Thiiranes: Intelligent Molecules for S-Persulfidation.

This study presents a global strategy for the transsulfuration of intracellular thiols (RSH) to persulfides (RSSH). Thiiranes comprising fluorenyl/diphenyl and malonate ester moieties directly convert intercellular RSH to low-molecular-weight RSSH in cells. The efficiency of transsulfuration is determined by counting the number of olefins produced as byproducts, providing ratiometric signals for the corresponding persulfide production. Specifically, the direct and rapid protein S-persulfidation by thiirane is validated. Thiiranes are expected to play a crucial role in the study of sulfur signaling.

Halogenated 9H-Indeno[1,2-b]Pyrazine-2,3-Dicarbonitrile End Groups Based Asymmetric Non-Fullerene Acceptors for Green Solvent-Processable, Additive-Free, and Stable Organic Solar Cells.

Non-fullerene acceptors (NFAs) significantly enhance photovoltaic performance in organic solar cells (OSCs) using halogenated solvents and additives. However, these solvents are environmentally detrimental and unsuitable for industrial-scale production, and the issue of OSCs' poor long-term stability persists. This report introduces eight asymmetric NFAs (IPCnF-BBO-IC2F, IPCnF-BBO-IC2Cl, IPCnCl-BBO-IC2F, and IPCnCl-BBO-IC2Cl, where n = 1 and 2). These NFAs comprise a 12,13-bis(2-butyloctyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2'',3'':4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno-[3,2-b]indole (BBO) core. One end of the core attaches to a mono- or di-halogenated 9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile (IPC) end group (IPC1F, IPC1Cl, IPC2F, or IPC2Cl), while the other end connects to a 2-(5,6-dihalo-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (IC) end group (IC2F or IC2Cl). The optical and electronic properties of these NFAs can be finely tuned by controlling the number of halogen atoms. Crucially, these NFAs demonstrate excellent compatibility with PM6 even in o-xylene, facilitating the production of additive-free OSCs. The di-halogenated IPC-based NFAs outperform their mono-halogenated counterparts in photovoltaic performance within OSCs. Remarkably, the di-halogenated IPC-based NFAs maintain 94‒98% of their initial PCEs over 2000 h in air without encapsulation, indicating superior long-term device stability. These findings imply that the integration of di-halogenated IPCs in asymmetric NFA design offers a promising route to efficient, stable OSCs manufactured through environmentally friendly processes.

Wafer-Scale Atomic Assembly for 2D Multinary Transition Metal Dichalcogenides for Visible and NIR Photodetection.

The tunable properties of 2D transition-metal dichalcogenide (TMDs) materials are extensively investigated for high-performance and wavelength-tunable optoelectronic applications. However, the precise modification of large-scale systems for practical optoelectronic applications remains a challenge. In this study, a wafer-scale atomic assembly process to produce 2D multinary (binary, ternary, and quaternary) TMDs for broadband photodetection is demonstrated. The large-area growth of homogeneous MoS2, Ni0.06Mo0.26S0.68, and Ni0.1Mo0.9S1.79Se0.21 is carried out using a succinct coating of the single-source precursor and subsequent thermal decomposition combined with thermal evaporation of the chalcogen powder. The optoelectrical properties of the multinary TMDs are dependent on the combination of heteroatoms. The maximum photoresponsivity of the MoS2-, Ni0.06Mo0.26S0.68-, and Ni0.1Mo0.9S1.79Se0.21-based photodetectors is 3.51 × 10-4, 1.48, and 0.9 A W-1 for 532 nm and 0.063, 0.42, and 1.4 A W-1 for 1064 nm, respectively. The devices exhibited excellent photoelectrical properties, which is highly beneficial for visible and near-infrared (NIR) photodetection.

Understanding global research trends in the control and prevention of infectious diseases for children: Insights from text mining and topic modeling.

INTRODUCTION: The emergence of novel infectious diseases has amplified the urgent need for effective prevention strategies, especially ones targeting vulnerable populations such as children. Factors such as the high incidence of both emerging and existing infectious diseases, delays in vaccinations, and routine exposure in communal settings heighten children's susceptibility to infections. Despite this pressing need, a comprehensive exploration of research trends in this domain remains lacking. This study aims to address this gap by employing text mining and modeling techniques to conduct a comprehensive analysis of the existing literature, thereby identifying emerging research trends in infectious disease prevention among children. METHODS: A cross-sectional text mining approach was adopted, focusing on journal articles published between January 1, 2003, and August 31, 2022. These articles, related to infectious disease prevention in children, were sourced from databases such as PubMed, CINAHL, MEDLINE (Ovid), Scopus, and Korean RISS. The data underwent preprocessing using the Natural Language Toolkit (NLTK) in Python, with a semantic network analysis and topic modeling conducted using R software. RESULTS: The final dataset comprised 509 journal articles extracted from multiple databases. The study began with a word frequency analysis to pinpoint relevant themes, subsequently visualized through a word cloud. Dominant terms encompassed "vaccination," "adolescent," "infant," "parent," "family," "school," "country," "household," "community," "HIV," "HPV," "COVID-19," "influenza," and "diarrhea." The semantic analysis identified "age" as a key term across infection, control, and intervention discussions. Notably, the relationship between "hand" and "handwashing" was prominent, especially in educational contexts linked with "school" and "absence." Latent Dirichlet Allocation (LDA) topic modeling further delineated seven topics related to infectious disease prevention for children, encompassing (1) educational programs, (2) vaccination efforts, (3) family-level responses, (4) care for immunocompromised individuals, (5) country-specific responses, (6) school-based strategies, and (7) persistent threats from established infectious diseases. CONCLUSION: The study emphasizes the indispensable role of personalized interventions tailored for various child demographics, highlighting the pivotal contributions of both parental guidance and school participation. CLINICAL RELEVANCE: The study provides insights into the complex public health challenges associated with preventing and managing infectious diseases in children. The insights derived could inform the formulation of evidence-based public health policies, steering practical interventions and fostering interdisciplinary synergy for holistic prevention strategies.

Hyperproliferation of Elschnig pearl-type posterior capsule opacification and spontaneous regression in two pseudophakic canine eyes.

OBJECTIVE: To describe the hyperproliferation of Elschnig pearl-type posterior capsule opacification and concurrent uveitis in two canine eyes after phacoemulsification, followed by spontaneous resolution of the Elschnig pearls. ANIMAL STUDIED: A 10-year-old castrated male Spitz (Case 1) and a 4-year-old spayed female Bichon Frise (Case 2). PROCEDURE: Elschnig pearls proliferating beyond the anterior capsulotomy site were observed in the right eye 10 months after bilateral diabetic cataract surgery (Case 1) and 7 months after unilateral cataract surgery (Case 2). In both cases, hyperproliferation occurred where the anterior capsule did not overlap with the intraocular lens (IOL), and was accompanied by aqueous flare. In Case 1, the pearls extended from the anterior capsule and adhered to the iris, causing focal posterior synechia. No other possible causes of uveitis were apparent. RESULTS: Initially, uveitis severity improved after the administration of topical and systemic anti-inflammatory drugs. However, uveitis recurred when the dosage of anti-inflammatory treatment was reduced. The Elschnig pearls underwent morphological changes throughout the follow-up period. In both cases, the pearls beyond the anterior capsulotomy resolved spontaneously after 5 months. Only a few pearls remained between the IOL and posterior capsule, and no recurrence of pearl proliferation was observed at the last follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneous Elschnig pearl regression in dogs. Lens-induced uveitis (LIU) may have been caused by anterior chamber hyperproliferative pearls. LIU associated with hyperproliferative pearls may be managed with appropriate anti-inflammatory treatment and monitoring.

Analyzing symptom experiences and pathways to enhancing quality of life in adolescents with Moyamoya disease.

PURPOSE: The psycho-emotional symptom experiences and health-related factors that influence the quality of life of adolescents with Moyamoya disease are still not fully understood. The aim of this study is to identify the daily physical and accompanying psychological symptom experiences of such adolescents, and to examine how health-related factors contribute to their quality of life. DESIGN AND METHOD: This study employed a descriptive cross-sectional research design. Data on a total of 134 adolescents with Moyamoya disease was analyzed in order to develop a path analysis. Data were collected from October 2019 to January 2021 in South Korea. The theory of salutogenesis was employed in order to develop a hypothetical model for this path analysis. Participants were given a self-reporting questionnaire. Descriptive analysis and path analysis were conducted based on the results. RESULTS: Adolescents with Moyamoya disease experienced several negative emotions simultaneously, regardless of the severity of their physical symptoms. The path analysis revealed that stress, a sense of coherence, behavior, and the support of friends were significant contributors to adolescents' quality of life. CONCLUSIONS: Adolescents with Moyamoya disease have multifaceted symptom experiences in their daily lives. To enhance their quality of life, it is crucial to provide support that can help strengthen their capacity for stress management and enhance their sense of coherence. PRACTICAL IMPLICATIONS: This study provides evidence that nurses should offer anticipatory information to adolescents with Moyamoya disease regarding the symptoms they will frequently encounter, and develop interventions to enhance their quality of life.

Inhibition of neuronal peroxisome proliferator-activated receptor-γ attenuates motor function improvement after spinal cord injury in rats.

Traumatic spinal cord injury (SCI) causes secondary damage in injured and adjacent regions due to temporal deprivation of oxygen and energy supply. Peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate cell survival mechanisms such as hypoxia, oxidative stress, inflammation and energy homeostasis in various tissues. Thus, PPARγ has the potential to show neuroprotective properties. However, the role of endogenous spinal PPARγ in SCI is not well established. In this study, under isoflurane inhalation, a 10-g rod was freely dropped onto the exposed spinal cord after T10 laminectomy using a New York University impactor in male Sprague-Dawley rats. Cellular localization of spinal PPARγ, locomotor function and mRNA levels of various genes including NFκB-targeted pro-inflammatory mediators after intrathecal administration of PPARγ antagonists, agonists or vehicles in SCI rats were then analysed. In both sham and SCI rats, spinal PPARγ was presented in neurons but not in microglia or astrocytes. Inhibition of PPARγ induced IκB activation and increased mRNA levels of pro-inflammatory mediators. It also suppressed recovery of locomotor function with myelin-related gene expression in SCI rats. However, a PPARγ agonist showed no beneficial effects on the locomotor performances of SCI rats, although it further increased the protein expression of PPARγ. In conclusion, endogenous PPARγ has a role in anti-inflammation after SCI. Inhibition of PPARγ might have a negative influence on motor function recovery through accelerated neuroinflammation. Nonetheless, exogenous PPARγ activation does not appear to effectively help with functional improvement after SCI.

Pathogen-Associated Molecular Pattern-Triggered Immunity Involves Proteolytic Degradation of Core Nonsense-Mediated mRNA Decay Factors During the Early Defense Response.

Nonsense-mediated mRNA decay (NMD), an mRNA quality control process, is thought to function in plant immunity. A subset of fully spliced (FS) transcripts of Arabidopsis (Arabidopsis thaliana) resistance (R) genes are upregulated during bacterial infection. Here, we report that 81.2% and 65.1% of FS natural TIR-NBS-LRR (TNL) and CC-NBS-LRR transcripts, respectively, retain characteristics of NMD regulation, as their transcript levels could be controlled posttranscriptionally. Both bacterial infection and the perception of bacteria by pattern recognition receptors initiated the destruction of core NMD factors UP-FRAMESHIFT1 (UPF1), UPF2, and UPF3 in Arabidopsis within 30 min of inoculation via the independent ubiquitination of UPF1 and UPF3 and their degradation via the 26S proteasome pathway. The induction of UPF1 and UPF3 ubiquitination was delayed in mitogen-activated protein kinase3 (mpk3) and mpk6, but not in salicylic acid-signaling mutants, during the early immune response. Finally, previously uncharacterized TNL-type R transcripts accumulated in upf mutants and conferred disease resistance to infection with a virulent Pseudomonas strain in plants. Our findings demonstrate that NMD is one of the main regulatory processes through which PRRs fine-tune R transcript levels to reduce fitness costs and achieve effective immunity.

14- and 17-Membered Macrocycles Containing Amide, Amino, and Carbamate Groups in The Monocyclic Skeleton: An Accidental Byproduct Obtained from a Residue after Separation.

A 14-membered cyclic compound (3) containing amide, amino, and carbamate groups, which was serendipitously obtained in the oily residue after the separation of 4-benzyl-1,4,7,10-tetraazacyldododecane-2,6-dione (2a) and 4,16-dibenzyl-1,4,7,10,13,16,19,22-octaazacyclo-tetracosane-2,6,14,18-tetraone (2b), is reported. The structure of 3 is formally a CO2 insertion between positions 3 and 4 of the 12-membered ring in 2a. The CO2 insertion was confirmed in the synthesis of diethyl 2,2'-(benzylazanediyl)diacetate (1) by the reaction of benzylamine with ethyl bromoacetate using K2CO3 as the base. In addition, the selective synthesis of 3 and ethyl N-benzyl-N-((2-ethoxy-2-oxoethoxy)carbonyl)glycinate (5) and their kinetic behavior are reported. The reaction of 5 with triethylenetetramine afforded a 17-membered macrocycle (7), which was obtained in an 18% yield. Compounds 6 and 8 were prepared from 3 and 7 by introducing benzyl groups to improve their solubility in organic solvents. Titration experiments using 1H NMR showed that both 6 and 8 exhibit Li+ selectivity.

Solvent-Dependent Self-Assembly of a Pillar[5]arene-Based Poly-Pseudo-Rotaxane Linked and Threaded by Silver(I) Trifluoroacetate: A Double Role.

In the supramolecule area, the fabrication of a new concept called polyrotaxanes or poly-pseudo-rotaxanes remains challenging. We herein report the formation of a poly-pseudo-rotaxane in which the same salt-type guest serves both linking and threading in the resulting structure. The combination of A1/A2-thiopyridyl pillar[5]arene (L) and silver(I) trifluoroacetate in CHCl3/CH3OH afforded a one-dimensional (1D) poly-pseudo-rotaxane. In this structure, to our surprise, the AgCF3CO2 guest not only links the di-armed L ligands via an infinite -L-Ag-L-Ag- arrangement but also threads into a pillar[5]arene cavity in a dimer form, (AgCF3CO2)2. In contrast, the same reaction in CH2Cl2/CH3OH yielded a simple 1D coordination polymer because an included CH2Cl2 molecule in the pillar[5]arene cavity prevents the threading of the silver(I) trifluoroacetate guest. Comparative 1H- and 19F-NMR studies support the solvent-dependent poly-pseudo-rotaxane formation at a lower concentration of L.

ROS-induced PADI2 downregulation accelerates cellular senescence via the stimulation of SASP production and NFκB activation.

Cellular senescence is closely related to tissue aging including bone. Bone homeostasis is maintained by the tight balance between bone-forming osteoblasts and bone-resorbing osteoclasts, but it undergoes deregulation with age, causing age-associated osteoporosis, a main cause of which is osteoblast dysfunction. Oxidative stress caused by the accumulation of reactive oxygen species (ROS) in bone tissues with aging can accelerate osteoblast senescence and dysfunction. However, the regulatory mechanism that controls the ROS-induced senescence of osteoblasts is poorly understood. Here, we identified Peptidyl arginine deiminase 2 (PADI2), a post-translational modifying enzyme, as a regulator of ROS-accelerated senescence of osteoblasts via RNA-sequencing and further functional validations. PADI2 downregulation by treatment with H2O2 or its siRNA promoted cellular senescence and suppressed osteoblast differentiation. CCL2, 5, and 7 known as the elements of the senescence-associated secretory phenotype (SASP) which is a secretome including proinflammatory cytokines and chemokines emitted by senescent cells and a representative feature of senescence, were upregulated by H2O2 treatment or Padi2 knockdown. Furthermore, blocking these SASP factors with neutralizing antibodies or siRNAs alleviated the senescence and dysfunction of osteoblasts induced by H2O2 treatment or Padi2 knockdown. The elevated production of these SASP factors was mediated by the activation of NFκB signaling pathway. The inhibition of NFκB using the pharmacological inhibitor or siRNA effectively relieved H2O2 treatment- or Padi2 knockdown-induced senescence and osteoblast dysfunction. Together, our study for the first time uncover the role of PADI2 in ROS-accelerated cellular senescence of osteoblasts and provide new mechanistic and therapeutic insights into excessive ROS-promoted cellular senescence and aging-related bone diseases.

The relationship between corneal calcareous degeneration and various ophthalmic diseases in dogs: A retrospective study.

OBJECTIVE: To investigate ocular factors that influence the development of corneal calcareous degeneration (CCD) in dogs. ANIMALS AND PROCEDURES: The medical records of 96 eyes of dogs with CCD and 288 eyes without CCD were retrospectively reviewed. Dogs with evidence of causative systemic illness associated with CCD were excluded from the study. Logistic regression analysis was used to identify the ocular factors associated with the development of CCD. To identify the effect of phosphate-containing eyedrops on CCD, the application periods of phosphate-containing antiglaucoma eyedrops were compared between the glaucomatous eyes in the CCD and non-CCD groups. RESULTS: Increased age, brachycephalic breed, keratoconjunctivitis sicca, advanced cataract, history of phacoemulsification, and topical corticosteroid application were significantly associated with CCD development. Glaucoma was significantly overrepresented in the non-CCD group, and the application period of phosphate-containing antiglaucoma eyedrops was significantly longer in eyes with CCD than in those without CCD. CONCLUSIONS: Ophthalmic diseases requiring long-term management of ocular inflammation and long-term application of phosphate-containing eyedrops may contribute to the development of CCD. Glaucoma is overrepresented in dogs without CCD, which is thought to be due to the differences in predisposed age and breeds between dogs with glaucoma and CCD.

Development of a mobile application based on the salutogenic model for self-management in adolescents with Moyamoya disease.

PURPOSE: Moyamoya disease (MMD) is a rare disease which has a high incidence of onset in adolescence. Disease self-management skills are imperative for adolescents with MMD. This study aimed to describe the systematic development, content, and usability of the Moyamoya Healthy Youth application (app), which was developed to enhance self-management skills for adolescents with MMD. DESIGN AND METHODS: The theoretical grounding for the app was salutogenic model and the development process of the app was guided by the intervention mapping (IM) protocol. Results of each IM step were applied to the next step leading to the design of the app. Additionally, a pilot test was conducted to determine the usability of the app. RESULTS: Following the salutogenic model, we identified the stressors, behaviors, and resources regarding managing symptoms of MMD by interviewing adolescents with MMD, their parents, and healthcare providers. Based on the findings of the interviews, we determined the program outcomes and performance objectives to improve the self-management of MMD in adolescents. The app was developed by translating the theoretical methods to achieve the performance objectives into practical strategies for delivering the program. A pilot test with eight participants showed satisfaction with the app in terms of its usefulness and ease of use. CONCLUSION: We delineated the development process of the Moyamoya Healthy Youth. Additionally, we presented the positive outcomes regarding the usability of the app. PRACTICE IMPLICATIONS: The Moyamoya Healthy Youth app could benefit adolescents with MMD, by improving their self-management skills which are crucial for their health.

Single-Cell RNA Sequencing Reveals Immuno-Oncology Characteristics of Tumor-Infiltrating T Lymphocytes in Photodynamic Therapy-Treated Colorectal Cancer Mouse Model.

Photodynamic therapy (PDT) has shown promise in reducing metastatic colorectal cancer (CRC); however, the underlying mechanisms remain unclear. Modulating tumor-infiltrating immune cells by PDT may be achieved, which requires the characterization of immune cell populations in the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). Here, we determined the effect of Chlorin e6 (Ce6)-mediated PDT on tumor-infiltrating T cells using scRNA-seq analysis. We used a humanized programmed death-1/programmed death ligand 1 (PD-1/PD-L1) MC38 cell allograft mouse model, considering its potential as an immunogenic cancer model and in combination with PD-1/PD-L1 immune checkpoint blockade. PDT treatment significantly reduced tumor growth in mice containing hPD-1/PD-L1 MC38 tumors. scRNA-seq analysis revealed that the PDT group had increased levels of CD8+ activated T cells and CD8+ cytotoxic T cells, but decreased levels of exhausted CD8+ T cells. PDT treatment also enhanced the infiltration of CD8+ T cells into tumors and increased the production of key effector molecules, including granzyme B and perforin 1. These findings provide insight into immune-therapeutic modulation for CRC patients and highlight the potential of PDT in overcoming immune evasion and enhancing antitumor immunity.

Antitumor Effect of Korean Red Ginseng through Blockade of PD-1/PD-L1 Interaction in a Humanized PD-L1 Knock-In MC38 Cancer Mouse Model.

Blocking immune checkpoints, programmed death-1 (PD-1) and its ligand PD-L1, has proven a promising anticancer strategy for enhancing cytotoxic T cell activity. Although we previously demonstrated that ginsenoside Rg3, Rh2, and compound K block the interaction of PD-1 and PD-L1, the antitumor effect through blockade of this interaction by Korean Red Ginseng alone is unknown. Therefore, we determined the effects of Korean Red Ginseng extract (RGE) on the PD-1/PD-L1 interaction and its antitumor effects using a humanized PD-1/PD-L1-expressing colorectal cancer (CRC) mouse model. RGE significantly blocked the interaction between human PD-1 and PD-L1 in a competitive ELISA. The CD8+ T cell-mediated tumor cell killing effect of RGE was evaluated using murine hPD-L1-expressing MC38 cells and tumor-infiltrating hPD-1-expressing CD8+ T cells isolated from hPD-L1 MC38 tumor-bearing hPD-1 mice. RGE also reduced the survival of hPD-L1 MC38 cells in a cell co-culture system using tumor-infiltrating CD8+ T cells as effector cells combined with hPD-L1 MC38 target cells. RGE or Keytruda (positive control) treatment markedly suppressed the growth of hPD-L1 MC38 allograft tumors, increased CD8+ T cell infiltration into tumors, and enhanced the production of Granzyme B. RGE exhibits anticancer effects through the PD-1/PD-L1 blockade, which warrants its further development as an immunotherapy.

Oxidative stress modulates expression of immune checkpoint genes via activation of AhR signaling.

Reactive oxygen species (ROS) are by-products of metabolism of oxygen and they play an important role in normal homeostasis and cell signaling, as well as in the initiation of diseases including cancer when their production is upregulated. Thus, it is imperative to understand the cellular and molecular basis by which ROS impact on various biological and pathological processes. In this report, we show that human keratinocyte cell line (HaCaT) treated with hydrogen peroxide displayed an increased activity of AhR, leading to enhanced expression of its downstream targets including cytochrome P450 genes. Intriguingly, preincubation of the complete culture medium with hydrogen peroxide accelerated AhR activation and its downstream signaling. Subsequent mass spectrometric analysis reveals that the oxidant elicits the production of oxindole, a tryptophan catabolic product. We further demonstrate that 2-oxindole (a major form of oxindole) is capable of activating AhR, strongly suggesting that ROS may exert a significant impact on AhR signaling. Consistent with this, we also observe that hexavalent chromium [Cr(VI)], a heavy metal known to generate ROS in vivo, enhances AhR protein levels, as well as stimulates expression of CYP1A2 in an AhR-dependent manner. Significantly, we show that hydrogen peroxide and 2-oxindole induce expression of IDO1 and PD-L1, two immune checkpoint proteins. Given the role of IDO1 and PD-L1 in mediating T cell activity and/or differentiation, we postulate that ROS in the tumor microenvironment may play a crucial role in immune suppression via perturbing AhR signaling.

Photo-Curable Lacquer Sap Resin Based on Urushiol-Mimicking, Tyrosine-Containing Additive.

Oriental lacquer sap is attracting considerable attention as a renewable and eco-friendly natural resin with high durability, heat resistance, insulation, insect repellency, and antiseptic and antibacterial properties. However, to ensure excellent coating performance, it is necessary to improve the drying/curing process of lacquer sap with a time-consuming drying time at high humidity [relative humidity (RH), 70-90%] and ambient temperature (20-30 °C). Drawing on an understanding of the polymerization mechanism of urushiol, the main component of the lacquer sap consisted of a water-in-oil (W/O) emulsion, and this study presents an eco-friendly additive that mimics the structure-function of urushiol composed of a polar catechol head group and a nonpolar hydrocarbon tail. A photo-curable lacquer sap was thus developed by adding a tyrosine amino acid-based lipid agent (denoted as Y-ADDA), which allows faster and more effective drying/curing at lower humidity while maintaining the nature-derived properties of lacquer sap. Y-ADDA easily coassembles with urushiol in the W/O emulsion droplets, thereby significantly accelerating the formation of a polymer network along with urushiol during water evaporation leading to fast drying/curing under ultraviolet (UV) light irradiation at low humidity (∼50% RH). The UV-cured lacquer sap resins showed higher performance in terms of film processing and physicochemical properties compared with that of the lacquer containing only tyrosine amino acids without aliphatic tail conjugation, N-(9-fluorenylmethoxycarbonyl)-O-tert-butyl-l-tyrosine Fmoc-Tyr(tBu)-OH. Furthermore, the drying and curing times, film morphology, transmittance, hardness, and adhesion strength of the UV-cured lacquer were markedly superior compared to those of shellac, a general eco-friendly fast-drying primer. The study provides useful strategies and insights to promote the industrial application of lacquer sap resins by employing biocompatible nanoagents developed with an understanding of the curing mechanism of natural resins and from the viewpoint of green and sustainable chemistry perspective.

Metallosupramolecules of Pillar[5]arene with Two Flexible Thiopyridyl Arms: A Heterochiral Cyclic Dimer and Organic Guest-Assisted Homochiral Poly-Pseudo-Rotaxanes.

The formation of a cyclic dimer complex (1) and a poly-pseudo-rotaxane (2) of a racemic A1/A2-thiopyridyl pillar[5]arene (rac-L) with different chirality is reported. A one-pot reaction of rac-L with HgCl2 afforded a heterochiral cyclic dimer complex, [Hg2(pR-L)(pS-L)Cl4]·8CH2Cl2 (1), in which two Hg2+ atoms and one (pR-L)/(pS-L) enantiomeric pair form a [2:2] metallacycle via a metal coordination-based cyclization. Interestingly, the same reaction in the presence of the linear dinitrile guest, CN(CH2)8CN (G), yielded a one-dimensional poly-pseudo-rotaxane, {[Hg(G@pR-L)Cl2][Hg(G@pS-L)Cl2]}n (2), probably due to the rigidified ligand structure resulting from the dinitrile guest (G) threading. In 2, pR-L and pS-L generate two separated homochiral poly-pseudo-rotaxanes in a crystal. Both products are new members of the pillararene-derivative family. This study improves our understanding of self-assembly in nature and leads to this approach being an engineering tool for the construction of mechanically interlocked supramolecules.

Development of an in vitro screening system for synthetic signal peptide in mammalian cell-based protein production.

Optimizing appropriate signal peptides in mammalian cell-based protein production is crucial given that most recombinant proteins produced in mammalian cells are thought to be secreted proteins. Until now, most studies on signal peptide in mammalian cells have replaced native signal peptides with well-known heterologous signal peptides and bioinformatics-based signal peptides. In the present study, we successfully established an in vitro screening system for synthetic signal peptide in CHO cells by combining a degenerate codon-based oligonucleotides library, a site-specific integration system, and a FACS-based antibody detection assay. Three new signal peptides were screened using this new screening system, confirming to have structural properties as signal peptides by the SignalP web server, a neural network-based algorithm that quantifies the signal peptide-ness of amino acid sequences. The novel signal peptides selected in this study increased Fc-fusion protein production in CHO cells by increasing specific protein productivity, whereas they did not negatively affect cell growth. Particularly, the SP-#149 clone showed the highest qp, 0.73 ± 0.01 pg/cell/day from day 1 to day 4, representing a 1.47-fold increase over the native signal peptide in a serum-free suspension culture mode. In addition, replacing native signal peptide with the novel signal peptides did not significantly affect sialylated N-glycan formation, N-terminal cleavage pattern, and biological function of Fc-fusion protein produced in CHO cells. The overall results indicate the utility of a novel in vitro screening system for synthetic signal peptide for mammalian cell-based protein production. KEY POINTS: • An in vitro screening system for synthetic signal peptide in mammalian cells was established • This system combined a degenerate codon-based library, site-specific integration, and a FACS-based detection assay • The novel signal peptides selected in this study could increase Fc-fusion protein production in mammalian cells.

Comparison of iridocorneal angle parameters measured by spectral domain optical coherence tomography and ultrasound biomicroscopy in dogs.

OBJECTIVE: To compare the measurements of iridocorneal angle parameters between spectral domain optical coherence tomography (SD-OCT) and ultrasound biomicroscopy (UBM) in dogs. ANIMALS STUDIED AND PROCEDURES: A total of 47 eyes of dogs were scanned at the temporal limbus using SD-OCT and UBM. Iridocorneal angle (ICA) and angle opening distance (AOD) were measured from the obtained images accordingly. The intra-observer and inter-observer reproducibility were evaluated using the intraclass correlation coefficient. To evaluate intra-observer reproducibility, measurements of the first and second grading from the first examiner were compared. To evaluate inter-observer reproducibility, measurements between the two examiners were compared. Agreement between ICA and AOD for SD-OCT and UBM was evaluated using Bland-Altman plots. RESULTS: In the first grading, the mean ICA and AOD for SD-OCT were 31.4 ± 6.4° and 641.4 ± 270.8 µm, respectively. The mean ICA and AOD for UBM were 32.0 ± 4.8° and 700.4 ± 238.8 µm, respectively. For ICA and AOD measurements, intra-observer reproducibility was excellent for both devices, whereas inter-observer reproducibility was excellent for SD-OCT and good for UBM. The mean difference in ICA between SD-OCT and UBM was 0.6° with a limit of agreement (LoA) span of 18.9°. The mean difference in AOD between SD-OCT and UBM was 58.9 µm with a LoA span of 804.4 µm. CONCLUSIONS: Spectral domain optical coherence tomography is an effective non-contact imaging modality for the evaluation of canine iridocorneal angle parameters in a clinical setting. Reproducibility of measurements obtained is comparable or superior to UBM, but values obtained by SD-OCT and UBM for AOD are not interchangeable between devices.