA, a large number of DNA-metal nanomaterials have emerged especially, which endowed with photochemical property, tissue penetration ability and drug loading ability, overcoming the defects of a single material and showing great potential in biosensing, bioimaging and targeted drug delivery fields. Here, DNA-copper nanomaterials, DNA-upconversion nanomaterials and DNA-metal-organic framework nanomaterials are reviewed, because of unique photostability or high pore volumes of these 3 kinds of representative metal nanomaterials in the nanotechnology field. What’s more, they are low-cost and easily available. According to the combination ways of DNA and metal nanomaterials, these 3 DNA-metal nanomaterials are classified reasonably, and their the latest applications in biomedical field are introduced, in order to provide therapeutic ideas for the clinical prevention and treatment of cancer. Finally, the opportunities and challenges for DNA-metal nanomaterials are overviewed and discussed.

Abstract:In recent years, several oncolytic virus preparations has been approved for marketing, leading to the oncolytic virus therapy to become the focus of tumor immunotherapy. Oncolytic viruses can selectively infect and lyse tumor cells, and release tumor-associated antigens (TAAs) to activate anti-tumor immune response to inhibit tumor growth. The safety and efficacy of oncolytic virus are determined by its targeted killing effect on tumor. In order to develop safe and efficient oncolytic viruses, the following strategies are mainly adopted: taking advantage of the natural target of some virus on tumor cells to make oncolytic viruses selectively replicate in tumor cells and kill tumor cells; alternatively, the viral genome can be modified by deletion of some virus gene or insertion of some exogenous gene to promote virus targeting tumor cell-specific surface receptors, intracellular signaling pathways, or the tumor microenvironment to improve the targeting ability of oncolytic viruses. In tumor microenvironment, hypoxia, neovascularization and immunosuppression usually can be targets of oncolytic viruses. In order to regulate immunosuppressive state, oncolytic viruses are commonly used to express cytokines and immune checkpoint inhibitors, or combine with CAR-T cells. In this paper, we will review the research progress of therapy strategies of the oncolytic virus-targeted tumor.

Abstract:Cell fusion is fundamental to various morphological and physiological events involved in the development of most eukaryotic organisms. Saccharomyces cerevisiae (S. cerevisiae) is a classic model organism for eukaryotic genome synthesis and transfer in the context of synthetic biology. However, the molecular mechanism underlying the yeast cell fusion remains to be fully understood, thereby limiting its synthetic biology application. In S. cerevisiae, mating initiates when cells respond to pheromones that trigger MAPK (mitogen-activated protein kinase) cascade, following with polarization, cell wall remodeling, membrane fusion, and karyogamy. This review discusses the current state of knowledge and progress regarding cell fusion in S. cerevisiae as well as the proteins involved in these events. Especially, the study of the possible “fusase” Prm1 provides a direction for promoting the manipulation of cell fusion. We further propose a hypothesis about the intracellular transport and maturation process of Prm1, which reasonably explains the regulation mechanism of site-directed aggregation of Prm1 at the plasma membrane. Notably, this review stresses the synthetic biology applications of yeast mating signaling pathway in biological components, biological devices and systems, and multicellular interactions. Such elements, including pheromone-responsive promoters, G protein-coupled receptors, scaffold proteins, transcription factors, bistable switches, tuners and chassis cells. Together they contribute to the applications of biosensors and metabolic engineering. Strategies such as rationally engineering of modular circuits and optimizing the reproductive pathway will promote the maneuverability of cell fusion. Moreover, many innovative synthetic biology tools, such as microfluidics, omics research, genome editing, and machine learning, allow researchers to examine the complex physiological activities and improve fusion efficiency. Our study lays foundation for the study of cell-fate decision system and the application of yeast cell fusion in the large genome transfer.

Abstract:Pulmonary fibrosis is an end-stage alteration in the respiratory disease characterized by fibroblast proliferation and massive accumulation of extracellular matrix and collagen associated with inflammatory damage. This disease is based on lung dysfunction and respiratory failure pathologically, and its incidence is rising year by year with the limited treatment method currently. Considering on regulation function in gut-lung axis, this dysbiosis caused by intestinal microflora not only modulates the immune response of the gastrointestinal tract but also can impact the onset process of chronic respiratory diseases including pulmonary fibrosis in a variety of ways. In addition, changes in microbial composition and function in the respiratory tract and the gut tract have recently been both linked to disorders in immune responses. In this opinion article, we summarize recent advances in the correlations and underlying pathogenic mechanisms of the relationship between intestinal microbiota and pulmonary fibrosis diseases, including multiple interventions of probiotics flora, diet and antibiotics against dysbiosis. However, direct evidence that pulmonary fibrosis injury changes the proportion of gut flora and composition of the metabolites in host is still lacking. Thus, this review can potentially provide effective theoretical and strategic support for the future exploration about regulatory mechanism and therapeutic drug development.

Abstract:Interleukin (IL)-33, a nuclear factor and a cytokine of the IL-1 family, has received a lot of attention in recent years because of its important role in chronic inflammatory and autoimmune diseases. It appears to be critically involved in the regulation of various physiological processes by influencing a wide range of immune cells. Previous reports and studies have primarily focused on the effects of IL-33 on traditional target cells, such as mast cells and type 2 innate lymphocytes. Dendritic cells (DC) are the most functionally specialized antigen-presenting cells that have been discovered to date. It has been demonstrated that IL-33 can activate DC via its specific receptor serum stimulation-2 (ST2), thereby regulating the host immune response and playing key roles in the pathogenesis of occurrence and progression of various diseases. The immune regulation of DC by IL-33 mainly involves signal pathways, such as NF-κB, p38 MAPK, and STAT1/3, in turn mediating the maturation, differentiation, and inflammatory response of DC. In addition, DC is an important source of the secretion of IL-33, which enhances the immune reaction and Th2 response through a positive feedback amplification loop. IL-33 activated DCs can promote tumor immunity and resist pathogen invasion, and also participate in the development of autoimmune and inflammatory diseases. This paper reviews the potential role and underlying mechanism of IL-33 in regulating DC immune response in order to provide a foundation for further research into its immune function and modulatory pathway in diseases.

Abstract:MicroRNAs (miRNAs) are a class of endogenous non-coding small RNAs with a length of 20-24 nucleotides that present widely in eukaryotes. miRNAs regulate the expression of their target genes post-transcriptionally through transcript cleavage or translation inhibition. Recent studies have shown that miRNAs are involved in a wide variety of biological processes of plant growth, development and stress responses, and play essential roles in regulating agronomic traits of crops. Maize is an important staple food, feed and industrial raw material, and thus it is crucial to improve maize yield and quality to ensure world food security. Compared to model plants Arabidopsis and rice, the studies on maize miRNAs are still relatively limited. The understanding of functions and regulatory mechanisms of miRNAs in maize is essential for engineering important agronomic traits genetically through molecular breeding. In this article, we review the discovery and identification of maize miRNAs, most of which are tissue-specific and spatiotemporally expressed. Up to now, a total of 325 mature miRNAs from 174 precursors were identified in maize genome, belonging to 29 miRNA families. We also systematically summarize the functions of key components in maize miRNA biogenesis pathways, including DCL, AGO and HEN1. Mutations in these miRNA processing proteins result in pleiotropic developmental phenotypes, suggesting the important regulatory roles for miRNAs in maize development. MiRNAs whose functions have been characterized in maize growth and development are discussed, including those involved in root formation, leaf morphogenesis, grain maturation and reproductive development. Furthermore, function of miRNAs in responses to abiotic stresses, such as salt stress, drought stress, temperature stress and nutrition stress are elaborated, with the highlight on miR169-NF-YA, miR399-PHO2, and miR528-LAC3 regulatory modules. We also discuss the current existed issues and future perspectives in maize miRNA study. Despite the identification of a large number of maize miRNAs, research on the functions and regulatory mechanisms of miRNAs in maize is still very limited, and it is still required to generate essential genetic materials and take advantage of multiple experimental strategies to perform in-depth and systematic studies on miRNA and their target genes. It is believed that miRNAs are valuable gene resources and a better understanding of miRNA-mediated regulatory network would be beneficial for engineering maize varieties with improved agronomic traits.

Abstract:Diabetes mellitus is a common clinical metabolic disease, and its destructive macrovascular complications and microvascular complications are one of the main reasons for the decline of patients’ life quality and even death. Therefore, many studies have been conducted to explore the pathogenesis of diabetic complications which is important for the diagnosis and treatment of diabetic patients. Exosomes (EXs) are vesicular bodies secreted by variety cells, and exchange intercellular information via bioactive molecules, such as microRNA (miRNA), proteins or lipids. It has been reported that EXs is a tool for the communication of miRNA and target cells due to its highly stability, lowly toxicity and immunogenicity and specifically targets. Current studies have found that EXs derived from different cells play different roles in diabetes complications. EXs miRNA can mediate renal tubular cell oxidative stress, pyroptosis and differentiation, and inhibit podocyte migration and apoptosis in diabetic kidney disease; EXs miRNA in diabetic retinopathy can inhibit endothelial cell growth, metastasis and angiogenesis, and inhibit retinal vascular inflammation and apoptosis; EXs miRNAs can regulate dorsal root ganglion neuron growth and inhibit neurovascular inflammation in diabetic peripheral neuropathy; EXs miRNAs in diabetic cardiomyopathy can regulate cardiomyocyte apoptosis and angiogenesis, inhibit myocardial inflammation and fibrosis. In addition, the change of EXs miRNA level can reflect the development of diabetes complications. Therefore, EXs miRNAs are expected to become new biomarkers and therapeutic targets for the prevention and treatment of diabetic complications in the future. However, the role of EXs miRNA on the diagnosis of diabetes complications is still unclear, and the mechanism of EXs miRNA on the improvement of diabetes complications are needs to be explored. It was reported that exercise benefits for the prevention and treatment of diabetes complications. Although acute or long-term exercise can regulate the expression of EXs miRNA, the regulation of EXs miRNA expression via acute or long-term interval and resistance exercise are few studies. Moreover, exercise plays a beneficial role in the pathological regulation of diabetes complications via the regulation of EXs miRNA or exerkines by improving endothelial cell function and insulin sensitivity, maintaining fat metabolism balance and inhibiting apoptosis, and promoting “cross talk” between tissues and organs. In the future, the specific mechanism of exercise-mediated EXs miRNA to improve diabetic complications still needs to be further explored.

Abstract:Adiponectin (ADPN) was initially thought to be a factor secreted by adipocytes. However, with the development of research and technology, it has been found that skeletal muscle is an important organ for the synthesis of ADPN, and its biological function can be effectively regulated by ADPN. Current studies have shown that ADPN can up-regulate the expression of slow-twitch muscle fiber and aerobic energy-related genes and proteins, and down-regulate the expression of fast-twitch muscle fiber and glycolysis energy-related genes and proteins. Our research group has previously proved that ADPN can up-regulate the expression of MOTS-C, and MOTS-C has recently been reported to be closely related to the conversion of fast muscle to slow-twitch muscle. This may be a new mechanism of ADPN-mediated myofiber conversion type. ADPN can significantly up-regulate mitochondrial number, inhibit autophagy, reduce membrane potential depolarization, and promote fatty acid β oxidation. However, the current reports are limited to the intervention of ADPN and its receptor, and its mechanism should be further explored in cells, in downstream factor knockout animals, and by omics. ADPN and its receptor activators can increase insulin sensitivity and promote blood glucose uptake, in which sex hormones may play an important role. However, long-term intervention of ADPN and its receptor activator may lead to abnormal tricarboxylic acid cycle and thus eliminate this effect. Although no study has directly proved the relationship between ADPN and muscle contractility, combined with current reports, it is speculated that the possible connection mechanism is calcium regulation. Considering the conversion of fiber type, endurance and strength should be taken into account in selecting indicators for measuring contractility in the future. ADPN plays an important role in skeletal muscle remodeling. However, it may not act directly on muscle cells but indirectly regulate the growth of undifferentiated myogenic or satellite cells to accelerate the remodeling. AdipoR1 agonist significantly improved the activity of skeletal muscle cells, and AdipoR1 expression was not affected by various muscle-related diseases, suggesting that AdipoR1 may be an effective therapeutic agent. Skeletal muscle, as an organ that is both regulated and accomplished by movement, is closely related to movement. However, the regulation effect of different forms and intensities of exercise on serum and skeletal muscle ADPN is still controversial. Serum experiments show that the change of ADPN after a single exercise is related to exercise duration, while long-term aerobic exercise up-regulates the expression of ADPN in pathological state. Skeletal muscle experiments show that exercise only seems to modulate fast muscle ADPN levels. In addition, the time of sample collection and measurement of ADPN subtypes are points that need to be considered in future studies. This paper reviews the new functions of ADPN in skeletal muscle and the exact effects of exercise on the expression of ADPN in skeletal muscle, in order to provide new ideas for the treatment of skeletal muscle related diseases.

Abstract:The method that decoding the electroencephalogram (EEG) signal from abnormal epileptiform discharge activity of neuron clusters in the preictal states can significantly decrease the lesions by predicting epileptic seizures effectively and implementing interventions in patients before the onset of seizures, and thus is considered the hotspot of the current research in epilepsy prevention and treatment. The key to epileptic seizure prediction based on EEG signals lies in the identification of abnormal states in the inter-ictal and pre-ictal states. Studying the differences in neurodynamic characteristics between the above two states contributes greatly to clarifying the pathogenesis of epilepsy, and is of great value for the prevention and prognosis of patients. By extracting the high-resolution features from the neurodynamic characteristics, the onset of this progressive disease can be effectively identified. Despite the prevailing feature extraction and pattern recognition methods have been investigated sufficiently, it appears that the existed research ignores the importance of identifying changes in neurodynamic characteristics for seizure prediction. Pointing at the deficiency aforementioned, this paper summarizes five typical analysis methods of seizure prediction in neurodynamics, including time domain, frequency domain, time-frequency domain, nonlinear dynamics and global synchronization analysis, as well as their specific characteristics. Since multiple properties of EEG before epileptic seizures, such as amplitude, phase, transient frequency, band power, brain area energy, system and dimensional complexity, and global synchronization level, will change correspondingly with the abnormal activity of brain neuron clusters, the dynamic changes of neurophysiological features are analyzed with emphasis to research neurodynamic properties from inter-ictal to pre-ictal. In addition, the prevailing machine learning and deep learning methods of feature recognition are compared. Facing the current challenges, this study finally synthesizes the latest findings in this field, aiming at providing new insights for establishing accurate and efficient technology for epileptic seizure prediction.

Abstract:Objective The comparative proteomic study on the paired lesional epidermis (LE) and non-lesional epidermis (NLE) from vitiligo patients to identify the differentially expressed proteins (DEPs) between LE and NLE, and to further explore the molecular mechanism of pathogenesis of vitiligo.Methods Firstly, the in solution digestion condition for proteins from epidermis were optimized to sequential tandem digestion with Lys-C and trypsin. Secondly, tandem mass tag (TMT) based quantitative proteomic strategy was performed to compare the proteome profile of the paired LE and NLE from three stable non-segmental vitiligo subjects, and differential expressed proteins (DEPs) were identified. At last, the functional enrichment analysis was performed via bioinformatics tool and database (GO, KEGG, STRING, GSEA).Results The optimal sequential tandem digestion condition was the combination of Lys-C (enzyme∶substrate, 1∶100) and trypsin (enzyme∶substrate, 1∶50). A total of 4 496 proteins were identified, and of which 181 were DEPs between LE and NLE from vitiligo patients. Bioinformatics analysis showed that DEPs were mainly related with metabolism, immunity, redox and cell adhesion. Among them, the 119 up-regulated proteins are mainly involved in the processes of keratinization, transcription, oxidative stress, and proteolysis. The 62 down-regulated proteins are mainly involved in intracellular transport, glutathione metabolism and actin filament capping.Conclusion The comparative proteomic study revealed that there were functional differences in keratinization, immunity, lipid metabolism and redox between LE and NLE in vitiligo patients. PRDX1, PRDX2, EEF2, ITGB1, SPTBN2, ANXA1 and PFKL were found as the key proteins to disfunction of LE.

Abstract:Objective This study was designed to observe different durations of simulated weightlessness induced depressive-like behaviors and the change of superoxide dismutase (SOD) and catalase (CAT) in hippocampi of rats, so as to explore its effects and possible mechanism.Methods Weightlessness was simulated by hindlimb suspension by tails (HLS) in rats. The rats were divided into the control and the HLS groups for each respective week (s), i.e., 1, 2, 3, and 4. The depressive-like behaviors in rats were investigated by using the open field test (OFT), novel object recognition test (NORT), forced swim test (FST), followed by hippocampal protein level estimation of SOD and CAT by ELISA.Results The OFT results showed increased stagnation time among HLS rats in each respective group compared to their corresponding control groups (P<0.05, P<0.01). In the NORT, the latency of exploration increased, while the number and the time of exploration decreased in the HLS groups in each week, compared to their corresponding control rats (P<0.05, P<0.01). Similarly, FST displayed enhanced immobility with the reduced climbing rate in HLS rats in each respective week, compared to the normal rats (P<0.05, P<0.01). Simulated weightlessness significantly reduced the SOD and CAT levels in the hippocampi in HLS rats compared to the normal rats (P<0.05, P<0.01).Conclusion Results suggest that short or long weightlessness could induce depressive-like behaviors in rats.

Abstract:Objective Since the first discovery that CRISPR-Cas system provides adaptive immunity of prokaryotic hosts to virus and other mobile genetic elements (MGEs). Numerous studies yielded vital insights into the immune mechanisms, and CRISPR-Cas system has been wildly utilized in gene editing and related research efforts. In the three major immune stages—adaptation, expression and maturation, interference spacer sequences play important roles separately. Although PAM (protospacer adjacent motif) determines the identification of targeted genes by CRISPR-Cas system, what drives the selection of specific genes and reservation on the CRISPR array remains uncertain. To explore the targeting characteristics of CRISPR-Cas systems, the virome of Yangshan harbor surface water and the CRISPR-Cas spacers available in public datasets were subjected to analysis.Methods Based on BLAST searching, viral sequence identification, gene function prediction, and gene conserved domain annotation, the final analysis results were obtained.Results As a result, 25 391 double-stranded DNA viral sequences were identified in the virome; 265 open reading frames (ORFs) were predicted for 238 sequences, and 134 CRISPR-Cas spacer sequences yielded 315 viral hits. 128 viral ORFs and 135 hits were functionally annotated, and the top 5 hits including terminase, capsid protein, portal protein, peptidase, and DNA methyltransferase. The matching of spacer (host)-protospacer (virus) often occurred in conserved domains or key structural domains of viral functional genes. Meanwhile, the number of CRISPR-Cas spacer sequence matches for Type_I systems under the Class 1 was much higher than that for other types of systems, accounting for 89.0% of the total. The results show that the CRISPR system will specifically identify and act on key functional genes of the virus.Conclusion The results of this study reveal the targeting specificity of the CRISPR-Cas system, showing new insights and providing new evidence for a better understanding of the mechanisms of virus-host immune interactions.

Abstract:Objective DUF538 (domain of unknown function 538) domain containing proteins are known as putative hypothetical proteins in plants. Until yet, there is no much information regarding their structure and function.Methods In the present research work, the homologous structures and binding potentials were identified between plant/mammalian lipocalins and plant DUF538 protein by using bioinformatics and experimental tools including molecular dynamics simulation, molecular docking and recombinant technology-based techniques.Results Molecular docking analysis of their interactions with lipidic ligands including cholesterol and palmitic acid revealed the similar and comparable binding potentials between DUF538 and lipocalin proteins. Both the test proteins were found to have more affinity to cholesterol molecule in compare to palmitic acid. By using recombinant technology-based experiments, the heterologously expressed and purified fused product of DUF538 protein exhibited about 61% cholesterol binding ability.Conclusion As a conclusion, plants DUF538 protein family was predicted to be the structural and may be the functional homologues of plants/animals lipocalin superfamily.

Abstract:Objective The reservoir of human immunodeficiency virus (HIV) latently infected cells is the major obstacle for eradication of acquired immunodeficiency syndrome (AIDS). Due to the noisy environment and multiple influencing factors in the organism, current dynamical models cannot reach a common understanding of the molecular mechanism of HIV latency. In this work, through a new dynamical structure decomposition, the deterministic part of the equation can be separated from the stochastic noise. Thus, the fixed-point analysis of ordinary differential equation is enough to obtain the different steady states of the system.Methods We established a dynamical model of HIV transcription process by using continuous stochastic differential equations, which simplifies the dimensions of equations needed to describe the system and increases the explorable space of the model. Different states between latency and activation of virus and their relations can be intuitively represented by potential functions and probability distribution functions.Results Based on our model, the influence of different dynamical parameters on stability is quantitatively analyzed, the parameter ranges of the system in bistable and monostable states are obtained respectively. The theoretical basis of this work is verified by comparing the effects of different factors on dynamic bifurcation with the results of biological experiments.Conclusion This paper goes beyond previous discrete stochastic methods, and can quantitatively analyze the dynamic mechanism of HIV transcriptional regulation through ordinary differential equations, which is beneficial to the promotion to deal with the high-dimensional situation, and further study the occurrence and development of AIDS in vivo, so as to guide the design of experiments and search for clinical treatment.

Abstract:Objective As a powerful tool in correcting genomic point mutations, base editors (BEs) show a promising prospect for biotechnology development and therapeutic applications. While editing the target single-nucleotide variant (SNV), it’s primary to select competent BEs and design single guide RNA (sgRNA). Currently, although there are multiple sgRNA design tools, no tools are available for integrating the design of sgRNA with the assessment of the specificity of BEs.Methods 27 cytosine base editors (CBEs) and 12 adenine base editors (ABEs) were used to design base editing schemes. BE-Hive, a third-party tool, was provoked to predict the editing efficiency. The off-target profiles of editing schemes were evaluated by using a combination of multiple off-target prediction tools. Finally, all possible off-target editing products were calculated by considering both base editor types and off-target sites, and then ANNOVAR, a variant annotation tool, was called for functional analysis of off-target products.Results We propose a comprehensive tool, BE-dot, which enables the complete process from a given SNV to designing sgRNAs, predicting off-target profiles, and annotating off-target products’ functions. Besides providing precise correction schemes at DNA level, in order to expand the range of editable SNVs, BE-dot can perform synonymous corrections at protein level by degeneracy. When predicting off-target profiles of single base editing systems, BE-dot integrates multiple tools such as Cas-OFFinder, CALITAS, CFD, uCRISPR and BEdeepoff, which allows BE-dot to evaluate the specificity of single base editing systems more comprehensively and provide users with consultations about BEs and sgRNA selection. In addition, BE-dot can automatically analyze all possible editing products at off-target sites, and convert them into avinput format for functional annotation by ANNOVAR, avoiding the tedious manual annotation.Conclusion BE-dot designs editing schemes for applying base editing to correct or introduce SNVs, and comprehensively evaluates the editing scheme in terms of editing efficiency, off-target profile, and off-target functional impact.

Abstract:Objective The conductivity in bioelectromagnetic parameters is directly related to the functional information of the tissue, and precise reconstruction of biological tissue conductivity is of great significance in the fields of medical imaging technology and medical diagnosis. In this paper, the microwave-induced thermoacoustic tomography (MTAT) algorithm is improved to improve the reconstruction accuracy of tissue conductivity.Methods On the basis of utilizing the finite element discrete method to solve thermoacoustic wave equation and Helmholtz equation, an improved method of quantitative reconstruction of biological tissue conductivity based on regularized Newton iteration method (RNIM) is proposed in this paper.Results The effectiveness of the algorithm improvement was verified by numerical simulation and phantom experiments with different concentrations of NaCl solution. The results of the tissue phantom experiments showed that the relative error of the phantom conductivity quantitatively reconstructed by the regularized Newton method is significantly lower than that of the quantitative MTAT with fitting, for the cases with different target positions, sizes and contrasts. And the accuracy of the reconstruction is improved. Simultaneously, the RNIM method was used to reconstruct the conductivity of a single target with the same concentration at different positions with smaller variation in the mimic experiments, as well as the relative ratio of the reconstructed conductivity of multiple targets was closer to the actual one, which the experimental results verified the stability of the improved method.Conclusion The results show that the optimized algorithm reconstruct the conductivity of the tissue phantom more accurately and quantitatively, which is of great significance for the early screening and precise diagnosis of tumor localization and staging, to prevent the deterioration of the disease.