Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis-a study using CoVariant protein arrays.

Objectives: RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants. Methods: We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously. Results: Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants. Conclusion: After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition.

Antibody Profiling of Dengue Severities Using Flavivirus Protein Microarrays.

Dengue is a viral disease transmitted by Aedes aegypti mosquitoes. According to the World Health Organization, about half of the world's population is at risk of dengue. There are four serotypes of the dengue virus. After infection with one serotype, it will be immune to such a serotype. However, subsequent infection with other serotypes will increase the risk of severe outcomes, e.g., dengue hemorrhagic fever, dengue shock syndrome, and even death. Since severe dengue is challenging to predict and lacks molecular markers, we aim to build a multiplexed Flavivirus protein microarray (Flaviarray) that includes all of the common Flaviviruses to profile the humoral immunity and cross-reactivity in the dengue patients with different outcomes. The Flaviarrays we fabricated contained 17 Flavivirus antigens with high reproducibility (R-square = 0.96) and low detection limits (172-214 pg). We collected serums from healthy subjects (n = 36) and dengue patients within 7 days after symptom onset (mild dengue (n = 21), hospitalized nonsevere dengue (n = 29), and severe dengue (n = 36)). After profiling the serum antibodies using Flaviarrays, we found that patients with severe dengue showed higher IgG levels against multiple Flavivirus antigens. With logistic regression, we found groups of markers with high performance in distinguishing dengue patients from healthy controls as well as hospitalized from mild cases (AUC > 0.9). We further reported some single markers that were suitable to separate dengue patients from healthy controls (AUC > 0.9) and hospitalized from mild outcomes (AUC > 0.8). Together, Flaviarray is a valuable tool to profile antibody specificities, uncover novel markers for decision-making, and shed some light on early preventions and treatments.

Developing magnetic barcode bead fluorescence assay for high throughput analyzing humoral responses against multiple SARS-CoV-2 variants.

The continuous mutation of SARS-CoV-2 highlights the need for rapid, cost-effective, and high-throughput detection methods. To better analyze the antibody levels against SARS-CoV-2 and its variants in vaccinated or infected subjects, we developed a multiplex detection named Barcode Bead Fluorescence (BBF) assay. These barcode beads were magnetic, characterized by 2-dimensional edges, highly multiplexed, and could be decrypted with visible light. We conjugated 12 magnetic barcode beads with corresponding nine spike proteins (wild-type, alpha, beta, gamma, delta, and current omicrons), two nucleocapsid proteins (wild-type and omicron), and one negative control. First, the conjugated beads underwent serial quality controls via fluorescence labeling, e.g., reproducibility (R square = 0.99) and detection limits (119 pg via anti-spike antibody). Next, we investigated serums from vaccinated subjects and COVID-19 patients for clinical applications. A significant reduction of antibody levels against all variant beads was observed in both vaccinated and COVID-19 studies. Subjects with two doses of mRNA-1273 exhibited the highest level of antibodies against all spike variants compared to two doses of AZD1222 and unvaccinated. We also found that COVID-19 patients showed higher antibody levels against spike beads from wild-type, alpha, beta, and delta. Finally, the nucleocapsid beads served as markers to distinguish infections from vaccinated subjects. Overall, this study developed the BBF assay for analyzing humoral immune responses, which has the advantages of robustness, automation, scalability, and cost-effectiveness.

Circadian rhythm-related factors of PER and CRY family genes function as novel therapeutic targets and prognostic biomarkers in lung adenocarcinoma.

The period (PER) and cryptochrome (CRY) families play critical roles in circadian rhythms. The imbalance of circadian factors may lead to the occurrence of cancer. Expressions of PER and CRY family members decrease in various cancers. Nevertheless, expression levels, genetic variations, and molecular mechanisms of PER and CRY family members in lung adenocarcinoma (LUAD) and their correlations with prognoses and immune infiltration in LUAD patients are still unclear. In this study, to identify their biological functions in LUAD development, comprehensive high-throughput techniques were applied to analyze the relationships of expressions of PER and CRY family members with genetic variations, molecular mechanisms, and immune infiltration. The present results showed that transcription levels of PER1 and CRY2 in LUAD were significantly downregulated. High expression levels of PER2, PER3, CRY1, and CRY2 indicated longer overall survival. Some cancer signaling pathways were related to PER and CRY family members, such as cell-cycle, histidine metabolism, and progesterone-mediated oocyte maturation pathways. Expressions of PER and CRY family members significantly affected the infiltration of different immune cells. In conclusion, our findings may help better understand the molecular basis of LUAD, and provide new perspectives of PER and CRY family members as novel biomarkers for LUAD.

Photonic Crystal Circular Nanobeam Cavity Laser with Type-II GaSb/GaAs Quantum Rings as Gain Material.

The optical emission from type-II semiconductor nanostructures is influenced by the long carrier lifetime and can exhibit remarkable thermal stability. In this study, utilizing a high quality photonic crystal circular nanobeam cavity with a high quality factor and a sub-micrometer mode volume, we demonstrated an ultra-compact semiconductor laser with type-II gallium antimonide/gallium arsenide quantum rings (GaSb/GaAs QRs) as the gain medium. The lasing mode localized around the defect region of the nanobeam had a small modal volume and significant coupling with the photons emitted by QRs. It leads the remarkable shortening of carrier lifetime observed from the time-resolved photoluminescence (TRPL) and a high Purcell factor. Furthermore, a high characteristic temperature of 114 K was observed from the device. The lasing performances indicated the type-II QRs laser is suitable for applications of photonic integrated circuit and bio-detection applications.

High-Efficiency Bifacial Dye-Sensitized Solar Cells for Application under Indoor Light Conditions.

High-efficiency, stable bifacial dye-sensitized solar cells (DSSCs) are prepared for application under indoor light conditions. A 3-methoxypropionitrile solvent and cobalt redox couples are utilized to prepare the electrolytes. To obtain the best cell performance, the components of the DSSCs, including electrolytes, photoanodes, and counter electrodes (CEs), are regulated. The experimental results indicate that an electrolyte comprising a Co (II/III) ratio of 0.11/0.025 M, 1.2 M 4-tert-butylpyridine, Y123 dye, a CE with the platinum (Pt) layer thickness of 0.16 nm, and a photoanode with titanium dioxide (TiO2) layer thickness of 10 µm (6 µm main layer and 4 µm scattering layer) are the best conditions under which to achieve a high power conversion efficiency. It is also found that the best cells have high recombination resistance at the photoelectrode/electrolyte interface and low charge transfer resistance at the counter electrode/electrolyte interface, which contributes to, respectively, the high current density and open-circuit voltage of the corresponding cells. This DSSC can achieve efficiencies of 22.66%, 23.48%, and 24.52%, respectively, under T5 light illumination of 201.8, 607.8, and 999.6 lx. For fabrication of bifacial DSSCs with a semitransparent property, photoanodes without the TiO2 scattering layer, as well as an ultrathin Pt film, are utilized. The thicknesses of the TiO2 main layer and Pt film are reregulated. This shows that a Pt film with 0.55 nm thickness has both high transmittance (76.01%) and catalytic activity. By using an 8 µm TiO2 main layer, optimal cell efficiencies of 20.65% and 17.31% can be achieved, respectively, for the front-side and back-side illuminations of 200 lx T5 light. The cells are highly stable during a long-term performance test at both 35 and 50 °C.

Importance of Compact Blocking Layers to the Performance of Dye-Sensitized Solar Cells under Ambient Light Conditions.

Power generation in indoor environments is the next step in dye-sensitized solar cell (DSSC) evolution. To achieve this goal, a critical recombination route which is usually inhibited by the TiCl4-derived blocking layers (BLs), that is, charge transfer at the fluorine-doped tin oxide substrate/electrolyte interface, is of concern. In this study, we demonstrate that because of low surface coverage, the conventional TiCl4 BLs are unable to suppress such electron leakage, thus limiting the photovoltaic performance of Co(bpy)32+/3+-mediated DSSCs (bpy = 2,2'-bipyridine) under ambient lighting. On the other hand, by introducing compact BLs prepared by spray pyrolysis, the DSSCs show lower dark current and operate efficiently not only under high-intensity sunlight but also under ambient light conditions. The better blocking function of the compact BL is verified by the cyclic voltammetry; other thin-film preparation methods, except for the common TiCl4 treatment, are anticipated to realize a similar blocking effect. This study illustrates that dense thin film with a predominant blocking function is highly required as the BL for DSSCs under low-light conditions, and this concept will pave the way for more development of indoor DSSCs.

Direct observation of impact propagation and absorption in dense colloidal monolayers.

Dense colloidal suspensions can propagate and absorb large mechanical stresses, including impacts and shocks. The wave transport stems from the delicate interplay between the spatial arrangement of the structural units and solvent-mediated effects. For dynamic microscopic systems, elastic deformations of the colloids are usually disregarded due to the damping imposed by the surrounding fluid. Here, we study the propagation of localized mechanical pulses in aqueous monolayers of micron-sized particles of controlled microstructure. We generate extreme localized deformation rates by exciting a target particle via pulsed-laser ablation. In crystalline monolayers, stress propagation fronts take place, where fast-moving particles (V approximately a few meters per second) are aligned along the symmetry axes of the lattice. Conversely, more viscous solvents and disordered structures lead to faster and isotropic energy absorption. Our results demonstrate the accessibility of a regime where elastic collisions also become relevant for suspensions of microscopic particles, behaving as "billiard balls" in a liquid, in analogy with regular packings of macroscopic spheres. We furthermore quantify the scattering of an impact as a function of the local structural disorder.

Wave propagation in one-dimensional microscopic granular chains.

We employ noncontact optical techniques to generate and measure stress waves in uncompressed, one-dimensional microscopic granular chains, and support our experiments with discrete numerical simulations. We show that the wave propagation through dry particles (150 µm radius) is highly nonlinear and it is significantly influenced by the presence of defects (e.g., surface roughness, interparticle gaps, and misalignment). We derive an analytical relation between the group velocity and gap size, and define bounds for the formation of highly nonlinear solitary waves as a function of gap size and axial misalignment.

Arbitrary waveform synthesis by multiple harmonics generation and phasing in aperiodic optical superlattices.

The process of generating periodic optical waveforms includes the generation and phasing of several harmonics of a fundamental frequency. In this work, we show that simultaneous generation and phasing of the harmonics can be performed in a monolithic aperiodic optical superlattice (AOS). Stable periodic waveforms can thus be delivered to a predetermined location by simply sending a laser beam through a properly designed and fabricated AOS crystal. A detailed mathematical description for generating the domain pattern in such an AOS crystal is given and the process is numerically demonstrated. The waveform that is generated from a monolithic AOS is highly reproducible and phase stable. We also use propagation in air as an example to show how any predictable phase and amplitude modifications such as air dispersion that will alter the desired waveform can be pre-compensated in the design phase of the AOS crystal.

Low-light-level all-optical switching.

We propose an all-optical switch that utilizes the technique of storage and retrieval of light pulses. A single photon (probe pulse) switched by another (switching pulse) is feasible, and the on-off ratio can be as large as 10 dB. We have experimentally demonstrated that the energy of the retrieved probe pulse is reduced to about 10% because of the presence of a switching pulse with an energy per unit area of one photon per lambda(2)/(2pi). The achieved result does not depend on the coupling intensity, the atomic optical density, or the width and shape of the switching pulse.