REEPing the harvest of reticulophagy and nucleophagy.

Under stress conditions, the endoplasmic reticulum and nucleus undergo turnover through selective macroautophagy/autophagy processes termed reticulophagy and nucleophagy, respectively. Our recent study has identified the protein Hva22/Rop1/Yep1, a member of the REEP1-REEP4 subfamily of the REEP protein family, as an essential factor for both processes in the fission yeast Schizosaccharomyces pombe. In the absence of Hva22/Yep1, reticulophagy and nucleophagy cargos without surrounding autophagic membranes accumulate in the cytoplasm. Interestingly, human proteins in the REEP1-REEP4 subfamily can functionally substitute for Hva22/Yep1 to facilitate reticulophagy. Phylogenetic and synteny analyses further reveal that the budding yeast reticulophagy receptor Atg40 is also a REEP1-REEP4 subfamily member. Similar to human REEP1-REEP4 subfamily proteins, Atg40 can functionally replace Hva22/Yep1. Based on our findings, we propose that promoting reticulophagy is a conserved function of REEP1-REEP4 subfamily proteins.

The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy/nucleophagy cargos in fission yeast.

Selective macroautophagy of the endoplasmic reticulum (ER) and the nucleus, known as ER-phagy and nucleophagy, respectively, are processes whose mechanisms remain inadequately understood. Through an imaging-based screen, we find that in the fission yeast Schizosaccharomyces pombe, Yep1 (also known as Hva22 or Rop1), the ortholog of human REEP1-4, is essential for ER-phagy and nucleophagy but not for bulk autophagy. In the absence of Yep1, the initial phase of ER-phagy and nucleophagy proceeds normally, with the ER-phagy/nucleophagy receptor Epr1 coassembling with Atg8. However, ER-phagy/nucleophagy cargos fail to reach the vacuole. Instead, nucleus- and cortical-ER-derived membrane structures not enclosed within autophagosomes accumulate in the cytoplasm. Intriguingly, the outer membranes of nucleus-derived structures remain continuous with the nuclear envelope-ER network, suggesting a possible outer membrane fission defect during cargo separation from source compartments. We find that the ER-phagy role of Yep1 relies on its abilities to self-interact and shape membranes and requires its C-terminal amphipathic helices. Moreover, we show that human REEP1-4 and budding yeast Atg40 can functionally substitute for Yep1 in ER-phagy, and Atg40 is a divergent ortholog of Yep1 and REEP1-4. Our findings uncover an unexpected mechanism governing the autophagosomal enclosure of ER-phagy/nucleophagy cargos and shed new light on the functions and evolution of REEP family proteins.

Effects of perchlorate, nitrate, and thiocyanate exposures on serum total testosterone in children and adolescents.

Perchlorate, nitrate, and thiocyanate are common thyroid disruptors in daily life and alter testosterone levels in animals. However, little is known about the effects of perchlorate, nitrate, and thiocyanate on serum total testosterone (TT) in the general population. The study was designed to assess the associations between urinary levels of perchlorate, nitrate, and thiocyanate and serum total testosterone (TT) in the general population. The present study utilized data from the 2011-2016 National Health and Nutritional Examination Survey (NHANES). A total of 6201 participants aged 6-79 with information on urinary perchlorate, nitrate, thiocyanate, and serum total testosterone were included. We conducted multiple linear regression models and Bayesian Kernel Machine Regression (BKMR) models to estimate the associations by sex-age groups. Children (ages 6-11) have higher levels of perchlorate and nitrate than the rest. After adjusting for covariates, urinary perchlorate was significantly negatively associated with serum TT in male adolescents (ß = -0.1, 95 % confidence interval: -0.2, -0.01) and female children [-0.13, (-0.21, -0.05)]. Urinary nitrate was significantly negatively associated with serum TT in female children, while urinary thiocyanate was significantly positively associated with serum TT in female adults aged 20 to 49 [0.05 (0.02, 0.08)]. BKMR analysis indicated that no other interactions were found between urinary perchlorate, nitrate, and thiocyanate. Our findings suggested that urinary perchlorate, nitrate, and thiocyanate levels may relate to serum total testosterone levels in specific sex-age groups. We identified male adolescents and female children as are most sensitive subgroups where testosterone is susceptible to interference.

Novel image features of optical coherence tomography for pathological classification of lung cancer: Results from a prospective clinical trial.

Background: This study aimed to explore the characteristics of optical coherence tomography (OCT) imaging for differentiating between benign and malignant lesions and different pathological types of lung cancer in bronchial lesions and to preliminarily evaluate the clinical value of OCT. Methods: Patients who underwent bronchoscopy biopsy and OCT between February 2019 and December 2019 at the Chinese PLA General Hospital were enrolled in this study. White-light bronchoscopy (WLB), auto-fluorescence bronchoscopy (AFB), and OCT were performed at the lesion location. The main characteristics of OCT imaging for the differentiation between benign and malignant lesions and the prediction of the pathological classification of lung cancer in bronchial lesions were identified, and their clinical value was evaluated. Results: A total of 135 patients were included in this study. The accuracy of OCT imaging for differentiating between benign and malignant bronchial lesions was 94.1%, which was significantly higher than that of AFB (67.4%). For the OCT imaging of SCC, adenocarcinoma, and small-cell lung cancer, the accuracies were 95.6, 94.3, and 92%, respectively. The accuracy, sensitivity, and specificity of OCT were higher than those of WLB. In addition, these main OCT image characteristics are independent influencing factors for predicting the corresponding diseases through logistic regression analysis between the main OCT image characteristics in the study and the general clinical features of patients (p<0.05). Conclusion: As a non-biopsy technique, OCT can be used to improve the diagnosis rate of lung cancer and promote the development of non-invasive histological biopsy.

Correlation between PD-L1 expression and radiomic features in early-stage lung adenocarcinomas manifesting as ground-glass nodules.

Background: Immunotherapy might be a promising auxiliary or alternative systemic treatment for early-stage lung adenocarcinomas manifesting as ground-glass nodules (GGNs). This study intended to investigate the PD-L1 expression in these patients, and to explore the non-invasive prediction model of PD-L1 expression based on radiomics. Methods: We retrospectively analyzed the PD-L1 expression of patients with postoperative pathological diagnosis of lung adenocarcinomas and with imaging manifestation of GGNs, and divided patients into positive group and negative group according to whether PD-L1 expression ≥1%. Then, CT-based radiomic features were extracted semi-automatically, and feature dimensions were reduced by univariate analysis and LASSO in the randomly selected training cohort (70%). Finally, we used logistic regression algorithm to establish the radiomic models and the clinical-radiomic combined models for PD-L1 expression prediction, and evaluated the prediction efficiency of the models with the receiver operating characteristic (ROC) curves. Results: A total of 839 "GGN-like lung adenocarcinoma" patients were included, of which 226 (26.9%) showed positive PD-L1 expression. 779 radiomic features were extracted, and 9 of them were found to be highly corelated with PD-L1 expression. The area under the curve (AUC) values of the radiomic models were 0.653 and 0.583 in the training cohort and test cohort respectively. After adding clinically significant and statistically significant clinical features, the efficacy of the combined model was slightly improved, and the AUC values were 0.693 and 0.598 respectively. Conclusions: GGN-like lung adenocarcinoma had a fairly high positive PD-L1 expression rate. Radiomics was a hopeful noninvasive method for predicting PD-L1 expression, with better predictive efficacy in combination with clinical features.

Mercury and selenium bioaccumulation in wild commercial fish in the coastal East China Sea: Selenium benefits versus mercury risks.

This study investigated the contents of total mercury (THg), methylmercury (MeHg) and selenium (Se) in 22 fish species and 10 invertebrate species from the coastal East China Sea. The THg and MeHg contents were significantly higher in benthic fishes. Both Hg and Se biomagnified in the food webs, with evidences of associations during trophic transfer. In addition, Se:Hg molar ratio and Se health benefit value (HBVSe) were used as novel criteria for Hg exposure risk assessments, showing that Se presented in molar excess of Hg in all samples, which would negate the risks of Hg toxicity. HBVSe provided more informative results than Se:Hg molar ratio, pointing to possibly lower health risks for some fishes containing high levels of Hg and Se. Although the HBVSe results challenge the traditional Hg health risk assessment, its future application still requires worldwide comprehensive investigations.

Development of a diagnostic model for malignant solitary pulmonary nodules based on radiomics features.

Background: This study proposed a precise diagnostic model for malignant solitary pulmonary nodules (SPNs). This model can be used to identify objective and quantifiable image features and guide the clinical treatment strategy adopted for SPNs. This model will help clinicians optimize management strategies for SPN. Methods: In this retrospective study, the clinical data of 455 patients of SPN with defined pathological diagnosis between September 2016 and August 2019 were collected and analyzed. The data included pathological diagnosis, preoperative computed tomography (CT) diagnosis, gender, age, smoking history, family history of tumor, previous history, and contact history data. The quantitative image features and radiomic information of the SPNs were provided using computer-aided detection (CAD) "digital lung" software. The Chi-squared test was used to assess the accuracy between CAD and conventional CT in the diagnosis of SPNs. The diagnostic model for benign or malignant SPNs was developed using a multivariate logistic regression analysis that comprises 6 radiomic factors (irregularity, average diameter, COPD910, proportion of emphysema, proportion of fat, and average density of related blood vessels). The area under the receiver operating characteristic curve was used to evaluate the performance of the model in determining SPN risk of malignancy. Results: There was a statistical difference in the accuracy of CAD and conventional CT in diagnosing SPNs. According to the golden standard pathological diagnosis, the diagnostic accuracy of CAD (81%) was higher than that of conventional CT (63.7%) (P<0.05). Six variables (i.e., irregularity, the mean diameter, COPD910, the proportion of emphysema, the proportion of fat, and the vascular density) were identified using multivariable logistic regression to establish the diagnostic model for distinguish benign or malignant SPNs. The area under the receiver operating characteristic (ROC) curve (AUC) of the diagnostic model was 0.876 (95% CI: 0.8445-0.9076), and its sensitivity and specificity were 81.25% and 82.56% respectively. Conclusions: The proposed diagnostic model, which comprises 6 radiomic factors, is accurate and effective at diagnosing benign or malignant SPNs.

MicroRNA-889-3p restrains the proliferation and epithelial-mesenchymal transformation of lung cancer cells via down-regulation of Homeodomain-interacting protein kinase 1.

Dysregulated microRNAs (miRNAs) are common in human cancers and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, the aim of this study was to evaluate the expression and biological function of miR-889-3p in lung cancer (LC). MiR-889-3p and Homeodomain-interacting protein kinase 1 (HIPK1) expression was detected in human LC tissues and cells. The correlation of miR-889-3p with the clinicopathology of LC patients was observed. After the transfection of miR-889-3p and HIPK1-related plasmids in human LC cell line A549, several studies were employed for detection of cell growth. In addition, the targeting of miR-889-3p with HIPK1 was verified. The results clarified miR-889-3p was down-regulated, while HIPK1 was up-regulated in LC tissues. Elevated miR-889-3p or repressed HIPK1 weakened the viability, epithelial-mesenchymal transition (EMT), invasion, migration of LC cells, whereas strengthened apoptosis. MiR-889-3p targeted HIPK1; MiR-889-3p mediated HIPK1 to affect the proliferation and EMT of LC cells. Therefore, it is concluded that miR-889-3p repressing HIPK1 restrains the proliferation and EMT of LC cells, providing a novel target for LC therapy.

A UPR-Induced Soluble ER-Phagy Receptor Acts with VAPs to Confer ER Stress Resistance.

Autophagic degradation of the endoplasmic reticulum (ER-phagy) is triggered by ER stress in diverse organisms. However, molecular mechanisms governing ER stress-induced ER-phagy remain insufficiently understood. Here we report that ER stress-induced ER-phagy in the fission yeast Schizosaccharomyces pombe requires Epr1, a soluble Atg8-interacting ER-phagy receptor. Epr1 localizes to the ER through interacting with integral ER membrane proteins VAPs. Bridging an Atg8-VAP association is the main ER-phagy role of Epr1, as it can be bypassed by an artificial Atg8-VAP tether. VAPs contribute to ER-phagy not only by tethering Atg8 to the ER membrane, but also by maintaining the ER-plasma membrane contact. Epr1 is upregulated during ER stress by the unfolded protein response (UPR) regulator Ire1. Loss of Epr1 reduces survival against ER stress. Conversely, increasing Epr1 expression suppresses the ER-phagy defect and ER stress sensitivity of cells lacking Ire1. Our findings expand and deepen the molecular understanding of ER-phagy.

Study on the Basic Performance of Three-phase Fluidized Bed Equipment for Solar Photocatalysis-Membrane Separation.

In this study, three-phase fluidized bed equipment for the solar photocatalysis-membrane separation (E-SPME), comprising solar photocatalytic degradation and membrane separation zones, was first introduced, and the photocatalytic degradation of acid red B wastewater (ARBW) with a TiO2 photocatalyst was investigated using the E-SPME. The experimental results indicated the circulating flow of wastewater between the two zones and the increase in the ARBW photocatalytic degradation efficiency with decreasing membrane flux. The same experimental phenomenon was observed with the change in the aeration rate in the lower water tank from 0.10 to 0.40 m3  h-1 , but the degradation efficiency started to decrease with further increase in the aeration rate to 0.50 m3  h-1 . The degradation efficiency on a clear day was greater than that on a cloudy day; however, it was significantly improved with the opened UV lamps on a cloudy day. The steady operation of the E-SPME was still possible by the opening of the UV lamps on completely cloudy and clear days with a solar light intensity of <13.0 W m-2 .