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1.
Nature ; 553(7687): 217-221, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29258297

RESUMO

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.


Assuntos
Proteínas Associadas a CRISPR/administração & dosagem , Edição de Genes/métodos , Genes Dominantes/genética , Terapia Genética/métodos , Perda Auditiva/genética , Estimulação Acústica , Alelos , Animais , Animais Recém-Nascidos , Limiar Auditivo , Sequência de Bases , Proteínas Associadas a CRISPR/metabolismo , Proteínas Associadas a CRISPR/uso terapêutico , Sistemas CRISPR-Cas , Sobrevivência Celular , Cóclea/citologia , Cóclea/metabolismo , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Fibroblastos , Células Ciliadas Auditivas/citologia , Perda Auditiva/fisiopatologia , Perda Auditiva/prevenção & controle , Humanos , Lipossomos , Masculino , Proteínas de Membrana/genética , Camundongos , Reflexo de Sobressalto
2.
BMC Plant Biol ; 23(1): 589, 2023 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-38001405

RESUMO

BACKGROUND: Platycodon grandiflorus (Jacq.) A. DC is a famous traditional Chinese medicine in China and an authentic medicine in Inner Mongolia. It has been traditionally used as an expectorant in cough and also has anti-inflammatory and other pharmacological effects. As a homologous plant of medicine and food, P. grandiflorus is widely planted in Northeast China. Soil salinity isa limiting factor for its cultivation. In this study, we comprehensively described the physiological characteristics of P. grandiflorus and combined transcriptomics and metabolomics to study the response of roots of P. grandiflorus to salt stress. RESULTS: Overall, 8,988 differentially expressed genes were activated and significantly altered the metabolic processes. In total, 428 differentially abundant metabolites were affected by salt stress. After moderate and severe salt stress, most of the differentially abundant metabolites were enriched in the L-phenylalanine metabolic pathway. Through the comprehensive analysis of the interaction between key genes and metabolites, the main pathways such as lignin compound biosynthesis and triterpene saponin biosynthesis were completed. The relative content of compounds related to lignin biosynthesis, such as caffeic acid, coniferin, and syringing, increased under salt stress, and the related genes such as PAL, C4H, and the key enzyme gene UGT72E2 were activated to adapt to the salt stress. Platycodon saponin is one of the major triterpene saponins in P. grandiflorus, and Platycodin D is its most abundant major bioactive component. Under severe salt stress, Platycodin D level increased by nearly 1.77-fold compared with the control group. Most of the genes involved insynthetic pathway of Platycodin D, such as HMGCR, GGPS, SE, and LUP, were upregulated under salt stress. CONCLUSION: Salt stress led to a decrease in the biomass and affected the activities of antioxidant enzymes and contents of osmotic regulators in the plant. These results provided not only novel insights into the underlying mechanisms of response of P. grandiflorus to salt stress but also a foundation for future studies on the function of genes related to salt tolerance in the triterpenoid saponin biosynthesis pathway.


Assuntos
Saponinas , Triterpenos , Transcriptoma , Lignina , Triterpenos/metabolismo , Tolerância ao Sal
3.
Appl Environ Microbiol ; 88(18): e0140322, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36094177

RESUMO

Type IV pili (Tfp) are known to mediate several biological activities, including surface-dependent twitching motility. Although a pil gene cluster for Tfp biosynthesis is found in all sequenced Streptococcus sanguinis strains, Tfp-mediated twitching motility is less commonly detected. Upon examining 81 clinical strains, 39 strains generated twitching zones on blood agar plates (BAP), while 27 strains displayed twitching on Todd-Hewitt (TH) agar. Although BAP appears to be more suitable for the development of twitching zones, 5 strains exhibited twitching motility only on TH agar, indicating that twitching motility is not only strain specific but also sensitive to growth media. Furthermore, different twitching phenotypes were observed in strains expressing comparable levels of pilT, encoding the retraction ATPase, suggesting that the twitching phenotype on agar plates is regulated by multiple factors. By using a PilT-null and a pilin protein-null derivative (CHW02) of twitching-active S. sanguinis CGMH010, we found that Tfp retraction was essential for biofilm stability. Further, biofilm growth was amplified in CHW02 in the absence of shearing force, indicating that S. sanguinis may utilize other ligands for biofilm formation in the absence of Tfp. Similar to SK36, Tfp from CGMH010 were required for colonization of host cells, but PilT only marginally affected adherence and only in the twitching-active strain. Taken together, the results suggest that Tfp participates in host cell adherence and that Tfp retraction facilitates biofilm stability. IMPORTANCE Although the gene clusters encoding Tfp are commonly present in Streptococcus sanguinis, not all strains express surface-dependent twitching motility on agar surfaces. Regardless of whether the Tfp could drive motility, Tfp can serve as a ligand for the colonization of host cells. Though many S. sanguinis strains lack twitching activity, motility can enhance biofilm stability in a twitching-active strain; thus, perhaps motility provides little or no advantage to the survival of bacteria within dental plaque. Rather, Tfp retraction could provide additional advantages for the bacteria to establish infections outside the oral cavity.


Assuntos
Proteínas de Fímbrias , Streptococcus sanguis , Adenosina Trifosfatases/metabolismo , Ágar/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes , Proteínas de Fímbrias/genética , Fímbrias Bacterianas/genética , Fímbrias Bacterianas/metabolismo , Ligantes , Prevalência , Streptococcus sanguis/genética , Streptococcus sanguis/metabolismo
4.
J Viral Hepat ; 29(9): 765-776, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35718996

RESUMO

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.


Assuntos
Antígenos de Superfície da Hepatite B , Hepatite B Crônica , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , DNA Viral , Feminino , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Polietilenoglicóis/uso terapêutico , Resultado do Tratamento
5.
Zhongguo Zhong Yao Za Zhi ; 47(5): 1343-1349, 2022 Mar.
Artigo em Zh | MEDLINE | ID: mdl-35343163

RESUMO

This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.


Assuntos
Medicamentos de Ervas Chinesas , Enterovirus Humano A , Doença de Mão, Pé e Boca , Animais , Chlorocebus aethiops , Medicamentos de Ervas Chinesas/farmacologia , Enterovirus Humano A/fisiologia , Células Vero
6.
Macromol Rapid Commun ; 42(3): e2000501, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33225568

RESUMO

The environment-friendly oxidation of cellulose by the 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)/laccase/O2 system is an alternative route with huge potential to prepare cellulose nanofibers. It is found that the concentration of TEMPO significantly affects the oxidation efficiency. An effective method for improving the oxidation effect is to increase the TEMPO concentration and prolong the oxidation time. To clarify the rate-limited step of TEMPO/laccase/O2 oxidation of cellulose, the academically accepted oxidation process is divided into individual pathways. A series of experiments is conducted with laccase and the three forms of organocatalyst (TEMPO, oxoammonium (TEMPO+), and hydroxylamine (TEMPOH)) to simulate individual reactions and calculate the reaction rates. The concentrations of TEMPO and oxoammonium are monitored by EPR spectroscopy. The oxidation rate of TEMPO by laccase varies at different pH conditions, and laccase activity is much higher at pH 4.5. Other reactions without laccase involved express a higher reaction rate when the pH value increased. TEMPO is mainly regenerated through a comproportionation reaction between oxoammonium and hydroxylamine. The acceleration of TEMPO regeneration by laccase is not obvious. The results indicate that the rate-limited reaction in TEMPO/laccase/O2 oxidation is cellulose oxidation by TEMPO+.


Assuntos
Lacase , Nanofibras , Celulose , Óxidos N-Cíclicos , Lacase/metabolismo , Oxirredução
7.
Biomacromolecules ; 21(4): 1625-1635, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32212687

RESUMO

Native biopolymer nanofibers (cellulose, chitin, and silk nanofiber) are one of the most important contributors to the outstanding functions and mechanical properties of natural materials. To enhance the mechanical performance, A great deal of top-down routes have been reported to prepare biopolymers nanofibers/nanowhiskers that retaining their nanostructures. Compared with advances in cellulose and chitin nanofibers/nanowhiskers, it remains difficult for direct downsizing the natural silk fibers into silk nanofibers/nanowhiskers (SNFs/SNWs) because of their high crystallinity and sophisticated structures. In this work, environmentally friendly and recyclable deep eutectic solvents (DESs) were used to direct pretreat and downsize natural silks into silk nanowhiskers with high yield. SNWs with similar diameter (3.1-22 nm for OA/ChCl DES treated SNWs, 2.7-20 nm for CA/ChCl DES treated SNWs) and contour length (329 ± 140 nm for OA/ChCl DES treated SNWs, 365 ± 200 nm for CA/ChCl DES treated SNWs) to individual nanofibers in natural silk fibers were obtained. In addition, the separated DES with a recovery yield of at least 92% could be reused four times to produce SNWs, indicating the possibility of DESs as green solvents for sustainable biopolymer nanomaterial extraction. Based on the inherent amphoteric properties of SNWs, multicompatibility was explored to facilely composite SNWs with various polymers for preparation of coextruded membranes with enhanced performance and endowed the composites with protein-endowed double adsorption properties. Overall, this work demonstrated that the DES pretreatment process is promising for green and low-cost biopolymer nanomaterial extraction and that the SNWs prepared via DES have good prospects as nanoscale materials in the environmental field and in development of smart biomaterials and drug delivery in biomedicine.


Assuntos
Nanofibras , Nanoestruturas , Celulose , Quitina , Seda
8.
J Am Chem Soc ; 141(10): 4406-4411, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30801185

RESUMO

The precise and highly efficient drug delivery of nanomedicines into lesions remains a critical challenge in clinical translational research. Here, an autocatalytic morphology transformation platform is presented for improving the tumor-specific accumulation of drugs by kinetic control. The in situ reorganization of prodrug from nanoparticle to ß-sheet fibrous structures for targeted accumulation is based on nucleation-based growth kinetics. During multiple administrations, the autocatalytic morphology transformation can be realized for skipping slow nucleating process and constructing the bulky nanoassembly instantaneously, which has been demonstrated to induce the cumulative effect of prodrug. Furthermore, the sustained drug release from fibrous prodrug depot in the tumor site inhibits the tumor growth efficiently. The autocatalytic morphology transformation strategy in vivo offers a novel perspective for targeted delivery strategy by introducing chemical kinetics and shows great potential in disease theranostics.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/farmacologia , Portadores de Fármacos/química , Nanofibras/química , Peptídeos/química , Animais , Antineoplásicos/metabolismo , Camptotecina/análogos & derivados , Camptotecina/metabolismo , Catepsina B/metabolismo , Preparações de Ação Retardada , Portadores de Fármacos/metabolismo , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/metabolismo , Peptídeos/metabolismo , Polietilenoglicóis/química , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Multimerização Proteica , Proteólise
9.
J Am Chem Soc ; 141(18): 7235-7239, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31010287

RESUMO

The morphology controlled molecular assemblies play vital roles in biological systems. Here we present endogenous reactive oxygen species (ROS)-triggered morphology transformation of polymer-peptide conjugates (PPCs) for cooperative interaction with mitochondria, exhibiting high tumor therapeutic efficacy. The PPCs are composed of (i) a ß-sheet-forming peptide KLVFF conjugated with poly(ethylene glycol) through ROS-cleavable thioketal, (ii) a mitochondria-targeting cytotoxic peptide KLAK, and (iii) a poly(vinyl alcohol) backbone. The self-assembled PPCs nanoparticles can enter cells and target mitochondria. Because of overgenerated ROS around mitochondria in most cancer cells, the thioketal linker can be cleaved, leading to transformation from nanoparticles to fibrous nanostructures. As a result, the locational nanofibers with exposure of KLAK exhibit enhanced multivalent cooperative interactions with mitochondria, which causes selective cytotoxicity against cancer cells and powerful tumor suppression efficacy in vivo. As the first example of ROS-triggered intracellular transformation, the locational assembly strategy in vivo may provide a new insight for disease diagnosis and therapy through enhanced interaction with targeting site.


Assuntos
Antineoplásicos/metabolismo , Mitocôndrias/metabolismo , Peptídeos/metabolismo , Álcool de Polivinil/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Mitocôndrias/química , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Imagem Óptica , Peptídeos/química , Peptídeos/farmacologia , Álcool de Polivinil/química , Álcool de Polivinil/farmacologia , Espécies Reativas de Oxigênio/química
10.
Crit Care ; 23(1): 350, 2019 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706360

RESUMO

BACKGROUND: For patients who survive a critical illness and have their oral endotracheal tube removed, dysphagia is highly prevalent, and without intervention, it may persist far beyond hospital discharge. This pre- and post-intervention study with historical controls tested the effects of a swallowing and oral care (SOC) intervention on patients' time to resume oral intake and salivary flow following endotracheal extubation. METHODS: The sample comprised intensive care unit patients (≥ 50 years) successfully extubated after ≥ 48 h endotracheal intubation. Participants who received usual care (controls, n = 117) were recruited before 2015, and those who received usual care plus the intervention (n = 54) were enrolled after 2015. After extubation, all participants were assessed by a blinded nurse for daily intake status (21 days) and whole-mouth unstimulated salivary flow (2, 7, 14 days). The intervention group received the nurse-administered SOC intervention, comprising toothbrushing/salivary gland massage, oral motor exercise, and safe-swallowing education daily for 14 days or until hospital discharge. RESULTS: The intervention group received 8.3 ± 4.2 days of SOC intervention, taking 15.4 min daily with no reported adverse event (coughing, wet voice, or decreased oxygen saturation) during and immediately after intervention. Participants who received the intervention were significantly more likely than controls to resume total oral intake after extubation (aHR 1.77, 95% CI 1.08-2.91). Stratified by age group, older participants (≥ 65 years) in the SOC group were 2.47-fold more likely than their younger counterparts to resume total oral intake (aHR 2.47, 95% CI 1.31-4.67). The SOC group also had significantly higher salivary flows 14 days following extubation (ß = 0.67, 95% CI 0.29-1.06). CONCLUSIONS: The nurse-administered SOC is safe and effective, with greater odds of patients' resuming total oral intake and increased salivary flows 14 days following endotracheal extubation. Age matters with SOC; it more effectively helped participants ≥ 65 years old resume total oral intake postextubation. TRIAL REGISTRATION: NCT02334774, registered on January 08, 2015.


Assuntos
Extubação/efeitos adversos , Deglutição , Boca/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Extubação/métodos , Estado Terminal/enfermagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Boca/fisiopatologia
11.
Angew Chem Int Ed Engl ; 58(14): 4632-4637, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30695128

RESUMO

In cancer treatment, the unsatisfactory solid-tumor penetration of nanomaterials limits their therapeutic efficacy. We employed an in vivo self-assembly strategy and designed polymer-peptide conjugates (PPCs) that underwent an acid-induced hydrophobicity increase with a narrow pH-response range (from 7.4 to 6.5). In situ self-assembly in the tumor microenvironment at appropriate molecular concentrations (around the IC50 values of PPCs) enabled drug delivery deeper into the tumor. A cytotoxic peptide KLAK, decorated with the pH-sensitive moiety cis-aconitic anhydride (CAA), and a cell-penetrating peptide TAT were conjugated onto poly(ß-thioester) backbones to produce PT-K-CAA, which can penetrate deeply into solid tumors owing to its small size as a single chain. During penetration in vivo, CAA responds to the weak acid, leading to the self-assembly of PPCs and the recovery of therapeutic activity. Therefore, a deep-penetration ability for enhanced cancer therapy is provided by this in vivo assembly strategy.


Assuntos
Antineoplásicos/farmacologia , Peptídeos/farmacologia , Polímeros/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Ácido Aconítico/administração & dosagem , Ácido Aconítico/análogos & derivados , Ácido Aconítico/química , Ácido Aconítico/farmacologia , Administração Intravenosa , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Tamanho da Partícula , Peptídeos/administração & dosagem , Peptídeos/química , Polímeros/administração & dosagem , Polímeros/química , Propriedades de Superfície
12.
Mol Pharm ; 12(8): 2869-78, 2015 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-26101892

RESUMO

Various nanomaterials have been demonstrated as autophagy inducers owing to their endocytosis cell uptake pathway and impairment of lysosomes. pH-dependent nanomaterials as drug delivery systems that are capable of dissociating in weakly acidic lysosomal environment (pH 4-5) and consequently releasing the payloads into the cytoplasm have been paid extensive attention, but their autophagy-modulating effects are less reported so far. In this study, we report pH-sensitive micelle-like nanoparticles (NPs) that self-assembled from poly(ß-amino ester)s to induce cell autophagy. By encapsulation of gold(I) compounds (Au(I)) into hydrophobic domains of NPs, the resultant Au(I)-loaded NPs (Au(I)⊂NPs) shows synergistic cancer cell killing performance. The Au(I)⊂NPs enter cells through endocytosis pathway and accumulate into acidic lysosomes. Subsequently, the protonation of tertiary amines of poly(ß-amino ester)s triggers the dissociation of micelles, damages the lysosomes, and blocks formation of autolysosomes from fusion of lysosomes with autophagosomes. In addition, Au(I) preferentially inhibits thioredoxin reductase (TrxR) in MCF-7 human breast cancer cells that directly links to up-regulate reactive oxygen species (ROS) and consequently induce autophagy and apoptosis. The blockade of autophagy leads to excessive depletion of cellular organelles and essential proteins and ultimately results in cell death. Therefore, pH-sensitive polymeric nanoparticles with gold(I) compound payloads can synergistically induce cancer cell death through regulation of autophagy. Identification of the pH-sensitive nanomaterials for synergistically inducing cell death through regulation autophagy may open a new avenue for cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ouro/química , Nanopartículas Metálicas/química , Polímeros/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lisossomos/metabolismo , Células MCF-7 , Micelas , Fagossomos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
13.
Nanotechnology ; 26(35): 355703, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26245834

RESUMO

Supramolecular self-assemblies with various nanostructures in organic and aqueous solutions have been prepared with desired functions. However, in situ construction of self-assembled superstructures in physiological conditions to achieve expected biological functions remains a challenge. Here, we report a supramolecular system to realize the in situ formation of nanoaggregates in living cells. The bis(pyrene) monomers were dispersed inside of hydrophobic domains of pH-sensitive polymeric micelles and delivered to the lysosomes of cells. In the acidic lysosomes, the bis(pyrene) monomers were released and self-aggregated with turn-on fluorescence. We envision this strategy for in situ construction of supramolecular nanostructures in living cells will pave the way for molecular diagnostics in the future.


Assuntos
Técnicas Citológicas/métodos , Corantes Fluorescentes/química , Nanoestruturas/química , Polímeros/química , Pirenos/química , Corantes Fluorescentes/metabolismo , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Polímeros/metabolismo , Pirenos/metabolismo
14.
Macromol Rapid Commun ; 36(4): 398-404, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25545630

RESUMO

Lignin-grafted copolymers, namely lignin-graft-poly(methyl methacrylate-co-butyl acrylate) (lignin-g-P(MMA-co-BA)), are synthesized via "grafting from" atom transfer radical polymerization (ATRP) with the aid of lignin-based macroinitiators. By manipulating the monomer feed ratios of MMA/BA, grafted copolymers with tunable glass transition temperatures (-10-40 °C) are obtained. These copolymers are evaluated as sustainable thermoplastic elastomers (TPEs). The results suggest that the mechanical properties of these TPEs lignin-g-P(MMA-co-BA) copolymers are improved significantly by comparing with those of linear P(MMA-co-BA) copolymer counterparts, and the elastic strain recovery is nearly 70%. Lignin-g-P(MMA-co-BA) copolymers exhibit high absorption in the range of the UV spectrum, which might allow for applications in UV-blocking coatings.


Assuntos
Elastômeros/química , Lignina/química , Elastômeros/síntese química , Metilmetacrilatos/química , Espectrofotometria Ultravioleta , Temperatura
15.
Int J Biol Macromol ; 270(Pt 2): 132339, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38754663

RESUMO

Xylan-type hemicellulose hydrolysis by an organic acid solution for the production of xylo-oligosaccharides (XOS) is efficient and eco-friendly, but the effects of different organic acids on XOS production from Toona sinensis branch (TB) biomass is limited. In this work, under the conditions of 170 °C for 60 min, 33.1 % and 38.7 % XOS yields were obtained from polysaccharides present in TB by 2 % lactic acid (LA) and 6 % propionic acid (PA), respectively. Then 77 % of the lignin was removed by hydrogen peroxide-acetic acid pretreatment system, and 39.5 % and 44.7 % XOS yield were obtained from polysaccharides in delignification TB by 2 % LA and 6 % PA, respectively. It was found that PA hydrolysis, especially from delignified TB, resulted in higher XOS yield and purity compared to LA hydrolysis. Moreover, the content of byproducts (xylose, hydroxymethyl-furfural and furfural) in PA hydrolysate was lower. Following the hydrolysis process, the simultaneous saccharification and fermentation of the TB solid residue achieved an ethanol yield of 71.5 %. This work proposed an integrated process to preferentially convert the TB hemicellulose into valuable XOS and then convert the cellulose into ethanol. This process had the advantages of eliminating the need for isolation and purification of xylan, and the potential to obtain multiple products from the same raw material.


Assuntos
Etanol , Ácido Láctico , Polissacarídeos , Propionatos , Hidrólise , Propionatos/química , Etanol/química , Polissacarídeos/química , Ácido Láctico/metabolismo , Ácido Láctico/química , Fermentação , Oligossacarídeos/química , Biomassa , Lignina/química , Glucuronatos
16.
Int J Biol Macromol ; 265(Pt 2): 131008, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38513903

RESUMO

The construction of functional cellulose plastics possessing strong UV-blocking, hydrophilicity, and biodegradability is challenging. Therefore, we provide a novel strategy to successfully prepare sustainable and hydrophilic glucose-cross-linked cellulose (GC) plastics showing effective UV-blocking and excellent mechanical properties via hydroxyl-yne click reaction at room temperature. The results demonstrated that hydroxyl-yne click chemistry enabled efficient crosslinking of cellulose with glucose using 4-dimethylamino pyridine (DMAP) as a catalyst. Moreover, the DMAP residue imparted good UV-shielding properties to GC films exhibiting nearly 100 % UVC (200-275 nm) and 100 % UVB (320-275 nm) shielding ratios. The introduction of glucose imparted superior hydrophilicity (water contact angle of 40.3-43.2°) and improved water adsorption. Additionally, the mechanical properties of the GC films increased with the increasing crosslinking density, and the highest tensile stress was 94 MPa. The water-induced breaking and hydrogen bond reforming strategy led to a stress of 127 MPa and a strain of 25.6 % for the final GC2 film, which were excellent compared to those of the most reported cellulose films. Additionally, GC films were biosafe, exhibited improved oxygen barrier, and good biodegradability. Hence, this study provides a promising and efficient approach for preparing high-performance cellulose plastics.


Assuntos
Celulose , Plásticos , Gravidez , Humanos , Feminino , Celulose/química , Glucose , Água/química , Adsorção
17.
Environ Pollut ; 360: 124649, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39095004

RESUMO

Dimethyl sulfide (DMS) is a prevalent volatile organic sulfur compound relevant to the global climate. Ecotoxicological effects of nano- and microplastics (NPs and MPs) on phytoplankton, zooplankton, and bacteria have been investigated by numerous studies. Yet, the influences of NPs/MPs on dimethylated sulfur compounds remains understudied. Herein, we investigated the impacts of polystyrene (PS) NPs/MPs (80 nm, 1 µm, and 10 µm) on zooplankton grazing, chlorophyll a (Chl a) concentration, bacterial community, dimethylsulfoniopropionate (DMSP), and DMS production in the microcosms. Our findings revealed that rotifer grazing increased the production of DMS in the absence of NPs/MPs but did not promote DMS production when exposed to NPs/MPs. The ingestion rates of the rotifer and copepod exposed to NPs/MPs at high concentrations were significantly reduced. NPs/MPs exposure significantly decreased DMS levels in the treatments with rotifers compared to the animal controls. In the bacterial microcosms, smaller NPs/MPs sizes were more detrimental to Chl a concentrations compared to larger sizes. The study revealed a stimulatory effect on Chl a concentrations, DMSPd concentrations, and bacterial abundances when exposed to 10 µm MP with low concentrations. The effects of NPs/MPs on DMS concentrations were both dose- and size-dependent, with NPs showing greater toxicity compared to larger MPs. NPs/MPs led to changes in bacterial community compositions, dependent on both dosage and size. NPs caused a notable decrease in the alpha diversities and richness of bacteria compared to MPs. These results provide insights into the influences of NPs/MPs on food webs, and subsequently organic sulfur compounds cycles.


Assuntos
Bactérias , Poluentes Químicos da Água , Zooplâncton , Animais , Zooplâncton/efeitos dos fármacos , Bactérias/metabolismo , Bactérias/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/metabolismo , Microplásticos/toxicidade , Compostos de Enxofre , Sulfetos/toxicidade , Nanopartículas/toxicidade , Clorofila A/metabolismo , Plásticos
18.
Int J Biol Macromol ; 278(Pt 3): 134921, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39173788

RESUMO

Recently, the utilization of the cellulose to fabricate the multifunctional materials with aim to replace the petroleum-based product, is receiving significant attentions. However, the development of cellulose-based multifunctional materials with high mechanical strength and temperature resistance is still a challenge. Herein, the intrinsic feature and property of cellulose and rosin were creatively employed to fabricate a novel cellulose-rosin based poly(esterimide) (PEI) by esterification reaction and imidization reaction, and the obtained cellulose-rosin derived PEI exhibits superior thermal stability. Then the as-prepared cellulose-rosin derived PEI was dissolved in polymerizable deep eutectic solvents (PDES) and in-situ formed the ionic conductive elastomer (ICE) with via UV-induced polymerization. These cellulose-rosin based ICE exhibited excellent mechanical properties, solvent resistance, and temperature tolerance. By adjusting the mass ratio of cellulose-rosin derived PEI and PDES, the as-prepared liquid-free ICE functions as UV shadowless adhesive and wearable sensors. The bonding strength of UV shadowless adhesive could 1.52 MPa, which could be applied to fix the broken glass toy models. Furthermore, wearable sensors based those ICE could monitor the large and subtle movements even under extreme environmental condition, such as being soaked in organic solvent (such as tetrahydrofuran) or at low/high temperature (-25 °C or 80 °C). This work opens a new avenue for the next-generation of multifunctional ICE.


Assuntos
Adesivos , Celulose , Elastômeros , Resinas Vegetais , Solventes , Temperatura , Celulose/química , Resinas Vegetais/química , Elastômeros/química , Adesivos/química , Solventes/química , Raios Ultravioleta , Condutividade Elétrica , Dispositivos Eletrônicos Vestíveis
19.
Environ Pollut ; 351: 124084, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697245

RESUMO

Due to the potential impacts of microplastics (MPs) and nanoplastics (NPs) on algal growth and thereby affect the climate-relevant substances, dimethylsulfoniopropionate (DMSP) and dimethyl sulfide (DMS), we studied the polystyrene (PS) MPs and NPs of 1 µm and 80 nm impacts on the growth, chlorophyll content, reactive oxygen species (ROS), antioxidant enzyme activity, and DMS/DMSP production in Emiliania huxleyi. E. huxleyi is a prominent oceanic alga that plays a key role in DMS and DMSP production. The results revealed that high concentrations of MPs and NPs inhibited the growth, carotenoid (Car), and Chl a concentrations of E. huxleyi. However, short-time exposure to low concentrations of PS MPs and NPs stimulated the growth of E. huxleyi. Furthermore, high concentrations of MPs and NPs resulted in an increase in the superoxide anion radical (O2.-) production rate and a decrease in the malondialdehyde (MDA) content compared with the low concentrations. Exposure to MPs and NPs at 5 mg L-1 induced superoxide dismutase (SOD) activity as a response to scavenging ROS. High concentrations of MPs and NPs significantly inhibited the production of DMSP and DMS. The findings of this study support the potential ecotoxicological impacts of MPs and NPs on algal growth, antioxidant system, and dimethylated sulfur compounds production, which maybe potentially impact the global climate.


Assuntos
Antioxidantes , Haptófitas , Espécies Reativas de Oxigênio , Sulfetos , Compostos de Sulfônio , Poluentes Químicos da Água , Antioxidantes/metabolismo , Compostos de Sulfônio/metabolismo , Haptófitas/crescimento & desenvolvimento , Haptófitas/metabolismo , Haptófitas/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Clorofila/metabolismo , Superóxido Dismutase/metabolismo , Nanopartículas/toxicidade , Poliestirenos/toxicidade
20.
Int J Biol Macromol ; 272(Pt 2): 132871, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38862321

RESUMO

Fabrication of sustainable bio-based malleable thermosets (BMTs) with excellent mechanical properties and reprocessing ability for applications in electronic devices has attracted more and more attention but remains significant challenges. Herein, the BMTs with excellent mechanical robustness and reprocessing ability were fabricated via integrating with radical polymerization and Schiff-base chemistry, and employed as the flexible substrate to prepare the capacitive sensor. To prepare the BMTs, an elastic bio-copolymer derived from plant oil and 5-hydroxymethylfurfural was first synthesized, and then used to fabricate the dynamic crosslinked BMTs through Schiff-base chemistry with the amino-modified cellulose and polyether amine. The synergistic effect of rigid cellulose backbone and the construction of dynamic covalent crosslinking network not only achieved high tensile strength (8.61 MPa) and toughness (3.77 MJ/m3) but also endowed the BMTs with excellent reprocessing ability with high mechanical toughness recovery efficiency of 104.8 %. More importantly, the BMTs were used as substrates to fabricate the capacitive sensor through the CO2-laser irradiation technique. The resultant capacitive sensor displayed excellent and sensitive humidity sensing performance, which allowed it to be successfully applied in human health monitoring. This work paved a promising way for the preparation of mechanical robustness malleable bio-thermosets for electronic devices.


Assuntos
Celulose , Furaldeído , Óleos de Plantas , Celulose/química , Furaldeído/química , Furaldeído/análogos & derivados , Óleos de Plantas/química , Capacitância Elétrica , Temperatura , Resistência à Tração , Humanos
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