Hyperbranched polymers and multiarm star polymers are a type of dendritic polymers which have attracted substantial interest during the last 30 years because of their unique properties. They can be used to modify epoxy thermosets to increase their toughness and flexibility but without adversely affecting other properties such as reactivity or thermal properties. In addition, the final properties of materials can be tailored by modifying the structure, molecular weight, or type of functional end-groups of the hyperbranched and multiarm star polymers. In this review, we focus on the modification of epoxy-based thermosets with hyperbranched and multiarm star polymers in terms of the effect on the curing process of epoxy formulations, thermal, mechanical, and rheological properties, and their advantages in fire retardancy on the final thermosets. Dendritic polymers have attracted great interest during the last 40 years due to their unique characteristics, facile structural modification, and potential applications. Among them, hyperbranched polymers (HBPs) have been the most exploited in technological applications at large scales, but multiarm star polymers (MASPs) have also played an important role. Since HBPs were first studied in the 1980s with the publication of some patents and research papers ,3, the nHBPs are a subclass of dendritic polymers that can be effectively used as modifiers of thermosetting polymers because of their interesting properties resulting from the branched architecture and a high number of functional groups . They haDendrimers are the most representative type of dendritic polymers, and their perfect structure defines the group’s architecture. They have a complete regularly branched and uniform structure a, but thPerfectly branched dendrimers are suitable for applications in medicine as drug carrier molecules or in gene delivery, as standards or models for biomolecules, or as catalytic active molecules . HoweverBased on a hyperbranched core structure, MASPs have attracted the attention of many researchers , some ofIn this review, the influence of HBPs and MASPs on the physical properties of epoxy thermosets is summarized through well-known studies on the topic, as well as through some of the most recent articles. Numerous reviews have been published regarding different aspects of HBPs and MASPs, such as synthesis, modification, and applications ,23,24,25gTs) and high hardness, tensile strength, shear strength, and Young’s modulus [Epoxy resins are widely used in applications such as coatings, adhesives, structural applications, or electronics because of their good mechanical properties, relatively low shrinkage, and high chemical and thermal resistance . The wid modulus . However modulus . During  modulus . StrateggT [There are many methodologies to enhance the toughness of epoxy resins. The more extensively used is the addition to the formulation of thermoplastics, block-copolymers, liquid rubbers, inorganic particles, core-shell particles, or nanoparticles ,40,41,42Tg . MoreoveTg .HBPs and MASP can be used as effective polymer modifiers of thermosetting epoxy-based materials because of the advantageous features discussed above. The improvement in the toughness is attributed to the flexibilizing effect induced by the homogeneous incorporation of the HBP or to the local inhomogeneities created in the crosslinked network by the formation of a phase-separated morphology, which hinders the propagation of cracks . In addiThe curing kinetics of hyperbranched-modified epoxy-based thermosetting materials is complex and depends on the curing agent/initiator used, the type and number of reactive functional groups of the HBP, its molecular weight, and the changes in viscosity and mobility modification produced by the characteristics of the HBP added. There is no consensus on how the addition of HBPs affects the curing kinetics. Although the presence of polymeric modifiers such as HBPs increases the viscosity of the formulations, it is not foreseeable if the reaction rate will decrease, by the reduced mobility or the topological restrictions, or it will decrease because of the effect of the HBPs end groups on the curing mechanism .As mentioned before, epoxy resins are extremely versatile due to the wide range of available curing agents. One of the most studied systems is the epoxy/amine, which in some previous works was modified by adding hydroxyl-ended HBP polyesters ,47,48. IChoosing suitable end groups or curing agents can allow the enhancement of the compatibility between HBPs and epoxy resins by the formation of covalent bonds. For instance, epoxy groups are reactive in amine curing systems while hydroxyl groups are not, at least at conventional curing temperatures <250 °C). However, when hydroxyl-ended HBPs are used under cationic conditions, they become incorporated into the network structure through hydroxyl-induced chain transfer reactions that occur, via monomer-activated mechanism, in the cationic ring-opening polymerization of epoxy groups  °C. Howe,52.The epoxy/anhydride system modified with hydroxyl-ended HBPs is another interesting system that has been widely studied ,54. The ® H30    as polym® E1 and E2  (® E1 as a modifier of a DGEBA thermoset cured with diamines. The HBP was compatible with DGEBA at the curing temperature used (100 °C), but as the reaction progressed, the epoxy groups of DGEBA reacted faster than the epoxy groups of the HBP. The curing reaction produced hydroxyl groups which decreased the compatibility of DGEBA and HBP leading to the formation of two-phase microstructures. The HBP did not modify the curing mechanism as the total enthalpy was close to the expected theoretical value [Epoxy-ended HBPs are another important class of tougheners for epoxy thermosets and have shown excellent results regarding the toughening effect and mechanical properties ,67,68,69Sweeden) . In the al value .There is evidence that a reaction occurs between epoxy groups of the epoxy-ended HBP with the epoxy network in epoxy/anhydride systems ,70,71. T® H20, H30, and H40 [® H20 and Boltorn® H40 as toughening agents using thermal curing and UV curing. Low contents of HBP decelerated the reaction but an acceleration was observed with 20 wt.% when thermal curing was selected. As mentioned before, the opposite effects of increased viscosities and increased number of hydroxyl groups explained these results. When UV curing was used, the temperature played a very important role. At low temperatures, the solubility of the HBP was poor and the curing reaction was hindered. However, at higher temperatures, the HBP was completely solubilized and promoted the curing reaction.UV-polymerization has attracted substantial interest due to its wide fields of applications such as printing inks, adhesives, or composites ,73,74. T and H40 , a notab and H40 . A decre and H40 ,79 compa® H2004 and a poly(tetramethylene ether glycol) (both with molecular weight around 2000 g/mol) on a cycloaliphatic epoxy resin cured with UV-light. The photopolymerization kinetics were significantly faster with the HBP than with the linear polyether. Reactive OH groups of both modifiers had a positive effect on the cationic UV-curing of the epoxy, but the HBP had a larger amount of hydroxy groups exposed to the surface layer while the random coil morphology of the linear poly(tetramethylene ether glycol) limited the number of active OH groups topologically available.More recently, Xia et al.  studied ® H30 with 10-undecenoyl moieties s to combine all the good characteristics previously obtained with the modification of Boltorns et al.  used 10-gT. To solve these issues, the same authors used allyl and 10-undecenoyl modified hyperbranched poly(glycidol) as modifiers of DGEBA thermosets cured by adipic dihydrazide [Tomuta et al.  synthesiydrazide . DihydraThe modification of hydroxyl-ended hyperbranched polymers led to a significant enhancement of mechanical and thermomechanical properties without significant changes in the curing kinetics. ® by reacting with allyl glycidyl ether  with amino groups Lupasolyl ether  or with c effect .Several studies about the synthesis or modification of HBPs can be found in the literature to introduce other reactive groups in their structure and their impact on curing kinetics. Santiago et al.  studied ® with phenyl isocyanate (PEI-PhNCO) to block all the N-H groups and two different proportions of t-butyl isocyanate to obtain a degree of modification of 75% and 100% (PEI-BuNCO75 and PEI-BuNCO100). The kinetic study revealed no changes in the curing reaction of DGEBA/hexahydro-4-methylphythalic anhydride formulations modified with PEI-BuNCO100, an acceleration effect with PEI-BuNCO75 and a deceleration with PEI-PhNCO. The acceleration effect, when PEI-BuNCO75 was used, was attributed to the unreacted N-H groups in the modifier structure, which could react with epoxides and anhydrides because of their nucleophilic character. The deceleration observed was explained based on the dilution effect of reactive groups and the increase in viscosity on adding PEI-PhNCO.Morancho et al.  synthesiIn the study carried out by Fei et al. , the aut®  was put into evidence. The curing mechanism was similar to both amines and followed a general epoxy/amine polycondensation mechanism. However, the curing rate was slower using the HBP polymer than the linear DETA because of the lower mobility of HBP. Gelation took place earlier with HBPs because of the higher number of functional groups, which reduce the conversion at the gel point.The effect of HBPs on the curing kinetics of different epoxy systems then becomes clear. However, it is interesting to compare the effect between HBPs and their linear counterparts. In the studies carried out by Santiago et al.  and FernAs previously stated, MASPs are another subclass of dendritic polymers that consist of linear polymeric chains radiating from one single branched point or core . The lowAcebo et al.  modifiedMASPs with poly(styrene) and poly(methyl methacrylate) arms were also used as modifiers in epoxy systems ,104 Sch. The addgT and thermal stability [gT. However, the inherent steric hindrance of the HBP structure often leaves unreacted functional groups in the system. When the miscibility of the HBP into the epoxy matrix is good enough, there is no phase separation and the reduction in the gT is attributed to a decrease in the crosslinking density. However, if the compatibility between the HBP and the epoxy resin is poor, the system becomes phase-separated upon curing. In many cases, the HBP is compatible with the epoxy at the cure temperature used and it is perfectly dissolved. However, when the homogeneous mixture of epoxy and HBP is cured, the epoxy groups often react faster with the curing agent than the HBP. This results in the formation of hydroxyl groups which decreases the compatibility of epoxy and HBP leading to the formation of a two-phase microstructure [gT value despite the crosslinking density achieved [The first attempts to enhance the mechanical properties of epoxy thermosets by introducing HBPs achieved significant improvements in tensile strength, flexural strength, and impact strength but at the expense of a decrease in the tability ,106,107.tructure . In someachieved ,108.gT and decreases again in the rubbery region. Below the gT, the damping behavior is low because the polymer chains are frozen, and the deformation is primarily elastic. Above the gT, the damping behavior is also low because in the rubbery region chains are free to move and their resistance to flow is very low. In the glass transition region, the damping behavior is high because of the micro-Brownian motion of the polymer chains [gT, but when some wt.% of HBP is added, if there is phase segregation, two domains are formed: an epoxy-rich domain and an HBP-rich domain. In such cases, another peak is observed at lower temperatures. This β-relaxation is associated with the gT of an HBP-rich phase. When the percentage of HBP is relatively low (<20%) the gT of the epoxy-rich phase does not change with HBP content but the gT of the HBP-rich phase decreases with increasing HBP content. This means that the epoxy resin dissolved in the HBP-rich phase is not sufficiently cured [gT of the epoxy-rich phase can be observed because there is HBP dissolved in the epoxy matrix that prevents the system from being fully cured or plasticized.DMA analysis is a useful technique to study phase segregation through tan δ vs. temperature plots. As the temperature increases the tan δ goes to a maximum, which is associated with the glass transition temperature r chains . Neat eply cured . With higT was observed in different epoxy systems by using HBPs with different generation numbers (Boltorn® H30 and H40) and different wt.% content (15% and 30%). SEM micrographs did not show any phase separation and the DMA thermograms did not show any bimodal relaxation curve in formulations with 15% of H30. In this case, the reduction in the gT can be attributed to a decrease in the crosslinked density in comparison with neat epoxy because of the steric hindrance of the HBP. When using 30% of H30, the system became phase-separated and did so when the system was modified with H40 (with 15 and 30 wt.%). Thus, increasing the content and the molecular weight led to a lower miscibility. When H40 was added, the reduction in the gT of the epoxy-rich phase was smaller compared to the blends modified with H30 but the β-relaxation increased significantly. The authors stated that H40 was less compatible with the epoxy because fewer polar OH groups, which contributed to the miscibility of the polymer, were exposed on the shell due to the folding-back of the dendritic arms.The reasons that might cause bad HBP/epoxy interaction are the structure  and the content of the HBP. In the work of Cicala et al. , one cangT of the epoxy-rich phase was lower than the gT of the neat epoxy formulation. This decrease is more notorious when the HBP with the lowest generation number was added because of the higher compatibility with the epoxy network.Cicala et al.  studied In another study, Dhevi et al.  synthesiEpoxy resins possess high thermal stability caused by their densely crosslinked network achieved during the curing reaction. However, this thermal stability can be a drawback for the reworkability, for instance, of electronic devices. Thermosetting materials cannot be recycled but they can be degraded under controlled conditions to remove them from the substrate, enabling the recovery of electronic components. Reworkability can be achieved by the introduction of thermally cleavable linkages such as esters of secondary or tertiary alkyl groups in the network structure which can degrade easily upon heating but with a decrease in thermal and mechanical properties ,112. A dgT. In both studies, a progressive decrease in gT was observed upon saponification time which indicated that the network structure was modified by the incorporation of the HBP containing chemically labile groups.Although hyperbranched aromatic polyesters also contain a high proportion of ester groups, no decrease in the thermal stability is often observed because aromatic and primary aliphatic esters are not as easily degradable as labile aliphatic tertiary esters . In suchgT was not influenced by the arm length of the MASP, but it decreased slightly on increasing the amount of MASP in the formulation. The presence of ester groups in the arms led to a reduction in the initial degradation temperatures that favored thermal reworkability. When hyperbranched poly(ethyleneimine) was selected as the core in the multiarm star of poly(ε-caprolactone) arms of different lengths, the initial degradation temperature of the final thermoset was slightly reduced on increasing the length of the arms, and the proportion of modifier in the thermoset [gT of the thermosets slightly decreased on increasing the amount of the star modifier in the formulation, but there is no change on increasing the number of arms of the MASP. However, the initial degradation temperatures decrease as increasing the amount of the star modifier in the formulation and also on increasing the number of arms [The modification of epoxy resins with MASPs additives can influence the thermal behavior differently, depending on the chemical structure of the stars. Morell et al. ,99 synthhermoset . In star of arms .Epoxy thermosets are amorphous and highly crosslinked materials. The crosslinking density is a key parameter in determining the mechanical properties of an epoxy resin after cure. The degree of crosslinking and the nature of the bonds in the cured epoxies give them many desirable characteristics, such as good mechanical and thermal properties, that have placed these thermosets as the standard option for a variety of applications e.g., adhesives, coatings, or matrix for composites. However, they have some disadvantages that limit their use in structural applications. Epoxy resins are brittle in general due to their highly crosslinked structure, which confers them low impact strength and poor resistance to crack propagation. The tight structure implies a shrinkage that is undergone during the curing process, which finally leads to the apparition of stresses and defects in the material. In coatings technology, scratch resistance is another issue that needs to be improved. Therefore, new strategies to overcome these drawbacks are needed but without compromising other properties .Toughness refers to the energy that a material can absorb before failure occurs . Thus, tToughening by micro/nanostructures can be achieved through chemically induced phase separation methodology (CIPS) from an initial homogeneous blend composed of the resin, curing agent, and modifiers. CIPS is an important method to produce phase-separated morphologies, which generally proceeds from an initially miscible solution to a regular phase-separated morphology during the curing reaction . The reaThe incorporation of HBPs can improve the toughness of epoxy thermosets without affecting other properties . The impGenerally speaking, the phase-separated toughening effect of HBPs increases to a maximum and then decreases with respect to the particle size domain. The toughening effect in phase-separated morphologies is due to the cavitation of rubbery HBP particles and shear yielding of the matrix. Cavitation absorbs energy and encourages the yielding of the polymer matrix. After the cavitation process, the particles can induce large stress concentrations and extensive shear deformation which is a high energy-absorbing mechanism ,127. BotIcK, increased from 0.63 MPa IcK values, from 0.63 MPa IcG from 120 J/m2 for the neat resin to 720 J/m2 for the modified resin. Similar results were obtained in other research studies regarding the toughening effect of epoxy-ended HBPs [Boogh et al.  studied ded HBPs ,68,69,70Traditionally, epoxy-ended HBPs showed to be better tougheners for epoxy resins due to their good compatibility compared to hydroxyl-ended HBPs . This waAlthough the mechanical performance in phase-separated HBP-modified epoxy systems is good in general, sometimes the toughening effect is dependent on the final phase-separated morphology, which is often difficult to control during processing. In addition, phase-separated morphologies can lead to unwanted interfacial effects, which is unacceptable for certain electronic and damping applications, and could also complicate the processing of the thermosets for applications when fibers or other reinforcements have to be added ,68. Thus® S1200 and H1500, as well as another one synthesized by the authors with higher molecular weight, in epoxy/anhydride systems. In general, the addition of HBPs led to an improvement in impact strength (up to 60% with respect to neat epoxy). This increase in toughness was attributed to the flexible structure of the HBPs introduced in the network. It was also observed that the addition of HBPs led to a slight increase in Young’s modulus of the thermosets (up to 10%) and microhardness values (up to 25%).Several research studies showed that toughness and other mechanical properties of epoxy thermosets could be simultaneously improved by adding compatible HBPs which did not lead to phase separation, such as by using ionic initiators, epoxy/anhydride systems catalyzed by tertiary amines, or by changing the surface structure of the HBP. From 2009, our research group adopted a new curing method to obtain homogeneous morphologies based on epoxy/anhydride systems modified with hydroxyl-terminated HBPs and tertiary amines as initiators ,56. UsingT was found in DMA curves of the systems modified with second-generation HBPs, indicating a homogeneous structure without any phase separation. The small molecular size of these HBPs helped them to disperse homogeneously in the DGEBA matrix. The epoxy groups of the HBPs and DGEBA reacted with the amine groups of the curing agent. The external crosslinking structure of the HBPs restricted the movement of the internal end-groups of the HBP and could not react with any group. Thus, many non-crosslinked intramolecular cavities absorbed energy, distorted, and formed protonema during impact, indicating high toughness. In addition, the HBP could penetrate the molecular chains of the DGEBA matrix due to its small hydrodynamic volume for increasing interactions between molecular chains during curing and reinforced tensile and flexural strength. Similar results can also be observed in other research studies regarding the use of epoxy-ended HBPs [gT. The simultaneous improvements are explained by the higher crosslinking density and increased nanoscale cavities. However, at higher loadings of HBPs, the mechanical performance decreased due to incomplete cure. Similar results were obtained in the study by Zhu et al. [Zhang’s research group reported the use of different aromatic epoxy-ended HBPs obtained by condensation of trimellitic anhydride and diethylene glycol or butanediol glycol and further glycidation of the free carboxylic groups, which increased the toughness of DGEBA as well as tensile and flexural strength ,131,132.ded HBPs ,133,134.ded HBPs ,136 syntu et al. , in whicInteresting research papers about the toughening effect of other types of HBPs  have been reported in recent years. Fei et al.  used a cLu et al.  synthesi® D400. In general, a steady decrease in gT was observed upon increasing the content of the HBPs because of a reduction in the crosslinking density and network stiffness. Tensile strength showed a maximum with 3 wt.% and 5 wt.% with poly(MA-DEA) and (poly(MA-EA), respectively, and elongation at break increased as increasing the content of HBPs. In the case of impact strength, when the HBP content was higher than 10 wt%, the steric hindrance effect of the HBP inhibited hydrogen bonding and led to a decrease in impact strength.Park and Choe  synthesiSeveral factors affect the performance of HBPs as toughening agents, such as the molecular weight or generation number ,110,115.® H1500 3 to chemically incorporate the HBP into the epoxy matrix. This result was attributed to the higher compactness of Boltorn® H30 before curing produced by the large number of intermolecular H-bond and intramolecular H-bond interactions which decreased when the terminal hydroxyl groups reacted with the epoxy groups. It was also reported a reduction in shrinkage after gelation [Another important issue regarding the mechanical properties of thermosets is shrinkage. Shrinkage is the reduction in volume brought about by an increase in density throughout the curing process of a thermoset. Chemical shrinkage occurs because of the formation of new covalent bonds during the curing process. Usually, the new bonds formed are shorter in the polymer than the distances between monomers. The curing process of epoxy resins is a critical point in the field of coatings since shrinkage can lead to the appearance of internal stresses and defects in the materials, such as microvoids, microcracks, or warping . The glogelation ,56, whicgT and thermal stability. 10-undecenoyl modified hyperbranched poly(glycidol) was also added to a cycloaliphatic epoxy resin and cationically cured with Yb(OTf)3 [® H30 was modified with several proportions of 10-undecenoyl chloride [® H30 polyesters allowed a regular microphase separation to be reached with excellent interfacial interaction, which leads to a cavitation effect on the fracture mechanism.The existence of a great number of terminal groups in the HBP structure allows the compatibility of the HBP to be tailored, and the epoxy matrix which, as said before, would affect phase separation and mechanical performance in an extensive way. Several HBPs were modified in different proportions with 10-undecenoyl groups, which allowed phase-separation or homogeneous materials to be achieved . HyperbrYb(OTf)3 . The modchloride . Four-foAlthough MASPs have been less used to improve the mechanical characteristics of epoxy thermosets, there are some studies in this field. Ren et. al.  synthesi3 [gT, but with a slight decrease in microhardness and elastic modulus [In our research team, a broad exploration has been carried out on the use of MASPs as toughness modifiers. Higher impact resistance, in comparison to the linear analogous, was reached when MASP with poly(glycidol) core and poly(ε-caprolactone) arms were added to DGEBA cured by Yb(OTf)3 . The imp modulus . Amphiph modulus .Some rheological parameters, such as viscosity, shear response, and pot life, have enormous importance in the processability, flowability, and stability of the epoxy system. One of the main advantages of HBPs is that they show low viscosity in comparison to their lineal counterparts with the same molecular weight per equivalent functional group. The variation in the viscosity of the blends depends on the difference in viscosity between the epoxy matrix and the HBP and the structure of the HBP. In some cases, even a small content of HBP may significantly increase the viscosity of the system ,95,144. Although gelation is not a rheological phenomenon itself, rheology provides useful tools to determine the gel time. Gelation corresponds to the formation of a giant macromolecular structure that percolates the reaction medium. The gel fraction extends and increases crosslinking of the system as the curing advances leading to a fully three-dimensional network. Macroscopically, a change from liquid to solid mass can be observed; the material ceases to flow and starts to build up mechanical properties . The gelRegarding the viscosity of formulations, the addition of MASPs as modifiers in epoxy resins leads to smaller increases than their linear analogs. Ren et al.  could obgT [Besides the inherent brittleness of epoxy resins, another disadvantage of these materials which could limit their application is that epoxy resins are more combustible than similar thermosets because of their reduced tendency to carbonize . The firTg ,161. In Tg ,164,165.gT was raised due to the increased crosslinking density and impact strength showed a slight increase due to the in situ energy dissipation of intra-molecular cavities and inter-molecular free volume between HBP molecules. In the case of HPUPO [Chao et al. ,167 syntdecT) overlap. When this decT overlap between flame retardant and matrix was higher, the chemical interaction was greater and led to effective flame retardancy in the form of higher char yield, reduced peak of heat release rate, and lower total heat release. Hyperbranched flame retardants offer the possibility of tuning the decT via molecular weight and thus the overlap temperature range can be adjusted. In another study, Battig et al. [Schartel’s group worked intensively on phosphorus based flame retardants, including the utilization of HBPs ,171,172.Hu et al.  synthesiDöring’s research groups have published several research papers on flame retardancy of epoxy-based composites and thermosets, including MASPs phosphorous-containing flame retardants ,174. In Finally, to summarize all the content of this review, HBPs and MASPs have been demonstrated to be excellent modifiers for increasing the toughness of epoxy thermosets without affecting other properties. This review has covered the effect of hyperbranched polymers and multiarm star polymers on the modification of epoxy thermosets regarding the effect on the curing process, thermal, mechanical, and rheological properties, and fire retardancy through the most relevant studies on the topic. They can be relatively easily obtained through a one-step polymerization reaction and their structure adjusted to obtain the desired properties of final materials.gT can increase due to an increase in the crosslinking density but, if the compatibility between the epoxy and the modifier is poor, HBP or MASP can phase separate and thus the gT of the epoxy-rich domain does not change with HBP or MASP content. However, the gT can decrease with HBP or MASP content if they have an aliphatic flexible structure. The incorporation of HBPs or MASP can improve the toughness of epoxy thermosets due to the flexibilizing effect induced by the homogeneous incorporation of them, or due to the local inhomogeneities created by the formation of an HBP/MASP rich separated phase. Due to their tunable structure, HBPs and MASPs can be synthesized to introduce properties at demand, such as increased chemical reworkability by introducing ester groups, or increased fire retardancy due to phosphorous-based HBPs or MASPs.There is not a general trend regarding the effect of HBPs and MASPs on the physical properties of epoxy-based thermosets because they depend on the type and content of HBPs or MASPs. For instance, the curing process is affected by several factors. The reactive functional groups of HBPs or MASPs can enhance the curing rate of the system but, at the same time, topological restrictions, and the increase in the viscosity of the formulation can worsen the curing rate. Thermal properties also depend on the type and content of HBP or MASP. The


DYRK1A gene, a highly haploinsufficient gene located at the “critical region” within 21q22. We found that both embryonic organizer and body axis were significantly impaired during early embryogenesis, producing abnormalities of the nervous, heart, visceral, and blood systems, similar to those observed with DS. Quantitative phosphoproteome analysis and related assays demonstrated that the DYRK1A-overexpressed zebrafish embryos had anomalous phosphorylation of β-catenin and Hsp90ab1, resulting in Wnt signaling enhancement and TGF-β inhibition. We found an uncovered ectopic molecular mechanism present in amniocytes from fetuses diagnosed with DS and isolated hematopoietic stem cells (HSCs) of DS patients. Importantly, the abnormal proliferation of DS HSCs could be recovered by switching the balance between Wnt and TGF-β signaling in vitro. Our findings provide a novel molecular pathogenic mechanism in which ectopic Wnt and TGF-β lead to DS physical dysplasia, suggesting potential targeted therapies for DS.Despite the high prevalence of Down syndrome (DS) and early identification of the cause (trisomy 21), its molecular pathogenesis has been poorly understood and specific treatments have consequently been practically unavailable. A number of medical conditions throughout the body associated with DS have prompted us to investigate its molecular etiology from the viewpoint of the embryonic organizer, which can steer the development of surrounding cells into specific organs and tissues. We established a DS zebrafish model by overexpressing the human  Down syndrome (DS), which affects 1 in 600–800 babies born in all populations, is the most frequently occurring chromosomal abnormality in humans . CongeniOrganizers, defined as groups of cells with the ability to instruct adjacent cells to differentiate into specific states, represent a key principle in developmental biology. In the context of an embryo, they are groups of cells with the ability to direct fates and morphogenesis in surrounding cells, steering their development into specific organs and tissues. As a result, organizers can position specific tissues and organs relative to each other . TherefoDYRK1A, have already been associated with specific clinical features of DS. It has been argued that human chromosome 21 (HSA21) protein-coding genes with high haploinsufficiency scores are more sensitive to three copies; therefore, they can be considered candidates for contributing to DS phenotypes [The gene-dosage hypothesis is the most accepted theory for the pathogenesis of DS; that is, the syndrome is caused by chromosome 21 trisomy in somatic cells, causing increased expression of chromosome 21 genes due to gene dosage , 7. Tranenotypes .DYRK1A, in 21q22, contributes to DS phenotypes [Dyrk1A in mice, mBACTgDyrk1A (Dyrk1A+/++), is sufficient to produce significant behavioral impairments, cognitive deficits, motor abnormalities, neuronal alterations, retinal defects, vascular defects, gastrointestinal tract abnormalities, immune response defects, abnormal maturation of the thymus, and impaired function of T lymphocytes [DYRK1A gene.Indeed, several studies have shown that the overexpression of enotypes –12. Overphocytes –15 that phocytes –18. Zebrphocytes . Based oDYRK1A overexpression, and the body axis, associated with multi-organ disorders in early development, was also disrupted. Our molecular characterization of this model demonstrated that Wnt and TGF-β signaling both changed significantly. We verified this mechanism in amniocytes, and isolated hematopoietic stem cells (HSCs) from fetuses and patients diagnosed with DS. We also tested switching Wnt and TGF-β signaling simultaneously to rescue these abnormalities in zebrafish embryos and DS patient HSCs, providing potential guidance for DS therapies. We also provide a new molecular mechanism for embryonic organizer formation and body axis development.The zebrafish embryonic organizer was disrupted by DYRK1A or zebrafish dyrk1a mRNA into zebrafish embryos. When higher amounts of mRNA (~100 pg) were injected, DYRK1A mRNAs produced frequent embryo death at 24 h post fertilization (hpf)  and Tg  embryos exhibited shortened/curved body axes and fusion of the eyes , while the expression level of the atrioventricular boundary markers bmp4 and has2 was decreased in the DYRK1A-overexpressed embryos  and cmyb (48 hpf), as well as those of the hematopoietic progenitor cell marker genes scl and gata1 (13 hpf), were significantly increased in model embryos , the macrophage marker gene csf1ra, and the primitive neutrophil marker gene mpx (24 hpf) showed decreased expression , expression levels of the dorsal organizer markers iod Fig. . These dgsc and chd in DYRK1A-overexpressed was a consequence of the increased proliferation of organizer cells, we analyzed organizer cells using a phospho-histone H3 (pH3) antibody and counterstaining with GFP in a Tg(gsc:GFP) transgenic fish line. We observed a significant increase in the number of proliferating cells in the organizer  is a protein kinase , we usedeviously . DespiteTo characterize the function of these alterations in protein phosphorylation, Gene Ontology (GO)-based classification of the ontology of cellular components, molecular functions, and biological processes was performed, which revealed widely different distributions between DYRK1A-overexpressed and control embryos  [Phosphorylation at Ser552 induces β-catenin accumulation in the nucleus and increases its transcriptional activity . InteresDYRK1A significantly impaired TGF-β-induced responses  and threonine (T) with alanine (A). Coimmunoprecipitation and immunostaining in HEK293 cells showed that either mutation abrogated the interaction between these two proteins Fig. . ImmunosWe next determined whether DYRK1A abolished the interaction between Hsp90ab1 and the TGF-β receptor. Coimmunoprecipitation showed that the Hsp90ab1-TGF-β receptor 1 interaction decreased when DYRK1A was overexpressed in HEK293 cells and zebrafish embryos Fig. . Next, wsqt mRNA and used the Wnt/β-catenin inhibitor ICG-001 to treat DYRK1A-overexpressed embryos. The model embryos injected with 0.1 pg sqt mRNA and treated with 10 μm Wnt/β-catenin inhibitor ICG001 simultaneously demonstrated a significant decrease in the occurrence of abnormality; moreover, the body axis of the majority of DYRK1A-overexpressed embryos was restored to normal length  gene consists of six exons and encodes the Na+/H+ exchanger regulatory factor 1 (NHERF1). The PDZ2 domain of NHERF1 selectively stabilized the interaction between β-catenin and E-cadherin. In the absence of NHERF1, the β-catenin/E-cadherin association is disrupted, leading to decreased β-catenin levels at the plasma membrane localization [Consistently, the proteomic work of Cho et al. with amniocytes  also sholization . PRKACB lization . Dickkoplization . Rock1 ilization .The decreased TGF-β-related protein MAPK3 (ratio 0.051538), THBS1 (ratio 0.12663), THBS2 (ratio 0.15078), TGFBI (ratio 0.19756), COMP (ratio 0.2643), PPP2R1B , TGFB1I1 ratio 0.39299), CTGF ratio 0.4179), and ROCK1 (ratio 0.56493) levels can also be found in their results  on cell smears for detection and then finally counted the cell content.As expected, we detected a positive correlation between DYRK1A expression and the phosphorylation level of the β-catenin Ser552 residue Fig. . MeanwhiNext, we treated isolated DS HSCs with 2 ng/ml TGF-β ligand recombinant TGF-β1 protein and 10 μm Wnt/β-catenin inhibitor ICG-001 simultaneously. Encouragingly, we detected a reduced proliferation of HSCs using the pH3 antibody (Extended Data Fig. Despite the high prevalence of DS and early identification of its cause, its molecular pathogenesis is poorly understood, with specific treatments practically unavailable . The curDyrk1a, for example, is sufficient to produce changes in stem/progenitor cell behavior, which correlates with clinical phenotypic observations, such as leukemia and cognitive defects [According to the gene-dosage hypothesis and haploinsufficiency rank, although HSA21 contains more than 300 genes, only a subset contributes to DS phenotypes. Interestingly, the DS critical region genes implicated in gene-dosage mechanisms are wild-type genes; thus, it is only an increase of 50% in expression that produces overall effects . Several defects .Dyrk1a in mice leads to important behavioral impairments, cognitive deficits, motor abnormalities, neuronal alterations, retinal defects, vascular defects, gastrointestinal tract abnormalities, immune response defects, abnormal maturation of the thymus, and impaired function of T lymphocytes [Overexpression of phocytes –15 that phocytes , 17.It is particularly noteworthy that we found that the key protein β-catenin of the Wnt pathway has abnormally increased phosphorylation at residues T551 and S552. Increased phosphorylation of S552 has been shown to enhance β-catenin transport into the nucleus and downstream transcription levels , while tDyrk1a+/++ mouse model, we established a DYRK1A-overexpressed model in zebrafish. Our data are summarized graphically as altered Wnt and TGF-β signaling through changes in β-catenin and Hsp90ab1 phosphorylation (Extended Data Fig. Taken together, we attempted to understand the molecular pathogenesis of DS from the perspective of embryonic organizer formation and body axis development, to provide an explanation as to why a number of diverse medical conditions are associated with DS. Based on the gene-dosage theory and the Methods+Extended data Fig 1-19Supplementary Table 1-4original data filesReproducibility checklist


Previously, we demonstrated that the disheveled binding antagonist of β-catenin 1 (DACT1) was involved in atrial fibrillation by regulating the reorganization of connexin 43 and β-catenin in cardiomyocytes. Little is known, however, about DACT1 in human normal myocardial cells. Therefore, we used cardiomyocytes (CMs) derived from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to investigate the role of DACT1 and its connection with β-catenin and connexin 43. While the ESC-CMs and iPSC-CMs were differentiated using commercial differentiation kits, the cardiac-specific markers were detected by immunofluorescence. The expression level of DACT1 was detected using western blotting, whereas the interaction of DACT1 and connexin 43 or β-catenin was detected by immunofluorescence and co-immunoprecipitation (co-IP) assays. Both H1-CMs and SF-CMs were immunostained for cardiac-specific markers, including Troponin I, Troponin T, α-actinin, NKX2.5, and GATA6. While DACT1 was not expressed in both H1 ESCs and SF-iPSCs, it was, however, highly expressed in differentiated CMs, being also localized in the cytoplasm and the nucleus of differentiated CMs. Interestingly, the DACT1 expression in different nuclei was different in the same multinucleated cell. Moreover, DACT1 colocalized with β-catenin in both the cytoplasm and nucleus of differentiated CMs, and it also colocalized with connexin 43 in the perinuclear region and the gap junctions of differentiated CMs. Co-IP results showed that DACT1 could directly bind to β-catenin and connexin 43. Taken together, DACT1 interacted with β-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.  DACT1 was localized in the cytoplasm and nucleus of differentiated CMs.DACT1 colocalized with β-catenin in the cytoplasm and nucleus of differentiatedCMs.DACT1 co-localizes with connexin 43 in the perinuclear region and the gapjunctions of CMs.DACT1 (Disheveled binding antagonist of β-catenin 1), which was first found to be a Dvl-interacting protein, plays a crucial role in the development of the normal vertebrate  by affecin vitro models for cardiac disease or other research applications that require careful characterization of the properties of cardiomyocytes [in vitro mechanism.Human-induced pluripotent stem cells (iPSCs) are characterized by pluripotency and a capacity for unlimited self-renewal . Cardiommyocytes . Our recmyocytes . iPSC-CMBased on our previous study data, we hypothesized that DACT1 interacted with β-catenin and connexin 43 in normal cardiomyocytes, affecting the myocardial function, and to confirm this hypothesis, CMs derived from human iPSCs were used to study the role of DACT1 and its connection with β-catenin and connexin 43 in the cardiac function.H1 embryonic stem cells (ESCs) were obtained from the University of Macau and had already been reported . Human aWhile differentiation methods for cardiomyocytes have been published recently , cardiacBearing in mind the technique that was used had already been previously described ,9,11, thAs was previously described ,9, the tBearing in mind the co-immunoprecipitation assay (co-IP) has been previously reported , the iPSHaving previously demonstrated that DACT1 was involved in atrial fibrillation by regulating the reorganization of connexin 43 and β-catenin, little is albeit known about DACT1 in human normal myocardial cells due to a lack of suitable research models. In this study, CMs derived from human iPSCs were used to investigate the role of DACT1 and its connection with β-catenin and connexin 43 in the cardiac function.H1 ESCs and SF-iPSCs were used to generate CMs (H1-CMs or SF-CMs) by commercial differentiation kits. While the differentiation procedure is shown in Bearing in mind that DACT1 serves as a signal transduction regulator in the cytoplasm or a transcription cofactor in the nucleus, we used western blotting and immunofluorescence assays to investigate the expression pattern of DACT1 in CMs. The former’s showed that DACT1 was not expressed in both H1 ESCs and SF-iPSCs but was highly expressed in CMs derived from H1 ESCs and SF-iPSCs . AdditioWhile our previous study showed that DACT1 could regulate connexin 43 via cytoskeletal organization induced by β-catenin accumulation in cardiomyocytes of atrial fibrillation patients [Moreover, the colocalization of DACT1 and connexin 43 was analyzed, and the results showed it colocalized with connexin 43 in both H1-CMs and SF-CMs, which could be observed in the perinuclear and gap junctions , furtherThe co-IP assay was used in the present study to investigate whether DACT1 could bind β-catenin and connexin 43 in iPSC-CMs. As shown in DACT1, a novel bidirectional regulator of β-catenin, was found to be important in normal vertebrate development and human disease by affecting β-catenin . DACT1 cIn the present study, human H1-CMs and SF-CMs were successfully obtained using a commercial cardiomyocyte differentiation method, having this way expressed cardiac-specific markers. DACT1 was not expressed in both H1 ESCs and SF-iPSCs but was highly expressed in CMs derived from H1 ESCs and SF-iPSCs. While DACT1 was localized in the cytoplasm and nucleus of differentiated CMs, the DACT1 expression in different nuclei was interestingly different in the same multinucleated cell, while it colocalized with β-catenin in both the cytoplasm and nucleus of differentiated CMs. Additionally, DACT1 colocalized with connexin 43 in the perinuclear region and gap junctions of differentiated CMs.in vivo abnormal β-catenin expressions could lead to hypertrophic cardiomyopathy, heart failure, arrhythmias, and AF [Our present study showed that DACT1 colocalized with β-catenin in both the cytoplasm and nucleus of differentiated CMs, which suggests that in human iPSC-CMs and ES-CMs, DACT1 could regulate the transcriptional activity, the cytoskeleton and signal transduction in which β-catenin was involved. Interestingly, in a previous study, we had found that β-catenin was not expressed in the nucleus of the myocardium of valve disease patients, while a positive correlation with DACT1 was also observed in the cytoplasm of the myocardium . It is, , and AF ,17,18.Connexin-43 is the most abundant connexin protein in the ventricular myocardium . AlteratIn summary, we demonstrated that even though DACT1 was not expressed in both H1 ESCs and SF-iPSCs, it was highly expressed in CMs derived from H1 ESCs and SF-iPSCs. Additionally, DACT1 was localized in the cytoplasm and nucleus of differentiated CMs, and it was also colocalized and directly interacted with β-catenin and connexin 43 in differentiated CMs. Finally, DACT1 interacted with β-catenin and connexin 43 in human-induced pluripotent stem cells-derived cardiomyocytes.DACT1 was not expressed in both H1 ESCs and SF-iPSCs but was highly expressed in ESCs-CMs and iPSCs-CMs, which was detected in the cytoplasm and the nucleus of differentiated CMs. Additionally, it was colocalized and directly interacted with β-catenin and connexin 43 in differentiated CMs and human-induced pluripotent stem cells-derived cardiomyocytes.


Porcn, a membrane bound O-acyl transferase required for palmitoylation of Wnts to activate multiple Wnt-dependent pathways. Wnt/β-catenin signaling is suppressed in the anterior neural plate for initiation of eye formation and is subsequently required during differentiation of the retinal pigment epithelium (RPE). Non-canonical Wnts are critical for early eye formation in frog and zebrafish. However, it is unclear whether this also applies to mammals. We performed ubiquitous conditional inactivation of Porcn in mouse around the eye field stage. In PorcnCKO, optic vesicles (OV) arrest in growth and fail to form an optic cup. Ventral proliferation is significantly decreased in the mutant OV, with a concomitant increase in apoptotic cell death. While pan-ocular transcription factors such as PAX6, SIX3, LHX2, and PAX2 are present, indicative of maintenance of OV identity, regional expression of VSX2, MITF, OTX2, and NR2F2 is downregulated. Failure of RPE differentiation in PorcnCKO is consistent with downregulation of the Wnt/β-catenin effector LEF1, starting around 2.5 days after inactivation. This suggests that Porcn inactivation affects signaling later than a potential requirement for Wnts to promote eye field formation. Altogether, our data shows a novel requirement for Porcn in regulating growth and morphogenesis of the OV, likely by controlling proliferation and survival. In FDH patients with ocular manifestations, growth deficiency during early ocular morphogenesis may be the underlying cause for microphthalmia.Microphthalmia, anophthalmia, and coloboma (MAC) are congenital ocular malformations causing 25% of childhood blindness. The X-linked disorder Focal Dermal Hypoplasia (FDH) is frequently associated with MAC and results from mutations in  Congenital ocular malformations—microphthalmia , anophthalmia , coloboma  (collectively hereafter MAC)—originate from defective morphogenesis during early eye development and cause 25% of childhood blindness . Eye devPorcn, a membrane bound O-acyl transferase localized to the endoplasmic reticulum  is an x-linked dominant disorder resulting from abnormal mesodermal and ectodermal development and is frequently associated with MAC . FDH is eticulum . Porcn ieticulum . Porcn ieticulum . We havemalities .Dkk1 and Axin2 can result in microphthalmia and coloboma , and activate canonical (Wnt/β-catenin) and non-canonical pathways. Wnt/β-catenin activation prevents cytoplasmic degradation of β-catenin, thereby allowing its nuclear translocation to activate Tcf/Lef1 transcription factors. Wnt/β-catenin exerts many distinct functions during different phases of eye development . Duringcoloboma . During coloboma , providivia multiple pathways, including intracellular Ca2+ release, activation of JNK and Planar Cell Polarity (PCP). It is essential for eye field formation in non-mammalian vertebrates by different mechanisms; it represses Wnt/β-catenin activity and promotes expression of EFTFs in frog and zebrafish . Close iew, see . In addiiew, see . HoweverPorcn inactivation around eye field formation leads to severely arrested OV 3 days later. Key regulatory genes for RPE differentiation OTX2, MITF, and NR2F2 are absent, proliferation and survival of ocular progenitors in the OV is decreased, and invagination during OC morphogenesis fails. Our studies reveal a novel role for Porcn during earliest stages of mouse eye development, recapitulating severe microphthalmia in FDH.To investigate the role of Porcn before OV morphogenesis, we performed temporally controlled inactivation before and during the eye field stage when Wnts are expressed in the cranial region . Our resPorcn inactivation, a conditional Porcn allele, tamoxifen-inducible, ubiquitous Gt(ROSA)26Sortm1(cre/ERT)Nat (hereafter ROSA26CreERT) and the recombination reporter RosaR26 were utilized, with established genotyping protocols or Transnetyx  using Taqman with custom-designed primers (Porcn (hereafter PorcnCKO) and control littermates were processed as previously published  was used to detect apoptotic cells. For EdU detection, the Click-iT® EdU Imaging Kit  was utilized. Cryostat sections were counter-labeled with DAPI and mounted in Prolong Gold Antifade. No obvious defects in morphology, proliferation or OV marker expression were observed in controls: conditional heterozygous female embryos (hereafter PorcnCHET) and embryos with or without Cre. Unless otherwise indicated, a minimum of 3 embryos from at least 2 individual litters were analyzed per genotype, time point and marker. For analyses of E9.5 embryos induced at E6.5, 3 embryos were analyzed and 2 showed indication of ocular development.Mouse lines were maintained on a mixed genetic C57BL/6 and CD-1 background. For temporally controlled  primers . Noon of primers . To deteublished . For antImages were captured using a U-CMAD3 camera, mounted on an Olympus SZX12 stereomicroscope, and a XM10 camera, mounted on an Olympus BX51 epifluorescence system. For confocal imaging, the Olympus FV100 or ZEISS LSM 880 systems were used. Images were processed using ImageJ (NIH) and Adobe Photoshop software .Quantification of EdU-labeled and Tunel-labeled cells was performed on cryostat sections midway through the OV, with separation of dorsal and ventral subdivisions. The percentage of labeled cells was calculated by determining the number of total cells using DAPI-labeled nuclei. Statistical analysis was performed using Prism version 9 (Graphpad) for One-Way ANOVA.Porcn using the ubiquitous ROSA26CreERT, allowing temporally controlled recombination. To account for delay of pathway inactivation in responding cells due to cell non-autonomous Wnt ligand production, extracellular release and downstream receptor activation, we started inactivating Porcn at E6.5. RosaR26 recombination confirmed ubiquitous Cre activity, as expected . In 5 PorcnCKO, no detectable eye phenotype was observed . In mildly affected PorcnCKO, telencephalic vesicles are slightly smaller . We also observed PorcnCKO embryos with a more severe developmental and ocular phenotype   . Here, wsomites) . In Porcorsal OV  suggestiorsal OV . Thus, iPorcn also prevents potentially confounding, concomitant upregulation of Wnt/β-catenin signaling. Consistent with this, arrested growth of the OV has not been observed by early Wnt/β−catenin pathway inactivation in other studies . We detected mosaic RosaR26 reporter expression in only one E10.5 embryo  suggesting that HesCreERT2 may not be sufficiently activated at this time point. However, we showed in an earlier study that Porcn disruption causes consistent RPE differentiation defects only when performed simultaneously in ocular and extraocular tissues in the OV  or OC stage (E10.5). The PorcnCKO OV or OC is small and OV expansion or OC invagination fails, respectively. Analysis of cell death (TUNEL) and proliferation (EdU incorporation) showed robustly downregulated proliferation and survival of ocular progenitors in the ventral OV 1 day earlier when morphology and expression of the Wnt/β−catenin readout appear normal , including microphthalmia (44%) and anophthalmia (11%)  . We propn allele . The latvia a requirement in proliferation, survival, and regionalization of ocular gene expression, recapitulating severe microphthalmia in FDH.Using temporally controlled, conditional inactivation in mouse, our studies reveal a novel role for Porcn in regulating growth and morphogenesis of the optic vesicle and optic cup,


Interventional radiology-operated endoscopy has a small but growing number of applications. In this clinical case report, we describe the use of an endoscope to assist the traversal of a high-grade ureteral stricture from percutaneous nephrostomy  access. Direct visualization of the stricture allowed the identification of a central channel that was not present in fluoroscopic images, making endoscopy essential to the technical success of the procedure. Endoscopy is a powerful adjunct to image-guided techniques, particularly in challenging interventions or cases with complex anatomy. Endoscopy provides valuable information to guide both diagnostic and therapeutic procedures. Direct visualization can be a powerful adjunct to image-guided techniques, particularly in complex or challenging interventions. The first documented use of endoscopy in the interventional radiology suite was reported by Yamakawa et al. , althougOur patient was a 65-year-old male with a history of stage IV bladder cancer and stage II prostate cancer, status post-robotic radical cystoprostatectomy, and creation of a right lower quadrant ileal conduit at an outside tertiary care cancer center. Following his initial surgery, a left ureteral stent was placed and subsequently removed after approximately six months. He later sought care at our institution, where he was found to have a mild right and severe left hydronephrosis. Interventional radiology was consulted for the decompression of the left collecting system.During the index procedure, the left kidney was accessed percutaneously in the usual fashion under image guidance. Antegrade nephrostogram confirmed severe hydronephrosis and revealed a focal, high-grade stricture in the distal ureter; however, there was a passage of contrast distally into the ileal conduit, indicating patency of the distal ureter and surgical anastomosis Figure . DespiteApproximately 3.5 months after the initial placement, the patient was brought back to attempt the conversion of the PCN to a PCNU with aid of an endoscope to directly visualize the ureteral stricture. Preprocedure serum creatinine was 1.49 mg/dL and blood urea nitrogen was 22 mg/dL. The complete blood count was within normal limits. Because this procedure would require the patient to lie prone for a prolonged period, the procedure was performed under general anesthesia. An initial antegrade nephrostogram obtained through the indwelling 12-French PCN tube redemonstrated the stricture in the distal ureter. The indwelling PCN was exchanged for a 12-French sheath over a wire. The endoscope  was introduced through the sheath and advanced to the distal ureter. On fluoroscopic images, contrast did not pass distal to the stricture into the ileal conduit Figure . HoweverNumerous attempts were made to traverse the stricture using various wire and catheter combinations Figure -2D. UltiThere was low suspicion of recurrent malignancy at the site of the stricture, as a PET/CT performed eight weeks before the procedure showed no evidence of recurrent, residual, or metastatic disease. As a result, a biopsy of the stricture was not performed. After discharge, the patient was referred back to the urology service for further management and possible internalization of the PCNU or conversion to a urinary diversion catheter. If no intervention was planned, we would exchange the PCNU catheter every six to eight weeks, at which point follow-up laboratory studies would be obtained. Nevertheless, no change in serum chemistries or renal function was expected, as the patient’s urine remained diverted following the procedure.The use of endoscopy in interventional radiology has traditionally been limited to a small number of indications and performed at only a handful of institutions. The primary benefit of endoscopy as an adjunct to image-guided techniques is the addition of direct visualization, which is especially useful in challenging interventions. Technical success in such procedures provides significant value to patients and obviates more invasive or complex interventions. Furthermore, the use of endoscopy may reduce fluoroscopy time and radiation dose to both the patient and the operator .The typical indications for interventional radiology-operated endoscopy concern the management of biliary diseases, such as gallstone retrieval or choledochoscopy . HoweverIn the genitourinary system, interventional radiology is routinely consulted for PCN placement in patients with obstructing calculi to enable subsequent nephrolithotripsy. However, the definitive endoscopy-assisted procedure is usually performed by urology. Only a few applications of interventional radiology-operated endoscopy have been reported in the genitourinary system. Chick et al reported the use of a disposable ureteroscope to place a stent across the stenotic anastomosis of a pyelovesicostomy in a renal transplant patient . Healey In this report, we present a case of interventional radiology-operated endoscopy to aid the traversal of a high-grade ureteral stricture and the conversion of a PCN to a PCNU. The use of endoscopy was critical to the technical success of the procedure. Intraluminal imaging provided an orthogonal cross-sectional plane to the typical coronal projection seen during fluoroscopy. Contrast injection under fluoroscopy failed to demonstrate patency of the distal ureter. Without the benefit of real-time direct visualization, a central tract would not have been identified and attempts to traverse the stricture would have likely failed. Thus, this case is particularly illustrative of the benefits of interventional radiology-operated endoscopy. In challenging cases that require the traversal of a stricture, balloon dilation, or placement of a nephroureteral stent, the combination of image guidance and direct visualization can be especially useful. Although interventional radiology has collaborated with urology in joint cases utilizing endoscopy, the primary operator  has typically been the urologist. In this case report, the interventional radiologist as the primary operator of the endoscope represents a shift in that paradigm. Interventional radiology-operated endoscopy likely reduces the total procedure time and time to scheduling, as coordination with another service is not necessary.Certain technical considerations must be made when evaluating a patient for endoscopy-assisted intervention. The location of percutaneous access should be selected based on the relevant anatomy while bearing in mind the ergonomics of using an endoscope. Choosing the length and diameter of the endoscope requires an understanding of its relative advantages and disadvantages. Although a longer endoscope enables more distal access, it can also be more challenging to navigate and manipulate in locations very distal to the access site. Whereas endoscopes with large diameters offer a larger working channel, a general principle is to select the smallest channel able to achieve technical success. Endoscopes also vary in their rigidity; for example, a flexible endoscope is preferred in distal genitourinary cases such as ours. Because endoscopy requires a well-formed tract, it is customary to wait four to six weeks after initial access before performing the endoscopy-assisted intervention in cases of infection, renal compromise, or massive dilatation of the collecting system. General anesthesia is preferred, especially for prolonged interventions or those that require prone positioning. Lastly, appropriate patient selection with multispecialty collaboration is paramount.Familiarity with the equipment required for endoscopy may promote better acceptance of endoscopic techniques among interventional radiologists. The endoscope is part of a portable endoscopy tower. The tower can be connected to the existing display in the angiography suite, allowing both fluoroscopic and endoscopic images to be displayed on the same monitor. Endoscopic images can also be saved and archived alongside fluoroscopic images from the procedure. Endoscopy requires saline irrigation and aspiration, which are performed through dedicated channels in the endoscope and can be controlled by the operator. Many modern endoscopes, such as SpyGlass used in our case, allow four-way articulation to direct and maneuver the endoscope in different directions. Interventional radiology-operated endoscopy has a small learning curve due to the readily translatable skills practiced in similar image-guided techniques.In the hands of an interventional radiologist, endoscopy is a valuable adjunct to image-guided techniques. We present a case in which endoscopy was used to assist the traversal of a high-grade ureteral stricture from PCN access. The direct visualization provided by the endoscope was essential to the technical success of the procedure. Interventional radiology-operated endoscopy is a useful asset in challenging interventions and provides meaningful value to patients and operators alike.


Beauveria bassiana and Metarhizium anisopliae, or water treatment as the control. The activity sensing device included an accelerometer, an amplifier, a digital recorder, and a signal transmitter that fed the data to a computer that excluded background noise and compared the rates of bursts of movement and feeding sound impulses among treated trees and controls. Observations were made daily for two months. The rates of bursts were representative of the feeding activity of RPW. The unique spectral pattern of sound pulses was typical of the RPW larval feeding activity in the date palm. The microphone confirmed that the same unique tone was produced in each burst. Two months after fungal injection, the RPW sound signal declined, while the RPW sound signal increased in the control date palms (water injection). The mean rates of bursts produced by RPW decreased to zero after the trees were injected with B. bassiana or M. anisopliae compared with the increased rates over time in the control treatment plants.The rate of the sounds  produced by the movement and feeding activity of red palm weevil (RPW) pest infestations in a date palm tree was monitored over time after trees were separately treated with injection of entomopathogenic fungal isolates,  Rhynchophorus ferrugineus  (Coleoptera: Dryophthoridae), is a serious pest of date palms in Saudi Arabia and was first reported in Al-Qatif Governorate in 1987 [Beauveria bassiana  Vuill. (1912)  and Metarhizium anisopliae (Metschn.) Sorokīn. (1883)  caused 95% mortality of adult RPW when applied under laboratory conditions via an auto-contamination trap [B. bassiana and M. anisopliae caused 80–82% mortality in eggs and hatched larvae, while adult mortality reached up to 100% within 2–3 weeks [8 spores/mL [B. bassiana and M. anisopliae were tested against the second and fourth instars of RPW, which resulted in significant mortality as well as decreased egg hatchability, pupation duration, and adult emergence rates [B. bassiana and M. anisopliae; however, only B. bassiana led to a high mortality rate of 93.3% after 21 days, whereas M. anisopliae only resulted in 66.7% [The red palm weevil (RPW), Olivier, 790  (Coleoptera: Scarabaeidae) [Oryctes elegans  (Coleoptera: Scarabaeidae) [The application of fungal species to infect the RPW larval stage has been investigated in date palms in greenhouses using acoustic sensors . Acoustibaeidae) , and frubaeidae) . In thisA field experiment was conducted during the period that began in February 2021, in a date palm orchard located in Al–Kharj Governorate, Riyadh Region, Kingdom of Saudi Arabia . The date palm variety in this farm was Khalas. The farm had been infested by RPW, according to confirmation from the farm manager. Date palms that were medium in size (ranging 3–4 m in height) and similar in age (around 15–16 years) were selected. Visual symptoms included evidence of tunnels in the trunk of the date palm around the base, which contained chewed plant tissue and an odor of fermentation, as well as the presence of brown liquid material. Furthermore, tree infestation was confirmed using an acoustic sensor to detect the RPW sound signal inside the trees.Two fungal isolates that were isolated from RPW in Saudi Arabia and were previously identified  were injFungal isolates successfully grown in potato–dextrose–agar (PDA) medium were selected for mass production using wheat medium ,31. The 9 conidia/mL [In preparing the fungal solution for date palm injection, the fungal concentration was determined under a microscope with a hemocytometer. In this experiment, the concentration was used similarly to a previous experiment under laboratory conditions, which was 1 × 10nidia/mL . Five liA preliminary experiment was performed by injecting each fungal solution (BbSA-1 or MaSA-1) into the infested date palm trees in three replicates in Al–Ammariah, near Riyadh, KSA. The effect of the fungal treatment was demonstrated 45 days after injection. The date palms were dissected lengthwise 1 m in length. Each meter log was cut into two equal halves and then into four quarters for more detailed internal observations. Each quarter was observed to record any signs of RPW infestation (destroyed tissue) and to collect dead RPW individuals. RPW larva mortality inside the date palm trunk was 100% after fungal injection in all trees. The dead RPW larvae were collected and transferred into sterile Petri dishes with moist filter paper and incubated at 28 ± 1 °C with 80 ± 5% RH under laboratory conditions. After 2–6 days of incubation of the dead larvae, the first fungal symptom that covered the RPW larval body appeared. Based on this preliminary study, the use of acoustic sensors was adopted as the preferred method for monitoring treatment effects, because palm dissection is a time-consuming, expensive, and destructive procedure for assessing treatment effectiveness in the field .The selected date palms were injected with fungal treatment or water control solution at multiple locations per tree using a balloon injector as follows: Four holes were drilled in a clockwise spiral around each date palm trunk, each pointed downward at a 30° angle, using a drill machine equipped with a brad point drill bit . The points of injection were 25, 50, 75, and 100 cm above the ground level. Immediately after drilling, the fungal solution was delivered to the trunk. Each balloon injector with 100 mL of the solution was inserted into each hole  for a toTemperatures were measured inside and outside each treated tree during the two months of acoustic data collection using Elitech Digital Thermometer Hygrometer Dt-2 .The RPW larval activity vibrations were monitored with a TreeVibes acoustic detection device  that included an accelerometer sensor; associated probes and adapters; and a protective box with an amplifier, headphone output, and a digital recorder. The latter contained a secure digital (SD) card, power supply, rechargeable battery and solar panel, and a signal transmitter system with an antenna . The ampPreliminary recordings of insect activity were collected from each date palm before its injection with treatment or control solution. The reading points were marked on each date palm trunk (one meter above the ground). A hole was drilled into the trunk using the brad point drill bit previously used to insert holes for fungal injection; a 35 cm waveguide probe was inserted into the hole, and the TreeVibes device was attached to the probe . For theRaven Pro interactive sound analysis software version 1.5  was usedp < 0.05.The experiment had a randomized complete block design with 12 replicates for each treatment. Analyses of variance were conducted using SAS (SAS 2004) for the comparisons of mean differences between temperatures measured outside and inside each date palm and mean rates of impulse bursts for different treatments. Means were separated using the Least Significant Difference (LSD) test at B. bassiana and M. anisopliae were not significantly different  of the RPW larval sounds were recorded for 24 h in an infested date palm, and the signals were divided into morning, afternoon, night, and early-morning periods . The purisopliae . By compB. bassiana through trunk injection suppressed RPW by up to 90% in the field [B. bassiana and M. anisopliae showed high survival rates when injected into coconut seedlings against Rynchophorus palmarum  (Coleoptera: Dryophthoridae) [The application of microbial agents, especially entomopathogenic fungi, can be a new strategy to control insect borers . The prehe field ,36. Conihoridae) . The effhoridae) . The rechoridae) ,27,29,39horidae) . In thishoridae) . A seriehoridae) .B. bassiana-treated trees was significantly lower than that in control trees [The use of an acoustic sensor to detect RPW activity in treated and control date palms showed that larval activity in the treated date palms was greatly reduced after two months compared with the water-injected date palm trees, indicating that the fungi greatly reduced the feeding and movement activity of RPW larvae. This result was confirmed by another study that found that RPW activity in ol trees . It is pol trees ,42. In tol trees .In this study, no other insect activity interfered with the recording of the target insect (RPW), nor were there other insect signs around the date palm recording site. Moreover, the spectral profile pattern, which is most likely the sound signal generated by RPW larval activity inside the date palm, could be distinguished from many other background sounds. In contrast, a study conducted in Malaysia on oil palms using an acoustic sensor to identify RPW activity showed the presence of RPW and termites (Blattodea: Termitidae) in the trees. However, the spectral profiles generated by termite and RPW activity were different . InfesteSitophilus oryzae  (Coleoptera: Curculionidae) in stored products [The acoustic sensor used in this study was sensitive enough to detect the sound of feeding and the movement of RPW larvae within date palms. This was confirmed by the results of another study in which other acoustic sensors were used. Another acoustic sensor, IoTree Smart, was evaluated to detect the sound signal of RPW larvae in coconuts and oil palms in Malaysia . Similarproducts . Acoustiproducts .Galleria mellonella  , between 15 and 30 °C, but low infectivity at 10 °C [B. bassiana, M. anisopliae, or Paecilomyces fumosoroseus (Wize) A.H.S. Br. & G. Sm. (1957)  did not infect G. mellonella at 35 °C; however, infection occurred when fungi were present at the low temperatures of 10–20 °C [This study was conducted during the period from winter to spring in 2021, and the minimum and maximum temperatures inside and outside the date palm trees varied , which might have supported fungal activity inside the palm trees, and it is believed that the fungus still caused infection in the host organism. In another study, a fungal isolate was found to have high infectivity against wax moth, at 10 °C . B. bass10–20 °C . It was 10–20 °C .The obtained results also clearly show the effectiveness of injecting fungal isolates into a date palm under field conditions, and an acoustic sensor can be used to demonstrate the efficacy of fungal isolates. The presence of the RPW larval gallery created by feeding the RPW larvae may have allowed the fungus to penetrate the palm tissue after injection, and the use of injection methods to introduce the fungus into infested date palms for an IPM program in the field is promising.Metarhizium anisopliae proved to be better than the Beauveria bassiana isolate. The larval activity was measured using the acoustic sensor in terms of the rate of impulse bursts; it declined faster for M. anisopliae than for B. bassiana. These fungal isolates can persist inside the date palm trees for several months and have the potential to protect date palm trees from RPW attack.The efficacy of the fungal isolates used in this field study using the injection system against RPW is promising. The acoustic sensor could be used to monitor the RPW sound signal within the date palm trunks during fungal treatment. In this study, the local fungal isolate of


The current study reports the preparation of thermally conductive polymeric nanocomposites. For this purpose, two epoxy-based nanocomposites were prepared by dispersing a different type of functionalized graphene oxide (GO) nanofiller in each series. Both these GO nanofillers were functionalized by covalently bonding oligoimide chains on their surfaces. In one series, these oligoimide chains were prepared by reaction of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) with a diamine 4,4′-methylenedianiline (MDA). While in the other case, BTDA was reacted with N,N′-[)bis(oxy))bis]bis(4-aminobenzamide) (BDM) to mount oligoimide chains on the surface of GO. Both types of oligoimide chains have amino groups as chain-end functional groups. These modified GO nanofillers were added to the epoxy matrices separately to prepare their respective nanocomposites (MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites). The chain-end amino groups of oligoimide chains reacted with the epoxy ring developing a covalent bonding between oligoimide chains of GO and the epoxy matrix. Moreover, these oligoimide chains prevented the agglomeration of GO by acting as spacer groups leading to the uniform dispersion of GO in the epoxy matrix. Various analytical techniques were used to examine the attachment of oligoimide chains to the GO surface, and to examine the morphology, curing potential, mechanical strength, thermal stability, and thermal conductivity of the prepared nanocomposites. We demonstrated that the thermal conductivity of MDA-B-GO-epoxy nanocomposites increased by 52% and an increase of 56% was observed in BDM-B-GO-epoxy nanocomposites. Similarly, a significant improvement was observed in the mechanical strength and thermal stability of both types of nanocomposites. The formation of polymer nanocomposites by incorporating nanofillers in polymer matrices has been studied for decades due to their extraordinary enhancement in chemical and mechanical properties ,2. In paSuch problems of epoxy resin are mitigated by the incorporation of nanofillers that can decrease the brittleness and improve the heat-dissipating ability . GraphenMaximum property enhancement in nanocomposites by the addition of GO filler can be achieved by ensuring the following: (i) exfoliation of graphene sheets in the polymer matrix so that it can transfer its intrinsic characteristics to composite materials and (ii) strong interfacial interaction with the matrix for effective load distribution in the nanocomposites . These tTg), and mechanical properties of prepared nanocomposites. However, they did not study degradation behavior of these nanocomposites bis(4 aminobenzamide) (BDM). The surface modification of GO in both cases was analyzed by FTIR and XPS analysis. The oligoimide moieties, on the surface of GO, contained amine end-functional groups. We hypothesized that these amino groups could cure the epoxy rings, and, thereby, could develop covalent bonding between the GO nanofiller and epoxy matrix, which was confirmed by evaluating the curing potentials of MDA-B-GO and BDM-B-GO by DSC analysis. Then, both these oligoimide modified GOs were dispersed separately in the epoxy matrix to prepare two types of epoxy nanocomposite series, MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites. As a reference, a neat epoxy system was also prepared by curing the same epoxy resin with a commercial harder Aradur-22962. We observed that both types of modified GO were able to disperse well, develop chemical bonding and enhanced the curing process of epoxy resin. Consequently, both nanocomposite systems performed with high thermal conductivity, thermal stability, and mechanical strength.In this work, two types of surface-functionalized GO were prepared by chemically attaching oligoimide chains to their surfaces. In the one type, which is called MDA-B-GO, oligoimide linkers were affixed to the GO surface by a reaction of 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) with a diamine 4,4′-methylenedianiline (MDA). Whereas, in the other type, which was coded as BDM-B-GO, oligoimide chains were attached to its surface by reacting BTDA with All the chemicals and reagents were of analytical grade and were used as received, unless otherwise mentioned. All chemicals were purchased from Sigma Aldrich , Fluka , and Merck . Diamine BDM was synthesized as reported in our previous article . (3-Amin-1 under an inert atmosphere. X-Ray photoelectron spectroscopy (XPS) spectra were recorded on XPS machine model k-Alpha . The surface morphologies of the prepared nanocomposites were studied by scanning electron microscopy (SEM)  with an accelerating voltage of 5kV. Thermal conductivity was measured by the hot disk method using TPS 2500 S. Nanoindentation tests were carried out using Nano indenter XP  (iNano Nano indenter with Berkovich diamond tip). X-Ray analysis was carried out on the RIGAKU D/MAX-2500 X-ray diffractometer.Fourier transform infrared (FTIR) spectra were recorded on an a-Alpha-P model  using the attenuated total reflection (ATR) method. Thermogravimetric analysis (TGA) was carried out using a TGA N-1000 Thermo gravimetric Analyzer . Differential scanning calorimetric (DSC) analysis was carried out on the DSC 25 TA instruments by keeping a scanning rate of 10 °C minThe surface modification of synthesized graphene oxide (GO) was carried out using BDM, MDA, and BTDA following a reported procedure , as giveFor this purpose, GO was dispersed in THF (0.1 mg/mL) at room temperature by sonication for 1 h. To this dispersion, APTMS was introduced  and the mixture was heated at 70 °C for 15 h. Afterwards, the resulting mixture was filtered and washed numerous times with THF to completely eliminate unreacted APTMS. The APTMS-functionalized GO was dried for 48 h in the vacuum oven. This dried APTMS-modified GO was then dispersed in anhydrous NMP (0.1 mg/mL) by sonication for 1 h to get homogenous dispersion. To this well-dispersed mixture, 3,3′,4,4′-benzophenonetetracarboxylic dianhydride (BTDA) was added  and refluxed again for 15 h. This mixture was allowed to cool to room temperature and anhydride terminated GO was obtained by filtration. After washing the residue several times with NMP and drying under vacuum for 24 h, it was again dispersed in anhydrous NMP. Then, the diamines  were added separately and the mixture was refluxed for 15 h to get functionalized GO with imide groups and amine end groups. The oligoimide synthesized using MDA and dianhydride BTDA was coded as MDA-B-GO, while the oligoimide obtained by reaction of diamine BDM was given the code BDM-B-GO.MDA-B-GO and BDM-B-GO-epoxy nanocomposites were prepared separately by the solution mixing method. As an example, the preparation of MDA-B-GO-epoxy nanocomposites is discussed here. The various amounts  of MDA-B-GO were dispersed (in three separate caped containers) in acetone by sonication for 2 h. A calculated amount of the commercial epoxy LY-564 was added to each suspension followed by sonication for another two hours. Then, the solvent was evaporated by gentle heating and a calculated amount of hardener aradur-22962 was added to each mixture. All the mixtures were subjected to shear mixing for 15 min to achieve homogeneous dispersion of hardener. After proper mixing of hardener, the entrapped air bubbles were removed from mixtures by placing them under vacuum for an adequate time. These mixtures were then transferred to the molds and were cured by heating them for one hour at 40 °C, 80 °C, 100 °C, and 120 °C, and for two hours at 150 °C. Along with these GO-epoxy nanocomposites, neat epoxy network (without the addition of MDA-B-GO and BDM-B-GO) was also prepared using the aforementioned procedure for the properties’ evaluation. Furthermore, a similar procedure was adopted to prepare BDM-B-GO-epoxy nanocomposites. The recipe and codes of prepared nanocomposites are given in To modify the surface of GO with the diamines , which were attributed to amino end-functional groups of oligoimide moieties. These peaks were present at 3442 and 3358 cm−1 in the FTIR spectrum of BDM-B-GO. The FTIR spectra of various stages of GO modification are represented in The covalent grafting of oligoimides to the surface of GO was also confirmed by XPS analysis. The XPS spectra are shown in The in-depth results of the XPS analysis are also summarized in As confirmed by FTIR and XPS analyses, both MDA-B-GO and BDM-B-GO contained amine end-functional groups which can cure the epoxy resin. So, the curing aptitude of both modified GOs was studied using DSC, and their thermograms are presented in Tmax) was presented in all the DSC thermograms. The Tmax values for the epoxy-GO nanocomposites having 5 wt % MDA-B-GO and 5 wt % BDM-B-GO were found to be 101.2 °C and 92.5 °C, respectively, while for the neat epoxy it was 106.6 °C. Moreover, ∆H values reduced to 76.6 and 45.7% when MDA-B-GO and BDM-B-GO were used for curing, respectively, in comparison to curing with Aradur-22962. So, a single exothermic peak (Tmax) at low temperature for both nanocomposites and reduced ∆H values, compared to those of neat epoxy, confirmed the curing aptitude of both MDA-B-GO and BDM-B-GO, due to the presence of the terminal −NH2 groups. The detailed curing data of both nanocomposites and neat epoxy are given in In order to assess the curing ability of MDA-B-GO and BDM-B-GO, their curing behavior was compared with data obtained from the curing of epoxy resin with a commercial hardener aradur-22962. As exhibited in −1 in the FTIR spectrum of MDA-B-GO, and at 1775 and 1717 cm−1 in the case of BD B-GO. However, no such characteristic peak of imide carbonyl group was observed in the FTIR spectra of neat epoxy. Moreover, the characteristic peaks of −NH2 group disappeared in the FTIR spectra of nanocomposites. Initially, these peaks were present in the FTIR spectra of MDA-B-GO and BDM-B-GO, as shown in 2 groups of oligoimides, present on the surface of GO, were utilized in the curing of epoxy resin leading to the creation of strong interfacial bonding of fillers with epoxy matrix and ensuring uniform dispersion of GO in the epoxy matrix [FTIR spectra of nanocomposites and neat epoxy films are shown in y matrix .The morphologies of pristine GO, both types of modified GOs, neat epoxy, and nanocomposite films were evaluated by FESEM, as shown in On the other hand, SEM images e,f of epMoreover, the EDX spectra of neat epoxy and nanocomposite films provided further confirmation of uniform dispersion of modified GO in the epoxy matrix. The silicon atom, which was only present in the oligoimide moieties, due to modification with APTMS, can be clearly observed in the EDX spectra of epoxy-GO nanocomposites b,c. The Notably, for further verification of filler exfoliation and uniform dispersion in epoxy matrix, XRD analysis of GO fillers, the neat epoxy, and nanocomposites was carried out, and the results presented in Thermal stability of the nanocomposites and the neat epoxy film were analyzed by thermogravimetric analysis to explore the effect of modified GO and its miscibility with the epoxy matrix. TGA thermograms are shown in T10, and T50, which could be due to the decomposition of labile oligoimide chains coupled with some residual solvent and moisture in the analyzed samples. However, Tmax values and residual yields gradually increased with increase in filler loading. The thermal decomposition temperature Tmax for neat epoxy was 626 °C, while for the MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites they were 148 °C and 37 °C, respectively, higher in comparison. The higher thermal stability of MDA-B-GO-epoxy nanocomposites than BDM-B-GO-epoxy nanocomposites could be assigned to higher solubility of MDA diamine. GO functionalized with oligoimide groups was well mingled and well adhered to the epoxy matrix due to chemical bonding between both domains, which imparted greater thermal stability. This chemical bonding was achieved by the ring opening reaction of amino groups of oligoimides with epoxy matrix. Similarly, both nanocomposites provided higher residual yields at 800 °C in contrast to neat epoxy. The delayed decomposition process of the nanocomposites illustrated that incorporation of modified GO hindered the oxygen diffusion into the epoxy matrix leading to reduction in degradation at higher temperature. Thus, it could be inferred that MDA-B-GO and BDM-B-GO can act as effective heat and mass transport barriers due to stronger bonding with the epoxy matrix, and, accordingly, are more capable of conserving the matrix.TGA analysis was carried out in a nitrogen environment with a heating rate of 10 °C. The TGA thermograms showed a two steps thermal degradation pattern. The first mass loss was observed near 300 °C, which might be related to the degradation of the pendant chain of the polymer matrix, and the second stage of weight loss might be due to the decomposition of the main chain of the epoxy . There wT10, T50, Tmax, and R800. Thus, it can be concluded that both MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites have greater potential as thermal conductors, in comparison to their previously reported counterparts [Previously reported epoxy/modified GO nanocomposites  were notterparts .max values in both types of the nanocomposites.The data derived from the thermogravimetric curves of neat epoxy and its nanocomposites are provided in g and, thereby, to check the thermal performance of the prepared epoxy-GO nanocomposites. The DSC thermograms of the two types of nanocomposites are presented in Similarly, DSC analysis was carried out to access the TTg values increased with increase of the filler contents. The Tg value of neat epoxy was found to be 92 °C, while for MDA-B-GO-epoxy nanocomposites and their BDM-GO based counterpart the Tg values were 123 °C and 119 °C, respectively, at 5 wt % loading of filler. However, at 1 and 3 wt % loading the Tg values were higher for BDM-GO-epoxy nanocomposites than for MDA-B-GO based nanocomposites, which could be attributed to more polar groups in the structure of BDM diamines than MDA. Thus, oligoimides derived from BDM can have greater inter-chain connectivity than MDA-oligoimides. Consequently, the former imparted greater Tg to resultant nanocomposites at 1 and 3 wt % filler loading. However, at 5 wt % filler contents, the higher solvent miscibility of MDA diamine than BDM compensated for lower chain interactions in its oligoimide. So, at higher filler loading MDA-B-GO-epoxy nanocomposites had higher Tg values. This linear increase in the Tg values of epoxy nanocomposites upon addition of modified GO can be credited to uniform dispersion of GO into the epoxy matrix, which, in turn, was made possible by strong connectivity between filler and matrix.These thermograms exhibit that the Tg values and other thermal properties.In various previous reports ,24,25,26Tg. Here, MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites exhibited values of Tg as high as 123 °C, whereas in the previous report it was 100 °C. Again, it can be inferred that MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites have superior properties as compared to previously reported epoxy/GO nanocomposites [Similarly, MDA-B-GO-epoxy nanocomposites and BDM-B-GO-epoxy nanocomposites can also be compared with previous reports  in termsmposites .−1 K−1, which increased constantly and reached a value of 0.304 W m−1 K−1 for MDA based nanocomposites and 0.311 W m−1 K−1 for BDM based nanocomposites, at 5 wt % filler loading in both cases, as shown in Thermal conductivity of the prepared nanocomposites was determined by the hot disc method and the results are presented in It can be inferred that fully exfoliated GO sheets, which possess excellent thermal conductivity, upon uniform distribution into epoxy matrix developed an interconnecting network, which could efficiently conduct heat .The mechanical properties, like hardness, elastic modulus and plasticity index, of the nanocomposites were determined by nanoindentation using the Oliver and Phar method .Typical indentation curves of neat epoxy and its nanocomposites are shown in Plasticity index is another parameter that determines relative elastic and plastic behavior of any material . This paFrom the data obtained through nanoindentation, it can be observed that the hardness value is significantly enhanced for 5 wt % BDM-B-GO-epoxy nanocomposite.These results were in a good agreement with the previously reported work of Ribeiro et al.  where thTg, were increased significantly for both types of nanocomposites at 5 wt % loading of respective GO filler, in comparison to neat epoxy. Importantly, the thermal conductivities of 5% MDA-B-GO-epoxy nanocomposite and 5% BDM-B-GO-epoxy nanocomposite were enhanced by factors of 52% and 56%, respectively, as compared to the neat epoxy. The mechanical properties of nanocomposites and neat epoxy were evaluated in terms of elastic modulus, hardness, and plasticity index. The values for hardness and elastic modulus increased 116% and 80%, respectively, for 5 wt % MDA-B-GO-epoxy nanocomposite, while increases of 142% and 96% were observed in hardness and elastic modulus, respectively, for 5 wt % BDM-B-GO-epoxy nanocomposite, in comparison to neat epoxy. Similarly, both types of nanocomposites exhibited a remarkable decrease in plasticity index, in comparison to neat epoxy. This significant improvement in thermal and mechanical properties of GO-epoxy nanocomposites over neat epoxy were attributed to oligoimide functionalized GO, which, upon uniform dispersion, cured the epoxy rings via pendant amino groups. These nanocomposites showed outstanding high thermal conductivity and mechanical properties, and could be utilized for the development of high-performance epoxy polymers in various applications, including a building block of electrical devices.In this study, two different types of surface modified GOs, MDA-B-GO and BDM-B-GO, were prepared by modifying oligoimide chains on the GO surface. Conjugating oligoimides was achieved by reacting BTDA with MDA diamine for the MDA-B-GO, and BTDA and BDM diamine for the BDM-B-GO. The successful functionalization of GO, in both cases, was confirmed by FTIR and XPS analysis. The property of modified GO to cure epoxy resin was assessed by DSC analysis. Then, two different series of epoxy nanocomposites were prepared by dispersing MDA-B-GO and BDM-B-GO into the epoxy matrix separately. One series was coded as MDA-B-GO-epoxy nanocomposites and the second series as BDM-B-GO-epoxy nanocomposites. For property evaluation, neat epoxy nanocomposites were also prepared by curing epoxy resin with a commercially available amine hardener Aradur-22962. Thermal conductivity, thermal stability, and mechanical properties of these nanocomposites and the neat epoxy were evaluated by relevant analysis techniques. Thermal analysis showed that parameters for thermal stability, like Tmax, residual yield, and