Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases.

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

New insights into the role of the Golgi apparatus in the pathogenesis and therapeutics of human diseases.

The Golgi apparatus is an essential cellular organelle that mediates homeostatic functions, including vesicle trafficking and the post-translational modification of macromolecules. Its unique stacked structure and dynamic functions are tightly regulated, and several Golgi proteins play key roles in the functioning of unconventional protein secretory pathways triggered by cellular stress responses. Recently, an increasing number of studies have implicated defects in Golgi functioning in human diseases such as cancer, neurodegenerative, and immunological disorders. Understanding the extraordinary characteristics of Golgi proteins is important for elucidating its associated intracellular signaling mechanisms and has important ramifications for human health. Therefore, analyzing the mechanisms by which the Golgi participates in disease pathogenesis may be useful for developing novel therapeutic strategies. This review articulates the structural features and abnormalities of the Golgi apparatus reported in various diseases and the suspected mechanisms underlying the Golgi-associated pathologies. Furthermore, we review the potential therapeutic strategies based on Golgi function.

Mapping the electrocatalytic water splitting activity of VO2 across its insulator-to-metal phase transition.

The electrocatalytic water splitting activity of V-based oxides has been rarely investigated, even though several polymorphs in VO2 are expected to exhibit different electrocatalytic activities depending on their crystal and electronic structures. The rutile structure of VO2(R), showing metallic character, is a good candidate for a new electrocatalyst since it undergoes insulator-to-metal transition (IMT) from the insulating VO2(M1) at a low temperature of 68 °C, and involves a substantially increased electrical conductivity by three orders of magnitude. The extensive improvements in the electrocatalytic activity for both the oxygen evolution reaction (OER) and the hydrogen evolution reaction (HER) are confirmed when the IMT is induced where the overpotential (η10) is reduced from 1056 mV to 598 mV in the OER and 411 mV to 136 mV in the HER, respectively. This improvement is attributed to the increased electrochemically active surface area (ECSA), reduced charge transfer resistance, and increased electron density, driven by the IMT to the metallic VO2(R) phase.

Effects of maternal branched-chain amino acid and alanine supplementation on growth and biomarkers of protein metabolism in dams fed a low-protein diet and their offspring.

A considerable number of studies have reported that maternal protein restriction may disturb fetal growth and organ development due to a lower availability of amino acids. Leucine, one of branched-chain amino acid (BCAA) promotes protein synthesis through mechanistic target of rapamycin signaling. Here, we investigated the effects of BCAA supplementation in the dams fed a low-protein diet on serum and hepatic biochemical parameters of protein metabolism of dams and their offspring. Female ICR mice were fed a control (20% casein), a low-protein (10% casein), a low-protein with 2% BCAAs or a low-protein with 2% alanine diet for 2 weeks before mating and then throughout pregnancy and lactation. Alanine was used as an amino nitrogen control for the BCAA. Dams and their male offspring were sacrificed at postnatal day 21. There were no changes in body weight and fat mass in low-protein fed dams; however, BCAA supplementation significantly increased fat mass and serum leptin levels. Low-protein diet consumption reduced maternal protein synthesis based on biochemical analysis of serum albumin and hepatic protein levels and immunoblotting of S6 protein, which were increased by BCAA and alanine supplementation. Offspring from dams fed a low-protein diet exhibited lower body and organ weights. Body weight and hepatic protein levels of the offspring were increased by alanine supplementation. However, the decreased serum biochemical parameters, including glucose, triglyceride, total protein and albumin levels in the low-protein offspring group were not changed in response to BCAA or alanine supplementation. A reduced density of the hepatic vessel system in the offspring from dams fed a low-protein diet was restored in the offspring from dams fed either BCAA and alanine-supplemented diet. These results suggest that supplementation of amino nitrogen per se may be responsible for inducing hepatic protein synthesis in the dams fed a low-protein diet and alleviating the distorted growth and liver development of their offspring.

Spin-Selective Hole-Exciton Coupling in a V-Doped WSe2 Ferromagnetic Semiconductor at Room Temperature.

While valley polarization with strong Zeeman splitting is the most prominent characteristic of two-dimensional (2D) transition metal dichalcogenide (TMD) semiconductors under magnetic fields, enhancement of the Zeeman splitting has been demonstrated by incorporating magnetic dopants into the host materials. Unlike Fe, Mn, and Co, V is a distinctive dopant for ferromagnetic semiconducting properties at room temperature with large Zeeman shifting of band edges. Nevertheless, little known is the excitons interacting with spin-polarized carriers in V-doped TMDs. Here, we report anomalous circularly polarized photoluminescence (CPL) in a V-doped WSe2 monolayer at room temperature. Excitons couple to V-induced spin-polarized holes to generate spin-selective positive trions, leading to differences in the populations of neutral excitons and trions between left and right CPL. Using transient absorption spectroscopy, we elucidate the origin of excitons and trions that are inherently distinct for defect-mediated and impurity-mediated trions. Ferromagnetic characteristics are further confirmed by the significant Zeeman splitting of nanodiamonds deposited on the V-doped WSe2 monolayer.

Gate-Tunable Magnetism via Resonant Se-Vacancy Levels in WSe2.

The confined defects in 2D van der Waals (vdW)-layered semiconductors can be easily tailored using charge doping, strain, or an electric field. Nevertheless, gate-tunable magnetic order via intrinsic defects has been rarely observed to date. Herein, a gate-tunable magnetic order via resonant Se vacancies in WSe2 is demonstrated. The Se-vacancy states are probed via photocurrent measurements with gating to convert unoccupied states to partially occupied states associated with photo-excited carrier recombination. The magneto-photoresistance hysteresis is modulated by gating, which is consistent with the density functional calculations. The two energy levels associated with Se vacancies split with increasing laser power, owing to the robust Coulomb interaction and strong spin-orbit coupling. The findings offer a new approach for controlling the magnetic properties of defects in optoelectronic and spintronic devices using vdW-layered semiconductors.

Doping-Mediated Lattice Engineering of Monolayer ReS2 for Modulating In-Plane Anisotropy of Optical and Transport Properties.

ReS2 exhibits strong anisotropic optical and electrical responses originating from the asymmetric lattice. Here, we show that the anisotropy of monolayer (1L) ReS2 in optical scattering and electrical transport can be practically erased by lattice engineering via lithium (Li) treatment. Scanning transmission electron microscopy revealed that significant strain is induced in the lattice of Li-treated 1L-ReS2, due to high-density electron doping and the resultant formation of continuous tiling of nanodomains with randomly rotating orientations of 60°, which produced a nearly isotropic response of polarized Raman scattering and absorption of Li-treated 1L-ReS2. With Li treatment, the in-plane conductance of 1L-ReS2 increased by an order of magnitude, and its angle dependence became negligible. Our result that the asymmetric phase was converted into the isotropic phase by electron injection could significantly expand the optoelectronic applications of polymorphic two-dimensional transition metal dichalcogenides.

Substitutional Vanadium Sulfide Nanodispersed in MoS2 Film for Pt-Scalable Catalyst.

Among transition metal dichalcogenides (TMdCs) as alternatives for Pt-based catalysts, metallic-TMdCs catalysts have highly reactive basal-plane but are unstable. Meanwhile, chemically stable semiconducting-TMdCs show limiting catalytic activity due to their inactive basal-plane. Here, metallic vanadium sulfide (VSn ) nanodispersed in a semiconducting MoS2 film (V-MoS2 ) is proposed as an efficient catalyst. During synthesis, vanadium atoms are substituted into hexagonal monolayer MoS2 to form randomly distributed VSn units. The V-MoS2 film on a Cu electrode exhibits Pt-scalable catalytic performance; current density of 1000 mA cm-2 at 0.6 V and overpotential of -0.08 V at a current density of 10 mA cm-2 with excellent cycle stability for hydrogen-evolution-reaction (HER). The high intrinsic HER performance of V-MoS2 is explained by the efficient electron transfer from the Cu electrode to chalcogen vacancies near vanadium sites with optimal Gibbs free energy (-0.02 eV). This study provides insight into ways to engineer TMdCs at the atomic-level to boost intrinsic catalytic activity for hydrogen evolution.

Deep Learning-Assisted Quantification of Atomic Dopants and Defects in 2D Materials.

Atomic dopants and defects play a crucial role in creating new functionalities in 2D transition metal dichalcogenides (2D TMDs). Therefore, atomic-scale identification and their quantification warrant precise engineering that widens their application to many fields, ranging from development of optoelectronic devices to magnetic semiconductors. Scanning transmission electron microscopy with a sub-Å probe has provided a facile way to observe local dopants and defects in 2D TMDs. However, manual data analytics of experimental images is a time-consuming task, and often requires subjective decisions to interpret observed signals. Therefore, an approach is required to automate the detection and classification of dopants and defects. In this study, based on a deep learning algorithm, fully convolutional neural network that shows a superior ability of image segmentation, an efficient and automated method for reliable quantification of dopants and defects in TMDs is proposed with single-atom precision. The approach demonstrates that atomic dopants and defects are precisely mapped with a detection limit of ≈1 × 1012 cm-2 , and with a measurement accuracy of ≈98% for most atomic sites. Furthermore, this methodology is applicable to large volume of image data to extract atomic site-specific information, thus providing insights into the formation mechanisms of various defects under stimuli.

Cooperative evolution of polar distortion and nonpolar rotation of oxygen octahedra in oxide heterostructures.

Polarity discontinuity across LaAlO3/SrTiO3 (LAO/STO) heterostructures induces electronic reconstruction involving the formation of two-dimensional electron gas (2DEG) and structural distortions characterized by antiferrodistortive (AFD) rotation and ferroelectric (FE) distortion. We show that AFD and FE modes are cooperatively coupled in LAO/STO (111) heterostructures; they coexist below the critical thickness (t c) and disappear simultaneously above t c with the formation of 2DEG. Electron energy-loss spectroscopy and density functional theory (DFT) calculations provide direct evidence of oxygen vacancy (V O) formation at the LAO (111) surface, which acts as the source of 2DEG. Tracing the AFD rotation and FE distortion of LAO reveals that their evolution is strongly correlated with V O distribution. The present study demonstrates that AFD and FE modes in oxide heterostructures emerge as a consequence of interplay between misfit strain and polar field, and further that their combination can be tuned to competitive or cooperative coupling by changing the interface orientation.

Ferromagnetic Order at Room Temperature in Monolayer WSe2 Semiconductor via Vanadium Dopant.

Diluted magnetic semiconductors including Mn-doped GaAs are attractive for gate-controlled spintronics but Curie transition at room temperature with long-range ferromagnetic order is still debatable to date. Here, the room-temperature ferromagnetic domains with long-range order in semiconducting V-doped WSe2 monolayer synthesized by chemical vapor deposition are reported. Ferromagnetic order is manifested using magnetic force microscopy up to 360 K, while retaining high on/off current ratio of ≈105 at 0.1% V-doping concentration. The V-substitution to W sites keeps a V-V separation distance of 5 nm without V-V aggregation, scrutinized by high-resolution scanning transmission electron microscopy. More importantly, the ferromagnetic order is clearly modulated by applying a back-gate bias. The findings open new opportunities for using 2D transition metal dichalcogenides for future spintronics.

Atomic Observation of Filling Vacancies in Monolayer Transition Metal Sulfides by Chemically Sourced Sulfur Atoms.

Chemical treatment using bis(trifluoromethane) sulfonimide (TFSI) was shown to be particularly effective for increasing the photoluminescence (PL) of monolayer (1L) MoS2, suggesting a convenient method for overcoming the intrinsically low quantum yield of this material. However, the underlying atomic mechanism of the PL enhancement has remained elusive. Here, we report the microscopic origin of the defect healing observed in TFSI-treated 1L-MoS2 through a correlative combination of optical characterization and atomic-scale scanning transmission electron microscopy, which showed that most of the sulfur vacancies were directly repaired by the extrinsic sulfur atoms produced from the dissociation of TFSI, concurrently resulting in a significant PL enhancement. Density functional theory calculations confirmed that the reactive sulfur dioxide molecules that dissociated from TFSI can be reduced to sulfur and oxygen gas at the vacancy site to form strongly bound S-Mo. Our results reveal how defect-mediated nonradiative recombination can be effectively eliminated by a simple chemical treatment method, thereby advancing the practical applications of monolayer semiconductors.