Impacts of oxidative stress and anti-oxidants on the development, pathogenesis, and therapy of sickle cell disease: A comprehensive review.

Sickle cell disease (SCD) is the most severe monogenic hemoglobinopathy caused by a single genetic mutation that leads to repeated polymerization and depolymerization of hemoglobin resulting in intravascular hemolysis, cell adhesion, vascular occlusion, and ischemia-reperfusion injury. Hemolysis causes oxidative damage indirectly by generating reactive oxygen species through various pathophysiological mechanisms, which include hemoglobin autoxidation, endothelial nitric oxide synthase uncoupling, reduced nitric oxide bioavailability, and elevated levels of asymmetric dimethylarginine. Red blood cells have a built-in anti-oxidant system that includes enzymes like sodium dismutase, catalase, and glutathione peroxidase, along with free radical scavenging molecules, such as vitamin C, vitamin E, and glutathione, which help them to fight oxidative damage. However, these anti-oxidants may not be sufficient to prevent the effects of oxidative stress in SCD patients. Therefore, in line with a recent FDA request that the focus to be placed on the development of innovative therapies for SCD that address the root cause of the disease, there is a need for therapies that target oxidative stress and restore redox balance in SCD patients. This review summarizes the current state of knowledge regarding the role of oxidative stress in SCD and the potential benefits of anti-oxidant therapies. It also discusses the challenges and limitations of these therapies and suggests future directions for research and development.

Adipose tissue macrophage heterogeneity in the single-cell genomics era.

It is now well-accepted that obesity-induced inflammation plays an important role in the development of insulin resistance and type 2 diabetes. A key source of the inflammation is the murine epididymal and human visceral adipose tissue. The current paradigm is that obesity activates multiple proinflammatory immune cell types in adipose tissue, including adipose-tissue macrophages (ATMs), T Helper 1 (Th1) T cells, and natural killer (NK) cells, while concomitantly suppressing anti-inflammatory immune cells such as T Helper 2 (Th2) T cells and regulatory T cells (Tregs). A key feature of the current paradigm is that obesity induces the anti-inflammatory M2 ATMs in lean adipose tissue to polarize into proinflammatory M1 ATMs. However, recent single-cell transcriptomics studies suggest that the story is much more complex. Here we describe the single-cell genomics technologies that have been developed recently and the emerging results from studies using these technologies. While further studies are needed, it is clear that ATMs are highly heterogeneous. Moreover, while a variety of ATM clusters with quite distinct features have been found to be expanded by obesity, none truly resemble classical M1 ATMs. It is likely that single-cell transcriptomics technology will further revolutionize the field, thereby promoting our understanding of ATMs, adipose-tissue inflammation, and insulin resistance and accelerating the development of therapies for type 2 diabetes.

Compositionally Sequenced Interfacial Layers for High-Energy Li-Metal Batteries.

Electrolyte additives with multiple functions enable the interfacial engineering of Li-metal batteries (LMBs). Owing to their unique reduction behavior, additives exhibit a high potential for electrode surface modification that increases the reversibility of Li-metal anodes by enabling the development of a hierarchical solid electrolyte interphase (SEI). This study confirms that an adequately designed SEI facilitates the homogeneous supply of Li+, nonlocalized Li deposition, and low electrolyte degradation in LMBs while enduring the volume fluctuation of Li-metal anodes on cycling. An in-depth analysis of interfacial engineering mechanisms reveals that multilayered SEI structures comprising mechanically robust LiF-rich species, electron-rich P-O species, and elastic polymeric species enabled the stable charge and discharge of LMBs. The polymeric outer SEI layer in the as-fabricated multilayered SEI could accommodate the volume fluctuation of Li-metal anodes, significantly enhancing the cycling stability Li||LiNi0.8Co0.1Mn0.1O2 full cells with an electrolyte amount of 3.6 g Ah-1 and an areal capacity of 3.2 mAh cm-2. Therefore, this study confirms the ability of interfacial layers formed by electrolyte additives and fluorinated solvents to advance the performance of LMBs and can open new frontiers in the fabrication of high-performance LMBs through electrolyte-formulation engineering.

NK cell-activating receptor NKp46 does not participate in the development of obesity-induced inflammation and insulin resistance.

Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46+ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesity-induced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

Investigating the electrical crosstalk effect between pixels in high-resolution organic light-emitting diode microdisplays.

Organic light-emitting diode (OLED) microdisplays have received great attention owing to their excellent performance for augmented reality/virtual reality devices applications. However, high pixel density of OLED microdisplay causes electrical crosstalk, resulting in color distortion. This study investigated the current crosstalk ratio and changes in the color gamut caused by electrical crosstalk between sub-pixels in high-resolution full-color OLED microdisplays. A pixel structure of 3147 pixels per inch (PPI) with four sub-pixels and a single-stack white OLED with red, green, and blue color filters were used for the electrical crosstalk simulation. The results showed that the sheet resistance of the top and bottom electrodes of OLEDs rarely affected the electrical crosstalk. However, the current crosstalk ratio increased dramatically and the color gamut decreased as the sheet resistance of the common organic layer decreased. Furthermore, the color gamut of the OLED microdisplay decreased as the pixel density of the panel increased from 200 to 5000 PPI. Additionally, we fabricated a sub-pixel circuit to measure the electrical crosstalk current using a 3147 PPI scale multi-finger-type pixel structure and compared it with the simulation result.

Interfacial-Water-Modulated Photoluminescence of Single-Layer WS2 on Mica.

Because of their bandgap tunability and strong light-matter interactions, two-dimensional (2D) semiconductors are considered promising candidates for next-generation optoelectronic devices. However, their photophysical properties are greatly affected by their surrounding environment because of their 2D nature. In this work, we report that the photoluminescence (PL) of single-layer WS2 is substantially affected by interfacial water that is inevitably present between it and the supporting mica substrates. Using PL spectroscopy and wide-field imaging, we show that the emission signals from A excitons and their negative trions decreased at distinctively different rates with increasing excitation power, which could be attributed to the more efficient annihilation between excitons than between trions. By gas-controlled PL imaging, we also prove that the interfacial water converted the trions into excitons by depleting native negative charges through an oxygen reduction reaction, which rendered the excited WS2 more susceptible to nonradiative decay via exciton-exciton annihilation. Understanding the role of nanoscopic water in complex low-dimensional materials will eventually contribute to devising their novel functions and related devices.

The Fabrication of Cesium Lead Bromide-Coated Cellulose Nanocomposites and Their Effect on the Detection of Nitrogen Gas.

In this work, we fabricate cesium lead bromide nanofibers (CsPbBr3 NFs) via the attachment of cesium lead bromide nanocrystals (CsPbBr3 NCs) on the surface of electrospun cellulose nanofibers (CNFs) and employ them in a sensor to effectively detect gaseous nitrogen. The CsPbBr3 NFs are produced initially by producing CsPbBr3 NCs through hot injection and dispersing on hexane, followed by dipping CNFs and ultrasonicate for 1 h. Morphological characterization through visual, SEM and TEM image, and crystalline structure analysis by XRD and FT-IR analysis of CsPbBr3 NFs and NCs show similar spectra except for PL due to unavoidable damage during the ultrasonication. Gaseous nitrogen is subsequently detected using the photoluminescence (PL) property of CsPbBr3 NFs, in which the PL intensity dramatically decreases under various flow rate. Therefore, we believe that the proposed CsPbBr3 NFs show significant promise for use in detection sensors in various industrial field and decrease the potential of fatal damage to workers due to suffocation.

Optical Imaging of Redox and Molecular Diffusion in 2D van der Waals Space.

Understanding charge transfer (CT) between two chemical entities and the subsequent change in their charge densities is essential not only for molecular species but also for various low-dimensional materials. Because of their extremely high fraction of surface atoms, two-dimensional (2-D) materials are most susceptible to charge exchange and exhibit drastically different physicochemical properties depending on their charge density. In this regard, spontaneous and uncontrollable ionization of graphene in the ambient air has caused much confusion and technical difficulty in achieving experimental reproducibility since its first report in 2004. Moreover, the same ambient hole doping was soon observed in 2-D semiconductors, which implied that a common mechanism should be operative and apply to other low-dimensional materials universally. Notably, a similar CT reaction has long been known for carbon nanotubes but is still controversial in its mechanism.In this Account, we review our breakthroughs in unraveling the chemical origin and mechanistic requirements of the hidden CT reactions using 2-D crystals. As a first step, we have developed in situ optical methods to quantify charge density using Raman and photoluminescence (PL) spectroscopy and imaging. To overcome the multimodal sensitivity of Raman frequencies, we established a novel analytical method based on theory and experiments with excellent resolution for the charge density (∼1 × 1012 cm-2) and lattice strain (∼0.02%) of graphene. For 2-D transition-metal dichalcogenides, PL spectroscopy and imaging provided a high precision and sensitivity that enabled rapid kinetic measurements in a spatially resolved manner.Using gas- and temperature-controlled in situ measurements, we revealed that the electrical holes are injected by the oxygen reduction reaction (ORR) O2 + 4H+ + 4e- ⇄ 2H2O, which was independently verified by the pH dependence in HCl solutions. In addition to oxygen and water vapor, the overall CT reaction requires hydrophilic dielectric substrates, which assist the hydration of the sample-substrate interface. We also found that the CT reaction is substantially enhanced when samples are thermally annealed. The amplification is due to the interfacial hydrophilicity increased by the thermal hydroxylation of substrates, which indicates that the CT reaction is localized at the interface and boosted by interfacial water.The interface-localized CT allowed us to study and control molecular diffusion through the 2-D van der Waals space between samples and substrates. Wide-field PL imaging showed how fast oxygen molecules diffuse through the interfacial space, subsequently inducing the CT reaction. By increasing the 2-D gap spacing, the diffusion kinetics could be accelerated. The rate of CT could also be enhanced by introducing defects on the basal plane of 2-D crystals, which demonstrates the decisive role of defects as CT centers.Because of their unique geometry, low-dimensional materials are highly susceptible to external perturbation including charge exchange. Because the vulnerability can be exploited to modify material properties, the complete mechanism of the fundamental charge exchange summarized in this Account will be essential to exploring material and device properties of other low-dimensional materials.

Thermal Conductivity Characterization of Thermal Grease Containing Copper Nanopowder.

As electronic devices and mainboards become smaller, the need for thermal conductive materials having excellent internal heat dissipation is increasing. In this study, nano thermal grease was prepared by mixing in copper nanopowder, which is used as a heat transfer medium in thermal grease, which is a kind of thermal conductive material, with silicon oil. In addition, copper powder was mixed with graphene and alumina, respectively, and the thermal conductivity performance was compared. As a result, the thermal conductivity improved by 4.5 W/m·k over the silicon base, and the upward trend of thermal conductivity increased steadily up to 15 vol. %, and the increasing trend decreased after 20 vol. %. In addition, the increased rate of thermal conductivity from 0 to 5 vol. % and 10 to 15 vol. % was the largest.

Redox-governed charge doping dictated by interfacial diffusion in two-dimensional materials.

Controlling extra charge carriers is pivotal in manipulating electronic, optical, and magnetic properties of various two-dimensional materials. Nonetheless, the ubiquitous hole doping of two-dimensional materials in the air and acids has been controversial in its mechanistic details. Here we show their common origin is an electrochemical reaction driven by redox couples of oxygen and water molecules. Using real-time photoluminescence imaging of WS2 and Raman spectroscopy of graphene, we capture molecular diffusion through the two-dimensional nanoscopic space between two-dimensional materials and hydrophilic substrates, and show that the latter accommodate water molecules also serving as a hydrating solvent. We also demonstrate that HCl-induced doping is governed by dissolved O2 and pH in accordance with the Nernst equation. The nanoscopic electrochemistry anatomized in this work sets an ambient limit to material properties, which is universal to not only 2D but also other forms of materials.

Interface-Confined Doubly Anisotropic Oxidation of Two-Dimensional MoS2.

Despite their importance, chemical reactions confined in a low dimensional space are elusive and experimentally intractable. In this work, we report doubly anisotropic, in-plane and out-of-plane, oxidation reactions of two-dimensional crystals, by resolving interface-confined thermal oxidation of a single and multilayer MoS2 supported on silica substrates from their conventional surface reaction. Using optical second-harmonic generation spectroscopy of artificially stacked multilayers, we directly proved that crystallographically oriented triangular oxides (TOs) were formed in the bottommost layer while triangular etch pits (TEs) were generated in the topmost layer and that both structures were terminated with zigzag edges. The formation of the Mo oxide layer at the interface demonstrates that O2 diffuses efficiently through the van der Waals (vdW) gap but not MoO3, which would otherwise sublime. The fact that TOs are several times larger than TEs indicates that oxidation is greatly enhanced when MoS2 is in direct contact with silica substrates, which suggests a catalytic effect. This study indicates that the vdW-bonded interfaces are essentially open to mass transport and can serve as a model system for investigating chemistry in low dimensional spaces.