Rationale: Phagocytosis of silicon dioxide (SiO2) into lung cells causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Circular RNAs (circRNAs) are a subclass of non-coding RNAs detected within mammalian cells; however, researchers have not determined whether circRNAs are involved in the pathophysiological process of silicosis. The upstream molecular mechanisms and functional effects on cell apoptosis, proliferation and migration were investigated to elucidate the role of circRNAs in SiO2-induced inflammation in pulmonary macrophages.Methods: Primary cultures of alveolar macrophages from healthy donors and patients as well as the RAW264.7 macrophage cell line were used to explore the functions of circHECTD1 (HECT domain E3 ubiquitin protein ligase 1) in macrophage activation.Results: The results of the experiments indicated that 1) SiO2 concomitantly decreased circHECTD1 levels and increased HECTD1 protein expression; 2) circHECTD1 and HECTD1 were involved in SiO2-induced macrophage activation via ubiquitination; and 3) SiO2-activated macrophages promoted fibroblast proliferation and migration via the circHECTD1/HECTD1 pathway. Tissue samples from silicosis patients confirmed the upregulation of HECTD1.Conclusions: Our study elucidated a link between SiO2-induced macrophage activation and the circHECTD1/HECTD1 pathway, thereby providing new insight into the potential use of HECTD1 in the development of novel therapeutic strategies for treating silicosis.

Phagocytosis of silicon dioxide (SiO) into lung cells causes an inflammatory cascade that results in fibroblast proliferation and migration, followed by fibrosis. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that are present within mammalian cells; however, researchers have not determined whether circRNAs are involved in the pathophysiologic process of silicosis. To elucidate the role of these RNAs in SiO-induced inflammation in pulmonary macrophages, we investigated the upstream molecular mechanisms and functional effects of circRNAs on cell apoptosis, proliferation, and migration. Primary cultures of alveolar macrophages from healthy donors and from patients and the RAW264.7 macrophage cell line were used to explore the functions of circZC3H4 RNA in macrophage activation. The experimental results indicated the following: 1) SiO concomitantly increased circZC3H4 RNA expression and increased ZC3H4 protein levels; 2) circular ZC3H4 (circZC3H4) RNA and ZC3H4 protein participated in SiO-induced macrophage activation; and 3) SiO-activated macrophages promoted fibroblast proliferation and migration via the circZC3H4 RNA/ZC3H4 pathway. The up-regulation of the ZC3H4 protein was confirmed in tissue samples from patients with silicosis. Our study elucidates a link between SiO-induced macrophage activation and the circZC3H4 RNA/ZC3H4 pathway, thereby providing novel insight into the potential use of ZC3H4 to develop novel therapeutic strategies for silicosis.-Yang, X., Wang, J., Zhou, Z., Jiang, R., Huang, J., Chen, L., Cao, Z., Chu, H., Han, B., Cheng, Y., Chao, J. Silica-induced initiation of circular ZC3H4 RNA/ZC3H4 pathway promotes the pulmonary macrophage activation.

Emerging countries are heading towards economic prosperity; however, the process of development has enhanced their ecological footprint. Therefore, to safeguard the environment, it is essential to identify the factors that affect the ecological footprint (EF). In this perspective, this study explores the effect of financial development, human capital, and institutional quality on the EF in emerging countries. Furthermore, we explore the effect of financial development on EF through the channel of human capital. In addition, we investigate the role of institutional quality in the financial development-EF nexus. Using the panel data from 1984 to 2017, we employed the cross-sectional autoregressive distributed lag (CS-ARDL) technique to conduct the short-run and long-run empirical analysis. The empirical outcomes unveiled that financial development degrades the ecological quality by raising the EF. The findings further unfolded that human capital and institutional quality reduce the EF. Moreover, financial development fosters environmental sustainability through the channel of human capital. Additionally, institution quality reduces the negative ecological impacts of financial development. The causality analysis suggested that any policy related to financial development, human capital, and institutional quality will affect EF but not the other way round. Based on these findings, emerging economies should promote environmental sustainability by promoting human capital and effectively using financial resources.

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Silicosis is characterized by fibroblast accumulation and excessive deposition of extracellular matrix. Although the roles of SiO2-induced chemokines and cytokines released from alveolar macrophages have received significant attention, the direct effects of SiO2 on protein production and functional changes in pulmonary fibroblasts have been less extensively studied. Sigma-1 receptor, which has been associated with cell proliferation and migration in the central nervous system, is expressed in the lung, but its role in silicosis remains unknown. To elucidate the role of sigma-1 receptor in fibrosis induced by silica, both the upstream molecular mechanisms and the functional effects on cell proliferation and migration were investigated. Both molecular biological assays and pharmacological techniques, combined with functional experiments, such as migration and proliferation, were applied in human pulmonary fibroblasts from adults to analyze the molecular and functional changes induced by SiO2. SiO2 induced endoplasmic reticulum stress in association with enhanced expression of sigma-1 receptor. Endoplasmic reticulum stress promoted migration and proliferation of human pulmonary fibroblasts-adult exposed to SiO2, inducing the development of silicosis. Inhibition of sigma-1 receptor ameliorated endoplasmic reticulum stress and fibroblast functional changes induced by SiO2. circHIPK2 is involved in the regulation of sigma-1 receptor in human pulmonary fibroblasts-adult exposed to SiO2. Our study elucidated a link between SiO2-induced fibrosis and sigma-1 receptor signaling, thereby providing novel insight into the potential use of sigma-1 receptor/endoplasmic reticulum stress in the development of novel therapeutic strategies for silicosis treatment.

Background and purpose: This study aimed to evaluate the efficacy of radical radiotherapy and assess prognostic factors in metachronous oligometastatic esophageal cancer (MOEC) patients after initial treatment with curative-intent surgery and/or chemoradiotherapy. Materials and methods: MOEC Patients during 2009-2018 in ÂÂÂ Central Hospital were retrospectively analyzed. Each patient had 5 oligometastatic lesions, and the primary lesions were controlled in this study. Patients were devided into radiotherapy (RT) and non-radiotherapy (NRT) groups. The study endpoints were overall survival (OS) and treatment toxicities. Results: This study included 82 patients who underwent intensity-modulated radiotherapy for MOEC. Median OS were 14 (95% confidence interval [CI], 11.0-17.0) and 7 (95% CI, 4.5-9.5) months for the RT and NRT groups, respectively (P = 0.016). Median OS were 18 (95% CI, 13.6-22.4) and 10 (95% CI, 5.1-14.9) months for lung and bone metastases, respectively (P = 0.010). Median OS were 15 (95% CI, 12.4-17.6) and 10 (95% CI, 7.6-12.4) months for interval time from initial diagnosis to metastasis !12 and <12 months, respectively (P = 0.026). Median OS were 16 (95% CI, 12.2-19.8) and 10 (95% CI, 5.0-15.0) months for biological effective dose (BED 10) ! 60 Gy and BED 10 < 60 Gy, respectively (P = 0.033). Cox multivariate regression analysis showed that treatment modality (RT vs. NRT) was an independent prognostic factor for MOEC patients (hazard ratio: 1.8, 95% CI: 1.1-3.0; P = 0.022). No toxic side effects greater than grade 3 were observed in all patients. Conclusions: Radiotherapy is a feasible and positive treatment for MOEC patients after initial treatment, a radical radiation dose with BED 10 ! 60 Gy has benefits in extending survival. Radical radiotherapy should thus be considered for MOEC patients.

Tight junctions (TJs) are an important component of cell connectivity; they maintain cell polarity, permeability and adhesion, and participate in the regulation of cell proliferation and differentiation. The claudin (cldn) family is integral to TJs, and cldn6 is an important member of this family. abnormal expression of cldn6 can destroy the integrity of TJs through various mechanisms and can serve multiple roles in the occurrence and development of tumours. cldn6 is widely expressed in various tumours but rarely expressed in healthy adult tissues. The aim of this review is to critically examine the recent literature on cldn6, including its structure, expression in different tumours, regulatory mechanisms and therapeutic prospects. although some conclusions are controversial, in certain tumours, such as liver, ovarian, endometrial and oesophageal cancer, and atypical teratoid/rhabdoid tumours, research consistently shows that cldn6 is expressed in tumour tissues but is not expressed or is expressed at low levels in surrounding tissues. in these tumours, cldn6 has potential as a carcinoembryonic antigen and a therapeutic target. Contents1. introduction 2. Structural characteristics of cldn6 3. expression and regulation mechanisms of cldn6 in tumours 4. cldn6 and drug resistance in cancer 5. Prospect of cldn6 in the treatment of tumours 6. discussion conclusionHuan du 1,2 , XiYue YanG 2 , JinJia Fan 2 and XiaoBo du 1

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