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A palladium-catalyzed cascade carbonylation reaction of 2-bromo-N-(2-iodophenyl)benzamides with benzylidenecyclopropanes for the synthesis of fused isoindolinone derivatives has been developed. A broad range of 6/5/6/6 tetracyclic isoindolinone products were efficiently prepared in moderate to good yields with diverse substitution. Two carbonyl groups were incorporated into the substrates in a single step with the formation of four carbon-carbon bonds and two carbon-heteroatom bonds.
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Boswellia sacra has the properties of activating blood circulation, fixing pain, subduing swelling and promoting muscle growth. However, the anti-inflammatory active ingredients and molecular mechanisms of Boswellia sacra are still not clearly explored. Boswellia sacra was grounded and extracted using 95% ethanol, the extracts were separated by column chromatography preparation to give compounds. Spectral analysis and quantum calculations confirmed the structures of compounds and identified compound 1 as a new compound. Compounds 1-3 showed potent inhibitory activities and their effects on inflammatory mediator NO and inflammatory cytokines were examined by ELISA assay. Furthermore, their modulatory mechanism on inflammatory signal pathways was explored.
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Organic-inorganic hybrid perovskite solar cells (PSCs) have recently been demonstrated to be promising renewable harvesters because of their prominent photovoltaic power conversion efficiency (PCE), although their stability and efficiency still have not reached commercial criteria. Trouble-oriented analyses showcase that defect reduction among the grain boundaries and interfaces in the prepared perovskite polycrystalline films is a practical strategy, which has prompted researchers to develop functional molecules for interface passivation. Herein, the pyridine-based bifunctional molecule dimethylpyridine-3,5-dicarboxylate (DPDC) was employed as the interface between the electron-transport layer and perovskite layer, which achieved a champion PCE of 21.37% for an inverted MAPbI3-based PSC, which was greater than 18.64% for the control device. The mechanistic studies indicated that the significantly improved performance was mainly attributed to the remarkably enhanced fill factor with a value greater than 83%, which was primarily due to the nonradiative recombination suppression offered by the passivation effect of DPDC. Moreover, the promoted carrier mobility together with the enlarged crystal size contributed to a higher short-circuit current density. In addition, an increase in the open-circuit voltage was also observed in the DPDC-treated PSC, which benefited from the improved work function for reducing the energy loss during carrier transport. Furthermore, the DPDC-treated PSC showed substantially enhanced stability, with an over 80% retention rate of its initial PCE value over 300 h even at a 60% relative humidity level, which was attributed to the hydrophobic nature of the DPDC molecule and effective defect passivation. This work is expected not only to serve as an effective strategy for using a pyridine-based bifunctional molecule to passivate perovskite interfaces to enhance photovoltaic performance but also to shed light on the interface passivation mechanism.
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Prolyl hydroxylase domain 2 (PHD2) is an important enzyme in the human body that perceives changes in oxygen concentration and regulates response in hypoxic environments. Evaluation of PHD2 inhibitory activity of natural products is crucial for drug development of hypoxia related diseases. At present, the detection of low concentration of α-ketoglutaric acid (the substrate of PHD2 enzymatic reaction) requires derivatization reactions or sample pretreatment, which undoubtedly increases the workload of PHD2 inhibitory activity evaluation. In this paper, a direct detection approach of α-ketoglutaric acid was established by using the online stacking strategy of capillary electrophoresis to evaluate the PHD2 inhibitory activity of natural products. Under optimized conditions, detection of a single sample can be achieved within 2 min. By calculation, the intraday precision RSD of the apparent electrophoretic mobility and peak areas of α-ketoglutaric acid are 0.92 % and 0.79 %, respectively, and the interday RSD were 1.27 % and 0.96 % respectively. The recoveries of the present approach were 97.9-105.2 %, and the LOQ and LOD were 2.0 µM and 5.0 µM, respectively. Furthermore, this approach was applied for the evaluation of inhibitory activity of PHD2 for 13 natural products, and PHD2 inhibitory activity of salvianolic acid A was firstly reported. The present work not only realizes evaluation of PHD2 inhibitory activity through direct detection of α-ketoglutaric acid, but also provides technical support for the discovery of potential drug molecules in hypoxia related diseases.
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Produtos Biológicos , Eletroforese Capilar , Prolina Dioxigenases do Fator Induzível por Hipóxia , Ácidos Cetoglutáricos , Humanos , Produtos Biológicos/farmacologia , Eletroforese Capilar/métodos , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Ácidos Cetoglutáricos/análiseRESUMO
A method involving a metal-free visible-light-promoted synthesis was developed for the construction of difluoroalkylated oxindoles with N-phenylacrylamides and bromodifluoroacetamides as starting materials in the presence of N,N,N',N'-tetramethylethylenediamine (TMEDA). Twenty-four examples of the photochemical reaction were successfully performed, with good yields (44-99%) and excellent substrate adaptability. Mechanistic studies showed that the visible-light-promoted reaction involved a radical addition to N-phenylacrylamide, intramolecular cyclization, dehydrogenation, and rearomatization. The difluoroacetamide radical was produced as a result of electron transfer to bromodifluoroacetamides from the electron donor TMEDA in their electron-donor-acceptor (EDA) complexes under visible light irradiation. This protocol is a promising photochemical method due to its advantages of mild conditions, simple operation, wide substrate scope and high yields. And the obtained products may have great potential in the field of medicine.
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[6,6]-Phenyl-C61-butyric acid methyl ester (PCBM), a star molecule in the fullerene field, has found wide applications in materials science. Herein, electrosynthesis of buckyballs with fused-ring systems has been achieved through radical α-C-H functionalization of the side-chain ester for both PCBM and its analogue, [6,6]-phenyl-C61-propionic acid methyl ester (PCPM), in the presence of a trace amount of oxygen. Two classes of buckyballs with fused bi- and tricyclic carbocycles have been electrochemically synthesized. Furthermore, an unknown type of a bisfulleroid with two tethered [6,6]-open orifices can also be efficiently generated from PCPM. All three types of products have been confirmed by single-crystal X-ray crystallography. A representative intramolecularly annulated isomer of PCBM has been applied as an additive to inverted planar perovskite solar cells and boosted a significant enhancement of power conversion efficiency from 15.83% to 17.67%.
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The cotton mealybug Phenacoccus solenopsis, a globally invasive insect, is listed as a national quarantine pest in agriculture and forestry, which seriously threatens biological safety of China. Niche conservatism is a key assumption of species distribution model. An evaluation of the applicability of using ecological niche models to assess the invasion risk of cotton mealybug, and further optimizing model complexity, are of both theoretical and practical significance. Based on 706 occurrence records and key bioclimatic variables, we used n-dimensional hypervolume niche analysis method to quantify the climatic niche hypervolumes of this pest in both native and invasive sites, and further tested the niche conservatism hypothesis. MaxEnt model parameters were optimized to predict the invasion risk of the mealybug under current and future climate scenarios in China. The results showed that four climatic variables (annual mean temperature, mean temperature of wettest quarter, mean temperature of warmest quarter, and precipitation of driest quarter) were the key climate factors affecting the distribution of cotton mealybug. Compared with native climatic niche (hypervolume volume, HV=40.43), the niche hypervolume of cotton mealybug in the invasive areas was significantly reduced (HV=6.04). Niche contraction (the net differences between the amount of space enclosed by each hypervolume was 0.84) explained 98.8% of niche differentiation, whereas niche shift (the replacement of space between hypervolumes was 0.01) contributed less than 2%. The direction of climatic niche contraction of the pest in different invasive areas was not exactly consistent. The default parameters of MaxEnt model were unreliable (ΔAICc=14.27), and the optimal parameter combination was obtained as follows: feature combination was linear-quadratic-hinge-product and regularization multiplier was 0.5. The most suitable habitats of cotton mealybug were concentrated in the south of Huaihe River-Qinling Mountains line, and the north-central provinces contained a large area of low suitable habitat. The increase of suitable habitat was not significant at the end of 21 century (SSP1-2.6: 1.7%, SSP5-8.5: 0.7%). The multidimensional climatic niche of P. solenopsis was highly conservative. The species distribution model was suitable for analyzing its invasion risk. The northward spread was obvious, and climate change had less impact on the pest.
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Formigas , Gossypium , Animais , Agricultura , China , Mudança ClimáticaRESUMO
BACKGROUND: Minerals have crucial biological functions in metabolism and are primarily obtained through diet. As a result, various dietary patterns can impact blood mineral levels. The aim of this study was to investigate the correlation between dietary patterns and the concentration of calcium, magnesium, iron, zinc, and copper in the bloodstream. METHODS: Three hundred eighty healthy children (53.7% male) were recruited in a region of Hunan Province in September 2019. We gathered basic information and measured physical proportions, along with completing a food frequency questionnaire (FFQ). Using principal component analysis (PCA), we determined dietary patterns. To analyze mineral levels in the blood, we used flame atomic absorption spectrometry (FAAS). We utilized linear regression models to investigate if certain dietary patterns are related to mineral concentration. RESULTS: Three dietary patterns were identified: 'Vegetables/Nuts,' 'Snacks/Beverages,' and 'Cereal/Beans.' Children from high-income families (annual average income > 50,000 yuan) prefer the 'Vegetables/Nuts' dietary pattern (P = 0.004). In comparison, those from low-income families (annual average income < 20,000 yuan) prefer the 'Snacks/Beverages' dietary pattern (P = 0.03). Following adjustment for age, gender, guardian's identity, education level, and annual household income. We found that an increase in the 'Vegetables/Nuts' pattern score (ß = 0.153, CI: 0.053 ~ 0.253; P = 0.003) and 'Snacks/Beverages' pattern score (ß = 0.103, CI: 0.002 ~ 0.204; P = 0.033) were significantly associated blood copper concentration. CONCLUSIONS: Household income was found to be associated with dietary behavior. Furthermore, higher blood copper concentration was significantly correlated with the 'Vegetables/Nuts' dietary pattern and 'Snacks/Beverages' dietary pattern, but the correlation is extremely low.
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Cobre , Comportamento Alimentar , Humanos , Masculino , Criança , Feminino , Dieta , Verduras , China , MineraisRESUMO
Predation is widely recognized as a powerful selective pressure on primate behavior and ecology, although knowledge of predator-prey relationships remains limited partly due to the rarity of directly observed attacks on primates. Here, we describe four confirmed or suspected instances of leopard (Panthera pardus) predation on free-ranging Sichuan (golden) snub-nosed monkeys (Rhinopithecus roxellana), a highly endangered colobine species endemic to China. We recorded predation events and the reactions of monkey group members. We suggest that the evolution of a multilevel society may be an adaptive response by Sichuan snub-nosed monkeys to the risk from leopards as well as other potential predators, one that balances the pressures of predation and intra-species competition and conflict.
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Colobinae , Panthera , Presbytini , Animais , Comportamento Predatório , Colobinae/fisiologia , ChinaRESUMO
Simultaneous electrochemical ring contraction and expansion reactions remain unexplored to date. Herein, the reductive electrosynthesis of heterocycle-fused fulleroids from fullerotetrahydropyridazines and electrophiles in the presence of a trace amount of oxygen has been achieved with concurrent ring contraction and ring expansion. When trifluoroacetic acid and alkyl bromides are employed as electrophiles, heterocycle-fused fulleroids with a 1,1,2,6-configuration are regioselectively formed. In contrast, heterocycle-fused fulleroids with a 1,1,4,6-configuration are regioselectively produced as two separable stereoisomers if phthaloyl chloride is used as the electrophile. The reaction proceeds through multiple steps of electroreduction, heterocycle ring-opening, oxygen oxidation, heterocycle contraction, fullerene cage expansion, and nucleophilic addition. The structures of these fulleroids have been determined by spectroscopic data and single-crystal X-ray diffraction analyses. The observed high regioselectivities have been rationalized by theoretical calculations. Representative fulleroids have been applied in organic solar cells as the third component and exhibit good performance.
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Fulerenos , Cristalografia por Raios X , Fulerenos/química , Estereoisomerismo , HalogêniosRESUMO
As a result of global warming, the Mytilus coruscus living attached in the intertidal zone experience extreme and fluctuating changes in temperature, and extreme temperature changes are causing mass mortality of intertidal species. This study explores the transcriptional response of M. coruscus at different temperatures (18 °C, 26 °C, and 33 °C) and different times (0, 12, and 24 h) of action by analyzing the potential temperature of the intertidal zone. In response to high temperatures, several signaling pathways in M. coruscus, ribosome, endocytosis, endoplasmic reticulum stress, protein degradation, and lysosomes, interact to counter the adverse effects of high temperatures on protein homeostasis. Increased expression of key genes, including heat shock proteins (Hsp70, Hsp20, and Hsp110), Lysosome-associated membrane glycoprotein (LAMP), endoplasmic reticulum chaperone (BiP), and baculoviral IAP repeat-containing protein 7 (BIRC7), may further mitigate the effects of heat stress and delay mortality in M. coruscus. These results reveal changes in multiple signaling pathways involved in protein degradation during high-temperature stress, which will contribute to our overall understanding of the molecular mechanisms underlying the response of M. coruscus to high-temperature stress.
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Mytilus , Animais , Mytilus/genética , Temperatura , Transcriptoma , Proteólise , Transdução de SinaisRESUMO
Antimicrobial peptides are small, cationic, and amphiphilic peptides found in most organisms, and many of these peptides have broad antimicrobial activity against Gram-negative, -positive bacteria and fungi. In the present study, a derivative of antimicrobial peptide Tatritin, 6His-Tatritin, was designed and expressed by Pichia pastoris using a constitutive vector pGAPZαA with the promoter of pGAP. The 6His-Tatritin had a broad-spectrum antibacterial activity based on the Oxford cup method and the micro broth dilution test. In addition, to explore the role of 6His-Tatritin in vivo, grass carps (Ctenopharyngodon idellus) were infected with Aeromonas hydrophila after they were fed with 6His-Tatritin as feed additives for 28 days. The results revealed that 6His-Tatritin could significantly up-regulate the expression levels of Hepcidin, Leap-2b, Nrf-2, CuZn-SOD and LZM (P < 0.05). In addition, 6His-Tatritin could significantly reduce the mortality (P < 0.05) and the intestinal injury of grass carps infected with bacteria. The 16S sequencing analysis showed that the structure of microbial community in intestine of fish was more diversified compared with control after treatment with 6His-Tatritin. In summary, the peptide of 6His-Tatritin could promote antimicrobial defense via regulating immune ability and intestinal microbial community in grass carp. This study provides an effective method and approach for the application of antimicrobial peptide Tatritin in aquaculture, and also provides insights into the function of antimicrobial peptides in immunity against pathogens in fish.
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Anti-Infecciosos , Carpas , Doenças dos Peixes , Infecções por Bactérias Gram-Negativas , Animais , Transdução de Sinais , Suplementos Nutricionais/análise , Dieta/veterinária , NF-kappa B/metabolismo , Carpas/genética , Carpas/metabolismo , Intestinos , Anti-Infecciosos/farmacologia , Peptídeos Antimicrobianos , Aeromonas hydrophila/fisiologia , Ração Animal/análiseRESUMO
As a prodrug-converting enzyme, ß-glucuronidase (ß-GCase) is a lysosomal enzyme participating in the release of glucose from glucopyranosyl glycoside. In this work, for the first time, we have developed an analytical method exhibiting fluorometric signals for straightforward determination of ß-GCase using silicon nanoparticles (Si NPs). Via hydrothermal treatment, in the water bath of 70 °C for 50 min, dopamine (DA) reacts with (3-[2-(2-aminoethylamino) ethylamino] propyltrimethoxysilane) (AEEA) to produce green fluorescent Si NPs. Enlightened by such easy reaction and ß-GCase-triggered specific hydrolysis of dopamine-4-ß-D-glucuronide (DA-GCU) into DA, we have designed an analytical method for ß-GCase sensing through the production of Si NPs. Therefore, through the designed sensing platform, ß-GCase activity was monitored, and the limit of detection (LOD) for this study was 0.02 U/L. Furthermore, the feasibility of the method was assessed by measuring ß-GCase activity in human serum where recoveries and RSD were in the ranges 99-104% and 1.37-3.44, respectively.
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Nanopartículas , Silício , Humanos , Glucuronidase , Dopamina , Fluorometria/métodosRESUMO
Oxygen is a necessary substance for life activities, but reduced oxygen utilization due to high altitude exposure and respiratory dysfunction diseases could lead to pathological changes in the organisms. Herein gypenosides, the active ingredients in the food and medicine resource plant Gynostemma pentaphyllum (Thunb.) Makino were found to alleviate hypoxia-induced injury in PC12 cells. Moreover, hypoxia induced an increase in Ca2+ and reactive oxygen species content, and such patterns were both significantly reduced by gypenosides treatment. At the same time, gypenosides significantly blocked the decrease of both NO content and mitochondrial membrane potential caused by hypoxia. Furthermore, gypenosides gavage treatment significantly prolonged the survival time of C57BL/6 mice in confinement up to 24.3% and enhanced the locomotor ability of mice. Therefore, gypenosides have good neuroprotective effects and hypoxia tolerance activity and have the prospect of being developed as a preventive and therapeutic drug for hypoxia-related diseases. PRACTICAL APPLICATIONS: Gypenosides can enhance tolerance of cells and mice to hypoxia and have the potential to be developed into hypoxia-resistant health food and drugs.
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Gynostemma , Hipóxia , Ratos , Camundongos , Animais , Células PC12 , Camundongos Endogâmicos C57BL , Hipóxia/tratamento farmacológico , OxigênioRESUMO
A base-promoted [4 + 2] annulation of pyrrole-2-carbaldehyde derivatives with ß,γ-unsaturated α-ketoesters for the syntheses of multisubstituted 5,6-dihydroindolizines was developed. Using DBN as a base, the reaction proceeds smoothly under mild conditions to provide the target products in moderate to high yields, and many useful functional groups can be tolerated.
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Ésteres , Pirróis , Catálise , CiclizaçãoRESUMO
Twenty-two isolates, including two previously undescribed compounds identified as benzoyltembamide (1) and P-benzoyphenethyl anisate (21), were isolated and identified from a methanol extract of the roots of Zanthoxylum bungeanum Maxim. (Rutaceae) using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data analysis such as HR-ESI-MS, 1D and 2D NMR, IR and UV, as well as single-crystal X-ray diffraction for crystalline compounds. All the compounds (except for compound 16) were isolated from the roots of Z. bungeanum for the first time. Selected compounds were evaluated for their antioxidant activities. Compound 18 attenuated the H2O2-induced cytotoxicity and blocked the accumulation of ROS in SH-SY5Y cells, and exhibited potent neuroprotective activity.
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Neuroblastoma , Zanthoxylum , Humanos , Zanthoxylum/química , Peróxido de Hidrogênio , Estrutura Molecular , Cromatografia Líquida de Alta PressãoRESUMO
Ribose plays an important role in the process of life. Excessive ribose in the human cerebrospinal fluid or urine can be used as an early diagnostic marker of leukoencephalopathy. Fluorinated phenylboronic acid combined with 19F NMR spectroscopy was a powerful method for molecular recognition. However, phenylboronic acid-based sensors for selective detection of ribose are rarely reported in the literature. In this study, the rapid and highly selective recognition of ribose was studied by 19F NMR and 2-fluorophenylboric acid. It was found that 2-fluoro-phenylboric acid was an appropriate 19F NMR-based sensor molecule for the determination of ribose under physiological conditions with high selectivity and robust anti-interference ability. When 2-fluorophenylboric acid was used for the detection of ribose in human urine without any sample pretreatment, a limit of detection of 78 µM was obtained at room temperature under given 19F NMR experimental conditions (400 MHz, 512 scans, ca. 12 min), which can well meet the needs of practical application.
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Imageamento por Ressonância Magnética , Ribose , Humanos , Espectroscopia de Ressonância Magnética/métodosRESUMO
Three unreported dammarane-type triterpenoids with rare skeletons (1-3), along with one undescribed gypenoside (4), were isolated from the aerial parts of Gynostemma pentaphyllum using diverse chromatographic materials and pre-HPLC. Their structures were elucidated on the basis of spectroscopic and spectrometric data, while the absolute configurations of 1-3 were assessed via electronic circular dichroism (ECD) analyses. Notably, compounds 1-3 possess a 3,19-hemiketal bridge in the A ring. Saponin 4 possesses an unreported 20,25-oxa structural moiety. Their antiproliferative effects against HepG2, MCF-7, and DU145 cell lines were screened. Compounds 1-3 displayed moderate cytotoxicity with IC50 values ranging from 13.7 ± 0.2 to 32.0 ± 1.7 µM.
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Antineoplásicos , Saponinas , Triterpenos , Gynostemma , Estrutura Molecular , Saponinas/farmacologia , Esqueleto , Triterpenos/química , Triterpenos/farmacologia , DamaranosRESUMO
Prolyl hydroxylase 2 (PHD2) is a key oxygen receptor regulating oxygen homeostasis in human body, and it is one of the important targets for drug research and development of hypoxia related diseases. In PHD2 enzymatic reaction, the structure of substrate (HIF-1α556-574) and product (hydroxylated HIF-1α) peptide only differ from one oxygen atom (MW>2000), which makes it a great challenge to separate them accurately and efficiently. In this work, the direct separation and detection of HIF-1α and hydroxylated HIF-1α has been firstly reported based on micellar electrokinetic chromatography (MEKC). Under optimized conditions, the intraday RSD of peak area and apparent electrophoretic mobility of hydroxylated HIF-1α were 1.87% and 0.81% respectively, and the interday RSD were 2.01% and 1.03% respectively. The LOD and LOQ of the MEKC method were 10 µM and 50 µM respectively, and the recoveries was 98.42-105.38%. Subsequently, the feasibility and accuracy of MEKC method to screen PHD2 inhibitors were confirmed by using roxadustat, and the IC50 (10.36 µM) and inhibitor type (competitive) were consistent with literature. Finally, the method was used to screen the PHD2 inhibitory activity of five traditional Chinese medicines (TCMs). The present work not only overcomes the difficulties of direct quantitative detection of hydroxylated HIF-1α, but also provides technical support for exploring and discovering new drug leads for hypoxia-related diseases from complex matrix such as TCMs.