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An efficient palladium-catalyzed [2 + 2 + 1] annulation of 3-iodochromones, bridged olefins, and iodomethane is described, affording a range of chromone-containing polycyclic compounds. Additionally, the corresponding deuterated products were smoothly obtained with iodomethane-d3 instead of iodomethane. Moreover, the synthetic utility of this method is further substantiated by gram scale preparation and application to late-stage modification of estrone.
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A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRTâPCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.
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MicroRNAs , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Vasos Coronários/metabolismo , Estudo de Associação Genômica Ampla , Movimento Celular , Lipoproteínas LDL/farmacologia , Células Cultivadas , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , MicroRNAs/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Moléculas de Adesão Celular/genéticaRESUMO
Inspired by the brilliant photochemical and photophysical properties of organic molecules containing chalcogenide substitutions that could be potentially applied across various disciplines, in this work, the effects of the atomic electronegativity of chalcogens (O, S, and Se) on hydrogen bond interactions and excited state proton transfer (ESPT) are mainly focused. We present characteristic oxygen-hydroxybenzazole-substituted 2,5-bis(4,5-diphenyl-1H-imidazol-2-yl)benzene-1,4-diol (BDIBD) derivatives that contain intramolecular double hydrogen bonds. The main objective of this study was to explore in detail the influence of the change of chalcogen atomic electronegativity on dual hydrogen bond interaction and ESPT behavior. By comparing the structural changes and infrared (IR) vibrational spectra of BDIBD derivative (BDIBD-O, BDIBD-S and BDIBD-Se) fluorophores in S0 and S1 states, combined with the preliminary detection of hydrogen bond interaction via the core-valence bifurcation (CVB) index and predicted hydrogen bonding energy (EHB), we conclude that dual hydrogen bonds should be strengthened in the S1 state, which is favorable for the occurrence of ESPT reactions. The charge recombination behavior of hydrogen bonds, induced by photoexcitation, further illustrates this point. By constructing potential energy surfaces (PESs) based on restrictive optimization and by searching the transition state (TS) structure, we finally elucidate stepwise excited-state double proton transfer (ESDPT). Specifically, we confirm that a change in atomic electronegativity has a regulatory effect on the ESDPT behavior in BDIBD derivatives, that is, lower atomic electronegativity is more conducive to stepwise ESDPT.
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Due to the extremely high bond energy of N≡N (â¼941 kJ/mol), the traditional Haber-Bosch process of ammonia synthesis is known as an energy-intensive and high CO2-emission industry. In this paper, a cascade N2 reduction process with dielectric barrier discharge (DBD) plasma oxidation and electrocatalytic reduction as an alternative route is first proposed. N2 is oxidized to be reactive nitrogen species (RNS) by nonthermal plasma, which would then be absorbed by KOH solution and electroreduced to NH4+. It is found that the production of NOx is a function of discharge length, discharge power, and gas flow rate. Afterward, the cobalt catalyst is used in the process of electrocatalytic reduction of ammonia, which shows high selectivity (Faradic efficiency (FE) above 90%) and high yield of ammonia (45.45 mg/h). Finally, the cascade plasma oxidation and electrocatalytic reduction for ammonia synthesis is performed. Also, the performance of the reaction system is evaluated. It is worth mentioning that a stable and sustainable ammonia production efficiency of 16.21 mg/h is achieved, and 22.16% of NOx obtained by air activation is converted into NH4+. This work provides a demonstration for further industrial application of ammonia production with DBD plasma oxidation and electrocatalytic reduction techniques.
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Amônia , Plasma , Oxirredução , Ar , Óxido NítricoRESUMO
Molecularly imprinted membranes (MIMs), the incorporation of a given target molecule into a membrane, are generally used for separating and purifying the effective constituents of various natural products. They have been in use since 1990. The application of MIMs has been studied in many fields, including separation, medicine analysis, solid-phase extraction, and so on, and selective separation is still an active area of research. In MIM separation, two important membrane performances, flux and permselectivities, show a trade-off relationship. The enhancement not only of permselectivity, but also of flux poses a challenging task for membranologists. The present review first describes the recent development of MIMs, as well as various preparation methods, showing the features and applications of MIMs prepared with these different methods. Next, the review focuses on the relationship between flux and permselectivities, providing a detailed analysis of the selective transport mechanisms. According to the majority of the studies in the field, the paramount factors for resolving the trade-off relationship between the permselectivity and the flux in MIMs are the presence of effective high-density recognition sites and a high degree of matching between these sites and the imprinted cavity. Beyond the recognition sites, the membrane structure and pore-size distribution in the final imprinted membrane collectively determine the selective transport mechanism of MIM. Furthermore, it also pointed out that the important parameters of regeneration and antifouling performance have an essential role in MIMs for practical applications. This review subsequently highlights the emerging forms of MIM, including molecularly imprinted nanofiber membranes, new phase-inversion MIMs, and metal-organic-framework-material-based MIMs, as well as the construction of high-density recognition sites for further enhancing the permselectivity/flux. Finally, a discussion of the future of MIMs regarding breakthroughs in solving the flux-permselectivity trade-off is offered. It is believed that there will be greater advancements regarding selective separation using MIMs in the future.
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It is an effective strategy to avoid obesity by inhibiting the activity of lipase. In this study, the binding mechanism of lipase and Lentinus edodes mycelia polysaccharide (LMP) were explored with multi-spectral methods, for example, three-dimensional (3D) fluorescence, Fourier-transformed infrared (FT-IR), and Raman spectra. At 290 K, the binding constant was 2.44 × 105 L/mol, there was only one binding site between LMP and lipase. Static quenching was the quenching mechanism. The major forces were hydrogen bonding and van der Waals force. The binding of LMP to lipase impacted the microenvironment around tyrosine and tryptophan residues. The polarity around these residues was decreased and hydrophobicity was enhanced. This study not only revealed the binding mechanism of LMP on lipase but also provided scientific evidence for expanding the application of LMP in functional food industries.
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Cogumelos Shiitake , Sítios de Ligação , Ligação de Hidrogênio , Lipase , Simulação de Acoplamento Molecular , Polissacarídeos , Ligação Proteica , Cogumelos Shiitake/química , Espectrometria de Fluorescência/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
We theoretically investigate the photoelectron momentum distribution of He atoms by numerically solving the time-dependent Schro¨dinger equation (TDSE) in few-cycle ionization gating, which is synthesized by two linearly polarized laser pulses. When applying the TDSE, we can clearly see the spider-like structures in the photoelectron momentum spectra. We also find that the spider-like structures can be isolated by changing the relative phase. The directionality of the spider-like structure is changed from right-side to left-side and the ring-like interference structure gradually appears in the photoelectron momentum spectra when increasing the relative phase. The interference patterns observed in TDSE are recaptured well by the quantum-trajectory Monte Carlo (QTMC) model. We separate the ionization time window of the tunneling electron by analyzing the ionization rate. With the help of QTMC simulation, we illustrate the change of the interference structure and its directionality in the photoelectron momentum spectra. By changing the relative phase, the forward-backward asymmetry of the momentum distribution of the emitted electrons can also be controlled. Moreover, we find that the relative contribution of the nonrescattering and the rescattering trajectories can be controlled. These properties are beneficial for the application of photoelecron holography in probing atomic and molecular structures and dynamics.
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Sepsis is a systemic inflammatory response syndrome caused by infection, resulting in organ dysfunction. Sepsis-induced acute kidney injury (AKI) is one of the most common potential complications. Increasing reports have shown that M1 and M2 macrophages both take part in the progress of AKI by influencing the level of inflammatory factors and the cell death, including pyroptosis. However, whether M1 and M2 macrophages regulate AKI by secreting exosome remains unknown. In the present study, we isolated the exosomes from M1 and M2 macrophages and used Western blot and enzyme-linked immunosorbent assay (ELISA) to investigate the effect of M1 and M2 exosomes on cell pyroptosis. miRNA sequencing was used to identify the different miRNA in M1 and M2 exosomes. Luciferase reporter assay was used to verify the target gene of miRNA. We confirmed that exosomes excreted by macrophages regulated cell pyroptosis in vitro by using Western blot and ELISA. miRNA sequencing revealed the differentially expressed level of miRNAs in M1 and M2 exosomes, among which miR-93-5p was involved in the regulation of pyroptosis. By using bioinformatics predictions and luciferase reporter assay, we found that thioredoxin-interacting protein (TXNIP) was a direct target of miR-93-5p. Further in vitro and in vivo experiments indicated that exosomal miR-93-5p regulated the TXNIP directly to influence the pyroptosis in renal epithelial cells, which explained the functional difference between different phenotypes of macrophages. This study might provide new targets for the treatment of sepsis-induced AKI.
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Injúria Renal Aguda/patologia , Exossomos/patologia , Macrófagos/patologia , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Sepse/complicações , Tiorredoxinas/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Exossomos/genética , Exossomos/metabolismo , Feminino , Regulação da Expressão Gênica , Camundongos , Camundongos Endogâmicos BALB C , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Tiorredoxinas/genéticaRESUMO
Uneven lithium (Li) electrodeposition hinders the wide application of high-energy-density Li metal batteries (LMBs). Current efforts mainly focus on the side-reaction suppression between Li and electrolyte, neglecting the determinant factor of mass transport in affecting Li deposition. Herein, guided Li+ mass transport under the action of a local electric field near magnetic nanoparticles or structures at the Li metal interface, known as the magnetohydrodynamic (MHD) effect, are proposed to promote uniform Li deposition. The modified Li+ trajectories are revealed by COMSOL Multiphysics simulations, and verified by the compact and disc-like Li depositions on a model Fe3 O4 substrate. Furthermore, a patterned mesh with the magnetic Fe-Cr2 O3 core-shell skeleton is used as a facile and efficient protective structure for Li metal anodes, enabling Li metal batteries to achieve a Coulombic efficiency of 99.5 % over 300 cycles at a high cathode loading of 5.0â mAh cm-2 . The Li protection strategy based on the MHD interface design might open a new opportunity to develop high-energy-density LMBs.
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Bronchopulmonary dysplasia (BPD) is a severe complication of preterm infants characterized by increased alveolarization and inflammation. Premature exposure to hyperoxia is believed to be a key contributor to the pathogenesis of BPD. No effective preventive or therapeutic agents have been created. Stimulator of interferon gene (STING) is associated with inflammation and apoptosis in various lung diseases. Long non-coding RNA MALAT1 has been reported to be involved in BPD. However, how MALAT1 regulates STING expression remains unknown. In this study, we assessed that STING and MALAT1 were up-regulated in the lung tissue from BPD neonates, hyperoxia-based rat models and lung epithelial cell lines. Then, using the flow cytometry and cell proliferation assay, we found that down-regulating of STING or MALAT1 inhibited the apoptosis and promoted the proliferation of hyperoxia-treated cells. Subsequently, qRT-PCR, Western blotting and dual-luciferase reporter assays showed that suppressing MALAT1 decreased the expression and promoter activity of STING. Moreover, transcription factor CREB showed its regulatory role in the transcription of STING via a chromatin immunoprecipitation. In conclusion, MALAT1 interacts with CREB to regulate STING transcription in BPD neonates. STING, CREB and MALAT1 may be promising therapeutic targets in the prevention and treatment of BPD.
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Displasia Broncopulmonar/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Regulação da Expressão Gênica , Proteínas de Membrana/genética , RNA Longo não Codificante/metabolismo , Transcrição Gênica , Animais , Apoptose/genética , Displasia Broncopulmonar/sangue , Linhagem Celular , Proliferação de Células/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Inativação Gênica , Humanos , Hiperóxia/genética , Recém-Nascido , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Proteínas de Membrana/sangue , Modelos Biológicos , Regiões Promotoras Genéticas/genética , RNA Longo não Codificante/genética , Ratos , Regulação para Cima/genéticaRESUMO
AarF domain containing kinase 4 (ADCK4) is identified as a candidate gene associated with hereditary nephrotic syndrome (NS). Kruppel-like factor 5 (KLF5) is reported to promote podocyte survival by blocking the ERK/p38 MAPK pathways. Both ADCK4 and KLF5 are involved in the occurrence and development of podocyte disease, but their interaction remains unclear. Firstly, we found that the mRNA levels of ADCK4 and KLF5 decreased in NS patients, and both levels showed an obvious linear relationship. Secondly, we cloned the ADCK4 promoter region and examined its promoter activity in Hela, A549, and HEK 293 cell lines. Deletion analysis showed that the region - 116/- 4 relative to the transcriptional start site (TSS) was the core region of ADCK4 promoter. Thirdly, mutation analysis showed that putative binding sites for KLF5 contributed to the ADCK4 promoter activity. In HEK293 cells, we found that KLF5 upregulated the mRNA and protein levels of ADCK4. Finally, our chromatin immunoprecipitation assay found that KLF5 could bind to the specific region of ADCK4 promoter. These results showed that KLF5 can positively regulate the transcriptional activity of ADCK4.
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Regulação da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Síndrome Nefrótica/genética , Regiões Promotoras Genéticas/genética , Proteínas Quinases/genética , Células A549 , Criança , Pré-Escolar , Feminino , Células HEK293 , Células HeLa , Humanos , Masculino , Podócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição Gênica , Regulação para CimaRESUMO
With the three-dimensional (3D) classical ensemble method, we theoretically investigate the recollision dynamics in strong-field nonsequential double ionization (NSDI) of Ar by counter-rotating two-color circularly polarized laser fields. With the analysis of the NSDI trajectories, we find that not only multiple-recollision but also single-recollision processes occur in the double ionization events. Furthermore, the multiple-recollision and single-recollision processes both undergo the recollision-induced excitation with subsequent ionization (RESI) and recollision-induced ionization (RII). The angle between the momentum and the force of the laser field at the recollision moment can affect the times of the recollision.
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The innovative applications of engineered nanoparticles (NPs) in medicine, such as diagnosis and therapy, have attracted considerable attention. It is highly important to predict the interactions between engineered NPs and the complex biological system as well as the impacts on the subsequent behaviors in living subjects. Herein, we report the use of T1 contrast-enhanced magnetic resonance imaging (MRI) to monitor the in vivo behaviors of NPs in a real-time manner. We chose ultrasmall Pd nanosheets (SPNSs) as the object of NPs because of their promise in theranostics and fitness for diverse surface chemistry. SPNSs were modified with different surface coating ligands (e.g., polyethylene glycol, zwitterionic ligands, polyethylenimine) and functionalized with Gd-chelates to render T1 contrast-enhanced capability. MRI real-time monitoring recorded the location and accumulation of SPNSs in small animals and revealed the prominent roles of surface coating ligands in pharmacokinetics. These results highlighted the significance of selecting proper surface coating for particular biomedical assignment. Moreover, we demonstrated a powerful and noninvasive means to predict and detect the behaviors of NPs in living subjects, which may be helpful for rational design and screening of engineered NPs in biomedical applications.
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Meios de Contraste/química , Imageamento por Ressonância Magnética , Nanopartículas Metálicas/química , Neoplasias Experimentais/diagnóstico , Paládio/química , Nanomedicina Teranóstica , Animais , Meios de Contraste/administração & dosagem , Meios de Contraste/farmacocinética , Células HeLa , Humanos , Nanopartículas Metálicas/administração & dosagem , Camundongos , Neoplasias Experimentais/terapia , Paládio/administração & dosagem , Fototerapia , Fatores de TempoRESUMO
CONTEXT: Inspired by the excellent potential application prospects from the precisely controlled attributes displayed by fluorine-substituted-bis(salicylidene)-1,5-diaminonaphthalene (F-BSD) and its derivatives in the domains of photochemistry and photophysics, our present undertaking predominantly focuses on exploring the complexities of photo-induced excited state reactions for F-BSD fluorophores dissolved in solvents with diverse levels of polarity. Our simulations reveal that the excited state intramolecular double proton transfer (ESIDPT) reaction for F-BSD chemosensor can be significantly regulated by solvent polarity-dependent hydrogen bonding interactions and charge recombination induced by photoexcitation, which result from variations in geometries and vertical excitation charge reorganizations. By constructing potential energy surfaces (PESs), we also demonstrate that the stepwise ESIDPT reaction of F-BSD occurs with alternative dual intramolecular hydrogen bonds (O1-H2···N3 or O4-H5···N6). Interestingly, we affirm polar solvents should be conducive to the first-step of ESIDPT process, while nonpolar solvents are in favor of the second step. We sincerely hope solvent polarity-dependent ESIDPT behavior will pave the way for future design of novel luminescent materials. METHODS: The molecular geometries were optimized by DFT//TDDFT D3-B3LYP/TZVP theoretical level with IEFPCM solvent model in S0 and S1 states, respectively. This work also explores the energy level of target molecules with the computational vertical absorption spectra by TDDFT. All the simulations were carried out based on Gaussian 16 software. The core-valence bifurcation (CVB) indexes were obtained by using Multiwfn 3.8. Potential energy surfaces were constructed by the DFT//TDDFT D3-B3LYP/TZVP level based on restricted optimization, also the transition state (TS) forms were searched using the same level.
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While electrochemical N2 reduction presents a sustainable approach to NH3 synthesis, addressing the emission- and energy-intensive limitations of the Haber-Bosch process, it grapples with challenges in N2 activation and competing with pronounced hydrogen evolution reaction. Here we present a tandem air-NOx-NOx--NH3 system that combines non-thermal plasma-enabled N2 oxidation with Ni(OH)x/Cu-catalyzed electrochemical NOx- reduction. It delivers a high NH3 yield rate of 3 mmol h-1 cm-2 and a corresponding Faradaic efficiency of 92% at -0.25 V versus reversible hydrogen electrode in batch experiments, outperforming previously reported ones. Furthermore, in a flow mode concurrently operating the non-thermal plasma and the NOx- electrolyzer, a stable NH3 yield rate of approximately 1.25 mmol h-1 cm-2 is sustained over 100 h using pure air as the intake. Mechanistic studies indicate that amorphous Ni(OH)x on Cu interacts with hydrated K+ in the double layer through noncovalent interactions and accelerates the activation of water, enriching adsorbed hydrogen species that can readily react with N-containing intermediates. In situ spectroscopies and density functional theory (DFT) results reveal that NOx- adsorption and their hydrogenation process are optimized over the Ni(OH)x/Cu surface. This work provides new insights into electricity-driven distributed NH3 production using natural air at ambient conditions.
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BACKGROUND: Eating disorders (EDs) present a growing concern due to their widespread occurrence and chronic course, the low access to evidence-based treatment, and the significant burden they place on the patients and society. This picture justifies intensive focus on the prevention of EDs. The current study provides the first bibliometric analysis of research on the prevention of EDs, focusing on trends and contributions, to prompt further prevention research. METHODS: We conducted a bibliometric analysis of publications on the prevention of EDs using the Web of Science database, from 1993 to 2023. Focusing on universal and selective prevention strategies, our study involved a rigorous selection process, narrowing down from 10,546 to 383 relevant papers through manual screening. The analysis utilized the "bibliometrix" R package (version 4.2.2) and Python (version 3.9.6) for data processing, with VOSviewer employed for mapping collaboration networks. RESULTS: Our analysis revealed a consistent annual growth rate of 10.85% in ED prevention research publications, with significant contributions from the "International Journal of Eating Disorders" and some notable authors. The United States emerged as the dominant contributor. The analysis also highlighted key trends, including a surge in publications between 2010 and 2017, and the role of major institutions in advancing research in this field. DISCUSSION: The increasing rate of publications on the prevention of EDs is encouraging. However, the actual number of studies on the prevention of EDs are limited, and the majority of this work is performed by a few research groups. Given the high concentration of publications within a few countries and research groups, increased funding, facilitation of prevention research on a wider scale, and engagement of more researchers and further collaboration are called for.
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Bibliometria , Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Transtornos da Alimentação e da Ingestão de Alimentos/prevenção & controle , Publicações/estatística & dados numéricos , Publicações/tendênciasRESUMO
Sensitive and rapid identification of volatile organic compounds (VOCs) at ppm level with complex composition is vital in various fields ranging from respiratory diagnosis to environmental safety. Herein, we demonstrate a SERS gas sensor with size-selective and multiplexed identification capabilities for VOCs by executing the pre-enrichment strategy. In particular, the macro-mesoporous structure of graphene aerogel and micropores of metal-organic frameworks (MOFs) significantly improved the enrichment capacity (1.68 mmol/g for toluene) of various VOCs near the plasmonic hotspots. On the other hand, molecular MOFs-based filters with different pore sizes could be realized by adjusting the ligands to exclude undesired interfering molecules in various detection environments. Combining these merits, graphene/AuNPs@ZIF-8 aerogel gas sensor exhibited outstanding label-free sensitivity (up to 0.1 ppm toluene) and high stability (RSD=14.8%, after 45 days storage at room temperature for 10 cycles) and allowed simultaneous identification of multiple VOCs in a single SERS measurement with high accuracy (error < 7.2%). We visualize that this work will tackle the dilemma between sensitivity and detection efficiency of gas sensors and will inspire the design of next-generation SERS technology for selective and multiplexed detection of VOCs.
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Organic photoelectrochemical transistor (OPECT) biosensor is now appearing in perspective of public, which characterized by amplified the grating electrode potential by ion transport. In this study, the DNA network formed by the hybridization chain reaction (HCR) detects the target adenosine triphosphate (ATP) by adjusting the surface potential of the new heterojunction of ZnIn2S4/MXene. The formation of DNA network amplifies the detection signal of ATP. Significantly, OPECT biosensor could further amplify the signal, which calculated the gain achieved 103, which is consistent with the gain signal of the previously reported OPECT biosensor. Furthermore, the OPECT biosensor achieved a highly sensitivity detection of the target ATP, which the linear detection range is 0.03 pM-30 nM, and the detection limit is 0.03 pM, and illustrated a high selectivity to ATP. The proposed OPECT biosensor achieved signal amplification by adjusting the surface potential of ZnIn2S4/MXene through cascade DNA network, which provides a new direction for the detection of biomolecules.
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Trifosfato de Adenosina , Técnicas Biossensoriais , DNA , Técnicas Eletroquímicas , Transistores Eletrônicos , Zinco , Trifosfato de Adenosina/análise , Trifosfato de Adenosina/química , Técnicas Biossensoriais/métodos , DNA/química , DNA/análise , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Zinco/química , Índio/química , Processos Fotoquímicos , Limite de Detecção , Hibridização de Ácido NucleicoRESUMO
Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α-Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α-ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long-standing catalysis challenge. Herein, an unprecedented TBD-switched Pd-catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late-stage modify pharmaceuticals, scalability to large-scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd-catalyzed double isocyanide insertion process, thereby selectively providing the desired α-ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α-ketoimine amide are successfully isolated and determined by X-ray analysis, confirming that they are probable intermediates in the catalytic pathway.