IRE1α-XBP1s axis regulates SREBP1-dependent MRP1 expression to promote chemoresistance in non-small cell lung cancer cells.

BACKGROUND: Inositol-requiring enzyme 1 (IRE1) is an endoplasmic reticulum (ER)-resident transmembrane protein that senses ER stress and mediates an essential arm of the unfolded protein response (UPR). IRE1 reduces ER stress by upregulating the expression of multiple ER chaperones through activation of X-box-binding protein 1 (XBP1). Emerging lines of evidence have revealed that IRE1-XBP1 axis serves as a multipurpose signal transducer during oncogenic transformation and cancer development. In this study, we explore how IRE1-XBP1 signaling promotes chemoresistance in lung cancer. METHODS: The expression patterns of UPR components and MRP1 were examined by Western blot. qRT-PCR was employed to determine RNA expression. The promoter activity was determined by luciferase reporter assay. Chemoresistant cancer cells were analyzed by viability, apoptosis. CUT & Tag (Cleavage under targets and tagmentation)-qPCR analysis was used for analysis of DNA-protein interaction. RESULTS: Here we show that activation of IRE1α-XBP1 pathway leads to an increase in MDR-related protein 1 (MRP1) expression, which facilitates drug extrusion and confers resistance to cytotoxic chemotherapy. At the molecular level, XBP1-induced c-Myc is necessary for SREBP1 expression, and SREBP1 binds to the MRP1 promoter to directly regulate its transcription. CONCLUSIONS: We conclude that IRE1α-XBP1 had important role in chemoresistance and appears to be a novel prognostic marker for lung cancer.

Exploring the Mechanism of Bergamot Essential Oil against Asthma Based on Network Pharmacology and Experimental Verification.

Asthma is a chronic respiratory disease. Bergamot essential oil (BEO) is extracted from the bergamot peel, which is widely used as a medicinal and food plant in China. Modern pharmacological studies have confirmed that BEO has anti-inflammatory properties, suggesting potential in treating asthma. First, the main active ingredients of BEO were detected and analyzed by gas chromatography-mass spectrometry (GC-MS). Network pharmacology methods were used to explore the possible core targets and main pathways of BEO in asthma treatment. Then ovalbumin (OVA)-induced in vivo and lipopolysaccharide (LPS)-induced in vitro models were established to investigate the antiasthmatic effects of BEO. BEO showed a good antiasthmatic effect by improving lung inflammation and inhibiting collagen deposition. Then, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) were used to explore the possible mechanism of BEO in asthma treatment. Furthermore, experimental verification showed that BEO could suppress the release of inflammatory factors in vitro and inhibit the activation of MAPK and JAK-STAT signaling pathways. This study demonstrated the anti-inflammatory effects of BEO against asthma. Moreover, it supplies a theoretical basis for the clinical application of BEO.

Chronic lead exposure induces histopathological damage, microbiota dysbiosis and immune disorder in the cecum of female Japanese quails (Coturnix japonica).

Lead (Pb) is one of the most hazardous metals to human and wildlife and it also has multiple negative impacts on birds. However, its influences on bird gut morphology and intestinal microbiota were still unclear. We used female Japanese quails (Coturnix japonica) to examine the effects of chronic lead exposure (0, 50 ppm and 1000 ppm) on cecal histology, microbial communities and immune function. The results showed 50 ppm lead exposure caused subtle damages of cecum cell structure. However, 1000 ppm lead exposure caused severe cecum histopathological changes characterized by mucosa abscission, Lieberkühn glands destruction and lymphocyte proliferation. Moreover, both lead concentrations induced ultrastructural damages featured by nucleus pyknosis, mitochondrial vacuolation and microvilli contraction. Meanwhile, microbial community structure, species diversity, taxonomic compositions and taxa abundance in the cecum were affected by lead exposure. Furthermore, the mRNA relative expression of immunity-related genes such as interleukin 2 (IL-2) and gamma interferon (IFN-γ) was significantly downregulated while that of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and natural killer kappa B (NF-κB) was significantly upregulated in the cecum of 50 and 1000 ppm lead exposure groups. We concluded that lead exposure may cause gut health impairment of female Japanese quails by inducing cecal histopathological changes, microbiota dysbiosis and cecal immune disorder.

Electrocardiogram generation with a bidirectional LSTM-CNN generative adversarial network.

Heart disease is a malignant threat to human health. Electrocardiogram (ECG) tests are used to help diagnose heart disease by recording the heart's activity. However, automated medical-aided diagnosis with computers usually requires a large volume of labeled clinical data without patients' privacy to train the model, which is an empirical problem that still needs to be solved. To address this problem, we propose a generative adversarial network (GAN), which is composed of a bidirectional long short-term memory(LSTM) and convolutional neural network(CNN), referred as BiLSTM-CNN,to generate synthetic ECG data that agree with existing clinical data so that the features of patients with heart disease can be retained. The model includes a generator and a discriminator, where the generator employs the two layers of the BiLSTM networks and the discriminator is based on convolutional neural networks. The 48 ECG records from individuals of the MIT-BIH database were used to train the model. We compared the performance of our model with two other generative models, the recurrent neural network autoencoder(RNN-AE) and the recurrent neural network variational autoencoder (RNN-VAE). The results showed that the loss function of our model converged to zero the fastest. We also evaluated the loss of the discriminator of GANs with different combinations of generator and discriminator. The results indicated that BiLSTM-CNN GAN could generate ECG data with high morphological similarity to real ECG recordings.

pH-Induced Switchable Superwettability of Efficient Antibacterial Fabrics for Durable Selective Oil/Water Separation.

The superhydrophobic antibacterial fabrics with intelligent switchable wettability were fabricated by the cross-link reaction among pH-responsive antibacterial copolymer tethered hydroxyl groups, methylol-contained poly(ureaformaldehyde) nanoparticles (PUF NPs), and hexamethylene diisocyanate. It was found that the surface concentration of N+ were heavily influenced by acid solutions, resulting in the rapid wettability conversion from superhydrophobicity/superoleophilicity to superhydrophilicity/underwater superoleophobicity in a remarkably short time. The above responsiveness feature of coated cotton fabric contributes a prominent selective oil/water separation property, and the separation efficiency invariably remained at greater than 95% even after 20 reuse cycles, which exhibited brilliant durability. More importantly, the coated cotton fabric possessed excellent self-cleaning performance after contamination by oil and held high bactericidal rate (more than 80%) regardless of pH treatment, and thus could abate the surface biological pollution caused by bacteria proliferation. The attractive properties of the prepared smart superwetting materials shows great promise for potential application in oil/water separation from an environmental-protection perspective.