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Machine learning-based scoring functions (MLSFs) have become a very favorable alternative to classical scoring functions because of their potential superior screening performance. However, the information of negative data used to construct MLSFs was rarely reported in the literature, and meanwhile the putative inactive molecules recorded in existing databases usually have obvious bias from active molecules. Here we proposed an easy-to-use method named AMLSF that combines active learning using negative molecular selection strategies with MLSF, which can iteratively improve the quality of inactive sets and thus reduce the false positive rate of virtual screening. We chose energy auxiliary terms learning as the MLSF and validated our method on eight targets in the diverse subset of DUD-E. For each target, we screened the IterBioScreen database by AMLSF and compared the screening results with those of the four control models. The results illustrate that the number of active molecules in the top 1000 molecules identified by AMLSF was significantly higher than those identified by the control models. In addition, the free energy calculation results for the top 10 molecules screened out by the AMLSF, null model and control models based on DUD-E also proved that more active molecules can be identified, and the false positive rate can be reduced by AMLSF.

Hematotoxicity has been becoming a serious but overlooked toxicity in drug discovery. However, only a few

Duck hepatitis A virus type 1 (DHAV-1) causes a highly contagious disease in domestic ducklings, which is traditionally characterized by lesions in the liver and rarely in the pancreas. However, several outbreaks of DHAV-1, which were characterized by yellow coloration and hemorrhage in pancreatic tissues, have occurred in China. The causative agent was named as pancreatitis-type DHAV-1. Genomic sequencing indicated variation rates of 3.4-6.5% in the genome of the pancreatitis-type DHAV-1 compared with those of the classical type DHAV-1. The antigenic relationship between the pancreatitis-type DHAV-1 and classical type DHAV-1 indicated large variation. However, the mechanism involved in infection of the pancreatitis-type DHAV-1 is still unclear. Transcriptome analysis of duck pancreas infected with classical type DHAV-1 and pancreatitis-type DHAV-1 was carried out. Following deep sequencing with Illumina-Solexa, a total of 53.9 Gb clean data were obtained from the cDNA library of the pancreas and a total of 29,597 unigenes with an average length of 993.43 bp were generated following de novo sequence assembly. The expression levels of D-3-phosphoglyceratedehydrogenase, phosphoserine aminotransferase, phosphoserine phosphatase, which are involved in glycine, serine and threonine metabolism pathway, were significantly downregulated in the pancreatitis-type DHAV-1-infected group compared with those of the classical type DHAV-1-infected group. These findings provide information regarding differential expression levels of metabolism-associated genes between pancreatitis-type DHAV-1 and classical type DHAV-1, indicating that intensive metabolism disorders may contribute to different subtypes of DHAV-1-infection.

Objective False positive and negative results are associated with biliary tract cell brushing cytology during endoscopic retrograde cholangiopancreatography (ERCP). The causes are uncertain. The purpose of this study was to evaluate the accuracy of diagnoses made via cell brushing in our center, and to explore the factors influencing diagnosis. Methods The clinical data of patients who underwent cell brushing at our center from January 2016 to August 2019 were retrospectively analyzed. These included age, gender, stricture location, thickness of the bile duct wall in the narrow segment, maximum diameter of the biliary duct above the stricture, number of cell brush smears, carbohydrate antigen 19-9, and carcinoembryonic antigen. Positive brush cytology results were compared with results of surgical histology or tumor biopsy as well as with the patient’s clinical course. Results Of the 48 patients who underwent cell brushing cytology, 27 (56.3%) had positive results. The sensitivity and specificity of biliary duct cell brushing was 79.4%, and 85.7%, respectively. None of the above-mentioned factors were associated with positive cytology brushing results. Conclusions Cell brushing cytology remains a reliable method for diagnosis of pancreaticobiliary malignancies.

Pyogenic liver abscess (PLA) of biliary origin in Southeast Asia mainly occurs in patients with intrahepatic bile duct stone (IBDS) and extrahepatic bile duct stone (EBDS), bilioenteric anastomosis, or biliary stent. IBDS, as an endemic to Southeast Asia, remains a frequent etiology of acute cholangitis and PLA. PLA related to IBDS is characterized by high incidences of PLA recurrence and death related to infection, and difficulties in diagnosis of concomitant cholangicarcinoma. PLA of biliary origin is more likely caused by Escherichia coli, more often presented as polymicrobial infections, and more associated with extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae isolates. In this review, the authors summarize the differences on the presumed causes, pathogens, multidrug resistance, treatment, and prognosis of PLA between biliary origin and cryptogenic origin, the latter serving as a first and foremost presumed etiology of PLA. The authors also discuss the existing problems on early diagnosis of concomitant cholangicarcinoma related to IBDS.

Goose parvovirus (GPV) continues to be a threat to goose farms and has significant economic effects on the production of geese. Current commercially available vaccines only rarely prevent GPV infection. In our study, Lactobacillus (L.) plantarum NC8 was selected as a vector to express the VP2 gene of GPV, and recombinant L. plantarum pSIP409-VP2/NC8 was successfully constructed. The molecular weight of the expressed recombinant protein was approximately 70 kDa. Mice were immunized with a 2 × 109 colony-forming unit/200 μL dose of the recombinant L. plantarum strain, and the ratios and numbers of CD11c+, CD3+CD4+, CD3+CD8+, and interferon gamma- and tumor necrosis factor alpha-expressing spleen lymphocytes in the pSIP409-VP2/NC8 group were higher than those in the control groups. In addition, we assessed the capacity of L. plantarum SIP409-VP2/NC8 to induce secretory IgA production. We conclude that administered pSIP409-VP2/NC8 leads to relatively extensive cellular responses. This study provides information on GPV infection and offers a clear framework of options available for GPV control strategies.

The southeastern part of the Nanling metallogenic province, South China contains numerous economically important granite-hosted, hydrothermal vein-type uranium deposits. The Miao’ershan (MES) uranium ore field is one of the most important uranium sources in China, hosts the largest Chanziping carbonaceous-siliceous-pelitic rock-type uranium deposit and several representative granite-hosted uranium deposits. The geology and geochemistry of these deposits have been extensively studied. However, accurate and precise ages for the uranium mineralization are scarce because uranium minerals in these deposits are usually fine-grained, and may have formed in several stages, thus hindering the understanding of the uranium metallogenesis of this province. The Menggongjie (MGJ) uranium deposit is one of the largest granite-hosted uranium deposits in the MES ore field. Uranium mineralization in this deposit occurs at the central part of the MES granitic complex, accompanied with silicification, fluorination, K-metasomatism and hematitization. The ore minerals are dominated by uraninite, occurring in quartz or fluorite veinlets along fractures in altered granite. In-situ SIMS U-Pb dating on the uraninite yields the U–Pb isotopic age of 1.9 ± 0.7 Ma, which is comparable to the chemical U-Th-Pbtol uraninite age of 2.3 ± 0.1 Ma. Such ages agree well with the eruption ages of the extension-related Quaternary volcanics (2.1–1.2 Ma) in South China, suggesting that the uranium mineralization have formed at an extensional setting, possibly related to the Quaternary volcanic activities. Therefore, our robust, new dating results of the MGJ uranium deposit make it the youngest granite-hosted uranium deposit reported so far in South China and the mineralization event represents a newly identified mineralization epoch.

Avian influenza virus (AIV) is spreading worldwide and is a serious threat to the health of poultry and humans. In many countries, low pathogenic AIVs, such as H9N2, have become an enormous economic burden on the commercial poultry industry because they cause mild respiratory disease and decrease egg production. A recombinant Lactobacillus plantarum NC8 strain expressing NP-M1-DCpep from H9N2 AIV has been studied in a mouse model. However, it remains unknown whether this L. plantarum strain can induce an immune response and provide protection against H9N2 AIV in chickens. In this study, chickens that were orally vaccinated with NC8-pSIP409-NP-M1-DCpep exhibited significantly increased T cell-mediated immune responses and mucosal sIgA and IgG levels, which provided protection against H9N2 AIV challenge. More importantly, compared with oral administration of NC8-pSIP409-NP-M1-DCpep, intranasal administration induced stronger immune responses and provided effective protection against challenge with the H9N2 virus by reducing body weight loss, lung virus titers, and throat pathology. Taken together, these findings suggest that L. plantarum expressing NP-M1-DCpep has potential as a vaccine to combat H9N2 AIV infection.

During a study of ornithophilous viruses in China, a new densovirus (DNV) was isolated from the lung tissue of Parus major (PmDNV-JL). The complete genome of PmDNV-JL was cloned and sequenced. Five open reading frames (ORFs) were identified in the 5166nt sequence, on the basis of deduced amino acids. It was further shown that this virus caused cytopathic effects (CPE) in Feline kidney cells. The NS1 gene sequence of PmDNV-JL shares 70-99% nucleotide sequence identity with isolates of the Blattella germanica densovirus (BgDNV) and BgDNV-like virus. Phylogenetic analysis indicated that the predicted amino acid sequences of capsid (VP) and non-structural domain (NS1) of PmDNV-JL clustered with the BgDNV and were similar to BgDNV-HB within the genus Densovirus.

The classical explanation of the shielding charges at the surface of a ferroelectric was looked back at first. Then based on the non-equilibrium (or irreversible) thermodynamic description of ferroelectric phase transitions, a new explanation of that was given out. They agree with each other. In particular, the former is a special case of the latter.

The pathogenesis of hypogonadism in male patients with cirrhosis is complex and not well explained. Systemic infection and inflammation can inhibit testicular functions of endocrine and spermatogenesis. The acute inflammation induced by lipopolysaccharide can cause testicular acute inflammation. Both clinical and animal experimental data indicate that the developing process of cholestasis/cirrhosis can lead to endotoxemia. Little is known about the long-term effects of cholestasis on the intratesticular macrophage population, cellular proliferation and apoptosis. A rat model of secondary cholestasis caused by common bile duct ligation (CBDL) was used to evaluate the impact of cholestasis on them, and the influence of biliary decompression (choledochoduodenostomy). Endotoxemia occurred in animals at 20 days CBDL (20dCBDL) and 30 days CBDL (30dCBDL), but disappeared after 30 days biliary decompression in rats with CBDL. There was a considerable increase in the numbers of intratesticular CD68(+) and CD163(+) macrophages following CBDL. After biliary decompression, CD68(+) macrophage numbers decreased, but remained higher than that of controls; meanwhile, CD163(+) remained elevated only in rats with 30dCBDL. After CBDL, there was a progressive decrease in the expression of Bcl-2 protein and in proliferating cell nuclear antigen (PCNA(+)) cells, and a dramatic increase in the expression of Bax, active caspase-3 and apoptotic cells. These data suggest that secondary cholestasis expands the population of CD68(+) and CD163(+) macrophages in the testicular interstitium, decreases testicular proliferative activity, and promotes testicular apoptosis, which may be one of the mechanisms of biliary cirrhosis-related hypogonadism.

A wideband planar hybrid coupler with an 82% bandwidth is proposed in this paper. The proposed hybrid coupler consists of a wideband two-section coupled-line power divider and a broadband 90° phase shifter. The two-section coupled lines, where, not only perform impedance matching, but also make the total circuit of this divider compact. The broadband shifter employs a pair of open- and short-circuit stubs inserted onto the reference transmission line to compensate the phase variation of a conventional transmission line which is in proportion to the operating frequency. Therefore, wideband impedance matching is achieved and the bandwidth of phase shifting is broadened. Thus, a wideband 90° hybrid coupler with good performance both on power dividing and quadrature phase shifting is accomplished. To prove the design methodology, a hybrid coupler operating at 3.0 GHz is designed and the simulation is accomplished with ANSYS HFSS 14.0. Across the frequency bandwidth for reflection coefficient no more than −15dB, the maximum amplitude unbalance is 0.3dB, the phase variation is ±5°, and the port isolation is better than 20 dB.

Cholangitis, bacteremia, and pyogenic liver abscess (PLA) can be often caused by intrahepatic bile ducts stone (IBDS), which is endemic to South-East Asia. The association between IBDS and cholangiocarcinoma has been well recognized. Concomitant cholangiocarcinoma in the PLA related to IBDS is often missed.A case-control study consisting of 64 patients with PLA related to IBDS and 256 control patients with PLA not related to IBDS was used to investigate clinical features of PLA and incidence of concomitant cholangiocarcinoma in patients with PLA related to IBDS.The main imaging manifestations of PLA related to IBDS was cystic-solid lesions and solid lesions. Of seven patients (10.9%) with pathology-proven cholangiocarcinoma in the same area of PLA related to IBDS among 64 patients, only two patients were initially diagnosed as having concomitant cholangiocarcinoma by biopsy, and other five patients diagnosed as acute inflammatory lesion. Within 60 days after onset, the infection-related death rate and recurrence rate in patients with PLA related to IBDS were 12.9% and 20.3%, respectively, whereas in patients with PLA not related to IBDS were 3.9% and 3.1%, respectively. Only 25% of patients with PLA related to IBDS underwent surgery after admission. The main pathogens in PLA patients related to IBDS were Escherichia coli and extended-spectrum beta-lactamase-producing Enterobacteriaceae.The imaging manifestations of PLA related to IBDS often present cystic-solid or solid lesions. PLA related to IBDS is characterized by high rate of recurrence and infection-related death, difficulty in diagnosis of concomitant cholangicarcinoma.

1. This study was aimed at developing a high sensitive and selective liquid chromatography-tandem mass spectrometry method to quantify neohesperidin dihydrochalcone (NHDC) in rat plasma and tissues for pharmacokinetic, bioavailability and tissue distribution studies. 2. Biological samples were processed with one-step protein precipitation. Rutin was chosen as the internal standard (IS). Chromatographical separation was achieved on an SB-C18 (2.1 mm× 150 mm, 5 μm) column with acetonitrile--0.1% formic acid in water as the mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in negative ion mode; selected ion monitoring mode was used for quantification using target fragment ions m/z 611.4 for NHDC and m/z 609.1 for IS. 3. Calibration plots were linear over the range of 10-3000 ng/mL for NHDC. Lower limit of quantification (LLOQ) for NHDC was 10 ng/mL. Mean recovery of NHDC from plasma and tissues was better than 80.3%. Coefficient of variation of intra-day and inter-day precision were both less than 15%. The bioavailability of NHDC was 21.8%. 4. In conclusion, a sensitive, simple and specific LC-ESI-MS method for the determination of NHDC in rat biological samples was developed. This developed method is successfully used in the pharmacokinetic and tissue distribution study of NHDC in rats.

Background & Aims Little is known about aetiology and morbidity and clinical characteristics of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Methods An analysis between pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates and those caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae was performed. Results Among 817 pyogenic liver abscess patients, there were 176 patients (21.5%) with pyogenic liver abscess of biliary origin, and 67 pyogenic liver abscess patients (8.2%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates (mainly Escherichia coli and Klebsiella pneumoniae). Of 176 pyogenic liver abscess patients related to biliary disorders, there were 48 pyogenic liver abscess patients (27.3%) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Within 67 pyogenic liver abscess patients caused by Enterobacteriaceae expressing extended-spectrum beta-lactamases, the occurrences of 48 pyogenic liver abscess patients (71.6%) were associated with biliary disorders. When compared with pyogenic liver abscess patients caused by non-extended-spectrum beta-lactamase-producing Enterobacteriaceae, there were significantly greater incidences of polymicrobial infections, bacteremia, pulmonary infection, recurrence and death in pyogenic liver abscess patients caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae. Carbapenems remain mainstay drugs against extended-spectrum beta-lactamase-producing E. coli and K. pneumoniae. Independent risk factors for occurrence of pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae were biliary disorders including extra- and intrahepatic cholangiolithiasis and an abnormal bilioenteric communication between bile and gut, a treatment history of malignancy such as operation and chemotherapy, pulmonary infection, and diabetes mellitus. Conclusions Pyogenic liver abscess caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae isolates mainly occurs in patients with biliary disorders or with a treatment history of malignancy. The mainstay of treatment remains carbapenems in combination with adequate aspiration or drainage.

Polycrystalline Diamond (PCD) tools are widely used while machining wood-based composites because of its outstanding hardness, thermal conductivity and abrasive resistance. However, the above mentioned beneficial properties such as super hardness also cause problems in manufacturing PCD tools using traditional process methods. The main problem now in manufacturing PCD tools is the low efficiency and difficulties while manufacturing PCD tools with complex curved surface. To manufacture PCD tools with complex curved surface more efficiently, in this paper, the mechanical structure, hardware circuit and software system of five-axis EDG CNC system are introduced. To satisfy the unique requirements of EDG, a proper mechanical structure of 5 CNC controlled axis and 2 manual axis are given, as well as the design of hardware circuit of EDG based on PCI Bus. The software system which is designed based on RT-Linux is divided into four modules: real-time cyclical tasks module, real-time gusty tasks module, non real-time tasks module and EDG process database. , This paper gives out the solutions of the specific functions of this special CNC system, including automatic measurement, automatic programming, automatic electrode wear compensation, and detection and control of spark gap. The detailed structure and organization of the software system is also provided. At last, through actual cutting experiments of woodworking PCD tools, the correctness and practicality of this system is verified.

Contrary to the problem that automobile switches have various kinds and large differences in the structure and performance so that traditional testing methods have been unable to meet the testing requirements of high performance switches, the paper designs a new detection system used to detect the functions of general auto switches which applies the developing environment LabVIEW based on virtual instrument technology and adopts the technology of embedded observe and control system. Using PC as the host computer, the system adopts the LabVIEW8.5 to compile a real-time monitoring system with good human-computer interface; S3C2440-ARM9 processor is used as the main controller of observe and control system in the inferior computer which collects output current signal when the circuit is conducted after switch is pressed. After the coding process of LwIP software protocol and the drive of Ethernet controller DM9000, the signal is transmitted to PC through Ethernet interface. Compared with conventional testing measures, this system greatly improves the real-time performance as well as working efficiency of detecting switch functions and reduces the corresponding human and material resources.

Near-infrared (NIR) organic light-emitting devices (OLEDs) are demonstrated by employing erbium fluoride (ErF 3 )-doped tris-(8-hydroxyquinoline) aluminum (Alq 3 ) as the emitting layer. The device structure is ITO/N,N′-di-1-naphthyl-N,N′-diphenylbenzidine (NPB)/Alq 3 : ErF 3 /2,2′,2″-(1,3,5-phenylene)tris(1-phenyl-1H-benzimidazole) (TPBI)/Alq 3 /Al. Room-temperature electroluminescence around 1530 nm is observed due to the 4 I 13/2 – 4 I 15/2 transition of Er 3+ . Full width at half maximum (FWHM) of the electroluminescent (EL) spectrum is ∼50 nm. NIR EL intensity from the ErF 3 -based device is ∼4 times higher than that of Er(DBM) 3 Phen-based device at the same current. Alq 3 –ErF 3 composite films are investigated by the measurements of X-ray diffraction (XRD), absorption, photoluminescence (PL) and PL decay time. Electron-only devices are also fabricated. The results indicate that energy transfer mechanism and charge trapping mechanism coexist in the NIR EL process.

Because of the poor reconfigurability of the existing test resource models and the faultiness of the intelligent modeling methods in automatic test system, the modeling method based on Multi-Agent was studied. By analyzing the characters of test resources, the test resource models were classified as device model, adapter model and configuration model. The typical test resource model based on Multi-Agent with three layers and five agents was built. The structure and function of system management agent, model reconfiguration agent, function management agent, channel control agent and function realization agent in the model were analyzed. Then its application in Intelligent Virtual Instrument was introduced. This model based on Multi-Agent has good reconfigurability and intelligence, and it can be used to build the general-purpose and intelligent automatic test system.

Background. Bacteremias, which are often caused by gram-negative bacteria, are the most frequently occurring infectious complications after liver transplantation (LT). The aim of this study was to investigate bacteremic incidence, pathogenic spectrum, risk factors for bacteremia due to multidrug resistant (MDR) gram-negative bacilli, and its impact on mortality after LT. Methods. A cohort analysis of prospectively recorded data was done in 475 LT recipients, who were divided into 3 categories: cases with gram-negative bacteremia, cases with MDR gram-negative bacteremia, and cases without bacteremia as controls. Results. In 475 LT recipients, there were 152 (32.0%) patients with gram-negative bacillus bacteremia in the first 6 months after LT. Out of 152 patients, there were 225 bacteremic episodes, which accounted for 69.7% in a total 323 bacteremic episodes. A total of 190 bacteremic episodes were caused by Stenotrophomonas maltophilia, Enterobacteriaceae, Ochrobactrum anthropi, Pseudomonas, and Acinetobacter baumanii, all of which were the most frequent gram-negative isolates in this study, and MDR bacilli constituted 56.3%. The most frequent source was intravascular catheters. There were 70 patients with MDR gram-negative bacillus bacteremia. Independent risk factors for bacteremia due to MDR gram-negative bacillus were as follows: post-LT abdominal infection (P

BACKGROUND: Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients. The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients. The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients. METHODS: A retrospective analysis was made of recorded data on the epidemiology, risk factors, and mortality of invasive fungal infections in 352 liver transplant recipients. RESULTS: Forty-two (11.9%) patients suffered from invasive fungal infection. Candida species infections (53.3%) were the most common, followed by Aspergillus species (40.0%). There were 21 patients with a superficial fungal infection. The median time to onset of first invasive fungal infection was 13 days, first invasive Candida infection 9 days, and first invasive Aspergillus infection 21 days. Fifteen deaths were related to invasive fungal infection, 10 to Aspergillus infection, and 5 to Candida infection. Invasive Candida species infections were associated with encephalopathy (P = 0.009) and postoperative bacterial infection (P = 0.0003) as demonstrated by multivariate analysis. Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy (P = 0.004), renal dysfunction (P = 0.005) and hemodialysis (P = 0.001). CONCLUSIONS: The leading etiologic species of invasive fungal infections are Candida and Aspergillus, which frequently occur in the first posttransplant month. Encephalopathy and postoperative bacterial infection predispose to invasive Candida infection. Posttransplant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection. More studies are needed to determine the effect of prophylactic antifungal therapy in high risk patients.

Recently, poly-γ-glutamic acid synthetase A (pgsA) has been applied to display exogenous proteins on the surface of Lactobacillus casei or Lactococcus lactis, which results in a surfacedisplayed component of bacteria. However, the ability of carrying genes encoded by plasmids and the expression efficiency of recombinant bacteria can be somewhat affected by the longer gene length of pgsA (1,143 bp); therefore, a truncated gene, pgsA, was generated based on the characteristics of pgsA by computational analysis. Using murine IL-10 as an exogenous gene, recombinant Lactobacillus plantarum was constructed and the capacity of the surface-displayed protein and functional differences between exogenous proteins expressed by these strains were evaluated. Surface expression of IL-10 on both recombinant bacteria with anchorins and the higher expression levels in L. plantarum-pgsA'-IL-10 were confirmed by western blot assay. Most importantly, up-regulation of IL-1β, IL-6, TNF-α, IFN-γ, and the nuclear transcription factor NF-κB p65 in RAW264.7 cells after stimulation with Poly(I:C) or LPS was exacerbated after co-culture with L. plantarum-pgsA. By contrast, IL-10 expressed by these recombinant strains could reduce these factors, and the expression of these factors was associated with recombinant strains that expressed anchorin (especially in L. plantarum-pgsA'-IL-10) and was significantly lower compared with the anchorin-free strains. These findings indicated that exogenous proteins could be successfully displayed on the surface of L. plantarum by pgsA or pgsA', and the expression of recombinant bacteria with pgsA' was superior compared with bacteria with pgsA.

The effects of β-glucans from Coriolus versicolor (CVP), which are extracted from a well-known immune stimulator C. versicolor, have been demonstrated extensively in vitro and in vivo. However, until now, the phagocytic activity has not been elucidated. Hence, the objective of the present study was to identify the antibacterial activity of CVP or CVP-treated macrophages by an analysis of cell cytotoxicity, phagocytic activity, intracellular bacterial survival, macrophage activation, production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in CVP-treated macrophages using flow cytometry, RT-PCR, a gentamicin protection assay, a Nitric oxide assay and an iNOS enzymatic activity assay. The results indicate that CVP-treated macrophages can phagocytize and kill bacteria, probably due to the production of NO and iNOS. More importantly, CVP-treated macrophages are effective at protecting mice against the challenge of Salmonella typhimurium. The results of this study suggest that the antibacterial effects of CVP are probably caused by the activation of innate immune cells, especially macrophages, because the activated macrophage produces NO, which kills bacteria. These phenomena indicate the possibility of CVP as a potential alternative for antibiotics against resistant bacteria.

Hemagglutinin (HA) has been demonstrated as an effective candidate vaccine antigen against AIVs. Dendritic cell-targeting peptide (DCpep) can enhance the robustness of immune responses. The purpose of this study was to evaluate whether DCpep could enhance the immune response against H9N2 AIV when utilizing Lactobacillus plantarum NC8 (NC8) to present HA-DCpep in mouse and chicken models. To accomplish this, a mucosal vaccine of a recombinant NC8 strain expressing HA and DCpep that was constructed in a previous study was employed. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. Orally administered NC8-pSIP409-HA-DCpep elicited high serum titers of hemagglutination-inhibition (HI) antibodies in mice and also induced robust T cell immune responses in both mouse and chicken models. These results revealed that recombinant L. plantarum NC8-pSIP409-HA-DCpep is an effective vaccine candidate against H9N2 AIVs.

Colorectal cancer (CRC) is one of the most prevalent forms of cancer that shows a high mortality and increasing incidence. There are numerous successful treatment options for CRC, including surgery, chemotherapy, radiotherapy and immunotherapy; however, their side effects and limitations are considerable. Probiotics may be an effective strategy for preventing and inhibiting tumour growth through stimulation of host innate and adaptive immunity. We investigated and compared potential anti-tumour immune responses induced by two isolated Lactobacillus strains, Lactobacillus plantarum A and Lactobacillus rhamnosus b, by pre-inoculating mice with lactobacilli for 14 days. Subsequently, subcutaneous and orthotopic intestinal tumours were generated in the pre-inoculated mice using CT26 murine adenocarcinoma cells and were assessed for response against the tumour. Our results indicated that oral administration with L. plantarum inhibited CT26 cell growth in BALB/c mice and prolonged the survival time of tumour-bearing mice compared with mice administered L. rhamnosus. L. plantarum produced protective immunity against the challenge with CT26 cells by increasing the effector functions of CD8+ and natural killer (NK) cell infiltration into tumour tissue, up-regulation of IFN-gamma (but not IL-4 or IL-17) production, and promotion of Th1-type CD4+ T differentiation. Consequently, our results suggest that L. plantarum can enhance the anti-tumour immune response and delay tumour formation.

Background Pyrogenic liver abscesses (PLA) can be caused by cholangitis associated with hepatolithiasis and cholangitis related to an abnormal bilioenteric communication, such as a hepaticojejunostomy or the presence of indwelling biliary stents. Our aim was to evaluate the clinical characteristics of PLA of biliary origin. Methods We compared patients with PLA related to biliary tract disease (PLA-B; n = 125) with patients with PLA not related to biliary tract disease (PLA-NB; n = 444). We also separated the patients with PLA-B into PLA related to biliary tract disease that involved an abnormal bilioenteric communication, including hepaticojejunostomy and indwelling biliary stents (PLA-B-AC; n = 38), and PLA-B not related to abnormal communication ( n = 87), and compared them. Results Among the 569 patients with PLA from 2008 to 2013, the most common etiologies were cryptogenic ( n = 341; 60%) and biliary ( n = 125; 22%). Patients with PLA-B tended to have a higher maximum body temperature and a greater leukocytosis. The incidences of bacteremia, septic shock, death, and postdischarge recurrence were greater in the PLA-B group when compared with the PLA-NB group. The most commonly isolated pathogenic bacteria in PLA-B group were Escherichia coli (36%) and Klebsiella pneumonia (23%). In contrast, in the PLA-NB group, the most common pathogen was K pneumonia (64%), whereas E coli was uncommon (only 5%). Independent risk factors for the occurrence of PLA-B were isolates with multidrug resistant (MDR) bacteria, bacteremia, E coli, and polymicrobial infection. In the group of PLA-B-AC, risk factors included MDR bacteria and a history of malignancy. Conclusion The occurrences of PLA-B are often infected with MDR bacteria and mixed infections caused mainly by E coli and other isolates and associated with bacteremia; PLA-B-AC are associated with MDR bacteria and a history of malignancy.

IEEE Instrumentat & Measurement Soc, Shanghai Univ Engn Sci, City Univ Hongkong, Changsha Univ Sci & Technol, Hunan Univ Sci & Technol

Problem Cholestasis can cause translocation of gut bacteria, and endotoxemia, and systemic inflammation. Now, little is known about the effects of cholestasis on the testicular inflammation and autophagy. Methods A rat biliary cholestasis model caused by common bile duct ligation (CBDL), together with biliary decompression (choledochoduodenostomy), was used. Results The magnitude of MCP-1 expression and CD68+ macrophage infiltration within testes was progressively up-regulated in rats along with increasing duration of CBDL and was maintained at relatively high level in rats with biliary decompression. The large up-regulation of testicular ATG-12, LC3II, and autophagic vacuoles was found with the extending duration of CBDL and kept at 5 weeks following biliary decompression. The autophagic contents were a large accumulation of mitophagy in testes in rats with CBDL, and cytosol components in rats with biliary decompression. Conclusion Secondary biliary cholestasis can promote inflammatory reaction and the activation of mitophagy and autophagy in testes.

Traditional Chinese medicine (TCM) has unique therapeutic effects for complex chronic diseases. However, for the lack of an effective systematic approach, the research progress on the effective substances and pharmacological mechanism of action has been very slow. In this paper, by incorporating network biology, bioinformatics and chemoinformatics methods, an integrated approach was proposed to systematically investigate and explain the pharmacological mechanism of action and effective substances of TCM. This approach includes the following main steps: First, based on the known drug targets, network biology was used to screen out putative drug targets; Second, the molecular docking method was used to calculate whether the molecules from TCM and drug targets related to chronic kidney diseases (CKD) interact or not; Third, according to the result of molecular docking, natural product-target network, main component-target network and compound-target network were constructed; Finally, through analysis of network characteristics and literature mining, potential effective multi-components and their synergistic mechanism were putatively identified and uncovered. Bu-shen-Huo-xue formula (BSHX) which was frequently used for treating CKD, was used as the case to demonstrate reliability of our proposed approach. The results show that BSHX has the therapeutic effect by using multi-channel network regulation, such as regulating the coagulation and fibrinolytic balance, and the expression of inflammatory factors, inhibiting abnormal ECM accumulation. Tanshinone IIA, rhein, curcumin, calycosin and quercetin may be potential effective ingredients of BSHX. This research shows that the integration approach can be an effective means for discovering active substances and revealing their pharmacological mechanisms of TCM.

Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. vaccae Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. vaccae BCG revealed that M. vaccae was more malignant than M. vaccae in mice. We also demonstrated that serum from the M. vaccae-infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3+CD4+IFN-γ+ and CD3+CD4+IL4+ cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3+CD4+IFN-γ+ cells. However, the Th1 response declined over time, which was associated with appearance of the CD4+CD25+FoxP3+ and CD4+CD25+CD152+Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.

Gram-positive bacteria such as Staphylococcus aureus have been a common cause of infection among liver transplant (LT) recipients in recent decades. The understanding of local epidemiology and its evolving trends with regard to pathogenic spectra and antibiotic susceptibility is beneficial to prophylactic and empiric treatment for LT recipients. This study aimed to investigate etiology, timing, antibiotic susceptibility and risk factors for multidrug resistant (MDR) Gram-positive coccal bacteremia after LT.A cohort analysis of prospectively recorded data was performed to investigate etiologies, timing, antibiotic susceptibility and risk factors for MDR Gram-positive coccal bacteremia in 475 LT recipients.In 475 LT recipients in the first six months after LT, there were a total of 98 episodes of bacteremia caused by Gram-positive cocci in 82 (17%) patients. Seventy-five (77%) bacteremic episodes occurred in the first post-LT month. The most frequent Gram-positive cocci were methicillin-resistant coagulase-negative staphylococcus (CoNS, 46 isolates), methicillin-resistant Staphylococcus aureus (MRSA, 13) and enterococcus (34, E. faecium 30, E. faecalis 4). In all Gram-positive bacteremic isolates, 59 of 98 (60%) were MDR. Gram-positive coccal bacteremia and MDR Gram-positive coccal bacteremia predominantly occurred in patients with acute severe exacerbation of chronic hepatitis B and with fulminant/subfulminant hepatitis. Four independent risk factors for development of bacteremia caused by MDR Gram-positive coccus were: LT candidates with encephalopathy grades II - IV (P = 0.013, OR: 16.253, 95%CI: 1.822 - 144.995), pre-LT use of empirical antibiotics (P = 0.018, OR: 1.029, 95%CI: 1.002 - 1.057), post-LT urinary tract infections (P0.001, OR: 20.340, 95%CI: 4.135 - 100.048) and abdominal infection (P = 0.004, OR: 2.820, 95%CI: 1.122 - 10.114). The main infectious manifestations were coinfections due to gram-positive cocci and gram-negative bacilli.Methicillin-resistant CoNS and enterococci are predominant pathogens among LT recipients with Gram-positive coccal bacteremia. Occurrences of Gram-positive coccal bacteremia may be associated with the severity of illness in the perioperative stage.

Pneumonia caused by multidrug-resistant (MDR) Gram-negative bacilli is associated with a higher mortality rate. The appropriate empiric therapy is based on the understanding of local etiology and MDR pattern. This study was to evaluate the spectrum of Gram-negative bacilli, MDR rate, risk factors and mortality in 475 liver transplantation (LT) recipients. In the first six months after LT, the incidence of bacterial pneumonia was 21.3% (101/475). The overall infectious incidence during the first post-transplant month was 80.2%. The most frequent pneumonia isolates were Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus. Gram-negative bacilli accounted for 69.6% of all pneumonia pathogens. Of the main 124 Gram-negative bacilli isolates, MDR rate was 58.9%. Four risk factors for post-LT pneumonia caused by MDR Gram-negative bacilli were LT candidates with grade II-IV encephalopathy (OR 2.275, 95%CI 1.249-4.124, p = 0.006), prolonged duration of endotracheal intubation (OR 8.224, 95%CI 4.276-15.815, p = 0.013), tracheostomy (OR 4.929, 95%CI 1.099-18.308, p = 0.027) and post-LT episode(s) of reoperations (OR 10.597, 95%CI 3.726-30.134, p0.001). MDR Gram-negative bacterial pneumonia-related mortality was significantly higher than that because of antibiotic-susceptible bacilli (45.6% vs. 11.4%, p = 0.010). Our data suggest that pneumonia caused by MDR Gram-negative bacilli after LT is common, and associated with the severity of underlying disease, prolonged mechanical ventilation and upper abdominal surgery.

GPS provides a method for accurate timing. The measurement of the time delay of timing receiver is a difficult task with the existing method, high in cost and complex in operation. A new and simpler measurement method is presented in this paper, based on the time difference between UTC(NTSC) which is the time scale kept in National Time Service Center and the output of 1pps signal by the GPS timing receiver. On the basis of the international comparison link of UTC(NTSC) and UTC, and the time difference between UTC and GPST, a new method for the measurement of the time delay of GPS timing receiver is given. This method is easy to do. The error of with this method is also analysized.

To reveal the molecular biological characteristics of genome of circovirus in infected ducks, two nucleotide fragments were amplified by overlapping PCRs using DNA extracted from various tissues of ducks. After they had been assembled together, the nucleotide components, the genome organization and the phylogenetic scale of the sequence were analyzed. The results showed that the obtained sequence is a circular DNA with a total length of 1995nt. It contains 6 open reading frames (ORFs), and shares a high identity of 97.4% with the MuDCV circovirus sequence presented in GenBank (AY228555). These results indicate that the amplified product stems from duck circovirus sequence.

Invasive fungal infections are an important cause of posttransplant mortality in solid-organ recipients. The current trend is that the incidence of invasive candidiasis decreases significantly and invasive aspergillosis occurs later in the liver posttransplant recipients. The understanding of epidemiology and its evolving trends in the particular locality is beneficial to prophylactic and empiric treatment for transplant recipients.A retrospective analysis was made of recorded data on the epidemiology, risk factors, and mortality of invasive fungal infections in 352 liver transplant recipients.Forty-two (11.9%) patients suffered from invasive fungal infection. Candida species infections (53.3%) were the most common, followed by Aspergillus species (40.0%). There were 21 patients with a superficial fungal infection. The median time to onset of first invasive fungal infection was 13 days, first invasive Candida infection 9 days, and first invasive Aspergillus infection 21 days. Fifteen deaths were related to invasive fungal infection, 10 to Aspergillus infection, and 5 to Candida infection. Invasive Candida species infections were associated with encephalopathy (P = 0.009) and postoperative bacterial infection (P = 0.0003) as demonstrated by multivariate analysis. Three independent risk factors of invasive Aspergillus infection were posttransplant laparotomy (P = 0.004), renal dysfunction (P = 0.005) and hemodialysis (P = 0.001).The leading etiologic species of invasive fungal infections are Candida and Aspergillus, which frequently occur in the first posttransplant month. Encephalopathy and postoperative bacterial infection predispose to invasive Candida infection. Posttransplant laparotomy and poor perioperative clinical status contribute to invasive Aspergillus infection. More studies are needed to determine the effect of prophylactic antifungal therapy in high risk patients.

To investigate the effects of tacrolimus-based immunosuppression regimens after orthotopic liver transplantation and search a reasonable regimen of combination therapy and suitable blood concentration of tacrolimus.Ninety-four adult recipients of cadaveric livers were randomly divided into 3 groups to undergo different tacrolimus-based immunosuppression regimens: dual (tacrolimus + glucocorticoid), triple [tacrolimus + mycophenolate mofetil (MMF) + glucocorticoid]; quadruple [tacrolimus + MMF + glucocorticoid in addition of induction treatment by daclizumab]. The efficacy and safety of the 3 groups 6 months after the transplantation were compared.The frequencies of acute rejection were 25.9%, 11.1%, and 7.5% for the dual, triple, and quadruple therapy groups, that of the quadruple therapy group being significantly lower than that of the dual therapy group (P = 0.038). There were no significant differences in the rates Three months after transplantation, the levels of ALT and total cholesterol of the dual therapy groups were significantly higher than those of the quadruple therapy group (P(ALT) = 0.011, P(Tch) = 0.002). Within the first month post-operatively the concentration of tacrolimus of the triple therapy group could be controlled at the level 8 ng x ml(-1)-13 ng x ml(-1).Quadruple tacrolimus-based immunosuppression regimen is the most effective and safest, followed by the triple therapy and dual therapy. Low-dose tacrolimus combination therapy provides an effective protection to the liver graft with mild drug toxicity to the patient.

To investigate the relation between the activity of nuclear factor kappaB (NF-kappaB) and the expression of interferon (IFN)-gamma gene transcription with or without ciclosporin treatment after liver transplantation.Orthotopic liver transplantation was performed in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar); Group III: acute rejection treated with ciclosporin by intramuscular route (SD-to-Wistar + ciclosporin). Electrophoretic mobility shift assay and reverse transcriptase polymerase chain reaction were used to analyze NF-kappaB activity of splenocytes and IFN-gamma gene transcription expression of grafted liver with or without ciclosporin treatment after liver transplantation. Histopathological examination was also used in this study.Low NF-kappaB activity was only detected at day 5 and day 7 in Wistar-to-Wistar group after transplantation, meanwhile low IFN-gamma mRNA expression was detected at any time in this group. In contrast, high NF-kappaB activity was detected in SD-to-Wistar group and high level IFN-gammamRNA expression was detected at all time points in this group. The activity of NF-kappaB and IFN-gammamRNA expression were significantly inhibited in SD-to-Wistar + ciclosporin group which was significantly lower than that of SD-to-Wistar group (P0.001). A good correlation was found between activity of NF-kappaB and IFN-gamma mRNA expression in this study (r=0.815, P0.01).The change of expression IFN-gamma mRNA is at least partially due to the activity change of NF-kappaB after orthotopic liver transplantation. CsA down-regulates NF-kappaB activity and further inhibit IFN-gamma gene transcription.

To investigate the inhibitory effect of tea polyphenols (TP) on the transforming growth factor-beta1 (TGF-beta1) expression in rat model of cyclosporine A (CsA)-induced chronic nephrotoxicity.The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL/kg/d sc), TP (80 mg/kg/d ig), CsA (15 mg/kg/d sc) and TP plus CsA (CsA 15 mg/kg/d sc+TP 80 mg/kg/d, ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-beta1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot.CsA-treated rats had increased renal expression of TGF-beta1 mRNA and its protein, compared with the vehicle- or TP-treated controls. The renal function and interstitial fibrosis were ameliorated and renal expression of TGF-beta1 mRNA and its protein was decreased in animals treated with CsA plus TP, compared with animals treated with CsA alone (P0.05).TP significantly inhibits renal expression of TGF-beta1 in rat model of cyclosporine-induced chronic nephrotoxicity, suggesting that the decreased renal expression of TGF-beta1 exerted by TP is one of mechanisms to protect renal function and tissue structure.