In hematological malignancies, specifically in acute myeloid leukemia, aberrant stem cells, also known as leukemic stem cells, may be responsible for the relapse of the disease. Since several authors have related the quiescence and chemoresistance of leukemic stem cells with the Wnt/β-catenin signaling pathway, new approaches to chemosensitize this population should be studied. Therefore, in this review, we summarize the current information about the Wnt/β-catenin signaling pathway in hematology.Wnt signaling is a highly conserved pathway in evolution which controls important processes such as cell proliferation, differentiation and migration, both in the embryo and in the adult. Dysregulation of this pathway can favor the development of different types of cancer, such as acute myeloid leukemia and other hematological malignancies. Overactivation of this pathway may promote the transformation of pre-leukemic stem cells into acute myeloid leukemia stem cells, as well as the maintenance of their quiescent state, which confers them with self-renewal and chemoresistance capacity, favoring relapse of the disease. Although this pathway participates in the regulation of normal hematopoiesis, its requirements seem to be greater in the leukemic stem cell population. In this review, we explore the possible therapeutic targeting of Wnt to eradicate the LSCs of AML. Acute myeloid leukemia (AML) is a group of hematopoietic neoplasms characterized by an increase in myeloid blasts. However, AML exhibits a high degree of molecular heterogeneity, as recently recognized in the new diagnostic classifications ,2. AML swingless (wg) gene of Drosophila melanogaster were found to produce aberrant embryonic development [Int-1 (Wnt1) was identified in mice as an homologue of wg [In 1980, mutations in the elopment . Later, ue of wg . This waue of wg ,6,7,8,9.2+). The process of Wnt maturation and secretion begins in the endoplasmic reticulum (ER) [Wnt proteins act as morphogens, inducing cell differentiation processes during embryonic development . In humalum (ER) ,13. Modilum (ER) ,15. Wnt lum (ER) , in exoslum (ER)  or lipoplum (ER) .In the canonical Wnt/β-catenin pathway, the absence of Wnt ligands subserves phosphorylation of the effector protein β-catenin by the destruction complex. This complex is formed by APC, Axin and two Ser/Thr kinases (CK1α and GSK3β). Phosphorylated β-catenin will be then ubiquitinated by β-TrCP and degraded in the proteosome. In the absence of nuclear β-catenin, TCF/LEF and TLE/Groucho complexes recruit histone deacetylases (HDACs) that repress expression of target genes. Binding of secreted Wnt proteins  to the Frizzled receptor (FZD) and receptor-related protein 5/6 (LRP5/6), which act as coreceptors, promotes phosphorylation of LRP5/6 by CK1α and GSK3β kinases. This phenomenon induces the recruitment and activation of Dishevelled protein (DVL), which binds to FZD and polymerizes. DVL polymers inactivate the destruction complex, resulting in the stabilization and accumulation of β-catenin in the cytosol. Finally, β-catenin translocates to the nucleus, where it will form a complex with TCF/LEF proteins to recruit transcriptional co-activators  and activate the expression of target genes ,19 Figu.MYC (Myc proto-oncogene protein), CCND1 (CyclinD1) and ABCB1 (ABC multidrug transporter) [Most of the target genes of the canonical Wnt pathway are cell-type specific and can promote cell proliferation, but also control postmitotic cell fate and differentiation . Some ofsporter) .2+  can activate non-canonical β-catenin-independent pathways, such as Wnt/PCP and Wnt/Ca2+ . These nThe Wnt/PCP pathway is usually initiated when non-canonical Wnt ligands bind to FZD and associated co-receptors, such as receptor tyrosine kinase-like ROR1/2. This binding recruits cytosolic adaptor proteins, such as DVL, which activates small GTPases of the Rho family . These GTPases activate ROCK and JNK kinases, resulting in cytoskeleton modifications and/or transcriptional responses through c-Jun protein (JUN) activation by JNK and ATF2 recruitment, among others  Figure .2+ pathway is activated by the binding of non-canonical Wnt ligands to FZD receptors and co-receptors such as ROR1/2, which induces the recruitment of DVL and the activation of phospholipase C (PLC) by G proteins. PLC transforms phosphatidylinositol 4,5-bisphosphate into diacylglycerol (DAG) and inositol triphosphate (IP3). IP3 promotes the outflow of Ca2+ from the ER to the cytosol, whose increase favors the activation of protein kinase C (PKC), calcium/calmodulin-dependent protein kinase type II (CAMKII) and calcineurin phosphatase. The activation of these proteins derives in Ca2+-dependent cytoskeleton responses through the small GTPase Cdc42 and/or changes in gene transcription through NFAT, NFκβ and CREB, among others [The Wnt/Cag others ,19,25 (FHematopoietic stem cells (HSCs) are multipotent cells with self-renewal capacity, precursors of blood cells of the myeloid and lymphoid lines. HSCs reside in the adult bone marrow, where they are usually in a quiescent state in a specialized stroma that regulates their migration and differentiation . HoweverDkk1 disrupted the quiescence state of HSCs or the deficiency of Wnt3a disrupted the self-renewal capacity of the same population [Wif1) in osteoblasts; a study in which it was also observed that the deregulation of two other pathways, such as Hedgehog and Notch, was involved in the maintenance of HSCs [Initially, Wnt ligands were described as growth factors (mainly WNT5A) that induced HSC proliferation in in vitro assays ,29. Latepulation ,31. The  of HSCs . This fa of HSCs , suggestHowever, several Wnt gain-of-function studies showed contradictory results. Some of them proposed that activation of the canonical Wnt pathway with WNT3A or by retroviral expression of a constitutively active form of β-catenin favored self-renewal of HSCs and their repopulation ability in vivo from irradiated mouse tissues ,35. On tApc mutant mice. The results revealed that elevated levels of Wnt reduced the repopulating capacity of HSCs, whereas a mild increase in the activity of this pathway favored the maintenance of their stem cell functions [The diversity of the exposed results suggested a possible dose-dependent regulation, which was supported by a study performed with different strains of unctions . Later, unctions .Although all these studies imply the importance of the Wnt pathway in the regulation of normal hematopoiesis, the requirements appear to be higher in fetal HSCs than in normal adult bone marrow HSCs . This coThe Wnt signaling pathway regulates the processes of cell proliferation, differentiation and migration. Therefore, any mutation in the elements of this pathway can favor the development of different types of cancer, such as AML and other hematological malignancies ,42. FurtWNT3, WNT5B, WNT6, WNT10A, WNT14, WNT16 or FZD3 [It has been shown that in B-cells of Chronic Lymphocytic Leukemia (CLL), mRNA related to Wnt elements is overexpressed, such as  or FZD3 . Further or FZD3 . If we s or FZD3 .Pten and, in this case, overexpression of C-Myc, favored expansion of LSCs in NOTCH1-independent T-ALL [The case in T-cell lymphoblastic leukemias is similar. Two studies carried out in mouse models suggested that activation of β-catenin, together with inactivation of nt T-ALL ,47. Meannt T-ALL .DVL are complex, since while reducing the signaling of Wnt/β-catenin and Wnt/PCP signaling, it increases the signaling of Wnt/Ca2+ [In myeloid leukemias, the Wnt signaling pathway also plays an important role. For example, it has been described that the deletion of β-catenin delays the recurrence of chronic myeloid leukemia (CML) after imatinib discontinuation . NeverthWnt/Ca2+ . FinallyWnt/Ca2+ .Gsk3β regulates Wnt; its deletion increases Wnt signaling in HSCs and favors the development of aggressive AML in mice; therefore, it appears to be involved in the development of hematological malignancies [On the other hand, several studies reported the upregulation of Wnt elements in primary samples of AML patients; some examples are the gene overexpression of ligands  and transcription factors (such as LEF-1), or the protein overexpression of receptors (such as FZD4) ,53,54,55gnancies  , among others ,68. The Regarding clinical trials in patients with AML , most ofAlthough all these drugs have a similar goal, they have different targets. CWP291 induces endoplasmic reticulum stress, which activates caspases. These proteins have been revealed to target β-catenin for degradation through a directed cleavage . PRI-724Celecoxib, a COX-2 inhibitor, is a non-steroidal anti-inflammatory drug; it has been shown that these kinds of treatments decrease the transcriptional activity of β-catenin . Indeed,In this review, it has been explained that Wnt is dispensable for adult hematopoiesis . HencefoSince 1980, the study of the elements involved in Wnt signaling has revealed the fundamental role of this pathway in cell proliferation, differentiation and migration processes during embryogenesis, as well as tissue renewal in adults . AlteratAlthough the canonical Wnt pathway is involved in the maintenance of normal HSCs, its function appears to be more relevant to and dependent on bone marrow niche signals in LSCs, suggesting the possibility of targeting Wnt without disrupting normal hematopoiesis in patients ,79. SeveOverexpression of β-catenin and other elements of the canonical Wnt pathway have been observed in samples from patients with AML and other types of hematological malignancies, suggesting that overactivation of this pathway plays a role in the physiopathology of these cancers ,47,52,53Likewise, several studies reveal a close relationship between the canonical Wnt pathway and LSCs, since its overactivation seems to be involved in the transformation of pre-LSCs into AML LSCs ,58, as wThe role of the Wnt pathway in embryogenesis and adult tissue renewal has been extensively studied; the activation of Wnt in adult normal hematopoiesis seems to be dose-dependent. Nevertheless, Wnt signaling pathways may be important in hematological malignancies, since the overexpression of β-catenin is observed in AML samples and its overactivation might regulate the quiescence state of LSC. Therefore, delving into the effects of this pathway, along with others such as Hedgehog and Notch, could open a new therapeutic window to chemosensitize LSCs and prevent patient relapse in AML.In order to avoid relapses in AML, it is important to eradicate the LSCs. One of the current approaches is to target this population; nevertheless, due to the similarities between LSCs and HSCs, it is hard to target the malignant cells correctly. In this review, we have summarized the role of Wnt in both populations to conclude that an overexpression in this pathway is common in AML. Furthermore, we have seen that the activation of Wnt entails an increase in the quiescent state. Both findings seem to suggest that the inhibition of Wnt could be a good therapeutic target to eradicate the LSCs of AML. Furthermore, it may be that the Wnt pathway is not necessary for adult hematopoiesis.It is likely that the best way to inhibit the Wnt pathway is to target β-catenin. This protein translocates to the nucleus and finally activates the expression of target genes. We believe that more experiments focusing on the inhibition of the correct Wnt signaling pathway, which could decrease the quiescent state of the LSC population to eradicate them with conventional chemotherapy, are required. Following this strategy, we could reduce AML relapses and improve the reduced overall survival of patients with this disease.


Wei Wei and colleagues  unveiled a new molecular mechanism underlying this coloring process inside banana cells.The green-to-yellow color of banana peels is an excellent indicator of fruit ripening. We can easily select ready-to-eat bananas from the grocery store just by looking at them. However, the color can trick us sometimes if the bananas are not stored properly. A banana with green peels may become soft and overripe at high temperatures . This phMaSGR2, has a dominant effect. Using a yeast one-hybrid screening assay, the authors identified a transcription factor MaMYB60 that directly bound to the promoter of MaSGR2.Their study started with examining the expression of 9 chlorophyll catabolic genes (CCGs) during banana ripening. The color of banana peels is associated with chlorophyll content, which degrades during the ripening process . The autFurther analysis showed that MaMYB60 was a positive regulator of chlorophyll degradation through activating all 5 CCGs. A transient transformation assay of MaMYB60 functions in banana peels showed a correlation between the color index and MaMYB60 expression levels. A negative correlation was also observed between chlorophyll content and MaMYB60 expression. The next question addressed was whether the expression of MaMYB60 is under the control of high temperature. Significantly lower levels of both the mRNA and protein of MaMYB60 were observed at 30 °C than at 20 °C. The authors were particularly interested in MaMYB60 protein stability since this protein level was highly correlated with and CCG transcript levels, chlorophyll content, and color index.Based on the above results, the authors hypothesized that ubiquitin-mediated proteolysis is involved in the enhanced degradation of MaMYB60 under high temperatures. With considerable effort, they identified a RING-type ubiquitin E3 ligase MaBAH1 that mediated the degradation of MaMYB60 directly. The specificity of ubiquitin-mediated proteolysis is usually defined by the E3 ligase, which recognizes and interacts with the target protein . Here, tTheir proposed model starts with the induction of MaBAH1 by high temperatures. As a ubiquitin E3 ligase, MaBAH1 recognizes MaMYB60 proteins and accelerates its degradation. MaMYB60 is a positive regulator of key chlorophyll CCGs, and less MaMYB60 under high temperatures affects chlorophyll metabolism, leading to a slower disappearance of green color in banana peels. This ubiquitin-mediated regulatory pathway explains why bananas do not turn yellow under high temperatures. Future studies may seek to uncover the complete signal transduction pathway from high temperatures to MaBAH1 expression. The authors also identified multiple banana genes involved in fruit degreening. In this era of genome editing, these genes could be tested and utilized as potential breeding targets for improving banana storage and fruit quality.


The results show that the final prepared BSi-MN patches exhibit an excellent drug loading capability, more than twice that of plain Si-MN patches with the same area, while maintaining comparable mechanical properties for practical skin piercing applications. Moreover, the BSi-MNs exhibit a certain antimicrobial activity that is expected to prevent bacterial growth and disinfect the affected area when applied to the skin.Silicon microneedle (Si-MN) systems are a promising strategy for transdermal drug delivery due to their minimal invasiveness and ease of processing and application. Traditional Si-MN arrays are usually fabricated by using micro-electro-mechanical system (MEMS) processes, which are expensive and not suitable for large-scale manufacturing and applications. In addition, Si-MNs have a smooth surface, making it difficult for them to achieve high-dose drug delivery. Herein, we demonstrate a solid strategy to prepare a novel black silicon microneedle (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The proposed strategy consists of a simple fabrication of plain Si-MNs and a subsequent fabrication of black silicon nanowires. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching. The nanowire structures were then prepared on the surfaces of the plain Si-MNs to form the BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag Transdermal drug delivery (TDD) is an attractive strategy for delivering therapeutic agents due to its ability to avoid the challenges associated with traditional oral administration and hypodermic injections, such as inducing gastric irritation and liver injury, low bioavailability, and poor patient compliance ,2. One oCoated MN systems for TDD have garnered considerable interest in both academia and the pharmaceutical industry due to their minimal invasiveness and ease of processing and application. A broad range of materials, including small molecules, biotherapeutics, and drug particles, can be applied to the surface of solid MNs as solid films, enabling their administration via this route ,14. AfteFor these reasons, research in this field is currently focused on the development and optimization of coating processes that can produce a reproducible and homogeneous coating on each MN arranged on the patch. Spray-, drip-, and dip-coating processes are capable of coating MNs in a high-volume production manner, but they can lead to significant drug wastage since the coating is deposited over the entire MN patch . Custom MNs can be made with different types of materials, such as silicon ,28,29, m+ and HF concentrations during Ag nanoparticle deposition and [HF/(HF + H2O2)] ratio during Ag-catalyzed chemical etching, on the morphology and properties of BSi-MNs were investigated in detail. Furthermore, the BSi-MN patch was preliminarily tested for drug loading and antibacterial activity.Herein, we report a solid strategy to fabricate a novel black silicon MN (BSi-MN) patch with ultra-hydrophilic surfaces for high drug loading. The BSi-MN patch fabrication involved two steps. First, plain Si-MNs were prepared via a simple method consisting of laser patterning and alkaline etching, which is much simpler than the conventional MEMS method. Second, nanowire structures were then prepared on the surfaces of the plain Si-MNs to form BSi-MNs through Ag-catalyzed chemical etching. The effects of preparation parameters, including Ag3, Macklin, Shanghai, China, 99%), hydrogen peroxide , nitric acid , propidium iodide , and 4′,6-diamidino-2-phenylindole . None of the above reagents required further purification. Deionized water (DIW resistivity of ~18 MΩ·cm) and phosphate-buffered solution were used throughout the whole experimental process.In this study, a <100>-oriented Cz-grown 8-inch single-side polished B-doped wafer with a starting thickness of 725 μm  was used as the substrate. The chemical reagents used in this study were potassium hydroxide , hydrofluoric acid , silver nitrate (AgNOx) with a thickness of 1~1.5 µm on both sides. The protective layer on one side was opened by using a fiber laser  to form an orthogonal grid pattern. The detailed laser parameters were as follows: a speed of 100 mm/s, a power output of 25 W, a frequency of 5 KHz, and a duty cycle of 35%. Subsequently, alkaline etching was carried out in a 20 wt% KOH solution at 8 °C to prepare plain silicon MNs. The 2 × 2 cm2 Si-MN patches were obtained from the 8-inch Si-MN wafer through laser cutting. The Si-MN patches were cleaned using a 5 wt% HF solution to remove the surface oxide layer. Then, these Si-MN patches were immersed in a AgNO3/HF aqueous solution at room temperature for 20 s to deposit Ag-NPs on their surfaces. The subsequent formation of BSi-MNs was performed in an HF/H2O2 aqueous solution through a Ag-catalyzed chemical etching process. Finally, the BSi-MN patches were sequentially cleaned in 30 wt% HNO3 and dilute HF aqueous solutions to remove Ag residues and the oxide layer, and then dried. Throughout the wet process, the patches were thoroughly rinsed with DIW between all steps.2. Specifically, normal saline was first added to the surfaces of both patches using a syringe until excess, and the patches were then gently vertically lifted to remove excess normal saline. The weight of the MN sample is subtracted from the weight obtained by weighing to obtain its actual loading capacity.To determine the actual drug loading capacity of the BSi-MN patches, weighing experiments were conducted on the Si-MN patches and BSi-MN patches with an area of 2 × 2 cmEscherichia coli (E. coli) ATCC 25922  was used in this experiment. The strain was incubated in a bacterial incubator at 37 °C until it reached the midlogarithmic phase. The optical density of the bacterial solution was adjusted to OD600 nm = 0.1. The Si-MN patches, including the plain Si-MN patches and BSi-MN patches, were immersed in 1 mL of the bacterial solution and incubated for 30 min in the dark. After incubation, all the patches were rinsed three times with phosphate-buffered solution and then stained successively with PI and DAPI. The patches were observed under an inverted confocal microscope  with a 63× oil objective. All images were taken under the same instrument settings. The fluorescence images were analyzed using ImageJ (version 1.51j8) software. We performed at least three independent experiments in each case.In order to determine the antimicrobial capacity of the patches, live–dead bacterial staining using the fluorescent dyes PI and DAPI was performed in this study ,44. The The morphologies of the patches were observed using a field emission scanning electron microscope . A contact angle measuring instrument  was employed to determine the contact angle. The reflectance spectra in the wavelength range of 400–1000 nm were measured using an ultraviolet–visible near-infrared spectrophotometer . A precision mechanical tester  was used to determine the mechanical properties of the MNs by using a probe to vertically compress the MN patch until the needle broke/collapsed. Fluorescence staining tests for live/dead bacteria were performed on Si-MNs and BSi-MNs using a laser scanning confocal microscope . The size distributions of Ag-NPs deposited on the surfaces of Si-MNs were analyzed using NanoMeasure1.2. The coverage of Ag-NPs and the porosity of black silicon nanowire structures were calculated using ImageJ (version 1.51j8) software.x protective layer on the wafer surface and to form deep kerfs in the wafer. x protective layer after laser grooving. The spacing between any two adjacent grooves is 500 µm. The corresponding enlarged image , the size of the Ag-NPs was relatively dispersed  software, as shown in Previous studies have shown that the HF concentration in AgNOsurfaces ,46,47. Asurfaces , thus pr2O2 aqueous solution with a ρ value of 68% to prepare the BSi-MN patches. The surface morphologies (30°-tilted SEM view) of the corresponding BSi-MNs are shown in 2O2 aqueous solution with increasing HF concentration in the AgNO3/HF aqueous solution. This is because the agglomeration of Ag-NPs is more severe at the tip and edge  system, the concentration of H2O2 is relatively low, and the holes are only preferentially injected into the silicon at the bottom of the Ag-NPs. The silicon oxide at the bottom of the Ag particle is then etched by HF, and this process is repeated over and over again, which causes the Ag particle to move forward in the silicon (2O2-rich) system, the concentration of H2O2 is relatively high, which can provide more hole injection. Apart from preferentially injecting silicon near the Ag particle through the Ag/Si interface [2O2 mixture, resulting in the formation of inverted cone-shaped micropores (Based on the aforementioned results, we proposed a mechanism for the Ag-catalyzed chemical etching of silicon in the HF/H silicon d. In thinterface , excess nterface . The stacropores e.Finally, the properties of the BSi-MNs prepared at a ρ value of 68% were evaluated and compared with typical Si-MNs. Photographs of the BSi-MN patch and Si-MN patch are shown in 2. Specifically, normal saline was first added to the surfaces of both patches using a syringe until excess, and the patches were then gently vertically lifted to remove excess normal saline. The weight of the MN sample is subtracted from the weight obtained by weighing to obtain its actual loading capacity. The weights of the two types of MN patches loaded with normal saline are shown in E. coli using plain Si-MNs as the control group. To quantitatively compare the antimicrobial performance of the two types of MNs, E. coli was cultured separately on the two patches. After staining with live/dead cells, fluorescence images were obtained under laser scanning confocal microscopy, as shown in In addition, we evaluated the antibacterial activity of the BSi-MNs against Gram-negative + concentration, relatively low HF concentration, and moderate ρ value are suitable for the preparation of ideal BSi-MNs. The mechanical strength of the as-prepared BSi-MNs is close to that of plain Si-MNs, which is beneficial for practical skin piercing applications. Moreover, the BSi-MNs exhibit excellent drug-loading capability and certain antimicrobial activity. Taken together, our fabrication method for BSi-MNs is simple and can facilitate manufacturing in a large area and on a large scale, which has great application potential in the TDD field.In summary, we propose a method to prepare a novel BSi-MN array with ultra-hydrophilic surfaces for high drug loading by using simple laser patterning, standard alkaline etching, and well-established Ag-catalyzed chemical etching. The preparation parameters of black silicon nanostructures on plain Si-MNs were investigated in detail. The experimental results show that a suitable Ag


During the past decades, gastric cancer (GC) has emerged as one of the most frequent malignancies with a growing rate of prevalence around the world. Despite considerable advances in therapeutic methods, the prognosis and management of patients with gastric cancer (GC) continue to be poor. As one of the candidate molecular targets in the treatment of many types of cancer, the Wnt/β-catenin pathway includes a family of proteins that have important functions in adult tissue homeostasis and embryonic development. The aberrant regulation of Wnt/β-catenin signaling is strongly correlated with the initiation and development of numerous cancers, including GC. Therefore, Wnt/β-catenin signaling has been identified as one of the main targets for extending therapeutic approaches for GC patients. Non-coding RNAs (ncRNAs), including microRNAs and long ncRNAs, are important components of epigenetic mechanisms in gene regulation. They play vital roles in various molecular and cellular processes and regulate many signaling pathways, such as Wnt/β-catenin pathways. Insights into these regulatory molecules involved in GC development may lead to the identification of potential targets for overcoming the limitations of current therapeutic approaches. Consequently, this review aimed to provide a comprehensive overview of ncRNAs interactions involved in Wnt/β-catenin pathway function in GC with diagnostic and therapeutic perspectives.Video AbstractThe online version contains supplementary material available at 10.1186/s12964-023-01092-6. Cancer, as the second foremost cause of death, is currently ranked the main public health problem affecting 19.3 million new cases and responsible for approximately 10.0 million deaths in 2020 [With 1.1 million new cases and nearly 1 million mortalities globally, GC is considered the 5th most prevalent malignancy and the 4th leading cause of cancer-related mortality, particularly among older males in 2020 . AccordiAlthough therapeutic approaches including adjuvant or neoadjuvant treatments combined with a surgical resection have helped to manage this disease, however, cancer invasion and metastasis result in a poor prognosis and low survival rate in GC patients. According to recent reports, the 5-year survival ranges from 60 to 80% for stage IA and IB tumors in patients undergoing surgery, and 18–50% for patients with stage III tumors undergoing surgery. These reports illustrate the urgency of an improved comprehension of molecular mechanisms participating in the initiation and progression of GC [First, it was regarded that RNA plays a central role as an informational mediator between a gene coding sequence of DNA and its encoded protein. Most recently, based on the findings from the comprehensive genome sequencing, the total human genome has been recognized to contain less than 2% protein-coding, while over 90% of that is related to non-coding RNAs (ncRNAs). ncRNAs with no protein-coding role are constantly transcribed and extensively expressed in various organs and cells . PreviouAs most characterized ncRNAs, miRNAs are short sequences of RNA with about 19–24 nt length. MiRNAs are highly conserved and single-stranded modulating diverse biological activities, including cellular differentiation, proliferation, apoptosis, invasion, and metastasis . Hence, LncRNAs are RNA molecules with a length of more than 200 nucleotides, that rarely indicate the protein-coding capacity  and playAccording to recent reports, large amounts of signaling pathways are involved in the pathogenesis of many types of malignancies. With the considerable improvement in the comprehensive analysis of genome structure in tumorigenesis using advanced sequencing technologies, it was identified that Wnt signaling pathway is one of the key oncogenic signaling cascades that is tightly associated with cancer pathogenesis and plays a vital role in cancer development and metastasis. It preserves genetic stability and has a central role in the determination of cell fate, cell proliferation, differentiation, motility, and apoptosis as well as the maintenance of stemness features . The Win+2) pathway. These pathways antagonize WNT/β-catenin-signaling in some conditions [2+ cascade, the binding of Wnt ligand to a Fz receptor activates phospholipase C (PLC), located on the plasma membrane of the cell [+2 ions which in turn activates effector molecules such as calmodulin-dependent kinase II (CAMKII), calcineurin, and protein kinase C (PKC). These events eventually activate the transcriptional regulator NFAT (nuclear factor of activated T cells), resulting in calcium-dependent cytoskeletal reorganization and/or transcriptional responses  and calcium  pRegarding the mechanism of Wnt signaling cascade, it participates in several biological activities, such as development, cellular growth, differentiation, tissue regeneration, organogenesis, and homeostasis . A dysreGenome and transcriptome analysis evidenced that about 46% of GC patients demonstrate the deregulated Wnt/β-catenin pathway. According to growing evidence, numerous mutated components of canonical Wnt signaling, which further lead to abnormal activity of this pathway, have a dominant function in malignant transformation and GC invasiveness. These abnormalities in GC can be related to Wnt ligands, cytoplasmic Wnt components, Wnt target genes, Wnt antagonists, and Wnt receptors. Numerous Wnt ligands are overexpressed in human GC, such as Wnt-1, Wnt-2b, Wnt-6, and Wnt-10a,b . ReportsCurrently, the interaction between miRNAs and Wnt/ β-catenin signaling pathways as well as their roles in many types of cancers such as GC was evaluated. It is manifested that Wnt/β-catenin signal and miRNAs are important modulators of development and almost all Wnt signaling components are controlled by miRNAs. Besides, the balance between the activity of miRNAs and Wnt cascades is accomplished through direct and indirect monitoring mechanisms which can lead to cellular homeostasis. Therefore, abnormalities in Wnt signaling pathways and miRNA levels cause an aberrant developmental process that can cause many types of cancer, such as GC. Hence, a deep understanding of miRNA roles in regulating Wnt/β-catenin cascade would be beneficial for the development of novel therapeutic methods for GC .Several miRNAs were reported to directly regulates Wnt/β-catenin signaling pathway by targeting Wnt components in GC Fig. . These mAs an oncogenic miRNA, miR-501-5p was revealed to be significantly overexpressed in GC cell lines and tissues and to increase the stem cell-like features in GC cells. Upregulated miR-501-5p led to hyper-activity of Wnt/β-catenin signaling by directly suppressing several repressors of this pathway, namely DKK1, GSK3β, and Naked cuticle 1 (NKD1). DKK1 is known to be a secreted protein that functions as a negative regulator of Wnt signaling that binds to and antagonizes the function of LRP6 . NKD1 isBesides the oncomiRs, some studies have proven that tumor suppressor miRNAs are also involved in the regulation of Wnt/β-catenin signaling through gastric tumorigenesis. As mentioned in the following, these miRNAs mainly target Wnt ligands and β-catenin. As an important example, a negative correlation was found between the expression of miR-200a, a known tumor suppressor in GC, and the activity of β-catenin pathway. The findings indicated that miR-200a directly targeted β-catenin mRNA and hindered gastric tumorigenesis by suppressing the pathway . AdditioTaken together, these findings illustrate the importance of miRNAs as alternative targets in the regulation of Wnt/β catenin signaling to be considered for targeted therapy of GC Table .Table 1Some miRNAs have been reported to modulate Wnt/β-catenin signaling by regulating other mediators which are not the main components of the pathway. The suppressor of fused homolog (SUFU), a negative regulator of Ηedgehog signaling, is targeted by various miRNAs and plays important role in the regulation of Wnt/β-catenin signaling. According to a recent study, miRNA-194 was upregulated in GC tissues while SUFU indicated low expression levels in GC. The inhibition of miR-194 expression, attenuated β-catenin nuclear accumulation by rescuing SUFU expression, and blocked Wnt/β-catenin signaling, leading to a decrease in malignant features . Also, mBy the way, other oncogenic miRNAs induce Wnt/ β-catenin cascade by regulating a wide array of molecular components rather than SUFU. A study reported that miR-188-5p reduces the expression of Phosphatase and tensin homolog (PTEN) as a tumor suppressor, and increases phospho-Ser9 of GSK3β to trigger Wnt/β-catenin cascade in GC. This leads to an increase in GC cell invasion and migration. In summary, a model of the miR-188-5p-PTEN-β-catenin axis, which facilitates the stimulation of Wnt/β-catenin signaling and triggers metastasis ability, was reported . Also, mOn the contrary, tumor suppressor miRNAs have been reported to target various oncogenes participating in positive regulation of Wnt/β-catenin signaling. As an example, miR-154 has been shown to suppress the proliferation and invasion of GC cells by directly targeting the Dishevelled–Axin domain containing 1 (DIXDC1), a positive regulator of Wnt/beta-catenin signaling. Further investigations indicated that restoration of DIXDC1 expression notably hindered the inhibitory effect of miR-154 on cellular growth, invasion, and WNT signaling in GC cells . FurtherNumerous recent studies have established the existence of many types of abnormally expressed lncRNAs in GC . It is dAccumulating studies have evidenced that oncogenic lncRNAs by sequestering miRNAs from their targets stimulate the activation of Wnt/β-catenin signaling. As an oncogenic lncRNA, SNHG11 is highly expressed in GC and contributes to its progression. Mechanically, SNHG11 was illustrated to provoke autophagy through upregulating ATG12 expression and activates β-catenin signaling, leading to an increase in stemness, proliferation, EMT, migration, and invasion in GC cells. SNHG11 upregulated ATG12 and β-catenin expression in post-transcriptional levels via targeting miR-483-3p/miR-1276. SNHG11 also prompted the ubiquitination of GSK-3β by interacting with CUL4A to further activate Wnt/β-catenin pathway . SNHG22 By the way, despite the oncogenic lncRNAs, some lncRNAs have a suppressive effect on Wnt/β-catenin signaling through interaction with miRNA in GC. A study evidenced that LINC02381 showed a low level of expression in GC samples, indicating its possible tumor suppressive function. By Further investigations, miR-21, miR-27a, and miR-590 were identified to be sponged and downregulated via LINC02381 ceRNA. Furthermore, the overexpression of LINC02381 diminishes Wnt pathway activity. Besides, LINC02381 has a central role in the cell cycle, apoptosis, cell survival, and proliferation of cell lines AGS and MKN45. Taken together, LINC02381, through binding to the candidate microRNAs, may hinder Wnt/β-catenin signal . For morLncRNAs also participate in the modulation of Wnt/β-catenin signaling cascade directly or by affecting molecular components rather than miRNAs in GC. Considering their targets, these lncRNAs are also divided into two groups of oncogenic and tumor suppressor lncRNAs. As a known oncogenic lncRNA, ZEB2-AS1, participates in the pathogenesis of GC by induction of β-catenin expression through ZEB2 overexpression . Also, uIn addition to oncogenic lncRNAs, there are some tumor suppressor lncRNAs that also regulate Wnt/ β-catenin signaling by affecting molecular components. It is found that suppression of LOC285194, which showed low expression levels in GC tissues and cell lines, stimulated GC progression via prompting Wnt signaling activity. LOC285194 was illustrated to directly regulate β‐catenin and GSK‐3 β protein levels . AnotherThe Wnt/β-catenin signaling pathway is considered a well-recognized oncogenic pathway in a wide array of human cancers, including GC, that is involved in cancer initiation and progression. Although a large number of studies assessed underlying molecular mechanisms related to Wnt/β-catenin mediated gastric tumorigenesis, and many therapeutic methods were investigated for the suppression of this oncogenic pathway, elimination of some drawbacks in therapies targeting Wnt/β-catenin signaling, such as resistance or unresponsiveness, need additional investigations. Accordingly, this review endeavored to elucidate the downstream and upstream regulators of Wnt/β-catenin signaling in GC cells to facilitate the understanding of pathways involved in the progression of this malignancy in terms of its treatment and diagnosis. As mentioned in this study, various miRNAs and lncRNAs, as dual role regulators, could directly or indirectly activate or suppress Wnt/β-catenin pathway, getting involved in GC progression. More importantly, a wide range of miRNAs, including miR-200b, which function as a tumor suppressor and targets the main component of Wnt/β-catenin signaling, such WNT1, are blocked by ceRNA functioning of lncRNAs, hereby oncogenic lncRNA ZFAS1, resulting in increased gastric cancer cell growth and proliferation. On the contrary, deregulated expression of some tumor suppressive lncRNAs, as an example LINC01133, leads to hyperactivity of some oncomiRs, such as miR-106a-3p targeting pivotal suppressors of Wnt/β-catenin signaling like APC, that contributes to gastric cancer development and metastasis. Consequently, the interplay between these ncRNAs and Wnt/β-catenin signaling seems to be a crucial mechanism in regulating gastric tumorigenesis. Therefore, targeting lncRNAs/miRNAs/β-catenin axis may be a promising alternative for other targeted therapies based on Wnt/β-catenin signaling. For instance, using of the RNA interference (RNAi) technique targeting ncRNAs has been evidenced to increase the hope of the successful treatment of GC patients by modulating Wnt/β-catenin signaling. These methods are also restricted by some obstacles such as low bioavailability and delivery into cancer cells. Nevertheless, applying novel methods using nanoparticles ensuring high cellular uptake through encapsulation of these regulatory RNA molecules and their site-specific delivery may pave GC therapy.


Tnf expression; and (c) localized TNF-α blockade abrogated this metastatic outcome. Last, β-catenin gene CTNNB1 and TNF expression levels were positively correlated in AMs of patients with lung cancer. Overall, our findings revealed a Wnt/β-catenin/TNF-α pro-metastatic axis in AMs with potential therapeutic implications against tumors refractory to the antineoplastic actions of TNF-α.The main cause of malignancy-related mortality is metastasis. Although metastatic progression is driven by diverse tumor-intrinsic mechanisms, there is a growing appreciation for the contribution of tumor-extrinsic elements of the tumor microenvironment, especially macrophages, which correlate with poor clinical outcomes. Macrophages consist of bone marrow–derived and tissue-resident populations. In contrast to bone marrow–derived macrophages, the transcriptional pathways that govern the pro-metastatic activities of tissue-resident macrophages (TRMs) remain less clear. Alveolar macrophages (AMs) are a TRM population with critical roles in tissue homeostasis and metastasis. Wnt/β-catenin signaling is a hallmark of cancer and has been identified as a pathologic regulator of AMs in infection. We tested the hypothesis that β-catenin expression in AMs enhances metastasis in solid tumor models. Using a genetic β-catenin gain-of-function approach, we demonstrated that (a) enhanced β-catenin in AMs heightened lung metastasis; (b) β-catenin activity in AMs drove a dysregulated inflammatory program strongly associated with   Metastasis remains the leading cause of solid cancer–related deaths worldwide . TherefoHowever, the mechanisms that control tumor progression extend beyond the malignant cells themselves to include multiple stromal and immune cell components of the tumor microenvironment (TME). This diverse collection of nonmalignant cells is capable of promoting tumor progression via varied immune-suppressive, angiogenic, and growth factor–mediated mechanisms . In patiLike primary tumor growth, tumor progression to metastasis is mediated by both tumor-intrinsic and -extrinsic factors . AlthougBone marrow–derived monocytes are known to traffic along chemokine gradients generated by the TME and differentiate into TAMs that are generally rendered pro-tumorigenic within the TME . Many inCtnnb1, is expressed in many tissues  (https://doi.org/10.1172/jci.insight.160978DS1) (Lyz2-Cre+/+Ctnnb1Δ/ΔEx3 model (βcat.CA), active β-catenin (ABC) levels were enhanced relative to the floxed controls (Ex3.Flox) in CD45+ cells, based on nonphosphorylated active β-catenin expression, but not in CD45– cells  . In this5– cells , C and D.CA mice . These f.CA mice .Lyz2 is expressed in type II alveolar epithelial cells, we only observed an increase in nonphosphorylated ABC in the CD45+ leukocyte compartment of βcat.CA lungs . Ta. TaLyz2 Lyz2, the promoter driving Cre-recombinase in our system, is known to be expressed by multiple myeloid cell populations  in cells with Lyz2-Cre activity, to our βcat.CA mouse (Lyz2-Cre+/+Ctnnb1Ex3Δ/wt+/–ROSA26-EYFP (+/+Lyz2-Cre+/–YFPCtnnb1Δ/wtEx3) progeny that were homozygous for the Lyz2 Cre-recombinase but heterozygous for the EYFP reporter and constitutively active β-catenin Ctnnb1 (Ex3Δ) alleles  control mice that would express the same intensity of the YFP Cre-reporter signal but lack β-catenin activation. These YFP models enabled us to make one-to-one comparisons between myeloid cells expressing constitutively active or WT Ctnnb1 alleles, respectively, without the potential confounding variable of Lyz2 penetrance.While our data established a causal role for constitutively active myeloid β-catenin in promoting tumor growth and metastasis, the specific myeloid cell type(s) responsible for these outcomes remained unclear. ulations . To addrCA mouse . This ma alleles , G and H+/+Lyz2-Cre+/–YFPCtnnb1Δ/wtEx3 mice showed increased E0771.ML-1 growth relative to the controls (+Ly6G+ polymorphonuclear cells (PMNs) and a concordant decrease in CD11b+CD11c+ dendritic cells (DCs) within the myeloid fraction of the CD45+ leukocytes . We. WeLyz2-pulation . Interespulation . Those fpulation .Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 mice  in whole-lung lysates . Wh. WhLyz2-pulation . As withpulation , which cpulation , F and GLyz2-Cre model, we quantified the penetrance of Cre-recombinase in E0771.ML-1-bearing mice using the YFP Cre-reporter. Interestingly, while PMN cell numbers were significantly increased in the primary TME of Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 mice, only about 20% of PMNs expressed the YFP Cre-reporter. On the contrary, approximately half of all CD11bhiLy6G–Ly6C+ monocytes, CD11bhiLy6G–Ly6CloF4/80+ macrophages, and CD11b+ DCs expressed the YFP Cre-reporter  between the 2 genotypes, with the majority (75%) being upregulated in AMs of Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 mice   . Interesytometry .Tnf expression. To further strengthen the findings based on our genetic approach, we leveraged publicly available single-cell RNA-Seq (scRNA-Seq) data of murine AMs from Zhu et al.  that used a pharmacological approach to activate β-catenin  clustering using Metascape . With th-catenin . In thei-catenin , left. Acontrols , right acontrols . TherefoAMs are the most abundant immune cell in the alveoli at steady sate; however, their total numbers within an individual mouse are low and represent a small proportion of the total lung tissue . TherefoLyz2-Cre+/++/–YFP control mice had high Lyz2-YFP penetrance when viewed by fluorescence microscopy ..Lyz2-CreLyz2-Cre+/++/–YFP and Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 mice faithfully reproduced the β-catenin–dependent mRNA expression findings observed in vivo. NLDMs derived from the Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 model maintained a robust increase in Axin2 and Ccnd1 expression, classical readouts of Wnt/β-catenin signaling  assay of untreated Lyz2-Cre+/++/–YFP control NLDMs guided by anti–β-catenin or isotype-matched IgG antibodies. We observed amplification of DNA fragments from the Tnf and Axin2 upstream regulatory regions in anti–β-catenin–treated samples. Signal was elevated above control IgG for both regions, while there was no difference in fold enrichment between Tnf and the Axin2 positive control . Mo. MoLyz2-nist LPS . NLDMs owt model . Taken tLyz2-Cre+/++/–YFP control or Lyz2-Cre+/++/–YFPCtnnb1Δ/wtEx3 mice 36 hours prior to E0771.ML-1 tail vein injection. After 1 week, NLDMs were replenished by an additional intranasal adoptive transfer before experimental endpoint, 14 days after tumor implantation  mice, initially in a preclinical model of TNBC, we observed that both primary tumor growth and metastasis to the lung were markedly enhanced relative to the floxed controls. We strengthened the importance of this signaling axis in breast cancer biology by revealing that Wnt signaling is a top-ranked pathway among those most associated with poor overall survival in a 1,006-patient breast cancer cohort with matched mRNA expression and survival data from TCGA. In addition, higher expression of the canonical Wnt ligand Wnt3a correlated with worse outcomes within the same data set.Wnt/β-catenin signaling is a known hallmark of cancer . Given trophages , we testLyz2-driven promoter used in these conditional β-catenin gain-of-function studies is known to be broadly expressed by mature myeloid cells and has been reported to be active in PMNs, monocytes, macrophages, and DCs , complement, regulation of cell adhesion, tissue remodeling, and vascular development, were upregulated as expected, there was a surprising increase in inflammatory and chemotactic pathways as well. In reference to the latter, a significant upregulation of the pro-tumorigenic cytokines observed , all knoobserved –67. Thes–derived BMDMs and primary tumor TAMs, which are mainly bone marrow monocyte derived, have suggested that β-catenin signaling induces an M2-like expression profile  this metastatic phenotype was ameliorated by localized TNF-α blockade. Together these findings highlight a potentially novel application for existing anti–TNF-α biologics in suppressing metastasis to the lung in settings wherein tumors are resistant or refractory to the antitumor actions of this complex cytokine.In summary, we demonstrated that 1) β-catenin activation in AMs heightened a pro-metastatic shift in the lung metastatic microenvironment; 2) AMs with enhanced β-catenin activity expressed an inflammatory metastatic program defined by multiple pathways, including increases in PMN chemoattractants and RNA-Seq data original to this paper and shown in t test. Statistical tests following RNA-Seq analyses were performed in R (v4.1.0) and are included in their respective figure legends. In all cases, P values less than 0.05 were considered statistically significant.Data were analyzed using GraphPad Prism (v9.1.2). Data represent mean ± SEM, with the number of mice or biologic or experimental replicates indicated. Differences between groups in primary tumor growth over time or TNF-α secretion were determined by a 2-way ANOVA. Differences in metastatic outcome or cell populations as assessed by flow cytometry between multiple treatment groups were determined by 1-way ANOVA with the Holm-Šídák correction applied for multiple comparisons in the specified figures. Differences in metastatic outcome, cell populations, or mRNA expression between only 2 treatment groups were determined by a 2-tailed unpaired All studies involving mice were approved under protocols 1108M and 1117M and conducted in accordance with the Institutional Animal Care and Use Committee at the Roswell Park Comprehensive Cancer Center.Further information can be found in EDK, SLT, and SIA supervised and designed the study. EDK, SHC, MLH, CMB, and SLT performed the experiments. BEC and MMT provided essential mouse models. EDK, SLT, and SIA analyzed the data. EDK and SIA verified statistical analyses. EDK, SHC, and SIA wrote the manuscript. SLT, CMB, BEC, and MMT provided crucial feedback and helped edit the manuscript.


This article presents a new technology for forming automotive connecting rod forgings by means of die forging from cast performs from EN AB-71100 (EN AB-AlZn10Si8Mg) aluminum alloy. A premise was made that the production process would be carried out on forging presses. The process of forming connecting rod forgings was analyzed considering different deformation rates related to the type of machine used: a crank press and a screw press. The billet in the form of in-house designed, shaped preforms cast into sand molds with two variants of geometry was used in the process. The numerical analysis of the new process was carried out on the basis of the finite element method using Deform 3D, the simulation software for metal forming. The simulations were conducted in the spatial deformation conditions, considering the full thermomechanical analysis. Based on the simulations, certain important findings concerning the novel process were acquired, including the distribution of stress, deformation, temperatures, cracking criterion and energy parameters. The results of numerical tests confirmed the possibility of producing defect-free forgings of connecting rods from EN AB-71100 aluminum alloy on forging presses by means of the proposed technology. The proposed process of forging using crank and screw presses was verified in the course of tests conducted in industrial conditions. The properly formed connecting rod forgings were subjected to quality tests in terms of their structure and mechanical properties. Currently, automotive connecting rods made of hardly deformable aluminum alloys from the 7XXX group  are manufactured using die forging, casting and machining ,2,3.The best strength-related properties of connecting rods used in the automotive industry are provided by metal forming processes described in the literature ,5,6,7. DAutomotive connecting rods manufactured by the casting technology have significantly lower mechanical and functional properties compared to elements produced by metal forming methods presented in the literature ,18,19,20In the production of automotive connecting rods, the machining technology described in the literature is used ,24,25. TDespite the existence of these technologies, new solutions are still being sought. The main objective in developing the new technology was to reduce the number of operations required to obtain a connecting rod compared to the currently used multistage forging of connecting rod forgings and to obtain improved product properties compared to the currently used casting machining technology. The current article presents a novel technology for forming automotive connecting rod forgings by die forging from preforms cast from EN AB-71100 aluminum alloy. In the new technology of forging an automotive connecting rod forging, the geometry of the cast preform will be similar in shape to the forging, particularly in terms of the outline in the die parting plane. The new process will be carried out in a single forging operation in the finishing impression using typical forging presses (crank and screw presses) and with the application of inexpensive methods of heating the tools . The proposed technology is unique in the world. Its basic principles were granted patent protection.The research concerned the novel process of forging an automotive connecting rod forging made of a billet in the form of a shaped preform made of EN AB-71100 aluminum alloy cast in sand molds ,27. The 3 (the mass is 0.127 kg), while that of the designed forging (3 (the mass is 0.166 kg). The material waste in the form of machining allowances is approx. 13,689.6 mm3 .The automotive connecting rod shown in  forging b is 58,2−1 to 10 s−1 and strain deformation values in the 0–1 range. The calculations were based upon the premise that the billet is heated up to 480 °C, and the temperature of the processing tools amounts to 250 °C. For the crank press, the movement in the Deform software was defined in line with the machine’s parameters, i.e., crank press; additionally, the total stroke of 15 mm and press cycle of 12 min−1 were given. For the screw press, the movement in the Deform software was defined in line with the machine’s parameters, i.e., screw press; additionally, the impact energy of 40 kJ, a moment of inertia of moving elements at 557.8 kgm2 and a thread lead of 188 mm were given. The friction conditions between the billet and the tools were described using the constant friction law assuming the friction coefficient m = 0.15 [2K, while between the billet and the environment, the coefficient was equal to 0.02 kW/m2K.Tests of the connecting rod die forging process from the designed preforms were carried out based on the FEM analysis in the Deform 3D software  . The numm = 0.15 . The assPreforms made by casting into sand molds from AB-71100 aluminum alloy were used in the experiments. On the basis of numerical tests, two geometries of preforms were developed, with a greater degree of forging (variant 1) a and a lPrior to die forging, all preform castings were subjected to the annealing process using furnace heating to the temperature of T = 480 °C, then holding at the temperature of T = 480 °C for 24 h and cooling in a furnace to room temperature . These c-I bath—warm water, 50–70 °C;-II bath—cold water;-III bath—nitric acid aqueous solution HNO3 (approx. 20–35%);-IV bath—cold water;-V bath—sodium hydroxide aqueous solution NaOH (approx. 10%) 50–70 °C.After forging on each of the machines , the forgings were trimmed of flash and etched in five baths with the following parameters :-I bath—Subsequently, heat treatment was conducted in the temperature conditions presented in In order to assess the quality of the connecting rod forgings made of AB-71100 aluminum alloy obtained during industrial trials, tests of the structure and mechanical properties were carried out.Microstructural tests were conducted on longitudinal sections of castings (preforms) and connecting rod forgings .The preparation of metallographic specimens was carried out by grinding the surface of the cross-sections using abrasive discs with grain sizes of 80, 120, 240, 320, 600, 800 and 1200. Subsequently, the specimens were polished using diamond slurries with grain sizes of 3 μm and 0.05 μm. The surfaces were etched with Keller’s reagent  by immersion for approx. 30 s. Microstructural tests were performed using a NIKON MA200 optical microscope . Hardness measurements were carried out using the Vickers method with the Future-tech FM800 hardness tester . The measurements were made on the HV 0.5 scale in accordance with the PN-EN ISO 6507-1:2006 standard.Mechanical tests were carried out on samples made of connecting rod shanks). The dimensions of the specimens for tensile testing and the sampling locations for testing mechanical properties are shown in The analysis of effective stress distribution showed that for forgings made of AB-71100 aluminum alloy, the maximum values of the discussed parameter reach 50 MPa . Stress On the basis of the analysis of temperature distribution in the connecting rod forgings formed following the proposed technology, it was detected that the type of forging machine used has the greatest influence on the temperature . This trmax is the maximum principal stress, σH is the equivalent stress according to Huber’s hypothesis, ε is the strain intensity, and C1 is the integral value.Along with the analysis of the above-mentioned parameters, the risk of crack formation in the forging was studied. For the theoretical analysis of this phenomenon, the Cockroft–Latham (C-L) failure criterion in a modified form was input in the Deform software ,38. The C1 = CCL, plastic fracture of the material will occur.The C-L criterion assumes that when the work performed by tensile stresses in uniform tension reaches a certain critical value Based on the analysis of the distribution of Cockcroft–Latham integral values , it was For further comparative analysis of the technology of forging connecting rods f from cast preforms, diagrams of the impact energy of the upper die as a function of time for individual preforms and forging presses were presented . For indA comparative analysis of the new technology of forging from cast preforms and the technology of multistage forging from a bar of diameter Ø30 mm and length 148 mm (one currently used in the industry) was carried out on the basis of the material consumption of the process. -On the basis of numerical simulations, it was found that in the proposed forging process, forgings of connecting rods made of AB-71100 aluminum alloy can be obtained from cast preforms;-Both geometric variants of preforms ensure that forging of the assumed shape and dimensions is obtained;-Forging from a preform with a lower degree of forging (variant 2) seems to be a safer option in terms of the possibility of losing the cohesion of the material; this is supported by lower values of the Cockcroft–Latham integral;-Forming a forging from variant 2 preform is characterized by lower energy consumption than in the case of variant 1;-Due to the final temperature of the forging, it seems more advantageous to forge on a screw press than on a crank press;-Forging of the connecting rod forging from the cast preform is carried out in a single step exclusively, which shortens production time in relation to the currently applied multistage technologies of their production.Based on the numerical analyses, the following conclusions were formulated:On the basis of the experimental tests, it can be observed that during the forging process of connecting rods forgings from preforms made of AB-71100 aluminum alloy on the screw press in accordance with variant 1, no defect-free products were obtained . The defDuring the process of forging the connecting rod forgings from variant 2 preform on a screw press, defect-free forgings were obtained . The forThe tests of the forging process performed on a crank press for the forging of connecting rods from preforms made of AB-71100 aluminum alloy in accordance with variant 1 made it possible to obtain defect-free products . The forThe process of forging connecting rod forgings from preforms in accordance with variant 2 on a crank press also resulted in the formation of defect-free forgings . The obtWhen analyzing the test results, it can be concluded that for each of the considered machines, a defect-free forging was obtained for variant 2 preforms. With a lower degree of forging, the material fills the impression well. The developed geometry allows the avoidance of cracks and bends in the shank part of the connecting rod. The results obtained for variant 2 also confirm the appropriate preparation of the billet in the form of cast preforms for the forging process by the application of annealing prior to the process. The defect-free forgings also testify to the correct selection of technological parameters for the forging process.While investigating the obtained test results for variant 1 preforms with a greater degree of forging, each machine should be considered separately. During the forging process carried out on the screw press, no defect-free forgings were obtained from variant 1 preforms. The application of variant 1 preform on the screw on a screw press with a high deformation rate resulted in the emergence of a defect in the form of cracks in the area where the shank of the rod transitions into the head. Improving the transition radius at the defect’s location in the preform might prove to be the solution to this problem.Defect-free forgings were formed on the crank press for both variants of the process. It can be assumed that the cast AB-71100 aluminum alloy should be deformed on forging machines with low deformation rates, such as a crank press or hydraulic press.On the basis of the microstructural tests of cast preforms of connecting rods made of AB-71100 aluminum alloy, the structures shown in AB-71100 aluminum alloy is multi-component. Its microstructure consists of an alpha aluminum solid solution and precipitates of varying natures. There are igneous Al-Si precipitates of eutectic character and slightly thicker intermetallic magnesium-containing phases, e.g., Mg-Si forming Chinese script-type patterns. Most of the zinc is dissolved in a solid solution, and iron forms isolated slightly smaller Al-Fe-Si precipitates. The precipitates are dispersively distributed on the analyzed surfaces.As a result of homogenization, the structure of the aluminum alloy does not undergo significant transformations . PreviouAfter forging on the screw press, the structure became significantly fragmented. Grain fragmentation and disintegration of parts of particularly larger separations were obtained .The structure after forging on the crank press is similar to the structure forged on the screw press. After heat treatment, slight grain growth and minor symptoms of the beginning of the spheroidization process of the separations are visible, mainly manifested by the rounding of sharp edges . Increas2Si. The alloy tends to age spontaneously. Therefore, initially, after homogenization, hardness is slightly lower. It returns to the initial level after the full process.The average values obtained in the tensile strength test are presented in The results of the tensile test indicate that forging improves the plastic properties of the cast AB-71100 aluminum alloy to the greatest extent. However, it does not significantly affect the value of Young’s modulus. The highest values of elongation and tensile strength were obtained for samples after forging on the crank press from variant 1 preform and full heat treatment.-Experimental verification in industrial conditions of the novel technology for the forging of connecting rod forgings from preforms cast from AB-71100 aluminum alloy showed that only the geometrical variant 2 of the preform ensures a forging of the assumed shape and dimensions for each machine  is obtained;-The geometrical variant 1 of the preform ensures a forging of the assumed shape and dimensions is obtained only for the forging process carried out on the crank press;-In order to obtain the correct connecting rod forging from variant 1 preform with a greater degree of forging on the machine with a high deformation rate-screw press, the preform’s geometry should be redesigned on the transition radius between the head and the shank part of the preform;-The main phenomenon disturbing the process of the forging of connecting rods from preforms cast from AB-71100 aluminum alloy on the screw press includes cracks;-The results of qualitative studies of the formed forgings indicate favorable changes in the functional properties of the forgings. Although no significant changes in the hardness of the alloy were observed at different stages of the technological process, the results of structural and tensile tests manifest significant differences;-The structure of the alloy is fragmented as a result of deformation, and AlSi separations are also fragmented;-The effect of temperature significantly affects the rounding off of crushed fragments of AlSi separations. Both the fragmentation and spheroidization of the separations can favorably influence the improvement of ductile properties;-Tensile test results indicate improved ductile properties while maintaining high strength-related properties in the form of Young’s modulus and tensile strength;-Although the studied alloy is mainly used for castings, the application of thermoplastic processes has significantly improved its ductile properties, which may have beneficial effects in selected applications.Based on the experimental research in industrial conditions, the following conclusions were formulated:-Enhancement of the efficiency and output of the manufacturing process due to shortening the processing time to a single forging operation, in comparison to the multistage forging from a rod and time-consuming mechanical processing of the casting in current operation in the industry;-Considerable material savings in relation to the multistage forging method in the current application. The technological waste for flash in the standard process amounts to 44.3% of the forging’s mass. In the novel technology of forging from preforms, the waste amounts to 13.5% for variant 2 preform and 18.7% for variant 1 preform;-Improvement of product quality. A higher product quality is associated with a more favorable structure and high smoothness of the surface. This translates into improved tensile and functional properties when compared with products manufactured by the mechanical processing of castings ,42,43,44-Possibility of forming connecting rods from less ductile alloys possessing better tensile properties. The use of a shaped, cast preform without metal forming will have a positive effect on the flow kinematics and deformability of the material during forging ,46,47,48-Ecofriendliness of the novel process. It stems from a more eco-friendly production method, i.e., lower waste volume in comparison to the connecting rod manufacturing method in current employment.The current study presents new possibilities for manufacturing automotive connecting rods using the innovative technology of die forging on presses from preforms cast from AB-71100 aluminum alloy. Based upon theoretical research and experimental tests, it can be argued that the proposed forming process enables the production of defect-free forgings of appropriate dimensions from preforms cast from AB-71100 alloy. The research also confirmed the possibility of deforming AB-71100 aluminum alloy. The advantages of the proposed technology of connecting rods’ manufacturing over the current production methods entail the following:The advantage of the proposed technology is its universality of application. The method can be applied to manufacture connecting rods made from other lightweight aluminum alloys.The numerical analyses conducted in the framework of the study confirmed the advantages of exploiting computer simulations when designing novel technologies . They enThe industrial tests enabled the determination of optimal technological parameters for the proper formation of the connecting rod forging from preforms, verification of the preform geometry on presses with varying deformation rates, and allowed technology demonstrators to be developed and qualitative studies to be conducted.Dziubińska A., Winiarski G., Surdacki P., Majerski K., Siemionek E., Szucki M., Method of forging a semi-finished component on a hydraulic press, particularly for the manufacture of a car connecting rod, Patent Office of the Republic of Poland. Patent no. P.431789, Registered 14 November 2019.Winiarski G., Dziubińska A., Surdacki P., Majerski K., Szucki M., Siemionek E., Method of forming a semi-finished product on a hydraulic press, especially for the manufacture of a car connecting rod, Patent Office of the Republic of Poland. Patent no. P.431788, Registered 14 November 2019.Dziubińska A., Winiarski G., Surdacki P., Majerski K., Szucki M., Siemionek E., Method of forming a semi-finished product in a forging device on a hydraulic press, especially for the manufacture of a car connecting rod, Patent Office of the Republic of Poland. Patent no. P.431790, Registered 14 November 2019.Dziubińska A., Winiarski G., Surdacki P., Majerski K., Siemionek E., Szucki M., Method of forging a semi-finished component in a forging device on a hydraulic press, especially for the manufacture of a car connecting rod, Patent Office of the Republic of Poland. Patent no. P.431791, Registered 14 November 2019.


Although the CNTs were more poorly dispersed in the epoxy/PCL/CNT/IL NCs than in the reference epoxy/CNT/IL NCs, which led to slightly lower electrical conductivity values, the epoxy/PCL/CNT/IL NCs were still semiconductive. Their low-strain mechanical properties  were similar or better than those of the reference epoxy/IL systems and their high-strain mechanical properties  were significantly better. In addition, the positive effects of the PCL and the CNTs on the adhesive properties of the epoxy/IL system were combined. The substitution of ILs for traditional amine-based curing agents and biodegradable PCL for part of the epoxy resin represents an important advance on the road towards greater sustainability.Electrically-conductive epoxy nanocomposites (NCs) with improved mechanical and adhesive properties were achieved through the combined addition of poly(ε-caprolactone) (PCL) and carbon nanotubes (CNTs). Three different ionic liquids (ILs) were used as dual role agents, i.e., as both curing and dispersing agents. Regardless of the IL used, the epoxy/PCL matrix of the NCs showed a single-phase behaviour and similar glass transition (T Epoxy resins are widely used thanks to their excellent mechanical, adhesive, chemical, and thermal properties. In addition, depending on the application, they can be modified to enhance these properties and/or compensate for any shortcomings. Their innate brittleness, for example, makes them unsuitable for use whenever toughness is required, so, traditionally, to overcome this, they have been blended with rubbers ,2, oils Morphology is known to be one of the main factors that define the final properties of polymer blends. Indeed, in the literature on epoxy resins blended with thermoplastics, different morphologies have been reported, depending on the nature of the thermoplastic, its molecular weight ,16,17 orAnother way to improve the properties of neat epoxy resins and epoxy/thermoplastic systems is by adding nanofillers. Carbon nanotubes (CNTs) are widely used because by adding them to polymer matrices, electrically-conductive materials with enhanced mechanical, thermal, and/or adhesive properties can be obtained. However, in order to obtain optimal results, the interaction between both components must be optimal, and this is why the functionalization of CNTs, either covalent or noncovalent, has attracted so much interest among researchers ,27,28 anIn ternary epoxy/PCL/CNT nanocomposites, the PCL increases the viscosity of the blend which, in turn, improves the dispersion of the CNTs ,40 so thFinally, one of the main environmental concerns associated with epoxy resins is the use of toxic, volatile hardeners. This is why imidazolium- ,44,45,46To summarise, epoxy/PCL and epoxy/CNT systems have already been widely studied, as is the case, to a lesser extent, of ternary epoxy/PCL/CNT NCs. However, no work has investigated, to the best of our knowledge, the advantages—in terms of mechanical, electrical, and adhesive properties—of simultaneously adding a PCL toughener and CNTs to IL-cured epoxy systems. Thus, in this work, and based on previous results, three ILs were selected for use as curing agents in ternary epoxy/PCL/CNT NCs, and the morphology as well as the thermal, mechanical, electrical, and adhesive properties were characterised and compared with those of the reference epoxy/CNT systems.2/g surface area, 90% purity) supplied by Nanocyl . Three different ionic liquids were used as curing agents for the epoxy resin: trihexyltetradecylphosphonium dicyanamide (IL-P-DCA) from IoLiTec-Ionic Liquid Technologies GmbH , and 1-ethyl-3-methylimidazolium dicyanamide (IL-I-DCA) and trihexyltetradecylphosphonium bis phosphinate (IL-P-TMPP) from Sigma Aldrich, St. Louis, MI, USA.The diglycidyl ether of bisphenol A (DGEBA) epoxy resin used in this work had an epoxy equivalent weight of 186 g and was purchased from Nazza, Eurotex . The poly(ε-caprolactone) (PCL) used was CAPA6800 , with a molecular weight of 80,000 g/mol. The multi-walled carbon nanotubes were Nanocyl NC7000 . After degassing the mixture, the CNTs were added and the resulting NC was mechanically mixed at 2000 rpm. It was subsequently ultrasonicated in a Hielscher UP400s at an amplitude of 100% for 20 min. Next, the IL was added and the blend was stirred at 100 °C until a homogenous mixture was obtained. Finally, the mixtures were either poured into moulds or between substrates, and the corresponding curing protocol was applied .Epoxy/IL: The DGEBA and IL were mechanically mixed at 50 °C for 5 min. Then, the mixtures were either poured into silicon moulds or between substrates and the corresponding curing protocol was applied .Epoxy/PCL/IL: The DGEBA and the PCL were mechanically mixed at 100 °C until a homogenous mixture was obtained (≈2 h). After degassing the mixtures, the IL was added and the blend was stirred at 100 °C until a homogenous mixture was obtained. Finally, the mixtures were poured into moulds or between substrates and the corresponding curing protocol was applied .Epoxy/CNT/IL: First, the epoxy resin and the CNTs were mixed and mechanically stirred at 2000 rpm. Next, the mixtures were ultrasonicated in a Hielscher UP400s at an amplitude of 100% for 20 min. After that, the IL was added and the mixtures were stirred at 50 °C for 5 min. Finally, they were poured into moulds or between substrates, and cured using the curing protocol shown in g) and the crosslinking density (eν) were determined by dynamic mechanical analysis (DMA) in a TA Q800 viscoelastometer  in single cantilever bending mode. A temperature range of −100 °C to 250 °C was used at a heating rate of 4 °C/min. The frequency and amplitude used were 1 Hz and 15 μm, respectively. Equation (1) was used to calculate the crosslinking density [R is the ideal gas constant (8.314 J/mol·K), rE is the storage modulus in the rubbery state, and rT is the temperature at which rE was taken (245 °C).The glass transition temperature (T density :(1)νe=ErDifferential scanning calorimetry (DSC) was performed in a Perkin Elmer DSC-7 calorimeter  calibrated with an indium standard. The samples, which were taken from the cured specimens, were heated from 30 °C to 250 °C at 20 °C/min under a nitrogen atmosphere.Scanning electron microscopy (SEM) was used to study the morphology. A Hitachi TM3030Plus microscope  equipped with a secondary electron detector and with an accelerating voltage of 15 kV was employed. Cryofractured cross sections were analysed, and the samples were gold-coated prior to observation.Transmission electron microscopy (TEM) was used to study the dispersion level of the CNTs. Samples were cut at a 45° angle using a Leica EM UCG ultramicrotome equipped with a diamond blade. A Tecnai G2 20 Twin microscope  was used at an accelerating voltage of 200 kV.σ) was calculated using Equation (2):V is the applied voltage, ρ is the resistivity, and I is the intensity reading on the picoammeter.Electrical conductivity measurements were carried out using a digital Keithley 6487 picoammeter . For the measurement, 2-mm-thick samples measuring 70 mm in diameter were used. A voltage of 1 V was applied, and intensity values were read after 1 min of electrification time. The electrical conductivity (3) were tested. A minimum of 5 specimens were tested for each composition.The mechanical properties were determined by performing bending tests in an Instron 5569 universal testing machine  equipped with a three-point bending device . Samples with the ISO 178 standard measurements (80 × 10 × 4 mmfE), flexural strength (Fσ), and deformation at break (Fε) were calculated using Equations (3), (4), and (5), respectively:F and maxF are the load and maximum load, respectively, L is the span, b is the width of the specimen, h is the thickness, and s is the deflection.The flexural modulus . Notched specimens  were used. At least 8 samples were tested for each reported value.3) were used as substrates . The tests were performed according to the ASTM D-1002 standard (adhesion area: 12.5 × 25 mm2). The lap shear strength was calculated by dividing the maximum force in the force-displacement curve by the adhesion area. At least 10 specimens were tested for each reported value.The adhesive properties were evaluated by means of lap shear strength tests. An Instron 5569 universal testing machine was used with a crosshead rate of 1 mm/min. Aluminium alloy 2021-T351 sheets  was observed for the NC cured with IL-P-DCA, followed by the IL-P-TMPP-cured NC. In contrast, the IL-I-DCA-cured NC showed the poorest dispersion. As previously mentioned, the viscosity of the epoxy/PCL mixture is one of the key factors that affects the dispersion of the CNTs in the NCs. During the preparation of the samples, the addition of the ILs to the epoxy/PCL mixture reduced the viscosity, partially compensating for the increase caused by the PCL. The epoxy/PCL/IL blend that contained IL-P-DCA was the least viscous, followed by the IL-P-TMPP NC. In contrast, the addition of the IL-I-DCA to the epoxy/PCL barely reduced the viscosity of the mixture. This is consistent with the dispersion observed by TEM, and was further confirmed by the electrical properties discussed below.−14–10−15 S/cm) [−9–10−3 S/cm for NCs containing 0.2–0.3 wt% CNT).15 S/cm) . When co15 S/cm) ,69,70, tThe mechanical performance of the epoxy/PCL/CNT/IL NCs and the reference epoxy/IL, epoxy/PCL/IL, and epoxy/PCL/CNT/IL blends was tested using bending and impact tests. Regarding the low-strain mechanical properties , it is clear from As for high-strain mechanical properties, the ductility and impact strength of the epoxy/PCL/CNT/IL NCs and the reference systems are shown in In conclusion, the epoxy/PCL/CNT NCs cured with the different ILs presented an excellent balance of mechanical properties, showing similar or superior low-strain properties to the reference epoxy/IL and epoxy/PCL/IL systems, and did not in any way affect the positive impact of PCL on the high-strain mechanical properties.The adhesive properties of the epoxy systems in the study were measured by lap shear tests. As reported in one of our previous studies  and reflg and the crosslinking density of the reference epoxy/IL systems, the effect of adding the CNTs was negligible.The effect of the simultaneous addition of PCL and CNTs to an epoxy resin cured with three different ionic liquids was studied. The miscibility of the epoxy resin and the PCL remained constant in the epoxy/PCL/CNT/IL NCs. While the addition of PCL led to a decrease in both the TRegardless of the IL used, the resulting epoxy/PCL/CNT/IL NCs had an excellent balance of mechanical properties. The low-strain properties  improved in most cases with respect to the reference epoxy/IL and epoxy/PCL/IL systems, while the high-strain mechanical properties (ductility and impact strength) improved or did not disimprove significantly compared to the epoxy/IL and epoxy/PCL/IL systems, respectively. Moreover, the low-strain mechanical properties were similar or better than the reference epoxy/CNT/IL systems, while the high-strain mechanical properties improved considerably.The combined addition of PCL and CNTs also led to an outstanding improvement in the adhesive properties; the lap shear strength of the epoxy/PCL/CNT/IL NCs was better than that of any of the reference blends.Finally, despite the decrease in electrical conductivity caused by the presence of PCL and the poorer dispersion of the CNTs caused by the increase in viscosity, the epoxy/PCL/CNT/IL NCs were still considered semiconductive.Thus, the simultaneous addition of PCL and CNTs to epoxy systems cured with different ILs resulted in semiconductive materials with enhanced mechanical and adhesive properties. Because ionic liquids are non-volatile hardeners and can be used in lower concentrations than traditional amine-based curing agents, and because part of the DGEBA epoxy resin was replaced with biodegradable PCL, the blends in the present work represent an important contribution to the production of more sustainable materials.The optimization of the CNT and PCL contents in the NCs achieved in this study and their resulting enhanced balance of properties could pave the way for these NCs being used in advanced applications such as electronics packaging, wind turbine blades, structural adhesives, and sporting goods, and could also provide an interesting area for future research.


The future belongs to biodegradable epoxies. In order to improve epoxy biodegradability, it is crucial to select suitable organic additives. The additives should be selected so as to  accelerate the decomposition of crosslinked epoxies under normal environmental conditions. However, naturally, such rapid decomposition should not occur within the normal (expected) service life of a product. Consequently, it is desirable that the newly modified epoxy should exhibit at least some of the mechanical properties of the original material. Epoxies can be modified with different additives  that can increase their mechanical strength but does not lead to their biodegradability. In this work, we present several mixtures of epoxy resins together with organic additives based on cellulose derivatives and modified soya oil. These additives are environmentally friendly and should increase the epoxy’s biodegradability on the one hand without deteriorating its mechanical properties on the other. This paper concentrates mainly on the question of the tensile strength of various mixtures. Herein, we present the results of uniaxial stretching tests for both modified and unmodified resin. Based on statistical analysis, two mixtures were selected for further studies, namely the investigation of durability properties. Composites are widely used in the automotive and aerospace industries. Their advantages include low weight and infinite durability. Unfortunately, infinite durability is also a disadvantage. A large amount of non-biodegradable waste is generated. Thus, a method is needed to recycle the waste. Pyrolysis is the most commonly used method of recycling in the case of carbon-fiber-reinforced composites with an epoxy matrix (CFRP) . The recThe degree of the composite degradation was determined using the methods utilized in the evaluation of the composite cracking resistance ,4. An efw/w, can change the mechanical properties of epoxy composites in a significant way. The structural integrity of the composites and the interface of bonded layers, such as metal and composite, is ensured by adequate adhesion. The role of such issues in relation to the mechanical properties of structures was described by Bellini and his team in a 2019 paper [Scientific and research literature on the use of organic additives is extensive and relates mainly to compounds modifying interactions at the interface between the glass (carbon) fiber and the liquid epoxy matrix ,6,7. Num19 paper . However19 paper ,13,14,15One type of additive used in epoxy–glass composites is epoxidized natural oils that change the properties of the epoxy matrix, mainly by increasing their mechanical strength and impact strength. The effect of adding inedible oils of natural origins, e.g., karanja oil from Pongam tree seeds, to epoxy resins is described in . In the Particularly interesting are the works on adding organic substances, including epoxidized edible and inedible oils known and used as additives for diesel fuels, e.g., biodiesel . These sEnvironmental pollution and climate protection have intensified work on ecological additives that limit the extraction of fossil raw materials and enable the recycling of products after their use. A novel degradable and recyclable thermoset hyperbranched epoxy resin (EFTH-n) synthesized from bio-based 2,5-furandicarboxylic acid was described in work . It has The issue of biodegradability has been raised frequently in recent times. This is due not only to massive and growing environmental pollution but also dwindling fossil resources. Among the many works from 2020, those in which the chemical aspect is related to the strength and durability of materials, such as ,23,24, aAlthough a new type of hardener was patented in 2021, Recylamine, which makes the epoxy resin biodegradable after curing, is not the only hardener used in the pyrolysis process; the Z-1 (triethylene tetramine) hardener is still used. The study investigated the effect of various organic additives and their content on the tensile strength of rowing specimens made from them.The main objective of the study is to determine the tensile strength of specimens made of epoxy resin mixtures with natural additives.A change in the crosslinking of a polymer is achieved by introducing an additive in a certain proportion. After a set finite time, such a change should cause the failure of the cured epoxy resin. A gradual degradation of the polymer crosslinking will allow for the separation of the epoxy matrix from fibers, which leads to the partial degradation of the composite and the segregation of its components. The types of analyzed mixtures are listed in Some basic properties of Epidian 601 are collected in All mixtures were prepared using the method described below. In total, 100 g of Epoxy resin 601 was RT mixed up with 3 g or 10 g of organic additive, and 13 g of Z-1 crosslinking agent (triethylene tetramine from Zakłady Chemiczne Ciech Sarzyna) was added next, vigorously mixed for 5 min, and vacuum degassed for 10 min. All specimens of Epidian 601 with the organic additive and crosslinking agent were at first, right after addition, opaque and more viscous, but within 2–3 min after mixing, the specimens turned yellow again and were more transparent and less viscous, similarly to the starting Epidian 601 resin. Only after the addition of 3 phr or 10 phr of ethyl cellulose to the Epidian 601 resin did the specimens turn into an opaque white color and were more viscous; even after prolongated RT mixing for 10 min, they still remained unchanged. This observation suggests that EC, being more hydrophobic than other cellulose derivatives, was incompatible with Epidian 601 resin, forming a separate phase that weakly interacted with the surrounding resin. This was later confirmed by the poor mechanical properties of the Epidian/EC system. In preparation of Epidian/organic additive/crosslinking agent Z-1, it should be remembered that all mixing/degassing procedures must be completed within 30 min, because after 40 min, these systems start to gel, and no mixing or degassing is possible.The described mixtures were used to create test specimens for uniaxial tensile tests. Polastosil AD4 (Zakłady Chemiczne Ciech Sarzyna) was used to prepare the silicone mold. There have to be holes in the mold that match the shape and dimensions of the specimens that will be created. The reference specimens shown in The silicone molds with holes are shown in In Biodegradable epoxy resins should indicate physical and chemical properties, as well as mechanical properties, that are similar to unmodified resins with practically unlimited disintegration time. Therefore, experimental uniaxial stretching tests according to ASTM638 were conducted on test specimens made of epoxy resins with an organic additive. A series of reference test specimens made of unmodified epoxy were also examined. The nominal dimension of the test specimen is shown in Proper experimental testing requires additional specimen preparation. The specimens were cleaned and specially marked. The places of grips have been marked, as well as measurement points (black dots) spaced 30 mm apart. An exemplary set of test specimens prepared for testing that are made of epoxy resin E601 with the addition of ESO10 (epoxidized soybean oil) is shown in The KAPPA 50 DS electromechanical loading system with a ZwickRoell video extensometer a and speThe specialized testXpert ZwickRoell b softwarν) and destructive stresses and strains, fσ and fε, respectively, were determined for each group of specimens after rejecting the extreme results in the group. Young’s modulus E was determined on the basis of the slope of the diagram of stresses as a function of strains. Poisson’s ratio is a measure of deformation and has been defined as the slope angle of the transverse strain curve versus the longitudinal strain. The values of failure stresses and strains were determined as extreme stress and the corresponding strain of the stress function—longitudinal strain. The average values of Young’s modulus, Poisson’s ratio, stresses and failure strains together with the number of specimens are summarized in The tensile test results were developed for each specimen separately. The tensile Young’s modulus E, the ratio of the transverse strain to longitudinal strain in the uniaxial stress state  (fσ) were averaged for each test and presented in the form of diagrams (fε) (fε) and their standard deviation, which are presented in The obtained values of failure stresses . The average values of the same quantities obtained for specimens with additives were related to these values. The results in the form of ratios are shown as graphs in To determine the optimal content of the organic additive, the average values of Young’s modulus, Poisson’s ratio, failure stress and failure strain were determined for the E601 resin as reference values (EWe do not recommend ethyl cellulose (EC) as an additive to the epoxy resin due to its poor miscibility. The best miscibility with epoxy resin and the best-looking test specimens were observed when using carboxymethyl cellulose (CMC) additives.Both maximum values of strains and stresses in the stress–strain curves, higher than for epoxy resin, were observed for epoxy resins modified with epoxidized soya oil. The highest stresses were detected for epoxy E601 resin modified with 3 phr soya oil (ESO3), whereas the highest strains occurred for epoxy modified with 10 phr soya oil (ESO10) specimens.The smallest standard deviation values of Young’s modulus, Poisson’s ratio and stress and strain values were observed for epoxy resins modified with 3 phr added epoxidized soya oil (ESO3).Despite the imperfections of the prepared specimens and the small population of the tests carried out, the obtained results seem interesting and indicate the desirability of further extended research in biodegradation testing. We propose continuing research with epoxy resin modified with 3 phr epoxidized soya oil (ESO3) and 10 phr of methyl cellulose (MC10).