Gallium nitride-based geometric and propagation metasurfaces for vortex beam emissions.

This work experimentally demonstrates the highly-efficient geometric and propagation metasurfaces for vortex beam emissions. These metasurfaces are respectively composed of high-aspect-ratio fin-like and cylindrical gallium nitride (GaN) meta-atoms. Remarkably, the optimized configuration of the fin-like GaN meta-atoms achieves a cross-polarization transmission efficiency of up to 99 %. Similarly, the cylindrical GaN meta-atoms exhibit an average co-polarization transmission efficiency of 97 %. Both metasurfaces, designed for vortex beam emission, exhibit annular intensity converging capabilities at distinct wavelengths in the visible. Notably, the geometric metasurface shows achromatic annular intensity distributions over a continuous wavelength range up to 100 nm, in sharp contrast to the propagation metasurface, which is subject to inherent wavelength dispersion limitations.

Wide-Angle Optical Metasurface for Vortex Beam Generation.

In this work, we have achieved an advancement by integrating wide-angle capacity into vortex beams with an impressive topological charge (TC) of 12. This accomplishment was realized through the meticulous engineering of a propagation-phase-designed metasurface. Comprising gallium nitride (GaN), meta-structures characterized by their high-aspect ratio, this metasurface exhibits an average co-polarization transmission efficiency, reaching a remarkable simulated value of up to 97%. The intricate spiral patterns, along with their respective quantification, have been meticulously investigated through tilt-view scanning electron microscopy (SEM) and were further analyzed through the Mach-Zehnder interferometer. A captivating revelation emerged, a distinctive petal-like interference pattern manifests prior to the metasurface's designed focal distance. The occurrence of this petal-like pattern at a specific z-axis position prompts a deliberate manipulation of the helicity of the spiral branches. This strategic helicity alteration is intrinsically tied to the achievement of a minimized donut diameter at the designed focal length. In regard to the angular capability of the device, the captured images continuously showcase prominent attributes within incident angles spanning up to 30 degrees. However, as incident angles surpass the 30-degree threshold, the measured values diverge from their corresponding theoretical projections, resulting in a progressive reduction in the completeness of the donut-shaped structure.

De-sialylated and sialylated IgG anti-dsDNA antibodies respectively worsen and mitigate experimental mouse lupus proteinuria and possible mechanisms.

BACKGROUND: The role of sialylated and de-sialylated (de-SIA) IgG anti-dsDNA antibodies in experimental mouse lupus remains unclear. AIM OF THE STUDY: To examine how sialylated and de-SIA IgG anti-dsDNA antibodies affect lupus mouse proteinuria and possible mechanisms. METHODS: Blood was serially obtained from pristane-induced female BALB/c lupus mice to assess correlations between alpha-2,6-sialic cid (SIA) ratios of serum IgG anti-dsDNA and proteinuria. Kidney C3 staining was correlated with blood IgG anti-dsDNA. Sialylated IgG anti-dsDNA with its de-SIA form was administered to determine the effect on lupus proteinuria and in vitro consequences. RESULTS: We observed that the SIA contents of IgG anti-dsDNA were lower in Week 16/1+ (Week 16 with 1 + proteinuria) and W24/2 + mice than those in W16 (no proteinuria) and W24/1 + mice, respectively (P < 0.005 for both). C3 staining densities in the kidney correlated inversely with the α-2,6-SIA content of plasma IgG anti-dsDNA (r = -0.660). Highly sialylated A52L1 IgG anti-dsDNA injection mitigated lupus proteinuria significantly from PBS injection; however, its de-SIA form worsened proteinuria (aggravation of proteinuria: the latter vs. the former [sialylated A52L1 IgG anti-dsDNA] with an infinite odds ratio). Highly sialylated A52L1 IgG anti-dsDNA resulted in higher interleukin (IL)-10/IL-12 ratios, higher transforming growth factor-ß1 levels, and lower tumor necrosis factor-α levels in sera than its de-SIA from. CONCLUSION: We concluded that a low SIA/serum IgG anti-dsDNA ratio indicated a high severity of nephritis in pristane-induced lupus mice. Highly sialylated IgG anti-dsDNA, in contrast to the de-SIA form, alleviated the severity of lupus proteinuria.

Polarization-insensitive GaN metalenses at visible wavelengths.

The growth of wide-bandgap materials on patterned substrates has revolutionized the means with which we can improve the light output power of gallium nitride (GaN) light-emitting diodes (LEDs). Conventional patterned structure inspection usually relies on an expensive vacuum-system-required scanning electron microscope (SEM) or optical microscope (OM) with bulky objectives. On the other hand, ultra-thin metasurfaces have been widely used in widespread applications, especially for converging lenses. In this study, we propose newly developed, highly efficient hexagon-resonated elements (HREs) combined with gingerly selected subwavelength periods of the elements for the construction of polarization-insensitive metalenses of high performance. Also, the well-developed fabrication techniques have been employed to realize the high-aspect-ratio metalenses working at three distinct wavelengths of 405, 532, and 633 nm with respective diffraction-limited focusing efficiencies of 93%, 86%, and 92%. The 1951 United States Air Force (USAF) test chart has been chosen to characterize the imaging capability. All of the images formed by the 405-nm-designed metalens show exceptional clear line features, and the smallest resolvable features are lines with widths of 870 nm. To perform the inspection capacity for patterned substrates, for the proof of concept, a commercially available patterned sapphire substrate (PSS) for the growth of the GaN LEDs has been opted and carefully examined by the high-resolution SEM system. With the appropriately chosen metalenses at the desired wavelength, the summits of structures in the PSS can be clearly observed in the images. The PSS imaging qualities taken by the ultra-thin and light-weight metalenses with a numerical aperture (NA) of 0.3 are comparable to those seen by an objective with the NA of 0.4. This work can pioneer semiconductor manufacturing to choose the polarization-insensitive GaN metalenses to inspect the patterned structures instead of using the SEM or the bulky and heavy conventional objectives.

High-performance gallium nitride dielectric metalenses for imaging in the visible.

Metalens is one of the most promising applications for the development of metasurfaces. A wide variety of materials have been applied to metalenses working at certain spectral bands in order to meet the requirements of high efficiency and low-cost fabrication. Among these materials, wide-bandgap gallium nitride (GaN) is one of the most promising materials considering its advantages especially in semiconductor manufacturing. In this work, GaN has been utilized to fabricate the high-performance metalenses operating at visible wavelengths of 405, 532, and 633 nm with efficiencies up to 79%, 84%, and 89%, respectively. The homemade 1951 United State Air Force (UASF) resolution test chart has also been fabricated in order to provide resolvable lines with widths as small as 870 nm. As shown in the experimental results for imaging, the metalens designed at 405 nm can provide extremely high resolution to clearly resolve the smallest lines with the nano-sized widths in the homemade resolution test chart. These extraordinary experimental results come from our successful development in design and fabrication for the metalenses composed of high-aspect-ratio GaN nanoposts with nearly vertical sidewalls.

Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy.

Highly expressed in cancer 1 (Hec1) plays an essential role in mitosis and is correlated with cancer formation, progression, and survival. Phosphorylation of Hec1 by Nek2 kinase is essential for its mitotic function, thus any disruption of Hec1/Nek2 protein-protein interaction has potential for cancer therapy. We have developed T-1101 tosylate (9j tosylate, 9j formerly known as TAI-95), optimized from 4-aryl-N-pyridinylcarbonyl-2-aminothiazole of scaffold 9 by introducing various C-4' substituents to enhance potency and water solubility, as a first-in-class oral clinical candidate for Hec1 inhibition with potential for cancer therapy. T-1101 has good oral absorption, along with potent in vitro antiproliferative activity (IC50: 14.8-21.5 nM). It can achieve high concentrations in Huh-7 and MDA-MB-231 tumor tissues, and showed promise in antitumor activity in mice bearing human tumor xenografts of liver cancer (Huh-7), as well as of breast cancer (BT474, MDA-MB-231, and MCF7) with oral administration. Oral co-administration of T-1101 halved the dose of sorafenib (25 mg/kg to 12.5 mg/kg) required to exhibit comparable in vivo activity towards Huh-7 xenografts. Cellular events resulting from Hec1/Nek2 inhibition with T-1101 treatment include Nek2 degradation, chromosomal misalignment, and apoptotic cell death. A combination of T-1101 with either of doxorubicin, paclitaxel, and topotecan in select cancer cells also resulted in synergistic effects. Inactivity of T-1101 on non-cancerous cells, a panel of kinases, and hERG demonstrates cancer specificity, target specificity, and cardiac safety, respectively. Subsequent salt screening showed that T-1101 tosylate has good oral AUC (62.5 µM·h), bioavailability (F = 77.4%), and thermal stability. T-1101 tosylate is currently in phase I clinical trials as an orally administered drug for cancer therapy.

Hierarchical structure and crystal orientation in poly(ethylene oxide)/clay nanocomposite films.

Water-cast nanocomposite films formed by poly(ethylene oxide) (PEO) and Laponite clay were found to display three characteristic levels of structure with large-scale orientation. The first level with the length scale of ca. 30-50 nm was the clay lamellar bundles, which tended to stack perpendicularly to the film surface. The second level with the characteristic length of 1.8 nm was associated with the alternating stacking of the silicate layers and the PEO chains sandwiched between them. The preferred orientations of these two levels of structure were independent of clay content, solvent removal rate for the film preparation, and the crystallization temperature of the PEO chains situating outside the clay bundles. The third level of structure was characterized by the preferred orientation of the PEO crystalline stems with respect to the surface of the silicate layers. Perpendicular orientation always dominated in the nanocomposite films prepared by slow solvent removal irrespective of crystallization temperature. In the films prepared by fast solvent removal, however, parallel crystal orientation set in as the clay concentration exceeded ca. 33 wt %. The preferred crystal orientation was ascribed to the confinement effect imposed by the clay bundles to the crystallization of the PEO chains situating in the interbundle region. In the films cast by slow solvent removal, the weaker confinement associated with the larger interbundle distance led to perpendicular crystal orientation. When the interbundle distance was reduced to ca. 30 nm in the films prepared by rapid solvent evaporation, the strong confinement directed the crystals to form parallel orientation.

Blood monocyte chemotactic protein-1 (MCP-1) and adapted disease activity Score28-MCP-1: favorable indicators for rheumatoid arthritis activity.

OBJECTIVE: We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect. METHODS: In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1. RESULTS: Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r  = 0.984, P<0.001) and DAS28-CRP (r  = 0.971, P<0.001), and modestly correlated with CRP (r  = 0.350, P<0.001), and ESR (r  = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r  = 0.944, P<0.001; r  = 0.951, P<0.001; r  = 0.862, P<0.001; and r  = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively). CONCLUSION: Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.

Synthesis and biological activity of pyridopyridazin-6-one p38α MAP kinase inhibitors. Part 2.

This manuscript concludes the Structure Activity Relationship (SAR) on the pyridazinone scaffold and identifies a compound with subnanomolar p38α activity and 24h coverage in the rat arthritis efficacy model.

Synthesis and biological activity of pyridopyridazin-6-one p38 MAP kinase inhibitors. Part 1.

The development and synthesis of potent p38α MAP kinase inhibitors containing a pyridazinone platform is described. Evolution of the p38α selective pyridopyridazin-6-one series from the p38α/ß dual inhibitor 2H-quinolizin-2-one series will be discussed in full detail.

Synthesis and biological activity of 2H-quinolizin-2-one based p38alpha MAP kinase inhibitors.

The development and synthesis of potent p38alpha MAP kinase inhibitors containing a 2H-quinolizin-2-one platform is described. Evolution of the 2H-quinolizin-2-one series from an early lead to solving off target activity and pharmacokinetic issues is also discussed.

Synthesis and biological activity of quinolinone and dihydroquinolinone p38 MAP kinase inhibitors.

Synthesis and biological activities of some quinolinone and dihydroquinolinone p38 MAP kinase inhibitors are reported. Modifications to the dihydroquinolinone pharmacophore revealed that dihydroquinolinone may be replaced with a quinolinone pharmacophore and lead to enhanced p38 inhibitory activity. From a study of C-7 substitutions by amino acid side chains, a very potent series of compounds in the p38 enzyme assays was identified. Translation of the in vitro activity into reasonable whole blood activity can be improved in this series of compounds by judicious modification of the physical properties at appropriate regions of the lead.

SAR of 3,4-dihydropyrido[3,2-d]pyrimidone p38 inhibitors.

Development for a class of potent 3,4-dihydropyrido(3,2-d)pyrimidone inhibitors of p38a MAP kinase is described. Modification of N-1 aryl and C-6 arylsulfide in 3,4-dihydropyrido(3,2-d)pyrimidone analogues for the interaction with the hydrophobic pockets in p38 active site is also discussed.