Hydrogen Sulfide Maintains Mesenchymal Stem Cell Function and Bone Homeostasis via Regulation of Ca2+ Channel Sulfhydration

Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one such gasotrasmitter which regulates multiple signaling pathways in mammalian cells, and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca2+ influx, due to reduced sulfhydration of cysteine residues on multiple Ca2+ TRP channels. This decreased Ca2+ flux downregulates PKC/Erk-mediated Wnt/β-catenin signaling which controls osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an osteoporotic phenotype, which can be rescued by small molecules which release H2S. These results demonstrate H2S regulates BMMSCs, and restoring H2S levels via non-toxic donors may provide treatments for diseases such as osteoporosis which can arise from H2S deficiencies

Antitumor Effect of Malaria Parasite Infection in a Murine Lewis Lung Cancer Model through Induction of Innate and Adaptive Immunity

BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer immune-based therapy

Characteristics of Microbiota in Different Segments of the Digestive Tract of <i>Lycodon rufozonatus</i>

The gastrointestinal tract of animals contains microbiota, forming a complex microecosystem. Gut microbes and their metabolites can regulate the development of host innate and adaptive immune systems. Animal immune systems maintain intestinal symbiotic microbiota homeostasis. However, relatively few studies have been published on reptiles, particularly snakes, and even fewer studies on different parts of the digestive tracts of these animals. Herein, we used 16S rRNA gene sequencing to investigate the microbial community composition and adaptability in the stomach and small and large intestines of Lycodon rufozonatus. Proteobacteria, Bacteroidetes, and Firmicutes were most abundant in the stomach; Fusobacteria in the small intestine; and Proteobacteria, Bacteroidetes, Fusobacteria, and Firmicutes in the large intestine. No dominant genus could be identified in the stomach; however, dominant genera were evident in the small and large intestines. The microbial diversity index was significantly higher in the stomach than in the small and large intestines. Moreover, the influence of the microbial community structure on function was clarified through function prediction. Collectively, the gut microbes in the different segments of the digestive tract revealed the unique features of the L. rufozonatus gut microbiome. Our results provide insights into the co-evolutionary relationship between reptile gut microbiota and their hosts

A high-quality chromosomal-level genome assembly of Greater Scaup (Aythya marila)

Abstract Aythya marila is one of the few species of Anatidae, and the only Aythya to live in the circumpolar. However, there is a relative lack of research on genetics of this species. In this study, we reported and assembled the first high-quality chromosome-level genome assembly of A. marila. This genome was assembled using Nanopore long reads, and errors corrected using Illumina short reads, with a final genome size of 1.14 Gb, scaffold N50 of 85.44 Mb, and contig N50 of 32.46 Mb. 106 contigs were clustered and ordered onto 35 chromosomes based on Hi-C data, covering approximately 98.28% of the genome. BUSCO assessment showed that 97.0% of the highly conserved genes in aves_odb10 were present intact in the genome assembly. In addition, a total of 154.94 Mb of repetitive sequences were identified. 15,953 protein-coding genes were predicted in the genome, and 98.96% of genes were functionally annotated. This genome will be a valuable resource for future genetic diversity and genomics studies of A. marila

IFI16 Inhibits Porcine Reproductive and Respiratory Syndrome Virus 2 Replication in a MAVS-Dependent Manner in MARC-145 Cells

Porcine reproductive and respiratory syndrome virus (PRRSV) is a single-stranded positive-sense RNA virus, and the current strategies for controlling PRRSV are limited. Interferon gamma-inducible protein 16 (IFI16) has been reported to have a broader role in the regulation of the type I interferons (IFNs) response to RNA and DNA viruses. However, the function of IFI16 in PRRSV infection is unclear. Here, we revealed that IFI16 acts as a novel antiviral protein against PRRSV-2. IFI16 could be induced by interferon-beta (IFN-&beta;). Overexpression of IFI16 could significantly suppress PRRSV-2 replication, and silencing the expression of endogenous IFI16 by small interfering RNAs led to the promotion of PRRSV-2 replication in MARC-145 cells. Additionally, IFI16 could promote mitochondrial antiviral signaling protein (MAVS)-mediated production of type I interferon and interact with MAVS. More importantly, IFI16 exerted anti-PRRSV effects in a MAVS-dependent manner. In conclusion, our data demonstrated that IFI16 has an inhibitory effect on PRRSV-2, and these findings contribute to understanding the role of cellular proteins in regulating PRRSV replication and may have implications for the future antiviral strategies

Effects of Water Masses and Circulation on the Surface Water Partial Pressure of Carbon Dioxide in Summer in Eastern Beibu Gulf, China

A gulf is a typical ecological zone where carbon cycle is jointly affected by complex environmental factors and strong human activities, and the Beibu Gulf has complex water masses and circulation structures. In this study, we used underway, continuous observational data of the surface water partial pressure of carbon dioxide (pCO2), temperature (SST), salinity (SSS), dissolved oxygen (DO), and chlorophyll α along with vertical profile observations of temperature, salinity, carbonate system parameters and nutrients to determine the spatiotemporal variations and research effects of water masses and circulation on summer pCO2 in the eastern part of Beibu Gulf. In the summers of 2011 and 2014, the mean pCO2 in the eastern part of Beibu Gulf was 417 μatm and 405 μatm, respectively, and the mean sea–air CO2 flux was 3.3 mmol m−2 d−1 and 1.6 mmol m−2 d−1, respectively. In the summer of 2011, the northern part of the Beibu Gulf was controlled by a cyclonic circulation, and pCO2 at the center of the cyclonic circulation increased by more than 15 μatm to a mean value of more than 10 μatm above that of the surrounding waters. The southern part of the Beibu Gulf was affected by an anticyclonic circulation and western coastal water masses, with a high temperature, low salinity, low pCO2, and downwelling surface waters. In the summer of 2011, the mean pCO2 was approximately 17 μatm lower than that in the surrounding waters, and no clear downwelling was observed in summer 2014. The eastern part of Beibu Gulf was a source of atmospheric CO2 in the summer, only the region affected by the northern coastal water in the eastern part of Beibu Gulf was a sink of atmospheric CO2, and pCO2 had distinctly different spatiotemporal distributions under the influence of complex water masses and circulation structures

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Inhibits RNA-Mediated Gene Silencing by Targeting Ago-2

Porcine reproductive and respiratory syndrome virus (PRRSV) infection strongly modulates the host’s immune response. The RNA silencing pathway is an intracellular innate response to viral infections. However, it is unknown whether PRRSV interacts with cellular RNA silencing to facilitate the viral infection. Here, we report for the first time the interaction between PRRSV and RNA silencing in both the porcine macrophages and African green monkey kidney cell line (MARC-145) cell line, which were derived from African green monkey kidney cells and highly permissive for PRRSV infection. Our data demonstrated that PRRSV suppressed RNA silencing induced by short-hairpin (sh) RNA, double-strand (ds) RNA and microRNA (miRNA) and downregulated the expression of argonaute protein-2 (Ago-2), which is a key protein of the RNA silencing pathway in animal cells. Further, exogenous introduction of siRNA and shRNA downregulated Dicer or Ago-2 proteins of the cellular RNA silencing apparatus in MARC-145 cells and porcine macrophages, which, in turn, increased the viral replication and titers. The viral non-structure protein 1α (nsp-1α) and nsp11 of PRRSV were identified as the suppressors for cellular RNA silencing (RSSs) to downregulate the Ago-2 protein. Our results identify that PRRSV, through its nsp proteins, suppresses the cellular RNA silencing apparatus in favor of viral infection and supports a co-evolutionary process of the virus and the cellular RNA silencing process

miR-541-3p Promoted Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) Replication by Targeting Interferon Regulatory Factor 7

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by PRRS virus (PRRSV), which seriously harms the pig industry. Revealing the mechanism by which PRRSV inhibits immune response will help prevent and control PRRS. Here, we found that PRRSV-2 may hijack host miR-541-3p to inhibit host innate immune response. Firstly, this work showed that miR-541-3p mimics could facilitate the replication of PRRSV-2 and the results of the quantitative real time polymerase chain reaction (qRT-PCR) showed that PRRSV-2 could up-regulate the expression of miR-541-3p in MARC-145 cells. Since previous studies have shown that type I interferon could effectively inhibit the replication of PRRSV-2, the present work explored whether miR-541-3p regulated the expression of type I interferon and found that miR-541-3p could negatively regulate the transcription of type I interferon by targeting interferon regulatory factor 7 (IRF7). More importantly, PRRSV-2 infection could down-regulate the expression of IRF7 and over-expression of IRF7 could down-regulate the replication of PRRSV-2 in MARC-145 cells. In conclusion, PRRSV-2 infection up-regulated the expression of miR-541-3p to promote its replication in MARC-145 cells, since miR-541-3p can negatively regulate the transcription of type I interferon by targeting IRF7