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1.
Chem Rev ; 123(8): 4510-4601, 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37022360

RESUMO

Lignin, as a precious resource given to mankind by nature with abundant functional aromatic structures, has drawn much attention in the recent decade from academia to industry worldwide, aiming at harvesting aromatic compounds from this abundant and renewable natural polymer resource. How to efficiently depolymerize lignin to easy-to-handle aromatic monomers is the precondition of lignin utilization. Many strategies/methods have been developed to effectively degrade lignin into monomers, such as the traditional methods of pyrolysis, gasification, liquid-phase reforming, solvolysis, chemical oxidation, hydrogenation, reduction, acidolysis, alkaline hydrolysis, alcoholysis, as well as the newly developed redox-neutral process, biocatalysis, and combinatorial strategies. Therefore, there is a strong demand to systemically summarize these developed strategies and methods and reveal the internal transformation principles of the lignin. Focusing on the topic of lignin depolymerization to aromatic chemicals, this review reorganizes and categorizes the strategies/methods according to their mechanisms, orbiting the center of critical intermediates during the lignin linkage transformation, which includes the critical anionic intermediates, cationic intermediates, organometallic intermediates, organic molecular intermediates, aryl cation radical intermediates, and neutral radical intermediates. The corresponding introduction involves the generation and the transformation chemistry of the critical intermediates via the corresponding C-H/O-H/C-C/C-O chemical bond transformations, leading to the cleavage of the C-C/C-O linkage bonds. Accompanying the brief introduction of lignin chemistry and the final concluding remarks and perspectives on lignin depolymerization, this review aims to provide a current research process of lignin depolymerization, which may provide useful suggestions for this vigorous research field.

2.
Chem Soc Rev ; 53(8): 4154-4229, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38470073

RESUMO

Iron-based materials with significant physicochemical properties, including high theoretical capacity, low cost and mechanical and thermal stability, have attracted research attention as electrode materials for alkali metal-ion batteries (AMIBs). However, practical implementation of some iron-based materials is impeded by their poor conductivity, large volume change, and irreversible phase transition during electrochemical reactions. In this review we critically assess advances in the chemical synthesis and structural design, together with modification strategies, of iron-based compounds for AMIBs, to obviate these issues. We assess and categorize structural and compositional regulation and its effects on the working mechanisms and electrochemical performances of AMIBs. We establish insight into their applications and determine practical challenges in their development. We provide perspectives on future directions and likely outcomes. We conclude that for boosted electrochemical performance there is a need for better design of structures and compositions to increase ionic/electronic conductivity and the contact area between active materials and electrolytes and to obviate the large volume change and low conductivity. Findings will be of interest and benefit to researchers and manufacturers for sustainable development of advanced rechargeable ion batteries using iron-based electrode materials.

3.
Protein Expr Purif ; 222: 106531, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38852715

RESUMO

The SARS-CoV-2 main protease (Mpro) plays a crucial role in virus amplification and is an ideal target for antiviral drugs. Currently, authentic Mpro is prepared through two rounds of proteolytic cleavage. In this method, Mpro carries a self-cleavage site at the N-terminus and a protease cleavage site followed by an affinity tag at the C-terminus. This article proposes a novel method for producing authentic Mpro through single digestion. Mpro was constructed by fusing a His tag containing TEV protease cleavage sites at the N-terminus. The expressed recombinant protein was digested by TEV protease, and the generated protein had a decreased molecular weight and significantly increased activity, which was consistent with that of authentic Mpro generated by the previous method. These findings indicated that authentic Mpro was successfully obtained. Moreover, the substrate specificity of Mpro was investigated. Mpro had a strong preference for Phe at position the P2, which suggested that the S2 subsite was an outstanding target for designing inhibitors. This article also provides a reference for the preparation of Mpro for sudden coronavirus infection in the future.

4.
J Environ Manage ; 352: 120039, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38218169

RESUMO

Microplastics (MPs)/nanoplastics (NPs) are widely found in the natural environment, including soil, water and the atmosphere, which are essential for human survival. In the recent years, there has been a growing concern about the potential impact of MPs/NPs on human health. Due to the increasing interest in this research and the limited number of studies related to the health effects of MPs/NPs on humans, it is necessary to conduct a systematic assessment and review of their potentially toxic effects on human organs and tissues. Humans can be exposed to microplastics through ingestion, inhalation and dermal contact, however, ingestion and inhalation are considered as the primary routes. The ingested MPs/NPs mainly consist of plastic particles with a particle size ranging from 0.1 to 1 µm, that distribute across various tissues and organs within the body, which in turn have a certain impact on the nine major systems of the human body, especially the digestive system and respiratory system, which are closely related to the intake pathway of MPs/NPs. The harmful effects caused by MPs/NPs primarily occur through potential toxic mechanisms such as induction of oxidative stress, generation of inflammatory responses, alteration of lipid metabolism or energy metabolism or expression of related functional factors. This review can help people to systematically understand the hazards of MPs/NPs and related toxicity mechanisms from the level of nine biological systems. It allows MPs/NPs pollution to be emphasized, and it is also hoped that research on their toxic effects will be strengthened in the future.


Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Microplásticos/toxicidade , Plásticos , Atmosfera , Metabolismo Energético , Ingestão de Alimentos , Poluentes Químicos da Água/toxicidade
5.
Angew Chem Int Ed Engl ; 63(17): e202400045, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385624

RESUMO

Zinc ion batteries (ZIBs) exhibit significant promise in the next generation of grid-scale energy storage systems owing to their safety, relatively high volumetric energy density, and low production cost. Despite substantial advancements in ZIBs, a comprehensive evaluation of critical parameters impacting their practical energy density (Epractical) and calendar life is lacking. Hence, we suggest using formulation-based study as a scientific tool to accurately calculate the cell-level energy density and predict the cycling life of ZIBs. By combining all key battery parameters, such as the capacity ratio of negative to positive electrode (N/P), into one formula, we assess their impact on Epractical. When all parameters are optimized, we urge to achieve the theoretical capacity for a high Epractical. Furthermore, we propose a formulation that correlates the N/P and Coulombic efficiency of ZIBs for predicting their calendar life. Finally, we offer a comprehensive overview of current advancements in ZIBs, covering cathode and anode, along with practical evaluations. This Minireview outlines specific goals, suggests future research directions, and sketches prospects for designing efficient and high-performing ZIBs. It aims at bridging the gap from academia to industry for grid-scale energy storage.

6.
Angew Chem Int Ed Engl ; 63(14): e202319091, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308095

RESUMO

Aqueous zinc-ion batteries are regarded as promising and efficient energy storage systems owing to remarkable safety and satisfactory capacity. Nevertheless, the instability of zinc metal anodes, characterized by issues such as dendrite growth and parasitic side reactions, poses a significant barrier to widespread applications. Herein, we address this challenge by designing a localized conjugated structure comprising a cyclic polyacrylonitrile polymer (CPANZ), induced by a Zn2+-based Lewis acid (zinc trifluoromethylsulfonate) at a temperature of 120 °C. The CPANZ layer on the Zn anode, enriched with appropriate pyridine nitrogen-rich groups (conjugated cyclic -C=N-), exhibits a notable affinity for Zn2+ with ample deposition sites. This zincophilic skeleton not only serves as a protective layer to guide the deposition of Zn2+ but also functions as proton channel blocker, regulating the proton flux to mitigate the hydrogen evolution. Additionally, the strong adhesion strength of the CPANZ layer guarantees its sustained protection to the Zn metal during long-term cycling. As a result, the modified zinc electrode demonstrates long cycle life and high durability in both half-cell and pouch cells. These findings present a feasible approach to designing high performance aqueous anodes by introducing a localized conjugated layer.

7.
Angew Chem Int Ed Engl ; 63(20): e202402987, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38436516

RESUMO

Zinc-based aqueous batteries (ZABs) are attracting extensive attention due to the low cost, high capacity, and environmental benignity of the zinc anode. However, their application is still hindered by the undesired zinc dendrites. Despite Zn-surface modification being promising in relieving dendrites, a thick separator (i.e. glass fiber, 250-700 µm) is still required to resist the dendrite puncture, which limits volumetric energy density of battery. Here, we pivot from the traditional interphase plus extra separator categories, proposing an all-in-one ligand buffer layer (ca. 20 µm) to effectively modulate the Zn2+ transfer and deposition behaviors proved by in situ electrochemical digital holography. Experimental characterizations and density functional theory simulations further reveal that the catechol groups in the buffer layer can accelerate the Zn2+ reduction reaction (ZRR) through the electron-donating p-π conjugation effect, decreasing the negative charge in the coordination environment. Without extra separators, the elaborated system endows low polarization below 28.2 mV, long lifespan of 4950 h at 5 mA cm-2 in symmetric batteries, and an unprecedented volumetric energy density of 99.2 Wh L-1 based on the whole pouch cells. The concomitantly "separator-free" and "dendrite-free" conjugation effect with an accelerated ZRR process could foster the progression of metallic anodes and benefit energetic aqueous batteries.

8.
J Am Chem Soc ; 145(17): 9434-9440, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37084265

RESUMO

Copper-catalyzed radical-relay reactions provide a versatile strategy for selective C-H functionalization; however, reactions with peroxide-based oxidants often require excess C-H substrate. Here, we report a photochemical strategy to overcome this limitation by using a Cu/2,2'-biquinoline catalyst that supports benzylic C-H esterification with limiting C-H substrate. Mechanistic studies indicate that blue-light irradiation promotes carboxylate-to-copper charge transfer, reducing resting-state CuII to CuI, which activates the peroxide to generate an alkoxyl radical hydrogen-atom-transfer species. This "photochemical redox buffering" introduces a unique strategy to sustain the activity of Cu catalysts in radical-relay reactions.

9.
Protein Expr Purif ; 203: 106208, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36403706

RESUMO

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a vital role in viral replication. To study the function of Mpro and screen inhibitors targeting Mpro, it is necessary to prepare high-purity and high-activity Mpro. In this study, four types of SARS-CoV-2 Mpros containing different termini were prepared, and their activities were determined successfully. The results showed that the activity of wild-type (WT) Mpro was the highest, and the additional residues at the N-terminus but not at the C-terminus had a major effect on the enzyme activity. To explain this, the alignment of structures of different forms of Mpro was determined, and the additional residues at the N-terminus were found to interfere with the formation of the substrate binding pocket. This study confirms the importance of the natural N-terminus to the activity of Mpro and suggests that WT-GPH6 (Mpro with eight additional residues at the C-terminus) can be used as a substitute for authentic Mpro to screen inhibitors. In short, this study provides a reference for the expression and purification of new coronaviruses confronted in the future.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , COVID-19/genética , Cisteína Endopeptidases/química , Inibidores de Proteases/farmacologia , Antivirais/química , Simulação de Acoplamento Molecular
10.
Org Biomol Chem ; 21(17): 3669-3674, 2023 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-37067779

RESUMO

The Cu(OAc)2-catalyzed one-pot three-component cycloaddition of malonates, nitrosoarenes and alkenes is described. A wide range of isoxazolidines could be obtained in moderate to excellent yields via this method. Mechanistic investigations indicated that the key step in this catalytic system is the straightforward formation of nitrone intermediates through the Cu(OAc)2-catalyzed reaction of malonates with nitrosoarenes.

11.
Bioorg Chem ; 134: 106443, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36857932

RESUMO

Lysine-specific demethylase 1 (LSD1/KDM1A) dysregulation is closely associated with the pathological processes of various diseases, especially hematologic malignancies. Significant progresses have been made in the field of LSD1-targeted drug discovery. Nine LSD1 inhibitors including tranylcypromine, ORY-1001, ORY-2001, GSK-2879552, IMG-7289, INCB059872, TAK-418, CC-90011 and SP-2577 have entered clinical stage for disease treatment as either mono- or combinational therapy. This review updates LSD1 inhibitors reported during 2022. Design strategies, structure-activity relationship studies, binding model analysis and modes of action are highlighted. In particular, the unique multiple-copies binding mode of quinazoline derivatives paves new ways for the development of reversible LSD1 inhibitors by blocking the substrate entrance. The design strategy of clinical candidate TAK-418 also provides directions for further optimization of novel irreversible LSD1 inhibitors with low hematological side effects. The influence of the stereochemistry on the potency against LSD1 and its homolog LSD2 is briefly discussed. Finally, the challenges and prospects of LSD1-targeted drug discovery are also given.


Assuntos
Antineoplásicos , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Relação Estrutura-Atividade , Histona Desmetilases
12.
BMC Pulm Med ; 23(1): 340, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697291

RESUMO

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality in the world. However, there are some patients who are not diagnosed early and correctly through routine methods because of inconspicuous or serious symptoms. This study aims to assess the diagnostic role of long non-coding RNA (lncRNA) in COPD. METHODS: We searched literature from electronic databases, after excluding non-COPD literature, the bibliometric analysis was performed, and VOSviewer software was used to represent the data analyzed. Literature evaluating the diagnostic test accuracy of lncRNA for COPD was eligible, and the QUADAS-2 checklist was used to evaluate the quality. The pooled sensitivity (SEN), specificity (SPE), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (sROC) were used to analyze the overall diagnostic performance. Subgroup and meta-regression analyses were performed to explore the heterogeneity, and a funnel plot was assessed for publication bias. Also, lncRNAs related to COPD were identified and explored for their potential biological function. RESULTS: An increased annual growth rate of literature on this subject from 2016 focused on COPD, humans, RNA, and lncRNA. The meta-analysis enrolled 17 literature indicated that the SEN, SPE, and DOR differentiating COPD patients from normal controls (NCs) were 0.86 (95% CI [0.80, 0.90]), 0.78 (95% CI [0.67, 0.86]), and 21.59 (95% CI [11.39, 40.91]), respectively. Meanwhile, lncRNAs had the ability to distinguish acute exacerbations of COPD (AECOPD) patients from COPD; the SEN, SPE, and DOR were 0.75 (95% CI [0.62, 0.85]), 0.81 (95% CI [0.71, 0.89]), and 13.02 (95% CI [7.76, 21.85]), respectively. The area under the sROC were calculated to be greater than 0.8 at least. Subgroup and meta-regression analysis showed that the types of specimens and dysregulated lncRNAs might affect the diagnostic accuracy. The funnel plot showed there was a certain publication bias. 41 lncRNAs related to COPD were identified and mainly located in the nucleus and cytoplasm, associated with proliferation, invasion, and prognosis. These lncRNA-binding proteins were involved in the spliceosome, Rap1 signaling pathway, MAPK signaling pathway, and so on. CONCLUSION: LncRNA suggests potential diagnostic biomarkers and therapeutic targets for COPD patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Bibliometria , Lista de Checagem , Bases de Dados Factuais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/genética
13.
Chin J Physiol ; 66(5): 351-358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929346

RESUMO

Aging, a crucial risk factor for ischemic heart disease, has negative impacts on cardioprotective mechanisms. As such, there is still an unmet requirement to explore potential therapies for improving the outcomes of myocardial ischemia/reperfusion (IR) injury in elderly subjects. Here, we aimed to confirm the cardioprotective function of irisin/Dendrobium nobile Lindl (DNL) combination therapy against myocardial IR injury in aged rats, with a focus on the involvement of pyroptosis and mitophagy. Male aged Wistar rats (22-24 months old, 400-450 g; n = 54) underwent myocardial IR or sham surgery. Before IR operation, rats were pretreated with irisin (0.5 mg/kg, intraperitoneally) and/or DNL (80 mg/kg, orally) for 1 or 4 weeks, respectively, at corresponding groups. Cardiac function, lactate dehydrogenase (LDH) and cardiac-specific isoform of troponin-I (cTn-I) levels, the expression of proteins involved in pyroptosis (nod-like receptor protein-3 (NLRP3), apoptosis-associated speck-like protein, c-caspase-1, and GSDMD-N) and mitophagy (PINK1 and Parkin), and pro-inflammatory cytokines levels were evaluated after 24 h of reperfusion. Irisin/DNL combined therapy significantly restored cardiac function and decreased LDH and cTn-I levels. It also downregulated pyroptosis-related proteins, upregulated PINK1 and Parkin, and decreased pro-inflammatory cytokines secretion. Pretreatment with Mdivi-1, as mitophagy inhibitor, abolished the cardioprotective action of dual therapy. This study revealed the cardioprotective effects of irisin/DNL combination therapy against IR-induced myocardial injury in aged rats, and also showed that the mechanism might be associated with suppression of NLRP3-related pyroptosis through enhancing the activity of the PINK1/Parkin mitophagy. This combination therapy is worthy of further detailed studies due to its potential to alleviate myocardial IR injury upon aging.


Assuntos
Dendrobium , Infarto do Miocárdio , Preparações de Plantas , Traumatismo por Reperfusão , Animais , Masculino , Ratos , Envelhecimento , Citocinas , Dendrobium/química , Fibronectinas , Mitofagia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas NLR , Proteínas Quinases , Piroptose , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Preparações de Plantas/farmacologia
14.
Chem Soc Rev ; 51(5): 1608-1628, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35188154

RESUMO

Due to the depletion of fossil sources, it is imperative to develop a sustainable and carbon-neutral biorefinery for supporting the fuel and chemical supply in modern society. Lignin, the only renewable aromatic source, is still an underutilized component in lignocellulose. Very recently, it has been found that hydrogenolysis is a promising technology for lignin valorization. However, high-pressure H2 is necessary during lignin hydrogenolysis, resulting in safety problems. Furthermore, H2 is mainly produced from steam reforming of fossil sources in industry, which makes the conversion of renewable lignin unsustainable and costly. Plentiful aliphatic hydroxyl and methoxy groups exist in native lignin and offer a renewable alternative to H2, and can be hydrogen sources for the depolymerization and upgradation of lignin via the intramolecular catalytic transfer hydrogenation. The hydrogen source in situ generated from lignin is a type of green hydrogen, decreasing the carbon footprint. The purpose of this review is to provide a summary and perspective of lignin valorization via self-transfer hydrogenolysis, mainly focusing on a comprehensive understanding of the mechanism of catalytic self-transfer hydrogenolysis at the molecular level and developing highly effective catalytic systems. Moreover, some opportunities and challenges within this attractive field are given to discuss future research directions.


Assuntos
Hidrogênio , Lignina , Carbono , Catálise , Hidrogênio/química , Lignina/química
15.
J Org Chem ; 87(22): 15564-15570, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36331982

RESUMO

A novel metal-free annulation of ynamides with 2H-azirines catalyzed by BF3·Et2O is described, leading to the construction of polysubstituted 2-aminopyrroles in a facile, flexible, and atom-economical way. This synthetic strategy proceeds with efficiency, broad substrate scope, and short reaction time under mild reaction conditions. Furthermore, the obtained annulation products could be modified to generate diverse 2-iminopyrrole frameworks in high yields.

16.
J Sep Sci ; 45(15): 2855-2864, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35671063

RESUMO

Coptis chinensis inflorescence is a by-product of Coptis chinensis Franch and riches in alkaloids. We screened the bioactive compounds in the by-product through an immobilized peroxisome proliferator-activated receptor gamma. The receptor was covalently immobilized on the macroporous silica gel through amino groups to generate the affinity stationary phase and was applied for screening. Berberine, palmatine, and jatrorrhizine were identified as the retained components of the herb on the affinity column. We evaluated the binding of the three bioactive compounds with the receptor by nonlinear chromatography and molecular docking. The affinities of the compounds to the receptor were (1.42 ± 0.10) ×108 /M, (4.88 ± 0.38) ×107 /M, and (1.65 ± 0.13) ×107 /M for berberine, palmatine, and jatrorrhizine, with dissociation rate constants of (17.70 ± 0.03) ×10-3 /S, (5.18 ± 0.25) ×10-2 /S, and (15.7 ± 0.05) ×10-2 /S, respectively. Cys285, Arg288, Ile326, Leu330, and His449 in the agonist binding pocket of the receptor participated in the formation of bioactive compound-receptor conjugates. These data indicated that the immobilized receptor is a reliable alternative for screening the bioactive compounds. In addition, Coptis chinensis inflorescence has the potential to be a source for drug discovery.


Assuntos
Berberina , Coptis , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Coptis/química , Coptis chinensis , Medicamentos de Ervas Chinesas/análise , Inflorescência/química , Simulação de Acoplamento Molecular , PPAR gama
17.
Phytother Res ; 36(10): 3911-3923, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35794782

RESUMO

Fibrosis is a pathological result of a dysfunctional repair response to tissue injury and occurs in several organs, including the lungs. Bryodulcosigenin (BDG) is a cucurbitane-type triterpene isolated from Siratia grosvenori and has clear-cut anti-inflammatory effects, yet its benefit of pulmonary fibrosis (PF) remains unclear. In this study, we investigated the protective effects of BDG (10 mg/kg/day, for 14 days) against TGF-ß1-stimulated mouse alveolar epithelial MLE-12 cells and bleomycin (BLM)-induced PF mice. In vitro experiments showed that BDG could inhibit epithelial-mesenchymal transition (EMT) and oxidative stress. In vivo experiments indicated that BDG could ameliorate BLM-induced PF in mice as evidenced by characteristic structural changes in histopathology, increased collagen deposition and reduced survival and weight of mice. The abnormal increased expressions of TGF-ß1, p-Smad2/3, α-SMA, COL-I, and NOX4 and decreased expressions for Sirt1 and p-AMPK were improved in BDG treatment. But these beneficial effects could be eliminated by co-treatment with Compound C (CC, a selective AMPK inhibitor). Molecular docking technology also revealed the potential of BDG to activate AMPK. In summary, AMPK activation modulated by BDG not only ameliorated TGF-ß1/Smad2/3 signaling pathways but also partially mediated the suppression effects on EMT and oxidative stress, thus mediating the anti-fibrotic effects.


Assuntos
Fibrose Pulmonar , Triterpenos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Bleomicina/efeitos adversos , Colágeno/metabolismo , Transição Epitelial-Mesenquimal , Camundongos , Simulação de Acoplamento Molecular , Estresse Oxidativo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Sirtuína 1/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Triterpenos/farmacologia
18.
Chembiochem ; 22(1): 124-128, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32789939

RESUMO

Optically active ß-amino alcohols are very useful chiral intermediates frequently used in the preparation of pharmaceutically active substances. Here, a novel cyclohexylamine oxidase (ArCHAO) was identified from the genome sequence of Arthrobacter sp. TYUT010-15 with the R-stereoselective deamination activity of ß-amino alcohol. ArCHAO was cloned and successfully expressed in E. coli BL21, purified and characterized. Substrate-specific analysis revealed that ArCHAO has high activity (4.15 to 6.34 U mg-1 protein) and excellent enantioselectivity toward the tested ß-amino alcohols. By using purified ArCHAO, a wide range of racemic ß-amino alcohols were resolved, (S)-ß-amino alcohols were obtained in >99 % ee. Deracemization of racemic ß-amino alcohols was conducted by ArCHAO-catalyzed enantioselective deamination and transaminase-catalyzed enantioselective amination to afford (S)-ß-amino alcohols in excellent conversion (78-94 %) and enantiomeric excess (>99 %). Preparative-scale deracemization was carried out with 50 mM (6.859 g L-1 ) racemic 2-amino-2-phenylethanol, (S)-2-amino-2-phenylethanol was obtained in 75 % isolated yield and >99 % ee.


Assuntos
Amino Álcoois/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Transaminases/metabolismo , Amino Álcoois/química , Arthrobacter/enzimologia , Biocatálise , Estrutura Molecular , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Estereoisomerismo , Transaminases/genética
19.
Acc Chem Res ; 53(2): 470-484, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-31999099

RESUMO

In recent decades, research on lignin depolymerization and its downstream product transformation has drawn an enormous amount of attention from academia to industry worldwide, aiming at harvesting aromatic compounds from this abundant and renewable biomass resource. Although the lignin conversion can be traced back to the 1930s and various noncatalytic and catalytic methods have been explored to depolymerize lignin via direct lignin conversion research or lignin models conversion studies, the complexity of the lignin structure, various linkages, the high stability of lignin bonds, and the diverse fragments condensation process make lignin depolymerization to monomers a highly challenging task. For the potential practical utilization of lignin, compared with lignin conversion to liquid fuel with extra H2 consumption, maintaining the aromatic structure and preparing high-value aromatic chemicals from renewable lignin is more profitable. Therefore, lignin depolymerization to easy-to-handle aromatic monomers with acceptable conversion and selectivity is of great importance. In this article, we present our recent studies on lignin's catalytic conversion to aromatic chemicals. First, we introduce our research on protolignin depolymerization via a fragmentation-hydrogenolysis process in alcohol solvents. Then, focusing on the catalytic cleavage of lignin C-C and C-O bonds, we shed light on a recapitulative adjacent functional group modification (AFGM) strategy for the conversion of lignin models. AFGM strategy begins with the adjacent functional group modification of the target C-C or C-O bond to directly decrease the bond dissociation enthalpy (BDE) of targeted bonds or generate new substrate sites to introduce the cleavage reagent for further conversion. Subsequently, on the basis of these two concepts from AFGM, we summarize our strategies on lignin depolymerization, which highlight the effects of lignin structure, catalyst character, and reaction conditions on the efficiency of strategies. In short, the key point for lignin depolymerization to aromatics is promoting the lignin conversion and restraining the condensation. Compared with the complex research on direct lignin conversion, this bottom-up research approach, beginning with lignin model research, can make the conversion mechanism study clear and provide potential methods for the protolignin/technical lignin conversion. In addition, one of our perspectives for lignin utilization is that the products from lignin conversion can be used as monomers for artificial polymerization, such as the simple phenol (PhOH) and other potential acid compounds, or that lignin derivative molecules can be used to synthesize high-value synthetic building blocks.


Assuntos
Hidrocarbonetos Aromáticos/química , Lignina/química , Álcoois/química , Biomassa , Catálise , Hidrólise , Estrutura Molecular , Oxirredução , Polimerização , Solventes/química
20.
Ecotoxicol Environ Saf ; 228: 112955, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34781127

RESUMO

Epidemiological and toxicological studies have demonstrated that exposure to fine particulate matter (PM2.5) during pregnancy is harmful to the tissues of the offspring. However, the mechanism by which PM2.5 exposure causes lung damage in the offspring or potential dietary therapy for this condition remains unclear. Mogrosides (MGs) are derived from the traditional plant Siraitia grosvenorii and are used medicinally, where they can moisten the lungs and relieve coughing. In this study, pregnant rats were exposed to PM2.5 by intratracheal instillation and treated with MGs by gavage to model the effect of PM2.5 in the offspring and the interventional effect of MGs on lung tissue. We then used transcriptomics, metabolomics, and RT-qPCR as tools to look for metabolite and genetic changes in the offspring. We found that when compared to the control group, the mRNA levels of the inflammatory mediator Pla2g2d and the metabolites lysophosphatidylcholines (LysoPCs) and arachidonic acid (AA) were up-regulated in the lung tissues of PM2.5 group. In contrast, these inflammatory changes were restored after treatment with MGs during pregnancy. In addition, the levels of AA, LPC 15:0 and LPC 18:0 were elevated in the PM2.5 group compared with control group. This increase was inhibited by co-administration of MGs. The change of PGA1 was adverse. In conclusion, even a relatively low exposure to PM2.5 in rats during pregnancy produces inflammation in the lungs of the male offspring, and an intervention with MGs could significantly alleviate this effect. Furthermore, Pla2g2d may represent a potential target for MGs resulting in the improvement of PM2.5-induced lung injury.

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