Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder.

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention

Enhancing therapeutic effects of murine cancer vaccine by reshaping gut microbiota with Lactobacillus rhamnosus GG and jujube powder

Cancer vaccines have gained widespread attention in recent years as an emerging treatment for tumors. However, most therapeutic cancer vaccines have failed in phase III clinical trials due to faint clinical benefits. In this study, we funded that a specific synbiotic composing Lactobacillus rhamnosus GG (LGG) and jujube powder significantly enhanced the therapeutic effects of whole cells cancer vaccine in MC38 cancer cells bearing-mouse. The utilization of LGG increased the abundance of Muribaculaceae, which is conductive to an enhanced anti-tumor effect, but reduced microbial α-diversity. The use of jujube nursed probiotic microorganisms in Lachnospiaceae and enriched microbial diversity, as indicated by increased Shannon and Chao index. The reshaped gut microbiota by this synbiotic improved lipid metabolism conductive to intensified infiltration of CD8+ T cells in the tumor microenvironment and enhanced the potency of above-mentioned cancer vaccine. These encouraging findings are helpful for further efforts towards enhancing the therapeutic effects of cancer vaccines through nutritional intervention

Exogenous N-acyl-homoserine lactones enhance the expression of flagella of Pseudomonas syringae and activate defence responses in plants

In order to cope with pathogens, plants have evolved sophisticated mechanisms to sense pathogenic attacks and to induce defence responses. The N-acyl-homoserine lactone (AHL)-mediated quorum sensing in bacteria regulates diverse physiological processes, including those involved in pathogenicity. In this work, we study the interactions between AHL-producing transgenic tobacco plants and Pseudomonas syringae pv. tabaci 11528 (P. syringae 11528). Both a reduced incidence of disease and decrease in the growth of P. syringae 11528 were observed in AHL-producing plants compared with wild-type plants. The present data indicate that plant-produced AHLs enhance disease resistance against this pathogen. Subsequent RNA-sequencing analysis showed that the exogenous addition of AHLs upregulated the expression of P. syringae 11528 genes for flagella production. Expression levels of plant defence genes in AHL producing and wild-type plants were determined by quantitative real-time polymerase chain reaction. These data showed that plant-produced AHLs activated a wide spectrum of defence responses in plants following inoculation, including the oxidative burst, hypersensitive response, cell wall strengthening, and the production of certain metabolites. These results demonstrate that exogenous AHLs alter the gene expression patterns of pathogens, and plant-produced AHLs either directly or indirectly enhance plant local immunity during the early stage of plant infection

Downregulating testosterone levels enhance immunotherapy efficiency.

Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency

Impacts of Human Activities on the Composition and Abundance of Sulfate-Reducing and Sulfur-Oxidizing Microorganisms in Polluted River Sediments

Water system degradation has a severe impact on daily life, especially in developing countries. However, microbial changes associated with this degradation, especially changes in microbes related to sulfur (S) cycling, are poorly understood. In this study, the abundance, structure, and diversity of sulfate-reducing microorganisms (SRM) and sulfur-oxidizing microorganisms (SOM) in the sediments from the Ziya River Basin, which is polluted by various human interventions (urban and agricultural activities), were investigated. Quantitative real-time PCR showed that the S cycling-related (SCR) genes (dsrB and soxB) were significantly elevated, reaching 2.60 × 107 and 1.81 × 108 copies per gram of dry sediment, respectively, in the region polluted by human urban activities (RU), and the ratio of dsrB to soxB abundance was significantly elevated in the region polluted by human agricultural activities (RA) compared with those in the protected wildlife reserve (RP), indicating that the mechanisms underlying water system degradation differ between RU and RA. Based on a 16S rRNA gene analysis, human interventions had substantial effects on microbial communities, particularly for microbes involved in S cycling. Some SCR genera (i.e., Desulfatiglans and Geothermobacter) were enriched in the sediments from both RA and RU, while others (i.e., Desulfofustis and Desulfonatronobacter) were only enriched in the sediments from RA. A redundancy analysis indicated that NH4+-N and total organic carbon significantly influenced the abundance of SRM and SOM, and sulfate significantly influenced only the abundance of SRM. A network analysis showed high correlation between SCR microorganisms and other microbial groups for both RU and RA, including those involved in carbon and metal cycling. These findings indicated the different effects of different human interventions on the microbial community composition and water quality degradation

Promoting intestinal IgA production in mice by oral administration with anthocyanins

While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields

Frequent mutation of hypoxia-related genes in persistent pulmonary hypertension of the newborn

AIMS: Persistent pulmonary hypertension of the newborn (PPHN) is characterized by sustained high levels of pulmonary vascular resistance after birth with etiology unclear; Arterial blood oxygen saturation of Tibetan newborns at high latitudes is higher than that of Han newborns at low latitudes, suggesting that genetic adaptation may allow sufficient oxygen to confer Tibetan populations with resistance to pulmonary hypertension; We have previously identified genetic factors related to PPHN through candidate gene sequencing; In this study, we first performed whole exome sequencing in PPHN patients to screen for genetic-related factors. METHODS AND RESULTS: In this two-phase genetic study, we first sequenced the whole exome of 20 Tibetan PPHN patients and compared it with the published genome sequences of 50 healthy high-altitude Tibetanshypoxia-related genes, a total of 166 PPHN-related variants were found, of which 49% were from 43 hypoxia-related genes; considering many studies have shown that the differences in the genetic background between Tibet and Han are characterized by hypoxia-related genetic polymorphisms, so it is necessary to further verify whether the association between hypoxia-related variants and PPHN is independent of high-altitude life. During the validation phase, 237 hypoxia-related genes were sequenced in another 80 Han PPHN patients living in low altitude areas, including genes at the discovery stage and known hypoxia tolerance, of which 413 variants from 127 of these genes were shown to be significantly associated with PPHN.hypoxia-related genes. CONCLUSIONS: Our results indicates that the association of hypoxia-related genes with PPHN does not depend on high-altitude life, at the same time, 21 rare mutations associated with PPHN were also found, including three rare variants of the tubulin tyrosine ligase-like family member 3 gene (TTLL3:p.E317K, TTLL3:p.P777S) and the integrin subunit alpha M gene (ITGAM:p.E1071D). These novel findings provide important information on the genetic basis of PPHN

Investigation of Range Profiles from a Simplified Ship on Rough Sea Surface and Its Multipath Imaging Mechanisms

The range profiles of a two-dimension (2 D) perfect electric conductor (PEC) ship on a wind-driven rough sea surface are derived by performing an inverse discrete Fourier transform (IDFT) on the wide band backscattered field. The rough sea surface is assuming to be a PEC surface. The back scattered field is computed based on EM numerical simulation when the frequencies are sampled between 100 MHz and 700 MHz. Considering the strong coupling interactions between the ship and sea, the complicated multipath effect to the range profile characteristics is fully analyzed based on the multipath imaging mechanisms. The coupling mechanisms could be explained by means of ray theory prediction and numerical extraction of the coupling currents. The comparison of the range profile locations between ray theory prediction and surface current simulation is implemented and analyzed in this paper. Finally, the influence of different sea states on the radar target signatures has been examined and discussed