Rhynchophorus ferrugineus (Coleoptera: Curculionidae) is a species of beetle that depends on palm trees to complete its life cycle. RPW larvae feed on the palm tree trunk and can result in tree death, thus having a major impact on both wild and cultivated palm trees in several countries. The resulting economic and biodiversity losses caused by invasive populations of the RPW gave it a major pest status, and now governments, companies, and researchers across multiple countries are interested in developing effective control strategies to prevent further damage. Managing agricultural pests in the face of pressures such as climate change, rising levels of insecticide resistance, and increasing demands for food production will require advanced knowledge of pest biology. In this review, after presenting basic aspects of RPW biology and pest status, we gather information on the use of omics technologies, such as transcriptomics, genomics, and metagenomics, and explore their achievements and potentials to illuminate RPW biology and improve management. We finalize the review by exploring current opportunities and challenges in the use of these technologies for RPW management.The red palm weevil (RPW) Rhynchophorus ferrugineus (Coleoptera: Curculionidae), is the most devastating pest of palm trees worldwide. Mitigation of the economic and biodiversity impact it causes is an international priority that could be greatly aided by a better understanding of its biology and genetics. Despite its relevance, the biology of the RPW remains poorly understood, and research on management strategies often focuses on outdated empirical methods that produce sub-optimal results. With the development of omics approaches in genetic research, new avenues for pest control are becoming increasingly feasible. For example, genetic engineering approaches become available once a species’s target genes are well characterized in terms of their sequence, but also population variability, epistatic interactions, and more. In the last few years alone, there have been major advances in omics studies of the RPW. Multiple draft genomes are currently available, along with short and long-read transcriptomes, and metagenomes, which have facilitated the identification of genes of interest to the RPW scientific community. This review describes omics approaches previously applied to RPW research, highlights findings that could be impactful for pest management, and emphasizes future opportunities and challenges in this area of research.The red palm weevil (RPW),  Phoenix dactylifera L.) is one of the oldest cultivated fruit trees in the world and the most extensively cultivated plant in arid and semi-arid regions [The date palm  (Coleoptera: Curculionidae), is a pest species indigenous to countries in the south and southeast regions of Asia. It was first noticed in the Gulf region in the late 20th century, where it caused severe damage to palm trees; later, it started expanding its range, significantly affecting other regions [The RPW, whose scientific name is  regions . Due to  regions . The cos regions , underscConventional pest management strategies such as chemical pesticides have been utilized for decades to control insect pests that attack food crops; however, the substances in a pesticide may pose hazards to human health and have off-target effects on other species, including natural enemies of the pest, harming the environment, and sometimes resulting in even more infestations following their use ,7. Due tThis paper aims to review the currently available literature on RPW omics as a means of identifying gaps in the knowledge and providing perspective on new areas for development. We start by reviewing RPW’s basic biology, pest status, and current management strategies. Then, we review transcriptome-based gene discovery efforts, whole-genome sequencing, metagenomics, and repeat analysis. Finally, we discuss the practical applications of omics-based approaches to RPW’s pest management.RPW is a holometabolous insect, and the life cycle passes through four distinct stages; namely egg, larva, pupa, and adult . The femThe pupal stage is usually categorized into two periods. The first is the pre-pupal stage, which lasts for three days, during which the pupa is approximately 25 to 35 mm in size. In the second pupal period, which takes from 12 to 20 days, the pupa initially transforms from a cream to brownish color . As its The RPW is a major insect pest that endangers native palm trees in multiple countries, as well as the sustainability of the crop and ornamental palm industries. It is one of the major invasive pest species globally, attacking over 30 species of palm trees. More precisely, the host range of the RPW expanded from only four species during the mid-1950s  to 40 spR. ferrugineus affects key agricultural and ornamental palms, such as date palms, coconut palms, Washingtonia palms, oil palms, and Canary Island palms. Its native range is thought to comprise Southeast Asia and Melanesia [elanesia ; it begaelanesia . The RPWelanesia ; in addielanesia . The weaelanesia . Due to elanesia   have been described in detail [Although new technologies are being developed for early infestation detection , it is on detail ,22; the n detail ,23.The date palm is a key fruit crop in arid regions, and the destruction of palm trees significantly impacts the region’s agriculture and the livelihoods of farmers. For instance, over 80,000 date palm trees in Saudi Arabia are infested with RPW, amounting to an economic burden of over 8 million USD spent on management and eradication with 5% infestation ,25. MostDue to the high value of date palms as a cash crop and the seriousness of RPW as a pest, the tolerance threshold is set at a low pest population, and 1% infestation is enough to warrant the initiation of control measures . Early dA sequential sampling plan was developed to accurately assess the status of the pest in coconut and date palms based on infestation reports, with the action threshold, RPW aggregation index, and risk of making the wrong decision all built into the plan ,32. The TM trap is commonly used in several European countries [Pheromone-baited traps are widely used in RPW management programs; however, over-reliance on pheromone trapping and neglect of other strategies leads to a build-up of weevil populations and eventual outbreaks . The fouountries . When usAlongside trapping, preventive and curative chemical treatments are essential for the efficient management of RPW ,36. CuraRecently, microwave radio frequencies were also investigated as a potential method for controlling weevil infestations. This method was shown to result in high weevil mortality, as well as lower fertility of the surviving weevils ,39.Pest control will remain crucial in securing a food supply that meets ever-increasing global demands . Yet, evTribolium castaneum was the only taxa from the species-rich order Coleoptera to be well-studied at the genomic level. Since its publication in 2008, the paper describing the T. castaneum genome has been cited over 1000 times, reflecting the usefulness of this resource to the scientific community [T. castaneum genome assembly was produced by means of capillary DNA sequencing technology, which had limited throughput and high per-base costs [The advancement of omics tools, such as genomics and transcriptomics, has permitted the emergence of new agricultural pest model organisms. Until recently, the red flour beetle ommunity . The orise costs . Additiose costs .Current sequencing technologies have much higher throughput and lower per-base costs, as well as much lower DNA input requirements for library preparation. Some technologies allow for whole-genome sequencing from a single individual, even for insects with very small body sizes . DevelopAlthough genomics has the power to characterize the entire gene repertoire of an organism, obtaining a high-quality genome assembly and annotation can be costly and time-intensive. For this reason, many researchers have turned to transcriptomics as an alternative to exploring the genomes of agricultural pests. This approach consists of characterizing the set of genes expressed at a given time using RNA sequencing (RNA-seq). Because only a small portion of the eukaryotic genome is transcribed into messenger RNA (mRNA), transcriptomics requires a much lower sequencing throughput compared to genomics, greatly reducing project costs. This approach has been applied in many agricultural pests for which no genome assembly was available at the time ,53,54,55In the RPW research community, the adoption of omics technologies has been slow, but many advances have already been achieved. In the following sections, we review the existing efforts in this system.A number of studies have utilized RNA-seq to identify genes in the RPW, either focusing on the annotation and analysis of a select group of genes or producing a general resource of identified transcripts.T. castaneum clustered transcripts (Unigenes) and Onthophagus Taurus expressed sequence tags (ESTs). These searches identified up to 72%, 50%, and 63% of contigs and 25%, 9%, and 13% of singletons as matching with the nr, T. castaneum, and O. taurus databases, respectively. The fact that almost 30% of sequences could not be annotated with this strategy might reflect the general lack of sequences from related species in the database at the time.The first study of this type was published in 2013 by Wang et al. , and adoThe next two studies were published in 2015 ,58. Yin Drosophila grimshawi and Bombyx mori was only identified for two genes. Interestingly, the authors determined the expression profiles of all chemoreceptor genes in multiple tissues through real-time PCR and observed that most were antennae-enriched. However, the number of chemoreceptor genes identified in this study is small compared to other Curculionidae beetles, such as Dendroctonus ponderosae [In the same year, Yan et al.  conductenderosae , raisingIn 2016, a second attempt to identify RPW chemoreceptor transcripts was performed by Antony et al. , in whicDrosophila Cyp6g1 (CYP6345J1) and Bemisia tabaci CYP4C64 (CYP4LE1). RNAi knockdown of select RPW P450 genes resulted in a negative impact on survival in toxicity assays, demonstrating that these genes could be important targets for control strategies. This study was an important addition in that it experimentally validated the involvement of the identified genes in insecticide resistance.In 2019, Antony et al.  identifiD. melanogaster, T. castaneum, and Hylobius abietis. Neuropeptides are involved in many behavioral processes, including reproduction, feeding, learning and memory, and social behavior, and also in many physiological processes, such as development, growth, metabolism, and pheromone biosynthesis. For these reasons, these neuropeptides and their receptors are promising targets for developing new pesticides.In 2020, a study by Zhang et al.  identifiIn 2020, two additional transcriptomic studies were conducted with the aim of identifying RPW genes ,65. BothIn 2021, Engsontia and Satasook  annotateSequencing and generating draft assemblies for non-model species, such as the RPW, has been hindered by the abundant heterozygosity present in diploid sexual populations. However, the rapid development of new approaches, such as linked-read and long-read sequencing, along with appropriate assembly tools, has allowed the generation of de novo genomes for diploid systems with high quality and contiguity, and thus more accurate representations of the genome structure and gene content . There aT. castaneum genome as a reference. This hybrid assembly (NCBI accession number GCA_012979105.1) is 782 Mb long and has a contig N50 of 23.8 Kb and a scaffold N50 of over 64 Mb. The high scaffold N50 metric could be artifactual since taking T. castaneum as the scaffolding reference assumes the colinearity of the two genomes, although the species diverged over 160 million years ago [The first publicly available RPW draft genome sequence was published in May 2020 . DNA wasears ago . In addiears ago . A high ears ago  have shoears ago  includesears ago  should bIn September 2021, a second draft genome was published for the RPW . This aszenodo.org. Available at https://doi.org/10.5281/zenodo.6878576 (Accessed 31 January 2023).An additional draft genome of the RPW was reported by Manee et al. , for whiInterestingly, the sizes of available RPW genome assemblies vary greatly, from 589.40 to 1121.36 Mb ,70,72. ASince comprehensive benchmark software was not available at the time when the first RPW transcriptomic studies were published, we have re-analyzed available transcriptomic/genomic data for the RPW using BUSCO, aiming at providing an updated picture of the available data. We utilized the public server gVolante  BUSCO v5According to our analysis, all available RPW resources have reasonably high BUSCO completeness, with >80% completeness for all datasets . The amoThe amount of fragmented and missing BUSCOs is highest in the transcriptome assembly published by Wang et al. , with 10Insect gut communities are dynamic and can be determined by factors such as developmental stage, host phylogeny, and environmental habitat ,79,80. MLactococcus lactis was found to be the most frequent gut microbe in July larvae and in adult samples, and Klebsiella pneumoniae in March and November larvae. Twenty-three percent of the species in November’s microbial population have been associated with cellulolytic digestion; the dominant bacteria during that period belonged to the Proteobacteria phylum, such as Enterobacter, Klebsiella, and Pantoea, which is recognized to have cellulolytic capabilities. In addition, the microbial groups identified in November and July were found to have roles in the symbiotic relationship between host and microbiota. The effect of high-temperature stress on microbial communities was also investigated.Few metagenomic studies have been published on the gut microbial community of the RPW ,82, althProteobacteria and Firmicutes, consistent with previous reports [Enterobacteriaceae, Streptococcaceae, Lactobacillaceae, Enterocococcaceae, Enterobacteriaceae, and Entomoplasmataceae for all RPW life stages, an observation similar to the existing literature [Klebsiella, Serratia, Enterobacter, and Citrobacter were demonstrated to break down cellulose in the gut of RPW larvae. Taken together, this and other studies suggest a high degree of stability for microbial communities in the RPW gut, with only slight variations in abundance across several life stages and host plants [In 2017, Muhammad et al.  investig reports ,82. At tterature . Seven bt plants ,82,83.The eukaryotic genome includes a significant portion of repeats. These can include dispersed repeats, mainly composed of transposable elements and segmental duplications, and tandem repeats such as satellite DNAs (satDNAs), minisatellites, and microsatellites . Aside fThe study of repeats in the RPW genome is in its infancy, but the use of genomics has greatly accelerated its progress. In the past year, two studies were published using short-read sequencing to characterize microsatellites and satDNAs in the RPW ,87. ManeMontiel et al.  carried Hazzouri et al.  used RepThe mitochondrial genome is an excellent and informative model for molecular evolution, comparative genomic research, and genetic and phylogenetic analysis because of its maternal inheritance mode, high evolutionary rate, lack of introns, and limited recombination ,90. A tyDue to the shortcomings of traditional RPW management techniques over the last 30 years, many omics studies have been carried out on the RPW with the hope of improving technologies for managing this pest in the field. However, truly understanding the RPW pest-plant dyad will also require understanding the palm trees it attacks. For instance, proteomics of palms attacked by the RPW may help identify opportunities for control and early detection . AdditioDiabrotica virgifera virgifera [R. ferrugineus, where both adults and larvae could be targeted using dsRNAs [Drosophila and employs a dominant genetic process that imposes genes essential for female viability and male sterility simultaneously, resulting in seamless sexing and sterilization. Eggs produced with this technique are released into the field, and upon hatching, only sterile males emerge [Genomic and transcriptomic data already available for the RPW may also be useful in identifying genes suitable for targeting with genetic/genomic engineering tools, such as RNAi and CRISPR/Cas-based approaches . RNA intirgifera . This teg dsRNAs . The CRIg dsRNAs  in the fs emerge .Laboratory experiments have successfully used RNAi to silence several genes in the RPW, namely eceptors ,97. The eceptors ,100,101.Additional approaches to using omics to manage RPW include the use of transgenic insect viruses, namely Baculoviruses , or micrHost-plant resistance against the RPW is not very well understood and offers a whole new area of exploration wherein traditional plant breeding techniques coupled with advanced molecular-based breeding techniques could be used to induce resistance against the RPW in popular palm cultivars. The entire genome of the date palm cultivar ‘Khalas’ has been sequenced ,105, whiR. ferrugineus. Alongside these, the technical difficulties in the production of transgenic date palms coupled with the lower tendency of consumers to accept such genetically modified crops [Some challenges that still face the application of omics-based approaches for controlling the RPW include the identification of suitable gene(s) for RNA-guided dominance and developing a robust CRISPR/Cas system for ed crops  represenDespite the success of omics approaches in advancing pest biological research, research communities have been slow to adopt these techniques, and pest management programs have traditionally focused on applied rather than basic research. Nonetheless, unexpected discoveries and conceptual advancements in our understanding of pest biology are being made due to the enhanced knowledge and insights garnered through pest omics. Omics data are also expected to boost our understanding of RPW evolution and thus to open comparative genomics avenues of research. For example, knowing more about the geographical distribution of RPW genetic variation will help reveal patterns of dispersal among palm tree farms that can inform transportation and treatment guidelines.As pest research moves toward a systems biology paradigm, the integration of an ever-growing number of data sources will help in future-proofing pest control and protecting our food supply and biodiversity.


CDKN2A and the methionine salvage gene methylthioadenosine phosphorylase (MTAP). A loss of MTAP increases the pool of its substrate methylthioadenosine (MTA), which binds to and inhibits activity of protein arginine methyltransferase 5 (PRMT5). PRMT5 utilises the universal methyl donor S-adenosylmethionine (SAM) to methylate arginine residues of protein substrates and regulate their activity, notably histones to regulate transcription. Recently, targeting PRMT5, or MAT2A that impacts PRMT5 activity by producing SAM, has shown promise as a therapeutic strategy in oncology, generating synthetic lethality in MTAP-negative cancers. However, clinical development of PRMT5 and MAT2A inhibitors has been challenging and highlights the need for further understanding of the downstream mediators of drug effects. Here, we discuss the rationale and methods for targeting the MAT2A/PRMT5 axis for cancer therapy. We evaluate the current limitations in our understanding of the mechanism of MAT2A/PRMT5 inhibitors and identify the challenges that must be addressed to maximise the potential of these drugs. In addition, we review the current literature defining downstream effectors of PRMT5 activity that could determine sensitivity to MAT2A/PRMT5 inhibition and therefore present a rationale for novel combination therapies that may not rely on synthetic lethality with MTAP loss.Approximately 15% of cancers exhibit loss of the chromosomal locus 9p21.3 – the genomic location of the tumour suppressor gene  This gene encodes for the p14   may create new “synthetically lethal” or “collateral” vulnerabilities to therapy , 2. The  the p14  and p16 e (MTAP) . MTAP isdeletion . The co-eukaemia , 13 and MTAP-negative leukaemia cells in vitro  in the methionine salvage cycle, regenerating methionine for further cycling Figure 1in vitro , whilst ro (MTAP –20. MTAPMTAP (Multiple studies in 2016 undertook short hairpin RNA (shRNA) screens to identify genes that cause synthetic lethality with both endogenous and genetically engineered loss of MTAP –20. All MTAP , 23; PRMMTAP  and MEP5MTAP , 26 utilMTAP-negative tumours, focusing on MAT2A and PRMT5, which are receiving increasing attention in clinical development. We discuss the function of MAT2A and PRMT5, including binding partners, current methods of inhibition, downstream signalling and effect on metabolic pathways. We review the interplay between these proteins, and how therapeutic inhibition impacts growth, cell cycle, apoptosis or DNA damage response. Finally, we highlight the challenges that face the therapeutic targeting of the MAT2A/PRMT5 axis, the need for additional predictive biomarkers other than MTAP status, and how these biomarkers could predict rational combination therapies.In this review, we examine the current understanding of therapeutic vulnerabilities intrinsic to 2PRMT5 is a member of the family of protein arginine methyltransferases responsible for methylating specific arginine residues of a wide range of proteins and thus regulate protein activity. This includes histones that regulate chromatin structure and epigenetic regulation of gene expression . The ninPRMT5 is the principal type II PRMT and functions mainly as a negative regulator of transcription . PRMT5 c3Many studies have identified that increased activity and upregulation of PRMT5 is a key regulator of cancer progression and marker for poor prognosis in multiple malignancies, including breast , gastric3.1ST7 and NM23 to inhibit their transcription  and metastasis activator genes. In the same conditions, a reduction of repressive marks (H4R3me2) at the tumour suppressor genes SPDEF and CDH1 was observed (CCNE1 (androgen receptor (AR) promoter was shown to be an epigenetic target of PRMT5, and knockdown of PRMT5 caused a reduction in H4R3me2 marks at the AR promoter and a subsequent reduction in AR expression (FOXP1 promoter to activate FOXP1 transcription both in vitro and in vivo. The expressed FOXP1 protein promoted breast cancer cell proliferation by activating oestrogen receptor (ER) signalling  and consequently defects in these processes. Further, PRMT5/E2F1 expression and cortactin/CTTN expression showed positive correlations across different types of cancer in the Cancer Genome Atlas datasets (TCGA)  , suggestPRMT5 has been reported to promote c-Myc expression and consequently up-regulate the NF-κB pathway . Further3.3in vivo  formed of Sm proteins and small nuclear RNA assemble to form the spliceosome . The splin vivo . Post-trin vivo , 64. Delnor site . This sthibitors .HNRNPC, HNRNPH1, RBM5, RBM23, RBM39 and U2AF1  complex acetylates H4K16, displaces the non-homologous end joining (NHEJ)-promoting 53BP1 protein and directs DNA damage repair towards the homologous recombination (HR) pathway , 73. By A damage .4MTAP-negative cell lines (MTAP-negative cancers) may reduce tumour growth.MAT2A was identified as a top synthetically-lethal hit in three independent shRNA screens in ll lines –20. The ll lines . The MATll lines . SAM canll lines , hepatocll lines , 80 and ll lines , 82. The5MTAP-negative background should, in principle, provide a suitable therapeutic window. However, since MTA and SAM bind competitively to the substrate binding pocket of PRMT5  and a phase 1/2 clinical trial in advanced and metastatic oesophageal squamous cell carcinoma (ESCC) (NCT05312372). A similar study used a fragment approach to design new MAT2A inhibitors that show a high potency and functionality in vivo .A series of further non-substrate competitive inhibitors was developed, including an orally bioavailable t models . AG-270  in vivo . The stu in vivo  and comp in vivo  showed hhibition . AnotherMTAP-negative tumour background, other clinical evidence is emerging that MTAP-negativity does not predict intra tumoral MTA accumulation as seen in model systems  and GSK3326595 (NCT04676516) have been completed and have reported disappointing clinical responses to the monotherapy , 100. Ju systems . This su6MTAP-negative cancer to MAT2A or PRMT5 inhibition is argued to result from abnormally high levels of MTA. While high MTA levels have been demonstrated extensively in MTAP-negative cancer cells in vitro (in vivo (MTAP-negative and MTAP-positive primary tumours (MTAP-negative tumours (shown by a lack of significant reduction in SDMA markers). Barekatain et al. showed evidence that MTA produced from the MTAP-negative tumour is being processed by the intratumour, MTAP-positive stromal cells. A noticeable finding highlighted that in vivo xenografts may not accurately model endogenous tumour response, as xenografts are less populated by stromal cells when comparing their histology to primary GBM tumour tissue  to form and lead to cell death by ferroptosis through lipid oxidation. This effect is amplified by a reduction in cysteine, which impairs the transsulfuration pathway that normally helps to resolve lipid oxidation and reduces the production of glutathione  state in macrophages through activation of the adenosine A2B receptor  drugs in different types of cancers. In murine melanoma cell lines, PRMT5 was shown to methylate IFN-γ-inducible protein 204 (IFI16/IFI204) and negatively regulate cription . Pharmaccription . PRMT5 icription . The com and reported evidence for and against the selectivity of these treatments for MTAP-negative tumours. Future generations of drugs that target PRMT5 activity in an MTAP-negative background must focus on maximising their selectivity for inhibiting PRMT5 specifically within the cancer cell (i.e. when PRMT5 is bound to MTA). Moving forward, to best understand the population of patients that will benefit from therapeutic treatment with MAT2A/PRMT5 inhibitors we require a greater understanding of the molecular rewiring after inhibition. Our current understanding of the downstream effects of PRMT5 inhibition include the impairment of pre-mRNA splicing and DNA damage repair, co-treatment of cancers with agents that target these pathways such as PARP inhibitors and chemotherapy, is potentially synergistic. Such a strategy provides an alternative rationale for the use of MAT2A/PRMT5 inhibitors beyond synthetic lethality with MTAP loss and presents additional predictive biomarkers for future clinical development of combination treatments.Deletion of CB: Writing – original draft. CB: Writing – review & editing. IM: Writing – review & editing. HK: Writing – review & editing.


Under high temperatures, fiber-reinforced polymers are destroyed, releasing heat, smoke, and harmful volatile substances. Therefore, composite structural elements must have sufficient fire resistance to meet the requirements established by building codes and regulations. Fire resistance of composite materials can be improved by using mineral fillers as flame-retardant additives in resin compositions. This article analyzes the effect of fire-retardant additives on mechanical properties and fire behavior of pultruded composite profiles. Five resin mixtures based on vinyl ester epoxy and on brominated vinyl ester epoxy modified with alumina trihydrate and triphenyl phosphate were prepared for pultrusion of strip profiles of 150 mm × 3.5 mm. A series of tests have been conducted to determine mechanical properties  and fire behavior  of composites. It was found that additives impair mechanical properties of materials, as they the take place of reinforcing fibers and reduce the volume fraction of reinforcing fibers. Profiles based on non-brominated vinyl ester epoxy have higher tensile, compressive, and flexural properties than those based on brominated vinyl ester epoxy by 7%, 30%, and 36%, respectively. Profiles based on non-brominated epoxy resin emit less smoke compared to those based on brominated epoxy resin. Brominated epoxy-based profiles have a flue gas temperature which is seven times lower compared to those based on the non-brominated epoxy. Mineral fillers retard the spread of flame over the composite material surface by as much as 4 times and reduce smoke generation by 30%. Fiber-reinforced polymer (FRP) structures are widely used in civil engineering, architecture, and the automotive industry ,4,5,6,7 Structural elements used in civil engineering must meet the fire resistance requirements specified in building codes and regulations ,28. FireUnder heating, fiber-reinforced polymers demonstrate a decrease in strength and stiffness ,36,37,38This work investigates the effects of flame retardants on fire behavior and mechanical properties of pultruded FRPs. Five resin mixtures were prepared for pultrusion of 150 mm × 3.5 mm glass fiber-reinforced flat profiles. The first resin mixture is based on non-brominated vinyl ester epoxy and the second one on brominated vinyl ester epoxy. The other resin mixtures are the compositions based on brominated vinyl ester epoxy with different mass content of alumina trihydrate and triphenyl phosphate fillers. A series of fire behavior tests were performed and ignitability, flammability, combustibility, toxicity, smoke generation, and flame spread properties were investigated. Based on the test results, the materials were classified according to their fire hazard potential. Mechanical tests were performed to obtain tensile, compression, interlaminar shear, and flexural properties in longitudinal and transverse directions.2 LT 0600/S 300/06H 01/125 GUS  with 0/90 layup were used as reinforcement for pultruded strip profiles with dimensions of 150 mm × 3.5 mm. One fabric layer was placed at the top and at the bottom of the profile for transverse reinforcement. The Pulstrand 2100  9600 Tex unidirectional glass fiber rovings with filament diameter of 35 microns and two layers of multiaxial non-crimp E-glass fabric with areal density of 900 g/mOne resin mixture based on Atlac 430 vinyl ester epoxy  and four resin mixtures based on Devinil 950 TG brominated vinyl ester epoxy  were prepared for the study. The following additives were used to obtain optimum resin properties for pultrusion applications: Trigonox C  as an initiator for (co)polymerization of ethylene, styrene, acrylonitrile, acrylates, and methacrylates; Perkadox 16  as an initiator for suspension polymerization of acrylates and methacrylates; BYK A555  as a deaerator; and zinc stearate  as a friction-reducing additive . To imprThe resin components were mixed with an electric mixer . First, the epoxy resin was added to the mixing container. Next, the main additives were added to the resin as follows: deaerator BYK-A555 (liquid), hardener Perkadox 16 (powder), hardener Trigonox C (liquid), and friction reducing additive zinc stearate (powder). Then, the mixing was started. At the last step, alumina trihydrate (powder) and triphenyl phosphate (powder) flame retardants and dispersing additive BYK-W996 (liquid) were added to the resin, and the components were mixed for 15 min.Flat profiles with a cross section of 150 mm × 3.5 mm were produced with the Pultrex Px500-6T pultrusion machine . The length of the pultrusion die is 600 mm. Six rectangular heaters 350 mm long and 90 mm wide were used to heat the die block. Two heaters were installed at the top and bottom sides of the die block, aligned with the longitudinal axis of the die. Two heaters were installed at the die block entrance, aligned with the transverse axis of the die. Three thermocouples embedded in the die block were used to control the temperature. The temperature was maintained in the range of 135–155 °C. Fire behavior is characterized by the following properties: flammability, ignitability, combustibility, flame spread over the surface, smoke generation, and toxicity of combustion products. The material property is described by the hazard group, which is determined based on test results. Based on the combination of its properties, the material is assigned to a fire hazard class. Material combustibility testing is conducted in accordance with the GOST 30244-94 procedure . The tes2. The experiment ends when a specimen ignites or after 15 min if a specimen fails to do so. If a specimen is ignited, at the next iteration the heat flux density is reduced. If the material has not ignited within 15 min, the heat flux density is increased at the next iteration. A new specimen is tested at each iteration. The tests are finished when the minimum heat flux sufficient to ignite a specimen is determined. Materials are classified into 3 groups according to their ignitability. Material classification based on ignitability test results is presented in Material ignitability tests are conducted in accordance with GOST 30402 . The tesSmoke generation tests are conducted in accordance with GOST12.1.044-89, Procedure 4.18 . The tesCombustion product toxicity tests are conducted in accordance with GOST 12.1.044-89, Procedure 4.20 . The tesFlammability tests are conducted in accordance with GOST 12.1.044-89, Procedure 4.3 . The tes2 when measured at a distance of 70 mm from the closest edge of a specimen. Pilot burner is located at a distance of 8 ± 1 mm from the specimen edge. Pilot burner flame length is set to 11 ± 2 mm. The test starts with placing the fixing frame with a specimen under the pilot burner flame and ends when the flame stops propagating over the surface of the specimen. The flame spread index is calculated as follows (Equation (4)):th section of the specimen surface, The flame spread index is determined in accordance with GOST 12.1.044-89, Procedure 4.19 . The tesSmoke-generating ability, flame spread index, toxicity of combustion products, and flammability were determined in accordance with GOST 12.1.044 procedures . CombustMechanical properties of tested profiles were determined with the Instron 5969 testing machine . Compression, tension, flexure, and interlaminar shear tests were performed in accordance with ASTM D6641/D6641M-16 , ISO 527Specimens for mechanical property and fire behavior tests were machined with the milling machine. Specimens were machined at 10,000 rpm and a feed of 1500 mm/min, using a face mill of 3.175 mm in diameter.The peak exothermic temperature of resin compositions was determined in accordance with the ASTM D2471  procedurAs Atlac 430 vinyl ester epoxy resin was already tested in previous pultrusion studies , and theFive batches of profiles were produced at a pulling speed of 0.5 m/min. Profiles are marked according to the resin mixture number—PRM-I, PRM-II, PRM-III, PRM-IV, and PRM-V. The PRM-I profile is based on non-brominated vinyl ester epoxy resin. PRM-II is based on brominated vinyl ester epoxy resin. PRM-III, PRM-IV, and PRM-V are brominated vinyl ester epoxy-based profiles with mineral fillers. In total, 31 m of strip profiles were produced. As fire retardants occupy a certain volume of a profile, the use of additives reduces the volume fraction of reinforcing fibers. Theoretical calculations of the tensile modulus were carried out according to the method proposed by Evans . Fabric d 76 GPa  in the cThe results of ILSS tests correlate well with results of resin reactivity analysis. Thus, the PRM-IV profile with the highest ILSS values has the exothermic peak temperature very close to the recommended peak temperature. At the same time, the highest exothermic peak temperature exceeding the desired temperature by 72 °C was observed in the case of the PRM-II profile that has the lowest ILSS value.2. The composite profiles based on the RM-V matrix ignited at a heat flux density of 25 kW/m2. Other materials ignited at a heat flux density of 20 kW/m2. Thus, all tested materials fall into B2 ignitability group.Ignitability test results are shown in 2/kg was obtained for the profile based on brominated vinyl ester epoxy resin without flame-retardant additives (PRM-II). The lowest value of 226 m2/kg was obtained for the glass fiber/vinyl ester epoxy resin profile without flame-retardant additives (PRM-I). The presence of the alumina trihydrate additive in the PRM-III and PRM-IV profiles reduced smoke generation. The increase in the mass fraction of alumina in resin composition reduces the smoke generation index. The PRM-V profile containing both alumina trihydrate and triphenyl phosphate has higher smoke generation compared to the PRM-IV profile with the same amount of alumina trihydrate and no triphenyl phosphate. All tested materials fall into the D2 group of smoke generation ability.Results of combustion product toxicity tests are shown in Flammability test results are shown in Classification of all materials based on fire behavior test results is shown in The highest combustion temperature during flammability and combustibility tests was measured for PRM-I profiles based on bisphenol A vinyl ester epoxy resin. The other tested profiles are based on the brominated vinyl ester epoxy resin and have low flue gas temperature. Brominated resins contain tetrabromobisphenol-A and have flame-retardant properties and higher charring ability ,81. AccoThis study investigated the effect of flame retardants on mechanical properties and fire behavior of pultruded composite profiles. Five batches of thermoset strip profiles with dimensions of 150 mm × 3.5 mm based on five resin mixtures were produced. Mixtures were based on vinyl ester epoxy resin and on brominated vinyl ester epoxy resin with different content of mineral fillers. Mechanical test results show that the tensile, compressive, and flexural strength of profiles based on vinyl ester epoxy is higher than that of profiles based on brominated vinyl ester epoxy by 7%, 30%, and 36% respectively. However, according to flammability tests, the temperature of the flue gas released by profiles based on brominated epoxy is seven times lower than that of flue gas released by non-brominated epoxy profiles. Non-brominated epoxy-based profiles emit less smoke than those based on brominated epoxy. Profiles filled with alumina trihydrate and triphenyl phosphate had a four times lower flame spread index. The combustion product toxicity index differs slightly between profiles based on non-brominated and brominated epoxy and profiles based on brominated epoxy with alumina trihydrate and triphenyl phosphate. All tested materials are moderately toxic. Fire behavior tests per GOST 30244-94 show that glass fiber-reinforced profiles based on brominated epoxy fall into combustibility Group 1 and are more fire-resistant than non-brominated epoxy-based profiles falling into combustibility group 3. According to GOST 12.1.044 and GOST 30402-96, all tested materials fall into the B2 flammability group, D2 smoke generation group, and T2 toxicity group, and can be classified as slowly spreading the flame over the surface.


Wnt signaling plays an important role in many biological processes such as stem cell self-renewal, cell proliferation, migration, and differentiation. The β-catenin-dependent signaling pathway mainly regulates cell proliferation, differentiation, and migration. In the Wnt/β-catenin signaling pathway, the Wnt family ligands transduce signals through LRP5/6 and Frizzled receptors to the Wnt/β-catenin signaling cascades. Wnt-targeted therapy has garnered extensive attention. The most commonly used approach in targeted therapy is small-molecule regulators. However, it is difficult for small-molecule regulators to make great progress due to their inherent defects. Therapeutic peptide regulators targeting the Wnt signaling pathway have become an alternative therapy, promising to fill the gaps in the clinical application of small-molecule regulators. In this review, we describe recent advances in peptide regulators for Wnt/β-catenin signaling. O-acyltransferase in the endoplasmic reticulum, lipid-modifies the Wnt proteins. Through the Evi/Wntless multiple-pass transmembrane protein, the Wnt proteins are transported and secreted  ChrSmall-molecule regulators are commonly used in targeted therapy. IWP and SB-216763 can exert effects on upstream and downstream components for inhibiting and activating the Wnt/β-catenin signaling pathway . The comWnt signaling is important to many physiological, developmental, and disease processes . The WntThe Klotho protein is an anti-aging protein abundantly expressed in normal kidneys. Klotho, a single-pass transmembrane protein, includes a short cytoplasmic tail (KL2) and a transmembrane segment (KL1). Based on the KL1 domain sequence of human Klotho, KP6 (sequence: QPVVTLYHWDLPQRLQDAYGGWANRALADH) was designed and synthesized by Chen et al. KP6 is 30 amino acids in length and contains a Wnt-binding motif ranging from Gln186 to His215 within the KL1 domain. KP6 can mimic Klotho's function. KP6 blocks the Wnt/β-catenin signaling pathway by binding to Wnt, which sequesters its ability to interact with LRP6. Furthermore, KP6 promotes survival and ameliorates kidney injury in diabetic mice .A study indicated that the expression level of Wnt3a is high in myocardial hypertrophy mice and is positively related to cardiomyocyte apoptosis . The lowN-terminal CRD domain of FZDs binds to Wnt ligands and LRP5/6 co-receptors. The C-terminus of FZDs is located in the cytoplasm, where it recruits and binds to Dsh for triggering subsequent signal cascades . Moreover, rhFzd7 may effectively repress angiogenesis, proliferation, and invasion and induce apoptosis of triple-negative breast cancer cells (The recombinant extracellular peptide fragment (rhFzd7), including the CRD sequence, was synthesized from er cells .d = 3 nM). The dFz7-21 may inhibit Wnt signaling by perturbing the formation of the Wnt–FZD–LRP ternary complex to further impair stem cell function  was the most potent peptide. A 5-carboxyfluorescein-labeled version of Fz7-21 (5FMA-Fz7-21) exhibited subtype-selective binding to Fc-tagged FZD1, FZD2, and FZD7 CRDs with half-maximal effective concentration values (19-58 nM). dFz7-21 exhibited an ~40-fold improvement in inhibiting Wnt3a signaling in HER293 cells as compared with monomeric Fz7-21. The crystal structure indicated that the dimeric form of Fz7-21 (dfz7-21) exhibits improved activity. dFz7-21 exhibited tight binding to the hFzd7 CRD  was synthesized as an inactive precursor (pro-ANP) that was converted to a mature active peptide after proteolytic cleavage by the membrane-related serine protease Corin, in which the extracellular region included Fzd1 and Fzd2  . ANP mayACBP is a polypeptide that was identified from goat spleen extract after immunization with gastric cancer lysates . ACBP caAmyloid β peptide (Aβ) is a small proteolytic fragment (40 to 42 amino acids) consisting of a glycosylated transmembrane protein and amyloid precursor protein . Aβ42 s Figure ; Table 4The destruction complex may be a dynamic multiprotein assembly. Its core components include the serine-threonine kinase GSK-3, APC protein, scaffolding protein Axin, CK1, and E3-ubiquitin ligase β-TrCP . PeptideAxin is a largely unstructured, flexible protein that contains β-catenin, GSK-3, and CK1-binding sites. Axin is a key control point for catenin destruction because of its ability to promote the phosphorylation of β-catenin . A previ182−195 (sequence: MEENAYQVFLTSDI) is designed and synthesized, which is centered on aggregation preventing polymerization and consists of Axin amino acids182−185. The short peptide can induce the polymerization of Axin and further block Wnt signaling and colorectal cancer growth  was initially identified in 1970 . It is cExendin-4  is an agonist of the glucagon-like peptide-1 receptor. EX-4 can reduce the degradation of β-catenin by inhibiting the expression of GSK-3β. The Wnt/β-catenin signaling pathway was activated to further protect the integrity of the BBB .50 value against DPPH of P1 and P3  was higher than that of the P2 antioxidant peptide (2.33 ± 0.56 mM). Therefore, P1 and P3 antioxidant peptides warrant further study , TTANIEDRR , and FSVVPSPK , were identified from a peptide fraction of 1–5 kDa obtained from blue mussels by peptic hydrolysis. It was found that the P1, P2, and P3 antioxidant peptides had a higher 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity than previously reported antioxidant peptides from blue mussels , 91. In er study . P1 and er study .in vivo  (Pituitary adenylate cyclase-activating polypeptide (PACAP) is a type of peptide hormone superfamily, including glucagon-like peptides, glucagon, and vasoactive intestinal peptides , which ein vivo . PACAP hLA AVKK)  was desiLA AVKK) .IAGIP (sequence: EPVPPPPTPRSSRHDSGLDSMKD) was designed by linking the IKK-recognized (inflammation-responsive) motif to the LRP peptide (the GSK-3β inhibitory motif) . IAGIP cAdiponectin (APN) is a 247-amino-acid polypeptide with a molecular weight of 30 kDa. BBB permeability was restricted by APN under physiological conditions. The APN peptide  was chemically synthesized based on the functional area in the globular domain of APN . APNp cop-GSK-3β can be upregulated by exogenous administration of apolipoprotein E (apoE), thereby promoting neuronal survival. However, apoE has difficulty crossing the BBB because of its 34-kDa molecular weight, thereby limiting its translational study . COG1410A novel peptide purified from the hydrolysates of tuna backbone protein  was identified to have strong antioxidant activity . APTBP hβ-Catenin is a type of plasma membrane-associated protein, and it plays a dual role in cellular signaling. On the one hand, β-catenin can stabilize cell–cell contact. On the other hand, it plays a role in activating gene transcription after β-catenin translocation to the nucleus . β-CatenApelin is the endogenous ligand for APJ, which is a seven-transmembrane G protein-coupled receptor . Apelin A novel peptide, EIF6-224 amino acid , was encoded by circ-EIF6. EIF6-224aa is responsible for the oncogenic effects of circ-EIF6. EIF6-224aa can interact with the oncogene MYH9 and subsequently decrease MYH9 degradation by upregulating the expression of β-catenin. The overexpression of MYH9 can enhance the metastasis of TNBC cells and promote the progression of TNBC .Gastrin-releasing peptide is a neuropeptide that acts through G protein-coupled receptors, which stimulate the proliferation of mesenchymal cells in the fetal monkey lung . GRP incThe C-peptide (sequence: EVEDPQVPQLELGGGPEAGDLQTLALEVARQ) initially identified was cleaved from proinsulin during proteolytic processing in 1970 . C-peptiN-acetylglucosaminyltransferase-V from the GnT-V gene intron, nt 38–67, which appeared to induce peptide-specific recognition of target cells (The peptide vaccine for melanoma includes four peptides: Melan-A (sequence: AAGI GILTV), gp100 (sequence: KTWGQYWQV), MAGE-3 (sequence: FLWGPRALV), and NA-17 (sequence: VLPDVFIRCV). Melan-A has a “bulged” and “stretched” conformation. To identify the MART-1 epitopes for tumor-infiltrating lymphocytes, 23 peptides were selected based on the known peptide-binding motif to HLA-A2.1 and synthesized (>90% purity). Among them, Malan-A could most effectively sensitize T2 cells for lysis. Gp100 is a melanocyte-derived lineage-restricted intracellular glycoprotein that can be presented on the cell surface in association with major histocompatibility complex molecules in T lymphocytes . Severalet cells . After tet cells .Buthus martensii Karsch (BmK) analgesic peptide was identified from a venom . In addition, the expression of the target gene of β-catenin, E-cadherin, is upregulated, thereby reducing breast cancer cell stemness and epithelial–mesenchymal transition (The first  a venom . Since t a venom . BmK AGA a venom . The rBm a venom . It can ansition .d = 60 ± 2 nM). The StAx-3 sequence was thus selected for further optimization. In a parallel series of experiments, affinity optimization of the Axin peptide sequence was examined. In addition, 32 new sequences were obtained. Among them, peptide fStAx-35R (sequence: RRWPRSILDSHVRRVWR) with high binding affinity for β-catenin (Kd = 53 ± 9 nM) and positive charge was obtained upon the addition of Arg and Trp at positions 467 and 468 (fStAx-34) and addition of arginine residues. Proteolysis-targeting chimera is a useful technology to degrade proteins in vivo. In this study, a novel proteolysis-targeting chimera β-catenin degrader was designed by coupling xStAx-35R with a von Hippel–Lindau protein (VHL) ligand via an Ahx chemical linker, termed xStAx-VHLL. xStAx-VHLL can sustain the degradation of β-catenin and significantly inhibit the Wnt/β-catenin signaling pathway  CBD StAx-1, 2, and 3 were further designed. Among them, StAx-3 exhibited the greatest α-helicity (51%). Moreover, fStAx-3 exhibited significantly enhanced affinity for β-catenin , PTHrP (38-94), and PTHrP (107–139) peptides. Among them, PTHrP (1–34) can bind to the PTHrP receptor (PTH1R), a common G protein-coupled receptor. PTHrP (1–34) warrants further study because of its important role in tooth and bone development . PTHrP . SOX9, tS9pep (sequence: ADSPHSSSGMSEVHSPGEHSG) was designed and synthesized based on the amino acid sequence located in the SOX9 central region. The peptide has S9pep, which could inhibit the expression of c-Myc (its oncogenic target gene) by interacting with and relocating β-catenin from the chromatin to the cytosol, like SOX9 .50 value = 288 μM). To promote entry into the cells, TAT-PEP8 (sequence: GRKKRRQRRRPPQDEMEEPQQTE) was designed and synthesized by attaching the cell-penetrating peptide TAT to PEP8. TAT-PEP8 can inhibit the growth of AsPC-1 cells   was selected and synthesized after a series of screenings, for example, the calculation of affinity energy values for each amino acid and the root mean square deviation from the reference conformation. Peptide PEP8 expanded the size of the repository of druggable target proteins. PEP8 can inhibit the formation of the β-catenin/LRH-1 complex, thereby inhibiting the Wnt/β-catenin signaling pathway. In addition, PEP8 can inhibit the growth of AsPC-1 cells (IC 111 μM) .in vivo and in vitro studies  positions, followed by ruthenium-catalyzed olefin metathesis to yield SAH-BCL9 peptides A through C. Among SAH-BCL9CA−, SAH-BCL9B (sequence: LSQEQLEHRERSLXTRXIQRMLF) was identified as the most effective β-catenin-targeting peptide. In addition, circular dichroism analysis confirmed that hydrocarbon stapling consistently enhanced peptide α-helicity compared with the corresponding unmodified peptide (BCL9HD2). SAH-BCL9 could target β-catenin in cells with a high affinity (IC50 = 135 nM) and selectively disrupt the BCL9/β-catenin complex in a dose-dependent manner. Blockade of these interactions inhibited β-catenin-dependent transcriptional activity and target gene expression and suppressed tumor cell growth, metastasis, and angiogenesis (B-cell lymphoma 9 (BCL9) is a type of co-activator of β-catenin, which was first discovered in some B-cell malignant tumors . Peptide studies , 119. Noogenesis   is a type of proto-oncogene. It encodes a phosphoprotein that acts in cellular transformation, apoptosis, and cell cycle progression . When KaAlthough it is challenging to directly target β-catenin, it is possible to indirectly activate it through transcriptional cofactors and by controlling its stabilization. TCF and LEF are transcription factors mainly involved in the Wnt/β-catenin signaling pathway . The mamCementum markers, such as cementum protein 1 (CEMP1), were shown to promote the proliferation and differentiation of periodontal ligament cells toward a “mineralizing-like” phenotype . The secThere is a crosstalk between the TGF-β/SMAD signaling pathway and the Wnt/β-catenin signaling pathway . TGF-β iOreochromis andersonii. OA-GL17d was degraded after 10 h, and its half-life was ~1.86 h, much longer than that of some peptides (OA-GL17d (sequence: GLFKWHPRCGEEQSMWT), a new natural peptide homodimer, was identified from the skin secretions of peptides . It may peptides .The pilose antler polypeptide  is one of the main components of pilose antler. PAP-3.2KD may decrease the expression of TGF-β1 and further reduce SMADs, which are the target proteins of TGF-β1 signal transduction. Ultimately, the TGF-β/SMAD signaling pathway is inhibited, which thereby ameliorates histopathological damage, myocardial fibrosis, and apoptosis in adriamycin-induced myocardial tissues .A total of 1,697 endogenous peptides in hypertrophic scar tissues and matched normal skin were identified using liquid chromatography-mass spectrometry/mass spectrometry. Among these, 78 peptides were highly expressed in normal tissues compared with the corresponding hypertrophic scar tissues. The peptides with fat solubility  and high stability (instability index < 0) were further screened. Considering that endogenous peptides were derived through hemoglobin reduction in hypertrophic scar tissues, LYENRL and ASGVAVSDGVIKV (ASGVA) were selected for further assessment of biological function. In addition, LYENPL could inhibit the proliferation of human skin fibroblast cells at a lower dose compared with ASGVA. LYENRL could reduce SMAD2/3 phosphorylation and the SMAD2/3/4 complexes to the SMAD Binding element, thereby inhibiting TGF-β1/SMAD signaling. Additionally, LYENRL can inhibit the proliferation, migration, and extracellular matrix production of scar fibroblasts in a concentration-dependent manner .A region termed the SMAD4-binding domain (SBD) was identified, which was an amino-terminal region of transactivation 2 of p65 (a main subunit of NF-κB), associated with the mad homology 1 domain of SMAD4 to inhibit bone morphogenetic protein signaling. Based on the SBD, a cell-permeable SBD peptide (sequence: RRRRRRRGGGQAGEGTLSEALLHLQF) was designed and synthesized, which could block the association of p65 with SMAD4. In addition, the SBD peptide enhances BMP2-induced osteoblast differentiation and mineralization .APNp could suppress mitochondrial and ATF4-CHOP apoptosis pathways in a SMAD3-dependent manner by targeting GSK-3β. Thus, neural survival was promoted following intracerebral hemorrhage injury in the diabetic setting  Figure .In summary, we have briefly explored the importance of the Wnt/β-catenin signaling pathway in human diseases. This signaling pathway is mainly involved in regulating biological processes such as cell proliferation, differentiation, and migration. In the Wnt/β-catenin signaling pathway, Wnt family ligands transduce signals to the Wnt/β-catenin signaling cascade through LRP5/6 and FZD receptors. Therefore, targeting molecules in the Wnt/β-catenin signaling pathway may modulate human diseases by activating or inhibiting this pathway, thereby affecting biological processes. Given recent research advancements, we summarize the peptide modulators in the Wnt/β-catenin signaling pathway. Studies have indicated that peptide regulators regulate the Wnt/β-catenin signaling pathway by targeting and antagonizing or agonizing molecules in the pathway.Peptide regulators of the Wnt/β-catenin signaling pathway have shown promising results in preclinical studies. They have the potential to treat several diseases such as cancer, osteoporosis, and Alzheimer's disease. A recent study has shown that the interaction of the protein FAM83A with catenin is very important for the regulation of the development process of pancreatic cancer. Multiple blocking short peptide drug precursors targeting FAM83A catenin were screened and obtained. Their effectiveness was verified in animal models such as zebrafish and mice . In the NZ and HS: conceptualization. NZ, HS, BC, and HH: writing. CL: supervision. YC and WC: project administration. All authors have read and agreed to the published version of the manuscript.


Protein-energy wasting (PEW) has been reported to be pretty common in maintenance dialysis patients. However, the existing PEW diagnostic standard is limited in clinical use due to the complexity of it. Bioelectrical impedance analysis (BIA), as a non-invasive nutritional assessment method, can objectively and quantitatively analyze the changes of body tissue components under different nutritional states. We aim to explore the association between PEW and BIA and establish a reliable diagnostic model of PEW.We collected cross-sectional data of 609 maintenance dialysis patients at the First Affiliated Hospital, College of Medicine, Zhejiang University. PEW was diagnosed according to International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Among them, 448 consecutive patients were included in the training set for the establishment of a diagnostic nomogram. 161 consecutive patients were included for internal validation. 52 patients from Zhejiang Hospital were included for external validation of the diagnostic model. Correlation analysis of BIA indexes with other nutritional indicators was performed. Logistic regression was used to examine the association of BIA indexes with PEW. 12 diagnostic models of PEW in maintenance dialysis patients were developed and the performance of them in terms of discrimination and calibration was evaluated using C statistics and Hosmer–Lemeshow-type χ2 statistics. After comparing to existing diagnostic models, and performing both internal and external validation, we finally established a simple but reliable PEW diagnostic model which may have great value of clinical application.A total of 609 individuals from First Affiliated Hospital, College of Medicine, Zhejiang University and 52 individuals from Zhejiang Hospital were included. After full adjustment, age, peritoneal dialysis , subjective global assessment  and water ratio were independent risk factors, while triglyceride, urea nitrogen, calcium, ferritin, BCM, VFA and phase angle were independent protective factors of PEW. The model incorporated water ratio, VFA, BCM, phase angle and cholesterol revealed best performance. A nomogram was developed according to the results of model performance. The model achieved high C-indexes of 0.843 in the training set, 0.841 and 0.829 in the internal and external validation sets, respectively, and had a well-fitted calibration curve. The net reclassification improvement (NRI) showed 8%, 13%, 2%, 38%, 36% improvement of diagnostic accuracy of our model compared with “PEW score model”, “modified PEW score model”, “3-index model”, “SGA model” and “BIA decision tree model”, respectively.BIA can be used as an auxiliary tool to evaluate PEW risk and may have certain clinical application value.The online version contains supplementary material available at 10.1186/s12937-023-00890-5. Protein-energy wasting (PEW) is a common complication in maintenance dialysis patients. The International Society of Renal Nutrition and Metabolism (ISRNM) described PEW as a group of clinical syndromes such as muscle tissue wasting and malnutrition in chronic kidney disease (CKD) patients but not just a state of malnutrition . In 2008In this study, we used convenience sampling method to select 609 patients in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2019 to June 2019 and 52 patients in Zhejiang Hospital from October 2018 to September 2020 as study participants. The inclusion criteria were: (1) patients aged 18–80 years (2) patients diagnosed as end-stage renal disease (ESRD) receiving renal replacement therapy (3) patients receiving regular peritoneal dialysis or hemodialysis for more than 3 months. The exclusion criteria were: (1) patients in unstable health status  (2) peritoneal dialysis and hemodialysis were performed at the same time (3) patients treated with glucocorticoids or other immunosuppressant (4) patients with metal stents or amputation (5) patients with mental illness. The study was approved by the local ethics committees and conducted in accordance with the principles of the Declaration of Helsinki.We used Korea InBody S10 Biospace multi-frequency bioelectrical impedance body composition analyzers, which apply the principle of bioelectrical impedance spectrum, and accurately calculate body composition through current measurement in different frequency ranging from 5 to 1000 kHz. The measurement time point was within 15 min after the end of dialysis. All BIA indexes were obtained using foot to hand technology.2 [2) = 0.0003207*weight0.7285−0.0188*log(weight)*height0.3 [2. Fat tissue index (FTI) = FAT/height2 [The data we collected were as follows: 1) Clinical data, including age, sex and dialysis duration; (2) Pre-dialysis laboratory test results, including albumin, prealbumin, urea clearance index (Kt/V), cholesterol, hemoglobin, serum creatinine, urea nitrogen, phosphorus, calcium, parathyroid hormone, serum iron, ferritin, C-reactive protein and normalized protein catabolic rate (nPCR); (3) Post-dialysis anthropometric indexes, including arm circumference, arm muscular circumference (AMC), triceps skinfold thickness (TST) and body mass index (BMI); (4) BIA indexes, including FFM, FAT, BCM, BFP, SLM, ECW, water ratio, VFA, impedance and phase angle. Among them, impedance and phase angle were measured at 5 kHz and all BIA indexes were performed using the whole body measurement method. (5) SGA questionnaire ; (3) muscle mass index: AMC decreased (3 months > 5% or 6 months > 10%); (4) dietary intake: nPCR < 0.8 g / (kg•d). PEW can be diagnosed only when a patient has at least three out of the above four groups of indicators, while at least one indicator meet the requirements in each group.According to the diagnostic criteria of ISRNM , (1) labKolmogorov-Smirnov’s test. Quantitative variables are presented as means ± standard deviations (SDs) and were compared using t-test for normally distributed data. Non-normally distributed variables are summarized as medians and interquartile ranges (IQRs), and were compared using Mann–Whitney test. Categorical variables are expressed as percentages or frequencies and were assessed with the chi-squared test. To determine the association of BIA indexes with nutritional indicators, a correlation heatmap was performed after using Pearson’s correlation analysis. Furthermore, logistic regression was used to examine the association between BIA indexes and PEW. After selecting BIA indexes that are independent influencing factors of PEW, 12 models were constructed to generate probability of PEW by using logistic regression. Variance inflation factors were used to test the collinearity among variables. Discrimination was quantified by calculating C statistics developed for models. Hosmer–Lemeshow- type χ2 statistics were used to assess calibration. A nomogram was developed according to the results of model performance of data from training set. Its discriminatory ability was validated in internal and external validation sets by using receiver operating characteristic (ROC) curves and the calibration was assessed with calibration curves in internal and external validation sets for which bootstraps with 40 resamples were used for calculations. Diagnostic test evaluation was conducted to compare the performance of the new model with previous models  -  [Participants from internal set were randomly divided into training set and validation set according to the ratio of 7:3. Normality of distribution was tested with nevents) . SPSS 25Participants from the First Affiliated Hospital, Zhejiang University School of Medicine were randomly divided into training set and validation set according to the ratio of 7:3. There’s no statistically significance of indexes between training set and validation set , SGA , water ratio  were risk factors of PEW, while hemodialysis , triglyceride , urea nitrogen , calcium , ferritin , BCM , VFA  and phase angle  were the protective factors of PEW  with (model 1-6b) or without (model 1-6a) 4 BIA indexes  were constructed respectively by the method of logistic regression. C statistics and H-L type χ2 statistics are shown in Table To visualize the final diagnostic model, a nomogram was constructed Fig. . To calcROC curves were built for internal and external validation set based on the final diagnostic model. The area under the curve (AUC) was 0.841 (95% CI: 0.806 ~ 0.880) in the internal validation set and 0.829 (95% CI: 0.719 ~ 0.939) in the external validation  with other previous diagnostic models  against the ISRNM diagnostic criteria, a comparison table  and single nutritional indicator from ISRNM  has a high predictive value for PEW. These objective parameters included in the model are based on regular laboratory results, consequently cost-effective and easy to carry out.Diagnosis of PEW is a challenging theme. Because there has been no single diagnostic marker or tool to perfectly determine whether a patient is PEW or not, clinical studies focusing on PEW inevitably require diagnostic definition of PEW by combining one or more of the nutrition-related surrogates to allocate patients into a binary variable pertaining to PEW. According to ISRNM, PEW diagnostic standard includes biochemical indicators, BMI, muscle mass, and diet. Optimally, each criterion should be documented on at least three occasions, preferably 2–4 weeks apart . This diSeveral nutrition-related tests have been proposed to assess nutritional status. The 3-point scaled Subjective Global Assessment (SGA-3)  scores pIn recent years, electrical bioimpedance has become the most useful, simple, and reproducible method for the study of body composition. According to the principle of Omron’s law, when the current passes through human tissues, it generates resistance and reactance. The resistance is related to the hydration state, while reactance is related to the capacitance. The composition of human body components can be derived by using the impedance value of current conduction in different tissues . In a muSimilarly, our BIA + PEW model also combined BIA indexes and ISRNM nutritional indicators. The model has an area under the curve of 0.843 and shows good discrimination and calibration in both internal and external validation. In the diagnostic test evaluation, we divided participants from the internal validation set into negative and positive groups using different PEW diagnostic methods. Compared to previous models, our BIA + PEW model has the highest C-index and NRI. This can be explained as follows. For SGA, its semi-quantitative character leads to difference of results from different observers. Only 27.5% of the patients with PEW were identified by SGA in our research, indicating the unreliability of SGA results. The results of PEW score and modified PEW score model are presented as 4 levels , the exact diagnostic bivariate thresholds for PEW of which have not been established. Therefore, we selected the optimal cutoff value as 2 by the principle of “Jordan Index maximum”, the score lower than which was diagnosed as PEW. In addition, the performance of 3-index model is slightly inferior to our model though it was established using the same logistic regression method as our BIA + PEW model. The decision tree model shows high specificity (88.3%) but low sensitivity (26.8%) in our research. These can be explained that these models originated from France, Japan, Spain and Germany, respectively, and there are slight differences in indicators from different races and populations, resulting in poor recognition of PEW in Chinese dialysis patients.The present study has as main strengths the total number of patients studied, adequate internal and external validation. But some weaknesses and limitations of this study should be considered. On the one hand, although BIA was also shown to be a valid method for assessing body fluids in persons with varying hydration status in some study , most exIn conclusion, it is hard to assess PEW in maintenance dialysis patients in daily clinical practice. Based on the recommendations of ISRNM, we suggest a new combination of parameters, which are readily available and strongly associated with other nutritional parameters. A single index of ISRNM combined with BIA indexes can also well diagnose PEW and evaluate its risk when it is impossible to obtain all the PEW diagnostic criteria.Below is the link to the electronic supplementary material.Supplementary Material 1


Static postural balance, using a stabilometric platform on firm and foam surfaces, and dynamic balance, using the Timed Up-and-Go Test (TUGT), were performed under various conditions, such as playing a game, watching videos, video calls, and listening to music. The center of pressure (CoP) values significantly increased (p < 0.05) during all smartphone activities (except listening to music) compared to the control condition in both groups, with the IDG demonstrated a more pronounced increase (p < 0.05) during playing video games and video calls on the firm surface. TUGT scores significantly increased (p < 0.05) during smartphone activities, with greater changes observed in the IDG (p < 0.05), and significantly decreased (p < 0.01) during listening to music in both groups. Our study suggests that adolescents with intellectual disabilities need special tools and guidance to ensure their safety and well-being when using smartphones.Considering the rising prevalence of smartphone usage among adolescents with intellectual disabilities and their frequent motor challenges, understanding its impact on their physical well-being is important. This study aims to investigate the impact of smartphone activities on postural balance in adolescents with intellectual disabilities. Two groups of adolescents participated in the study: an intellectual disability group (IDG) ( Adolescents with intellectual disabilities frequently exhibit diminished postural balance, as indicated by a consistent body of research ,2,3,4,5,The rapid rise in smartphone usage, accelerated by the COVID-19 pandemic, has also affected adolescents with intellectual disabilities ,13. It hWhile the adoption of smartphones among adolescents with intellectual disabilities has provided potential benefits, including enhanced communication, education, and social engagement ,13, it hHence, the aim of this study is to investigate the effects of smartphone activities on postural balance in adolescents with intellectual disabilities. By exploring these effects, we aim to gain a better understanding of the challenges faced by this population and develop targeted interventions to optimize balance performance, reduce the risk of falls, and improve overall quality of life. We hypothesize that engaging in smartphone activities, such as playing games, watching videos, listening to music, and engaging in video calls would significantly affect postural balance in adolescents with intellectual disabilities, and that this effect varies depending on the specific activities involved.The sample size was a priori calculated using the software G*power for Windows . Values for alpha, power, correlation among repeated measures, and non-sphericity correction (ε) were set at 0.05, 0.80, 0.50, and 1, respectively. To reach the desired power, data from at least 12 participants were deemed to be sufficient to minimize the risk of Type II statistical error. To accommodate the possible withdrawal of some participants, we recruited more participants than the number indicated by G*power .The present study specifically targeted adolescents with intellectual disabilities who were enrolled in a specialized educational center. To ensure ethical compliance, formal permissions were obtained from the center authorities before initiating data collection. To recruit the sample, a three-stage screening process was employed. In the first stage, 24 adolescents with moderate to mild intellectual disabilities, as determined by the educational center psychologist using the Wechsler Intelligence Scale for Children—Fourth Edition (WISC-IV) , were raPrior to initiating the study, a detailed explanation of the experimental protocol was delivered to the participants, parents, and caregivers involved. Written informed consent was obtained from the parents, and assent was sought from the adolescent participants. The assent process involved explaining the study’s purpose, procedures, and potential risks in a developmentally appropriate manner to ensure that the adolescents understood the study and were willing to participate. This study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of the Vasile Alecsandri University of Bacău Romania (40/2/24 October 2023).This study employed a crossover comparative design to assess the effect of smartphone activities on static and dynamic balance in IDG and TDG participants. Static postural balance was measured using a stabilometric platform with firm and foam surfaces, while dynamic balance was evaluated using the Timed Up-and-Go Test (TUGT) . These m®, Cereste, France). This platform is recognized in the field of postural balance assessments for its high sampling frequency (40 Hz) and precise data acquisition (12-bits A/D conversion), which are essential for capturing subtle postural changes and fluctuations. It has been utilized in numerous postural studies, which adds to its validity and reliability [In this study, participants were instructed to maintain a stable bipedal stance, barefoot, on a static stabilometric platform . The foam block had a density of 21.3 kg/mControlClosed eyes (CE)Playing gameWatching videosCalling videoListening to musicThe center of pressure (CoP) sways of each participant were recorded in a counter-balanced order in bipedal stance in each surface  under six different conditions, including:All these conditions were designed and conducted to examine the effects of different surface conditions and sensory factors on the participants’ postural balance.Vm). The CoPVm parameter is the sum of the scalar displacements of the CoP divided by the total time of the recording, expressed in mm/s. The CoPVm reflects the efficiency of the postural control system and characterizes the net neuromuscular activity required to maintain balance [During the control condition, participants were instructed to maintain their gaze fixed on a 3 cm diameter target placed on the wall 3 m away from them in their horizontal field of view, which was chosen to establish a stable and controlled visual reference. In the CE condition, participants wore a blindfold to eliminate visual input and its contribution to postural balance. The inclusion of these conditions was to investigate the impact of visual input elimination on postural control, a well-documented aspect of static balance research . Concern balance . A small balance .Dynamic balance was evaluated using the Timed Up-and-Go Test (TUGT). This test is a well-established and recommended tool for evaluating dynamic balance and functional mobility, particularly in individuals with intellectual disabilities ,26. PartControlPlaying gameWatching videosCalling videoListening to musicThis test was assessed in five different conditions in a counter-balanced order as follows:For the playing game condition, we conducted interviews with parents and caregivers of participants in the IDG to gather information about their child’s favorite game. The majority of participants mentioned puzzle games as their preferred choice, while a few expressed interest in other types of games, although they were still capable of playing puzzle games . Based oFor the watching videos condition, we conducted interviews with the parents of the participants and discovered that they spent an average of 3 to 4 h daily watching videos on social media platforms such as TikTok and/or Instagram. All participants were either regular users with active accounts on these platforms or utilized their parents’ accounts for accessing them. Furthermore, both parents and participants were asked about their preferences regarding TikTok and/or Instagram videos. Based on the interview, the majority of participants had a particular interest in videos featuring cats and pets. Indeed, previous research showed that watching animal videos have several benefit on the psychological health ,30 whichPrevious study showed that individuals with intellectual disabilities can use video call through social platforms ,32. In oRegarding the listening to music condition, we conducted interviews with participants and/or parents and/or caregivers to determine their favorite songs. It was revealed that they enjoyed listening to pop music with fast tempo. Therefore, in the experimental protocol, participants were instructed to listen to pop music using headphones during postural balance tests. In fact, several studies in typical development individuals indicated that listening to music, regardless of the type and tempo, can have a positive effect on exercise behavior and/or perception ,34. To cData were analyzed using the program SPSS 25.0 . The Kolmogorov–Smirnov test was used to verify the normality of the data distribution.Vm values. In addition, a two-way (5 Condition × 2 Group) ANOVA with repeated measures was used to determine the effect of Condition  and/or Group (IDG/TDG) on TUGT scores. To evaluate the changes in CoPVm values and TUGT scores after each condition, Δ CoPVm% and TUGT% were calculated using the formula: Δ CoPVm% or TUGT% = 100 × (condition − control)/condition. Subsequently, another two-way ANOVA with repeated measures was carried out to examine the effects of Δ changes in Condition and Group on CoPVm values  and TUGT scores . A 95% confidence interval (CI) was calculated for means and Δ changes.A three-way (6 Condition × 2 Group × 2 Surface) ANOVA with repeated measures was used to determine the effect of Condition  and/or Group (IDG/TDG) and/or Surface (Firm/Foam) on the CoP2) formula was calculated for the main effects and interactions , and the Cohen’s d was calculated for the pairwise differences  [p < 0.05.To determine whether the statistically significant differences found were practically significant, the effect size of each outcome measure was calculated. The partial eta squared (ηpd ≤ 0.8) . To accoIn the analysis of the three-way ANOVA, significant main effects were found for Group, Condition, and Surface. As well, significant (Group × Condition), (Surface × Condition), and (Group × Surface) interactions were observed. However, (Group × Surface × Condition) interaction was not statistically significant .Vm values significantly increased (p < 0.001) in the conditions CE, playing games, watching videos, and video call, compared to the control condition in both the IDG and the TDG , and significantly decreased in the listening to music condition  compared to the CE condition. The CoPVm values significantly increased in the watching videos  and video call  conditions, and significantly decreased in the listening to music condition  compared to the playing game condition. Moreover, CoPVm values significantly increased in the video call condition , and significantly decreased in the listening to music condition  compared to the watching video condition, as well as significantly decreased in the listening to music condition  compared to the video call condition. However, in the TDG, the CoPVm values significantly decreased only in the listening to music condition  compared to the CE, playing game, watching video, and video call conditions, respectively.In the IDG, the CoPVm values were significantly lower (p < 0.001) in the IDG compared to the TDG in all conditions on both surfaces  on the firm surface compared to the foam surface in all conditions for both the IDG and the TDG.Concerning the effect of Surface, the post hoc analyses revealed that the CoPVm% analysis on the firm surface, the two-way ANOVA revealed significant main effects of Condition and Group. However, there was no significant (Group × Condition) interaction  and significantly decreased in the listening to music condition  compared to the CE condition. Moreover, Δ CoPVm% values decreased in the watching video , video call (Firm only: p = 0.001), and listening to music  conditions compared to the playing game condition. Moreover, Δ CoPVm% values increased in the video call condition  and decreased in the listening to music condition  compared to the watching video condition. Furthermore, Δ CoPVm% values decreased in the listening to music condition  compared to the video call condition  and video call  conditions, and decreased in the listening to music condition , compared to the CE condition. In addition, Δ CoPVm% values increased in the video call condition compared to the playing game  and watching video  conditions. Δ CoPVm% values decreased in the listening to music condition  compared to the playing game and watching video conditions. Furthermore, Δ CoPVm% values decreased in the listening to music condition  compared to the video call condition.In the IDG, the post hoc analyses revealed that the Δ CoPondition . HoweverVm% values were significantly greater only on firm surface under the playing game (p = 0.011) and video call (p = 0.013) conditions  interaction was observed .p < 0.001), and decreased in the listening to music condition (p = 0.005) compared to the control condition. The TUGT scores significantly decreased in the watching video (p = 0.017) and listening to music (p < 0.001) conditions compared to the playing game condition. Furthermore, the TUGT scores significantly increased in the video call condition (p = 0.001) and decreased in the listening to music condition (p < 0.001) compared to the watching video condition. The TUGT scores significantly decreased in the listening to music condition (p < 0.001) compared to the video call condition. In the TDG, the results showed that the TUGT scores significantly increased in the playing game, watching video, and video call conditions (p < 0.001), and decreased in the listening to music condition (p = 0.01), compared to the control condition. Moreover, the TUGT scores significantly decreased in the watching video condition (p = 0.01) and significantly decreased in the listening to music condition (p < 0.001) compared to the playing game condition. The TUGT scores significantly increased in the video call condition (p = 0.03) and decreased in the listening to music condition (p = 0.049) compared to the watching video condition. The TUGT scores significantly decreased in the listening to music condition (p = 0.002) compared to the video call condition.In the IDG, the post hoc analyses revealed that the TUGT scores significantly increased in the playing game, watching video, and video call conditions (p < 0.001) in the IDG compared to the TDG in all conditions  interaction .p = 0.003, p < 0.001, respectively) compared to the playing game condition. Moreover, the Δ TUGT% significantly increased in the video call condition (p < 0.001), and decreased in the listening to music condition (p < 0.001) compared to the watching video condition. Furthermore, the Δ TUGT% significantly decreased in the listening to music condition (p < 0.001) compared to the video call condition. Regarding the TDG, the results showed that the Δ TUGT% scores significantly decreased in the watching video (p = 0.006) and listening to music (p = 0.001) conditions compared to the playing game condition. Additionally, the Δ TUGT% significantly increased in the video call condition (p = 0.02) and decreased in the listening to music condition (p < 0.001) compared to the watching video condition. The Δ TUGT% significantly decreased in the listening to music condition (p < 0.001) compared to video call condition   .Vm values and TUGT scores were significantly deteriorated during various smartphone activities (except listening to music) compared to the control condition in both the IDG and the TDG. Our study findings align with previous research in individuals with intellectual disabilities [Our study aimed to investigate the influence of various smartphone activities, including playing video games, watching videos, engaging in video calls, and listening to music, on the static and dynamic postural balance of adolescents with intellectual disabilities, in comparison with their typically developing counterparts. The main findings revealed that the CoPbilities ,36,37 asbilities ,38,39 thVm values increased during various activities under both surfaces in the IDG and the TDG. Consistent with previous studies [Our study showed that CoP studies ,41,42,43 studies , as well studies . Engagin studies ,36,46 an studies . Moreove studies . As indi studies . In addi studies  or engag studies . Further studies ,53. This studies ,34,54,55In addition, the study results showed that the significant difference in CoP values between the CE condition and engaging in activities like playing video games, watching videos, and video calls in the IDG underscores the unique challenges faced by individuals with intellectual disabilities in maintaining postural balance. The increased postural sway in the IDG participants during these activities indicates that they struggled to maintain a stable posture compared to the CE condition, where sensory inputs are minimized, and they might rely more on proprioceptive and vestibular inputs. Engaging in activities like playing video games and watching videos involves dynamic visual stimuli, which may disrupt postural stability in individuals with intellectual disabilities. Furthermore, video calls may introduce an additional layer of complexity as they require the integration of both auditory and visual inputs, potentially leading to increased postural sway as the IDG participants focus on answering the questions.Vm% in response to playing games and participating in video calls was more pronounced in the IDG compared to the TDG. This finding suggests that adolescents with intellectual disabilities may have a more significant challenge in maintaining postural stability while performing these activities compared to typically developing adolescents. Indeed, individuals with intellectual disabilities may have differences in sensory processing, which could affect how they perceive and respond to sensory cues related to balance and postural control [It is important to note that, on a firm surface, this study found that the increase in Δ CoP control . It seem control  may have control ,5,57. In control  responsiVm% on the foam surface revealed that there were no significant differences in postural sway between the IDG and the TDG across all conditions studied. This finding suggests that the foam surface, which provides an unstable and challenging base of support, had a similar impact on static postural balance for both groups. In fact, the foam surface is known to elicit greater postural instability by reducing the proprioceptive and tactile feedback from the feet [The analysis of Δ CoPthe feet ,60. ThisConcerning dynamic balance, similar results were observed in the effect of smartphone activities. Playing video games, watching videos, and engaging in video calls led to an increase in TUGT scores in both the IDG and the TDG compared to the control condition. These findings align with previous studies that have reported impaired walking during dual-tasking activities and smartphone use ,18. In fIt is important to note that a unique result emerged in the listening to music condition, where both groups exhibited improved dynamic balance. Participants might have experienced a positive emotional response while listening to music, which could have led to increased confidence and focus ,65 durinThis study was the first of its kind to investigate the effects of various smartphone activities on both static and dynamic postural balance in adolescents with intellectual disabilities compared to their typically developing counterparts. The unique focus on smartphone activities provided valuable insights into a relatively unexplored area of research. Moreover, this study assessed a diverse range of smartphone activities, including playing games, watching videos, and engaging in video calls. By examining multiple activities, this study captured a comprehensive understanding of their impact on postural balance. Furthermore, by comparing the results between adolescents with intellectual disabilities and their typically developing counterparts, this study highlighted potential differences in how smartphone activities affect postural balance in these two groups.Despite the valuable insights gained from our study, several limitations should be acknowledged. While our study’s controlled experimental conditions provided valuable insights, they may not fully capture the complexities of real-world mobile device use, potentially restricting the generalizability of our findings to everyday situations. Future research endeavors should consider conducting investigations in more naturalistic settings, encompassing the dynamic and multifaceted nature of mobile device utilization in daily life, to gain a deeper understanding of its impact on postural balance. In addition, we did not explore the possibility that augmentation of postural sway might, in certain circumstances, represent a positive adaptation to task constraints, affording individuals greater degrees of freedom for dynamic postural adjustments. We also did not employ non-linear methods to investigate the potential benefits of increased noise in postural responses. This limitation underscores the need for future research to delve deeper into these nuances and expand our understanding of postural balance. Moreover, this study primarily focused on static and dynamic postural balance assessments. While these are valuable indicators of postural balance, other factors such as muscle strength and joint stability were not extensively examined. Future research could incorporate a more comprehensive assessment of various aspects of postural balance to gain a greater understanding of the relationship between smartphone activities and postural balance. Likewise, while our study focused on the postural balance task while listening to music, it did not investigate the concept of a “resonant effect” induced by music as well as other variables, such as the type of music, tempo, or individual differences in music preferences, which could have significant effects on postural balance. Future research to include these factors would offer a more comprehensive understanding of the influence of music on postural balance. Furthermore, this study did not investigate the potential long-term effects of smartphone activities on postural balance. This would be essential for considering the broader implications for individuals with intellectual disabilities and typically developing individuals.The findings of this study hold significant practical implications for adolescents with intellectual disabilities, healthcare professionals, and caregivers alike. In fact, educating caregivers about the potential effects of smartphone activities on postural balance is crucial. By raising awareness and providing guidance on responsible smartphone use, caregivers can play a vital role in ensuring the safety and well-being of adolescents with intellectual disabilities. In addition, collaboration between healthcare professionals, educators, therapists, and technology experts can lead to the development of innovative solutions and interventions to enhance postural balance during smartphone activities. Long-term monitoring is also recommended to track changes in postural control and balance over time. By regularly assessing postural balance, healthcare professionals can identify trends and implement timely interventions, contributing to better outcomes for individuals with intellectual disabilities. These practical measures align with the broader goal of preventing and reducing the risk of falls, ultimately enhancing the quality of life for adolescents with intellectual disabilities.This study highlighted that engaging in smartphone activities, including playing video games, watching videos, and participating in video calls, has significant effects on both static and dynamic postural balance in both groups. These activities present challenges to postural balance and can lead to increased postural sway, affecting the performance during tasks like the TUGT. Moreover, adolescents with intellectual disabilities demonstrated more pronounced alterations in postural balance in response to playing games and video call smartphone activities compared to their typically developing counterparts. This highlighted the unique challenges that smartphone interactions pose for adolescents with intellectual disabilities, with cognitive and attentional demands potentially playing a crucial role in affecting their postural balance during these tasks. In addition, the finding that listening to music led to increased dynamic balance scores in both groups raises interesting questions about the influence of music genre on postural responses. Future research could explore the specific effects of different music genres on postural control to gain a deeper understanding of this phenomenon. In practical term, our study highlights the need for assistive devices and caregiver education to improve smartphone usage safety for adolescents with intellectual disabilities. Collaboration between healthcare professionals, educators, therapists, and technology experts can lead to the development of innovative solutions and interventions to enhance postural balance during smartphone activities in order to prevent and reduce the risk of falls, ultimately enhancing individuals’ quality of life.