The development, establishment and repair of apical periodontitis (AP) isdependent of several factors, which include host susceptibility, microbialinfection, immune response, quality of root canal treatment and organism'sability to repair. The understanding of genetic contributions to the risk ofdeveloping AP and presenting persistent AP has been extensively explored inmodern Endodontics. Thus, this article aims to provide a review of theliterature regarding the biochemical mediators involved in immune responsesignaling, osteoclastogenesis and bone neoformation, as the genetic componentsinvolved in the development and repair of AP. A narrative review of theliterature was performed through a PUBMED/MEDLINE search and a hand search ofthe major AP textbooks. The knowledge regarding the cells, receptors andmolecules involved in the host's immune-inflammatory response during theprogression of AP added to the knowledge of bone biology allows theidentification of factors inherent to the host that can interfere both in theprogression and in the repair of these lesions. The main outcomes of studiesevaluated in the review that investigated the correlation between geneticpolymorphisms and AP in the last five years, demonstrate that genetic factors ofthe individual are involved in the success of root canal treatment. Thediscussion of this review gives subsides that may help to glimpse thedevelopment of new therapies based on the identification of therapeutic targetsand the development of materials and techniques aimed at acting at the molecularlevel for clinical, radiographic and histological success of root canaltreatment. When microorganisms infect dental mineralized tissues, the components of the immunesystem recognize these invading microorganisms as non-self ,Root canal treatment aims to eliminate the infection of the root canal system (RCS),through the neutralization of the aggressive agents of bacterial origin, by use ofan adequate biomechanical preparation protocol, including the use of irrigatingsolutions and intracanal medication ,,,,,However, the presence of apical periodontitis (AP) is associated with a higherfailure rate after root canal treatment In some situations, it is possible to eliminate the aggressor agent by means of theimmune and inflammatory responses triggered to neutralize/destroy these agents,resulting in the resolution of AP ,,,,Considering the differences in the human DNA sequence, not all individuals have thesame response to a certain stimulus or treatment due to differences in the human DNAsequence, which influence the organism's susceptibility to disease and its responsesto the environment When there is a substitution of one nucleotide for another, occurring the exchange ofa base pair, they are called single nucleotide polymorphisms (SNPs), which are themost common type of polymorphism. This exchange can still affect protein expression,structure and function of a gene ,,Both genetic polymorphisms and mutations can be located in various regions of thegene, such as the promoter region, coding region (exons) and non-coding region(introns). In general, genetic variations in the promoter and coding region are morelikely to modify the function of the gene and consequently alter protein formation.Changes in the coding region may, for example, lead to an amino acid substitution inthe protein sequence, which may cause structural and functional modifications in theprotein and a potential biological effect. Thus, genetic polymorphisms can alterprotein synthesis and cellular function, which may affect the progression of AP,,,,Considering that, AP is a multifactorial disease ,,,,,,,,,,,,,,,,,,,,,In recent years, interactions between genetic polymorphisms and the development,progression and repair of AP have been evidenced in genes linked to inflammation andbone metabolism processes The localized, destructive and progressive infection of mineralized tissues ofthe tooth, dental caries, when untreated can result in implications for thedental pulp In response to infection in the dental pulp and periapical tissues, activation ofinnate immune system cells occurs locally ,,,,,,After the activation of pathogen recognition receptors and the expression ofintra- and extracellular biochemical mediators, the activation of different celltypes occurs. As part of the immune-inflammatory response, neutrophils,macrophages, lymphocytes, plasma cells, dendritic cells and natural killer cellsare recruited to the site of inflammation in order to eliminate the aggressoragent ,,Initially, upon encountering pathogens, tissue macrophages stimulate aninflammatory process via the release of cytokines and chemokines, resulting inthe recruitment and activation of other cells, such as neutrophils and monocytes,,With the progression of AP, there is an infiltration of cellular elements ofadaptive immunity, including the participation of B and T lymphocytes ,,In addition to cellular recruitment, during the inflammatory response, severalbiochemical mediators are released locally with the aim of stimulating thecellular and humoral immune response. Among these inflammatory mediators are theeicosanoids, which are synthesized from the metabolism of arachidonic acid,produced by the action of phospholipase enzymes. Through the action ofcyclooxygenases (COX) or lipoxygenases (LO) enzymes, structural modificationsoccur in the arachidonic acid chain, leading to the synthesis of prostaglandinsand thromboxanes or leukotrienes and lipoxins, respectively ,,,,Pro- and anti-inflammatory cytokines are also important signalers for hostdefense. Cytokines function as messengers and represent a family ofglycoproteins that coordinate biological processes such as embryonicdevelopment, immunity, hematopoiesis and repair ,,,,IL-22 is a cytokine belonging to the IL-10 family ,Cytokines act on different signaling networks and it has been described that TNF-α, IL-17, IFN-γ and IL-1β influence some effects of IL-22 ,,,,,,,,,As a way of controlling the immune response, the host cells have a mechanism toinhibit the exacerbated production of pro-inflammatory cytokines. This processhappens by cytokine signaling suppressor proteins called SOCS-1, SOCS-2 andSOCS-3 ,,,,The main players involved in the resorption process of bone and tooth structures areknown as canonical mediators of osteoclastogenesis and include the nuclear factoractivating receptor NF-kB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG),,The cellular component of bone tissue is comprised of osteoblasts, surface or liningcells (lining cells), osteoclasts and osteocytes. Among these cell types, osteocytesrepresent more than 95% of the cells present and increase in number according to theage and size of the bone ,Thus, another important mechanism in the process of bone remodeling occurs viasignaling by osteocytes. These cells participate in bone formation through theexpression of proteins such as type I collagen and osteocalcin in addition toproteins involved in the mineralization of this tissue such as alkaline phosphatase,,,In root canal infection, microorganisms and their by-products stimulate the localinflammatory response and intense production of proteases that degrade theextracellular matrix and facilitate the resorption process of mineralized tissues,both bone and teeth ,,,In parallel to the disorganization of the collagen matrix in AP, resorption ofinorganic mineralized tissue also occurs from osteoclastogenesis. In this process,monocytes coming from the circulation are recruited by macrophage colony-stimulatingfactor (M-CSF), fuse and form osteoclasts, differentiated cells specialized in theprocess of degradation of bone matrix components ,,,The immune response generated against bacteria or by-products, although it is adefense response, may lead to different degrees of injury to the organism. Ininflammation near bone tissue, for example, there is a close relationship betweenthe mediators of the inflammatory response and the metabolism of mineralized tissue.In periapical injury, pro-inflammatory cytokines stimulate the resorption processand inhibit bone neoformation ,The increased synthesis of prostaglandin E2 in teeth with periapical inflammation isrelated to inflammatory and catabolic (pro-resorptive) changes that occur in AP,Similarly, on the tooth surface, during the process of resorption of dentin andcementum, the presence of dentinoclasts and cementoclasts from the monocytic lineageis observed and present functions similar to those of osteoclasts ,,,The persistence of AP, after root canal treatment, may be related to differentfactors, including aspects of the quality of root canal treatment, such as presenceof root perforations, instrument fractures and quality of root canal filling, aswell as the non-effective removal of microorganisms and their by-products from theRCS, including the external root surface in the form of biofilm ,,,,,,,,,,,,,,,,,,,,,In recent years, understanding the genetic contributions to the risk of developing APand the risk of presenting persistent AP has been investigated From this, we performed a review of the literature, regarding the influence ofgenetic components on AP. The search strategy included the terms “geneticpolymorphisms” AND “apical periodontitis”, was performed in October 2021, onPUBMED/MEDLINE database, and only studies written in English were selected. Theinclusion criteria include studies that evaluated the association between geneticpolymorphisms with the development, persistence and clinical signs and symptoms ofAP, performed in the last five years. From a total of 46 studies, 14 were includedand their main outcomes were represented in ,,,The differences in the outcomes obtained by these studies, is explained by the factthat functional effects of genetic polymorphisms are dependent of the region of thegene that occurs the exchange of a base pair ,,It is noteworthy that these studies are still controversial regarding methodologicaland sampling variables, from the point of view of disease, treatment, and ethnic andindividual factors Genetic polymorphisms in genes related to the host immune response, as well as genesinvolved in bone repair mechanisms, are involved in the individual's response totreatment and may in the future serve as biomarkers in clinical practice. Moreover,the knowledge regarding the cells, receptors and molecules involved in the host'simmune-inflammatory response during the progression of AP added to the knowledge ofbone biology, especially the role of osteoblasts, osteocytes and osteoclasts in boneturnover allows the identification of factors inherent to the host that caninterfere both in the progression and in the repair of these lesions. This may helpto glimpse the development of new therapies based on the identification oftherapeutic targets and the development of materials and techniques aimed at actingat the molecular level for clinical, radiographic and histological success of rootcanal therapy.


Visual impairment is the most common clinical feature of cerebral venous sinus occlusion or cerebral venous thrombosis-induced intracranial hypertension, which can result in optic atrophy, leading to irreversible vision loss, visual field defections, and finally, permanent blindness. Papilledema is a typical early pathophysiological alteration in visual impairment. Optic nerve sheath fenestration (ONSF) has become increasingly accepted as an option to prevent or halt progressive visual loss owing to its low risk and complications. The objective of this study is to review the latest research progress on ONSF for the treatment of visual impairment related to cerebral venous diseases.Study were searched following PRISMA guidelines based on three electronic databases . We used the following keywords and variations as keywords to identify studies: “optic nerve sheath fenestration, papilledema, cerebral venous diseases, cerebral venous stenosis, cerebral venous thrombosis, idiopathic intracranial hypertension”. The publication date of studies was restricted between 1,872.1.1 and 2,021.12.31. The application of ONSF in papilledema due to cerebral venous diseases is reviewed. Additionally, the common surgical approaches as well as advantages and disadvantages are also described graphically.With the improvement of specific details of the ONSF procedure and surgical instruments, complications of ONSF have reduced and its safety has been significantly improved, although the number of clinically investigated cases in the literature remains low.We recommend that ONSF should be considered as an imperative alternative to reduce or delay the visual morbidity of cerebral venous diseases, although there is yet no consensus on the optimal surgical timing. Proper functioning of the brain relies on coordination of the functions of the arterial and cerebral venous systems. A disturbance in the cerebral venous return can lead to a wide range of neuropathological insults, including cranial hypertension, blood-brain barrier breakdown, abnormal cerebrospinal fluid circulation, impaired glymphatic system function, and hemodynamic disturbances. Causes of cerebral venous reflux disorders can be classified as thrombotic and non-thrombotic: thrombotic disorders include cerebral venous thrombosis (CVT), whereas non-thrombotic disorders include cerebral venous sinus stenosis (CVSS).The cerebral venous circulation consists of a superficial venous system and a deep venous system, both of which eventually drain into the right atrium CVT is a specific type of cerebrovascular disease characterized by disturbed cerebral venous return and cranial hypertension, which presents clinically as headache, visual impairment, seizures, and focal neurological dysfunction , 2. CVT The clinical manifestations of cerebral venous sinus thrombosis (CVST) are complex and heterogeneous. Blockage of the venous sinus by thrombotic tissue leads to an increase in pressure and venous dilatation in the distal sinus and at the same time, a decrease in cerebral perfusion pressure. These pathological changes can lead to insufficient local perfusion of brain tissue, tissue hypoxia, and reduced cerebrospinal fluid (CSF) absorption, and finally, venous infarction and high intracranial pressure , 10. In Cerebral venous stenosis is a cerebrovascular disease characterized by disturbed cerebral venous flow return. Based on the location of the lesion, it can be divided into cerebral venous sinus stenosis (CVSS) and internal jugular vein stenosis (IJVS). The mechanism of the generation of CVSS is as follows: (1) Endotype: malformation of the venous sinus wall . The emergence of anatomical variations of the venous sinus wall (venous partition and blind pouch structures), result in a decline in venous compliance and capacity. Stagnation of blood flow or an excessively fast flow rate can thus be produced, eventually leading to an increase in the intravenous pressure and subsequently to an increase in intracranial pressure; (2) Exogenous: is mostly found in patients with self-limited venous sinus collapse caused by increased CSF pressure and extrusion of the intracranial space; however, the etiology remains unknown .Obstruction of venous return by venous sinus stenosis causes increased venous sinus pressure distal to the stenosis, which in turn results in malabsorption of the CSF and increased intracranial pressure. Magnetic resonance imaging identified venous sinus stenosis is up to 93% of patients with idiopathic cranial hypertension (IIH) . HoweverRegarding the causes of visual impairment in CVT patients, the site of embolization was divided into two types: (1) Focal brain injury due to cortical vein thrombosis: focal cerebral edema (including vasogenic edema and cytotoxic edema), cerebral infarction, and intracerebral hemorrhage, which occurs in the visual center of the occipital cortex and will cause visual field defects; 2) Intracranial hypertension due to dural sinus thrombosis: Normally, the CSF drains through the arachnoid granulation located in the sagittal and transverse sinuses; however, dural sinus thrombosis can disrupt this buffering mechanism, resulting in increased venous pressure, decreased CSF absorption, and increased intracranial pressure. The patient's excessive intracranial pressure can involve the third, IV, and VI cranial nerves to cause diplopia and also directly causes optic nerve damage  recanalization by local thrombolysis, stenting, or mechanical devices; (2) cerebrospinal fluid diversion procedures such as ventriculoperiotoneal shunting; and (3) specific treatment for conditions such as dural arteriovenous fistula (DAVF) occurring as a late complication –21. HowePatients with ocular symptoms and signs despite maximally tolerated medical treatment, ONSF is an effective and safe surgical option for the treatment of papilledema due to CVT/CVSS after medical treatment has failed . ONSF isExcept for cerebral venous diseases, ONSF is widely applicated in papilledema due to IIH, cryptococcal meningitis, chronic inflammatory demyelinating polyneuropathy, intracranial mass or tumors, shunt malfunction –27. AlthAt present, there is no consensus on the timing of ONSF surgery. However, strict follow-up and timely ONSF are important to prevent irreversible visual impairment.ONSF was first reported and proposed by De Wecker in 1872 adapted in neuroretinitis. In 1964, Hayreh et al. successfully made an animal model of intracranial hypertension, implemented ONSF in this animal model and eliminated papilledema after surgery. In 1988, Brourman et al. believed that ONSF was the preferred surgical method to maintain or improve visual function in patients with IIH. In 1991, Sergott et al. first applied ONSF to the treatment of CVST and concluded that the prognosis was closely related to the intervention time. In 2005, Cunha et al. reported a case of chronic intracranial hypertension secondary to multiple cerebral venous thrombosis, after ONSF treatment, papilledema eliminated, but visual acuity continued to deteriorate. In the following years, several authors such as Nithyanandam, Murdock, and Moreau successively published original articles on the application of ONSF for cerebral venous diseases. And the development of history of ONSF as a treatment for intracranial hypertension is presented in There are many surgical routes for ONSF, including the transconjunctival approach, transcranial route, and transnasal approach. According to a 2015 survey of ophthalmologists who performed ONSF , the thrThe physician makes an incision on the bulbar conjunctiva along the nasal limbus of the affected eye, bluntly separates the bulbar conjunctiva and fascial tissue, and exposes and separates the medial rectus muscle. The physician makes a traction suture and pulls the eyeball against the temporal side, deflects, pushes the periocular and retro-orbital fat against the nasal side, and fully exposes the optic nerve sheath and posterior ciliary vessels and nerves. Finally, the optic nerve sheath is incised to drain the CSF, the rectus muscle is repositioned, and the conjunctiva is sutured . ThroughThe physician makes an incision in the skin and orbicularis oculi muscle along the medial upper palpebral fold, uses sutures to secure the margins, bluntly separates the medial fat in the upper eyelid, exposes the optic nerve sheath, and incises and drains the CSF . The traThe physician creates a 1-cm lateral canthal incision, uses sutures to secure the lateral rectus muscle by traction under the lateral rectus muscle, and separates the overlying periosteum superiorly and inferiorly at the lateral margin. During the operation, the physician aims to expose the patient's near orbital rim eyeball, lift the deep lacrimal gland, expose the optic nerve sheath, and make an incision . Using tThe physician uses nasendoscopy to pass through the nostril, resect part of the middle turbinate of the patient, expose the uncinate process and ethmoid bullae of the patients' maxillary sinus, and incise the lower 1/3 of the maxillary sinus to expose and enlarge the maxillary sinus to prevent mucous cyst formation. Then, the physician resects the ethmoid and sphenoid sinuses, revealing the patients' sphenoid plateau and sellar base, identifies the optic nerve carotid crypts as well as the optic nerve bulging, and then chisels the medial and superior wall of optic nerve canal and makes an incision from medial to lateral . The advvia Dolenc. The patient takes the supine position, and the head is rotated to the contralateral side by 30 degrees and is fixed using a head frame so that the supraorbital rim and zygomatic arch junction are at the highest point. The physician cuts the patients' scalp and temporalis muscle hierarchically, generating a free bone flap. The physician resects the sphenoid crest and part of the orbital roof of the patient under the microscope, cuts the dural sheath transversely through the supraorbital fissure, and uses an ultrasonic aspirator to separate the two-layered dural gaps in the lateral wall of the patient's cavernous sinus. The physician grinds off the patients' anterior bed process and continues with the abrasive decompression along the optic column to the sphenoid bone to decompress the patients' optic nerve at 270 degrees from superior, medial, and inferolateral. The physician then incises the patients' optic nerve sheath, which, together with the drilled bone, forms a channel for CSF outflow, and the fistula in this way communicates with the overlying muscles and the frontal and temporal lobes for systemic absorption  can achieve the purpose of decompression of the optic nerve sheath, with few complications , 51–56. With the improvement of specific details of the ONSF procedure and surgical instruments, complications of ONSF have reduced and its safety has been significantly improved. Although the number of clinically investigated cases in the literature remains low and there is a lack of controlled studies, the available studies are sufficient to suggest that ONSF can be used to prevent, or even reverse, visual impairment in patients with cerebral venous diseases, especially in patients who fail to respond to other treatments and still have progressive visual loss. Operation time is essential to save the patient's visual function; the earlier the operation time, the less damaged the optic nerve, and the greater the likelihood of recovery of visual function. Therefore, scholars are actively studying the optimal surgical timing of patients. In addition, it is necessary to develop a screening model for the patient's suitability for surgery. Furthermore, while pursuing improvements in visual function, we should actively search for a cause, cooperate with other regimens, and allow patients to receive timely and appropriately effective treatment.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Depression is a common psychiatric disease caused by various factors, manifesting with continuous low spirits, with its precise mechanism being unclear. Early life stress (ELS) is receiving more attention as a possible cause of depression. Many studies focused on the mechanisms underlying how ELS leads to changes in sex hormones, neurotransmitters, hypothalamic pituitary adrenocortical (HPA) axis function, and epigenetics. The adverse effects of ELS on adulthood are mainly dependent on the time window when stress occurs, sex and the developmental stage when evaluating the impacts. Therefore, with regard to the exact sex differences of adult depression, we found that ELS could lead to sex-differentiated depression through multiple mechanisms, including 5-HT, sex hormone, HPA axis, and epigenetics. Major depression disorder (MDD) affects 17% of the population worldwide as a significant cause of disability . DepressEarly life stress is defined as a series of adverse, stressful events occurring during the neonate, childhood, and adolescence period , includiThe incidence rate of depression differs among different sexes. Before the stage of adolescent transition, the incidence of depression between both sexes is similar and relatively low, with about 3% of the children qualifying the diagnostic criteria of MDD over the past year . However5-HT is an essential neurotransmitter in emotional regulation whose function is mainly to regulate functional activities in the central nervous system, such as pain and analgesia, mental mood, sleep, body temperature, sexual behavior, pituitary endocrine, cardiovascular regulation, and somatic movement . A few sSerotonin transporter (5-HTT) is one of the critical regulators of serotonin neurotransmission , with thThere is sex dimorphism in the serotonin system. First of all, compared with women, men show higher rates of 5-HT synthesis , a signiThe animal models of ELS used in the studies include maternal-infant nesting (MS), limited nesting, and the bedding material paradigm, and the study results also varied according to the animal type, pattern-making method, and the brain area detected. There have been a series of studies on the relationship between depression and sex hormones, and the studied hormones include estradiol, testosterone, rostenedione, estrone, 5β-dihydrotestosterone, etc. Lower estrogen levels in women and lower testosterone levels in men both could increase the risk of MDD . The funAs for the treatment of MDD in humans, a large number of clinical trials have been conducted on the application of gonadal hormones, such as estrogen replacement therapy (ERT) or hormone replacement therapy (HRT = estrogen + progestin) for perimenopausal or postmenopausal, testosterone for depression symptoms in patients with HIV and AIDS, etc. . TreatmeThe effects of PNS on plasma sex hormones in male and female rodents were manifested as the decrease in the estradiol and testosterone in female rodents and the increase in testosterone in male ones. Postnatal early stress has no effect on estradiol levels in female rats, and the effect on testosterone in males is inconsistent. Sex hormones can produce effects on psychiatric disorders by enhancing the release of DA in the reward system and helping the sex differentiation in the brain .Failure of rodent ELS models to replicate the effects of sex factors may be associated with the insensitivity of rodents to behavioral measurement methods and the susceptibility of female rodents in different stages of the estrous cycle . These eAggravation/remission of anxiety/depression after sex hormone injection: The HPA axis comprises the hypothalamic PVN, adenohypophysis, and adrenal cortex. PVN is the central part of the neuroendocrine axis. Its ascending fibers are connected widely with the amygdala complex, hippocampal formation, and marginal cortex of the limbic system. Its descending nerve fibers control the release of pituitary ACTH through CRH to regulate the synthesis and secretion of adrenal glucocorticoid (GC) . HPA axiThe fetal hypothalamus begins to form soon after the appearance of the hypothalamic sulcus in the 32-day embryo. The hypothalamus and pituitary portal vein systems develop mainly during the third trimester of pregnancy. Along with the ninth month of gestation, the maternal-placental – fetal steroid-producing unit activates the fetal HPA axis. CRH secretion by the placenta is related to the length of pregnancy. With the approach of delivery, CRH in maternal plasma increases and reaches its peak at delivery. Human placental CRH production may have evolved to stimulate fetal ACTH release and adrenal steroidogenesis, thus satisfying the high demand for synthesis of dehydroepiandrosterone (DHEA), the predominant source of placental estradiol (E2) .Hypothalamic pituitary adrenocortical axis excitation after stress can produce central effects, such as depression, anxiety, and anorexia. These effects are mainly caused by the increase of CRH secretion. During stress, the CRH neurons of PVA have a dense nerve fiber connection with the central nucleus of the amygdala complex. From the seventh month of pregnancy or earlier, the fetus can secrete CRH and ACTH  after maAfter controlling factors such as trauma type, severity, and post-traumatic support, women who experienced ELS were more likely to suffer from PTSD than men . ElevatePrevious studies have shown that early damage will affect the function of the HPA axis, such as the decrease of CRF and ACTH in animal models exposed to inflammatory pain and the decrease of the serum corticosterone level in male rats during recovery. Besides, ELS was related to the higher level of basic CRH, increased apoptosis of PVN , increasPatients with MDD with childhood trauma (CT) have a low baseline cortisol level, together with reduced ACTH levels at the baseline and Trier Social Stress Test . PS causBefore birth, GRmRNA expression in hippocampus, mPFC, amygdala, PVN, and anterior pituitary is lower than those in adults , so the A study in Dutch showed that children with CT had a significantly higher level of cortisol arousal response and cumulative HPA axis markers than those without CT . Nia FogDuring estrus, plasma and adrenal CORT were the highest in the ovarian cycle, suggesting the relationship between the ovarian hormone and HPA activity. Both PVN injection of estrogen and ERα agonists could increase the levels of GC, while injection of antagonistic agents was on the contrary. These results indicated that E2 could reduce the negative feedback effect of HPA through ERα . At the Gene–environment interaction plays a vital role in mental diseases, and is also a research hotspot. ELS affects epigenetic modification, including DNA methylation, post-translational histone modification , and non-coding RNA. These modifications are stable, inducible, and reversible, which is why short-term environmental stimulation leads to lasting changes in gene expression and behavior . In the Previous studies have shown that the inhibition of negative feedback on the HPA axis can be completed by GR, which is a kind of an intracellular receptor regulated by a series of chaperone proteins . The mosFirst, FKBP5 gene variation and ELS may increase the risk of emotional disorders, resulting in a series of behavioral phenotypic abnormalities. Rs160780 of the FKBP5 gene has significant interaction with childhood adversity in brain white matter integrity involved in emotional processing . In a meDNA methylation is a kind of epigenetic modification, in which methyl is added to the cytosine of DNA sequence. It is usually related to the inhibition of gene expression, but, in a few cases, the expression would be increased . It can There are few studies exploring the relationship between DNA methylation and non-coding RNA related to histone modification and depression in humans, so the relationship between histone modification and non-coding RNA and depression is still unclear. Many animal studies have shown that mRNA expression of histone deacetylases (HDACs) 1, 3, 7, and 8 decreased, while the expression of acetylated histone H4 protein increased in the prefrontal lobe of MS mice. The increase of HDACs expression was observed in the VTA of MS rats , while tIt is indisputable that epigenomes have sex duality in many mechanisms in the development and the whole life cycle. It has been reported that there are sex differences in the expression of MeCP2, Gadd45b, and Dnmt3a in the amygdala of developing rats in the expression of MeCP2 in the ventral center of the hypothalamus and preoptic chiasma of developing rats, and in the methylation of steroid receptors in the brain region of sex duality. It is reported that different kinds of maternal care could lead to the difference in methylation patterns in the offsprings of adult male rats . It is rMicroRNAs also play a subtle role in enhancing gene expression by reducing rather than eliminating specifically targeted mRNA transcripts, which may also be involved in the development of mental disorder through gene dysregulation involved in specific disease-related processes . PS can Except for epigenetics, the genome itself may directly lead to sex differences in neurotransmitters and behavior after stress . After eIn addition, BDNF, NPY, TNF, and inflammatory factors have been reported to be involved in ELS-mediated depression regulation . The expEarly life stress can cause depression in childhood or pre-puberty, and the depression is sex specific. The mechanisms underlying the difference between different sexes are that there is sex duality in the serotonin system in 5-HT synthesis rates, 5-HT metabolite levels, receptor- and transporter-binding potentials, SSRI responses, and tolerance. The methylation levels of the 5-HTT gene are different between men and women. Moreover, E2 might be helpful to increase the level of 5-HT and the expression of the 5-HT receptor. Besides, there are sex differences in CRH expression caused by severe trauma, in HPA axis function after stress, i.e., a trend of plasma CORT and its receptor. In addition, FKBP5 can enhance the activities of ER and AR. Furthermore, FKBP51 can negatively regulate ERα through chaperone protein interaction. There are sex differences in the expression of a variety of proteins or enzymes that affect epigenetics. BDNF, NPY, and TNF have been reported to be involved in the regulation of depression mediated by ELS, showing sex differences, too. The paper highlights the important role of ELS in human mental health and helps to screen possible clinically effective anti-depression targets, which will help promote the healthy development of children and adolescents.XA and WG wrote the first draft. HW, XF, and ML provided writing reviewing and editing. YZ, YL, and RC provided conceptualization of ideas. WY, ZZ, and GZ provided supervision. All authors approved the final version of the manuscript for submission.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.


As a natural linear polysaccharide, alginate can be gelled into calcium alginate fiber and exploited for functional material applications. Owing to its high hygroscopicity, biocompatibility, nontoxicity and non-flammability, calcium alginate fiber has found a variety of potential applications. This article gives a comprehensive overview of research on calcium alginate fiber, starting from the fabrication technique of wet spinning and microfluidic spinning, followed by a detailed description of the moisture absorption ability, biocompatibility and intrinsic fire-resistant performance of calcium alginate fiber, and briefly introduces its corresponding applications in biomaterials, fire-retardant and other advanced materials that have been extensively studied over the past decade. This review assists in better design and preparation of the alginate bio-based fiber and puts forward new perspectives for further study on alginate fiber, which can benefit the future development of the booming eco-friendly marine biomass polysaccharide fiber. The me, et al. d 51]. T. T2 aque the MST .The microfluidic spinning device not only can be used to fabricate the alginate microfiber with various structures but also offer the fiber with different functions by the addition of a bioactive small molecule substance, making it an ideal candidate for controlled release as the biomimetic material. Some other works have incorporated the bioactive substance such as the protein or cell in alginate solution to fabricate the multi-functional alginate fiber with various micro-structures including the flat, hollow and grooved anisotropic structure via the MST, that was used as the micro-vascular application in the field of tissue engineering ,52,53. E2) solution combined with the indissolvable calcium salt solution to reduce free calcium cation concentration. Some other scholars chose other metal cations with better gelation ability to tune the ion exchange rate with alginate polymer, which retarded the Ca–Na cross-linking rate and achieved the homogeneous structure of metal-alginate fiber, following the order of the metal ion exchange rate: Pb2+ > Cu2+ > Cd2+ > Ba2+ > Sr2+ > Ca2+ > Co2+ ≈ Ni2+ ≈ Zn2+ > Mn2+ [Calcium alginate fiber and its nonwoven fabric are ideal materials in the field of textiles due to the abundant marine resource and being environmentally friendly. Among them, the mechanical performance of fiber is the focal spot, which directly affects its range of application. The well-known setback of alginate fiber fabricated by different techniques is the formation rate is too fast to control, resulting in uneven structure in the fibers. The prevalence of structural defects of fiber can easily cause stress concentration and lead to fiber failure. A slower gelation and formation rate is an effective method to optimize the fiber structure and improve mechanical performance. Based on this, some researchers have resorted to a calcium salt composite solution with different solubility by choosing the compound coagulation bath system to retard the formation rate of fiber . That wa+ > Mn2+ . These wWhile the above works succeed in retarding the formation rate of fiber by reducing the Ca–Na ion exchange rate, and decreasing the uneven structure in the fiber, the prolonged formation time caused another problem, delamination between the core and sheath layers of fiber. Some other researchers focused on the incorporation of reinforced materials in the spinning solution, which helped to strengthen the cross-linking interaction between the fiber molecular chain. The popular doping additive materials include the hydrophilic polymers such as collagen ,57, chitHence, to eliminate the defect in fiber, it is significant to investigate and disclose the formation mechanism of fiber. What is more, the impact of defects on fibrous mechanical performance is also needed to be further studied. Controlling the formation rate and improving the uniformity of fiber is the key to enhancing fibrous mechanical properties.Alginate is one of the most preferred biomaterials as an abundant natural biopolymer, which was approved by the United States Food and Drugs Administration ,67. CalcS. aureus bacterial infected wound, and the histological analysis indicated that the alginate fibrous scaffold acted a positive effect on the acceleration of wound healing [The alginate fiber has excellent moisture absorption capacity, which can absorb 10 times more than its own weight of water ,71. Its  healing . The hea2+ by the supramolecular interaction sites to achieve outstanding inherent flame retardancy, because of the inert metal ions during the heating. Calcium alginate fiber as a common alginate-based material exhibited excellent intrinsic flame retardant properties due to the presence of calcium cation and abundant oxygen atoms in its molecule, as displayed in 2) gas and gaseous water vapor in burning, which cover the fiber surface and then impede the penetration of oxygen (O2) and the heat, which will effectively retard the further combustion. Furthermore, the heat release rate, the total heat release, the smoke production rate and the total smoke production of the calcium alginate fiber are far less than other materials in the whole burning [Alginate can cross-link with most of the divalent or trivalent metal ions such as Ca burning , making Xia et al.  and Zhu The treatment of acute and chronic wounds with inflammation caused by burns, scalds or the complications of chronic diseases, is an urgent medical need ,76,77. TAlginate wound dressing can appear in the form of a hydrogel, fiber, nonwoven fabric, freeze-dried scaffold and foam, all of which are prepared by Ca–Na ionic cross-linking interaction. Calcium alginate fiber or the corresponding nonwoven fabric employed as a kind of typical wound dressing, can absorb the wound exudates and then formed gel to keep the wound wet. That provided a safe, sealed and physiological microenvironment, and minimized the bacterial infection possibility around the wound. Furthermore, the hypoxia microenvironment stimulates angiogenesis and facilitates cells to secret the growth factor, which promotes the new granulation tissue formation and accelerated wound healing . HoweverStaphylococcus aureus and methicillin-resistant Staphylococcus epidermidis, displaying an outstanding antibacterial ability. The results of in vivo microbiological and histological analysis illustrated that alginate dressing containing the functional addition facilitated the migration of human dermal fibroblasts and human umbilical vein endothelial cells, which stimulated angiogenesis and accelerated wound healing. In addition, Vieira et al. [For enriching the function of alginate fiber dressing, many works have combined alginate with some special therapeutic effects of drugs , variousa et al.  immobiliThe other major application of calcium alginate-based fiber is tissue engineering scaffold, as a cost-effective material for cell immobilization and encapsulation. Compared to the wound dressing, the tissue engineering scaffold has additional requirements such as serving as an extracellular medium matrix to support cell growth, migration, differentiation, and eventually cell normal function. Multiple pieces of literature reported alginate hydrogel serving as the tissue engineering scaffold, in a bulky form , or as aThere are a few challenges that remained. Though the microfluidic spinning technique described above was used by several reports as the bioactive scaffold, the general problem of micrometer-diameter fiber is that the space between them is too large for cells, which may require extra time for the cell to fill the space. People turn to electrospinning to reduce the diameter of the fiber to match the cell size. However, there are more challenges, particularly for alginate in electrospinning. Alginate is an ionic polymer that hydrolyzes in water to increase its conductivity, making the solution extremely difficult to electrospin because of the risk of a power surge. Moreover, its lack of shear strength in the sodium salt form and being too dense in the calcium salt form makes it difficult to electrospin. Additionally, there is a very limited choice of solvents because of the hydrophilic nature of the alginate molecule, leaving the only choice to be water with a high boiling point. Many researchers overcome this problem by adding other water-soluble polymers to help overcome mentioned problems. Commonly used polymers include PCL , chitosa2+, Mg2+ and Cu2+. Those bivalent charge cations can replace calcium without destroying its gelation property. For example, calcium can be replaced with copper cations [As a tissue engineering fiber, the alginate was used to carry different drugs to facilitate the regeneration speed, including small chemical drugs, nucleic acid  and prot cations . A small cations ,98.With the development of smart materials, some researchers used the active groups of alginate molecular chains such as -OH and -COOH groups to cross-link with polymers to obtain special intelligent response performance. The covalent compounds such as polyacrylamide or poly  were incorporated into the alginate molecular chain to introduce the covalent bond for fabricating the highly stretchable fiber strain sensor utilization as the ionic skin, wearable and implantable sensors for innovative electronics ,100. TheWith a tightening low-carbon policy, bio-based materials have received more attention than petroleum-based materials. The commercial fire-resistant materials receive flameproof treatment by using halogen or phosphorus-based flame retardants. However, the fabric treated by the fire-retardant finishing will release some toxic volatile gaseous compounds in the thermal degradation process, which is harmful to human health and violates the eco-friendly concept. What is more, the flame retardancy of that fabric is not durable, decreasing with the increase in usage times. Therefore, the bio-based flame-resistant material has become a research hotspot due to its sustainability, environmental friendliness and recyclability, such as protein, chitosan, DNA, starch, phytic acid and so forth. Among them, the abundant marine material has been widely used to prepare film ,107, hyd2 and smoke production rates of the alginate fiber in burning were very little, which was in accordance with a low carbon concept [The environmentally sustainable flame retardants for textiles and inherently flame-retardant fiber materials thereby have become mainstream. There were some reports that illustrate that the toxic gaseous compound including CO, CO concept ,117. Rec concept . The alg concept . The mixHence, it is urgent to eliminate the smoldering combustion behavior of alginate fiber and the simple mixture of other synthetic fibers is not a good strategy. The molecular chain of alginate fiber displays a good deal of active groups, which can be easily modified and grafted with the corresponding groups to optimize the flame retardant property of alginate fiber in the future.Compared to the numerous research and review articles on alginate hydrogel, a review on fabrication, physicochemical performance and application properties of alginate fiber is very rare, resulting in the lack of corresponding knowledge. Nevertheless, alginate fiber, as a family of emerging advanced functional materials, has demonstrated great utility and potential, particularly in the wound healing, tissue engineering and flame retardancy fields. The most attractive features of alginate fiber for these applications are attributed to its excellent moisture absorption performance, biocompatibility and intrinsic flame retardant property. Therefore, this work mainly summarized the fabrication of alginate fiber and compared their respective characteristics, and then analyzed the corresponding application properties.As a wound dressing or tissue engineering scaffold, alginate fiber has a track record of clinical safety and was safely implanted in various hosts including the islet transplantation for treatment of type 1 diabetes, chondrocyte transplantation for treatment of urinary incontinence and vesicoureteral reflux, and the infected wound transplantation for healing of the inflammatory. Although, alginate fiber is widely used in the field of biomaterials and is likely to evolve considerably. It already plays a fairly passive role during treatment due to a shortage of multi-functions. Future dressing or tissue scaffold will likely play a much more active role, which requires the material itself to cure and accelerate the wound healing or repairing impaired tissue in the host. One or more bioactive agents such as proteins, DNA, antibiotics and other polymers that reduce inflammation and promote bone growth, can be incorporated into the alginate fiber as a facile and efficient method to endow it with a multi-functional design, which has been proven to be the future trend.In addition, the alginate fiber as a burgeoning bio-based flame retardant material has proven to be the future trend, due to the rare limited significant toxicity combustion product and the intrinsic eco-friendly behavior. However, the decrease in its minor afterglow profile and the enhancement of mechanical properties is an urgent need before its widespread application in the fireproof construction and building field. As one looks to the future, the elimination of fibrous structure irregularity is the future development. For addressing the hurdle of the afterglow behavior of alginate fiber in burning, the grafted modification of the alginate molecular chain is probably a new and efficient strategy. In conclusion, alginate fiber as a novel eco-friendly bio-based material was proven to have a broad application prospect in the biomaterial and fireproof construction fields.


Compared to conventional two-dimensional (2D) culture, their use has been expanding in numerous research areas owing to their advantages such as long-term culture under a physiological environment, high culture success rate, and faithful retention of the heterogeneity of the original tumor tissues. Toxicological evaluation and mechanistic elucidation of drugs/environmental chemicals have been conducted using immortalized 2D cell lines and/or experimental animals; however, whether the data obtained could be extrapolated to human disease is controversial in toxicological research. Moreover, treatment with chemicals at toxicologically admitted doses may induce clinical signs in animals, which may force discontinuation of the experiment. Therefore, development of an alternative method for safe assessment of such chemicals is urgently required. From this point of view, organoids have potential as a bridge between human and conventional experimental models, because they reproduce toxicologic reactions in a way similar to those of in vitro models for toxicologic and pharmacological evaluation. Selected models include, but are not limited to, those of toxicogenomic approaches, non-rodent species, and genetic models for carcinogenesis.This Research Topic is focused on organoid-based Matsui and Shinozawa reviewed the potential usefulness, limitations, and future perspectives of human liver, heart, kidney, gut, and brain-derived organoids, based on predictive toxicology research and drug development. Since human organoids mimic numerous aspects of the in vivo physiological functions of the relevant tissues, it is likely that they could bridge the toxicological profiles between animals and humans.Nguyen et al. conducted anthracycline analog-exposed experiments accompanied by translational proteomic analysis. They employed cardiac organoids/microtissues comprising induced pluripotent stem cell (iPSC)-derived cardiomyocytes and human heart biopsies, which provide insights into understanding their toxic mechanisms. Finally, they concluded that the in vitro outcomes could be linked to clinical phenomena through the integration of proteomic data.Komiya et al. generated lung, liver, and colon-derived organoids from gpt delta mice, (transgenic mice commonly employed in in vivo genotoxicity assay) and performed comparative analysis between in vivo and in vitro treatment of the environmental chemicals. This approach enables the avoidance of chemical treatment at maximum tolerated doses in vivo and the detection of the intra-organoid metabolic activation capacity of the chemicals, which has not been feasible using other in vitro genotoxicity assay systems.Naruse et al. confirmed the carcinogenic potential of a known carcinogen by administering it to murine mammary organoids in vitro and their subsequent injection to nude mice. The developed tumors in mice showed genetic characteristics distinct from those induced by oral administration of the chemical, suggesting that the organoid system could be applied to the clarification of a novel mode-of-action in chemical carcinogenesis.These articles underscore the advantages of organoids in minimizing the gap in drug/chemical responses among species and also in the elucidation of the mode of action of toxicologic effects of drugs and environmental factors, especially by integration into toxicogenomic approaches. In addition, they illustrate future perspectives such as a co-culturing system of organoids with endothelial cells, immune cells, and other mesenchymal cells in relevant tissues/organs that would likely improve the accuracy of the toxicological assessment of each drug/chemical.Sekine. The advantage of PDOs include the ease of in vitro genetic manipulation, the availability of normal (non-cancerous) cells as well as iPSC-derived epithelial cells, and the ability to generate patient-derived xenografts. Reproducing a small number of mutations by genome editing in normal PDOs and subsequently using them for carcinogenesis and toxicology research may deepen our understanding of carcinogenesis.The current status and future perspectives of the use of patient-derived organoids (PDOs) in cancer and toxicology research are outlined by Kopper et al. outlined the utility of canine models and their resultant intestinal organoids in the analysis of inflammatory bowel disease (IBD). Although genetically modified mice have commonly been used as disease models for IBD, it should be noted that they do not always faithfully reproduce the pathogenesis and pathophysiology of the disease as observed in humans. In contrast, canine and human IBD share common clinical and molecular features. Based on their review, they discuss the value of gut organoids derived from canine IBD model, and how they can heighten understanding of the interplay among dietary interventions, gut microbiota, and intestinal inflammation.A review by Maru and Hippo reviewed two genetically engineered models of endometrial cancer. One of these models consisted of in vivo mouse models reflecting gene mutations detectable in human endometrial cancers. Recently developed Cre transgenic mice with a highly specific gene recombination in the endometrial cell lineage warrant accurate in vivo modeling of cancers. The second model consisted of a hybrid model of lentivirus-based in vitro gene transduction of endometrial organoids, followed by subcutaneous transplantation into immunodeficient mice. In this modeling system, a certain combination of gene alterations was found to induce carcinosarcoma. The other combination did not develop tumors, unlike the previous study using genetically engineered mice of the identical genotype, suggesting that the functional cooperation of gene mutations with the microenvironment may play a critical role in carcinogenesis.A review by Takeda outlined a method to validate the carcinogenicity of colorectal cancer driver mutations by taking advantage of organoids, which enable an accurate evaluation based on their genetic homogeneity. Genomic analysis of human colorectal cancers and transposon-based in vivo genetic screens in mice allow the identification of many candidate genes that potentially participate in colorectal multistep carcinogenesis, which have to be further validated by functional assay. Unfortunately, it was difficult for standard Apc inactivation-driven in vivo tumorigenesis models to analyze later stages of carcinogenesis, such as invasion and metastasis, because of early death due to rapid development of multiple benign tumors. On the other hand, transplantation of organoids genetically modified by CRISPR/Cas into mice resulted in the development of a single tumor, which provides a suitable period of time to fully analyze these processes.A review by One of the greatest advantages of organoids compared to other culturing conditions is that, they can be generated from tissue samples from both healthy and diseased states. In addition, they can be established from not only mouse and human samples, but also other species, from companion animals to fish to name a few. This enables us to conduct toxicological research of environmental pollutants. Differences in toxicologic reactions to drugs/environmental chemicals and disease process among various species can also be evaluated at the cellular level. Studies on human organoids derived from iPSC and cancer tissues has remarkably increased in number recent years, and further attempts for establishment and utilization of organoids are warranted from non-cancerous human tissue and tissues from other species.


This study aims to determine the heat transfer properties of a magnetohydrodynamic Prandtl hybrid nanofluid over a stretched surface in the presence of bioconvection and chemical reaction effects. This article investigates the bio-convection, inclined magnetohydrodynamic, thermal linear radiations, and chemical reaction of hybrid nanofluid across stretching sheets. Also, the results are compared with the nanofluid flow. Moreover, the non-Newtonian fluid named Prandtl fluid is considered. Microfluidics, industry, transportation, the military, and medicine are just a few of the real-world applications of hybrid nanofluids. Due to the nonlinear and convoluted nature of the governing equations for the problem, similarity transformations are used to develop a simplified mathematical model with all differential equations being ordinary and asymmetric. The reduced mathematical model is computationally analyzed using the MATLAB software package’s boundary value problem solver, Runge-Kutta-fourth-fifth Fehlberg’s order method. When compared to previously published studies, it is observed that the acquired results exhibited a high degree of symmetry and accuracy. The velocity profiles of basic nanofluid and hybrid nanofluid are increased by increasing the Prandtl parameters’ values, which is consistent with prior observations. Additionally, the concentration and temperature of simple and hybrid nanofluids increase with the magnetic parameter values. The behavior of boundary layers across a stretched surface is essential because it happens in many engineering systems, such as extrusion-produced materials, paper and glass-fiber production. Polymer is constantly extruded to a windup roller from a die in industry, where it is used to make a variety of sheets and filaments. In these circumstances, the rate of cooling in the process and the stretching process determine the final product’s admirable characteristics. Researchers are currently interested in nanofluids flow across an expanding sheet.Sakiadis  presenteThe importance of heat transfer in engineering and industry has piqued the interest of researchers. In various systems, including electron devices and heat exchangers, convectional fluids such as water and ethylene glycol may be used to convey heat. However, these base liquids have low or restricted thermal conductivities. Engineers, mathematicians, and researchers from other professions are attempting to increase the thermal conductivity of the above-stated liquids by adding a single type of nanosized particle into a mixture known as ’nanofluid’, which was introduced by Choi and Eastman . The abiIn physics, chemistry, and engineering, the study of magnetic field effects is crucial. Several metalworking procedures use the drawing of continuous filaments or strips through a quiescent fluid to cool and stretch metal strips. The techniques referred to are drawing, annealing, and thinning copper wire. Consequently, the quality of the final product is highly reliant on the rate at which these strips are dragged through an electrically conducting fluid subjected to a magnetic field and the desired feature in each of these conditions. Ali et al.  and HamaRadiation heat transfer flow is crucial for the efficient design of nuclear power plants, gas turbines, and other propulsion engines used in airplanes, missiles, satellites, and spacecraft. Consequently, Wang et al.  examinedBioconvection is a natural phenomenon that results from microorganisms’ random movement in single-cell or colony-like forms. Numerous bioconvection systems are based on the movement of microorganisms in two specific directions. For instance, when there is no movement, gyrotactic bacteria can travel in the opposite direction of gravity. Microorganisms move in a direction determined by bioconvection’s asymmetric mass distribution balance. Bioconvection is required for various bio-micro systems, including biotechnology and enzyme biosensors. A floating algae solution was introduced to demonstrate the bioconvection mechanism . PlessetWe observed no study on bio-convective Prandtl hybrid nanofluid flow in the literature. The aim of the current article is to boost the heat transfer rate. The novelties of our research are: (i) Prandtl non-Newtonian fluid is considered, (ii) how effect inclined MHD, Brownian motion and thermophoresis diffusion, and motile microorganism on fluid flow, (iii) convective boundary effect is also considered, and (iv) nanofluid and hybrid nanofluid flow results are compared.What is the impact of multi-buoyancy forces, inclined magnetic field, and Prandtl parameters on the fluid velocity subject to mono and hybrid nanofluids flow?What is the effect of the magnetic field, Prandtl parameters, Brownian motion, and thermophoresis on the temperature and heat transfer rate for mono and hybrid nanofluid flow?How is the concentration affected by the magnetic field, Lewis number, chemical reaction parameter, Brownian motion, and thermophoresis for mono and hybrid nanofluid flow?Determine how bio-convection influences motile dispersion and mass transfer of motile microbe density?In this investigation, the following scientific research questions are answered:x-axis and a is constant) is the velocity with which the plate is expanded along the x-axis as shown in Considered Prandtl hybrid nanofluid with two-dimensional incompressible steady flow due to an expanding sheet with motile microorganisms. The coordinate system The governing equations of Prandtl hybrid nanofluid are given as ,31):(1)C:(1)C31])All the involved terms in these equations are defined in nomenclature. The following are the suitable boundary limits :(6)whenyBy utilizing the similarity relations given below, the above PDEs can be transformed into ODEs (8)η=aνff , By the above similarity relations Equation  is justiThe thermo-physical attributes are given in AlsoThe following are the definitions for the physical quantities :(19)C˜fxAt the surface Utilizing the predefined similarity relations, expressions (19) becomeDue of the nonlinear nature of the DEs (9–12), with the limits , these are unable to be solved analytically. We use Runge-Kutta approach to solve the given problem numerically. The problem presented here illustrates ODEs with boundary conditions. At the start of the process, the coupled nonlinear ODEs (9–12) are simplified into first order DEs utilizing the following procedure:The Runge-Kutta (RK) method is used to predict omitted initial conditions. This method helps in determining the missing initial conditions, such that conditions at A solution for Prandtl hybrid nanofluid over an expanding surface is produced by running the mathematical coding described earlier via a Matlab script. The numerical findings of physical parameters such as the Nusselt number earchers ,38,39,40M, the Lorentz forces slowdown the fluid motion.Numerical results of physical parameters for two cases of fluid flow are determined as follows: a = The impacts of  has been illustrated in M, but it declines with the increase in The velocity profile of both fluids has positive behavior for large values of Prandtl fluid parameters and opposite behavior for the angle of inclination, magnetic parameter, and bioconvection Rayleigh number.The boosting valuation of Prandtl fluid parameters, simple nanofluid, and hybrid nanofluid temperature profiles are declined.Temperature profiles are enhanced for the large values of the magnetic parameter, thermophoresis parameter, Brownian motion parameter, and Biot number. Also, the temperature profiles of hybrid nanofluids are more significant than those of simple nanofluids.The behavior of concentration of simple nanofluid and hybrid nanofluid is negative for the increasing values of Brownian motion, chemical reaction, and Lewis parameters.The volumetric concentration of simple and hybrid nanofluids has positive nature for a higher valuation of magnetic and thermophoresis parameters.The negative feature of microorganisms of simple and hybrid nanofluids is observed for Peclet and bioconvection numbers.Hybrid nanofluid results are more prominent than the nanofluid flow.The skin friction coefficient of both fluids has a decreasing trend for boosted inputs of The Nusselt number rises for The hybrid nanofluid flow has been studied with bioconvection and chemical reaction over an expanding surface. This paper solves the PDEs system through similarity transformation and obtains ordinary differential equations. The numerical method RKF-45 package built-in MATLAB is applied to solve these ODEs. The significant findings are summarized as follows:


Bio and Synthetic Based Polymer Composite Materials is a newly opened Special Issue of Polymers, which aims to publish original and review papers on new scientific and applied research and make contributions to the findings and understanding of the reinforcing effects of various bio and synthetic-based polymers on the performance of polymer composites. This Special Issue also covers the fibre-reinforced polymer composites’ fundamentals, characterisation, and applications.It is recognised that synthetic-based polymer or petroleum-based plastics have great barrier and thermomechanical properties, as well as a low production cost and require lightweight materials, which produce good performance in terms of overall criteria . The envOn the other hand, synthetic fibers have been the leading commodity in the composites industry. However, synthetic fibers possess many disadvantages as they are non-biodegradable. Since synthetic fibers have many shortcomings, researchers have expressed growing interest in producing polymers that incorporate natural fibers ,8,9. NatThus, in this Special Issue, we aim to capture the cutting edge of the state of the art in research pertaining to bio and synthetic-based polymer composite materials and their advanced applications. Contributions to the processing of bio and synthetic polymers, the use of diverse polymer sources, the reinforcement of fiber materials with polymers, and applications of these polymers composites constitute the backbone of this Special Issue.


Ischemic stroke is the most common type of stroke with limited treatment options. Although the pathological mechanisms and potential therapeutic targets of ischemic stroke have been comprehensively studied, no effective therapies were translated into clinical practice. Gut microbiota is a complex and diverse dynamic metabolic ecological balance network in the body, including a large number of bacteria, archaea, and eukaryotes. The composition, quantity and distribution in gut microbiota are found to be associated with the pathogenesis of many diseases, such as individual immune abnormalities, metabolic disorders, and neurodegeneration. New insight suggests that ischemic stroke may lead to changes in the gut microbiota and the alterations of gut microbiota may determine stroke outcomes in turn. The link between gut microbiota and stroke is expected to provide new perspectives for ischemic stroke treatment. In this review, we discuss the gut microbiota alterations during ischemic stroke and gut microbiota-related stroke pathophysiology and complications. Finally, we highlight the role of the gut microbiota as a potential therapeutic target for ischemic stroke and summarize the microbiome-based treatment options that can improve the recovery of stroke patients. Ischemic stroke accounts for about 70–80% of all stroke patients . The maiGut microbiota is a complex and diverse dynamic metabolic ecological balance network, including a large number of bacteria, archaea, and eukaryotes. Gut microbiota is formed at birth and retains maternal characteristics. After exposure to a complex microbiome, babies develop a largely stable gut microbiota by the time they are 1–3 years old . But it This article reviews the gut microbiota alterations during ischemic stroke, gut microbiota-related stroke pathophysiology and complications, as well as potential therapeutic strategies targeting gut microbiota for ischemic stroke.Multiple clinical and animal studies have revealed the changes in gut microbiota following ischemic stroke. One case-control study showed that the gut microbiota was significantly disrupted in patients with ischemic stroke and transient ischemic attack compared to controls. The main manifestations were the increase of opportunistic pathogens and the decrease of commensal or beneficial genera . In anotIn addition to causing gut microbiota dysbiosis, ischemic stroke may also facilitate the translocation and dissemination of selective strains of bacteria that originated from the host gut microbiota. Infection is usually more likely to be observed after an ischemic stroke. Changes in gut bacteria can also be a factor in ischemic stroke. Significant microbiological disorders have been detected in inflammatory bowel disease (including Crohn’s disease and ulcerative colitis) and chronic kidney disease, all of which were found to be risk factors for ischemic stroke . In addiThere are also differences in gut microbiota among stroke patients of different ages. The incidence of stroke is closely related to age, with about 70–80% of ischemic strokes occurring in people over 65 years of age , and ageIn addition, differences in the performance of gut microbiota after stroke also exist between genders. As two common intestinal bacteria, Bacteroidetes and Firmicutes, there are more Firmicutes detected in the males’ gut when they had a BMI of less than 33 compared with females. And when BMI is greater than 33, males have an advantage over females in the abundance of Bacteroidetes. In addition, the abundance of Lactobacilli in female is much higher than that in male . And theThe interaction between gut microbiota and ischemic stroke plays an important role in the occurrence, development and outcomes of stroke. We summarize the relevant pathophysiological mechanisms, including neuroendocrine pathways, bacterial metabolite, and immune response . The stuGut-brain-microbiota axis plays an important role in gut microbiota-related stroke pathophysiology. There are several neural pathways for GBMAx communication, such as spinal and vagal pathways, autonomic nervous system (ANS), enteric nervous system (ENS), and hypothalamic-pituitary-adrenal (HPA) axis . The funHormone levels are also thought to play a role in ischemic stroke. Deficiency of estrogen and other ovarian hormones was found to be a risk factor for ischemic stroke in post-menopausal women . In animE. coli bacteria can produce branched SCFAs  through this pathway  is a kind of metabolic product of gut microbiota, mainly derived from the dietary nutrients rich in phosphatidylcholine, choline, and L-carnitine. First, Gut microbes metabolize foods such as eggs and beef to produce the intermediate trimethylamine by the activity of trimethylamine (TMA) lyases. In the second step, TMA is oxidized to TMAO by hepatic flavin-containing monooxygenases . TMAO caAccording to the current study, TMAO can aggravate brain injury after ischemic stroke through a variety of pathophysiological processes. In addition to accelerating atherosclerosis and enhancing thrombogenesis potential, it can also promote vascular inflammation and endothelial dysfunction . TMAO alAs a gathering place of immune cells, gastrointestinal tract affects the growth and development of immune cells and plays an important role in regulating immune response . After iAfter the occurrence of stroke, activation of cerebral resident immune cells such as microglia, astrocytes, neutrophils and macrophages increase the production of pro-inflammatory cytokines, chemokines, proteases, and adhesive proteins . The actPeripheral immune inflammatory cells are involved in the cerebral immune inflammatory response following ischemic stroke and play an important role in the process of brain injury and tissue repair. The main cells involved in the human immune system are B lymphocytes, T lymphocytes, MHC and effector cells . In ischIntestinal microbiome dysregulation can reduce systemic anti-inflammatory cytokines such as TGF-β and IL-10 . As a baPost-stroke infection is an important factor causing worsen outcomes of stroke patients, and more than one-third of patient’s condition and treatment are complicated by post-stroke infection complications . IncreasAfter ischemic stroke, the sympathetic nervous system is activated, the intestinal permeability is increased, the intestinal barrier is damaged, and the antibacterial function of the body is reduced. These changes promote the transfer of bacteria to extra-intestinal organs, blood or lymph, participates in local and systemic immunity, and may lead to organ infections and even sepsis . The β-aIn an mice experimental study, germ-free mice were modeled by two methods. The results showed that the intestinal microbiota of mice with post-filament middle cerebral artery occlusion model (fMCAo) had significantly imbalance and the diversity was decreased while those in mice with permanent distal middle cerebral artery occlusion model (cMCAo) had relatively little influence. This suggests that the changes in microbiome are secondary to the stroke and the degree of disturbance is affected by the severity of stroke .In turn, gut microbiota disturbance may be one of the important causes of enterogenic infection, sepsis even multiple-organ dysfunction syndromes (MODS) . After sBacterial pneumonia is the most common complication of ischemic stroke patients and one of the early nosocomial infections . Blood oNeuropsychiatric disorders are also common complications of stroke, includes depression, anxiety, mania, dementia, and cognitive impairment . About oCurrent studies on the gut-brain axis mainly focus on patients with ischemic stroke. Compared with ischemic stroke, there are fewer clinical and experimental studies on the association between hemorrhagic stroke and intestinal flora. The occurrence probability of intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH) are less than that of cerebral infarction, but the mortality and disability rate of ICH and SAH are not low. Although the pathogenesis and clinical manifestations of the two types of stroke patients are different, similar results of microbiome disruption were found between the two stroke patients. Some studies have even shown that the stability disruptions of gut microbiota in patients with hemorrhagic stroke or high NIHSS scores are more severe than those with ischemic stroke and TIA . Like isAs the most common cause of SAH, intracranial aneurysms have a prevalence of about 3% in the population and are associated with 80–85% of non-traumatic SAH . The curCavernous hemangioma (CA) is also a kind of common vascular disorder will cause cerebral hemorrhage. More abundance Gram-negative bacteria O. splanchnicus and lower levels of gram-positive bacteria F. prausnitzii and B. adolescentis can be found in CA patients, compared with the non-CA patients. However, the most valuable combination of bacteria for diagnosing disease and assessing its severity was not found in this experiment. This indicates that the influence of bacteria on CA is not independent but may play a role together with other factors.Currently, it has been proved that there is a correlation between intestinal microbiota dysbiosis after stroke and the incidence and progression of stroke. Therefore, it is feasible to predict the disease recovery of patients by indicators related to intestinal microbiome. By comparing samples from stroke patients and control group, several studies got the similar conclusions that stroke patients had a reduction in Firmicutes and Bacteroidetes, while the abundance of Proteobacteria was increased. And the difference of composition ratio in the microbiome was correlated with the severity of the disease. The abundance of TMA-producing bacteria was significantly higher, and the levels of intestinal butyrate-producing bacteria decreased in severe patients compared with mild patients. And the metabolites like TMA or butyrate of these bacterias also had a similar situation .By examining the difference in intestinal microbiota distribution between acute ischemic stroke patients and healthy participants, a study established a Stroke Dysbiosis Index (SDI), as an independent predictor of severe disease (NIHSS > 8) and poor prognosis (MRS > 2) . IncreasDietary regulation is an important measure to improve the prognosis of stroke . At the In addition, increasing the consumption of fruits and vegetables can increase fiber intake, which can increase the level of SCFAs production. For example, resistant starches (such as whole grains and legumes) and fructo-oligosaccharides , as metabolic food sources for butyric acid producing bacteria, can increase butyric acid production in the gut .Energy control is an effective way to promote good health and reshape the intestinal symbiotic microbiome. Some studies suggest that energy restriction to 60–70% of the recommended intake is protective against ischemic stroke . The proin vivo, promote the generation of anti-inflammatory cytokines, and improve the activity of antioxidant enzymes , prebiotics can be hydrolyzed and used as nutrients by the beneficial bacteria in the intestinal tract, such as bifidobacterium, and promoting the reproduction and growth of these bacteria. In addition, prebiotics can also affect the production of SCFAs and regulate the production of mucin, thus enhancing the phagocytosis of macrophages . In one The transfer of the entire microbiome from the stool of a healthy donor to the patient’s gastrointestinal tract is known as fecal microbiome transplantation (FMT). The technique is already being used to treat patients with severe infections, such as refractory bronchiolitis and pseudomembranous colitis . In addiIn clinical work, about 30% of patients with stroke will have bacterial infection within 1 week of onset , so a siAs the most common type of stroke, treatment options for ischemic stroke remain limited despite extensive research. New insights have highlighted the role of gut microbiota in the pathophysiology of ischemic stroke. Ischemic stroke could cause gut microbiota dysbiosis as well as translocation and dissemination of gut microbiota-derived selective strains of bacteria. In turn, changes in gut microbiota affect ischemic stroke-induced brain injury and determine stroke outcomes through multiple mechanisms, including neuroendocrine pathways, bacterial metabolite, and immune response. Gut microbiota dysbiosis may also contribute to some stroke complications such as pneumonia, sepsis, and neuropsychiatric disorders. Some gut microbiota-targeted therapies have shown potential in the treatment and management of ischemic stroke, including dietary interventions, probiotics supplementation, FMT, and rationalization of antibiotic use. Gut microbiota is expected to provide new perspectives for ischemic stroke treatment. However, the efficacy and safety of this treatment strategy for ischemic stroke have not been verified in large scale clinical trials. In addition, it must be recognized that gut microbiota dysbiosis is only one component of the multifactorial brain injury mechanisms of ischemic stroke. Further studies are necessary to broaden our knowledge of the role of gut microbiota in the pathogenesis of ischemic stroke and to facilitate the development of novel therapeutic strategies for ischemic stroke.ZB wrote the manuscript. ZZ directed the writing of the manuscript, revised the manuscript, and made the figures and the table. GZ and AZ checked the manuscript. AS proposed the idea. FZ supervised the writing of the manuscript. All authors 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. 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The number of students enrolled in higher education who are taking care of older adults, many of whom may be suffering from an illness, is expanding. The numerous factors in care partnering can compromise student success and persistence towards graduation. While most care partners experience challenges, the care partnering experience of Black students is magnified because Historically Black Colleges and Universities (HBCUs) have a higher enrollment of nontraditional and first-generation college students. Students may be primary care partners who provide most of the care, or they may provide supportive care as secondary, tertiary, and auxiliary care partners within an extended family or kinship network. Aging in place, within the context of family and community, emerges from African culture and tradition deeply grounded in filial loyalty. Care partnering is nuanced in the interaction of race, ethnicity, gender, family relationships, and student status; however, little is known about the lived experience of Black student care partners and how to support them to facilitate their persistence towards graduation. This poster describes initial efforts to understand Black student experiences in care partnering in the context of a Mid-Atlantic HBCU and suggests the next steps in a multi-year research program.


In order to improve the performance of concrete, it is of great significance to have a better understanding the mechanism and main influencing factors of concrete bubble evolution under the action of polycarboxylate and air-entraining agents. In the present review, with respect to the generation, growth, stability, and rupture of concrete bubbles under the action of polycarboxylate and air-entraining agents, this paper discusses the influence of bubble characteristics on concrete performance and studies bubble regulation by air-entraining agents and polycarboxylate (PCE) superplasticizer. The results show that the acid-to-ether ratio, sulfonic acid group, ester group, and the type of air entraining agent of the polycarboxylate acid structure have a significant impact on the bubbles. The bubble size, specific area, spacing factor, and bubble content have a significant impact on the rheological properties and related mechanical properties of fresh concrete and also affect the appearance quality of concrete. The problems with the experimental methods and theoretical models of concrete bubble research were analyzed, and future research ideas were put forward. For concrete, as a multiphase and porous material, pore structure is an important part of its microstructure which affects multiple of its properties. By adding an appropriate number of bubbles into concrete through admixtures, it is possible to increase the fresh concrete workability and effectively enhance its frost resistance and durability, but too many bubbles will also significantly reduce the concrete strength. Hence, it is particularly important to study the evolution mechanism and influencing factors of concrete bubbles. As a third-generation high-performance water reducer, PCE superplasticizer has various molecular structures. PCE with a special structure can be used as an air-entraining water reducer. Factors such as molecular mass, main chain density, and side-chain length significantly affect its air-entraining properties and the structure characteristics of the generated bubbles . At the The traditional experiment process consumes a lot of time and energy. Nowadays, given the rapidly developing network and computers, developed computer technology can be used to establish appropriate models which provide an intuitive and low-carbon experiment approach to simulate the progress of related experiments and finally reveal the evolution and regulation mechanism of concrete bubbles under the action of PCE. Focusing on the concrete bubble research by domestic and foreign scholars, this paper summarizes the effects of air-entraining agents and the PCE superplasticizer structure on bubbles, as well as the effect of bubbles on concrete properties. Moreover, it anticipated experimental methods and mathematical models for future research of bubble mechanisms. Our research can be reflected in There are generally two or more flow states involving mixtures of different phases in nature; the most common is the gas–liquid two-phase flow state. In this process, bubbles play an important role . Bubbles2+ concentration in the cement slurry increased continuously until reaching the maximum value near the end of the induction period. The air solubility in the pore solution lowered during the induction period, with air released and bubbles formed [According to the volume change of bubbles, the bubble life cycle has four stages: generation, growth, stability, and rupture. The generation of concrete bubbles involves both macroscopic and microscopic factors. Macroscopically, the artificially or mechanically created vortex swirls into the air to form a large number of bubbles with an uneven volume, and a small number of bubbles comes from the air dissolved in the water . Microscs formed . The relThere are two commonly used nucleation mechanisms in bubble evolution: 1. Classical nucleation theory, including two cases of homogeneous nucleation and heterogeneous nucleation; this theory is limited to static fluids in the scope of the application . HoweverEssentially, bubble growth in concrete is when the gas surrounding the bubble diffuses into the bubble interior through the bubble film, generating a pressure difference between the interior and exterior. Scholars generally believe that the pressure gradient between bubbles leads to gas diffusion. Small bubbles have a high gas pressure, while large bubbles have a low gas pressure. Macroscopically, small bubbles converge to large bubbles and gradually become smaller until their disappearance, while large bubbles gradually become larger until they burst. The schematic diagram of gas diffusion is shown in In their process of formation, concrete bubbles will be subjected to upward buoyancy, downward surface tension, bubble inertial forces and drag forces, etc. Bubbles have vertical and horizontal movements. In vertical movements, the rise of bubbles is negatively correlated with the liquid phase viscosity, a process affected by buoyancy, viscous resistance, and self-gravity , as showBubbles have unobvious boundaries between the growth and stabilization stages, and the volume does not change significantly in the stabilization stage. Many factors affect the stability of concrete bubbles including separation pressure and ionic strength, bubble liquid film strength , and the2+ concentration increased during the induction period and the bubble liquid film produced electrostatic repulsion [Separation pressure and ionic strength. Separation pressure refers to the electrostatic repulsion between the two sides of the bubble liquid film, which consists of van der Waals forces and short-range repulsion ,18. Careepulsion  which hiepulsion .Bubble liquid film strength. Film strength is often determined by the surface elasticity and surface viscosity of the adsorption film on the liquid film surface ,24,25. SDiffusion rate of gas through the liquid film. The barrier to gas migration between the gas–liquid interface in fresh concrete, namely, the ability of gas to penetrate the liquid film, determines the bubble diffusion rate . Gas difDeformation is common during the concrete bubble movement, and bubble deformation is the premise of instability and rupture . The watThe stability of concrete bubbles is dynamically balanced. Nonetheless, when the degree of bubble deformation causes the bubble film to rupture and lose its elastic properties, bubble will lose stability and rupture and finally exist in the interior and surface of the hardened concrete in the form of open or closed pores. There are three main reasons for the instability and rupturing of bubbles : coalescCoalescence. According to the classic model of bubble coalescence in aqueous solutions , bubble Using computer CT three-dimensional reconstruction technology, the existence of the bubble coalescence phenomenon in fresh concrete was intuitively proved. Under the action of long side-chain PCE, the small pore-size bubbles in concrete decreased and the large pore-size bubbles increased. Moreover, long side-chain PCE caused earlier bubble coalescence time and earlier bubble rupture time.Liquid film drainage. Drainage means liquid flow relative to the bubble . Bubble Coarsening. Coarsening refers to the process in which bubble size increases through gas diffusion between adjacent tiny bubbles . After cAt present, most research on bubble behavior stays in the stage of clear water solutions. Appropriate mesh size and bubble parameters are important guarantees for reliable and effective simulation results, which are also difficult problems in simulation calculations. Nguyen et al.  studied Some scholars carried out three-dimensional numerical simulations of the interactions between parallel bubbles under the VOF model . A gas–lThe behavior of concrete bubbles is affected by multiple factors such as different types of air-entraining agents and the PCE structure, raw material composition, construction technology, link temperature, ambient air pressure, etc. Air-entraining agents and PCE superplasticizer have the most significant effects. Using the image analysis method, Rath et al.  tested tUnder the same air void in the fresh concrete, the addition of different types of air-entraining agents also created obviously different effects on the average bubble diameter, as shown in Atahan et al.  comparedQiao et al.  and ChenMost PCE graft copolymers contain carboxylic acid adsorption groups on the main chain, while the polyether side chains on the branched chains provide steric groups. Hydrophilic side-chain polyether groups have a strong air-entraining performance. When PCE was added to the concrete, the surface tension of the mixing water decreased, and a large number of unstable bubbles were introduced during the mixing process. Low surface energy facilitated the formation of harmful large bubbles. The bubbles entrained by different molecular PCEs had varying stabilities. For PCEs with carboxyl groups and ester groups, the bubbles easily ruptured, but this was not the case for PCEs with ester groups. It suggests that bubble regulation is closely related to the PCE structure.Acid-to-ether ratio. He Yan  synthesiSulfonic acid group. When a small number of sulfonic acid groups was used to replace the carboxyl groups in the main PCE chain, the fresh mortar with sulfonic acid group-containing PCE had a significantly increased or decreased air void of 5–6%, as shown in Ester group. The ester group is a neutral group that reduces the ionic density and adsorption capacity in the PCE molecule. As the content of ester groups grafted onto the side chain of PCE increased, the concentration of PCE adsorbed on the cement particle surface decreased, while the concentration of PCE left in the pore solution increased, resulting in significantly decreased surface tension at the gas–liquid interface, thereby increasing the air void entrained in the fresh cement mortar. The ester group-containing PCE, as shown in In recent years, some scholars have synthesized low air-entraining PCEs by adjusting the molecular structure or molecular weight of PCE, such as by introducing the antifoaming functional group, PPGA400 (poly (propylene glycol) diacrylate), into the molecular structure  using thBubble parameter is an important condition for establishing bubble structure as an important index affecting the concrete appearance. There are generally three parameters to characterize the bubble structure: gas content, average bubble diameter, and bubble spacing coefficient. Bubble structure is commonly controlled by the control of raw materials, adjustment of the mixing ratio, and composite mixing of chemical admixtures, among which the use of admixtures is the most efficient . Under tBoth durability and construction quality of concrete are affected by its rheological properties . Guo et Khoshroo et al.  found thWhen fresh concrete contains a large number of uniform and tiny bubbles, energy can be better transferred under vibration and compaction. By analyzing the experimental data, Haddad et al.  found thA large number of evenly distributed tiny bubbles can relieve the compressive stress on the solid phase particles due to an increased surface tension, which helps to reduce the drying shrinkage and deformation of concrete . MaghfouDurability has become a major issue for concrete materials and structures in cold regions ,80. A loShon  found thThe structural parameters of concrete bubbles greatly affected rheological and mechanical properties of concrete and the appearance quality after hardening. Chemical admixtures such as PCE and air-entraining agents had highly adjustable chemical structures, but the research on their structural design was not sufficient, so it is necessary to further improve the molecular structure and optimize the structural characteristics of the introduced concrete bubbles, thereby increasing the concrete durability and improving the pore quality after concrete hardening. We can also consider using PFC software to simulate the impact of the number and size of bubbles on the mechanical properties of concrete test blocks.Bubble stability was affected by bubble film strength. The viscosity, elasticity and permeability of bubble film could be used to characterize the bubble film strength. Research on the bubble film interface characteristics, liquid film drainage, bubble coalescence, etc., mostly target clean water; foam and cement mortar lack systematic quantification. In addition, the reported quantitative research on the stability of foam focused on the stability of foam. However, the mechanism of foam stability cannot be fully applied to the stability of foam in fresh concrete. There is no in situ observation or detection of the bubble behavior of fresh concrete, so it is applicable to study the bubble generation and development via the isotope trace method.The “cell model”, as well as the commonly used geometric interface reconstruction VOF-PLIC method, CT three-dimensional reconstruction technology, and the fluid volume VOF model, etc., are mathematical models established for foamed plastics, water, or two-phase systems. Concrete is a three-phase complex system of solid, liquid, and gas. Hence, it is necessary to set reasonable model hypotheses and parameters to qualitatively or semi-quantitatively describe the generation and development of bubbles.To sum up, with the progress of cement hydration in fresh concrete, the physical and chemical properties of concrete experienced constant variations, with its bubble behavior greatly different from that in aqueous solution. The entire evolution process of concrete bubbles was simultaneously affected by multiple factors and then affected the rheological and mechanical properties of concrete. The current scholars’ research on the generation, growth, stability, and rupture of bubbles basically stayed in clean water solutions, and there is no literature on the in situ monitoring of concrete bubbles. Offline experiments need a lot of time and material costs, and it is more economical to use PFC software to simulate and study the impact of bubbles on the performance of concrete. In this work, the formation and rupture process of bubbles in concrete and the main influencing factors were described; the research progress on the effect of air bubbles on the performance of concrete was reviewed: