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Abstract Survival in host macrophages is an effective strategy for pathogenic bacterial transmission and pathogenesis. Our previous study found that viable but non-culturable (VBNC) Cronobacter Sakazakii (C. sakazakii) can survive in macrophages, but its survival mechanism is not clear. In this study, we investigated the possible mechanisms of VBNC C. sakazakii survival in macrophages in terms of environmental tolerance within macrophages and evasion of macrophages recognition. The results revealed that VBNC C. sakazakii survived under oxidative conditions at a higher rate than the culturable C. sakazakii. Moreover, the stringent response gene (relA and spoT) and the antioxidant-related genes (sodA, katG, and trxA) were up-regulated, indicating that VBNC C. sakazakii may regulate antioxidation through stringent response. On the other hand, compared with culturable C. sakazakii, VBNC C. sakazakii caused reduced response (Toll-like receptor 4) in macrophages, which was attributed to the suppression of biosynthesis of the lipopolysaccharides (LPS). Furthermore, we found that ellagic acid can reduce the survival rate of bacteria in macrophages by improving the immune TLR4 recognition ability of macrophages. In conclusion, VBNC C. sakazakii may survive in macrophages by regulating oxidative tolerance through stringent response and altering LPS synthesis to evade TLR4 recognition by macrophages, which suggests the pathogenic risk of VBNC C. sakazakii.

The purpose of this study was to investigate the effects of dietary saccharin sodium supplementation on production performance, serum biochemical indicators, and rumen fermentation of dairy goats in summer. Twelve Guanzhong dairy goats with similar body weight, days in milk, and milk yield were randomly divided into two dietary treatments: (1) CON: basal diet; (2) SS: basal diet + 150 mg/kg saccharin sodium on the basis of dry matter. The experiment lasted 35 d, including 7 d for adaptation and 28 d for dietary treatments, sampling and data collection. Each dairy goat was housed individually in a clean separate pen with ad libitum access to diet and water. The goats fed SS diet had increased dry matter intake (DMI; P = 0.037), 4% fat corrected milk yield (P = 0.049), energy corrected milk yield (P = 0.037), milk protein yield (P = 0.031), and total solids yield (P = 0.036). Serum activity of aspartate aminotransferase (P = 0.047) and concentrations of 70-kDa heat shock protein (P = 0.090), malondialdehyde (P = 0.092), and total protein (P = 0.057) were lower in goats fed SS diet than those fed CON diet. Supplementation of saccharin sodium tended to increase activity of glutathione peroxidase in serum (P = 0.079). The concentrations of rumen total volatile fatty acid (P = 0.042) and butyrate (P = 0.038) were increased by saccharin sodium supplementation. Dietary supplementation of saccharin sodium increased the relative abundance of Lachnobacterium (P = 0.022), Pseudoramibacter (P = 0.022), Shuttleworthia (P = 0.025), and Syntrophococcus (P = 0.037), but reduced the relative abundance of Prevotella_1 (P = 0.037) and Lachnospiraceae_UCG_008 (P = 0.037) in rumen. Saccharin sodium was observed in feces and urine of goats fed diet supplemented with saccharin sodium, but saccharin sodium was undetectable in the milk of goats receiving SS diet. In conclusion, administration of saccharin sodium was effective in increasing fat and energy corrected milk yield by increasing DMI and improving rumen fermentation and antioxidant capacity of dairy goats in summer. In addition, saccharin sodium residue was undetectable in the milk.

IntroductionAlthough the composition and succession of microbial communities in soy sauce fermentation have been well-characterized, the understanding of phage communities in soy sauce remains limited.MethodsThis study determined the diversity, taxonomic composition, and predicted function of phage communities and the phage-host interactions in two types of raw soy sauce (Cantonese-type fermentation, NJ; Japanese-type fermentation, PJ) using shotgun metagenomics.Results and discussionThese two raw soy sauces showed differences in phage composition (121 viral operational taxonomic units (vOTUs) in NJ and 387 vOTUs in PJ), with a higher abundance of the family Siphoviridae (58.50%) in the NJ phage community and a higher abundance of Myoviridae (33.01%) in PJ. Auxiliary metabolic functional annotation analyses showed that phages in the raw soy sauces mostly encoded genes with unknown functions (accounting for 66.33% of COG profiles), but the NJ sample contained genes mostly annotated to conventional functions related to carbohydrate metabolism (0.74%) and lipid metabolism (0.84%), while the PJ sample presented a higher level of amino acid metabolism functions (0.12%). Thirty auxiliary metabolism genes (AMGs) were identified in phage genomes, which were associated with carbohydrate utilization, cysteine and methionine metabolism, and aspartic acid biosynthesis for the host. To identify phage-host interactions, 30 host genomes (affiliated with 22 genera) were also recruited from the metagenomic dataset. The phage-host interaction analysis revealed a wide range of phage hosts, for which a total of 57 phage contigs were associated with 17 host genomes, with Shewanella fodinae and Weissella cibaria infected by the most phages. This study provides a comprehensive understanding of the phage community composition, auxiliary metabolic functions, and interactions with hosts in two different types of raw soy sauce.

Abstract Background Ruminal microbiota in early life plays critical roles in the life-time health and productivity of ruminant animals. However, understanding of the relationship between gut microbiota and ruminant phenotypes is very limited. Here, the relationship between the rectum microbiota, their primary metabolites, and growth rate of a total of 76 young dairy goats (6-month-old) were analyzed, and then 10 goats with the highest or lowest growth rates respectively were further compared for the differences in the rectum microbiota, metabolites, and animal’s immune parameters, to investigate the potential mechanisms by which the rectum microbiota contributes to the health and growth rate. Results The analysis of Spearman correlation and microbial co-occurrence network indicated that some keystone rectum microbiota, including unclassified Prevotellaceae, Faecalibacterium and Succinivibrio, were the key modulators to shape the rectum microbiota and closely correlated with the rectum SCFA production and serum IgG, which contribute to the health and growth rate of young goats. In addition, random forest machine learning analysis suggested that six bacterial taxa in feces could be used as potential biomarkers for differentiating high or low growth rate goats, with 98.3% accuracy of prediction. Moreover, the rectum microbiota played more important roles in gut fermentation in early life (6-month-old) than in adulthood stage (19-month-old) of goats. Conclusion We concluded that the rectum microbiota was associated with the health and growth rate of young goats, and can be a focus on the design of the early-life gut microbial intervention.

Soy isoflavones (SI) have been shown to modulate the structure of gut microbiota, while the biotransformation mechanism of SI under the effect of gut microbiota remains unclear. Here, an equol-producing human microbiota-associated (HMA) mice model was used to examine the possible mechanisms that affect SI biotransformation. The metagenomic sequencing data show that SI supplement significantly modulates the gut microbiota composition and promotes enrichment of genes. Taxonomic and functional annotation indicated that the secretion of some regulatory factors in carbon metabolism and glycolysis might promote SI biotransformation. In addition, differences in dosing are critical, as they might be related to changes in the gut microbiota. This study demonstrated that mid-dose SI treatment significantly improved carbon metabolism and glycolysis and its key metabolic regulatory factors, thereby promoting the biotransformation ability of SI. Mastering these results will provide a new perspective for the biological activity and health effects of SI.

Mucormycosis is a rare fungal infection caused by fungi of the order Mucorales. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas pulmonary mucormycosis is a rare manifestation in patients with hematological malignancy and transplant recipients. We report a case of a 40-year-old male, with history of poorly controlled diabetes, who presented to the emergency room with a one-week history of hemoptysis. Computed Tomography (CT) of the chest was concerning for a lung mass or abscess. Flexible bronchoscopy revealed an endobronchial lesion that was biopsied with a cryoprobe. Histopathologic examination showed non-septate right-angle branching hyphae, typical of mucormycosis. He underwent surgical resection of the right middle and lower lobes and treatment with antimycotic agents with a complete recovery. This case highlights the importance of early histopathological diagnosis of pulmonary mucormycosis in preventing a fatal outcome.

Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.

The dynamic vibration absorbers have been applied to attenuate the critical or unbalanced vibration but may create the fluid-induced vibration instability in the rotor/seal system. The major purpose of this study is devoted to the effects of the dynamic vibration absorber on the nonlinear dynamic behavior and stability of the fluid-induced vibration in the rotor/seal system. The dynamic vibration absorber is attached on the shaft in the perpendicular directions. The model of the rotor/seal-dynamic vibration absorber system is established as the modified Jeffcott rotor system, and Muszynska nonlinear seal force is applied. The numerical method is used for the dynamic behavior analysis. The effects of the natural frequency and damping ratio of the dynamic vibration absorber on the dynamic behavior are discussed. The stability of the rotor/seal-dynamic vibration absorber system is judged by the eigenvalue theory. The variations of the instability threshold with the parameters of the dynamic vibration absorber are obtained. The results show that the instability threshold and instability vibration frequency are changed by the dynamic vibration absorber. The parameters of the dynamic vibration absorber must be selected carefully to avoid reducing the instability threshold and causing the instability vibration to occur in advance when the dynamic vibration absorber is applied to attenuate the critical or unbalanced vibration of the rotor/seal system.

A theoretical research on eliminating the instability vibration and improving the stability of the rotor/seal system using the inerter-based dynamic vibration absorber (IDVA) is presented in this paper. The modified Jeffcott rotor and Muszynska nonlinear seal force models are employed. The proposed IDVA is the damping element of the traditional dynamic vibration absorber (DVA) replaced by one of the six configurations of the inerter. The instability threshold speed of the system is obtained by applying the Routh–Hurwitz stability criterion. The quantum particle swarm optimization (QPSO) method is utilized to optimize the parameters of the IDVA. The numerical method is applied to investigate the nonlinear dynamic responses and stability. The results show that the IDVA can effectively improve the stability and reduce the instability vibration of the rotor/seal system. Furthermore, the performance of the IDVA is more effective than that of the traditional DVA.

The dynamic vibration absorbers have been applied to attenuate the rotor unbalance and torsional vibrations. The major purpose of this paper is to research the elimination of the fluid-induced vibration in the rotor/seal system using the absorber. The simplified rotor model with the absorber is established, and the Muszynska fluid force model is employed for the nonlinear seal force. The numerical method is used for the solutions of the nonlinear differential equations. The nonlinear responses of the rotor/seal system without and with the absorber are obtained, and then the rotating speed ranges by which the fluid-induced instability can be eliminated completely and partially are presented, respectively. The absorber parameters ranges by which the instability vibration can be eliminated completely and partially are obtained. The results show that the natural frequency vibration due to the fluid-induced instability in the rotor/seal system can be eliminated efficiently using the absorber. The appropriate natural frequency and damping ratio of the absorber can extend the complete elimination region of the instability vibration and postpone the occurrence of the instability vibration.

Doublecortin-like kinase 1 (DCLK1) is a putative pancreatic stem cell marker and is upregulated in pancreatic cancer, colorectal cancer, and many other solid tumors. It marks tumor stem cells in mouse models of intestinal neoplasia. Here we sought to determine whether DCLK1 protein can be detected in the bloodstream and if its levels in archived serum samples could be quantitatively assessed in pancreatic cancer patients. DCLK1 specific ELISA, western blotting, and immunohistochemical analyses were used to determine expression levels in the serum and staining intensity in archived tumor tissues of pancreatic ductal adenocarcinoma (PDAC) patients and in pancreatic cancer mouse models. DCLK1 levels in the serum were elevated in early stages of PDAC (stages I and II) compared to healthy volunteers (normal controls). No differences were observed between stages III/IV and normal controls. In resected surgical tissues, DCLK1 expression intensity in the stromal cells was significantly higher than that observed in tumor epithelial cells. Circulating tumor cells were isolated from KPCY mice and approximately 52% of these cells were positive for Dclk1 staining. Dclk1 levels in the serum of KPC mice were also elevated. We have previously demonstrated that DCLK1 plays a potential role in regulating epithelial mesenchymal transition (EMT). Given the increasingly recognized role of EMT derived stem cells in cancer progression and metastasis, we hypothesize that DCLK1 may contribute to the metastatic process. Taken together, our results suggest that DCLK1 serum levels and DCLK1 positive circulating tumor cells should be further assessed for their potential diagnostic and prognostic significance.