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An aminomethylation reaction of fulleropyrrolidines bearing ketone moieties in the presence of N-unsubstituted fulleropyrrolidines and paraformaldehyde with the aid of p-toluenesulfonic acid afforded a series of scarce pendant fullerene dimers. A simple change of reaction substrates from ketone to ketone-containing fulleropyrrolidines successfully realized the synthesis of a variety of novel pendant fullerene dimers, including those from methyl ketone-containing fulleropyrrolidines, which were considered to produce the known bridged fullerene dimers. It should be noted that pendant fullerene dimers are usually difficult to prepare by other methods and may have promising applications in perovskite solar cells. Density functional theory (DFT) has been employed to elucidate the regioselectivity of methyl ketone-containing fulleropyrrolidines to yield exclusively pendant fullerene dimers by investigating the Gibbs free energy profile of the reaction starting from methyl ketone-containing fulleropyrrolidines and iminium intermediates.
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This study aims to dynamically assess tumor changes after variable treatments with vascular endothelial growth factor (VEGF) inhibitor and/or immune checkpoint inhibitor (ICI) using multimodal imaging of MRI and 18F-FDG PET/CT in a hepatocellular carcinoma (HCC) mice model. Based on different treatments, 24 mice were randomly divided into four groups: control (isotype-matched IgG antibody 10 mg/kg), VEGF inhibitor (sorafenib 50 mg/kg), ICI (anti-PD-L1 antibody 10 mg/kg), and combination groups (sorafenib 50 mg/kg + anti-PD-L1 antibody 10 mg/kg). Quantitative imaging assessments, including volume transfer constant (Ktrans), apparent diffusion coefficient (ADC), lactate/choline ratio, and the maximum standardized 18F-FDG uptake value ratio of tumor to muscle (SUVtumor/SUVmuscle ratio), were acquired at different time points (before treatment and 7, 14, and 21 days after treatment). Quantitative data were presented as the mean ± standard errors and two-way repeated-measure ANOVA tests were performed for intergroup and intertime point comparisons. After 21 days from the initiation of therapies, combination group showed the lowest tumor volume and weight, followed by ICI, VEGF inhibitor, and control group, with no significance between the VEGF inhibitor and control groups. In addition, Ktrans values significantly decreased, and the lactate/choline ratio and SUVtumor/SUVmuscle ratio were significantly elevated in the VEGF inhibitor group. ADC significantly increased in the ICI and combination groups, with no significant differences in ADC observed between the control and VEGF inhibitor groups, which showed a similar dynamic change to the tumor volume. Furthermore, Ktrans, lactate/choline ratio, and ADC were significantly correlated with CD31+ area, hypoxyprobe+ area, and apoptosis, respectively. Our results suggest that the singular treatment and combination of the VEGF inhibitor and ICI treatments for HCC present different multimodal imaging changes in accordance with the specific histopathological features. These findings might facilitate the formulation of better treatment response criteria; besides, we find ADC is probably an indicator easily to obtain for treatment response evaluation.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Colina , Fluorodesoxiglucosa F18 , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoglobulina G , Lactatos , Neoplasias Hepáticas/metabolismo , Ratones , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Sorafenib , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
A series of scarce amino-substituted cyclopentafullerenes instead of the expected N-alkyl-2,5-disubstituted fulleropyrrolidines were synthesized in moderate to excellent yields via the simple one-step reaction of [60]fullerene with cheap and easily available ß-substituted propionaldehydes and secondary amines in the absence/presence of magnesium perchlorate. The in situ generation of allylic amines from ß-substituted propionaldehydes and secondary amines played a crucial role in the successful preparation of amino-substituted cyclopentafullerenes without additional carbons. With the addition of magnesium perchlorate, secondary amines containing ethyl group(s) could produce novel amino-substituted cyclopentafullerenes with two additional carbons. All the obtained cyclopentafullerenes displayed high stereoselectivity with cis isomers as the exclusive or major products. Plausible reaction mechanisms are proposed to elucidate the above-mentioned reaction process.
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A facile one-step reaction of [60]fullerene with cinnamaldehydes and amines promoted by magnesium perchlorate/ferric perchlorate under air conditions afforded a series of rare amino-substituted cyclopentafullerenes in moderate to good yields. Stereoselectivity was readily achieved. Secondary amines exclusively produced N,N-disubstituted cyclopentafullerenes as cis isomers, while arylamines gave N-monosubstituted cyclopentafullerenes with a preference of cis isomers as major products. N-Monosubstituted cyclopentafullerenes could be further converted into other scarce cyclopentafullerenes in the presence of acid chloride or paraformaldehyde. A possible reaction pathway was proposed to elucidate the formation of amino-substituted cyclopentafullerenes.
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A series of scarce N-alkyl-2,5-unsubstituted/monosubstituted fulleropyrrolidines were synthesized in moderate to excellent yields by the simple one-step thermal reaction of [60]fullerene with primary/secondary amines in the presence of paraformaldehyde without the addition of valuable metal salts. Intriguingly, the reaction with primary amines unexpectedly afforded N-alkyl-2,5-unsubstituted fulleropyrrolidines instead of the anticipated 2,5-monosubstituted fulleropyrrolidines. A plausible reaction pathway is proposed to elucidate the above-mentioned reaction process based on the experimental results.
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BACKGROUND: Although the mechanism of chronic migraine (CM) is unclear, it might be related to central sensitization and neuronal persistent hyperexcitability. The tyrosine phosphorylation of NR2B (NR2B-pTyr) reportedly contributes to the development of central sensitization and persistent pain in the spinal cord. Central sensitization is thought to be associated with an increase in synaptic efficiency, but the mechanism through which NR2B-pTyr regulates synaptic participation in CM-related central sensitization is unknown. In this study, we aim to investigate the role of NR2B-pTyr in regulating synaptic plasticity in CM-related central sensitization. METHODS: Male Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections to model recurrent trigeminovascular or dural nociceptor activation, which is assumed to occur in patients with CM. We used the von Frey test to detect changes in mechanical withdrawal thresholds, and western blotting and immunofluorescence staining assays were performed to detect the expression of NR2B-pTyr in the trigeminal nucleus caudalis (TNC). NR2B-pTyr was blocked with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)-pyrazolo [3,4-d] pyrimidine (PP2) and the protein tyrosine kinase inhibitor genistein to detected the changes in calcitonin gene-related peptide (CGRP), substance P (SP), and the synaptic proteins postsynaptic density 95 (PSD95), synaptophysin (Syp), synaptotagmin1 (Syt-1). The synaptic ultrastructures were observed by transmission electron microscopy (TEM), and the dendritic architecture of TNC neurons was observed by Golgi-Cox staining. RESULTS: Statistical analyses revealed that repeated infusions of IS induced mechanical allodynia and significantly increased the expression of NR2B Tyr-1472 phosphorylation (pNR2B-Y1472) and NR2B Tyr-1252 phosphorylation (pNR2B-Y1252) in the TNC. Furthermore, the inhibition of NR2B-pTyr by PP2 and genistein relieved allodynia and reduced the expression of CGRP, SP, PSD95, Syp and Syt-1 and synaptic transmission. CONCLUSIONS: These data indicate that NR2B-pTyr might regulate synaptic plasticity in central sensitization in a CM rat model. The inhibition of NR2B tyrosine phosphorylation has a protective effect on threshold dysfunction and migraine attacks through the regulation of synaptic plasticity in central sensitization.
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Sensibilización del Sistema Nervioso Central/fisiología , Modelos Animales de Enfermedad , Trastornos Migrañosos/metabolismo , Plasticidad Neuronal/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Tirosina/metabolismo , Animales , Hiperalgesia/metabolismo , Hiperalgesia/patología , Masculino , Trastornos Migrañosos/patología , Neuronas/metabolismo , Neuronas/patología , Dolor/metabolismo , Dolor/patología , Fosforilación/fisiología , Ratas , Ratas Sprague-Dawley , Núcleo Caudal del Trigémino/metabolismo , Núcleo Caudal del Trigémino/patologíaRESUMEN
A series of scarce fulleropyrrolidin-2-ols were synthesized by the facile one-step reaction of [60] fullerene with inexpensive and readily accessible amines and 2,2-disubstituted acetaldehydes without the addition of valuable metal salts in moderate yields, comparable to those for most monoadducts reported previously. This strategy exhibits a broad substrate scope and excellent functional group tolerance. A plausible reaction pathway for the formation of fulleropyrrolidin-2-ols is proposed to elucidate the above reaction process.
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Acid-sensing ion channel 3 (ASIC3) is abundant in the trigeminal nervous system and is most sensitive to a slight pH decrease. Recent studies have indicated that ASIC3 in the peripheral trigeminal ganglia is likely involved in the pathogenesis of migraine pain. However, it is unclear whether this receptor plays a role in recurrent migraine, namely, migraine chronicity. Here, we aimed to investigate the role of ASIC3 in an animal model of recurrent migraine (RM). In this study, we established a rat model of RM through repeated administration of inflammatory soup (IS) onto the dura. Then, we tested the mechanical pain thresholds of the face and hindpaws by von Frey filaments. qRT-PCR, Western blot and immunofluorescence labelling were used to detect the expression and localization of ASIC3 in the trigeminal nucleus caudalis (TNC). The protein levels of calcitonin gene-related peptide (CGRP), its receptor component receptor activity modifying protein 1 (RAMP1) and c-Fos were analysed following treatment with the ASIC3 inhibitor APETx2 and activator 2-guanidine-4-methylquinazoline (GMQ). We found decreased pain thresholds after repeated dural inflammatory stimulation, which suggested the establishment of an RM model. Based on this model, we observed elevated expression of ASIC3 in the TNC group compared to that in the Sham group. ASIC3 was primarily expressed in neurons but not in astrocytes of the TNC. Moreover, APETx2 attenuated tactile allodynia and significantly decreased the expression of c-Fos, CGRP and RAMP1, while GMQ aggravated these effects compared to those observed in the IS + vehicle group. These findings indicate a critical role of ASIC3 channels in the pathophysiology of RM, and ASIC3 might represent a potential therapeutic target to prevent the progression of migraine.
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Canales Iónicos Sensibles al Ácido/genética , Trastornos Migrañosos/metabolismo , Núcleo Caudal del Trigémino/metabolismo , Canales Iónicos Sensibles al Ácido/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/genética , Péptido Relacionado con Gen de Calcitonina/metabolismo , Masculino , Trastornos Migrañosos/etiología , Umbral del Dolor , Ratas , Ratas Sprague-Dawley , Proteína 1 Modificadora de la Actividad de Receptores/genética , Proteína 1 Modificadora de la Actividad de Receptores/metabolismoRESUMEN
miR156 is a highly conserved plant miRNA and has been extensively studied because of its versatile roles in plant development. Here, we report a novel role of miR156 in regulating somatic embryogenesis (SE) in citrus, one of the most widely cultivated fruit crops in the world. SE is an important means of in vitro regeneration, but over the course of long-term sub-culturing there is always a decline in the SE potential of the preserved citrus embryogenic callus, and this represents a key obstacle for citrus biotechnology. In this study, the SE competence of citrus callus of wild kumquat (Fortunella hindsii) was significantly enhanced by either overexpression of csi-miR156a or by individual knock-down of the two target genes, CsSPL3 and CsSPL14, indicating that the effect of miR156-SPL modules was established during the initial phases of SE induction. Biological processes that might promote SE in response to miR156 overexpression were explored using RNA-seq, and mainly included hormone signaling pathways, stress responses, DNA methylation, and the cell cycle. CsAKIN10 was identified as interacting protein of CsSPL14. Our results provide insights into the regulatory pathway through which miR156-SPL modules enhance the SE potential of citrus callus, and provide a theoretical basis for improvement of plant SE competence.
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Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , Técnicas de Embriogénesis Somática de Plantas , Rutaceae/embriología , MicroARNs/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
The reaction of [60]fullerene with aromatic aldehydes and triethylamine/diethylamine in the absence or presence of manganese(iii) acetate under air conditions afforded a series of N-ethyl-2-arylvinyl-5-methyl fulleropyrrolidines in moderate to good yields, which would be difficult to synthesize by reported protocols. The in situ generation of arylvinyl aldehydes by the aldol reaction of aromatic aldehydes with acetaldehyde from an unusual C-N bond cleavage of triethylamine/diethylamine played a crucial role in the successful preparation of the corresponding fulleropyrrolidines. Depending on the reaction conditions, both cis and trans isomers of fulleropyrrolidines could be selectively synthesized. Cis isomers as major products could be obtained by reacting with triethylamine at 160 °C without the addition of manganese(iii) acetate, while trans isomers as major products, with rare exceptions, could be observed via the reaction with diethylamine at 120 °C under the assistance of manganese(iii) acetate. Moreover, the in situ generated arylvinyl aldehydes displayed higher reactivity towards diethylamine as compared with aryl aldehydes, leading to the formation of arylvinyl-substituted fulleropyrrolidines. A plausible formation mechanism for fulleropyrrolidines was provided based on the experimental observations.
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A series of scarce tetrahydropyridinofullerenes were synthesized by the metal-free-mediated reaction of [60]fullerene with cheap and easily available α-methyl-substituted arylmethanamines and aldehydes in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 4-dimethylaminopyridine (DMAP) in moderate to good yields comparable to the previously reported data for most monoadducts. The in situ generation of azadienes played a crucial role in the successful synthesis of tetrahydropyridinofullerenes. A plausible reaction mechanism was proposed to elucidate the reaction process.
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The metal-free-mediated thermal reaction of [60]fullerene with aromatic aldehydes and inactive primary amines bearing electron-donating groups at the α-position afforded a series of 2-aryl-5-alkyl-fulleropyrrolidines, including the scarce 2-aryl-5-benzyl-fulleropyrrolidines as a mixture of cis and trans isomers. With rare exceptions, the mixture of cis and trans isomers could be easily isolated by column chromatography, with a preference of cis isomers as major products. A plausible mechanism for the formation of fulleropyrrolidines is also proposed.
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A series of scarce fulleropyrrolines were synthesized via DMAP-mediated one-step reaction of [60]fullerene with commercially inexpensive aromatic aldehydes and arylmethanamines in the absence or presence of manganese(III) acetate. In the case of aminodiphenylmethane, novel 2,5,5-trisubstituted fulleropyrrolines could be easily obtained without the addition of manganese(III) acetate. As for arylmethanamines without α-substitutions, the addition of manganese(III) acetate was required to suppress the formation of fulleropyrrolidines, in order to generate the desired 2,5-disubstituted fulleropyrrolines. Two tautomers were produced as expected when different aryl groups (Ar1 ≠ Ar2) from aromatic aldehydes and arylmethanamines were employed in the synthesis. A plausible reaction mechanism for the formation of fulleropyrrolines is proposed.
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The facile one-step reaction of [60]fullerene with aldehydes and primary amines in the presence of cheap and easily available Cu(OAc)2·H2O afforded a series of new types of fulleropyrrolines with trisubstituted CâC bonds in good to excellent yields, which would be difficult to prepare by known methods. The formed fulleropyrroline under the assistance of Pd(OAc)2 and CuCl2·2H2O could be further converted to 1-fulleropyrrolidine by the chlorohydroxylation reaction of CâC bond. Subsequent elimination reaction of 1-fulleropyrrolidine with the aid of TsOH·H2O generated the scarce 1-fulleropyrroline derivative.
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Thermal reaction of [60]fullerene with various arylmethanamines in the presence of aromatic aldehydes under air conditions afforded a series of rare 2,5-diaryl fulleropyrrolidines. Intriguingly, the obtained fulleropyrrolidines exhibited different stereoselectivity. N-unsubstituted arylmethanamines exclusively produced 2,5-diaryl fulleropyrrolidines as cis isomers, while N-substituted arylmethanamines with rare exceptions always gave 2,5-diaryl fulleropyrrolidines as trans isomers. Theoretical calculations at the level of B3LYP/6-31G (d,p) were employed to elucidate the stereoselectivity of N-substituted 2,5-diaryl fulleropyrrolidines as trans isomers by investigating the transition-state structures of different cycloaddition pathways.
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BACKGROUND: RNA secondary structure is highly conserved throughout evolution. The higher order structure is fundamental in establishing important structure-function relationships. Nucleotide sequences from ribosomal RNA (rRNA) genes have made a great contribution to our understanding of Ascomycota phylogeny. However, filling the gaps between molecular phylogeny and morphological assumptions based on ascus dehiscence modes and type of fruitbodies at the higher level classification of the phylum remains an unfulfilled task faced by mycologists. METHODOLOGY/PRINCIPAL FINDINGS: We selected some major groups of Ascomycota to view their phylogenetic relationships based on analyses of rRNA secondary structure. Using rRNA secondary structural information, here, we converted nucleotide sequences into the structure ones over a 20-symbol code. Our structural analyses together with ancestral character state reconstruction produced reasonable phylogenetic position for the class Geoglossomycetes as opposed to the classic nucleotide analyses. Judging from the secondary structure analyses with consideration of mode of ascus dehiscence and the ability of forming fruitbodies, we draw a clear picture of a possible evolutionary route for fungal asci and some major groups of fungi in Ascomycota. The secondary structure trees show a more reasonable phylogenetic position for the class Geoglossomycetes. CONCLUSIONS: Our results illustrate that asci lacking of any dehiscence mechanism represent the most primitive type. Passing through the operculate and Orbilia-type asci, bitunicate asci occurred. The evolution came to the most advanced inoperculate type. The ascus-producing fungi might be derived from groups lacking of the capacity to form fruitbodies, and then evolved multiple times. The apothecial type of fruitbodies represents the ancestral state, and the ostiolar type is advanced. The class Geoglossomycetes is closely related to Leotiomycetes and Sordariomycetes having a similar ascus type other than it was originally placed based on nucleotide sequence analyses.
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Ascomicetos/clasificación , Ascomicetos/genética , Evolución Biológica , Filogenia , ARN Ribosómico/genética , Conformación de Ácido NucleicoRESUMEN
OBJECTIVE: To study the effects of hydroxy safflower yellow A (HSYA) on tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice. METHODS: BGC-823 cells were injected subcutaneously into the right anterior armpit of nude mice to establish an animal model of transplanted tumors. After 24 h, 18 nude mice injected with tumor cells were randomized into model, control, and HSYA 0.028 g/L groups, with six mice in each group. Transplanted tumors were excised on day 20. Tumor inhibition ratios were calculated for the transplanted tumors. Pathological changes and capillary angiogenesis in the tumors were observed by light microscopy. RESULTS: Tumors in the model group grew more quickly than those in the control and HSYA groups, with inhibition ratios of 48% and 30%, respectively. The microvessel count in the HSYA group was lower than in the model group (P < 0.01), and microvessel density was also lower in the HSYA group (P < 0.05). Pathological changes were more obvious in tumors in the model group compared to the HSYA group. CONCLUSION: HSYA inhibits the growth of transplanted BGC-823 tumors, and its effects on tumor capillary angiogenesis may represent one of the mechanisms responsible for this antineoplastic effect.
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Adenocarcinoma/irrigación sanguínea , Antineoplásicos Fitogénicos/uso terapéutico , Chalcona/análogos & derivados , Neovascularización Patológica/tratamiento farmacológico , Quinonas/uso terapéutico , Neoplasias Gástricas/irrigación sanguínea , Animales , Capilares/patología , Chalcona/uso terapéutico , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
It is desirable for an atomic frequency standard that clock transition signal is of both high S/N rate and narrow linewidth. While for a passive coherent population trapping (CPT) frequency standard, increasing S/N rate is at the expense of enwidened lidnewidth, therefore it is crucial to choose a proper combination of S/N rate and linewidth. The present paper presents the experimental results of our systematically study on the relations between clock transition signal and parameters such as temperature and laser intensity with an optical table top CPT frequency standard. The obtained results provide us the criterion of choosing the combination of S/N rate and lidnewidth. The paper also presents experimental study results of de-coherent effect caused by unperfect circular polarization laser. Those experimental results were the good reference in the realization of CPT frequency standard, and they are also the general reference to CPT phenomenon and CPT frequency standard studies.
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OBJECTIVE: To investigate the clinical effect of continuous renal replacement therapy (CRRT) on patients of multiple organ dysfunction syndrome (MODS) with acute renal failure (ARF). METHODS: Twenty-two MODS cases with ARF underwent CRRT. Blood urea nitrogen (BUN), serum creatinine (SCr), hydrocarbons, serum potassium, and artery blood pH were detected in all patients every morning after hemopurification, in all patients volumes of infused fluid were recorded. The experience in 17 MODS cases with ARF treated with intermittent hemodialysis (IHD) in our hospital before October 1999 was present. RESULTS: The volumes of infused fluid were (5,237+/-106) ml and (2,319+/-87) ml in CRRT and IHD group respectively (P<0.05). In IHD group, 8 cases had cardiac failure between two hemodialysis sessions, and 13 cases had hypotension during hemodialysis; but in CRRT group there were only 1 and 3 cases respectively (both P<0.01). Mean levels of above BUN, SCr in IHD group were significantly higher than those in CRRT group (both P<0.05). The survival rates were 35.3% (6/17) and 45.5% (10/22) in IHD and CRRT group respectively, in the survival group, there were significantly less need of mechanical ventilation and vasoactive supporting. CONCLUSION: CRRT has benefits in improving fluid balance, acid-base balance and azotemia beyond IHD. The patient's age, need of mechanical ventilation and vasoactive drugs are predictors of a worse prognosis in patients of MODS with ARF. The prognosis of MODS with ARF is improved with CRRT.