RESUMO
An effective and straightforward Ag(I)-mediated annulation of 2-(2-enynyl)quinolines and N'-(2-alkynylbenzylidene)hydrazides was developed, forging various synthetically challenging 17bH-isoquinolino[2'',1'':1',6']pyridazino[4',5':3,4]pyrrolo[1,2-a]quinolines, including different nitrogen-containing fused rings, in moderate to excellent yields. This one-pot cycloaddition strategy features exclusive regioselectivity, high atom economy, and broad substrate scope under mild conditions. The practicality and reliability of this cycloaddition reaction was demonstrated by a successful scale-up synthesis.
RESUMO
An effective Ag(I)-mediated annulation of 2-(2-enynyl)pyridines and propargyl amines was developed, unexpectedly affording a broad range of functionalized 1-(2H-pyrrol-3-yl)indolizines in moderate to excellent yields. The developed method is characterized by operational simplicity, ready availability of starting materials, high regioselectivity, and broad substrate scope under mild reaction conditions. The Ag(I)-promoted cyclization of 2-(2-enynyl)pyridines and propargyl amines possibly results in the formation of the spiroindolizine, the ring-opening rearrangement of which may give the 1-(2H-pyrrol-3-yl)indolizine. Furthermore, a gram-scale reaction and synthetic transformations are also studied.
RESUMO
Exposure to pesticides induces oxidative stress and deleterious effects on various tissues in non-target organisms. Numerous models investigating pesticide exposure have demonstrated metabolic disturbances such as imbalances in amino acid levels within the organism. One potentially effective strategy to mitigate pesticide toxicity involves dietary intervention by supplementing exogenous amino acids and their derivates to augment the body's antioxidant capacity and mitigate pesticide-induced oxidative harm, whose mechanism including bolstering glutathione synthesis, regulating arginine-NO metabolism, mitochondria-related oxidative stress, and the open of ion channels, as well as enhancing intestinal microecology. Enhancing glutathione synthesis through supplementation of substrates N-acetylcysteine and glycine is regarded as a potent mechanism to achieve this. Selection of appropriate amino acids or their derivates for supplementation, and determining an appropriate dosage, are of the utmost importance for effective mitigation of pesticide-induced oxidative harm. More experimentation is required that involves large population samples to validate the efficacy of dietary intervention strategies, as well as to determine the effects of amino acids and their derivates on long-term and low-dose pesticide exposure. This review provides insights to guide future research aimed at preventing and alleviating pesticide toxicity through dietary intervention of amino acids and their derivates.
Assuntos
Aminoácidos , Estresse Oxidativo , Praguicidas , Praguicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Glutationa/metabolismo , Suplementos Nutricionais , HumanosRESUMO
BACKGROUND: Research on the co-production of multiple enzymes by Bacillus velezensis as a novel species is still a topic that needs to be studied. This study aimed to investigate the fermentation characteristics of B. velezensis D6 co-producing α-amylase and protease and to explore their enzymatic properties and applications in fermentation. RESULTS: The maximum co-production of α-amylase and protease reached 13.13 ± 0.72 and 2106.63 ± 64.42 U mL-1, respectively, under the optimal fermented conditions (nutrients: 20.0 g L-1 urea, 20.0 g L-1 glucose, 0.7 g L-1 MnCl2; incubation conditions: initial pH 7.0, temperature 41 °C, 8% inoculation size and 30% working volume). Moreover, the genetic co-expression of α-amylase and protease increased from 0 to 24 h and then decreased after 36 h at the transcriptional level, which coincided with the growth trend of B. velezensis D6. The optimal reaction temperature of α-amylase was 55-60 °C, while that of protease was 35-40 °C. The activities of α-amylase and protease were retained by over 80% after thermal treatment (90 °C, 1 h), which indicated that two enzymes co-produced by B. velezensis D6 demonstrated excellent thermal stability. Moreover, the two enzymes were stable over a wide pH range (pH 4.0-8.0 for α-amylase; pH 4.0-9.0 for protease). Finally, the degrees of hydrolysis of corn, rice, sorghum and soybeans by α-amylase from B. velezensis D6 reached 44.95 ± 2.95%, 57.16 ± 2.75%, 52.53 ± 4.01% and 20.53 ± 2.42%, respectively, suggesting an excellent hydrolysis effect on starchy raw materials. The hydrolysis degrees of mackerel heads and soybeans by protease were 43.93 ± 2.19% and 26.38 ± 1.72%, respectively, which suggested that the protease from B. velezensis D6 preferentially hydrolyzed animal-based protein. CONCLUSION: This is a systematic study on the co-production of α-amylase and protease by B. velezensis D6, which is crucial in widening the understanding of this species co-producing multi-enzymes and in exploring its potential application. © 2024 Society of Chemical Industry.
RESUMO
A simple and efficient base-mediated decarboxylative annulation of ynones with methyl 2-(2-bromophenyl)acetates has been developed. A broad range of benzoxepines were prepared with a broad substrate scope and high regioselectivity in moderate to excellent yields under transition-metal-free conditions. This method proceeds through a tandem [2 + 4] annulation, ring-opening decarboxylative reaction, and the intramolecular nucleophilic aromatic substitution reaction. Additionally, the key intermediates were successfully obtained and characterized unambiguously by single-crystal X-ray crystallography, which could favorably support a decarboxylative annulation mechanism. Furthermore, gram-scale reaction and synthetic applications for the further functionalization are also studied.
RESUMO
A facile and effective tandem reaction of ynones and methyl salicylates was developed to obtain a broad range of 3-acyl chromones in moderate-to-excellent yields. This protocol underwent a Michael addition and cyclization process, which exhibited easily accessible substrates, broad substrate scope, and high regioselectivity under mild and transition-metal-free conditions. Moreover, gram-scale reaction and further chemical transformation of the products were also further studied.
Assuntos
Cromonas , Elementos de Transição , Estereoisomerismo , Ciclização , SalicilatosRESUMO
A facile and efficient base-mediated divergent annulation of methyl 2-(cyanomethyl)benzoates and conjugated ynones has been described. A broad range of 1-naphthols and xanthones were formed in moderate to excellent yields. The notable features of this protocol include readily available precursors, broad substrate scope, complete regioselectivity, and substrate-controlled divergent synthesis. The gram-scale preparation and synthetic transformations of the resulting 1-naphthols and xanthones demonstrate their utility.
Assuntos
Naftóis , Xantonas , Benzoatos , Catálise , Estrutura MolecularRESUMO
Tropomyosin (TM) is an important crustacean (Scylla paramamosain) allergen. This study aimed to assess Maillard-reacted TM (TM-G) induction of allergenic responses with cell and mouse models. We analyzed the difference of sensitization and the ability to induce immune tolerance between TM and TM-G by in vitro and in vivo models, then we compared the relationship between glycation sites of TM-G and epitopes of TM. In the in vitro assay, we discovered that the sensitization of TM-G was lower than TM, and the ability to stimulate mast cell degranulation decreased from 55.07 ± 4.23% to 27.86 ± 3.21%. In the serum of sensitized Balb/c mice, the level of specific IgE produced by TM-G sensitized mice was significantly lower than TM, and the levels of interleukins 4 and interleukins 13 produced by Th2 cells in spleen lymphocytes decreased by 82.35 ± 5.88% and 83.64 ± 9.09%, respectively. In the oral tolerance model, the ratio of Th2/Th1 decreased from 4.05 ± 0.38 to 1.69 ± 0.19. Maillard reaction masked the B cell epitopes of TM and retained some T cell epitopes. Potentially, Maillard reaction products (MRPs) can be used as tolerance inducers for allergen-specific immunotherapy.
Assuntos
Braquiúros , Tropomiosina , Alérgenos , Animais , Reação de Maillard , Camundongos , Alimentos MarinhosRESUMO
In line with the Healthy China strategy, new requirements for medical education have been raised. Medical education against the background of a new model of medicine demands an effective response to its inherent complex elements concerning the rule of law. During the course of the implementation of the new medicine strategy, in face of the widening scope of medical risks, the growing awareness of patient rights, and the conventional logic of medical education, elements concerning the rule of law should be incorporated in medical education in the early stage so as to help medical practitioners develop the appropriate legal literacy and rely on ideas of rules, equality and ethical bottomlines to analyze and solve problems. Thus, medical practitioners would be better equiped to effectively respond to the legal problems they encounter in their medical practice. Legal education is the route of choice in response to the transformation in the mode of medical education and the attempt to solve complicated problems through medicine and the rule of law. Through legal education, the risks of technology embeddedness could be avoided, the relationship between patients and medical practitioners could be regulated in a standardized way, and the medical humanistic environment could be reshaped, thereby improving the quality and level of new medical education.
Assuntos
Educação Médica , China , HumanosRESUMO
To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of â 3) ß-D-galactose (1 â 4) 3,6-anhydro-α-L-galactose (1 â, and â 3) ß-D-galactose (1 â 4) α-L-galactose-6-S (1 â, and â 3) 6-O-methyl-ß-D-galactose (1 â 4) 3,6-anhydro-α-L-galactose (1 â. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.
Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Porphyra/química , Animais , Compostos de Bifenilo , Configuração de Carboidratos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Peso Molecular , Óxido Nítrico/metabolismo , Picratos , Células RAW 264.7RESUMO
A simple and effective tandem reaction of diynones and allylic alcohols was developed to afford functionalized 3-allyl-4-pyrones in moderate to excellent yields. This protocol underwent a Michael additionâClaisen rearrangementâO-cyclization process, which exhibited broad substrate tolerance, high regioselectivity, and atom economy under a metal-free condition. Moreover, functional transformation of the products was also further studied.
Assuntos
Pironas , Catálise , Ciclização , Estrutura Molecular , FosfinasRESUMO
A simple and effective annulation of ynediones and (iso)quinoline N-oxides was developed to afford various functionalized pyrrolo[2,1-a]isoquinolines and pyrrolo[1,2-a]quinolines in moderate to excellent yields. This protocol underwent a tandem [3 + 2] cycloaddition/ring-opening/N-nucleophilic addition, which exhibited high regioselectivity, broad substrate tolerance, and atom economy under catalyst-, additive-free, and air conditions. Moreover, indolizine was also successfully prepared using pyridine N-oxide.
RESUMO
Vestibular compensation is responsible for the spontaneous recovery of postural, locomotor, and oculomotor dysfunctions in patients with peripheral vestibular lesion or posterior circulation stroke. Mechanism investigation of vestibular compensation is of great importance in both facilitating recovery of vestibular function and understanding the postlesion functional plasticity in the adult CNS. Here, we report that postsynaptic histamine H1 receptor contributes greatly to facilitating vestibular compensation. The expression of H1 receptor is restrictedly increased in the ipsilesional rather than contralesional GABAergic projection neurons in the medial vestibular nucleus (MVN), one of the most important centers for vestibular compensation, in unilateral labyrinthectomized male rats. Furthermore, H1 receptor mediates an asymmetric excitation of the commissural GABAergic but not glutamatergic neurons in the ipsilesional MVN, which may help to rebalance bilateral vestibular systems and promote vestibular compensation. Selective blockage of H1 receptor in the MVN significantly retards the recovery of both static and dynamic vestibular symptoms following unilateral labyrinthectomy, and remarkably attenuates the facilitation of betahistine, whose effect has traditionally been attributed to its antagonistic action on the presynaptic H3 receptor, on vestibular compensation. These results reveal a previously unknown role for histamine H1 receptor in vestibular compensation and amelioration of vestibular motor deficits, as well as an involvement of H1 receptor in potential therapeutic effects of betahistine. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery in the CNS, but also a novel potential therapeutic target for vestibular disorders.SIGNIFICANCE STATEMENT Vestibular disorders manifest postural imbalance, nystagmus, and vertigo. Vestibular compensation is critical for facilitating recovery from vestibular disorders, and of great importance in understanding the postlesion functional plasticity in the adult CNS. Here, we show that postsynaptic H1 receptor in the medial vestibular nucleus (MVN) contributes greatly to the recovery of both static and dynamic symptoms following unilateral vestibular lesion. H1 receptor selectively mediates the asymmetric activation of commissural inhibitory system in the ipsilesional MVN and actively promotes vestibular compensation. The findings provide not only a new insight into the postlesion neuronal circuit plasticity and functional recovery of CNS, but also a novel potential therapeutic target for promoting vestibular compensation and ameliorating vestibular disorders.
Assuntos
Receptores Histamínicos H1/efeitos dos fármacos , Vestíbulo do Labirinto/fisiopatologia , Animais , beta-Histina/uso terapêutico , Orelha Interna , Lateralidade Funcional/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H3/uso terapêutico , Locomoção/efeitos dos fármacos , Masculino , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiopatologia , Neurônios/efeitos dos fármacos , Nistagmo Fisiológico/efeitos dos fármacos , Técnicas de Patch-Clamp , Equilíbrio Postural/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Doenças Vestibulares/tratamento farmacológico , Núcleos Vestibulares/citologia , Núcleos Vestibulares/efeitos dos fármacos , Núcleos Vestibulares/fisiopatologia , Ácido gama-AminobutíricoRESUMO
Effective transition-metal-free formal [4+2] benzannulation for the preparation of 1-cyano-3-acylnaphthalenes from 2-(2-alkynylphenyl)acetonitriles and alkynones through sequential C-C bond coupling has been developed. This protocol is characterized by mild conditions, excellent functional group tolerance, complete regioselectivity, and atom economy. The plausible mechanism, gram-scale synthesis, and further transformations of the product were studied.
RESUMO
An effective and facile transition-metal-free method has been developed for the synthesis of ß-ketophosphine oxides from alkynylphosphine oxides with benzaldehyde oxime as a hydroxide surrogate. The current methodology provides simple access to various ß-ketophosphine oxides in moderate to excellent yields with a broad substrate scope.
RESUMO
An effective transition-metal-free strategy was developed for the preparation of chromones from o-bromoaryl ynones and benzaldehyde oxime through sequential C-O bond formation. This cyclization reaction could well tolerate a wide range of functional groups, and the corresponding chromones were given in moderate to excellent yields. Mechanistically, benzaldehyde oxime as a hydroxide source and 1,3-diketone derivatives as reaction intermediates were involved in this transformation.
RESUMO
BACKGROUND: To investigate the effects of levosimendan on right ventricular (RV) function in patients with acute decompensated heart failure (ADHF). METHODS: Patients with ADHF admitted from January 2017 to October 2017 were enrolled in this study. The patients were randomized to receive 24-h intravenous levosimendan or placebo. Echocardiographic examinations were performed and the parameters were compared. Epidemiological data were recorded and compared before and after treatment. Major adverse cardiac events during hospitalization and during 1-month follow-up were compared. RESULTS: The baseline characteristics were comparable. After 24-h infusion of levosimendan and placebo, the left ventricular ejection fraction and S' were significantly increased in the levosimendan group compared with the control group (both p < 0.05). The E value in the levosimendan group significantly decreased (75.38 ± 8.32 vs. 88.21 ± 10.36, p < 0.0001), and E/e' significantly increased in the control group (19.61 ± 6.52 vs. 27.58 ± 8.22, p < 0.0001). The levels of right ventricular fractional area change (24 ± 3 vs. 20 ± 2, p < 0.0001) and tricuspid annular plane systolic excursion (1.56 ± 0.36 vs. 1.38 ± 0.21, p < 0.0001) were significantly higher in the levosimendan group than in the control group. After treatment, the values of systolic pulmonary artery pressure (SPAP) decreased in both groups (both p < 0.05), and the value of SPAP in the levosimendan group was lower than that in the control group (47.22 ± 5.6 vs. 55.85 ± 7.41, p < 0.0001). After 1-month follow-up, there was no significance in readmissions due to recurrent heart failure. CONCLUSIONS: Levosimendan seems to provide more beneficial effects among patients with ADHF to improve RV function, along with a decrease in pulmonary pressure.
RESUMO
An effective phosphine-catalyzed protocol has been established for the syntheses of 1,3-diketones and nitriles from alkynones with oximes as hydroxide surrogates. This method features the use of a phosphine catalyst, compatibility with various functional groups and ambient temperature, which makes this approach very practical. A plausible mechanism was proposed.
RESUMO
BACKGROUND/AIMS: Renal calculi, or kidney stones, are masses made of crystals that affect people of all geographical, cultural, and racial groups. We conduct this study with the aim of comparing the efficacy of various surgical methods in the treatment of renal calculi. METHODS: Controlled clinical trials (CCTs) related to different surgical treatment approaches for renal calculi were included in this study by retrieving them from electronic English databases. The odds ratios (OR), the weighted mean difference (WMD), 95% confidence intervals (95% CI) and surface under the cumulative ranking curves (SUCRA) were evaluated, followed by a cluster analysis. RESULTS: Compared with the extracorporeal shockwave lithotripsy (SWL), minimally invasive percutaneous nephrolithotomy (mini-PCNL), retrograde intrarenal surgery (RIRS), standard percutaneous nephrolithotomy (standard PCNL), ureterorenoscopy (URS) and micro-percutaneous nephrolithotomy (microperc) regimens, the open anatrophic nephrolithotomy (Open AN), URS + RIRS and laparoscopic pyelolithotomy (LP) surgical procedures all presented with a higher stone-free rate in renal calculi. Lower auxiliary procedures were found in the URS + RIRS treatment approach compared with SWL, RIRS, URS and microperc regimens. In addition, the SWL regimen indicated a lower stone-free rate than the mini-PCNL, standard PCNL, Open AN, URS + RIRS and LP regimens. Finally, the RIRS regimen presented with the shortest in-patient stay compared to the mini-PCNL, standard PCNL, Open AN, URS, URS + RIRS and LP regimens. CONCLUSION: This meta-analysis demonstrated that the URS + RIRS surgical procedure has the best stone-free rate and the lowest number of auxiliary procedures. The RIRS and Microperc both have the shortest hospital stay and operative time.
Assuntos
Cálculos Renais/cirurgia , Procedimentos Cirúrgicos Urológicos/normas , Humanos , Tempo de Internação , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.