Oral immunization with recombinant L. lactis expressing GCRV-II VP4 produces protection against grass carp reovirus infection.

The hemorrhagic disease causing by grass carp reovirus (GCRV) infection, is associated with major economic losses and significant impact on aquaculture worldwide. VP4 of GCRV is one of the major outer capsid proteins which can induce an immune response in the host. In this study, pNZ8148-VP4/L. lactis was constructed to express recombinant VP4 protein of GCRV, which was confirmed by the Western-Blot and enzyme-linked immunosorbent assay. Then we performed the oral immunization for rare minnow model and the challenge with GCRV-II. After oral administration, pNZ8148-VP4/L. lactis can continuously reside in the intestinal tract to achieve antigen presentation. The intestinal and spleen samples were collected at different time intervals after immunization, and the expression of immune-related genes was detected by real-time fluorescence quantitative PCR. The results showed that VP4 recombinant L. lactis could induce complete cellular and humoral immune responses in the intestinal mucosal system, and effectively regulate the immunological effect of the spleen. The immunogenicity and the protective efficacy of the oral vaccine was evaluated by determining IgM levels and viral challenge to vaccinated fish, a significant level (P < 0.01) of antigen-specific IgM with GCRV-II neutralizing activity was able to be detected, which provided a effective protection in the challenge experiment. These results indicated that an oral probiotic vaccine with VP4 expression can provide effective protection for grass carp against GCRV-II challenge, suggesting a promising vaccine strategy for fish.

Tailoring Spin State of Perovskite Oxides by Fluorine Atom Doping for Efficient Oxygen Electrocatalysis.

Promoting the initially deficient but economical catalysts to high-performing competitors is important for developing superior catalysts. Unlike traditional nano-morphology construction methods, this work focuses on intrinsic catalytic activity enhancement via heteroatom doping strategies to induce lattice distortion and optimize spin-dependent orbital interaction to alter charge transfer between catalysts and reactants. Experimentally, a series of different concentrations of fluorine-doped lanthanum cobaltate (Fx -LaCoO3 ) exhibiting excellent electrocatalytic activity is synthesized, including a low overpotential of 390 mV at j = 10 mA cm-2 for OER and a large half-wave potential of 0.68 V for ORR. Meanwhile, the assembled rechargeable Zn-air batteries deliver an excellent performance with a large specific capacity of 811 mAh/gZn under 10 mA cm-2 and stability of charge/recharge (120 h). Theoretically, taking advantage of density functional theory calculations, it is found that the prominent OER/ORR performance arises from the spin state transition of Co3+ (Low spin state (LS, t2g 6 eg 0 ) → Intermediate spin state (IS, t2g 5 eg 1 ) and the mediated d-band center upshift by F atom incorporation. This work establishes a novel avenue for designing superior electrocatalysts in perovskite-based oxides by regulating spin states.

T cells participate in bone remodeling during the rapid palatal expansion.

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force-induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3-day, 5-day, 7-day, and retention for 28-day, micro-computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy.

Effects of whitening toothpaste and bleaching treatment on resin composite discoloration caused by cigarette smoke and electronic vapor aerosol.

PURPOSE: To compare the effects of whitening toothpaste and bleaching with 6% hydrogen peroxide (H2O2) on discoloration of dental resin composite caused by cigarette smoke (CS) and electronic vapor product (EVP) aerosol. METHODS: 40 resin composite discs were divided into three groups: 15 each for CS and EVP aerosol exposure and 10 for air exposure (control). Exposures were performed for 15 days, with daily brushing with regular toothpaste. Two whitening sessions, including 21 days of brushing with whitening toothpaste and 3 days of treatments with take-home bleaching (6% H2O2), were performed after the exposure. Color and gloss were assessed before exposure, at every 5 days of exposure, and after each whitening session. RESULTS: After 15 days of exposure, marked discoloration of resin composite was observed in the CS group (ΔE = 23.66 ± 2.31), minimal color change in the EVP group ((ΔE = 2.77 ± 0.75), and no color change in the control group. Resin composites exposed to CS did not recover their original color after treatment with whitening toothpaste ((ΔE = 20.17 ± 2.68) or take-home bleaching ((ΔE = 19.32 ± 2.53), but those exposed to EVP aerosol reverted to baseline after treatment with whitening toothpaste ((ΔE = 0.98 ± 0.37), and no further change in color was observed following take-home bleaching. The gloss of resin composites exposed to CS, EVP aerosol, and air decreased equally with exposure time. Brushing with whitening toothpaste recovered the gloss similarly in all groups, but no further change was observed following take-home bleaching. CLINICAL SIGNIFICANCE: Aerosol from electronic vapor products induced minimal discoloration of resin composites that can be completely reverted by brushing with whitening toothpaste alone. Bleaching with 6% H2O2 did not revert discoloration caused by cigarette smoke. Whitening toothpaste could help revert the decreased gloss of resin composites.

Enhancement of Histone Deacetylase Inhibitor Sensitivity in Combination with Cyclin-Dependent Kinase Inhibition for the Treatment of Oral Squamous Cell Carcinoma.

BACKGROUND/AIMS: Previous research has indicated that the currently available histone deacetylase inhibitors (HDACis) are not effective as monotherapies against oral squamous cell carcinoma (OSCC). However, HDACis act synergistically with other therapeutic agents to exert significant antitumor activities. Thus, a strategy to develop chemotherapeutic agents by combining several active groups based on histone deacetylase (HDAC) into a single molecule as a conjugate that modulates multiple cellular pathways may be useful for the treatment of OSCC. METHODS: The novel inhibitor Roxyl-ZR was prepared by organic synthesis and its anticancer effects on OSCC were investigated by cell metabolism (n=5), colony formation (n=3), cell cycle (n=3), cell apoptosis (n=3), wound healing (n=3), transwell migration (n=3), and 5-bromo-2'-deoxyuridine staining (n=3) assays in vitro and in in vivo xenograft mice models (4 mice/group for subcutaneous xenograft and 3 mice/group for orthotopic xenograft ). The abundance of Ki67, Bcl-2, and p-STAT3 was detected by immunohistochemistry staining (n=4). Apoptotic cells in the tumor tissues of mice were detected by terminal deoxynucleotidyl transferase dUTP nickend labeling assay (n=3). The abundance of related proteins levels were evaluated by western blot (n=3). E-cadherin expression was detected by an immunofluorescence assay (n=3). RESULTS: Compared with the approved HDACi, conjugated Roxyl-ZR exhibited significantly higher antitumor effects in OSCC cells. Roxyl-ZR suppressed OSCC cell proliferation by inducing the reduction of S phase and inducing caspase-dependent apoptosis by down-regulating Bcl-2 expression. Moreover, Roxyl-ZR attenuated the epithelial-mesenchymal transition, which is closely associated with migration and invasion. In addition, Roxyl-ZR inhibited OSCC xenograft mice models and showed low toxicity. The mechanism underlying the Roxyl-ZR-enhanced sensitivity to HDACi may be attributed to the inhibition of key regulators of JAK1-STAT3 signaling pathway. CONCLUSION: HDAC-cyclin-dependent kinase conjugates represent a novel approach to the development of OSCC treatment. Our findings may open a new avenue for the development of novel inhibitors for the treatment of OSCC.

Epidemiology and risk factors for nosocomial infection in the respiratory intensive care unit of a teaching hospital in China: A prospective surveillance during 2013 and 2015.

BACKGROUND: To determine the epidemiology and risk factors for nosocomial infection (NI) in the Respiratory Intensive Care Unit (RICU) of a teaching hospital in Northwest China. METHODS: An observational, prospective surveillance was conducted in the RICU from 2013 to 2015. The overall infection rate, distribution of infection sites, device-associated infections and pathogen in the RICU were investigated. Then, the logistic regression analysis was used to test the risk factors for RICU infection. RESULTS: In this study, 102 out of 1347 patients experienced NI. Among them, 87 were device-associated infection. The overall prevalence of NI was 7.57% with varied rates from 7.19 to 7.73% over the 3 years. The lower respiratory tract (43.1%), urinary tract (26.5%) and bloodstream (20.6%) infections accounted for the majority of infections. The device-associated infection rates of urinary catheter, central catheter and ventilator were 9.8, 7.4 and 7.4 per 1000 days, respectively.The most frequently isolated pathogens were Staphylococcus aureus (20.9%), Klebsiella pneumoniae (16.4%) and Pseudomonas aeruginosa (10.7%). Multivariate analysis showed that the categories D or E of Average Severity of Illness Score (ASIS), length of stay (10-30, 30-60, ≥60 days), immunosuppressive therapy and ventilator use are the independent risk factors for RICU infection with an adjusted odds ratio (OR) of 1.65 (95% CI: 1.15~2.37), 5.22 (95% CI: 2.63~10.38)), 2.32 (95% CI: 1.19~4.65), 8.93 (95% CI: 3.17~21.23), 31.25 (95% CI: 11.80~63.65)) and 2.70 (95% CI: 1.33~5.35), respectively. CONCLUSION: A relatively low and stable rate of NI was observed in our RICU through year 2013-2015. The ASIS-D、E, stay ≥10 days, immunosuppressive therapy and ventilator use are the independent risk factors for RICU infection.

TORCH screening used appropriately in China?─three years results from a teaching hospital in northwest China.

OBJECTIVES: TORCH infections caused by Toxoplasma gondii (TOX), rubella virus (RV), cytomegalovirus (CMV) and herpes simplex virus 1,2 (HSV-1,2) are associated with congenital anomalies. The study aimed to analyze the characteristics of TORCH screening in reproductive age women. METHODS: A total of 18,104 women (2015-2017) from a teaching hospital in Xi'an, China, were enrolled in the study. The characteristics of TORCH screening, i.e., the application of TORCH test, the seroprevalence, the impact of age, periods of gestation and woman with bad obstetric history (BOH) on the serological data were investigated. RESULTS: In the study, 319 women (1.76%) performed dynamic TORCH test. 51.66, 20.44 and 3.83% of the population did the test in the pre-gestation period, the first and third trimester, respectively. Quite a few pre-gestation women (29.74%) ignored screening of IgG antibodies. The overall IgG/IgM seropositvity of TOX, RV, CMV, HSV-1 and HSV-2 was 4.35%/0.35, 90%/0.63, 96.79%/0.97, 81.11%/0.14 and 6.1%/0.19%, respectively. The age-specific distributions and periods of gestation had no significant effect on the seroprevalence of TORCH agents, p>0.05. However, BOH was significantly associated with higher seropositvity of IgM (RV, CMV, HSV-1 and HSV-2) and IgG (CMV and HSV-1) antibodies, p < 0.05. CONCLUSION: In Xi'an region, more attentions should be paid to TOX, CMV, HSV-2 and the women with BOH for TORCH screening. Meanwhile, a greater emphasis needs to be placed on TORCH test used inappropriately in China.

Sample-to-cutoff ratios using Architect HIV Ag/Ab Combo: The influence with the results of supplemental tests and optimal cutoff value to predict HIV infection.

BACKGROUND: The Architect HIV Ag/Ab Combo has excellent performance for HIV screening; however, the false-positive rate (FPR) was high in low HIV prevalence setting. OBJECTIVES: The purpose of this study was to analyze the influence of sample-to-cutoff (s/co) ratios by Architect HIV Ag/Ab Combo with the results of confirmatory test and explore the potential utility of s/co to predict HIV infection. METHODS: A retrospective review on Architect HIV Ag/Ab Combo reactive results was performed at a teaching hospital in Xi'an. The s/co values in different groups, that is, true positives (TP) and false positives (FP), different Western blotting (WB) bands among WB-positive cases, were compared. The receiver operating characteristic curve (ROC) analysis was used to determine the optimal cutoff value for predicting HIV infection. RESULTS: During the study period, 219 out of 84 702 patients were reactive by ARCHITECT with a 0.0992% of HIV prevalence and a 56.25% of FPR. The mean s/co ratios in TP were significantly higher than that in FP (458.15 vs 3.11, P < 0.0001). Among the WB-positive cases, the s/co ratios increased significantly with the increase in the number of bands, P = 0.0065. The optimal cutoff (24.44) by ROC analysis can provide the highest sum of sensitivity (100%) and specificity (100%) with no FP results. CONCLUSIONS: For Architect HIV Ag/Ab Combo, the FPR is reduced when s/co ratios increase, and the s/co ≥24.44 may be reliable to predict HIV infection.

Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone.

To repair bone defects, we evaluate the in-vitro and in-vivo osteogenic activities of a novel tissue-engineered bone (TEB) by elaborately combining biomimetic calcium phosphate (BioCaP) granules with internally-incorporated simvastatin (SIM) and human adipose-derived stem cells (hASCs). First, we constructed BioCaP with SIM internally incorporated (SIM-BioCaP). Then we characterized the morphology and chemical composition of SIM-BioCaP. The release kinetics of SIM was monitored in vitro spectroscopically. Thereafter, we explored the in-vitro cellular responses of hASCs to SIM-BioCaP by performing scanning electron microscopy observation, proliferation assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and real-time PCR. Finally, we investigated the in-vivo osteogenic activities of the novel TEB in a subcutaneous bone induction model in nude mice. We found that SIM was successfully incorporated internally in BioCaP and showed a slow release manner without significantly affecting the attachment and proliferation of hASCs. The released SIM from BioCaP could significantly enhance the proliferation, ALP activities, mineralized nodules formation and osteogenic genes of hASCs. The in-vivo tests showed this TEB could induce new bone formation while the other groups could not. Taken together, the present data show that this novel TEB represented a very promising construct to treat critical-volume bone defects.

Development of indirect immunofluorescence assay for TCID50 measurement of grass carp reovirus genotype II without cytopathic effect onto cells.

Grass carp reovirus (GCRV) caused severe hemorrhagic disease with significant losses of fingerling and yearling grass carp, Cyenopharyngodon idellus, in southeast Asian. It was first isolated in 1983 in China, and clade analysis of the different GCRV isolates indicates there are at least three different genotypes I, II, and III. In recent years, GCRV genotype II has been determined as a dominant virus type which cause severe obvious clinical signs in fish but no cytopathic effect onto presently available cell culture. TCID50 is one of standard method to quantity infectious virus particles. In the present study, an indirect immunofluorescence assay (IFA) was developed using antibody against a protein encoded by segment 10 of GCRV genotype II. Moreover, the specific assay to differentitate GCRV of different genotypes and a sensitive assay for determination of GCRV genotype II were developed respectively. The results showed the IFA only can recognize genotype II virus at the lowest initial concentration of 550 genomic copies/ml. Furthermore, comparison of results obtained from qPCR and the TCID50 assay combined IFA was conducted. The results indicated that TCID50 of GCRV isolates JX0901 and HZ08 differs with 2 log steps reduction in the numbers of viruses compared with the number of genome copies detected by qPCR. The immunofluorescence assay developed is sensitive, specific, and the TCID50 combined with IFA will be a standardizable technique for the quantitation and detection of infectious GCRV in cell culture without cytolysis.

Utility of enzyme-linked immunosorbent assays to test core antigen in the diagnosis and antiviral therapy management of hepatitis C virus infections.

In this study, we evaluate the performance of the enzyme-linked immunosorbent assays (ELISAs) for HCV Ag detection in the diagnosis and antiviral therapy management of HCV infections. For the diagnosis of an active HCV infection, the limit of detection of HCV Ag corresponding to HCV RNA level was approximately 7300 IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of HCV-Ag were 88.96, 100, 100, and 91.33%, respectively. The Pearson's correlation coefficient between HCV Ag and HCV RNA was 0.891. All patients with negative HCV Ag at interferon-α2α/ribavirin therapy week 1 achieved a sustained viral response (SVR), and the PPV was 100%; whereas in patients with positive HCV Ag at therapy weeks 12, the NPV for achieving non-response (NR) was 100%. The results showed that ELISAs for HCV Ag detection could be cost effectively applied to diagnose and evaluate the response to antiviral therapy for HCV infections.

The Performance of the Abbott i2000 for Measuring Serum Markers of Infectious Diseases.

BACKGROUND: To date, there is a trend that the chemiluminescent microparticle immunoassays (CMIA) and electrochemiluminescence immunoassays (ECIA) technology gradually replacing the enzyme-linked immunosorbent assay (ELISA). But the performance such as the limit of quantitation (LOQ), precision, linear range of CMIA, or ECIA for serum markers of infectious diseases has rarely been reported. METHODS: Using proficiency testing samples and standard materials, we confirmed the LOQ of the ELISA and the precision, linear range, LOQ, and instrument biases of the Abbott i2000 for eight serum markers. We used the Abbott i2000 and ELISAs to assess five HIV samples; the researchers were blinded to the true status of the samples. RESULTS: For the Abbott i2000, the coefficients of variation (CV) for the low, medium, and high concentration samples ranged from 1.06 to 12.74%, which were less than the allowable error; the linear ranges of HBsAg and HBsAb were 0.66-304.11 IU/ml and 8.16-1205.9 mIU/ml, respectively. For the Abbott i2000, the LOQs of HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, anti-HCV, anti-TP, and anti-HIV were 0.026 IU/ml, 4 mIU/ml, 0.14 NCU/ml, 0.56 NCU/ml, 0.99 NCU/ml, 0.5 NCU/ml, 8.8 mIU/ml, and 1.92 NCU/ml, respectively, and these values were 0.16 IU/ml, 6.97 mIU/ml, 1.16 NCU/ml, 1.63 NCU/ml, 1.79 NCU/ml, 1.03 NCU/ml, 8.33 mIU/ml, and 1.3 NCU/ml, respectively, for the ELISA. When five HIV samples were blindly assessed, two cases were missed by the Abbott i2000 and the ELISA results were consistent with the expected results. CONCLUSIONS: The Abbott i2000 performed significantly better than the ELISA on HBV and HCV screening; however, for anti-TP and anti-HIV, the ELISA remained the preferred method.

Developing antifouling biointerfaces based on bioinspired zwitterionic dopamine through pH-modulated assembly.

The use of synthetic biomaterials as implantable devices typically is accompanied by considerable nonspecific adsorption of proteins, cells, and bacteria. These may eventually induce adverse pathogenic problems in clinical practice, such as thrombosis and biomaterial-associated infection. Thus, an effective surface coating for medical devices has been pursued to repel nonspecific adsorption from surfaces. In this study, we employ an adhesive dopamine molecule conjugated with zwitterionic sulfobetaine moiety (SB-DA), developed based on natural mussels, as a surface ligand for the modification of TiO2. The electrochemical study shows that the SB-DA exhibits fully reversible reduction-oxidation behavior at pH 3, but it is irreversible at pH 8. A contact angle goniometer and X-ray photoelectron spectroscopy were utilized to explore the surface hydration, chemical states, and bonding mechanism of SB-DA. The results indicate that the binding between hydroxyl groups of SB-DA and TiO2 converts from hydrogen bonds to bidentate binding upon the pH transition from pH 3 to 8. In order to examine the antifouling properties of SB-DA thin films, the modified substrates were brought into contact with bovine serum albumin and bacteria solutions. The fouling levels were monitored using a quartz crystal microbalance with dissipation sensor and fluorescence optical microscope. Tests showed that the sample prepared via the pH transition approach provides the best resistance to nonspecific adsorption due to the high coverage and stability of the SB-DA films. These findings support the mechanism of the pH-modulated assembly of SB-DA molecules, and for the first time we demonstrate the antifouling properties of the SB-DA to be comparable with traditional thiol-based zwitterionic self-assemblies. The success of modification with SB-DA opens an avenue for developing a biologically inspired surface chemistry and can have applications over a wide spectrum of bioapplications. The strategy of the pH transition can also be applied to other functional dopamine derivatives.

Exploration and improvement of QuantiFERON-TB assay in patients with indeterminate results in clinical practice: A head-to-head study.

BACKGROUND: We implemented the QuantiFERON-TB Gold In-Tube (QFT-GIT) based on peripheral blood mononuclear cells (QFT-PBMCs) and QFT Gold Plus (QFT-Plus) in patients with indeterminate results, and use Mit-Nil value to identify false negatives and impaired cellular immunity. METHODS: One hundred seventy-one out of 2480 patients who had a QFT-GIT test were prospectively recruited and classified as high Nil (n = 35), low Mit (n = 75) and control (n = 61) cohorts. Head-to-head comparisons, i.e., QFT-PBMCs vs. QFT-GIT in high Nil cohort, QFT-Plus vs. QFT-GIT in low Mit cohort, and QFT-PBMCs vs. QFT-GIT in controls, were performed. Lymphocyte subsets counts were conducted in low Mit and control cohorts. RESULTS: A significant reduction of positive rate only occurred in Mit-Nil < 6 IU/ml (p < 0.001). QFT-PBMCs yielded 100 % valid results and had a significant Nil decline in high Nil cohort (0.98 ± 1.06 vs. 9.55 ± 0.64 IU/ml, p < 0.0001), while correlated well with QFT-GIT for qualitative (Cohen's k = 0.93) and quantitative (TB-Ag [R2 = 0.91] and Mit [R2 = 0.94]) analyses. QFT-Plus produced 61.3 % valid results and had a significant Mit increase in low Mit cohort (0.82 ± 0.95 vs. 0.17 ± 0.11 IU/ml, p < 0.0001). Mit-Nil value significantly correlated with lymphocyte subsets counts (R:0.49-0.56, p < 0.0001), separately corresponding to thresholds of 4.26, 5.33, 5.55 and 5.81 IU/ml for predicting decreased total lymphocyte, T lymphocyte, CD4+ and CD8+ cells. CONCLUSIONS: QFT that replacing whole blood with PBMCs should be recommended to handle high Nil samples, and QFT-Plus can declined the frequency of low Mit results. In addition, Mit-Nil < 6 and 5.81 IU/ml are potential thresholds to identify the risk of false negatives and impaired cellular immunity, respectively.

DMPC/Chol liposomal copper CX5461 is therapeutically superior to a DSPC/Chol formulation.

CX5461, a compound initially identified as an RNA polymerase inhibitor and more recently as a G-quadruplex binder, binds copper to form a complex. Our previous publication showed that the complexation reaction can be leveraged to formulate copper-CX5461 inside liposomes, improving the apparent solubility of CX5461 by over 500-fold and reducing the elimination of CX5461 from the plasma compartment following intravenous administration. In mouse models of acute myeloid leukemia, the resulting formulation was more effective than the free drug solution of CX5461 (pH 3.5) currently used in clinical trials. However, the gains observed with the liposomal formulation were minimal, despite significant increases in circulation half-life. Since the formulation technology used relied on liposomes and the fate of most compounds associated with liposomes is dependent on liposomal lipid composition, the studies described here were designed to evaluate how simple changes in lipid composition could affect therapeutic activity. The previously reported formulation method was simplified to ensure an easy scale-up process. In the modified method, pre-measured solid CX5461 was added to copper-containing liposomes prior to an incubation at 60 °C, which enabled copper-CX5461 complexation inside DSPC/Chol or DMPC/Chol liposomes. Efficacy was determined in BRCA-normal (BxPC3) and BRCA-deficient (Capan-1) models of pancreatic cancer. Both liposomal formulations enhanced the circulation lifetime of CX5461 compared to the free drug solution (pH 3.5). Unlike most compounds that are loaded using a transmembrane pH-gradient, the dissociation of CX5461 from liposomes prepared using the copper complexation method were comparable for DSPC/Chol and DMPC/Chol liposomes, in vitro and in vivo. Nonetheless, copper CX5461 prepared using DMPC/Chol liposomes exhibited superior efficacy. The reason for the improved activity of DMPC/Chol copper-CX5461 was not readily explained by the release data and may be due to the fact that DMPC/Chol liposomes are less stable following localization in the tumor. The results indicate that the therapeutic effects of copper-CX5461 will be dependent on liposomal lipid composition and that liposomal CX5461 should exhibit superior benefits when used to treat BRCA-deficient cancers.

The Role, Function, and Mechanism of Long Intergenic Noncoding RNA1184 (linc01184) in Colorectal Cancer.

BACKGROUND: Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. METHODS: The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. RESULTS: We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. CONCLUSIONS: The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.

A comparison of voxel- and surface-based cone-beam computed tomography mandibular superimposition in adult orthodontic patients.

OBJECTIVE: To evaluate the accuracy, reliability, and efficiency of voxel- and surface-based registrations for cone-beam computed tomography (CBCT) mandibular superimposition in adult orthodontic patients. METHODS: Pre- and post-orthodontic treatment CBCT scans of 27 adult patients were obtained. Voxel- and surface-based CBCT mandibular superimpositions were performed using the mandibular basal bone as a reference. The accuracy of the two methods was evaluated using the absolute mean distance measured. The time that was required to perform the measurements using these methods was also compared. Statistical differences were determined using paired t-tests, and inter-observer reliability was assessed by intraclass correlation coefficients (ICCs). RESULTS: The absolute mean distance on seven mandible surface areas between voxel- and surface-based registrations was similar but not significantly different. ICC values of the surface-based registration were 0.918 to 0.990, which were slightly lower than those of voxel-based registration that ranged from 0.984 to 0.996. The time required for voxel-based registration and surface-based registration was 44.6 ± 2.5 s and 252.3 ± 7.1 s, respectively. CONCLUSIONS: Both methods are accurate and reliable and not significantly different from each other. However, voxel-based registration is more efficient than surface-based registration for CBCT mandibular superimposition.

The Entrepreneur's Psychological Capital, Creative Innovation Behavior, and Enterprise Performance.

In order to analyze the relationship between entrepreneur psychological capital, creative innovation behavior, and enterprise performance based on the actual situation of Chinese enterprises and provide a theoretical basis for the application of entrepreneur psychological capital in enterprise innovation and performance development, in this study, 536 entrepreneurs from 517 enterprises in different fields in Anhui region were selected, and a questionnaire survey on the psychological capital of entrepreneurs, creative innovation behaviors, and corporate performance was conducted. A hypothesis model of the relationship between entrepreneur's psychological capital, creative innovation behavior, and enterprise performance was constructed. The correlation between entrepreneur's psychological capital, creative innovation behavior, and enterprise performance and the intermediation of creative innovation behavior were analyzed using multiple-regression model and structural equation model. The results show that there is a significant positive correlation between dimensions of self-efficacy (regression coefficient = 0.682, p = 0.000), toughness (regression coefficient = 0.526, p = 0.000), and enterprise performance; there is a significant positive correlation between the dimensions of optimism (regression coefficient = 0.471, p = 0.003), hope (regression coefficient = 0.590, p = 0.006), and enterprise performance; there is a significant positive correlation between entrepreneurs' technological innovation behavior (regression coefficient = 0.506, p = 0.000), business innovation behavior (regression coefficient = 0.562, p = 0.000), and enterprise performance; there is a significant positive correlation between entrepreneurial relationship acquisition behavior (regression coefficient = 0.632, p = 0.004) and enterprise performance. Taking entrepreneurs' creative innovation behavior as the intermediary variable, the authors conclude that the dimensions of entrepreneurs' self-efficacy, hope, optimism, toughness, and the standardized path coefficient of enterprise performance are significantly reduced; through the analysis of structural equation model, it is found that the fitting index of the model of entrepreneur's psychological capital, creative innovation behavior, and enterprise performance meets the fitting standard, which shows that both the psychological capital and the creative innovation behavior of entrepreneurs can promote the improvement of enterprise performance. Entrepreneur's creative innovation behavior plays an intermediary effect in the positive influence of entrepreneur's psychological capital on enterprise performance.

Shift in HIV/AIDS Epidemic and Factors Associated with False Positives for HIV Testing: A Retrospective Study from 2013 to 2018 in Xi'an, China.

BACKGROUND: In China, although quite a few bold programmes have been made for HIV/AIDS, the epidemic has still shown an increasing trend. OBJECTIVES: The study was aimed to investigate the characteristics of new HIV/AIDS and the major factors of false positives (FP) for HIV testing. METHODS: A retrospective review was performed in a teaching hospital in Xi'an between 2013 and 2018. The overall characteristics and trends of new HIV/AIDS were described. Moreover, the major factors of FP were determined by the Pareto analysis. RESULTS: A total of 469 new HIV/AIDS were diagnosed, with an increasing prevalence of the new HIV/AIDS from 0.0626% (41/65503) in 2013 to 0.0827% (115/139046) in 2018. Of them, the majority occurred in the males (88.50%), people aged 21-50 years (76.97%), migrants (60.98%), and sexual contact route (88.70%). There was a rapid increase in the annual number of new HIV/AIDS and increasing trends in groups of young individuals, students, and homosexual mode; however, a downward trend in the percentage of injecting drug use was also observed. Over 50 years old and patients from oncology, obstetrics, hepatobiliary surgery, nephrology, cardiology, and infectious disease constituted the major factors of FP. CONCLUSION: The HIV/AIDS epidemic in Xi'an is still evolving, therefore, effective strategies, appropriate education and scaling up HIV testing should be developed. In addition, old adults and specific departments were associated with FP.

Survival outcomes of low prostate-specific antigen levels and T stages in patients with high-grade prostate cancer: a population-matched study.

Objective: To evaluate the prostate cancer-specific survival (PCSS) of low T stages or low prostate-specific antigens (PSA) levels in men with high-grade prostate cancer. Materials and Methods: Patients with non-metastatic prostate cancer (T1-4N0M0) and Gleason score 8-10 in the Surveillance, Epidemiology, and End Results database from 2004-2010 were identified. These men were stratified by T stages (T1, T2, T3a, T3b-4) and PSA levels (<4.0 ng/ml, 4.0-10.0 ng/ml, 10.1-20.0 ng/ml, >20.0 ng/ml). Propensity-score matching (PSM) was conducted to balance the covariates. Kaplan-Meier analysis and multivariable Cox regressions were performed to analyze the PCSS in different T stage or PSA levels groups. Results: A total of 33231 patients aging 69(62~76) years were identified. The overall cohort results showed that the PCSS of T1 group was significantly worse than that of T2 and T3a groups [T2 HR: 0.62(0.57~0.67); T3 HR: 0.70(0.63~0.77)]. There were no significant difference between T2 and T3a groups [T2 HR: 0.98 (0.91~1.05)]. The PSA <4.0 ng/ml group had significantly worse PCSS than PSA 4.0-10.0 ng/ml [PSA 4.0-10.0 ng/ml HR: 0.77(0.68~0.88)]. PSM methods were implemented in the comparison of T1 vs T2, T1 vs T3a, T2 vs T3a. and PSA< 4.0 ng/ml vs PSA 4.0-10.0 ng/ml, The results in these matched cohorts showed that T1 group was associated with significantly worse PCSS than T2 group [T1 HR: 1.31(1.20~1.44)] and T3a group [T1 HR: 1.33(1.16~1.52)]. There were no significant differences between T2 and T3a groups [T3a HR: 1.14(0.99~1.32)]. The PCSS of patients with PSA< 4.0 ng/ml was significantly worse that these with PSA 4.0-10.0 ng/ml in the matched cohort [PSA< 4.0 ng/ml HR: 1.3(1.08~1.56)]. Conclusions: For patients with high-grade PCa, the PCSS of patients seems to be worse in the T1 stage than those in T2 and T3a stages. Patients with PSA <4.0 ng/ml appears to have poorer prognosis than those with PSA 4.0-10.0 ng/ml.