Unlike mammals, zebrafish can regenerate their injured spinal cord and regain control of caudal tissues. It was recently shown that Wnt/β-catenin signaling is necessary for spinal cord regeneration ...in the larval zebrafish. However, the molecular mechanisms of regeneration may or may not be conserved between larval and adult zebrafish. To test this, we assessed the role of Wnt/β-catenin signaling after spinal cord injury in the adult zebrafish. We show that Wnt/β-catenin signaling is increased after spinal cord injury in the adult zebrafish. Moreover, overexpression of Dkk1b inhibited Wnt/β-catenin signaling in the regenerating spinal cord of adult zebrafish. Dkk1b overexpression also inhibited locomotor recovery, axon regeneration, and glial bridge formation in the injured spinal cord. Thus, our data illustrate a conserved role for Wnt/β-catenin signaling in adult and larval zebrafish spinal cord regeneration.
•Wnt/β-catenin signaling is increased after spinal cord injury in adult zebrafish.•Dkk overexpression inhibits Wnt/β-catenin signaling in the injured spinal cord.•Dkk overexpression inhibits locomotor recovery after spinal cord injury.•Dkk overexpression inhibits axon regeneration & glial bridge formation.
Background. Patients with dengue can experience a variety of serious complications including hypovolemic shock, thrombocytopenia, and bleeding. These problems occur as plasma viremia is resolving and ...are thought to be immunologically mediated. Early corticosteroid therapy may prevent the development of such complications but could also prolong viral clearance. Methods. We performed a randomized, placebo-controlled, blinded trial of low-dose (0.5 mg/kg) or high-dose (2 mg/kg) oral prednisolone therapy for 3 days in Vietnamese patients aged 5–20 years admitted with dengue and fever for ≤72 hours, aiming to assess potential harms from steroid use during the viremic phase. Intention-to-treat analysis was performed using linear trend tests with a range of clinical and virological endpoints specified in advance. In addition to recognized complications of dengue, we focused on the are under the curve for serial plasma viremia measurements and the number of days after enrollment to negative viremia and dengue nonstructural protein 1 status. Results. Between August 2009 and January 2011, 225 participants were randomized to 1 of the 3 treatment arms. Baseline characteristics were similar across the groups. All patients recovered fully and adverse events were infrequent. Aside from a trend toward hyperglycemia in the steroid recipients, we found no association between treatment allocation and any of the predefined clinical, hematological, or virological endpoints. Conclusions. Use of oral prednisolone during the early acute phase of dengue infection was not associated with prolongation of viremia or other adverse effects. Although not powered to assess efficacy, we found no reduction in the development of shock or other recognized complications of dengue virus infection in this study. Clinical Trials Registration. ISRCTN39575233.
An La0.6Sr0.4CoO3 strontium-doped lanthanum cobaltite perovskite was prepared via a gelation and calcination approach and used as a heterogeneous catalyst for the synthesis of triphenylpyridines via ...the cyclization reaction between ketoximes and phenylacetic acids. The transformation proceeded via the oxidative functionalization of the sp3 C–H bond in phenylacetic acid. The La0.6Sr0.4CoO3 catalyst demonstrated a superior performance to that of the pristine LaCoCO3 as well as a series of homogeneous and heterogeneous catalysts. Furthermore, the La0.6Sr0.4CoO3 catalyst was facilely recovered and reused without considerable decline in its catalytic efficiency. To the best of our knowledge, the combination of ketoximes with easily available phenylacetic acids is novel.
Drug resistance and off-target toxicity are two of the greatest challenges to chemotherapeutic melanoma treatments. Nitric oxide (NO) represents an attractive alternative to conventional therapeutics ...due to its numerous anticancer properties and low probability of engendering resistance. As NO is highly reactive, macromolecular NO donors are needed for the controlled and targeted delivery of NO for therapeutic applications. Herein, mesoporous silica nanoparticles (MSNs) coated with hyaluronic acid (HA) were developed as a NO delivery system to facilitate controlled delivery to cancer cells through both passive and active targeting via the enhanced permeation and retention effect and directed binding of HA with CD44 receptors, respectively. The aminosilane modification, HA concentration, and HA molecular weight were systematically evaluated to facilitate the MSN coating and NO loading. The hydrodynamic diameter and dispersity of the nanoparticles increased after HA coating due to the hydrophilic nature of HA, with greater increases observed at higher HA molecular weight. Lower starting concentrations of HA and aminosilanes with longer alkyl chains favored more efficient HA coating. Faster NO-release kinetics and lower NO payloads were observed for the HA-coated MSNs relative to uncoated MSNs. However, the localized delivery of NO to cancer cells through the active targeting conferred by HA increased levels of oxidative stress and induced mitochondria-mediated apoptosis in melanoma cells. Cytotoxicity was also evaluated against human dermal fibroblasts, with the use of 6 kDa HA-coated MSNs resulting in the greatest therapeutic indices. Enhanced internalization of HA-coated nanoparticles into melanoma cells versus uncoated nanoparticles was visualized with confocal microscopy and quantified by fluorescence spectroscopy. In total, HA-coated MSNs represent a promising NO delivery system for potential use as a chemotherapeutic for skin melanomas.
An La
Sr
CoO
strontium-doped lanthanum cobaltite perovskite was prepared
a gelation and calcination approach and used as a heterogeneous catalyst for the synthesis of triphenylpyridines
the ...cyclization reaction between ketoximes and phenylacetic acids. The transformation proceeded
the oxidative functionalization of the sp
C-H bond in phenylacetic acid. The La
Sr
CoO
catalyst demonstrated a superior performance to that of the pristine LaCoCO
as well as a series of homogeneous and heterogeneous catalysts. Furthermore, the La
Sr
CoO
catalyst was facilely recovered and reused without considerable decline in its catalytic efficiency. To the best of our knowledge, the combination of ketoximes with easily available phenylacetic acids is novel.
An off-season community influenza outbreak with high prevalence of amantadine-resistant influenza A/H3N2 occurred during September-October 2005 in Nagasaki Prefecture, Japan, prior to standard ...influenza circulation. A total of 48 patients with influenza-like-illness (ILI) visited a clinic during the outbreak and 27 (69.2%) of 39 ILI patients were positive for influenza A with rapid antigen testing (Quick Vue Rapid SP Influ). Nine patients were not tested because their symptoms were compatible for influenza without examination. Nasopharyngeal swabs were obtained from 4 of 27 rapid test positive patients, and influenza H3N2 strain was isolated from one out of four. The 4 nasopharyngeal samples were positive for influenza A M2 gene in polymerase chain reaction, and sequencing results all showed identical mutation at position 31, serine to asparagine (S31N) in the gene, conferring amantadine resistance. The phylogenetic tree analysis demonstrated that the hemagglutinin (HA) gene sequences of the 4 samples formed a distinct cluster (named clade N) from recent circulating H3N2 strains, characterized by dual mutations at position 193, serine to phenylalanine (S193F), and at position 225, asparatic acid to asparagine (D225N). Our findings suggested that an off-season community influenza outbreak in Nagasaki was caused by a distinct clade in H3N2 (named clade N), which possessed characteristics of amantadine resistance.
A copper-based metal-organic framework Cu-CPO-27 was synthesized, and used as a recyclable catalyst for the amidation of unactivated alkanes by benzamides via direct oxidative C(sp3)-H/NH coupling ...under ligand-free conditions. Using a catalytic amount of the Cu-CPO-27 for the transformation, high yields of N-cyclohexyl benzamides were achieved. The Cu-CPO-27 was more catalytically active than other Cu-MOFs such as Cu3(BTC)2, Cu(BDC), Cu(EDB), Cu2(BPDC)2(BPY), Cu2(BDC)2(DABCO), and Cu2(EDB)2(BPY). The Cu-CPO-27 also exhibited advantages as compared to several copper-based salts, including Cu(OAc)2, CuCl2, CuBr, CuI, CuCl, Cu(NO3)2, and CuSO4. The Cu-CPO-27 catalyst could be reused several times for the amidation transformation while its catalytic activity was not decreased significantly. To the best of our knowledge, the amidation of unactivated alkanes by benzamides via direct oxidative C(sp3)-H/NH coupling was not previously performed under heterogeneous catalysis conditions.
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An La
0.6
Sr
0.4
CoO
3
strontium-doped lanthanum cobaltite perovskite was prepared
via
a gelation and calcination approach and used as a heterogeneous catalyst for the synthesis of triphenylpyridines
...via
the cyclization reaction between ketoximes and phenylacetic acids. The transformation proceeded
via
the oxidative functionalization of the sp
3
C-H bond in phenylacetic acid. The La
0.6
Sr
0.4
CoO
3
catalyst demonstrated a superior performance to that of the pristine LaCoCO
3
as well as a series of homogeneous and heterogeneous catalysts. Furthermore, the La
0.6
Sr
0.4
CoO
3
catalyst was facilely recovered and reused without considerable decline in its catalytic efficiency. To the best of our knowledge, the combination of ketoximes with easily available phenylacetic acids is novel.
An La
0.6
Sr
0.4
CoO
3
strontium-doped lanthanum cobaltite perovskite was prepared
via
a gelation and calcination approach and used as a heterogeneous catalyst for the synthesis of triphenylpyridines
via
the cyclization reaction between ketoximes and phenylacetic acids.
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