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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124357, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38692110

RESUMO

This study described the preparation of an azide covalent organic framework-embedded molecularly imprinted polymers (COFs(azide)@MIPs) platform for urea adsorption and indirect ethyl carbamate (EC) removal from Chinese yellow rice wine (Huangjiu). By modifying the pore surface of COFs using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, COFs(azide) with a high fluorescence quantum yield and particular recognition ability were inventively produced. In order to selectively trap urea, the COFs(azide) were encased in an imprinted shell layer via imprinting technology. With a detection limit (LOD) of 0.016 µg L-1 (R2 = 0.9874), the COFs(azides)@MIPs demonstrated a good linear relationship with urea in the linear range of 0-5 µg L-1. Using real Huangjiu samples, the spiking recovery trials showed the viability of this sensing platform with recoveries ranging from 88.44 % to 109.26 % and an RSD of less than 3.40 %. The Huangjiu processing model system achieved 38.93 % EC reduction by COFs(azides)@MIPs. This research will open up new avenues for the treatment of health problems associated with fermented alcoholic beverages, particularly Huangjiu, while also capturing and removing hazards coming from food.


Assuntos
Polímeros Molecularmente Impressos , Ureia , Uretana , Vinho , Uretana/análise , Uretana/química , Polímeros Molecularmente Impressos/química , Ureia/análise , Ureia/química , Vinho/análise , Espectrometria de Fluorescência/métodos , Azidas/química , Limite de Detecção , Adsorção , Estruturas Metalorgânicas/química , Impressão Molecular/métodos
2.
Water Res ; 256: 121638, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691899

RESUMO

In this study, we investigated the recovery of nitrogen (N) and phosphorus (P) from fresh source-separated urine with a novel electrochemical cell equipped with a magnesium (Mg) anode and carbon-based gas-diffusion cathode. Recovery of P, which exists primarily as phosphate (PO43-) in urine, was achieved through pH-driven precipitation. Maximizing N recovery requires simultaneous approaches to address urea and ammonia (NH3). NH3 recovery was possible through precipitation in struvite with soluble Mg supplied by the anode. Urea was stabilized with electrochemically synthesized hydrogen peroxide (H2O2) from the cathode. H2O2 concentrations and resulting urine pH were directly proportional to the applied current density. Concomitant NH3 and PO43- precipitation as struvite and urea stabilization via H2O2 electrosynthesis was possible at lower current densities, resulting in urine pH under 9.2. Higher current densities resulted in urine pH over 9.2, yielding higher H2O2 concentrations and more consistent stabilization of urea at the expense of NH3 recovery as struvite; PO43- precipitation still occurred but in the form of calcium phosphate and magnesium phosphate solids.


Assuntos
Eletrodos , Peróxido de Hidrogênio , Magnésio , Fósforo , Ureia , Ureia/química , Fósforo/química , Magnésio/química , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Urina/química , Fosfatos/química , Estruvita/química , Amônia/química , Compostos de Magnésio/química , Nitrogênio/química , Humanos
3.
J Am Chem Soc ; 146(19): 12919-12924, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38691627

RESUMO

RNA is a key biochemical marker, yet its chemical instability and complex secondary structure hamper its integration into DNA nanotechnology-based sensing platforms. Relying on the denaturation of the native RNA structure using urea, we show that restructured DNA/RNA hybrids can readily be prepared at room temperature. Using solid-state nanopore sensing, we demonstrate that the structures of our DNA/RNA hybrids conform to the design at the single-molecule level. Employing this chemical annealing procedure, we mitigate RNA self-cleavage, enabling the direct detection of restructured RNA molecules for biosensing applications.


Assuntos
DNA , Nanoporos , RNA , RNA/química , RNA/análise , DNA/química , Técnicas Biossensoriais/métodos , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , Nanotecnologia/métodos , Ureia/química
4.
Bioorg Chem ; 147: 107403, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38691909

RESUMO

A novel series of pyrazole derivatives with urea/thiourea scaffolds 16a-l as hybrid sorafenib/erlotinib/celecoxib analogs was designed, synthesized and tested for its VEGFR-2, EGFRWT, EGFRT790M tyrosine kinases and COX-2, pro-inflammatory cytokines TNF-α and IL-6 inhibitory activities. All the tested compounds showed excellent COX-2 selectivity index in range of 18.04-47.87 compared to celecoxib (S.I. = 26.17) and TNF-α and IL-6 inhibitory activities (IC50 = 5.0-7.50, 6.23-8.93 respectively, compared to celecoxib IC50 = 8.40 and 8.50, respectively). Screening was carried out against 60 human cancer cell lines by National Cancer Institute (NCI), compounds 16a, 16c, 16d and 16 g were the most potent inhibitors with GI% ranges of 100 %, 99.63-87.02 %, 98.98-43.10 % and 98.68-23.62 % respectively, and with GI50 values of 1.76-15.50 µM, 1.60-5.38 µM, 1.68-7.39 µM and 1.81-11.0 µM respectively, in addition, of showing good safety profile against normal cell line (F180). Moreover, compounds 16a, 16c, 16d and 16 g had cell cycle arrest at G2/M phase with induced necrotic percentage compared to sorafenib of 2.06 %, 2.47 %, 1.57 %, 0.88 % and 1.83 % respectively. Amusingly, compounds 16a, 16c, 16d and 16 g inhibited VEGFR-2 with IC50 of 25 nM, 52 nM, 324 nM and 110 nM respectively, compared to sorafenib (IC50 = 85 nM), and had excellent EGFRWT and EGFRT790M kinase inhibitory activities (IC50 = 94 nM, 128 nM, 160 nM, 297 nM), (10 nM, 25 nM, 36 nM and 48 nM) respectively, compared to both erlotinib and osimertinib (IC50 = 114 nM, 56 nM) and (70 nM, 37 nM) respectively and showed (EGFRwt/EGFRT790M S.I.) of (range: 4.44-9.40) compared to erlotinib (2.03) and osmertinib (1.89).


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Inibidores de Proteínas Quinases , Pirazóis , Tioureia , Ureia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Humanos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Tioureia/farmacologia , Tioureia/química , Tioureia/síntese química , Estrutura Molecular , Ureia/farmacologia , Ureia/química , Ureia/análogos & derivados , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/síntese química , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Descoberta de Drogas , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química
5.
Int J Biol Macromol ; 268(Pt 1): 131741, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38649083

RESUMO

Glycogen, a complex branched glucose polymer, is responsible for sugar storage in blood glucose homeostasis. It comprises small ß particles bound together into composite α particles. In diabetic livers, α particles are fragile, breaking apart into smaller particles in dimethyl sulfoxide, DMSO; they are however stable in glycogen from healthy animals. We postulate that the bond between ß particles in α particles involves hydrogen bonding. Liver-glycogen fragility in normal and db/db mice (an animal model for diabetes) is compared using various hydrogen-bond breakers (DMSO, guanidine and urea) at different temperatures. The results showed different degrees of α-particle disruption. Disrupted glycogen showed changes in the mid-infra-red spectrum that are related to hydrogen bonds. While glycogen α-particles are only fragile under harsh, non-physiological conditions, these results nevertheless imply that the bonding between ß particles in α particles is different in diabetic livers compared to healthy, and is probably associated with hydrogen bonding.


Assuntos
Ligação de Hidrogênio , Animais , Camundongos , Dimetil Sulfóxido/química , Glicogênio Hepático/metabolismo , Ureia/química , Guanidina/química , Guanidina/farmacologia , Fígado/metabolismo , Masculino
6.
Biotechnol J ; 19(4): e2300466, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581094

RESUMO

The bacterium Sporosarcina pasteurii is the most commonly used microorganism for Microbial Induced Calcite Precipitation (MICP) due to its high urease activity. To date, no proper fed-batch cultivation protocol for S. pasteurii has been published, even though this cultivation method has a high potential for reducing costs of producing microbial ureolytic biomass. This study focusses on fed-batch cultivation of S. pasteurii DSM33. The study distinguishes between limited fed-batch cultivation and extended batch cultivation. Simply feeding glucose to a S. pasteurii culture does not seem beneficial. However, it was exploited that S. pasteurii is auxotrophic for two vitamins and amino acids. Limited fed-batch cultivation was accomplished by feeding the necessary vitamins or amino acids to a culture lacking them. Feeding nicotinic acid to a nicotinic acid deprived culture resulted in a 24% increase of the specific urease activity compared to a fed culture without nicotinic acid limitation. Also, extended batch cultivation was explored. Feeding a mixture of glucose and yeast extract results in OD600 of ≈70 at the end of cultivation, which is the highest value published in literature so far. These results have the potential to make MICP applications economically viable.


Assuntos
Carbonato de Cálcio , Ácidos Nicotínicos , Sporosarcina , Carbonato de Cálcio/química , Urease/metabolismo , Biomassa , Ureia/química , Ureia/metabolismo , Vitaminas , Aminoácidos , Glucose
7.
Molecules ; 29(8)2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38675519

RESUMO

The massive amount of water-soluble urea used leads to nutrient loss and environmental pollution in both water and soil. The aim of this study was to develop a novel lignin-based slow-release envelope material that has essential nitrogen and sulfur elements for plants. After the amination reaction with a hydrolysate of yak hair keratin, the coating formulation was obtained by adding different loadings (2, 5, 8, 14 wt%) of aminated lignin (AL) to 5% polyvinyl alcohol (PVA) solution. These formulations were cast into films and characterized for their structure, thermal stability, and mechanical and physicochemical properties. The results showed that the PVA-AL (8%) formulation had good physical and chemical properties in terms of water absorption and mechanical properties, and it showed good degradation in soil with 51% weight loss after 45 days. It is suitable for use as a coating material for fertilizers. Through high-pressure spraying technology, enveloped urea particles with a PVA-AL (8%) solution were obtained, which showed good morphology and slow-release performance. Compared with urea, the highest urea release was only 96.4% after 30 days, conforming to Higuchi model, Ritger-Peppas model, and second-order dynamic model. The continuous nitrogen supply of PVA-AL coated urea to Brassica napus was verified by potting experiments. Therefore, the lignin-based composite can be used as a coating material to produce a new slow-release nitrogen fertilizer for sustainable crop production.


Assuntos
Lignina , Álcool de Polivinil , Ureia , Lignina/química , Álcool de Polivinil/química , Ureia/química , Preparações de Ação Retardada/química , Fertilizantes , Polímeros/química
8.
Int J Biol Macromol ; 266(Pt 2): 131230, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574909

RESUMO

Due to the biodegradable and biocompatible nature of chitin and chitosan, they are extensively used in the synthesis of hydrogels for various applications. In this work, deacetylation of chitin is carried out with alkaline poly(dimethyldiallylammonium-hydroxide) that gave a higher amount of water-soluble chitin (with 84 % of the degree of deacetylation = chitosan0.84) compared to deacetylation using NaOH. The water-soluble chitosan0.84 is used as intercalating chains for the preparation of acrylic acid and vinylimidazole-based hydrogels. The quaternization of imidazole groups is done with 1,ω-dibromoalkanes, which sets off the crosslinking in the above polymer network. A set of three chitosan0.84 intercalated hydrogels, namely Cs-C4-hydrogel, Cs-C5-hydrogel, and Cs-C10-hydrogel are prepared bearing butyl, pentyl, and decyl chains as respective crosslinkers. The swell ratios of these intercalated hydrogels are compared with those of non-intercalated hydrogels (C4-hydrogel, C5-hydrogel, and C10-hydrogel). Chitosan0.84 intercalated Cs-C10-hydrogel has excellent swelling properties (2330 % swelling ratio) among six synthesized hydrogels. SEM analysis reveals that decyl crosslinker-bearing hydrogels are highly porous. The multi-functionality of Cs-C10-hydrogel and C10-hydrogel is explored towards -the controlled release of paracetamol/urea, and methyleneblue dye absorption. These studies disclose that chitosan0.84 intercalated hydrogels are showing superior-swelling behavior, high paracetamol/urea loading capacities and better dye entrapment than their non-intercalated counterparts.


Assuntos
Acetaminofen , Quitina , Preparações de Ação Retardada , Hidrogéis , Líquidos Iônicos , Ureia , Hidrogéis/química , Hidrogéis/síntese química , Líquidos Iônicos/química , Quitina/química , Acetaminofen/química , Ureia/química , Liberação Controlada de Fármacos , Acetilação , Quitosana/química , Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Polímeros/química , Polímeros/síntese química
9.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124332, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38676982

RESUMO

Studies on the interactions between ligands and proteins provide insights into how a possible medication alters the structures and activities of the target or carrier proteins. The natural flavonoid aglycone Chrysin (CHR) has demonstrated anti-inflammatory, antioxidant, antiapoptotic, neuroprotective, and antineoplastic effects, both in vitro and in vivo. In this work, we investigated the impact of CHR binding on the as-yet-unexplored conformation, dynamics, and unfolding mechanism of human serum albumin (HSA). We determined CHR binding to HSA domain-II with the association constant (Ka) of 2.70 ± 0.21 × 105 M-1. The urea-induced sequential unfolding mechanism of HSA was used to elucidate the debatable binding location of CHR. CHR binding induced both secondary and tertiary structural alterations in the protein as studied by far-UV circular dichroism and intrinsic fluorescence spectroscopy. Red edge excitation shift (REES) indicated a decrease in conformational dynamics of the protein on the complex formation. This suggested an ordered compact and spatial arrangement of the CHR-boundmolecule. The binding of CHR was found to significantly modulate the urea-induced unfolding pathway of HSA. Urea-induced unfolding pathway of HSA became a two-state process (N-U) from a three-state process (N-I-U). The interaction of CHR is found to increase the thermal stability of the protein by ∼4 °C. This study focuses on the fundamental sciences and demonstrates how prospective medication compounds can alter the dynamics and stability of protein structure.


Assuntos
Flavonoides , Ligação Proteica , Desdobramento de Proteína , Albumina Sérica Humana , Humanos , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/metabolismo , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Desdobramento de Proteína/efeitos dos fármacos , Ureia/farmacologia , Ureia/química , Dicroísmo Circular , Espectrometria de Fluorescência , Conformação Proteica
10.
J Med Chem ; 67(9): 7176-7196, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38679872

RESUMO

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, a series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, with the aim of pursuing a PRDX1-specific inhibitor. Among them, derivative 15 displayed potent anti-PRDX1 activity (IC50 = 0.35 µM) and antiproliferative potency against colon cancer cells. It covalently bound to Cys-173 of PRDX1 (KD = 0.37 µM), which was secured by the cocrystal structure of PRDX1 with an analogue of 15 while exhibiting weak inhibitory effects on PRDX2-PRDX6 (IC50 > 50 µM), indicating excellent PRDX1 selectivity. Treatment with 15 dose-dependently decreased the mitochondria membrane potential of SW620 cells, probably due to ROS induced by PRDX1 inhibition, leading to cell apoptosis. In colorectal cancer cell xenograft model, it displayed potent antitumor efficacy with superior safety to celastrol. Collectively, 15 represents a promising PRDX1 selective inhibitor for the development of anticolorectal cancer agents.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Triterpenos Pentacíclicos , Peroxirredoxinas , Ureia , Humanos , Peroxirredoxinas/antagonistas & inibidores , Peroxirredoxinas/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ureia/análogos & derivados , Ureia/farmacologia , Ureia/química , Linhagem Celular Tumoral , Camundongos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos Nus , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/síntese química , Camundongos Endogâmicos BALB C , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/síntese química , Espécies Reativas de Oxigênio/metabolismo , Descoberta de Drogas , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Ensaios de Seleção de Medicamentos Antitumorais
11.
J Am Chem Soc ; 146(17): 11592-11598, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38630123

RESUMO

Cocrystal screening and single-crystal growth remain the primary obstacles in the development of pharmaceutical cocrystals. Here, we present a new approach for cocrystal screening, microspacing in-air sublimation (MAS), to obtain new cocrystals and grow high-quality single crystals of cocrystals within tens of minutes. The method possesses the advantages of strong designable ability of devices, user-friendly control, and compatibility with materials, especially for the thermolabile molecules. A novel drug-drug cocrystal of favipiravir (FPV) with salicylamide (SAA) was first discovered by this method, which shows improved physiochemical properties. Furthermore, this method proved effective in cultivating single crystals of FPV-isonicotinamide (FPV-INIA), FPV-urea, FPV-nicotinamide (FPV-NIA), and FPV-tromethamine (FPV-Tro) cocrystals, and the structures of these cocrystals were determined for the first time. By adjusting the growth temperature and growth distance precisely, we also achieved single crystals of 10 different paracetamol (PCA) cocrystals and piracetam (PIR) cocrystals, which underscores the versatility and efficiency of this method in pharmaceutical cocrystal screening.


Assuntos
Amidas , Cristalização , Niacinamida , Pirazinas , Niacinamida/química , Pirazinas/química , Amidas/química , Salicilamidas/química , Ureia/química , Modelos Moleculares , Cristalografia por Raios X
12.
Biomacromolecules ; 25(5): 2823-2837, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38602228

RESUMO

Self-assembled nanostructures such as those formed by peptide amphiphiles (PAs) are of great interest in biological and pharmacological applications. Herein, a simple and widely applicable chemical modification, a urea motif, was included in the PA's molecular structure to stabilize the nanostructures by virtue of intermolecular hydrogen bonds. Since the amino acid residue nearest to the lipid tail is the most relevant for stability, we decided to include the urea modification at that position. We prepared four groups of molecules (13 PAs in all), with varying levels of intermolecular cohesion, using amino acids with distinct ß-sheet promoting potential and/or containing hydrophobic tails of distinct lengths. Each subset contained one urea-modified PA and nonmodified PAs, all with the same peptide sequence. The varied responses of these PAs to variations in pH, temperature, counterions, and biologically related proteins were examined using microscopic, X-ray, spectrometric techniques, and molecular simulations. We found that the urea group contributes to the stabilization of the morphology and internal arrangement of the assemblies against environmental stimuli for all peptide sequences. In addition, microbiological and biological studies were performed with the cationic PAs. These assays reveal that the addition of urea linkages affects the PA-cell membrane interaction, showing the potential to increase the selectivity toward bacteria. Our data indicate that the urea motif can be used to tune the stability of a wide range of PA nanostructures, allowing flexibility on the biomaterial's design and opening a myriad of options for clinical therapies.


Assuntos
Ligação de Hidrogênio , Ureia , Ureia/química , Interações Hidrofóbicas e Hidrofílicas , Peptídeos/química , Peptídeos/farmacologia , Nanoestruturas/química , Tensoativos/química
13.
Waste Manag ; 182: 259-270, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38677143

RESUMO

Phosphogypsum (PG) presents considerable potential for agricultural applications as a secondary primary resource. However, it currently lacks environmentally friendly, economically viable, efficient, and sustainable reuse protocols. This study firstly developed a PG-based mineral slow-release fertilizer (MSRFs) by internalization and fixation of urea within the PG lattice via facet-engineering strategy. The molecular dynamics simulations demonstrated that the binding energy of urea to the (041) facet of PG surpassed that of the (021) and (020) facets, with urea's desorption energy on the (041) facet notably higher than on the (021) and (020) facets. Guided by these calculations, we selectively exposed the (041) dominant facet of PG, and then achieving complete urea fixation within the PG lattice to form urea-PG (UPG). UPG exhibited a remarkable 48-fold extension in N release longevity in solution and a 45.77% increase in N use efficiency by plants compared to conventional urea. The facet-engineering of PG enhances the internalization and fixation efficiency of urea for slow N delivery, thereby promoting nutrient uptake for plant growth. Furthermore, we elucidated the intricate interplay between urea and PG at the molecular level, revealing the involvement of hydrogen and ionic bonding. This specific bonding structure imparts exceptional thermal stability and water resistance to the urea within UPG under environmental conditions. This study has the potential to provide insights into the high-value utilization of PG and present innovative ideas for designing efficient MSRFs.


Assuntos
Sulfato de Cálcio , Fertilizantes , Fósforo , Sulfato de Cálcio/química , Fósforo/química , Ureia/química , Minerais/química , Nitrogênio/química , Simulação de Dinâmica Molecular , Agricultura/métodos , Nutrientes
14.
Int J Biol Macromol ; 267(Pt 2): 131592, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38621571

RESUMO

Nanocellulose is a kind of renewable natural polymer material with high specific surface area, high crystallinity, and strong mechanical properties. RC nanofibers (RCNFs) have attracted an increasing attention in various applications due to their high aspect ratio and good flexibility. Herein, a novel and facile strategy for RCNFs preparation with high-speed shear induced in urea solution through "bottom-up" approach was proposed in this work. Results indicated that the average diameter and yield of RCNF was approach to 136.67 nm and 53.3 %, respectively. Meanwhile, due to the regular orientation RC chains and arrangement micro-morphology, RCNFs exhibited high crystallinity, strong mechanical properties, stable thermal degradation performance, and excellent UV resistance. In this study, a novel regeneration process with high-speed shear induced was developed to produce RCNFs with excellent properties. This study paved a strategy for future low-energy production of nanofibers and high value-added conversion applications of agricultural waste.


Assuntos
Celulose , Nanofibras , Ureia , Zea mays , Nanofibras/química , Celulose/química , Zea mays/química , Ureia/química , Soluções
15.
J Hazard Mater ; 471: 134334, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38642498

RESUMO

The spectral database-based mass spectrometry (MS) matching strategy is versatile for structural annotating in ingredient fluctuation profiling mediated by external interferences. However, the systematic variability of MS pool attributable to aliasing peaks and inadequacy of present spectral database resulted in a substantial metabolic feature depletion. An amended procedure termed multiple-charges overlap peaks extraction algorithm (MCOP) was proposed involving identifying collision-trigged dissociation precursor ions through iteratively matching mass features of fragmentations to expand the spectral reference library. We showcased the versatility and utility of established strategy in an investigation centered on the stimulation of milk mediated by diphenylolpropane (BPA). MCOP enabled efficient unknown annotations at metabolite-lipid-protein level, which elevated the accuracy of substance annotation to 85.3% after manual validation. Arginase and α-amylase (|r| > 0.75, p < 0.05) were first identified as the crucial issues via graph neural network-based virtual screening in the abnormal metabolism of urea triggered by BPA, resulting in the accumulation of arginine (original: 1.7 µg kg-1 1.7 times) and maltodextrin (original: 6.9 µg kg-1 2.9 times) and thus, exciting the potential dietary risks. Conclusively, MCOP demonstrated generalisation and scalability and substantially advanced the discovery of unknown metabolites for complex matrix samples, thus deciphering dark matter in multi-omics.


Assuntos
Leite , Leite/química , Animais , Algoritmos , alfa-Amilases/metabolismo , Redes Neurais de Computação , Espectrometria de Massas , Ureia/química , Arginina/química , Contaminação de Alimentos/análise
16.
ACS Nano ; 18(18): 11828-11836, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38659192

RESUMO

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.


Assuntos
Microcystis , Nitrogênio , Microcystis/efeitos dos fármacos , Microcystis/metabolismo , Microcystis/crescimento & desenvolvimento , Nitrogênio/química , Nitrogênio/metabolismo , Microcistinas/metabolismo , Poliestirenos/química , Tamanho da Partícula , Microplásticos/metabolismo , Nanopartículas/química , Nitratos/metabolismo , Nitratos/química , Ureia/metabolismo , Ureia/química , Ureia/farmacologia
17.
ACS Appl Bio Mater ; 7(5): 3041-3049, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38661721

RESUMO

Drug-coated balloon (DCB) therapy is a promising endovascular treatment for obstructive arterial disease. The goal of DCB therapy is restoration of lumen patency in a stenotic vessel, whereby balloon deployment both mechanically compresses the offending lesion and locally delivers an antiproliferative drug, most commonly paclitaxel (PTX) or derivative compounds, to the arterial wall. Favorable long-term outcomes of DCB therapy thus require predictable and adequate PTX delivery, a process facilitated by coating excipients that promotes rapid drug transfer during the inflation period. While a variety of excipients have been considered in DCB design, there is a lack of understanding about the coating-specific biophysical determinants of essential device function, namely, acute drug transfer. We consider two hydrophilic excipients for PTX delivery, urea (UR) and poly(ethylene glycol) (PEG), and examine how compositional and preparational variables in the balloon surface spray-coating process impact resultant coating microstructure and in turn acute PTX transfer to the arterial wall. Specifically, we use scanning electron image analyses to quantify how coating microstructure is altered by excipient solid content and balloon-to-nozzle spray distance during the coating procedure and correlate obtained microstructural descriptors of coating aggregation to the efficiency of acute PTX transfer in a one-dimensional ex vivo model of DCB deployment. Experimental results suggest that despite the qualitatively different coating surface microstructures and apparent PTX transfer mechanisms exhibited with these excipients, the drug delivery efficiency is generally enhanced by coating aggregation on the balloon surface. We illustrate this microstructure-function relation with a finite element-based computational model of DCB deployment, which along with our experimental findings suggests a general design principle to increase drug delivery efficiency across a broad range of DCB designs.


Assuntos
Materiais Revestidos Biocompatíveis , Interações Hidrofóbicas e Hidrofílicas , Paclitaxel , Paclitaxel/química , Paclitaxel/farmacologia , Paclitaxel/administração & dosagem , Materiais Revestidos Biocompatíveis/química , Teste de Materiais , Polietilenoglicóis/química , Tamanho da Partícula , Humanos , Ureia/química , Angioplastia com Balão , Sistemas de Liberação de Medicamentos , Propriedades de Superfície
18.
Biomacromolecules ; 25(5): 2838-2851, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38567844

RESUMO

A comprehensive study focusing on the combined influence of the charge sequence pattern and the type of positively charged amino acids on the formation of secondary structures in sequence-specific polyampholytes is presented. The sequences of interest consisting exclusively of ionizable amino acids (lysine, K; arginine, R; and glutamic acid, E) are (EKEK)5, (EKKE)5, (ERER)5, (ERRE)5, and (EKER)5. The stability of the secondary structure was examined at three pH values in the presence of urea and NaCl. The results presented here underscore the combined prominent effects of the charge sequence pattern and the type of positively charged monomers on secondary structure formation. Additionally, (ERRE)5 readily aggregated across a wide range of pH. In contrast, sequences with the same charge pattern, (EKKE)5, as well as the sequences with the equivalent amino acid content, (ERER)5, exhibited no aggregate formation under equivalent pH and concentration conditions.


Assuntos
Arginina , Lisina , Lisina/química , Arginina/química , Concentração de Íons de Hidrogênio , Ureia/química
19.
Bioorg Med Chem Lett ; 106: 129735, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38588785

RESUMO

A series of 1,4-benzoxazin-3-one analogs were investigated to discover mode-selective TRPV1 antagonists, since such antagonists are predicted to minimize target-based adverse effects. Using the high-affinity antagonist 2 as the lead structure, the structure activity relationship was studied by modifying the A-region through incorporation of a polar side chain on the benzoxazine and then by changing the C-region with a variety of substituted pyridine, pyrazole and thiazole moieties. The t-butyl pyrazole and thiazole C-region analogs provided high potency as well as mode-selectivity. Among them, antagonist 36 displayed potent and capsaicin-selective antagonism with IC50 = 2.31 nM for blocking capsaicin activation and only 47.5 % inhibition at 3 µM concentration toward proton activation, indicating that more than a 1000-fold higher concentration of 36 was required to inhibit proton activation than was required to inhibit capsaicin activation. The molecular modeling study of 36 with our homology model indicated that two π-π interactions with the Tyr511 and Phe591 residues by the A- and C-region and hydrogen bonding with the Thr550 residue by the B-region were critical for maintaining balanced and stable binding. Systemic optimization of antagonist 2, which has high-affinity but full antagonism for activators of all modes, led to the mode-selective antagonist 36 which represents a promising step in the development of clinical TRPV1 antagonists minimizing side effects such as hyperthermia and impaired heat sensation.


Assuntos
Benzoxazinas , Canais de Cátion TRPV , Ureia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Relação Estrutura-Atividade , Benzoxazinas/química , Benzoxazinas/farmacologia , Benzoxazinas/síntese química , Ureia/análogos & derivados , Ureia/química , Ureia/farmacologia , Ureia/síntese química , Humanos , Estrutura Molecular , Animais , Capsaicina/farmacologia , Capsaicina/química , Descoberta de Drogas , Relação Dose-Resposta a Droga
20.
J Environ Manage ; 356: 120615, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38518499

RESUMO

Anaerobic digestion (AD) is a prevalent waste activated sludge (WAS) treatment, and optimizing methane production is a core focus of AD. Two DESs were developed in this study and significantly increased methane production, including choline chloride-urea (ChCl-Urea) 390% and chloride-ethylene glycol (ChCl-EG) 540%. Results showed that ChCl-Urea mainly disrupted extracellular polymeric substances (EPS) structures, aiding in initial sludge solubilization during pretreatment. ChCl-EG, instead, induced sludge self-driven organic solubilization and enhanced hydrolysis and acidification processes during AD process. Based on the extent to which the two DESs promoted AD for methane production, the AD process can be divided into stage Ⅰ and stage Ⅱ. In stage Ⅰ, ChCl-EG promoted methanogenesis more significantly, microbiological analysis showed both DESs enriched aceticlastic methanogens-Methanosarcina. Notably, ChCl-Urea particularly influenced polysaccharide-related metabolism, whereas ChCl-EG targeted protein-related metabolism. In stage Ⅱ, ChCl-Urea was more dominant than ChCl-EG, ChCl-Urea bolstered metabolism and ChCl-EG promoted genetic information processing in this stage. In essence, this study investigated the microbial mechanism of DES-enhanced sludge methanogenesis and provided a reference for future research.


Assuntos
Solventes Eutéticos Profundos , Esgotos , Esgotos/química , Anaerobiose , Eliminação de Resíduos Líquidos/métodos , Colina/química , Metano , Ureia/química , Reatores Biológicos
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