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Vascular aging, characterized by brain endothelial cells (ECs) senescence and dysfunction, has been known to lead to various age-related cerebrovascular and neurodegenerative diseases. However, its underlying mechanisms remain elusive. ECs derived microvesicles (EMVs) and exosomes (EEXs) carry the characteristics of parent cells and transfer their contents to modulate the functions of recipient cells, holding the potential to evaluate or regulate vascular aging. Here, we found that young or aged ECs released EMVs were more effective than their released EEXs on alleviating or aggravating mice cerebrovascular and brain aging as indicated by SA-β-gal staining, cerebral blood flow, blood brain barrier function, aging related markers and cognitive ability test. We further identified that these EMVs regulated cerebrovascular and brain aging by transferring miR-17-5p and could modulate ECs senescence and functions via miR-17-5p/PI3K/Akt pathway. Plasma EMVs and their contained miR-17-5p (EMV-miR-17-5p) were significantly increased or decreased in the elderly, and were closely correlated with vascular aging. Receiver Operating Characteristic (ROC) analysis showed that the area under the curve was 0.724 for EMVs, 0.77 for EMV-miR-17-5p and 0.815 for their combination for distinguishing vascular aging. Our results revealed the novel roles for EMVs that could more effectively modulate vascular and brain aging than EEXs by regulating ECs functions through miR-17-5p/PI3K/Akt pathway, and also suggested that EMVs and EMV-miR-17-5p represent promising biomarkers and therapeutic targets for vascular aging.

BackgroundAnatidae contains numerous waterfowl species with great economic value, but the genetic diversity basis remains insufficiently investigated. Here, we report a chromosome-level genome assembly of Lion-head goose (Anser cygnoides), a native breed in South China, through the combination of PacBio, Bionano, and Hi-C technologies.FindingsThe assembly had a total genome size of 1.19 Gb, consisting of 1,859 contigs with an N50 length of 20.59 Mb, generating 40 pseudochromosomes, representing 97.27% of the assembled genome, and identifying 21,208 protein-coding genes. Comparative genomic analysis revealed that geese and ducks diverged approximately 28.42 million years ago, and geese have undergone massive gene family expansion and contraction. To identify genetic markers associated with body weight in different geese breeds, including Wuzong goose, Huangzong goose, Magang goose, and Lion-head goose, a genome-wide association study was performed, yielding an average of 1,520.6 Mb of raw data that detected 44,858 single-mucleotide polymorphisms (SNPs). Genome-wide association study showed that 6 SNPs were significantly associated with body weight and 25 were potentially associated. The significantly associated SNPs were annotated as LDLRAD4, GPR180, and OR, enriching in growth factor receptor regulation pathways.ConclusionsWe present the first chromosome-level assembly of the Lion-head goose genome, which will expand the genomic resources of the Anatidae family, providing a basis for adaptation and evolution. Candidate genes significantly associated with different goose breeds may serve to understand the underlying mechanisms of weight differences.

Infectious bronchitis (IB) is a highly contagious avian disease caused by infection with infectious bronchitis virus (IBV), which seriously affects the development of the global poultry industry. The distribution of TW I-type IBV in China has increased in recent years, becoming a widespread genotype. We previously isolated a TW I-type IBV strain termed CK/CH/GD/GZ14 in 2014, but its pathogenicity and possibility for vaccine development were not explored. Therefore, this research aimed to develop a live-attenuated virus vaccine based on the CK/CH/GD/GZ14 strain. The wild type IBV CK/CH/GD/GZ14 strain was serially passaged in SPF embryos for 145 generations. The morbidity and mortality rate of wild-type strain in 14 day-old chickens is 100% and 80% respectively, while the morbidity rate in the attenuated strain was 20% in the 95th and 105th generations and there was no death. Histopathological observations showed that the pathogenicity of the 95th and 105th generations in chickens was significantly weakened. Further challenge experiments confirmed that the attenuated CK/CH/GD/GZ14 strain in the 95th and 105th generations could resist CK/CH/GD/GZ14 (5th generation) infection and the protection rate was 80%. Tracheal cilia stagnation, virus shedding, and viral load experiments confirmed that the 95th and 105th generations provide good immune protection in chickens, and the immunogenicity of the 105th generation is better than that of the 95th generation. These data suggest that the attenuated CK/CH/GD/GZ14 strain in the 105th generation may be applied as a vaccine candidate against TW I-type IBV. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00419-2.

Flooding is the main natural factor in snail diffusion, and it has a negative impact on schistosomiasis transmission. There are few studies on the spread and migration of snails following a flood; therefore, we aimed to investigate the influence of flooding on snail diffusion and explore the characteristics and laws of snail diffusion in Jiangxi Province. By using a retrospective survey and cross-sectional survey, the data on snail spreading in Jiangxi Province from 2017 to 2021 were collected. The distribution, nature, and area of snail spread were systematically analyzed in combination with the hydrological situation, types of region, and types of flood. From 2017 to 2021, a total of 120 snail-spread environments were found, including in 92 hilly areas and in 28 lake areas. The areas caused by flood and by other means numbered 6 and 114, respectively. The proportions of recurrence, expansion, and first-time occurrences were 43.42%, 38.16%, and 18.42%, respectively, and the 14 new snail environments were only distributed in the hilly areas. With the exception of 2018, the ratio of snail-spread areas in the hilly region was higher than that in lake region in other years. The average density of live snails was 0.0184–1.6617 no./0.1 m2 and 0.0028–0.2182 no./0.1 m2 in the hilly region. Among the 114 environments affected by floods, 86 consisted of hilly environments, including 66 spreading environments affected by rainstorm floods, and 20 rainstorm debris flow environments. There were 28 lake areas, of which 10 were in the Jiangxi section of Yangtze River and were affected by rainstorm floods. Snail spread following flooding has a certain ‘lag effect,’ and = simple annual changes in hydrological characteristics have little effect on the diffusion of snails or on their density = in the affected environment, but it is more closely related to local floods. The hilly environments are more susceptible to floods than the lake region, and the risk of snail spread is much higher in the hilly than in the lake region.

Objective: People suffering from coronavirus disease 2019 (COVID-19) are prone to develop pulmonary fibrosis (PF), but there is currently no definitive treatment for COVID-19/PF co-occurrence. Kaempferol with promising antiviral and anti-fibrotic effects is expected to become a potential treatment for COVID-19 and PF comorbidities. Therefore, this study explored the targets and molecular mechanisms of kaempferol against COVID-19/PF co-occurrence by bioinformatics and network pharmacology.Methods: Various open-source databases and Venn Diagram tool were applied to confirm the targets of kaempferol against COVID-19/PF co-occurrence. Protein-protein interaction (PPI), MCODE, key transcription factors, tissue-specific enrichment, molecular docking, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to clarify the influential molecular mechanisms of kaempferol against COVID-19 and PF comorbidities.Results: 290 targets and 203 transcription factors of kaempferol against COVID-19/PF co-occurrence were captured. Epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase SRC (SRC), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 8 (MAPK8), RAC-alpha serine/threonine-protein kinase (AKT1), transcription factor p65 (RELA) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA) were identified as the most critical targets, and kaempferol showed effective binding activities with the above critical eight targets. Further, anti-COVID-19/PF co-occurrence effects of kaempferol were associated with the regulation of inflammation, oxidative stress, immunity, virus infection, cell growth process and metabolism. EGFR, interleukin 17 (IL-17), tumor necrosis factor (TNF), hypoxia inducible factor 1 (HIF-1), phosphoinositide 3-kinase/AKT serine/threonine kinase (PI3K/AKT) and Toll-like receptor signaling pathways were identified as the key anti-COVID-19/PF co-occurrence pathways.Conclusion: Kaempferol is a candidate treatment for COVID-19/PF co-occurrence. The underlying mechanisms may be related to the regulation of critical targets (EGFR, SRC, MAPK3, MAPK1, MAPK8, AKT1, RELA, PIK3CA and so on) and EGFR, IL-17, TNF, HIF-1, PI3K/AKT and Toll-like receptor signaling pathways. This study contributes to guiding development of new drugs for COVID-19 and PF comorbidities.

The goal of the study was testing the effects of chlorogenic acid (CA) supplementation on small intestine healthiness, growth performance, oxidative stress, inflammatory response, and blood biochemical indices in specific-pathogen-free (SPF) chickens after infection with Clostridium perfringens (CP) type A. In this study, 324 1-day-old male SPF chickens were randomly distributed into 6 groups: control group; CA group; CP infection group; CA + CP group; antibiotic group; antibiotic + CP group. All 1-day-old chickens were fed with CA or antibiotic in corresponding treatment group for 13 d. On the 14 d, the chickens in corresponding infection group were challenged with CP type A for 3 d. Samples in each group were collected when the chickens were 17 and 21 d old. This study proves for the first time that CA, a Chinese herbal medicine, can effectively improve growth performance, inhibit small intestine structural damage, improve antioxidant capacity, inhibit damage to ileal mucosal layer construction and tight junctions, inhibit inflammatory cytokines, and ameliorate blood biochemical indices. Therefore, this study provides data for CA being able to effectively alleviate small intestine damage caused by CP type A infection in chickens.

To study the effects of antibacterial peptides (ABPs) on feeding broilers, this experiment compared the 2 combinations of ABP with antibiotics by separately adding the supplement to the diet of 818 broilers as follows—antibiotics, Pratt and Full-tide, and Pratt and plant essential oil—and then the effect of them on production performance, immune function, antioxidant capacity, serum biochemical indicators, and microorganisms of the experimental flocks was investigated and compared. It was found that the aforementioned indicators among the 2 groups of ABP and the antibiotic group were close to or even better than those of antibiotics, and the combination added with plant essential oils had generally better effects. These results indicated that ABPs could improve economic benefits by promoting growth, preventing disease, and reducing the rate of death. This study deepened the research on the action mechanism of ABPs and not only explored the feasibility of ABPs as a novel feed additive for broilers but also provided experimental data and theoretical basis for the application of ABPs.

Autophagy and apoptosis, which are important processes for host immunity, are commonly exploited by viruses to facilitate their survival. However, to the best of our knowledge, very few studies have researched the mechanisms of action of the autophagic and apoptotic signaling pathways following viral infection. Thus, the present study aimed to investigate the mechanisms of action of growth arrest and DNA-damage-inducible β (GADD45β), an important resistance gene involved in the host resistance to ALV-J. Both ALV-J infection and the overexpression of GADD45β inhibited autophagy during the early stages, which prevented the autophagosomes from binding to the lysosomes and resulted in an incomplete autophagic flux. Notably, GADD45β was discovered to interact with MEKK4 in DF-1 cells. The genetic knockdown of GADD45β and MEKK4 using small interfering RNA-affected ALV-J infection, which suggested that ALV-J may promote the binding of GADD45β to MEKK4 to activate the p38MAPK signaling pathway, which subsequently inhibits autophagy. Furthermore, ALV-J was revealed to affect the autophagic pathway prior to affecting the apoptotic pathway. In conclusion, to the best of our knowledge, the present study was the first to investigate the combined effects of ALV-J infection on autophagy and apoptosis, and to suggest that ALV-J inhibits autophagy via the GADD45β/MEKK4/p38MAPK signaling pathway.

Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells is a pleiotropic hormone with beneficial potential related to islet function, diet control, glucose homeostasis, inflammation r...

Asthma patients may increase their susceptibility to SARS-CoV-2 infection and the poor prognosis of coronavirus disease 2019 (COVID-19). However, anti-COVID-19/asthma comorbidity approaches are restricted on condition. Existing evidence indicates that luteolin has antiviral, anti-inflammatory, and immune regulation capabilities. We aimed to evaluate the possibility of luteolin evolving into an ideal drug and explore the underlying molecular mechanisms of luteolin against COVID-19/asthma comorbidity. We used system pharmacology and bioinformatics analysis to assess the physicochemical properties and biological activities of luteolin and further analyze the binding activities, targets, biological functions, and mechanisms of luteolin against COVID-19/asthma comorbidity. We found that luteolin may exert ideal physicochemical properties and bioactivity, and molecular docking analysis confirmed that luteolin performed effective binding activities in COVID-19/asthma comorbidity. Furthermore, a protein–protein interaction network of 538 common targets between drug and disease was constructed and 264 hub targets were obtained. Then, the top 6 hub targets of luteolin against COVID-19/asthma comorbidity were identified, namely, TP53, AKT1, ALB, IL-6, TNF, and VEGFA. Furthermore, the enrichment analysis suggested that luteolin may exert effects on virus defense, regulation of inflammation, cell growth and cell replication, and immune responses, reducing oxidative stress and regulating blood circulation through the Toll-like receptor; MAPK, TNF, AGE/RAGE, EGFR, ErbB, HIF-1, and PI3K–AKT signaling pathways; PD-L1 expression; and PD-1 checkpoint pathway in cancer. The possible “dangerous liaison” between COVID-19 and asthma is still a potential threat to world health. This research is the first to explore whether luteolin could evolve into a drug candidate for COVID-19/asthma comorbidity. This study indicated that luteolin with superior drug likeness and bioactivity has great potential to be used for treating COVID-19/asthma comorbidity, but the predicted results still need to be rigorously verified by experiments.

Autophagy is a conserved process by which cells maintain homeostasis. However, abnormalities in autophagy can lead to the development of various diseases, including cancer. Avian leukosis virus Subgroup J (ALV-J) is an oncogenic exogenous retrovirus, which induces severe immunosuppression and development of tumors in susceptible host. This study reveals for the first time that ALV-J inhibits autophagy through the envelope protein gp37. Here we demonstrate that envelope protein gp37 blocks the fusion of autophagosomes to lysosomes and induces incomplete autophagy. Interestingly, additional experiments revealed that the host chaperone protein TCP1 is also an autophagy inhibitor and blocking the process of autophagic flow in DF-1 cells. Through immunoprecipitation assays, we found that TCP1 interacts with gp37. In addition, TCP1 knockdown also abolished gp37-mediated inhibition of autophagy in DF-1 cells. Furthermore, TCP1 mediates gp37 of ALV-J to inhibit autophagy through activating AKT for promoting viral replication in DF-1 cells.

Subgroup J avian leukosis virus (ALV-J) is a highly oncogenic retrovirus that has been devastating the global poultry industry since the late 1990s. The major infection model of ALV-J is vertical transmission, which is responsible for the congenital infection of progeny from generation to generation. Increasing evidence has suggested that extracellular vesicles (EVs) derived from virus-infected cells or biological fluids have been thought to be vehicles of transmission for viruses. However, the role of EVs in infection and transmission of ALV-J remains obscure. In the present study, semen extracellular vesicles (SE) were isolated and purified from ALV-J-infected rooster seminal plasma (SE-ALV-J), which was shown to contain ALV-J genomic RNA and partial viral proteins, as determined by RNA sequencing, reverse transcription-quantitative PCR and Western blotting. Furthermore, SE-ALV-J was proved to be able to transmit ALV-J infection to host cells and establish productive infection. More importantly, artificial insemination experiments showed that SE-ALV-J transmitted ALV-J infection to SPF hens, and subsequently mediated vertical transmission of ALV-J from the SPF hens to the progeny chicks. Taken together, the results of the present study suggested that ALV-J utilized host semen extracellular vesicles as a novel means for vertical transmission, enhancing our understanding on mechanisms underlying ALV-J transmission.

Pasteurella multocida, an important gram-negative pathogen that mainly inhibits the upper respiratory tracts of domestic and wild animals such as chicken, duck, cattle and pig, which can cause cholera fowl, haemorrhagic septicaemia and infectious pneumonia. Currently, the prevalence and infection of P. multocida is still one of the most serious threats to the poultry industry in China, but studies on its characteristics are still insufficient. Here, this study was conducted to isolate and identify P. multocida in infected ducks and determined the leading serotypes and epidemiology of the diseases this pathogen causes. Results indicated that all the isolates were positive for KMT1 gene and the PCR amplified products were approximately 460 bp, demonstrating that these strains were all P. multocida. Moreover, all the isolated strains were identified as capsular type A and lipopolysaccharide type L1. Virulence factor identification results revealed that all strains possessed genes related to pili, adhesin, iron metabolism and uptake. In contrast, toxin coding gene (toxA) and sialidase encodes genes (nan B and nan H) were not detected in any isolates. The drug susceptibility results indicated that all the isolates were resistant to Lincomycin, Chloramphenicol, Clindamycin and Oxacillin but were sensitive to Ceftriaxone and Cefalotin. The animal experiments were also performed to further determine the pathogenicity of these isolated strains. Animal experiment revealed that the liver, kidney, and heart of infected ducks were swollen and had bleeding spots. We also observed hepatocyte hypertrophy, hepatic sinus congestion and single-cell infiltration in infected ducks through H&E staining. In summary, this study demonstrated that all the isolated strains belong to capsular A and lipopolysaccharide type L1 P. multocida, but their virulence factors, drug resistance and pathogenicity were different.

Although the combined cooling, heating and power (CCHP) microgrid is feasible for achieving a high energy utilization efficiency, the fluctuation of energy sources, such as a photovoltaic system and multiple loads, may affect the safety, economics and stability in CCHP microgrid operation. For this reason, this paper establishes a mathematical model using a multi-objective optimization mechanism for resolving the influence of economy and energy allocation in the mixed photovoltaic type CCHP microgrid. It is based on analytic hierarchy process (AHP) to determine the individual weight of objective function optimization for the multi-objective power capacity allocation. The improved artificial bee colony (IABC) based on the whale search and dynamic selection probability can achieve an optimization solution, reaching a stable operation state and reasonable capacity configuration in the microgrid system. The performance results confirm that the proposed algorithm is superior to others in both convergence speed and accuracyfor the capacity allocation of the CCHP microgrid.

H9N2 subtype avian influenza virus (H9N2 AIV) is a low pathogenic virus that is widely prevalent all over the world. H9N2 AIV causes immunosuppression in the host and often leads to high rates of mortality due to secondary infection with Escherichia. Due to the drug resistance of bacteria, many antibiotics are not effective in the treatment of secondary bacterial infection. Therefore, the purpose of this study is to find effective nonantibiotic drugs for the treatment of H9N2 AIV infection-induced secondary bacterial infection and inflammation. This study proves, for the first time, that baicalin, a Chinese herbal medicine, can regulate Lactobacillus to replace Escherichia induced by H9N2 AIV, so as to resolve the intestinal flora disorder. In addition, baicalin can effectively prevent intestinal bacterial translocation of SPF chickens’ post-H9N2 AIV infection, thus inhibiting secondary bacterial infection. Furthermore, baicalin can effectively treat H9N2 AIV-induced inflammation by inhibiting intestinal structural damage, inhibiting damage to ileal mucus layer construction and tight junctions, improving antioxidant capacity, affecting blood biochemical indexes, and inhibiting the production of inflammatory cytokines. Taken together, these results provide a new theoretical basis for clinical prevention and control of H9N2 AIV infection-induced secondary bacterial infection and inflammation.

Control of ALV-J in breed of chicken is still a serious issue that need more attention to be paid. Vertical transmission of ALV-J often give rise to more adverse pathogenicity. However, the way to elimination of ALV-J underlying vertical transmission remains not-well understood. In addition, effective vaccines or drugs have not been developed to prevent and control the transmission of ALV-J so far. CD81, a member of the tetraspanins superfamily, plays important roles in regulating membrane proteins, facilitating cells adhesion or fusion, and also participates in viral infection. The purpose of this study was to investigate whether antibodies against certain tetraspanins affect infection of ALV-J. Here, we showed that anti-CD81 antibody could inhibit viral RNA and protein level. We also found that anti-CD81 antibody interacts with viral protein p27, p32 and gp37. Moreover, treatment with antibody to CD81 can effectively prevent the vertical transmission of ALV-J in animal model. Collectively, current study provides new avenues for the control of ALV-J transmission.

The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of Lycium ruthenicum, a traditional herb for treatment of postmenopausal metabolic disorders. Structural identification indicated that LRP-S2A, with a relative molecular weight of 2.65 × 106 Da and an uronic acid content of 41.8%, contained Rha, Ara, Gal, Glc and GlcA in a molar ratio of 1.00 : 2.07 : 0.57 : 2.59 : 4.33 and was composed of a backbone consisting of 6-O-Me-α-(1→4)-D-GlcpA, 2-O-acetyl-α-(1→4)-D-Glcp, α-(1→2,4)-L-Rhap, β-(1→3)-D-Galp andα-(1→3,5)-L-Araf, and some branches consisting of 6-O-Me-α-(1→4)-D-GlcpA and terminal α-L-Araf. These results suggested that LRP-S2A with the potential of promoting osteoblast differentiation was a new acidic polysaccharide.

With fluorescent end-labeling method, a homogenous Dendrobium huoshanense polysaccharide (GXG) that was orally administrated to mice was found to be degraded into a stable fragment (dGXG) in the stomach, where dGXG was propelled into the small intestine and absorbed into the systemic circulation. The residual GXG in the stomach could pass through the gastrointestinal tract and was excreted into faeces with a very slow fermentation in the large intestine. The simulated digestion of GXG indicated that the acidic pH condition in the gastric fluid was responsible for GXG degradation, which was supported by the oral digestion of dGXG. Chemical analysis not only showed a change in the molar ratio of monosaccharide compositions and glycosidic linkage types, but also found the loss of the sugar residue (1→4)-linked Galp after the acid treatment of GXG, suggesting that the cleavage of glycosidic linkage, especially (1→4)-linked Galp linkage, resulted in GXG degradation in the gastrointestinal tract.

The role of miR-503 in brain endothelium and ischemic stroke (IS) remains unclear. We aimed to study the relationship between plasma miR-503 and the onset time, severity, subtypes, and von Willebrand Factor (vWF) level in IS patients and to investigate the roles and underlying mechanisms of miR-503 in middle cerebral artery occlusion (MCAO) mice and cultured cerebral vascular endothelial cells (ECs). In MCAO mice, the effects of plasma from acute severe IS patients (ASS) with or without miR-503 antagomir on brain and ECs damage were determined. In cultured human ECs, the effects of miR-503 overexpression or knockdown on the monolayer permeability, apoptosis, ROS, and NO generation were investigated. For mechanism study, the PI3K/Akt/eNOS pathway, cleaved caspase-3, and bcl-2 were analyzed. Results showed that plasma miR-503 was significantly increased in IS patients, especially in acute period and severe cases and subtypes of LAA and TACI, and was positively correlated with vWF. Logistic analysis indicated that miR-503 was an independent risk factor for IS, with the area under curve of 0.796 in ROC analysis. In MCAO mice, ASS pretreatment aggravated neurological injury, BBB damage, brain edema, CBF reduction, and decreased NO production while increased apoptosis and ROS generation in brain ECs, which were partly abolished by miR-503 antagomir. In cultured ECs, miR-503 overexpression and knockdown confirmed its effects on regulating monolayer permeability, cell apoptosis, NO, and ROS generation via PI3K/Akt/eNOS pathway or bcl-2 and cleaved caspase-3 proteins. These together indicate that miR-503 is a promising biomarker and novel therapeutic target for IS.

A homogenous polysaccharide (GXG) from Dendrobium huoshanense with stable digestive behavior and effective immunoregulatory function was employed to explore its underlying molecular basis regulating intestinal mucosal immune response from the view of interaction between GXG and intestinal epithelial cells (IECs). Using in vitro established co-culture system consisting of IECs and lamina propria cells (LPCs), we found the immune response of LPCs could be effectively regulated by GXG-stimulated IECs, and three cytokines including IL-6, MCP-1 and CINC-1 produced from GXG-stimulated IECs were the main factors involved in modulating immune response of LPCs. Toll-like receptor 4 (TLR4) was identified as an essential receptor for IECs to directly bind GXG. Receptor intervention experiments demonstrated that TLR4 mediated GXG-induced activation of IECs, which further induces immunomodulating effects on LPCs. These results suggest that GXG could modulate the immune response in LPCs by the direct interaction with IECs via TLR4.

The present work aimed at investigating the pattern recognition receptor (PRR) and immunostimulatory mechanism of a purified Dendrobium huoshanense polysaccharide (DHP). We found that DHP could bind to the surface of macrophages and stimulate macrophages to secrete NO, TNF-α and IL-1β. To unravel the mechanism for the binding of DHP to macrophages, flow cytometry, confocal laser-scanning microscopy, affinity electrophoresis, SDS-PAGE and western blotting were employed to verify the type of PRR responsible for the recognition of DHP by RAW264.7 macrophages and peritoneal macrophages of C3H/HeN and C3H/HeJ macrophages. Results showed that toll-like receptor 4 (TLR4) was an essential receptor for macrophages to directly bind DHP. Further, the phosphorylation of ERK, JNK, Akt and p38 were observed to be time-dependently promoted by DHP, as well as the nuclear translocation of NF-κB p65. These results suggest that DHP activates macrophages via its direct binding to TLR4 to trigger TLR4 signaling pathways.

Objective To investigate the expression and the mechanism of interleukin-1 beta (IL-1β) in human A549 cells regulated by lipopolysaccharide (LPS) combined with adenosine triphosphate (ATP). Methods The protein expressions of NLRP3, ASC and caspase-1 in A549 cell lines were firstly assessed by Western blotting, and then the effects of different concentrations (0, 1, 5, 10, 50 and 100µg/ml) of LPS on the protein expression of NLRP3 inflammasome pathway and the secretion of IL-1βin A549 cell lines were determined by Western blotting and ELISA, respectively. Secondly, the effects of co-stimulation of LPS and ATP on the activation of inflammasome and the secretion of IL-1βin A549 cell lines were detected. Finally, the effects were observed of siRNA interference to the NLRP3 gene expression in A549 cell lines on the secretion of proinflammatory cytokines-IL-1βinduced by LPS+ATP. Results NLRP3, ASC and caspase-1 proteins were observed in A549 cell lines. The expressions of NLRP3, caspase1p45 and pro-IL-1βin A549 cell lines increased by treatment of LPS alone compared with that of control group (P

A homogeneous polysaccharide fraction (DOP-W3-b) with a high intestinal immunomodulating activity was obtained from the stems of Dendrobium officinale through a bioactivity-guided sequential isolation procedure based on the screening of Peyer's patch-mediated immunomodulating activity. Oral administration experiments of mice showed that DOP-W3-b could effectively regulate intestinal mucosal immune activity by changing intestinal mucosal structures, promoting the secretions of cytokines from Peyer's patches (PPs) and mesenteric lymph nodes (MLNs), and increasing the production of secretory immunoglobulin A (sIgA) in the lamina propria. Structure analysis indicated that DOP-W3-b was composed of mannose and glucose in a molar ratio of 4.5 with a relatively low molecular weight of 1.543 × 10(4) Da, and its repeat unit contained a backbone consisting of β-(1→4)-d-Manp, β-(1→4)-d-Glcp and β-(1→3,6)-d-Manp residues, a branch consisting of β-(1→4)-d-Manp, β-(1→4)-d-Glcp and terminal β-d-Glcp, and O-acetyl groups attached to O-2 of β-(1→4)-d-Manp. These results suggested that DOP-W3-b was a new polysaccharide with an essential potential for modulating body's immune functions.

The present study investigated the effects of a homogeneous Dendrobium huoshanense polysaccharide (GXG) on mucosal barrier function and microbiota composition in different intestinal regions of mice. Results exhibited, besides changing the intestinal physiological status, orally administrated GXG could improve the intestinal physical barrier function by modulating mucosal structures and up-regulating the expression of tight junction proteins, reinforce the intestinal biochemical barrier function by elevating the expression and secretion of mucin-2, β-defensins and sIgA, and regulate the intestinal immunological barrier function by stimulating the production of cytokines and the functional development of immune cells. Simultaneously, GXG could differentially impact the composition and metabolism of microbiota along intestinal tract. In addition, the immune response in spleen and peripheral blood were effectively regulated by GXG. These results indicated that GXG might be used as functional agent to improve host health.

The enhanced osteoblast differentiation is beneficial to the prevention of osteoporosis. In this study, a homogeneous polysaccharide (LRP-S2A) with the potential of promoting osteoblast differentiation was obtained from the fruits of

Based on the essence of the behavior, the driver's lane changing behavior is analyzed, and the lane changing process is divided into the lane changing intent recognition phase and the lane changing phase according to the lane changing trajectory. For different drivers, the use of principal component analysis and K clustering methods for style division. The differences between different drivers in lane changing time, expected speed and lane changing psychology were analyzed.

Porous titanium with porosity of 60% was prepared by metal injection molding (MIM), and coated with gelatin sustained-release microspheres which were made by improved emulsified cold condensation method. The effects of porous titanium coated with insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1) gelatin microspheres on the function of MG63 cells were evaluated in vitro. The results show that porous titanium coated with gelatin sustained-release microspheres has no cytotoxicity. The IGF-1 and TGF-β1 loading concentrations are positively correlative with the proliferation and differentiation of MG63 after co-culturing with the concentrations of IGF-1 and TGF-β1 gelatin microspheres in the range of 0.1–10 ng/mg and 0.25–2.5 ng/mg, respectively. The MG63 cells exhibit the best proliferation and differentiation with the IGF-1 and TGF-β1 loading concentrations of 10 ng/mg and 2.5 ng/mg, respectively. The joint application of IGF-1 and TGF-β1 group, which promote adhesion, proliferation and differentiation of MG63 cells, is superior to a single application group.

This paper considers the problem of single-machine batch delivery scheduling with an assignable common due date where all jobs have identical processing times. Finished jobs are delivered in batches and the cost per batch delivery is fixed and independent of the number of jobs in the batch. For our problem, the penalties of earliness-tardiness are assumed to be arbitrarily weighted but the holding costs are equally weighted. The objective is to determine the common due date and find an optimal schedule to minimize the sum of total weighted earliness, tardiness, holding, due date, and delivery costs. We present some basic properties of the structure of the optimal schedule for the problem, and provide a polynomial dynamic programming algorithm.

Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) of the cyanotic type. Studies on ventricular functions have received an increasing amount of attention as the development of diagnosis and treatment technology for CHD continues to advance. Reasonable options for imaging examination and accurate assessment of preoperative and postoperative left ventricular functions of TOF patients are important in improving the cure rate of TOF radical operation, therapeutic evaluation, and judgment prognosis. Therefore, with the aid of dual-source computed tomography (DSCT), cardiac images with high temporal resolution and high definition, we measured the left ventricular time-volume curve using image data and calculating the left ventricular function parameters to conduct the preliminary evaluation on TOF patients. To comprehensively evaluate the cardiac function, the segmental ventricular wall function parameters were measured, and the measurement results were mapped to a bull's eye diagram to realize the standardization of segmental ventricular wall function evaluation. Finally, we introduced a new clustering method based on auto-regression model parameters and combined this method with Euclidean distance measurements to establish an intelligent diagnosis of TOF. The results of this experiment show that the TOF evaluation and the intelligent diagnostic methods proposed in this article are feasible.

To investigate the curative effect of antiphlogistic agent series on treating chronic nonbacterial prostatitis (CNP).One hundred and sixty patients were randomized into 4 groups for an 8-week clinical observation: group A (oral antiphlogistic medicinal granules only), group B (oral antiphlogistic medicinal granules + retention enema), group C (oral antiphlogistic medicinal granules + rectal), and group D (antiphlogistic medicinal granules + rectally + hip bath). Single blind trials were employed.The curative rates of the 4 groups were 37.5%, 57.5%, 52.5% and 82.5% respectively, while the total efficacy rates were 42.5%, 82.5%, 77.5% and 92.5% respectively. Compared with groups A, B and C, the curative rate of group D was significantly higher (P0.05). The difference in efficacy rates was slight between groups B and D (P0.05), but significant between groups A and C (P0.05).Combined treatment therapy can improve the effect of CNP treatment and clear away heat and toxic material. The antiphlogistic agent series, with the effect of motivating blood circulation and removing blood stasis, turned out to be an effective traditional Chinese medicine in treating CNP.