GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol.

Autologous Stem Cell Transplant (ASCT) is increasingly used to treat hematological malignancies. A key requisite for ASCT is mobilization of hematopoietic stem cells into peripheral blood, where they are collected by apheresis and stored for later transplantation. However, success is often hindered by poor mobilization due to factors including prior treatments. The combination of G-CSF and GPC-100, a small molecule antagonist of CXCR4, showed potential in a multiple myeloma clinical trial for sufficient and rapid collection of CD34+ stem cells, compared to the historical results from the standards of care, G-CSF alone or G-CSF with plerixafor, also a CXCR4 antagonist. In the present study, we show that GPC-100 has high affinity towards the chemokine receptor CXCR4, and it potently inhibits ß-arrestin recruitment, calcium flux and cell migration mediated by its ligand CXCL12. Proximity Ligation Assay revealed that in native cell systems with endogenous receptor expression, CXCR4 co-localizes with the beta-2 adrenergic receptor (ß2AR). Co-treatment with CXCL12 and the ß2AR agonist epinephrine synergistically increases ß-arrestin recruitment to CXCR4 and calcium flux. This increase is blocked by the co-treatment with GPC-100 and propranolol, a non-selective beta-adrenergic blocker, indicating a functional synergy. In mice, GPC-100 mobilized more white blood cells into peripheral blood compared to plerixafor. GPC-100 induced mobilization was further amplified by propranolol pretreatment and was comparable to mobilization by G-CSF. Addition of propranolol to the G-CSF and GPC-100 combination resulted in greater stem cell mobilization than the G-CSF and plerixafor combination. Together, our studies suggest that the combination of GPC-100 and propranolol is a novel strategy for stem cell mobilization and support the current clinical trial in multiple myeloma registered as NCT05561751 at www.clinicaltrials.gov.

Magnetically Enhanced Intracellular Uptake of Superparamagnetic Iron Oxide Nanoparticles for Antitumor Therapy.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed in biomedical fields, including targeted delivery of antitumor therapy. Conventional magnetic tumor targeting has used simple static magnetic fields (SMFs), which cause SPIONs to linearly aggregate into a long chain-like shape. Such agglomeration greatly hinders the intracellular targeting of SPIONs into tumors, thus reducing the therapeutic efficacy. In this study, we investigated the enhancement of the intracellular uptake of SPIONs through the application of rotating magnetic fields (RMFs). Based on the physical principles of SPION chain disassembly, we investigated physical parameters to predict the chain length favorable for intracellular uptake. Our prediction was validated by clear visualization of the intracellular distributions of SPIONs in tumor cells at both cellular and three-dimensional microtissue levels. To identify the potential therapeutic effects of enhanced intracellular uptake, magnetic hyperthermia as antitumor therapy was investigated under varying conditions of magnetic hyperthermia and RMFs. The results showed that enhanced intracellular uptake reduced magnetic hyperthermia time and strength as well as particle concentration. The proposed method will be useful in the development of techniques to determine the optimized physical conditions for the enhanced intracellular uptake of SPIONs in antitumor therapy.

The nucleolus is the site for inflammatory RNA decay during infection.

Inflammatory cytokines are key signaling molecules that can promote an immune response, thus their RNA turnover must be tightly controlled during infection. Most studies investigate the RNA decay pathways in the cytosol or nucleoplasm but never focused on the nucleolus. Although this organelle has well-studied roles in ribosome biogenesis and cellular stress sensing, the mechanism of RNA decay within the nucleolus is not completely understood. Here, we report that the nucleolus is an essential site of inflammatory pre-mRNA instability during infection. RNA-sequencing analysis reveals that not only do inflammatory genes have higher intronic read densities compared with non-inflammatory genes, but their pre-mRNAs are highly enriched in nucleoli during infection. Notably, nucleolin (NCL) acts as a guide factor for recruiting cytosine or uracil (C/U)-rich sequence-containing inflammatory pre-mRNAs and the Rrp6-exosome complex to the nucleolus through a physical interaction, thereby enabling targeted RNA delivery to Rrp6-exosomes and subsequent degradation. Consequently, Ncl depletion causes aberrant hyperinflammation, resulting in a severe lethality in response to LPS. Importantly, the dynamics of NCL post-translational modifications determine its functional activity in phases of LPS. This process represents a nucleolus-dependent pathway for maintaining inflammatory gene expression integrity and immunological homeostasis during infection.

Quantification of physical stress experienced by obstetrics and gynecology sonographers: A comparative study of two ultrasound devices.

This study aims to quantify the stresses of sonographers using two different ultrasound devices, one of conventional and one of ergonomic design. A total of 20 obstetricians and gynecologists participated in this study, and two types of tasks (scanning and positioning) were evaluated while using the two different devices. To quantify workload, four dependent variables (muscle activity, estimated grip force, subjective comfort rating, and task time) were measured. The muscular activity required while using the conventional device was 14.4% MVC (Maximum voluntary contraction) for the scanning task, which was significantly higher than that of the ergonomic device. The subjective comfort rating for the conventional design was lower than that of the ergonomic design. For the positioning task, the ergonomic device (33.2% MVC) resulted in significantly higher muscle activity in the extensor digitorum (ED) and flexor digitorum superficialis (FDS) than the conventional design (22.2% MVC), whereas the deltoid muscle showed significantly lower activity than in users of conventional design (4.5% MVC). Ergonomically-designed ultrasound devices improve ease of moving and the probe's supporters, reduce physical load and increase ease of use for sonographers. Our results may be used as guidelines for usability testing of ultrasound devices.

Defect spectroscopy of sidewall interfaces in gate-all-around silicon nanosheet FET.

Through time-dependent defect spectroscopy and low-frequency noise measurements, we investigate and characterize the differences of carrier trapping processes occurred by different interfaces (top/sidewall) of the gate-all-around silicon nanosheet field-effect transistor (GAA SiNS FET). In a GAA SiNS FET fabricated by the top-down process, the traps at the sidewall interface significantly affect the device performance as the width decreases. Compare to expectations, as the width of the device decreases, the subthreshold swing (SS) increases from 120 to 230 mV/dec, resulting in less gate controllability. In narrow-width devices, the effect of traps located at the sidewall interface is significantly dominant, and the 1/f 2 noise, also known as generation-recombination (G-R) noise, is clearly appeared with an increased time constant (τ i ). In addition, the probability density distributions for the normalized current fluctuations (ΔI D) show only one Gaussian in wide-width devices, whereas they are separated into four Gaussians with increased in narrow-width devices. Therefore, fitting is performed through the carrier number fluctuation-correlated with mobility fluctuations model that separately considered the effects of sidewall. In narrow-width GAA SiNS FETs, consequently, the extracted interface trap densities (N T ) distribution becomes more dominant, and the scattering parameter ([Formula: see text]) distribution increases by more than double.

Recent Progress in Magnetically Actuated Microrobots for Targeted Delivery of Therapeutic Agents.

Therapeutic agents, such as drugs and cells, play an essential role in virtually every treatment of injury, illness, or disease. However, the conventional practices of drug delivery often result in undesirable side effects caused by drug overdose and off-target delivery. In the case of cell delivery, the survival rate of the transplanted cells is extremely low and difficulties with the administration route of cells remain a problem. Recently, magnetically actuated microrobots have started offering unique opportunities in targeted therapeutic delivery due to their tiny size and ability to access hard-to-reach lesions in a minimally invasive manner; considerable advances in this regard have been made over the past decade. Here, recent progress in magnetically actuated microrobots, developed for targeted drug/cell delivery, is presented, with a focus on their design features and mechanisms for controlled therapeutic release. Additionally, the practical challenges faced by the microrobots, and future research directions toward the swift bench-to-bedside translation of the microrobots are addressed.

Crack density in bloodstains.

We construct a theoretical framework to understand the crack density of bloodstains by modeling whole blood as a suspension of binary size colloid particles. Our analysis based upon theories of soft capillarity and porous flows explains the observed increase of the crack density with increase of blood viscosity and decrease of environmental humidity. The results have direct implications on forensic science and medical diagnosis.

Improving the optical properties of organic light-emitting diodes using random nanoscale rods with a double refractive index.

In this study, random nanoscale rods (RNRs) with a double refractive index were fabricated via spin coating, dry etching, and sputtering, which are processes that are extensively applied in industry. With regard to optical properties, the RNRs with a double refractive index (RNRsD) exhibited a total transmittance that was >90% in the visible range and an optical haze in the range of 42%-50% at a wavelength of 520 nm. Organic light-emitting diodes (OLEDs) with RNRsD, where SiO2 was deposited on the RNRs via radiofrequency sputtering, exhibited an enhancement of 34.5% in the external quantum efficiency compared with OLEDs with the bare substrate. Furthermore, the color variation of the OLEDs with the optimal RNRsD with respect to a change in the viewing angle was improved from color coordinates of Δ(x, y) = (0.032, 0.034) to Δ(x, y) = (0.014, 0.014). Therefore, the proposed film can be used as a scattering layer for enhancing the light extraction and viewing angle of OLEDs by reducing the substrate mode light loss and changing the direction of light. In addition to using a low-temperature fabrication process that does not employ a photomask and a lithographic template, the proposed method is applicable to flexible devices because it uses a polymer and a thin inorganic film.

Real-time effect of electron beam on MoS2 field-effect transistors.

Irradiation of MoS2 field-effect transistors (FETs) fabricated on Si/SiO2 substrates with electron beams (e-beams) below 30 keV creates electron-hole pairs (EHP) in the SiO2, which increase the interface trap density (Nit ) and change the current path in the channel, resulting in performance changes. In situ measurements of the electrical characteristics of the FET performed using a nano-probe system mounted inside a scanning electron microscope show that e-beam irradiation enables both multilayer and monolayer MoS2 channels act as conductors. The e-beams mostly penetrate the channel owing to their large kinetic energy, while the EHPs formed in the SiO2 layer can contribute to the conductance by flowing into the MoS2 channel or inducing the gate bias effect. The analysis of the device parameters in the initial state and the vent-evacuation state after e-beam irradiation can clarify the effect of the interplay between the e-beam-induced EHPs and ambient adsorbates on the carrier behavior, which depends on the thickness of the MoS2 layer. DC and low frequency noise analysis reveals that the e-beam-induced EHPs increase Nit from 109-1010 to 1011 cm-2 eV-1 in both monolayer and multilayer devices, while the interfacial Coulomb scattering parameter αSC increases by three times in the monolayer and decreases to one-tenth of its original value in the multilayer. In other words, an MoS2 layer with a thickness of ∼30 nm is less sensitive to adsorbates by surface screening. Thus, the carrier mobility in the monolayer device decreases from 45.7 to 40 cm2 V-1 s-1, while in the 30 nm-thick multilayer device, it increases from 4.9 to 5.6 cm2 V-1 s-1. This is further evidenced by simulations of the distribution of interface traps and channel carriers in the MoS2 FET before and after e-beam irradiation, demonstrating that Coulomb scattering decreases as the effective channel moves away from the interface.

Ag-fiber/graphene hybrid electrodes for highly flexible and transparent optoelectronic devices.

Transparent conducting electrodes (TCEs) have attracted considerable attention towards the development of flexible optoelectronic devices. In this study, mixed-dimensional TCEs are fabricated based on the two-dimensional graphene and one-dimensional electrospun metal fiber that can address the shortcomings of each electrode. In comparison with other TCEs, the Ag fiber/graphene hybrid electrodes exhibited a highly stable morphology (67% lower peak-to-valley ratio), low sheet resistance (approximately 11 Ω/sq), high transmittance (approximately 94%), high oxidation stability with excellent flexibility, and outstanding chemical stability. The multiple functionalities of the transparent and flexible hybrid structure highlight its potential for applications in emerging electronics and highly stable optoelectronics.

Self-catalytic-grown SnO x nanocones for light outcoupling enhancement in organic light-emitting diodes.

Light extraction in organic light-emitting diodes (OLEDs) was improved by applying SnO x nanocones grown via thermal annealing in a low-O2 atmosphere. SnO x was easily fabricated through thermal processing after Sn deposition. The diameter of the SnO x nanocones was controlled by changing the deposition thickness of Sn. The SnO x nanocones induced strong Mie scattering, which reduced the total internal reflection in the glass substrate. Consequently, the OLED with SnO x nanocones exhibited a 23% increase in the external quantum efficiency compared with a reference device.

Transfer of transition-metal dichalcogenide circuits onto arbitrary substrates for flexible device applications.

Transition-metal dichalcogenide (TMD) materials with two-dimensional layered structures and stable surfaces are well suited for transparent and flexible device applications. In order to completely utilize the advantages of thickness control and fabrication of various heterostructure stacks, we proposed a transfer method of TMD field-effect transistors (FETs) and TMD complementary metal-oxide-semiconductor (CMOS) circuits from a Si/SiO2 substrate to a flexible substrate. We compared the characteristics of transferred MoS2 and WSe2 FETs with those of the corresponding devices transferred after channel passivation with an Al2O3 layer on a flexible substrate. Al2O3 passivation further stabilized the transfer of the entire device with electrodes. A CMOS circuit with MoS2 and WSe2 materials could be successfully transferred to a polyethylene terephthalate substrate after the channel passivation. This implies that TMD circuits can be easily fabricated on polymer substrates, which makes them suitable for use in semiconductor processes, for various applications.

The Design and Optimization of a Compressive-Type Vector Sensor Utilizing a PMN-28PT Piezoelectric Single-Crystal.

Underwater sensors that detect the distance and direction of acoustic sources are critical for surveillance monitoring and target detection in the water. Here, we propose an axial vector sensor that utilizes a small (~1 cm3) compressive-type piezoelectric accelerometer using piezoelectric single crystals. Initially, finite element analysis (FEA) was used to optimize the structure that comprised piezoelectric Pb(Mb1/3Nb2/3)O3-28%PbTiO3 single crystals on a tungsten seismic mass. The receiving voltage sensitivity (RVS) was enhanced through geometric optimization of the thickness and sensing area of the piezoelectric material and the seismic mass. The estimated maximum RVS of the optimized vector sensor was -212 dB. FEA simulations and practical measurements were used to verify the directivity of the vector sensor design, which exhibited a dipole pattern. The dipole beam pattern was used to obtain cardioid patterns using the simulated and measured results for comparison. The results clearly showed the feasibility of using the proposed piezoelectric single-crystal accelerometer for a compressive-type vector sensor.

Extraction of Light Using Random Nanocone on Poly(vinyl-butyral) for Flexible OLEDs.

In this study, we designed a smooth, highly flexible, mechanically robust poly(vinyl-butyral) (PVB)/silver nanowire (AgNW) composite transparent conducting electrode (TCE) integrated with a random nanocone (RNC) to enhance the light extraction of flexible organic light-emitting diodes (OLEDs). The RNC was fabricated by reactive-ion etching (RIE) on AgNW embedded in PVB. As the etching time increased, the size of the RNC became larger. The sheet resistance and transmittance of PVB/AgNW with the RNC was 21.7 Ω/sq and ~87%, respectively. For the PVB/AgNW, the change in sheet resistance was only 2.6% when a 2,000-bend test was performed. The maximum external quantum efficiency was 28.3% when RNC 700 s was used as a green phosphorescent OLED. In addition, for current efficiency and power efficiency, RNC 700 s increased 1.4 times over RNC 0 s. RNC is free of viewing-angle-dependent color and brightness distortion. PVB/AgNW and RNC are practical ways to overcome the brittleness of conventional indium tin oxide and improve the efficiency of flexible OLEDs. Finally, this product is expected to be applied to various flexible optical devices.

Influence of hydrogen incorporation on conductivity and work function of VO2 nanowires.

We report improved conductance by reducing the work function via incorporation of hydrogen into VO2 nanowires. The VO2 nanowires were prepared using the chemical vapor deposition method with V2O5 powder on silicon substrates at 850 °C. Hydrogenation was carried out using the high-pressure hydrogenation method. Raman spectroscopy confirmed that the incorporated hydrogen atoms resulted in a change in the lattice constant of the VO2 nanowires (NWs). To quantitatively measure the work function of the nanowires, Kelvin probe force microscopy (KPFM) was employed at ambient conditions. We found that the work function decreased with increasing H2 pressure, which also resulted in increased conductance. This is associated with hydrogen diffused into the VO2 that acts as a donor to elevate the Fermi level, which was also confirmed by KPFM. From these results, tuning of the reversible electrical properties of VO2 NWs, including the conductance and work function, can be achieved by incorporating hydrogen at relatively moderate temperatures.

Ag fiber/IZO Composite Electrodes: Improved Chemical and Thermal Stability and Uniform Light Emission in Flexible Organic Light-Emitting Diodes.

Electrospun metal fiber is a promising flexible transparent electrode owing to its extremely long length and facile fabrication process. However, metal-fiber electrodes have problems with chemical and thermal stability and nonuniform emission in organic light-emitting diode (OLED) at low luminance. In this study, we proposed a Ag fiber/IZO composite electrode with high stability. Ag fiber/IZO composite electrodes exhibited chemical and thermal stability. In addition, it was demonstrated that the OLED with the Ag fiber/IZO composite electrode operated stably, and the uniform emission of the OLED with metal-fiber electrodes improved by using highly conductive IZO film.

Simple method for fabricating scattering layer using random nanoscale rods for improving optical properties of organic light-emitting diodes.

We investigated a low-temperature mask-free process for preparing random nanoscale rods (RNRs) as a scattering layer. The process involves spin coating and dry etching, which are already widely applied in industry. Our film exhibited 17-33% optical haze at 520 nm wavelength and 95% total transmittance in the visible range. Therefore, this film can be used as a scattering layer for improving viewing angle characteristics and decreasing substrate mode loss in organic light-emitting diodes (OLEDs). Specifically, we focussed on varying the height and density of the RNRs to control the optical characteristics. As a result, the OLEDs with RNRs revealed a variation in colour coordinates of Δ(x, y) = (0.007, 0.014) for a change in the viewing angle, which was superior to those without the RNRs that displayed a variation of Δ(x, y) = (0.020, 0.034) in CIE 1931. Moreover, the OLEDs with RNRs exhibited 31% enhanced external quantum efficiency compared to those of the OLEDs with the bare substrate. The flexibility of the polymer used for the RNRs and the plasma treatment suggests that the RNRs can be applied to flexible OLED displays and lighting systems.

Nano-arrayed OLEDs: enhanced outcoupling efficiency and suppressed efficiency roll-off.

Organic light-emitting diodes (OLEDs) with an enhanced outcoupling efficiency and a suppressed efficiency roll-off were fabricated by inserting a nanosize pixel-defining layer (nPDL) that defines the OLED emission region as an array of nanoholes. The outcoupling efficiency of the nano-arrayed OLEDs was increased through the reduced surface plasmon polariton loss caused by the wavy diffraction grating at the metal-organic interface, and their efficiency roll-off was suppressed through the diffusive exciton outside the exciton-formation zone. As a result, the nano-arrayed OLEDs exhibited enhancements of 148.7% in the power efficiency and 137.0% in the external quantum efficiency at 1000 cd m-2 compared with a reference device. Furthermore, the critical current density (J0) where the external quantum efficiency decreased to half of its initial value was improved by a factor of 2.5.

Light Extraction Enhancement in Flexible Organic Light-Emitting Diodes by a Light-Scattering Layer of Dewetted Ag Nanoparticles at Low Temperatures.

We demonstrated light extraction improvement by applying a scattering layer of Ag nanoparticles physically synthesized through a low-temperature annealing process to flexible organic light-emitting diodes (OLEDs). In general, increasing the size of Ag nanoparticles is preferred to increase light scattering, but a high-temperature annealing process (∼400 °C) is required to produce them. However, flexible substrates generally cannot withstand high-temperature processes. In this study, we formed Ag nanoparticles at a low temperature of ∼200 °C by inserting a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate buffer layer, thus promoting Ag dewetting. As a result, the scattering layer of enlarged Ag nanoparticles formed at low temperatures increased the external quantum efficiency by 24% in a flexible OLED compared to a reference device.

Junction-Free Electrospun Ag Fiber Electrodes for Flexible Organic Light-Emitting Diodes.

Fabrication of junction-free Ag fiber electrodes for flexible organic light-emitting diodes (OLEDs) is demonstrated. The junction-free Ag fiber electrodes are fabricated by electrospun polymer fibers used as an etch mask and wet etching of Ag thin film. This process facilitates surface roughness control, which is important in transparent electrodes based on metal wires to prevent electrical instability of the OLEDs. The transmittance and resistance of Ag fiber electrodes can be independently adjusted by controlling spinning time and Ag deposition thickness. The Ag fiber electrode shows a transmittance of 91.8% (at 550 nm) at a sheet resistance of 22.3 Ω â–¡-1 , leading to the highest OLED efficiency. In addition, Ag fiber electrodes exhibit excellent mechanical durability, as shown by measuring the change in resistance under repeatable mechanical bending and various bending radii. The OLEDs with Ag fiber electrodes on a flexible substrate are successfully fabricated, and the OLEDs show an enhancement of EQE (≈19%) compared to commercial indium tin oxide electrodes.