Similar to other industries, aquaculture constantly requires new techniques to increase production yields. Modern technologies and different scientific fields, such as biotechnology and microbiology, provide important tools that could lead to a higher quality and a greater quantity of products. New feeding practices in farming typically play an important role in aquaculture, and the addition of various additives to a balanced feed formula to achieve better growth is a common practice of many fish and shrimp feed manufacturers and farmers. As 'biofriendly agents', immunostimulants, such as biological factors, probiotics and vitamins, can be introduced into the culture environment to control and kill pathogenic bacteria, as well as to promote growth of the cultured organisms. In addition, immunostimulants are non-pathogenic and nontoxic and do not produce undesirable side effects when administered to aquatic organisms. In this review, we summarize previous studies performed with both traditional immunostimulants and the most promising new generation of immunostimulants, such as polysaccharides, nutrients, oligosaccharides, herbs, microorganisms, prebiotics and different biological factors. This review primarily focuses on their protective efficacies and on what is known concerning their effects on the immune systems of aquatic organisms when delivered in vivo.

Graphene oxide (GO) has shown great potential for biological, medical, energy and electronic applications. As a consequence of these diverse applications, GO release into the ecosystem is inevitable; however, the corresponding risks are largely unknown, particularly with respect to the critical period of embryogenesis. This study revealed that GO adhered to and enveloped the chorion of zebrafish embryos mainly via hydroxyl group interactions, blocked the pore canals of the chorionic membrane, and caused marked hypoxia and hatching delay. Furthermore, GO spontaneously penetrated the chorion, entered the embryo via endocytosis, damaged the mitochondria and primarily translocated to the eye, heart and yolk sac regions, which are involved in the circulatory system of zebrafish. In these organs, GO induced excessive generation of reactive oxygen species and increased oxidative stress, DNA damage and apoptosis. Graphene oxide also induced developmental malformation of the eye, cardiac/yolk sac edema, tail flexure and heart rate reduction. In contrast to the common dose-effect relationships of nanoparticles, the adverse effects of GO on heart rate and tail/spinal cord flexure increased and then decreased as the GO concentration increased. These findings emphasize the specific adverse effects of GO on embryogenesis and highlight the potential ecological and health risks of GO.

To date, no report has demonstrated the use of beneficial microbes for contributing to the flavour characteristics and gut microbiota diversity of chicken. Here, we selected six probiotics obtained from our laboratory and supplemented them in six different combinations to 420 newborn male Qingjiaoma chickens under the same controlled living environment (60 birds, no probiotic supplements). The results showed that chicken supplemented with Bacillus species showed beneficial effects in body weight. Acetate is the major fermentation production in the chicken caecum, and chicken supplemented with Pediococcus pentosaceus had the average higher short chain fatty acids (SCFAs) contents. In chicken caecal microflora, the abundance of Bacteroidetes bacteria was positively correlated with the content of propionate, butyrate, and isobutyrate, whereas an increase in acetate content was positively correlated to the abundance of Firmicutes. Compared to chickens without probiotic supplement, chickens supplemented with P. pentosaceus had more characteristic flavour compounds in the sampled breast meat, especially higher concentrations of (E)-2-heptenal, (E,E)-2,4-nonadienal, and certain C6-C9 unsaturated fatty acids. This resulted in a stronger chicken-fatty or fatty odour which directly improved the flavour. These findings suggest that probiotics can improve chicken meat flavour and increase gut microbiota diversity.It is generally known that the diverse gut microbiota play an important role in host metabolism, nutrient digestion, growth performance and health of the host 1-4 . However, during the livestock production process, the widespread use of antibiotics and other drugs not only changs the gut micro-ecosystem but also causes the emergence of pathogenic bacteria resistant to antimicrobials, which has seriously threatened animal husbandry and human health 5,6 . Therefore, the search for green and pollution-free additives to improve the immunity and nutrient utilization of livestock and poultry is an inevitable trend in green animal husbandry development in the 21 st century.Probiotics are new green additives developed in recent years and are defined as mono-or mixed cultures of living microorganisms that beneficially affect the host animal by modulating gut microbiota in livestock 7-9 . Meanwhile, probiotics have been shown to reduce disease risk, possibly through a reduction in the proliferation of pathogenic species, maintaining microbiota balance in the gut and increasing resistance to infection 10 . For example, Pascual et al. 11 reported that probiotics have a preventive effect against Salmonella 11 . In addition, probiotic application has been reported in the poultry industry with an emphasis on their influence on the growth performance of chickens and their carcass compositions 12,13 . In this context, recent studies reveal that probiotics supplements in chicken also improve pH, colour, water-holding capacity, fatty acid profile and oxidative stability in fresh meat 14,15 . However, most research in this field has ...

2523 Background: T-cell targeting of mutation-derived epitopes (neoantigens) has been demonstrated to drive anti-tumor responses. Immunizing patients against such neoantigens in combination with a checkpoint inhibitor (CPI) may elicit greater anti-tumor responses than CPI alone. Mutations are rarely shared between patients, thus requiring a personalized approach to vaccine design. Methods: A phase I dose escalation study of mRNA-4157 as adjuvant monotherapy in patients with resected solid tumors (melanoma, bladder carcinoma, HPV negative HNSCC, NSCLC, SCLC, MSI-High, or TMB High cancers) and in combination with pembrolizumab in patients with advanced or metastatic cancer is being conducted to evaluate safety. mRNA-4157 is a lipid encapsulated personalized vaccine encoding multiple neoantigens selected using a proprietary algorithm designed to induce neoantigen specific T cells and associated anti-tumor responses. Patients may receive up to 9 cycles (Q3W) of mRNA-4157 by intramuscular injection (0.04 – 1 mg). In the combination arm, pembrolizumab (200 mg) is administered for two cycles prior to combination with mRNA-4157; patients may continue pembrolizumab after completion of 9 cycles of combination therapy. Primary end points include safety, tolerability, and recommended phase 2 dose. Results: 33 patients received mRNA-4157; 13 as monotherapy and 20 in combination with pembrolizumab. No DLTs were reported, and treatment related AEs have generally been of low grade and reversible, and no drug related SAEs or AEs ≥ grade 3 have been observed. Of the 13 patients on adjuvant monotherapy (3 melanoma, 8 NSCLC, 2 MSI-High), 12 patients remain disease free on study, median follow-up of 8 months. 20 patients have been treated in combination (1 TMB-high, 4 bladder, 2 HNSCC, 1 melanoma, 7 NSCLC, 2 SCLC, 3 MSI-high), 12 had progressed on prior CPI, 16 have been restaged and there are 1 CR (on pembrolizumab prior to vaccination), 2 PR, 5 SD for at least 5 combination cycles, 5 PD, 2 iuPD, and 1 patient is non-evaluable for response but remains on study. Neoantigen specific T cell responses have been detected by IFN-γ ELISpot from PBMCs. Conclusions: mRNA-4157 is safe and well tolerated at all dose levels tested. Clinical responses have been observed in combination with pembrolizumab and neoantigen-specific T cells have been induced, supporting the advancement of mRNA-4157 to phase 2. Clinical trial information: NCT03313778.

Dendrobium is one of the largest genera in Orchidaceae, comprising about 800–1500 species mainly distributed in tropical Asia, Australasia, and Australia. There are 74 species and two varieties of this genus in China. Because of their ornamental and commercial value, Dendrobium orchids have been studied at low taxonomic levels. However, structural changes and effective mutational hotspots of Dendrobium plastomes have rarely been documented. Here, 30 Dendrobium plastomes were compared, comprising 25 newly sequenced in this study and five previously published. Except for their differences in NDH genes, these plastomes shared identical gene content and order. Comparative analyses revealed that the variation in size of Dendroubium plastomes was associated with dramatically changed length of InDels. Furthermore, ten loci were identified as the top-ten mutational hotspots, whose sequence variability was almost unchanged with more than 10 plastomes sampled, suggesting that they may be powerful markers for Dendrobium species. In addition, primer pairs of 47 polymorphic microsatellites were developed. After assessing the mean BS values of all combinations derived from the top-ten hotspots, we recommend that the combination of five hotspots—trnT-trnL, rpl32-trnL, clpP-psbB, trnL intron, and rps16-trnQ—should be used in the phylogenetic and identification studies of Dendrobium.

GDP-L-fucose:j8-D-galactoside a-2-L-fucosyltransferase (EC 2.4.1.69) is a key enzyme in the biosynthesis of fucosylated type 1 and 2 lactoseries structures, such as Lewis b and the H type 2 and Lewis Y, respectively, that are accumulated in colon adenocarcinoma. Analysis of the mRNA transcript level for the human H gene-encoded ,B-Dgalactoside a-2-L-fucosyltransferase revealed 40-and 340-fold increases in the mRNA levels in all adenocarcinomas and tumor cell lines, respectively, compared to normal colon mucosa where a low level of mRNA transcript was detected. A variable increase in mRNA transcript levels was observed in 50% of adenomatous polyps. Nucleotide sequence analysis of the protein coding region of the cDNAs derived from normal colon, adenoma, and colon adenocarcinoma revealed 100% homology, suggesting that there are no tumor-associated allelic variations within the H j3-D-galactoside at-2-Lfucosyltransferase cDNA. These results suggest that f8-Dgalactoside ca-2-L-fucosyltransferase expression highly correlates with malignant progression of colon adenocarcinoma.

Porcine diarrhea is a global problem that leads to large economic losses of the porcine industry. There are numerous factors related to piglet diarrhea, and compelling evidence suggests that gut microbiota is vital to host health. However, the key bacterial differences between non-diarrheic and diarrheic piglets are not well understood. In the present study, a total of 85 commercial piglets at three pig farms in Sichuan Province and Chongqing Municipality, China were investigated. To accomplish this, anal swab samples were collected from piglets during the lactation (0–19 days old in this study), weaning (20–21 days old), and post-weaning periods (22–40 days), and fecal microbiota were assessed by 16S rRNA gene V4 region sequencing using the Illumina Miseq platform. We found age-related biomarker microbes in the fecal microbiota of diarrheic piglets. Specifically, the family Enterobacteriaceae was a biomarker of diarrheic piglets during lactation (cluster A, 7–12 days old), whereas the Bacteroidales family S24–7 group was found to be a biomarker of diarrheic pigs during weaning (cluster B, 20–21 days old). Co-correlation network analysis revealed that the genus Escherichia-Shigella was the core component of diarrheic microbiota, while the genus Prevotellacea UCG-003 was the key bacterium in non-diarrheic microbiota of piglets in Southwest China. Furthermore, changes in bacterial metabolic function between diarrheic piglets and non-diarrheic piglets were estimated by PICRUSt analysis, which revealed that the dominant functions of fecal microbes were membrane transport, carbohydrate metabolism, amino acid metabolism, and energy metabolism. Remarkably, genes related to transporters, DNA repair and recombination proteins, purine metabolism, ribosome, secretion systems, transcription factors, and pyrimidine metabolism were decreased in diarrheic piglets, but no significant biomarkers were found between groups using LEfSe analysis.

Heavy metal contamination attracted a wide spread attention due to their strong toxicity and persistence. The Ganxi River, located in Chenzhou City, Southern China, has been severely polluted by lead/zinc ore mining activities. This work investigated the heavy metal pollution in agricultural soils around the Ganxi River. The total concentrations of heavy metals were determined by inductively coupled plasma-mass spectrometry. The potential risk associated with the heavy metals in soil was assessed by Nemerow comprehensive index and potential ecological risk index. In both methods, the study area was rated as very high risk. Multivariate statistical methods including Pearson's correlation analysis, hierarchical cluster analysis, and principal component analysis were employed to evaluate the relationships between heavy metals, as well as the correlation between heavy metals and pH, to identify the metal sources. Three distinct clusters have been observed by hierarchical cluster analysis. In principal component analysis, a total of two components were extracted to explain over 90% of the total variance, both of which were associated with anthropogenic sources.