Visible-light-driven photochemistry has continued to attract heightened interest due to its capacity to efficiently harvest solar energy and its potential to solve the global energy crisis. Plasmonic nanostructures boast broadly tunable optical properties coupled with catalytically active surfaces that offer a unique opportunity for solar photochemistry. Resonant optical excitation of surface plasmons produces energetic hot electrons that can be collected to facilitate chemical reactions. This review sums up recent theoretical and experimental approaches for understanding the underlying photophysical processes in hot electron generation and discusses various electron-transfer models on both plasmonic metal nanostructures and plasmonic metal/semiconductor heterostructures. Following that are highlights of recent examples of plasmon-driven hot electron photochemical reactions within the context of both cases. The review concludes with a discussion about the remaining challenges in the field and future opportunities for addressing the low reaction efficiencies in hot-electron-induced photochemistry.

Pulmonary hypertension (PH) is an unremitting disease defined by a progressive increase in pulmonary vascular resistance leading to right-sided heart failure. Using mice with genetic deletions of caveolin 1 (Cav1) and eNOS (Nos3), we demonstrate here that chronic eNOS activation secondary to loss of caveolin-1 can lead to PH. Consistent with a role for eNOS in the pathogenesis of PH, the pulmonary vascular remodeling and PH phenotype of Cav1 -/-mice were absent in Cav1 -/-Nos3 -/-mice. Further, treatment of Cav1 -/-mice with either MnTMPyP (a superoxide scavenger) or l-NAME (a NOS inhibitor) reversed their pulmonary vascular pathology and PH phenotype. Activation of eNOS in Cav1 -/-lungs led to the impairment of PKG activity through tyrosine nitration. Moreover, the PH phenotype in Cav1 -/-lungs could be rescued by overexpression of PKG-1. The clinical relevance of the data was indicated by the observation that lung tissue from patients with idiopathic pulmonary arterial hypertension demonstrated increased eNOS activation and PKG nitration and reduced caveolin-1 expression. Together, these data show that loss of caveolin-1 leads to hyperactive eNOS and subsequent tyrosine nitration-dependent impairment of PKG activity, which results in PH. Thus, targeting of PKG nitration represents a potential novel therapeutic strategy for the treatment of PH.

KD ICI are most likely virus induced; bronchial cells with ICI contain VLP that share morphologic features among several different RNA viral families. Expedited autopsies and tissue fixation from acute KD fatalities are urgently needed to more clearly ascertain the VLP. These findings are compatible with the hypothesis that the infectious etiologic agent of KD may be a "new" RNA virus.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is often characterized by tissue eosinophilia that is associated with poor prognosis. Recent findings that proton pump inhibitors (PPIs) directly modulate expression of eotaxin-3, an eosinophil chemoattractant, in eosinophilic diseases suggest therapeutic potential for PPIs in CRSwNP. Objective We assessed the effect of type-2 mediators, particularly IL-13 and eotaxin-3, on tissue eosinophilia and disease severity in CRS. Further investigation focused on PPI suppression of eotaxin-3 expression in vivo and in vitro with exploration of underlying mechanisms. Methods Type-2 mediator levels in nasal tissues and secretions were measured by multiplex immunoassay. Eotaxin-3 and other chemokines expressed in IL-13-stimulated human sinonasal epithelial cells (HNECs) and BEAS-2Bs with or without PPIs was assessed by using ELISA, Western blot, real-time PCR, and intracellular pH (pHi) imaging. Results Nasal tissues and secretions from CRSwNP patients had increased IL-13, eotaxin-2 and eotaxin-3 levels, and these were positively correlated with tissue ECP and radiographic scores in CRS (P<.05). IL-13-stimulation of HNECs and BEAS-2Bs dominantly induced eotaxin-3 expression, which was significantly inhibited by PPIs (P<.05). CRS patients taking PPIs also showed lower in vivo eotaxin-3 levels compared with those without PPIs (P<.05). Using pHi imaging and by altering extracellular [K+], we found that IL-13 enhanced H+,K+-exchange, which was blocked by PPIs and the mechanistically unrelated H,K-ATPase inhibitor, SCH-28080. Furthermore, knockdown of ATP12A (gene for the non-gastric H,K-ATPase [ngH,K-ATPase]) significantly attenuated IL-13-induced eotaxin-3 expression in HNECs. PPIs also had effects on accelerating IL-13-induced eotaxin-3 mRNA decay. Conclusion Our results demonstrated that PPIs reduce IL-13-induced eotaxin-3 expression by airway epithelial cells. Furthermore, mechanistic studies suggest that the ngH,K-ATPase is necessary for IL-13-mediated epithelial responses, and its inhibitors, including PPIs, may be of therapeutic value in CRSwNP by reducing epithelial production of eotaxin-3.

The metal/oxide interface has been extensively studied due to its importance for heterogeneous catalysis. However, the exact role of interfacial atomic structures in governing catalytic processes still remains elusive. Herein, we demonstrate how the manipulation of atomic structures at the Au/TiO 2 interface significantly alters the interfacial electron distribution and prompts O 2 activation. It is discovered that at the defect-free Au/TiO 2 interface electrons transfer from Ti 3+ species into Au nanoparticles (NPs) and further migrate into adsorbed perimeter O 2 molecules (i.e., in the form of Au−O−O−Ti), facilitating O 2 activation and leading to a ca. 34 times higher CO oxidation activity than that on the oxygen vacancy (V o )-rich Au/TiO 2 interface, at which electrons from Ti 3+ species are trapped by interfacial V o on TiO 2 and hardly interact with perimeter O 2 molecules. We further reveal that the calcination releases those trapped electrons from interfacial V o to facilitate O 2 activation. Collectively, our results establish an atomiclevel description of the underlying mechanism regulating metal/oxide interfaces for the optimization of heterogeneous catalysis.

Background: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and an intolerance of medications that inhibit cyclooxygenase-1. Patients with AERD have more severe upper and lower respiratory tract disease than do aspirintolerant patients with CRSwNP. A dysregulation in arachidonic acid metabolism is thought to contribute to the enhanced sinonasal inflammation in AERD. Objective: Our aim was to utilize an unbiased approach investigating arachidonic acid metabolic pathways in AERD. Methods: Single-cell RNA sequencing (103 Genomics, Pleasanton, Calif) was utilized to compare the transcriptional profile of nasal polyp (NP) cells from patients with AERD and patients with CRSwNP and map differences in the expression of select genes among identified cell types. Findings were confirmed by traditional real-time PCR. Lipid mediators in sinonasal tissue were measured by mass spectrometry. Localization of various proteins within NPs was assessed by immunofluorescence. Results: The gene encoding for 15-lipooxygenase (15-LO), ALOX15, was significantly elevated in NPs of patients with AERD compared to NPs of patients with CRSwNP (P < .05) or controls (P < .001). ALOX15 was predominantly expressed by epithelial cells. Expression levels significantly correlated with radiographic sinus disease severity (r 5 0.56; P < .001) and were associated with asthma. The level of 15-oxo-eicosatetraenoic acid (15-Oxo-ETE), a downstream product of 15-LO, was significantly elevated in NPs from patients with CRSwNP (27.93 pg/mg of tissue) and NPs from patients with AERD (61.03 pg/mg of tissue) compared to inferior turbinate tissue from controls (7.17 pg/mg of tissue [P < .001]). Hydroxyprostaglandin dehydrogenase, an enzyme required for 15-Oxo-ETE synthesis, was predominantly expressed in mast cells and localized near 15-LO 1 epithelium in NPs from patients with AERD. Conclusions: Epithelial and mast cell interactions, leading to the synthesis of 15-Oxo-ETE, may contribute to the dysregulation of arachidonic acid metabolism via the 15-LO pathway and to the enhanced sinonasal disease severity observed in AERD. (J Allergy Clin Immunol 2020;nnn:nnn-nnn.)

Objective To evaluate if molecular markers of eosinophilia in olfactory enriched mucosa are associated with olfactory dysfunction. Study Design Cross-sectional study of tissue biopsies from 99 patients, and a further 30 patients who underwent prospective olfactory testing prior to sinonasal procedures. Methods Tissue biopsies were processed for analysis of inflammatory markers using qRT-PCR. Ipsilateral olfactory performance was assessed using the Sniffin Sticks threshold component and the UPSIT and age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from CT and endoscopy. Results Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in CRS with nasal polyps (CRSwNP) compared to ST and inferior turbinate (IT) tissue in CRS without nasal polyps (CRSsNP) and control patients (all p < 0.001 respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all p<0.001; r = 0.65 and 0.49 respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (p<0.001; r=0.-76) and ST CLC expression was inversely related to olfactory threshold (p = 0.002, r = −0.57) and discrimination scores (p = 0.05, r = −0.42). In multiple linear regression of CLC gene expression, polyp status, radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (p<0.05). Conclusions Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft.

Glial cell line-derived neurotrophic factor (GDNF) gene transfer is being developed as a treatment for Parkinson's disease (PD). Due to the potential for side effects, external transgene regulation should enhance this strategy's safety profile. Here, we demonstrate dynamic control during long-term expression of GDNF using a recombinant adeno-associated virus (rAAV)-based bicistronic tetracycline (tet)-off construct. Nigrostriatal GDNF overexpression induces body weight alterations in rodents, enabling longitudinal in vivo tracking of GDNF expression after nigral vector delivery. Regulated GDNF expression was highly sensitive to dietary doxycycline (DOX), displaying undetectable striatal GDNF levels at serum DOX levels below those required for antimicrobial activity. However, in the absence of DOX, striatal GDNF levels exceeded levels required for efficacy in PD models. We also demonstrate the absence of a series of known GDNF-associated side effects when using direct intrastriatal vector delivery. Therefore, this single rAAV vector system meets most of the requirements for an experimental reagent for treatment of PD.