Abstract:The 2023 Nobel Prize in Physiology or Medicine was awarded to medical scientists Katalin Karikó and Drew Weissman for their discovery of nucleoside base modification. The two researchers found that mRNA produced from modified nucleoside bases can evade innate immune recognition and improve protein expression. The discovery of these modifications is essential for the development of an effective mRNA vaccine against novel coronavirus SARS-CoV-2. Vaccination is the most economical and effective measure to prevent infectious diseases. So far, the vaccine has entered the third generation of nucleic acid vaccine from inactivated vaccine, subunit vaccine and recombinant protein vaccine. mRNA vaccine has the potential of high efficiency, rapid development, low-cost production and safe use. It is not a replication vector, and it does not have the characteristics of antibiotic resistance, genome integration and strong immunogenicity. Furthermore, corresponding mRNA vaccine can be quickly produced for different strains in large-scale, which speeds up the production process. However, mRNA synthesized in vitro is the ligand of Toll-like receptors. Once mRNA synthesized in vitro activates these receptors, the innate immune responses in the body will be turned on and a large amount of type I interferon will be produced, and mRNA will face the risk of degradation. The study of Katalin Karikó and Drew Weissman found that in vitro transcribed mRNA with modified bases can escape poor immune activation and solve the problem of inflammatory response stimulated by in vitro transcribed mRNA. Further studies have found that mRNA containing pseudouridine can be translated more effectively. At the same time, Drew Weissman has made an important contribution to the research and development of delivery system. After the outbreak of COVID-19, based on the research of two scientists, together with the development of efficient delivery systems such as lipid nanoparticles (LNPs) delivery system and one-component ionizable amphiphilic Janus dendrimer delivery system, the stability of SARS-CoV-2 prickle antigen and unparalleled investment by industry and government, the research and development technology system of mRNA vaccine was improved. Two very successful mRNA-based SARS-CoV-2 vaccines were approved at the end of 2020, which played a very important role in fighting COVID-19 during COVID-19 epidemic and paved the way for future mRNA applications. mRNA vaccine also has great potential in inhibiting tumor growth and regenerative medicine. Therefore, the circular RNA vaccine can also be studied. This paper introduces the process of vaccine development, the important nucleotide modification and lipid nanoparticles technology in mRNA vaccine, the in vivo effect of mRNA vaccine and the summary and prospect of technical development.

Abstract:Optically Pumped Magnetometer Lights up The Era of Vector Detection for Magnetoencephalography: an Experimental Evidence

Abstract:In the past two decades, there have been outbreaks caused by 3 types of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MRES-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These highly pathogenic coronavirus infections are usually accompanied by immune system dysfunction, with clinical manifestations such as lymphopenia, cytokine storm, acute respiratory distress syndrome and even death due to multiple organ failure. Revealing the effects of highly pathogenic coronaviruses on immune responses and the underlying mechanisms is of great significance for preventing and controlling coronaviruses infection. The cell receptors of these 3 highly pathogenic coronaviruses are different, which determines the differences in the types of cells they infect. This review firstly introduces the entry mechanisms of coronavirus and receptor characteristics as well as infected cells of SARS-CoV, MRES-CoV and SARS-CoV-2. Unlike other coronaviruses, SARS-CoV, MRES-CoV, and SARS-CoV-2 are able to infect immune cells, including innate immune cells, T and B lymphocytes, which lays the foundation for highly pathogenic coronaviruses to interfere with the host immune responses. Secondly, we summarize the mechanisms by which highly pathogenic coronaviruses impair the innate immune responses. Researches demonstrate that highly pathogenic coronaviruses can effectively evade innate immune recognition through cap and methylation modification as well as the formation of double-membrane vesicle (DMV). And, highly pathogenic coronaviruses can directly interfere with the pattern recognition receptor (PRR) signaling pathway, affecting the secretion of type I interferon, blocking interferon signaling and inhibiting the formation of stress particles. Notably, these highly pathogenic coronavirus can damage innate immune cells, inducing the secretion of cytokines and chemokines by macrophages, and the formation of neutrophil extracellular traps (NET) by neutrophils, which leads to cytokine storm and subsequent PANoptosis. In addition, the functions of dendritic cells and NK cells are also damaged by highly pathogenic coronavirus infection. Thirdly, we summarize the mechanisms by which highly pathogenic coronaviruses affect the adaptive immune response. Studies show highly pathogenic coronaviruses cause dysregulation of adaptive immune responses by disrupting T and B cell immune responses. Coronavirus infection can decrease the number of lymphocytes through a variety of ways. T cells in patients with highly pathogenic coronavirus infection are in an over-activated or exhausted state, and the specific T cell response and inflammation state will maintain for a long time. The continuous evolution of highly pathogenic coronaviruses often leads to the failure of neutralizing antibodies. Additionally, non-neutralizing antibodies can cause antibody-dependent enhancement (ADE) effects that triggers tissue damage. The duration of memory B cell-mediated response induced by different highly pathogenic coronaviruses is different, but the formation of germinal centers is often affected. Studies have highlighted the complex interaction between highly pathogenic coronaviruses and host immune responses. Finally, we discuss the adverse effects and treatment strategies of coronavirus disease 2019 (COVID-19) in order to provide reference for the prevention and treatment of coronavirus infection.

Abstract:Pyroptosis, a type of regulated cell death, has been shown to be immunogenic in quite a few studies. Pyroptosis has been observed since 1986 and was found to be mediated by GSDM family proteins until recently. Gasdermines (GSDMs) are a group of intracellular proteins that mediates cell pyroptosis. Although GSDMs are expressed in inactive forms, some proteolytic enzymes can activate them. The N-terminus of activated GSDMs perforate the plasma membrane, resulting in cell lysis. Pyroptosis is a double-edged sword that is closely related to the tumor immune microenvironment. Pro-inflammatory molecules and DAMPs will be quickly and effectively released into the microenvironment from the pyroptotic cells, and trigger inflammation and immune response, while these immune responses are not always positive. Inductions of pyroptotic cell death have been shown to promote anti-tumor immunity and improve the efficacy of immune checkpoint inhibitors, which involves the cytotoxic effects of effector T lymphocytes, or reprogramming of the tumor microenvironment to an immunostimulatory state. In this review, we not only summarize the mechanisms of different types of pyroptosis and the key molecules that promote inflammatory and immune response during pyroptosis, but also compare its common features with apoptosis. In addition, we discuss the potential positive and negative factors to cancer therapy during pyroptosis. Although our understanding of pyroptosis in cancer is growing, many mechanisms remain unclear: how pyroptosis activates the immune system, how pyroptosis is regulated, and how pyroptosis can be harnessed therapeutically to improve cancer immunotherapy or to reduce therapy related toxicity. We hope this review will help further understanding the role of pyroptosis in tumor microenvironment and cancer immune therapy, promoting the improvement of cancer therapy strategies.

Abstract:Autophagy and apoptosis are two important life processes that share similar protein components, play essential role in the survival and development of the organisms and especially cancers. During the development of cancer, the two processes can trigger simultaneously with a delicate and complex relationship. Tumor suppressor Ras association domain family 1A (RASSF1A) is an important downstream effector of Ras superfamily proteins. RASSF1A is widely expressed in human tissues but is down-regulated in a variety of tumor cells due to its promoter methylation and transcription inhibition. Recent studies have shown that RASSF1A can regulate both apoptosis and autophagy through multiple pathways upon different cancer cellular state. In this article, we mainly review the regulatory mechanism of RASSF1A on autophagy through the mTORC1 signaling pathway, microtubule stability, and Rho subfamily proteins, and the regulatory mechanism of RASSF1A on apoptosis through MOAP1 proteins, or the Hippo pathway, or DNA damage pathway. As different kinases phosphorylate RASSF1A to convey different "mantras" and thus stimulate different biological functions, we also analyze the role of post-translational modification in the functional switching of RASSF1A in regulating autophagy and apoptosis. Although RASSF1A can alter the nuclear localization of the downstream effector YAP, a core effector of the Hippo signaling, the phenotypes presented are largely distinct in different tumors. These observation further suggest that therapeutic strategies using demethylation alone are not applicable to all RASSF1A-methylated tumors. Therefore, in-depth investigation of the regulatory mechanism of RASSF1A in autophagy, apoptosis and cancer cell fate determination is of great significance in providing more precise and effective treatment strategies for tumor patients.

Abstract:RAS-related signaling system plays an important role in the occurrence and development of colorectal cancer, which is closely related to the proliferation, metastatic potential, and apoptosis of colorectal cancer cells. However, treating this type of cancer with a single medicine, either targeted therapies or chemotherapies, is not always the best option. In recent years, RAS-related signaling pathway inhibitors have been utilized in conjunction with other medications with promising outcomes in clinical trials and preclinical investigations. When used in concert with other anti-cancer drugs, EGFR inhibitors, VEGF inhibitors, RAS direct inhibitors, MEK inhibitors, and RAF inhibitors have shown particularly impressive performance. In terms of clinical value, combining cetuximab with chemotherapy regimens, EGFR inhibitors with chemotherapy regimens, and EGFR inhibitors with other anti-cancer drugs dramatically enhanced important indicators in patients with colorectal cancer who had wild-type RAS. However, treatment options for patients with RAS-mutant colorectal cancer have been less favorable, and in this context, anti-angiogenic and anti-EGFR agents and immune checkpoint inhibitors have been approved as second-line treatment options. In preclinical studies, inhibitors that directly target RAS have been shown to be effective in combination with other drugs, and other treatment options have also shown good results, giving patients with colorectal cancer unlimited hope. This review focuses on the relationship between RAS-related signaling pathways and colorectal cancer, combination tactics in clinical trials and preclinical studies, and research on drug resistance mechanisms linked with composition administration in order to lay the foundation for future clinical multidrug therapy strategies.

Abstract:Colorectal cancer (CRC) is the second leading cause of cancer death, and patients tend to be more younger. Although chemotherapy, immunotherapy and targeted therapy have made progress, the toxicity, drug resistance and high price of drugs have seriously affected the comprehensive treatment effect of CRC. Therefore, seeking new, more sensitive and effective drugs and drug targets is the current research focus. Ferroptosis, a recently discovered regulation mode of cell death, which is closely related to cancer drug resistance. Activating ferroptosis has become a potential strategy to overcome the drug resistance mechanism of traditional cancer treatment. The development and application of drugs that induce ferroptosis is expected to become an effective means to treat CRC. This review describes the latest progress in the research of metabolic pathway drugs related to ferroptosis in CRC, so as to comprehensively understand the specific mechanism of ferroptosis based drugs in CRC, fully tap its therapeutic potential, and provide new methods for the diagnosis and treatment of CRC and the solution of drug resistance.

Abstract:Transient receptor potential melastatin 7 (TRPM7), a member of the TRPM subfamily, is a ubiquitously expressed bifunctional transmembrane protein with a channel domain fused to an active kinase domain. As a non-selective cation channel, TRPM7 is permeable to Ca²⁺, Mg²⁺, Zn²⁺, Na⁺, K⁺, and other trace metals. As an α-kinase, TRPM7 can autophosphorylate its serine and threonine residues, or phosphorylate endogenously targeted substrates such as myosin II. Through the joint action of the two domains, TRPM7 participates in various physiological processes such as Mg²⁺ homeostasis regulation, cell proliferation, differentiation, adhesion and migration, and ultimately affects cell differentiation and embryonic development. Dysfunction of TRPM7 has been associated with multiple neurodegenerative diseases, tissue fibrosis, ischemic injury as well as the occurrence and development of tumors. Genetic or pharmacological deficit of the TRPM7 relieves ischemic neuronal injury and inhibits the proliferation and migration of tumors, while up-regulating or restoring TRPM7 decreases blood pressure, maintains normal embryonic development and may be an effective strategy to treat the neurodegenerative disorders. However, whether TRPM7 is a promising target for the development of clinical drugs remains elusive. Nowadays, several small molecules display activation or inhibitory activities on the TRPM7 channel, and have been successfully used to uncover new cellular roles of TRPM7 in physiological and pathological conditions. Nonetheless, selective and potent TRPM7 modulators are limited. This review summarizes the research progress on the physiological and pathological functions of TRPM7 and its small-molecule modulators, which may provide new therapeutic strategies for TRPM7-related diseases and new directions for the development of novel TRPM7 regulators.

Abstract:Human milk oligosaccharides (HMOs) present in breast milk are a family of highly complex oligosaccharides that play a positive role in the intestinal flora, immune barrier, and brain development of infants. Due to the complex matrix in breast milk, the variety of oligosaccharides, the span of abundance, and the presence of many isomers, the detection of breast milk is faced with many challenges. A variety of techniques have been used for the analysis of human milk oligosaccharides and over 200 HMOs have been identified. Liquid chromatography and capillary electrophoresis have been effective in separating human milk oligosaccharides. Nuclear magnetic resonance spectroscopy, mass spectrometry and infrared multiphoton dissociation spectroscopy have promoted the comprehensive structural resolution of HMOs. This paper reviews the various techniques used to achieve high sensitivity and specificity for the analysis of HMOs and compares the advantages and disadvantages of the different techniques. It also focuses on the breakthroughs in mass spectrometry and the combination of different techniques to facilitate the analysis and determination of HMOs, providing a comprehensive technical support to explore the structure-function relationship of oligosaccharides and to gain a deeper understanding of the biological functions of HMOs.

Abstract:Variations in human vital sign will lead to changes of blood composition and quality. As for a basic screening project to assess human health, blood analysis has been extensively applied to health monitoring, disease diagnosis and rehabilitation evaluation. With the rapid development of economy and the continuous improvement of national living standards, human’s awareness of life and health is increasingly enhanced, which greatly promotes the evolution of sample, fast and sensitive disease screening technology. At present, developing the rapid blood analysis device has become a hot spot in the medical field for disease screening. There are many kinds of existing studies, but the whole blood analysis has not been systematically sorted and classified. This study systematically reviews the main development research and the latest progress of whole blood analysis. Starting from two aspects of whole blood analysis, direct whole blood analysis and indirect whole blood analysis, the current equipment methods and applications has been clarified based on direct whole blood analysis, the core processing technology and detection technology has been concluded based on indirect whole blood analysis. Finally, the problems of non-portability, low efficiency and high price for the whole blood analysis device at the present stage has been discussed, and the prospect of whole blood analysis in the direction of integration, intellectualization and low-cost has been summarized and prospected, which provided new ideas for the future research direction of rapid blood analysis.

Abstract:Brain source localization technology aims to identify the source of neural activity in the brain through the EEG and MEG signals on the scalp surface, which is the basis of studying the neural activity, cognitive process, and pathological function of the cerebral cortex. Its millisecond temporal resolution can effectively make up for the shortcomings of fMRI in low temporal resolution. Brain source localization contains two processes, forward problem, and inverse problem. The forward problem is to simulate the electric potential of the head surface generated by the neural source of brain activity, which is calculated by the volume conduction model, and the model is mainly built by the boundary element method, finite element method, and finite difference method. The inverse problem aims to reconstruct the distribution of current sources in the brain. The main solutions include the distributed source model and the equivalent current dipole model. But the solution to the inverse problem is not unique, and the regularization method is the classical means to resolve it, including the minimum L1 norm and the minimum L2 norm methods. Nonlinear optimization, beamforming, the Bayes approach, deep learning, and other technologies have been created in recent years to increase the accuracy of the brain source localization technique. However, due to the ill pose of the inverse problem and the errors caused by different recording methods, the number of electrodes, and head model construction in practice, the accuracy evaluation is still challenging in brain source localization, which greatly limits the practical application of brain source localization methods in neuroscience and psychology research, clinical diagnosis, and treatment. In this work, the existing brain source localization methods and analysis of the accuracy evaluation methods of brain source localization technology and its practical application in basic research and clinical diagnosis and treatment are introduced. Specifically, different recording methods, the number and density of electrodes, and the head volume conduction model all have a certain influence on the source positioning accuracy. In practice, because different inverse problem algorithms produce different source location results, this study summarizes the evaluation methods based on spatial resolution, point diffusion, and crosstalk function on the degree of source overlap among different brain source localization methods and the influence of other sources on target sources. In addition, the application of brain source localization technology in time-frequency analysis and connectivity analysis is introduced, which can help researchers better understand the connections and functions of various brain regions in cognitive activities. Currently, brain source localization technology has been used clinically in epilepsy, attention deficit, hyperactivity disorder, and other brain abnormalities or diseases. The main progresses of brain source localization technology about the abovementioned five aspects which include the process of brain source localization, the method of inverse solution, influencing factors of positioning accuracy, accuracy evaluation method, and the research and clinical application are reviewed. Furthermore, some scientific problems concerning accuracy evaluation are discussed in this paper. We hope to provide certain references and help with the development and application of brain source localization.

Abstract:Lipid metabolism is one of the three major metabolisms in human body. Lipid metabolism is usually in a balanced state under the regulation of hormones and other signaling factors. When the homeostasis is disrupted, the level of triglyceride (TG) and cholesterol in the blood changes, eventually causing atherosclerosis (AS), obesity and other lipid dysfunction diseases. Long non-coding RNA (lncRNA) is a group of RNAs that do not have the ability to code proteins with more than 200 nucleotides in length. Recent studies have found that lncRNAs are closely related to the regulation of metabolism, inflammation, immune system, and vascular function. A large body of research suggests that lncRNAs are involved in the regulation of lipid metabolism and thus are expected to be potential therapeutic targets for some lipid metabolic diseases.

Abstract:Mitochondria are responsible for cellular aerobic respiratory function. The nervous system is a huge energy consuming tissue of the body and highly depends on the structure and functional stability of mitochondria. Multiple research shows that mitochondrial abnormality is an essential reason for the occurrence and development of various neurological diseases. The mitochondria-targeted treatment for neurological disorders has become a frontier and hot spot. This review focuses on the research progress of mitochondrial transplantation in the treatment of various neurological diseases, mainly discussing its cellular and molecular mechanisms and the challenges which it faces, in order to provide clues and basis for clinical development of new therapeutic methods. There are 11 neurological models that have been reported to be effective for mitochondrial transplantation: middle cerebral artery occlusion cerebral ischemia reperfusion model, focal cerebral ischemia model, traumatic brain injury model, schizophrenia model, depression model, diabetic cognitive dysfunction model, Parkinson’s disease model, aging model, sepsis model, nerve compression model and spinal cord injury model. According to the source of transplanted mitochondria, the mitochondrial transplantation methods used in the above studies can be divided into direct transplantation and indirect transplantation. Direct transplantation refers to the transfer of mitochondria themselves, while indirect transplantation refers to the transfer of other carriers carrying mitochondria. There are three sources of mitochondria for direct transplantation: cell lines, human umbilical cord mesenchymal stem cells, and allografts. Mitochondria are derived from skeletal muscle, placenta, liver, brain and platelets. There are six methods of mitochondrial transplantation into the body: arterial injection, intraventricular injection, intravenous injection, vitreous injection, epineural injection, and spinal injection. The number of injections varies from a single injection to multiple injections in a row. The amount of mitochondria injected varied greatly. The duration of therapeutic or ameliorative effects after mitochondrial transplantation varied widely in reports. The effect after transplantation was to reduce the degree of disease in the animals. Biological mechanisms of mitochondrial transplantation consists of tunneling nanotubes (TNTs) and extracellular vesicles (EVs). And EVs are further classified into three categories according to their diameter size, including exosomes, microvesicles, and apoptotic body. The key issues to be addressed in mitochondrial transplantation for neurological diseases include: source of transplanted mitochondrial; pathway of mitochondrial transplantation; storage of the mitochondria; immune response. Mitochondrial transplantation has achieved great results in the treatment of neurological diseases in less than a decade, and it is considered to have great clinical value. This review predicts that future studies will gradually reveal mitochondrial quality control strategies and their molecular and cellular mechanisms in mitochondrial transplantation, and will form clinical standardized diagnosis and treatment plans for mitochondrial transplantation.

Abstract:Botulinum toxin type A (BTX-A) induces a reversible muscle paralysis at the injection site. There is evidence that BTX-A injection in specific facial muscles affects emotional experience and the processing of emotional stimuli (e.g., facial expressions, emotional language, and videos). Neuroscience research showed that BTX-A injection could attenuate amygdala activity, and could affect the neurocognitive function of reward system and other cerebral cortex as well. These findings can be interpreted by facial feedback hypothesis and social feedback hypothesis from the individual and social perspectives respectively. For subjects who received the injection, BTX-A reduces feedback from facial muscles thus impairing emotional experience and processing. According to this hypothesis, proprioceptive signals from facial muscles are conducted to the mesencephalic trigeminal nucleus and locus coeruleus, the latter of which sends direct projections to the thalamus, basal ganglia, and cerebral cortex related to motor, cognition, and emotion. In interpersonal communication, the observer’s emotional experience becomes similar to the subject who has received BTX-A injection through facial mimicry, and the subject’s emotional experience is also affected by the observer in turn. The mirror neuron system plays an important role in the process. Based on the existing researches, this review proposed an integrated model to explain the cognitive and neural mechanisms of how BTX-A injection affects emotional processing, which deepens the neural basis of facial feedback and social feedback for expression recognition and emotion processing. The model illustrates the roles of facial feedback and social feedback respectively as “signal resource” and “amplifier” of emotional processing caused by BTX-A injection, and the relationship between them. Specifically, the changes in muscles induced by facial mimicry causing emotional synchronization in social feedback process is in line with facial feedback process. The interaction of the two emotional processes could also cause multiple overlapping effects, which exist in both individual emotional processes and interpersonal interactions. Future studies should expand the aspects and levels of emotional processing, such as focusing on subliminal emotion processing and emotion regulation; further explore the mechanisms of how BTX-A injection affects emotional processing using neuroimaging technologies; improve the research paradigms to study the causal relationship between facial feedback and emotional processing; explore the mechanisms and application of BTX-A in the treatment of mental illness like depression; compare the effects of BTX-A injection and other invasive facial procedures on emotional processing. Further research will not only improve the understanding of cognitive and neural mechanisms underlying emotion but also have potential implications in mental health and medical cosmetology.

Abstract:Objective To study the anti-breast cancer effects and molecular mechanisms of syringin, and to provide a theoretical basis for the clinical application of syringin.Methods The inhibitory effect of syringin on the proliferation of breast cancer cells was measured with MTT assay. Trypan blue, TdT-mediated dUTP nick-end labeling (TUNEL), and Annexin V-FITC/PI staining were used to detect apoptosis. Caspase-3 activation was detected via Western blot to determine whether apoptosis occurred. The expression of apoptosis-associated protein B-cell lymphoma-2 (Bcl-2) was detected and the effect of syringin on the mitochondrial apoptosis pathway was investigated via JC-1 staining. The PI3K agonist Recilisib was used for comparison. qRT-PCR and Western blot were used to assess the role of syringin in regulating the PI3K/Akt/mTOR pathway and inducing the apoptosis of cancer cells.Results Syringin had a time- and dose-dependent inhibitory effect on the proliferation of breast cancer cells and induced their apoptosis. A further study showed that after syringin treatment, Caspase-3 was activated, Bcl-2 expression decreased, the mitochondrial membrane potential was significantly reduced, and the mRNA and protein expressions of PI3K, Akt, and mTOR were not significantly changed, but the protein phosphorylation levels were significantly decreased. Recilisib partially limits the effect of syringin on the apoptosis of breast cancer cells.Conclusion Syringin has a good inhibitory effect on MDA-MB-231 and MCF-7 breast cancer cells. It can inhibit cell proliferation and induce mitochondrial apoptosis by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway. Syringin is a potential anti-breast cancer drug.

Abstract:Objective In recent years, accumulating evidence indicated that epigenetic alterations may be used as the potential biomarkers to detect toxicity caused by metal nanoparticles (MNPs). Thus, the effects of MNPs exposure on the phosphorylation of histone H3 at serine 10 (p-H3S10) were clarified, and the changes of whole gene expression in cells exposed to typical MNPs were explored in this study to provide a theoretical basis for screening the biomarkers of early toxicity of MNPs.Methods The effects of ten kinds of MNPs exposure on the p-H3S10 were evaluated using Western blotting and flow cytometry. In addition, the effects of copper oxide (CuO) NPs, which is a typical MNPs, on the whole gene expression of cells were explored at the transcriptional level by RNA sequencing technology.Results All the tested MNPs except nickel oxide NPs induced p-H3S10 to different degrees. Among, upregulation of p-H3S10 was observed at immediately after CuO-NPs and zinc oxide NPs treatment, and continued for 10 h. Moreover, p-H3S10 increased slightly after aluminium oxide NPs and antimony (III) oxide NPs treatment, and reached the highest point at 0.5 h. After that, p-H3S10 began to decrease and obtained the lowest value at 2 h. However, p-H3S10 began to rise again after treatment over 2 h until the final observation time point. In addition, p-H3S10 was temporarily induced after treatment with iron (II,III) oxide NPs, silica NPs, cobalt (II,III) oxide NPs, chromium (III) oxide NPs or titanium dioxide NPs, but rapidly ceased. Further analysis indicated that MNP-induced p-H3S10 was highly related to the cellular uptake of MNPs, and the sustained release of ions from MNPs inside cells might generate p-H3S10 for an extended period after the initial uptake of MNPs. In addition, RNA sequencing analysis revealed that CuO-NPs treatment caused significant differential expression of 275 genes (P<0.05), 185 of which were upregulated and 90 of which were downregulated. Gene Ontology (GO) analysis showed that the majority of differentially expressed genes (DEGs) were involved in regulation of signaling, transcription factor activity and kinase activity. Through analyzing enriched GO pathways related to stress, two prominent membrane-activated cascades emerged: the mitogen-activated protein kinase (MAPK) cascade, and Janus kinase/signal transducers and activators of transcription (JAK/STAT) cascade. Genetic markers specific to extracellular signal-regulated kinases ERK1/ERK2 regulation, stress-activated MAPK cascades, and JAK/STAT cascade were also significantly altered after CuO-NPs treatment. It was observed that a large number of genes related to MAPK tyrosine/serine/threonine phosphatase activity were differentially expressed due to CuO-NPs treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed strong associations between the DEGs and signal transduction, signaling molecules and interactions, immune and endocrine systems. Moreover, several DEGs were also correlated with transport, catabolism, cell growth and cell death. MAPK cascades were also significantly upregulated after CuO-NPs exposure.Conclusion These results indicated that early induction of p-H3S10 by MNPs is highly related to the cellular uptake of MNPs, and the persistent release of ions from MNPs inside cells might generate p-H3S10 for a long time after the initial uptake of MNPs. Taken together, the p-H3S10 has potential as a suitable candidate biomarker for evaluating the toxicity of MNPs.

Abstract:Objective To construct an analysis process for identity-by-descent (IBD) algorithm to predict distant relatives and evaluate the prediction accuracy.Methods 253 family samples were detected by using high-density whole genome single nucleotide polymorphism (SNP) chip. IBD algorithm was used to predict the genetic relationship between pairs of individuals, and the prediction accuracy was evaluated. The number of SNPs was randomly reduced to evaluate the effect of SNP numbers on the accuracy of the algorithm prediction.Results Among 1-7th kinship degree, the average confidence interval accuracy of IBD algorithm was 94.72%, and the prediction credibility was 99.77%. The false negative of IBD algorithm was found when kinship degree is 6 or higher. When the number of SNPs decreases, the prediction accuracy will decline to a certain extent.Conclusion The IBD algorithm can accurately predict the genetic relationship within the seventh kinship degree, and it has important application value in population genetics, forensic genealogy inference and other fields.

Abstract:Objective The warm sensors located in keratinocytes have the ability to directly detect warm temperature, with TRPA1 in dorsal root ganglion (DRG) neurons being a potential mediator of the downstream transduction process. The present study aimed to elucidate the mechanism by which warm information is transmitted from keratinocytes to TRPA1.Methods TRPA1-transfected HKE293T cells as well as DRG neuron cells from wild-type and TRPA1 knockout mice were cultured separately, and stimulated with warm temperatures using a perfusion apparatus. Single cell calcium imaging was used to monitor calcium influx during stimulation, and the role of H₂O₂ in this process was also examined. Additionally, RNA-seq analysis was performed on primary keratinocytes cultured at different temperatures to identify potential candidates responsible for keratinocytes-TRPA1 warm transduction.Results Our finding indicated that TRPA1-transfected HEK293T cells or DRG neurons could be activated by warm temperature in the presence of H₂O₂. However, when TRPA1 was knocked out or blocked by HC-030031, the H₂O₂-potentiated warm response was significantly reduced. Moreover, Chemokine C—C motif ligand 2 (CCL2) and decorin (DCN), two H₂O₂ related factors, exhibited different expression patterns in keratinocytes cultured at 33℃ and 37℃, respectively. This result is consistent with previous research showing that mice stimulated at 37℃ induced more DRG activation than those stimulated at 33℃.Conclusion H₂O₂ can potentiate the TRPA1-dependent warm response, and H₂O₂-related factors in keratinocytes can be affected by warm temperature, suggesting the possible role of H₂O₂ related factors in warm transduction from keratinocytes to downstream TRPA1 in DRG neurons.

Abstract:Objective For people with impaired central vision, novel artificial optical devices can provide access to simplified images by projecting them onto retina regions out of the macula, thus allowing them to utilize peripheral vision to perceive information. We investigate perceptual characteristics of peripheral visual field and provide clues for the design of implantable optical artificial vision devices.Methods We propose an experimental environment for investigating perceptual characteristics of peripheral vision, in which pattern stimuli of symbols, numerals, and Chinese characters are applied to the subjects, with variables including the size, the color combination, the eccentricity, and the motion controlled. The relation between perceptual capability and the variables are analyzed using graphical methods.Results The perceptual capability declines as the eccentricity increases, forming two appreciable trends, and it is significantly influenced by color combination and size.Conclusion Variable combinations with considerable perception rate are provided. The results may promisingly act as a reference for the implantation of artificial optical devices in eyes, the development of color symbol codes for special communication, etc.

Abstract:Objective Many studies have shown that a high-sugar diet can do a lot of harm to the health of teenagers. As one of the important windows for human to perceive the world, the visual system plays an important role in teenagers’ perception ability. Many studies have confirmed that high-sugar diet can damage visual function, but the current research on the effects of high-sugar diet on visual function mainly focuses on the front of the visual pathway, focusing on the eye system and the optic ganglion, the posterior of the visual pathway, such as the visual central cortex, has not been reported. In order to understand the effect of high sugar diet on visual function, the effect of high sugar diet on central cortex was studied.Methods In this study, we used the behavioral paradigm of GO/NO-GO orientation discrimination task and in vivo multi-channel electrophysiological techniques to explore the effects of high-sugar diet on the primary visual cortex of young mice.Results Behavioral results showed that young mice that had undergone two months of high-sugar diet had a reduced ability to distinguish orientation. The response characteristics of single neurons in the primary visual cortex (V1) were analyzed by electrophysiological techniques. It was found that the ability of orientation tuning of single neurons in the primary visual cortex decreased in mice fed with high-sugar diet, the response variability of neurons increased and the signal-to-noise ratio (SNR) decreased significantly. We further analyzed the changes of SNR and response variability at population level. The results showed that SNR decreased significantly and response variability increased significantly at population level. The results of neuron correlation analysis showed that the noise correlation of primary visual cortex in the high-sugar diet group was significantly up-regulated.Conclusion These results suggest that a high-sugar diet impairs the ability of young mice to discriminate orientation by affecting the receptive field characteristics of individual neurons in the primary visual cortex, as well as the information processing capacity of neuronal populations.

Abstract:Objective Optically pumped magnetometer (OPM)-magnetoencephalography (MEG) is a rapidly developing new-generation brain function imaging technology compared to the traditional MEG. Due to the proximity of the detectors and the scalp, OPM-MEG offers higher signal intensity and, with its multiaxis detection capability, can detect signals in the “blind area” of traditional MEG. It provides a powerful tool to the research of brain function and clinical diagnosis. This paper aims to investigate the signal distribution differences of biaxial OPM-MEG when measuring true physiological responses and to compare its performance with traditional MEG.Methods In this study, ten healthy subjects were examined using a 9-channel biaxial OPM-MEG during an auditory task involving frequency following responses (FFR). FFR-related magnetic responses were acquired along both tangential (Y-axis) and radial (Z-axis) directions. We analyzed the OPM-MEG data features in different axial directions and different regions, including signal intensity and regional mean energy. Additionally, we compared the results with the data detected by traditional MEG.Results After processing 800 trials, the average signal energy in the Y-axis and Z-axis was found to be 0.971 0 and 0.767 3 respectively, with no statistical significance (P=0.438). However, a regional analysis revealed distinct signal distribution patterns in the left temporal area compared to the other two regions, which was statistically significant (P=0.049). Topographical mapping showed a clear left-sided lateralization, similar to SQUID-MEG results. PSD analysis and wavelet time-frequency analysis further supported these findings. In-depth analysis of peak-to-peak values from all sensors during the stimulus period (0-0.2 s) revealed that within-participant measurements showed consistency, whereas between-participant variability was considerable. This highlights the importance of considering individual differences in future studies, as they can significantly impact measurement outcomes. The analysis revealed that the biaxial OPM-MEG signals were stronger than traditional MEG signals. Furthermore, there were significant differences in signal distribution and intensity between the two axes. In most subjects, tangential signals were found to be significantly stronger than radial signals, which are generally difficult to capture using traditional MEG.Conclusion Our findings demonstrate the capability of biaxial OPM-MEG in capturing real physiological signals and show that it provides richer information compared to uniaxial measurement. This study suggests that traditional MEG may be missing critical brain activities in its “blind areas”, highlighting the need for optimizations in brain electrical activity models based on uniaxial (radial) MEG recordings. With its multi-axis recording capability, OPM-MEG holds great potential in brain science research and the diagnosis of neurological diseases, offering a more comprehensive and precise tool for understanding brain functions.

Abstract:Objective N⁶-methyladenosine (m⁶A) is the most common and abundant chemical modification in RNA and plays an important role in many biological processes. Several computational methods have been developed to predict m⁶A methylation sites. However, these methods lack robustness when targeting different species or different tissues. To improve the robustness of the prediction performance of m⁶A methylation sites in different tissues, this paper proposed a double-layer bidirectional gated recurrent unit (BiGRU) network model that combines reverse sequence information to extract higher-level features of the data.Methods Some representative mammalian tissue m⁶A methylation site datasets were selected as the training datasets. Based on a BiGRU, a double-layer BiGRU network was constructed by collocation of the model network, the model structure, the number of layers and the optimizer.Results The model was applied to predict m⁶A methylation sites in 11 human, mouse and rat tissues, and the prediction performance was compared with that of other methods using the same tissues. The results demonstrated that the average area under the receiver operating characteristic curve (AUC) predicted by the proposed model reached 93.72%, equaling that of the best prediction method at present. The values of accuracy (ACC), sensitivity (SN), specificity (SP) and Matthews correlation coefficient (MCC) were 90.07%, 90.30%, 89.84% and 80.17%, respectively, which were higher than those of the current methods for predicting m⁶A methylation sites.Conclusion Compared with that of existing research methods, the prediction accuracy of the double-layer BiGRU network was the highest for identifying m⁶A methylation sites in the 11 tissues, indicating that the method proposed in this study has an excellent generalizability.