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The rapid development of smart vehicles has made collaborative control of unmanned vehicles a highly focused research field. Owing to the time-varying traffic context, collaborative control of unmanned vehicles always faces the challenges of complex and uncertain scenario characteristics. It is supposed to develop a robust mathematical modeling scheme that integrates these factors, for the above technical demand. Firstly, the Markov jump system is introduced as the core of mathematical modeling to extract information from vehicle space. Then, the collaborative control of driving conflicts and local conflicts on signalless road sections is fused and calculated. By capturing the transition probability of the system state, the behavior of unmanned vehicles was predicted, Based on the prediction results, corresponding control strategies are adopted. Finally, lane changing, following, obstacle warning, and automatic parking case analysis can be completed. To verify the effectiveness of the proposed method, we conducted a series of simulation experiments and compared them with traditional methods. Some typical instance cases including lane changing, vehicle following, obstacle warning, and automatic parking, are completed under collaborative control. The experimental results show that the proposed mathematical modeling method can significantly improve the prediction accuracy and effectiveness of delayed driving events, providing more reliable prediction capabilities for collaborative control of unmanned vehicle.

The objective of this study was to investigate the protective effect of Crataegus pinnatifida polysaccharide (CPP) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The findings demonstrated that CPP improved free fatty acid (FFA)-induced lipid accumulation in HepG2 cells and effectively reduced liver steatosis and epididymal fat weight in NAFLD mice, as well as decreased serum levels of TG, TC, AST, ALT, and LDL-C. Furthermore, CPP exhibited inhibitory effects on the expression of fatty acid synthesis genes FASN and ACC while activating the expression of fatty acid oxidation genes CPT1A and PPARα. Additionally, CPP reversed disturbances in intestinal microbiota composition caused by HFD consumption. CPP decreased the firmicutes/Bacteroidetes ratio, increased Akkermansia abundance, and elevated levels of total short-chain fatty acid (SCFA) content specifically butyric acid and acetic acid. Our results concluded that CPP may intervene in the development of NAFLD by regulating of intes-tinal microbiota imbalance and SCFAs production. Our study highlights that CPP has a potential to modulate lipid-related pathways via alterations to gut microbiome composition thereby ex-erting inhibitory effects on obesity and NAFLD development.

Abstract Background Dysbiosis of gut microbiota has been linked to numerous diseases, including cancer. The unique role of gut microbiota in urological tumors is gaining prominence. However, it is still controversial whether the dysbiosis of gut microbiota should be one of the etiological factors of bladder cancer (BCa), prostate cancer (PCa) or kidney cancer (KCa). Materials and methods The microbiome genome-wide association study (GWAS) from the MiBioGen consortium (18,340 samples of 24 population-based cohorts) was utilized as the exposure data. Additionally, outcomes data (951 BCa cases and 307,092 controls; 1,631 KCa cases and 238,678 controls; 79,148 PCa cases and 61,106 controls) were extracted from the GWAS of the FinnGen and PRACTICAL consortia. To detect the potential causative bacterial traits for BCa, PCa, and KCa, a two-sample Mendelian randomization (MR) analysis was performed, employing the inverse-variance weighted or Wald ratio method. Sensitivity analyses were subsequently conducted to explore the robustness of the primary results. Finally, the reverse MR analysis was undertaken to mitigate the reverse causation. Results This study suggested that Bifidobacterium (p = 0.030), Actinobacteria (p = 0.037 for phylum, 0.041 for class), and Ruminococcustorques group (p = 0.018), exhibited an association with an increased risk of BCa using either the inverse-variance weighted or Wald ratio method. By utilizing the Wald ratio method, Allisonella (p = 0.004, p = 0.038) was associated with a decreased risk of BCa and PCa, respectively. Furthermore, Ruminococcustorques group (p = 0.028) and Erysipelatoclostridium (p = 0.048) were causally linked to an elevated risk of KCa. Conclusions This MR study supports that genetically predicted gut microbiota is causally related to BCa, PCa and KCa. Additionally, distinct bacterial traits are identified in relation to each tumor type.

Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.

【Objective】With the continuous development of the information age, science and technology has become the fundamental driving force for the development of rural industries. In order to further activate the vitality of rural development and promote the integration of three industries in rural areas, it has become a strong support for rural revitalization.【Method】Based on the vector auto regression (VAR) model and relevant data of science and technology and industry in China from 2011 to 2019, the study explores the relationship between the integration of three industries in rural areas and the input of scientific and technological innovation through nine secondary indicators under three first-level indicators corresponding to the output of science and technology, the input of science and technology, and the integration of three industries in rural areas.【Result】Empirical analysis results show that, there is still a lot of room for continuous improvement in the degree of integration of three industries in rural areas. There are dynamic interactions and high correlations among the input intensity of science and technology, the output level of science and technology and the integration of three industries in rural areas in the index systems; the input of science and technology innovation can promote the development of integration of three industries in rural areas, which will increase 0.767% when the output of science and technology is increased by 1% in the current period; the development of integration of three industries in rural areas will promote further investment in science and technology innovation. When the comprehensive score of integration of three industries in rural areas increases by 0.881%, the comprehensive score of science and technology output increases by 1%.【Conclusion】Based on the above conclusions, we should focus on promoting agricultural scientific and technological innovation to overcome technical barriers, support and encourage agricultural scientific research workers to develop products and technological innovation, build a platform for scientific and technological innovation alliances, increase investment in scientific and technological research and development, create an environment for scientific research and innovation, and accelerate the pace of agricultural technological innovation in our country to realize the deep integration between traditional agriculture and high-tech industries.

Microbes play a crucial role in maintaining health by aiding in digestion, regulating the immune system, producing essential vitamins, and preventing the colonization of harmful bacteria. The stability of the microbiota is, therefore, necessary for overall well-being. However, several environmental factors can negatively affect the microbiota, including exposure to industrial waste, i.e., chemicals, heavy metals, and other pollutants. Over the past few decades, industries have grown significantly, but the wastewater from those industries has seriously harmed the environment and the health of living beings both locally and globally. The current study investigated the effects of salt-contaminated water exposure on gut microbiota in chickens. According to our findings, amplicon sequencing showed 453 OTUs across control and salt-contaminated water exposure groups. Proteobacteria, Firmicutes, and Actinobacteriota were the most dominant phyla in the chickens regardless of treatment. However, exposure to salt-contaminated water resulted in a remarkable decline in gut microbial diversity. While, the beta diversity revealed substantial differences in major gut microbiota components. Moroever, microbial taxonomic investigation indicated that the proportions of one bacterial phylum and nineteen bacterial genera significantly decreased. Also, the levels of one bacterial phylum and thirty three bacterial genera markedly increased under salt-contaminated water exposure, which indicates a disruption in gut microbial homeostasis. Hence the current study provides a basis to explore the effects of salt-contaminated water exposure on the health of vertebrate species.

A component of licorice polysaccharide (GPS-1) was extracted from licorice, its primary structure was identified and characterized for the first time, and its immunomodulatory activity was studied. Crude licorice polysaccharide was isolated and purified by DEAE sepharose FF ion-exchange column chromatography and Chromdex 200 PG gel filtration column chromatography to obtain a purified Glycyrrhiza polysaccharide named GPS-1. NMR and methylation analysis revealed that GPS-1 is composed of homogalacturonan (HG)-type pectin with 4)-D-GalpA-(1 as the backbone. This study of GPS-1 also examined its significant role in regulating immune activity in vitro and in vivo. As a result, GPS-1 promoted the secretion of IFN-γ and IL-4 in mice and increased the proportion of CD3+CD4+ and CD3+CD8+ T lymphocytes in their spleens. Dendritic cells (DCs) treated with GPS-1 showed promotion of DC maturation, antigen presentation, and phagocytic capacity. The results suggest that GPS-1 is a potential immunomodulator that stimulates the immune system by regulating multiple signaling pathways. Combined with our characterization of the primary structure of GPS-1, the present investigation provides the basis for future study of the form-function relationship of polysaccharides.

Abstract Background Nano-drug delivery systems show considerable promise for effective cancer therapy. Polymeric micelles have attracted extensive attention as practical nanocarriers for target drug delivery and controlled drug delivery system, however, the distribution of micelles and the release of the drug are difficult to trace in cancer cells. Therefore, the construction of a redox-sensitive multifunctional drug delivery system for intelligent release of anticancer drugs and simultaneous diagnostic imaging and therapy remains an attractive research subject. Results To construct a smart drug delivery system for simultaneous imaging and cancer chemotherapy, mPEG-ss-Tripp was prepared and self-assembled into redox-sensitive polymeric micelles with a diameter of 105 nm that were easily detected within cells using confocal laser scanning microscopy based on aggregation-induced emission. Doxorubicin-loaded micelles rapidly released the drug intracellularly when GSH reduced the disulfide bond. The drug-loaded micelles inhibited tumor xenografts in mice, while this efficacy was lower without the GSH-responsive disulfide bridge. These results establish an innovative multi-functional polymeric micelle for intracellular imaging and redox-triggered drug deliver to cancer cells. Conclusions A novel redox-sensitive drug delivery system with AIE property was constructed for simultaneous cellular imaging and intelligent drug delivery and release. This smart drug delivery system opens up new possibilities for multifunctional drug delivery systems.

The overuse of antibiotics in poultry farming causes the accumulation of drug residue in animals' bodies and the occurrence of antibiotic-resistant bacteria, which not only compromise animals' health but ultimately endanger human health. Thus, there is an urgent need for a novel poultry feed additive to substitute for excessive antibiotics. Glycyrrhiza polysaccharides (GPS) derived from Chinese licorice have shown promising immunomodulatory effects in previous studies. The present study investigated the pharmacological effects of GPS on poultry intestines to assess whether it can be used as a feed additive. The results show that GPS can increase production of sIgA, promote the secretion activity of goblet cells, alter the gut microbial composition and lead to changes in short-chain fatty acids. GPS also elevated both Th1 and Th2 immune responses by facilitating the expression of IL-2, IL-4, IL-1β, and IFN-γ while increasing the proportion of both CD4+ and CD8+ cells in the intestine. Moreover, the results of 16S rRNA gene sequencing showed that GPS could significantly change intestinal microbiota composition in the intestine, evidenced by the increased proportion of Bacteroides, Butyricicoccus and Eisenbergiella, as well as a decreased portion of Erysipelatoclostridium, leading to a healthier intestinal microbiota composition for the host. Taken together, it can be concluded that GPS is safe to use as a novel feed additive that can be used as an alternative to prophylactic antibiotics in poultry feeding.

Abstract Background The expression level of ribonucleotide reductase subunit M1 (RRM1) is closely related to the effect of gemcitabine-based therapy in advanced bladder cancer. However, the value of RRM1 expression in predicting progression-free survival in non-muscle-invasive bladder cancer (NMIBC) patients treated with intravesical gemcitabine chemotherapy has not been elucidated. Methods This study randomly assigned 162 patients to either the RRM1-known group or the unknown group. We collected cancer tissues from 81 patients to evaluate the mRNA expression of RRM1 by using liquid chip technology. All patients were diagnosed and then treated with intravesical gemcitabine monotherapy immediately after transurethral resection of the bladder tumour (TURBT). Results RRM1 expression was high in 21% (17/81) of patients. The RRM1 mRNA level was not correlated with sex, age, weight, performance status, or CUA/EAU risk (p > 0.05). Progression-free survival (PFS) was significantly longer for patients with low RRM1 expression than for patients with high and unknown RRM1 expression (p = 0.009). Additionally, the 1- and 2-year relapse rates also differed according to RRM1 expression level. The 1-year relapse rates for RRM1-low, RRM1-high and RRM1-unknown patients were 0, 17.7 and 6.2% (p = 0.009), while the 2-year relapse rates for these groups were 3.1, 29.4, and 11.1% (p = 0.005), respectively. Conclusions This preliminary study showed that low RRM1 expression was associated with longer progression-free survival and lower 1-year/2-year relapse rates in NMIBC patients treated with intravesical gemcitabine monotherapy, despite the need for further verification with large sample sizes and considering more mixed factors and biases.

Diabetes is commonly treated with glucagon-like peptide-1 receptor (GLP-1R) agonists including liraglutide and others. However, liraglutide was found to raise plasma glucose levels in normal rats. The current study aims to determine how liraglutide causes this contentious condition in rats, both normal and diabetic. An adrenalectomy was performed to investigate the relationship between steroid hormone and liraglutide. To investigate the effect of central liraglutide infusion on blood glucose in rats, rats were intracerebroventricularly administrated with liraglutide with or without HPA axis inhibitors such as berberine and dexamethasone. The results showed that a single injection of liraglutide caused a temporary increase in blood glucose in healthy rats. Another GLP-1R agonist, Exendin-4 (Ex-4), increased blood sugar in a manner similar to that of liraglutide. The effects of liraglutide were also blocked by guanethidine pretreatment and vanished in normal rats with adrenalectomy. Additionally, central infusion of liraglutide via intracerebroventricular (icv) injection into normal rats also causes a temporary increase in blood glucose that was blocked by GLP-1R antagonists or the inhibitors such as berberine and dexamethasone. Similarly, central liraglutide treatment causes temporary increases in plasma glucose, adrenocorticotropic hormone (ACTH), and cortisol levels, which were reversed by inhibitors for the hypothalamic-pituitary-adrenal (HPA) axis. In normal rats, the temporary glucose-increasing effect of liraglutide was gradually eliminated during consecutive daily treatments, indicating tolerance formation. Additionally, liraglutide and Ex-4 cross-tolerance was also discovered in normal rats. Liraglutide was more effective in diabetic rats than in normal rats in activating GLP-1R gene expression in the isolated adrenal gland. Interestingly, the effect of liraglutide on glycemic control varied depending on whether the rats were diabetic or not. In normal rats, bolus injection of liraglutide, such as Ex-4, may stimulate the HPA axis, resulting in hyperglycemia. The cross-tolerance of liraglutide and Ex-4 provided a novel perspective on GLP-1R activation.

ObjectiveTo explore the efficacy and safety of EGFR-TKI combined with thymosin therapy in advanced non-small cell lung cancer (NSCLC) patients harboring active EGFR mutations.MethodsPatients confirmed as advanced NSCLC with active EGFR mutations were recruited from August 2008 to July 2018 retrospectively. Patients treated with EGFR-TKI were classified as the EGFR-TKI group. And those received EGFR-TKI and thymosin therapy were designated as the EGFR-TKI plus thymosin group. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), tumor response and adverse effects.ResultsThe median PFS was significantly longer in EGFR-TKI plus thymosin group than that in EGFR-TKI group (14.4 months vs. 9.2 months; HR=0.433, 95% CI 0.322 - 0.582, P

To evaluate the expression of ALDH1A1 in lung adenoma stem cells (LASCs) and maintenance of their stemness through the Notch pathway.LASCs (A549s) were isolated from lung adenoma cells (A549) and identified by their coexpression of CD133 and CD326 and their capacity formulti-directional differentiation. Expression of ALDH1A1 in A549 and A549s cells were evaluated by Real-time PCR. Effects of ALDH1A1 upregulation in A549 cells and its downregulation in A549s cells on the clonogenicity and cell cycle were assessed by colony-forming unit assay. Moreover, the effects of ALDH1A1 on the Notch pathway, and thus on the cell cycle, were studied.A549s cells were successfully isolated and identified.ALDH1A1expression was significantly higher in A549s than in A549 cells. Clonogenicity was significantly decreased in A549s cells treated with ALDH1A1 siRNA. Duration of the G1 stage of the cell cycle increased after ALDH1A1 was overexpressed, or decreased with ALDH1A1 siRNA. ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 expression levels were higher in A549s cells than in A549 cells. Expression of Notch1, -2, and -3, CDK2, and CCNE1 was significantly decreased by upregulation of ALDH1A1 in A549 cells, but increased by its interruption in A549s cells. When Notch3 or CDK2 expression was downregulated, the expression levels of ALDH1A1, Notch1, -2, and -3, CDK2, and CCNE1 were reduced in all cell types.ALDH1A1 expression improved clonogenicity and inhibited the cell cycle, maintaining the stemness of the A549s cells; this may involve suppression of the Notch/CDK2/Cyclin pathway.

BACKGROUND: To assess the level of CR6-interacting factor 1 (CRIF1), a cell cycle negative regulator, in patients with leukemia and investigate the role of CRIF1 in regulating leukemia cell cycle. METHODS: We compared the CRIF1 level in bone marrow (BM) samples from healthy and acute myeloid leukemia (AML), iron deficiency anemia (IDA) and AML-complete remission (AML-CR) subjects. We also manipulated CRIF1 level in the Jurkat cells using lentivirus-mediated overexpression or siRNA-mediated depletion. Co-culture with the BM stromal cells (BMSCs) was used to induce leukemia cell cycle arrest and mimic the BM microenvironment. RESULTS: We found significant decreases of CRIF1 mRNA and protein in the AML group. CRIF1 overexpression increased the proportion of Jurkat cells arrested in G0/G1, while depletion of endogenous CRIF1 decreased cell cycle arrest. Depletion of CRIF1 reversed BMSCs induced cell cycle arrest in leukemia cells. Co-immunoprecipitation showed a specific binding of CDK2 to CRIF1 in Jurkat cells during cell cycle arrest. Co-localization of two proteins in both nucleus and cytoplasm was also observed with immunofluorescent staining. CONCLUSION: CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor.

BACKGROUND: The association of the three Glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1 and GSTP1) genotypes with their individual susceptibilities to renal cell carcinoma (RCC) has not been well established. We performed a quantitative meta-analysis to assess the possible associations between the GSTM1, GSTT1 and GSTP1 genotypes and their individual susceptibilities to renal cell carcinoma. METHODS: We systematically searched the PubMed, CNKI and Embase databases to identify the relevant studies. Finally, 11 eligible studies were selected. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between the GSTs polymorphisms and the risk of RCC. Multiple subgroup analyses and quality assessment of the included studies were performed based on the available information. RESULTS: None of the GSTs polymorphisms had a significant association with the RCC risk. Similar results were found in the subgroup analyses, except for the GSTs polymorphisms in the situations described below. The GSTM1 and GSTT1 active genotypes in subjects exposed to pesticides (GSTM1: OR = 3.44; 95% CI, 2.04-5.80; GSTT1: OR = 2.84; 95% CI, 1.75-4.60), most of the GSTs genotypes in Asian populations (GSTT1: OR = 2.39, 95% CI = 1.63-3.51; GSTP1: Dominant model: OR = 1.50, 95% CI = 1.14-1.99; Additive model: OR = 1.39, 95% CI = 1.12-1.73; AG vs. AA: OR = 1.47, 95% CI = 1.10-1.97; GG vs. AA: OR = 1.82, 95% CI = 1.07-3.09) and the dual null genotype of GSTT1-GSTP1 (OR = 2.84, 95% CI = 1.75-4.60) showed positive associations with the RCC risk. CONCLUSION: Our present study provides evidence that the GSTM1, GSTT1 and GSTP1 polymorphisms are not associated with the development of RCC. However, more case-control studies are needed for further confirmation.

Red blood cell (RBC) storage lesions have been shown to be associated with some adverse reactions; numerous studies have focused on the lesions caused by storage, and few data on the RBC storage lesions caused by prestorage treatments of leucocyte filtration and irradiation. In this study, we examined the changes related with the RBC storage lesions, including 2,3-diphosphatidylglyceric acid (2,3-DPG), pH, free hemoglobin (Hb), supernatant free K+ and Na+ concentration, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH). Along with the increasing storage time, decreases in 2, 3-DPG levels, pH and Na+ concentration, increases in K+ and free Hb concentrations, and significant morphological changes in RBC in all groups were found. The changes in the groups of irradiation, leucocyte filtration and the combined irradiation and leucocyte filtration were more significant than those in the untreated group. Meanwhile, the MCV levels of the three treated groups were significantly lower than those in the untreated group, while the MCH variations were significantly higher. Our results suggest that irradiation and leucocyte filtration before storage may aggravate blood storage lesions.

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