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Chiral cyclobutane presents as a popular motif in natural products and biologically active molecules, and its derivatives have been extensively used as key synthons in organic synthesis. Herein, we report an efficient synthetic method toward enantioenriched cyclobutane derivatives. The reaction proceeds in a cascade fashion involving Ir-catalyzed asymmetric allylic etherification and visible-light induced [2 + 2] cycloaddition. Readily available branched allyl acetates and cinnamyl alcohols are directly used as the substrates under mild reaction conditions, providing a broad range of chiral cyclobutanes in good yields with excellent diastereo- and enantioselectivities (up to 12:1 dr, >99% ee). It is worth noting that all substrates and catalysts were simultaneously added without any separated step in this approach. The gram-scale reaction and diverse transformations of product further enhance the potential utility of this method.
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An iridium-catalyzed asymmetric allylic benzylation of aryl vinyl carbinols under light irradiation is described. 2-Methylbenzophenone derivatives are employed and activated to hydroxy-o-quinodimethanes by an ultraviolet (UV) light. This approach enables asymmetric allylic benzylation with high enantioselectivity (up to 99 % ee) from readily available 2-methylbenzophenones without the utilization of strong bases, and pre-activation or pre-functionalization of the substrates. Moreover, deuterium experiments reveal the generation of nucleophilic benzyl species from 2-methylbenzophenone under UV irradiation.
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Iridio , Estereoisomerismo , CatálisisRESUMEN
Prenatal ethanol exposure (PE) leads to increased addiction risk which could be mediated by enhanced excitatory synaptic strength in ventral tegmental area (VTA) dopamine (DA) neurons. Previous studies have shown that PE enhances excitatory synaptic strength by facilitating an anti-Hebbian form of long-term potentiation (LTP). In this study, we investigated the effect of PE on endocannabinoid-mediated long-term depression (eCB-LTD) in VTA DA neurons. Rats were exposed to moderate (3 g/kg/d) or high (6 g/kg/d) levels of ethanol during gestation. Whole-cell recordings were conducted in male offspring between 4 and 10 weeks old.We found that PE led to increased amphetamine self-administration. Both moderate and high levels of PE persistently reduced low-frequency stimulation-induced eCB-LTD. Furthermore, action potential-independent glutamate release was regulated by tonic eCB signaling in PE animals. Mechanistic studies for impaired eCB-LTD revealed that PE downregulated CB1 receptor function. Interestingly, eCB-LTD in PE animals was rescued by metabotropic glutamate receptor I activation, suggesting that PE did not impair the synthesis/release of eCBs. In contrast, eCB-LTD in PE animals was not rescued by increasing presynaptic activity, which actually led to LTP in PE animals, whereas LTD was still observed in controls. This result shows that the regulation of excitatory synaptic plasticity is fundamentally altered in PE animals. Together, PE leads to impaired eCB-LTD at the excitatory synapses of VTA DA neurons primarily due to CB1 receptor downregulation. This effect could contribute to enhanced LTP and the maintenance of augmented excitatory synaptic strength in VTA DA neurons and increased addiction risk after PE.SIGNIFICANCE STATEMENT Prenatal ethanol exposure (PE) is among many adverse developmental factors known to increase drug addiction risk. Increased excitatory synaptic strength in VTA DA neurons is a critical cellular mechanism for addiction risk. Our results show that PE persistently alters eCB signaling and impairs eCB-LTD at the excitatory synapses, an important synaptic plasticity that weakens synaptic strength. These effects combined with PE-induced anti-Hebbian long-term potentiation reported in a previous study could result in the maintenance of enhanced excitatory synaptic strength in VTA DA neurons, which in turn contributes to PE-induced increase in addiction risk. Our findings also suggest that restoring normal eCB signaling in VTA DA neurons could be a useful strategy for treating behavioral symptoms caused by PE.
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Neuronas Dopaminérgicas/efectos de los fármacos , Endocannabinoides/metabolismo , Etanol/envenenamiento , Plasticidad Neuronal/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Transmisión Sináptica/efectos de los fármacos , Área Tegmental Ventral/fisiopatología , Animales , Relación Dosis-Respuesta a Droga , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas Sprague-Dawley , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/patologíaRESUMEN
A TBAB-mediated brominative 5-exo-dig oxy-cyclization of 2-alkynylbenzamide is described here for the synthesis of isobenzofuran-1-imines and isobenzofuran derivatives at room temperature with a high efficiency and a broad reaction scope. The resulting isobenzofuran derivatives are also applied for synthesising various substituted isobenzofuran derivatives.
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Honeycomb structures are widely used in the field of impact resistance and are constantly being developed and updated. In this paper, the design of three new aluminum alloy rotating thin-walled structures (NRTS) are examined. These structures combine common concave structures and rotating, rigid-body structures. The purpose of this study is to solve the problem of the poor energy absorption capacity of rotating, rigid-body structure due to small deformation and to provide a reference for honeycomb mechanism designs. The Young's modulus, the critical velocity, and the platform stress of the NRTS structure are derived from theoretical analysis. The dynamic response of the NRTS structure at different impact velocities is investigated using finite element simulation software. The results show that the rotating, thin-walled recessed honeycomb (RTRH) increases the plateau stress by 124% and 51% as compared to rotating, thin-walled square tubes (RTSTs) and the re-entrant hexagonal structure (RH), respectively; the rotating, thin-walled quadruple-arc honeycomb structure (RTQH) increases the SEA by 21% and 20% as compared to the RTST and RH, respectively; and the rotating thin-walled double-arc honeycomb structure (RTDH) increases the CEF by 54% and 51% as compared to the RTST and RH, respectively. During the study, it was demonstrated that NTRS also exhibits good energy absorption capacity. Then, the effect of rotation angle on the energy absorption performance was analyzed. The cell and wall thickness of the NTRS structure were optimized according to the gradient theory. It was proved that the gradient optimized structure has better energy absorption performance as compared to the uniform structure.
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BACKGROUND: The aim of this study was to explore the association between CD24âAla/Val polymorphism and susceptibility of multiple sclerosis (MS). METHODS: A comprehensive literature search for relevant studies was performed on google scholar, PubMed, Web of science, Embase, the Chinese National Knowledge Infrastructure and the Chinese Biology Medicine. This meta-analysis was conducted using the STATA 11.0 software and the pooled odds ratio with 95% confidence interval was calculated. RESULTS: Seven case-control studies were included in this meta-analysis. The results showed significant association between CD24âAla/Val polymorphism and susceptibility to MS. Stratified analysis by areas also showed significant association in Asians. However, no association was found in Europeans. CONCLUSION: This study suggested that the CD24 Val allele was associated with an increased risk of MS and larger-scale studies of populations are needed to explore the role of CD24âAla/Val polymorphism during the pathogenesis of MS.
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Antígeno CD24/genética , Esclerosis Múltiple/genética , Sustitución de Aminoácidos , Predisposición Genética a la Enfermedad , HumanosRESUMEN
BACKGROUND: Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is still unclear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance and inflammatory factors to investigate the effects of dexmedetomidine on postoperative cognitive dysfunction (POCD) and inflammation in patients after general anaesthesia. METHODS: Literatures were searched in several electronic databases and studies were selected by following precise inclusion criteria. We searched PubMed, EMBASE, the Cochrane Library, China Academic Journals full-text database (CNKI), and Google Scholar to find randomized controlled trials (RCTs) of the influence of dexmedetomidine on POCD and inflammation in patients who had undergone general anaesthesia. Two researchers independently screened the literature, extracted data, and evaluated quality of methodology against inclusion and exclusion criteria. Meta-analyses of pooled ORs of POCD incidences and mean differences in neurocognitive assessment scores and inflammation levels were carried out and subgroup analyses were performed. Stata 12.0 was used to conduct our meta-analysis. RESULTS: Twenty-six RCTs were included. Compared with controls, perioperative dexmedetomidine treatment significantly reduced the incidence of POCD (pooled ORsâ=â0.59, 95% confidence interval (CI) 0.45-2.95) and improved Mini-Mental State Examination (MMSE) score (standardized mean difference (SMD)â=â1.74, 95% CI 0.43-3.05) on the first postoperative day. Furthermore, perioperative dexmedetomidine treatment significantly decreased IL-6 (SMDâ=â-1.31, 95% CI -1.87-0.75, Pâ<â.001) and TNF-α (SMDâ=â-2.14, 95% CI -3.14-1.14, Pâ<â.001) compared to saline/comparators treatment. In the stratified analysis by surgical type, age, type of control, and study region, the differences were also significant between dexmedetomidine- and saline-treated patients. CONCLUSION: Perioperative dexmedetomidine treatment is associated with significantly reduced incidence of POCD and inflammation and better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics.
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Agonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Anestesia General/efectos adversos , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/prevención & control , Dexmedetomidina/administración & dosificación , China , Humanos , Inflamación/tratamiento farmacológico , Mediadores de Inflamación/metabolismo , Interleucina-6/biosíntesis , Pruebas de Estado Mental y Demencia , Oportunidad Relativa , Periodo Perioperatorio , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Reasonable design and synthesis of Fe/N/C-based catalysts is one of the most promising way for developing precious metal-free oxygen reduction reaction (ORR) catalysts in acidic mediums. Herein, we developed a highly active metal-organic framework-derived S-doped Fe/N/C catalyst [S-Fe/Z8/2-aminothiazole (2-AT)] prepared by thermal treatment. The S-Fe/Z8/2-AT catalyst with uniform S-doping possesses a three-dimensional macro-meso-micro hierarchically porous structure. Moreover, the chemical composition and structural features have been well-optimized and characterized for such S-Fe/Z8/2-AT catalysts; and their formation mechanism was also revealed. Significantly, applying the optimal S-Fe/Z8/2-AT catalysts into electrocatalytic test exhibits remarkable ORR catalytic activity with a half-wave potential of 0.82 V (vs reversible hydrogen electrode) and a mass activity of 18.3 A g-1 at 0.8 V in 0.1 M H2SO4 solution; the polymer electrolyte membrane fuel cell test also confirmed their excellent catalytic activity, which gives a maximal power density as high as 800 mW cm-2 at 1 bar. A series of designed experiments disclosed that the favorable structural merits and desirable chemical compositions of S-Fe/Z8/2-AT catalysts are critical factors for efficient electrocatalytic performance. The work provides a new approach to open an avenue for accurately controlling the composition and structure of Fe/N/C catalysts with highly activity for ORR.
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A new highly sensitive luminescent iridium(III) chemosensor, 1, was designed and synthesized for tandem detection of fluoride ions (F-) and aluminum ions (Al3+). This sensor 1 exhibited obvious luminesce quenching by hydrogen bond interactions with F-. In addition, the resulting 1-F complex can be further used to detect Al3+ through a luminesce enhancement. The detection limit (0.02 µM) of 1-F for Al3+ is far lower than the World Health Organization (7.41 µM) limit for drinking water. Importantly, chemosensor 1-F could be used to detect and quantify F- and Al3+ reversibly. This sensor achieved rapid detection of two ions, which relies on only one probe.
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A novel nanostructured catalyst of platinum nanoparticles supported on 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate) (TMPyP) functionalized graphene (TMPyP-graphene) is synthesized by the hydrothermal polyol process. The as-synthesized nanocomposites are characterized by Fourier transform infrared (FTIR) spectroscopy, UV-vis absorption spectroscopy, Raman spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and electrochemical tests. It has been found that Pt nanoparticles of ca. 3.4 nm are uniformly dispersed on the surface of TMPyP-graphene, and hold a high electrochemical active surface area (ECSA) of 126.2 m(2) g(-1). The results demonstrate that the Pt/TMPyP-graphene catalyst exhibits a much higher electrocatalytic activity and stability than the Pt/graphene and commercial Pt/C catalysts for methanol oxidation, which is of significant importance in improving the efficiency of Pt-based electrocatalysts for DMFCs applications.