Protective effects of a novel chimeric virus-like particle vaccine against virulent NDV and IBDV challenge.

Newcastle disease (ND) and infectious bursal disease (IBD) pose significant threats to the chicken industry, causing substantial economic losses. Currently, immunization through vaccination is the most effective strategy to prevent ND and IBD but currently used traditional vaccines, including inactivated or attenuated vaccines, face challenges in achieving a balance between immunogenicity and safety. To develop a green and efficient novel vaccine for ND and IBD, we developed a bivalent chimeric virus-like particle vaccine (ND-IBD cVLPs) displaying the ND virus (NDV) HN protein and the IBD virus (IBDV) VP2 protein based on the ND VLPs carrier platform and insect baculovirus expression system. This study aimed to evaluate the immunogenicity and protective efficacy of ND-IBD cVLPs in specific pathogen-free chickens. Chickens were immunized with 50 µg of purified ND-IBD cVLPs at 7 days old, boosted at 21 days old, and challenged at 42 days old. The results demonstrated that ND-IBD cVLPs stimulated highly effective hemagglutination inhibition antibody levels against NDV HN protein and enzyme-linked immunosorbent assay antibody levels against the IBDV VP2 protein. Furthermore, ND-IBD cVLPs provided complete protection against virulent NDV and IBDV challenges and mitigated pathological damage to the lung caused by NDV infection and the bursa of Fabricius caused by IBDV infection. These findings suggest that ND-IBD cVLPs hold promise as a safe and efficient novel vaccine candidate for the effective prevention of ND and IBD, extending the development of a foreign protein delivery platform of ND VLPs.

Circular RNAcirc_0076305 Promotes Cisplatin (DDP) Resistance of Non-Small Cell Lung Cancer Cells by Regulating ABCC1 Through miR-186-5p.

Background: Lung cancer is a social problem of increasing concern, and non-small cell lung cancer (NSCLC) accounts for 80%-85% incidence of lung cancer. Cisplatin (DDP) is reported as a first-line chemotherapy drug for NSCLC, but the resistance has became a main obstacle for NSCLC treatment. The high level of circular RNA circ_0076305 was related to the DDP resistance in NSCLC. However, the mechanism of circ_0076305 remains unclear in DDP resistance of NSCLC. Materials and Methods: Exosomes were detected by a transmission electron microscope and nanoparticle tracking analysis. The protein levels of CD63, CD81, P-glycoprotein (P-gp), Lung resistance-related protein, and ATP-binding cassette subfamily C member 1 (ABCC1) were examined by Western blot assay. Circ_0076305, microRNA-186-5p (miR-186-5p), and ABCC1 levels were tested by real-time quantitative polymerase chain reaction. DDP resistance was examined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay. The binding relationship between miR-186-5p and circ_0076305 or ABCC1 was predicted by circRNA interactome or starBase, and then verified by dual-luciferase reporter and RNA immunoprecipitation assays. The effect of circ_0076305 on DDP resistance in NSCLC was examined by xenograft tumor model in vivo. Results: Circ_0076305 was increased in NSCLC cell-derived exosomes, DDP-resistant NSCLC tissues and cells. Circ_0076305 knockdown elevated DDP sensitivity in vitro. Mechanically, circ_0076305 enhanced ABCC1 expression through sponging miR-186-5p, thus regulating DDP resistance of NSCLC. Furthermore, circ_0076305 silencing improved DDP sensitivity of NSCLC in vivo. Conclusion: The results from this study disclosed that circ_0076305 knockdown improved DDP sensitivity by the miR-186-5p/ABCC1 axis in NSCLC, hinting a potential circRNA-targeted therapy for NSCLC.

High-precision micro-displacement sensor based on tunnel magneto-resistance effect.

A high-precision micro-displacement sensor based on tunnel magneto-resistance effect is reported.We designed and simulated magnetic characteristics of the sensor, and employed chip-level Au-In bonding to implement low-temperature assembly of the TMR devices. We employed the subdivision interpolation technique to enhance the resolution by translating the sine-cosine outputs of a TMR sensor into an output that varies linearly with the displacement. Simultaneously, using the multi-bridge circuit method to suppress external magnetic and geomagnetic interference. Experimental result shows that the micro-displacement sensor has a resolution of 800 nm, accuracy of 0.14[Formula: see text] and a full-scale range of up to millimeter level. This work enables a high-performance displacement sensor, and provides a significant guide for the design of a micro-displacement sensor in practical applications.

Circ_0011292 Enhances Paclitaxel Resistance in Non-Small Cell Lung Cancer by Regulating miR-379-5p/TRIM65 Axis.

Background: Non-small cell lung cancer (NSCLC) is the most prevalent cancer in the world. Chemotherapy resistance is a major obstacle to NSCLC therapy. This study explored the role and molecular mechanism of circular RNA 0011292 (circ_0011292) in tumorigenesis and chemoresistance of NSCLC. Methods: The levels of circ_0011292, miR-379-5p, and tripartite motif-containing protein 65 (TRIM65) were measured by quantitative real-time polymerase chain reaction or Western blot assay. Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was monitored by flow cytometry. Cell migration and invasion were detected by transwell assay. The levels of apoptosis-related and epithelial-mesenchymal transition-related proteins were examined by Western blot. The half-inhibition concentration (IC50) of paclitaxel (PTX) was evaluated by CCK-8 assay. Xenograft model was established to analyze the effect of circ_0011292 on PTX resistance of NSCLC in vivo. The interaction among circ_0011292, miR-379-5p, and TRIM65 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: Circ_0011292 and TRIM65 were upregulated, while miR-379-5p was downregulated in NSCLC tissues and cells. Circ_0011292 knockdown hindered NSCLC progression and enhanced PTX sensitivity of NSCLC. Circ_0011292 silencing reduced PTX resistance in vivo. Besides, miR-379-5p potentiated PTX sensitivity by targeting TRIM65. Also, circ_0011292 increased PTX resistance by sponging miR-379-5p. Conclusion: Circ_0011292 facilitated tumorigenesis and PTX resistance in NSCLC by regulating the miR-379-5p/TRIM65 axis, suggesting that circ_0011292 was a promising therapeutic target for NSCLC chemotherapy.

Prognostic factors and treatment outcomes in patients with non-ampullary small bowel adenocarcinoma: Long-term analysis.

Small bowel adenocarcinoma (SBA) is a relatively rare malignancy in gastrointestinal tumors. In addition, the difficulty of early diagnosis, its poor prognosis compared to large bowel adenocarcinoma, and inadequate treatment experiences due to lack of prospective randomized trials make it necessary to explore the characteristics of the disease for early diagnosis and treatment.Patients diagnosed with primary malignant tumor of small intestine in West China Hospital of Sichuan University between January 2001 and 2013 were reviewed retrospectively. A total of 208 patients with SBA were selected and 160 patients with duodenal periampullary tumor were excluded. Forty-two cases of patients were finally enrolled for statistical analysis as 6 patients were lost of follow-up. The clinical characteristics, the response to treatment and their overall survival (OS) time were reviewed and analyzed.Of the 42 patients, 11 (26.2%) primary tumors were originated from duodenum, 29 (69.0%) from jejunum, and 2 (4.8%) from ileum. All patients (64.3% male; median age, 54.7 years) included in this study underwent primary resection of the tumor to confirm final diagnosis. Three-year survival rate is 21% and 5-year survival rate is 9%. Median OS were 24.2 months (95% CI: 4.0-72.0). The univariate predictors for prognosis of SBA were as follows: age (P = .021), severe intestinal symptoms at first diagnosis (P < .001), T4 of tumor stage (P = .011), tumor size (P = .004), relatively late clinical stage (P < .001), peritoneal metastasis (P < .001), and no chemotherapy (P = .011). The multivariate predictors for poor prognosis were age of more than 60 years old (P = .035), intestinal obstruction or perforation at first diagnosis (P = .026), relatively late clinical stage (P = .000), and no chemotherapy (P = .027).SBA was a relatively rare malignancy that was difficult for early diagnosis and treatment. Intestinal obstruction was the common clinical manifestation at first diagnosis, with a tendency of early peritoneal metastasis. Precaution of the disease in early phase, radical resection of the primary tumor while resectable, followed with in-time chemotherapy might improve prognosis and survival of patients with SBA.

Bleeding after bevacizumab treatment in patients with metastatic colorectal cancer.

AIMS AND BACKGROUND: To evaluate the adverse events (AEs) of bleeding caused by bevacizumab/5-fluorouracil/leucovorin (5-FU/LV) combination chemotherapy with addition of irinotecan or oxaliplatin in patients with metastatic colorectal cancer (mCRC). METHODS: A retrospective study was conducted to evaluate the bleeding AEs associated with bevacizumab and to explore potential associations between bleeding and baseline patient characteristics. The National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 were used to classify the severity of AEs. AEs were divided into five grades: grade 1, mild: intervention not indicated; grade 2, moderate: medical intervention or minor cauterization indicated; grade 3, severe: transfusion, radiological, endoscopic or elective surgical intervention indicated; grade 4, life threatening: urgent intervention indicated; and grade 5, death. RESULTS: Sixty-two patients were evaluated. Bleeding occurred in 26 (41%) patients; the incidence of grade 3 bleeding was 1.6% while no grade 4-5 bleeding occurred. Grade 1 epistaxis and grade 2 hemoptysis events were observed in 25.8% and 3.2% of patients, respectively. Hematochezia events occurred in 12 (19.4%) patients, one (1.6%) of whom required bevacizumab discontinuation. The incidence of hematochezia was higher in patients with unresected primary tumors, prior intestinal bleeding, and tumor response (p<0.05). CONCLUSIONS: These data provide important information about the incidence of clinically significant bleeding AEs, including minor mucocutaneous hemorrhage and major tumor-related bleeding such as hemoptysis and hematochezia in bevacizumab-treated mCRC patients. In addition, unresected primary tumor, prior bleeding, and tumor response were significant risk factors for hematochezia.