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A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described. A complete approach, not wedded to semisynthesis, toward both the A-ring and CD-ring is reported. From a retrosynthetic standpoint, hidden symmetry within the decorated A-ring is disclosed, which allowed for scalable quantities of this advanced intermediate. In addition, a radical retrosynthetic approach is described, which highlights an electrochemical reductive coupling as well as an intramolecular hydrogen atom transfer Giese addition to establish the 6,5-transcarbon skeleton found in the vitamin D family. Finally, a late-stage decarboxylative cross-coupling approach allowed for the facile preparation of various C20-arylated derivatives that show promising biological activity in an initial bioassay.
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Psoríase , Vitamina D , Calcitriol/análogos & derivados , Humanos , Psoríase/tratamento farmacológico , VitaminasRESUMO
Because internal alkenes are more challenging synthetic targets than terminal alkenes, metal-catalyzed olefin mono-transposition (i.e., positional isomerization) approaches have emerged to afford valuable E- or Z- internal alkenes from their complementary terminal alkene feedstocks. However, the applicability of these methods has been hampered by lack of generality, commercial availability of precatalysts, and scalability. Here, we report a nickel-catalyzed platform for the stereodivergent E/Z-selective synthesis of internal alkenes at room temperature. Commercial reagents enable this one-carbon transposition of terminal alkenes to valuable E- or Z-internal alkenes via a Ni-H-mediated insertion/elimination mechanism. Though the mechanistic regime is the same in both systems, the underlying pathways that lead to each of the active catalysts are distinct, with the Z-selective catalyst forming from comproportionation of an oxidative addition complex followed by oxidative addition with substrate and the E-selective catalyst forming from protonation of the metal by the trialkylphosphonium salt additive. In each case, ligand sterics and denticity control stereochemistry and prevent over-isomerization.
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Multistep organic synthesis enables conversion of simple chemical feedstocks into a more structurally complex product that serves a particular function. The target compound is forged over several steps, with concomitant generation of byproducts in each step to account for underlying mechanistic features of the reactions (e.g., redox processes). To map structure-function relationships, libraries of molecules are often needed, and these are typically prepared by iterating an established multistep synthetic sequence. An underdeveloped approach is designing organic reactions that generate multiple valuable products with different carbogenic skeletons in a single synthetic operation. Taking inspiration from paired electrosynthesis processes that are widely used in commodity chemical production (e.g., conversion of glucose to sorbitol and gluconic acid), we report a palladium-catalyzed reaction that converts a single alkene starting material into two skeletally distinct products in a single operation through a series of carbon-carbon and carbon-heteroatom bond-forming events enabled by mutual oxidation and reduction, a process that we term redox-paired alkene difunctionalization. We demonstrate the scope of the method in enabling simultaneous access to reductively 1,2-diarylated and oxidatively [3 + 2]-annulated products, and we explore the mechanistic details of this unique catalytic system using a combination of experimental techniques and density functional theory (DFT). The results described herein establish a distinct approach to small-molecule library synthesis that can increase the rate of compound production. Furthermore, these findings demonstrate how a single transition-metal catalyst can mediate a sophisticated redox-paired process through multiple pathway-selective events along the catalytic cycle.
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A new fluorescent ribonucleoside alphabet (mth N) consisting of pyrimidine and purine analogues, all derived from methylthieno[3,4-d]pyrimidine as the heterocyclic core, is described. Large bathochromic shifts and high microenvironmental susceptibility of their emission relative to previous alphabets derived from thieno[3,4-d]pyrimidine (th N) and isothiazole[4,3-d]pyrimidine (tz N) scaffolds are observed. Subjecting the purine analogues to adenosine deaminase, guanine deaminase and T7 RNA polymerase indicate that, while varying, all but one enzyme tolerate the corresponding mth N/mth NTP substrates. The robust emission quantum yields, high photophysical responsiveness and enzymatic accommodation suggest that the mth N alphabet is a biophysically viable tool and can be used to probe the tolerance of nucleoside/tide-processing enzymes to structural perturbations of their substrates.
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RNA , Ribonucleosídeos , Antimetabólitos , Corantes , NucleosídeosRESUMO
BACKGROUND: Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites. METHODS: A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites. RESULTS: A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = - 0.405 and - 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and - 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05). CONCLUSIONS: This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic.
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Aterosclerose , Betaína , Carnitina , LDL-Colesterol , Colina/metabolismo , Humanos , Lipídeos , Metilaminas , Rosuvastatina Cálcica/uso terapêutico , Espectrometria de Massas em TandemRESUMO
The tolerance of cytidine deaminase (CDA) to expanded heterocycles is explored via three fluorescent cytidine analogues, where the pyrimidine core is fused to three distinct five-membered heterocycles at the 5/6 positions. The reaction between CDA and each analogue is followed by absorption and emission spectroscopy, revealing shorter reaction times for all analogues than the native substrate. Pseudo-first order and Michaelis-Menten kinetic analyses provide insight into the enzymatic deamination reactions and assist in drawing comparison to established structure activity relationships. Finally, inhibitor screening modalities are created for each analogue and validated with zebularine and tetrahydrouridine, two known CDA inhibitors.
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Citidina DesaminaseRESUMO
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a major regulator of cholesterol homeostasis, is associated with glucose metabolism. Liraglutide, a glucagon-like peptide-1 receptor agonist, can increase insulin secretion in a glucose-dependent manner and lower blood glucose. We aimed to investigate the relationship between liraglutide and PCSK9. METHODS: At the cellular level, the expressions of PCSK9 and hepatocyte nuclear factor 1 alpha (HNF1α) protein in HepG2 cells stimulated by liraglutide was examined using Western blot. Seven-week old db/db mice and wild type (WT) mice were administered either liraglutide (200 µg/kg) or equivoluminal saline subcutaneously, twice daily for 7 weeks. Fasting glucose level, food intake and body weight were measured every week. After the 7-week treatment, the blood was collected for lipid and PCSK9 levels detection and the liver was removed from the mice for oil red O staining, immunohistochemical analysis, immunofluorescence test and Western bolt. RESULTS: Firstly, liraglutide suppressed both PCSK9 and HNF1α expression in HepG2 cells in a time and concentration dependent manner. Secondly, liraglutide induced weight loss in WT and db/db mice, decreased serum PCSK9, glucose and lipid levels and improved hepatic accumulation in db/db but not WT mice. Thirdly, liraglutide reduced both hepatic PCSK9 and low-density lipoprotein receptor (LDLR) expression with a decrease in HNF1α in db/db mice but not in WT mice. CONCLUSIONS: Liraglutide suppressed PCSK9 expression through HNF1α-dependent mechanism in HepG2 cells and db/db mice, and decreased LDLR possibly via PCSK9-independent pathways in db/db mice.
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Diabetes Mellitus/tratamento farmacológico , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Hepatócitos/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Liraglutida/farmacologia , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/enzimologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Células Hep G2 , Hepatócitos/enzimologia , Humanos , Lipídeos/sangue , Masculino , Camundongos , Receptores de LDL/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND/AIMS: Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD). METHODS: In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA. RESULTS: The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; r = 0.28, p = 0.016), WBCC (r = 0.261, p = 0.02), neutrophil, r = 0.268, p = 0.018, and monocyte, r = 0.228, p = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (ß = 0.317, p = 0.004), WBCC (ß = 0.278, p = 0.020), neutrophil (ß = 0.262, p = 0.032), and monocyte (ß = 0.245, p = 0.032). CONCLUSIONS: The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients.
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Doença da Artéria Coronariana/sangue , Leptina/sangue , Adulto , Idoso , Povo Asiático , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , China , Angiografia Coronária , Feminino , Humanos , Inflamação/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Previous studies have suggested that people with obesity showed elevated serum levels of leptin as well as lipid dysfunction and proprotein convertase subtilisin/kexin type 9 (PCSK9) played an important role in the regulation of lipid metabolism recently. The aim of this study was to determine if leptin participated in regulating the uptake of low-density lipoproteins (LDL) in hepatocytes via PCSK9. METHODS: HepG2 cells were treated with human recombinant leptin. The impact of leptin on cellular low density lipoprotein receptor (LDLR) and PCSK9 protein levels was determined by Western blot. Dil-LDL uptake assay was performed to examine the LDLR function. Specific small interfering RNAs (siRNAs) were used to interfere the expressions of target proteins. RESULTS: The expression of LDLR and LDL uptake could be significantly down-regulated by leptin treatment while the expressions of PCSK9 and hepatocyte nuclear factor 1α (HNF1α) were enhanced in HepG2 cells. Furthermore, inhibition of PCSK9 or HNF1α expression by siRNAs rescued the reduction of LDLR expression and LDL uptake by leptin. We found that leptin activated the p38 mitogen-activated protein kinase (p38MAPK) signaling pathway. Moreover, the changes of the expressions of HNF1α, PCSK9, LDLR, and LDL uptake induced by leptin could be blocked by p38MAPK inhibitor (SB203580). Additionally, leptin attenuated the up-regulation of LDLR caused by atorvastatin in HepG2 cells. CONCLUSIONS: These findings indicated firstly that leptin reduced LDLR levels in hepatocyte via PCSK9 pathway, suggesting that PCSK9 might be a alternative target for dyslipidemia in the obesity.
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BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be involved in not only lipid metabolism but also glucose homeostasis. Glycated haemoglobin (HbA1c ) is a 'gold standard' for monitoring long-term glycaemic control. However, the correlation of plasma PCSK9 levels with HbA1c remains undetermined. METHODS: We consecutively enrolled 805 subjects undergoing coronary angiography, including 176 patients with type 2 diabetes mellitus (T2DM) and 629 non-diabetic patients. The baseline characteristics were collected, and serum PCSK9 level was assessed by ELISA. Univariable regression analysis and multiple-variable regression analysis were used to examine the associations of PCSK9 with HbA1c . Furthermore, the HbA1c was compared across the tertiles of PCSK9 levels. And also, PCSK9 levels were compared in poorly controlled (HbA1c ≥ 7.0%) and well-controlled (HbA1c < 7.0%) patients with T2DM. RESULTS: PCSK9 levels were positively correlated with low-density lipoprotein cholesterol in both T2DM and non-T2DM. Univariable regression analysis revealed a positive association between PCSK9 and HbA1c in patients with T2DM (ß = 0.255, p = 0.001) but not in patients without diabetes (ß = 0.061, p = 0.128). Multiple-variable regression analysis exhibited that PCSK9 was independently correlated with HbA1c in T2DM after adjustment for traditional atherosclerotic risk factors (ß = 0.197, p = 0.020). Moreover, HbA1c level was higher in patients with the highest tertile of PCSK9 than that in the lowest tertile (p = 0.042). Additionally, higher levels of PCSK9 were found in poorly controlled group compared with the well-controlled group (p = 0.029). CONCLUSIONS: Data suggest a positive correlation of PCSK9 levels with HbA1c in patients with T2DM but not in patients without T2DM, indicating a potential role of PCSK9 in T2DM. Copyright © 2015 John Wiley & Sons, Ltd.
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Biomarcadores/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Hemoglobinas Glicadas/análise , Pró-Proteína Convertases/sangue , Serina Endopeptidases/sangue , Estudos de Casos e Controles , Angiografia Coronária , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Pró-Proteína Convertase 9 , Fatores de RiscoRESUMO
Cryptosporidium spp., Giardia spp. and Enterocytozoon bieneusi are common zoonotic pathogens in humans and animals. Although rodents are important parts of the ecosystem and common hosts for these pathogens, little is known of the distribution, genetic diversity and zoonotic potential of these pathogens in wild rodents. A total of 442 fecal samples were collected from eleven wild rodent species in three provinces of China, and analyzed for these pathogens by PCR and DNA sequencing. The infection rates of Cryptosporidium spp., Giardia spp. and E. bieneusi were 19.9% (88/442), 19.8% (75/378) and 12.2% (54/442), respectively. Altogether, 23 known Cryptosporidium species/genotypes were identified and their distribution varied among different sampling locations or rodent species. Subtyping of the zoonotic Cryptosporidium species identified two novel subtype families XVe and XVf in C. viatorum, the subtype family XIIh and a novel subtype family XIIj in C. ubiquitum, and the subtype family IId in C. parvum. Three Giardia species were identified, including G. microti (n = 57), G. muris (n = 15) and G. duodenalis (n = 3), with G. duodenalis assemblages A and G identified in brown rats in urban areas of Guangdong. In addition, 13 E. bieneusi genotypes including eight known and five novel ones were identified, belonging to Groups 1, 2, 10, 14 and 15. Within nine genotypes in the zoonotic Group 1, common human-pathogenic genotypes D, Type IV, PigEbITS7 and Peru8 were detected only in brown rats and Lesser rice-field rats in urban areas of Guangdong. Apparent host adaptation and geographical differences were observed among Cryptosporidium spp., Giardia spp. and E. bieneusi genotypes in wild rodents in the present study. Furthermore, the zoonotic Cryptosporidium species and E. bieneusi genotypes commonly found here suggest a high zoonotic potential of these pathogens in wild rodents, especially in brown rats in urban areas. Hygiene and One Health measures should be implemented in urban streets and food stores to reduce the possible direct and indirect transmission of these rodent-related pathogens.
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Chiroptical micro/nanomaterials with circularly polarized luminescence (CPL) properties have aroused ever-increasing attention. However, the variety of such materials is seriously limited in self-assembly systems from small organic molecules. Herein, we report an unprecedented, facile strategy to achieve monodispersed polymer-based CPL-active core/shell particles using maleic anhydride copolymer as core and chiral helical polyacetylene as shell. Noticeably, the obtained core/shell particles carry no conventional fluorescent units, but can show intense blue-emitting nonconventional fluorescence with both aggregation-induced emission and concentration-enhanced emission performance. In particular, it is interesting that excitation-dependent CPL emission behavior is further observed in the core/shell particles, with the highest luminescence dissymmetry factor of 5 × 10-3. The present work provides a versatile platform with wide universality for constructing polymeric CPL nano/microarchitectures.
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Introduction: The optimal percutaneous coronary intervention (PCI) strategy for coronary left main (LM) bifurcation lesions remains controversial. This meta-analysis compared the medium and long-term follow-up clinical outcomes of single vs. systematic dual stenting strategies of LM bifurcation lesions. Methods: We systematically identified studies published within 5 years comparing single vs. systematic double stenting strategies for LM bifurcation lesions. The primary endpoint was medium-term (1 year) and long-term (at least 3 years) all-cause death. Secondary outcomes included major adverse cardiovascular events (MACEs), target lesion revascularization (TLR), overall occurrence of stent thrombosis (ST), cardiovascular (CV) mortality, and myocardial infarction (MI). Results: Two randomized controlled trials and nine observational studies with 7,318 patients were included in this meta-analysis. In terms of the medium-term follow-up clinical outcomes, our pooled analysis showed that use of the systematic dual stenting strategy was associated with a lower ST risk (odds ratio [OR] = 0.43, 95% confidence interval [CI]: 0.20-0.89, P = 0.02) and cardiac death risk (OR = 0.43, 95% CI: 0.21-0.89, P = 0.02) compared to the single stenting strategy; there was no significant difference between the two strategies regarding rates of all-cause death, MACE, TLR, and MI. Patients with long-term follow-up showed comparable observed clinical outcomes between the two strategies. Most importantly, for patients with true LM bifurcation, the risk of all-cause death, ST, and CV mortality following the systematic dual stenting strategy was significantly lower than the single stenting strategy. Conclusions: For patients with LM bifurcation lesions, both the systematic dual stenting strategy and single stenting strategy demonstrated comparable results in terms of all-cause mortality during medium-term and long-term follow-up. However, the systematic dual stenting strategy showed a tendency towards lower incidence of ST and CV mortality compared to the single stenting strategy during medium-term follow-up. Consequently, the systematic dual stenting strategy yielded superior clinical outcomes for patients with LM bifurcation lesions.
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The main purpose of this paper is to synthesize a new kind of green and environmental protection emulsion, which can be used as water erosion resistant materials. Here, a non-toxic polymer was prepared by grafting acrylic acid (AA) and methyl methacrylate (MMA) onto the long chains of tara gum (TG) to synthesize a copolymer emulsion (TG-g-P (AA-co-MMA)). The structure, thermal stability, morphology and wettability of the polymer were characterized by conventional methods, and the effects of key synthesis conditions on the performance of the emulsion (viscosity) were optimized. The erosion resistance and compressive strength of polymer-treated loess and laterite soils were evaluated under laboratory conditions. The results showed that the successful grafting of AA and MMA monomers onto TG improved its thermal stability and viscosity. In soil performance tests with low amounts of polymer additive, a 0.3 wt% application of TG-g-P (AA-co-MMA) to loess could resist continuous precipitation for >30 h with an erosion rate of 2.0 %. The compressive strength of the laterite treated with 0.4 % TG-g-P (AA-co-MMA) was 3.7 MPa, which was about three times that of the untreated soil. The results from this study suggest that TG-g-P (AA-co-MMA) emulsions have good potential for soil remediation applications.
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Polímeros , Água , Metilmetacrilato , Emulsões , Metacrilatos/químicaRESUMO
The accumulation of free cholesterol in macrophage lysosomes significantly enhances atherogenesis. Our recent study demonstrated that the cluster of differentiation 38 (CD38)/nicotinic acid adenine dinucleotide phosphate (NAADP)/Ca2+ signaling pathway plays a critical role in the efflux of lysosomal free cholesterol from macrophages in atherosclerosis. Niacin, known as nicotinic acid, is one of the oldest lipid-lowering medications showing unique anti-atherosclerotic activity. However, it is unknown whether this anti-atherosclerosis activity is associated with the efflux of lysosomal compartmentalized cholesterol in macrophages. In this study, we investigated the anti-atherosclerotic effects of niacin on the reduction of lysosomal free cholesterol via CD38/NAADP signaling in macrophages derived from low-density lipoprotein receptor (LDLr-/-) mice. Fluorescent filipin and Nile red labeling coupled with confocal microscopy demonstrated that niacin reduced free cholesterol accumulation in lysosomes in a concentration-dependent manner. Transmission electron microscopy also showed that niacin markedly decreased cholesterol crystal formation in lysosomes in oxidized LDL-containing LDLr-/- bone marrow-derived macrophages. Enzyme-linked immunosorbent assays showed that niacin increased NAADP production in a concentration-dependent manner, which was inhibited by small interfering RNA interference of CD38. Therefore, niacin may promote the efflux of lysosomal cholesterol from macrophages via the CD38/NAADP signaling pathway.
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Aterosclerose , Niacina , Animais , Aterosclerose/metabolismo , Colesterol/metabolismo , Lisossomos/metabolismo , Macrófagos , Camundongos , NADP/análogos & derivados , Niacina/farmacologia , Transdução de SinaisRESUMO
Cool flames have been studied for more than three centuries since the first observation. However, there are few achievements on the effects of the pressure on cool flames. In this work, a diffusion cool flame has been for the first time established using a counterflow configuration under a wide range of pressures. Dimethyl ether is used as the fuel because its low-temperature chemistry has been well tested. The pressure range of the experiments is from 0.05 to 0.15 MPa. The extinction limits, flame temperatures, and combustion products have been measured and simulated. In general, the reactivity of cool flames is stronger with increasing pressure. Specifically, at a fixed fuel mass fraction, the cool flame has a higher extinction strain rate, temperature, and concentration of products under higher pressure. However, the enhancement effect decreases with the increase of pressure. Interestingly, it was observed that the flame became thicker when the pressure increased. Moreover, the cool flame would deflagrate and transform to a hot flame when the pressure exceeds a certain value. The model captures the trends well but underpredicts the extinction limits and overpredicts the flame temperatures and product concentration. Path flux analyses and heat release rate analyses were carried out. It was found that the main heat release reactions are the reactions with CH3OCH2 radicals under low pressure, and CO prefers to form CO2 indirectly through HOCHO radicals. The study advances the understanding of cool flames in a wide range of pressures and provides experimental data for the improvement of the models.
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Selenocystine (SeC) has been identified as a novel compound with broad-spectrum anticancer activity. However, the effects of SeC on modifying DNA repair mechanism were less addressed. In this study, we demonstrated that SeC selectively induced cytotoxicity and genotoxicity against HepG2 hepatoma cell line. Comet assay revealed SeC-induced DNA damage in HepG2 cells, particularly in the form of DNA double strand breaks (DSBs), corroborated by the increase expression of the DSB marker, gamma-H2AX. We further demonstrated that SeC suppressed DNA homologous recombination repair, exacerbating DNA damage accumulation. Such effects on DNA damage and cell viability inhibition were alleviated by antioxidants, glutathione and Trolox, suggesting the involvement of reactive oxygen species (ROS). High levels of intracellular and mitochondrial ROS were detected in SeC-treated HepG2. In addition, SeC impaired the expression of antioxidant enzymes (superoxidase mutases and catalase), prompting the imbalance between antioxidant protection and excessive ROS formation and eliciting DSBs and cellular death. Decreased procaspase-3, 7, and 9 and Bcl-2 proteins and an increased Bax/Bcl-2 ratio, were observed after SeC treatment, but could be reversed by Torlox, confirming the action of SeC on ROS-induced apoptosis. In vivo, the xenograft tumor model of HepG2 cells validated the inhibition of SeC on tumor growth, and the induction of DSBs and apoptosis. In summary, SeC has the capability to induce ROS-dependent DNA damage and impeded DBS repair in HepG2 cells. Thus, SeC holds great promise as a therapeutic or adjuvant agent targeting DNA repair for cancer treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Antioxidantes/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Cistina/análogos & derivados , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Dano ao DNA , Reparo do DNA , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Compostos Organosselênicos , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Reparo de DNA por RecombinaçãoRESUMO
This paper reports on the assembly of a compact, low-cost, pulsed-power facility used for plasma studies. The construction uses two modules placed on opposite sides of the test chamber to minimize the system impedance and improve access to test samples. The stored energy is 1 kJ with a peak current of 135 kA and a 1592 ns quarter-period time. Up until now, an imploding conical-wire array has been studied by using time-integrated (visible) imaging, and time-resolved laser imaging, providing a measure of the plasma jet speed in the range of 170 km/s. Our future plans will continue to investigate high-energy-density plasmas that are relevant to the space environment, fusion, and spectroscopy.
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Chirality has become an important research subject. The research areas associated with chirality are under substantial development. Meanwhile, graphene is a rapidly growing star material and has hard-wired into diverse disciplines. Rational combination of graphene and chirality undoubtedly creates unprecedented functional materials and may also lead to great findings. This hypothesis has been clearly justified by the sizable number of studies. Unfortunately, there has not been any previous review paper summarizing the scattered studies and advancements on this topic so far. This overview paper attempts to review the progress made in chiral materials developed from graphene and their derivatives, with the hope of providing a systemic knowledge about the construction of chiral graphenes and chiral applications thereof. Recently emerging directions, existing challenges, and future perspectives are also presented. It is hoped this paper will arouse more interest and promote further faster progress in these significant research areas.
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Amorphous nonconjugated room-temperature phosphorescent (RTP) polymers have aroused ever-increasing attention. However, the variety of such polymers is still rare due to limited preparation strategies. Herein, we report a facile strategy to achieve ultralong RTP emission in biobased nonconjugated polymers through a hydrolyzation process. The investigated polymers are synthesized by free radical solution copolymerization using biomass methyl isoeugenol and maleic anhydride as monomers. Noticeably, the obtained polymers carry no conventional fluorescent units but can exhibit blue fluorescence. More interestingly, after hydrolysis in sodium hydroxide aqueous solution, the resulting hydrolyzed polymers emit both enhanced blue emission and persistent RTP (up to 400 ms) under air conditions, with reversible emission performance switched via the uptake and removal of water. Also worthy to be highlighted is that the emission can be remarkably regulated by the cations in carboxylate or the substituents on the benzene ring. The as-obtained polymers demonstrate potential applications in anticounterfeiting and information encryption.