Molecular Design of Encapsulin Protein Nanoparticles to Display Rotavirus Antigens for Enhancing Immunogenicity.

Rotavirus considerably threatens global health, particularly for children <5 years. Current, licensed oral attenuated vaccine formulations have limitations including insufficient efficacy in children in low- and middle-income countries, warranting urgent development of novel vaccines with improved efficacy and safety profiles. Herein, we present a novel approach utilizing an encapsulin (ENC) nanoparticle (NP)-based non-replicating rotavirus vaccine. ENC, originating from bacteria, offers a self-assembling scaffold that displays rotavirus VP8* antigens on its surface. To enhance the correct folding and soluble expression of monomeric antigens and their subsequent assembly into NP, we adopted an RNA-interacting domain (RID) of mammalian transfer RNA synthetase as an expression tag fused to the N-terminus of the ENC-VP8* fusion protein. Using the RID-ENC-VP8* tripartite modular design, insertion of linkers of appropriate length and sequence and the universal T cell epitope P2 remarkably improved the production yield and immunogenicity. Cleavage of the RID rendered a homogenous assembly of ENC-P2-VP8* into protein NPs. Immunization with ENC-P2-VP8* induced markedly higher levels of VP8*-specific antibodies and virus neutralization titers in mice than those induced by P2-VP8* without ENC. Altogether, these results highlight the potential of the designed ENC NP-based rotavirus vaccine as an effective strategy against rotavirus disease to address global health challenges.

Strain-graded quantum dots with spectrally pure, stable and polarized emission.

Structural deformation modifies the bandgap, exciton fine structure and phonon energy of semiconductors, providing an additional knob to control their optical properties. The impact can be exploited in colloidal semiconductor quantum dots (QDs), wherein structural stresses can be imposed in three dimensions while defect formation is suppressed by controlling surface growth kinetics. Yet, the control over the structural deformation of QDs free from optically active defects has not been reached. Here, we demonstrate strain-graded CdSe-ZnSe core-shell QDs with compositionally abrupt interface by the coherent pseudomorphic heteroepitaxy. Resulting QDs tolerate mutual elastic deformation of varying magnitudes at the interface with high structural fidelity, allowing for spectrally stable and pure emission of photons at accelerated rates with near unity luminescence efficiency. We capitalize on the asymmetric strain effect together with the quantum confinement effect to expand emission envelope of QDs spanning the entire visible region and exemplify their use in photonic applications.

Impact of Alternating-Current Operation on All-Inorganic Quantum Dot Light-Emitting Diodes.

In colloidal quantum dot light-emitting diodes (QD-LEDs), replacing organic hole transport layers (HTLs) with their inorganic counterparts is expected to yield distinct advantages due to their inherent material robustness. However, despite the promising characteristics of all-inorganic QD-LEDs, some challenges persist in achieving stable operation; for example, the electron overflow toward the inorganic HTL and charge accumulation within working devices return a temporal inconsistency in device characteristics. To address these challenges, we propose an operational approach that employs an alternating-current (AC) in all-inorganic QD-LEDs. We carry out comprehensive studies on the optoelectrical characteristics of all-inorganic QD-LEDs under direct-current (DC) or AC operation and demonstrate that AC operation can facilitate efficient charge carrier recombination within the QD emissive layer, leading to improved device efficiency and temporally invariant optoelectronic characteristics. Leveraging the intrinsic material robustness of inorganic charge transport layers (CTLs), our current study suggests a promising pathway toward enhancing the performance and stability of QD-LEDs, particularly for futuristic display applications.

Growth Control of InP/ZnSe Heterostructured Nanocrystals.

The morphology of heterostructured semiconductor nanocrystals (h-NCs) dictates the spatial distribution of charge carriers and their recombination dynamics and/or transport, which are the main performance indicators of photonic applications utilizing h-NCs. The inability to control the morphology of heterovalent III-V/II-VI h-NCs composed of heavy-metal-free elements hinders their practical use. As a case study of III-V/II-VI h-NCs, the growth control of ZnSe epilayers on InP NCs is demonstrated here. The anisotropic morphology in InP/ZnSe h-NCs is attributed to the facet-dependent energy costs for the growth of ZnSe epilayers on different facets of InP NCs, and effective chemical means for controlling the growth rates of ZnSe on different surface planes are demonstrated. Ultimately, this article capitalizes on the controlled morphology of InP/ZnSe h-NCs to expand their photophysical characteristics from stable and pure emission to environment-sensitive one, which will facilitate their use in a variety of photonic applications.

One-year antibody durability induced by EuCorVac-19, a liposome-displayed COVID-19 receptor binding domain subunit vaccine, in healthy Korean subjects.

OBJECTIVE: EuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. METHODS: To assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. RESULTS: Median anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the "early" period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the "late" period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). CONCLUSION: These data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Coherent heteroepitaxial growth of I-III-VI2 Ag(In,Ga)S2 colloidal nanocrystals with near-unity quantum yield for use in luminescent solar concentrators.

Colloidal Ag(In,Ga)S2 nanocrystals (AIGS NCs) with the band gap tunability by their size and composition within visible range have garnered surging interest. High absorption cross-section and narrow emission linewidth of AIGS NCs make them ideally suited to address the challenges of Cd-free NCs in wide-ranging photonic applications. However, AIGS NCs have shown relatively underwhelming photoluminescence quantum yield (PL QY) to date, primarily because coherent heteroepitaxy has not been realized. Here, we report the heteroepitaxy for AIGS-AgGaS2 (AIGS-AGS) core-shell NCs bearing near-unity PL QYs in almost full visible range (460 to 620 nm) and enhanced photochemical stability. Key to the successful growth of AIGS-AGS NCs is the use of the Ag-S-Ga(OA)2 complex, which complements the reactivities among cations for both homogeneous AIGS cores in various compositions and uniform AGS shell growth. The heteroepitaxy between AIGS and AGS results in the Type I heterojunction that effectively confines charge carriers within the emissive core without optically active interfacial defects. AIGS-AGS NCs show higher extinction coefficient and narrower spectral linewidth compared to state-of-the-art heavy metal-free NCs, prompting their immediate use in practicable applications including displays and luminescent solar concentrators (LSCs).

Electrically driven amplified spontaneous emission from colloidal quantum dots.

Colloidal quantum dots (QDs) are attractive materials for realizing solution-processable laser diodes that could benefit from size-controlled emission wavelengths, low optical-gain thresholds and ease of integration with photonic and electronic circuits1-7. However, the implementation of such devices has been hampered by fast Auger recombination of gain-active multicarrier states1,8, poor stability of QD films at high current densities9,10 and the difficulty to obtain net optical gain in a complex device stack wherein a thin electroluminescent QD layer is combined with optically lossy charge-conducting layers11-13. Here we resolve these challenges and achieve amplified spontaneous emission (ASE) from electrically pumped colloidal QDs. The developed devices use compact, continuously graded QDs with suppressed Auger recombination incorporated into a pulsed, high-current-density charge-injection structure supplemented by a low-loss photonic waveguide. These colloidal QD ASE diodes exhibit strong, broadband optical gain and demonstrate bright edge emission with instantaneous power of up to 170 µW.

Linearly polarized emission from CdSe/CdS core-in-rod nanostructures: Effects of core position.

Semiconductor nanocrystals with an anisotropic morphology exhibit unique properties, most notably their linear polarization. The colloidal growth of semiconductor nanorods with core dots inside, also referred to as dot-in-rod (DIR) structure, has enabled the synthesis of anisotropic nanocrystals with better stability and controllable fluorescence polarization. In this study, we synthesize CdSe/CdS DIR nanocrystals, in which the position of the CdSe core particle can be controlled by using different ligand compositions during the CdS growth. Varying the core position within the DIR structure, e.g., from the center to the end of the DIR particles, results in a change in the degree of linear polarization. When the core is positioned at the center of the nanorod, the linear polarization turns out to be higher compared with tip-core DIRs. Time-resolved photoluminescence analysis reveals that the center-core DIRs have higher electron-hole interaction than tip-core DIRs because of weak uniaxial strain in center-core DIR that arises from lattice dislocations at the interface to relieve accumulated strain.

Optically Excited Lasing in a Cavity-Based, High-Current-Density Quantum Dot Electroluminescent Device.

Laser diodes based on solution-processable materials can benefit numerous technologies including integrated electronics and photonics, telecommunications, and medical diagnostics. An attractive system for implementing these devices is colloidal semiconductor quantum dots (QDs). The progress towards a QD laser diode has been hampered by rapid nonradiative Auger decay of optical-gain-active multicarrier states, fast device degradation at high current densities required for laser action, and unfavorable competition between optical gain and optical losses in a multicomponent device stack. Here we resolve some of these challenges and demonstrate optically excited lasing from fully functional high-current density electroluminescent (EL) devices with an integrated optical resonator. This advance has become possible due to excellent optical gain properties of continuously graded QDs and a refined device architecture, which allows for highly efficient light amplification in a thin, EL-active QD layer.

Impact of Morphological Inhomogeneity on Excitonic States in Highly Mismatched Alloy ZnSe1-XTeX Nanocrystals.

ZnSe1-XTeX nanocrystals (NCs) are promising photon emitters with tunable emission across the violet to orange range and near-unity quantum yields. However, these NCs suffer from broad emission line widths and multiple exciton decay dynamics, which discourage their practicable use. Here, we explore the excitonic states in ZnSe1-XTeX NCs and their photophysical characteristics in relation to the morphological inhomogeneity of highly mismatched alloys. Ensemble and single-dot spectroscopic analysis of a series of ZnSe1-XTeX NC samples with varying Te ratios coupled with computational calculations shows that, due to the distinct electronegativity between Se and Te, nearest-neighbor Te pairs in ZnSe1-XTeX alloys create localized hole states spectrally distributed approximately 130 meV above the 1Sh level of homogeneous ZnSe1-XTeX NCs. This forms spatially separated excitons (delocalized electron and localized hole in trap), accounting for both inhomogeneous and homogeneous line width broadening with delayed recombination dynamics. Our results identify photophysical characteristics of excitonic states in NCs made of highly mismatched alloys and provide future research directions with potential implications for photonic applications.

Interim analysis from a phase 2 randomized trial of EuCorVac-19: a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine.

BACKGROUND: Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. METHODS: Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19-75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 µg RBD), 96 received low-dose ECV19 (10 µg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). RESULTS: Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. CONCLUSIONS: ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that neutralized SARS-CoV-2. The unique liposome display approach of ECV19, which lacks any immunogenic protein components besides the antigen itself, coupled with the lack of increased adverse events during boosting suggest the vaccine platform may be amenable to multiple boosting regimes in the future. Taken together, these findings motivate further investigation of ECV19 in larger scale clinical testing that is underway. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov as # NCT04783311.

Incidence and Prevalence of Peripheral Arterial Disease in South Korea: Retrospective Analysis of National Claims Data.

BACKGROUND: Peripheral arterial disease (PAD) causes blood vessel narrowing that decreases blood flow to the lower extremities, with symptoms such as leg pain, discomfort, and intermittent claudication. PAD increases risks for amputation, poor health-related quality of life, and mortality. It is estimated that more than 200 million people worldwide have PAD, although the paucity of PAD research in the East detracts from knowledge on global PAD epidemiology. There are few national data-based analyses or health care utilization investigations. Thus, a national data analysis of PAD incidence and prevalence would provide baseline data to enable health promotion strategies for patients with PAD. OBJECTIVE: This study aims to identify South Korean trends in the incidence and prevalence of PAD and PAD treatment, in-hospital deaths, and health care utilization. METHODS: This was a retrospective analysis of South Korean national claims data from 2009 to 2018. The incidence of PAD was determined by setting the years 2010 and 2011 as a washout period to exclude previously diagnosed patients with PAD. The study included adults aged ≥20 and <90 years who received a primary diagnosis of PAD between 2011 and 2018; patients were stratified according to age, sex, and insurance status for the incidence and prevalence analyses. Descriptive statistics were used to assess incidence, prevalence, endovascular revascularization (EVR) events, amputations, in-hospital deaths, and the health care utilization characteristics of patients with PAD. RESULTS: Based on data from 2011 to 2018, there were an average of 124,682 and 993,048 incident and prevalent PAD cases, respectively, in 2018. PAD incidence (per 1000 persons) ranged from 2.68 to 3.09 during the study period. From 2012 to 2018, the incidence rate in both sexes showed an increasing trend. PAD incidence continued to increase with age. PAD prevalence (per 1000 persons) increased steadily, from 3.93 in 2011 to 23.55 in 2018. The number of EVR events varied between 933 and 1422 during the study period, and both major and minor amputations showed a decreasing trend. Health care utilization characteristics showed that women visited clinics more frequently than men, whereas men used tertiary and general hospitals more often than women. CONCLUSIONS: The number of incident and prevalent PAD cases generally showed an increasing trend. Visits to tertiary and general hospitals were higher among men than women. These results indicate the need for attention not only to Western and male patients, but also to Eastern and female patients with PAD. The results are generalizable, as they are based on national claims data from the entire South Korean population, and they can promote preventive care and management strategies for patients with PAD in clinical and public health settings.

Inhibitory Effects of Acetyloctadecadienediynoic Acid Isolated from Leaves of Dendropanax morbiferus on Viability and Self-Renewal Activity of Glioma Stem-Like Cells.

Glioblastoma (GBM) is one of the most dangerous brain tumors in humans. The median survival of patients with GBM is <18 months. Glioma stem-like cells (GSCs), a small subpopulation of cells with stem cell-like characteristics found within GBM, are regarded as the main cause of GBM malignancy. Therefore, targeting GSCs presents an important therapeutic strategy for reducing the aggressiveness of tumors. In this study, we examined effects of (9Z,16S)-16-O-acetyl-9,17-octadecadiene-12,14-diynoic acid (AODA), a diacetylenic carboxylic acid isolated from leaves of Dendropanax morbiferus, on viability and self-renewal activity of GSCs. AODA substantially decreased GSC growth, causing apoptotic cell death as assessed by Annexin V/PI staining and morphological alterations by optical diffraction tomography. Interestingly, treatment with AODA suppressed ''stem-like features'' in vitro by limiting dilution assays and real-time polymerase chain reaction analysis. In addition, Western blotting revealed that AODA treatment decreased expression levels of phosphorylated AKT and phosphorylated ERK in GSC11 cells. Taken together, our results indicate that AODA could be considered a new therapeutic candidate to target GSCs.

Direct patterning of colloidal quantum dots with adaptable dual-ligand surface.

Colloidal quantum dots (QDs) stand at the forefront of a variety of photonic applications given their narrow spectral bandwidth and near-unity luminescence efficiency. However, integrating luminescent QD films into photonic devices without compromising their optical or transport characteristics remains challenging. Here we devise a dual-ligand passivation system comprising photocrosslinkable ligands and dispersing ligands to enable QDs to be universally compatible with solution-based patterning techniques. The successful control over the structure of both ligands allows the direct patterning of dual-ligand QDs on various substrates using commercialized photolithography (i-line) or inkjet printing systems at a resolution up to 15,000 pixels per inch without compromising the optical properties of the QDs or the optoelectronic performance of the device. We demonstrate the capabilities of our approach for QD-LED applications. Our approach offers a versatile way of creating various structures of luminescent QDs in a cost-effective and non-destructive manner, and could be implemented in nearly all commercial photonics applications where QDs are used.

Efficient, Selective CO2 Photoreduction Enabled by Facet-Resolved Redox-Active Sites on Colloidal CdS Nanosheets.

Advances in nanotechnology have enabled precise design of catalytic sites for CO2 photoreduction, pushing product selectivity to near unity. However, activity of most nanostructured photocatalysts remains underwhelming due to fast recombination of photogenerated electron-hole pairs and sluggish hole transfer. To address these issues, we construct colloidal CdS nanosheets (NSs) with the large basal planes terminated by S2- atomic layers as intrinsic photocatalysts (CdS-S2- NSs). Experimental investigation reveals that the S2- termination endows ultrathin CdS-S2- NSs with facet-resolved redox-catalytic sites: oxidation occurs on S2--terminated large basal facets and reduction happens on side facets. Such an allocation of redox sites not only promotes spatial separation of photoinduced electrons and holes but also facilitates balanced extraction of holes and electrons by shortening the hole diffusion distance along the (001) direction of the ultrathin NSs. Consequently, the CdS-S2- NSs exhibit superb performance for photocatalytic CO2-to-CO conversion, which was verified by the isotope-labeled experiments to be a record-breaking performance: a CO selectivity of 99%, a CO formation rate of 2.13 mol g-1 h-1, and an effective apparent quantum efficiency of 42.1% under the irradiation (340 to 450 nm) of a solar simulator (AM 1.5G). The breakthrough performance achieved in this work provides novel insights into the precise design of nanostructures for selective and efficient CO2 photoreduction.

Two-band optical gain and ultrabright electroluminescence from colloidal quantum dots at 1000 A cm-2.

Colloidal quantum dots (QDs) are attractive materials for the realization of solution-processable laser diodes. Primary challenges towards this objective are fast optical-gain relaxation due to nonradiative Auger recombination and poor stability of colloidal QD solids under high current densities required to obtain optical gain. Here we resolve these challenges and achieve broad-band optical gain spanning the band-edge (1S) and the higher-energy (1P) transitions. This demonstration is enabled by continuously graded QDs with strongly suppressed Auger recombination and a current-focusing device design, combined with short-pulse pumping. Using this approach, we achieve ultra-high current densities (~1000 A cm-2) and brightness (~10 million cd m-2), and demonstrate an unusual two-band electroluminescence regime for which the 1P band is more intense than the 1S feature. This implies the realization of extremely large QD occupancies of up to ~8 excitons per-dot, which corresponds to complete filling of the 1S and 1P electron shells.

Light-Driven Ammonia Production by Azotobacter vinelandii Cultured in Medium Containing Colloidal Quantum Dots.

There is an evergrowing demand for environment-friendly processes to synthesize ammonia (NH3) from atmospheric nitrogen (N2). Although diazotrophic N2 fixation represents an undeniably "green" process of NH3 synthesis, the slow reaction rate makes it less suitable for industrially meaningful large-scale production. Here, we report the photoinduced N2 fixation using a hybrid system composed of colloidal quantum dots (QDs) and aerobic N2-fixing bacteria, Azotobacter vinelandii. Compared to the case where A. vinelandii cells are simply mixed with QDs, NH3 production increases significantly when A. vinelandii cells are cultured in the presence of core/shell InP/ZnSe QDs. During the cell culture of A. vinelandii, the cellular uptake of QDs is facilitated in the exponential growth phase. Experimental results as well as theoretical calculations indicate that the photoexcited electrons in QDs within A. vinelandii cells are directly transferred to MoFe protein, the catalytic component of nitrogenase. We also observe that the excess amount of QDs left on the outer surface of A. vinelandii disrupts the cellular membrane, leading to the decrease in NH3 production due to the deactivation of nitrogenase. The successful uptake of QDs in QD-A. vinelandii hybrid with minimal amount of QDs on the outer surface of the bacteria is key to efficient photosensitized NH3 production. The comprehensive understanding of the QD-bacteria interface paves an avenue to novel and efficient nanobiohybrid systems for chemical production.

Multiple metabolic comorbidities and their consequences among patients with peripheral arterial disease.

Older adults with peripheral arterial disease (PAD) have increased risks of major cardiovascular events and hospitalization. Metabolic comorbidities, such as hypertension, diabetes mellitus, and dyslipidemia, are common risk factors for these unfavorable health events. This study aimed to determine how multiple metabolic comorbidities affect the risk of adverse health outcomes in older adults with PAD. A retrospective cohort study was adopted using administrative claim data from the Health Insurance Review and Assessment Service Agency. The study sample included 3,122 older adults (≥ 65 years old) with at least one PAD diagnosis in an inpatient setting from 2011 to 2013 and who had at least one follow-up visit after hospitalization by 2018. The three metabolic comorbidities were defined as having at least two diagnostic claims or one prescription per year of anti-hypertensive, anti-diabetic, or anti-dyslipidemic medications for the corresponding diagnosis. The outcome variables included major adverse cardiovascular events (MACEs) and major adverse limb events (MALE). Kaplan-Meier survival curves demonstrated that PAD patients with more metabolic comorbidities had shorter MACE-free and MALE-free periods. Adjusted Cox proportional hazards analyses suggested significant additive effects of multiple metabolic comorbidities on increased risks of MACE and MALE among older adults with PAD. Lower socioeconomic status and non-metabolic comorbidities also increased the risk of MACE. Male sex, being young-old (65-74 years), and a higher proportion of inpatient claims increased the risk of MALE. The findings of this study suggest the need for a comprehensive care program for older adults with PAD and metabolic comorbidities. In addition, the healthcare utilization pattern should be considered when designing preventive care for older patients with comorbidities to manage PAD at an earlier stage.