Effects of food concentration and photoperiod on egg production, female life expectancy and population dynamics of the paracalanid copepod, Bestiolina amoyensis

The paracalanid copepod, Bestiolina amoyensis, is a widely distributed species occurring in subtropical inshore waters across the Pacific Ocean. Its small size, herbivorous feeding habit, and high adaptability make the species one of the most promising candidates as potential live feed for hatchery larval rearing. This study investigated effects of different feeding density of microalgae Isochrysis spp. (1 × 105, 2 × 105, 3 × 105, 4 × 105, and 5 × 105 cells ml–1) and photoperiod (8L:16D, 12L:12D, and 16L:8D) on productivity-related parameters, including egg production, female life expectancy and population dynamics of B. amoyensis. Results showed that total egg output over female lifespan, final population size and intrinsic rate of population of 12L:12D photoperiod treatments were always the highest among three photoperiod conditions, especially at the food concentration of 4 × 105 cells ml–1, indicating B. amoyensis had high reproductive performance and the population was in a more stable status. The number of nauplii from 4 × 105 cells ml–1 algal concentration treatment accounted for 75% of the population, and the ratio of females to males approaching 1:1 when photoperiod was 12L:12D; female life expectancy was 10.5 ± 0.6 days. In conclusion, our results showed that Isochrysis spp. is a suitable feed for B. amoyensis with an optimal concentration at 4 × 105 cells mL–1; the optimal photoperiod for B. amoyensis rearing is 12L:12D. The relatively long reproductive lifespan and high intrinsic population increase rate make B. amoyensis a good candidate to develop culture techniques for hatchery larval rearing

Unsupervised SAR Image Segmentation Based on a Hierarchical TMF Model in the Discrete Wavelet Domain for Sea Area Detection

Unsupervised synthetic aperture radar (SAR) image segmentation is a fundamental preliminary processing step required for sea area detection in military applications. The purpose of this step is to classify large image areas into different segments to assist with identification of the sea area and the ship target within the image. The recently proposed triplet Markov field (TMF) model has been successfully used for segmentation of nonstationary SAR images. This letter presents a hierarchical TMF model in the discrete wavelet domain of unsupervised SAR image segmentation for sea area detection, which we have named the wavelet hierarchical TMF (WHTMF) model. The WHTMF model can precisely capture the global and local image characteristics in the two-pass computation of posterior distribution. The multiscale likelihood and the multiscale energy function are constructed to capture the intrascale and intrascale dependencies in a random field (X,U). To model the SAR data related to radar backscattering sources, the Gaussian distribution is utilized. The effectiveness of the proposed model for SAR image segmentation is evaluated using synthesized and real SAR data

Low-dose metformin reprograms the tumor immune microenvironment in human esophageal cancer:Results of a phase II clinical trial

PURPOSE: The tumor immune microenvironment (TIME) has an important impact on response to cancer immunotherapy using immune checkpoint inhibitors. Specifically, an "infiltrated-excluded"/"cold" TIME is predictive of poor response. The antidiabetic agent metformin may influence anti-cancer immunity in esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: We analyzed matched pre- and post-treatment ESCC specimens in a phase II clinical trial of low-dose metformin treatment (250 mg/day) to evaluate direct anti-ESCC activity and TIME-reprogramming. Follow-up correlative studies using a carcinogen-induced ESCC mouse model were performed with short-term (1 week) or long-term (12 weeks) low-dose metformin (50 mg/kg/day) treatment. RESULTS: In the clinical trial, low-dose metformin did not affect proliferation or apoptosis in ESCC tumors as assayed by Ki67 and cleaved caspase-3 immunostaining. However, metformin reprogrammed the TIME towards "infiltrated-inflamed" and increased the numbers of infiltrated CD8+ cytotoxic T-lymphocyte and CD20+ B-lymphocyte. Further, an increase in tumor-suppressive (CD11c+) and a decrease in tumor-promoting (CD163+) macrophages were observed. Metformin augmented macrophage-mediated phagocytosis of ESCC cells in vitro. In ESCC mouse model, short-term metformin treatment reprogrammed the TIME in a similar fashion to humans, whereas long-term treatment further shifted the TIME towards an active state (e.g., reduction in CD4+ FoxP3+ Tregs) and inhibited ESCC growth. In both humans and mice, metformin triggered AMPK activation and STAT3 inactivation, and altered the production of effector cytokines (i.e. TNF-α, IFN-γ, IL-10) in the immune cells. CONCLUSIONS: Low-dose metformin reprograms the TIME to an activated status and may be a suitable immune response modifier for further investigation in ESCC patients

Neoantigen-based cancer vaccination using chimeric RNA-loaded dendritic cell-derived extracellular vesicles

Cancer vaccines critically rely on the availability of targetable immunogenic cancer-specific neoepitopes. However, mutation-based immunogenic neoantigens are rare or even non-existent in subgroups of cancer types. To address this issue, we exploited a cancer-specific aberrant transcription-induced chimeric RNA, designated A-Pas chiRNA, as a possible source of clinically relevant and targetable neoantigens. A-Pas chiRNA encodes a recently discovered cancer-specific chimeric protein that comprises full-length astrotactin-2 (ASTN2) C-terminally fused in-frame to the antisense sequence of the 18th intron of pregnancy-associated plasma protein-A (PAPPA). We used extracellular vesicles (EVs) from A-Pas chiRNA-transfected dendritic cells (DCs) to produce the cell-free anticancer vaccine DEXA-P . Treatment of immunocompetent cancer-bearing mice with DEXA-P inhibited tumour growth and prolonged animal survival. In summary, we demonstrate for the first time that cancer-specific transcription-induced chimeric RNAs can be exploited to produce a cell-free cancer vaccine that induces potent CD8+ T cell-mediated anticancer immunity. Our novel approach may be particularly useful for developing cancer vaccines to treat malignancies with low mutational burden or without mutation-based antigens. Moreover, this cell-free anticancer vaccine approach may offer several practical advantages over cell-based vaccines, such as ease of scalability and genetic modifiability as well as enhanced shelf life

Repurposing dextromethorphan and metformin for treating nicotine-induced cancer by directly targeting CHRNA7 to inhibit JAK2/STAT3/SOX2 signaling

Smoking is one of the most impactful lifestyle-related risk factors in many cancer types including esophageal squamous cell carcinoma (ESCC). As the major component of tobacco and e-cigarettes, nicotine is not only responsible for addiction to smoking but also a carcinogen. Here we report that nicotine enhances ESCC cancer malignancy and tumor-initiating capacity by interacting with cholinergic receptor nicotinic alpha 7 subunit (CHRNA7) and subsequently activating the JAK2/STAT3 signaling pathway. We found that aberrant CHRNA7 expression can serve as an independent prognostic factor for ESCC patients. In multiple ESCC mouse models, dextromethorphan and metformin synergistically repressed nicotine-enhanced cancer-initiating cells (CIC) properties and inhibited ESCC progression. Mechanistically, dextromethorphan non-competitively inhibited nicotine binding to CHRNA7 while metformin downregulated CHRNA7 expression by antagonizing nicotine-induced promoter DNA hypomethylation of CHRNA7. Since dextromethorphan and metformin are two safe FDA-approved drugs with minimal undesirable side-effects, the combination of these drugs has a high potential as either a preventive and/or a therapeutic strategy against nicotine-promoted ESCC and perhaps other nicotine-sensitive cancer types as well