Diffusion Mechanism of Cinnamon Essential Oils Release from Calcium Alginate Based Controlled Release Films in Contact with Food Simulating Solvent

Calcium alginate based controlled release films with moderate mechanical properties were fabricated in this paper. The diffusion mechanism of these films contacting food simulating solvent (FSS) was explored in some detail. With the increase of glycerol content, the diffusion coefficient (D) values of cinnamon essential oils (CEOs) diffusing to ethanol first increased slowly (0.3–0.6 mL), then vigorously (0.6–0.9 mL), and then mildly (0.9–1.2 mL). The D values of the CEOs diffused to water are all in the order of magnitude of 10⁻¹⁰ cm²/s. The D values of CEOs diffused from films EG3 and EGC1 to aqueous ethanol altered enormously at a small moisture percentage (w = 0.3), then continuously varied vigorously, and at last altered mildly in the range of w = 0.3–1. All the results above indicate that, considering the FSS, the diffusion ability of molecules is jointly determined by the size and distribution of free volume in the system (polymer + diffusive substance + solvents), the intermolecular interaction, and the partition coefficient of the solvents. In addition, several pairs of D values, such as D_EG and D_GA, are very close to each other, indicating that different kinds of interactions between different groups may have the same effect on the diffusion ability of molecules. The correlation between D₁ and D₂ indicates that polymeric emulsifier chains also exist in the polymer-rich layer. All the findings and analysis could provide the theoretical basis and data support for further molecular dynamic simulation and could guide the design of controlled release food packaging for food protection.     

Recombinant Lactococcus Expressing a Novel Variant of Infectious Bursal Disease Virus VP2 Protein Can Induce Unique Specific Neutralizing Antibodies in Chickens and Provide Complete Protection

Recent reports of infectious bursal disease virus (IBDV) infections in China, Japan, and North America have indicated the presence of variant, and the current conventional IBDV vaccine cannot completely protect against variant IBDV. In this study, we constructed recombinant Lactococcus lactis (r-L. lactis) expressing a novel variant of IBDV VP2 (avVP2) protein along with the Salmonella resistance to complement killing (RCK) protein, and Western blotting analysis confirmed that r-L. lactis successfully expressed avVP2-RCK fusion protein. We immunized chickens with this vaccine and subsequently challenged them with the very virulent IBDV (vvIBDV) and a novel variant wild IBDV (avIBDV) to evaluate the immune effect of the vaccine. The results show that the r-L. lactis-avVP2-RCK-immunized group exhibited a 100% protection rate when challenged with avIBDV and 100% survival rate to vvIBDV. Furthermore, this immunization resulted in the production of unique neutralizing antibodies that cannot be detected by conventional ELISA. These results indicate that r-L. lactis-avVP2-RCK is a promising candidate vaccine against IBDV infections, which can produce unique neutralizing antibodies that cannot be produced by other vaccines and protect against IBDV infection, especially against the variant strain.     

A temporal requirement for Hippo signaling in mammary gland differentiation,growth, and tumorigenesis

Despite recent progress, the physiological role of Hippo signaling in mammary gland development and tumorigenesis remains poorly understood. Here we show that the Hippo pathway is functionally dispensable in virgin mammary glands but specifically required during pregnancy. In contrast to many other tissues, hyperactivation of YAP in mammary epithelia does not induce hyperplasia but leads to defects in terminal differentiation. Interestingly, loss of YAP causes no obvious defects in virgin mammary glands but potently suppresses oncogene-induced mammary tumors. The selective requirement for YAP in oncogenic growth highlights the potential of YAP inhibitors as molecular targeted therapies against breast cancers.     

TolC-Dependent Modulation of Host Cell Death by the Francisella tularensis Live Vaccine Strain

Francisella tularensis is a facultative intracellular, Gram-negative pathogen and the causative agent of tularemia. We previously identified TolC as a virulence factor of the F. tularensis live vaccine strain (LVS) and demonstrated that a ΔtolC mutant exhibits increased cytotoxicity toward host cells and elicits increased proinflammatory responses compared to those of the wild-type (WT) strain. TolC is the outer membrane channel component used by the type I secretion pathway to export toxins and other bacterial virulence factors. Here, we show that the LVS delays activation of the intrinsic apoptotic pathway in a TolC-dependent manner, both during infection of primary macrophages and during organ colonization in mice. The TolC-dependent delay in host cell death is required for F. tularensis to preserve its intracellular replicative niche. We demonstrate that TolC-mediated inhibition of apoptosis is an active process and not due to defects in the structural integrity of the ΔtolC mutant. These findings support a model wherein the immunomodulatory capacity of F. tularensis relies, at least in part, on TolC-secreted effectors. Finally, mice vaccinated with the ΔtolC LVS are protected from lethal challenge and clear challenge doses faster than WT-vaccinated mice, demonstrating that the altered host responses to primary infection with the ΔtolC mutant led to altered adaptive immune responses. Taken together, our data demonstrate that TolC is required for temporal modulation of host cell death during infection by F. tularensis and highlight how shifts in the magnitude and timing of host innate immune responses may lead to dramatic changes in the outcome of infection.     

Heterogeneous Immunoreactivity of Emerin,a Nuclear Envelope LEM-domain Protein,in Normal Thyroid Follicles

Emerin is a LEM domain-containing integral membrane protein of the vertebrate nuclear envelope. Recently it has been reported that emerin regulates tissue-specific gene/protein expression. We studied the relationship between emerin expression and follicle function in normal and hyperplastic human thyroid tissues using immunohistochemistry and statistical methods. Emerin immunoreactivity was heterogeneous among follicular cells and follicles in normal thyroid tissue. It tended to be strong in the nuclei of tall follicular cells of small follicles and weak or negative in the nuclei of flat follicular cells of large follicles. Follicles with strong expression of emerin were also strongly positive for thyroglobulin (Tg) and thyroxine (T4) in follicular cells and colloid substance, suggesting active functioning follicles. In contrast, large follicles with weak expression of emerin were also weak or negative for Tg and T4. Emerin immunoreactivity was strong in almost all nuclei of hyperplastic follicular cells in Graves’ disease tissues. These findings suggest that emerin expression may be related with follicular function and may contribute to the understanding of hormonogenesis in normal thyroid follicles.     

Can Experience from Adults Regarding Acute Liver Failure Fit Children?

Till date, comparison of clinical characteristics in acute liver failure (ALF) between adults and children has not been performed. In this study, authors retrospectively collected data on adult acute liver failure (AALF) and pediatric acute liver failure (PALF) in seven hospitals in different areas of China from January 2007 through December 2012. A total of 177 AALF cases and 32 PALF cases were eventually included. Several vital clinical variables were significantly different between AALF and PALF, including serum alkaline phosphatase, serum creatinine, serum urea nitrogen, serum lactate dehydrogenase, platelet count, prothrombin activity, international normalized ratio and blood ammonia. It is concluded that experience from AALF could not be proper for PALF.     

Highly sensitive and specific screening of EGFR mutation using a PNA microarray-based fluorometric assay based on rolling circle amplification and graphene oxide

Screening epidermal growth factor receptor (EGFR) mutations, especially deletions, is essential for diagnosis of non-small cell lung cancer (NSCLC) and also critical to inform treatment decisions for NSCLC patients. Here, we demonstrated a facile peptide nucleic acid (PNA) microarray-based fluorometric method for sensitive and specific detection of EGFR mutation, using rolling circle amplification (RCA), graphene oxide (GO), and a fluorescently-labeled detection probe (F-DP). First, the EGFR gene sequence was efficiently captured by the label-free PNA probe which was attached on the surface of a 96-well plate. And then, the EGFR mutation sequence was specifically amplified by RCA using the circular DNA, which was formed by the ligation of the padlock probe when hybridizing with the EGFR mutation, as a template. The single-stranded RCA product (RCAP) was then sensitively detected with the F-DP and GO system. This method has a detection limit of 0.3 pM for EGFR mutation and a high discrimination capability to target EGFR mutation against EGFR wildtype. The use of a PNA microarray and a fluorescence quenching platform make this system quite suitable for high-throughput analysis of EGFR mutations in resource-limited settings without the need of costly and cumbersome equipment. Furthermore, this detection system provides a novel way for the diagnosis of other diseases that are caused by gene deletion mutations.

A facile peptide nucleic acid microarray-based fluorometric method was developed for sensitive and specific detection of EGFR mutation by using rolling circle amplification, graphene oxide, and a fluorescently-labeled detection probe.