Meta-analysis of antiviral protection of white spot syndrome virus vaccine to the shrimp.

Currently, white spot syndrome virus (WSSV) is one of the most serious pathogens that impacts shrimp farming around the world. A WSSV vaccine provides a significant protective benefit to the host shrimp. Although various types of vaccines against WSSV have emerged, the immune effects among them were not compared, and it remains unclear which type of vaccine has the strongest protective effect. Meanwhile, due to the lack of effective routes of administration and immunization programs, WSSV vaccines have been greatly limited in the actual shrimp farming. To answer these questions, this study conducted a comprehensive meta-analysis over dozens of studies and compared all types WSSV vaccines, which include sub-unit protein vaccines, whole virus inactivated vaccines, DNA vaccines and RNA-based vaccines. The results showed that the RNA-based vaccine had the highest protection rate over the other three types of vaccines. Among the various sub-unit protein vaccines, VP26 vaccine had the best protective effects than other sub-unit protein vaccines. Moreover, this study demonstrated that vaccines expressed in eukaryotic hosts had higher protection rates than that of prokaryotic systems. Among the three immunization modes (oral administration, immersion and injection) used in monovalent protein vaccines, oral administration had the highest protection rate. In natural conditions, shrimp are mostly infected by the virus orally. These results provide a guide for exploration of a novel WSSV vaccine and help facilitate the application of WSSV vaccines in shrimp farming.

High intensity focused ultrasound inhibits melanoma cell migration and metastasis through attenuating microRNA-21-mediated PTEN suppression.

High intensity focused ultrasound (HIFU) technology is becoming a potential noninvasive treatment for solid tumor. To explore whether HIFU can be applied to treat melanoma and its metastasis, we investigated the effect of HIFU on murine melanoma model. While there was little influence on cell survival, viability or apoptosis, HIFU exposure suppressed melanoma cell migration in vitro and metastasis in vivo. The expression of microRNA-21(miR-21) was down-regulated and PTEN expression was up-regulated in response to HIFU exposure, which was in concomitant with the reduction of AKT activity. Furthermore, ectopic miR-21 expression suppressed this effect of HIFU. These results demonstrate that HIFU exposure can inhibit AKT-mediated melanoma metastasis via miR-21 inhibition to restore PTEN expression. Therefore, targeting the miR-21/PTEN/AKT pathway might be a novel strategy of HIFU in treatment of melanoma.

High intensity focused ultrasound enhances anti-tumor immunity by inhibiting the negative regulatory effect of miR-134 on CD86 in a murine melanoma model.

HIFU has been demonstrated to enhance anti-tumor immunity, however, the mechanism of which has not been well elucidated. Emerging evidence indicates that miRNAs play important roles in immune response. In this study, we used the B16F10 melanoma allograft mouse model to investigate the role of miRNAs in HIFU-enhanced anti-tumor immunity. We found that HIFU treatment decreased circulating B16F10 cells and pulmonary metastasis nodules while increased IFN-γ and TNF-α in the peripheral blood and cumulative mouse survival, which was associated with inhibition of miR-134 expression and activation of CD86 expression in tumor tissues. Further, we determined that miR-134 directly binds to the 3'UTR of CD86 mRNA to suppress its expression in B16F10 cells. When B16F10 cells transfected with miR-134 were co-cultured with normal splenic lymphocytes, the secretion of IFN-γ and TNF-α from lymphocytes was reduced and B16F10 cell survival was increased. HIFU exposure efficiently decreased miR-134 while increased CD86 expression in B16F10 cells in vitro. CD86 knockdown with siRNA markedly rescued the viability of HIFU-treated B16F10 cells that co-cultured with lymphocytes. Altogether, our results suggest that HIFU down-regulates miR-134 to release the inhibition of miR-134 on CD86 in melanoma cells, thereby enhancing anti-tumor immune response.

[Metabolic detoxification of bakuchiol is mediated by cytochrome P450 enzymes in human liver microsomes].

OBJECTIVE: To analyze cytochrome P450 (CYP) phenotyping for bakuchiol metabolism and study the mechanism of detoxification of bakuchiol by human liver microsomes (HLM) in vitro. METHODS: The CYP phenotyping for bakuchiol metabolism was determined using HLM combined with CYP specific inhibitors and recombinant human CYP isoforms. The relative activities of CYP isoforms were determined by analyzing the formation of the substrate metabolites using HPLC-MS/MS, in presence or absence of 1-aminobenzotriazole (ABT) which was CYP enzymes' broad spectrum inhibitor. The residual concentrations of bakuchiol in microsomal incubates were determined using HPLC to investigate ABT's effect on the metabolism of bakuchiol. The effects of CYP enzymes on the nephrotoxicity of bakuchiol were investigated using human kidney-2(HK-2) by MTT assay, in presence or absence of ABT. RESULTS: CYP1A2, CYP2C9, CYP2C19 and CYP3A4 in HLM were involved in bakuchiol metabolism, among which CYP2C19 showed the highest metabolic rate. Co-incubation with ABT (2.5 mmol/L) could inhibit more than 90% of the enzyme activities for CYP1A2, CYP2C9, CYP2C19 and CYP3A4. ABT (2.5 mmol/L) could inhibit the HLM metabolism of bakuchiol with inhibition ratio 83.24%±2.13%. When preincubated with ABT, the metabolic detoxification of bakuchiol by HLM was significantly reduced (P<0.05). CONCLUSION: The mechanism of metabolic detoxification of bakuchiol by HLM is associated with bakuchiol metabolism by CYP enzymes to form non toxic or lower toxic metabolites. The broad spectrum inhibitor of CYP could inverse the detoxification of HLM.

Anion complexation and sensing using modified urea and thiourea-based receptors.

This critical review highlights recent advances in the structurally modified (thio)urea-based receptors for anion complexation and sensing. Modifications of the (thio)urea structure are aimed at a better anion binding in terms of higher binding constant, anion selectivity and feasibility. Major (thio)urea receptors are reviewed as N-alkyl, N-aryl and N-amido/N-amino (thio)ureas. Hints for designing (thio)urea-based receptors for anions are discussed (102 references).

Specific Hg(2+)-mediated perylene bisimide aggregation for highly sensitive detection of cysteine.

Hg(2+) was found to specifically induce the aggregation of perylene bisimide in a "thymine-Hg(2+)-thymine" binding motif and the resultant aggregates showed a highly selective and sensitive turn-on fluorescence response for cysteine, with a detection limit down to 9.6 nM.

Molecular logic gates and switches based on 1,3,4-oxadiazoles triggered by metal ions.

Organic molecular devices for information processing applications are highly useful building blocks for constructing molecular-level machines. The development of "intelligent" molecules capable of performing logic operations would enable molecular-level devices and machines to be created. We designed a series of 2,5-diaryl-1,3,4-oxadiazoles bearing a 2-(para-substituted)phenyl and a 5-(o-pyridyl) group (substituent X=NMe(2), OEt, Me, H, and Cl; 1a-e) that form a bidentate chelating environment for metal ions. These compounds showed fluorescence response profiles varying in both emission intensity and wavelength toward the tested metal ions Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) and the responses were dependent on the substituent X, with those of 1d being the most substantial. The 1,3,4-oxadiazole O or N atom and pyridine N atom were identified as metal-chelating sites. The fluorescence responses of 1d upon metal chelation were employed for developing truth tables for OR, NOR, INHIBIT, and EnNOR logic gates as well as "ON-OFF-ON" and "OFF-ON-OFF" fluorescent switches in a single 1,3,4-oxadiazole molecular system.

N-(Acetamido)thiourea based simple neutral hydrogen-bonding receptors for anions.

N-(Acetamido)-N'-phenylthioureas (4-6) were found to be efficient anion receptors with higher anion affinity than their N-benzamido-N'-phenylthiourea counterparts (1 and 2). The N'-phenylthiourea moiety in 4-6 was shown to be the chromophore with an absorption maximum at ca. 270 nm. It was found that, in the presence of anions, the absorption at ca. 270 nm of 4-6 (except 5f) in acetonitrile (MeCN) was blue shifted and enhanced while a red-shifted shoulder appeared at ca. 295 nm, together with an isosbestic point at ca. 240 nm. The 1:1 anion binding constants of 4-6, for example at 10(6)-10(7) M(-1) order of magnitude for AcO(-) in MeCN, were found to be higher than those of 1 and 2, although the acidity of the thioureido -NH protons in 4-6 is lower than that in 1 and 2. (1)H NMR data indicates that the N-N single bond in 4-6 is twisted but less than that in 1 and 2. A conformation change at the N-N single bond of 4-6 was suggested to occur upon anion binding which leads to a planar hydrogen-bonding network in the anion binding complex in which a charge transfer takes place with the N-acyl moiety being the electron acceptor. Variations in the CD signals of a proline derivative 6 bearing a chiral center in the N-amido moiety provide direct evidence for this conformation change upon its binding with anions in MeCN. The amplified effect of substituent X at the N'-phenyl ring of 5 on the anion binding constant supports the conclusion of anion-binding switched charge transfer in the anion binding complex. (1)H NMR and absorption titrations for 5 indicated that the anion-receptor interaction was of a hydrogen-bonding nature until the N'-phenyl substituent X is as electron-withdrawing as m-CF(3) (5e). With X being the more electron-withdrawing p-NO(2) (5f), deprotonation of the thioureido -NH occurs in the presence of anion. Results reported here confirm that N-amidothioureas derived from both N-aliphatic and N-aromatic amides can in general be a family of efficient hydrogen-bonding receptors, with the aliphatic N-amido derivatives being more efficient. This provides a wider structural diversity for designing thiourea-based functional molecules such as anion receptors and organocatalysts. Preliminary experiments confirm that 6 could catalyse efficiently the reduction of nitrostyrene in CH(2)Cl(2) and MeCN.

Oxidative cyclization of N-acylhydrazones. Development of highly selective turn-on fluorescent chemodosimeters for Cu2+.

A series of N-acylhydrazones were synthesised and found to be "turn-on" fluorescent chemodosimeters for Cu(2+). Among the tested transition metal ions such as Cu(2+), Pb(2+), Zn(2+), Cd(2+), Hg(2+), and Ni(2+), a prominent fluorescence enhancement of up to 1000-fold was only observed for Cu(2+) in acetonitrile (CH(3)CN). This was indicated by an onset of unprecedented structured emission. Detailed experiments established that the highly Cu(2+) selective fluorescence enhancement resulted from an oxidative cyclization by Cu(2+)of the originally nonfluorescent N-acylhydrazones into highly fluorescent rigid 1,3,4-oxadiazoles, n-dope type blocks in optoelectronic materials. The chemodosimeters can be applied to sense Cu(2+) at nM levels in CH(3)CN and sub-microM levels in neutral aqueous environments, despite a slower response in the latter case. It is expected that these redox-based chemodosimeters might be of general applicability.

Enhanced anion binding of N-(anilino)thioureas. Contribution of the N-anilino-NH proton acidity.

We report here that N-anilino-N'-phenythioureas in general function as a new family of thiourea-based efficient anion receptors superior to classical N-alkyl(aryl)thioureas, when the N-anilino-NH proton is acidic enough; that is, the N-phenyl substituent is not less electron-withdrawing than m-Cl. Changes due to anion binding in the absorption spectra of these N-anilinothioureas are much more substantial than those of N-alkyl(aryl)thioureas, and anion binding constants in MeCN, at 10(6)-10(7) mol(-1) L order of magnitude for AcO(-) for example, are much higher despite a similar acidity of the thioureido-NH protons. Crystal structure and (1)H NMR data show that the N-aniline chromophore is electronically decoupled from the thiourea anion binding site by the N-N bond, and an intramolecular hydrogen bond exists in MeCN but not in DMSO between the N-anilino-NH nitrogen atom and the other thioureido-NH proton. Conformation changes in the N-anilinothioureas upon anion binding were assumed to occur and lead to a much higher increment in the electron-donating ability in the N-aniline chromophore that the charge transfer (CT) is enhanced or switched on, compared to not switching on a CT in the case of N-phenylthioureas. The anion binding constant shows a stronger dependence on the N-phenyl substituent than on the N'-phenyl substituent, opposite to that observed with N-benzamidothioureas, and the CT band position of the anion binding complex depends much more on the N-phenyl substituent than that of the anion binding complexes of N-benzamidothioureas. The implications of these findings for new anion-receptors design and thiourea-based organocatalysts development are discussed.