Presence of Delocalized Ti 3d Electrons in Ultrathin Single-Crystal SrTiO3.

Strontium titanate (STO), with a wide spectrum of emergent properties such as ferroelectricity and superconductivity, has received significant attention in the community of strongly correlated materials. In the strain-free STO film grown on the SrRuO3 buffer layer, the existing polar nanoregions can facilitate room-temperature ferroelectricity when the STO film thickness approaches 10 nm. Here we show that around this thickness scale, the freestanding STO films without the influence of a substrate show the tetragonal structure at room temperature, contrasting with the cubic structure seen in bulk form. The spectroscopic measurements reveal the modified Ti-O orbital hybridization that causes the Ti ion to deviate from its nominal 4+ valency (3d0 configuration) with excess delocalized 3d electrons. Additionally, the Ti ion in TiO6 octahedron exhibits an off-center displacement. The inherent symmetry lowering in ultrathin freestanding films offers an alternative way to achieve tunable electronic structures that are of paramount importance for future technological applications.

A Unified View on Varied Ultrafast Dynamics of the Primary Process in Microbial Rhodopsins.

All-trans to 13-cis photoisomerization of the protonated retinal Schiff base (PRSB) chromophore is the primary step that triggers various biological functions of microbial rhodopsins. While this ultrafast primary process has been extensively studied, it has been recognized that the relevant excited-state relaxation dynamics differ significantly from one rhodopsin to another. To elucidate the origin of the complicated ultrafast dynamics of the primary process in microbial rhodopsins, we studied the excited-state dynamics of proteorhodopsin, its D97N mutant, and bacteriorhodopsin by femtosecond time-resolved absorption (TA) spectroscopy in a wide pH range. The TA data showed that their excited-state relaxation dynamics drastically change when pH approaches the pKa of the counterion residue of the PRSB chromophore in the ground state. This result reveals that the varied excited-state relaxation dynamics in different rhodopsins mainly originate from the difference of the ground-state heterogeneity (i.e., protonation/deprotonation of the PRSB counterion).

Real-world effectiveness of second-line Afatinib versus chemotherapy for the treatment of advanced lung squamous cell carcinoma in immunotherapy-naïve patients.

BACKGROUND: Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. METHODS: In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1-7.5] vs. 2.6 months [95% CI, 0.9-6.7]; hazard ratio (HR) 0.53 [95% CI 0.32-0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1-22.0] vs. 12.3 months [6.2-33.9]; HR 0.65 [95% CI 0.38-1.11], p = 0.112). CONCLUSIONS: Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

Deterministic optical control of room temperature multiferroicity in BiFeO3 thin films.

Controlling ferroic orders (ferroelectricity, ferromagnetism and ferroelasticity) by optical methods is a significant challenge due to the large mismatch in energy scales between the order parameter coupling strengths and the incident photons. Here, we demonstrate an approach to manipulate multiple ferroic orders in an epitaxial mixed-phase BiFeO3 thin film at ambient temperature via laser illumination. Phase-field simulations indicate that a light-driven flexoelectric effect allows the targeted formation of ordered domains. We also achieved precise sequential laser writing and erasure of different domain patterns, which demonstrates a deterministic optical control of multiferroicity at room temperature. As ferroic orders directly influence susceptibility and conductivity in complex materials, our results not only shed light on the optical control of multiple functionalities, but also suggest possible developments for optoelectronics and related applications.

Acid-base equilibrium of the chromophore counterion results in distinct photoisomerization reactivity in the primary event of proteorhodopsin.

Proteorhodopsin (PR) is a proton-pumping rhodopsin, and it is known to exhibit a multi-phasic decay of the excited-state population in the primary process. So far, this complex excited-state decay has been attributed to the branching of the relaxation pathway on the excited-state potential energy surface. However, a recent ultrafast spectroscopic study on a sodium-pumping rhodopsin suggested that such a complex decay may originate from the heterogeneity in the ground state due to the acid-base equilibrium of the counterion of the protonated retinal Schiff base (PRSB). In this study, we studied the excited-state dynamics of PR at pH 11 and 4, in which the counterion of the PRSB, Asp97, is completely deprotonated and protonated, respectively. The obtained time-resolved absorption data revealed that the excited-state lifetime is decisively governed by the protonation state of Asp97, and the photoisomerization of the PRSB chromophore proceeds faster and more efficiently when Asp97 is deprotonated. This conclusion was further supported by high similarity of the excited-state dynamics between PR at pH 4 and the D97N mutant in which Asp97 is replaced with neutral Asn. The results of this study suggest that the protonation state of the PRSB counterion plays a decisive role in determining the excited-state dynamics and the photoisomerization reactivity of rhodopsins in general, by making a significant influence on the exited-state potential energy surface of the PRSB chromophore.

Enhanced polarization switching characteristics of HfO2 ultrathin films via acceptor-donor co-doping.

In the realm of ferroelectric memories, HfO2-based ferroelectrics stand out because of their exceptional CMOS compatibility and scalability. Nevertheless, their switchable polarization and switching speed are not on par with those of perovskite ferroelectrics. It is widely acknowledged that defects play a crucial role in stabilizing the metastable polar phase of HfO2. Simultaneously, defects also pin the domain walls and impede the switching process, ultimately rendering the sluggish switching of HfO2. Herein, we present an effective strategy involving acceptor-donor co-doping to effectively tackle this dilemma. Remarkably enhanced ferroelectricity and the fastest switching process ever reported among HfO2 polar devices are observed in La3+-Ta5+ co-doped HfO2 ultrathin films. Moreover, robust macro-electrical characteristics of co-doped films persist even at a thickness as low as 3 nm, expanding potential applications of HfO2 in ultrathin devices. Our systematic investigations further demonstrate that synergistic effects of uniform microstructure and smaller switching barrier introduced by co-doping ensure the enhanced ferroelectricity and shortened switching time. The co-doping strategy offers an effective avenue to control the defect state and improve the ferroelectric properties of HfO2 films.

Suppressing Structure Delamination for Enhanced Electrochemical Performance of Solid Oxide Cells.

Reversible solid oxide cells (rSOCs) have significant potential as efficient energy conversion and storage systems. Nevertheless, the practical application of their conventional air electrodes, such as La0.8Sr0.2MnO3-δ (LSM), Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), and PrBa0.8Ca0.2Co2O5+δ (PBCC), remains unsatisfactory due to interface delamination during prolonged electrochemical operation. Using micro-focusing X-ray absorption spectroscopy (µ-XAS), a decrease (increase) in the co-valence state from the electrode surface to the electrode/electrolyte interface is observed, leading to the above delamination. Utilizing the one-pot method to incorporate an oxygen-vacancy-enriched CeO2 electrode into these air electrodes, the uniform distribution of the Co valence state is observed, alleviating the structural delamination. PBCC-CeO2 electrodes exhibited a degradation rate of 0.095 mV h-1 at 650 °C during a nearly 500-h test as compared with 0.907 mV h-1 observed during the 135-h test for PBCC. Additionally, a remarkable increase in electrolysis current density from 636 to 934 mA cm-2 under 1.3 V and a maximum power density from 912 to 989 mW cm-2 upon incorporating CeO2 into PBCC is also observed. BSCF-CeO2 and LSM-CeO2 also show enhanced electrochemical performance and prolonged stability as compared to BSCF and LSM. This work offers a strategy to mitigate the structural delamination of conventional electrodes to boost the performance of rSOCs.

Emissive osmium(II) complexes with tetradentate bis(pyridylpyrazolate) chelates.

A tetradentate bis(pyridylpyrazolate) chelate, L, is assembled by connecting two bidentate 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole chelates at the 6 position of the pyridyl fragment with a phenylamido appendage. This chelate was then utilized in the synthesis of three osmium(II) complexes, namely, [Os(L)(CO)2] (4), [Os(L)(PPh2Me)2] (5), and [Os(L)(PPhMe2)2] (6). Single-crystal X-ray structural analyses were executed on 4 and 5 to reveal the bonding arrangement of the L chelate. Phosphine-substituted derivatives 5 and 6 are highly emissive in both solution and the solid state, and their photophysical properties were measured and discussed on the basis of computational approaches. For application, fabrication and analysis of organic light-emitting diodes (OLEDs) were also carried out. The OLEDs using 5 and 6 as dopants exhibit saturated red emission with maximum external quantum efficiencies of 9.8% and 9.4%, respectively, which are higher than that of the device using [Ir(piq)3] as a red-emitting reference sample. Moreover, for documentation, 5 and 6 also achieve a maximum brightness of 19540 cd·m(-2) at 800 mA·cm(-2) (11.6 V) and 12900 cd·m(-2) at 500 mA·cm(-2) (10.5 V), respectively.

Effects of the Unique Chromophore-Protein Interactions on the Primary Photoreaction of Schizorhodopsin.

Schizorhodopsin (SzR) is a newly discovered microbial rhodopsin subfamily, functioning as an unusual inward-proton (H+) pump upon absorbing light. Two major protein structural differences around the chromophore have been found, resulting in unique chromophore-protein interactions that may be responsible for its unusual function. Therefore, it is important to elucidate how such a difference affects the primary photoreaction dynamics. We study the primary dynamics of SzR and its C75S mutant by femtosecond time-resolved absorption (TA) spectroscopy. The obtained TA data revealed that the photoisomerization in SzR proceeds more slowly and less efficiently than typical outward H+-pumping rhodopsins and that it further slows in the C75S mutant. We performed impulsive stimulated Raman measurements to clarify the effect of the cysteine residue on the retinal chromophore and found that interactions with Cys75 flatten the retinal chromophore of wild-type SzR. We discuss the effect of the unique chromophore-cysteine interaction on the retinal isomerization dynamics and structure of SzR.

Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment.

Purpose: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated. Materials and methods: From January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB-IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis. Results: The univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR <5.0 (p = 0.008). Conclusion: The benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients.

Enhanced Exchange Bias in Epitaxial High-Entropy Oxide Heterostructures.

High-entropy oxides (HEOs) have gained significant interest in recent years due to their unique structural characteristics and potential to tailor functional properties. However, the electronic structure of the HEOs currently remains vastly unknown. In this work, combining magnetometry measurements, scanning transmission electron microscopy, and element-specific X-ray absorption spectroscopy, the electronic structure and magnetic properties of the perovskite-HEO La(Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)O3 epitaxial thin films are systemically studied. It is found that enhanced magnetic frustration emerges from competing exchange interactions of the five transition-metal cations with energetically favorable half-filled/full-filled electron configurations, resulting in an unprecedented large vertical exchange bias effect in the single-crystalline films. Furthermore, our findings demonstrate that the La(Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)O3 layer with a thickness down to 1 nm can be used as a pinning layer and strongly coupled with a ferromagnetic La0.7Sr0.3MnO3 layer, leading to a notable exchange bias and coercivity enhancement in a cooling field as small as 5 Oe. Our studies not only provide invaluable insight into the electronic structure of HEOs but also pave the way for a new era of large bias materials for spintronics devices.

Spin State Disproportionation in Insulating Ferromagnetic LaCoO3 Epitaxial Thin Films.

The origin of insulating ferromagnetism in epitaxial LaCoO3 films under tensile strain remains elusive despite extensive research efforts are devoted. Surprisingly, the spin state of its Co ions, the main parameter of its ferromagnetism, is still to be determined. Here, the spin state in epitaxial LaCoO3 thin films is systematically investigated to clarify the mechanism of strain-induced ferromagnetism using element-specific X-ray absorption spectroscopy and dichroism. Combining with the configuration interaction cluster calculations, it is unambiguously demonstrated that Co3+ in LaCoO3 films under compressive strain (on LaAlO3 substrate) is practically a low-spin state, whereas Co3+ in LaCoO3 films under tensile strain (on SrTiO3 substrate) have mixed high-spin and low-spin states with a ratio close to 1:3. From the identification of this spin state ratio, it is inferred that the dark strips observed by high-resolution scanning transmission electron microscopy indicate the position of Co3+ high-spin state, i.e., an observation of a spin state disproportionation in tensile-strained LaCoO3 films. This consequently explains the nature of ferromagnetism in LaCoO3 films. The study highlights the importance of spin state degrees of freedom, along with thin-film strain engineering, in creating new physical properties that do not exist in bulk materials.

Photonic-Crafting of Non-Volatile and Rewritable Antiferromagnetic Spin Textures with Drastic Difference in Electrical Conductivity.

Antiferromagnetic spintronics is an emerging field of non-volatile data storage and information processing. The zero net magnetization and zero stray fields of antiferromagnetic materials eliminate interference between neighbor units, leading to high-density memory integrations. However, this invisible magnetic character at the same time also poses a great challenge in controlling and detecting magnetic states in antiferromagnets. Here, two antiferromagnetic spin states close in energy in strained BiFeO3 thin films at room temperature are discovered. It can be reversibly switched between these two non-volatile antiferromagnetic states by a moderate magnetic field and a non-contact optical approach. Importantly, the conductivity of the areas with each antiferromagnetic textures is drastically different. It is conclusively demonstrated the capability of optical writing and electrical reading of these newly discovered bistable antiferromagnetic states in the BiFeO3 thin films.

Twisted oxide lateral homostructures with conjunction tunability.

Epitaxial growth is of significant importance over the past decades, given it has been the key process of modern technology for delivering high-quality thin films. For conventional heteroepitaxy, the selection of proper single crystal substrates not only facilitates the integration of different materials but also fulfills interface and strain engineering upon a wide spectrum of functionalities. Nevertheless, the lattice structure, regularity and crystalline orientation are determined once a specific substrate is chosen. Here, we reveal the growth of twisted oxide lateral homostructure with controllable in-plane conjunctions. The twisted lateral homostructures with atomically sharp interfaces can be composed of epitaxial "blocks" with different crystalline orientations, ferroic orders and phases. We further demonstrate that this approach is universal for fabricating various complex systems, in which the unconventional physical properties can be artificially manipulated. Our results establish an efficient pathway towards twisted lateral homostructures, adding additional degrees of freedom to design epitaxial films.

Mechanically tunable exchange coupling of Co/CoO bilayers on flexible muscovite substrates.

The employment of flexible muscovite substrates has given us the feasibility of applying strain to heterostructures dynamically by mechanical bending. In this study, this novel approach is utilized to investigate strain effects on the exchange coupling in ferromagnetic Co and anti-ferromagnetic CoO (Co/CoO) bilayers. Two different Co/CoO bilayer heterostructures were grown on muscovite substrates by oxide molecular beam epitaxy, with the CoO layer being purely (111)- and (100)-oriented. The strain-dependent exchange coupling effect can only be observed on Co/CoO(100)/mica but not on Co/CoO(111)/mica. The origin of this phenomenon is attributed to the anisotropic spin re-orientation induced by mechanical bending. The strain-dependent magnetic anisotropy of the bilayers determined by anisotropic magnetoresistance measurements confirms this conjecture. This study elucidates the fundamental understanding of how magnetic exchange coupling can be tuned by externally applied strain via mechanical bending and, hence, provides a novel approach for implementing flexible spintronic devices.

Directly Probing Intermolecular Structural Change of a Core Fragment of ß2-Microglobulin Amyloid Fibrils with Low-Frequency Raman Spectroscopy.

Amyloid fibrils, which are ordered aggregates of proteins or peptides, have attracted keen interest because their deposition causes serious human diseases. Despite many studies utilizing X-ray crystallography, solid-state NMR, and other methods, intermolecular interactions governing the fibril formation remain largely unclear. Here, we used low-frequency Raman (LFR) spectroscopy to investigate the intermolecular ß-sheet structure of a core fragment of ß2-microglobulin amyloid fibrils, ß2m21-29, in aqueous buffer solutions. The LFR spectra (approximately 10-200 cm-1) of ß2m21-29 amyloid fibrils measured at different pH values (ranging from 6.8 to 8.0) revealed a broad-spectral pattern with a maximum at ∼80 cm-1 below pH 7.2 and at ∼110 cm-1 above pH 7.4. This observation is attributed to a pH-dependent structural change from an antiparallel to a parallel intermolecular ß-sheet structure. Multivariate curve resolution-alternating least-squares (MCR-ALS) analysis enabled us to decompose the apparently monotonous LFR spectra into three distinctly different contributions: intermolecular vibrations of the parallel and antiparallel ß-sheets and intramolecular vibrations of the peptide backbone. Peak positions of the obtained LFR bands not only exhibit a much more pronounced difference between the two ß-sheets than the conventional amide I band, but they also suggest stronger intermolecular interaction, due presumably to the hydrophobic effect, in the parallel ß-sheet than in the antiparallel ß-sheet. The present results show that LFR spectroscopy in combination with the MCR-ALS analysis holds promise for real-time tracking of the intermolecular dynamics of amyloid fibril formation under physiological conditions.

Fabrication and Characterization of Indium Tin Oxide Films.

BACKGROUND: Transparent conducting oxide (TCO) films are of particular interest in the field of optoelectronics, due to the requirement for transparent electrodes in applications such as organic light-emitting diodes, solar cells and so on. The aim of this study was to obtain a better understanding of the effects of preparation temperature on indium tin oxide (ITO) films, to improve their performance for optoelectronic applications. METHODS: ITO films were deposited on glass substrate at different temperatures, using direct current (DC) magnetron sputtering. The influence of substrate temperature on the microstructure and electrical and optical properties was studied. The surface topography and microstructure of the films were analyzed by atomic force microscopy. The electrical resistivity and optical transmittance of the films were measured using the Hall effect measurement and spectrometer, respectively. RESULTS: The results showed that both the surface roughness and film thickness increased as the substrate temperature increased. Transmittance increased from 78% to 80% in the visible wavelength region, while resistivity decreased from 6.05 × 10-4 to 3.27 × 10-4 Ω-cm as the substrate temperature increased from 25°C to 275°C. CONCLUSIONS: High-quality ITO films with low resistivity and high transmittance can be achieved by increasing the deposition temperature.

Heteroepitaxy of Fe3O4/Muscovite: A New Perspective for Flexible Spintronics.

Spintronics has captured a lot of attention since it was proposed. It has been triggering numerous research groups to make their efforts on pursuing spin-related electronic devices. Recently, flexible and wearable devices are in a high demand due to their outstanding potential in practical applications. In order to introduce spintronics into the realm of flexible devices, we demonstrate that it is feasible to grow epitaxial Fe3O4 film, a promising candidate for realizing spintronic devices based on tunneling magnetoresistance, on flexible muscovite. In this study, the heteroepitaxy of Fe3O4/muscovite is characterized by X-ray diffraction, high-resolution transmission electron microscopy, and Raman spectroscopy. The chemical composition and magnetic feature are investigated by a combination of X-ray photoelectron spectroscopy and X-ray magnetic circular dichroism. The electrical and magnetic properties are examined to show the preservation of the primitive properties of Fe3O4. Furthermore, various bending tests are performed to show the tunability of functionalities and to confirm that the heterostructures retain the physical properties under repeated cycles. These results illustrate that the Fe3O4/muscovite heterostructure can be a potential candidate for the applications in flexible spintronics.

Imaging molecular crystal polymorphs and their polycrystalline microstructures in situ by ultralow-frequency Raman spectroscopy.

Ultralow-frequency Raman spectroscopy that can measure vibrational bands at as low as ±10 cm(-1) has enabled facile in situ imaging of polycrystalline microstructures such as grains and grain boundaries with high polymorph specificity. We demonstrate this method by investigating microcrystals of two distinct polymorphs of 1,1'-binaphthyl using a microscope.