Corrigendum: Transcriptional inhibition of STAT1 functions in the nucleus alleviates Th1 and Th17 cell-mediated inflammatory diseases.

[This corrects the article DOI: 10.3389/fimmu.2022.1054472.].

Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis.

Regulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.

Integrative analysis of metabolite and transcriptome reveals biosynthetic pathway and candidate genes for eupatilin and jaceosidin biosynthesis in Artemisia argyi.

Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.

Design of a CMOS Image Sensor with Bi-Directional Gamma-Corrected Digital-Correlated Double Sampling.

We present a 640 × 480 CMOS image sensor (CIS) with in-circuit bi-directional gamma correction with a proposed digital-correlated double sampling (CDS) structure. To operate the gamma correction in the CIS, the transfer function of the analog-to-digital converter can be changed by controlling the clock frequency of the counter using analog CDS. However, the analog CDS is vulnerable to capacitor mismatch, clock feedthrough, etc. Therefore, we propose a digital-CDS method with a hold-and-go counter structure to operate the bi-directional gamma correction in the CIS. The proposed CIS achieves a 10-bit resolution using a global log-exponential counter and configurable column reset counter with a resolution of 8/9 bits. The sensor was fabricated in a 0.11 µm CIS process, and the full chip area was 5.9 mm × 5.24 mm. The measurement results showed a maximum SNR improvement of 10.41% with the proposed bi-directional gamma-corrected digital-CDS with the hold-and-go counter. The total power consumption was 6.3 mW at a rate of 16.6 frames per second with analog, pixel, and digital supply voltages of 3.3 V, 3.3 V, and 1.5 V, respectively.

Intranasal administration of nucleus-deliverable GATA3-TMD alleviates the symptoms of allergic asthma.

Although the T helper 2 (Th2) subset is a critical player in the humoral immune response to extracellular parasites and suppression of Th1-mediated inflammation, Th2 cells have been implicated in allergic inflammatory diseases such as asthma, allergic rhinitis, and atopic dermatitis. GATA binding protein 3 (GATA3) is a primary transcription factor that mediates Th2 differentiation and secretion of Th2 cytokines, including IL-4, IL-5, and IL-13. Here, a nucleus-deliverable form of GATA3-transcription modulation domain (TMD) (ndG3-TMD) was generated using Hph-1 human protein transduction domain (PTD) to modulate the transcriptional function of endogenous GATA3 without genetic manipulation. ndG3-TMD was shown to be efficiently delivered into the cell nucleus quickly without affecting cell viability or intracellular signaling events for T cell activation. ndG3-TMD exhibited a specific inhibitory function for the endogenous GATA3-mediated transcription, such as Th2 cell differentiation and Th2-type cytokine production. Intranasal administration of ndG3-TMD significantly alleviated airway hyperresponsiveness, infiltration of immune cells, and serum IgE level in an OVA-induced mouse model of asthma. Also, Th2 cytokine secretion by the splenocytes isolated from the ndG3-TMD-treated mice substantially decreased. Our results suggest that ndG3-TMD can be a new therapeutic reagent to suppress Th2-mediated allergic diseases through intranasal delivery.

Content Swapping: A New Image Synthesis for Construction Sign Detection in Autonomous Vehicles.

Construction signs alert drivers to the dangers of abnormally blocked roads. In the case of autonomous vehicles, construction signs should be detected automatically to prevent accidents. One might think that we can accomplish the goal easily using the popular deep-learning-based detectors, but it is not the case. To train the deep learning detectors to detect construction signs, we need a large amount of training images which contain construction signs. However, collecting training images including construction signs is very difficult in the real world because construction events do not occur frequently. To make matters worse, the construction signs might have dozens of different construction signs (i.e., contents). To address this problem, we propose a new method named content swapping. Our content swapping divides a construction sign into two parts: the board and the frame. Content swapping generates numerous synthetic construction signs by combining the board images (i.e., contents) taken from the in-domain images and the frames (i.e., geometric shapes) taken from the out-domain images. The generated synthetic construction signs are then added to the background road images via the cut-and-paste mechanism, increasing the number of training images. Furthermore, three fine-tuning methods regarding the region, size, and color of the construction signs are developed to make the generated training images look more realistic. To validate our approach, we applied our method to real-world images captured in South Korea. Finally, we achieve an average precision (AP50) score of 84.98%, which surpasses that of the off-the-shelf method by 9.15%. Full experimental results are available online as a supplemental video. The images used in the experiments are also released as a new dataset CSS138 for the benefit of the autonomous driving community.

Fabrication of conductive silver paste recovered from leaching of waste catalyst using hydrochloric acid.

Transition metal compounds based on silver (Ag) and palladium (Pd) are extensively used as catalysts in the petrochemical industries. The catalytic activities of Ag and Pd decrease over time and hence need to be discarded. The recovery of elements like Ag from waste catalyst is essential because of its limited availability and cost, and it is environmentally beneficial with regards to recycling. In this study, Pd and Ag were leached from waste catalyst providing an alternative source suitable for a Ag paste electrode. Through an efficient reduction process, AgCl particles were obtained which serve as a precursor to synthesize Ag using ammonia as the solvent. The obtained Ag was fabricated to Ag paste by using mixed dispersion and solvent. The electrical resistivity of the Ag paste was recorded as 6.14 µΩ cm at 417 °C in a hydrogen atmosphere.

Interactomic inhibition of Eomes in the nucleus alleviates EAE via blocking the conversion of Th17 cells into non-classic Th1 cells.

Th17 cells are implicated in the pathogenesis of several autoimmune diseases. During the inflammation, Th17 cells exposed to IL-12 can shift towards the Th1 phenotype. These shifted cells are defined as 'non-classic Th1 cells'. Th17-derived non-classic Th1 cells play a critical role in late-onset chronic inflammatory diseases and are more pathogenic than the unshifted Th17 cells. Eomes is a transcription factor highly expressed in non-classic Th1 cells. To study the functional role of Eomes without genetic alteration, novel recombinant protein, ntEomes-TMD, was generated by fusing TMD of Eomes and Hph-1-PTD that facilitate intracellular delivery of its cargo molecule. ntEomes-TMD was delivered into the nucleus of the cells without influencing the T cell activation and cytotoxicity. ntEomes-TMD specifically inhibited the Eomes- and ROR-γt-mediated transcription and suppressed the Th1 and Th17 differentiation. Interestingly, ntEomes-TMD blocked the generation of non-classic Th1 cells from Th17 cells, leading to the inhibition of IFN-γ and GM-CSF secretion. In EAE, ntEomes-TMD alleviated the symptoms of EAE, and the combination treatment using ntEomes-TMD and anti-IL-17 mAb together showed better therapeutic efficacy than anti-IL-17 mAb treatment. The results suggest that ntEomes-TMD can be a new therapeutic reagent for treating chronic inflammatory diseases associated with non-classic Th1 cells.

Comparison between T2-weighted two-dimensional and three-dimensional fast spin-echo MRI sequences for characterizing thoracolumbar intervertebral disc disease in small-breed dogs.

Magnetic resonance imaging (MRI) is a standard test for diagnosis and treatment planning in dogs with degenerative thoracolumbar intervertebral disc disease (IVDD). However, published studies evaluating three-dimensional fast-spin echo (3D-FSE) pulse sequences for dogs with IVDD are currently limited. Aims of this retrospective, observational study were to compare findings from T2-weighted two- and three-dimensional fast spin-echo sequences (2D- and 3D-FSE, respectively) for a group of small breed dogs with thoracolumbar IVDD. Inclusion criteria were dogs with IVDD that underwent 1.5-Tesla MRI using both 2D-FSE and 3D-FSE sequences. For each dog and sequence, five pathologic indices were recorded: epidural fat discontinuation, vertebral canal compromise, spinal cord signal change, disc degeneration, and nerve root compression. Two independent investigators also scored visibility of the facet joint, intervertebral foramen, nerve roots, spinal cord grey-white matter differentiation, intervertebral discs, and epidural fat. The Wilcoxon signed-rank test was used to evaluate the between-sequence differences in pathologic indices and visibility scores. Interobserver agreement was measured using Cohen's weighted kappa along with 95% confidence intervals. A total of 21 dogs were sampled. The 3D-FSE sequences had higher pathologic indices of vertebral canal compromise (P = 0.020) and spinal cord signal change (P = 0.046) than 2D-FSE sequences. Furthermore, 3D-FSE sequences had higher visibility scores for the facet joint, intervertebral foramen, and nerve root structures (P < 0.001). Findings from the current supported the use of 3D-FSE sequences over 2D-FSE sequences for the evaluation of IVDD and visualization of spinal structures in small breed dogs.

Transcriptional inhibition of STAT1 functions in the nucleus alleviates Th1 and Th17 cell-mediated inflammatory diseases.

T helper 1 cells (Th1 cells) and T helper 17 cells (Th17 cells) play pivotal roles in the pathogenesis of various autoimmune diseases, including psoriasis and inflammatory bowel disease (IBD). Signal transducer and activator of transcription 1 (STAT1) regulates the Th1 and Th17 cell lineage commitment at an early stage and maintains their immunological functions in vitro and in vivo. The previous strategies to block STAT1 functions to treat autoimmune diseases inhibit Th1 cell activity but simultaneously cause hyper-activation of Th17 cells. Herein, to modulate the functions of pathogenic Th1 and Th17 cells without genetic modification in normal physiological conditions, we generated the nucleus-deliverable form of the transcription modulation domain of STAT1 (ndSTAT1-TMD), which can be transduced into the nucleus of the target cells in a dose- and time-dependent manner without affecting the cell viability and T cell activation signaling events. ndSTAT1-TMD significantly blocked the differentiation of naïve CD4+ T cells into Th1 or Th17 cells via competitive inhibition of endogenous STAT1-mediated transcription, which did not influence Th2 and Treg cell differentiation. When the gene expression profile of Th1 or Th17 cells after ndSTAT1-TMD treatment was analyzed by mRNA sequencing, the expression of the genes involved in the differentiation capacity and the immunological functions of Th1 or Th17 cells were substantially reduced. The therapeutic potential of ndSTAT1-TMD was tested in the animal model of psoriasis and colitis, whose pathogenesis is mainly contributed by Th1 or/and Th17 cells. The symptoms and progression of psoriasis and colitis were significantly alleviated by ndSTAT1-TMD treatment, comparable to anti-IL-17A antibody treatment. In conclusion, our study demonstrates that ndSTAT1-TMD can be a new therapeutic reagent for Th1/17 cell-mediated autoimmune diseases by modulating the functions of pathogenic Th1 and Th17 cells together.

Comparison of shear-wave velocities obtained with shear-wave elastography of various peripheral lymph nodes in healthy Beagles.

OBJECTIVE: To compare shear-wave velocities (SWVs) with shear-wave elastography of various peripheral lymph nodes (LNs). ANIMALS: 11 healthy Beagles. PROCEDURES: For each dog, bilateral mandibular, medial retropharyngeal, superficial cervical, axillary, superficial inguinal, and popliteal LNs were evaluated with shear-wave elastography in sagittal and transverse scanning planes. Depth of each lymph node was recorded, and intra- and interobserver reliability was determined. RESULTS: SWVs for all LNs were significantly higher in the sagittal scanning plane, compared with those in the transverse scanning plane. The SWV of the most superficial LN, the mandibular LN, was significantly higher, compared with that for the other LNs, except for the medial retropharyngeal LN. The SWV of the deepest LN, the medial retropharyngeal LN, was as high as that for the mandibular LN. Intra- and interobserver reliability was excellent. CONCLUSIONS AND CLINICAL RELEVANCE: SWVs for normal peripheral LNs of Beagles may serve as a reference to compare with those for other breeds and diseased LNs. Scanning plane, LN depth, and interfering tissues between the LN and the transducer may affect SWV. Shear-wave elastography may not be operator dependent.

Post Fire Residual Strength of the Wall-Slab Using Siliceous Concrete.

It is very important to understand the residual performance of a structure for repair, retrofit, and reuse of a building after a fire. In this study, an experiment is conducted on the residual performance of real-scale siliceous aggregates-based reinforced concrete (RC) wall-slab connection (WSC) after the fire, using the simple calculation method (SCM) of standards (Eurocode, ACI, and NIST) for comparison and analysis. A description of the WSC specimen and detailed methods for the experiment are introduced. The fire test is conducted according to the fire scenario by dividing it into one-sided and two-sided heating based on the wall. In the post-fire residual performance test, the load-displacement and moment-deflection angle relationship according to the fire time are derived and discussed. In addition, the residual mechanical properties after the fire are derived for the 35 MPa siliceous concrete used in the wall-slab specimen. The load and moment, derived using SCM, are compared with the experimental results. Our results show that the one-sided heating test result is close to that of Eurocode's SCM, and the two-sided heating test result is close to that of ACI (NIST)'s SCM. This study provides a database on the residual strength through a real-scale fire test and standard comparison.

Understanding of the aging pattern in quantum dot light-emitting diodes using low-frequency noise.

The negative and positive aging effects of quantum dot (QD) light-emitting diodes (QLEDs) have received considerable attention in recent years and various analysis methods have been discussed. Here, we introduce a new approach to understand the aging effect of QLEDs, which is to diagnose the behavior of carriers and traps at interfaces between each layer of the QLEDs and inside the layers themselves. In particular, low-frequency noise (LFN) measurement and the analysis of current in the QLEDs were introduced to investigate the trapping/de-trapping behaviors of carriers in the defect states in the devices. A flicker noise was observed before the carriers are injected into the QD emitting layer, while the exciton generation-recombination (G-R) noise and shot noise were observed when the electrons were injected. A correlated noise, which is the correlated model of the trapping/de-trapping of the carriers near and/or inside the QDs and the exciton recombination, was also observed above the turn-on voltage. In addition, when the devices were aged with a constant current source, rapid increases in the luminance and external quantum efficiency (EQE) were observed for up to 50 h. After 100 h of the current aging, however, the devices were negatively aged with the reduced EQE. The LFN analysis results imply that the aging phenomena mainly depend on the trapping/de-trapping of carriers. In addition to the LFN analysis, we also investigated the current density-voltage-luminance and capacitance-voltage characteristics of the devices to clarify the aging behaviors in QLEDs.

NAMPT enzyme activity regulates catabolic gene expression in gingival fibroblasts during periodontitis.

Periodontal disease is one of the most prevalent chronic disorders worldwide. It is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss. Here, we focused on the role of adipokines, which are locally expressed by periodontal tissues, in the regulation of catabolic gene expression leading to periodontal inflammation. The expression of the nicotinamide phosphoribosyltransferase (NAMPT) adipokine was dramatically increased in inflamed human and mouse gingival tissues. NAMPT expression was also increased in lipopolysaccharide- and proinflammatory cytokine-stimulated primary cultured human gingival fibroblasts (GF). Adenovirus-mediated NAMPT (Ad-Nampt) overexpression upregulated the expression and activity of COX-2, MMP1 and MMP3 in human GF. The upregulation of IL-1ß- or Ad-Nampt-induced catabolic factors was significantly abrogated by the intracellular NAMPT (iNAMPT) inhibitor, FK866 or by the sirtuin (SIRT) inhibitor, nicotinamide (NIC). Recombinant NAMPT protein or extracellular NAMPT (eNAMPT) inhibition using a blocking antibody did not alter NAMPT target gene expression levels. Moreover, intragingival Ad-Nampt injection mediated periodontitis-like phenotypes including alveolar bone loss in mice. SIRT2, a part of the SIRT family, was positively associated with NAMPT actions in human GF. Furthermore, in vivo inhibition of the NAMPT-NAD+-SIRT axis by NIC injection in mice ameliorated the periodontal inflammation and alveolar bone erosion caused by intragingival injection of Ad-Nampt. Our findings indicate that NAMPT is highly upregulated in human GF, while its enzymatic activity acts as a crucial mediator of periodontal inflammation and alveolar bone destruction via regulation of COX-2, MMP1, and MMP3 levels.

Massive Hemoptysis due to Endotracheal Hemangioma: A Case Report and Literature Review.

Tracheal hemangioma is a rare benign vascular tumor in adults. We reported a case of massive hemoptysis caused by a cavernous hemangioma in a 75-year-old man. This is the first report, to our knowledge, of a tracheal cavernous hemangioma that presented with massive hemoptysis. The lesion was removed with a CO2 laser under rigid laryngoscopy. Endovascular tumors, such as tracheobronchial hemangiomas, should be considered a diagnostic option in cases of massive hemoptysis without a significant underlying lung lesion.

A Case of Delayed Diagnosis of Pulmonary Paragonimiasis due to Improvement after Anti-tuberculosis Therapy.

Here, we report a case of pulmonary paragonimiasis that was improved with initial anti-tuberculosis (TB) therapy but confused with reactivated pulmonary TB. A 53-year-old Chinese female presented with a persistent productive cough with foul smelling phlegm and blood streaked sputum. Radiologic findings showed subpleural cavitary consolidation in the right upper lobe (RUL). Bronchoscopic and cytological examination showed no remarkable medical feature. She was diagnosed with smear-negative TB, and her radiologic findings improved after receiving a 6-month anti-TB therapy. The chest CT scans, however, obtained at 4 months after completion of anti-TB therapy showed a newly developed subpleural consolidation in the RUL. She refused pathologic confirmation and was re-treated with anti-TB medication. Nevertheless, her chest CT scans revealed newly developed cavitary nodules at 5 months after re-treatment. She underwent thoracoscopic wedge resection; the pathological examination reported that granuloma caused by Paragonimus westermani. Paragonimiasis should also be considered in patients assessed with smear-negative pulmonary TB.