A novel circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk in pancreatic cancer

Background Pancreatic cancer is a lethal malignancy in both sexes throughout the world. Circular RNAs (circRNAs) have been implicated in the development of pancreatic cancer by operating as competing endogenous RNAs (ceRNAs). Here, we explored circ_0099999-mediated ceRNA activity in regulating pancreatic tumorigenesis. Methods Ribonuclease R (RNase R) and subcellular localization assays were utilized to characterize circ_0099999. The levels of circ_0099999, microRNA (miR)-330-5p, and fascin actin-bundling protein 1 (FSCN1) were gauged by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation, colony formation, apoptosis, migration, and invasion were evaluated by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays, respectively. The levels of glucose consumption and lactate production were determined using the assay kits. A direct relationship between miR-330-5p and circ_0099999 or FSCN1 was validated by dual-luciferase reporter assay. Tumour xenograft assays were used to analyse the role of circ_0099999 in vivo. Results Circ_0099999 was highly up-regulated in pancreatic cancer tissues and cells. Knockdown of circ_0099999 impeded cell proliferation, migration, invasion, glycolysis, and promoted apoptosis in vitro, as well as diminished tumour growth in vivo. Circ_0099999 targeted miR-330-5p, and miR-330-5p was a downstream mediator of circ_0099999 function. FSCN1 was a direct and functional target of miR-330-5p. Furthermore, circ_0099999 operated as a ceRNA for miR-330-5p to modulate FSCN1 expression. Conclusions Our findings established a novel causal mechanism, circ_0099999/miR-330-5p/FSCN1 ceRNA crosstalk, in regulating pancreatic carcinogenesis and provided that inhibition of circ_0099999 might have therapeutic benefits in pancreatic cancer

Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth

Background Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and the primary treatment of this malignancy is chemotherapy and radiotherapy. Delta-like 3 (DLL3) is an attractive target for SCLC immunotherapy since its expression is highly restricted to SCLC with a neglectable appearance on normal adult tissues. In the current study, we aimed to explore the efficacy of DLL3-targeted SCLC immunotherapy via the engagement of T cell.Methods As a proof of concept, we constructed DLL3-targeted bispecific antibody and chimeric antigen receptor (CAR)-modified T cells. In vitro and in vivo tumor-suppression activity of these treatments alone or in combination with a Program Death-1 (PD-1) inhibitory antibody was evaluated.Results In vitro studies showed that both DLL3 bispecific antibody and CAR-T efficiently killed DLL3-positive cancer cells, including the native SCLC cell lines H446, H196, H82, and the artificial A431 cells that were forcefully overexpressing DLL3. In vivo studies in xenograft mouse models demonstrated that both bispecific antibody and CAR-T suppressed the tumor growth, and combination therapy with PD-1 inhibitory antibody dramatically improved the efficacy of the DLL3 bispecific antibody, but not the CAR-T cells.Conclusions Our results demonstrated that DLL3-targeted bispecific antibody plus PD-1 inhibition was effective in controlling SCLC growth

Limited artemisinin resistance-associated polymorphisms in Plasmodium falciparum K13-propeller and PfATPase6 gene isolated from Bioko Island, Equatorial Guinea

Objective: With emergence and geographically expanding of antimalarial resistance worldwide, molecular markers are essential tool for surveillance of resistant Plasmodium parasites. Recently, single-nucleotide polymorphisms (SNPs) in the PF3D7_1343700 kelch propeller (K13-propeller) domain are shown to be associated with artemisinin (ART) resistance in vivo and in vitro. This study aims to investigate the ART resistance-associated polymorphisms of K13-propeller and PfATPase6 genes in Plasmodium falciparum isolates from Bioko Island, Equatorial Guinea (EG). Methods: A total of 172 samples were collected from falciparum malaria patients on Bioko Island between 2013 and 2014. The polymorphisms of K13-propeller and PfATPase6 genes were analyzed by Nest-PCR and sequencing. Results: Sequences of K13-propeller and PfATPase6 were obtained from 90.74% (98/108) and 91.45% (139/152) samples, respectively. The 2.04% (2/98) cases had non-synonymous K13-propeller A578S mutation but no found the mutations associated with ART resistance in Southeast Asia. For PfATPase6, the mutations were found at positions N569K and A630S with the mutation prevalence of 7.91% (11/139) and 1.44% (2/139), respectively. In addition, a sample with the mixed type at position I723V was discovered (0.72%, 1/139). Conclusions: This study initially offers an insight of K13-propeller and PfATPase6 polymorphisms on Bioko Island, EG. It suggests no widespread ART resistance or tolerance in the region, and might be helpful for developing and updating guidance for the use of ART-based combination therapies (ACTs). Keywords: Plasmodium falciparum, Polymorphism, Artemisinin resistance, K13-propelle

Research on Technological Innovation as Seen through the Chinese Looking Glass

The rapid development of the Chinese economy during the 1990's has intensified research on technological innovation. Recent policy emphasis on innovation as a path to sustainable economic growth will only accelerate work on this important topic. The work by individuals and groups at various research institutes and universities has mainly been published in leading Chinese scholarly journals. In this paper, we develop a framework and do a substantive review of the literature to characterize the state of knowledge about technological innovation in China, with special emphasis on: 1) conceptual contributions, 2) empirical results, and 3) connections between innovation and performance