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Yi Zhao - Top 30 Publications

In Vitro Anticoagulant Activity and Active Components of Safflower Injection.

Safflower injection is well-known as a traditional Chinese medicine used to improve the blood circulation. In this study, seven safflower injection samples from different companies were evaluated for their in vitro anticoagulant activity by measuring their activated partial thromboplastin time (APTT) and prothrombin time (PT) against human plasma. The screening results suggested that the safflower injections exhibited a significant prolonging influence on APTT (p < 0.05 vs. the control group), but not on prolonging PT (p > 0.05 vs. the control group). The safflower injection was separated into four fractions, and among them, fraction four demonstrated the most anticoagulant activity, with an APTT of 95.4 ± 1.4 s at a concentration of 4.0 μg/μL (p < 0.01 vs. control group). In addition, three active components, p-hydroxybenzaldehyde, p-hydroxy-cinnamic acid, and (8Z)-decaene-4,6-diyne-1-O-β-d-glucopyranoside were isolated from fraction four with Sephadex LH-20 and C18 column chromatography. All three active components showed significant prolonging of APTT (p < 0.05 vs. control group). Among them, p-hydroxy-cinnamic acid exhibited the most activity (p < 0.01 vs. control group). The results indicated that safflower injection strongly affects the intrinsic coagulation system, and we suggest that this might be the mechanism by which the safflower injection activates and promotes blood circulation.

MiR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway in vulvar lichen sclerosis by targeting FOXO3 and CDKN1B.

Vulvar lichen sclerosis (VLS) is a chronic inflammatory skin disorder. Evidence is accumulating that microRNAs (miRNAs) exert crucial roles in initiation and development of a wide range of human diseases. MiR-155-5p has been frequently reported to be implicated in the tumorigenesis and progression of multiple types of cancers, however, its biological role in VLS remains unclear. This study aimed to explore the role of miR-155-5p in VLS and clarify the potential molecular mechanisms involved. In the present study, miR-155-5p was observed to be significantly upregulated in VLS tissues. Functional studies showed that miR-155-5p facilitated cell proliferation, accelerated cell cycle progression and inhibited forkhead box O (FOXO) signaling pathway in fibroblast cells. Mechanical studies demonstrated that miR-155-5p exerted its promoting effects on fibroblast cell proliferation via targeting both forkhead box O3 (FOXO3) and cyclin-dependent kinase inhibitor 1B (CDKN1B). Besides, Pearson's correlation analysis revealed that miR-155-5p expression was negatively correlated with the mRNA expression of FOXO3 and CDKN1B in VLS tissues. Taken together, our results indicate that miR-155-5p promotes fibroblast cell proliferation and inhibits FOXO signaling pathway by negative modulation of both FOXO3 and CDKN1B in VLS, and that miR-155-5p may be used to be a potential therapeutic target for VLS.

A microfluidic device for study of the effect of tumor vascular structures on the flow field and HepG2 cellular flow behaviors.

To build a microfluidic device with various morphological features of the tumor vasculature for study of the effects of tumor vascular structures on the flow field and tumor cellular flow behaviors. The designed microfluidic device was able to approximatively simulate the in vivo structures of tumor vessels and the flow within it. In this models, the influences of the angle of bifurcation, the number of branches, and the narrow channels on the flow field and the influence of vorticity on the retention of HepG2 cells were significant. Additionally, shear stress below physiological conditions of blood circulation has considerable effect on the formation of the lumen-like structures (LLSs) of HepG2 cells. These results can provide some data and reference in the understanding of the interaction between hemorheological properties and tumor vascular structures in solid tumors.

Semisynthesis and insecticidal activity of some novel fraxinellone-based thioethers containing 1,3,4-oxadiazole moiety.

Two series of novel fraxinellone-based thioethers containing 1,3,4-oxadiazole moiety were prepared as insecticidal agents against the oriental armyworm, Mythimna separata Walker. The structural assignment was based on the spectroscopic and X-ray analysis data. Among all the target compounds, compounds 4b, 4k, 5b, 5j and 5k exhibited more potent insecticidal activity with final mortality rates (FMRs) of more than 65%, especially 4k with the FMR of 75.9%, when compared with toosendanin. Some interesting results of structure-activity relationships are also discussed.

Writing Wrinkles on Poly(dimethylsiloxane) (PDMS) by Surface Oxidation with a CO2 Laser Engraver.

Surface wrinkles formed by the buckling of a strained stiff layer attached to a soft elastomer foundation have been widely used in a variety of applications. Micropatterning of wrinkled topographies is, however, limited by process/system complexities. In this article, we report an approach to write surface wrinkles with desired pattern geometries on poly(dimethylsiloxane) (PDMS) elastomers using a commercial infrared laser engraver with a spot size of 127 μm. Wrinkled micropatterns with wavelength from <50 to >300 μm were obtained in minutes without using special facilities or atmospheres. The minimal achievable pattern sizes of one-dimensional and two-dimensional patterns and the change of the minimal achievable pattern size with wrinkle orientation were investigated under a given set of operating parameters. Sub-spot size patterning was also demonstrated. To reduce surface cracking, a typical problem in large-area wrinkle patterning, a patterning scheme that separates neighboring laser exposure areas by nonexposure gaps was developed. In addition, micropatterns with gradient wrinkles were created on the surface. This is the first report that patterns microscale surface wrinkles on elastomer surfaces using infrared laser irradiation. The simple and versatile approach is expected to provide a fast yet controllable way to create wrinkled micropatterns at low cost to facilitate a broad array of studies in surface engineering, cellular biomechanics, and optics.

Comparison of naturally aging and D-galactose induced aging model in beagle dogs.

Animal models have been used to study aging for decades. In numerous aging studies, beagles are the most commonly used breed of dog. However, few studies have compared between naturally aging models and experimentally induced aging models in beagle dogs. In the present study, a D-galactose induced aging model was compared with a naturally aging model, and young adult dogs were considered as the young control group. The level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum, and brain tissue were measured. Histopathological comparisons of the liver, kidneys, heart, lungs and spleen were evaluated using hematoxylin and eosin (H&E) staining, in addition, the brain was evaluated by H&E staining, and Nissl staining. The expression levels of aging-associated factors in the hippocampus, including proliferating cell nuclear antigen (PCNA), P16 and P21 were also determined through reverse transcription quantitative-polymerase chain reaction, and western blot analysis. The results indicated that D-galactose induced aging significantly increased the MDA level, while the levels of SOD and GSH-Px were diminished when compared with the young control group, which was similar to the naturally aging group. Parallel histopathological features were observed in the D-galactose induced aging and naturally aging groups compared with the young control group. However, a reduced expression level of PCNA, and increased expression levels of P16 and P21 were observed in the naturally ageing and induced aging groups compared with the young control group. The results of the current study demonstrated that the beagle dogs in D-galactose induced aging model exhibited significant similarities with the naturally aging model, providing evidence to support that the D-galactose induced aging model may be applied to aging studies.

The effects of marsupialization on bone regeneration adjacent to keratocystic odontogenic tumors, and the mechanisms involved.

Bone resorption in the jaws is one of the most severe complications of keratocystic odontogenic tumors (KCOTs), and can be treated by either enucleation or marsupialization. However, the effects of marsupialization on bone regeneration adjacent to KCOTs, and the mechanisms involved, are still unclear. In this study, samples of 27 KCOTs were collected (20 before marsupialization and 7 after marsupialization) to detect the expression of bone regeneration-related molecules adjacent to KCOTs by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR). The results showed that bone formation was significantly enhanced in the KCOT capsule wall adjacent to bone after marsupialization, as demonstrated by alkaline phosphatase activity assay and immunostaining for bone morphogenetic protein. Moreover, immunohistochemistry revealed that osteoprotegerin (OPG) was up-regulated in the KCOT capsule wall adjacent to bone after marsupialization, while receptor activator of nuclear factor-κB ligand (RANKL) was down-regulated. Real-time qPCR also demonstrated increased expression of OPG after marsupialization, accompanied by a decrease in the expression of osteoclastogenesis-related molecules such as cathepsin K, matrix metalloproteinase-9, NFATc1, RANK and RANKL. This study provides further evidence that marsupialization may promote bone regeneration adjacent to KCOTs partially through regulation of the OPG/RANK/RANKL signaling pathway.

Achieving High Capacitance of Paper-Like Graphene Films by Adsorbing Molecules from Hydrolyzed Polyimide.

To date, graphene-based electric double layer supercapacitors have not shown the remarkable specific capacitance as theoretically predicted. An efficient strategy toward boosting the overall capacitance is to endow graphene with pseudocapacitance. Herein, molecules of hydrolyzed polyimide (HPI) are used to functionalize N-doped graphene (NG) via π-π interaction and the resulting enhanced electrochemical energy storage is reported. These aromatic molecules in monolayer form on graphene contribute strong pseudocapacitance. Paper-like NG films with different areal mass loadings ranging from 0.5 to 4.8 mg cm-2 are prepared for supercapacitor electrodes. It is shown that the gravimetric capacitance can be increased by 50-60% after the surface functionalization by HPI molecules. A high specific capacitance of 553 F g-1 at 5 mV s-1 is achieved by the HPI-NG film with a graphene mass loading of 0.5 mg cm-2 in H2 SO4 aqueous electrolyte. For the HPI-NG film with highest mass loading, the gravimetric specific capacitance drops to 340 F g-1 while the areal specific capacitance reaches a high value of 1.7 F cm-2 . HPI-NG films are also tested in Li2 SO4 aqueous electrolyte, over an extended voltage window of 1.6 V. High specific energy densities up to 40 Wh kg-1 are achieved with the Li2 SO4 electrolyte.

Profiling long noncoding RNA of multi-tissue transcriptome enhances porcine noncoding genome annotation.

To construct a comprehensive pig noncoding transcriptome and further enhance porcine noncoding genome annotation.

Evaluation of the diagnostic value of preoperative sentinel lymph node (SLN) imaging in penile carcinoma patients without palpable inguinal lymph nodes via single photon emission computed tomography/computed tomography (SPECT/CT) as compared to planar scintigraphy.

Sentinel lymph node (SLN) biopsy represents a well-established diagnostic tool for the assessment of lymphatic metastasis. Correct pre- and intraoperative visualization of SLN is of the utmost importance to ensure the safety and feasibility of the procedure. Aim of this study was to evaluate the diagnostic value of preoperative SLN imaging via single photon emission computed tomography/computed tomography (SPECT/CT) and planar scintigraphy in patients with penile carcinoma with nonpalpable inguinal lymph nodes.

Biostimulation of nutrient additions on indigenous microbial community at the stage of nitrogen limitations during composting.

Microorganisms can play a crucial role in the efficiency for composting, which are essential for converting the organic wastes into a well-stabilized, value added product. However, the activity of most of the key functional microorganisms were inhibited due to the limited special nutrient substances or other physiochemical factors during composting, which further affected the quality of compost. The study was conducted to investigate the effects of enriched ammonium (NH4+-N) and organic nitrogen (Org-N) on indigenous microbial community and whether nitrogen (N) nutrient additions could modify the special species during composting. The results showed that the abundance and structure of bacterial community had distinctly diverse responses to different N nutritional treatments (no nutrient addition, NH4+-N addition, and Org-N addition). The addition of N sources enhanced the abundance of corresponding uncultured indigenous species negatively related to the factor of NH4+ and Org-N in redundancy analysis (RDA) during composting but the effect of NH4+ was more significant than Org-N. Nonmetric multidimensional scaling ordination (NMDS) demonstrated that both the two N additions changed bacterial community but had different duration for affecting bacterial composition. Conclusively, an optimized method for regulating the key stains with special biological capacity is proposed by controlling the single limiting-nutrient factor sharply decreasing at one of composting stages and negatively related to the key species in RDA.

Modeling the impacts of ambient temperatures on cardiovascular mortality in Yinchuan: evidence from a northwestern city of China.

No evidence is available on whether cardiovascular mortality is affected by the ambient temperatures in Yinchuan, which is located in the northwestern region of China, with a typical continental semi-humid semi-arid climate. Daily data on cardiovascular mortality and meteorological factors was collected from Yinchuan city for the period of 2010-2015. A distributed lag non-linear model with quasi-Poisson link was used to assess the association between daily temperatures and cardiovascular deaths, after controlling for seasonality, day of the week, atmospheric pressure, humidity, sunshine duration, and wind speed. The relationship between ambient temperature and cardiovascular mortality was non-linear, with a U-shaped exposure-response curve. For all cardiovascular mortality, the effects of high temperatures appeared at lag 2-5 days, with the largest hot effect at lag 3 day (RR 1.082, 95% CI 1.021-1.146), while the effects of cold temperatures were insignificant. Both cold and high temperatures have more serious influence on the elderly (age ≥ 65) and males than the youth and females, respectively. The study has shown that both cold and high temperatures affect cardiovascular mortality. The findings may be helpful to identify the susceptible subgroups of cardiovascular mortality induced by temperatures, and to provide useful information for establishing public health programs that would better protect local population health from ambient temperatures.

Inhibiting proliferation and migration of lung cancer using small interfering RNA targeting on Aldo-keto reductase family 1 member B10.

Lung cancer is the leading cause of global cancer‑associated mortality. Genomic alterations in lung cancers have not been widely characterized, however, the molecular mechanism of tumor initiation and progression remain unknown, and no molecularly targeted have been specifically developed for its treatment and diagnosis. The present study observed the upregulation of Aldo‑keto reductase family 1 member Bio10 (AKR1B10) lung cancer tissues by analyzing two public lung cancer gene expression datasets. Further experiments in silencing AKR1B10 demonstrated that the expression of AKR1B10 was associated with cell proliferation, cell cycle, adhesion and invasion, as well as extracellular‑signal‑regulated kinase/mitogen activated protein kinase signal pathway. The overexpression of AKR1B10 in lung cancer indicates the important role of AKR1B10 in tumorigenesis. These findings suggest that AKR1B10 could be a potential diagnosis and treatment mark of lung cancer.

Ginsenoside Rg3 sensitizes hypoxic lung cancer cells to cisplatin via blocking of NF-κB mediated epithelial-mesenchymal transition and stemness.

Cisplatin is a first line chemotherapy in lung cancer, but decreased susceptibility may limit its application. In solid tumors, hypoxia alters the microenvironment and is associated with proliferation, metastasis, and drug sensitivity. The hypoxia-induced desensitization of cisplatin is not clearly elucidated. 20 (R)-Ginsenoside (Rg3), the traditional Chinese medicine, is extracted from ginseng and has antitumor activities. In this study, we evaluated if Rg3 is effective in improving cisplatin sensitivity by blocking hypoxia. We found that the inhibition of proliferation potential by cisplatin was reduced in cobalt chloride (CoCl2)-induced hypoxia in lung cancer cells. Hypoxia caused alterations in epithelial-mesenchymal transition (EMT), which were detected by cellular morphology and EMT protein markers, and in stemness analyzed by spheroid formation and marker molecules. Hypoxia also activated EMT, which was mediated by the nuclear factor κB (NF-κB) pathway, and stemness, and Rg3 inhibited the activation of the NF-κB pathway. Furthermore, Rg3 could increase the sensitivity to cisplatin by inhibiting EMT and stemness in hypoxic lung cancer cells, and this effect was confirmed in vivo. In conclusion, Rg3 may improve the sensitivity of cisplatin in lung cancer therapy.

Biomarkers identified for prostate cancer patients through genome-scale screening.

Prostate cancer is a threat to men and usually occurs in aged males. Though prostate specific antigen level and Gleason score are utilized for evaluation of the prostate cancer in clinic, the biomarkers for this malignancy have not been widely recognized. Furthermore, the outcome varies across individuals receiving comparable treatment regimens and the underlying mechanism is still unclear. We supposed that genetic feature may be responsible for, at least in part, this process and conducted a two-cohort study to compare the genetic difference in tumorous and normal tissues of prostate cancer patients. The Gene Expression Omnibus dataset were used and a total of 41 genes were found significantly differently expressed in tumor tissues as compared with normal prostate tissues. Four genes (SPOCK3, SPON1, PTN and TGFB3) were selected for further evaluation after Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis and clinical association analysis. MIR1908 was also found decreased expression level in prostate cancer whose target genes were found expressing in both prostate tumor and normal tissues. These results indicated that these potential biomarkers deserve attention in prostate cancer patients and the underlying mechanism should be further investigated.

Reporting characteristics of case reports of acupuncture therapy with CARE guidelines.

To investigate the reporting characteristics of case reports of acupuncture therapy with CAse Report (CARE) guidelines, and to explore the applicability of the guidelines for these case reports.

A Bacterial Type III Effector Targets the Master Regulator of Salicylic Acid Signaling, NPR1, to Subvert Plant Immunity.

Most plant bacterial pathogens rely on type III effectors to cause diseases. Although it is well known that the plant hormone salicylic acid (SA) plays an essential role in defense, whether the master regulator of SA signaling, NPR1, is targeted by any plant pathogen effectors is unknown. SA facilitates the reduction of cytosolic NPR1 oligomers into monomers, which enter the nucleus and function as transcriptional coactivators of plant defense genes. We show that SA promotes the interaction between the Pseudomonas syringae type III effector AvrPtoB and NPR1. In the presence of SA, AvrPtoB mediates the degradation of NPR1 via the host 26S proteasome in a manner dependent on AvrPtoB's E3 ligase activity. Intriguingly, we found that NPR1 plays an important role in MAMP-triggered immunity (MTI), inducing the expression of MTI marker genes. Thus, this work uncovers a strategy in which AvrPtoB targets NPR1 and represses NPR1-dependent SA signaling, thereby subverting plant innate immunity.

Mechanism underlying inhibition of proliferation and promotion of apoptosis by lapatinib in HL60 cells.

Objective To investigate the effect of lapatinib on cell proliferation and apoptosis in acute myeloid leukemia HL60 cells in vitro and the related molecular mechanisms. Methods The HL60 cells were treated with 5, 10, 15 μmol/L lapatinib for 24 hours, and then morphological changes of the cells were observed under optical microscope. CCK-8 assay was used to assess the cell viability. Colony formation assay was performed to detect the cell proliferation ability. Cell apoptosis labeled by annexinV-FITC/PI were analyzed by flow cytometry. Wright modified LIU's staining and Hoechst33342 fluorescent staining were used to observe the morphology of the nucleus. Western blotting was utilized to detect the expressions of Bax, Bcl2, caspase-3, caspase-9, cleaved caspase-3, cleaved caspase-9, cleaved poly-ADP-ribose polymerase (cleaved PARP), cell proliferation regulating inhibitor of protein phosphatase 2A (CIP2A), c-MYC, AKT and p-AKT. Results Compared with the control group, lapatinib inhibited cell proliferation and promoted apoptosis, induced nuclear fragmentation, chromatin condensation of HL60 cells in a dose-dependent manner. Meanwhile, it down-regulated the expression of Bcl2, up-regulated the levels of Bax, cleaved caspase-3, cleaved caspase-9 and cleaved PARP, and decreased the levels of CIP2A, p-AKT and c-MYC. Conclusion Lapatinib could inhibit cell proliferation and promote apoptosis in HL60 cells by inhibiting the CIP2A/AKT/c-MYC signal pathway.

Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations.

Esophageal squamous cell carcinoma is a major histological type of esophageal cancer, with distinct incidence and survival patterns among races. Although previous studies have characterized somatic mutations in this disease, a rigorous comparison between different patient populations has not been conducted. Here we sequence the samples of 316 Chinese patients, combine them with those from The Cancer Genome Atlas, and perform a comparative analysis between Asian and Caucasian patients. We find that mutated CSMD3 is associated with better prognosis in Asian patients. Applying a robust computational strategy that adjusts for both technical and biological confounding factors, we find that TP53, EP300, and NFE2L2 show higher mutational frequencies in Asian patients. Moreover, NFE2L2 mutations correlate with the allele status of a nearby high-Fst SNP, suggesting their potential interaction. Our study provides insights into the molecular basis underlying the striking racial disparities of this disease, and represents a general computational framework for such a cross-population comparison.

Perturbation expansions of stochastic wavefunctions for open quantum systems.

Based on the stochastic unravelling of the reduced density operator in the Feynman path integral formalism for an open quantum system in touch with harmonic environments, a new non-Markovian stochastic Schrödinger equation (NMSSE) has been established that allows for the systematic perturbation expansion in the system-bath coupling to arbitrary order. This NMSSE can be transformed in a facile manner into the other two NMSSEs, i.e., non-Markovian quantum state diffusion and time-dependent wavepacket diffusion method. Benchmarked by numerically exact results, we have conducted a comparative study of the proposed method in its lowest order approximation, with perturbative quantum master equations in the symmetric spin-boson model and the realistic Fenna-Matthews-Olson complex. It is found that our method outperforms the second-order time-convolutionless quantum master equation in the whole parameter regime and even far better than the fourth-order in the slow bath and high temperature cases. Besides, the method is applicable on an equal footing for any kind of spectral density function and is expected to be a powerful tool to explore the quantum dynamics of large-scale systems, benefiting from the wavefunction framework and the time-local appearance within a single stochastic trajectory.

Simultaneous Measurements of Geometric and Viscoelastic Properties of Hydrogel Microbeads Using Continuous-Flow Microfluidics with Embedded Electrodes.

Geometric and mechanical characterizations of hydrogel materials at the microscale are attracting increasing attention due to their importance in tissue engineering, regenerative medicine, and drug delivery applications. Contemporary approaches for measuring the these properties of hydrogel microbeads suffer from low-throughput, complex system configuration, and measurement inaccuracy. In this work, a continuous-flow device is developed to measure geometric and viscoelastic properties of hydrogel microbeads by flowing the microbeads through a tapered microchannel with an array of interdigitated microelectrodes patterned underneath the channel. The viscoelastic properties are derived from the trajectories of microbeads using a quasi-linear viscoelastic model. The measurement is independent of the applied volumetric flow rate. The results show that the geometric and viscoelastic properties of Ca-alginate hydrogel microbeads can be determined independently and simultaneously. The bulky high-speed optical systems are eliminated, simplifying the system configuration and making it a truly miniaturized device. A throughput of up to 394 microbeads min-1 is achieved. This study may provide a powerful tool for mechanical profiling of hydrogel microbeads to support their wide applications.

NONCODEV5: a comprehensive annotation database for long non-coding RNAs.

NONCODE ( is a systematic database that is dedicated to presenting the most complete collection and annotation of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs). Since NONCODE 2016 was released two years ago, the amount of novel identified ncRNAs has been enlarged by the reduced cost of next-generation sequencing, which has produced an explosion of newly identified data. The third-generation sequencing revolution has also offered longer and more accurate annotations. Moreover, accumulating evidence confirmed by biological experiments has provided more comprehensive knowledge of lncRNA functions. The ncRNA data set was expanded by collecting newly identified ncRNAs from literature published over the past two years and integration of the latest versions of RefSeq and Ensembl. Additionally, pig was included in the database for the first time, bringing the total number of species to 17. The number of lncRNAs in NONCODEv5 increased from 527 336 to 548 640. NONCODEv5 also introduced three important new features: (i) human lncRNA-disease relationships and single nucleotide polymorphism-lncRNA-disease relationships were constructed; (ii) human exosome lncRNA expression profiles were displayed; (iii) the RNA secondary structures of NONCODE human transcripts were predicted. NONCODEv5 is also accessible through

HLA-B27 Correlates with the Intracellular Elimination, Replication, and Trafficking of Salmonella Enteritidis Collected from Reactive Arthritis Patients.

BACKGROUND The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. MATERIAL AND METHODS Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. RESULTS HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. CONCLUSIONS HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.

Correlation of MMP-9 and p53 protein expression with prognosis in metastatic spinal tumor of lung cancer.

The aim of the study was to compare the protein expression of MMP-9 and p53 and examine their correlation with prognosis in lung cancer metastatic spinal tumor. Tissue samples were obtained from 30 cases of para-cancerous tissue (group I), 75 cases of non-metastatic lung cancer tissue (group II) and 100 cases of metastatic spinal tumor tissue of lung cancer (group III). The protein expression of MMP-9 and p53 was detected by immunohistochemistry and was present in all three groups. The positive rate for MMP-9 was 20, 67 and 83%, respectively. There was a significant difference among the three groups (p<0.05). The positive rate for p53 was 16.7, 78.7 and 92%, respectively. There was a highly significant difference among the three groups (p<0.01). There was a positive correlation between the protein expressions of MMP-9 and p53 (Spearman's correlation coefficient r=0.351, p<0.05). The positive or negative expression of the two proteins was statistically significant (p<0.05) for 5-year survival. The expression of MMP-9 and p53 proteins in metastatic spinal tumors of lung cancer showed increasing trends, and the expression of MMP-9 and p53 proteins was significantly higher compared to non-metastatic lung cancer tissue and para-cancerous tissue samples. This likely was associated with the invasion and metastasis of lung cancer to the spine. Survival analysis suggested that the overexpression of p53 and MMP-9 were correlated with poor prognosis.

Effect of estrogen on prostaglandin synthetase in bovine oviduct smooth muscle.

Gamete and embryo transport is an important function of the oviduct. This type of transport involves both smooth muscle contraction and epithelial cell secretions, and the former is mediated by prostaglandins (PGs) and their receptors. Our objective was to study the regulation of prostaglandin synthetase (prostaglandin-endoperoxide synthase-1 (PTGS1), prostaglandin-endoperoxide synthase-2 (PTGS2), mPGES-1, mPGES-2, cPGES, and PGFS) by estradiol (E2) in bovine oviduct smooth muscle. Prostaglandin synthetase mRNA and protein expression were investigated using real-time RT-PCR and Western blot analyses, respectively. Prostaglandin synthetase mRNA and protein expression were increased in oviductal smooth muscle tissue after treatment with different concentrations of estradiol for various time periods. The results indicated that there was no increase in expression observed after treatment with fulvestrant, a selective antagonist of the E2 receptor, indicating that E2 interacts with specific E2 nuclear receptors to upregulate PTGS1, PTGS2, mPGES-1, and PGFS expression. In conclusion, E2 increases PTGS1, mPGES-1, and PGFS mRNA and protein expression in bovine oviductal smooth muscle when added for different periods of time and at different concentrations. Additionally, E2 is transported intracellularly and interacts with specific E2 nuclear receptors to increase PTGS1, PTGS2, mPGES-1 and PGFS expression.

A perforated microhole-based microfluidic device for improving sprouting angiogenesis in vitro.

Microfluidic technology is an important research tool for investigating angiogenesis in vitro. Here, we fabricated a polydimethylsiloxane (PDMS) microfluidic device with five cross-shaped chambers using a coverslip molding method. Then, the perforated PDMS microhole arrays prepared by soft lithography were assembled in the device as barriers; a single microhole had a diameter of 100 μm. After injecting type I collagen into the middle gel chamber, we added a culture medium containing a vascular endothelial growth factor (VEGF) into the middle chamber. It would generate a linear concentration gradient of VEGF across the gel region from the middle chamber to the four peripheral chambers. Human umbilical vein endothelial cells (HUVECs) were then seeded on the microhole barrier. With VEGF stimulation, cells migrated along the inner walls of the microholes, formed annularly distributed cell clusters at the gel-barrier interface, and then three-dimensionally (3D) sprouted into the collagen scaffold. After 4 days of culture, we quantitatively analyzed the sprouting morphogenesis. HUVECs cultured on the microhole barrier had longer sprouts than HUVECs cultured without the barrier (controls). Furthermore, the initial distribution of sprouts was more regular and more connections of tube-like structures were generated when the microhole barrier was used. This study introduces a novel microfluidic device containing both microtopographic structures and 3D collagen. HUVECs cultured with the microhole barrier could form well-interconnected tube-like structures and are thus an ideal in vitro angiogenesis model.

Proteonmic Analysis And Immunoregulation Mechanism Of Wheat Germ Globulin.

Wheat germ, one of the byproducts of flour milling, contains many physiologically active components. In this study, the immunoregulatory effects of wheat germ globulin (WGG) on immunosuppressed mice induced by cyclophosphamide were investigated, and the immunological activity of this molecule was explored. The main components, functions and metabolic signaling pathways of this protein were analyzed by a combination of proteomic technology and bioinformatics. The structure of WGG was predicted with the Phyre2 tool. The results indicated that the main functional components of WGG were wheat germ globulins, histones, heat shock proteins (HSPs), and other functional proteins. Histones and HSPs were the major immune components of WGG. The present study manifested that WGG components improved the immune system. The underlying mechanisms might be related to the variational proportion of Thl/Th2 cells resulted from the control of the mRNA expression levels of T-Bet and GATA-3.

GLUT1 -mediated venlafaxine-thiamine disulfide system-glucose conjugates with "lock-in" function for central nervous system delivery.

Venlafaxine, a novel third-generation antidepressant drug, has been described as a reference treatment for major depression, owing to its ability of inhibiting both noradrenalin and serotonin neuronal reuptake, and inhibiting dopamine reuptake slightly. However, its clinical application is hampered by a limited brain distribution. Glucosylation is an effective way to enhance the brain targeting ability of drugs, but the bidirectional transport of glucose transporter 1 (GLUT1 ) might decrease the concentrations of venlafaxine-glucose (V-G) in brain before the release of parent drug venlafaxine. To conquer this drawback of GLUT1 , "lock-in" thiamine disulfide system (TDS) was introduced to modify the V-G conjugate. Both conjugates could release venlafaxine when incubated with the various buffers, mice plasma, and brain homogenate. The evaluation in vivo demonstrated that venlafaxine-TDS-glucose (V-TDS-G) had an improved targeting ability and significantly increased the level of venlafaxine in brain compared to the naked venlafaxine and V-G. The relative uptake efficiency (RE) and concentration efficiency (CE) were enhanced to 5.69 and 5.70 times higher than that of naked venlafaxine, respectively. The results of this study suggest that the conjugate strategy based on the glucose-TDS (G-TDS) is available to enhance the delivery of central nervous system (CNS) drugs into brain.

Feed additives shift gut microbiota and enrich antibiotic resistance in swine gut.

Antibiotic resistance genes (ARGs) are emerging environmental contaminants posing a threat to public health. Antibiotics and metals are widely used as feed additives and could consequently affect ARGs in swine gut. In this study, high-throughput quantitative polymerase chain reaction (HT-qPCR) based ARG chip and next-generation 16S rRNA gene amplicon sequencing data were analyzed using multiple statistical approaches to profile the antibiotic resistome and investigate its linkages to antibiotics and metals used as feed additives and to the microbial community composition in freshly collected swine manure samples from three large-scale Chinese pig farms. A total of 146 ARGs and up to 1.3×1010 total ARG copies per gram of swine feces were detected. ARGs conferring resistance to aminoglycoside, macrolide-lincosamide-streptogramin B (MLSB) and tetracycline were dominant in pig gut. Total abundance of ARGs was positively correlated with in-feed antibiotics, microbial biomass and abundance of mobile genetic elements (MGEs) (P<0.05). A significant correlation between microbial communities and ARG profiles was observed by Procrustes analysis. Network analysis revealed that Bacteroidetes and Firmicutes were the most dominant phyla co-occurring with specific ARGs. Partial redundancy analysis indicated that the variance in ARG profiles could be primarily attributed to antibiotics and metals in feed (31.8%), gut microbial community composition (23.3%) and interaction between feed additives and community composition (16.5%). These results suggest that increased levels of in-feed additives could aggravate the enrichment of ARGs and MGEs in swine gut.

Progress and future prospect of in vitro spermatogenesis.

Infertility has become a major health issue in the world. It affects the social life of couples and of all infertility cases; approximately 40-50% is due to "male factor" infertility. Male infertility could be due to genetic factors, environment or due to gonadotoxic treatment. Developments in reproductive biotechnology have made it possible to rescue fertility and uphold biological fatherhood. In vitro production of haploid male germ cell is a powerful tool, not only for the treatment of infertility including oligozoospermic or azoospermic patient, but also for the fertility preservation in pre-pubertal boys whose gonadal function is threatened by gonadotoxic therapies. Genomic editing of in-vitro cultured germ cells could also potentially cure flaws in spermatogenesis due to genomic mutation. Furthermore, this ex-vivo maturation technique with genomic editing may be used to prevent paternal transmission of genomic diseases. Here, we summarize the historical progress of in vitro spermatogenesis research by using organ and cell culture techniques and the future clinical application of in vitro spermatogenesis.