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Alternative strategies to design sustainable-element-based electrocatalysts enhancing oxygen evolution reaction (OER) kinetics are demanded to develop affordable yet high-performance water-electrolyzers for green hydrogen production. Here, it is demonstrated that the spontaneous-spin-polarized 2D π-d conjugated framework comprising abundant elements of nickel and iron with a ratio of Ni:Fe = 1:4 with benzenehexathiol linker (BHT) can improve OER kinetics by its unique electronic property. Among the bimetallic NiFex:y-BHTs with various ratios with Ni:Fe = x:y, the NiFe1:4-BHT exhibits the highest OER activity. The NiFe1:4-BHT shows a specific current density of 140 A g-1 at the overpotential of 350 mV. This performance is one of the best activities among state-of-the-art non-precious OER electrocatalysts and even comparable to that of the platinum-group-metals of RuO2 and IrO2. The density functional theory calculations uncover that introducing Ni into the homometallic Fe-BHT (e.g., Ni:Fe = 0:1) can emerge a spontaneous-spin-polarized state. Thus, this material can achieve improved OER kinetics with spin-polarization which previously required external magnetic fields. This work shows that a rational design of 2D π-d conjugated frameworks can be a powerful strategy to synthesize promising electrocatalysts with abundant elements for a wide spectrum of next-generation energy devices.
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Sacran is a cyanobacterial supergiant polysaccharide with carboxylate and sulfate groups that exhibits antiallergic and antiinflammatory properties. However, its high anionic functions restrict cell compatibility. Quaternary ammonium groups were substituted to form sacran ampholytes, and the cell compatibility of the cationized sacran hydrogels was evaluated. The cationization process involved the reaction of N-(3-chloro-2-hydroxypropyl)trimethylammonium chloride with the primary amine or hydroxyl groups of sacran. The degree of cationization ranged from 32 to 87% for sugar residues. Hydrogels of sacran ampholytes were prepared by annealing their dried sheets by thermal cross-linking; these hydrogels exhibited anisotropic expansion properties. The water contact angle on the hydrogels decreased from 26.5 to 15.3° with an increase in the degree of cationization, thereby enhancing hydrophilicity. The IC50 values of sacran ampholytes decreased with an increased degree of cationization, resulting in a reduction in cytotoxicity toward the L-929 mouse fibroblast cell line. This reduction was associated with an increase in the cell proliferation density after 3 days of incubation. Scanning electron microscopy images showed fibroblast intercellular connections. Therefore, the sacran ampholyte hydrogel exhibited increased hydrophilicity and cell compatibility, which is beneficial for various biomedical applications.
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Adsorbents with hydrophilic and hydrophobic natures were designed by intercalating a bioderived molecule; 4,4'-diammonium-α-truxillic acid (4ATA) and 4,4'-diammonium-α-truxillic acid dimethyl ester (E4ATA), which both are bioderived molecules, into a smectite (purified bentonite) to concentrate o-phenylphenol and biphenyl, respectively, from water. The adsorption isotherm showed high affinity between the 4ATA-smectite hybrid and o-phenylphenol with a high Langmuir constant (0.98 L mg-1). Meanwhile, the E4ATA-smectite hybrid adsorbed biphenyl with a high Langmuir constant (3.61 L mg-1). The adsorption properties of 4ATA- and E4ATA-smectite hybrid were contributed by the chemical characteristics of 4ATA and E4ATA in the interlayer space of the smectite.
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Polybenzimidazoles (PBIs) are recognized for their remarkable thermal stability due to their unique molecular structure, which is characterized by aromaticity and rigidity. Despite their remarkable thermal attributes, their tensile properties limit their application. To improve the mechanical performance of PBIs, we made a vital modification to their molecular backbone to improve their structural flexibility. Non-π-conjugated components were introduced into PBIs by grafting meta-polyamide (MA) and para-polyamide (PA) onto PBI backbones to form the copolymers PBI-co-MA and PBI-co-PA. The results indicated that the cooperation between MA and PA significantly enhanced mechanical strain and overall toughness. Furthermore, the appropriate incorporation of aromatic polyamide components (20 mol% for MA and 15% for PA) improved thermal degradation temperatures by more than 30 °C. By investigating the copolymerization of PBIs with MA and PA, we unraveled the intricate relationships between composition, molecular structure, and material performance. These findings advance copolymer design strategies and deepen the understanding of polymer materials, offering tailored solutions that address thermal and mechanical demands across applications.
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OBJECTIVE: To examine the patterns of pretreatment facial soft tissue shape in orthodontic cases with premolar extraction using artificial intelligence (AI) and to investigate the corresponding changes. METHODS: One hundred and fifty-two patients who underwent orthodontic treatment with premolar extraction were enrolled. Lateral cephalograms were obtained before and after the treatment. For each record, the outlines of the nose-lip-chin profile and corresponding 21 cephalometric variables were extracted. The AI method classified pretreatment records into three subject groups based on the feature variables extracted from the outline. Dentoskeletal and soft tissue facial form changes observed after treatment were compared statistically (P < 0.05) between the groups using ANOVA. Multivariate regression models were used for each group. RESULTS: Group 1 (n = 59) was characterized by Class II high-angle retrognathic mandible with an incompetent lip, group 2 (n = 55) by Class I malocclusion with retruded and thin lips, and group 3 (n = 38) by Class I malocclusion with an everted superior lip before treatment. The ratios of anteroposterior soft tissue to hard tissue movements in Group 1 were 56% (r = 0.64) and 83% (r = 0.75) for the superior and inferior lips, respectively, whereas those in Group 2 were 49% (r = 0.78) and 91% (r = 0.80), and 40% (r = 0.54) and 79% (r = 0.70), respectively, in Group 3. CONCLUSIONS: The modes of facial form changes differed depending on the pre-treatment profile patterns classified by the AI. This indicates that the determination of the pre-treatment profile pattern can help in the selection of soft tissue to hard tissue movement ratios, which helps estimate the post-treatment facial profile with a moderate to high correlation.
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Inteligência Artificial , Dente Pré-Molar , Cefalometria , Face , Lábio , Má Oclusão Classe I de Angle , Nariz , Extração Dentária , Humanos , Cefalometria/métodos , Face/anatomia & histologia , Feminino , Masculino , Lábio/anatomia & histologia , Adolescente , Nariz/anatomia & histologia , Nariz/patologia , Má Oclusão Classe I de Angle/terapia , Queixo/anatomia & histologia , Queixo/patologia , Má Oclusão Classe II de Angle/terapia , Má Oclusão Classe II de Angle/diagnóstico por imagem , Mandíbula , Técnicas de Movimentação Dentária/métodos , Criança , Adulto Jovem , Má Oclusão/terapia , Má Oclusão/classificaçãoRESUMO
Heterostructures of two-dimensional materials realise novel and enhanced physical phenomena, making them attractive research targets. Compared to inorganic materials, coordination nanosheets have virtually infinite combinations, leading to tunability of physical properties and are promising candidates for heterostructure fabrication. Although stacking of coordination materials into vertical heterostructures is widely reported, reports of lateral coordination material heterostructures are few. Here we show the successful fabrication of a seamless lateral heterojunction showing diode behaviour, by sequential and spatially limited immersion of a new metalladithiolene coordination nanosheet, Zn3 BHT, into aqueous Cu(II) and Fe(II) solutions. Upon immersion, the Zn centres in insulating Zn3 BHT are replaced by Cu or Fe ions, resulting in conductivity. The transmetallation is spatially confined, occurring only within the immersed area. We anticipate that our results will be a starting point towards exploring transmetallation of various two-dimensional materials to produce lateral heterojunctions, by providing a new and facile synthetic route.
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Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-15 , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Receptores Proteína Tirosina Quinases/genéticaRESUMO
Recent studies on molecular 2D materials with high tunability of structure and function have focused mostly on the discovery of new precursors. Here, we demonstrate a facile one-pot synthesis of laminated 2D coordination polymer films comprising bis(terpyridine)iron and cobalt at a water/dichloromethane interface. Cross-sectional elemental mapping unveiled the stratum-like structure of the film and revealed that the second layer grows to the dichloromethane side below the first layer. Cyclic voltammetry clarified that the bottom layer mediates charge transfer between the top layer and the substrate in a narrow potential region of mixed-valence states. Furthermore, the bilayer film sandwiched by electrodes in a dry condition shows stable rectification character, and the barrier voltage corresponds to the redox potential difference between the two layers. This study introduces a new strategy for polymer design to explore the materials science of molecular 2D materials.
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Invited for the cover of this issue is the group of Hiroshi Nishihara at Tokyo University of Science. The image depicts the moment of the growth of the second layer at the liquid-liquid interface to form a heterolaminated film. Read the full text of the article at 10.1002/chem.202201316.
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Nanomembranes are effective coating materials for protecting substrates from external stimuli; however, they are generally not self-standing owing to their low mechanical toughness. Self-standing nanomembranes would be an innovative development in the field of nanotechnology including miniaturized devices. In this study, self-standing nanomembranes were developed by spin-casting supertough polyamides over dimethylformamide solution. The polyamides were synthesized by the polycondensation of two derivatives of 4,4'-diamino-α-truxillic acid (4ATA) with slightly bent diphenylcyclobutane in the core. Mechanical evaluation of the 4ATA polyamides having an appropriate composition of aliphatic diacids revealed a high strain-energy density of 231 MJ m-3 at its maximum, which is significantly tougher than spider silk. The nanocoats with a thickness of several hundred nanometers showing interference fringes were able to be peeled off the glass substrate without breaking, owing to its ultrahigh toughness. The self-standing nanomembrane would be applied to flexible devices in the future.
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Nylons , Plásticos , Nanotecnologia , Seda/químicaRESUMO
The aromatic diamine 2-(4-aminophenyl)ethylamine (4APEA) is a potential monomer for polymers and advanced materials. Here, 4APEA was produced by fermentation using genetically engineered Escherichia coli (Masuo et al.2016). Optimizing fed-batch cultures of this strain produced the highest reported yield to date of 4APEA (7.2%; 3.5 g/L versus glucose) within 72 h. Appropriate aeration was important to maximize production and avoid unfavorable 4APEA degradation. Fermented 4APEA was purified from culture medium and polymerized with methylene diphenyldiisocyanate and hexamethylene diisocyanate to produce polyureas PU-1 and PU-2, respectively. The decomposition temperatures for 10% weight loss (Td10) of PU-1 and PU-2 were 276 °C and 302 °C, respectively, and were comparable with that of other thermostable aromatic polyureas. This study is the first to synthesize polyureas from the microbial aromatic diamine. Their excellent thermostability will be useful for the industrial production of heat-resistant polymer materials.
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Escherichia coli , Temperatura Alta , Diaminas/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Glucose/metabolismo , Engenharia Metabólica , FenetilaminasRESUMO
Photoluminescent coordination nanosheets (CONASHs) comprising three-way terpyridine (tpy) ligands and zinc(II) ions are created by allowing the two constitutive components to react with each other at a liquid/liquid interface. Taking advantage of bottom-up CONASHs, or flexibility in organic ligand design and coordination modes, we demonstrate the diversity of the tpy-zinc(II) CONASH in structures and photofunctions. A combination of 1,3,5-tris[4-(4'-2,2':6',2â³-terpyridyl)phenyl]benzene (1) and Zn(BF4)2 affords a cationic CONASH featuring the bis(tpy)Zn complex motif (1-Zn), while substitution of the zinc source with ZnSO4 realizes a charge-neutral CONASH with the [Zn2(µ-O2SO2)2(tpy)2] motif [1-Zn2(SO4)2]. The difference stems from the use of noncoordinating (BF4-) or coordinating and bridging (SO42-) anions. The change in the coordination mode alters the luminescence (480 nm blue in 1-Zn; 552 nm yellow in 1-Zn2(SO4)2). The photophysical property also differs in that 1-Zn2(SO4)2 shows solvatoluminochromism, whereas 1-Zn does not. Photoluminescence is also modulated by the tpy ligand structure. 2-Zn contains triarylamine-centered terpyridine ligand 2 and features the bis(tpy)Zn motif; its emission is substantially red-shifted (590 nm orange) compared with that of 1-Zn. CONASHs 1-Zn and 2-Zn possess cationic nanosheet frameworks with counteranions (BF4-), and thereby feature anion exchange capacities. Indeed, anionic xanthene dyes were taken up by these nanosheets, which undergo quasi-quantitative exciton migration from the host CONASH. This series of studies shows tpy-zinc(II) CONASHs as promising potential photofunctional nanomaterials.
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ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: New approach for the diagnosis of extractions with neural network machine learning. Seok-Ki Jung and Tae-Woo Kim. Am J Orthod Dentofacial Orthop 2016;149:127-33. SOURCE OF FUNDING: Not reported. TYPE OF STUDY/DESIGN: Mathematical modeling.
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Inteligência Artificial , Sistemas Inteligentes , Tomada de Decisões , Humanos , Aprendizado de Máquina , Redes Neurais de ComputaçãoRESUMO
Galnt3, UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3, transfers N-acetyl-D-galactosamine to serine and threonine residues, initiating mucin type O-glycosylation of proteins. We searched the target genes of Runx2, which is an essential transcription factor for chondrocyte maturation, in chondrocytes and found that Galnt3 expression was up-regulated by Runx2 and severely reduced in Runx2(-/-) cartilaginous skeletons. To investigate the function of Galnt3 in chondrocytes, we generated Galnt3(-/-) mice and chondrocyte-specific Galnt3 transgenic mice under the control of the Col2a1 promoter-enhancer. Galnt3(-/-) mice showed a delay in endochondral ossification and shortened limbs at embryonic day 16.5, suggesting that Galnt3 is involved in chondrocyte maturation. Galnt3 transgenic mice presented dwarfism, the chondrocyte maturation was retarded, the cell cycle in chondrocytes was accelerated, premature chondrocyte apoptosis occurred, and the growth plates were disorganized. The binding of Vicia villosa agglutinin, which recognizes the Tn antigen (GalNAc-O-Ser/Thr), was drastically increased in chondrocytes, and aggrecan (Acan) was highly enriched with Tn antigen. However, safranin O staining, which recognizes glycosaminoglycans (GAGs), and Acan were severely reduced. Chondroitin sulfate was reduced in amount, but the elongation of chondroitin sulfate chains had not been severely disturbed in the isolated GAGs. These findings indicate that overexpression of Galnt3 in chondrocytes caused dwarfism due to the increase of mucin-type O-glycans and the reduction of GAGs, probably through competition with xylosyltransferases, which initiate GAG chains by attaching O-linked xylose to serine residues, suggesting a negative effect of Galnt family proteins on Acan deposition in addition to the positive effect of Galnt3 on chondrocyte maturation.
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Condrócitos/metabolismo , Sulfatos de Condroitina/metabolismo , Nanismo/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , Processamento de Proteína Pós-Traducional , Agrecanas/genética , Agrecanas/metabolismo , Animais , Apoptose , Cartilagem/metabolismo , Cartilagem/patologia , Proliferação de Células , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Feminino , Expressão Gênica , Glicosilação , Lâmina de Crescimento/metabolismo , Lâmina de Crescimento/patologia , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , N-Acetilgalactosaminiltransferases/genética , Osteogênese , Polipeptídeo N-AcetilgalactosaminiltransferaseRESUMO
A proton-electron dual-responsive system based on a hybrid of ferrocene and metalladithiolene (1) was developed. The formation of the dithiafulvenium moiety was driven by protonation of the metalladithiolene unit of 1 and by oxidation. The change in the electronic structure caused by the protonation was combined with the redox properties of the two components of 1, generating two radical species with different spin density distributions (3d spin and π spin). Furthermore, a spin-reconstructed proton-coupled electron transfer, i.e., the transformation from 3d spin to π spin accompanied by deprotonation, was achieved by a temperature change, the third external stimulus.
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A series of electrochromic metal complex nanosheets comprising 1,3,5-tris(4-(2,2':6',2â³-terpyridyl)phenyl)benzene or 1,3,5-tris((2,2':6',2â³-terpyridyl)ethynyl)benzene and Fe(2+) or Co(2+) was synthesized. The preparation of multilayered nanosheets was achieved by liquid/liquid interfacial synthesis using an organic ligand solution and an aqueous metal-ion solution. The resultant nanosheet had a flat, smooth morphology and was several hundreds of nanometers thick. Upon its deposition on an indium tin oxide (ITO) electrode, the nanosheet underwent a reversible and robust redox reaction (Fe(3+)/Fe(2+) or Co(2+)/Co(+)) accompanied by a distinctive color change. Electrochromism was achieved in a solidified device composed of the nanosheet, a pair of ITO electrodes, and a polymer-supported electrolyte. The combination of Fe(2+) and Co(2+) nanosheets in one device-deposited on each ITO electrode-demonstrated dual-electrochromic behavior.
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AIMS: This case report describes the management of an adult patient presenting with a skeletal Class II malocclusion with congenitally missing lower second premolars, maxillary dentoalveolar protrusion, and an excessive gingival display in full smile. METHODS: The treatment plan consisted of a combination of a segmental osteotomy to reposition the anterior part of the maxilla after upper premolar extractions and a bilateral sagittal split osteotomy (BSSO) to advance the mandible. Because the upper left permanent second molar required extraction, the upper left third molar was moved mesially during post-surgical orthodontic treatment. RESULTS: After active treatment, bilateral Class I molar and canine relationships were achieved. Two years after retention, a satisfactory facial profile and dental occlusion remained with optimum overjet and overbite. Treatment also produced changes in the threedimensional (3D) configuration of the face, which was characterised by decreased labial protrusion, increased protrusion of the chin, and increased cheek prominence. CONCLUSION: A segmental osteotomy of the anterior part of the maxilla produced favourable treatment results by reducing excessive gingival display, but also by a relative improvement in cheek prominence.
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Cefalometria/métodos , Gengiva/patologia , Imageamento Tridimensional/métodos , Má Oclusão Classe II de Angle/cirurgia , Osteotomia Maxilar/métodos , Anodontia/diagnóstico , Dente Pré-Molar/anormalidades , Bochecha/patologia , Queixo/patologia , Feminino , Seguimentos , Gengiva/cirurgia , Humanos , Lábio/patologia , Avanço Mandibular/métodos , Dente Serotino/patologia , Osteotomia Sagital do Ramo Mandibular/métodos , Planejamento de Assistência ao Paciente , Retrognatismo/cirurgia , Sorriso , Extração Dentária , Técnicas de Movimentação Dentária/métodos , Resultado do Tratamento , Adulto JovemRESUMO
Ionic polymers are intriguing materials whose functionality arises from the synergy between ionic polymer backbones and counterions. A key method for enhancing their functionality is the post-synthetic ion-exchange reaction, which is instrumental in improving the chemical and physical properties of polymer backbones and introducing of the functionalities of the counterions. Electronic interaction between host polymer backbone and guest ions plays pivotal roles in property modulation. The current study highlights the modulation of responses to external electric field in cationic bis(terpyridine)cobalt(II) polymer nanofilms through anion-exchange reactions. Initially, as-prepared chloride-containing polymers exhibited supercapacitor behaviour. Introducing anionic metalladithiolenes into the polymers altered the behaviour to either conductive or insulative, depending on the valence of the metalladithiolenes. This modulation was accomplished by fine tuning of charge-transfer interactions between the bis(terpyridine)cobalt(II) complex moieties and redox-active anions. Our findings open up new avenue for ionic polymers, showcasing their potential as versatile platform in materials science.
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The effects of water absorption on the electric resistivity and dielectric constant of polyimide (PI) and poly(ethylene terephthalate) (PET) were investigated, and the mechanism of deterioration in electrical insulation properties was discussed. The polyimides are poly(oxydianiline pyromellitimide) (PMDA-ODA) and poly(para-phenylene diamine biphenyltetracarboxydiimide) (BPDA-PDA). These polymer films were immersed in pure water for various immersion times at room temperature, and the water absorption ratio was evaluated. The electric resistance for these films was measured at room temperature using a high-resistance meter, and the dielectric constant at room temperature was measured using an LCR meter in a frequency range of 200 kHz to 2 MHz. The absorption ratios at equilibrium absorption for PMDA-ODA, BPDA-PDA, and PET were 2.7, 2.5, and 0.5%, respectively. The critical volume fraction of the percolation threshold of electric conductivity due to water absorption was 0.034 for both PMDA-ODA and BPDA-PDA. On the other hand, PET did not show a significant decrease in the resistivity. For both PIs and PET, the dielectric constant observed could be explained by a series model of the respective capacitances of pure water and polymer. Actually, the resistivity of samples cut from the edges of the film after water absorption was almost the same value as that in the dry state. These results suggest that the absorbed water molecules are not uniformly dispersed in the film but are localized at the edges of the film even after the absorption equilibrium has been reached.
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PURPOSE: Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC. METHODS: We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003). RESULTS: A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046). CONCLUSION: ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.