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Antimicrobial compounds from the commensal gut microbiota have gained much attention due to their multifunctionality in maintaining good health in the host and killing multidrug-resistant bacteria. Our previous study showed that

Extracellular trap (ET) appears as a double-edged sword for the host since it participates in host immune defense by entrapping pathogens, while excessive ET release also contributes to various diseases progression including atherosclerosis, cancer, and autoimmune disorders. A better understanding of ET formation and regulation will be beneficial for developing strategies for infection control and ET-associated disease treatment. There is some evidence indicating that prior infection can enhance extracellular killing. Neutrophils from cancer or sepsis are predisposed to generate ET. It is reasonable to suspect that ET may be trained to form as a memory response, just like cytokine memory response termed "trained immunity." The mice were intraperitoneally injected with heat-killed

Pure cultures of chicken intestinal microbial species may still be crucial and imperative to expound on the function of gut microbiota, and also contribute to the development of potential probiotics and novel bioactive metabolites from gut microbiota. In this study, we isolated and identified 507 chicken intestinal bacterial isolates, including 89 previously uncultured isolates. Among these, a total of 63 Lactobacillus strains, belonging to L. vaginalis, L. crispatus, L. gallinarum, L. reuteri, L. salivarius, and L. saerimneri, exhibited antibacterial activity against S. Pullorum. Acid tolerance tests showed Limosilactobacillus reuteri strain YPG14 (L. reuteri strain YPG14) has a particularly strong tolerance to acid. We further characterized other probiotic properties of L. reuteri strain YPG14. In simulated intestinal fluid, the growth of L. reuteri strain YPG14 remained stable after incubation for 4 h. The auto-aggregation test showed the auto-aggregation percentage of L. reuteri strain YPG14 was recorded as 15.0  ±  0.38%, 48.3  ±  2.51%, and 75.1  ±  4.44% at 3, 12, and 24 h, respectively. In addition, the mucin binding assay showed L. reuteri strain YPG14 exhibited 12.07 ±  0.02% adhesion to mucin. Antibiotic sensitivity testing showed that L. reuteri strain YPG14 was sensitive to the majority of the tested antibiotics. The anti-Salmonella Pullorum (S. Pullorum) infection effect in vivo revealed that the consumption of L. reuteri strain YPG14 could significantly improve body weight loss and survival rate of chicks infected by S. Pullorum; reduce the loads of S. Pullorum in the jejunum, liver, spleen, and feces; and alleviate the jejunum villi morphological structure damage, crypt loss, and inflammatory cell infiltration caused by S. Pullorum. Overall, this study may help us to understand the diversity of chicken intestinal microflora and provide some insights for potential probiotic development from gut microbiota and may find application in the poultry industry.

The tumor and tissue microbiota of human beings have recently been investigated. Gut permeability is known as a possible resource for the positive detection of tissue bacteria. Herein, we report that microbiota were detected in high abundance in the hepatocytes of healthy rats and that they were shared with the gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After the rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50 ± 6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67 ± 70.14 , 729–893). Rats showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of the genomes of annotated bacteria was correlated with metabolism ( 79.92 ± 0.24 % ). Gram negativity was about 1.6 times higher than gram positivity. The liver microbiome was shared with both the small and large intestines but showed significantly higher richness and evenness than the gut microbiome, and the β-diversity results showed that the liver microbiome exhibited significantly higher similarity than the small and large intestines ( P < 0.05 ). Our results suggest that the bacteria in the liver microbiome are hidden intracellular inhabitants in healthy rat livers.

Background: The occurrence of serious diseases, such as inflammatory diseases and cancer, in the small intestine is significantly lower than that in the colon. The differentiation of small-intestine microbiota from large-intestine microbiota might hold great significance. Materials and methods: To compare floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats, and the V3–V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was amplified and sequenced. We subjected the data to bioinformatics analyzing. Results: Compared with feces, about 50% of bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units [OTUs] P < 0.05). A high-fat diet (HFD) and specific-pathogen–free (SPF) conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or β-diversity of samples. Intestinal microbiota were composed of high-prevalence dominant, low-prevalence dominant, and less-dominant bacteria. Conclusions: The present findings suggested that ileal and fecal bacteria were different structurally and functionally. These differences might be key to the fundamental protection of the small intestine from diseases.

The tumor and tissue microbiomes of human beings have recently been investigated. Gut permeability is known as a possible resource for the positive detection of tissue bacteria. Herein, we report that bacteria were detected in high abundance in the hepatocytes of healthy rats, and that they were shared with the gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50 ± 6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67 ± 70.14, 729–893). Individuals showed conservation of bacterial richness, abundance, and evenness. LPS and 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of the genomes of the annotated bacteria was correlated with metabolism (79.92 ± 0.24%). Gram negativity was about 1.6 times higher than gram positivity. Liver bacteria were shared with both the small and large intestines but showed significantly higher richness, evenness, and β-diversity results showed that the liver microbiota exhibited significantly higher similarity than the small and large intestines (P < 0.05). The liver microbiota were hidden intracellular inhabitants in healthy rat livers and were shared with the gut microbiota.

Abstract The tumor and tissue microbiomes of human beings have recently been investigated. Gut permeability was known as a possible resource for the positive detection of tissue bacteria. Herein, we report that bacteria were detected in high abundance in the hepatocyte nucleus of healthy rats, and that they were shared with gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50 ± 6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67 ± 70.14, 729–893). Individuals showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function composition of genomes of the annotated bacteria was correlated with metabolism (79.92 ± 0.24%). Gram negativity was about 1.6 times higher than gram positivity, and the aerobic and anaerobic phenotypes were nearly the same. Liver microbiota also showed high expression of mobile elements, biofilm formation, and stress tolerance, as well as potentially pathogenic phenotypes. Chemoheterotrophy, fermentation, and aerobic chemoheterotrophy were the main heterotrophic functions. Liver bacteria were shared with both the small and large intestines but showed significantly higher richness, evenness, and the β-diversity results showed that the liver microbiota exhibited significantly higher similarity than the small and large intestines (P < 0.05). The liver microbiota were hidden intracellular inhabitants in healthy rat livers and were shared with the gut microbiota.

Interferon-inducible protein 204 (IFI204) is an intracellular DNA receptor that can recognize DNA viruses and intracellular bacteria. Extracellular traps (ETs) have been recognized as an indispensable antimicrobial barrier that play an indispensable role in bacterial, fungal, parasitic, and viral infections. However, how ETs form and the mechanisms by which IFI204 function in Staphylococcus aureus pneumonia are still unclear. Moreover, by in vitro experiments, we proved that IFI204 deficiency decreases the formation of ETs induced by Staphylococcus aureus in a NOX-independent manner. More importantly, Deoxyribonuclease I (DNase I) treatment significantly inhibited the formation of ETs. IFI204 contributed to ETs formation by promoting citrullination of histone H3 and the expression of PAD4 (peptidylarginine deiminase 4). Altogether, these findings highlight the potential importance of IFI204 for host defense against S. aureus USA300-TCH1516 infection.

Background: The occurrence of serious diseases, such as inflammatory diseases and cancer, in the small intestine is significantly lower than that in the colon. The differentiation of small-intestine microbiota from large-intestine microbiota might hold great significance. To compare floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats, and the V3–V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was amplified and sequenced. We subjected the data to bioinformatics analyzing.Results: Compared with feces, about 50% of bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units [OTUs] P < 0.05). A high-fat diet (HFD) and specific-pathogen–free (SPF) conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or β-diversity of samples. Intestinal microbiota were composed of high-prevalence dominant, low-prevalence dominant, and less-dominant bacteria.Conclusions: The present findings suggested that ileal and fecal bacteria were different structurally and functionally. These differences might be key to the fundamental protection of the small intestine from diseases.

The tumor and tissue microbiomes of human beings have recently been investigated. Gut permeability was known as a possible resource for the positive detection of tissue bacteria. Herein, we report that bacteria were detected in high abundance in the hepatocyte nucleus of healthy rats, and that they were shared with gut microbiota to an extent. We assessed male Sprague Dawley (SD) rats for the 16S ribosomal ribonucleic acid (rRNA) gene. After rats were sacrificed by blood drainage from the portal vein, we extracted total deoxyribonucleic acid (DNA) from their ileal and colonic contents and liver tissues. The V3–V4 region of the 16S rRNA gene was amplified by polymerase chain reaction (PCR) and sequenced using an Illumina HiSeq 2500 platform. Sequences were assigned taxonomically by the SILVA database. We also detected bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in situ using immunofluorescence (IF) and western blotting, and the 16S rRNA gene using fluorescent in situ hybridization (FISH). In the livers of six rats, we detected 54,867.50 ± 6450.03 effective tags of the 16S rRNA gene and clustered them into 1003 kinds of operational taxonomic units (OTUs; 805.67 ± 70.14, 729–893). Individuals showed conservation of bacterial richness, abundance, and evenness. LPS and the 16S rRNA gene were detected in the nuclei of hepatocytes. The main function of the annotated bacteria was correlated with metabolism (79.92 ± 0.24%). Gram negativity was about 1.6 times higher than gram positivity, but aerobic and anaerobic phenotypes were nearly the same. Liver flora also showed high expression of mobile elements, biofilm formation, and stress tolerance, as well as potentially pathogenic phenotypes. Chemoheterotrophy, fermentation, and aerobic chemoheterotrophy were the main heterotrophic functions. Liver bacteria were shared with both the small and large intestines but showed significantly higher richness, evenness, and β-diversity than the small and large intestines (P < 0.05). Liver flora were hidden intracellular inhabitants in healthy rat livers and were shared with gut microbiota.

Abstract Uncariae Ramulus Cum Uncis (Gou-Teng), the dried hook-bearing stems of several Uncaria plants (Rubiaceae), is a well-known herbal medicine in China. The clinical application of Gou-Teng is bewildered for the morphological and chemical similarity between different species. In order to discern their chemical and biological difference, an ultra-fast liquid chromatography equipped with ion trap time-of-flight mass spectrometry (UFLC-IT/TOF-MS) combining with melatonin (MT1 and MT2) and 5-hydroxytryptamine (5-HT1A and 5-HT2C) receptors agonistic assay in vitro was conducted on seven Uncaria species. As a result, 57 compounds including 35 indole alkaloids, ten flavonoids, five triterpenoids, five chlorogenic analogues, and two other compounds were characterized based on their MS/MS patterns and UV absorptions. Specifically, cadambine-type and corynanthein-type alkaloids were exclusively present in U.rhynchophylla and U.scandens, whereas corynoxine-type alkaloids were commonly detected in all the seven Uncaria plants. Three Uncaria species, U. rhynchophylla, U. macrophylla, and U. yunnanensis showed obviously agnostic activity on four neurotransmitter receptors (MT1, MT2, 5-HT1A, and 5-HT2C). This first-time UFLCMS-IT-TOF analyses integrated with biological assay on seven Uncaria plants will provide scientific viewpoints for the clinical application of Gou-Teng. Graphic Abstract

To evaluate the prognostic significance of peripheral lymphocyte count and its derived inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), in a cohort of patients with gastric cancer (GC).In this retrospective study, the clinical characteristics and follow-up information, both pre- and post-operative within one week of laboratory findings, of 338 patients with GC who underwent radical gastrectomy were retrieved, and their prognostic significance was evaluated.Both lower pre- and post-operative lymphocyte counts and higher NLR and SSI were significantly related to advanced tumour (pT) and disease stages (American Joint Committee on Cancer [AJCC]) in patients with GC. Log-rank survival analysis showed that, in addition to traditional pT, pN, pM, and AJCC stages, both lower pre- (p = 0.041) and post-operative (p = 0.002) lymphocyte counts and higher NLR (pPre-operative NLR is an independent prognostic factor for patients with GC and has stratified prognostic value for patients with AJCC stage III GC.

Obesity is one of the prevalent chronic diseases in human and companion animals usually associated with several metabolic disorders. The gut commensal bacterium Akkermansia muciniphila (A. muciniphila) is known for its therapeutic effects on metabolic disorders and inflammations. Here, we isolated the A. muciniphila AKK2 strain from the feces of interferon-inducible protein 204−/− (IFI204−/−) mice and further evaluated its anti-obesity effects on high-fat diet (HFD)-fed C57BL/6J mice and beagles. The results showed that it effectively controlled weight gain. Microbiome analysis using 16S rRNA gene sequencing revealed that HFD alters gut microbiota composition and A. muciniphila AKK2 increases the Firmicutes/Bacteroidetes (F/B) ratio in beagles. Furthermore, we prepared microcapsules containing A. muciniphila AKK2, and tolerance tests showed the encapsulation maintained high viability and stability in an aerobic environment and simulated the secretion of gastrointestinal fluids. Overall, this study widens the spectrum of A. muciniphila applications to prevent obesity.

The paper established a conventional bus traffic network and a subway network by using the method of space R based on the existing public traffic network model. Regarding these two networks as the ...

A complex mode-locking (entrainment) topology underlying the continuous stirred tank reactor reaction model subjected to impulsive perturbations is identified. Employing high-resolution stability diagrams, we exhibit the global structure of mode-locking oscillations and describe how they are interconnected and how their complexity unfolds with control parameters varying. The scenarios shown in the bi-parametric planes revealed that the skeleton of Arnold’s tongues is organized according to the symmetric Stern–Brocot sum tree. Moreover, the mode-locking organization is controlled by an invariant torus (a pair of frequencies) initiated from Hopf bifurcations. Interestingly, the mode-locking order is unfolded in an elusive way, that is, in perfect agreement with the reciprocal of the Stern–Brocot sum tree. The findings reported here contribute to providing a description and classification of mode-locking oscillations for the impulsive system.

Signaling pathway between human leukocyte antigen (HLA)-G and immune inhibitory receptors immunoglobulin-like transcript (ILT)-2/4 has been acknowledged as one of immune checkpoints, and as a potential target for cancer immunotherapy. Like other immune checkpoints, inter- and even intratumor heterogeneity of HLA-G could render a rather complexity for HLA-G-target immunotherapy. However, little information for intratumor heterogeneity of HLA-G is available. In this study, HLA-G expression in a serial section of colorectal cancer (CRC) lesions from three CRC patients (each sample with serial section of 50 slides, 10 randomized slides for each antibody), three different locations within a same sample (five CRC), and three case-matched blocks that each includes 36 esophageal cancer samples, were evaluated with immunohistochemistry using anti-HLA-G antibodies (mAbs 4H84, MEM-G/1 and MEM-G/2 probing for all denatured HLA-G isoforms, 5A6G7, and 2A12 probing for denatured HLA-G5 and HLA-G6 isoforms). Our results revealed that, in addition to the frequently observed inter-tumor heterogeneity, intratumor heterogeneous expression of HLA-G is common in different areas within a tumor in CRC and esophageal cancer samples included in this study. Moreover, percentage of HLA-G expression probed with different anti-HLA-G antibodies also varies dramatically within a tumor. Given HLA-G has been considered as an important immune checkpoint, intratumor heterogeneity of HLA-G expression, and different specificity of anti-HLA-G antibodies being used among studies, interpretation and clinical significance of HLA-G expression in cancers should be with caution.

Background Abnormal peripheral immunological features are associated with the progression of coronavirus disease 2019 (COVID-19). Methods Clinical and laboratory data were retrieved in a cohort of 146 laboratory-confirmed COVID-19 patients. Potential risk factors for the development of severe COVID-19 were evaluated. Results On admission, lymphocytes, CD3+, CD4+ and CD8+ T cells, eosinophils, and albumin and pre-albumin were dramatically lower, whereas neutrophils, and interleukin (IL)-10, C-reactive protein (CRP), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were significantly higher in severe cases. By the second week after discharge, all variables improved to normal levels. Covariate logistic regression results showed that the CD8+ cell count and CRP level were independent risk factors for severe COVID-19. Conclusion Lower peripheral immune cell subsets in patients with severe disease recovered to normal levels as early as the second week after discharge. CD8+ T cell counts and CRP levels on admission are independent predictive factors for severe COVID-19.

Objectives Pandemic COVID-19 has become a seriously public health priority worldwide. Comprehensive strategies including travel restrictions and mask-wearing have been implemented to mitigate the virus circulation. However, detail information on community transmission is unavailable yet. Methods From January 23 to March 1, 2020, 127 patients (median age: 46 years; range: 11–80) with 71 male and 56 female, were confirmed to be infected with the SARS-CoV-2 in Taizhou, Zhejiang, China. Epidemiological trajectory and clinical features of these COVID-19 cases were retrospectively retrieved from electronic medical records and valid individual questionnaire. Results The disease onset was between January 9 to February 14, 2020. Among them, 64 patients are local residents, and 63 patients were back home from Wuhan from January 10 to 24, 2020 before travel restriction. 197 local residents had definite close-contact with 41 pre-symptomatic patients back from Wuhan. 123 and 74 of them contact with mask-wearing or with no mask-wearing pre-symptomatic patients back from Wuhan, respectively. Data showed that incidence of COVID-19 was significantly higher for local residents close-contact with no mask-wearing Wuhan returned pre-symptomatic patients (19.0% vs. 8.1%, p

Background Pneumonia coronavirus disease 2019 (COVID-19) has became a pandemic. However, information on early risk factors for the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral positivity is not yet available. Methods In this prospective study, a cohort of 137 patients with confirmed SARS-CoV-2 were enrolled. Clinical information and laboratory data were retrieved from electronic medical records. Viral positivity duration was calculated by the interval from the day of confirmed SARS-CoV-2 positive results to the day SARS-CoV-2 testing showed negative results in these 137 patients with COVID-19. Early risk factors for the duration of SARS-CoV-2 viral positivity were evaluated. Results The median SARS-CoV-2 viral positivity duration is 12 days (range, 4 to ~45) for this cohort. Cox regression results showed a significantly shorter viral positivity duration was related to younger age (hazard ratio [HR], .658; P = .017); disease not being severe (HR, .653; P = .076); higher lymphocyte (HR, 1.464; P = .033), eosinophil (HR, 1.514; P = .020), and CD8+ T-cell (HR, 1.745; P = .033) counts; and lower IL-6 (HR, .664; P = .036) and IL-10 (HR, .631; P = .021). Multivariate analysis with covariable-adjusted results showed that the CD8+ T-cell count (HR, 2.376; P= .114) was a predominant risk factor for the duration of SARS-CoV-2 viral positivity. Conclusions Our findings show early laboratory parameters such as CD8+ T-cell count to be risk factors for the duration of SARS-CoV-2 viral positivity, which has significance in the control and prevention of the disease.

Objectives Host immune responses are indispensable to combat the disease. We report the dynamics of peripheral immune cells, cytokines, and human leucocyte antigen‐G (HLA‐G) and its receptor expressions in a patient suffering from critical COVID‐19 pneumonia to convalescence. Methods Clinical data of the patient were collected from medical records. The expressions of HLA‐G and receptors ILT2, ILT4 and KIR2DL4 in peripheral immune cells were measured with flow cytometry. Results From critical COVID‐19 to the convalescent stage, early lymphopenia was improved (median: 0.6 × 109 L−1 vs. 0.9 × 109 L−1, P = 0.009), and an obvious fluctuation in WBC and neutrophil counts was observed. Initially, low levels of CD4+ T cells (from 120 to 528 μL−1) and CD8+ T cells (from 68 to 362 μL−1) gradually increased to normal levels. Meanwhile, high IL‐6 (from 251.8 to 6.32 pg mL−1), IL‐10 (from 39.53 to 5.21 pg mL−1) and IFN‐γ (from 13.55 to 3.16 pg mL−1) levels decreased, and IL‐4 (from 2.36 to 3.19 pg mL−1) and TNF‐α (from 2.27 to 20.2 pg mL−1) levels increased quickly when the viral RNA returned negative. Moreover, the percentage of HLA‐G+ T cells, B cells and monocytes follows high–low–high pattern, while the percentage of receptors ILT2‐, ILT4‐ and KIR2DL4‐expressing cells remained relatively stable. Conclusion Our findings provide valuable information on the dynamics of early peripheral immunological responses in SARS‐CoV‐2 infection. CD4+ and CD8+ T cells, cytokines and HLA‐G+ immune cells are associated with the natural history of the critical COVID‐19 patient; however, future studies are necessary., Pneumonia COVID‐19 is threatening public health. Host immune responses are indispensable to combat the disease. In this paper, we report on the dynamics of early CD4+ and CD8+ T cells, cytokines and HLA‐G+ immune cells that are associated with the natural history of a critical COVID‐19 patient.

The clinical significance of metastasis‐associated in colon cancer‐1 (MACC1) has been investigated but the relevance of peripheral MACC1 levels was rather limited. Herein, our data revealed that plasma MACC1 levels in 117 colorectal cancer patients (CRC) were dramatically higher than that in normal controls (P < 0.001), and with a strong discrimination power between the two groups (AUC = 0.960, P < 0.001). Moreover, MACC1 is an independent prognostic factor for CRC patients. When clinical parameters stratified by MACC1low and MACC1high, MACC1 levels exhibited further significant predictive value. Summary, plasma MACC1 levels could be a useful prognostic and diagnostic biomarker, and could improve the prognostic value of traditional prognosticators for colorectal cancer patients.

The gloomy outcome of liver cancer is mainly due to the high rates of metastasis and recurrence, even after curative resection for early stage liver cancer. Our study was conducted to find the animal model suitable for the study of liver cancer metastasis. In our study, two liver cancer cells were obtained from N-nitrosodiethylamine (DEN) and N-nitrosomorpholine (NMOR) induced rats, and they were cultivated, screened and cloning cultivated. Bionomics of cells was analyzed. The results show that 2 cells had different metastatic potentiality. They were named Wrh-f2 and Wrh-s2, and they have the characteristics of Hepatocellular carcinoma cells. The bionomics of 2 cells showed: (1) The chromosome karyotype analysis showed that the mode of Wrh-f2 was 80–83 and Wrh-s2 was 55–57; (2) AFP positive cytoplasmic staining was observed in Wrh-f2 and Wrh-s2. Cytokeratin (CK) 7 and CK8 positive staining was present in Wrh-f2. CK8 positive staining was present in Wrh-s2; (3) The numbers of Wrh-f2 and Wrh-s2 that passed through the Transwells were 98 ± 12 and 55 ± 15;(4) Wrh-f2 had the significant higher colony formation (78%) than Wrh-s2(8%) (P in vivo and in vitro.

In order to study the traffic jams and congestion, this paper investigated the stability of a car-following model on the basis of synchronisation theory of complex network. By using the Lyapunov st...

The stability and Hopf bifurcation of a delayed SIS epidemic model with double epidemic hypothesis are investigated in this paper. We first study the stability of the unique positive equilibrium of the model in four cases, and we obtain the stability conditions through analyzing the distribution of characteristic roots of the corresponding linearized system. Moreover, we choosing the delay as bifurcation parameter and the existence of Hopf bifurcation is investigated in detail. We can derive explicit formulas for determining the direction of the Hopf bifurcation and the stability of bifurcation periodic solution by center manifold theorem and normal form theory. Finally, we perform the numerical simulations for justifying the theoretical results.

The global dynamical behaviors of a hexagonal centrifugal governor with a spring are expanded in this paper. The high-definition resolution phase diagrams are used to identify how the complex mode-locking behaviors arise with the parameters changed. By calculating the rotation number, it is unfolded that the interesting “Devils staircase” is presented with the parameter changed, meanwhile, the mode-locking structure is organized according to the broken Farey tree sequence. In addition, the fractal structure with self-similarity can also be observed in this system.

Differential expression of HLA-G has been observed among cancer types and tumors from individuals with the same type of cancer; however, its clinical significance is rather limited. In this study, expression and predictive relevance of HLA-G expression in 457 primary colorectal cancer (CRC, ncolon = 232, nrectal = 225) patients was investigated. Data showed 70.7% (323/457) of the CRC were HLA-G expression when the above 5% (HLA-GLow) was considered as positive, which wasn't associated with patient survival (p = 0.109). However, HLA-G expression above 55% (HLA-GHigh) was associated with a worse prognosis of CRC patients (p = 0.042). Furthermore, a shorter survival was found for the female (p = 0.042) and elder (p = 0.037) patients whose HLA-G expression was above HLA-GLow level. HLA-G expression above HLA-GHigh level showed a worse prognosis for female (p = 0.013), elder (p = 0.023), colon cancer (p = 0.016), advanced tumor burden (T3+4, p = 0.018), regional lymph node status (N1+2, p = 0.044), and advanced clinical stage patients (AJCC III+IV, p = 0.037). In conclusion, our results demonstrated for the first time that combination of differential lesion HLA-G expression notably improved the value of traditional survival prediction for CRC patients.

The global structure of nonlinear response of mechanical centrifugal governor, forming in two-dimensional parameter space, is studied in this paper. By using three kinds of phases, we describe how responses of periodicity, quasi-periodicity and chaos organize some self-similarity structures with parameters varying. For several parameter combinations, the regular vibration shows fractal characteristic, that is, the comb-shaped self-similarity structure is generated by alternating periodic response with intermittent chaos, and Arnold’s tongues embedded in quasi-periodic response are organized according to Stern–Brocot tree. In particular, a new type of mixed-mode oscillations (MMOs) is found in the periodic response. These unique structures reveal the natural connection of various responses between part and part, part and the whole in parameter space based on self-similarity of fractal. Meanwhile, the remarkable and unexpected results are to contribute a valid dynamic reference for practical applications with respect to mechanical centrifugal governor.

In this paper, the stochastic stability and bifurcation of a stochastic differential equation modeling a hexagonal governor system are investigated. More precisely, we introduced the stochasticity into the model based on the parameter perturbation, and simplified the stochastic hexagonal governor system by using the stochastic center manifold theory and stochastic average theory. Besides, we investigated the local stochastic stability and global stochastic stability of the stochastic hexagonal governor system through the use of the Lyapunov exponent and singular boundary theory. And based on the invariant measure and stationary probability density, we studied the stochastic bifurcation of the stochastic hexagonal governor system. Finally, we obtained some new criteria to ensure the stochastic pitchfork bifurcation and P-bifurcation of the stochastic hexagonal governor system.

An organization structure of global oscillation with respect to a cracked rotor system with oil-film force is investigated in this paper. We profit from GPU cluster parallel computing to present a number of high-quality phase diagrams, and exhibit global dynamic characteristics of the system. An interesting scenario, “eye” of chaos, is discovered in this cracked rotor system, emerging as the accumulation limit of forward and reverse period-doubling bifurcation cascades. In this system, it is a common phenomenon that the vibration response of the rotor presents three typical characteristics in parameter space with the rotation speed increasing. Moreover, these phase diagrams assist us to identify multi-attractor coexisting that makes the dynamics behavior of this system become more enrich and complex. These results we represent get us better to understand the nonlinear response of the cracked rotor system and are beneficial to control and diagnose the crack.

Uncaria genus( Rubiaceae) contains 34 species all over the world,of which 11 species and one variant are present in China. Five species,namely U. rhynchophylla,U. macrophylla,U. hirsuta,U. sinensis and U. sessilifructus,are documented in Chinese Pharmacopoeia as the raw materials of Uncariae Ramulus Cum Uncis. Indole alkaloids are the characteristic constituents of Uncaria plants,in addition to triterpenes,lignans and flavones. This paper reviews the progress of indole alkaloids and their distribution within the five Uncaria species documented in Chinese Pharmacopoeia for better understanding the active constituents of Uncariae Ramulus Cum Uncis.

Background: The existing meta-analyses and randomized studies on comparing the effects of carvedilol and metoprolol are of poor quality, with small sample sizes, and involve a homogeneous population. Therefore, to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to compare the mortality benefits of carvedilol with metoprolol head to head and determine the better beta-blocker in acute myocardial infarction (AMI) setting. Methods: Seven electronic databases including Web of Science, Embase, PubMed, Wanfang Data, Scopus, Science Direct, Cochrane Library will be searched in May 2021 by 2 independent reviewers. The protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. The primary outcome is all-cause mortality; secondary outcomes include complex cardiovascular events, sudden death, cardiovascular death, reinfarction, revascularization, readmission, ventricular arrhythmias, and drug withdrawal for all causes except death. All outcomes are pooled on random-effect model. A P value of

The structure of complex oscillations with two time scales generated by a novel memristor-based Shinriki’s circuit is studied in detail. Employing the stability phase diagrams, we identify the parameter regions of mixed-mode oscillations (MMOs) produced by each state variable, and classify the fast and slow properties of state variables according to the characteristics of these MMOs. Additionally, we exhibit the self-organizations of phases and describe how they are interconnected and how their complexity unfolds with control parameters varying. For several parameter combinations, in addition to recently reported shrimp-shaped cascades and “eye” of chaos, two kinds of interesting self-organizations, the shrimp cascade covered by four distinct numbers of peaks and “eye” of anti-chaos, are also discovered. A significant feature of these structures indicates that the fast-slow dynamics of the system depend not only on the state variables but also strongly on the parameter interval. The results of theoretical analyses obtained are verified by the Multisim simulation experiments. This paper will contribute to understanding the profound dynamical behaviors of the memristor-based circuit and open the possibility of studying hitherto unobserved phenomena.

// Zejun Fang 1 , Aifen Lin 2 , Jiaoe Chen 1 , Xiaomin Zhang 1 , Hong Liu 3 , Hongzhang Li 1 , Yanyan Hu 1 , Xia Zhang 2 , Jiangang Zhang 2 , Lanlan Qiu 1 , Lingming Mei 1 , Jimin Shao 4 , Xiang Chen 1 1 Central Laboratory, Sanmen People’s Hospital of Zhejiang, Sanmen, Zhejiang, 317100, China 2 Human Tissue Bank, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, 317000, China 3 Zhejiang Normal University - Jinhua People’s Hospital Joint Center for Biomedical Research, Jinhua, Zhejiang, 321004, China 4 Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China Correspondence to: Xiang Chen, email: sychenxiang@126.com Jimin Shao, email: shaojimin@zju.edu.cn Keywords: CREB1, ribonucleotide reductase small subunit M2, aggressiveness, colorectal cancer Received: March 16, 2016 Accepted: October 17, 2016 Published: October 27, 2016 ABSTRACT As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation. Knockdown of CREB1 decreased the expression of RRM2 at both mRNA and protein levels. Moreover, knockdown of RRM2 attenuated CREB1-induced aggressive phenotypes of CRC cells in vitro and in vivo . Analysis of the data from TCGA database and clinical CRC specimens with immunohistochemical staining also demonstrated a strong correlation between the co-expression of CREB1 and RRM2. Decreased disease survivals were observed in CRC patients with high expression levels of CREB1 or RRM2. Our results indicate CREB1 as a critical transcription factor of RRM2 which promotes tumor aggressiveness, and imply a significant correlation between CREB1 and RRM2 in CRC specimens. These may provide the possibility that CREB1 and RRM2 could be used as biomarkers or targets for CRC diagnosis and treatment.

Ethnopharmacological relevance Anoectochilus roxburghii (Wall.) Lindl. 1832 is an herbal medicine used to treat diabetes in China. Considering that Anoectochilus roxburghii polysaccharose (ARP) is the main constituent of Anoectochilus roxburghii, the present study is aimed to investigate the renal protection of ARP and its possible mechanism in diabetic mice. Materials and methods Institute of Cancer Research (ICR) mice were induced to diabetes with high-fat diet (HFD) and low-dose streptozotocin (STZ). ARP (100, 300 mg/kg) was orally administrated to diabetic mice once a day for consecutive 15 days. The fasting glucose level, expressions of key proteins of p38 MAP kinase cascade, inflammatory factors, fibronectin (FN) and the activities of matrix metalloproteinases (MMPs) were measured. Furthermore, the histological examination of the separated kidneys was also carried out. Results Compared with the diabetic mice, ARP administration induced a significant decrease in blood glucose level and improved the body weight of diabetic mice. In addition, ARP inhibited the expression of renal p38 MAP kinase cascade and its downstream inflammatory factors including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), FN as well as MMP2/9. Moreover, the histological examination showed an apparent reduction of mesangial matrix deposition and damage of microvascular structure after ARP administration. Conclusions The protective effects of ARP on diabetic renal damage may be attributed to the inhibition of p38 MAP kinase cascade and then attenuating the inflammatory responses and high glucose-induced renal damage.

The up-regulated metastasis-associated in colon cancer 1 (MACC1) expression and its clinical significance has been explored in a varity of malignancies. In this study, lesion MACC1 expression in 503 CRC patients (Ncolon = 332, Nrectal = 171) were analyzed with immunohistochemistry, and its correlation with clinical parameters, patient survival, and its impact on prognostic stratification were evaluated. Data revealed the survival of patient with MACC1high is markedly worse than that of MACC1low (mean overall survival: 80.1 vs. 90.4 months; p = 0.001) and is an independent prognostic predictor (hazard ratio = 1.533; p = 0.005). More importantly, for the first time, we demonstrated that MACC1 status exhibited a significantly prognostic power for stratified clinical parameters such as patient age and gender, particular TNM status, and distinct AJCC disease stage. In summary, our findings indicated that MACC1 is a valuable prognostic and risk stratification biomarker for colorectal cancer patients.

Molecular research is increasingly dependent on high-quality biobanked biospecimens. Preanalytical variables in tissue processing and preservation may influence the RNA quality and research results. Hence, the effect of long-term storage and clinicopathological parameters on RNA quality needs to be elucidated.Ninety gastric cancer tissue samples were collected and fresh-frozen in a -80°C freezer for 12 years (2006-2017). The histology was assessed and RNA integrity number (RIN) was detected by an Agilent 2100 Bioanalyzer. The impact of storage duration on RNA integrity and histomorphology was analyzed. The difference between RIN values and clinical variables was analyzed. Correlations between pathological parameters such as tumor cell percentage, stroma percentage, necrosis extent, cellularity, and RIN were assessed, respectively.Long-term storage at -80°C for 12 years did not adversely affect RNA integrity and histomorphology. RNA integrity was also not influenced by tumor location, estimated blood loss, cold/warm ischemia time, and surgical approach. However, RIN values were significantly correlated with the tumor cell percentage and stroma percentage. Gastric cancer tissues with higher tumor cell percentage or lower stroma percentage had higher RIN values.RNA quality of fresh-frozen gastric cancer tissues is influenced by clinical and histological parameters. Standard tissue collection procedure and histological quality control remain essential for tissue biobanking.

The ectopic HLA-G expression in malignancies has been extensively explored and clinical significance of the molecule was widely acknowledged. Besides previously well-documented seven isoforms (HLA-G1~-G7), other novel isoforms of HLA-G have been reported but their clinical relavenace remians evaluated. In this study, lesion HLA-G expression in 379 case-matched serial section primary colorectal cancers (CRC) were evaluated with mAb 4H84 (recognizing an epitope in HLA-G α1 domain), and mAb 5A6G7 (recognizing an epitope encoded by intron 4), respectively. Data showed that HLA-G positive staining with mAbs 4H84 and 5A6G7 was 70.7 and 60.4%, respectively. When percentage of HLA-G expression detected with mAb 4H84 subtracted that with mAb 5A6G7, the difference (ΔHLA-G) with negative (ΔHLA-Gneg), comparable (ΔHLA-Gcom) and positive (ΔHLA-Gpos) were observed in 64 (16.9%), 159 (42.0%), and 156 (41.2%) cases, respectively. Noteworthy, unexpected immunostaining was observed in 44 (11.6%) lesions that no staining was detected with mAb 4H84 but positive with mAb 5A6G7 (4H84neg5A6G7pos). This staining pattern was unpredictable because all seven known HLA-G isoforms containing the α 1 domain could be recognized by the mAb 4H84. Moreover, patients with ΔHLA-Gneg had obviously better survival than those with ΔHLA-Gcom and ΔHLA-Gpos (p = 0.017), and ΔHLA-G could be an independent prognostic factor for CRC patients (p = 0.008). Our findings provides the first report that potential unidentified HLA-G isoforms is of distinct clinical significance in CRC patients.

Regarding single bus transfer junction as a research object, this paper constructs the urban traffic network models with multi-weights taking different bus lines in bus transfer junction as the network nodes, that is, the urban traffic network with multi-weights is given different properties weights at every edge. According to the method of network split, the complex network with multi-weights is split into several different single weighted complex networks. Then, we study the global synchronization of the new network model by changing congestion degrees, transfers coefficient and passenger flow density between different bus lines. Finally, analytical and simulated results are given to show the impact of different properties weights to the public traffic network balance.

Ethnopharmacological relevance Anoectochilus roxburghii is a traditional Chinese herb used for treatment of diabetes and some other diseases. Anoectochilus roxburghii polysaccharose (ARP) is the main constituent of Anoectochilus roxburghii. The present study aimed to investigate the antidiabetic effects of ARP in diabetic mice induced by high-fat diet and streptozotocin. Materials and methods Two doses of ARP (100 or 300 mg/kg) were administered once daily for 25 days to diabetic mice. To evaluate the antidiabetic effects of ARP, the fasting glucose levels, aspartate aminotransferase (AST), alanine transaminase (ALT) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) content, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and liver glycogen were examined. Furthermore, histological examinations were carried out on the separated pancreas and liver of mice. Results Compared with untreated diabetic mice, ARP (100 or 300 mg/kg) caused a significant decrease in blood glucose levels, activities of AST and ALT, and MDA contents, and a significant increase in liver glycogen contents, SOD activities, thymus index and spleen index. Simultaneously, the alteration in lipid metabolism was partially attenuated as evidenced by decreased serum TC, TG and LDL-C concentrations in diabetic mice. In addition, histological examinations showed that administration of ARP (100 or 300 mg/kg) significantly attenuated the pathologic lesions in pancreas and liver of diabetic mice, and improved pancreas and liver function. Conclusions The antidiabetic activity of ARP may be attributed to the improvement of glucose and lipid metabolism, increase of immune protection and reduction of oxidative stress.

Uncaria rhynchophylla (Gou-Teng) as the monarch herb of many formulae (Fufang), e.g. "Tian-Ma-Gou-Teng-Yin," "Ling-Jiao-Gou-Teng-Yin," and "Yi-Gan-San", is a famous traditional Chinese medicine documented in the Chinese pharmacopoeia for mental and cardiovascular diseases. In the traditional Chinese medicine system, only the hook-bearing stems are used as the crude materials for Gou-Teng, and the hooks are always considered more effective than the stems. Focusing on the mono-herb and its active constituents from combinatorial formulae is the core idea of reductionism of traditional Chinese medicine theory. Detailed liquid chromatography with mass spectrometry analysis on the hooks of U. rhynchophylla was performed to profile the chemical constituents based on tandem mass spectrometry fragmentation and UV absorption. Under the guidance of liquid chromatography with ion trap/time-of-flight mass spectrometry, one new indole alkaloid triglycoside (1), together with five known compounds 2-6 as the main constituents, were isolated from the hooks of U. rhynchophylla by various column chromatography methods. Compound 1 showed moderate activity on MT1 and MT2 melatonin receptors with agonistic rates of 79.6 and 46.3% at the concentration of 1 mM. This dereplication strategy can be equally applicable to rapidly disclose the active constituents of other Chinese herbs through targeted purification.

Uncaria rhynchophylla (Gou-Teng in Chinese) is officially documented in Chinese pharmacopoeia as one of the authentic sources for the crude drug of Gou-Teng which has long been used for mental and cardiovascular diseases. Indole alkaloids are the characteristic constituents responsible for the desired hypotensive effect; however, the psychiatric active constituents of Gou-Teng are still unclear. According to traditional Chinese medicine theory, only the hook-bearing stems of U. rhynchophylla are used as the crude materials for Gou-Teng, while its leaves and fruits are scarcely used. The present study aimed to compare the metabolic fingerprints of different parts (hooks, stems, leaves and fruits) of U. rhynchophylla by LC-DAD-MS/MS analysis and further evaluate their psychiatric activities on HEK293 cell line in vitro. A total of 38 constituents including 26 alkaloids, six flavonoids, two triterpenoids, two chlorogenic acid analogs and two other compounds were characterized. The different parts of U. rhynchophylla can be well differentiated from their chemical profiles. Leaves displayed the most potent activity on both MT1 and MT2 receptors, with agonistic rates of 39.7% and 97.6%. For 5-HT1A and 5-HT2C receptors, hooks showed the strongest activity with agonistic rates of 92.6% and 83.1%, respectively. This investigation provided valuable information for understanding the chemical divergence between different parts of U. rhynchophylla, and their substantial bases for psychiatric purposes.

On the basis of traditional weighted network, we study a new complex network model with multi-weights, which has one or several different types of weights between any two nodes. According to the method of network split, we split the complex network with multi-weights into several different complex networks with single weight, and study its global synchronization. Taking bus lines as the network nodes, a new public traffic roads network model with multi-weights is established by the proposed network model and space R modeling approach. Then based on the Lyapunov stability theory, the criteria is designed for the global synchronization of the public traffic roads networks with multi-weights. By changing the different weights and taking the Lorenz chaotic system for example, some numerical examples are given to discuss the balance of the whole public traffic roads network.

We study the bifurcations and sliding mode control of chaotic vibrations in an autonomous system. More precisely, a Hopf bifurcation controller is designed so as to control the unstable subcritical Hopf bifurcation to the stable supercritical Hopf bifurcation. Research result shows that the control method can work very well in Hopf bifurcation control. Besides, we controlled the system to any fixed point and any periodic orbit to eliminate the chaotic vibration by means of sliding mode method. And the numerical simulations were presented to confirm the effectiveness of the controller.

Under the framework of drive-response systems, a new method of complete dislocated general hybrid projective synchronization (CDGHPS) is proposed. In this design, every state variable of drive system does not equal the corresponding state variable of response system, but equal other ones of response system while evolving in time. Especially, complete dislocated synchronization, dislocated anti-synchronization and projective dislocated synchronization can be considered all as the special cases of the proposed method. In addition, this method is applied to secure communication through chaotic masking, the unpredictability of the scaling factor in projective synchronization can additionally enhance the security of communication. In consideration of random white noise, we study the random white noise perturbing for the transmission of an information signal. Finally, eliminate noise using wavelet transform. Numerical simulations are given to show the effectiveness of these methods.