S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp.

BACKGROUND: Chronic inflammation triggers tissue remodeling in human nasal epithelial (HNE) cells. S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS). METHODS: Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed. RESULTS: GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL-17 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline-rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub-epithelium was co-expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino-nasal outcome test-22 (r = 0.294, p = 0.022) and Lund-Mackay scores (r = 0.348, p = 0.006). CONCLUSION: S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.

Comparative analyses of post-infectious olfactory dysfunction between COVID-19 and non-COVID-19 cases.

To identify the differences between COVID-19-associated and non-COVID-19-associated olfactory dysfunction (OD), we analyzed demographic and clinical characteristics based on the causative virus (COVID versus non-COVID groups) in patients with post-infectious olfactory dysfunction (PIOD) who underwent the olfactory questionnaire and olfactory function test. Out of 169 patients with PIOD, 99 were diagnosed with COVID-19 (COVID group), while 70 were not (non-COVID group). The COVID group was younger and had a higher percentage of male patients as well as patients with parosmia than the non-COVID group. In the initial olfactory function tests, the TDI, discrimination and identification scores were significantly higher in the COVID group than in the non-COVID group. TDI scores were significantly increased in patients with PIOD after treatment, regardless of the group. The threshold score was significantly increased by 1.38 in the COVID group while the identification score was significantly increased by 2.67 in the non-COVID group. Patients with COVID-19-associated OD were younger in age, tended to be male, had a higher incidence of parosmia, and had better initial olfactory function test results compared to those with non-COVID-19-associated OD. Following treatment, odor detection threshold improved in the COVID group, whereas odor identification improved in the non-COVID group.

Distinctive CD39+CD9+ lung interstitial macrophages suppress IL-23/Th17-mediated neutrophilic asthma by inhibiting NETosis.

The IL-23-Th17 axis is responsible for neutrophilic inflammation in various inflammatory diseases. Here, we discover a potential pathway to inhibit neutrophilic asthma. In our neutrophil-dominant asthma (NDA) model, single-cell RNA-seq analysis identifies a subpopulation of CD39+CD9+ interstitial macrophages (IMs) suppressed by IL-23 in NDA conditions but increased by an IL-23 inhibitor αIL-23p19. Adoptively transferred CD39+CD9+ IMs suppress neutrophil extracellular trap formation (NETosis), a representative phenotype of NDA, and also Th17 cell activation and neutrophilic inflammation. CD39+CD9+ IMs first attach to neutrophils in a CD9-dependent manner, and then remove ATP near neutrophils that contribute to NETosis in a CD39-dependent manner. Transcriptomic data from asthmatic patients finally show decreased CD39+CD9+ IMs in severe asthma than mild/moderate asthma. Our results suggest that CD39+CD9+ IMs function as a potent negative regulator of neutrophilic inflammation by suppressing NETosis in the IL-23-Th17 axis and can thus serve as a potential therapeutic target for IL-23-Th17-mediated neutrophilic asthma.

Differential regulation of viral entry-associated genes modulated by inflammatory cytokines in the nasal epithelium.

This study aimed to investigate the impact of different types of nasal inflammation on the regulation of entry-associated genes of respiratory viruses, including severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus 229E (HCoV-229E), and influenza virus, in the nasal epithelium. Subjects were classified into three groups: control, eosinophilic chronic rhinosinusitis (ECRS), and noneosinophilic CRS (NECRS) groups. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine subtype 2 (TMPRSS2), alanyl aminopeptidase (ANPEP), dipeptidyl peptidase 4 (DPP4), and beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1), and beta-galactoside alpha-2,3-sialyltransferase 4 (ST3GAL4) were selected as key entry-associated genes for SARS-CoV-2, HCoV-229E, MERS-CoV, and influenza, respectively, and were evaluated. Brushing samples obtained from each group and human nasal epithelial cells cultured using an air-liquid interface system were treated for 7 days with typical inflammatory cytokines and analyzed using real-time polymerase chain reaction. Western blot analysis and confocal microscopy were performed. The entry-associated genes showed distinct regulation patterns in response to each interleukin-4 (IL-4), interleukin-13 (IL-13), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Specifically, ACE2 significantly decreased in type 2 cytokines (IL-4 and IL-13), while TMPRSS2 significantly decreased in type 1 cytokines (TNF-α and IFN-γ). ANPEP significantly decreased in both types of cytokines. Remarkably, DPP4 significantly increased in type 2 cytokines and decreased in type 1 cytokines. Moreover, ST6GAL1 and ST3GAL4 significantly increased in type 2 cytokines and decreased in type 1 cytokines, particularly IFN-γ. These findings were supported by western blot analysis and confocal imaging results, especially for ACE2 and DPP4. The findings regarding differential regulation suggest that patients with ECRS, primarily mediated by type 2 inflammation, may have lower susceptibility to SARS-CoV-2 and HCoV-229E infections but higher susceptibility to MERS-CoV and influenza infections.

Using a Built-in Clinical Decision Support to Improve Phosphate Repletion Practice: A Quasi-Experimental Study.

BACKGROUND: Inpatient serum phosphate replacement is common, but there is great variability in replacement practice, which leads to overuse. Electronic health record (EHR) interventions with clinical decision support (CDS) can be effective tools to guide clinicians toward best clinical practices. The authors' objective was to use CDS tools to reduce overuse of hypophosphatemia corrections at a large safety-net health care system. METHODS: The first intervention involved enhancing an existing order set for phosphate repletion by incorporating CDS to guide appropriate repletion orders based on deficit severity and simplifying ordering. The second intervention was a Best Practice Advisory (BPA) that triggered when an intravenous (IV) phosphate repletion was ordered for a patient with mild to moderate phosphate deficiency without an existing nil per os (NPO) order. The primary outcome measure was the number of patients with mild and moderate hypophosphatemia receiving IV replacement without NPO orders per 1,000 patient-days. RESULTS: Across all hospitals, rate of IV replacement in patients with mild to moderate hypophosphatemia (1.0 to 1.9 mg/dL) without NPO orders decreased from 7.22 to 3.40 per 1,000 patient-days (53.0% reduction, p < 0.001), while the oral replacements in this population increased from 6.39 to 8.87 (38.8% increase, p < 0.001). For patients with phosphate levels ≥ 2.0, IV replacements decreased from 10.66 to 5.36 (49.8% reduction, p < 0.001), and oral replacements from decreased 19.78 to 16.69 (15.6% reduction, p < 0.01). CONCLUSION: This intervention successfully reduced inpatient IV phosphate replacements by 53.0% in patients with mild to moderate hypophosphatemia using a two-pronged EHR intervention across a large safety-net setting.

An inquiry into the radial patterning of root hair cell distribution in eudicots.

The root epidermis of tracheophytes consists of hair-forming cells (HCs) and nonhair cells (NCs). The HC distribution pattern is classified into three types: random (Type I), vertically alternating (Type II), and radial (Type III). Type III is found only in core eudicots and is known to be position-dependent in superrosids with HCs positioned between two underlying cortical cells. However, the evolution of Type III and the universality of its position dependency in eudicots remain unclear. We surveyed the HC distribution in basal and Type III-exhibiting core eudicots and conducted genomic analyses to get insight into whether eudicots share the same genetic network to establish Type III. Our survey revealed no canonical Type III in basal eudicots but a reverse Type III, with NCs between two cortical cells and HCs on a single cortical cell, in Papaveraceae of basal eudicots. Type III-exhibiting species from both superrosids and superasterids showed the canonical position dependency of HCs. However, some key components for Type III determination were absent in the genomes of Papaveraceae and Type III-exhibiting superasterids. Our findings identify a novel position-dependent type of HC patterning, reverse Type III, and suggest that Type III emerged independently or diversified during eudicot evolution.

SARS-CoV-2 spike-specific nasal-resident CD49a+CD8+ memory T cells exert immediate effector functions with enhanced IFN-γ production.

Virus-specific nasal resident T cells are important for protection against subsequent infection with a similar virus. Here we examine the phenotypes and functions of SARS-CoV-2-specific T cells in the nasal mucosa of vaccinated individuals with breakthrough infection (BTI) or without infection. Nasal tissues are obtained from participants during sinus surgery. Analysis of activation-induced markers implicates that a considerable proportion of spike (S)-reactive nasal CD8+ T cells express CD103, a tissue-resident marker. MHC-I multimer staining is performed to analyze the ex vivo phenotype and function of SARS-CoV-2 S-specific CD8+ T cells. We detect multimer+CD8+ T cells with tissue-resident phenotypes in nasal tissue samples from vaccinees without infection as well as vaccinees with BTI. Multimer+CD8+ T cells remain present in nasal tissues over one year after the last exposure to S antigen, although the frequency decreases. Upon direct ex vivo stimulation with epitope peptides, nasal multimer+CD8+ T cells-particularly the CD49a+ subset-exhibit immediate effector functions, including IFN-γ production. CITE-seq analysis of S-reactive AIM+CD8+ T cells confirms the enhanced effector function of the CD49a+ subset. These findings indicate that among individuals previously exposed to S antigen by vaccination or BTI, S-specific nasal-resident CD49a+CD8+ memory T cells can rapidly respond to SARS-CoV-2 during infection or reinfection.

A dose-dependent bimodal switch by homologous Aux/IAA transcriptional repressors.

Combinatorial interactions between different regulators diversify and enrich the chance of transcriptional regulation in eukaryotic cells. However, a dose-dependent functional switch of homologous transcriptional repressors has rarely been reported. Here, we show that SHY2, an auxin/indole-3-acetic acid (Aux/IAA) repressor, exhibits a dose-dependent bimodal role in auxin-sensitive root-hair growth and gene transcription in Arabidopsis, whereas other Aux/IAA homologs consistently repress the auxin responses. The co-repressor (TOPLESS [TPL])-binding affinity of a bimodal Aux/IAA was lower than that of a consistently repressing Aux/IAA. The switch of a single amino acid residue in the TPL-binding motif between the bimodal form and the consistently repressing form switched their TPL-binding affinity and transcriptional and biological roles in auxin responses. Based on these data, we propose a model whereby competition between homologous repressors with different co-repressor-binding affinities could generate a bimodal output at the transcriptional and developmental levels.

Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases.

Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment.

Microbiome and mycobiome analyses in continuous positive airway pressure devices.

Objectives: Microorganisms are likely present in continuous positive airway pressure (CPAP) devices used daily. Considering the potential risk of infections among CPAP device users, here we aimed to compare the microbiomes in CPAP devices with those in nasal mucosal samples obtained from corresponding individuals using these devices. Methods: We conducted a prospective cohort study at tertiary medical institutes. Samples were collected from the tubes and filters of CPAP devices and the nasal mucosa of corresponding individuals using these devices. Microbiomes and mycobiomes were analyzed using 16S ribosomal RNA and internal transcribed spacer region sequencing. Results were compared according to the sampling site and usage duration for each patient. Results: Overall, 27 paired human nasal mucosa and CPAP samples were analyzed. Bacteria were present in 7 of 27 tubes (29.6%) and 22 of 27 filters (81.5%). Fungi were present in 2 of the 27 tubes (7.4%) and 16 of the 27 filters (59.3%). Actinobacteria and Firmicutes were the predominant phyla among all samples. Fungi were not detected in any of the nasal mucosal samples. However, Basidiomycota and Ascomycota were predominant in the CPAP filters and tube samples. No significant associations were identified among the results according to sampling site and usage duration. Conclusion: Bacteria or fungi can be detected to some extent in CPAP samples even if the CPAP usage period is short. The association between respiratory infections and these microbiomes or mycobiomes was not investigated. Further research might be required to determine the risk posed by CPAP devices as a microbial contamination source.

Achalasia in Klinefelter syndrome: A suspected pediatric case as well as prevalence analysis suggesting increased risk in this population.

A 4-year-old male with Klinefelter syndrome (KS), speech delay, and intermittent history of coughing and choking during meals was referred for evaluation. Prior evaluation with computed tomography showed a dilated esophagus at the gastroesophageal junction. The patient was unable to tolerate a barium swallow. Upper endoscopy was performed, and an intraoperative esophagogram, demonstrated a "birds beak" appearance suggestive of achalasia. There is no documented relationship between achalasia and KS. However, we utilized TriNetX (a large-scale data clearinghouse) to demonstrate a higher prevalence of achalasia in patients with KS as compared to the general population.

Cerebral hemodynamics as biomarkers for neuropathic pain in rats: a longitudinal study using a spinal nerve ligation model.

ABSTRACT: Neuropathic pain is one of the most challenging types of pain to diagnose and treat, a problem exacerbated by the lack of a quantitative biomarker. Recently, several clinical and preclinical studies have shown that neuropathic pain induces cerebral hemodynamic changes as a result of neuroplasticity in the brain. Our hypothesis in this study is that neuropathic pain leads to cerebral hemodynamic changes over postoperative time in a spinal nerve ligation (SNL) rat model, which has not been longitudinally explored previously. Furthermore, by identifying multiple regional hemodynamic features that are the most distinct between SNL and sham groups, where the sham group underwent only an incision without SNL, it may be possible to classify the SNL group regardless of when the onset of pain occurs. We investigate cerebral hemodynamic changes using dynamic susceptibility contrast magnetic resonance imaging in a rat model up to 28 days after ligating L5/L6 spinal nerves. We trained a linear support vector machine with relative cerebral blood volume data from different brain regions and found that the prediction model trained on the nucleus accumbens, motor cortex, pretectal area, and thalamus classified the SNL group and sham group at a 79.27% balanced accuracy, regardless of when the onset of pain occurred (SNL/sham: 60/45 data points). From the use of the SNL model without prior knowledge of the onset time of pain, the current findings highlight the potential of relative cerebral blood volume in the 4 highlighted brain regions as a biomarker for neuropathic pain.

Photoassisted Water Purification through an Electrochemically Artificially Adjusted p-Cu2O Light Absorption Layer.

The implementation of photoelectrochemical water purification technology can address prevailing environmental challenges that impede the advancement and prosperity of human society. In this study, Cu, which is abundant on Earth, was fabricated using an electrochemical deposition process, in which the preferential orientation direction and carrier concentration of the Cu-based oxide semiconductor were artificially adjusted by carefully controlling the OH- and applied voltage. In particular, Cu2O grown with a sufficient supply of OH- ions exhibited the (111) preferred orientation, and the (200) surface facet was exposed, independently achieving 90% decomposition efficiency in a methyl orange (MO) solution for 100 min. This specialized method minimizes the recombination loss of electron-hole pairs by increasing the charge separation and transport efficiency of the bulk and surface of the Cu2O multifunctional absorption layer. These discoveries and comprehension not only offer valuable perspectives on mitigating self-photocorrosion in Cu2O absorbing layers but also provide a convenient and expeditious method for the mass production of water purification systems that harness unlimited solar energy. These properties enable significant energy saving and promote high-speed independent removal of organic pollutants (i.e., MO reduction) during the water purification process.

Outcomes and Predictors of Success Following Multilevel Surgery in Positional and Nonpositional Obstructive Sleep Apnea.

OBJECTIVE: To assess the surgical outcomes and identify predictors of surgical success in patients with positional and non-positional obstructive sleep apnea following multilevel airway surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Singe-tertiary medical center. METHODS: This study included 158 patients with obstructive sleep apnea who underwent multilevel airway surgery. Patients were divided into 2 groups according to position dependency: "positional patients" group (n = 100), and "nonpositional patients" group (n = 58). The characteristics and surgical outcomes of the 2 groups were compared. RESULTS: The nonpositional group included younger and more obese patients in comparison to the positional group. Moreover, the nonpositional group had more severe disease than the positional group. Both groups showed overall improvement after surgery, and the surgical success rate did not differ significantly between the 2 groups (nonpositional, 41.4% vs positional, 48.0%; P = .424). Notably, 69.0% of patients belonging to the non-positional group converted to positional group postoperatively. Logistic regression analysis revealed that larger tonsil size, female sex, and higher mean O2 saturation were associated with higher success rate in the positional group, whereas larger tonsil size was associated with surgical success in the nonpositional group. CONCLUSION: Both nonpositional and positional groups showed improvements following multilevel airway surgery, and surgery induced a transition from nonpositional to positional group. Given that the factors related to surgical success differed between the two groups, surgeons should consider position dependency and these distinct factors during decision-making.

Molecular surveillance of zoonotic pathogens from wild rodents in the Republic of Korea.

BACKGROUND: Rodents are recognized as major reservoirs of numerous zoonotic pathogens and are involved in the transmission and maintenance of infectious diseases. Furthermore, despite their importance, diseases transmitted by rodents have been neglected. To date, there have been limited epidemiological studies on rodents, and information regarding their involvement in infectious diseases in the Republic of Korea (ROK) is still scarce. METHODOLOGY/PRINCIPAL FINDINGS: We investigated rodent-borne pathogens using nested PCR/RT-PCR from 156 rodents including 151 Apodemus agrarius and 5 Rattus norvegicus from 27 regions in eight provinces across the ROK between March 2019 and November 2020. Spleen, kidney, and blood samples were used to detect Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato group, Coxiella burnetii, Leptospira interrogans, and severe fever with thrombocytopenia syndrome virus (SFTSV). Of the 156 rodents, 73 (46.8%) were infected with Bartonella spp., 25 (16.0%) with C. burnetii, 24 (15.4%) with L. interrogans, 21 (13.5%) with A. phagocytophilum, 9 (5.8%) with SFTSV, and 5 (3.2%) with Borrelia afzelii. Co-infections with two and three pathogens were detected in 33 (21.1%) and 11 rodents (7.1%), respectively. A. phagocytophilum was detected in all regions, showing a widespread occurrence in the ROK. The infection rates of Bartonella spp. were 83.3% for B. grahamii and 16.7% for B. taylorii. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first report of C. burnetii and SFTSV infections in rodents in the ROK. This study also provides the first description of various rodent-borne pathogens through an extensive epidemiological survey in the ROK. These results suggest that rodents harbor various pathogens that pose a potential threat to public health in the ROK. Our findings provide useful information on the occurrence and distribution of zoonotic pathogens disseminated among rodents and emphasize the urgent need for rapid diagnosis, prevention, and control strategies for these zoonotic diseases.

Evaluation of bovine coronavirus in Korean native calves challenged through different inoculation routes.

Bovine coronavirus (BCoV) is a pneumoenteric virus that can infect the digestive and respiratory tracts of cattle, resulting in economic losses. Despite its significance, information regarding BCoV pathogenesis is limited. Hence, we investigated clinical signs, patterns of viral shedding, changes in antibody abundance, and cytokine/chemokine production in calves inoculated with BCoV via intranasal and oral. Six clinically healthy Korean native calves (< 30 days old), initially negative for BCoV, were divided into intranasal and oral groups and monitored for 15 days post-infection (dpi). BCoV-infected calves exhibited clinical signs such as nasal discharge and diarrhea, starting at 3 dpi and recovering by 12 dpi, with nasal discharge being the most common symptoms. Viral RNA was detected in nasal and fecal samples from all infected calves. Nasal shedding occurred before fecal shedding regardless of the inoculation route; however, fecal shedding persisted longer. Although the number of partitions was very few, viral RNA was identified in the blood of two calves in the oral group at 7 dpi and 9 dpi using digital RT-PCR analysis. The effectiveness of maternal antibodies in preventing viral replication and shedding appeared limited. Our results showed interleukin (IL)-8 as the most common and highly induced chemokine. During BCoV infection, the levels of IL-8, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1ß were significantly affected, suggesting that these emerge as potential and reliable biomarkers for predicting BCoV infection. This study underscores the importance of BCoV as a major pathogen causing diarrhea and respiratory disease.

Two-Phase Particle Image Velocimetry Visualization of Rewetting Flow on the Micropillar Interfacial Surface.

Boiling heat transfer has a high thermal efficiency by latent heat absorption, which makes it an attractive process for cooling electronic device chips. Critical heat flux (CHF), the maximum heat flux, is a crucial factor determining the operating range of the boiling applications. The CHF can be enhanced by improving the fluid supply to the boiling surface. Herein, micropillar interfacial surfaces have been proposed to increase the CHF by increasing the rewetting flow, which determines the fluid-supply capacity near the bubble contact line. A state-of-art two-phase particle image velocimetry (two-phase PIV) technique is introduced for rewetting flow measurement on micropillar structures (MPSs) to analyze the CHF-enhancement mechanism. The two-phase PIV visualization setup offers high spatial (∼120 µm) and temporal (∼2000 Hz) resolutions for measuring rewetting flow during bubble growth. The MPS samples exhibit enhanced CHF and rewetting flows compared to those on a plain surface. The roughest case, D04G10 sample, had a CHF of 164 W/cm2, 1.84 times higher than that of the plain surface. The D04G10 sample also recorded the highest rewetting velocity of 0.311 m/s, 4.7 times higher than that of the plain surface. The comparison between the rewetting flow and wicking performance shows that wicking-induced flow accounted for a substantial part (∼17%) of the rewetting flow and contributed significantly to the CHF enhancement owing to large rewetting flow by delaying vapor-film formation. Based on these findings, a new CHF model suggested by introducing the rewetting parameter shows a high CHF prediction accuracy of 94%.

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression.

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air-liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

Low-Intensity Light Detection with a High Detectivity Using 2D-Sb2Se3 Nanoflakes on 1D-ZnO Nanorods as Heterojunction Photodetectors.

Multifunctional photodetectors (PDs) with broadband responsivity (R) and specific detectivity (D*) at low light intensities are gaining significant attention. Thus, we report a bilayer PD creatively fabricated by layering two-dimensional (2D) Sb2Se3 nanoflakes (NFs) on one-dimensional (1D) ZnO nanorods (NRs) using simple thermal transfer and hydrothermal processes. The unique coupling of these two layers of materials in a nanostructured form, such as 2D-Sb2Se3 NFs/1D-ZnO NRs, provides an effective large surface area, robust charge transport paths, and light-trapping effects that enhance light harvesting. Furthermore, the combination of both layers can effectively facilitate photoactivity owing to proper band alignment. The as-fabricated device demonstrated superior overall performance in terms of a suitable bandwidth, good R, and high D* under low-intensity light, unlike the single-layered 1D-ZnO NRs and 2D-Sb2Se3 NF structures alone, which had poor detectivity or response in the measured spectral range. The PD demonstrated a spectral photoresponse ranging from ultraviolet (UV) to visible (220-628 nm) light at intensities as low as 0.15 mW·cm-2. The PD yielded a D* value of 3.15 × 1013 Jones (220 nm), which reached up to 5.95 × 1013 Jones in the visible light region (628 nm) at a 3 V bias. This study demonstrated that the 2D-Sb2Se3 NFs/1D-ZnO NRs PD has excellent potential for low-intensity light detection with a broad bandwidth, which is useful for signal communications and optoelectronic systems.