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Background: T cell-based immunotherapies including immune checkpoint blockade and chimeric antigen receptor T cells can induce durable responses in patients with cancer. However, clinical efficacy is limited due to the ability of cancer cells to evade immune surveillance. While T cells have been the primary focus of immunotherapy, recent research has highlighted the importance of natural killer (NK) cells in directly recognizing and eliminating tumor cells and playing a key role in the set-up of an effective adaptive immune response. The remarkable potential of NK cells for cancer immunotherapy is demonstrated by their ability to broadly identify stressed cells, irrespective of the presence of neoantigens, and their ability to fight tumors that have lost their major histocompatibility complex class I (MHC I) expression due to acquired resistance mechanisms.However, like T cells, NK cells can become dysfunctional within the tumor microenvironment. Strategies to enhance and reinvigorate NK cell activity hold potential for bolstering cancer immunotherapy., Methods: In this study, we conducted a high-throughput screen to identify molecules that could enhance primary human NK cell function. After compound validation, we investigated the effect of the top performing compounds on dysfunctional NK cells that were generated by a newly developed in vitro platform. Functional activity of NK cells was investigated using compounds alone and in combination with checkpoint inhibitor blockade. The findings were validated on patient-derived intratumoral dysfunctional NK cells from different cancer types., Results: The screening approach led to the identification of a Casitas B-lineage lymphoma (Cbl-b) inhibitor enhancing the activity of primary human NK cells. Furthermore, the Cbl-b inhibitor was able to reinvigorate the activity of in vitro generated and patient-derived dysfunctional NK cells. Finally, Cbl-b inhibition combined with T-cell immunoreceptor with Ig and ITIM domains (TIGIT) blockade further increased the cytotoxic potential and reinvigoration of both in vitro generated and patient-derived intratumoral dysfunctional NK cells., Conclusions: These findings underscore the relevance of Cbl-b inhibition in overcoming NK cell dysfunctionality with the potential to complement existing immunotherapies and improve outcomes for patients with cancer., Competing Interests: Competing interests: ARom and OG reports personal fees from Hoffmann-La Roche during the conduct of the study and personal fees from Hoffmann-La Roche outside the submitted work. AZ received consulting/advisor fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Hoffmann–La Roche, NBE Therapeutics, Engimmune, and maintains further non-commercial research agreements with Hoffmann–La Roche, T3 Pharma, Bright Peak Therapeutics, AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We experimentally and theoretically demonstrate that electron correlation can cause the bond-length sensitivity of a shape resonance to induce an unexpected vibrational state-dependent ionization delay in a nonresonant channel. This discovery was enabled by a high-resolution attosecond-interferometry experiment based on a 400-nm driving and dressing wavelength. The short-wavelength driver results in a 6.2-electron volt separation between harmonics, markedly reducing the spectral overlap in the measured interferogram. We demonstrate the promise of this method on O 2 , a system characterized by broad vibrational progressions and a dense photoelectron spectrum. We measure a 40-attosecond variation of the photoionization delays over the X 2 Π g vibrational progression. Multichannel calculations show that this variation originates from a strong bond-length dependence of the energetic position of a shape resonance in the [Formula: see text] channel, which translates to the observed effects through electron correlation. The unprecedented energy resolution and delay accuracies demonstrate the promise of visible-light-driven molecular attosecond interferometry.

The quality of human life has improved thanks to the rapid development of wearable electronics. Previously, bulk structures were usually selected for the fabrication of high performance electronics, but these are not suitable for wearable electronics due to mobility limitations and comfortability. Fibrous material-based triboelectric nanogenerators (TENGs) can provide power to wearable electronics due to their advantages such as light weight, flexibility, stretchability, wearability, etc. In this work, various fiber materials, multiple fabrication methods, and fundamentals of TENGs are described. Moreover, recent advances in functional fiber-based wearable TENGs are introduced. Furthermore, the challenges to functional fiber-based TENGs are discussed, and possible solutions are suggested. Finally, the use of TENGs in hybrid devices is introduced for a broader introduction of fiber-based energy harvesting technologies.

Renewable energy has been a focus in recent years. Triboelectric nanogenerators (TENGs) have potential for converting mechanical energy into electricity. However, there are restrictions on the use of biological materials and bionanocomposites, such as the high cost and complexity of the synthesis process, poor stability, and inadequate output performance. To overcome the constraints of TENGs, we have turned to hydroxyapatite, a biological substance with great biocompatibility and high mechanical strength that can be manufactured from waste materials. We successfully developed a negative triboelectric bionanocomposite hydroxyapatite (HA) loaded polydimethylsiloxane (PDMS) to harness energy from biomechanical sources such as wearable devices. A TENG (2 × 2 cm 2 ) with a pushing force of 2 N and different amounts of HA in PDMS can produce highly stable output voltage, current, surface charge density, and power density values of 300 V, 22.4 μA, 90.36 μC m -2 , and 27.34 W m -2 , which are 6, 9, and 10 times higher than those without HA, respectively. These improvements were attributed to the highest observed surface potential of 1512 mV. After 20 000 cycles of contact-separation, the HA/PDMS-TENG shows exceptionally stable performance. Furthermore, adding HA improves the mechanical properties and the stretchability of the bionanocomposite. The HA/PDMS bionanocomposite exhibits remarkable stretchability of more than 290%. Effectively harvesting energy from body movements, the TENG gadget may be used to charge multiple commercial capacitors, drive up to 100 LEDs, and power a low-power electronic device. Self-powered sensing and wearable devices are made possible by the HA/PDMS-TENG, which allows their large-scale preparation and deployment.

The transplantation of mesenchymal stem cell (MSC) sheets derived from human umbilical cords (hUCs) was investigated in this study as a potential application in treating myocardial infarction (MI). Two groups of hUC-MSC sheets were formed by populating LunaGel TM , which are 3D scaffolds of photo-crosslinkable gelatin-based hydrogel with two different cell densities. An MI model was created by ligating the left anterior descending coronary artery of healthy BALB/c mice. After two weeks, the cell sheets were applied directly to the MI area and the efficacy of the treatment was evaluated over the next two weeks by monitoring the mice's weight, evaluating the left ventricle ejection fraction, and assessing the histology of the heart tissue at the end of the experiment. Higher cell density showed significantly greater efficiency in MI mice treatment in terms of weight gain and the recovery of ejection fraction. The heart tissue of the groups receiving cell sheets showed human-CD44-positive staining and reduced fibrosis and apoptosis. In conclusion, the hUC-MSC sheets ameliorated heart MI injury in mice and the efficacy of the cell sheets improved as the number of cells increased.

High-harmonic radiation can be generated when an ultra-intense laser beam is reflected from an over-dense plasma, known as a plasma mirror. It is considered a promising technique for generating intense attosecond pulses in the extreme ultraviolet and X-ray wavelength ranges. However, a solid target used for the formation of the over-dense plasma is completely damaged by the interaction. Thus, it is challenging to use a solid target for applications such as time-resolved studies and attosecond streaking experiments that require a large amount of data. Here we demonstrate that high-harmonic radiation can be continuously generated from a liquid plasma mirror in both the coherent wake emission and relativistic oscillating mirror regimes. These results will pave the way for the development of bright, stable, and high-repetition-rate attosecond light sources, which can greatly benefit the study of ultrafast laser-matter interactions., (© 2023. The Author(s).)

We report a combined experimental and theoretical study on the effect of autoionizing resonances in time-resolved photoelectron spectroscopy. The coherent excitation of N_{2} by ∼14.15  eV extreme-ultraviolet photons prepares a superposition of three dominant adjacent vibrational levels (v^{'}=14-16) in the valence b^{'} ^{1}Σ_{u}^{+} state, which are probed by the absorption of two or three near-infrared photons (800 nm). The superposition manifests itself as coherent oscillations in the measured photoelectron spectra. A quantum-mechanical simulation confirms that two autoionizing Rydberg states converging to the excited A ^{2}Π_{u} and B ^{2}Σ_{u}^{+} N_{2}^{+} cores are accessed by the resonant absorption of near-infrared photons. We show that these resonances apply different filters to the observation of the vibrational wave packet, which results in different phases and amplitudes of the oscillating photoelectron signal depending on the nature of the autoionizing resonance. This work clarifies the importance of resonances in time-resolved photoelectron spectroscopy and particularly reveals the phase of vibrational quantum beats as a powerful observable for characterizing the properties of such resonances.

Stem cells have significant potential in regenerative medicines. However, a major issue with implanting stem cells in the regeneration of new tissue is the methods to implant them and cell viability and functions before and after implantation. Here we developed a simple yet effective method that used photo-crosslinkable gelatin-based hydrogel (LunaGel TM ) as a scaffold for the encapsulation, expansion, and eventually, transplantation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) into mice subcutaneously. We demonstrated the proliferation and maintenance of the original expression of mesenchymal stem cell markers as well as the ability to differentiate into mesoderm-derived cells. The hydrogel was highly stable with no signs of degradation after 20 days in PBS. The hUC-MSCs remained viable after transplantation into mice's subcutaneous pockets and migrated to integrate with the surrounding tissues. We showed a collagen-rich layer surrounding the transplanted cell-laden scaffold indicating the effects of growth factors secreted by the hUC-MSCs. A connective tissue layer was found between the implanted cell-laden scaffold and the collagen layer, and immunohistochemical staining results suggested that this tissue was derived from the MSCs which migrated from within the scaffold. The results, thus, also suggested a protective effect the scaffold has on the encapsulated cells from the antibodies and cytotoxic cells of the host immune system.

Natural killer (NK) cells recognize virally infected cells and tumors. NK cell function depends on balanced signaling from activating receptors, recognizing products from tumors or viruses, and inhibitory receptors (such as KIR/Ly49), which recognize major histocompatibility complex class I (MHC-I) molecules. KIR/Ly49 signaling preserves tolerance to self but also conveys reactivity toward MHC-I-low target cells in a process known as NK cell education. Here, we found that NK cell tolerance and education were determined by the subcellular localization of the tyrosine phosphatase SHP-1. In mice lacking MHC-I molecules, uneducated, self-tolerant Ly49A + NK cells showed accumulation of SHP-1 in the activating immune synapse, where it colocalized with F-actin and the signaling adaptor protein SLP-76. Education of Ly49A + NK cells by the MHC-I molecule H2D d led to reduced synaptic accumulation of SHP-1, accompanied by augmented signaling from activating receptors. Education was also linked to reduced transcription of Ptpn6 , which encodes SHP-1. Moreover, synaptic SHP-1 accumulation was reduced in NK cells carrying the H2D d -educated receptor Ly49G2 but not in those carrying the noneducating receptor Ly49I. Colocalization of Ly49A and SHP-1 outside of the synapse was more frequent in educated compared with uneducated NK cells, suggesting a role for Ly49A in preventing synaptic SHP-1 accumulation in NK cell education. Thus, distinct patterning of SHP-1 in the activating NK cell synapse may determine NK cell tolerance.

We present an apparatus for attosecond transient-absorption spectroscopy (ATAS) featuring soft-X-ray (SXR) supercontinua that extend beyond 450 eV. This instrument combines an attosecond table-top high-harmonic light source with mid-infrared (mid-IR) pulses, both driven by 1.7-1.9 mJ, sub-11 fs pulses centered at 1.76 [Formula: see text]m. A remarkably low timing jitter of [Formula: see text] 20 as is achieved through active stabilization of the pump and probe arms of the instrument. A temporal resolution of better than 400 as is demonstrated through ATAS measurements at the argon L[Formula: see text]-edges. A spectral resolving power of 1490 is demonstrated through simultaneous absorption measurements at the sulfur L[Formula: see text]- and carbon K-edges of OCS. Coupled with its high SXR photon flux, this instrument paves the way to attosecond time-resolved spectroscopy of organic molecules in the gas phase or in aqueous solutions, as well as thin films of advanced materials. Such measurements will advance the studies of complex systems to the electronic time scale., (© 2023. The Author(s).)

Penicillium oxalicum has been reported as a multienzyme-producing fungus and is widely used in industry due to great potential for cellulase release. Until now, there are only 10 available genome assemblies of P. oxalicum species deposited in the GenBank database. In this study, the genome of the I1R1 strain isolated from the root of Ixora chinensis was completely sequenced by Pacbio Sequel sequencing technology, assembled into 8 chromosomes with the genome size of 30.8 Mb, as well as a mitogenome of 26 kb. The structural and functional analyses of the I1R1 genome revealed gene model annotations encoding an enzyme set involved in significant metabolic processes, along with cytochrome P450s and secondary metabolite biosynthesis. The comparative analysis of the P. oxalicum species based on orthology and gene family duplications indicated their large and closed pan-genome of 9,500 orthologous groups. This is valuable data for future phylogenetic and population genomics studies., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Genetics Society of America.)

This study used red mud modified with chitosan (RM/CS) as a novel adsorbent to remove Ni(II) ions from an aqueous solution. The adsorbent was characterized by the techniques of the BET method, X-ray diffraction (XRD), and scanning electron microscopy (SEM) analysis. According to the findings, the surface area of RM/CS is nearly doubled compared to CS, from 68.6 to 105.7 m 2 .g -1 . The Ni(II) batch adsorption of RM/CS was performed as a function of pH value, contact time, and volume of adsorbent. Three isotherm adsorption models (Langmuir, Freundlich, and Sips) and three kinetic models (the pseudo-first-order, the pseudo-second-order, and the intra-diffusion models) were fitted with the experimental data to calculate the maximum adsorption capacity and to estimate the uptake in nature. The Langmuir monolayer adsorption capacity for Nickel (II) is 31.66 mg.g -1 at a pH of 6.0, with an adsorption time of 180 min and a temperature of 323 K. The Ni(II) adsorption on RM/CS is the exothermic process and is controlled by the intra-diffusion model., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Directly contrasting ultrafast excited-state dynamics in the gas and liquid phases is crucial to understanding the influence of complex environments. Previous studies have often relied on different spectroscopic observables, rendering direct comparisons challenging. Here, we apply extreme-ultraviolet time-resolved photoelectron spectroscopy to both gaseous and liquid cis-stilbene, revealing the coupled electronic and nuclear dynamics that underlie its isomerization. Our measurements track the excited-state wave packets from excitation along the complete reaction path to the final products. We observe coherent excited-state vibrational dynamics in both phases of matter that persist to the final products, enabling the characterization of the branching space of the S 1 -S 0 conical intersection. We observe a systematic lengthening of the relaxation timescales in the liquid phase and a red shift of the measured excited-state frequencies that is most pronounced for the complex reaction coordinate. These results characterize in detail the influence of the liquid environment on both electronic and structural dynamics during a complete photochemical transformation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

By applying the protection motivation theory, the study aims to investigate factors influencing tourism and hospitality (T&H) workers' career resilience when faced with health-related risks at work during a pandemic. Data were collected from 495 part-time and full-time employees in the Vietnamese tourism and hospitality sector. The study found that workers' perceived vulnerability and perceived severity of the pandemic were positively associated with career resilience. Perceived severity was positively related to self-efficacy and response efficacy, while perceived vulnerability was positively associated with self-efficacy only. Both self-efficacy and response efficacy positively influenced career resilience through the mediating role of health risk preventative behavior. Theoretically, the study advances the stream of research in resilience in general and career resilience in particular among T&H workers when faced with a health-related crisis. Practical implications are provided with recommendations on how to facilitate career resilience among T&H employees working in the current high-risk environment., (© 2022 Elsevier Ltd. All rights reserved.)

We present the energy scaling of a sub-two-cycle (10.4 fs) carrier-envelope-phase-stable light source centered at 1.76 µm to 1.9 mJ pulse energy. The light source is based on an optimized spectral-broadening scheme in a hollow-core fiber and a consecutive pulse compression with bulk material. This is, to our knowledge, the highest pulse energy reported to date from this type of sources. We demonstrate the application of this improved source to the generation of bright water-window soft-X-ray high harmonics. Combined with the short pulse duration, this source paves the way to the attosecond time-resolved water-window spectroscopy of complex molecules in aqueous solutions.

Natural killer (NK) cells play roles in viral clearance and early surveillance against malignant transformation, yet our knowledge of the underlying mechanisms controlling their development and functions remain incomplete. To reveal cell fate-determining pathways in NK cell progenitors (NKP), we utilized an unbiased approach and generated comprehensive gene expression profiles of NK cell progenitors. We found that the NK cell program was gradually established in the CLP to preNKP and preNKP to rNKP transitions. In line with FOXO1 and FOXO3 being co-expressed through the NK developmental trajectory, the loss of both perturbed the establishment of the NK cell program and caused stalling in both NK cell development and maturation. In addition, we found that the combined loss of FOXO1 and FOXO3 caused specific changes to the composition of the non-cytotoxic innate lymphoid cell (ILC) subsets in bone marrow, spleen, and thymus. By combining transcriptome and chromatin profiling, we revealed that FOXO TFs ensure proper NK cell development at various lineage-commitment stages through orchestrating distinct molecular mechanisms. Combined FOXO1 and FOXO3 deficiency in common and innate lymphoid cell progenitors resulted in reduced expression of genes associated with NK cell development including ETS-1 and their downstream target genes. Lastly, we found that FOXO1 and FOXO3 controlled the survival of committed NK cells via gene regulation of IL-15Rβ (CD122) on rNKPs and bone marrow NK cells. Overall, we revealed that FOXO1 and FOXO3 function in a coordinated manner to regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luu, Søndergaard, Peña-Pérez, Kharazi, Krstic, Meinke, Schmied, Frengen, Heshmati, Kierczak, Bouderlique, Wagner, Gustafsson, Chambers, Achour, Kutter, Höglund, Månsson and Kadri.)

Objectives: As a cancer model recommended by numerous governments and health care systems, multidisciplinary teams (MDTs) can improve clinical decision-making and overall patient care quality. This paper aims to discuss key elements and resources, as well as contingencies for effectiveness MDTs and their meetings., Methods: We derived elements, resources, and contingencies for effective MDTs by analyzing articles on the themes of MDTs and MDT meetings., Results: This paper identifies key elements comprising MDT characteristics, team governance, infrastructure for MDM, MDM organization, MDM logistics, and clinical decision-making in light of patient-centeredness. Resources that facilitate an MDM functioning consist of human resources and non-human resources. The paper further detects barriers to the sustainable performance of MDTs and provide suggestions for improving their functioning in light of patients' and healthcare providers' perspectives., Conclusions: MDTs are vital to cancer care through enabling healthcare professionals with diversity of clinical specialties to collaborate and formulate optimal treatment recommendations for patients with suspected or confirmed cancer., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

We report the first observation of intermolecular Coulombic decay (ICD) in liquid water following inner-valence ionization. By combining a monochromatized tabletop high-harmonic source with a liquid microjet, we record electron-electron coincidence spectra at two photon energies that identify the ICD electrons, together with the photoelectrons originating from the 2a_{1} inner-valence band of liquid water. Our results confirm the importance of ICD as a source of low-energy electrons in bulk liquid water and provide quantitative results for modeling the velocity distribution of the slow electrons that are thought to dominate radiation damage in aqueous environments.

The COVID-19 pandemic has taken a severe hit on the health of workers in the tourism industry. It is crucial to understand how to help the workforce in this service industry become resilient and adaptive through this crisis. The primary objective of this research is to examine how family support nurtures tourism workers' posttraumatic growth (PTG), an adaptation form in the resilience process. The valid data were collected from 384 tourism workers who were on unpaid leave or layoff during the COVID-19 crisis. The results demonstrated the positive relationship between family support and tourism workers' PTG, for which positive stress mindset was identified as a mediation mechanism. Deliberate and intrusive ruminative thinking styles moderated the effect of family support on positive stress mindset. Theoretical and practical implications of the mechanisms through which family support promotes tourism workers' PTG are discussed., Competing Interests: Authors declare that they have no conflict of interest., (© 2021 Elsevier Ltd. All rights reserved.)

Red mud modified by chitosan (RM/CS) was utilized as an adsorbent to effectively remove Pb(II) from aqueous solution. The surface area of RM/CS was found to significantly increase by more than 50% compared to that of original red mud. Different factors that affected the Pb(II) removal on this material, such as initial Pb(II) concentration, pH, and contact time, were investigated. The pseudo-first-order, pseudo-second-order, and intra-diffusion models were used to fit the experimental data to investigate the Pb(II)'s removal kinetics. The Pb(II) removal followed the intra-diffusion model. Additionally, the non-zero C value obtained from this model indicates that the removal was controlled by many different mechanisms. We also found that the interaction of Pb(II) and carbonate group on the material's surface played a primary role once the adsorption equilibrium was reached. Finally, the maximum adsorptive capacity was found to be about 209 mg/g. This obtained value is higher than those obtained for some other materials. Therefore, the present RM/CS should be a potential material for removing Pb(II) from aqueous solution., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This work studies the Pb(II) removal onto bentonite clay modified by hexadecyl trimethyl ammonium bromide (HDTMA). Characterizations of the unmodified and modified materials were performed by using XRD, SEM, TG-DSC, FT-IR, and BET surface area analyses. Factors influencing the uptake of Pb(II) from aqueous solution, such as pH solution , ion strength, uptake time, adsorbent dosage, and initial Pb(II) concentration, were examined. The obtained results showed that bentonite clay was successfully modified by HDTMA, resulting in an increase in its surface area by about 70 %. The Pb(II) adsorption onto modified bentonite clay reached equilibrium at pH = 5.0 after 120 min. Studies within the isotherm and kinetic models demonstrated that the adsorption followed the Sips isotherm and pseudo-second-order kinetic models. The maximum monolayer adsorption capacity calculated from the Langmuir model at 30 °C was 25.8 mg/g, which is much higher than that obtained for the unmodified sample (18.9 mg/g). The FT-IR and TG-DSC analyses indicated that the formation of inner-sphere complexes plays a fundamental role in the mechanism of Pb(II) uptake onto HDTMA-bentonite clay. This mechanism of Pb(II) adsorption was further investigated, for the first time, by using the positron annihilation lifetime (PAL) and electron momentum (EMD) measurements. The PAL and EMD analyses indicated that the existence of Al and Si mono-vacancies in the HDTMA-bentonite should have essential contributions to the adsorption mechanism. In particular, we found a very interesting mechanism that the Pb(II) adsorption should occur inside the interlayer spaces of the HDTMA-bentonite., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pancreatic cancer is one of the cancer types with poor prognosis and high rate of mortality. Diagnostic modalities for early detection of pancreatic cancer have been among the academic concerns. On account of the potential role of immunohistochemistry (IHC) biomarkers in overcoming certain limitations of imaging diagnostic tools in discriminating pancreatic cancer tissues from benign ones, a growing scholarly attention has been given to the diagnostic efficacy of IHC biomarkers for pancreatic cancer. This review will analyze and synthesize published articles to provide an insight into potential IHC biomarkers for pancreatic cancer diagnosis., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Luu.)

The present work investigates the primary adsorption mechanisms of lead (II) and cadmium (II) cations onto pomelo fruit peel (PFP) from aqueous solution. pH, adsorption time, ion strength, and initial metal cation concentrations, which are factors affecting the uptake of these cations, are investigated. Results show that pH and ion strengths strongly affect the removal of these cations from aqueous solution. Different isotherm adsorption models, such as Langmuir, Freundlich, and Sips, are utilized to fit the experimental data in order to determine the adsorption in nature. The Langmuir monolayer adsorption capacities are found to be 47.18 mg/g for lead (II) and 13.35 mg/g for cadmium (II). Kinetic and thermodynamic studies based on a combination of FT-IR and TG-DSC spectroscopies demonstrate that electrostatic attraction plays a primary adsorption mechanism of lead (II) and cadmium (II) cations onto pomelo fruit peel., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Laboratory-based coherent light sources enable a wide range of applications to investigate dynamical processes in matter. High-harmonic generation (HHG) from liquid samples is a recently discovered coherent source of extreme-ultraviolet (XUV) radiation potentially capable of achieving few-femtosecond to attosecond pulse durations. However, the polarization state of this light source has so far remained unknown. In this work, we characterize the degree of polarization of both low- and high-order harmonics generated from liquid samples using linearly polarized 400 nm and 800 nm drivers. We find a remarkably high degree of linear polarization of harmonics ranging all the way from the deep-ultraviolet (160 nm) across the vacuum-ultraviolet into the XUV domain (73 nm). These results establish high-harmonic generation in liquids as a promising alternative to conventional sources of XUV radiation, combining the benefits of high target densities comparable to solids with a continuous sample renewal that avoids the limitations imposed by laser-induced damage.

It is crucial to understand how to promote workforce resilience to a crisis such as the COVID-19 outbreak. The main aim of this study is to examine the role of workers' core beliefs challenge in fostering their resilience. Core beliefs challenge is the constructive rebuilding of an individual's fundamental assumptions about life, the world, the self and others. The data were collected from 672 tourism employees during the pandemic crisis. The results revealed the positive association between workers' core beliefs challenge and their resilience. Cognitive reappraisal was detected as a mediator for the relationship between core beliefs challenge and resilience, while evidence was not found for the mediating role of expressive suppression for such a relationship. Family strain negatively moderated the links between core beliefs challenge and both emotion regulation strategies. Discussions on theoretical and practical implications are displayed., Competing Interests: Authors declare that they have no conflict of interest., (© 2021 Elsevier Ltd. All rights reserved.)

The present paper reports the fabrication of inverse opal photonic crystals (IOPCs) by using SiO 2 spherical particles with a diameter of 300 nm as an opal photonic crystal template and poly(ethylene glycol) diacrylate (PEGDA) as an inverse opal material. Characteristics and fluorescence properties of the fabricated IOPCs were investigated by using the Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), reflection spectroscopy, and fluorescence microscopy. The results clearly showed that the IOPCs were formed comprising of air spheres with a diameter of ∼270 nm. The decrease in size led to a decrease in the average refractive indexes from 1.40 to 1.12, and a remarkable stopband blue shift for the IOPCs was thus achieved. In addition, the obtained results also showed a fluorescence enhancement over 7.7-fold for the Fluor® 488 dye infiltrated onto the IOPCs sample in comparison with onto the control sample., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Van-Phuc Dinh et al.)

IL-15 priming of NK cells is a broadly accepted concept, but the dynamics and underlying molecular mechanisms remain poorly understood. We show that as little as 5 min of IL-15 treatment in vitro, followed by removal of excess cytokines, results in a long-lasting, but reversible, augmentation of NK cell responsiveness upon activating receptor cross-linking. In contrast to long-term stimulation, improved NK cell function after short-term IL-15 priming was not associated with enhanced metabolism but was based on the increased steady-state phosphorylation level of signalling molecules downstream of activating receptors. Inhibition of JAK3 eliminated this priming effect, suggesting a cross talk between the IL-15 receptor and ITAM-dependent activating receptors. Increased signalling molecule phosphorylation levels, calcium flux, and IFN-γ secretion lasted for up to 3 h after IL-15 stimulation before returning to baseline. We conclude that IL-15 rapidly and reversibly primes NK cell function by modulating activating receptor signalling. Our findings suggest a mechanism by which NK cell reactivity can potentially be maintained in vivo based on only brief encounters with IL-15 trans-presenting cells., (© 2021 Luu et al.)

Natural killer (NK) cells can kill target cells via the recognition of stress molecules and down-regulation of major histocompatibility complex class I (MHC-I). Some NK cells are educated to recognize and kill cells that have lost their MHC-I expression, e.g., tumor or virus-infected cells. A desired property of cancer immunotherapy is, therefore, to activate educated NK cells during anti-tumor responses in vivo. We here analyze NK cell responses to α-galactosylceramide (αGC), a potent activator of invariant NKT (iNKT) cells, or to exosomes loaded with αGC. In mouse strains which express different MHC-I alleles using an extended NK cell flow cytometry panel, we show that αGC induces a biased NK cell proliferation of educated NK cells. Importantly, iNKT cell-induced activation of NK cells selectively increased in vivo missing self-responses, leading to more effective rejection of tumor cells. Exosomes from antigen-presenting cells are attractive anti-cancer therapy tools as they may induce both innate and adaptive immune responses, thereby addressing the hurdle of tumor heterogeneity. Adding αGC to antigen-loaded dendritic-cell-derived exosomes also led to an increase in missing self-responses in addition to boosted T and B cell responses. This study manifests αGC as an attractive adjuvant in cancer immunotherapy, as it increases the functional capacity of educated NK cells and enhances the innate, missing self-based antitumor response.

In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N -(4-fluorobenzyl)-1,3-dimethyl-1 H -indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC 50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Though leadership has been highlighted as a salient skill for medical teachers in the medical education literature, the role of authentic leadership style among medical teachers in activating medical students' learning behaviors has not been explored. Our study seeks to examine the effects of medical teachers' authentic leadership on study task crafting behaviors among medical students., Methods: Our study adopted a mixed-methods research design comprising observations of 100 surgical operations and 100 ward conferences led by medical teachers, and surveys on authentic leadership, study task crafting, and promotion focus. Structural equation modelling was utilized in the data analysis., Results: Medical teachers' authentic leadership demonstrated positive effects on the two study task crafting behaviors (seeking resources (B = 0.36, p < 0.001) and seeking challenges (B = 0.21, p < 0.05)) but not on reducing study task demands (B = 0.11, p > 0.10). Promotion focus was found to strengthen such positive effects of authentic leadership on seeking resources (B = 0.23, p < 0.05) and seeking challenges (B = 0.18, p < 0.05). Illustrative excerpts of intraoperative and conference conversations are presented., Conclusions: Our study provided empirical evidence that medical students guided by authentic teachers expressed increased levels of study task crafting, which were further increased if medical students were promotion-focused.

In this report, the adsorption of Cr(VI) onto MnO 2 /CS nanocomposite material from aqueous solution is investigated. All the factors, which affect the adsorption, such as pH, adsorption time, Cr(VI) initial concentration and adsorbent dosage, are also examined. The results obtained show that the Cr(VI) uptake is strongly affected by pH and ion strength. Analysis within the nonlinear isotherm models indicates that the Sips isotherm combining with the Langmuir and Freundlich models offer the best fit to the experimental data due to the obtained highest R 2 and smallest RMSE and χ 2 values. The calculated Langmuir monolayer adsorption capacity is 61.56 mg g -1 at pH of 2.0 and adsorption time of 120 min. Moreover, the mechanism studies by combining theoretical models with analytical spectroscopies reveal that the electrostatic attraction plays the important role to the uptake of Cr(VI) onto MnO 2 /CS nanocomposite. Therefore, the present nanocomposite material can be applied to remove total Cr from wastewater produced by the galvanized manufacturing factory with a relatively high efficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

NK cells are innate immune cells characterized by their ability to spontaneously lyse tumor and virally infected cells. We have recently demonstrated that IL-15-sufficient DC regulate NK cell effector functions in mice. Here, we established that among ITAM-proximal signaling molecules, the expression levels of the scaffold molecule Linker for Activation of T cells (LAT) and its transcription factor ELF-1 were reduced 4 days after in vivo depletion of DC. Addition of IL-15, a cytokine presented by DC to NK cells, regulates LAT expression in NK cells with a significant effect on the DNAM1 + subset compared to DNAM1 - cells. We also found that LAT expression is regulated via interaction of the DNAM1 receptor with its ligand CD155 in both immature and mature NK cells, independently of NK cell education. Finally, we found that LAT expression within DNAM1 + NK cells might be responsible for enhanced calcium mobilization following the triggering of activating receptors on NK cells. Altogether, we found that LAT expression is tightly regulated in DNAM1 + NK cells, via interaction(s) with DC, which express CD155 and IL-15, resulting in rapid activation of the DNAM1 + subset during activating receptor triggering., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background/aim: The resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib or erlotinib, is considered a major challenge in the treatment of patients with non-small cell lung cancer (NSCLC). Herein, we identified the critical roles of anterior gradient 2 (AGR2) in gefitinib (Gef) resistance of mutant NSCLC cells., Materials and Methods: Using datasets from a pair of NSCLC-sensitive and NSCLC-resistant cells, immunoblotting, immunofluorescence and immunohistochemistry, and cell viability assays were applied to identify the effects of AGR2., Results: AGR2 was found to be significantly over-expressed in Gef-resistant cells and was highly associated with drug resistance, proliferation, migration, and invasion of cancer cells. Moreover, AGR2 and ADAMTS6 formed a negative feedback loop in drug-resistant cells., Conclusion: Modulation of overexpression of AGR2 in mutant NSCLC cells may be an attractive therapeutic strategy for the treatment of EGFR-TKI-resistant NSCLC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A flavonoid glycoside, quercitrin ( 1 ), and two phenylpropanoyl sucrose derivatives, vanicoside B ( 2 ) and lapathoside C ( 3 ), were isolated for the first time from the herb Persicaria dissitiflora . Vanicoside B ( 2 ) exhibited antiproliferative activity against a panel of cancer cell lines in triple-negative breast cancer (TNBC) MDA-MB-231 cells. The underlying mechanisms of the antitumor activity of 2 were investigated in TNBC cells. Upregulation of cyclin-dependent kinase 8 (CDK8) was observed in a claudin-low molecular subtype of TNBC cells. A molecular modeling study indicated that 2 showed a high affinity for CDK8. Further investigations revealed that 2 suppressed CDK8-mediated signaling pathways and the expression of epithelial-mesenchymal transition proteins and induced cell cycle arrest and apoptosis in MDA-MB-231 and HCC38 TNBC cells. Moreover, 2 inhibited tumor growth without overt toxicity in a nude mouse xenograft model implanted with MDA-MB-231 cells. Taken together, these findings demonstrate the significance of CDK8 activity in TNBC and suggest a potential use of 2 as a therapeutic candidate for the treatment of aggressive human triple-negative breast cancer.

Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. AXL has been reported to mediate EGFR-TKIs. Recently, third generation EGFR-TKI osimertinib has been approved and yet its acquired resistance mechanism is not clearly understood. We found that AXL is involved in both gefitinib and osimertinib resistance using in vitro and in vivo model. In addition, AXL overexpression was correlated with extended protein degradation rate. We demonstrate targeting AXL degradation is an alternative route to restore EGFR-TKIs sensitivity. We confirmed that the combination effect of YD, an AXL degrader, and EGFR-TKIs can delay or overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells, xenograft tumors, and patient-derived xenograft (PDX) models. Therefore, combination of EGFR-TKI and AXL degrader is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC.

Forkhead box (FOX) proteins are multifaceted transcription factors that are significantly implicated in cancer, with various critical roles in biological processes. Herein, we provide an overview of several key members of the FOXA, FOXC, FOXM1, FOXO and FOXP subfamilies. Important pathophysiological processes of FOX transcription factors at multiple levels in a context-dependent manner are discussed. We also specifically summarize some major aspects of FOX transcription factors in association with cancer research such as drug resistance, tumor growth, genomic alterations or drivers of initiation. Finally, we suggest that targeting FOX proteins may be a potential therapeutic strategy to combat cancer.

High-harmonic generation (HHG) in gases has been the main enabling technology of attosecond science since its discovery. Recently, HHG from solids has been demonstrated, opening a lively area of research. In contrast, harmonic generation from liquids has so far remained restricted to low harmonics in the visible regime. Here, we report the observation and detailed characterization of extreme ultraviolet HHG from liquid water and several alcohols extending beyond 20 eV. This advance was enabled by the implementation of the recent liquid flat-microjet technology, which we show to facilitate the spatial separation of HHG from the bulk liquid and the surrounding gas phase. We observe striking differences between the HHG spectra of water and several alcohols. A comparison with a strongly-driven few-band model establishes the sensitivity of HHG to the electronic structure of liquids. Our results suggest liquid-phase high-harmonic spectroscopy as a new method for studying the electronic structure and ultrafast scattering processes in liquids.

Lung cancer is the leading cause of cancer-associated deaths worldwide. In particular, non-small-cell lung cancer (NSCLC) cells harboring epidermal growth factor receptor (EGFR) mutations are associated with resistance development of EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. Recent findings suggest that bone morphogenetic proteins (BMPs) and microRNAs (miRNAs) might act as oncogenes or tumor suppressors in the tumor microenvironment. In this study, for the first time, we identified the potential roles of BMPs and miRNAs involved in EGFR-TKI resistance by analyzing datasets from a pair of parental cells and NSCLC cells with acquired EGFR-TKI resistance. BMP4 was observed to be significantly overexpressed in the EGFR-TKI-resistant cells, and its mechanism of action was strongly associated with the induction of cancer cell energy metabolism through the modulation of Acyl-CoA synthetase long-chain family member 4. In addition, miR-139-5p was observed to be significantly downregulated in the resistant NSCLC cells. The combination of miR-139-5p and yuanhuadine, a naturally derived antitumor agent, synergistically suppressed BMP4 expression in the resistant cells. We further confirmed that LDN-193189, a small molecule BMP receptor 1 inhibitor, effectively inhibited tumor growth in a xenograft nude mouse model implanted with the EFGR-TKI-resistant cells. These findings suggest a novel role of BMP4-mediated tumorigenesis in the progression of acquired drug resistance in EGFR-mutant NSCLC cells., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used clinically as target therapies for lung cancer patients, but the occurrence of acquired drug resistance limits their efficacy. Nicotinamide N-methyltransferase (NNMT), a cancer-associated metabolic enzyme, is commonly overexpressed in various human tumors. Emerging evidence also suggests a crucial loss of function of microRNAs (miRNAs) in modulating tumor progression in response to standard therapies. However, their precise roles in regulating the development of drug-resistant tumorigenesis are still poorly understood. Herein, we established EGFR-TKI-resistant non-small-cell lung cancer (NSCLC) models and observed a negative correlation between the expression levels of NNMT and miR-449a in tumor cells. Additionally, knockdown of NNMT suppressed p-Akt and tumorigenesis, while re-expression of miR-449a induced phosphatase and tensin homolog (PTEN), and inhibited tumor growth. Furthermore, yuanhuadine, an antitumor agent, significantly upregulated miR-449a levels while critically suppressing NNMT expression. These findings suggest a novel therapeutic approach for overcoming EGFR-TKI resistance to NSCLC treatment., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Coherent extreme ultraviolet (EUV) radiation using high-harmonic generation (HHG) in α-quartz is demonstrated from 10 to 200 kHz, using 50 fs laser pulses at the center wavelength of 1030 nm. The EUV radiation extends beyond 25 eV in the nondamaging regime. The number of photons generated in a single harmonic order at 15.6 eV is measured to be ≈(3.5±2.5)×10 10 per second which, to the best of our knowledge, is a first and record value reported to date using EUV HHG from solids. This Letter demonstrates one of the first all-solid-state EUV sources based on industrial-grade fiber lasers, enabling the possibility of bringing reliable EUV sources to the mass market.

Berry phase and Berry curvature have become ubiquitous concepts in physics, relevant to a variety of phenomena, such as polarization, various Hall effects, etc. Studies of these phenomena call for characterization of Berry phase or curvature which is largely limited to theory, and a few measurements in optical lattices. In this work, we report polarimetry of high-harmonic emission from solids and exploit this novel capability to directly retrieve the Berry curvature of α-quartz. We show that the two manifestations of broken inversion symmetry in solids lead to perpendicular or parallel polarization of even harmonics with respect to the driving field. Using semiclassical transport theory, we retrieve the Berry curvature from spectra measured in perpendicular polarization, the results being supported by ab initio calculation. Our work demonstrates an approach for the direct measurement of Berry curvature in solids, which could serve as a benchmark for theoretical studies.

In developing countries, the simple biogas digesters installed underground without heating or stirring are seen as a 'green' technology to convert animal waste into biogas, a source of bio-energy. However, quantitative estimates of biogas production of manures from steers fed local feed diets at actual incubation temperatures have yet to be carried out. The aim of this study was to determine the methane (CH 4 ) production potential of manures from steers in Vietnam offered traditional feed rations or supplemental diets. Biochemical CH 4 production (BMP) was measured in batch tests at 30°C using manures collected from two different experiments of steers fed diets containing feed supplements. BMP was 110.1 (NLkg -1 VS) for manure from steers receiving a control diet, significantly lower 79.0 (NL kg -1 VS) for manure from steers fed a diet containing 0.3% tannin (%DM), but then showed an increasing trend to 90.9 and 91.2 (NL kg -1 VS) for manures from steers receiving 0.4 and 0.5% tannin (%DM) supplements, respectively. Similarly, the CH 4 production (NL kg -1 VS) of manure from steers was 174 for control, 142 for control supplemented concentrate (C), 143 for control added rice straw treated with urea (R), and 127 for control supplemented C and R. Our results show there was a decrease in CH 4 emissions from steer manures through using supplemented rations., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Natural killer (NK) cell responsiveness in the mouse is determined in an education process guided by inhibitory Ly49 and NKG2A receptors binding to MHC class I molecules. It has been proposed that inhibitory signalling in human NK cells involves Abl-1 (c-Abl)-mediated phosphorylation of Crk, lowering NK cell function via disruption of a signalling complex including C3G and c-Cbl, suggesting that NK cell education might involve c-Abl. Mice deficient in c-Abl expression specifically in murine NK cells displayed normal inhibitory and activating receptor repertoires. Furthermore, c-Abl-deficient NK cells fluxed Ca 2+ normally after triggering of ITAM receptors, killed YAC-1 tumour cells efficiently and showed normal, or even slightly elevated, capacity to produce IFN-γ after activating receptor stimulation. Consistent with these results, c-Abl deficiency in NK cells did not affect NK cell inhibition via the receptors Ly49G2, Ly49A and NKG2A. We conclude that signalling downstream of murine inhibitory receptors does not involve c-Abl and that c-Abl plays no major role in NK cell education in the mouse., (© 2017 The Foundation for the Scandinavian Journal of Immunology.)

The overproduction of nitric oxide (NO) plays an important role in a variety of pathophysiological processes, including inflammation. Therefore, the suppression of NO production is a promising target in the design of anti-inflammatory agents. In the present study, a series of phthalimide analogs was synthesized, and their anti-inflammatory activities were evaluated using lipopolysaccharide (LPS)-stimulated NO production in cultured murine macrophage RAW264.7 cells. A structure-activity relationship study showed that the free hydroxyl group at C-4 and C-6 and the bulkiness of the N-substituted alkyl chain are associated with biological activity. Among the series of phthalimide derivatives, compound IIh exhibited potent inhibitory activity, with an IC 50 value of 8.7µg/mL. Further study revealed that the inhibitory activity of compound IIh was correlated with the down-regulation of the mRNA and protein expression of LPS-stimulated inducible nitric oxide synthase (iNOS). Compound IIh also suppressed the induction of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1β in LPS-stimulated RAW 264.7 cells. The anti-inflammatory activity of compound IIh was also found to be associated with the suppression of the Toll-like receptor (TLR)4 signaling pathway by down-regulating the activation of interferon regulatory factor 3 (IRF-3) and interferon-β and signal transducer expression. These findings demonstrate that novel phthalimides might be potential candidates for the development of anti-inflammatory agents., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this paper, we propose a simple method to embed transparent reactive materials in a microfluidic cell, and to observe in situ the dissolution of the material. As an example, we show how to obtain the dissolution rate of a calcite window of optical quality, dissolved in water and hydrochloric acid (HCl). These fluids circulate at controlled flowrates in a channel which is obtained by xurography: double sided tape is cut out with a cutter plotter and placed between the calcite window and a non-reactive support. While the calcite window reacts in contact with the acid, its topography is measured in situ every 10 s using an interference microscope, with a pixel resolution of 4.9 μm and a vertical resolution of 50 nm. In order to avoid inlet influence on the reaction, a thin layer of photoresist is added on the calcite surface at the inlet and outlet. This layer is also used as a non reactive reference surface.

During infection and inflammation, dendritic cells (DC) provide priming signals for natural killer (NK) cells via mechanisms distinct from their antigen processing and presentation functions. The influence of DC on resting NK cells, i.e. at steady-state, is less well studied. We here demonstrate that as early as 1 day after DC depletion, NK cells in naïve mice downregulated the NKG2D receptor and showed decreased constitutive phosphorylation of AKT and mTOR. Subsequently, apoptotic NK cells appeared in the spleen concomitant with reduced NK cell numbers. At 4 days after the onset of DC depletion, increased NK cell proliferation was seen in the spleen resulting in an accumulation of Ly49 receptor-negative NK cells. In parallel, NK cell responsiveness to ITAM-mediated triggering and cytokine stimulation dropped across maturation stages, suggestive of a functional deficiency independent from the homeostatic effect. A role for IL-15 in maintaining NK cell function was supported by a gene signature analysis of NK cell from DC-depleted mice as well as by in vivo DC transfer experiments. We propose that DC, by means of IL-15 transpresentation, are required to maintain not only homeostasis, but also function, at steady-state. These processes appear to be regulated independently from each other.

The frequency of electric currents associated with charge carriers moving in the electronic bands of solids determines the speed limit of electronics and thereby that of information and signal processing. The use of light fields to drive electrons promises access to vastly higher frequencies than conventionally used, as electric currents can be induced and manipulated on timescales faster than that of the quantum dephasing of charge carriers in solids. This forms the basis of terahertz (10 12 hertz) electronics in artificial superlattices, and has enabled light-based switches and sampling of currents extending in frequency up to a few hundred terahertz. Here we demonstrate the extension of electronic metrology to the multi-petahertz (10 15 hertz) frequency range. We use single-cycle intense optical fields (about one volt per ångström) to drive electron motion in the bulk of silicon dioxide, and then probe its dynamics by using attosecond (10 -18  seconds) streaking to map the time structure of emerging isolated attosecond extreme ultraviolet transients and their optical driver. The data establish a firm link between the emission of the extreme ultraviolet radiation and the light-induced intraband, phase-coherent electric currents that extend in frequency up to about eight petahertz, and enable access to the dynamic nonlinear conductivity of silicon dioxide. Direct probing, confinement and control of the waveform of intraband currents inside solids on attosecond timescales establish a method of realizing multi-petahertz coherent electronics. We expect this technique to enable new ways of exploring the interplay between electron dynamics and the structure of condensed matter on the atomic scale.