L-serine restored lysosomal failure in cells derived from patients with BPAN reducing iron accumulation with eliminating lipofuscin.

Defective mitochondria and autophagy, as well as accumulation of lipid and iron in WDR45 mutant fibroblasts, is related to beta-propeller protein-associated neurodegeneration (BPAN). In this study, we found that enlarged lysosomes in cells derived from patients with BPAN had low enzyme activity, and most of the enlarged lysosomes had an accumulation of iron and oxidized lipid. Cryo-electron tomography revealed elongated lipid accumulation, and spectrometry-based elemental analysis showed that lysosomal iron and oxygen accumulation superimposed with lipid aggregates. Lysosomal lipid aggregates superimposed with autofluorescence as free radical generator, lipofuscin. To eliminate free radical stress by iron accumulation in cells derived from patients with BPAN, we investigated the effects of the iron chelator, 2,2'-bipyridine (bipyridyl, BIP). To study whether the defects in patient-derived cells can be rescued by an iron chelator BIP, we tested whether the level of iron and reactive oxygen species (ROS) in the cells and genes related to oxidative stress were rescued BIP treatment. Although BIP treatment decreased some iron accumulation in the cytoplasm and mitochondria, the accumulation of iron in the lysosomes and levels of cellular ROS were unaffected. In addition, the change of specific RNA levels related to free radical stress in patient fibroblasts was not rescued by BIP. To alleviate free radical stress, we investigated whether l-serine can regulate abnormal structures in cells derived from patients with BPAN through the regulation of free radical stress. l-serine treatment alleviated increase of enlarged lysosomes and iron accumulation and rescued impaired lysosomal activity by reducing oxidized lipid accumulation in the lysosomes of the cells. Lamellated lipids in the lysosomes of the cells were identified as lipofuscin through correlative light and electron microscopy, and l-serine treatment reduced the increase of lipofuscin. These data suggest that l-serine reduces oxidative stress-mediated lysosomal lipid oxidation and iron accumulation by rescuing lysosomal activity.

Snowflake relocated Cu2O electrocatalyst on an Ag backbone template for the production of liquid C2+ chemicals from CO2.

In this study, we performed the CO2 reduction reaction (CO2RR) using a structural composite catalyst of cuprous oxide (Cu2O) and silver (Ag) that was simultaneously electrodeposited. While the underneath Ag electrodeposits maintained their spiky backbone structures even after the CO2RR, the Cu2O deposits were reduced to Cu(111) and relocated on the backbone template. The structural changes in Cu2O to Cu increase the active area of the Cu-Ag interface, resulting in a remarkable production rate of 125.01 µmol h-1 of liquid C2+ chemicals via the stabilization of the C-C coupling of the key intermediate species of acetaldehyde. This study provides new insights into designing a bimetallic catalyst for producing sustainable C2+ products from CO2 without any selectivity towards the production of methane.

Defect Passivation of 2D Semiconductors by Fixating Chemisorbed Oxygen Molecules via h-BN Encapsulations.

Hexagonal boron nitride (h-BN) is a key ingredient for various 2D van der Waals heterostructure devices, but the exact role of h-BN encapsulation in relation to the internal defects of 2D semiconductors remains unclear. Here, it is reported that h-BN encapsulation greatly removes the defect-related gap states by stabilizing the chemisorbed oxygen molecules onto the defects of monolayer WS2 crystals. Electron energy loss spectroscopy (EELS) combined with theoretical analysis clearly confirms that the oxygen molecules are chemisorbed onto the defects of WS2 crystals and are fixated by h-BN encapsulation, with excluding a possibility of oxygen molecules trapped in bubbles or wrinkles formed at the interface between WS2 and h-BN. Optical spectroscopic studies show that h-BN encapsulation prevents the desorption of oxygen molecules over various excitation and ambient conditions, resulting in a greatly lowered and stabilized free electron density in monolayer WS2 crystals. This suppresses the exciton annihilation processes by two orders of magnitude compared to that of bare WS2 . Furthermore, the valley polarization becomes robust against the various excitation and ambient conditions in the h-BN encapsulated WS2 crystals.

Mitochondrial fragmentation and donut formation enhance mitochondrial secretion to promote osteogenesis.

Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we demonstrate that mitochondria and mitochondrial-derived vesicles (MDVs) are secreted from mature osteoblasts to promote differentiation of osteoprogenitors. We show that osteogenic induction stimulates mitochondrial fragmentation, donut formation, and secretion of mitochondria through CD38/cADPR signaling. Enhancing mitochondrial fission and donut formation through Opa1 knockdown or Fis1 overexpression increases mitochondrial secretion and accelerates osteogenesis. We also show that mitochondrial fusion promoter M1, which induces Opa1 expression, impedes osteogenesis, whereas osteoblast-specific Opa1 deletion increases bone mass. We further demonstrate that secreted mitochondria and MDVs enhance bone regeneration in vivo. Our findings suggest that mitochondrial morphology in mature osteoblasts is adapted for extracellular secretion, and secreted mitochondria and MDVs are critical promoters of osteogenesis.

Highly enhanced ferroelectricity in HfO2-based ferroelectric thin film by light ion bombardment.

Continuous advancement in nonvolatile and morphotropic beyond-Moore electronic devices requires integration of ferroelectric and semiconductor materials. The emergence of hafnium oxide (HfO2)-based ferroelectrics that are compatible with atomic-layer deposition has opened interesting and promising avenues of research. However, the origins of ferroelectricity and pathways to controlling it in HfO2 are still mysterious. We demonstrate that local helium (He) implantation can activate ferroelectricity in these materials. The possible competing mechanisms, including He ion-induced molar volume changes, vacancy redistribution, vacancy generation, and activation of vacancy mobility, are analyzed. These findings both reveal the origins of ferroelectricity in this system and open pathways for nanoengineered binary ferroelectrics.

Black Si Photocathode with a Conformal and Amorphous MoSx Catalytic Layer Grown Using Atomic Layer Deposition for Photoelectrochemical Hydrogen Evolution.

We demonstrated how the photoelectrochemical (PEC) performance was enhanced by conformal deposition of an amorphous molybdenum sulfide (a-MoSx) thin film on a nanostructured surface of black Si using atomic layer deposition (ALD). The a-MoSx is found to predominantly consist of an octahedral structure (S-deficient metallic phase) that exhibits high electrocatalytic activity for the hydrogen evolution reaction with a Tafel slope of 41 mV/dec in an acid electrolyte. The a-MoSx has a smaller work function (4.0 eV) than that of crystalline 2H-MoS2 (4.5 eV), which induces larger energy band bending at the p-Si surface, thereby facilitating interface charge transfer. These features enabled us to achieve an outstanding kinetic overpotential of ∼0.2 V at 10 mA/cm2 and an onset potential of 0.27 V at 1 mA/cm2. Furthermore, the a-MoSx layer provides superior protection against corrosion of the Si surface, enabling long-term PEC operation of more than 50 h while maintaining 87% or more performance. This work highlights the remarkable advantages of the ALD a-MoSx layer and leads to a breakthrough in the architectural design of PEC cells to ensure both high performance and stability.

Octahedral Symmetry Modification Induced Orbital Occupancy Variation in VO2.

Octahedral symmetry is one of the parameters to tune the functional properties of complex oxides. VO2, a complex oxide with a 3d1 electronic system, exhibits an insulator-metal transition (IMT) near room temperature (∼68 °C), accompanying a change in the octahedral structure from asymmetrical to symmetrical. However, the role of octahedral symmetry in VO2 on the IMT characteristics is unclear. Crystal and electronic structure analyses combined with density-functional-theory calculations showed the bandwidth-controlled IMT characteristics of monoclinic VO2 with high octahedral symmetry. The expanded apical V-O length for a high octahedral symmetry of a VO2 film increased the bandwidth of the conduction band by depressing V 3d-O 2p hybridization. As a result, the interdimer hopping energy increased and thereby decreased the IMT temperature, although the short V-V chain enhanced electron correlation. These findings suggest that octahedral symmetry can control the IMT characteristics of VO2 by changing the orbital occupancy.

Is a cutoff value of 12 still useful in stage II right-sided colon cancer without risk factors?

Purpose: Various clinical practice guidelines recommend at least 12 regional lymph nodes should be removed for resected colon cancer. According to a recent study, the lymph node yield (LNY) in colon cancer surgery in the last 20 years has tended to increase from 14.91 to 21.30. However, it is unclear whether these guidelines adequately reflect recent findings on the number of harvested lymph nodes in colon cancer surgery. The aim of this study is to assess the impact of an LNY of more than 25 on survival in right-sided colon cancer. Methods: We included 285 patients who underwent a right hemicolectomy during the period from January 2010 through December 2015. Patients were divided into two groups (<25 nodes and ≥25 nodes). Primary endpoints included 5-year and 10-year survival including disease-free and overall. Results: We found that survival outcomes of patients with a harvest of ≥25 nodes were not significantly different compared with a <25 group. Large tumor size (5 cm) is significantly associated with poor 5-year and 10-year overall survival. Conclusion: Survival outcomes of patients with a harvest of ≥25 nodes were not significantly different compared with the <25 group in stage II colon cancer with no risk.

Single- or double-membrane-bound vesicles and P, Ca, and Fe-containing granules in Xanthomonas citri cultured on a solid medium.

The organelle-like structures of Xanthomonas citri, a bacterial pathogen that causes citrus canker, were investigated using an analytical transmission electron microscope. After high-pressure freezing, the bacteria were then freeze-substituted for imaging and element analysis. Miniscule electron-dense structures of varying shapes without a membrane enclosure were frequently observed near the cell poles in a 3-day culture. The bacteria formed cytoplasmic electron-dense spherical structures measuring approximately 50 nm in diameter. Furthermore, X. citri produced electron-dense or translucent ellipsoidal intracellular or extracellular granules. Single- or double-membrane-bound vesicles, including outer-inner membrane vesicles, were observed both inside and outside the cells. Most cells had been lysed in the 3-week X. citri culture, but they harbored one or two electron-dense spherical structures. Contrast-inverted scanning transmission electron microscopy images revealed distinct white spherical structures within the cytoplasm of X. citri. Likewise, energy-dispersive X-ray spectrometry showed the spatial heterogeneity and co-localization of phosphorus, oxygen, calcium, and iron only in the cytoplasmic electron-dense spherical structures, thus corroborating the nature of polyphosphate granules.

Data Mining of Heterogeneous Electrical Conduction in the Electrode Components of Fuel Cells.

The electrodes of a polymer electrolyte membrane fuel cell (PEMFC) primarily contain a Pt/C catalyst and Nafion binder. Since these components play crucial roles in the redox reaction and proton transport, respectively, their distributions can directly affect the electrochemical reactivity and thus the device performance. Although analyzing the component distribution is important to understand its electrochemical reactivity and improve the device performance, determining it for the PEMFC electrode remains a challenging task. Herein, we propose a strategy for visualizing the spatial distribution of the electrode components and their heterogeneous electrical properties using multidimensional current-voltage (I-V) spectroscopy combined with data mining. The electrical properties of the electrode components, i.e., the Pt/C catalyst and Nafion binder, were explored by I-V spectroscopy, and their electrical heterogeneity was spatially classified based on the shapes of the measured I-V curves by cluster analysis. The results show that the components and their interfacial structure can be spatially visualized from the surface electrical heterogeneity. The proposed method is expected to be applicable for investigating in detail not only the spatial properties of PEMFC electrodes but also the properties of various material systems.

Resolving Dirac electrons with broadband high-resolution NMR.

Detecting the metallic Dirac electronic states on the surface of Topological Insulators (TIs) is critical for the study of important surface quantum properties (SQPs), such as Majorana zero modes, where simultaneous probing of the bulk and edge electron states is required. However, there is a particular shortage of experimental methods, showing at atomic resolution how Dirac electrons extend and interact with the bulk interior of nanoscaled TI systems. Herein, by applying advanced broadband solid-state 125Te nuclear magnetic resonance (NMR) methods on Bi2Te3 nanoplatelets, we succeeded in uncovering the hitherto invisible NMR signals with magnetic shielding that is influenced by the Dirac electrons, and we subsequently showed how the Dirac electrons spread inside the nanoplatelets. In this way, the spin and orbital magnetic susceptibilities induced by the bulk and edge electron states were simultaneously measured at atomic scale resolution, providing a pertinent experimental approach in the study of SQPs.

Jumping Tensegrity Robot Based on Torsionally Prestrained SMA Springs.

This paper introduces the addition of torsional prestrain into the manufacturing process of shape memory alloy (SMA) springs to form torsionally prestrained SMA springs. These springs have a better performance at the same power input for the same loads and same coil dimensions as regular SMA springs. A modified thermoconstitutive model was presented that can predict the behavior of the actuator based on the amount of torsional prestrain added into the manufacturing process, and a simple two-state model is used to predict its actuation stroke. These improved actuators were used in the development of a tensegrity robots capable of fast rolling motions and jumping both vertically and horizontally. This robot is capable of rolling at 0.14 BL/s (body length per second) and can jump up to nearly a full body length.

Mechanistic Insight into Surface Defect Control in Perovskite Nanocrystals: Ligands Terminate the Valence Transition from Pb2+ to Metallic Pb0.

Organolead halide perovskite nanocrystals (NCs) have emerged as promising materials for various optoelectronic applications. However, their practical applications have been limited due to low structural integrity and poor luminescence stability associated with fast attachment-detachment dynamics of surface capping molecules during postprocessing. At present, a framework for understanding how the functional additives interact with surface moieties of organolead halide perovskites is not available. Methylammonium lead bromide NCs without surfactants on their surface provide an ideal system to investigate the direct interactions of the perovskite with functional molecules. When the oleic acid is used in a combination with n-octylamine, its contribution to surface passivation is significantly increased by protonating the alkyl amine to the corresponding ammonium ion. Our results demonstrate that the Br vacancies at the nonpassivated surface result in a reduction of Pb2+ to Pb0 by trapping electrons generated from the exciton dissociation, which provides a main pathway for exciton trapping.

Diverse Structural Conversion and Aggregation Pathways of Alzheimer's Amyloid-ß (1-40).

Complex amyloid aggregation of amyloid-ß (1-40) (Aß1-40) in terms of monomer structures has not been fully understood. Herein, we report the microscopic mechanism and pathways of Aß1-40 aggregation with macroscopic viewpoints through tuning its initial structure and solubility. Partial helical structures of Aß1-40 induced by low solvent polarity accelerated cytotoxic Aß1-40 amyloid fibrillation, while predominantly helical folds did not aggregate. Changes in the solvent polarity caused a rapid formation of ß-structure-rich protofibrils or oligomers via aggregation-prone helical structures. Modulation of the pH and salt concentration transformed oligomers to protofibrils, which proceeded to amyloid formation. We reveal diverse molecular mechanisms underlying Aß1-40 aggregation with conceptual energy diagrams and propose that aggregation-prone partial helical structures are key to inducing amyloidogenesis. We demonstrate that context-dependent protein aggregation is comprehensively understood using the macroscopic phase diagram, which provides general insights into differentiation of amyloid formation and phase separation from unfolded and folded structures.

Anastomotic Leak Does Not Impact Oncologic Outcomes After Preoperative Chemoradiotherapy and Resection for Rectal Cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship of anastomotic leakage, local recurrence, and overall survival in rectal cancer patients treated with preoperative chemoradiotherapy (CRT) and curative resection. BACKGROUND: Little is known about the association between anastomotic leakage and oncologic outcomes after preoperative CRT. METHODS: A total of 698 consecutive primary rectal cancer patients after preoperative CRT between April 19, 2000, and December 27, 2013, were retrospectively reviewed. Forty-seven patients who had anastomotic leakage were compared with 651 patients who had no anastomotic leakage. RESULTS: Of 698 patients, 47 (6.7%) patients had anastomotic leakage. Among these 47 patients, 39 (83.0%) had grade C leak that required urgent operation, while 8 (17.0%) had grade B leak that was managed expectantly or by percutaneous drainage. The median follow-up period was 47.6 months (range, 27.1 to 68.9 months). One hundred twenty (17.2%) recurrences were identified among all patients. The median overall disease-free survival was 43 months (range, 22.4 to 66.7 months). Five-year disease-free survival did not differ significantly between the 2 groups (80.5% vs 80.4%, P = 0.839). Five-year local recurrence-free survival did not differ significantly either between the 2 groups (93.7% vs 94.9%, P = 0.653). Five-year overall survival rates of patients with or without leakage were 90.9% and 86.3%, respectively (P = 0.242). Five-year cancer-specific survival rates of patients with or without leakage were 92.2% and 86.3%, respectively (P = 0.248). CONCLUSION: After preoperative CRT, an anastomotic leak is not associated with a significant increase in local recurrence or long-term survival in rectal cancer.

Field-Effect Device Using Quasi-Two-Dimensional Electron Gas in Mass-Producible Atomic-Layer-Deposited Al2O3/TiO2 Ultrathin (<10 nm) Film Heterostructures.

We report the field-effect transistors using quasi-two-dimensional electron gas generated at an ultrathin (∼10 nm) Al2O3/TiO2 heterostructure interface grown via atomic layer deposition (ALD) on a SiO2/Si substrate without using a single crystal substrate. The 2DEG at the Al2O3/TiO2 interface originates from oxygen vacancies generated at the surface of the TiO2 bottom layer during ALD of the Al2O3 overlayer. High-density electrons (∼1014 cm-2) are confined within a ∼2.2 nm distance from the Al2O3/TiO2 interface, resulting in a high on-current of ∼12 µA/µm. The ultrathin TiO2 bottom layer is easy to fully deplete, allowing an extremely low off-current, a high on/off current ratio over 108, and a low subthreshold swing of ∼100 mV/decade. Via the implementation of ALD, a mature thin-film process can facilitate mass production as well as three-dimensional integration of the devices.

Material structure, properties, and dynamics through scanning transmission electron microscopy.

Scanning transmission electron microscopy (STEM) has advanced rapidly in the last decade thanks to the ability to correct the major aberrations of the probe-forming lens. Now, atomic-sized beams are routine, even at accelerating voltages as low as 40 kV, allowing knock-on damage to be minimized in beam sensitive materials. The aberration-corrected probes can contain sufficient current for high-quality, simultaneous, imaging and analysis in multiple modes. Atomic positions can be mapped with picometer precision, revealing ferroelectric domain structures, composition can be mapped by energy-dispersive X-ray spectroscopy (EDX) and electron energy loss spectroscopy (EELS), and charge transfer can be tracked unit cell by unit cell using the EELS fine structure. Furthermore, dynamics of point defects can be investigated through rapid acquisition of multiple image scans. Today STEM has become an indispensable tool for analytical science at the atomic level, providing a whole new level of insights into the complex interplays that control material properties.

Four-Bits-Per-Cell Operation in an HfO2 -Based Resistive Switching Device.

The quadruple-level cell technology is demonstrated in an Au/Al2 O3 /HfO2 /TiN resistance switching memory device using the industry-standard incremental step pulse programming (ISPP) and error checking/correction (ECC) methods. With the highly optimistic properties of the tested device, such as self-compliance and gradual set-switching behaviors, the device shows 6σ reliability up to 16 states with a state current gap value of 400 nA for the total allowable programmed current range from 2 to 11 µA. It is demonstrated that the conventional ISPP/ECC can be applied to such resistance switching memory, which may greatly contribute to the commercialization of the device, especially competitively with NAND flash. A relatively minor improvement in the material and circuitry may enable even a five-bits-per-cell technology, which can hardly be imagined in NAND flash, whose state-of-the-art multiple-cell technology is only at three-level (eight states) to this day.

In Situ Observation of Oxygen Vacancy Dynamics and Ordering in the Epitaxial LaCoO3 System.

Vacancy dynamics and ordering underpin the electrochemical functionality of complex oxides and strongly couple to their physical properties. In the field of the epitaxial thin films, where connection between chemistry and film properties can be most clearly revealed, the effects related to oxygen vacancies are attracting increasing attention. In this article, we report a direct, real-time, atomic level observation of the formation of oxygen vacancies in the epitaxial LaCoO3 thin films and heterostructures under the influence of the electron beam utilizing scanning transmission electron microscopy (STEM). In the case of LaCoO3/SrTiO3 superlattice, the formation of the oxygen vacancies is shown to produce quantifiable changes in the interatomic distances, as well as qualitative changes in the symmetry of the Co sites manifested as off-center displacements. The onset of these changes was observed in both the [100]pc and [110]pc orientations in real time. Additionally, annular bright field images directly show the formation of oxygen vacancy channels along [110]pc direction. In the case of 15 u.c. LaCoO3 thin film, we observe the sequence of events during beam-induced formation of oxygen vacancy ordered phases and find them consistent with similar processes in the bulk. Moreover, we record the dynamics of the nucleation, growth, and defect interaction at the atomic scale as these transformations happen. These results demonstrate that we can track dynamic oxygen vacancy behavior with STEM, generating atomic-level quantitative information on phase transformation and oxygen diffusion.