Effect of WISP1 on paraquat-induced EMT.

BACKGROUND: Paraquat (PQ) can induce pulmonary fibrosis (PF) by modulating epithelial-mesenchymal transition (EMT) of alveolar epithelial cells, but the molecular mechanism is unknown. In this paper, the role of Wnt-inducible signaling protein-1 (WISP1) in PQ-induced EMT was inspected. METHODS: The morphology, apoptosis, and mortality of A549 cells were observed through a microscope. The mRNA and protein levels of WISP1, E-cadherin, and Vimentin were confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. RESULTS: With the increase of PQ concentration, the morphology of A549 cells was apparently changed, cell apoptosis and mortality were enhanced. Besides, the E-cadherin abundance was reduced (p < 0.01), however, WISP1 and Vimentin contents were boosted after PQ treatment (p < 0.01). With the increase of PQ treatment time, the epithelial index of cells first increased and then decreased. The expression of WISP1 gene increased significantly with the increase of PQ treatment time (p < 0.01). Silence of WISP1 abolished the effect of PQ treatment on E-cadherin and Vimentin levels (p < 0.01). Downregulation of WISP1 curbed morphology change and PQ-induced EMT in A549 cells. CONCLUSION: Knockdown of WISP1 inhibited PQ-induced EMT in A549 cells. This conclusion might provide a new therapeutic target for PQ poisoning treatment.

Ubiquitin signaling in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor of the digestive system, characterized by rapid progression and being prone to metastasis. Few effective treatment options are available for PDAC, and its 5-year survival rate is less than 9%. Many cell biological and signaling events are involved in the development of PDAC, among which protein post-translational modifications (PTMs), such as ubiquitination, play crucial roles. Catalyzed mostly by a three-enzyme cascade, ubiquitination induces changes in protein activity mainly by altering their stability in PDAC. Due to their role in substrate recognition, E3 ubiquitin ligases (E3s) dictate the outcome of the modification. Ubiquitination can be reversed by deubiquitylases (DUBs), which, in return, modified proteins to their native form. Dysregulation of E3s or DUBs that disrupt protein homeostasis is involved in PDAC. Moreover, the ubiquitination system has been exploited to develop therapeutic strategies, such as proteolysis-targeting chimeras (PROTACs). In this review, we summarize recent progress in our understanding of the role of ubiquitination in the development of PDAC and offer perspectives in the design of new therapies against this highly challenging disease.

Proteomic and Metabolomic Characterization of SARS-CoV-2-Infected Cynomolgus Macaque at Early Stage.

Although tremendous effort has been exerted to elucidate the pathogenesis of severe COVID-19 cases, the detailed mechanism of moderate cases, which accounts for 90% of all patients, remains unclear yet, partly limited by lacking the biopsy tissues. Here, we established the COVID-19 infection model in cynomolgus macaques (CMs), monitored the clinical and pathological features, and analyzed underlying pathogenic mechanisms at early infection stage by performing proteomic and metabolomic profiling of lung tissues and sera samples from COVID-19 CMs models. Our data demonstrated that innate immune response, neutrophile and platelet activation were mainly dysregulated in COVID-19 CMs. The symptom of neutrophilia, lymphopenia and massive "cytokines storm", main features of severe COVID-19 patients, were greatly weakened in most of the challenged CMs, which are more semblable as moderate patients. Thus, COVID-19 model in CMs is rational to understand the pathogenesis of moderate COVID-19 and may be a candidate model to assess the safety and efficacy of therapeutics and vaccines against SARS-CoV-2 infection.

Application of a Convolutional Neural Network for Multitask Learning to Simultaneously Predict Microvascular Invasion and Vessels that Encapsulate Tumor Clusters in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer death worldwide, and the prognosis remains dismal. In this study, two pivotal factors, microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC) were preoperatively predicted simultaneously to assess prognosis. METHODS: A total of 133 HCC patients who underwent surgical resection and preoperative gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) were included. The statuses of MVI and VETC were obtained from the pathological report and CD34 immunohistochemistry, respectively. A three-dimensional convolutional neural network (3D CNN) for single-task learning aimed at MVI prediction and for multitask learning aimed at simultaneous prediction of MVI and VETC was established by using multiphase Gd-EOB-DTPA-enhanced MRI. RESULTS: The 3D CNN for single-task learning achieved an area under receiver operating characteristics curve (AUC) of 0.896 (95% CI: 0.797-0.994). Multitask learning with simultaneous extraction of MVI and VETC features improved the performance of MVI prediction, with an AUC value of 0.917 (95% CI: 0.825-1.000), and achieved an AUC value of 0.860 (95% CI: 0.728-0.993) for the VETC prediction. The multitask learning framework could stratify high- and low-risk groups regarding overall survival (p < 0.0001) and recurrence-free survival (p < 0.0001), revealing that patients with MVI+/VETC+ were associated with poor prognosis. CONCLUSIONS: A deep learning framework based on 3D CNN for multitask learning to predict MVI and VETC simultaneously could improve the performance of MVI prediction while assessing the VETC status. This combined prediction can stratify prognosis and enable individualized prognostication in HCC patients before curative resection.

Wnt-induced secreted proteins-1 play an important role in paraquat-induced pulmonary fibrosis.

BACKGROUND: The objective of this article is to observe the expression of Wnt-induced secreted proteins-1 (WISP1) in paraquat (PQ)-induced pulmonary fibrosis (PF) to explore the role of WISP1. METHODS: Healthy individuals were included in the control group. Patients who had acute lung injury or PF were included in the PF group. Venous blood samples were collected from the patients on days 1 and 3 following PQ poisoning to detect the expression levels of the WISP1 gene and protein concentration. Any changes in the patients' blood gas analysis index were reviewed. In addition, chest computed tomography (CT) and x-ray images were observed to evaluate the relationship between WISP1 expression and disease severity. RESULTS: The expression of the WISP1 gene and the serum WISP1 protein concentration were higher in patients with PQ poisoning combined with PF than in patients without PF (P < 0.01). Serum PQ concentration was positively correlated with WISP1 gene expression (r = 0.621, P < 0.01), and serum WISP1 protein concentration (r = 0.596, P < 0.01) was considered a risk factor [odds ratio (OR) = 4.356, P < 0.05] for PQ-induced PF. Concurrently, the results of the adjusted and non-adjusted OR value for WISP1 gene expression and WISP1 protein concentration on day 1 was, respectively, as follows: OR = 12.797, 95% confidence interval (CI) (2.478-66.076), P = 0.002, OR' = 11.353, P = 0.005; and OR = 1.545, 95% CI (1.197-1.995), P = 0.001, OR' = 1.487, P = 0.003. The CT scan of a 20-year-old male with PQ-induced PF (20 ml) was observed, and it showed a typical hyaline-like lesion in the lungs on day 22 after poisoning; on day 33 after poisoning, the lungs showed localised consolidation combined with air bronchography. CONCLUSION: The expression of WISP1 was higher in the patients with PQ-induced PF compared with the patients without PF. Accordingly, WISP1 plays an important role in PQ-induced PF.

Preparation and Properties of sc-PLA/PMMA Transparent Nanofiber Air Filter.

Particulate matter (PM) pollution is a serious concern for the environment and public health. To protect indoor air quality, nanofiber filters have been used to coat window screens due to their high PM removal efficiency, transparency and low air resistance. However, these materials have poor mechanical property. In this study, electrostatic induction-assisted solution blowing was used to fabricate polylactide stereocomplex (sc-PLA), which served as reinforcement to enhance the physical cross-linking point to significantly restrict poly(methyl methacrylate) (PMMA) molecular chain motion and improve the mechanical properties of sc-PLA/PMMA nanofibers. Moreover, the introduction of sc-PLA led to the formation of thick/thin composite nanofiber structure, which is beneficial for the mechanical property. Thus, sc-PLA/PMMA air filters of ~83% transparency with 99.5% PM2.5 removal and 140% increase in mechanical properties were achieved when 5 wt % sc-PLA was added to PMMA. Hence, the addition of sc-PLA to transparent filters can effectively improve their performance.

LeMAPK4 participated in cold-induced ethylene production in tomato fruit.

BACKGROUND: Mitogen-activated protein kinase (MAPK, EC 2.7.11.24) cascade from several plant species has been shown to be activated during response to abiotic stress. Ethylene plays an important role in fruit tolerance to environmental stress. However, the mechanisms by which MAPK regulates defence systems in fruit and the relationship between MAPK and ethylene remain to be determined. RESULTS: MAPK inhibitor significantly decreased the chilling tolerance of tomato (Lycopersicon esculentum cv. Lichun) fruit during cold storage. Moreover, decreases in ethylene content, LeACS2 expression and activities of 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS, EC 4.4.1.14) and ACC oxidase (ACO, EC 1.14.17.4) due to MAPK inhibitor occurred within 24 h after cold treatment. Upon treatment with cold and ethephon, the ethylene content, activities of ACS and ACO and expression of LeACS2, LeACO1 and LeMAPK4 increased. CONCLUSION: The results showed the regulation of MAPK in ethylene biosynthesis to protect tomato fruit from cold stress. In addition, the participation of LeMAPK4 in cold-induced ethylene biosynthesis in tomato fruit was indicated.

Preharvest L-arginine treatment induced postharvest disease resistance to Botrysis cinerea in tomato fruits.

L-arginine is the precursor of nitric oxide (NO). In order to examine the influence of L-arginine on tomato fruit resistance, preharvest green mature tomato fruits (Solanum lycopersicum cv. No. 4 Zhongshu) were treated with 0.5, 1, and 5 mM L-arginine. The reduced lesion size (in diameter) on fruit caused by Botrytis cinerea, as well as activities of phenylalanine ammonia-lyase (PAL), Chitinase (CHI), ß-1,3-glucanase (GLU), and polyphenoloxidase (PPO), was compared between L-arginine treated fruits and untreated fruits. We found that induced resistance increased and reached the highest level at 3-6 days after treatment. Endogenous NO concentrations were positively correlated with PAL, PPO, CHI, and GLU activities after treatment with Pearson coefficients of 0.71, 0.94, 0.97, and 0.87, respectively. These results indicate that arginine induces disease resistance via its effects on NO biosynthesis and defensive enzyme activity.

Ethylene and cold participate in the regulation of LeCBF1 gene expression in postharvest tomato fruits.

C-repeat/dehydration-responsive element binding factor (CBF) is a transcription factor regulating cold response in plants, of which little is known in fruits. We showed a double-peak expression pattern of Lycopersicon esculentum putative transcriptional activator CBF1 (LeCBF1) in mature green fruit. The peaks appeared at 2 and 16 h after subjection to cold storage (2 degrees C). The second peak was coincident with, and thus caused by a peak in endogenous ethylene production. We showed that LeCBF1 expression was regulated by exogenous ethylene and 1-methylcyclopropene, and was not expressed without cold induction. LeCBF1 expression was different in the five maturation stages of fruits, but expression peaked at 2 h at all stages.