The miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis

Background Heat shock protein 27 (HSP27) is overexpressed during pulmonary fibrosis (PF) and exacerbates PF; however, the upregulation of HSP27 during PF and the therapeutic strategy of HSP27 inhibition is not well elucidated. Methods We have developed a mouse model simulating clinical stereotactic body radiotherapy (SBRT) with focal irradiation and validated the induction of RIPF. HSP25 (murine form of HSP27) transgenic (TG) and LLC1-derived orthotropic lung tumor models were also used. Lung tissues of patients with RIPF and idiopathic pulmonary fibrosis, and lung tissues from various fibrotic mouse models, as well as appropriated cell line systems were used. Public available gene expression datasets were used for therapeutic response rate analysis. A synthetic small molecule HSP27 inhibitor, J2 was also used. Results HSP27 expression with its phosphorylated form (pHSP27) increased during PF. Decreased mRNA expression of SMAD-specific E3 ubiquitin-protein ligase 2 (Smurf2), which is involved in ubiquitin degradation of HSP27, was responsible for the increased expression of pHSP27. In addition, increased expression of miRNA15b was identified with decreased expression of Smurf2 mRNA in PF models. Inverse correlation between pHSP27 and Smurf2 was observed in the lung tissues of PF animals, an irradiated orthotropic lung cancer models, and PF tissues from patients. Moreover, a HSP27 inhibitor cross-linked with HSP27 protein to ameliorate PF, which was more effective when targeting the epithelial to mesenchymal transition (EMT) stage of PF. Conclusions Our findings identify upregulation mechanisms of HSP27 during PF and provide a therapeutic strategy for HSP27 inhibition for overcoming PF.This work was supported by grants from the National Research Foundation of Korea, (NRF-2018R1A5A2025286, NRF-2020R1A2C3013255, NRF-2020M2D9A2093974, NRF-2020R1I1A1A01070841, NRF-2020M2D9A2093976 and NRF-2022R1A2C3011611), funded by the Korean government (Ministry of Science and ICT)

Detection of Infectious Hypodermal and Hematopoietic Necrosis Virus (IHHNV, Decapod Penstylhamaparvovirus 1) in Commodity Red Claw Crayfish (Cherax quadricarinatus) Imported into South Korea

Freshwater crayfish, which are cultivated in aquaculture, are economically important for food and ornamental purposes. However, relatively few studies have focused on potentially pathogenic viruses in crayfish compared to in penaeid shrimp. Commodity red claw crayfish (Cherax quadricarinatus; 400 crayfish in 10 batches) and red swamp crayfish (Procambarus clarkii; 40 crayfish in 2 batches) imported into South Korea from Indonesia and China were screened by PCR to detect infectious hypodermal and hematopoietic necrosis virus (IHHNV or Decapod penstylhamaparvovirus 1). IHHNV was detected in tissue samples pooled from nine out of ten batches of red claw crayfish imported from Indonesia. Phylogenetic analysis of PCR amplicons from representative pools clustered the IHHNV strain with infectious-type II sequences commonly detected in Southeast Asian countries rather than with type III strains detected previously in whiteleg shrimp (Penaeus vannamei) cultured in South Korea. IHHNV DNA was detected most frequently in the muscle (eight batches, 66.7% samples), followed by in the hepatopancreas (five batches, 41.7% samples) and gills tissue (three batches, 25.0% samples). These data suggest that red claw crayfish could be a potential carrier of the virus and that quarantine procedures must be strengthened in South Korea to avoid importing infectious types of IHHNV in commodity crustaceans such as red claw crayfish. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.1

Observation of tW production in the single-lepton channel in pp collisions at root s=13 TeV

A measurement of the cross section of the associated production of a single top quark and a W boson in final states with a muon or electron and jets in proton-proton collisions at root s = 13 TeV is presented. The data correspond to an integrated luminosity of 36 fb(-1) collected with the CMS detector at the CERN LHC in 2016. A boosted decision tree is used to separate the tW signal from the dominant t (t) over bar background, whilst the subleading W+jets and multijet backgrounds are constrained using data-based estimates. This result is the first observation of the tW process in final states containing a muon or electron and jets, with a significance exceeding 5 standard deviations. The cross section is determined to be 89 +/- 4 (stat) +/- 12 (syst) pb, consistent with the standard model.Peer reviewe

Identification of radiation response genes and proteins from mouse pulmonary tissues after high-dose per fraction irradiation of limited lung volumes

<p><b>Purpose:</b> The molecular effects of focal exposure of limited lung volumes to high-dose per fraction irradiation (HDFR) such as stereotactic body radiotherapy (SBRT) have not been fully characterized. In this study, we used such an irradiation system and identified the genes and proteins after HDFR to mouse lung, similar to those associated with human therapy.</p> <p><b>Methods and materials:</b> High focal radiation (90 Gy) was applied to a 3-mm volume of the left lung of C57BL6 mice using a small-animal stereotactic irradiator. As well as histological examination for lungs, a cDNA micro array using irradiated lung tissues and a protein array of sera were performed until 4 weeks after irradiation, and radiation-responsive genes and proteins were identified. For comparison, the long-term effects (12 months) of 20 Gy radiation wide-field dose to the left lung were also investigated.</p> <p><b>Results:</b> The genes <i>ermap</i>, <i>epb4.2</i>, <i>cd200r3</i> (up regulation) and <i>krt15</i>, <i>hoxc4</i>, <i>gdf2</i>, <i>cst9</i>, <i>cidec</i>, and <i>bnc1</i> (down-regulation) and the proteins of AIF, laminin, bNOS, HSP27, β-amyloid (upregulation), and calponin (downregulation) were identified as being responsive to 90 Gy HDFR. The <i>gdf2</i>, <i>cst9</i>, and <i>cidec</i> genes also responded to 20 Gy, suggesting that they are universal responsive genes in irradiated lungs. No universal proteins were identified in both 90 Gy and 20 Gy. Calponin, which was downregulated in protein antibody array analysis, showed a similar pattern in microarray data, suggesting a possible HDFR responsive serum biomarker that reflects gene alteration of irradiated lung tissue. These genes and proteins also responded to the lower doses of 20 Gy and 50 Gy HDFR.</p> <p><b>Conclusions:</b> These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans.</p

Nicotinamide adenine dinucleotide phosphate oxidase 2 deletion attenuates polyhexamethylene guanidine-induced lung injury in mice

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes

Upconversion Nanoparticles/Hyaluronate-Rose Bengal Conjugate Complex for Noninvasive Photochemical Tissue Bonding

The recent progress in photonic nanomaterials has contributed greatly to the development of photomedicines. However, the finite depth of light penetration is still a serious limitation, constraining their clinical applications. Here, we developed a. poly(allylamine) (PAAm)-modified upconversion nanoparticle/hyaluronate rose bengal (UCNP/PAAm/HA-RB) conjugate complex for photochemical bonding of deep tissue with near-infrared (NIR) light illumination. Compared to the conventional invasive treatment via suturing and stapling, the UCNP/PAAm/HA-RB conjugate complex could be noninvasively delivered into the deep tissue and accelerate the tissue bonding upon NIR light illumination. HA in the outer layer of the complex facilitated the penetration of RB into the collagen layer of the dermis. The NIR light triggered UCNP of NaYF4: Yb/Er (Y:Yb:Er = 78:20:2) in the complex to illuminate visible green light under the skin tissue. The activated RB in the HA-RB conjugate by the green light induced radical formation for the cross linking of incised collagen matrix. An in vitro light propagation test and collagen fibrillogenesis analysis, an in vivo animal tissue bonding test, and an ex vivo tensile strength test of dissected skin tissues confirmed the successful photochemical tissue bonding effect of the UCNP/PAAm/HA-RB conjugate complex.117sciescopu

Perovskite quantum dot-induced monochromatization for broadband photodetection of wafer-scale molybdenum disulfide

Two-dimensional transition metal dichalcogenide (2D TMD) crystals are versatile platforms for realizing emergent optoelectronic devices. However, the ability to produce large-area 2D TMDs with spatial homogeneity and to accomplish broadband photodetection by tuning the operating wavelengths in photodetectors are two paramount prerequisites for practical applications of 2D TMD-based photodetectors. Here, we demonstrated all-solution-processed broadband photodetectors based on the wafer-scale perovskite quantum dots (PQDs)/MoS2 through light management via the monochromatization effect of the PQDs. The photodetectors exhibited broadband photodetection behavior that retained high photocurrents over a wide spectral range (254, 365, and 532 nm) by enhancing the photoresponse in the UV region through light management via the monochromatization effect of the PQDs. This intriguing strategy was proven with (i) electrical isolation realized by inserting an Al2O3 insulator between the PQDs and MoS2 and (ii) alteration of the PQD density. The rational nanohybrid-based photodetectors also exhibited superb air stability and exceptional bending durability