Hepatitis E is a liver disease caused by the pathogen hepatitis E virus (HEV). The largest polyprotein open reading frame 1 (ORF1) contains a nonstructural Y-domain region (YDR) whose activity in HEV adaptation remains uncharted. The specific role of disordered regions in several nonstructural proteins has been demonstrated to participate in the multiplication and multiple regulatory functions of the viruses. Thus, intrinsic disorder of YDR including its structural and functional annotation was comprehensively studied by exploiting computational methodologies to delineate its role in viral adaptation.Based on our findings, it was evident that YDR contains significantly higher levels of ordered regions with less prevalence of disordered residues. Sequence-based analysis of YDR revealed it as a “dual personality” (DP) protein due to the presence of both structured and unstructured  regions. The evolution of YDR was shaped by pressures that lead towards predominance of both disordered and regularly folded amino acids . Additionally, the predominance of characteristic DP residues  further showed the order as well as disorder characteristic possessed by YDR. The intrinsic disorder propensity analysis of YDR revealed it as a moderately disordered protein. All the YDR sequences consisted of molecular recognition features (MoRFs), i.e., intrinsic disorder-based protein–protein interaction (PPI) sites, in addition to several nucleotide-binding sites. Thus, the presence of molecular recognition  signifies the YDR’s interaction with specific partners, host membranes leading to further viral infection. The presence of various disordered-based phosphorylation sites further signifies the role of YDR in various biological processes. Furthermore, functional annotation of YDR revealed it as a multifunctional-associated protein, due to its susceptibility in binding to a wide range of ligands and involvement in various catalytic activities.As DP are targets for regulation, thus, YDR contributes to cellular signaling processes through PPIs. As YDR is incompletely understood, therefore, our data on disorder-based function could help in better understanding its associated functions. Collectively, our novel data from this comprehensive investigation is the first attempt to delineate YDR role in the regulation and pathogenesis of HEV.The online version contains supplementary material available at 10.1186/s43141-021-00238-8. Hepeviridae [Hepatitis E virus (HEV) is a non-enveloped RNA virus of the family eviridae . HEV is eviridae . Recentleviridae .HEV is currently segregated into eight genotypes (GT 1 to GT 8). GT 1 and GT 2 infect humans and are mainly transmitted through contaminated water causing acute hepatitis while GT 3 and GT 4 strains have an expanded range of hosts which includes humans, rabbits, wild boars, and pigs  and are 410, S412, and W413) in the predicted YDR alpha-helix homolog (LYSWLFE). These critical residues have been demonstrated to play crucial role in the RNA replication of the virion [336–C337), attributed to membrane binding, completely abolished RNA replication. Such functional and/or structural integrity clearly suggests YDR essentiality in replication of HEV that might embody common principles of YDR and cytoplasmic membrane interaction [The HEV genome is systematized into three partially over-lapped ORFs  . The lare virion . It was eraction . Althougeraction , a direcThe present study analyzed the structurally “unknown” regions  of the HEV YDR. This fraction we call it as the “dark proteome.” These disordered protein regions exist as extremely active ensembles that are rapidly interconvertible under different physiological conditions –33. Due The protein sequences of HEV YDR were obtained from the GenBank. The individual protein sequence considered for the present analysis included a total of eight study sequences. The individual sequence included different genotypes, i.e., GT 1–GT 8 as currently eight genotypes have been recognized in HEV. The obtained sequences were accumulated in such a way that they encompassed different host organisms . Thus, we carried out multiple predictions of these eight study sequences by computational methods and comparative analyses were performed.http://www.sbg.bio.ic.ac.uk/~phyre2/html/page.cgi?id=index) [The 3D models of HEV YDR sequences were predicted using Phyre2  server (d=index)  and analhttps://web.expasy.org/protparam/).The amino acid composition of the individual sequences of HEV YDR was computed and thoroughly analyzed. The analysis was conducted using the online webserver Expasy ProtParam  of the YDR sequences were predicted using the PONDR®  at its default settings. Multiple predictors such as members of the PONDR® family including PONDR®VLS2 , PONDR®VMoRFpred  online bVarious online servers are available to predict the RNA- and DNA-binding regions within the YDR sequences. DisoRDPbind webserver predicts the RNA-, DNA-, and protein-binding residues located in the intrinsically disordered region of proteins. DRNApred webserver provides a sequence-based prediction of DNA- and RNA-binding residues within proteins. PPRInt webserver predicts the RNA-interacting amino acid residues in the given sequence. Thus, these tools were used in combination to predict the RNA- and DNA-interacting residues within the HEV YDR sequences.For RNA-binding residue identification, we used a combination of three webservers, i.e., DisoRDPbind , DRNApreFor DNA-binding residue identification, we used a combination of two webservers, i.e., DisoRDPbind  and DRNAhttp://www.pondr.com/cgi-bin/depp.cgi). The disorder information is used by the DEPP algorithm to improve the discrimination between phosphorylation and non-phosphorylation sites. The accuracy of DEPP reaches 76.0 ± 0.3%, 81.3 ± 0.3%, and 83.3 ± 0.3% for Ser, Thr, and Tyr respectively.The phosphorylated Ser, Thr, and Tyr residues in HEV YDR sequences were predicted using the online tool DEPP (Disorder enhanced phosphorylation prediction)  and an alpha-helix segment (L410Y411S412W413L414F415E416). These segments are found to be indispensable for cytoplasmic membrane binding and are highly conserved within HEV genotypes. The YDR of HEV GT 1 (accession number: AF444002) is represented in Fig. The HEV genome comprises three ORFs : The ORF1 consists of seven domains, i.e., MTase, methyltransferase; Y, undefined; PCP, papain-like cysteine protease; P/HVR, proline-rich/hypervariable region; X, macro; Hel/NTPase, helicase/nucleotide triphosphatase; and RdRp, RNA-dependent RNA polymerase. The Y-domain region (YDR) is of 228 amino acids in length (650–1339 nucleotides) and consists of a potential palmitoylation site  as well as few hydrophilic  amino acids. These amino acids are prevalent in D fragments, while deficient in O fragments.The second group comprises mostly hydrophilic amino acids . Most of these amino acids show a higher preference towards DP fragments.The third group constitutes the mostly hydrophobic amino acids . These amino acids are deficient in D fragments while showing abundance in O fragments.Unexpectedly, the presence of both hydrophobic and polar residues was favored in YDR sequences. The amino acids on the basis of their relative abundance ratios are clustered into three major classes: ordered (O), disordered (D), and dual personality (DP) .The firThe considered study sequences of YDR for our analysis were observed with a higher preference towards both ordered  and disordered amino acid residues  –54 Fig.. Our resThe webserver predicts the natural disordered regions upon single protein sequences. The resulting disorder profiles of YDR sequences with the predicted disorder scores clearly revealed them as moderately disordered proteins Fig. A–H. Theystructured proteins (0–10%), moderately disordered proteins (10–30%), and highly disordered proteins (30–100%) [The individual YDR sequences were analyzed for the prediction of disordered regions. Based on the overall degree of intrinsic disorder, i.e., predicted fraction of disordered residues, the proteins are categorized into different intrinsic disorder variants: 30–100%) , 56. TheThus, it was revealed that the presence of disordered residues in the conserved “LYSWLFE” counterpart in all the YDR sequences clearly indicated that this conserved motif was characterized by structural flexibility.MoRFpred: The results of MoRFs (protein-binding regions) analysis are elaborated  was used to find out the situated protein residues that had propensity to bind to nucleotides (DNA and RNA).DisoRDPbind: Several RNA-binding residues were identified at the C-terminus of the YDR sequences . Moreover, the residues were also identified within the highly conserved “LYSWLFE” segment (α-helix counterpart) of the YDR (predicted by DisoRDPbind and PPRInt).DisoRDPbind: The DNA-binding residues were found to be absent in the YDR sequences.DRNApred: The DNA-binding residues were observed at both the N- and C-terminals of the YDR sequences  of the YDR (as predicted by DRNApred).Therefore, our nucleotide propensity analysis indicated the high propensities of these predicted residues towards RNA and DNA. Moreover, the residues predicted within the “LYSWLFE” segment indicated its involvement in the critical function of viral replication.Our phosphorylation analysis showed the presence of phosphorylation sites (P-sites) in all the YDR sequences. The predicted phosphorylated residues, i.e., Ser, Thr, and Tyr, in HEV YDR sequences with the DEPP score are summarized Table  Fig. 8)8).Table. VLXT is considered the most accurate predictor due to the different attributes that make up this algorithm and good accuracy [Our results revealed that Ser was found in higher fractions in comparison to the other phosphorylated residues, i.e., Thr and Tyr Fig. A-H. It waccuracy . Thus, wThe putative molecular functions of the YDR based on the predicted 3D structures were identified using the COFACTOR algorithm. The consensus GO annotations associated to the models are summarized in Table The molecular functions included heme binding, copper ion binding, ubiquinone binding, nucleotide binding, ATP binding, ion binding, electron transfer activity, cytochrome-c oxidase activity, N-glycosylase activity, ligase activity, kinase activity, and citrate-synthase activity. Thus, binding interactions and catalytic activities were the major functional roles that were attributed to YDR in respective hosts. The binding interactions, such as heme binding (GO:0020037), ion binding GO:0043167), and nucleotide binding (GO:0000166), revealed the propensity of YDR to bind to a variety of molecules , similar to our earlier results. Furthermore, the predicted different catalytic activities, such as electron transfer activity (GO:0009055) and cytochrome c oxidase activity (GO:0004129), revealed the significant mitochondrial functional roles associated with YDR in respective host organisms , beta-strand (β), and coils. All the YDR sequences consisted of higher percentage of α-helices as compared to β-strands with the predominance of coils which is in agreement with the recent study . Then, wIn line with this, our intrinsic disorder propensity analysis also revealed YDR to be moderately disordered proteins. Based on the overall degree of intrinsic disorder, i.e., predicted fraction of disordered residues, the different intrinsic disorder variants are categorized into structured proteins (0–10%), moderately disordered proteins (10–30%), and highly disordered proteins (30–100%) , 56. TheFurthermore, it has been well documented that disordered protein segments possess enormous flexibility . These iMoRFs specifically focus on interactions between proteins and are considered as a specific subset of DP fragments . MoRFs aFluctuation in the conformation of the intrinsically disordered regions in proteins transiently reveals dynamic interaction motifs, which lead to post-translational modifications (PTMs), resulting in their interaction with several target protein molecules that have an effect on cell cycle control , 64. PTMFurthermore, the predicted YDR 3D models were used to predict the molecular functions using GO annotations , 36. TheMoreover, several disordered regions in nonstructural proteins have been demonstrated to play specific regulatory functions in viruses . For insTo sum up our observations, it can be hypothesized that YDR has regulatory functions in addition to its role in the replication of HEV that is essential for viral adaptation. The inclusive information provided in this prospective study thus strongly proposes the role of YDR in HEV adaptation.The current study provides novel data on the role of YDR in HEV adaptation. The amino acid distribution revealed the signature residues prevalent in DP fragments. The presence of both ordered and disordered amino acid residues revealed YDR as protein hybrids. The occurrence of the unstructured region in YDR sequences suggested their disorder and flexibility. We also established that all the YDR sequences consisted of MoRFs, thus revealing its disorder-based propensity towards protein-binding partners. Furthermore, identification of several RNA- and DNA-binding sites in the YDR sequences suggested its critical role in the interaction with the hosts and further viral infection. The presence of various phosphorylation sites in YDR further signified it as an important constituent of mechanisms involving cellular and signaling pathways. Additionally, the presence of P-sites within the disordered segments of YDR further substantiated our findings, as PTM sites are located at/close to DP fragments. Furthermore, structure-based analysis of YDR models revealed several potential sites which further signifies their role in vital processes like cellular signaling transduction, phosphorylation, transcription, and translation by interacting with several ligand molecules, which suggested its noteworthy multiple functions associated with it. The involvement of YDR in mitochondrial functions further revealed its association with regulatory functions. Due to the DP flexibility to associate with different physiological partners, our analysis is envisaged to assist in producing important knowledge in the interaction of YDR with other HEV proteins. Furthermore, delineations of these interactions could possibly contribute to future research in revealing the molecular biology of HEV.Additional file 1 : S1 Figure (A). Generated 3D models of the HEV YDR. (A) JF443720 (GT 1); (B) M74506 (GT 2); (C) AB222182 (GT 3); (D) GU119961 (GT 4); (E) AB573435 (GT 5); (F) AB602441 (GT 6); KJ496143 (GT 7); and (H) KX387865 (GT 8). The prediction was carried out using Phyre2.Additional file 2 : S2 Figure. Correlation between disordered and phosphorylated residues within HEV YDR (A) JF443720 (GT 1); (B) M74506 (GT 2); (C) AB222182 (GT 3); (D) GU119961 (GT 4); (E) AB573435 (GT 5); (F) AB602441 (GT 6); KJ496143 (GT 7); and (H) KX387865 (GT 8). The prediction of disordered residues was carried out using three members of the family PONDR , i.e., VLXT, VL3 and VSL2. The specific amino acid position of the prediction phosphorylated residue was carried out using DEPP (Disorder Enhanced Phosphorylation Predictor). The predicted disordered residues are shown with alphabet ‘D’ while the predicted phosphorylated residues in the YDR proteins are marked with asterisk (*). This suggests that the phosphorylated residues are present within the disordered regions of YDR.Additional file 3 : S1 Table. List of HEV YDR sequences analyzed in the present study


Schizophrenia has a complex and heterogeneous molecular and clinical picture. Over the years of research on this disease, many factors have been suggested to contribute to its pathogenesis. Recently, the inflammatory processes have gained particular interest in the context of schizophrenia due to the increasing evidence from epidemiological, clinical and experimental studies. Within the immunological component, special attention has been brought to chemokines and their receptors. Among them, CX3C chemokine receptor 1 (CX3CR1), which belongs to the family of seven-transmembrane G protein-coupled receptors, and its cognate ligand (CX3CL1) constitute a unique system in the central nervous system. In the view of regulation of the brain homeostasis through immune response, as well as control of microglia reactivity, the CX3CL1–CX3CR1 system may represent an attractive target for further research and schizophrenia treatment. In the review, we described the general characteristics of the CX3CL1–CX3CR1 axis and the involvement of this signaling pathway in the physiological processes whose disruptions are reported to participate in mechanisms underlying schizophrenia. Furthermore, based on the available clinical and experimental data, we presented a guide to understanding the implication of the CX3CL1–CX3CR1 dysfunctions in the course of schizophrenia. IL-2, IL-6, IL-10 and TNF-α are likely to be a risk factor for this disease [Schizophrenia is a chronic and severe mental illness, ranked among the leading causes of disability worldwide in recent years –3. Despi disease –51. Some disease . In the  disease . Even th disease , they reCX3CL1 gene is polymorphic and its genetic variants may be related to HIV infection [C-X3-C motif chemokine ligand 1 (CX3CL1) was firstly described in 1997 under the name “fractalkine” in humans  and simunfection , postopenfection , coronarnfection , 73 and nfection  as well nfection . CX3CL1 nfection  and to anfection . In the nfection . The hignfection . On the nfection  along winfection , endothenfection , 80, epinfection , fibroblnfection , macrophnfection  and smoonfection . Within nfection –87 or asnfection .Fig. 1Sci protein-coupled receptor (GPCR) and belongs to the A class, which includes rhodopsin-like receptors [CX3CR1 V249I polymorphism has been also suggested as a factor that improved overall and progression-free survival in low-grade gliomas [CX3CL1 interacts with only one known receptor  , Ca2+ [12+ , 114, cA2+ , inosito2+ , nuclear2+ , 118 as 2+ , 119. Th2+ –122, ext2+ , 123, Ja2+ , c-Jun N2+ , p38 mit2+ , 115, ph2+ , 125 and2+ , 127 . As presented by Bolós et al. [Cx3cr1−/− knockouts exhibited alterations in postnatal functional maturation of thalamocortical synapses [It is widely recognized that the CX3CL1–CX3CR1 pair takes part in synapse-related processes, including synaptic formation, maturation, integration, pruning and transmission. The evidence has been provided by many data, including the research on i et al. , these ai et al. . Rogers i et al.  demonstrs et al. , the depsynapses . The abosynapses , 145.Synaptic remodeling and plasticity contribute to the development of neural networks –148. TheCX3CR1 mRNA levels in the subjects affected by this condition. The finding was further confirmed by RT-qPCR examination in the peripheral blood mononuclear cells (PBMCs) obtained from the suffering from schizophrenia. The dysregulation of the gene expression in PBMCs was independent of confounding variables  and correlated with a depression–anxiety phenotype [CX3CR1 level in PBMCs from veterans with a diagnosis of schizophrenia. Similarly, the datasets-integrated analysis showed that the CX3CR1 expression was decreased in the hippocampi of individuals with this illness [CX3CL1 and CX3CR1 levels in postmortem cortical samples from patients with schizophrenia. The authors confirmed and expanded these findings in further examinations applying large-scale RNA-sequencing-based quantifications that integrated genetic and genomic data from numerous well-curated, high-quality postmortem brain specimens from individuals with the disease and controls [CX3CL1 and CX3CR1 as well as the presence of variously expressed isoforms [CX3CR1 gene contributes to the increased risk of this condition [CX3CR1. Consequently, the Ala55Thr variant affected the gene interplay with a G protein and resulted in inhibition of the CX3CL1–CX3CR1 signaling. Complementary experiments on HEK293 cells transfected with Ala55Thr-expressing vector demonstrated a reduction in Akt phosphorylation-mediated signaling upon CX3CL1 treatment [CX3CR1. In another study, Zhang et al. [CX3CR1 transcript level was increased in the anterior cingulate cortex of suicide completers with schizophrenia when compared to the subjects affected by this condition who died of other causes. However, when the investigated cohort was analysed holistically and compared to controls, the mRNA expression of the receptor was unchanged in this brain structure . These postmortem data emphasized the importance of accurate characteristic of examined groups in terms of symptoms of the disease and anamneses. Nonetheless, the latest articles implicate that the disruption in the CX3CL1–CX3CR1 signaling in schizophrenia may be limited to a shift in the ligand production. Hill et al. [CX3CL1 nor CX3CR1 in the orbitofrontal cortex. The observations regarding the protein and mRNA levels of the CX3CL1–CX3CR1 dyad were unrelated to such contributory factors as body mass index, serum C-reactive protein release, alcohol consumption, prescribed antidepressants or mood stabilizers, death by suicide and a subtype of schizophrenia (undifferentiated or paranoid). As noted by the authors, sex had an effect only on the CX3CL1 production in the control group as males were characterized by higher levels of the ligand than females [To date, only a few studies have evaluated the expression of CX3CL1 and CX3CR1 in patients with schizophrenia  and an increase at P7 and P60. It showed that the expression of the receptor gene was particularly up-regulated at the beginning of synaptogenesis (P7) and declined during the peak of this process and spine formation (P14). These age-specific changes in the Cx3cr1 transcript level implicate MIA-induced microglial dysfunctions that trigger alterations in cortical networks [Cx3cr1 in the hippocampus of male offspring mice.One of the approaches to investigate schizophrenia-like disturbances in animals involves the maternal immune activation (MIA) paradigm , 164 Ta. Most ofA models . Along wA models . In anotA models , the expficiency . In simi deficit . Simultat in PPI . The rest in PPI , 176. Mat in PPI  presentet in PPI . In contt in PPI  showed ds et al.  in theirnetworks . The evinetworks –181. Connetworks . MIA witnetworks  reportedCx3cr1-deficient mice and examined the schizophrenia-related behaviors. Unlike control animals exposed to the procedure, the knockouts did not display deficits in PPI. Moreover, the CX3CR1 level was up-regulated in the medial prefrontal cortex, hippocampus and nucleus accumbens of the isolated wild-type mice, suggesting that the receptor might participate in the examined schizophrenia-like behaviors [Cx3cr1−/− animals was a transient reduction of microglia during the early postnatal period that resulted in impaired synaptic pruning [Cx3cr1 gene could contribute to defects in postnatal synaptogenesis and cortical networks. Besides, Cx3cr1 knockouts exhibited reduced baseline connectivity from the prefrontal cortex to the dorsal hippocampus during the habituation phase in the social interaction test [Further evidence regarding the involvement of the CX3CL1–CX3CR1 pair in the pathogenesis of schizophrenia has been contributed by multiple studies on genetic models with a knockout of the receptor gene. Zhou et al.  applied ehaviors . Another pruning . The aut pruning  suggesteion test . This reion test , 189.Cx3cr1GFP/GFP knockout animals allowed to demonstrate that MMD-reared descendants developed the changes in behavior due to dysfunction of the CX3CL1–CX3CR1 signaling and disrupted synaptic modeling. Notably, the presence of a gut commensal bacterium strain, Lactobacillus murinus HU-1, was sufficient to prevent social alterations and microglial activation in MMD-affected offspring [Cx3cr1 transcript level [The current study by Lebovitz et al.  revealedffspring . Experimpt level . As presThe literature data from reports in patients concerning the role of the CX3CL1–CX3CR1 axis in the pathogenesis of schizophrenia remain inconsistent and, thus, difficult to unambiguously interpret. More information has been provided by the studies in animal models of the disease ; however, those are often confounded with the discrepancies in experimental conditions, including species or strains of animals, a protocol of immunostimulant administration or even paradigm of behavioral examinations. Nevertheless, all of the observations shed a light and increasingly implicate the involvement of CX3CR1 and its ligand in mechanisms underlying schizophrenia. To date, the particular interest in the CX3CL1–CX3CR1 system seems to indirectly result from its extensive role in maintaining the homeostasis of processes in the CNS that are often indicated as disturbed in the course of that disorder Fig. . Yet, fu


The radial distribution function, interface binding energy, and hydrogen bonding of the composite were investigated. The results show that the epoxy resin/C-S-H composite has the maximum stress strength when TEPA is used as the curing agent. Furthermore, the interface binding energy between epoxy resin and cement matrix increases with increasing strain before the stress reaches its peak value. The cured epoxy resin can enhance both the interfacial adhesion and the ductility of the composite, which can meet the needs of crack repair of microcapsule-based self-healing cementitious materials.Microcapsule-based self-healing concrete can effectively repair micro-cracks in concrete and improve the strength and durability of concrete structures. In this paper, in order to study the effect of epoxy resin on the cement matrix at a microscopic level, molecular dynamics were used to simulate the mechanical and interfacial properties of microcapsule-based self-healing concrete in which uniaxial tension was carried out along the  As a new type of concrete material, microcapsule-based self-healing concrete has been proven to repair micro cracks in concrete and improve the strength and durability of concrete . The repAt present, scholars have carried out experimental and simulation studies on microcapsule-based self-healing concrete. Its performance, such as its strength compared with ordinary cement, has been a concern of many scholars, and various studies have been conducted in its experimental aspects ,5,6,7. WIn recent years, molecular dynamics (MD) simulation has been widely used in the microscopic study of cement-based materials ,16,17,18The main factors influencing the repair effect of microcapsule-based self-healing concrete are as follows: (1) curing reaction of repair agent; (2) permeability of repair agent in crack; (3) destruction patterns of microcapsules; and (4) the bonding strength of the remediation agent on the surface of the cement matrix. In the authors’ previous studies on microcapsule-based self-healing concrete using molecular dynamics ,25, the However, there is still a lack of research on the interface behavior between epoxy resin and C-S-H composites under tensile process. In this study, molecular dynamics simulation was used to study the mechanical properties of the interface between C-S-H and the microcapsule core (epoxy resin). Since the curing of epoxy resin is one of the important reasons affecting the effect of fracture repair, the purpose of this paper is to study the influence of two different epoxy curing agents on the bonding energy of epoxy resin and cement matrix during tensile process. Three kinds of C-S-H/epoxy resin models were established in this paper: one was the epoxy resin model without curing, and the others were the epoxy resin models using MC120D and tetrethylenepentamine (TEPA) as curing agents, respectively. The interfacial properties of the composite model were studied by uniaxial tensile simulation in the Z-direction. Finally, the simulation results were analyzed by the stress-strain curve, interface binding energy, and radial distribution function.According to Zhang’s experiment study , E-51 epUniaxial tensile simulation of the model in the Z direction was carried out to obtain the stress strength and failure strain under the NPT ensemble condition. The specific steps were as follows: (1) the temperature was set as 300 K, the external pressure was set as 0 GPa and the calculation time was 1 ns; (2) after the stress relaxation in each direction is zero, input the set stress parameters and set the stretching step of the model in the Z direction as 1 fs in the simulation process. In order to analyze the simulation results, the calculation results were saved every 10,000 steps.The stress-strain curve obtained by uniaxial tensile simulation is shown in The mechanical properties of the models were calculated after structural optimization, and the maximum strain is set as 0.003 to ensure the model is within the elastic stage. In order to ensure the accuracy of the calculation results, the module was repeated three times for each model, and the two close values were averaged to obtain the final results. The bulk modulus, shear modulus, and elastic modulus of the three composite models in X, Y, and Z directions are shown in Based on the bulk modulus and shear modulus calculated, the Poisson’s ratio According to the molecular dynamics and experimental results of Du et al. , the Youi and j in the composite material, respectively. According to Equations (3) and (4), the shear modulus and volume modulus of composites with different epoxy resin volume fractions were calculated, and then Young’s modulus was calculated from Equation (2). The results are shown in In the actual microcapsule-based self-healing concrete, the epoxy resin is not just a chain, but has a certain proportion in concrete. In order to study the influence of different volume ratios of epoxy resin in the cement matrix on the elastic modulus of the whole model and obtain the elastic modulus closer to the actual situation, the shear modulus and elastic modulus of the composite models with different epoxy resin content were calculated using the Mori-Tanaka method (MT method) , which iIt can be seen from The interfacial binding energy can directly reflect the interaction between the tobermorite and epoxy layers, therefore the change of interfacial binding energy during the complete tensile process was studied. The binding energy changes of the three models in the uniaxial stretching process were obtained from Equation (5) , which iIt can be directly seen from By comparing the strain energy of the three models in the tensile process, it can be seen that the interface binding energy of the epoxy resin-tobermorite model with the curing agent increases over 50% compared with that of the uncured epoxy resin-tobermorite model, and the use of TEPA as curing agent can better increase the interface binding energy. Thus, the strength of the whole model is increased, which corresponds to the result of the stress-strain curve. In general, after curing, epoxy resin can increase the bonding effect between epoxy resin and cement matrix, improve the strength of concrete, and thus delay the interface failure.Radial distribution function (RDF) is a characterization method for calculating the adsorption points on composite surfaces of two materials and is used to describe the spatial correlation between atoms . The RDFwo atoms ,45.The radial distribution function was chosen to analyze the atomic interaction between the two layers of tobermorite and epoxy resin in the tensile process. The conformation with the highest stress among the three models was selected for analysis, and the results are shown in Another important interaction between the tobermorite layer and epoxy layer is hydrogen bonding, in addition to the main atoms mentioned in z-axis was carried out. The following conclusions can be drawn:(1)The stress-strain curves proved that using a curing agent can increase the strength of the model, in which the highest strength was from TEPA.(2)The stress in the epoxy resin/C-S-H composite increases due to the increase of interface binding energy in the two stages before failure in the tensile process.(3)The reason why the model using TEPA as curing agent has the greatest strength should be attributed to the greater interaction between O and N atoms in the epoxy resin cured by TEPA and Ca ions in tobermorite, as well as stronger hydrogen bonding between tobermorite and epoxy resin.(4)The tensile simulation in this paper proves that the cured epoxy resin can enhance both the ductility and the strength of concrete, so that it can achieve self-healing function of concrete.(5)In this study, we mainly focus on studying the influence of curing agents on the repairing effect. In fact, there are still other factors that have not been considered , which should be studied in future.In order to study the effect of epoxy resin on the strength of concrete, in this paper, through establishing three models, namely the non-curing model and the epoxy resin/C-S-H composite models using MC120D and TEPA as curing agents, uniaxial tensile simulation of the models along the


Microcapsules encapsulated within epoxy as a curing agent have been successfully applied in self-healing materials, in which the healing performance significantly depends on the binding behaviour of the epoxy curing agent with the cement matrix. In this paper, the binding energy was investigated by molecular dynamics simulation, which could overcome the shortcomings of traditional microscopic experimental methods. In addition to the construction of different molecular models of epoxy, curing agents, and dilutants, seven models were established to investigate the effects of chain length, curing agent, and epoxy resin chain direction on the interfacial binding energy. The results showed that an increase of chain length exhibited had limited effect on the binding energy, while the curing agent and the direction of the epoxy significantly affected the interfacial binding energy. Among different factors, the curing agent tetrethylenepentamine exhibited the highest value of interfacial binding energy by an increment of 31.03 kcal/mol, indicating a better binding ability of the microcapsule core and the cement matrix. This study provides a microscopic insight into the interface behaviour between the microcapsule core and the cement matrix. As the most widely used building material worldwide , the safn-butyl glycidyl ether, BGE) was used as the healing agent, while the MC120D or tetrethylenepentamine (TEPA) was mixed as an epoxy curing agent. When cracks inside the concrete occur, the microcapsules are broken, releasing the epoxy resin. Due to the capillary siphon effect caused by the cracks, the epoxy resin can quickly penetrate into the cracks and solidify with a curing agent to fill the cracks, so as to achieve the purpose of repairing the concrete cracks [Currently, microcapsules with a urea-formaldehyde (UF) shell have been proven to be one of the most effective microcapsules for repairing concrete cracks ,11. Accoe cracks .There are many factors affecting the repairing efficiency of microencapsulated self-healing concrete, among which, the bond strength between the healing agent and the cement matrix has been identified as one of the most important factors influencing the repairing efficiency of microcapsules. It is generally agreed that the interfacial bond strength is affected by curing agent type, dosage, curing temperature, and other factors. For example, Zhang et al.  investigCSH–Ca–Opolymer connection. Hou et al. [S–Ca–Op. Du et al. [2+) and water molecules to the resin molecules. It was reported that the interface failure was caused by brittle failure due to the simultaneous separation of epoxy atoms from the matrix, and the tensile strength of the interface was almost unaffected by unloading and reloading before reaching the failure strength. In summary, MD provides a powerful tool for studying the properties of cement materials at the molecular level, which can be used to explain the various properties of the cement paste, mainly the microstructure and mechanical properties, as well as the interface behaviour between the composite models [MD is a method to obtain the phase trajectory of a molecular system by numerically solving the equations of motion and to count the structural characteristics and properties of the aiming system. In the study of cement and concrete, MD has been extensively applied to simulate the mechanical behaviour of cement materials at the molecular scale, particularly with calcium silicate hydrate (C–S–H), one of the most important hydration products of cement. Wang et al.  studied u et al.  applied u et al.  studied e models ,19,20,21e models , it is eThis paper aims to investigate the binding behaviour between tobermorite, the hydration product of cement and epoxy resin, from the perspective of the molecular level. To obtain a comprehensive understanding, the effects of epoxy chain length, curing agent type, and epoxy direction on the interfacial behaviour were investigated by determining the mean square displacement (MSD), the radial distribution function (RDF), and the interfacial binding energy of the established composite models between tobermorite and epoxy resin with different chemical structures.The force field illustrates the interaction of an atom with its surrounding atoms, which is the core of mechanical simulation. In this study, the COMPASS force field is used to describe the interaction between atoms, which is an ab initio force field, and its algorithm is largely derived from the early force field, namely the CFF force field. The potential function of the COMPASS force field can be expressed in Equation (1) :(1)EtotThe COMPASS force field covers a wide range of covalent molecules, including polymers; organic molecules and small inorganic molecules; and non-covalent bond models covering a range of ionic materials including metals, metal oxides, and metal halides. It has been proven that the COMPASS force field shows good compatibility with cementitious materials ,24,25,265Si6O16(OH)2•7H2O [The simulation in this paper was carried out using Biovia Materials Studio 2016 . It has been widely agreed that tobermorite has a similar interlayer structure to C–S–H ,30,31,32H)2•7H2O , the tobH)2•7H2O .n less than or equal to 2 were a fluid phase [n was set as 0, 1, 2 in the epoxy resin model. Moreover, in order to study the influence of the curing agent and chain length, six epoxy resin models were established, namely, the epoxy resin model without curing and the epoxy resin model after the reaction with diluent and curing agent. The model established according to the chemical structure formula of epoxy resin is shown in Since epoxy is commonly used as a healing agent in self-healing systems ,39, it wid phase , therefoIn this study, a total of 7 models of composites were established, which are shown in NPT  isothermal–isobaric ensembles, in which the pressure was set to 0 GPa. Second, a further 2000 ps run was conducted in the NVT  ensembles to output the result of MD simulation.During the entire MD simulation process, the time step was set as 1 fs and the temperature was fixed at 298 K. The temperature and pressure were monitored and controlled by Nose Thermostat and Berendsen Barostat. Meanwhile, periodic boundary conditions were used . The entThe initial cell lengths in the Z direction before and after MD are listed in t) could be applied to describe atoms deviating from their initial position as the function of time.i and i at time t, N is the number of atoms in the system.The binding energy mainly depends on the interaction between O and N in cured epoxy resin and Ca in tobermorite, which can be reflected by the mean square displacement (MSD) to indicate the repairing efficiency of the cured epoxy resin. The MSD is often used to analyse the displacement of atoms with time, and the estimation of the motion parameters can be obtained in Equation (2). MSD . This may be because the O atoms in epoxy received more attraction from tobermorite than in model 2 and model 3. The deduction can be further proven with the increased binding energy between layers, which will be discussed in In the polymer composite, the MSD for the oxygen atoms in polymers and the Oructures . The MSDSimilarly, the MSD of Si atoms in tobermorite is also shown in Since N-atoms only existed in the epoxy with a curing agent, the MSD of N atoms in the epoxy resin chain in models 5 and 6 are presented in The different configurations and dynamic behaviour of the composites could be attributed to the change in interaction between the polymers and the substances. Therefore, in this study, the binding energy, which is the opposite of the interaction energy between the tobermorite and the epoxy, was calculated by following Equation (3) :(3)Eb=−EThe interfacial binding energy between the epoxy resin and the tobermorite on both sides is presented in T–HEX, CaT–OEX, CaT–CEX, and CaT–NEX of model 5 appeared at 2.35 Å, 2.35 Å, 2.65 Å, and 3.05 Å, respectively, while model 6 appeared at 2.45 Å, 2.25 Å, 2.65 Å, and 2.35 Å, respectively. Obviously, Ca–O appears earlier than others, indicating that there is a good spatial correlation between Ca and O. Therefore, the Ca–O bond played a major role in the interaction between the tobermorite and the epoxy resin layers. Moreover, by comparing the two figures, it can be clearly seen that the value of r of the Ca and O atoms of model 6 is smaller than that of model 5, which may suggest that TEPA offered a better interaction between O in the epoxy and Ca in the tobermorite. Furthermore, it can be clearly seen that the appearance of the first peaks of N and Ca in model 6 was earlier than that in model 5, which suggested that N in the TEPA played a better role in connecting with Ca. Therefore, the epoxy resin using TEPA acting as the curing agent had better interfacial binding energy with tobermorite compared with MC120D.The radial distribution function (RDF), which deals with spatial atomic correlations, can provide abundant structural information for the tobermorite/polymer composites . TherefoIn addition, because the O and H atoms between the interface may form hydrogen bonds and increase the interfacial binding energy , the RDF(1)After the molecular dynamic simulation, the layers of the three-layer structure of the tobermorite and epoxy resin in the model permeate each other due to the interaction between atoms, and the cracks between the models were reduced.(2)The MSD results showed that there was a larger displacement of O in the cured epoxy, which indicated the strong mutual attraction between epoxy resin and tobermorite. Meantime, the N atom in the TEPA showed a larger displacement than that in MC120D, revealing that TEPA can offer better binding behaviour between the epoxy resin and the cementitious matrix.(3)Based on the MD simulation, the incorporation of a curing agent significantly increased the binding energy, with a higher value of TEPA  suggesting that the system of epoxy with a TEPA curing agent may provide a better repairing performance.(4)According to RDF analysis, the earliest appearance of the first peak of Ca in tobermorite and the O in epoxy was observed, indicating the strongest interaction between O atoms and Ca atoms. Additionally, the RDF of Ca in tobermorite and N in cured epoxy further confirmed that the epoxy cured by TEPA can offer a better binding effect on repairing cementitious materials. In addition, O and H atoms between the interfaces will form hydrogen bonds, thus increasing the interfacial binding energy.(5)The results revealed that the chain length and chain direction showed limited influence on the binding energy between the epoxy and the tobermorite, while the type of curing agent significantly boosted the binding energy. Based on the simulation, it exhibited a better ability to repair cracks in cementitious material.In this work, seven composite models were established to investigate the interfacial binding energy between C–S–H and epoxy resin via molecular dynamics simulation. Based on the simulation, the following conclusions can be summarized:Although the binding effect between epoxy resin and a cementitious matrix has been simulated, which may guide the selection of a curing agent to offer better repairing performance, an experimental investigation should be conducted to verify the simulation.


Schizophrenia is a very complex syndrome involving widespread brain multi-dysconnectivity. Schizophrenia is marked by cognitive, behavioral, and emotional dysregulations. Recent studies suggest that inflammation in the central nervous system (CNS) and immune dysfunction could have a role in the pathogenesis of schizophrenia. This hypothesis is supported by immunogenetic evidence, and a higher incidence rate of autoimmune diseases in patients with schizophrenia. The dysregulation of the WNT/β-catenin pathway is associated with the involvement of neuroinflammation in schizophrenia. Several studies have shown that there is a vicious and positive interplay operating between neuroinflammation and oxidative stress. This interplay is modulated by WNT/β-catenin, which interacts with the NF-kB pathway; inflammatory factors ; factors of oxidative stress such as glutamate; and dopamine. Neuroinflammation is associated with increased levels of PPARγ. In schizophrenia, the expression of PPAR-γ is increased, whereas the WNT/β-catenin pathway and PPARα are downregulated. This suggests that a metabolic-inflammatory imbalance occurs in this disorder. Thus, this research’s triptych could be a novel therapeutic approach to counteract both neuroinflammation and oxidative stress in schizophrenia. Schizophrenia is a neurodevelopmental and mental illness affecting nearly 1% of the world’s population, and the age of onset age is between 23 and 34 years in women and close to 30 years in men . One posRecent investigations have observed that the inflammation of the central nervous system (CNS) and immune dysfunction may have a role in the pathogenesis of schizophrenia. This hypothesis developed from immunogenetic evidence and the high propensity of schizophrenic patients to develop autoimmune diseases ,7. NeuroThe WNT/β-catenin pathway is mainly involved in the control of cell development and regeneration, as well as tissue homeostasis ,9. This Understanding the complexity of the relationship between the WNT/β-catenin pathway and neuroinflammation in schizophrenia will help to identify new therapeutic targets. Thus, this review focuses on describing the main role of neuroinflammation in schizophrenia and its relationship with the WNT/β-catenin pathway, which leads to the development of oxidative stress, and highlighting possible therapeutic targets. The interrelationship between the immune and neuroinflammatory systems plays a major role in the neurobiology of schizophrenia . Recent Several studies, including meta-analyses, have found immune dysfunction in schizophrenia ,20. In cMany inflammatory endothelial cell molecules are involved in schizophrenic disorders, including creatine kinase m/B, angiotensin-converting enzyme, matrix metalloproteinase, thyroid-stimulating hormone, thyroxine-binding globulin, intercellular adhesion molecule 1, cortisol, macroglobulin α-2, and thrombopoietin. The altered expression of these molecules contributes to the activation of the acute phase response, leading to the stimulation of the coagulation/fibrinolytic system, which affects vascular permeability and nitric oxide production by endothelial cells . This reC-Reactive Protein (CRP) is one of the main markers of inflammation. CRP modulation is a major marker of therapeutic response for anti-inflammatory treatment ,28. CRP The oxidative stress observed in schizophrenia is associated with the secretion of pro-inflammatory cytokines, leading to a chronic neuroinflammatory process and genetic damage that in turn promotes chronic inflammation, surrounding oxidative stress impacting cells, and immune impairment . A vulneThe association between oxidative stress and chronic inflammation increases the release of pro-inflammatory cytokines, the stimulation of astrocyte activity, dopaminergic and glutamatergic pathway dysregulation, and finally the onset of schizophrenia symptoms. The oxidative stress seen in schizophrenia interacts with inflammation , suggestThe name WNT (Wingless-related integration site) is derived from Wingless drosophila melanogaster and its mouse homolog Int. The WNT/β-catenin pathway is involved in many regulatory pathways, such as embryogenesis, cell proliferation, migration and polarity, apoptosis, and organogenesis . HoweverThe WNT proteins are members of the family of glycoproteins produced by modified lipids . WNT ligAs mentioned previously, WNT/β-catenin pathway dysregulation leads to many deleterious effects in neuronal development, contributing to the pathogenesis of neurodevelopmental diseases, such as schizophrenia ,52. MoreThe activation of the nuclear factor-kappa B (NF-κB) pathway and stimulation of the expression of cytokines and prostaglandins are responsible, in part, for neuroinflammation ,66. NumeTo this effect, β-catenin signaling can complex with RelA and p50 to stop the NF-κB DNA binding and its transactivation activity. However, the protein–protein relationship between β-catenin and the NF-κB pathway is indirect. These two pathways do not directly bind to each other, as stimulated β-catenin decreases the expression of the NF-κB target gene named FAS . SimilarThe disruption of the WNT/β-catenin pathway is observed in several diseases associated with chronic neuroinflammation, such as neurodegenerative diseases, but also in psychotic disorders, such as obsessive-compulsive disorder, depression, and autism spectrum disorder ,78,79,80The inflammatory process stimulates peripheral immunoinflammatory pathways, such as IL-6, high-mobility box protein 1 (HMGB1), Dickkopf 1 (DKK1), and CCL11 (eotaxin) ,82. ThusPrevious studies have shown that a vicious and positive interplay operates between oxidative stress and neuroinflammation . Indeed, the activation of the NF-κB pathway leads to the production of prostaglandins and the development of oxidative stress . SimilarA strong relationship between oxidative stress and the immune system has been shown to be involved in schizophrenia . GlutathPro-inflammatory cytokines are associated with the schizophrenic process via the disruption of major neurotransmitter systems . Pro-infOxidative stress is a well-known process in schizophrenia ,96. AlthA large number of studies have evaluated peripheral biomarkers of oxidative stress, including antioxidant levels. Recent studies have observed that oxidative stress biomarkers, such as GSH, are at low levels in the plasma of schizophrenic patients ,99. In cFurthermore, redox dysfunction leading to oxidative stress in schizophrenia ,108 is cRapid excitatory neurotransmission is modulated in the CNS by glutamate. In neurons, glutamate is stored in synaptic vesicles, from which it is released. The release of glutamate leads to a sharp increase in its concentration in the synaptic cleft, which connects the ionotropic glutamate receptors. Glutamate is then removed from the synaptic cleft to be transported to the astrocytes by glutamate transporters (such as GLT-1 or excitatory amino acid transporters 1 and 2: EAATs 1 and 2) to prevent the upregulation of glutamate receptors . AstrocySchizophrenic patients may present with low levels of glutamate in the CSF . This hyGSH shows a protective role in protecting cells from ROS damage generated by dopamine (DA) metabolism. The observed deficit in GSH results in membrane peroxidation and lesions forming around dopaminergic terminals, leading to a loss of connectivity . FurtherThus, to corroborate this hypothesis, it turns out that NMDA receptor antagonists, such as ketamine, can lead to psychosis in healthy participants . This psPhysiologically, within astrocytes, β-catenin stimulates the gene expression of EAAT2 and GS . This stThe β-catenin pathway directly controls the expression of EAAT2, GLT-1, and GS ,126,127.A vicious circle can occur between a decrease in the expression of β-catenin, a decrease in the activity of EAAT2 and GS, neuroinflammation, and the excitotoxicity of glutamate ,127. Few effective treatments exist for schizophrenia, so it is essential to find new therapeutic pathways. One possible interesting pathway is the use of peroxisome proliferator-activated receptor (PPAR) agonists through their multiple applications in neuroinflammation, oxidative stress, and their interaction with the WNT/β-catenin pathway.PPARs are ligand-activated transcription factors that bind PPRE (PPAR response elements). PPARs are subdivided into three isoforms: PPARα, PPARγ, and PPAR β/δ . In the Recent studies have shown that PPARα may modulate the neuroinflammatory mechanisms observed in psychiatric diseases, such as depression  and schiThe decrease in PPARα expression is associated with the development of schizophrenia . It has Numerous studies have shown that the WNT/β-catenin pathway and PPARγ act in an opposite manner, including psychiatric disorders, neurodegenerative diseases, and fibrosis processes ,152,153 In many diseases, the expression of PPARγ is downregulated by the overexpression of the WNT/β-catenin pathway ,155,156.A growing body of evidence has shown the important role of neuroinflammation in the pathogenesis of schizophrenia. In addition, the relationship between neuroinflammation and oxidative stress is well documented in this disorder. The WNT/β-catenin pathway is essential for several cellular events that take place in development, homeostasis, and regeneration. However, there is limited knowledge regarding its dysregulation in schizophrenia. Therefore, further studies are still needed in order to clarify the role of the WNT/β-catenin pathway in schizophrenia. Understanding the molecular mechanism of the WNT/β-catenin pathway will contribute to the development of novel therapeutic strategies for schizophrenia. Recently, new evidence has been provided on the protective effects of activation of PPARα expression. In schizophrenia, the WNT/β-catenin pathway and the expression of PPARα act in a positive interplay, which in turn leads to this complex negatively interacting with the expression of PPARγ. This triptych could be a new therapeutic approach to counteract neuroinflammation and oxidative stress in schizophrenia.


Polylactic acid (PLA) was melt-blended with epoxy resin to study the effects of the reaction on the mechanical and thermal properties of the PLA. The addition of 0.5% (wt/wt) epoxy to PLA increased the maximum tensile strength of PLA (57.5 MPa) to 67 MPa, whereas the 20% epoxy improved the elongation at break to 12%, due to crosslinking caused by the epoxy reaction. The morphology of the PLA/epoxy blends showed epoxy nanoparticle dispersion in the PLA matrix that presented a smooth fracture surface with a high epoxy content. The glass transition temperature of PLA decreased with an increasing epoxy content owing to the partial miscibility between PLA and the epoxy resin. The Vicat softening temperature of the PLA was 59 °C and increased to 64.6 °C for 0.5% epoxy. NMR confirmed the reaction between the -COOH groups of PLA and the epoxy groups of the epoxy resin. This reaction, and partial miscibility of the PLA/epoxy blend, improved the interfacial crosslinking, morphology, thermal properties, and mechanical properties of the blends. Biodegradable polymers have attracted considerable attention in recent years owing to their environmental effects. Petroleum plastics are being replaced by renewable, eco-friendly materials. Biodegradable polymers, such as PLA , polybutEpoxy resin is a reactive polymer that contains epoxide groups in the structure, which are used to crosslink with variant functional groups such as amides and carboxylic . BisphenTherefore, in this study, the effect of epoxy resin on PLA blending was investigated. PLA was melt-blended with 0–20% epoxy at 170 °C for 10 min. Mechanical properties, morphology, thermal properties, thermal stability, and the reaction mechanism were investigated.Poly(lactic acid) (PLA) pellet  was purchased from PTT Global Chemical Pub Co., Ltd., Bangkok, Thailand. Diglycidyl ether of bisphenol A epoxy resin  was purchased from EASY Resin Co., Ltd., Nonthaburi, Thailand.PLA was blended with epoxy resin using a two-roll mill machine  at 170 °C for 10 min, and then compressed into sheets by a hot compress at 170 °C for 10 min, followed by quenching at 10–25 °C. PLA was blended with 0.5–20% (wt/wt), a monomer of epoxy resin without a hardener to study the effects of the epoxy content. Code name and composition of the sample are shown in The tensile properties were measured following JISK-6251-7 using a tensile tester at a crosshead speed of 10 mm/min with a gauge length of 10 mm. Bone-shaped specimens of 30 × 10 × 0.2 mm (length × width × thickness) were prepared using compression molding at 170 °C for 5 min.Morphologies of the blended samples were characterized using SEM  at 15 kV. The samples were broken in liquid nitrogen, followed by the coating of the fracture surface with a thin layer of gold using sputtering .mH and ΔcH are the enthalpy of melting and cold crystallization, respectively. Δ3.7 J/g) .The samples with dimensions of 10 mm × 10 mm × 3 mm (width × length × thickness) were prepared using hot-compression molding at 170 °C for 5 min. The prepared samples were then tested by increasing the temperature until the flattened needle penetrated 1 mm into the surface using the ASTM D1525 standard. At least five specimens of each sample were tested.The spectra were acquired using NMR . Samples were dissolved in a chloroform solvent (CDCL3) at 25 mg/mL before observation. Analysis of NMR intensities via different statistical models was evaluated using a custom-written Topspin 4.0.8 .p < 0.05) were evaluated using Duncan’s test.The one-way ANOVA with the Statistical Package for the Social Sciences, SPSS Version 17  was used to analyze the data. The differences found (w/w) to observe the effect of epoxy on the mechanical properties of the blends. The stress–strain curve, maximum tensile strength, and elongation at break are shown in PLA was melt-blended with epoxy resin  at 30.7, oxirane ring carbons at 43.9 and 49.7 ppm, and bisphenol A carbons at 41.2, 68.0, 113.6, 127.3, 143.1, and 156.0 ppm [3), 69.1 (methylene carbon), and 169.70 ppm (-C=O) [13C NMR spectra of the PLA/epoxy blends showed the characteristic peaks of PLA and epoxy resin at the same position as that of neat epoxy and PLA. New peaks were observed at 21 and 67 ppm, corresponding to C10 and C11, respectively. 1H NMR spectra of PLA, epoxy, and the PLA/epoxy20 blend. Epoxy showed peaks -CH3 of bisphenol A at 1.6 ppm (b), -CH2 of oxirane ring at 2.6 and 2.8 ppm (c), -CH of oxirane ring at 3.29 ppm (d), -CH2 at 3.9 and 4.29 ppm (e), and aromatic protons of bisphenol A at 6.8 and 7.1 ppm [3) and 5.1 ppm . The 1H NMR spectra of the PLA/epoxy blend showed characteristic peaks of -CH3 (1.6) and -CH (5.1) at the same position as that of neat PLA. Furthermore, the 1H epoxy peaks of bisphenol A  shifted to lower positions, while the peaks of the oxirane ring  shifted to higher positions. New peaks were observed at 2.57 and 3.40 which indicated H7 and H6, respectively. The shifting of bisphenol A and the oxirane ring, and the appearance of two new peaks, confirmed the reaction between PLA and the epoxy. This also suggested a reaction between the epoxy groups of the epoxy resin and the -COOH end groups of PLA (56.0 ppm . Neat PLm (-C=O) . The 13C 7.1 ppm . Neat PLs of PLA c. PreviomT and gT of the PLA/epoxy blends decreased with increasing epoxy content, owing to the nucleating effect of small epoxy particle sizes, and the partial miscibility between PLA and epoxy acting as a plasticizer, respectively. The VST of PLA increased with 2% epoxy, while an excessive amount of epoxy reduced the VST due to reduced crystal formation. NMR results confirmed the reaction between the -COOH groups of PLA and the epoxy groups of the epoxy resin. This reaction improved the mechanical properties, toughness, morphology, and thermal properties of the blends, additionally resulting in high optical transparency. The PLA/epoxy blends also contained unreacted epoxy groups that could react with other reactive functional groups for reactive blending as a compatibilizer. PLA/epoxy can be applied for packaging, medical, and agriculture applications.Epoxy resin was successfully blended with PLA to improve the mechanical properties and reaction mechanism of the blends. The maximum tensile strength of PLA was improved from 57.5 MPa (neat PLA) to 66.9 MPa with 0.5% epoxy, whereas the elongation at break showed a significant increase with 20% epoxy. Morphology of the PLA/epoxy blends showed nanoparticles dispersed in the PLA matrix, while a smooth fracture surface of the 5–10% PLA/epoxy blends was observed due to the high interfacial adhesion between PLA and epoxy. The


Cellulose nanocrystals (CNCs) have unparalleled advantages in the preparation of nanocomposites for various applications. However, a major challenge associated with CNCs in nanocomposite preparation is the lack of compatibility with hydrophobic polymers. The hydrophobic modification of CNCs has attracted increasing interest in the modern era standing with long challenges and being environmentally friendly. Here, we synthesized CNCs by using cotton as raw material and then modified them with 2-carboxyethyl acrylate to improve their corresponding mechanical, adhesive, contact angle, and thermal properties. Different concentrations (1–5 wt%) of CNCs were used as modifiers to improve the interfacial adhesion between the reinforced CNCs and E-51 (Bisphenol A diglycidyl ether) epoxy resin system. CNCs offered a better modulus of elasticity, a lower coefficient of energy, and thermal expansion. Compared with the standard sample, the modified CNCs (MCNCs) showed high shear stress, high toughness, efficient degradation, thermal stability, and recycling due to the combined effect of the hyperbranched topological structure of epoxy with good compatibility. The native CNCs lost their hydrophilicity after modification with epoxy, and MCNCs showed good hydrophobic behavior (CA = 105 ± 2°). The findings of this study indicate that modification of CNCs with 2-carboxyethyl acrylate in the presence of epoxy resin and the enhancement of the features would further expand their applications to different sectors. Cellulose nanocrystals (CNCs) or nanoparticles have drawn a lot of attention due to their abundance, biocompatibility, renewability, and excellent mechanical properties, paving the way to innovative and sustainable applications. CNCs are crystalline and rod-shaped, depending on their source. These have been used as reinforcing agents due to their excellent mechanical properties . These hThere are several limitations associated with the use of CNCs, mainly caused by their relatively low thermal stability. Therefore, using their hydroxyl surface chemistry to give these nanoparticles a new functionality is very interesting. There are many examples of modifying the CNCs’ synthesis routes . PresentThe 2-Carboxyethyl acrylate is a new auspicious substitute monomer due to its molecular composition and high mechanical properties that can potentially replace the toxic water-soluble monomers. The carboxyl group in 2-carboxyethyl acrylate is expected to positively affect the adhesive behavior of CNCs suspension . The 2-CHerein, we synthesized CNCs using cotton as raw material, and these were further modified with 2-carboxyethyl acrylate to improve their adhesion and thermal properties. CNCs were selected as modifiers to improve the interfacial adhesion in E-51 epoxy resin. The novel strategy used in this study will help prepare regenerated cellulose nano-materials with excellent mechanical properties and biodegradability as alternatives to petrochemical plastics for the development of sustainable materials and could be applied in food packaging.Cotton was supplied by the Guangzhou Liqi textile industry (China). 2-Carboxyethyl acrylate was purchased from ChemSrc China (98% purity). Analytical grade ethanol (purity 99.7%), methanol (purity 99.5%), and acetone (purity 99.5%) were obtained from Aladdin . Tianjin Hengxing Chemical industry (China) supplied sulfuric acid (purity 98%). Bisphenol-A epoxy resin E-51 for the adhesive property was supplied by Helin Resin Co., Ltd. The commercially available epoxy was used for comparison and purchased from the local market . Shanghai Macklin Biochemical Co. Ltd. China supplied potassium persulfate (KPS). Triethylenetetramine (TETA) (purity 97%) was obtained from Sigma-Aldrich. Lab-made distilled water was used.2SO4. The final white product (CNC powder) was dried in a vacuum oven at 90°C for 12 h. A schematic of the preparation of CNCs from cotton is illustrated in .First, wax and pectin were removed from cotton. A 20-g cotton was cut into small pieces and washed with hot water at 50–60°C. The washed cotton was heated in a hot air oven at 40°C for 6–8 h. Then, the cotton was mixed with 500 ml of 20% NaOH at 45°C for 4–5 h. The alkali-treated cotton slurry was allowed to cool down to room temperature, and the solution was transferred to 2.5 L of distilled water until the pH was neutralized. The neutral suspension was filtered using a Buckner filter. The sample was then heated and stirred in 500 ml of 60% sulfuric acid for 12 h at 35°C. The resulting particles formed a white suspension that was transferred to the 2 L of water to deactivate the white suspension. The suspension was kept statically for 12 h to allow the settling of cellulose particles. After decantation, the white slurry was again treated with distilled water to remove sodium and sulfate ions. The suspension was centrifuged at 8,000 rpm three times for 10 min. The nanocrystals were vigorously shaken at 40°C with 45–60 wt% to remove Hg-poly (2-carboxyethyl acrylate) is shown in First, CNCs were dispersed in 40 ml of lab-made distilled water at 60°C with stirring for 30 min at room temperature in a nitrogen environment. Then 66.6 mg of potassium persulfate (KPS) was dissolved in 20 ml of distilled water and injected into the solution with the help of a syringe. After 30 min, 2.1 ml of 2-carboxyethyl acrylate monomer was also injected, and the reaction was allowed to stir at 60°C for 3 h. The synthesis of CNCs-2 flow using a TGA analyzing system . The crystalline properties of CNCs and MCNCs were investigated via an x-ray diffractometer . An ultrasonic cleaner ultrasound Instrument Co., Ltd. was used for sonication of CNCs. The high-speed desktop centrifuge (Cence TG16-WS) was used for the isolation of modified CNCs. For contact angle (Contact angle meter DSA 25) with interfacial and surface tension 0.01–2000 mN/m having resolution 0.01°/0.01 mN/m with illumination high power monochromatic LED. The mechanical and adhesive properties of native and modified CNCs were also determined .FTIR spectroscopy was used to examine the chemical structure of modified CNCs with 2-carboxyethyl acrylate (Nicolet. 5700). The surface morphology of native and modified CNCs was observed through a scanning electron microscope  operated at 20 kV. A transmission electron microscope  was used for structural analysis of CNCs. Thermogravimetric and DTG properties of 2-carboxyethyl acrylate were investigated under constant NE-51 epoxy resin was placed on the sample glass bottle, and then the CNCs were added. The resultant mixture was sonicated at 45°C for more than 30 min, and then its suspension was prepared by mechanical mixing. The suspension was then circulated through the agitator until all samples of CNCs were thoroughly dispersed in 1 g of E-51 epoxy resin at room temperature with a magnetic bar for adhesive performance. After 1 h of stirring on a hot plate at room temperature, 0.2 g of TETA was added and stirred slowly for the next 20–25 min until a completely homogeneous solution was obtained. The homogeneous solution was stored in a vacuum oven at 45°C for 10–15 min to remove bubbles from the solution. The CNCs and E-51 epoxy resin mixture was poured onto steel plates, as shown in A TEM view of the native CNCs produced from cotton through acid hydrolysis is shown in −1 was due to the C-H bending  of native CNCs and MCNCs is a dynamic phenomenological approach to investigate the response to change in temperature. The thermal behavior of native CNCs is different from that of MCNCs, as shown in 2 groups, which allow the splitting into β-carbons. Evaluation of the thermal stability of the initial mass loss temperature was determined by the intersection of the initial plated additional mass at the maximum TG curve. The different peaks were first obtained at the maximum temperature. It is only once happening in the process of changing the temperature. The second phase is defined as the temperature that begins and represents the same value for both samples. TGA is an important parameter because of information about the dynamics of mass loss. Unstable emissions during the decomposition process are of great value . This peak intensity directly depends on the absorption of epoxide groups in the mixture of E-51 epoxy resin. The peaks near 2θ degree = 48 and 58 show that the epoxide ring deformation is weaker, which is in accordance with previous reports . The othvia hydrosilylation. This silane coupling agent enhanced the connection between CNCs and epoxy matrix to achieve sustainable and environment-friendly products. A eugenol-based epoxy silane coupling agent with high purity was prepared and used for the surface modification of nano-cellulose crystals. The eugenol epoxy silane-coupling agent, bearing a long-chain structure of benzene ring in the molecular structure, could improve the compatibility of CNCs with the E-51 epoxy system, contributing to the dispersion state in the matrix, enhancing the overall performance of epoxy-cured products.Eugenol-based silane coupling agent (EBSCA) was synthesized We studied the adhesive properties of MCNCs with an epoxy system by measuring the average shear strength  and sheaThe main challenges for using epoxy resins and their composites include the design of high processability (low-viscosity and cured) epoxy with high strength and toughness that can be recycled and reused. Here, we also studied the epoxy system for mechanical properties. The results showed good mechanical properties of MCNCs with the E-51 epoxy system . The MCNWe faced challenges like highly efficient recycling, understanding the homogeneous reinforcing and toughening mechanism, and sustainable development of thermoset epoxy resins. We prepared degradable hyperbranched epoxy resins by esterification and a thiol-ene reaction based on high-performance inexhaustible based epoxy. The cured epoxy composites showed good mechanical properties and degradability, including high shear stress, high toughness, highly efficient degradation, and recycling, resulting from the combined effects of the hyperbranched topological structure of epoxy and good compatibility.The inherent properties of hydrophilicity and environmental preferability of CNCs make them great candidates for application in water-treatment membranes. Here, investigations on anisotropic wetting induced by roughness texture after traditional surface generation methodologies such as CNCs milling may be helpful to optimize the selection of machining condition tools. The proposed model can evaluate the wettability of hydrophilic target materials with a non-composite wetting state, incorporating the liquid spreading dynamics, geometrical aspects, and roughness parameters of the solid surface. Considering the practical applications, a verification of the model is presented through systematic experiments. An investigation on the wettability of CNCs with high illumination power monochromatic LED surfaces establishes a hydrophilic, non-composite wetting state during its interaction with water drops. The contact angle is conventionally measured through the liquid, where a liquid–vapor interface meets a solid surface. The contact angle of water on native and modified CNCs with E-51 epoxy were carried out to demonstrate the wettability of native and modified CNCs, as shown in via the β-glycoside bond. Therefore, CNCs play an important role in different industrial applications in this preliminary work.This study synthesized CNCs and then observed their different properties. The matrix of CNCs was successfully modified by 2-carboxyethyl acrylate using a modified approach. CNC matrix modification has been verified through different spectroscopic techniques. MCNCs studied as a reinforcing material for different polymers have been found to have good adhesive performance, achieving high shear strength (15.1 MPa) at 5 wt% and modulus  at 1 wt%. 2-carboxyethyl acrylate introduction to CNCs has significant effects on the physicochemical properties of CNCs. MCNCs of adhesive properties are improved due to the dispersion and better interaction between grafted CNCs and the E-51 epoxy system. The mechanical properties were also enhanced and improved. The effects of EBSCA on the adhesive and mechanical properties with epoxy systems indicated that silane-coupling agents could effectively improve the toughness of the epoxy system. CNCs consist of linear polymers without water units, connected to four carbon atoms


Fusarium oxysporum f. sp. cubense TR4 (Foc TR4) causing Fusarium wilt of Cavendish banana. Forty-nine out of the total 357 fungal endophytes from the roots of weeds exhibited antagonistic activity against Foc TR4. High inhibitory activity at 79.61–99.31% based on dual culture assay was recorded in endophytes Lasiodiplodia theobromae TDC029, Trichoderma asperellum TDC075, Ceratobasidium sp. TDC037, Ceratobasidium sp. TDC241, and Ceratobasidium sp. TDC474. All five endophytes were identified through DNA sequencing with 86–100% identity. Endophyte-treated Grand Naine and GCTCV 218 plantlets showed significantly lower disease incidence (p = 0.014), significantly lower degree of leaf yellowing (p = 0.037) and rhizome discoloration (p = 0.003). In addition, the cultivar Grand Naine was consistently highly susceptible compared with the tolerant cultivar GCTCV 218.The antagonistic activity of fungal endophytes isolated from weeds growing in Cavendish banana farms was determined against  Banana is among the world’s most valuable primary agricultural commodities and one of the most traded fruits worldwide. The Philippines which ranked the second largest exporter behind Ecuador, produced 3.4 million tons (USD 1.5 billion) in 2018 and contributed 90% of the total export volume in Asia [Fusarium oxysporum f. sp. cubense (Foc) Tropical race 4 (TR4). The disease is confirmed present in Cavendish banana plantations in Mindanao and has so far caused damage to many farms [Being grown in genetically uniform banana plantations, the crop is very susceptible to diseases, one of which is the most devastating disease Fusarium wilt caused by ny farms . While tny farms . As suchFoc TR4 infection. It is plausible that this is influenced by beneficial microorganisms particularly those intimately associated with the bananas.The use of biological control agents as part of a sustainable and integrated plant disease management is increasingly becoming important especially in crops like Cavendish banana which are grown in monocultures with large pesticides inputs. Biological control of Fusarium wilt in banana has been studied for years . Many stWeeds literally grow anywhere in diverse conditions. Like any other plants, weeds may have rich microbiota that may contribute to their survival in varying conditions. According to van Wees et al. , plant tFoc TR4 in laboratory and greenhouse tests using the susceptible cultivar Grand Naine and the tolerant cultivar GCTCV 218.This study aimed to identify fungal endophytes associated with roots of weeds growing in Cavendish banana farms, and determine their potential in controlling ®, Mumbai, India). The parafilm-sealed plates were incubated at 26–27 °C with 12 h-dark/light cycle. The plates were monitored daily and mycelial tips of growing fungal colonies were transferred to PDA slants for pure culture. Each isolate was labeled properly with corresponding accession number.Weeds growing in commercial and abandoned Cavendish banana farms were collected as sources of fungal endophytes. Root segments that appeared healthy or without necrosis  were cutVirus-indexed and tissue-cultured Cavendish banana cv. Grand Naine and GCTCV 218 were sourced from the Tissue Culture Laboratory—Research Information and Compliance Division of TADECO. Grand Naine is highly susceptible to Fusarium Wilt while GCTCV 218 is tolerant . The rooFoc TR4 isolate collected from an FW-infected Cavendish banana was used as control in laboratory and greenhouse tests. The infected banana manifested symptoms typical of Fusarium wilt disease, such as vascular discoloration of the pseudostem and intense yellowing of older leaves. This was confirmed as TR4 through DNA-based detection. Single spore culture of the isolate was generated and maintained as pure culture.A Foc TR4 culture was isolated using a modified CTAB method [Foc TR4 was used in real-time PCR detection of the pathogen.DNA from a B method . The priB method  specificFoc TR4 based on dual culture assay were identified by molecular method. The fungal genomic DNA was extracted from the culture of the five fungal endophytes using the commercially available DNeasy Plant Minikit  following the manufacturer’s procedures. Amplification of the internal transcribed spacer (ITS) region was performed with primers ITS1 (5′-TCC GTA GGT GAA CCT GCG G-3′) and ITS4 (5′-TCC TCC GCT TAT TGA TAT GC-3′) by White et al. [Five fungal endophytes which gave the highest inhibitory activity against e et al.  on a CFXThe endophytes were checked based on their morphological characteristics, such as colony growth on PDA and spores growing on hyphal tips. Microscopic structures were referred to the manual of Watanabe . An agarFoc TR4 disc at the center, was carried out. The plates were incubated at 26–27 ± 1 °C for 7 days and the antagonistic activity was observed as inhibition of the growth of the pathogen through niche or resource competition; or by antibiosis marked by a clear zone of inhibition. The fungal endophytes with observed antagonistic activities against TR4 were selected for further studies.A preliminary test to check antifungal activity of 357 endophytic fungal isolates was done using 4-point assay involving inoculation of 5-mm discs of endophytes to four points in the plate with Foc TR4 culture were placed at 30 mm apart in PDA medium. As control, a mycelial disc of Foc TR4 alone was placed at 30 mm from the edge of the plate. Parafilm-sealed plates were incubated for 7 days at 26–27 ± 1 °C. The inhibition of radial growth of the pathogen was determined using the formula by Sonawane et al. [Foc TR4 in the control plate; R2 = growth radius of Foc TR4 towards the antagonist. Using the assessment by Soytong [Out of the 357 fungal endophyte isolates, 49 isolates were evaluated further by dual culture method. The 5-mm mycelial discs from the actively growing edge of a 5-day old fungal endophyte and e et al. :PIRG %=  Soytong  as cited Soytong , the antThere were three replications with five plates per replication.Foc TR4 in in-vitro assay were inoculated to 5-week old banana plantlets to determine if they are pathogenic to Cavendish banana. The four non-spore-bearing endophytes were grown for 7 days in 10 mL potato dextrose agar to standardize the inoculum. Inoculation was done by burying cultures from half of a petri dish to four equidistant holes around the base of the plantlet. The spore-bearing endophyte was inoculated by drenching 50 mL spore suspension (106 per mL) of a 7-day old culture to the base of the plantlets. Second inoculation was done a week after the first inoculation or to 6-week old banana plantlets. Eight weeks after, banana plantlets were assessed for the presence of leaf yellowing, rhizome discoloration and other symptoms of diseases.Five fungal endophytes which showed the highest antagonistic activity against Foc TR4 in dual culture assay were tested against the pathogen in pot test using cvs. Grand Naine and GCTCV 218. Four fungal endophytes were non-spore-forming hence cultured for 7 days in 10 mL PDA to standardize the inoculum. Inoculation of non-spore-bearing endophytes was done to 5-week old plantlets by burying cultures from half of a petri dish to four equidistant holes around the base of the plant. One fungal endophyte was spore-forming and inoculated to banana as drench at 50 mL per plantlet with 1 × 106 spores per mL. Second endophyte application was done 1 week after the first endophyte application or to 6-week old banana plantlets. Two weeks after endophyte inoculation, Foc TR4 was inoculated to 8-week old banana plantlets by drenching 50 mL Foc TR4 solution adjusted to 1 × 106 spores per mL. The sample plants were watered regularly to maintain high moisture necessary for infection. There were three replications with 15 plantlets per replication. Eight weeks after Foc TR4 inoculation, disease incidence and the degree of disease severity were assessed.Five fungal endophytes with highest antagonistic activity against Disease incidence was calculated as:Disease severity based on leaf yellowing was assessed using a modified disease rating scale on leaf yellowing by Dita et al.  while thPercent disease severity was calculated as:All data were statistically analyzed using analysis of variance (ANOVA) and Tukey’s HSD post-hoc test using IBM SPSS v.22 statistical software.Portulaca oleraceae L., Hedyotis corymbosa (L.) Lam., Cleome rutidosperma DC., Commelina diffusa Burm. F., Cyperus kyllingia Endl., Euphorbia hirta L., Eleusine indica (L.) Gaertn., Echinocloa colona (L.) Link, Brachiarya mutica (Forsk.) Stapf., Peperomia pellucida (L.) H.B. and K., Borreria-like, Ipomoea acquatica Forsk., Rottboellia cochinchinensis (Lour.) W.D. Clayton, Phyllantus amarus Schum. and Thonn., Vernonia cineria L. Less.Fifteen weed species belonging to 10 families were collected from commercial and abandoned Cavendish banana farms as sources of fungal endophytes. The three classes of weeds, grasses, broadleaves and sedges, were represented in the weed species collected from the sampling sites. The weed species were Foc TR4  of the fungal endophytes application on the percent disease incidence of Fusarium wilt (Trichoderma asperellum TDC075 gave the significantly lowest mean of 85.39%.Eight weeks after ium wilt . The conp = 0.000) between the two cultivars with the susceptible Grand Naine showing a higher mean of 97.39% disease incidence compared to GCTCV 218 at 83.69%. Data showed a high percent disease incidence even with the tolerant cultivar GCTCV 218 as it succumbed to the high Foc TR4 inoculum load. Even if endophyte-treated plantlets showed lower disease incidence, infection of Fusarium wilt can still be considered high. This confirms actual observations of the author in the field that tolerant cultivars, i.e., GCTCV 218 could succumb to Fusarium wilt in a highly infected soil due to high inoculum load. This is true in farms which do not practice eradication of Fusarium wilt-diseased plants in the field by leaving infected banana mats to rot in the field. This leads to the increase of Foc TR4 inoculum in the soil and causes further spread of the disease. A tolerant cultivar does not have a high chance of survival when confronted with a very high Foc TR4 inoculum. This highlights the importance of farm operations aimed at reducing inoculum load of Foc TR4 in the soil.There was a significant difference (p = 0.037) on the degree of leaf yellowing was noted as shown in Ceratobasidium sp. TDC037 gave the significantly lowest mean on % leaf yellowing at 26.72%. The untreated control gave the highest mean of 36.77%. Percent leaf yellowing significantly differ (p = 0.000) between the two cultivars with a significantly higher mean of 36.44% in the susceptible Grand Naine.A significant effect of the fungal endophyte application (p = 0.003) of 44.71% which was statistically different from endophyte-treated Cavendish banana plantlets. Significantly lower comparable means ranging from 31.57% to 34.71% were recorded from banana plantlets treated with fungal endophytes  through BLAST showed that TDC029, TDC075, TDC037, and TDC241 gave 99.66–100% similarity to a known sequence. TDC474 on the other hand gave a lower percent similarity at 86%. All of the top isolates except TDC075 were non-spore-forming. Hence, DNA sequencing results provided accurate identification to endophytic fungal isolates which could not be identified morphologically due to the absence of identifiable structures such as fungal spores.Ceratobasidium sp. isolates were recovered from separate weed species. Ceratobasidium sp. TDC037, Ceratobasidium sp. TDC241 and Ceratobasidium sp. 474 were isolated from Rottboellia cochinchinensis, Commelina diffusa and Echinocloa colona, respectively. On the other hand, Lasiodiplodia theobromae and Trichoderma asperellum were both isolated from the broadleaf weed Commelina diffusa. The endophytes Lasiodiplodia theobromae TDC029, Trichoderma asperellum TDC075, Ceratobasidium sp. TDC037, and Ceratobasidium sp. TDC241 were isolated from commercial Cavendish farm while Ceratobasidium sp. TDC474 was isolated from an abandoned Cavendish farm.The three Glomus spp. protected Lakatan plantlets from Foc R4 and at the same time improved plant growth. The combined application of Trichoderma harzianum and Glomus sp. also delayed disease progression of Fusarium wilt in Lakatan.Monoculture production of Cavendish banana necessitates the large input of pesticides. This is necessary since growing the same crop all throughout long periods of time in vast lands means constant availability of hosts to pathogens. With the strict requirements for quality in the international market, banana growers rely on massive use of pesticides to maintain the level of diseases to a minimum such that quality of the fruits for export will be maintained. However, this raises environmental and safety concerns on the improper use of agricultural pesticides. Biological control against Fusarium wilt of banana which involves the use of antagonists as biological control agents offer promising potential as an effective strategy for the management of the disease. One of the most recent studies involving the use of biological control agents against Fusarium wilt of banana was of Castillo et al.  where thFoc TR4. The question on whether these fungi can be introduced to economic crops like Cavendish banana and offer protection against destructive diseases is the basis of this research.Management of banana Fusarium wilt in which biological control plays an important part, the endophyte biology is an emerging field due to increasing research works on characterization of natural products, discoveries on their potential for biological control and crop production improvement . EndophyFusarium endophytes from this test agrees with the organism’s wide distribution in many types of ecosystems. Fusarium spp. is a large genus of fungi commonly found in the soil and associated with plants and at the same time includes plant beneficial endophytes. Studies have been conducted on the potential of nonpathogenic F. oxysporum (npFoxys) to manage Fusarium wilt in banana. Fusarium wilt incidence in the greenhouse was significantly reduced in Cavendish banana plantlets treated with npFoxys isolates CAV 553, CAV 552 and CAV 563 isolated from Fusarium wilt- suppressive soils in South Africa [Foc R1) by 80% in banana cultivar Rasthali when treated with two npFoxys Ro-3 and Ra-1. Despite the potential of nonpathogenic Fusarium being commonly associated with plants as endophytes, thorough evaluation should be done prior to wide-scale or commercial use of these endophyte as a biological control agent against diseases including Fusarium wilt as some strains can increase Fusarium wilt in banana [Foxys into pathogens [This study confirmed that fungal endophytes which are inhibitory against Fusarium wilt disease of Cavendish banana are present and can be isolated from weeds commonly growing in Cavendish banana farms. Furthermore, the higher number of recovered h Africa . Moreoveh Africa  reportedn banana  and the athogens .Foc TR4 in the laboratory showed antagonistic activity against the pathogen through competition for space and nutrients as shown by the endophytes overgrowth vs. Foc TR4 in dual culture assay. Pathogens can be deprived of space and nutrients when beneficial organisms such as fungal endophytes colonize the shared habitat with the pathogen. Through competition of limited resources, growth of the pathogen is suppressed leading to reduction of the incidence and severity of the disease.All of the 49 endophytic fungi tested against Lasiodiplodia theobromae based on its inhibitory activity against Foc TR4 in this test is an interesting microorganism. In a study by Pandi et al. [L. theobromae from the medicinal plant Morinda citrifolia was found to produce taxol, an effective antitumor agent. Taxol has been used for effective treatment of cancer such as refractory ovarian cancer, breast cancer, nonsmall cell lung cancer, AIDS-related Kaposi’s sarcoma, head and neck carcinoma, and other cancer types [Solanum nigrum. Through metabolomics technology, the endophyte was found to produce different classes of bioactive metabolites such as sterols, y-lactone and plant auxin [Lasiodiplodia theobromae produced the hormone jasmonic acid. Jasmonates regulate plant immunity through induction of the expression of defensive genes against pathogen attack and feeding insects [The top 1 endophytic fungus i et al. , L. theoer types ,39,40. Int auxin . In a stnt auxin , submerg insects .Trichoderma species have been used commercially for the management of many pathogens including Fusarium spp. In a study by Thangevalu and Gopi [Trichoderma sp. NRCB + endophytic Trichoderma asperellum prr2 resulted in 100% reduction of Fusarium wilt disease and increased plant growth parameters up to 250%. Results of their study was further validated in the field through application at 15 days before planting, second and fourth month after planting, and resulted in a significant reduction of Fusarium wilt disease in the field as well as an increase in bunch weight. This means that the efficacy of biological control agents entails repeated and sustained application in the field.and Gopi , greenhoCeratobasidium sp. are originally isolated from roots of terrestrial orchid species. These fungi act as symbionts in orchids and play critical roles in germination of orchid seeds due to the orchid’s lack of sufficient food reserves [Ceratobasidium spp. isolates have been reported to control Rhizoctonia solani in cotton [Ceratobasidium spp. isolated from roots of Colombian orchids were tested for biocontrol of rice sheath blight caused by Rhizoctonia solani. The fungus Ceratobasidium spp. isolates significantly reduced disease expression of R. solani in rice seedlings when inoculated 3 days before R. solani [Many isolates of reserves . Ceratobn cotton , soybeann cotton , vegetabn cotton , and gran cotton . Ceratob. solani .Results of the test revealed the potential of fungal endophytes isolated from common weeds in Cavendish banana farms as biological control agents against the destructive disease Fusarium wilt. Promising research studies include optimization of the endophytes’ delivery to the plants in the field. To provide protection to Cavendish banana plantlets, endophytes may be applied to tissue-cultured plantlets while growing in the nursery through various methods; as cultures grown in corn grits, rice hull or as fungal suspension of spores and mycelia. Information on the effective amount or rates of endophytes against Fusarium wilt is necessary. It is important to check the effect of repeated or sustained endophytes application in the field towards the protection of growing Cavendish banana or towards reduction of Fusarium wilt incidences in the farm. Further studies to identify active metabolites in these endophytes as well as the optimization of its application to Cavendish banana plantlets in the field is in order. The fact remains that even with the diverse array of BCAs studied for Fusarium wilt control, tests on performance of these microorganisms in the field were not very common, hence, there is limited information on their long-term efficacy in the area. Most studies were short-term and mostly done in vitro. Due to this, Ploetz  recommen