Type 1 diabetes and neurodevelopmental disorders are common chronic conditions in childhood and adolescence, and having one may lead to an increased chance of developing the other. Type 1 diabetes mellitus is mainly manifested by elevated blood glucose, while neurodevelopmental diseases are composed of a variety of diseases, which are relatively complex. The purpose of this meta-analysis was to find out the prevalence of type 1 diabetes-related neurodevelopmental disorders in children and adolescents and to explore the potential association between neurodevelopmental disorders and type 1 diabetes. PubMed, Embase and Web of science databases were searched from the inception to May 22, 2022 to identify relevant studies, Finally, 24 original studies were included in the meta-analysis. Prevalence estimates for neurodevelopmental disorders in the type 1 diabetes adolescent and their 95% confidence intervals were pooled using random effects models. The pooled estimates for autism spectrum disorders (ASD) and attention deficit hyperactivity disorder (ADHD) in the type 1 diabetes population were 1.2 and 5.3%, respectively, both of which are higher than the 2019 global prevalence of ASD and ADHD in the general population. The results of the subgroup analysis showed that the prevalence of ASD and ADHD in the T1DM population tended to increase with age. In conclusion, there may be a potential link between the occurrence of type 1 diabetes mellitus and the development of neurodevelopmental disorders in children and adolescents, but more relevant studies are needed to understand the link between the underlying pathogenesis of type 1 diabetes and neurodevelopmental disorders.https://www.crd.york.ac.uk/PROSPERO/], identifier [CDR42022333443].[ Neurodevelopmental disorders (NDDs) are a group of complex disorders that are not easily conceptualized. In the DSM-5, NDDs are defined as a group of disorders that occur during development, including autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), intellectual disability (ID), communication disorders (CD), specific learning disabilities (SLD), and motor disorders (MDs) , 2. TheyDiabetes is another chronic disease that can be extremely dangerous, which can seriously damage many systems of the body, especially nerves and blood vessels. It is defined as a group of metabolic diseases characterized by hyperglycemia caused by defective insulin secretion, defective insulin action or both. There are two types of diabetes, type 1 diabetes mellitus (T1DM) and type 2 diabetes . The preType 1 diabetes is characterized by elevated blood glucose levels due to insulin deficiency caused by loss of pancreatic b-cells, and it is a common chronic disease in children and adolescents, along with mental disorders , 21, 22.NDDs and T1DM are common in children and adolescents, may have similar pathogenesis, and may occur together. The purpose of this study was to investigate the prevalence of T1DM and NDDs in children and adolescents through meta-analysis and to explore the potential association between these two diseases.The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline were followed by this systematic review . The proWe searched Embase, PubMed, and Web of Science databases for relevant articles published as of May 22, 2022. We selected subject terms and keywords related to diabetes, autism, ADHD, ID, CD, SLD, and motor disabilities in different databases, and the detailed retrieval strategy is shown in The inclusion criteria of the studies were as follows: (a) the age of population was 18 years old or below; (b) the population is accompanied by T1DM with NDDs or NDDs with T1DM; (c) The reported study must be published in English; (d) Prevalence estimates or raw data can be used to calculate the prevalence are available in the study; (e) The study to be included must be original studies, and reviews or systematic reviews are excluded. All papers that meet the criteria will be included in the systematic review.A standardized form was used to extract the following data from the included studies: Author and year of publication, study content , diagnosis and criteria of T1DM and NDDs, outcome . If the prevalence estimates were not directly provided in the study, raw data from the article are collected and calculated to obtain prevalence. In addition, we also extracted the types of scales used in the diagnosis of different diseases and the judgment criteria used in the table, which are respectively, expressed as diagnosis and criteria in the table header . Two resThe 14-item rating scale National Institutes of Health Study Quality Assessment Tool for Observational Cohort and Cross-sectional Studies were used to assess the quality of each included study. The quality assessment was performed independently by two researchers (X.L. and XN.-X.) and resolved by negotiation or discussion with the third author (XY.-L).I2 statistics were used to evaluate heterogeneity between studies  and 5.3% (95%CI: 4.3–6.4%), respectively , 2. SubgDetection of publication bias by funnel plot, Begg test and Egger test , 4. The Except ASD and ADHD, other NDDs retrieved in this study were not included in our meta-analysis.There were two studies on T1DM among the included children and adolescents with ASD, which were conducted in the United States from 2001 to 2010. One was a clinical study and the other was a population-based study, with a prevalence rate of 0.93 and 0.67%, respectively. The quality evaluation was of general quality. There is only one study related to T1DM in children and adolescent ADHD patients, which is a population-based study conducted in China with a prevalence rate of 0.1%, and it is rated as good quality.Except ASD and ADHD, there is no study on type 1 diabetes in children and adolescents with other neurodevelopmental disorders that met our inclusion criteria.The results of the study showed that the prevalence of ASD and ADHD in T1DM children and adolescents was 1.1% (95% CI: 0.8–1.5) and 5.3% , respectively, both higher than the global prevalence of ASD and ADHD in the general population in 2019 (0.4 and 1.1%), suggesting that T1DM has an impact on the prevalence of ASD and ADHD. Present study analyzed the prevalence of concurrent NDDs with T1DM in children and adolescents and explored the potential association between T1DM and NDDs.A growing number of studies have explored the relationship between metabolic disorders and psychiatric disorders, and there has been a gradual increase in research on the relationship between diabetes and psychiatric disorders, as well as a large body of literature exploring the effect of maternal diabetes on the development of neurodevelopmental disorders in offspring –65, but There may be some limitations to our analysis. First, the prevalence of mental developmental disorders among people with type 1 diabetes and the incidence of type 1 diabetes among people with mental developmental disorders may be underestimated, as there are still areas where low awareness of mental disorders or inadequate understanding of type 1 diabetes may lead to underdiagnosis and thus affect the accuracy of prevalence. Secondly, the literature is limited, and the results of our regional subgroup analysis for existing literature may not be applicable to all regions of the world. In addition, in the subgroup analysis results of prevalence of ASD in T1DM patients, the low prevalence in some age groups may lead to the unreliable prevalence of ASD in T1DM patients. However, mental disorders include six diseases, but there are few literatures related to some of them and more relevant researches are needed. Finally, recall bias can occur when recording situations through self-reports or parental reports.In conclusion, this systematic review and meta-analysis suggests that type 1 diabetes is associated with the neurodevelopmental disorders in children and adolescents. There was a significant increase in the prevalence of ASD or ADHD in the adolescent T1DM population compared with that in the general population, and there was a trend for the prevalence of ASD and ADHD to increase with age in the T1DM population, but there is less literature on the association of the prevalence of T1DM in the children and adolescent neurodevelopmental disorders population. The potential link between the two disorders was also explored in this systematic review and meta-analysis, but the mechanisms behind T1DM and psychiatric disorders are not fully understood, and more high-quality studies are needed to elucidate the pathogenesis of T1DM and psychiatric disorders and to explore their intrinsic connections.The original contributions presented in this study are included in the article/Y-ML and X-YL conceived the study design. C-YX and XL conducted data analysis. X-NX conducted study evaluation and wrote the manuscript. All authors have reviewed and approved the submitted version of the manuscript.


We found that chronic uridine administration reduced fibrosis in the skeletal muscles of mdx mice, but it had no effect on the intensity of degeneration/regeneration cycles and inflammation, pseudohypetrophy, and muscle strength of the animals. Analysis of TEM micrographs showed that uridine also had no effect on the impaired mitochondrial ultrastructure of mdx mouse skeletal muscle. The administration of uridine was found to lead to an increase in the expression of the Drp1 and Parkin genes, which may indicate an increase in the intensity of organelle fission and the normalization of mitophagy. Uridine had little effect on OXPHOS dysfunction in mdx mouse mitochondria, and moreover, it was suppressed in the mitochondria of wild type animals. At the same time, uridine restored the transport of potassium ions and reduced the production of reactive oxygen species; however, this had no effect on the impaired calcium retention capacity of mdx mouse mitochondria. The obtained results demonstrate that the used dose of uridine only partially prevents mitochondrial dysfunction in skeletal muscles during Duchenne dystrophy, though it mitigates the development of destructive processes in skeletal muscles.Duchenne muscular dystrophy is caused by the loss of functional dystrophin that secondarily causes systemic metabolic impairment in skeletal muscles and cardiomyocytes. The nutraceutical approach is considered as a possible complementary therapy for this pathology. In this work, we have studied the effect of pyrimidine nucleoside uridine , which plays an important role in cellular metabolism, on the development of DMD in the skeletal muscles of dystrophin deficient  Duchenne muscular dystrophy is one of the most common forms of hereditary neuromuscular pathologies with an incidence of about one in 3500–5000 newborns, primarily boys . This di2+, ROS overproduction, and the depolarization of organelles; this leads to mitochondrial permeability transition pore (PTP) opening and subsequent muscle fiber death, as well as the development of severe necrotic inflammation [One of the important secondary signs of DMD is considered to be systemic metabolic impairment, which leads to a decrease in the production of ATP; this is necessary for the operation of the contractile apparatus and the normal functioning of the muscle fiber ,4. In paammation ,11,12. Gammation . In partOur attention was drawn to pyrimidine nucleoside uridine, which plays an important role in many processes in mammalian organisms . It is u+ channel [There are fragmentary data on the possibility of using uridine when treating DMD. In particular, the use of a cocktail of nucleosides and nucleotides containing adenosine, AMP, ADP, ATP, guanosine, guanosine monophosphate, uridine, uridine monophosphate, and cytidine monophosphate in the treatment of boys with DMD has been reported, and some improvement in enzymatic and functional capacity was shown . The pos channel ,20,21,22mdx mice. Taking into account the known role of uridine in the regulation of energy homeostasis, we also evaluated the effect of this nutraceutical on the mitochondrial dysfunction that accompanies this pathology, as well as the violation of the ultrastructure of organelles and the malfunctions that occur within the mitochondrial quality control system.In this work, we have studied the effect of the intraperitoneal administration of uridine (30 mg/kg/day for 28 days) on the development of destructive processes in the skeletal muscles of model dystrophin deficient mdx mice every day for 28 days , as well as the intensive development of muscle degeneration and fibrosis, accompanied, among other things, by pseudohypertrophy, leading to accelerated weight gain. All these phenomena are also observed in the present work. Indeed, ing test . In addiing test . This ising test A–D,I, a ing test E–H,J, thght gain K.mdx mice and wild type animals. The muscle strength of the animals, the level of inflammatory markers, and the intensity of degeneration/regeneration cycles in mice do not change. We only noted a significant decrease in the level of fibrosis in the skeletal muscles of uridine treated mdx mice. In addition, the administration of uridine not only fails to suppress the development of pseudohypetrophy, but rather, it leads to increased weight gain in mice, which is especially noticeable in the case of wild type animals.The administration of uridine does not significantly affect most of these parameters in both mdx mice show a sharp increase in the number of mitochondria under the sarcolemma with signs of severe destruction  in mdx mouse skeletal muscle mitochondria compared with wild type animals. Treatment with uridine leads to a significant decrease in the state 4 respiration rate of mdx mice mitochondria, and there is also a tendency for the rate of oxygen consumption to further decrease in states 3 and 3UDNP. Moreover, in the case of wild type animals, the administration of uridine leads to a significant decrease in the rate of mitochondrial respiration in states 3 and 3UDNP; thus, uridine suppresses respiration and oxidative phosphorylation in skeletal muscle mitochondria, which is most pronounced in wild type animals, who exhibit higher respiratory rates when compared with mdx mice.Violations of the ultrastructure of skeletal muscle mitochondria and the quality control system in Duchenne dystrophy is also accompanied by mitochondrial dysfunction. This is manifested in a decrease in the efficiency of oxidative phosphorylation, which is necessary for the production of ATP. Indeed, mdx mice show an increased level of malondialdehyde (MDA)  . In thisATP) [+ from skeletal muscle mitochondria, which was mediated by the inversion of the mitoKATP [+ release from mitochondria , an activator of the mitochondrial ATP-dependent potassium channel (mitoKATP) ; therefomitoKATP . One canchondria A. Moreovmdx mice B. The usmdx mice show an approximate 1.6 fold reduction in Ca2+ retention capacity  towards enhanced body weight gain. We hypothesized that the latter is due to the known ability of uridine to increase muscle and liver glycogen synthesis, as well as to inhibit lipolysis in adipose tissue [Previously, it has been shown that intravenous administration of uridine, in combination with a number of other nucleotides and precursors, improves the enzymatic and functional capacity of DMD patients . Here, w animals . DMD fib animals , Table 1 animals K. Moreove tissue ,32.mdx mice  were used in this work. All the animals were purchased from the Animal Breeding Facility, Branch of the Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Russia . Upon arrival, mice were singly housed and given a minimum of 72 h to acclimatize before experiments were performed. All animals were provided access to standard chow and water ad libitum. Mitochondrial isolation was performed on fresh samples of skeletal muscle. The rest of the tissue was stored at −80 °C until analyzed.Male mice of the C57BL/10  and dystrophin deficient Mdx and WT mice (eight weeks old) were injected interperitoneally with uridine , and were resuspended in sterile saline every day for up to four weeks (30 mg/kg body weight). Sham-injected controls received saline alone. The mice were then killed and tissues were removed for analysis.At the end of the treatment period, all mice were sacrificed. Blood was collected to analyze the activity of creatine kinase, AST, and LDH using the appropriate reagent kits  and Multiskan GO plate reader .To examine the degree of severity of the histological changes, samples of skeletal muscle tissue  were fixed in a neutral buffered 10% formalin, and the specimens were impregnated in paraffin wax. The paraffin blocks were cut using a microtome MC-2, into serial sections, at a 5 μm thickness. The slides obtained from each specimen were stained with the haematoxylin and eosin (H&E) and haematoxylin van Gieson (HvG) stain protocol. Examinations of the slides were carried out using an EVOS M5000 imaging system . All histological images were analyzed using free ImageJ software. The level of fibrosis in the muscles of mice was evaluated as the percentage ratio of the HvG staining areas (pink) which represented collagen and other connective tissue elements in the common area of the tissue on the histological slides, wherein at least 10 sections were analyzed for each organ sample. Quantitative data concerning the centrally nucleated fibers (CNF) from H&E staining are from, on average, 8–10 unique visual fields (20× objective) from each animal, and they were expressed as a percentage of the total number of myofibers counted.Muscle function and the endurance of the mice were assessed using a wire-hanging test. For this purpose, each animal was placed on a 3 mm string . The mouse was held on the string by its front paws and hung for 30 s. The scoring of the test results was carried out according to a well-known approach : hangingSamples of the skeletal muscle  were fixed for 2 h in a 2.5% glutaraldehyde solution in 0.1 M PBS (pH = 7.4). The preparations were examined and photographed using a JEM-100B electron microscope  and analyzed using Image Tool 3.0 software.Rplp2 mRNA, and a comparative CT method was used to quantify the results [Total RNA was isolated from 100 mg of deep-frozen samples from the quadriceps of the mice using an ExtractRNA kit and its corresponding protocol . The real-time PCR was performed on a QuantStudio 1  using the qPCRmix-HS SYBR reaction mixture . The selection and analysis of gene-specific primers were performed using Primer-BLAST  the oli. The rel results .ND4 gene of the mouse mitochondrial genome and the nuclear encoded GAPDH gene. A comparison of ND4 DNA expression, relative to GAPDH DNA expression, gives a measure of the mtDNA copy number to nDNA copy number ratio. Primers for mtDNA and nDNA are presented in Total DNA (nuclear and mtDNA) was extracted from 10 mg of quadriceps using DNA-Extran 2 kit and protocol . Of the total DNA, 1 ng was taken for the reaction. The evaluation of mtDNA content in the samples was performed by PCR, as described in , and exp2 consumption by mitochondrial samples was measured using Oxygraph-2k  [2PO4, 2.5 mM potassium malate, 2.5 mM potassium glutamate, and 10 mM Hepes/KOH (pH 7.4). Lipid peroxidation in mitochondria was assessed using the quantification of thiobarbituric acid-reactive substances (TBARS), which was represented mainly by malondialdehyde and some other minor aldehyde species [+ in mitochondria was determined by the rate of the DNP-induced release of K+ from the organelles using K+- selective electrode [2PO4, 1 μg/mL oligomycin, and 10 mM Tris/HCl, pH 7.4. Ca2+ transport and retention by mitochondria was recorded using arsenazo III color indicator at 675–685 nm and a plate reader Tecan Spark 10 M  [2PO4, 2.5 mM malate, 2.5 mM glutamate, 10 μM EGTA, 50 μM arsenazo III, and 10 mM HEPES-KOH (pH 7.4.). The total amount of the added Ca2+ ions that induced their spontaneous release from mitochondria due to the induction of the PTP opening was reflected in the calcium retention capacity (CRC) of the organelles.Mitochondria were isolated from skeletal muscle (quadriceps of both hindlimbs) tissue using the differential centrifugation method . Final mAustria) . The res species . Transpolectrode . The medzerland) . The medThe data were analyzed using the GraphPad Prism 8.0.1 software  and were presented as the mean ± SEM of 4–10 biological replicates (excluding electron microscopy data). The results of the transmission electron microscopy analysis were presented as representative images from two biological replicates. The statistical significance of the differences between the experimental groups was evaluated using one-way analysis of variance (ANOVA) followed by the Tukey multiple comparison post hoc test.mdx mice, but does not affect the intensity of degeneration/regeneration cycles and inflammation, nor the pseudohypetrophy and muscle strength of animals; (2) uridine at the dose used has no significant effect on the disturbed ultrastructure of the skeletal muscles and mitochondria of mdx mice; (3) uridine possibly favors the intensive fission of organelles in the skeletal muscles of mdx mice, thus increasing the expression of the Drp1 gene, and causing an increase in the expression of the Parkin gene responsible for mitophagy, however, the level of mtDNA and the expression of the Ppargc1a gene responsible for organelle biogenesis do not change; (4) uridine has a weak effect on the dysfunctionality of the mdx mitochondrial OXPHOS system, and moreover, it suppresses it in the mitochondria of wild type mice. At the same time, uridine restores the functioning of potassium ion transport systems in mdx mice mitochondria and reduces the production of reactive oxygen species; however, this does not contribute to the normalization of the calcium retention capacity of organelles, and thus, the prolonged administration of uridine only partially restores the functioning of skeletal muscle mitochondria in Duchenne dystrophy and mitigates the development of destructive processes in skeletal muscles, subsequently reducing the level of fibrosis. This is not enough to significantly improve the quality of life of dystrophin deficient animals that still display the hallmarks of DMD—intense degeneration, inflammation, and calcium dysregulation; however, this approach, and the reduction of fibrosis can be used as an adjunctive therapy to maintain a sufficient amount of target muscle that may be available for therapy and repair.The present work shows the effect of prolonged administration of nucleoside uridine (30 mg/kg for 4 weeks) on the progression of DMD and its concomitant mitochondrial dysfunction in skeletal muscle mitochondria. The following results were obtained: (1) uridine reduces the level of fibrosis in the skeletal muscles of


N6-methyladenosine (m6A) RNA methylation is one of the most common epigenetic modifications in RNA nucleotides. It is known that m6A methylation is involved in regulation, including gene expression, homeostasis, mRNA stability and other biological processes, affecting metabolism and a variety of biochemical regulation processes, and affecting the occurrence and development of a variety of diseases. Cardiovascular disease has high morbidity, disability rate and mortality in the world, of which heart failure is the final stage. Deeper understanding of the potential molecular mechanism of heart failure and exploring more effective treatment strategies will bring good news to the sick population. At present, m6A methylation is the latest research direction, which reveals some potential links between epigenetics and pathogenesis of heart failure. And m6A methylation will bring new directions and ideas for the prevention, diagnosis and treatment of heart failure. The purpose of this paper is to review the physiological and pathological mechanisms of m6A methylation that may be involved in cardiac remodeling in heart failure, so as to explain the possible role of m6A methylation in the occurrence and development of heart failure. And we hope to help m6A methylation obtain more in-depth research in the occurrence and development of heart failure. M6A methylation is the process of methylation modification on the nitrogen atom of adenine in RNA molecule, that is, the methyl provided by S-adenosylmethionine (SAM) is added to the N6 site of adenosine . M6A metHeart failure is a complex cardiovascular syndrome, which often occurs in the final stage of a variety of cardiovascular diseases, or secondary to other disease states. The core of its occurrence and development is the structural or functional abnormalities caused by acute or chronic injury, resulting in ventricular filling disorder or abnormal cardiac output , 26. CliThe upsurge of m6A methylation research may bring new directions and new ideas for the in-depth study of the pathogenesis of heart failure. Targeted regulation of m6A methylation related processes may contribute to the diagnosis, treatment and drug development of patients with heart failure. Therefore, in this review, we summarize the possible mechanism of m6A methylation in the occurrence and development of heart failure, in order to illustrate the importance of exploring the role of m6A.M6A methylation needs three main parts to complete together, namely the Writers, the Erasers, the Readers .M6A Writer is completed by m6A methyltransferase complex, namely methyltransferase like 3 (METTL3) and METTL14 and their cofactor Wilms tumor 1 associated protein (WTAP). METTL3 contains S-adenosylmethionine (SAM) binding domain and DPPW motif (Asn-Pro-Trp), which can transfer methyl from SAM to N6 position of target adenosine , 39; METin vivo and in vitro, and co-locate with nuclear spots to complete RNA regulation  and fat mass and obesity associated protein (FTO), revealing the reversibility of RNA modification. The demethylation activity of FTO makes contribution to the normal development of human central nervous system and cardiovascular system , 49. The5 and fatgulation .M6A Reader binding sites are overlapped with m6A localization, both near the stop codon of CDS and 3 ′ UTR on mRNA . At pres2+ ATPase 2a (SERCA2a), ryanodine 2 (RyR2), myosin heavy chain (MYH) 6/7, and increasing their protein expression level, and even reversing cardiac fibrosis and inducing angiogenesis in heart failure after myocardial infarction. M6A methylase METTL3 can promote cardiomyocyte hypertrophy in vitro and in vivo. And increasing m6A methylation will promote compensatory cardiomyocyte hypertrophy, while reducing m6A methylation will induce eccentric cardiomyocyte remodeling and dysfunction , but also affects the transmission of ECG signals  and myocardial apoptosis and hypertrophy.+-Ca2+ exchange (NCX) function competing with SERCA2a for Ca2+, the Ca2+ released by SR after LTCC activation is reduced, which can not meet the transient of calcium ions in cardiomyocytes, resulting in the significant decrease of myocardial contractility , and some calcium ions flow into cardiomyocytes, acting on the calcium ion channel of SR, triggering the release of a large amount of calcium ions from sarcoplasmic reticulum, so that the calcium ion level in cardiomyocytes quickly reaches the peak, that is, calcium ion spark. The sum of time and space of calcium ion sparks is called calcium ion transient. Subsequently, calcium ions bind to troponin on the fine myofilament, causing changes in the spatial conformation of the fine myofilament, exposing the binding sites of actin and myosin on the thick myofilament, and the two bind to complete a myocardial contraction. However, when heart failure occurs, on the one hand, due to the reduction of SERCA2a function, the increase of RyR leakage, the increase of Naactility . On the actility . This isactility . Howeveractility –71. ThisIn vivo and in vitro studies show that FTO can improve the amplitude of Ca2+, accelerate the attenuation of Ca2+, shorten the sarcomere, reduce the increase of m6A induced by ischemia, and improve the corresponding systolic dysfunction of cardiomyocytes. After enrichment and screening of pathways, FTO can selectively act on pathways related to cardiac sarcomere tissue, myofibril assembly, calcium treatment and contraction, and can cause various heart diseases, such as hypertrophic cardiomyopathy, ventricular septal defect, atrioventricular defect, arrhythmia and coronary heart disease  participate in vascular inflammatory response. Among them, inflammatory response has always been the key point of cardiovascular disease research. ROS plays a significant role in inflammatory response.Endothelial cells are the main cell type involved in coordinating the pathological changes of heart failure, and their surface is often the direct place of a variety of inflammatory reactions . During As we all know, cardiac hypertrophy is the main sign of heart failure. MiRNA molecules, such as non-coding RNA members, can also play an essential role in the pathological changes of heart failure by mediating myocardial hypertrophy, and can be modified by m6A . For exaAs we all know, during the occurrence and development of heart failure, with the activation of nerve body fluid and the increase of hemodynamic load, myocardial compensatory hypertrophy increases the volume of cardiomyocytes and the number of mitochondria, so as to maintain close to normal cardiac output and supply the needs of the body and tissue cells. However, when the myocardium is irreversibly and continuously hypertrophic, the cardiomyocytes are gradually in the state of ischemia and hypoxia, and can not bear the continuous pressure load, decompensated heart failure eventually occurring.Autophagy is a process in which eukaryotic cells play a degradation function through lysosomes to inactivate and phagocytize proteins and cell components. It plays an important role in normal physiological function, proliferation, death and maintaining intracellular homeostasis. The main processes include: forming phagocytic vesicles of phospholipid bilayer, phagocytizing and wrapping damaged organelles and abnormally expressed proteins to form autophagosomes, which are the landmark products of autophagy; then, the vesicles are transported to the lysosome and combined with the lysosome to form autophagic lysosomes, which are finally degraded , 93. In Autophagy plays a vital role in the occurrence and development of heart failure guided by myocardial hypertrophy , 99. SomM6A methylation can affect the expression of autophagy related genes, regulate autophagy, and play an important role in the occurrence and development of heart failure , 112. ItIn conclusion, m6A methylation may affect myocardial hypertrophy, cardiac remodeling and promote the occurrence and development of heart failure by regulating autophagy.M6A methylation is involved in regulating mRNA stability, protein expression and various physiological reactions of cells. It is also a key molecule in the process of affecting the contractile function of cardiomyocytes due to ischemia and hypoxia, which can cause ischemic myocardial damage. This is the main cause of cardiovascular diseases including myocardial infarction and heart failure, so it also deserves attention.in vitro, which can cause myocardial damage  is a known hypoxia response gene. The increase of MIAT expression level was detected in the whole blood of patients with non-ST segment elevation myocardial infarction (NSTEMI) and ST segment elevation myocardial infarction (STEMI) , 116. Sil damage .Therefore, in the future, the research on FTO and METTL3 related myocardial ischemia and hypoxia may find a breakthrough for the therapeutic target of heart failure.Oxidative stress is a common reaction of cell aging and affecting cell function. When the balance between oxidants and antioxidants is broken, it will lead to oxidative stress. Among them, a variety of oxides mainly play an essential role, such as ROS, RON (a kind of tyrosine kinase receptor) and so forth. These substances will affect the normal replication, transcription and translation of genetic substances, such as DNA, and can affect the normal function of cardiomyocytes, resulting in cardiomyocyte damage and promoting the occurrence and development of heart failure.METTL3/METTL4 may eventually improve the translation level of p21 by promoting other forms of mRNA methylation (like m5C), so as to affect its expression in the process of oxidative stress and cell aging, promote the accumulation of oxides such as ROS and start the oxidative stress response . TherefoThe role of m6A methylation in the mechanism of heart failure is still unknown: on the one hand, it is necessary to build heart failure models with the help of more animals and cells to explore the relationship between m6A methylation and known mechanisms, pathways and molecules that may be involved. Gradually expanding and exploring the regulatory process of m6A methylation, such as the upstream and downstream regulatory pathway of m6A methylation, count a lot. This may improve the understanding of m6A methylation in the pathogenesis of heart failure and bring new breakthroughs. On the other hand, it is necessary to improve the detection technology and functional verification method of m6A methylation, and to increase bioinformatics analysis to find new biomarkers of m6A methylation involved in the occurrence and development of heart failure. In addition, the role of m6A methylation in multiple systems and multiple organs is still unclear in the clinical study of the prevention and treatment of heart failure. With the deepening exploration of research, it needs the efforts of several generations to explore whether we can realize the targeted treatment scheme and drug research and development like tumor targeted drugs in the future, simplify the dosage of drugs, reduce the side effects of drugs, improve the quality of life of patients, and reduce the mortality and disability rate. We still have a long way to go in the treatment and prevention of heart failure .In conclusion, m6A methylation, as one of the most abundant types of RNA modification, has been gradually studied in cardiovascular diseases. This paper reviews the possible mechanisms of m6A methylation in the occurrence and development of heart failure, hoping to summarize the possible role of m6A, so as to lay a foundation for the accurate treatment of heart failure. The main effect of m6A methylation on heart failure is to promote calcium homeostasis, inflammatory response and autophagy, causing cardiomyocyte hypertrophy, myocardial mitochondrial dysfunction, reducing myocardial contractility and cardiac remodeling, resulting in serious consequences. However, there is still a lack of research on the related mechanisms of m6A methylation in the neurohumoral and renin angiotensin aldosterone systems of heart failure, which may provide new ideas for research and new perspectives for treatment.SF: conception, design, and manuscript writing. YH: manuscript revising. Both authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The Altai Republic (AR) is the national subject of the Russian Federation where suicidal situation is unfavorable as the death rate from suicide exceeds the national rates by three times. The high level of suicide among adolescents and young people is especially alarming.To analyze the dynamics of mortality from suicide among adolescents and young people in the AR for the period from 1990 to 2019.Data on mortality of the population were obtained from the Russian databases of demographic indicators and analyzed in terms standardized per 100,000 population.The highest mortality rates from suicide are recorded in the 20-24 age group. The suicide rate, compared to 1990, decreased slightly from 82.5 (in 1990) to 79.7 per 100 thousand (in 2019). The dynamics of mortality from suicide among adolescents aged 15-19 is also unstable. When comparing the indicators in 1990 and in 2019, one can verify the negative dynamics in the form of a 4-fold increase in the suicide rate – from 14.4 (in 1990) to 58 (in 2019). An analysis of the ethnicity of young people who committed complete suicide showed that the majority of suicides (90%) were indigenous Altaians.In adolescents and young people of the AR, the death rate from suicide exceeds the all-Russian indicators from 7.9 to 9.3 times. Effective preventive measures are needed to improve the situation.No significant relationships.


The spent caustic with strong alkali first replaced the alkali activator to prepare the geopolymer. The influence of spent caustic to the geopolymer was characterized through compressive strength measurement, XRD, MIP analysis and NMR, and the immobilization efficiency of organic in geopolymer was evaluated through the measurement of total organic carbon (TOC). The results show that the spent caustic can partially replace the alkali activator to prepare the geopolymer, and it shows a better performance than that which was activated with pure NaOH solution when the alkalinity is between 4 mol and 14 mol. The organic matter in the spent alkali can be effectively fixed in the geopolymer, which will hinder the geopolymerization in the initial stage of the polymerization reaction but has little effect on the chemical structure and mechanical properties of the final product. With the degree of alkalinity increasing, the immobilization efficiency is improved, and the maximum can reach 84.5%. The organics in the spent caustic will hinder geopolymerization at the initial stage but has little effect on the chemical structure and mechanical property of the final product. This study proposes a new method for the recycling of spent caustic, which also reduces the preparation cost of geopolymers. However, treated spent caustic still needs additional treatment, such as acid neutralition, before being discharged to the sewage treatment plant, due to its high COD level and high alkalinity [Spent caustic is a kind of the liquid wastes generated in various chemical industries, especially in oil and gas refineries . It may kalinity . This tr2 footprint in most life cycle categories and was also associated with high costs [2CO3 in the treated spent caustic can reach about 20% [2 emission of geopolymer preparation.Geopolymers are a kind of environmentally friendly aluminosilicate material with a comparable strength performance to the Ordinary Portland Cement, and are considered to be a good potential substitute for the latter . The lowgh costs ,16. Danigh costs . Fortunabout 20% , which hIn this work, we have studied the preparation of geopolymers using spent caustic to partially replace NaOH solution as an alkali activator, and pure NaOH solution with comparable alkalinity was used as a control group. The effect of spent caustic on the compressive strength and microstructure of geopolymers was studied, and the immobilization efficiency of organics in geopolymers was evaluated. This study proposes a new method for the utilization of spent caustic, which also reduces the preparation cost of geopolymers.The class F fly ash used in this paper was purchased from a plant in Hubei province, China, which was used as a raw material in the synthesis of geopolymers. The activator solution was prepared by mixing NaOH with spent caustic or deionized water in different proportions. According to the Chinese Ministry of Environmental Protection Standard HJ/T 300–2007, the immobilization efficiency of organics in geopolymers was evaluated by the leaching toxicity of organics. In this method, the leaching process was performed with the liquid/solid ratio of 20 mL/g for 18 h, which is the same as it in the USEPA TCLP method. However, the extraction solution was prepared by dissolving 17.25 mL acetic acid into 1 L deionized water, and the amount of acid was almost three times that of the latter, so this standard is more severe. In addition, a zero-headspace extraction vessel was used to prevent the volatilization during the leaching process; the specific operation refers to Reference [29Si nuclear magnetic resonance  spectra were used to analyze the microstructure of geopolymer gel. The spectra were collected at 79.5 kHz on a 7 mm probe with a spinning speed of 5 kHz, a pulse width of 6.5 μs and a relaxation delay of 10 s. The 29Si chemical shift was referenced to an external standard of tetramethylsilane.The mechanical property of geopolymers was tested by a mechanical tester  in accordance with the ASTM Test C-39. In the measurement, at least three specimens were tested, and the average value was used. The mineralogical study of geopolymers was characterized by X-ray diffraction  with Cu Ka radiation. The pore distribution of geopolymers was analyzed by mercury intrusion porosimetry analysis . 2CO3, it can be attributed to the combined effect of Na2CO3 and NaOH as alkaline activator in preparation of geopolymers. Zhang et al. [2CO3-activated system showed higher compressive and flexural strengths than the NaOH-activated system. When the alkalinity is further increased to higher than 12 mol/L, the proportion of alkali in the spent caustic is much less than that of sodium hydroxide, which has less of an effect on the geopolymer, resulting in a similar strength.g et al.  investigIn order to study the activation effect of spent caustic on the structure of fly ash-based geopolymers, XRD analyses carried out on NaOH-activated geopolymers and spent caustic-activated geopolymers is shown in 29Si NMR spectra of geopolymers synthesized with different alkali activator after 28 days. The Gaussian peak deconvolution of this spectrum can be used to separate and quantify Q4(mAl) species of silicon  [4(mAl) center with the replacement of each aluminum by silicon is an approximate −5 ppm difference in δ, with Q4(4Al), Q4(3Al), Q4(2Al), Q4(1Al) and Q4(0Al) resonating at approximately −84, −89, −93, −99 and −108 ppm, respectively [2 structure in C-S-H gel [29Si NMR date for the samples after deconvolution. For the samples No. 3 and No. 10, a broad peak ranged from −70 to −120 ppm was shown, which is similar to the spectrum of fly ash. It indicated that a large number of fly ash was not activated to form geopolymer gel. Compared with sample No. 10, the content of Q4(4Al) and Q4(3Al) in sample No. 3 is higher, while that of Q4(0Al) and Crystalline silica is opposite. Considering that the Al-rich gel is the primary reaction product of the alkali activation of fly ash [ ≤ 4, m) . The resectively . It was -S-H gel . The pea-S-H gel . Table 3 fly ash , it suggThe porosity and pore distribution of geopolymers with different alkali activators is shown in The measurement of total organic carbon (TOC) was used to quantify the leaching of organics from geopolymers . The org(1)The spent caustic can partially replace the NaOH to synthesize geopolymers, and the organics in spent caustic can be immobilized in geopolymers. The method can not only make the spent caustic harmless, but also utilize the strong alkalinity of the spent caustic to reduce the cost of preparing the geopolymer.(2)When the degree of alkalinity is higher than 4 mol/L, the geopolymers prepared by the mixed activator of spent caustic and sodium hydroxide have better 28 days compressive strength than that synthesized with pure NaOH solution, and the highest strength can reach 21.86 Mpa.(3)With the degree of alkalinity increasing, the immobilization efficiency of organics in geopolymers is improved, and the maximum can reach 84.5%. The organics in the spent caustic will hinder geopolymerization at the initial stage but has little effect on the chemical structure and phase of the final product.In this study, fly ash-based geopolymers were prepared by using spent caustic as alkali activator and the influence of spent caustic on the formation of geopolymers was studied. The result is as follows:


The objective of this study was to investigate errors on death certificates and factors associated with the occurrence of major errors. A retrospective analysis was conducted for six months in 2020 at a university training hospital. Errors were judged as major and minor errors according to the contribution to the process of determining the cause of death. Death certificates were classified into two groups with major errors (ME group) and without major errors (non-ME group). General characteristics of the death certificates, the main cause of death , the number of causes of deaths written on the death certificate, and major and minor errors were investigated. The ME group had 127 cases out of 548 death certificates. The number of causes of deaths written on the death certificates and the total number of errors were higher in the ME group than in the non-ME group. Cardiovascular disease, cerebrovascular disease, digestive disease, respiratory disease, external causes, and other diseases as causes of deaths had higher risks of major errors on death certificates than cancer as a cause of death. The group with cancer as a cause of death had the lowest incidence of major errors and fewer causes of deaths. To reduce major errors, continuous education and feedback are needed for those who are qualified to issue a death certificate. To accurately reflect the underlying cause of death (UCOD) of a patient based on the death certificate only, all relevant information should be recorded. The certifier should not intentionally select some conditions related to the death for entry and reject others. The World Health Assembly has established a common format with guidelines to improve the international accuracy and usefulness of death certificates . Most deNevertheless, errors on death certificates are common worldwide. Korea is no exception ,3,4. SevPreviously, most studies on death certificate errors have focused on general characteristics and the frequency of errors ,18,19,20This study performed a retrospective analysis of death certificates issued at a university training hospital located in South Korea from January 2020 to June 2020. The study hospital was the only university training hospital in a metropolitan city with 1.1 million people. Therefore, more severely ill patients were admitted in the study hospital than in other hospitals of the region. It was approved by the relevant Institutional Review Board. The judgment of errors was first made by three residents in the Department of Emergency Medicine who had received an education on issuing a death certificate, who had experience in issuing a death certificate, and who were currently training in the emergency room. A senior emergency physician who had previous research experience with death certificate errors conducted a secondary review of the judgment of errors. In the case of an ambiguous judgment even after the second review, a final consensus process with four people was carried out. All available medical records, laboratory tests, and radiologic tests were reviewed. A total of 553 death certificates were issued by the hospital over six months (from January 2020 to June 2020). Among them, there were five cases in which the UCOD was unknown or it was difficult to judge the error in the manner of death after the final consensus process. These cases were excluded. Postmortem examination reports of 11 cases during the study period were also excluded. The final error analysis was performed for 548 cases.Errors on death certificates were classified into major errors and minor errors according to the contribution to the process of determining the UCOD  6,7,8,9,23,24,25Major errors were defined as errors that affected the determination of the UCOD, including the following: (1) mode of death such as cardiac arrest, heart failure, or respiratory failure as the UCOD; (2) secondary conditions such as sepsis and esophageal varix bleeding as the UCOD without an antecedent cause of death; (3) ill-defined conditions such as cachexia, senility, symptoms or signs, or abnormal clinical or laboratory findings not elsewhere classified corresponding to ICD-10 codes for R00-R94 and R96-R99 as the UCOD; (4) improper sequence of time between the causes of death, such as aspiration pneumonia for UCOD and cerebral infarction for cause of death; (5) incompatible causal relationships, such as esophageal varix bleeding and cerebral infarction; (6) more than one cause of death on a single line; (7) incorrect manner of death; (8) unacceptable cause of death without evidence of an logical decision, such as pneumonia as the cause of death even though it should have been myocardial infarction; and (9) early-stage cancer as the UCOD in a cancer patient, regardless of the stage.Minor errors were defined as errors that did not directly affect the determination of the UCOD, including the following: (1) mode of death as the cause of death with an appropriate UCOD; (2) a blank line between the causes of death or duplication of the same cause of death; (3) no record for the date of onset; (4) incorrect record for the date of onset; (5) incorrect record for the time of death; (6) incorrect or no record of the time interval; (7) incorrect or no record of other significant conditions; (8) abbreviations, typographic errors, and unnecessary comments; (9) incorrect or no record of the place of death; (10) no record of detailed information for poisoning; (11) no record of poisoning as the UCOD, even if the recorded accident was classified with ICD-10 code V01-Y89; (12) no record of a surgical opinion; (13) no record for the date of surgery; (14) incorrect classification or no records for the type of accident; (15) incorrect or no records for the intention of the accident; (16) incorrect or no record for the time of the accident; (17) incorrect or no record for the place of the accident; (18) incorrect or no record of the trauma mechanism; and (19) no record of the cause of death, even if the trauma mechanism was recorded.As for general characteristics on death certificates, the basic information of the patient present on the death certificate was investigated. The number of causes of deaths listed on the death certificate, the analysis of each detailed error, the number of major and minor errors, the total number of errors, the manner of death , the place where the death certificate was issued, the department that issued the death certificate, and the main UCODs were also investigated. The place where the death certificate was issued was classified into three categories: the emergency department, intensive care unit, and general ward. The department that issued the death certificate was classified into nine categories  in the order of the number of issuances. The main UCOD was classified into nine categories  based on systematic classification with ICD-10 codes. Circulatory diseases and diseases by an external cause of morbidity were subdivided into cardiovascular disease, cerebrovascular disease, and intentional self-harm, and external causes according to the death rank in 2019 published by Statistics Korea . Pneumonp < 0.05. A multivariate logistic regression was then performed using significant factors identified in the univariate analysis. Among different variables, frequent UCODs and departments that issued the death certificate were highly correlated. Thus, only the frequent UCODs were included in the univariate logistic regression. To compare characteristics of death certificates according to the UCOD, death certificates were classified into a cancer group and a non-cancer group, since cancer was the leading UCODs on death certificates with fewer major errors. All statistical analyses were performed with IBM SPSS version 24.0 . Statistical significance was defined as p < 0.05.Death certificates were classified into groups with major errors (ME group) and groups without major errors (non-ME group). The Chi-squared test and Fisher’s exact test for categorical variables and the Mann–Whitney U test for non-normally distributed continuous variables were used to analyze the general characteristics and frequency of death certificate errors. To identify factors related to the occurrence of major death certificate errors, a univariate logistic regression analysis of general characteristics of death certificates was first performed to identify variables with p < 0.001) in the non-ME group. The most common department of issuance was the department of pulmonology (26.0%) followed by the department of emergency medicine (24.4%) in the ME group, whereas it was the department of hemato–oncology (45.1%) followed by the department of emergency medicine (14.3%) and the department of pulmonology (12.6%) in the non-ME group. In the case of the manner of death, 9.4% of deaths in the ME group and 10.0% of deaths in the non-ME group were due to external causes. There was no significant difference in the number of lines filled for the cause of death. In both groups, most had only one line filled for the cause of death. The number of total death certificate errors was higher than the non-ME group (p < 0.001), but there was no difference in the number of minor errors. The main underlying causes of death were other diseases (23.6%) and cardiovascular disease (15.7%) in the ME group. However, cancer (64.4%) was the most common UCOD in the non-ME group . More than one cause of death was listed on 22.8% and 51.9% of death certificates in the cancer group and the non-cancer group, respectively. The number of major errors was 0.2 in the cancer group, which was less than that (0.5) in the non-cancer group (p < 0.001) (There were 290 (52.9%) cases in which cancer was the leading UCOD. They were assigned to the cancer group. There were 258 (47.1%) cases with other underlying causes of deaths. They were assigned to the non-cancer group. The most common place of issuance was the general ward  in the cancer group and the intensive care unit  in the non-cancer group. The most common department of issuance was the department of hemato–oncology  in the cancer group and the department of emergency medicine  in the non-cancer group. The median number of lines filled for the cause of death was 1.3 in the cancer group, which was less than 1.8 in the non-cancer group (< 0.001) .Categories with fewer major errors in the cancer group than in the non-cancer group included the mode of death, secondary conditions, and ill-defined conditions as underlying causes of death, incompatible causal relationships, more than one cause of death on a single line, an incorrect manner of death, and an unacceptable cause of death .Previous studies have reported that major errors occur in more than half of death certificates and that minor errors occur in most death certificates. However, only 23.2% (127/548) of death certificates in this study had major errors. The reason might be because cancer as the UCOD was high at 52.9% (290/548) in the present study, unlike previous studies.Cancer has characteristics that are comparable to those of other diseases. If cancer (whether primary or metastatic) is the focus of care during a relevant episode of health care, it should be recorded and coded as the “main condition” . That isThere was a significant difference in the occurrence of major errors according to the place of death certificate issuance . This seBefore the start of this study, it was thought that there would be a difference in the occurrence of major errors according to the number of causes of deaths listed on the death certificate. However, the multivariate analysis did not show statistically significant results . This miConsidering all these points, he findings of this study support the argument that death certificate errors can be reduced and that the quality of death certificates is improved when the UCOD is cancer ,28. ThusWe found some cases with multiple causes of deaths listed on death certificates, in which major errors did not occur even if the UCOD was not cancer because it was easy to follow up by detailed progress notes during long-term hospitalization. On the other hand, we found some cases in which major errors occurred by listing only the mode of death such as cardiac arrest and unspecified (ICD-10 code I46.9) as the UCOD or listing only secondary conditions such as pneumonia and unspecified (ICD-10 code J18.9) as the UCOD. Despite the fact that the death certificate should have few errors, there is also a lack of awareness of the importance of death certificates. Major errors are inevitable due to the lack of verification systems and feedback after issuance of a death certificate . Many prThis study had several limitations. First, this study targeted only death certificates issued in one training hospital. Thus, there is a limitation in generalizing the results of this study. Considering that distribution of the UCOD is highly variable depending on the issuing institution, in the case of death certificates issued by higher medical institutions, the proportion of cancer listed as the UCOD was high. Thus, the distribution of UCODs should vary when interpreting the results of this study. Second, there might have been differences in the education on death certificate issuance, experience with death certificate issuance, and clinical experience depending on the certifier of the death certificate. However, we did not investigate differences in the certifiers in this study. Third, some studies have been conducted on the presence of death certificate errors for specific cancers ,33. HoweOf all death certificates in this study, 23.2% had major errors. When cancer was listed as the UCOD, there was a lower risk of major errors occurring on the death certificate compared to when the UCOD was a cardiovascular disease, cerebrovascular disease, digestive disease, respiratory disease, external causes, or other diseases, considering the clarity of a diagnosis and accessibility of medical records. It is important to understand the main characteristics of death certificate errors. Continuous education and feedback are needed for those who are qualified to issue a death certificate to reduce major errors.


Adjacent tunnel construction and environmental disturbances can lead to longitudinal deformation in pipe-jacking tunnels. The longitudinal deformation of the tunnel is closely related to the occurrence of joint dislocation, joint opening, and other defects. In view of the difficulty of obtaining 3D longitudinal deformation curves, a method is proposed to obtain 3D longitudinal deformation curves based on a large number of 3D point cloud data with high spatial resolution and large spatial dimensions. Combined with the mechanism of defects occurrence, a theoretical basis for tunnel defects assessment based on tunnel longitudinal deformation is proposed. Taking one pipe jacking tunnel as an example, the longitudinal settlement curve and the 3D longitudinal deformation curve are compared. The correlation between the 3D longitudinal deformation curve and defects such as mud leakage, cracks, and differential deformation is illustrated from the perspective of three indexes: deformation amount, bending deformation, and shearing deformation. The accuracy and reliability of the 3D longitudinal deformation curve in tunnel defects detection and assessment are verified. Different from structures with critical features such as buildings and bridges, tunnel structures are characterized by longitudinal linearity and fractal self-similarity. Proactive assessment of critical tunnel defects becomes a key issue in tunnel inspection-assessment-maintenance . Since tLongitudinal tunnel deformation includes not only longitudinal settlement, but also longitudinal horizontal displacement ,12,13. AFor the detection of tunnel structural deformation, the mainly adopted equipment and methods include total station, static level, distributed fiber optic, and so on. Total station and static levels are simple to operate, have accurate results, and are easy to realize long-term automated monitoring ,20. DistTo address the challenges of accurate detection and assessment of tunnel structural defects, this study proposes a novel method for measuring the longitudinal 3D deformation curve (3D-LDC) of tunnels based on 3D laser scanning point cloud data. The main contents of this study include: (1) the calculation method of 3D-LDC and tunnel structural defects based on 3D laser scanning technology; (2) the comparison analysis of the measured 2D longitudinal deformation curve (2D-LDC) and 3D-LDC; (3) the detection and assessment method of key defects and corresponding index based on 3D-LDC.Pipe-jacking method is one kind of tunnel construction method in soil ground, consists of jacking segmental pipes by means of hydraulic jacks to complete underground network. Due to the segmental structure, there will be joints connecting lining rings. Joints are design to bear the loads and should have the water-proof capacity. However, in the tunnel service phase, which is designed to be 100 or 120 years usually, the soil and water conditions will suffer from the disturbance of adjacent construction or inner evolution. Hence the performance of tunnel structure will be affected and then kinds of tunnel defects will occur.A power transmission tunnel in Shanghai constructed by concrete pipe jacking has a total length of 2780 m. The inner diameter of pipe jacking tunnel is 3000 mm, with the lining thickness of 270 mm and ring length of 2.5 m. Deformation joints were set for every 15 rings in the tunnel. In May 2013, a large disengagement between pavement and the tunnel lining, occurring between 290 m and 310 m from work shaft 9# , was revealed during a field tunnel inspection. The maximum amount of disengagement, up to 80 mm, appeared at 295 m from the 9# work shaft . As well, cracks were found in the concrete pavement. The joint openings between 290 m and 330 m from 9# work shaft . The multilayer composite plate liner had fallen off. At the same time, the longitudinal settlement curve showed that significant deformation had occurred, as depicted in In March 2021, a mud leak was found in the tunnel during inspection. Emergency repairing was carried out using polyurethane, and the leakage had been sealed. Although the sealing was finally completed, the exact location of the mud leakage could not be accurately judged during the repair process due to the obscuration of the mud, which seriously affected the repair efficiency and effect.This subsection descripts the theory of tunnel defect assessment method based on 3D-LDC. The main tunnel defects include deformation-induced cracks and joint failures, as well as consequent water leakage and falling block. The magnitude and direction of displacement, the curvature and normal direction of tunnel axis, and the amount of joint shearing deformation, can be extracted from 3D-LDC, as the indexes for tunnel defect assessment.Geotechnical-structural interaction is the most important factor affecting the structural performance of tunnels. On the one hand, geotechnical loading and unloading will cause displacement of the geotechnical body and structure. In turn, the displacement of the tunnel will change the geotechnical-structural interaction. In addition, the location of the largest tunnel deformation is often where the tunnel is closest to the external loads.tε and curvature κ, the occurrence of cracks can be judged by the magnitude of curvature. The relationship between lining strain and curvature can be expressed as an equation:ty is the distance from the edge of the tensile zone to the neutral axis in the section. Cracks occur when the lining strain exceeds the maximum tensile strain that the lining material can withstand. Similarly, the relationship between lining strain and joint opening angle θ can be expressed as an equation:Cracks, as one of the main tunnel defects, may occur on the tunnel lining structure or on the subsidiary structures inside the tunnel. Cracks on the lining are mainly related to the lining bending deformation. Because of the positive correlation between lining strain The 3D longitudinal deformation of the tunnel is reflected in the joints as opening and dislocation. From mathematical perspective, the integration of the joint opening and dislocation equals the longitudinal deformation. In turn, the differential of the longitudinal deformation at the joint is the opening and dislocation. Failure of the joint may occur when joint opening and dislocation exceed the design capability, resulting in water leakage. Taking the F-shaped joint of the pipe jacking tunnel as an example, the joint failure modes are shown in The Terrestrial Laser Scanner (TLS) can be used to obtain high precision point cloud data. The core technology of the TLS is the LiDAR technique, which is used to obtain the distance of each object point from the lens. The acronym LiDAR stands for light detection and ranging. The laser system produces and emits a beam (or a pulse series) of highly collimated, directional, coherent, and in-phase electromagnetic radiation. When the light reflected by the surface of an object is received, the system can calculate the range by the flight time and acquire the reflectivity of the surface. Regardless of the increasing of the laser’s spot dimension, the scanner records the center of the spot as a point; therefore, the point density is lower than 1 mm even in the maximum distance.The TLS used in this paper is Leica ScanStation P40, of which the technical parameters are shown in i-th and (i + 1)-th stations ; (c) Carry out the 3D laser scanning of the i-th station; (d) Carry out the 3D laser scanning of the n-th station.The data acquisition steps are listed as follows: (a) Determine the station distance and the number of stations n according to the tunnel size and inspection area; (b) Layout the target between the The data pre-processing steps are listed as follows: (a) Extract the target coordinates; (b) Realize the alignment of cloud data from adjacent stations according to the target coordinates; (c) Perform coordinate conversion according to the relationship between the point cloud coordinate system and the world coordinate system; (d) Remove the noise point clouds generated by other objects in the tunnel; (e) Identify the point clouds of the tunnel lining and joints.There are some existing point cloud processing solutions and software, such as Leica Cyclone and CloudCompare, of which the above mentioned pre-processing methods are built-in features. Hence the proposed pre-processing procedure can be carried out feasibly. Related pre-processing methods include target locating, alignment, segmentation of point cloud. The adopted laser scanner offers target coordination with accuracy of 2 mm @ 50 m. Taking CloudCompare, an open source project, for example, the alignment, noise removal, segmentation can be operated in the graphic interactive way, which is easy to conduct. Noise removal will help improve the robust of the following calculation procedure, due to the elimination of disturbance from noise points.u is the displacement of the tunnel center point in the horizontal direction, v is the displacement of the tunnel center point in the vertical direction, and w is the distance from the tunnel center point along the longitudinal direction to the center of the starting ring within the inspection interval.The 3D-LDC of the tunnel can be calculated from the continuously distributed point cloud data of the tunnel. A local coordinate system is established at the tunnel center point, then the longitudinal 3D deformation curve can be expressed as:f(w) and g(w) are linear function, and ua, ub, va and vb are undetermined coefficients. For assembled tunnels such as pipe jacking and shield tunnels, each ring can be divided as one measurement unit. For mountain tunnels, a relatively smaller length can be intercepted as a measurement unit depending on the deformation.Intercepting the measurement unit along the longitudinal direction of the tunnel, the displacement can be approximated as linear to the mileage in a sufficiently small range, and then Equations (3) and (4) can be expressed respectively as:jP within the measurement unit, which can reflect the 3D longitudinal attitude of tunnel. There may be some leftover noise points which are difficult to determine in the pre-processing, due to the limitation of manual operation. Different from direct cylindrical fitting based on least squares only, RANSAC enables the further filtration of leftover noise points. As well, the parameters of fitted cylinder, including coordinates of endpoints and diameter, will also be determined by using RANSAC [The random sample consensus (RANSAC) algorithm is used for cylindrical fitting of point set g RANSAC ,38. The Q1(u1 v1 w1)T, Q2(u2 v2 w2)T and Q3(u3 v3 w3)T are assumed to be endpoints obtained from adjacent measurement units. The estimated curvature in the horizontal plane hκ at Q2 can be calculated as:a1, a2, a3, b1, b2 and b3 are undetermined coefficients, and t12 and t12 are the distance of Q1 to Q2 and Q2 to Q3 respectively. Similarly, the curvature vκ in the vertical plane can be calculated.LDC calculation can be performed based on the results of the above longitudinal deformation calculation. The curvature of the quadratic curve determined by three adjacent axial endpoints is used as the estimated curvature, carried out in the horizontal and vertical planes respectively. Three points θ and the curvature κ is shown as:For the assembled tunnels, the longitudinal rotation of tunnel lining is mainly concentrated at the joints. Therefore, there is approximated correspondence between the joint opening angle and the curvature. In practical applications, the bending deformation can also be characterized by measuring the relative rotation angle between the measurement units. For a certain length of measurement unit, the relationship between the turning angle jQ2(ju2 jv2 jw2)T and Qj+1)1((uj+1)1( vj+1)1( wj+1)1T are assumed to be the endpoint of j-th ring joint (between the j-th ring and the j + 1 − t ring). The horizontal dislocation Δu and vertical dislocation Δv of the j-th joint can be calculated as:The amount of joint dislocation can also be calculated on the same theory. The workflow of proposed method is shown in In this paper, a field experiment has been conducted for the interval with severe tunnel deformation and defects, i.e., from Ring 105 to Ring 153. TLS was used to collect 3D point clouds from Ring 105 to Ring 153, with 5 stations. The pipe jacking tunnel is one type of assembled tunnel with a large difference in stiffness between the joint and the lining, which allows each ring to be assumed as a measurement unit. Programs for data processing are coded in Python. A total station was used for elevation measurement to verify and compare the 3D laser scanning measurement results. The coordinates of reference points were recorded using total station and TLS. The data measured by both methods were converted under the local coordinate system. The local coordinate system was defined as a right-handed spiral coordinate system, with v-axis representing vertically upwards, w-axis representing the tunnel forwarding direction and u-axis representing the right side of the tunnel forwarding direction.Vertical LDP, representing settlement, obtained by using the proposed methods and the total station are compared, as shown in Compared with the traditional tunnel longitudinal deformation measurement method, the proposed method not only has a higher spatial resolution, but also can obtain more dimensional data, i.e., 3D-LDC. 3D-LDC shows that the tunnel is deformed in different directions in space, as shown in Tunnels are buried underground, resulting in difficulty in observing and determining the location of the defect. This section illustrates the accuracy and advantage of 3D-LDC indexes in tunnel defect assessment through the comparison of 3D LDC and vertical LDC.The rotation angle between the measurement units can reflect the longitudinal bending deformation of the tunnel. According to the curvature calculation method mentioned in The joint dislocation is a reflection of the longitudinal tunnel shearing deformation. According to the calculation method of dislocation proposed in (1)This paper verifies the feasibility and accuracy of the proposed method in a pipe jacking tunnel, which has a broad application prospect. However, the number of defects used to validate the proposed method is limited due to the uncommon occurrence of severe defects in tunnel projects in practice. In addition, the 3D-LDC measurement method for tunnels proposed in this paper is theoretically applicable to various structural forms of tunnels, such as shield tunnels and rock tunnels. It can be subsequently verified by testing more engineering practices.(2)A tunnel is a structure buried in rock and soil, and there are hidden surfaces that cannot be measured. As a result, some deformation indexes, such as joint dislocation, are difficult to be measured directly. Therefore, some indexes in this paper have not been verified by other measurement methods.(3)The advantages of 3D laser scanning incldeu fast non-contact data acquisition procedure and a huge amount of acquired data. One station of scanning, which takes less than 5 minutes, will cover tens of meters, depending on tunnel diameter. The non-contact scanning procedure allows the power transmission tunnel to function normally during the detection and assessment. The point cloud data is distributed in three-dimensional space, which is hard to be realized by other methods, such as distributed fiber optic sensors and static hydraulic levels. The whole scanning process is automatic, which is not possible for a traditional method using a total station. The process of 3D laser scanning point cloud data processing, however, is still time-consuming and requires improvement in automatic processing. As well, the measurement method based on a 3D point cloud is to be improved for the measurement of local deformation at the joint.(4)For 3D-LDC, more detailed criteria for disease determination can be proposed through theoretical analysis and numerical simulation, and. The 3D-LDC can also be combined with the information model to visualize the tunnel performance in a more intuitive way.(1)The inspection method proposed in this paper can improve the acquisition efficiency and spatial resolution of tunnel deformation measurement results, and obtain high accuracy of 3D-LDC. 3D-LDC provided in this paper has higher spatial resolution and larger spatial dimension, which includes the spatial deformation data of any part of the tunnel and can obtain various deformation indexes in 3D space.(2)This paper illustrates the mechanism of tunnel disease and longitudinal deformation, and proposes the theoretical basis of 3D-LDC for tunnel disease assessment. The correlation between deformation amount, bending deformation, shearing deformation and tunnel defect in 3D-LDC of tunnels is verified through field experiments. This paper is a guide to the performance assessment based on tunnel longitudinal deformation.(3)Comparing the accuracy of 3D-LDC and 2D-LDC indexes in tunnel defect assessment, it is shown that 3D LDC contains more accurate and comprehensive data and information. The assessment of tunnel defects requires consideration of both horizontal displacement and vertical settlement. Considering only settlement when evaluating tunnel performance may lead to overestimation of the structure performance and misjudgment of the defects.


The article is devoted to the study of the influence of residual sulfuric and phosphoric acids on the process of processing large-tonnage phosphogypsum (PG) waste into calcium carbonate. In the Russian Federation, about 10 percent of existing phosphogypsum waste is processed into construction materials. Acidic impurities (phosphoric and sulfuric acids) in their composition are an obstacle to the use of phosphogypsum for the production of binders. This study finds that impurities also reduce the chemical activity of phosphogypsum. At the same time, the paper focuses on the potential of phosphogypsum for the production of calcium carbonate. This article investigated the amount of impurities in phosphogypsum. The results show that during automatic washing of phosphogypsum, losses are approximately 30–35 wt. %. It was also found that phosphogypsum by 22% consists of impurities of phosphoric and sulfuric acid. These acids are characteristic waste products of extraction phosphoric acid (EPA) production. By ASTM C471M-20ae1, the content of calcium sulfate dehydrate and hemihydrate before and after washing was determined. A thermodynamic calculation of the proposed interaction of phosphogypsum with carbonates showed that the characteristic reaction is possible. The conversion process of phosphogypsum to get the corresponding calcium carbonate was carried out at 70 °C. Data on the chemical composition of the reaction products, obtained by X-ray fluorescence analysis on a Shimadzu EDX-7000 spectrometer, showed that some reactions proceed incompletely and need the selection of optimal conditions. The potential commercial benefits of processing phosphogypsum by carbonization were defined for products such as calcium carbonate or its derivatives. Phosphorus compounds are part of the impurities (phosphoric and sulfuric acids) that give the name to the waste phosphogypsum (PG) or phosphohydrate. However, both secondary material resources are referred to as phosphogypsum when considering transportation, storage and use. From 4.2 to 6.5 tons of phosphogypsum is formed in the process of producing 1 ton of P2O5 to EPA , depending on the quality of the processed phosphate rock .,23.22,23From the calculations, we can conclude that reactions (1) and (2) are possible under normal conditions without heat and pressure increase. Obtaining products by reaction (3) is not so effective, which may be due to the course of side reactions (reaction (4)):Furthermore, atm = 760 mm∙Hg) the change in Gibbs energy is less than 0. The negative value of the Gibbs energy change, ranging from −17 to −58 kJ/mol indicates the possibility of the reaction of formation of calcium carbonate in the decomposition of phosphogypsum.The graph shows that under normal conditions 2CO3 is endothermic and requires additional heat.The change in the enthalpy of the reactions showed that the reactions using NaAfter washing the phosphogypsum, potential titration was carried out. The content of sulfuric and phosphoric acids was calculated from the titration curves. The first point of equivalence corresponds to the neutralization of all sulfuric and phosphoric acids. The second point shows the neutralization of the second hydrogen ion of phosphoric acid. Separate titration of the first and second hydrogen ions phosphoric acid is possible due to a large difference in the values of the ionization constants of phosphoric acid in the first and second steps. This is because the titration results in a one-substituted and then a two-substituted salt of sodium phosphate. The substitution of the third hydrogen ion of the acid occurs without a visible titration jump due to the very small value of the ionization constant ,28,29.The pH of water was measured after each washing procedure. The average values were: 2.45 to 2.67 after the 1st wash; 3.26 to 4.25 after the 2nd wash; 4.25 to 5.26 after the 3rd wash; and 4.83 to 6.6 after the 4th wash. Removal of soluble acid-containing impurities is observed when phosphogypsum is washed with water. Studies show that phosphogypsum storage without washing has a significant negative impact on the environmental situation during heavy rains and snow melting.3—59.89; SiO2—3.17; SrO—2.17. During the study, it was found that the mass ratio of insoluble substances in phosphogypsum practically does not change. According to the obtained data on the chemical composition, we can conclude that only acids are washed out of phosphogypsum.According to the results of the chemical analysis the oxides content was, mass %: CaO—34.89; SO4∙2H2O) and hemihydrate calcium sulfate (CaSO4∙0.5H2O) after washing the phosphogypsum by gravimetrical method.The results from According to the data obtained, it follows that the yield of calcium carbonate directly depends on the content of the remaining acids in phosphogypsum. For the reaction with sodium carbonate (reaction (1)), the content of calcium carbonate in washed phosphogypsum is 1.15 times higher than in acid-containing phosphogypsum. For the reaction with potassium carbonate (reaction (2)), the same value was 1.2 times, respectively.3 ranged from 0.2 to 5 nm for all obtained samples [Examination of the sediment by laser diffraction showed that the coarseness of the CaCO samples .3 particles was also carried out by the method of adsorption and desorption of nitrogen . The BET method showed that the surface area of particles having a diameter of 500 ± 90 nm, is 16.1 m2/g, and the particles themselves are mesoporous [Evaluation of the pore size in the synthesized CaCOsoporous ,33.To confirm the particle size of the obtained calcium carbonate and the completeness of the conversion studies of phosphogypsum  washed from residual acids and the obtained sample of calcium carbonate with particle size fixation were performed .In the course of investigations on a scanning electron microscope, images of calcium sulfate and calcium carbonate crystals were obtained. The needle shape of the crystals corresponds to washed phosphogypsum; the cubic shape of the crystals corresponds to calcium carbonate. In confirmation of the laser diffraction studies, the size of the crystals was measured for calcium sulfate was 3–4 microns, for calcium carbonate 1–2 microns, respectively.2O and SO3 in product 1. Consequently, this reaction requires the selection of optimal conditions for the complete reaction, so that the product of this reaction is marketable CaCO3 and K2SO4. The data obtained from the reaction with sodium carbonate indicate that the reaction proceeded completely. Despite the small amount of Na2O in the calcium carbonate compared to the amount of K2O. Reactions 1 and 3 require the selection of conditions [According to nditions ,35.3) and calcium hydroxide (Ca(OH)2) [The chemical compositions of calcium carbonate determined by X-ray fluorescence are shown in Ca(OH)2) ,36.The basis of the study is the choice of the direction of effective integrated processing of raw materials of man-made origin. The implementation of such solutions contributes to the rational use of the mineral resource base of the country and improves the efficiency of its reproduction, as well as reduces environmental pollution.3, despite the absence of thermodynamic bans. Acidic impurities contained in phosphogypsum reduce its chemical activity because the residues of sulfuric and phosphoric acids also interact with the cations of the introduced carbonates, which prevents the target conversion reaction.Conducting the conversion reaction of phosphogypsum without preliminary preparatory operations showed a low yield of CaCO3 was achieved up to 70.6% in the reaction with sodium carbonate and 65.0% with potassium carbonate. The washed phosphogypsum was analyzed according to ASTM c412M-20ae1 standards by the following methods: photometry, weight loss, etc. The results obtained indicate that the obtained laboratory sample of calcium carbonate can be used in the construction industry and in the paper industry as a bleaching agent.By developing special regimes of washing of initial phosphogypsum it was possible to increase the reactivity of PG by 1.2 times by removing acidic impurities. The yield of CaCOFurther study of the issue of phosphogypsum conversion with obtaining calcium carbonate will have the aim of obtaining calcium carbonate of higher purity.


The adhesion work of asphalt and aggregate oxides was calculated. With the increase of wax modifier content, the adhesion work of asphalt and aggregate oxides (CaCO3 and SiO2) first increases and then decreases. When the wax modifier is increased to 3 wt%, the adhesion works of the WWMA-SiO2 and WWMA-CaCO3 increase by 31.2% and 14.0%, compared with that of matrix asphalt. In this study, the accuracy of the MD calculation result was verified by the pull-off experiments and the contact angle experiments. WWMA was prepared by a high-shear mixer emulsifier. In the pull-off experiments and the contact angle experiments, the tensile strength and the adhesion work between the aggregate and the asphalt containing 3% wax modifier reaches peak values. These values are 140.7% and 124.9%, compared with those between the aggregate and the matrix asphalt. In addition, the results of the pull-off experiments and the contact angle experiments are in good agreement with that of the MD simulation. Finally, Fourier transform infrared spectroscopy (FTIR) shows that the carbonyl content of WWMA is greater than that of matrix asphalt. It explains well that the wax modifier promotes the adhesion between asphalt and aggregate. This paper provides an important theoretical basis to understand the adhesion performance of WWMA and aggregate.Compared with traditional hot mix asphalt (HMA), wax based warm mix asphalt (WWMA) can be mixed with the aggregate at a lower temperature and achieve the desired compaction. However, the adhesion performance of WWMA on aggregate is uncertain. To evaluate the adhesion performance of asphalt and aggregate, researchers used contact angle test, pull-off test, and ultrasonic washing experiments. However, these tests cannot adequately explain the microscopic mechanism of the interface between asphalt and aggregate. Molecular dynamics (MD) can better explain the adhesion mechanism of asphalt aggregates because they can be simulated at the molecular scale. So, the purpose of this research is to use the MD method to study the adhesion performance between WWMA and aggregate. Two aggregate oxides (CaCO Compared with hot mix asphalt (HMA), warm mix asphalt (WMA) can be mixed with aggregate at lower temperatures and reduces energy consumption. The mixing temperature of WMA is usually 20 to 40 °C lower than that of HMA ,2,3,4. WThere are three main methods for producing WMA by use of synthetic or organic additives, which are zeolite ,6, surfaThe adhesion performance of asphalt and aggregate is directly related to the water damage resistance of asphalt pavement . Enhanci2). They found that the adhesion work of phenol molecules and SiO2 is much larger than that of other molecules and SiO2. The above researches show that MD has been widely used to study the adhesion performance of asphalt-aggregate. However, there are few studies on the adhesion performance of WWMA and aggregate by using the MD method.In recent years, MD simulation has been an effective method to study the microscopic mechanism of material components from the perspective of molecular motion. Many researchers have evaluated the adhesion performance between asphalt and aggregate by calculating the adhesion work of the asphalt-aggregate model in MD simulation. Tarefder et al.  used the3 and SiO2) was calculated by MD simulation. Then, the accuracy of the MD simulation calculation results was verified by the pull-off experiments and the contact angle experiments. The Fourier transform infrared spectroscopy (FTIR) was conducted to reveal the chemical mechanism of adhesion performance between WWMA and aggregate.In this study, we studied the adhesion between WWMA and aggregates using the MD method. Twelve different molecules were first selected to represent the asphalt component models. Then, wax molecules were chosen as the wax modifier to construct WWMA models. The adhesion work between asphalt and two aggregate oxides  can accurately simulate the interaction of organic and inorganic molecules. The COMPASS force field has been successfully applied to simulate the adhesion performance of asphalt and aggregate in previous study . The COMThe American Society for Testing and Materials  D4124-09 proposed the SARA  classification scheme. Li and Greenfield . In this3. Then, the asphalt was placed in a periodic cube box. The constructed matrix asphalt model is shown in First, the Amorphous Cell Calculation module in the MS software was used to construct an amorphous asphalt model. The initial density of asphalt was set to 0.1 g/cm11H24. The molecular model of wax is shown in The wax molecular model constructed by Samieadel et al.  was usedThe molar mass of the matrix asphalt model is 32,710.4 g/mol. The molar mass of wax is 156.4 g/mol. A total of 2, 4, 6, and 8, mol of wax molecules were added to the matrix asphalt to construct WWMA models. The WWMA models are shown in The matrix asphalt and WWMA models were geometrically optimized in the Forcite module. In order to minimize the energy of the asphalt system, the asphalt models were subjected to 5000 iterations under the COMPASS force field to achieve geometric optimization. Then, the asphalt models were used for dynamics simulation in the NPT (constant pressure and constant temperature) ensemble and the NVT (constant temperature and constant volume) ensemble for 100 ps to be stable. Finally, asphalt models with stable volume and energy fluctuations were obtained. The asphalt models after geometric optimization and dynamics simulation are shown in 2, CaCO3, Al2O3, MgO, and other components. In this paper, two oxide molecules (SiO2 and CaCO3) were selected in MD simulation. The SiO2 and CaCO3 models are shown in 2 and CaCO3 are listed in Limestone, basalt, granite, diabase, and amphibolite, are mostly used as aggregates. The aggregates mainly contain SiO2 supercell model and the CaCO3 supercell model are shown in In MS, the aggregate model is represented by a supercell. First, the single-cell oxide was cut along the  direction to expose the surface. Then, the Supercell function in the Build toolbar was used to build the supercell model. A 10 Å vacuum layer was inserted in the Z direction of the constructed supercell model. Finally, geometric optimization was used to optimize its structure. The SiOThe asphalt-aggregate interface system was constructed by attaching an asphalt layer to the surface of the aggregate. Then, a 30 Å vacuum layer was placed on top of the asphalt layer. In the MD simulation, the asphalt-aggregate models were first geometrically optimized. Then, the dynamic balance of the NVT ensemble of 100 ps was performed to optimize the structure of the asphalt-aggregate models further. In this study, all the MD simulated temperatures were performed at 298 K, and the specific parameters refer to the literature .MBW) and the adhesion work of the asphalt-aggregate (∇MBE) can be calculated by Equations (4) and (5) [In order to quantitatively evaluate the adhesion strength of asphalt and aggregate, this study calculated the adhesion work of the asphalt-aggregate model. Adhesion work is defined as the energy required to separate an interface per unit area into two free surfaces in a vacuum . The adh and (5) .(4)WMB=A is the contact area between asphalt and aggregate. In Equation (5), ME and BE are the potential energy of aggregate and asphalt at thermodynamic equilibrium, respectively. MBE is the asphalt-aggregate system in thermodynamics potential energy at equilibrium. Since the A of the asphalt-aggregate system is constant, ∇MBE can directly reflect the adhesion work of the asphalt-aggregate system.In Equation (4), In this study, the used 90# matrix asphalt is produced by Maoming Petrochemical Company in Guangdong Province, China. Its physical properties are listed in First, 90# matrix asphalt was heated. Then, 1 wt%, 2 wt%, 3 wt%, and 4 wt%, of wax modifier were mixed with the hot 90# matrix asphalt, respectively. The WWMA were prepared by a high-shear mixer and stirred at a speed of 5000 r/min for 15 min. The WWMA samples containing 1 wt%, 2 wt%, 3 wt%, and 4 wt%, of wax modifier are referred to as WWMA-1, WWMA-2, WWMA-3, and WWMA-4, respectively.3). Then, the limestone cubes and asphalt were placed in an oven at 170 °C. When the asphalt was heated into a fluid state, asphalt was dropped on to the surface of the bottom limestone cube. After the asphalt spreads evenly to the surface of the bottom limestone, the upper limestone was placed on the bottom limestone. When the asphalt sample was cooled to 20 °C, the upper and bottom limestone cubes adhered to the pull head and the marble slab with epoxy glue, respectively. Afterward, the height of the pull head was adjusted until the pull force reading of the pull-off instrument was 0. Pull force was applied to the pull head through the handle until the asphalt breaks. In the breaking process of asphalt, the tensile strength can be recorded by a digital display sensor. The tensile strength of each asphalt sample and limestone was tested in three replicates to obtain an average value.In this experiment, the ZQS6 pull-off instrument was used to measure the tensile strength. The pull-off instrument is shown in σ) of each asphalt sample and limestone can be calculated by Equation (6).dF is the maximum tensile force when the asphalt is broken. A is the contact area of asphalt and limestone cube.The results of the pull-off experiment can directly evaluate the adhesion strength of each asphalt sample and limestone. The tensile strength 0.5. The solubility range of the asphalt models constructed is 17.398–17.697 (J/cm3)0.5 within the reference value range. It shows that the constructed asphalt models can reflect the properties of the natural asphalt from the perspective of density and solubility parameters.The density and solubility parameters of the optimized asphalt models are listed in 3 . After g2 and CaCO3 increased to 248.3 kcal/mol and 271.5 kcal/mol, respectively. Besides, the adhesion works of WWMA-3 with SiO2 and CaCO3 are higher than those of others. This shows that 3 wt% wax modifier improves the adhesion strength of asphalt with SiO2 and CaCO3 most significantly. In addition, it can also be seen that the adhesion work between asphalt and CaCO3 is greater than that between asphalt and SiO2. This indicates that the adhesion strength of asphalt and CaCO3 is higher than that of asphalt and SiO2. This is consistent with the results of previous laboratory measurements [2 is greater than that between asphalt and CaCO3. This indicates that the adhesion strength of asphalt and SiO2 is less than that of asphalt and CaCO3. This is because the adhesion strength between aggregate and asphalt is determined by their atomic interaction force. The atomic interaction force mainly includes Coulomb electrostatic force and van der Waals force [3 is better than that of SiO2. The follow-up of this article will systematically study the adhesion mechanism of asphalt and CaCO3.The adhesion work of each asphalt and two aggregate oxides is shown in urements ,33. The ls force . The inc3 in the Z direction, derived in the MS software, are shown in 3 in 3.In order to explore the adhesion mechanism of WWMA and aggregate, the relative concentration curves of matrix asphalt, WWMA-3, WWMA-4, and CaCOThe tensile strength of asphalt and limestone cube are shown in The surface free energy theory can be used to study the adhesion of asphalt and aggregate ,36. The In According to the measured contact angles of water and glycerin on all asphalt surfaces in θ is contact angle of the liquid on the solid surface. In Equation (8): γ is the indicated surface free energy of the asphalt or limestone.In Equation (7): 2, which is higher than those of other asphalts.The surface free energy parameters of all asphalt samples and limestone are shown in adhesionW) of asphalt and limestone can be calculated by Equation (9) [From a microscopic point of view, the adhesion work is expressed as the energy required to separate the asphalt from the aggregate. According to the dispersion and polar components obtained in tion (9) :(9)Wadhe2. WWMA-3 has a higher adhesion work with limestone than other asphalts. It indicates that WWMA-3 has the best adhesion strength with limestone. The results of the contact angle experiment also verify the accuracy of the MD simulation calculation results.The calculated adhesion works of asphalts and limestone are shown in The FTIR spectra of matrix asphalt, WWMA-3, and WWMA-4, are shown in −1 and 2926 cm−1 is ascribed to the carbonyl group and methylene [3, Ca2+ is positively charged with +2 valence. This may lead to the mutual attraction of carbonyl and Ca2+ to improve the adhesion of asphalt and aggregate. In addition, it can be seen that the relative carbonyl content in WWMA-3 is higher than those in matrix asphalt and WWMA-4. This reveals the inherent mechanism that the adhesion strength of WWMA-3 and CaCO3 is higher than that of matrix asphalt and WWMA-4. Based on the above calculated adhesion work, it can be inferred that the adhesion work between asphalt and aggregate is positively correlated with the relative carbonyl content.The peak at 1745 cmethylene ,42. The 2 and CaCO3) were selected to construct the asphalt-aggregate interface model. The molecular interaction between WWMA-aggregate was quantitatively studied with MD simulation. Pull-off and contact angle experiments verify the simulation result. The conclusions are as follows:(1)2 and CaCO3 increase to the peak values. They increase by 31.2% and 14.0% compared to the matrix asphalt on SiO2 and CaCO3. The pull-off experiments and the contact angle experiments are also in good agreement with that of the MD simulation.In MD simulation, the adhesion work of the WWMA and the two aggregate oxides is larger than that of matrix asphalt and the two aggregate oxides. The adhesion works of the WWMA-3 on SiO(2)The pull-off and contact angle experiments prove that WWMA can increase the tensile strength and adhesion work between the asphalt and the limestone cube. The tensile strength and the adhesion work between the aggregate and the asphalt containing 3 wt% wax modifier reach the peak values. These values are 140.7% and 124.9% compared with those between the aggregate and the matrix asphalt.(3)FTIR reveals that the carbonyl content in WWMA is much higher than that in matrix asphalt. It explains well that carbonyl can enhance the adhesion strength of asphalt and aggregate.This paper uses MD simulation to study the adhesion of WWMA and aggregate. Two typical aggregate oxides (SiOIn this paper, the performances of WWMA are only studied indoors, and field experiments will be a new direction to further prove the accuracy of MD simulation results.