Actinic keratoses (AKs) are lesions of epidermal keratinocyte dysplasia and are precursors for invasive cutaneous squamous cell carcinoma (cSCC). Identifying the specific genomic alterations driving the progression from normal skin to skin with AK to skin with invasive cSCC is challenging because of the massive UVR-induced mutational burden characteristic at all stages of this progression. In this study, we report the largest AK wholeexome sequencing study to date and perform a mutational signature and candidate driver gene analysis on these lesions. We demonstrate in 37 AKs from both immunosuppressed and immunocompetent patients that there are significant similarities between AKs and cSCC in terms of mutational burden, copy number alterations, mutational signatures, and patterns of driver gene mutations. We identify 44 significantly mutated AK driver genes and confirm that these genes are similarly altered in cSCC. We identify azathioprine mutational signature in all AKs from patients exposed to the drug, providing further evidence for its role in keratinocyte carcinogenesis. cSCCs differ from AKs in having higher levels of intrasample heterogeneity. Alterations in signaling pathways also differ, with immune-related signaling and TGFf3 signaling significantly more mutated in cSCC. Integrating our findings with independent gene expression datasets confirms that dysregulated TGFf3 signaling may represent an important event in AK-cSCC progression.

Aims: This study aimed at investigating the role of Brusatol (BR) on human laryngeal squamous carcinoma cell (Hep-2) to study its underlying mechanism through in vitro and in vivo approaches. Materials and method: In the present research, we employed various cell-based assays, such as cell proliferation, apoptosis, cell cycle assessment, migration and invasion assays were used to examine the anti-tumor effect of BR on Hep-2 cells. Immunohistochemistry (IHC), qRT-PCR and Western blotting were performed to study the underlying molecular mechanisms. To validate our in vitro findings we used a subcutaneous tumor-bearing model of Balb/c mice with Hep-2 cells of laryngeal carcinoma (LC) to study the inhibitory effect of BR on Hep-2 cells in vivo. Key findings: The results indicated that BR markedly inhibited the viability, migration and invasion capacity of Hep-2 cells, with no significant toxic effect on normal Human bronchial epithelial cell line (BEAS-2B). Also, BR induced cellular apoptosis by blocking the cells in S phase to suppress cell proliferation. Immunohistochemistry results revealed that BR inhibited the protein expression levels of epithelial-mesenchymal transition (EMT)related markers. Mechanistically, western blotting results exhibited that BR could suppress the protein expression of both JAK2/STAT3 and their phosphorylation levels. Our in vivo experiments further validated the anti-tumor effect of BR on Hep-2 cells in vitro, where BR suppressed the growth of xenograft laryngeal tumor without apparent toxicity. Significance: The present study highlights the anti-LC effect of BR by possibly abrogating JAK2/STAT3 signaling mediated EMT process. BR may be a promising therapeutic candidate for the treatment of LC.

Utilizing the solar and geothermal energy in space heating systems can save fossil fuels and reduce emissions. In this study, compound parabolic concentrator (CPC) photovoltaic/thermal collectors (PV/T), absorption and ground source heat pumps are integrated to a novel space heating system for use in hotel and office buildings. A full simulation model of the system is constructed and validated by using the Engineering Equation Solver software. The heating system is analyzed against its energy, environmental, economic, and flexibility performance using multiple variables including the PV coverage ratio, ambient temperature, solar beam irradiance, and electricity price. The results show that integrating solar and geothermal energy can be effective to supplement the space heating demand. The best integrated performance point of the office building gives a 32% energy saving ratio, 9% annual cost savings ratio, 23% emission reduction ratio, and 67% excess adjustable ratio compared to a pure ground heat pump system. This research provides new directions of integrated performance evaluation of heating systems assisted by renewable energy resources. (C) 2021 Elsevier Ltd. All rights reserved.

At present, a series of challenges are impeding large-scale application of high temperature radar absorbing coatings (RACs), such as complex preparation of raw material and complicated technology of processing. In this paper, we designed and experimentally demonstrated a high-temperature metamaterial RAC (MRAC) with strong absorption and thin thickness, which is composite of radar absorbing coating and a layer of metamaterial. To avoid complex preparation of raw materials, pure alumina was selected as the radar absorbing coating. Plasma spraying and screen printing were employed to simplify the sample preparation to produce the absorbing coating and the metamaterial layer, ensuring its feasibility and practicality. The metamaterial layer was prepared with a high temperature conductive paste and it improved the impedance matching of the coating and regulated the electromagnetic (EM) resonance, which allows more EM waves to be absorbed. Therefore, excellent high temperature absorption was also achieved with relatively small thickness. At 800 degrees C, the MRAC reflection loss (RL) below -5 dB almost covered the frequency of 10-18 GHz with a thickness of only 1.5 mm. This new metamaterial has broad application prospects by the virtue of its simplicity and convenience in manufacture. (c) 2021 Elsevier B.V. All rights reserved.

The effects of low-temperature oxy-nitriding (LTON) treatment on the liquid lead-bismuth eutectic (LBE) corrosion behaviors of 316 L ASS were investigated in the stagnant liquid LBE under vacuum at 823 K. Results show that the untreated samples were severely selective leaching in contact with liquid LBE. LTON treatment produced an outer porous Fe-Cr spinel film and inner S phase layer on the sample surface, which transformed into a thicker spinel film containing gamma(low-N) and a region distributed with CrN precipitates after liquid LBE corrosion. This was mainly attributed to the oxidation and decomposition of S phase and inward diffusion of the interstitials, owing to S phase is a metastable phase and is easier to be oxidized than matrix at elevated temperatures. This inspired us that improving the ability to form protective oxide film for materials was maybe a good method to mitigate the liquid LBE corrosion. (C) 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

We apply the methods of Fukaya, Kato and Sharifi to refine Mazur's study of the Eisenstein ideal. Given prime numbers N and p >= 5 such that p vertical bar phi(N), we study the quotient of the cohomology group of modular curve X-0(N) by the square of the Eisenstein ideal. We study two invariants b, c attached to this quotient and compute c. We propose a conjecture about the invariant b which relates the structure of the ray class group of conductor N to the modular symbols of X-0(N). Assuming this conjecture, we compute the invariant b. (C) 2021 Elsevier Inc. All rights reserved.