Multiple linear epitopes (B-cell, CTL and Th) of JEV expressed in recombinant MVA as multiple epitope vaccine induces a protective immune response

Epitope-based vaccination might play an important role in the protective immunity against Japanese encephalitis virus (JEV) infection. The purpose of the study is to evaluate the immune characteristics of recombinant MVA carrying multi-epitope gene of JEV (rMVA-mep). The synthetic gene containing critical epitopes (B-cell, CTL and Th) of JEV was cloned into the eukaryotic expression vector pGEM-K1L, and the rMVA-mep was prepared. BALB/c mice were immunized with different dosages of purified rMVA-mep and the immune responses were determined in the form of protective response against JEV, antibodies titers (IgG1 and IgG2a), spleen cell lymphocyte proliferation, and the levels of interferon-γ and interleukin-4 cytokines. The results showed that live rMVA-mep elicited strongly immune responses in dose-dependent manner, and the highest level of immune responses was observed from the groups immunized with 107 TCID50 rMVA-mep among the experimental three concentrations. There were almost no difference of cytokines and neutralizing antibody titers among 107 TCID50 rMVA-mep, recombinant ED3 and inactivated JEV vaccine. It was noteworthy that rMVA-mep vaccination potentiates the Th1 and Th2-type immune responses in dose-dependent manner, and was sufficient to protect the mice survival against lethal JEV challenge. These findings demonstrated that rMVA-mep can produce adequate humoral and cellular immune responses, and protection in mice, which suggested that rMVA-mep might be an attractive candidate vaccine for preventing JEV infection

Event-based adaptive neural network asymptotic tracking control for a class of nonlinear systems

In this work, an event-triggered adaptive neural network asymptotic tracking control scheme is developed for non-lower-triangular nonlinear systems by using the command-filtered backstepping technique. To reduce the communication burden and unnecessary waste of communication resources, an event-triggered control signal based on a relative threshold is designed. In the design process, neural networks are used to approximate the nonlinear function existing in the system, and the upper bounds for the approximation error and the external disturbance together form an adaptive law with one parameter to achieve the asymptotic tracking performance. Additionally, the problem of “explosion of complexity” is avoided by utilizing the command-filtered technique in the backstepping framework. Based on the Lyapunov stability theory and Barbalat's lemma, this developed scheme guarantees that the tracking error asymptotically converges to zero. At the end, two simulation examples are shown to verify the effectiveness of the control method

Endogenous n-3 Fatty Acids Alleviate Carbon-Tetrachloride-Induced Acute Liver Injury in Fat-1

n-3 polyunsaturated fatty acids (PUFAs) are beneficial for numerous models of liver diseases. The probable protective effects of n-3 PUFA against carbon-tetrachloride- (CCl4-) induced acute liver injury were evaluated in a fat-1 transgenic mouse that synthesizes endogenous n-3 from n-6 PUFA. Fat-1 mice and their WT littermates were fed a modified AIN93 diet containing 10% corn oil and were injected intraperitoneally with a single dose of CCl4 or vehicle. CCl4 challenge caused severe liver injury in WT mice, as indicated by serum parameters and histopathological changes, which were remarkably ameliorated in fat-1 mice. Endogenous n-3 PUFA decreased the elevation of oxidative stress induced by CCl4 challenge, which might be attributed to the activation of Nrf2/keap1 pathway. Additionally, endogenous n-3 PUFA reduces hepatocyte apoptosis via suppressing MAPK pathway. These findings indicate that n-3 PUFA has potent protective effects against acute liver injury induced by CCl4 in mice, suggesting that n-3 PUFA can be used for the prevention and treatment of liver injury

Long‐Lived Second Near‐Infrared Luminescent Probes: An Emerging Role in Time‐Resolved Luminescence Bioimaging and Biosensing

Luminescence bioimaging and biosensing in the second near‐infrared (NIR‐II) spectral window (1,000–1,700 nm wavelengths) is a newly emerging technique that is extensively used in fundamental research and clinical practice. Owing to its advantages, including deep tissue penetration and excellent temporal resolution, this technique has shown tremendous promise for target‐specific imaging and noninvasive monitoring. However, developing bioimaging modalities that enable target‐specific imaging with high resolution and sensitivity remains a great challenge today. Compared with NIR‐II fluorescence imaging, NIR‐II luminescence lifetime imaging with advantages such as lower background noises, higher sensitivity, and higher spatial resolution has opened up new avenues for deep tissue imaging and biomedical applications. Herein, various types of long‐lived NIR‐II luminescent probes, including complex dyes, rare‐earth‐doped nanoparticles, organic compound‐loaded nanoparticles, inorganic‐based dots and nanotubes, as well as the main types of time‐resolved luminescence techniques including time‐domain (e.g., time‐correlated single‐photon counting, time‐gated detection, pulse sampling, etc.) and frequency‐domain systems are first summarized. The unique advantages of long‐lived NIR‐II luminescent probes and their critical roles in bioimaging and biosensing are also highlighted. Finally, the present challenges and future directions of long‐lived NIR‐II luminescent probes in biomedical research, translational research, and (pre‐)clinical studies are discussed

Coptidis rhizoma and its main bioactive components: recent advances in chemical investigation, quality evaluation and pharmacological activity

Abstract Background Coptidis rhizoma (CR) is the dried rhizome of Coptis chinensis Franch., C. deltoidea C. Y. Cheng et Hsiao or C. teeta Wall. (Ranunculaceae) and is commonly used in Traditional Chinese Medicine for the treatment of various diseases including bacillary dysentery, typhoid, tuberculosis, epidemic cerebrospinal meningitis, empyrosis, pertussis, and other illnesses. Methods A literature survey was conducted via SciFinder, ScieneDirect, PubMed, Springer, and Wiley databases. A total of 139 selected references were classified on the basis of their research scopes, including chemical investigation, quality evaluation and pharmacological studies. Results Many types of secondary metabolites including alkaloids, lignans, phenylpropanoids, flavonoids, phenolic compounds, saccharides, and steroids have been isolated from CR. Among them, protoberberine-type alkaloids, such as berberine, palmatine, coptisine, epiberberine, jatrorrhizine, columamine, are the main components of CR. Quantitative determination of these alkaloids is a very important aspect in the quality evaluation of CR. In recent years, with the advances in isolation and detection technologies, many new instruments and methods have been developed for the quantitative and qualitative analysis of the main alkaloids from CR. The quality control of CR has provided safety for pharmacological applications. These quality evaluation methods are also frequently employed to screen the active components from CR. Various investigations have shown that CR and its main alkaloids exhibited many powerful pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetic, neuroprotective, cardioprotective, hypoglycemic, anti-Alzheimer and hepatoprotective activities. Conclusion This review summarizes the recent phytochemical investigations, quality evaluation methods, the biological studies focusing on CR as well as its main alkaloids

Hepatoprotective properties of Penthorum chinense Pursh against carbon tetrachloride-induced acute liver injury in mice

Abstract Background Penthorum chinense Pursh (Penthoraceae, PCP), a well-known Miao ethnomedicine, has been traditionally used to treat several liver-related diseases, such as jaundice and viral hepatitis. The aims of the present study were to evaluate the probable properties of the aqueous extract of PCP on carbon tetrachloride (CCl4)—induced acute liver injury in mice. Methods C57BL/6 mice were orally administered an aqueous extract of PCP (5.15 and 10.3 g/kg BW) or silymarin (100 mg/kg) once daily for 1 week prior to CCl4 exposure. Silymarin serves as a positive drug to validate the effectivenes of PCP. Results A single dose of CCl4 exposure caused severe acute liver injury in mice, as evidenced by the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alanine phosphatase (ALP), and the increased TUNEL-positive cells in liver, which were remarkably ameliorated by the pretreatment of PCP. PCP was also found to decrease the levels of malondialdehyde (MDA), restore the glutathione (GSH) and enhance the activities of superoxide dismutase (SOD) and catalase (CAT) in the liver. In addition, the pretreatment of PCP inhibited the degradation of hepatic cytochrome P450 2E1 (CYP2E1), up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its target proteins in CCl4-treated mice. Conclusion Results indicated that the pretreatment of PCP (10.3 g/kg BW) effectively protected against CCl4-induced acute liver injury, which was comparable to efficacy of silymarin (100 mg/kg). This hepatoprotective effects might be attributed to amelioration of CCl4-induced oxidative stress via activating Nrf2 signaling pathway

Solvothermal-assisted liquid-phase exfoliation of large size and high quality black phosphorus

Black phosphorus (BP), especially for BP nanosheets, with unique layered structure among two dimensional (2D) materials has attracted much attention due to its outstanding physical properties, such as ultra-high mobility, in-plane anisotropic properties. However, the small horizontal-size of reported BP limits its applications in the integrated circuit or some functional devices. In this work, a solvothermal-assisted liquid-phase exfoliation technique is firstly employed for preparing large size and high-quality BP nanosheets. In the high-polar acetonitrile solvent, solvothermal treatment weakens the Van der Waals forces of block BP. Together with the subsequently ultrasonic processing, effective exfoliation of large size and high-quality BP nanosheets are realized. The TEM, AFM and Raman results indicate that the prepared BP nanosheets are high quality with an average thickness of about 2 nm, and the horizontal-size is up to 10 μm. This facile and effective method for exfoliated BP nanosheets provides a promising strategy for the exfoliation of other 2D materials. Keywords: Two dimensional materials black phosphorus, Liquid exfoliation, Solvothermal metho

A dynamic mouse peptidome landscape reveals probiotic modulation of the gut-brain axis

Certain probiotics have beneficial effects on the function of the central nervous system through modulation of the gut-brain axis. Here, we describe a dynamic landscape of the peptidome across multiple brain regions, modulated by oral administration of different probiotic species over various times. The spatiotemporal and strain-specific changes of the brain peptidome correlated with the composition of the gut microbiome. The hippocampus exhibited the most sensitive response to probiotic treatment. The administration of heat-killed probiotics altered the hippocampus peptidome but did not substantially change the gut microbiome. We developed a literatu-remining algorithm to link the neuropeptides altered by probiotics with potential functional roles. We validated the probiotic-regulated role of corticotropin-releasing hormone by monitoring the hypothalamic-pituitary-adrenal axis, the prenatal stress-induced hyperactivity of which was attenuated by probiotics treatment. Our findings provide evidence for modulation of the brain peptidome by probiotics and provide a resource for further studies of the gut-brain axis and probiotic therapies.</p