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• A novel compound-ring resonator of an optical fiber laser configurated with two interleaved sub-ring resonators has been developed. • Single-longitudinal-mode laser has been emitted from the optical fiber laser. • A Fabry-Perot etalon has been designed as a criterion to which the frequency of the laser has been locked. • The frequency of the laser has been stabilized by the Fabry-Perot etalon and an active feedback controlling circuit. In this paper we report the development of a robust highly stable frequency single-longitudinal-mode optical fiber laser based on a Fabry-Perot etalon and an active feedback controlling system. The laser is fundamentally structured on an all-fiber compound-ring resonator which is configurated with two interleaved and optical-path-overlapped sub-ring resonators. By employing a length of erbium-doped fiber as the gain medium and a FBG as a reflector, the effective linewidth of the gain spectrum of the compound-ring resonator is restricted to be as narrow as the reflected spectrum of the FBG, which is about 0.043 nm. Because of the vernier effect between the two interleaved sub-ring resonators, the longitudinal mode spacing of the compound-ring resonator can be expanded to be as wide as the effective linewidth of the gain spectrum of it, which permits only one longitudinal mode oscillating. By employing an external Fabry-Perot etalon as a criterion and using an active feedback controlling system to tune the length of the cavity of the compound-ring resonator, the ambiance disturbances to the cavity can be compensated and the frequency of the emitted laser is locked to the offset frequency of the Fabry-Perot etalon. Therefore the frequency of the emitted laser has been stabilized to be 10−8. [ABSTRACT FROM AUTHOR]

Lon proteases are a family of ATP-dependent proteases that are involved in the degradation of abnormal proteins in bacteria exposed to adverse environmental stress. An analysis of the genome sequence of Actinobacillus pleuropneumoniae revealed the unusual presence of two putative ATP-dependent Lon homologues, LonA and LonC. Sequence comparisons indicated that LonA has the classical domain organization of the LonA subfamily, which includes the N-terminal domain, central ATPase (AAA) domain, and C-terminal proteolytic (P) domain. LonC belongs to the recently classified LonC subfamily, which includes Lon proteases that contain neither the N-terminal domain of LonA nor the transmembrane region that is present only in LonB subfamily members. To investigate the roles of LonA and LonC in A. pleuropneumoniae , mutants with deletions in the lonA and lonC genes were constructed. The impaired growth of the △ lonA mutant exposed to low and high temperatures and osmotic and oxidative stress conditions indicates that the LonA protease is required for the stress tolerance of A. pleuropneumoniae . Furthermore, the △ lonA mutant exhibited significantly reduced biofilm formation compared to the wild-type strain. However, no significant differences in stress responses or biofilm formation were observed between the △ lonC mutant and the wild-type strain. The △ lonA mutant exhibited reduced colonization ability and attenuated virulence of A. pleuropneumoniae in the BALB/c mouse model compared to the wild-type strain. Disruption of lonC gene did not significantly influence the colonization and virulence of A. pleuropneumoniae . The data presented in this study illustrate that the LonA protease, but not the LonC protease, is required for the stress tolerance, biofilm formation and pathogenicity of A. pleuropneumoniae . [ABSTRACT FROM AUTHOR]

Abstract: We explored the mechanisms underlying the differential effects of two olfactory toxicants, the herbicide 2,6-dichlorobenzonitrile (DCBN) and the anti-thyroid drug methimazole (MMZ), on olfactory receptor neuron (ORN) regeneration in mouse olfactory epithelium (OE). DCBN, but not MMZ, induced inflammation-like pathological changes in OE, and DCBN increased interleukin IL-6 levels in nasal-wash fluid to much greater magnitude and duration than did MMZ. At 24h after DCBN injection, the population of horizontal basal cells (HBCs; reserve, normally quiescent OE stem cells) lining the DMM became severely depleted as some of them detached from the basal lamina, and sloughed into the nasal cavity along with the globose basal cells (GBCs; heterogeneous population of stem and progenitor cells), neurons, and sustentacular cells of the neuroepithelium. In contrast, the layer of HBCs remained intact in MMZ-treated mice, as only the mature elements of the neuroepithelium were shed. Despite the respiratory metaplasia accompanying the greater severity of the DCBN lesion, residual HBCs that survived intoxication were activated by the injury and contributed to the metaplastic respiratory epithelium, as shown by tracing their descendants in a K5CreErT2::fl(stop)TdTomato strain of mice in which recombination causes HBCs to express TdTomato in advance of the lesion. But, contrary to published observations with MMZ, the HBCs failed to form ORNs. A role for IL-6 in suppressing ORN regeneration in DCBN-treated mice was rejected by the failure of the anti-inflammatory drug dexamethasone to prevent the subsequent respiratory metaplasia in the DMM, suggesting that other factors lead to HBC neuro-incompetence. [Copyright &y& Elsevier]

Abstract: A novel approach to fabricate an ordered array of ZnO nanoflowers, consisting of uniform polymer cores of 100s of nanometer diameter decorated with ZnO nanorods of 10s of nanometer diameter, is presented. The 2-stage method combines the formation of ZnO seed layer by pulsed laser deposition (PLD) onto a colloidally assembled polystyrene sphere monolayer and the subsequent hydrothermal growth of ZnO nanowires (NWs). The main advantages of this methodology are low cost and the large area scalability of perfectly ordered hierarchical structures. More importantly, the process enables a versatile control of dimensions and morphologies of ZnO NWs as well as control of the core diameter by changing the polystyrene sphere diameter. A strong improvement of light scattering by such arrays is observed, offering promise as building blocks in different types of solar cells and potentially useful for a wide variety of applications in optoelectronic devices. [Copyright &y& Elsevier]

Abstract: The herbicide 2,6-dichlorobenzonitril (DCBN) is a potent and tissue-specific toxicant to the olfactory mucosa (OM). The toxicity of DCBN is mediated by cytochrome P450 (P450)-catalyzed bioactivation; however, it is not known whether target-tissue metabolic activation is essential for toxicity. CYP2A5, expressed abundantly in both liver and OM, was previously found to be one of the P450 enzymes active in DCBN bioactivation in vitro. The aims of this study were to determine the role of CYP2A5 in DCBN toxicity in vivo, by comparing the extents of DCBN toxicity between Cyp2a5-null and wild-type (WT) mice, and to determine whether hepatic microsomal P450 enzymes (including CYP2A5) are essential for the DCBN toxicity, by comparing the extents of DCBN toxicity between liver-Cpr-null (LCN) mice, which have little P450 activity in hepatocytes, and WT mice. We show that the loss of CYP2A5 expression did not alter systemic clearance of DCBN (at 25mg/kg); but it did inhibit DCBN-induced non-protein thiol depletion and cytotoxicity in the OM. Thus, CYP2A5 plays an essential role in mediating DCBN toxicity in the OM. In contrast to the results seen in the Cyp2a5-null mice, the rates of systemic DCBN clearance were substantially reduced, while the extents of DCBN-induced nasal toxicity were increased, rather than decreased, in the LCN mice, compared to WT mice. Therefore, hepatic P450 enzymes, although essential for DCBN clearance, are not necessary for DCBN-induced OM toxicity. Our findings form the basis for a mechanism-based approach to assessing the potential risks of DCBN nasal toxicity in humans. [ABSTRACT FROM AUTHOR]

Abstract: A novel method was established for simultaneous quantitation of testosterone (T) and dihydrotestosterone (DHT) in murine tissue and serum samples. Endogenous T and DHT, together with the internal standards 17α-methyl-T and 17α-methyl-DHT, were extracted from tissues and then derivatized by reaction with 2-hydrazino-4-(trifluoromethyl)-pyrimidine (HTP). Analysis by liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) resulted in product ion spectra of HTP derivatives of both T and DHT that showed analyte-specific fragmentations; the latter fragmentations were characterized by the use of high-resolution Orbitrap MS/MS. These specific fragmentations enabled quantitation of T and DHT in the multiple-reaction monitoring (MRM) mode. The method was validated with charcoal-stripped serum as the matrix. The lower limit of quantitation (LLOQ) was 0.10ng/ml for T and 0.50ng/ml for DHT. The method was then used for determination of serum and tissue levels of T and DHT in transgenic mice carrying a hypomorphic NADPH–cytochrome P450 reductase gene (Cpr-low mice). Remarkably, ovarian T levels in Cpr-low mice were found to be 25-fold higher than those in wild-type mice, a finding that at least partly explains the female infertility seen in the Cpr-low mice. In conclusion, our method provides excellent sensitivity and selectivity for determination of endogenous levels of T and DHT in mouse tissues. [Copyright &y& Elsevier]

• The laser can emits simultaneously multi-wavelength single longitudinal mode laser. • The number of emitted wavelengths can be adjusted according to requirements. • The laser includes several resonators and each of which uses EDF as gain medium. • No mode competition between the emitted wavelengths. • FBG and FBG-based F-Ps are used as wavelength selector and frequency selector. A multi-wavelength single-longitudinal-mode optical fiber laser using fiber Bragg grating (FBG) as wavelength selector and FBG based Fabry-Perot filters as frequency selector is studied. The optical fiber laser includes several fiber laser resonators and there is a length of erbium-doped fiber used as gain medium in each resonator. Each of the laser resonators uses a FBG as wavelength selector and there are two FBG based Fabry-Perot filters used as frequency selectors in each resonator and thus each resonator can emit single longitudinal mode laser. Experiments show that the fiber laser can emit multiple wavelengths simultaneously, and each wavelength is single longitudinal mode. The stability of each wavelength can reach 10−6. [ABSTRACT FROM AUTHOR]

Abstract: Multiple lines of evidence have indicated that the inability of adult mammalian central nervous system (CNS) axons to regenerate after injury is partly due to the growth inhibitory property of central myelin. Three prototypical myelin-associated inhibitors of neurite outgrowth have been identified, including Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp). These inhibitory ligands, their receptors and signaling pathways are being intensively investigated for their roles in CNS axon regeneration failure. In addition, several members of the axon guidance molecules have been implicated in restricting CNS axon regeneration, some of which are expressed by mature oligodendrocytes. Here we review in vitro and in vivo studies of these molecules in neurite growth and in axon regeneration failure and discuss the implications of these studies. While the increasing number of potential axon regeneration inhibitors highlights the complexity of the restrictive CNS environment, it provides new windows of opportunity as well as new challenges for therapeutic development for spinal cord injury and related neurological conditions. [Copyright &y& Elsevier]

Abstract: We previously demonstrated that male mice deficient in the soluble adenylyl cyclase (sAC) are sterile and produce spermatozoa with deficits in progressive motility and are unable to fertilize zona-intact eggs. Here, analyses of sAC−/− spermatozoa provide additional insights into the functions linked to cAMP signaling. Adenylyl cyclase activity and cAMP content are greatly diminished in crude preparations of sAC−/− spermatozoa and are undetectable after sperm purification. HCO3 − is unable to rapidly accelerate the flagellar beat or facilitate evoked Ca2+ entry into sAC−/− spermatozoa. Moreover, the delayed HCO3 −-dependent increases in protein tyrosine phosphorylation and hyperactivated motility, which occur late in capacitation of wild-type spermatozoa, do not develop in sAC−/− spermatozoa. However, sAC−/− sperm fertilize zona-free oocytes, indicating that gamete fusion does not require sAC. Although ATP levels are significantly reduced in sAC−/− sperm, cAMP-AM ester increases flagellar beat frequency, progressive motility, and alters the pattern of tyrosine phosphorylated proteins. These results indicate that sAC and cAMP coordinate cellular energy balance in wild-type sperm and that the ATP generating machinery is not operating normally in sAC−/− spermatozoa. These findings demonstrate that sAC plays a critical role in cAMP signaling in spermatozoa and that defective cAMP production prevents engagement of multiple components of capacitation resulting in male infertility. [Copyright &y& Elsevier]

To gain insight into the mechanisms of cAMP signaling in germ cells, the expression and subcellular localization of the full-length form of the soluble adenylyl cyclase (sAC) was investigated during rat spermatogenesis and in spermatozoa. A full-length sAC-specific antibody was generated by using a glutathione S-transferase (GST)-sAC carboxyl-terminal region (1399aa–1608aa) fusion protein as the antigen. The selectivity of the purified antibody was confirmed by immunoblotting with lysates from HEK293 cells overexpressing full-length sAC or truncated sAC. Western blot analysis demonstrated that full-length sAC protein appeared on day 25 during testis development. The expression levels increased progressively on days 30 and 35 and remained elevated in adult testis. Full-length sAC protein is retained in spermatozoa from the cauda epididymis. Consistent with the timing of the appearance of the Western blot signal, immunohistochemistry with testis sections at different stages of development detected sAC in late pachytene spermatocytes as well as round and elongating spermatids. Further experiments on the subcellular localization of native or recombinant enzymes revealed that full-length sAC is not only recovered in soluble fractions but also in particulate fractions of testis extracts. Immunofluorescence detection showed localization of the protein in the cytoplasm as well as in organelles of pachytene spermatocytes and spermatids. These findings indicate that cAMP production in spermatids and spermatozoa may occur at sites other than the plasma membrane and suggest that full-length sAC may play a role during spermatid differentiation. [Copyright &y& Elsevier]

Nitric oxide (NO) donating drugs such as organic nitrates have been used to treat cardiovascular diseases for more than a century. These donors primarily produce NO systemically. It is however sometimes desirable to control the amount, location, and time of NO delivery. We present the design of a novel pH-sensitive NO release system that is achieved by the synthesis of dipeptide diphenylalanine (FF) and graphene oxide (GO) co-assembled hybrid nanosheets (termed as FF@GO) through weak molecular interactions. These hybrid nanosheets were characterised by using X-ray diffraction, Raman spectroscopy, Fourier transform infrared spectroscopy, zeta potential measurements, X-ray photoelectron spectroscopy, scanning and transmission electron microscopies. The weak molecular interactions, which include electrostatic, hydrogen bonding and π-π stacking, are pH sensitive due to the presence of carboxylic acid and amine functionalities on GO and the dipeptide building blocks. Herein, we demonstrate that this formulation can be loaded with NO gas with the dipeptide acting as an arresting agent to inhibit NO burst release at neutral pH; however, at acidic pH it is capable of releasing NO at the rate of up to 0.6 μM per minute, comparable to the amount of NO produced by healthy endothelium. In conclusion, the innovative conjugation of dipeptide with graphene can store and release NO gas under physiologically relevant concentrations in a pH-responsive manner. pH responsive NO-releasing organic-inorganic nanohybrids may prove useful for the treatment of cardiovascular diseases and other pathologies. • NO donors are a mainstay of cardiovascular pharmacology but new ways of delivering NO in a controlled manner is desirable. • Dipeptide and graphene oxide co-assembled hybrid nanosheets exhibit pH-responsive switchable/reversible characteristics. • Delivery of NO gas by co-assembled hybrid nanosheets allows the on-demand release of NO under acidic conditions. • These hybrids could serve as a promising strategy for use in stimuli-responsive systems for the delivery of biomolecules. [ABSTRACT FROM AUTHOR]

• CUMS mice exhibits hippocampal BBB dysfunction accompanied with loss of Cldn5. • Enhanced recruitment of EZH2-dependent H3K27me3 modification at the Cldn5 promoter triggers its transcriptional repression and the subsequent depression in stressed individuals. • Chronic stress-induced BBB hyperpermeability is sufficient to allow TNF-α to infiltrate into the hippocampus contributing to depression-like behaviors. • Antidepressant treatment inhibits H3K37me3 deposition at the Cldn5 promoter to restore its expression and BBB function. Growing evidence suggests that neurovascular dysfunction characterized by blood–brain barrier (BBB) breakdown underlies the development of psychiatric disorders, such as major depressive disorder (MDD). Tight junction (TJ) proteins are critical modulators of homeostasis and BBB integrity. TJ protein Claudin-5 is the most dominant BBB component and is downregulated in numerous depression models; however, the underlying mechanisms remain elusive. Here, we demonstrate a molecular basis of BBB breakdown that links stress and depression. We implemented an animal model of depression, chronic unpredictable mild stress (CUMS) in male C57BL/6 mice, and showed that hippocampal BBB breakdown was closely associated with stress vulnerability. Concomitantly, we found that dysregulated Cldn5 level coupled with repression of the histone methylation signature at its promoter contributed to stress-induced BBB dysfunction and depression. Moreover, histone methyltransferase enhancer of zeste homolog 2 (EZH2) knockdown improved Cldn5 expression and alleviated depression-like behaviors by suppressing the tri-methylation of lysine 27 on histone 3 (H3K27me3) in chronically stressed mice. Furthermore, the stress-induced excessive transfer of peripheral cytokine tumor necrosis factor-α (TNF-α) into the hippocampus was prevented by Claudin-5 overexpression and EZH2 knockdown. Interestingly, antidepressant treatment could inhibit H3K27me3 deposition at the Cldn5 promoter, reversing the loss of the encoded protein and BBB damage. Considered together, these findings reveal the importance of the hippocampal EZH2-Claudin-5 axis in regulating neurovascular function and MDD development, providing potential therapeutic targets for this psychiatric illness. [ABSTRACT FROM AUTHOR]

• Serum NLRP3 levels are elevated in septic patients, especially in septic shock patients. • NLRP3 is useful for the early identification of high-risk septic patients. • Elevated NRLP3 levels could predict poor outcome of septic patients. Over-activation of the NLRP3 inflammasome can lead to sepsis. NLRP3 is an essential protein in the classical pathway of pyroptosis. This study assessed the use of serum NLRP3 level as a potential inflammatory biomarker in septic patients. Patients were categorized into five groups: healthy controls (n = 30), ICU controls (n = 22), infection (n = 19), septic non-shock (n = 33), and septic shock (n = 83). Serum NLRP3 levels were measured by enzyme-linked immunosorbent assay for all patients upon enrollment. Clinical parameters and laboratory test data (APACHE II, SOFA, and lactate) were also assessed. Moreover, the ability of serum NLRP3 levels to predict sepsis was determined by the area under the curve (AUC) analysis. The NLRP3 levels in the septic shock group was significantly higher (431.89, 386.61–460.21 pg/mL) than that in the healthy control group (23.24, 9.38–49.73 pg/mL), ICU control group (74.82, 62.71–85.93 pg/mL), infection group (114.34, 99.21–122.56 pg/mL), and septic non-shock group (136.99, 128.80–146.98 pg/mL; P＜0.001 for all comparisons). Additionally, the AUC indicated that the ability of serum NLRP3 levels to predict sepsis and septic shock incidences was not lower than that of the SOFA score. Patients with higher NLRP3 serum levels (>147.72 pg/mL) had significantly increased 30-day mortality rate. NLRP3 is useful for the early identification of high-risk septic patients, particularly septic shock patients. Moreover, elevated NRLP3 levels could result in poor septic prediction outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Chloroform causes hepatic and renal toxicity in a number of species. In vitro studies have indicated that chloroform can be metabolized by P450 enzymes in the kidney to nephrotoxic intermediate, although direct in vivo evidence for the role of renal P450 in the nephrotoxicity has not been reported. This study was to determine whether chloroform renal toxicity persists in a mouse model with a liver-specific deletion of the P450 reductase (Cpr) gene (liver-Cpr-null). Chloroform-induced renal toxicity and chloroform tissue levels were compared between the liver-Cpr-null and wild-type mice at 24 h following differing doses of chloroform. At a chloroform dose of 150 mg/kg, the levels of blood urea nitrogen (BUN) were five times higher in the exposed group than in the vehicle-treated one for the liver-Cpr-null mice, but they were only slightly higher in the exposed group than in the vehicle-treated group for the wild-type mice. Severe lesions were found in the kidney of the liver-Cpr-null mice, while only mild lesions were found in the wild-type mice. At a chloroform dose of 300 mg/kg, severe kidney lesions were observed in both strains, yet the BUN levels were still higher in the liver-Cpr-null than in the wild-type mice. Higher chloroform levels were found in the tissues of the liver-Cpr-null mice. These findings indicated that loss of hepatic P450-dependent chloroform metabolism does not protect against chloroform-induced renal toxicity, suggesting that renal P450 enzymes play an essential role in chloroform renal toxicity. [Copyright &y& Elsevier]

Abstract: OX40 ligand (CD252), a molecule originally identified as human gp34, is an important costimulatory molecule during immune response. Here, we describe a sandwich ELISA for the detection and quantification of soluble OX40L using anti-OX40L monoclonal antibodies 1G1 and 4C12 as capture and detecting antibody, respectively. With this ELISA, the existence and concentration of soluble forms of OX40L (sOX40L) was demonstrated for the first time. It was found that soluble OX40L is detectable in the sera of elderly persons (above 60 years old) and patients with Graves’ disease which has the highest mean serum concentration of sOX40L, suggesting the potential diagnostic significance of sOX40L in the disease. Surprisingly, the quantitation of sOX40L was correlated with the age and among these subjects, those of 70s and 80s have much higher sOX40L concentration than those of 60s. [Copyright &y& Elsevier]

Selenium-enriched peptide (SP) is a new type of selenium supplement with unique bioactivities; however, its instability jeopardizes its industrial applications. Hence, a system stabilizing and delivering SP is a prerequisite to overcome this defect. This study developed a microcapsule, dextran–whey protein isolate–selenium-enriched peptide (DX–WPI–SP), encapsulating SP within the WPI–DX glycation product via electrospraying technology, and its properties were characterized. Results showed that DX–WPI–SP considerably surpassed the physical mixture of WPI, DX, and SP, with respect to antioxidant capacity, thermal stability, and cell cytotoxicity. The in vitro gastrointestinal digestion results showed that over 42% of the SP in DX–WPI–SP survived the gastric fluids and was then released in the intestinal phase. The stability of SP in long-term storage was also observed after its encapsulation in DX–WPI–SP, signifying its stability in this delivery system. This study demonstrated that the DX–WPI–SP microcapsule is a valid strategy to stabilize SP in intestinal delivery. • The microcapsule was consisted of dextran, whey protein isolate, and selenium-enriched peptide. • The Maillard reaction was utilized in the creation of a microcapsule via the electrospraying technology. • Over 42% of the selenium-enriched peptide was released in the intestinal phase. • The Maillard reaction led to an enhancement in the performance of the microcapsules. [ABSTRACT FROM AUTHOR]

Magnesium-aluminum hydrotalcite (Mg-Al HT)/boehmite (AlOOH) composite supported Pt catalysts were obtained via one-pot microemulsion synthesis of Mg-Al HT/AlOOH composite and NaBH 4 -reduction of Pt precursor processes. The catalytic performances of the catalysts were evaluated for formaldehyde (HCHO) removal at room temperature. The performance tests showed that the catalyst obtained by immobilizing Pt nanoparticles (NPs) on Mg-Al HT/AlOOH support with Al/Mg molar ratio equivalent to 9:1 (Pt/Al 9 Mg 1 ) displayed a superior catalytic activity and stability for HCHO removal. In order to find out the causes of its higher activity, X-ray diffraction, transmission electron microscopy, N 2 adsorption/desorption, X-ray photoelectron spectroscopy, temperature programmed desorption of CO 2 and reduction of H 2 were used to analyze the physicochemical properties of Pt/Al 9 Mg 1 and Pt/AlOOH. The remarkable catalytic performance of Pt/Al 9 Mg 1 is mainly attributed to the relatively larger amount of surface oxygen species, and more reactive oxygen species led by the interaction of Mg-Al HT and AlOOH/Pt, and relatively larger number of weak base sites caused by Mg-Al HT. The formate species are the main reaction intermediate over Pt/Al 9 Mg 1 during HCHO oxidation at room temperature, which could be further oxidized into CO 2 and H 2 O in the presence of O 2 . This study might shed some light on further improving the catalytic performance of the catalyst for indoor air purification at room temperature. [ABSTRACT FROM AUTHOR]

The papillomavirus (PV) E2 protein activates transcription and replication by recruiting cellular proteins and the E1 DNA helicase to their binding sites in the viral genome. We recently demonstrated that phosphorylation of tyrosine 102 in the bovine papillomavirus (BPV-1) E2 protein restricts these activities and that fibroblast growth factor receptor-3 (FGFR3) tyrosine kinase binds PV E2. Expression of FGFR3 decreased viral replication with both wild-type and the phenylalanine substitution at position 102, inferring that another kinase targets Y102. Here we tested FGFR- 1, −2 and −4 for association with PV E2 proteins. FGFR2 but not FGFR1 or FGFR4 co-immunoprecipitated with BPV-1 E2. We found that FGFR2 suppressed replication but did not depend on phosphorylation of BPV-1 Y102. HPV-16 and −31 E2 interacted with FGFR1, −2, and −4. These results imply that the expression and activity of FGF receptors in epithelial cells can regulate the function of E2 in viral replication. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies demonstrated that melittin, the main peptide in bee venom, could cause persistent spontaneous pain, primary heat and mechanical hyperalgesia, and enhance the excitability of spinal nociceptive neurons. However, the underlying mechanism of melittin-induced cutaneous hypersensitivity is unknown. Effects of melittin applied topically to acutely dissociated rat dorsal root ganglion neurons were studied using whole-cell patch clamp and calcium imaging techniques. Melittin induced intracellular calcium increases in 60% of small (<25μm) and medium (<40μm) diameter sensory neurons. In current clamp, topical application of melittin evoked long-lasting firing in 55% of small and medium-sized neurons tested. In voltage clamp, melittin evoked inward currents in sensory neurons in a concentration-dependent manner. Repeated application of melittin caused increased amplitude of the inward currents. Most melittin-sensitive neurons were capsaicin-sensitive, and 65% were isolectin B4 positive. Capsazepine, the TRPV1 receptor inhibitor, completely abolished the melittin-induced inward currents and intracellular calcium transients. Inhibitions of signaling pathways showed that phospholipase A2, but not phospholipase C, was involved in producing the melittin-induced inward currents. Inhibitors of cyclooxygenases (COX) and lipoxygenases (LOX), two key components of the arachidonic acid metabolism pathway, each partially suppressed the inward current evoked by melittin. Inhibitors of protein kinase A (PKA), but not of PKC, also abolished the melittin-induced inward currents. These results indicate that melittin can directly excite small and medium-sized sensory neurons at least in part by activating TRPV1 receptors via PLA2-COXs/LOXs cascade pathways. [Copyright &y& Elsevier]

Abstract: A series of hexadentate 8-quinolinolato manganese(III) complexes were synthesized and proven to own a distorted octahedral geometry via elemental analysis, solid UV–vis spectroscopy and Hartree–Fock/3-21G+ calculation. These Mn(III) complexes were found to be more efficient than their corresponding tetradentate 8-quinolinolato manganese(II) and salen-MnIIIOAc for the oxidation of alcohols in acetone medium, being due to their special hexadentate binding structures that could open an axial Mn form the more active pentadentate structures in the presence of aqueous hydrogen peroxide, as supported by UV–vis spectra. The halogen substituents in ligand''s aryl ring could significantly enhance the catalytic activities and 5-chloro-7-iodo-8-quinolinolato manganese(III) gave the highest turnover number (TON). A reasonable mechanism for the present catalytic system was proposed. [Copyright &y& Elsevier]

Abstract: Novel hexadentate binding 8-quinolinolato manganese(III) complexes were proposed and conveniently synthesized for the epoxidation of olefins with aqueous hydrogen peroxide in water–acetone media with ammonium acetate and acetic acid as additives. The catalytic efficiencies of the suggested catalysts were found to be obviously superior to the traditional tetradentate salen–MnIIICl, due to their special hexadentate binding structures that could be easily converted to the corresponding pentadentate with pendant hydroxyl groups by opening an axial Mn the reaction media, as supported by UV–vis spectra, in situ cyclic voltammetry, and quartz crystal microbalance characterizations. [Copyright &y& Elsevier]