Search

Zearalenone (ZEA) and deoxynivalenol (DON) are two common mycotoxins produced by the genus Fusarium and have potential immunotoxic effects that may lead to a weak immune response against bacterial infections. Listeria monocytogenes (L. monocytogenes), a food-borne pathogenic microorganism ubiquitous in the environment, actively multiplies in the liver, where hepatocytes are capable of resistance through mediated innate immune responses. At present, it is not clear if ZEA and DON affect hepatocyte immune responses to L. monocytogenes infection or the mechanisms involved. Therefore, in this study, in vivo and in vitro models were used to investigate the effects of ZEA and DON on the innate immune responses of hepatocytes and related molecules after L. monocytogenes infection. In vivo studies revealed that ZEA and DON inhibited the toll-like receptors 2 (TLR2)/nuclear factor kappa-B (NFκB) pathway in the liver tissue of L. monocytogenes-infected mice, downregulating the expression levels of Nitric oxide (NO), in the liver and repressing the immune response. In addition, ZEA and DON inhibited Lipoteichoic acid (LTA)-induced expression of TLR2 and myeloid differentiation factor 88 (MyD88) in Buffalo Rat Liver (BRL 3A) cells in vitro, downregulating the TLR2/NFκB signaling pathway and resulting in the decreased expression levels of NO, causing immunosuppressive effects. In summary, ZEA and DON can negatively regulate NO levels through TLR2/NFκB, inhibiting the innate immune responses of the liver, and aggravate L. monocytogenes infections in mouse livers.

Purpose The purpose of this study is to propose an adaptive fault-tolerant control approach based on output feedback for a class of quadrotor unmanned aerial vehicles system. In the event of a controlled actuator failure, a stable flying of the aircraft can be achieved by selecting an appropriate sliding mode surface. Design/methodology/approach Aiming at the actuator failure of quadrotor aircraft during flight in the controllable range, a dynamic surface sliding mode passive fault-tolerant controller based on output feedback is designed based on the strong robustness of sliding mode method. Due to the unknown nonlinearity dynamics and parameter uncertainties in the system, a nonlinear observer is used to estimate them online. Findings The stability of the suggested algorithm is established using appropriate Lyapunov functions, and the performance of the proposed control approach is demonstrated using hardware-in-the-loop simulation. Originality/value An error performance function is introduced into the controller to ensure the convergence speed and accuracy of errors are within the predetermined range. By using the norm estimation method, there is only one parameter that needs to be updated in each step of the control process, which considerably minimizes the calculation burden. Finally, the validity of the proposed control scheme is verified on the hardware-in-the-loop simulation, and the results show that the proposed control method has achieved the desired results.

African swine fever (ASF) is a contagious and lethal hemorrhagic disease of pigs caused by the African swine fever virus (ASFV), leading to significant economic consequences for the global pig industry. The development of an effective and safe ASF vaccine has been unsuccessful.

IntroductionHepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood.MethodsIn our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211.ResultsThree clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (PDiscussionIn conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC.

Prophages as a part of Staphylococcus aureus genome contribute to the genetic diversity as well as survival strategies of their host. Some S. aureus prophages also have an imminent risk of host cell lysis and become a lytic phage. Nonetheless, interactions among S. aureus prophages, lytic phages, and their hosts, as well as the genetic diversity of S. aureus prophages, remain unclear. We identified 579 intact and 1,389 incomplete prophages in the genomes of 493 S. aureus isolates obtained from the NCBI database. The structural diversity and gene content of intact and incomplete prophages were investigated and compared with 188 lytic phages. Mosaic structure comparison, ortholog group clustering, phylogenetic analysis, and recombination network analysis were performed to estimate genetic relatedness among S. aureus intact prophages, incomplete prophages, and lytic phages. The intact and incomplete prophages harbored 148 and 522 distinct mosaic structures, respectively. The major difference between lytic phages and prophages was the lack of functional modules and genes. Compared to the lytic phages, both the S. aureus intact and incomplete prophages harbored multiple antimicrobial resistance (AMR) and virulence factor (VF) genes. Several functional modules of lytic phages 3_AJ_2017 and 23MRA shared more than 99% nucleotide sequence identity with S. aureus intact (ST20130943_p1 and UTSW_ MRSA_55_ip3) and incomplete prophages (SA3_LAU_ip3 and MRSA_FKTN_ip4); other modules showed little nucleotide sequence similarity. Ortholog and phylogenetic analyses revealed a common gene pool shared between the prophages and lytic Siphoviridae phages. Moreover, most shared sequences existed within intact (43428/137294, 31.6%) and incomplete prophages (41248/137294, 30.0%). Therefore, the maintenance or loss of functional modules in intact and incomplete prophages is key to balance the costs and benefits of large prophages harboring various AMR and VF genes in the bacterial host. The shared identical functional modules between S. aureus lytic phages and prophages are likely to result in the exchange, acquisition, and loss of functional modules, and therefore contribute to their genetic diversity. Moreover, constant recombination events within prophages globally were responsible for the coevolution of lytic phages and their bacterial hosts.

Pestiviruses are a class of viruses that in some cases can cause persistent infection of the host, thus posing a threat to the livestock industry. Interferons (IFNs) are a group of secreted proteins that play a crucial role in antiviral defense. In this review, on the one hand, we elaborate on how pestiviruses are recognized by the host retinoic acid-inducible gene-I (RIG-I), melanoma-differentiation-associated protein 5 (MDA5), and Toll-like receptor 3 (TLR3) proteins to induce the synthesis of IFNs. On the other hand, we focus on reviewing how pestiviruses antagonize the production of IFNs utilizing various strategies mediated by self-encoded proteins, such as the structural envelope protein (Erns) and non-structural protein (Npro). Hence, the IFN signal transduction pathway induced by pestiviruses infection and the process of pestiviruses blockade on the production of IFNs intertwines into an intricate regulatory network. By reviewing the interaction between IFN and pestiviruses (based on studies on BVDV and CSFV), we expect to provide a theoretical basis and reference for a better understanding of the mechanisms of induction and evasion of the innate immune response during infection with these viruses.

Since the outbreak of short beak and dwarfish syndrome (SBDS) in Cherry Valley Pekin ducks in China, novel goose parvovirus (NGPV) has been isolated. Till now, little is known about the NGPV pathogenesis toward Cherry Valley Pekin ducks. Besides, due to detection of duck circovirus co-infection in SBDS clinical cases, whether sole NGPV infection can reproduce all the typical symptoms of SBDS remains unclear. In this study, based on the NGPV isolate SDJN19, an infectious plasmid clone pJNm containing the entire SDJN19 genome was constructed. Transfection of pJNm in embryonated duck eggs resulted in generation of the infectious virus carrying the genetic marker, named rJNm. rJNm infection of 2-day-old Cherry Valley Pekin ducks reproduced all the typical signs of SBDS, including beak atrophy, tongue protrusion, and growth retardation. rJNm can infect Cherry Valley Pekin ducks through the horizontal transmission route, and the infected ducks exhibited the characteristic SBDS symptoms. A high level of serum precipitation antibodies (above 5log

OBJECTIVE To explore the diagnostic value of noncontrast computed tomography (NCCT) in differentiating pyonephrosis from nonpyogenic hydronephrosis on the basis of CT values (in Horsfield unit [HU]). METHODS Data from patients diagnosed with obstructive uropathy at the First affiliated hospital of University of South China from November 2017 to January 2021 were subjected to retrospective analysis. In accordance with the gold standard-the presence of pus during the operation-all patients were divided into the nonpyogenic hydronephrosis group and the pyonephrosis group. The relationship between CT values and the presence or absence of pyonephrosis was performed using binary logistic regression. A receiver operating characteristic (ROC) curve was constructed to determine threshold values for classification on the basis of mean HU. RESULTS A total of 207 patients, including 100 males and 107 females, were enrolled. Out of the 207 cases, 124 cases of obstructive uropathy were nonpyogenic hydronephrosis and 83 cases were of pyonephrosis. The CT values of the pyonephrosis group were significantly higher than that of the nonpyogenic hydronephrosis group (t = 9.15, P

Bacterial infections caused by Gram-negative pathogens represent a growing burden for public health worldwide. Despite the urgent need for new antibiotics that effectively fight against pathogenic bacteria, very few compounds are currently under development or approved in the clinical setting. Repurposing compounds for other uses offers a productive strategy for the development of new antibiotics. Here we report that the multifaceted melatonin effectively improves survival rates of mice and decreases bacterial loads in the lung during infection. Mechanistically, melatonin specifically inhibits the activity of citrate synthase of Gram-negative pathogens through directly binding to the R300, D363, and H265 sites, particularly for the notorious Pasteurella multocida. These findings highlight that usage of melatonin is a feasible and alternative therapy to tackle the increasing threat of Gram-negative pathogen infections via disrupting metabolic flux of bacteria.

Background Ticks are medically important vectors capable of transmitting a variety of pathogens to and between host species. Although the spectrum of tick-borne RNA viruses has been frequently investigated, the diversity of tick-borne DNA viruses remains largely unknown. Methods A total of 1571 ticks were collected from forests and infested animals, and the diversity of the viruses they harbored was profiled using a DNA-specific virome method. The viromic data were phylogenetically analyzed and validated by PCR assays. Results Although diverse and abundant prokaryotic viruses were identified in the collected ticks, only eukaryotic DNA viruses with single-stranded circular genomes covering the anelloviruses and circular replication-associated (Rep) protein-encoding single-stranded (CRESS) DNA viruses were recovered from ticks. Anelloviruses were detected only in two tick pools, but CRESS DNA viruses were prevalent across these ticks except in one pool of Dermacentor spp. ticks. Phylogenetic analyses revealed that these tick-borne CRESS DNA viruses were related to viruses recovered from animal feces, tissues and even environmental samples, suggesting that their presence may be largely explained by environmental factors rather than by tick species and host blood meals. Conclusions Based on the results, tick-borne eukaryotic DNA viruses appear to be much less common than eukaryotic RNA viruses. Investigations involving a wider collection area and more diverse tick species are required to further support this speculation. Graphical Abstract

In order to reduce the negative impact of severe occlusion in dense scenes on the performance degradation of the tracker, considering that the head is the highest and least occluded part of the pedestrian’s entire body, we propose a new multiobject tracking method for pedestrians in dense crowds combined with head tracking. For each frame of the video, a head tracker is first used to generate the pedestrians’ head movement tracklets, and the pedestrians’ whole body bounding boxes are detected at the same time. Secondly, the degree of association between the head bounding boxes and the whole body bounding boxes are calculated, and the Hungarian algorithm is used to match the above calculation results. Finally, according to the matching results, the head bounding boxes in the head tracklets are replaced with the whole body bounding boxes, and the whole body motion tracklets of the pedestrians in the dense scene are generated. Our method can be performed online, and experiments suggested that our method effectively reduces the negative effects of false negatives and false positives on the tracker caused by severe occlusion in dense scenes.

Avian meningitis Escherichia coli (E. coli) can cause acute bacterial meningitis which threatens poultry health, causes great economic losses in the poultry industry, and has recently been speculated as a potential zoonotic pathogen. Melatonin can counteract bacterial meningitis-induced disruption of the blood–brain barrier (BBB), neuroinflammation, and reduce mortality. There are increasing data showing that melatonin’s beneficial effects on bacterial meningitis are associated with intestinal microbiota. In this study, our data showed that melatonin alleviated neurological symptoms, enhanced survival rate, protected the integrity of the BBB, reduced the bacterial load in various tissues and blood, and inhibited inflammation and neutrophil infiltration of brain tissue in an APEC TW-XM-meningitis mice model. The results of 16S rRNA showed that melatonin pretreatment significantly maintained the composition of intestinal microbiota in APEC-meningitis mice. The abundance and diversity of intestinal microbiota were disturbed in APEC TW-XM-meningitis mice, with a decreased ratio of Firmicutes to Bacteroides and an increased the abundance of Proteobacteria. Melatonin pretreatment could significantly improve the composition and abundance of harmful bacteria and alleviate the decreased abundance of beneficial bacteria. Importantly, melatonin failed to affect the meningitis neurologic symptoms caused by APEC TW-XM infection in antibiotic-pretreated mice. In conclusion, the results suggest that melatonin can effectively prevent meningitis induced by APEC TW-XM infection in mice, depending on the intestinal microbiota. This finding is helpful to further explore the specific target mechanism of melatonin-mediated intestinal microbiota in the prevention of and protection against Escherichia coli meningitis.

The classic neurotransmitter γ-aminobutyric acid (GABA) has been shown to shape the activation and function of immune cells. There are four high-affinity GABA transporters (GATs, including GAT-1, GAT-2, GAT-3, and GAT-4) responsible for the transmembrane transport of GABA in mice. To explore the effect of GAT-2 on type 1 helper T (Th1) cells, naive CD4+ T cells were isolated from splenocytes of GAT-2 knockout (KO) and wild-type (WT) mice and cultured for Th1 cell differentiation, and then, metabolomics analysis of Th1 cells was performed via gas chromatography coupled to time-of-flight mass spectrometry added with multivariate analyses. Based on the variable importance projection value > 1 and P < 0.05, a total of nine differentially expressed metabolites (DEMs) were identified between WT and KO. Then, DEMs were mapped to the KEGG database, and five metabolic pathways were significantly enriched, including the cysteine and methionine metabolism, the riboflavin metabolism, the purine metabolism, the glycerolipid metabolism, and the glycerophospholipid metabolism. Collectively, our metabolomics analysis revealed that deficiency of GAT-2 influenced the metabolomics profile of Th1 cells, which will provide insights into T cell response to GAT-2 deficiency in mice. Data are available via MetaboLights with identifier MTBLS3358.

Avian pathogenic E. coli (APEC) caused avian colibacillosis is mostly common in poultry industry worldwide. APEC virulence factors lead to pathogenesis and the quorum sensing (QS) system is actively involved in the regulation of these virulence factors. Signaling molecules in QS are known as autoinducers (AIs). In QS-1, E. coli encodes a single LuxR homolog, i.e., SdiA, but does not express the LuxI homolog, an acyl-homoserine lactone (AHL) synthase of producing AI-1. Avian pathogenic E. coli (APEC) regulates its virulence genes expression in response to exogenous AHLs, but regulatory mechanisms of AHL and QS-1 are still unknown. This study targeted the APEC CE129 isolate as the reference strain, and the Yersinia enterocolitica yenI gene was expressed into APEC CE129. CE129/pyenI was conferred the ability to produce AHL signal. The CE129 SdiA mutant strain with an in-frame sdiA (AHL receptor) gene deletion was constructed by a λRed recombination system, which lost the ability to sense AHL. The goal of this study was to explore the function of QS-1 upon virulence and elucidate the regulatory effect of QS-1/AHL signals in the APEC strain. Adherence and invasion assays revealed that QS-1 affected APEC adherence and survival ability. APEC biofilm formation was also suppressed under C6HSL. Interestingly, APEC exhibited different phenotypes of acid tolerance and flagella expression when compared to enterotoxigenic E. coli or enterohemorrhagic E. coli (ETEC and EHEC, respectively). These findings enhance our understanding of the QS mechanism.

Colibactin is synthesized by a 54-kb genomic island, leads to toxicity in eukaryotic cells, and plays a vital role in many diseases, including neonatal sepsis and meningitis. Avian pathogenic Escherichia coli (APEC) is speculated to be an armory of extraintestinal pathogenic Escherichia coli and can be a potential zoonotic bacterium that threatens human and animal health. In this study, the APEC XM meningitis mouse model was successfully established to investigate the effect of colibactin in in vivo infection. The clbH-deletion mutant strain induced lower γ-H2AX expression, no megalocytosis, and no cell cycle arrest in bEnd.3 cells, which showed that the deletion of clbH decreased the production of colibactin in the APEC XM strain. The deletion of clbH did not affect the APEC XM strain’s ability of adhering to and invading bEnd.3 cells. In vitro, the non-colibactin-producing strain displayed significantly lower serum resistance and it also induced a lower level of cytokine mRNA and few disruptions of tight junction proteins in infected bEnd.3 cells. Meningitis did not occur in APEC ΔclbH-infected mice in vivo, who showed fewer clinical symptoms and fewer lesions on radiological and histopathological analyses. Compared with the APEX XM strain, APEC ΔclbH induced lower bacterial colonization in tissues, lower mRNA expression of cytokines in brain tissues, and slight destruction of the brain blood barrier. These results indicate that clbH is a necessary component for the synthesis of genotoxic colibactin, and colibactin is related to the development of meningitis induced by APEC XM.

Avian meningitis

Avian pathogenic

As one of the crucial enterotoxins secreted by enterotoxigenic Escherichia coli (ETEC), heat-labile enterotoxin (LT) enhances bacterial adherence both in vivo and in vitro; however, the underlying mechanism remains unclear. To address this, we evaluated the adherence of LT-producing and LT-deficient ETEC strains using the IPEC-J2 cell model. The expression levels of inflammatory cytokines and chemokines, and tight-junction proteins were evaluated in IPEC-J2 cells after infection with various ETEC strains. Further, the levels of adhesins and enterotoxins were also evaluated in F4ac-producing ETEC (F4 + ETEC) strains after treatment with cyclic AMP (cAMP). The adherence of the ΔeltAB mutant was decreased compared with the wild-type strain, whereas adherence of the 1836-2/pBR322-eltAB strain was markedly increased compared with the 1836-2 parental strain. Production of LT up-regulated the expression of TNF-α, IL-6, CXCL-8, and IL-10 genes. However, it did not appear to affect tight junction protein expression. Importantly, we found that cAMP leads to the upregulation of adhesin production and STb enterotoxin. Moreover, the F4 + ETEC strains treated with cAMP also had greater adhesion to IPEC-J2 cells, and the adherence of ΔfaeG, ΔfliC, and ΔestB mutants was decreased. These results indicate that LT enhances the adherence of F4 + ETEC due primarily to the upregulation of F4 fimbriae, flagellin, and STb enterotoxin expression and provide insights into the pathogenic mechanism of LT and ETEC.

Salmonella Entertidis (SE) often causes persistent infections and egg contamination in laying ducks. Hcp, the core structural and effector proteins of the Type VI Secretion System (T6SS) in SE, contributes to bacterial invasion, adhesion and virulence. However, little is known about the effect of Hcp on the host’s infection responses and egg contamination incidences in duck. Herein, we generated an hcp deletion mutant SE MY1△hcp and detected its ability to invade duck granulosa cells (dGCs) and contaminate eggs. In comparison with MY1-infected group, the SE adhesion decreased by 15.96% in MY1△hcp-infected dGCs, and the apoptosis in MY1△hcp-infected dGCs decreased by 26.58% and 30.99% at 3 and 6 hours postinfection, respectively. However, the expression levels of immunogenic genes TLR4, NOD1, TNFα, IL-1β and proinflammatory cytokines IL-6, IL-1β, TNF-α release were markedly lower in the dGCs inoculated with MY1△hcp than that of the wild type. Besides, the laying ducks were challenged with MY1 or MY1△hcp in vivo, respectively. The lower egg production and higher egg contamination were observed in MY1-infected ducks in comparison with MY1△hcp-infected birds. Furthermore, the host’s infection response of differentially abundant proteins (DAPs) to Salmonella effector Hcp was identified using quantitative proteomics. A total of 164 DAPs were identified between the MY1- and MY1△hcp-infected cells, which were mainly engaged in the immune, hormone synthesis, cell proliferation and cell apoptotic process. Among them, STAT3, AKT1, MAPK9, MAPK14, and CREBBP were the center of the regulatory network, which might serve as key host response regulators to bacterial Hcp. In conclusion, we demonstrated that effector Hcp contributed to not only SE invasion, induction of dGCs apoptosis, and trigger of immune responses, but also enhanced contamination incidences. Also, the STAT3, AKT1, MAPK9, MAPK14, and CREBBP were identified as host’s infection response regulators of bacterial Hcp in duck. Overall, these results not only offered a novel evidence of SE ovarian transmission but also identified some promising candidate regulators during SE infection.

Short beak and dwarfism syndrome (SBDS) emerged in Cherry Valley duck flocks in China in 2015, and novel goose parvovirus (NGPV) was shown to be the etiological agent of SBDS. To date, it is not known whether SBDS-related NGPV isolates possess common molecular characteristics. In this study, three new NGPV strains (namely, SDHT16, SDJN19, and SDLC19) were isolated from diseased ducks showing typical signs of SBDS and successfully passaged in embryonated goose or Cherry Valley duck eggs. The complete genome sequences of these NGPV strains were 98.9%-99.7% identical to each other but showed slightly less similarity (95.2%-96.1% identity) to classical GPV strains. A total of 16 common amino acid substitutions were present in the VP1 proteins of six NGPV strains (SDHT16, SDJN19, SDLC19, QH, JS1, and SDLC01) compared with the classical Chinese GPV strains, nine of which were identical to those found in European GPV strain B. The non-structural protein Rep1 of the six NGPV strains had 12 common amino acid substitutions compared with the classical GPV strains. Phylogenetic analysis indicated that the Chinese NGPV strains clustered with the European SBDS-related NGPV strains, forming a separate branch that was distinct from the group formed by the classical GPV strains. The present study shows the common molecular characteristics of NGPV isolates and suggests that the Chinese NGPV isolates probably share a common ancestor with European SBDS-related NGPV strains.

Escherichia coli is a leading cause of bovine mastitis worldwide. The bacteria can rapidly grow in milk and elicit a strong lipopolysaccharide (LPS)/toll-like receptor-4 (TLR4)-dependent inflammatory response. Recently, the long polar fimbriae (LPF) were identified as a promising virulence factor candidate widely distributed in mammary pathogenic E. coli (MPEC) strains. Mammary pathogenic E. coli possess 2 lpf loci encoding LPF1 and LPF2, respectively. By deleting the major fimbrial subunit gene, lpfA, we found that both LPF1 and LPF2 contribute to MPEC adhesion, invasion, and biofilm formation in vitro. The lpf1A and lpf2A mutants showed reduced cytotoxicity in our in vitro cell infection model. Furthermore, we observed that LPF2 induced a mild TLR4-independent proinflammatory response. The median lethal dose (LD50) of both ∆lpf2A and ∆lpf1A∆lpf2A mutants to BALB/c mice increased by 0.38 and 0.15 logs, respectively, whereas that of wild-type strain MPJS13 was 8.69 logs. In contrast, LPF1 deficiency significantly enhanced the LPS/TLR4-mediated inflammatory response in mammary epithelial cells, and the LD50 of the mutant decreased to 8.18 logs. In conclusion, our data suggested that LPF are important in MPEC colonization of mammary cells and may provide a benefit to bacterial intracellular survival that induces persistent bovine mastitis.

When microorganisms invade a host, the innate immune system first recognizes the pathogen-associated molecular patterns of these microorganisms through pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are known transmembrane PRRs existing in both invertebrates and vertebrates. Upon ligand recognition, TLRs initiate a cascade of signaling events; promote the pro-inflammatory cytokine, type I interferon, and chemokine expression; and play an essential role in the modulation of the host's innate and adaptive immunity. Therefore, it is of great significance to improve our understanding of antimicrobial immune responses by studying the role of TLRs and their signal molecules in the host's defense against invading microbes. This paper aims to summarize the specificity of TLRs in recognition of conserved microbial components, such as lipoprotein, lipopolysaccharide, flagella, endosomal nucleic acids, and other bioactive metabolites derived from microbes. This set of interactions helps to elucidate the immunomodulatory effect of TLRs and the signal transduction changes involved in the infectious process and provide a novel therapeutic strategy to combat microbial infections.

Intestinal infectious diseases refer to the inflammatory changes in the intestinal tract caused by pathogens (including bacteria, viruses, fungi, protozoa, or parasites) or their toxic products. A large number of microorganisms colonize the intestinal tract of healthy people, which together with the intestinal epithelium constitute the biological barrier of the intestinal tract to resist infectious diseases. As an “invisible organ,” the intestinal flora is closely related to human nutrition metabolism and intestinal infections. A variety of intestinal flora participates in the nutritional metabolism of amino acids, and the small molecular substances produced by the amino acid metabolism through the intestinal flora can enhance intestinal immunity and resist bacterial infections. In turn, amino acids can also regulate the composition of the intestinal flora, maintain the steady-state of the intestinal flora, protect the intestinal barrier, and inhibit colonization by pathogenic bacteria. As a model animal with a clear microbial background, germ-free (GF) animals can clarify the mechanisms of interactions between intestinal microbes and amino acid metabolism in intestinal infections by combining genetic engineering technology and multi-omics studies. This article reviews related researches on the involvement of intestinal microbes in host amino acid metabolism and resistance to intestinal infections and discusses the advantages of GF animal models for studying the underlying mechanisms. The GF animal model is helpful to further study the intervention effects of amino acid metabolism of targeted intestinal flora on intestinal infections.

The stromal layer is the thickest layer of the cornea, and corneal stromal cells play an important role in the inflammatory response and wound repair. This study investigated the effect of MCC950, an inhibitor of NLRP3 inflammasome, on the inflammatory response and proliferation of canine corneal stromal cells (CCSCs) induced by Staphylococcus pseudintermedius (S. pseudintermedius).CCSCs were pretreated with MCC950 and infected with S. pseudintermedius. The phosphorylation of p65, IκBα, PI3K, and AKT and the expression of NLRP3, caspase-1 p20, cleaved IL-1β, ASC, β-catenin, c-Myc, and CyclinD1 were detected by western blotting. The expression of inflammatory factors (IL-1β, IL-6, IL-8, IL-18, and TNF-α) and growth factors (EGF, FGF, TGF-β1, VEGF, and CTGF) were measured by RT-PCR. The levels of MDA content and LDH activity were detected by an assay kit. The cell cycle was detected by flow cytometry.MCC950 down-regulated the phosphorylation of p65, IκBα, PI3K, and AKT and decreased the expression of NLRP3, caspase-1 p20, cleaved IL-1β, ASC, β-catenin, c-Myc, and CyclinD1 compared to those in the S. pseudintermedius infection group (p 0.05). MCC950 significantly inhibited the expression of inflammatory factors (IL-1β, IL-6, IL-8, IL-18, and TNF-α) and growth factors (EGF, FGF, TGF-β1, VEGF, and CTGF) induced by S. pseudintermedius (p 0.01). Compared to the S. pseudintermedius infection group, the MDA content and LDH activity of CCSCs were significantly decreased after treatment with MCC950 (p 0.01).MCC950 attenuates S. pseudintermedius-induced inflammatory responses in CCSCs. At the same time, MCC950 can inhibit excessive proliferation of cells, which is beneficial for alleviating corneal fibrosis healing.

Bacterial flagellin is a potent powerful adjuvant, which exerts its adjuvant activity by activating the Toll-like receptor 5 (TLR5) signaling pathway to induce host pro-inflammatory responses. Flagellin of Salmonella typhimurium (S. typhimurium) has shown strong adjuvant effects for a variety of vaccine candidates, however, the adjuvanticity of different serotypes of Escherichia coli (E. coli) flagellin (FliC) is unclear. To explore the adjuvant activity of different serotypes of E. coli flagellin, FliCH1, FliCH7, and FliCH19 recombinant flagellins were prokaryotically-expressed and purified. The adjuvanticity of three recombinant flagellins was evaluated by analyzing their abilities to induce the IL-8 production in human colorectal adenocarcinoma (Caco-2) cells and the immune responses to co-administrated FaeG antigen in mice. Sequence analysis showed that the N-and C-terminal regions are highly conserved, whereas the central region is hypervariable. The TLR5 recognized site is identical among these three serotypes of flagellins. Coomassie blue staining SDS-PAGE showed the molecular mass of FliCH1, FliCH7, and FliCH19 recombinant flagellin are 66 kDa, 64 kDa, and 68 kDa, which can be recognized by anti-FliCH1, FliCH7, and FliCH19 serum, respectively. Moreover, the flagellin serotypes induced similar levels of IL-8 and TNF-α production in Caco-2 cells, anti-FaeG specific IgG antibodies in mice, and IL-4 production in mice spleen cells. Our results indicated that E. coli flagellins can be an adjuvant for vaccine candidates and that different serotypes of E. coli flagellins possess identical adjuvant effects.

Motor function evaluation plays an important role in post-stroke rehabilitation. However, the traditional evaluation is subjective and laborious, which may bring a heavy burden to both physicians and stroke survivors. Therefore, an automatic and objective rehabilitation evaluation is needed to minimize the burden of physician, so as to achieve a simplified and objective evaluation process. The main purpose of this study is to investigate the minimum number of tasks for upper-extremity actions in objective assessment of stroke survivors with a Brunnstrom stage (BS) based on wearable sensing device, which can achieve a satisfactory result to reduce the burden of stroke survivors. In this study, we employed 20 stroke survivors and 7 healthy participants, performing three types of daily living activities (drinking, teeth brushing, face washing). The acceleration, angular velocity and surface Electromyography signals on five parts of the forearm were simultaneously acquired. Then, we compared the effects of each action combination under multiple classifiers. The results show that the use of a single action can achieve competitive results compared with multiple action combination classifications, and the use of K nearest neighbor (KNN) algorithm for the average recognition accuracy of face washing action shows better performance, with the highest accuracy reaching 85.65±6.21% (mean ± standard error), 23 of the 27 subjects were accurately classified. These findings indicate that the predominant qualitative assessment after stroke can be supplemented by corresponding quantitative solutions, and that stroke rehabilitation can be automated with less professional therapist involvement.

Cross-river bridges located in seismically active areas are exposed to two major natural hazards, namely earthquakes and flooding. As the scour depth increases, more parts of the bridge substructure will inevitably be exposed to unfavorable conditions such as chloride ion (Cl−) corrosion. To investigate the seismic performance of highway bridges under the action of scour and Cl− corrosion, a spatial finite element dynamic model of a continuous rigid bridge was established and a Cl−-accelerated electrochemical corrosion test and quasi-static test were carried out. The results showed that a reasonable scour depth and the combination sub-factors under the joint probability density of scour action and seismic action can be obtained to establish the combined expression of the action effect. Cl− corrosion can cause a reduction in displacement ductility, load-bearing, and energy dissipation capacity, and increase inequivalent viscous damping coefficient of the columns. Seismic damage of the columns grows linearly to twice the ultimate displacement under Cl− corrosion, which becomes more significant with the increase of the reinforcement ratio.

The study on the failure difference of deep hard rock based on the comparison between conventional and true triaxial tests can help us better understand the fracture processes and failure characteristics of the deep rock mass. Therefore, this article carries out a comparative analysis of the failure of hard rock under conventional and true triaxial stress states. Within the scope of this study, it is found that the brittle–ductile transformation properties can be intuitively reflected in the rock stress–strain curve and failure mode. The brittle–ductile transition point of rock can also be determined by the difference between peak and residual strengths. The rock failure strength increases with the increase of σ2, the peak strain decreases with the increase of σ2, the stress drop of the post-peak curve becomes more obvious with the increase of σ2, and the rock tends toward Class II brittle failure after the peak with the increase of σ2. When σ3 is relatively high, the rock fracture angle increases with the increase of σ2 with obvious regularity. Compared with conventional triaxial stress conditions, the differential stress-induced anisotropy failure is the biggest difference in rock fracture characteristics between true and conventional triaxial stress states. This study can supply useful references to the study of failure properties of hard rock under complex stress states.

Diabetes mellitus is a global public health problem, and the epidemic situation in China is particularly serious. The prevalence of the disease has been increasing in recent years, and the number of patients is the highest in the world. Diabetes has become another chronic non-communicable disease that seriously endangers the health of our people after cardiovascular and cerebrovascular diseases and tumors. In this study, urine sample data were collected from 37 diabetic patients and 37 healthy volunteers using Raman spectroscopy. The collected data were preprocessed using an adaptive iterative reweighted penalized least squares (airPLS) algorithm and a polynomial Savitzky-Golay smoothing algorithm. After extracting features using principal component analysis (PCA) dimensionality reduction algorithm, ResNet, support vector machine (SVM) and linear discriminant analysis (LDA) classification models were selected to classify and identify diabetic patients and healthy controls. The results show that ResNet has the best discrimination effect, and the average accuracy, recall and F1-score can reach 84.28%, 86.20% and 84.02% respectively after five cross-validations, and the area under the subject working characteristic (ROC) curve is 0.93. The experimental results show that the model established in this paper is simple to operate, highly accurate and has good reference value for rapid screening of diabetes.

To analyze the characteristics of fosA and fosA3 in Enterobacter cloacae isolated from aspirated and catheterized urine culture specimens of companion pets in Taiwan. A total of 19 E. cloacae isola...

Small non-coding RNA RyhB is a key regulator of iron homeostasis in bacteria by sensing iron availability in the environment. Although RyhB is known to influence bacterial virulence by interacting with iron metabolism related regulators, its interaction with virulence genes, especially the Type III secretion system (T3SS), has not been reported. Here, we demonstrate that two RyhB paralogs of Salmonella enterica serovar Enteritidis upregulate Type III secretion system (T3SS) effectors, and consequently affect Salmonella invasion into intestinal epithelial cells. Specifically, we found that RyhB-1 modulate Salmonella response to stress condition of iron deficiency and hypoxia, and stress in simulated intestinal environment (SIE). Under SIE culture conditions, both RyhB-1 and RyhB-2 are drastically induced and directly upregulate the expression of T3SS effector gene sipA by interacting with its 5′ untranslated region (5′ UTR) via an incomplete base-pairing mechanism. In addition, the RyhB paralogs upregulate the expression of T3SS effector gene sopE. By regulating the invasion-related genes, RyhBs in turn affect the ability of S. Enteritidis to adhere to and invade into intestinal epithelial cells. Our findings provide evidence that RyhBs function as critical virulence factors by directly regulating virulence-related gene expression. Thus, inhibition of RyhBs may be a potential strategy to attenuate Salmonella.

This article aims to realize a precise position and attitude tracking control for the quadrotor using a proposed fuzzy approximator-based compound adaptive fuzzy quantized control scheme. In the control scheme, a quantized output-feedback control for position tracking and a state-feedback quantized control for attitude trajectory tracking are combined to deal with the underactuated and strong coupling problems of the quadrotor. The main contributions are: 1) the adaptive fuzzy quantized control is realized, then the strong nonlinearities caused by the quantizer are effectively mitigated, which implies that the control precision can be improved when a low communication rate is required in the real-time control system of quadrotor; 2) by applying the adaptive fuzzy dynamic surface control (DSC) technique to the underactuated quadrotor control system, the “explosion of complexity” problem in the backstepping method is overcome and the $ {L}_{\infty }$ tracking performance is achieved with the proposed initializing technique inspired by Zhang et al. This guarantees that the attitude signals promptly converge to the desired trajectories, then the underactuated problem of the quadrotor is overcome by solving the designed adaptive fuzzy-quantized control equations; and 3) the experiments on the platform of the Quanser Qball-X4 quadrotor are conducted and the effectiveness of the proposed control scheme is validated.