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With the development of China's economy, more and more Chinese companies are developing and growing out of China to connect with the world. In the field of e-commerce industry, a lot of research has been conducted by scholars. However, the research on self-operated e-commerce in the context of the COVID-19 is still a blank. As the largest self-operated e-commerce platform in China, JD's development is significantly representative for the whole field. This paper focuses on SWOT analysis combined with specific data and the current situation of the e-commerce industry to analyze the current development of JD.com and draw conclusions. While JD.com continues to invest in maintaining its existing warehousing and logistics advantages, it is not enough for the development of emerging live markets and sinking markets. At this stage, Chinese companies are increasingly going global, and whether they can seize the development of policy and communication technology is a decisive factor in whether self-operated e-commerce can become bigger and stronger. At the same time, it is found that JD.com's marketing model at this stage is lacking in sustained innovation. This paper enriches the post-epidemic era for the development of China's self-operated e-commerce research has positive implications for the development of this industry

Six new 16-residue peptaibols, acremopeptaibols A-F (1-6), along with five known compounds, were isolated from the cultures of the sponge-associated fungus Acremonium sp. IMB18-086 grown in the presence of the autoclaved bacterium Pseudomonas aeruginosa on solid rice medium. The peptaibol sequences were established based on comprehensive analysis of 1D and 2D NMR spectroscopic data in conjunction with HRESIMS/MS experiments. The configurations of the amino acid residues were determined by advanced Marfey's analysis. Compounds 1-6 feature the lack of the highly conserved Thr6 and Hyp10 residues in comparison with other members of the SF3 subfamily peptaibols. A plausible biosynthetic pathway of compounds 1-6 was proposed on the basis of genomic analysis. Compounds 1, 5, 7, and 10 exhibited significant antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Candida albicans. Compounds 7-10 showed potent cytotoxicities against the A549 and/or HepG2 cancer cell lines.

Zelkovamycins F and G (

Cholangiocarcinoma (CCA) is a type of solid tumor derived from the bile duct epithelium that features universal gemcitabine resistance. Here, we utilized a gene-encoded ROS biosensor probe (HyPer3 probe) to sort subpopulations with different redox statuses from CCA cells. The isolated HyPer-low subpopulation CCA cells, which exhibited relatively lower cellular ROS levels, exhibited higher chemoresistance to gemcitabine than HyPer-high subpopulation CCA cells in vitro and in vivo. Mechanistically, increased expression of MTHFD1 was found in HyPer-low cells. Knocking down MTHFD1 in HyPer-low cells enhanced cellular ROS and restored sensitivity to gemcitabine. Furthermore, the MTHFD1 inhibitor antifolate compound methotrexate (MTX) increased cellular ROS, and combining gemcitabine with MTX effectively suppressed cholangiocarcinoma cell growth. In summary, the MTHFD1 level mediated the heterogeneous cellular redox status in CCA, which resulted in chemoresistance to gemcitabine. Our data suggest a novel strategy for CCA chemotherapy.

Lasso peptides are a unique family of natural products whose structures feature a specific threaded fold, which confers these peptides the resistance to thermal and proteolytic degradation. This stability gives lasso peptides excellent pharmacokinetic properties, which together with their diverse reported bioactivities have garnered extensive attention because of their drug development potential. Notably, the threaded fold has proven quite inaccessible by chemical synthesis, which has hindered efficient generation of structurally diverse lasso peptides. We herein report the discovery of a new lasso peptide stlassin (1) by gene activation based on a Streptomyces heterologous expression system. Site-directed mutagenesis on the precursor peptide-encoding gene is carried out systematically, generating 17 stlassin derivatives (2–17 and 21) with residue-replacements at specific positions of 1. The solution NMR structures of 1, 3, 4, 14 and 16 are determined, supporting structural comparisons that ultimately enabled the rational production of disulfide bond-containing derivatives 18 and 19, whose structures do not belong to any of the four classes currently used to classify lasso peptides. Several site-selective chemical modifications are first applied on 16 and 21, efficiently generating new derivatives (20, 22–27) whose structures bear various decorations beyond the peptidyl monotonicity. The high production yields of these stlassin derivatives facilitate biological assays, which show that 1, 4, 16, 20, 21 and 24 possess antagonistic activities against the binding of lipopolysaccharides to toll-like receptor 4 (TLR4). These results demonstrate proof-of-concept for the combined mutational/chemical generation of lasso peptide libraries to support drug lead development., A new class II lasso peptide stlassin (1) was discovered and stlassin derivatives (2–27) were rationally generated by biosynthetic gene mutations and site-selective chemical modifications, expanding the structural diversity of lasso peptides.

Salvia miltiorrhiza Bunge and Panax ginseng C. A. Meyer have special curative effect on cancer treatment. The optimizing component formula (OCF) extracted from those two herbs was in line with the anti-lung cancer treatment principle of activating blood and supplementing 'Qi'. However, the study on the mechanism of component formula has always been an insurmountable challenge. Nowadays, the application of network pharmacology and artificial intelligence (AI) in the field of TCM provides new ideas for the study of new targets and mechanisms of TCM, which promotes the modernization of TCM.This study aims to further explore the anti-lung cancer mechanism of OCF by using an integrated strategy of network pharmacology and AI technology.Bioinformatic analysis was used to analyze the expression levels, prognosis and survival of DTL and PDCD4 in cancer patients. The binding strength of OCF and DTL was simulated by molecular docking, and the affinity between them was detected by Bio-layer interferometry. Network pharmacology was used to predict the active components, potential targets and pathways of OCF. The association between key targets and their corresponding components and DTL was analyzed by Ingenuity Pathway Analysis (IPA). MTT assay, colony formation assay, wound-healing assay and transwell assay were used to verify the inhibitory effects of OCF on lung cancer cells in vitro. qRT-PCR and Western blot assay were used to detect the effects of OCF on mRNA and protein expression of DTL, PDCD4 and key genes in MAPK/JNK pathways.Bioinformatics analysis showed that DTL was significantly up-regulated in lung cancer, which was associated with high malignancy rate, high metastasis rate and poor prognosis of primary tumor. PDCD4 was down-regulated in lung cancer, and associated with high metastasis rate and poor prognosis. The good affinity between OCF and DTL was predicted and verified by molecular docking and Bio-layer interferometry. Based on the network pharmacological databases, 40 active components and 220 corresponding targets of OCF were screened out. KEGG analysis showed that OCF component targets were mainly enriched in MAPK signaling pathway. IPA results showed the interrelationship between DTL, PDCD4, MAPK pathway genes and their corresponding OCF components. In addition, in vitro experiments demonstrated anti-lung cancer activity of OCF, as validated, via impairing cell viability and cell proliferation, as well as inhibiting migration and invasion abilities in lung cancer cells. qRT-PCR showed that OCF down-regulated the mRNA expression of DTL, MAP4K1, JNK, c-Jun and c-Myc, and up-regulated the mRNA expression of PDCD4 and P53 genes in A549 lung cancer cells. Western blot suggested that OCF suppressed the protein level of DTL and blocked the ubiquitination of PDCD4 in A549 lung cancer cells, and down-regulated the protein levels of MAP4K1, p-JNK and p-c-Jun while up-regulated the proteins expression level of P53.OCF might elicit an anti-lung cancer effect by blocking DTL-mediated PDCD4 ubiquitination and suppression of the MAPK/JNK pathway. Meanwhile, our work revealed that network pharmacology and AI technology strategy are cogent means of studying the active components and mechanism of TCM.

Severe plastic deformation such as equal channel angular pressing (ECAP) could change the mechanical and corrosion resistance of Mg alloys. The effects of ECAP extrusion on the mechanical and biode...

Seven new 4-acyl-2-aminoimidazoles, designated strepimidazoles A-G (1-7), were discovered from the endophytic Streptomyces sp. PKU-EA00015 isolated from Salvia miltiorrhiza Bunge, whose dry root "Danshen" is one of the most widely used traditional Chinese medicines. The resonance signals of the 2-aminoimidazole moiety in 1-7 were absent in the NMR spectra due to tautomerization, and the structures of 1-7 were identified after preparation of their acetylation products 1a-7a, respectively. Compounds 1-7 represent a new family of 2-aminoimidazole-containing natural products, enriching the structural diversity of natural products from endophytic origin. Compounds 1-7 showed different degrees of inhibitory activities against the plant pathogenic fungus Verticillium dahliae V991, revealing structure-activity relationships on the acyl moieties. The plant pathogenic fungus V. dahliae has been confirmed to cause serious chlorosis of cultivated S. miltiorrhiza Bunge in China. This study opens the door for further investigation of mutualistic relationships between S. miltiorrhiza Bunge and their endophytic actinomycetes and for possible antifungal agent development for biological control of V. dahliae in the future.

Since pepticinnamin E was discovered almost 30 years ago, no other pepticinnamin family of natural products has been reported to date. Here, we report the discovery of pepticinnamins G-I (1-3) from a marine Streptomyces sp. PKU-MA01144 and pepticinnamins J-M (4-7) from several mutants, and these new compounds contain different N-methyl-l-alanine and l-tyrosine residues compared to pepticinnamin E. Genome sequencing, heterologous expression, gene deletion, and reconstitution of enzymatic reaction in vitro identified the biosynthetic gene cluster of 1-7 and first experimentally established the biosynthesis of the nonproteinogenic 2-chloro-3-hydroxy-4-methoxy-l-phenylalanine residue by a biopterin-dependent hydroxylase Pep10, an O-methyltransferase Pep9, and a flavin-dependent halogenase Pep1. The biosynthetic research and heterologous expression system in this study set the stage for pathway engineering for more pepticinnamins generation in the future.

Cholestasis occurs in many clinical circumstances and leads to severe liver disorders. MCC950, a small-molecule NLRP3 inhibitor, was previously shown to have anti-inflammatory effects. However, these effects have not yet been examined in cholestatic liver injury. This study aimed to investigate the role of NLRP3 inflammasome and test the therapeutic efficacy and molecular mechanisms of MCC950 in cholestatic liver injury through the common bile duct ligation (BDL) model in mice. The influence of MCC950 on histological changes, levels of liver damage, neutrophil infiltration, liver cell death, inflammatory cytokine levels, and NLRP3 inflammasome expression were examined. The results of the current study confirmed that NLRP3 components were up-regulated during bile duct obstruction. MCC950 treatment significantly alleviated BDL-induced liver injury by reducing production of the pro-inflammatory cytokines IL-1β and IL-18 and inhibiting neutrophil infiltration and hepatic cell death. Moreover, MCC950 significantly inhibited NLRP3 activation during cholestatic liver injury. In addition, transcriptome analysis indicated that Toll-like receptor signaling may be involved in the protective effects of MCC950 in cholestatic liver injury. In conclusion, experimental findings demonstrate that MCC950 exerted protective effects in cholestatic liver injury and liver fibrosis by blocking NLRP3 inflammasome activation and the mechanism was partially attributed to inhibition of Toll-like receptor signaling. The present study indicates MCC950 could potentially be an effective therapeutic strategy for the treatment of cholestatic liver injury.

A new phenylamine-incorporated angucyclinone (1) featuring a unique 1-phenylbenzo[ cd]indol-3(1 H)-one moiety was discovered from marine Streptomyces sp. PKU-MA00218. A series of experimental investigations identified that 1 was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone (2) with phenylamine. Utilizing the nonenzymatic conversion, 18 phenylamine-incorporated angucyclinone derivatives with halogen, methyl, methoxy, and carboxy substitutions were efficiently generated under mild conditions. These results highlighted the impressive roles of nonenzymatic reactions in expanding the structural diversity of angucyclinones.

Exposure to fine particulate matter (PM2.5) is linked to various respiratory outcomes. However, the associations of concentrations of PM2.5-bound polycyclic aromatic hydrocarbons (PM2.5-bound PAHs) with airway inflammatory indices remains unclear. To assess effects of short-term exposure to PM2.5-bound PAHs on fractional exhaled nitric oxide (FeNO), we conducted a pilot study with repeated measures. We recruited 20 postgraduate students in Wuhan city, China, and repeatedly measured outdoor and indoor (including dormitories, offices and laboratories) PM2.5-bound PAHs concentrations, urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) and FeNO levels in the four seasons. Subsequently, we estimated inhaled doses of PM2.5-bound PAHs based on the micro-environmental PM2.5-bound PAHs concentrations, time-activity patterns and referred inhalation rates. We assessed the association of inhaled doses of PM2.5-bound PAHs with FeNO using linear mixed-effects regression models. We found the positive associations of urinary ∑OH-PAHs levels with inhaled doses of indoor PM2.5-bound PAHs (including dormitories and offices) (all p

Chronic hepatitis B virus (HBV) infection is a serious health problem worldwide. Evaluating liver injury in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) with detectable HBV DNA and normal alanine aminotransferase (ALT) is crucial to guide their clinical management. We aimed to investigate the stages of liver inflammation and fibrosis as well as the predictive accuracy of gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in these patients.A total of 184 treatment-naïve HBeAg-negative CHB patients with detectable HBV DNA and normal ALT were enrolled. The Scheuer scoring system was used to classify liver inflammation and fibrosis.The distribution of patients with different liver inflammation grades were as follows: G0, 0 (0%); G1, 97 (52.7%); G2, 68 (37.0%); G3, 12 (6.5%); and G4, 7 (3.8%). The distribution of patients with different liver fibrosis stages were as follows: S0, 22 (12.0%); S1, 72 (39.1%); S2, 42 (22.8%); S3, 19 (10.3%); and S4, 29 (15.8%). The areas under the receiver operating characteristic (AUROC) curves of GPR in predicting significant inflammation, severe inflammation, and advanced inflammation were 0.723, 0.895, and 0.952, respectively. The accuracy of GPR was significantly superior to that of ALT in predicting liver inflammation. The AUROCs of GPR in predicting significant fibrosis, severe fibrosis, and cirrhosis were 0.691, 0.780, and 0.803, respectively. The predictive accuracy of GPR was significantly higher than that of aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on four factors (FIB-4) in identifying advanced fibrosis and cirrhosis, and it was superior to FIB-4 but comparable to APRI in identifying significant fibrosis.Nearly half of the HBeAg-negative CHB patients with detectable HBV DNA and normal ALT levels had significant liver inflammation or fibrosis. GPR can serve as an accurate predictor of liver inflammation and fibrosis in these patients.

Angucyclinones are aromatic polyketides that possess impressive structural diversity and significant biological activities. The structural diversity of these natural products is attributed to various enzymatic or nonenzymatic modifications on their tetracyclic benz(a)anthracene skeleton. Previously, we discovered an unusual phenylamine-incorporated angucyclinone (1) from a marine Streptomyces sp. PKU-MA00218, and identified that it was produced from the nonenzymatic conversion of a C-ring-cleaved angucyclinone (2) with phenylamine. In this study, we tested the nonenzymatic conversion of 2 with more phenylamine analogues, to expand the utility of this feasible conversion in unusual angucyclinones generation. The (3-ethynyl)phenylamine and disubstituted analogues including (3,4-dimethyl)phenylamine, (3,4-methylenedioxy)phenylamine, and (4-bromo-3-methyl)phenylamine were used in the conversion of 2, which was isolated from the fermentation of Streptomyces sp. PKU-MA00218. All four phenylamine analogues were incorporated into 2 efficiently under mild conditions, generating new compounds 3–6. The activation of 3–6 on nuclear factor erythroid 2-related factor 2 (Nrf2) transcription were tested, which showed that 4 possessing a dimethyl-substitution gave most potent activity. These results evidenced that disubstitutions on phenylamine can be roughly tolerated in the nonenzymatic reactions with 2, suggesting extended applications of more disubstituted phenylamines incorporation to generate new bioactive angucyclinones in the future.

Autonomous emergency braking (AEB) system enables vehicles to avoid collisions or mitigate the damage. Due to large braking distance, a safety distance model on the basis of the vehicles driving state and the process of vehicle braking is established. The driver's reaction time and early warning vehicle speed following controller are established, and the predictive AEB algorithm based on the driver's operation intention is established. Finally, TruckSim-Matlab/Simulink co-simulation for the AEB control strategy is conducted. The simulation result shows that the proposed control strategy can hierarchically warn and automatically brake, which is effective.

Background Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, showing aggressive clinical behaviors and poor outcomes. It urgently needs new therapeutic strategies to improve the prognosis of TNBC. Bioinformatics analyses have been widely used to identify potential biomarkers for facilitating TNBC diagnosis and management. Methods We identified potential biomarkers and analyzed their diagnostic and prognostic values using bioinformatics approaches. Including differential expression gene (DEG) analysis, Receiver Operating Characteristic (ROC) curve analysis, functional enrichment analysis, Protein-Protein Interaction (PPI) network construction, survival analysis, multivariate Cox regression analysis, and Non-negative Matrix Factorization (NMF). Results A total of 105 DEGs were identified between TNBC and other breast cancer subtypes, which were regarded as heterogeneous-related genes. Subsequently, the KEGG enrichment analysis showed that these genes were significantly enriched in ‘cell cycle’ and ‘oocyte meiosis’ related pathways. Four (FAM83B, KITLG, CFD and RBM24) of 105 genes were identified as prognostic signatures in the disease-free interval (DFI) of TNBC patients, as for progression-free interval (PFI), five genes (FAM83B, EXO1, S100B, TYMS and CFD) were obtained. Time-dependent ROC analysis indicated that the multivariate Cox regression models, which were constructed based on these genes, had great predictive performances. Finally, the survival analysis of TNBC subtypes (mesenchymal stem-like [MSL] and mesenchymal [MES]) suggested that FAM83B significantly affected the prognosis of patients. Conclusions The multivariate Cox regression models constructed from four heterogeneous-related genes (FAM83B, KITLG, RBM24 and S100B) showed great prediction performance for TNBC patients’ prognostic. Moreover, FAM83B was an important prognostic feature in several TNBC subtypes (MSL and MES). Our findings provided new biomarkers to facilitate the targeted therapies of TNBC and TNBC subtypes.

Seven new 4-acyl-2-aminoimidazoles, designated strepimidazoles A-G (

Personal exposure to fine particulate matter (PM2.5)-bound polycyclic aromatic hydrocarbons (PAHs) can cause serious adverse health effects. However, limited information is available on the impact of a mixture of PAHs in air-borne PM2.5 on lung function. We conducted a repeated-measures pilot study for four seasons during the period of 2014–2015, monitored the concentrations of 13 PAHs in PM2.5 samples from the outdoor and indoor microenvironments using a gas chromatograph-mass spectrometry, estimated inhaled dose of PM2.5-bound PAHs based on the outdoor and indoor PM2.5-bound PAHs concentrations as well as individual time-activity diary, and analyzed independent and joint effects of PM2.5-bound 13 PAHs on lung function by linear mixed effect (LME) and Bayesian kernel machine regression (BKMR) models, respectively. LME models indicated the negative association of phenanthrene or benzo[a]pyrene with forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) in warm season. BKMR models revealed that an overall negative association of the mixture of 13 PAHs in PM2.5 with FVC, FEV1, PEF or MVV values in warm season but only overall negative association of the mixture of 13 PAHs in PM2.5 with MVV values in cold season. In warm season, young adults with higher exposure to certain PAHs or the mixture of 13 PAHs in PM2.5 showed significant impairment in lung function, implying that health risk assessment of the mixture of PAHs in PM2.5 attributed to PM2.5 from traffic emission.

The well layout can provide fluid channels, which is important for enhanced geothermal system (EGS), then the thermal energy in the rock mass can be used for heat extraction and power generation. The heat extraction rate analysis of injection-production well patterns can provide reference for the heat extraction condition of EGS. Based on the local thermal non-equilibrium theory and random fracture model, the EGS model of four injection and one production was established in this paper. Effects of reservoir parameters and injection-production parameters on production temperature and thermal extraction rate was studied. The results show that the injection temperature and injection-production distance are important parameters affecting the thermal performance of the EGS system. Increasing of injection temperature can increases the production temperature and prolongs the EGS system life. When the injection temperature increases from 293.15K to 323.15K, the production temperature increases from 340.04K to 354.21K. The higher the injection-production distance is, the higher the thermal extraction rate is. When the injection-production distance increases from 210m to 325m, the thermal extraction rate increases from 41.9% to 56.4%. In addition, heat extraction rates of four injection-production well patterns were compared and analyzed. The heat extraction performance of three-injections and one-production is obviously better than other methods. For the heating demand, the heat extraction rate of this well pattern is 60.34% and its service life is 39.7a. For power generation demand, its heat extraction rate of the well pattern is 55.9%, and its life is 32.7a.

Curcumin has been reported to have anti-fibrotic effect. However, the anti-fibrotic mechanism of curcumin for liver fibrosis remains obscure. In the presenting study, we aimed to investigate whether curcumin reduce chemokines secretion by inhibiting kupffer cells (KCs) activation to decrease Ly6Chi monocyte infiltration in the treatment of liver fibrosis. Liver fibrosis was induced by intraperitoneal carbon tetrachloride (CCl4)-injection in mice. Mice in curcumin group received curcumin treatment by gavage. Pretreatment with curcumin significantly protected mice from liver inflammation and fibrosis. Compared to CCl4 group, mice in the curcumin group showed significantly less intrahepatic infiltration of Ly6Chi monocytes, but no difference of other leucocyte subtypes. Moreover, curcumin significantly reduced Ly6Chi monocytes associated pro-inflammatory and pro-fibrogenic cytokines, which was in line with the decreased numbers of intrahepatic Ly6Chi monocytes. Further study found that curcumin is able to decrease KCs activation and monocyte chemokines, which explains why curcumin can reduce Ly6Chi monocytes infiltration during liver fibrosis. In vitro, we discovered that curcumin prevents the polarization of macrophages toward M1 and reduces monocyte chemokines secretion, which is involved with ERK1/2 and p38 pathways. Taken together, for the first time, we verified that curcumin can reduce chemokines secretion by inhibiting KCs activation to decrease Ly6Chi monocyte infiltration in the treatment of liver fibrosis. These results suggested that curcumin may be considered a promising candidate in the prevention and treatment of liver fibrosis.

Exposure to phthalates may affect thyroid hormone status. However, there were inconsistent observations for the associations of phthalates exposure with altered thyroid hormones.The aim of this study was to investigate effects of urinary excretion of phthalate metabolites on the levels of thyroid hormones among workers engaged in waste plastic recycling in China.We measured serum levels of thyroid hormones and urinary levels of eight phthalate metabolites among 317 participants (165 workers engaged in waste plastic recycling and 152 farmers), analyzed relationships between urinary phthalate metabolites and thyroid function parameters by multivariate linear regression analysis and structural equation modelling as well as assessed the dose-response relationships between them by restricted cubic spline functions.Maximum urinary values of eight phthalate metabolites in the occupational exposed workers were higher than the controls. Compared with the controls, the workers had higher levels of urinary monobenzyl phthalate (MBzP, 1.12 vs. 0.92 μg/g creatinine), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, 38.84 vs. 32.55 μg/g creatinine), mono-n-octyl phthalate (MOP, .11 vs. 0.09 μg/g creatinine), serum total triiodothyronine (T3, 1.04 vs. 0.92 ng/mL) and the T3 to thyroxine (T4) ratio (1.44 vs. 1.09) (all P 0.05). The results from structural equation modelling analysis showed that phthalates metabolites were positively associated with total T3 (β = 0.044, SE = 0.021, P 0.05) or the T3/T4 ratio (β = 0.053, SE = 0.022, P 0.05) among all participants. Among the workers, there were the non-monotonic dose-response associations between urinary monomethyl phthalate (MMP) and serum total T3 or the T3/T4 ratio, as well as between urinary monoethyl phthalate (MEP) and the T3/T4 ratio (all P 0.05).The dose-response relationships between urinary phthalate metabolites and thyroid hormone parameters may be non-monotonic among the workers. Further investigations are needed to corroborate these findings.

Hepatitis B surface antibody (HBsAb) plays a critical role in protecting against infection of hepatitis B virus (HBV) and were extensively studied in literature. At the same time, the status of hepatitis B surface antigen (HBs)-specific B cells in both vaccinated and HBV infected people received limited attention. In the current study, we adopted a highly specific B-cell Enzyme Linked ImmunoSpot (ELISpot) assay to analyze HBs-specific B cells in various clinical settings: healthy individuals with the history of HBV vaccination before and after receiving an extra HBV vaccine boost, people chronically infected with HBV (CHB) in various clinical stages, with or without a particular type anti-viral treatment, or whether receiving a dose of HBV vaccine. In all of these cases, B-cell ELISpot assay was used effectively in enumerating the frequency of HBs-specific B cells. While the focus of the current report was to establish the utility of this assay for HBV research, a number of interesting observations were made in this pilot study based on the profiles and dynamics of HBs-specific B cells in various conditions. Such information is useful to guide the future work in designing novel therapeutic strategies against CHB.

Background Inflammation may play an important role in the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain unclear. Objectives To investigate the association of PAHs exposure with ASCVD risk and effects of mean platelet volume (MPV) or Club cell secretory protein (CC16) on the association. Methods A total of 2022 subjects (689 men and 1333 women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort study. Data on demography and the physical examination were obtained from each participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured by a gas chromatography-mass spectrometry. We estimated the association between each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk using logistic regression models, and further analyze the mediating effect of MPV or plasma CC16 on the association by using structural equation modeling. Results The results of multiple logistic regression models showed that some OH-PAHs were positively associated with ASCVD risk but not CHD risk, including 2-hydroxyfluoren (β = 1.761; 95% CI: 1.194–2.597), 9-hydroxyfluoren (β = 1.470; 95% CI: 1.139–1.898), 1-hydroxyphenanthrene (β = 1.480; 95% CI: 1.008–2.175) and ΣOH-PAHs levels (β = 1.699; 95% CI: 1.151–2.507). The analysis of structural equation modeling shows that increased MPV and increased plasma CC16 levels contributed 13.6% and 15.1%, respectively, to the association between PAHs exposure and the 10-year ASCVD risk (p Conclusions Exposure to PAHs may increase the risk of atherosclerosis, which was partially mediated by MPV or CC16.

This paper designs the performance index of the automatic train operation (ATO) speed curve model. In addition, based on the principle of genetic algorithm, it optimizes the ATO speed curve. At last, combined with train operation route and train parameters, we design the optimization process of the ATO speed curve in details. System speed protection index, punctuality index, accurate parking index, comfort index and energy saving index meet the requirements, and at the same time achieve the purpose of optimal optimization. The result of this paper shows that using the characteristics of global optimization of genetic algorithm has significant advantages in solving the optimization of complex nonlinear ATO speed curve. Therefore, it can be concluded that it is feasible and advantageous to apply genetic algorithm to the optimization of ATO speed curve, which has reference value in the practical application of ATO speed curve optimization.

Emodin, as a major active component of Rheum palmatum L. and Polygonum cuspidatum, has been reported to have antifibrotic effect. However, the mechanism of emodin on antifibrotic effect for liver fibrosis was still obscure. In the present study, we aimed to investigate whether emodin can alleviate carbon tetrachloride- (CCl4-) induced liver fibrosis through reducing infiltration of Gr1hi monocytes. Liver fibrosis was induced by intraperitoneal CCl4 injection in mice. Mice in the emodin group received emodin treatment by gavage. Pretreatment with emodin significantly protected mice from liver inflammation and fibrosis revealed by the decreased elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis and fibrosis by analysis of hematoxylin-eosin (HE) staining, Masson staining, α-smooth muscle actin (α-SMA), and collagen-I immunohistochemistry staining. Further, compared to CCl4 group, mice in the emodin group showed significantly less intrahepatic infiltration of Gr1hi monocytes. Moreover, emodin significantly inhibited hepatic expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), granulin (GRN), monocyte chemoattractant protein 1 (MCP-1), and chemokine ligand 7 (CCL7), which was in line with the decreased numbers of intrahepatic Gr1hi monocytes. In conclusion, emodin can alleviate the degree of liver fibrosis by reducing infiltration of Gr1hi monocytes. These results suggest that emodin is a promising candidate to prevent and treat liver fibrosis.

The gamma-glutamyl transpeptidase to platelet ratio (GPR) is a novel index to estimate liver fibrosis in chronic hepatitis B (CHB). Few studies compared diagnostic accuracy of GPR with other non-invasive fibrosis tests based on blood parameters. We analyzed diagnostic values of GPR for detecting liver fibrosis and compared diagnostic performances of GPR with APRI (aspartate aminotransferase-to-platelet ratio index), FIB-4 (fibrosis index based on the four factors), NLR (neutrophil-to-lymphocyte ratio), AAR (aspartate aminotransferase/alanine aminotransferase ratio) and RPR (red cell distribution width-to-platelet ratio) in HBeAg positive CHB and HBeAg negative CHB. We found AUROCs of GPR in predicting significant liver fibrosis, advanced liver fibrosis and liver cirrhosis were 0.732 (95% CI 0.663 to 0.801), 0.788 (95% CI 0.729 to 0.847) and 0.753 (95% CI 0.692 to 0.814), respectively. Further comparisons showed the diagnostic performance of GPR was not significantly different with APRI, FIB-4 and RPR in identifying significant fibrosis, advanced fibrosis and cirrhosis, but it was significantly superior to AAR and NLR in both HBeAg positive CHB and HBeAg negative CHB. In conclusion, GPR does not show advantages than APRI, FIB-4 and RPR in identifying significant liver fibrosis, advanced liver fibrosis and liver cirrhosis in both HBeAg positive CHB and HBeAg negative CHB in China.

// Jian Wang 1 , Xiaomin Yan 2 , Yue Yang 1 , Haiyan Chang 1 , Bei Jia 2 , Xiang-An Zhao 3 , Guangmei Chen 4 , Juan Xia 2 , Yong Liu 5 , Yuxin Chen 5 , Guiyang Wang 2 , Li Wang 2 , Zhaoping Zhang 2 , Weimao Ding 6 , Rui Huang 2 and Chao Wu 1, 2 1 Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China 2 Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China 3 Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China 4 Department of Infectious Diseases, Affiliated Hospital of Nanjing, University of Traditional Chinese Medicine, Nanjing, Jiangsu, China 5 Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China 6 Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China Correspondence to: Chao Wu, email: dr.wu@nju.edu.cn Rui Huang, email: doctor_hr@126.com Keywords: chronic hepatitis B, liver biopsy, liver fibrosis, serum biomarkers, non-invasive fibrosis model Received: June 01, 2017 Accepted: June 28, 2017 Published: July 22, 2017 ABSTRACT Objectives: Noninvasive models have been established for the assessment of liver fibrosis in patients with chronic hepatitis B(CHB). However, the predictive performance of these established models remains inconclusive. We aimed to develop a novel predictive model for liver fibrosis in CHB based on routinely clinical parameters. Results: Platelets(PLT), the standard deviation of red blood cell distribution width(RDW-SD), alkaline phosphatase(ALP) and globulin were independent predictors of significant fibrosis by multivariable analysis. Based on these parameters, a new predictive model namely APRG(ALP/PLT/RDW-SD/globulin) was proposed. The areas under the receiver-operating characteristic curves(AUROCs) of APRG index in predicting significant fibrosis(≥F2), advanced fibrosis(≥F3) and liver cirrhosis(≥F4) were 0.757(95%CI 0.699 to 0.816), 0.763(95%CI 0.711 to 0.816) and 0.781(95%CI 0.728 to 0.835), respectively. The AUROCs of the APRG were significantly higher than that of aspartate transaminase(AST) to PLT ratio index(APRI), RDW to PLT ratio(RPR) and AST to alanine aminotransferase ratio(AAR) to predict significant fibrosis, advanced fibrosis and cirrhosis. The AUROCs of the APRG were also significantly higher than fibrosis-4 score (FIB-4) (0.723, 95%CI 0.663 to 0.783) for cirrhosis(P=0.034) and better than gamma-glutamyl transpeptidase(GGT) to PLT ratio(GPR) (0.657, 95%CI 0.590 to 0.724) for significant fibrosis(P=0.001). Materials and Methods: 308 CHB patients who underwent liver biopsy were enrolled. The diagnostic values of the APRG for liver fibrosis with other noninvasive models were compared. Conclusions: The APRG has a better diagnostic value than conventionally predictive models to assess liver fibrosis in CHB patients. The application of APRG may reduce the need for liver biopsy in CHB patients in clinical practice.