Abstract:Alzheimer’s disease (AD) is a clinically common neurodegenerative disease characterized by progressive cognitive dysfunction and memory loss. In recent years, studies have found that various epigenetic modifications such as DNA modification, histone modification, RNA modification and non-coding RNA play pivotal roles in the regulation of Aβ deposition, hyperphosphorylated Tau proteins, nerve regeneration, synaptic plasticity and cognitive function, thereby improving or aggravating the pathological process of AD. Decreasing 5-methylcytosine of PSEN1 and BACE1 genes may cause Aβ production via promotion of PSEN1 and BACE1 expression. Increasing DNA modifications of 5-hydroxymethylcytosine by Tet1/Tet2/Tet3 protein can regulate proliferation, differentiation and function of neurons, neural stem cells, and neural progenitor cells. Moreover, increasing histone methylation (H3K9me2 and H3K4me3) and demethylation (H3K27me3) catalyzed by histone methyltransferase and demethylase respectively can decrease neuronal differentiation and cognition. Low acetylation levels of histones maintained by the suppression of histone acetylases and activation of histone deacetylases (HDAC2, HDAC3 and HDAC6) can be contributed to inducing cognitive impairment. Furthermore, N⁶-methyladenosine (m6A) RNA modification catalyzed by the RNA methyltransferases Mettl3 and Mettl14 (writers), removed by the demethylases FTO (erasers), and interacted with m6A-binding proteins YTHDF1 and YTHDF (readers) is involved in synaptic plasticity, neuronal apoptosis and synaptic transmission. In addition, low expression of miR-29, miR-31 and miR-101 causes Aβ deposition by improving BACE1 and APP levels. Either declining miR-34a, miR-219 or raising miR-128a, miR-125b, and miR-124 can lead to high levels of Tau protein and Tau hyperphosphorylation. The up-regulation of miR-137 and miR-142 can reduce synaptic plasticity and stimulate neuroinflammation, respectively. Overexpression of lncRNA BACE1-AS and BC200 can promote Aβ deposition by boosting BACE1 expression, while enhancing BDNF-AS and GDNFOS result in neurodevelopment disorder by inhibiting BDNF and GDNF expression. Clinical data shows that changes in epigenetic modifications are significantly correlated with AD risk. The use of drugs, physical stimulation, siRNA and other interventions to change the level of epigenetic modifications in AD animal models can ameliorate AD pathology and cognitive impairment. Our paper reviews the regulatory effects of various epigenetic modifications in AD and in the hope of providing a theoretical basis for further understanding of the epigenetic mechanism in AD and a feasible interventions for preventing or treating AD via alteration epigenetic modifications.

Abstract:Alzheimer’s disease (AD), a serious degenerative disease of the central nervous system, is the most common cause of dementia in the elderly. Its etiology has not yet been elucidated. ATP-binding cassette transporter A7 (ABCA7) has a high level expression in the brain. Since the genome-wide association studies identified ABCA7 as a risk gene for AD, more and more evidence from in vitro, in vivo, and human-based studies has confirmed that ABCA7 is one of the most important risk genes for early-onset and late-onset AD. ABCA7 mediates phospholipid efflux and its distribution in neurons, and plays a weak but significant role in cholesterol regulation, so as to maintain the lipid homeostasis in the brain. ABCA7 is also closely related to microglia phagocytosis and immune function. When lipid homeostasis in the brain is unbalanced or ABCA7 is defective, it will reduce the ability of microglia to process Aβ, causing abnormal accumulation of Aβ and triggering the inflammatory response in the brain. ABCA7 single nucleotide polymorphism (SNP) variants or loss-of-function (LOF) mutations are also significantly associated to the risk of AD. We suggest that ABCA7 may be a potential biomarker or therapeutic target for early detection and diagnosis of AD. In this paper, the role of ABCA7 in the occurrence and development of AD is reviewed, in order to provide therapeutic ideas for the clinical prevention and treatment of AD.

Abstract:Objective To explore the key E3 ubiquitin ligases and their expression profile in the pathogenesis of Alzheimer’s disease (AD).Methods Bioinformatics method was used to screen the differential expression genes (DEGs) in the development of AD. The DEGs were analyzed by gene ontology (GO) and protein-protein interaction (PPI) network. Then, the E3 ubiquitin ligases were looked up through The Human Protein Atlas and Alzdata databases to find their histocytological localization in different brain regions. It was verified by qPCR in AD mice brain tissue.Results Ubiquitin-proteasome system (UPS) and ubiquitin conjugating enzyme from Trypanosoma cruzi (UBCc) domains of ubiquitin-conjugating enzyme were ranked top in the biological functions and domains involved in the process of AD; PPI network revealed multiple UPS molecules are the key node proteins; brain tissues specific and highly expressed E3 ubiquitin ligases (MKRN2, NEDD4L, LNX1, RNF41, TRIM36, RNF8 and DTX4) are reduced in AD patients and AD mice.Conclusion These 7 E3 ubiquitin ligases may function as driving factors to participate in the progress of AD, which provides important clues for further searching for new targets for the diagnosis, treatment and in-depth mechanism exploration in AD progression.

Abstract:Objective Alzheimer’s disease (AD) is the most common form of dementia. There are two main risk factors for developing AD—age and gender. By aging, preclinical and clinical symptoms are emerging in succession. Anxiety is one of the typical early symptoms during AD processing. Besides, the incidence of AD is higher in women than in men. However, although the differences were observed in the AD cohort, there is a lack of the assessment of AD experimental animal models within age and gender.Methods We choose the APP London mutation (Val717Ile) transgenic (Tg) mice for study. This is one of the first described mutations in APP, with the early onset of AD. To illustrate if the gender difference occurred in APP V717I mice during AD processing, we made use of animal behavior tests, such as open field test, step-down test and Morris water maze to evaluate the non-cognitive symptom and cognitive symptom.Results In this study, we found that at 6-month age, female Tg mice showed significant anxiety, while male Tg mice only showed anxiety at 10-month age. At 6-month age, both male and female Tg mice did not show cognitive deficits; but, at 10-month age, both genders showed significant cognitive impairments.Conclusion These results indicated that APP V717I Tg mice showed anxiety-like activity before the occurrence of memory deficits; in the process of AD, APP V717I Tg mice have a clear difference in age and gender. This study provides favorable evidence for age and gender differences in the process of AD. The mouse model is also expected to become an essential tool for AD drug research, aiming to help precision medicine and distinguish gender differences in drug use.

Abstract:Objective Aberrant promoter methylation of multiple genes is associated with various diseases, including Alzheimer’s disease (AD), however, the relationship between disrupted-in-schizophrenia-1 (DISC1) promoter methylation and the progress of AD is unclear.Methods The methylation levels of the DISC1 promoter were measured in 51 AD patients and 63 controls using bisulfite pyrosequencing assay. Blood biochemical indicators were detected using standard methods.Results DISC1 promoter methylation was significantly higher in AD patients than in controls (P=0.002). Moreover, Both apolipoprotein A (ApoA) and Lipoprotein A (Lp(a)) are significantly correlated with the DISC1 CpG3 methylation. DISC1 methylation is positively correlated with blood ApoA in female (P=0.003). DISC1 methylation is positively correlated with blood Lp(a) in male (P<0.000 1). The area under curve (AUC) of DISC1 promoter methylation is 0.726 (95% CI: 0.626-0.827), the sensitivity is 0.560 and specificity is 0.869.Conclusion The results of the present study demonstrated that elevated DISC1 promoter methylation was associated with AD risk in males, and it may be a potential biomarker for the diagnosis of AD.

Abstract:Artery calcification (AC) is a pathological phenomenon in the process of atherosclerosis, especially the coronary artery calcification (CAC) of the arterial intima. Originally, CAC is a self-protection mechanism to reduce atherosclerotic inflammation. However, it also acts as a significant cause of atherosclerotic plaque rupture, particularly of the microcalcification in the early stage of CAC, which is the leading cause of plaque rupture. From the microcalcification in the early stage to the stable fusion in the late stage, different degrees of CAC have different effects on cardiovascular events. Chinese herbal medicine (CHM) has been used to treat atherosclerotic cardiovascular diseases for centuries. How CHM is effective in the treatment and what mechanism is involved in CAC need further investigation. Here, we review the molecular mechanisms of the development of CAC and the influence of CHM on those pathological processes.

Abstract:Respiratory infection in humans and animals caused by influenza A viruses (IAV) is a severe economic and public health problem worldwide. Influenza virus will make the body’s innate immune signal activated during the early infection, which plays the role of defending, clearing the virus, and assisting the adaptive immune response. However, the influenza virus has developed a variety of escape strategies in the process of co-evolution with the host that mainly blocks the host’s innate immune pathway and inhibits the production of interferon and inflammatory factors through influenza virus self-proteins. We reviewed recent advances in host innate immune mechanisms against IAV infection and viral strategies for immune escaping, which may benefit the monitoring, target discovery, and vaccination development to prevent and control the influenza virus.

Abstract:Based on the mechanical, cavitation and biochemical effects of ultrasound in the organs and tissues, ultrasound intervention can effectively ablate the plaques or thrombi in blood vessels. In this paper, we focused on the ultrasound intervention treatment of atherosclerotic cardiovascular disease (ASCVD) and reviewed the effect of treatment methods and parameters on the efficacy and safety, discussing some recent clinical, in vivo and in vitro experimental researches. Low-frequency (<300 kPa) ultrasound causes severe bleeding due to the generation of standing waves and large cavitation bubbles that induce high stress on the vessel wall. High frequencies (>3 MHz) lead to the attenuation of acoustic pressure, reducing the therapeutic efficacy. In general, the frequency of 0.8-2 MHz is used for clinical treatment while guaranteeing therapeutic efficacy and safety. In order to avoid side effects such as tissue damage and temperature rise at high intensity, low-intensity (0.7-1.25 W/cm²) ultrasound was employed in clinical trials. Ultrasound pulse parameters and exposure time should be determined in relation to the lesion, ultrasound intensity and frequency. In ultrasound therapy, the administration of drugs (rtPA, atorvastatin, tongxinluo, streptokinase, urokinase) and microbubbles (MBs) encapsulated by a lipid shell, such as ultrasound contrast agent (UCA), provides an opportunity to further enhance the therapeutic effects. Their concentration and dosage used in treatment varied depending on the treatment object, and they should be reasonably selected considering adverse effects including hemorrhage. The debris removed from plaques should be small enough (<10 μm) not to cause blockage of the capillaries. Otherwise, a suction technology that can collect the debris in the vessel must be incorporated with this ultrasound technology. In addition, it is necessary to combine a monitoring system that can evaluate and monitor the degree of tissue damage in real time during treatment. Magnetic resonance imaging (MRI) and computed tomography (CT) can be combined to detect the sign of bleeding, while a thermocouple, ultrasound imaging, infrared thermal imaging and MRI can be used to predict the thermal damage by measuring tissue temperature invasively or non-invasively.

Abstract:Circular RNAs (circRNAs) are RNA molecules with closed ring structure and are widely distributed in various tissues. circRNAs are more stable than linear RNAs. They can be divided into three categories: exonic circular RNA, exon-intron circular RNA, and circular intronic RNA. The main functions of circRNAs are acting as a sponge of microRNAs, binding to RNA binding proteins, affecting the formation of homologous linear mRNAs and regulating transcription. Besides, the latest research found that some circRNAs can directly code protein, which changed the impression that circRNAs only act as noncoding RNAs. This may provide a new idea for future studies of circRNAs. In recent years, a large number of studies have shown that the abnormal expression of circRNAs plays an important role in the occurrence and development of gastric cancer. The expression of circRNAs in tissues, plasma and exosomes is variable between healthy individuals and patients with gastric cancer. Some gastric cancer-associated circRNAs are more sensitive and more specific than traditional gastric cancer markers. For example, hsa_circ_0065149 level is significantly decreased in exosome of gastric cancer patient, while the levels of circPTPN22, hsa_circ_0004771, and hsa_circ_0141633 in the plasma of gastric cancer patients are increased, indicating the potential of circRNAs as novel diagnostic markers for gastric cancer. Studies on gastric cancer-associated drug resistance have found that some circRNAs including circ-PVT1, circCUL2, hsa_circ_0001313, hsa_circ_0110805, and circVAPA affect the chemoresistance of gastric cancer cells through the circRNA/miRNA/mRNA arises. The main functions of circRNAs are by acting as microRNA sponge to regulate the expression of targeted mRNAs, functioning as tumor promoter or suppressor, thereby affecting gastric cancer proliferation, differentiation and metastasis. The aberrant expression of circRNAs plays a crucial role in gastric carcinogenesis. For example, circRBM33, one of the gastric cancer-associated upregulated circRNAs, upregulates the expression of interleukin-6 (IL-6) through miR-149/IL-6 axis, which in turn promotes gastric cancer proliferation. Hsa_circ_002059 inhibits gastric cancer proliferation and migration by inhibiting the expression of miR-182 and inducing the expression of Metastasis suppressor 1 (MTSS1). In addition, hsa_circ_0005529, circRanGAP1, circPIP5K1A, circMAT2B, and circMTO1 may be promising as novel targets for the treatment of gastric cancer. The results of studies on gastric cancer-related circRNAs are helpful for us to understand the mechanism underlying gastric cancer occurrence and provide basics for the diagnosis and treatment of gastric cancer.

Abstract:The balance of cartilage and bone cells (osteoblasts and osteocytes) plays a crucial role in cartilage homeostasis and bone remodeling. This review focuses on the TGF-β canonical signaling pathway, highlights its influence on cartilage homeostasis and bone remodeling and presents different inhibitor and clinical applications in bone diseases. This review aims at providing new ideas and directions for the prevention and treatment of bone diseases.

Abstract:Chemical cross-linking coupled with mass spectrometry (CXMS) is an important tool to analyze protein structures and protein-protein interactions. In the last five years, CXMS has made great progress in both methods and applications. In terms of methods, on the one hand, cleavable cross-linkers and new separation and enrichment methods have shown good prospects, and on the other hand, more efficient cross-linked peptide search engines and quality control methods provide powerful tools for CXMS data analysis. In terms of applications, on the one hand, CXMS combined with cryo-electron microscopy has determined a large number of protein structures, and on the other hand, CXMS has shown the potential to analyze protein-protein interaction networks at a proteome scale. The intensive research on CXMS in methods and applications reflect the important role of this technology. Here we review the various aspects of CXMS, including cross-linker selection, cross-linking reaction, protein digestion, separation and enrichment, data acquisition, cross-linked peptide identification, quality control, and application, and mainly focus on progress in the last five years. Lastly, we discuss the challenges and opportunities of CXMS in the future. In section 1, we review cross-linkers from the aspects of reactive group and spacer arm. In section 2, we give tips for the cross-linking reaction. In section 3, we describe the sequential digestion strategy for cross-linked proteins. In section 4, we elaborate enrichment methods for cross-linked peptides, including affinity purification, chromatographic separation, and ion mobility mass spectrometry. In section 5, we elaborate data acquisition methods for cross-linked peptides, and compare three methods for MS-cleavable cross-linked peptides. In section 6, we elaborate search engines for cross-linked peptide identification. In section 7, we describe quality control methods for cross-linked peptide identification. In section 8, we review applications of CXMS and list some proteome-wide CXMS studies. In section 9, we conclude the paper and discuss the challenges and opportunities of CXMS in the future.

Abstract:Erythroferrone (ERFE) is a newly identified erythroid regulator of iron metabolism in recent years. In response to the stimuli of erythropoiesis, erythropoietin (EPO) stimulates the increased production of ERFE in erythroblasts of the bone marrow, which strongly suppresses the transcription of hepcidin in the liver; thereby increases iron absorption from dietary to blood through stabilizing the iron exporter ferroportin 1 (FPN1). Plasma iron is critical for erythropoiesis, and more iron is needed for heme and hemoglobin synthesis to meet the demands of increased erythropoiesis. ERFE in the blood plays an important role in ensuring stable iron supply during erythropoiesis. This review focuses on the discovery of ERFE in phlebotomy and hypoxia, and its gene is Fam132b with the coding sequence of 10 kb. ERFE protein is a glycol protein which belongs to the C1q/TNF-related protein family, and there are 340 and 354 amino acids in mouse and human, respectively. It has been reported that Fam132b mRNA was detected in colon, skeletal muscle, brain, heart and other tissues, while it was rich in bone marrow after phlebotomy. It has been shown that ERFE plays important roles in glucose and fat metabolism, erythropoiesis and iron metabolism through hepcidin and transferrin receptors. Moreover, recent advances in relationships between ERFE dysregulation and diseases including β-thalassemia and chronic kidney disease, as well as the detection of ERFE in clinic and fundamental researches, give a further understanding the role of EPO/ERFE/hepcidin-FPN1 in regulating iron metabolism to provide a potential therapeutic target for treating diseases with iron metabolism disorders.

Abstract:Polycystic ovary syndrome (PCOS) is a common chronic inflammatory metabolic disease in women of reproductive age, and is considered as a potential risk factor for infertility because it is often characterized by insufficient or non-ovulation, and over 70% of patients suffer from hyperandrogenemia. High androgen levels not only inhibit follicular growth, promote premature luteinization of follicles, hinder the selection of dominant follicles, but also induce the formation of inflammation, which is an important factor for PCOS to maintain chronic inflammatory state. Abnormally high LH pulses reflect the overactivity of GnRH neural circuit, reflecting the neuroendocrine basis of the etiology or phenotype of PCOS. Kisspeptin secreted by brain neurons not only promotes androgen-related chronic inflammation by activating GnRH, but also directly inhibits the production of NK cells, such as IL-4, IL-10, and IFN. Melatonin reduces androgen levels, inhibits inflammatory factors and improves oocyte quality through the extracellular signal-regulated kinase pathway of granulosa cells. C1QTNF6, a newly identified inflammatory adiponectin byproduct, affects inflammatory responses through the AKT/NF-κB signaling pathway and may be a good new diagnostic target of PCOS. This paper reviewed the relationship between neuro-endocrine regulation and inflammatory factors, and found that the upstream nerve of hypothalamus can promote the formation of hyperandrogenemia by regulating the hypothalamic-pituitary-gonad axis, which leads to the occurrence of inflammation and participate in the occurrence and development of PCOS. Meanwhile, melatonin, GNRH-AAB and C1QTNF6 may be new targets for the treatment or diagnosis of PCOS. It is hoped that this can provide some new ideas for the research of PCOS.

Abstract:Objective Renal cell carcinoma is a malignant tumor originating from the renal tubular epithelial system. In the field of miRNA biomarkers for renal cancer, many previous researches had ignored the large gap in the amounts of samples between different subtypes of renal cancer, this may lead to differences in the diagnostic ability of selected miRNA biomarkers among patients with different subtypes of renal cancer, and may cause missed diagnosis and misdiagnosis. Therefore, we considered two subtypes of kidney cancer common markers for the study.Methods Statistics and two machine learning methods were performed to screen the expression profile data of clear renal cell carcinoma (ccRCC, KIRC) and papillary renal cell carcinoma (pRCC, KIRP) respectively and the results were intersected to obtain common miRNA markers for both types of kidney cancer. Then, ROC curve was used to verify the diagnostic ability of these biomarkers, machine learning methods using external data set (KICH) were also conformed to these biomarkers, the two methods further proved that these miRNA biomarkers’ diagnostic ability and avoided over-fitting. The rationality of these biomarkers was also verified by existing experimental literature. The molecular mechanisms of miRNA markers were investigated using bioinformatics methods.Results A total of 6 common miRNA markers for both types of kidney cancer were obtained (miR-21, mir-210, mir-185, mir-188, mir-362, mir-199a-2), 4 of them have been reported to be associated with renal cancer. Mir-188 and mir-199a-2 have not been reported to be associated with renal cancer, and maybe novel miRNA biomarkers of renal cancer. Then, we performed bioinformatic analysis on these 6 miRNA biomarkers, the results showed that the newly discovered biomarkers (mir-188 and mir-199a-2), were involved in the regulation of two renal cancer related pathway, MAPK signaling pathway and TGF-β signaling pathway. The differential expression of miRNA and its target genes in the pathway was verified, which further proved the reliability of miRNA as a marker and its regulatory effect on target genes. Also a possible mechanism of how 9 target genes of mir-185 (all belonging to the UGT1A gene family) participate in renal cancer was found, and there was no related literature.Conclusion The present study identifies possible new common miRNA markers for both types of kidney cancer and discovers a mechanism of kidney carcinogenesis that has not been seen in kidney cancer-related fields.

Abstract:Objective To explore the mechanism of heat shock factor (HSFl) alleviating coagulatory dysfunction in sepsis and protecting mice from acute lung injury.Methods In this study, a mouse model of sepsis was established by cecal ligation and puncture (CLP). We tested the coagulation indexes and pathological changes in the lungs of mice. Protein C expression was detected by ELISA, qRT-PCR and Western blotting. The expression level of protein C was observed by inhibiting or enhancing the expression of HSF1 by plasmid transfection, and the mechanism of HSF1 regulating protein C transcription was explored by bioinformatics, EMSA and dual luciferase reporter gene experiments.Results In the mouse model of sepsis, we discovered that the coagulatory activity of the HSF^-/- mice was significantly enhanced and the lung injury was aggravated after CLP, compared with the HSF1^+/+ mice. ELISA, qRT-PCR and Western blot showed that the expression level of protein C in the plasma and lung tissue of the HSF^-/- mice was lower than that in the wild-type mice in sepsis. In vitro studies also demonstrated that HSF1 interference inhibited lipopolysaccharide (LPS)-induced protein C expression, while HSF1 overexpression enhanced protein C expression in bEnd.3 vascular endothelial cells. Further bioinformatics analysis indicated that the protein C promoter region contains HSF1 binding element (HSE). EMSA and dual luciferase reporter gene experiments showed that HSF1 bound to the HSE in the promoter region of protein C, thereby directly upregulating protein C transcription.Conclusion This study revealed that HSF1 was involved in acute lung injury in sepsis mouse model. HSF1 alleviated the coagulatory dysfunction in sepsis by directly upregulating protein C transcription, thus playing a protective role in mouse lung tissue.

Abstract:Objective We investigated the role of glutathione transferase omega 1 (GSTO1) in regulating function of bone marrow-derived dendritic cells (BMDCs).Methods The expression of MHCII on the surface of Gsto1^-/- BMDCs and GSTO1 inhibitor-treated BMDCs was detected by flow cytometry and confocal microscope. To investigate the role of BMDCs, they were cocultured with CD4 T cells from OTII mice in the presence of OVA and IFN-γ production was measured. The recycling and internalization of MHCII molecule in BMDCs treated with GSTO1 inhibitor were measured by flow cytometry. The transcriptional level of MHCII molecule in BMDCs treated by GSTO1 inhibitor was detected by real-time quantitative PCR. The total protein level of MHCII molecule in BMDCs treated by GSTO1 inhibitor was detected by Western blot. The ubiquitination level of MHCII after GSTO1 inhibitor treatment was detected by co-immunoprecipitation assay.Results GSTO1 deficiency and GSTO1 inhibitor did not affect proliferation and apoptosis of BMDCs, but reduced the surface expression of antigen presentation molecule MHCII. Gsto1^-/- BMDCs and BMDCs treated with GSTO1 inhibitor showed impaired CD4 T cell-activating capability. In GSTO1 inhibitor-treated BMDCs, the recycling and internalization of MHCII molecule were normal. GSTO1 inhibitor showed no influence on the transcription of MHCII but reduced its total protein level. Furthermore, BMDCs treated with GSTO1 inhibitor showed higher level of ubiquitinated MHCII molecule and treatment with proteasomes inhibitor MG132 recovered the surface MHCII expression in these cells.Conclusion These data demonstrate that GSTO1 in BMDCs promotes MHCII expression and thus CD4 T cell-activating capacity by inhibiting ubiquitination of MHCII molecule.

Abstract:Objective We propose a dual-contrast optical projection tomography (DC-OPT) based on principal component analysis (PCA) to obtain a three-dimensional (3D) visualization of the blood-flow network and skeleton in a live organism.Methods The PCA method was used to extract the absorption and flow contrast images (15 images/projection position). The absorption image was obtained with the use of the first principal component of the raw image sequence. The flow images were obtained based on the computation of the modulation depth of each pixel. The flow and absorption contrast images at different projection positions are combined to achieve a synchronous reconstruction of a 3D image.Results The combination of PCA and OPT is used to realize the 3D imaging of the blood-flow network and skeleton of the biological sample by separating the dynamic blood flow signal and the static background signal of the sample.Conclusion The novelty of our study is attributed to the fast, simultaneous, dual-contrast 3D images of the blood-flow network and skeleton by the same optical system. The experimental result can be applied in physiological development studies in live model organisms.

Abstract:神经胶质细胞在神经系统的发育和分化中扮演着重要角色。近期，研究人员在心脏中发现一种新型神经胶质细胞，命名为连接胶质细胞（Nexus glia）。该细胞具有神经胶质细胞的特性，能够影响心脏内神经细胞的发育，继而调节心脏节律。连接胶质细胞的发现为胶质细胞在外周器官中的功能机制研究提供了重要的物质基础，也为临床维持心脏稳态和控制心脏自主节律提供了潜在的药物靶标。

Abstract: