Internalization Degradation Research Articles

Abstract 2647: Novel FGFR2 biparatopic antibodies for the treatment of cholangiocarcinoma

Abstract Translocations involving Fibroblast Growth Factor Receptor 2 (FGFR2) are found in up to 45% of Intrahepatic Cholangiocarcinoma (ICC). Treatment of patients bearing FGFR2 fusions with FGFR kinase inhibitors induces tumor regressions, though response rate and durability of response appear limited due to the emergence of resistance or to sub-optimal dosing which is limited by drug adverse effects. Thus, therapeutics that drive activity specifically towards FGFR2 are needed to enhance drug efficacy and reduce adverse effects. We first asked whether the extracellular domain (ECD) of FGFR2-BICC1 fusion is functional and important for receptor dimerization and signaling using NanoBiT system and western blotting. FGFR ECD consists of 3 Ig-fold domains D1, D2, and D3. Using focus transformation and viability assays, we found that deletions in D1, D2, D3, and D2-3 ECD FGFR2-BICC1 decreased growth and transformation of FGFR2 fusion driven cells. Next, we sought to investigate if antibodies against the ECD could perturb the growth of FGFR2 fusion transformed cells. We identified six FGFR2 specific antibodies that bind to epitopes in the ECD and confirmed the ligand blocking activity of these bivalent antibodies. In the absence of ligand, however, most of the bivalent antibodies were relatively inactive. As standard bivalent antibodies engage two receptors at a time, they are at risk for agonism or the maintenance of tonic signaling. Thus, to enhance efficacy and prevent the potential agonist or tonic activity of bivalent antibodies, all possible biparatopic antibodies (15), recognizing two distinct epitopes on the FGFR2 ECD, were engineered from the six parental antibodies. The biparatopic antibodies exhibited enhanced efficacies in FGFR2-fusion driven NIH3T3/BaF3 and ICC13-7 cancer cell lines and significantly improved binding affinities (~10-fold) as analyzed by Octet, MSD-SET, and SPR. Two biparatopic antibodies (BpAb-1, BpAb-2) showed the highest antiproliferative activity and induced apoptosis in FGFR2 fusion driven cells. BpAb-1, BpAb-2 were superior to their parental antibodies in reducing FGFR2-fusion driven growth, transformation and downstream signaling (pFGFR2, pFRS) in vitro and in reducing tumor growth in xenograft models. Importantly, BpAb-1 and BpAb-2 significantly induced FGFR2 internalization and lysosomal-mediated degradation as compared to their parental antibodies. Moreover, BpAb-1 and BpAb-2 had anti-growth activities against ICC patient-derived oncogenic FGFR2 ECD in-frame deletions, and FGFR kinase resistance mutations, including the gatekeeper mutation V565F. BpAb-1 and BpAb-2 were also active in FGFR2 WT amplified cells SNU-16. These results suggest that these FGFR2 biparatopic antibodies are a novel treatment option for ICC patients with tumors harboring FGFR2 fusions. Citation Format: Saireudee Chaturantabut, Sydney Oliver, John Kim, Dennie Frederick, Foxy Robinson, Alessandro Sinopoli, Diego J. Rodriguez, Liang Chang, Nabeel Bardeesy, William Sellers. Novel FGFR2 biparatopic antibodies for the treatment of cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2647.

A Hierarchical Optimal Control of Uncertain and Time-Varying Knowledge Dissemination Model in Complex Network

In this paper, considering the multifactor influence of the knowledge dissemination process, a new ignorant-knower-spreader-forgetter (IKSF) knowledge dissemination model is proposed, which considers internalization mechanism, degradation mechanism, communication, and willingness, as well as time-varying and uncertain parameters. First, we prove that the knowledge loss equilibrium of the model is globally asymptotically stable when the basic reproduction number R 0 < 1 , and knowledge is permanent when R 0 > 1 . Next, improving the willingness of knower individuals and reducing the knowledge degradation function of spreader individuals can make the best effect of propagation; a hierarchical control strategy is designed. At the upper layer, an effective optimal control mechanism of the IKSF knowledge dissemination model is studied to provide optimal control action and minimization costs. At the lower layer, to guarantee robustness control performance and track the control targets, an intervention optimal guaranteed cost control strategy for the IKSF knowledge dissemination system with uncertain parameters is studied. Converting the controller’s design problem into a minimization problem with linear matrix inequalities, not only the impact of uncertain parameters is reduced but also the propagation effect of the knowledge dissemination model is guaranteed. Simulation results confirm our method.

Air- and Moisture Robust Surface Modification for Ni-Rich Layered Cathode Materials for Li-Ion Batteries.

The mainstream of high-energy cathode development is focused on increasing the Ni-ratio in layered structured cathode materials. The increment of the Ni portion in the layered cathode material escalates not only the deliverable capacity but also the structural degradation. High-Ni layered cathodes are highly vulnerable to exposure to air that contains CO2 and H2 O, forming problematic residual lithium compounds at the surface. In this work, a novel air- and moisture robust surface modification is reported for LiNi0.8 Co0.1 Mn0.1 O2 (NCM811) via the sol-gel coating method that selectively coats the internal surface area of the polycrystalline morphology secondary particles. Bare-, Li2 SnO3 -coated and LiCoO2 -coated NCM811 are exposed to different ambient environments (air, hot-air, and moisture-air) to systematically investigate the correlation between the internal/external coating morphology and performance degradations. The LiCoO2 -coated NCM811s exhibit high-capacity retention after exposure to all environments, due to the internal surface coating that prevents the penetration of harmful compounds into the polycrystalline NCM811. On the other hand, the Li2 SnO3 -coated NCM811s exposed to the ambient environments show gradual capacity fading, implying the occurrence of internal degradation. This paper highlights the impact of the internal degradation of polycrystalline NCM811 after environmental exposure and the correct coating mechanisms required to successfully prevent it.

Novel drug delivery system and characterization in advance techniques

Inflammatory diseases, cancer, cardiovascular diseases, Alzheimer's disease, atherosclerosis, and other degenerative diseases are all primarily brought on by oxidative damage disorders, also known as oxidative stress. This article seeks to provide an overview of the therapeutic potential of Gallic acid as a nanocarrier for disorders caused by oxidative damage. Gallic acid has also been found to have anti-inflammatory, antiviral, antibacterial, and significant antioxidant properties. Because of its slow absorption and low bioavailability, the usage of Gallic acid is constrained. The use of nanoformulation can help to remedy this. Nanotechnology has made it possible to deliver medications to the target site quickly and effectively. The medicinal efficacy of naturally occurring potential natural plant compounds has been hampered by poor water solubility and bioavailability.Nanocarriers have been used in recent studies to try to diagnose these issues because they are a logical method. They are created for controlled release at the target place in addition to safeguarding the medication from the internal environment and degradation after administration. Nanotechnology can be employed as a promising new method of medicine delivery to decrease the negative effects of natural substances.

Component Maintenance Strategies and Risk Analysis for Random Shock Effects Considering Maintenance Costs

Maintenance can improve a system’s reliability in a long operation period or when a component has failed. The reliability modeling method that uses the stochastic process degradation model to describe the system degradation process has been widely used. However, the existing reliability models established using stochastic processes only consider the internal degradation process, and do not fully consider the impact of external random shocks on their reliability modeling. Furthermore, the existing theory of importance does not consider the actual factors of maintenance cost. In this paper, based on the reliability modeling of random processes, the degradation rate under the influence of random shocks is introduced into the time scale function to solve the impact of random shocks on product reliability, and two cost importance measures are proposed to guide the maintenance selection of the components under limited resources in the system.Finally, a subsystem of an aircraft hydraulic system is analyzed to verify the proposed method’s performance.

The role of EphA2 in ADAM17- and ionizing radiation-enhanced lung cancer cell migration.

Ionizing radiation (IR) enhances the migratory capacity of cancer cells. Here we investigate in non-small-cell-lung-cancer (NSCLC) cells a novel link between IR-enhanced ADAM17 activity and the non-canonical pathway of EphA2 in the cellular stress response to irradiation. Cancer cell migration in dependence of IR, EphA2, and paracrine signaling mediated by ADAM17 was determined using transwell migration assays. Changes of EphA2 pS897 and mRNA expression levels upon different ADAM17-directed treatment strategies, including the small molecular inhibitor TMI-005, the monoclonal antibody MEDI3622, and shRNAs, were mechanistically investigated. ADAM17-mediated release and cleavage of the EphA2 ligand ephrin-A1 was measured using ELISA and an acellular cleavage assay. Irradiation with 5 Gy enhanced tumor cell migration of NSCLC NCI-H358 cells in dependence of EphA2. At the same time, IR increased growth factor-induced EphA2 S897 phosphorylation via auto- and paracrine signaling. Genetic and pharmaceutical downregulation of ADAM17 activity abrogated growth factor (e.g. amphiregulin) release, which reduced MAPK pathway-mediated EphA2 S897 phosphorylation in an auto- and paracrine way (non-canonical EphA2-pathway) in NCI-H358 and A549 cells. These signaling processes were associated with reduced cell migration towards conditioned media derived from ADAM17-deficient cells. Interestingly, ADAM17 inhibition with the small molecular inhibitor TMI-005 led to the internalization and proteasomal degradation of EphA2, which was rescued by amphiregulin or MG-132 treatment. In addition, ADAM17 inhibition also abrogated ephrin-A1 cleavage and thereby interfered with the canonical EphA2-pathway. We identified ADAM17 and the receptor tyrosine kinase EphA2 as two important drivers for (IR-) induced NSCLC cell migration and described a unique interrelation between ADAM17 and EphA2. We demonstrated that ADAM17 influences both, EphA2 (pS897) and its GPI-anchored ligand ephrin-A1. Using different cellular and molecular readouts, we generated a comprehensive picture of how ADAM17 and IR influence the EphA2 canonical and non-canonical pathway in NSCLC cells.

PV Defects Identification through a Synergistic Set of Non-Destructive Testing (NDT) Techniques

A synergistic set of NDT techniques, including I-V analysis, UVF imaging, IR thermography, and EL imaging, supports a diagnostics methodology developed in this work to qualitatively and quantitatively identify a wide range of PV defects. The methodology is based on (a) the deviation of the module electrical parameters at STC from their nominal values, for which a set of mathematical expressions was developed that provide an insight into potential defects and their quantitative impact on the module electrical parameters, and (b) the variation analysis of EL images captured at a sequence of bias voltages for a qualitative investigation on the spatial distribution and strength of the defects. The synergy of these two pillars, supported by UVF imaging, IR thermography, and I-V analysis cross-correlating their findings, makes the diagnostics methodology effective and reliable. It was applied on c-Si and pc-Si modules operating from 0-24 years, exhibiting a diversity of defects of varying severity, either pre-existing or formed by natural ageing or externally induced degradation. Defects such as EVA degradation, browning, corrosion in the busbar/interconnect ribbons, EVA/cell-interface delamination, pn-junction damage, e-+hole recombination regions, breaks, microcracks, finger interruptions, and passivation issues are detected. Degradation factors triggering a cascade of internal degradation processes through cause and effect are analysed and additional models are proposed for the temperature pattern under current mismatch and corrosion along the busbar, further empowering the cross-correlation of NDT results. Power degradation was determined from 1.2% in 2 years of operation to more than 50% in modules with film deposition.

Low-Density Polyethylene Degradation and Energy Yield Using Dielectric Barrier Discharge under Various Electrical Conditions

The increased use of plastics has seen the emergence of microplastics, which have become progressively more problematic. Although many degradation studies have been conducted to address the problem of microplastics, their impact has not been significant, and much time has been consumed. In this study, low-density polyethylene (LDPE) was degraded using a dielectric barrier discharge (DBD) plasma under various electrical conditions. The experimental results showed that after 120 min of treatment, the removal efficiency reached 5.44%, the carbonyl index (CI) was 1.7308, and the O/C ratio was 0.028. The degree of degradation shown in previous studies was achieved rapidly, and experimental results showed that the degree of LDPE degradation and energy yield was proportional to the voltage and frequency—more specifically, the degree of LDPE surface and internal degradation differed, which should be considered in terms of reducing the extent of mass loss. The results of this study should be helpful for future studies on microplastic degradation using DBD techniques.

Modeling coupled effects of dynamic environments and zoned shocks on systems under dependent failure processes

In this paper, we focus on systems suffering from multiple dependent competing failure processes under coupled effects of zoned shocks and dynamic environments. A reliability and maintenance model is developed for a real-time inspected system subject to linear degradation and random shocks, in which the internal degradation rate and shock arrival rate are affected by a dynamic environment. Shocks are classified into four zones based on their magnitude, including the safety zone, probability damage zone, damage zone, and fatal zone. Explicit formulas for calculating reliability indexes of systems are derived, including the reliability function, availability function, and steady-state availability. Meanwhile, simulation algorithms for calculating these reliability indexes are provided based on the Monte Carlo method, which is beneficial to the verification of the analytical method. Finally, a case study of micro-engine systems is given to illustrate the proposed models and obtained results, exhibiting that zoned shocks and dynamic environments have a significant effect on system performance.

Optimal Stopping and Loading Rules Considering Multiple Attempts and Task Success Criteria

Numerous engineering systems gradually deteriorate due to internal stress caused by the working load. The system deterioration process is directly related to the workload, providing opportunities for decision-makers to manage system deterioration by modifying the workload. As one of the most effective ways to control system malfunction risk, mission stopping has been extensively studied. Most existing research on mission stopping ignores the effect of working loads on the internal deterioration of safety-critical systems. The purpose of this work is to examine the optimal joint loading and stopping rules for systems subject to internal degradation under two types of mission success requirements (MSR). The problem is formulated using the recursive algorithm to minimize the expected cost over the mission. Mission reliability and system safety are assessed, and the optimal loading and stopping rules are investigated. The established models are illustrated by practical examples, and comprehensive policy comparison and parameter sensitivity analysis on the allowable mission time, mission duration and the number of mission tries are conducted. Our findings indicate that dynamic load level modification has a substantial effect on system deterioration and predicted long-term costs. For the purpose of decision-making, several managerial implications for the joint development of load adjustment and abort implementation are obtained.

Degradation of mortar fully buried in saline soil containing sodium sulfate or magnesium sulfate

The sulfate attack of salt solution and saline soil on concrete structures is an essential factor threatening their durability. The degradation of saline soil to concrete structures has attracted more attention than the salt solution in recent years. Thus, the degradation of mortar buried in saline soil containing sulfate ions was investigated in this study. Combined with the macro and micro degradation results, the saline soil does not change the internal degradation mechanism of mortar because the degradation products are also mainly composed of gypsum and ettringite. The degradation rate of soil containing sodium sulfate to mortar is more vital than that of the corresponding salt solution. However, the results are contrary for soil containing magnesium sulfate and the corresponding salt solution. An evident and movable degradation interface in the eroded mortar is observed based on a color difference along the direction of degradation; The fly ash with a high replacement (60 wt%) is unfavorable to the resistance of the mortar under sulfate attack, because it contains a high aluminum phase to form ettringite. The slag can increase the resistance of the mortar under sulfate attack due to its smaller content of aluminum phase and higher activity.

Enzymatically-Crosslinked Gelatin Hydrogels with Nanostructured Architecture and Self-Healing Performance for Potential Use as Wound Dressings.

Development of natural protein-based hydrogels with self-healing performance and tunable physical properties has attracted increased attention owing to their wide potential not only in the pharmaceutical field, but also in wounds management. This work reports the development of a versatile hydrogel based on enzymatically-crosslinked gelatin and nanogels loaded with amoxicillin (Amox), an antibiotic used in wound infections. The transglutaminase (TGase)-crosslinked hydrogels and encapsulating nanogels were formed rapidly through enzymatic crosslinking and self-assembly interactions in mild conditions. The nanogels formed through the self-assemble of maleoyl-chitosan (MAC5) and polyaspartic acid (PAS) may have positive influence on the self-healing capacity and drug distribution within the hydrogel network through the interactions established between gelatin and gel-like nanocarriers. The physicochemical properties of the enzymatically-crosslinked hydrogels, such as internal structure, swelling and degradation behavior, were studied. In addition, the Amox release studies indicated a rapid release when the pH of the medium decreased, which represents a favorable characteristic for use in the healing of infected wounds. It was further observed through the in vitro and in vivo biocompatibility assays that the optimized scaffolds have great potential to be used as wound dressings.

Reaction mechanism and mechanical properties of geopolymer based on kaolinitic coal tailings

Valorization of coal tailings as supplementary cementitious material is vital for green development, including their application as aluminosilicate in geopolymer materials. Coal tailings from southern Brazil were activated mechanically and thermally. This work analyzed the effect of calcium addition via Portland cement and flue gas desulfurization on the reaction mechanism of geopolymer using setting times and semi-adiabatic calorimetry. Additionally, un-calcined coal gangue was added to geopolymer cement to evaluate the effect of sulfur in the microstructure of geopolymer. The experimental results showed kaolinitic coal sludge was transformed into a metastable phase with higher reactivity, while X-ray pyrite reflection was observed for un-calcined coal gangue. The findings showed that calcium modified the reaction mechanism by accelerating the monomers' condensation and increasing the energy released, promoting the hardening of the geopolymer at 24 h. In addition, a solid matrix of geopolymer was developed compounded mainly by an amorphous inorganic polymer and C-A-S-H gel as a secondary phase. The thermodynamic simulation confirmed the addition of coal gangue reduced the pH of the pore solution and increased the content of SO42− and Fe2+. These results evidenced that partial oxidation of pyrite in an alkaline medium releases iron and sulfate ions and this process can lead to acidification of the pore solution resulting in internal degradation.

Battery State-of-Health Prediction-Based Clustering for Lifetime Optimization in IoT Networks

The Internet of Things (IoT) represents a pervasive system that continuously demonstrates an expanded application in various domains. The energy-efficiency problem has always been a crucial issue linked to this type of network where the system lifetime strongly depends on devices’ batteries. Numerous energy-efficient networking protocols have been proposed in the literature to increase the system lifetime. However, most of the proposed approaches deal with the short-term vision of energy consumption and omit to consider the rechargeable battery degradation when evaluating the network lifetime. Indeed, the major parts of the network devices use rechargeable batteries that age and degrade over time due to several factors (temperature, voltage, charging/discharging cycle, etc.). Therefore, it is essential to promptly detect these internal and environmental degradation factors to avoid network failures. Clustering represents one of the main wireless network protocols and plays an essential role in network self organizing. In this work, we propose a novel long-term energy optimization clustering approach based on battery State of Health (SoH) prediction, called LECA_SOH. The objective is to predict the impact of cluster heads election on the rechargeable batteries SoH before applying the clustering. LECA_SOH fosters the selection of the nodes, which will less suffer from battery degradation during the future rounds, leading to extend the system lifetime. The obtained results demonstrate that the proposed clustering approach improves the network lifetime in the long term and extends the number of recharging cycles compared to the conventional energy-efficient approaches.

Biomimetic Nanovaccines Potentiating Dendritic Cell Internalization via CXCR4-Mediated Macropinocytosis.

Although targeted delivery of nanoparticulate vaccines to dendritic cells (DCs) holds tremendous potential, it still faces insufficient internalization and endosome degradation via the receptor-mediated endocytosis pathway. Inspired by the advantages of CXC-chemokine receptor type 4 (CXCR4)-mediated macropinocytosis in the internalization of DCs, a multifunctional vaccine is constructed based on a reactive oxygen species (ROS)-responsive nanoparticulate core and macropinocytosis-inducing peptide-fused cancer membrane shell, allowing the direct cytosolic delivery of cancer membrane-associated antigen and a stimulator of interferon genes (STING) agonist, cGAMP for highly efficient cancer immunotherapy. The biomimetic nanovaccines show a dramatically enhanced cellular uptake by DCs via CXCR4-mediated macropinocytosis. Such a direct delivery process promotes cytosolic release of cGAMP in response to ROS, and together promoted DC maturation and T cell priming by activating the STING pathway. Consequently, the biomimetic nanovaccines not only result in a great tumor rejection in prophylactic B16-F10 melanoma murine model, but also markedly suppress the growth of established melanoma tumors when combined with anti-PD-1 checkpoint blockade. This study advances the design of biomimetic nanovaccines and provides a promising strategy for macropinocytosis-mediated cancer vaccination.

Automotive Diesel Fuel Internal Stability Testing with the Use of UV and Temperature as Degradation Factors

Diesel fuel stability can be considered from many points of view, of which the two considered most important are stability in contact with the environment and internal stability. Fuel stability in touch with the environment is often defined as oxidation stability, of which measurement procedures are well developed. The presented paper shows that fuel's internal stability can also be important. The internal stability of diesel fuel with the local use of thermal and ultraviolet radiation (UV) as degradation factors and fluorescence signals as a probe is presented in this paper. We show that the internal degradation of fuel with temperature use differs from that with UV and simultaneous both factors use. Our study shows that using temperature as a degradation factor introduces significant fluorescence fading. Moreover, the fluorescence signal restores significantly later than the sample stabilizes at room temperature. The novelty proposed based on examination is hybrid degradation and an examination cycle that enables the simultaneous use of degradation factors and fluorescence reading. For this purpose, a dedicated measurement setup of signal control and processing was constructed and programmed. The measurement procedure of the data series for specific wavelength enables calculation of signal shifts that allow the internal stability classification of diesel fuel samples in less than 30 min with the cost of a single disposable capillary probe and one polymer plug. Premium and regular fuel examination results show that internal fuel stability can be related to polycyclic aromatic hydrocarbons (PAH) concentrations and can be modified with dedicated additives.

Interactions of the Fungal Community in the Complex Patho-System of Esca, a Grapevine Trunk Disease.

Worldwide, Esca is a complex and devastating Grapevine Trunk Disease (GTD), characterized by inconstant foliar symptoms and internal wood degradation. A large range of fungal taxa have been reported as causal agents. We applied both culture-dependent and culture-independent methods (Illumina Technology and q-PCR) to investigate this concerning disease. Woods from vines with asymptomatic leaves and vines with leaf Esca symptoms were compared. Internally, different types of wood were found, from healthy wood with black necrosis to wood with white rot. A combination of leaf and wood Esca symptoms resulted in four experimental categories. Although there was no relation with symptoms, culture-independent mycobiome composition revealed Phaeomoniella chlamydospora, a GTD pathogen, as the most abundant species (detected in 85.4% of wood samples, with 14.8% relative abundance). Using TaqMan q-PCR, P. chlamydospora DNA was detected in 60.4% of samples (far from the 18.8% of positive results in the culture-dependent approach). There was a predominance of saprotrophs, even if their abundance was not affected by Esca symptoms. Concerning pathotrophs, the white rot development within grapevines was linked to the abundance of fungi belonging to the Hymenochaetaceae family. The Botryosphaeriaceae family was identified as an indicator for expression of Esca foliar symptoms. Lastly, the Aureobasidiaceae family was found to be a potential biocontrol agent for Esca, since it was most abundant in the control asymptomatic plants.

Bifunctional Compounds as Molecular Degraders for Integrin-Facilitated Targeted Protein Degradation.

As effective ways to regulate protein levels, targeted protein degradation technologies have attracted great attention in recent years. Here, we established a novel integrin-facilitated lysosomal degradation (IFLD) strategy to degrade extracellular and cell membrane proteins using bifunctional compounds as molecular degraders. By conjugation of a target protein-binding ligand with an integrin-recognition ligand, the resulting molecular degrader proved to be highly efficient to induce the internalization and subsequent degradation of extracellular or cell membrane proteins in an integrin- and lysosome-dependent manner. As demonstrated in the development of BMS-L1-RGD, which is an efficient programmed death-ligand 1 (PD-L1) degrader validated both in vitro and in vivo, the IFLD strategy expands the toolbox for regulation of secreted and membrane-associated proteins and thus has great potential to be applied in chemical biology and drug discovery.

Thermal cycle degradation of alumina-silica refractories exposed to molten Al-5Mg alloy

In this study, degradation by so-called “Obake” , an advanced stage of an external corundum growth on alumina-silica refractory surfaces, was investigated. The Obake was successfully recreated by melting Al-5%Mg in the alumina-silica crucible under thermal cycle conditions. The thermal test temperatures were chosen at 1000°C or 1150°C. It was confirmed that internal degradation occurred by formation of spinel (MgAl2O4) where the refractory was in touch with molten Al-5Mg and by corundum growth at completely separate location that is at or in the vicinity of the melt line of the refractory surface where the following reaction would take place.

Selective oxidation and possible mode of porous oxide formation on welded Al alloy at high-temperature condition

High-temperature exposure leads to a non-protective oxide scale that involves selective oxidation of a welded aluminum alloy. This process resulted in a change of alloy composition, especially in the subsurface of the welded zone which is also known as fusion metal. This paper focused on a phase transformation in the welded A6061 Al alloy. It has been assumed that phase transformation involves the formation of new phases and the dissolution of current phases, depending on the system being welded. In this study, the welded A6061 Al alloy was subjected to a high-temperature oxidation test in the hot air furnace at 600 °C for 40 h. The oxidized samples were studied using a LEO 1450 model scanning electron microscope (SEM) is typically equipped with an energy dispersive X-ray analyzer (EDX) to determine the oxide flake morphology, oxides cross-sectional images, and pre-existing structures. Meanwhile, phase identification analysis was carried out using a Bruker AXS: D8 Advance X-ray diffractometer (XRD). The result shows that the selective oxidation of Al from welded A6061 alloy forms MgO on the alloy surface. The MgO was suggested to inhibit further oxidation underneath the oxide scale and allowed the oxygen to diffuse into the internal welded substrate and react. This could lead to the formation of Al2O3. Inward diffusion of Al and Mg causes the formation of MgAl2O4 spinel and Al2O3 alumina which leads to the internal degradation of the welded substrate. A thick outer oxide layer is formed, consisting of the oxides of the base metal (MgO, Al2O3), with layers of different oxide combinations (MgO or Al2O3 or MgO + Al2O3, forming MgAl2O4). Below this layer is a region depleted of the alloying element Al.