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1.
Small ; : e2102485, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34605169

RESUMO

The therapeutic potential of nanomaterials toward oxidative damage relevant diseases has attracted great attentions by offering promising advantages compared with conventional antioxidants. Although different kinds of nanoantioxidants have been well developed, the facile fabrication of robust and efficient nanoscavengers is still met with challenges like the use of toxic and high-cost subunits, the involvement of multistep synthetic process, and redundant purification work. Herein, a direct fabrication strategy toward polyphenol nanoparticles with tunable size, excellent biocompatibility, and reactive oxygen species (ROS) scavenging capacities from grape seed via an enzymatic polymerization method is reported. The resulting nanoparticles can efficiently prevent cell damage from ROS and exert promising in vivo antioxidant therapeutic effects on several oxidative stress-related diseases, including accelerating wound healing, inhibiting ulcerative colitis, and regulating the oxidative stress in dry eye disease. This study can stimulate the development of more kinds of low-cost, safe, and efficient biomass-based antioxidative nanomaterials via similar fabrication methodologies.

2.
Theranostics ; 11(19): 9262-9295, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646370

RESUMO

The rapid development of chiral inorganic nanostructures has greatly expanded from intrinsically chiral nanoparticles to more sophisticated assemblies made by organics, metals, semiconductors, and their hybrids. Among them, lots of studies concerning on hybrid complex of chiral molecules with achiral nanoparticles (NPs) and superstructures with chiral configurations were accordingly conducted due to the great advances such as highly enhanced biocompatibility with low cytotoxicity and enhanced penetration and retention capability, programmable surface functionality with engineerable building blocks, and more importantly tunable chirality in a controlled manner, leading to revolutionary designs of new biomaterials for synergistic cancer therapy, control of enantiomeric enzymatic reactions, integration of metabolism and pathology via bio-to nano or structural chirality. Herein, in this review our objective is to emphasize current research state and clinical applications of chiral nanomaterials in biological systems with special attentions to chiral metal- or semiconductor-based nanostructures in terms of the basic synthesis, related circular dichroism effects at optical frequencies, mechanisms of induced optical chirality and their performances in biomedical applications such as phototherapy, bio-imaging, neurodegenerative diseases, gene editing, cellular activity and sensing of biomarkers so as to provide insights into this fascinating field for peer researchers.

3.
Acta Biochim Pol ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648253

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is in the first place of the causes that lead to end-stage renal disease in the world. Thus, it is urgent to develop a novel diagnostic or therapeutic strategy that could stop the progression of diabetic nephropathy. METHODS: RNA-sequencing was conducted in high glucose (HG)-treated MPC5 cells (podocytes). Cell morphology was examined under a light microscope. Upon high-glucose challenge, the effects of lncRNA Hoxb3os overexpression on MPC5 cells apoptosis, viability, autophagy and Akt-mTOR signaling were evaluated using flow cytometry, Cell Counting Kit-8, qRT-PCR, and Western blotting. TUNEL staining and ELISA were performed to confirm the establishment of DN model in db/db mice. RESULTS: High-glucose exposure dramatically altered lncRNA expression profile in MPC5 cells (fold change>2), including 305 upregulated lncRNAs and 451 downregulated lncRNAs. LncRNA Hoxb3os expression was significantly reduced in the HG-induced podocyte damage model, as well as in the renal tissues from db/db mice with spontaneous DN. Overexpression of Hoxb3os significantly reduced the apoptosis rate and increased the viability of MPC5 cells under HG conditions. Further study revealed that exogenous Hoxb3os increased autophagy level in HG-exposed MPC5 cells via abrogating Akt-mTOR signaling pathway and that the process was possibly implicated in the upregulation of SIRT1. CONCLUSION: LncRNA Hoxb3os protected podocytes from HG-induced damage by regulating Akt-mTOR pathway and cell autophagy. Thus, lncRNA Hoxb3os appears as a potential biomarker in the diagnosis and treatment of DN in the future.

4.
ACS Appl Mater Interfaces ; 13(33): 39126-39134, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34383476

RESUMO

The usage of exogenous antioxidant materials to relieve oxidative stress offers an important strategy for the therapy of oxidative stress-induced injuries. However, the fabrication processes toward the antioxidant materials usually require the involvement of extra metal ions and organic agents, as well as sophisticated purification steps, which might cause tremendous environmental stress and induce unpredictable side effects in vivo. To address these issues, herein, we proposed a novel strategy to fabricate green nanoparticles for efficiently modulating oxidative stress, which was facilely prepared from tea polyphenol extracts (originated from green tea) via a green enzymatic polymerization-based chemistry method. The resulting nanoparticles possessed a uniform spherical morphology and good stability in water and biomedium and demonstrated excellent radical scavenging properties. These nanoparticle scavengers could effectively prevent intracellular oxidative damage, accelerate wound recovery, and protect the kidneys from reactive oxygen species damaging in the acute kidney injury model. We hope this work will inspire the further development of more types of green nanoparticles for antioxidant therapies via similar synthetic strategies using green biomass materials.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antioxidantes/química , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/química , Chá/química , Células 3T3 , Células A549 , Animais , Antioxidantes/farmacologia , Catecóis/química , Sobrevivência Celular/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/metabolismo , Química Verde , Peroxidase do Rábano Silvestre/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Peróxido de Hidrogênio/química , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica , Cicatrização/efeitos dos fármacos
6.
Handb Exp Pharmacol ; 267: 357-378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34247283

RESUMO

ATP-sensitive K+ channels (KATP) are inwardly-rectifying potassium channels, broadly expressed throughout the body. KATP is regulated by adenine nucleotides, characteristically being activated by falling ATP and rising ADP levels thus playing an important physiological role by coupling cellular metabolism with membrane excitability. The hetero-octameric channel complex is formed of 4 pore-forming inward rectifier Kir6.x subunits (Kir6.1 or Kir6.2) and 4 regulatory sulfonylurea receptor subunits (SUR1, SUR2A, or SUR2B). These subunits can associate in various tissue-specific combinations to form functional KATP channels with distinct electrophysiological and pharmacological properties. KATP channels play many important physiological roles and mutations in channel subunits can result in diseases such as disorders of insulin handling, cardiac arrhythmia, cardiomyopathy, and neurological abnormalities. The tissue-specific expression of KATP channel subunits coupled with their rich and diverse pharmacology makes KATP channels attractive therapeutic targets in the treatment of endocrine and cardiovascular diseases.


Assuntos
Trifosfato de Adenosina , Humanos , Mutação , Receptores de Sulfonilureias/genética
7.
New Phytol ; 232(1): 279-289, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34160845

RESUMO

Hybrid necrosis, caused by complementary genes Ne1 and Ne2, is a serious barrier for combining desirable traits from different genotypes of wheat, affecting the full utilisation of heterosis. To date, both Ne1 and Ne2 are still not isolated although they were documented decades ago. We report here the map-based cloning and functional characterisation of Ne2, encoding a coiled coil-nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR) protein. Homozygous frameshift mutations generated using the CRISPR/Cas9 approach confirmed the Ne2-inducing hybrid necrosis in wheat. Upregulated expression of Ne2 induced by Ne1 and excess hydrogen peroxide accumulation are associated with the necrosis formation. Genetic analyses of a Ne2 allele (Ne2m ) and leaf rust resistance gene LrLC10/Lr13 revealed that they might be the same gene. Furthermore, we demonstrated that the frequency of the Ne2 allele was much lower in landraces (2.00%) compared with that in modern cultivars (13.62%), suggesting that Ne2 allele has been partially applied in wheat genetic improvement. Our findings open opportunities of thoroughly investigating the molecular mechanism of hybrid necrosis, selecting Lr13 and simultaneously avoiding hybrid necrosis in wheat breeding through marker-assisted selection.


Assuntos
Basidiomycota , Triticum , Genes de Plantas , Necrose , Melhoramento Vegetal , Doenças das Plantas/genética , Triticum/genética
8.
Chem Soc Rev ; 50(14): 8319-8343, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34100489

RESUMO

Stimuli responsiveness has long been a fascinating feature of smart material design. Polydopamine (PDA), a nature inspired polymeric pigment, exhibits excellent photo-responsive properties and has active surface functionality for loading various responsive motifs, making it a promising candidate for the construction of stimuli-responsive smart functional materials. PDA has long been considered as a robust coating material, but its responsive feature has rarely been emphasized in the past reviews. Herein, we present the first effort to summarize recent advances in the design strategies, responsive mechanisms, and diverse applications of stimuli-responsive PDA-based smart materials; the stimuli include light, pH, chemicals, temperature, humidity, electric fields, mechanical force, magnetic fields, and ultrasound. Moreover, the current trends, challenges, and future directions of stimuli-responsive PDA-based materials are also elaborated.

9.
Eur J Clin Nutr ; 75(9): 1407-1413, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34131302

RESUMO

BACKGROUND/OBJECTIVES: Patients undergoing maintenance hemodialysis dialysis (MHD) are at high risk of sarcopenia. Diagnosing sarcopenia requires measurement of both muscle mass and muscle function. However, few studies have rigorously evaluated the best timing for assessment. This study aimed to evaluate the changes in body composition following hemodialysis in an Asian population. SUBJECTS/METHODS: Overall, 87 MHD patients were included. Body composition was estimated using bioelectrical impedance analysis. Handgrip strength was measured using a quantitative handgrip dynamometer, and physical performance was assessed using the 6-m usual gait speed. All measurements were performed pre and post dialysis. Blood samples were collected before and after the same dialysis session. RESULTS: The prevalence of sarcopenia ranged from 6.9% to 18.8% pre dialysis (40-59-year group, 6.9%; 60-80-year group, 16.7%; >80-year group, 18.8%) and from 13.8% to 62.5% post dialysis. The body weight decreased from 59.32 ± 11.20 kg pre dialysis to 57.71 ± 11.05 kg post dialysis. Both the extracellular and intracellular water levels decreased post dialysis (from 14.70 ± 3.81 to 13.6 ± 2.82 L, P < 0.001, and from 21.30 ± 4.20 to 20.8 ± 4.13 L, P < 0.001, respectively). Albumin and creatinine levels were significantly lower in patients with sarcopenia. Elevated high-sensitivity C-reactive protein and interleukin-6 levels were observed in sarcopenia patients. CONCLUSION: The prevalence of sarcopenia in MHD patients varies greatly according to the timing of measurements. Although predialysis measurement is preferred, it underestimates the prevalence of sarcopenia in MHD patients.

10.
Appl Opt ; 60(17): 5124-5133, 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34143079

RESUMO

Aero-engine blades are an integral part of the aero-engine, and the integrity of these blades affects the flight performance and safety performance of an aircraft. The traditional manual detection method is time-consuming, labor-intensive, and inefficient. Hence, it is particularly important to use intelligent detection methods to detect and identify damage. In order to quickly and accurately identify the damage of the aero-engine blades, the present study proposes a network based on the Improved Cascade Mask R-CNN network-to establish the damage related to the aero-engine blades and detection models. The model can identify the damage type and locate and segment the area of damage. Furthermore, the accuracy rate can reach up to 98.81%, the Bbox-mAP is 78.7%, and the Segm-mAP is 77.4%. In comparing the Improved Cascade Mask R-CNN network with the YOLOv4, Cascade R-CNN, Res2Net, and Cascade Mask R-CNN networks, the results revealed that the network used in the present is excellent and effective.

11.
Ecotoxicol Environ Saf ; 220: 112360, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058680

RESUMO

Recently, emerging pollutants, such as anthelmintics have attracted an increasing attention worldwide due to their extensive use and notable stability. However, the information on anthelmintics in the environment of southwest China is scarce. Thus, the occurrence, ecological risk and exposure evaluation of nineteen anthelmintics in Tuojiang River, which is one of the largest tributaries of Yangtze River, and drinking water source of Sichuan, southwest China, were investigated. The result showed that the detection frequency of anthelmintics was relatively high in Tuojiang River, ranging from 65% to 100% in river water. Among the seven kinds of anthelmintics, benzimidazoles are the primary anthelmintics, with concentrations up to 61.12 ng/L and 596.06 ng/g in water and sediment of the Tuojiang river, respectively. The total concentration of 19 anthelmintics in sediment samples from non-agricultural area was higher than that in agricultural area(p = 0.000 < 0.05). This could be attributed to anthropogenic activities, which lead to greater discharge and accumulation of anthelmintics in residential area along the river. It's worth to mention that the highest total concentrations of anthelmintics (109.28 ng/L) was found at the junction of rivers in R31 site. The results could be ascribed to the complexity of junction of Tuojiang River and Yangtze River, which could influence the distribution of pollutant. Besides, the ecological risk assessment showed that the macrocyclic lactones rather than benzimidazoles had relatively high toxicity to non-target organisms in aquatic environment (p = 0.000 < 0.05), with the highest RQEcotox value of 101 for Daphnia magna, while benzimidazoles had relatively high concentrations. The exposure risk could be ignored for both children and adults because the daily intake of anthelmintics via water ingestion were below 10 ng/kg/d. In addition, strong correlations were found between sucralose and most of the selected anthelmintics in Tuojiang River, indicating that sucralose might be a good tracer to evaluated the source of anthelmintics in surface water. This study provides the levels, risks and even some tracer information of pollutants for better understanding of anthelmintics in southwest China.


Assuntos
Anti-Helmínticos/análise , Exposição Ambiental/análise , Rios/química , Poluentes Químicos da Água/análise , Adulto , Animais , Anti-Helmínticos/toxicidade , Organismos Aquáticos/efeitos dos fármacos , Criança , China , Daphnia/efeitos dos fármacos , Sedimentos Geológicos/química , Humanos , Medição de Risco , Sacarose/análogos & derivados , Sacarose/análise , Poluentes Químicos da Água/toxicidade
12.
Theor Appl Genet ; 134(8): 2603-2611, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33970284

RESUMO

KEY MESSAGE: Hybrid necrosis gene Ne1 was delimited into an approximate 4.06 Mb region on chromosome arm 5BL and an InDel marker that co-segregated with Ne1 alleles was developed. Hybrid necrosis in wheat, characterized by progressive chlorosis and necrosis of plant leaves, tillers or whole plants in certain hybrids, is caused by complementary genes Ne1 and Ne2 located on chromosome arms 5BL and 2BS, respectively. Hybrid necrosis can be a barrier in combining desirable traits from various wheat genotypes. In this study, we fine mapped Ne1 on chromosome arm 5BL, and delimited it to a 4.06 Mb region using large segregating recombinant inbred line families from cross 'Zhengnong 17' × 'Yangbaimai'. Genetic characterization confirmed that the ne1 allele was closely associated with a 2.89 Mb deletion in Zhengnong 17. A tightly linked InDel marker, 5B-InDel385, for Ne1 was developed and was used to predict the presence of Ne1 in a diverse panel of 501 common wheat accessions. Among those accessions, 122 (61%) of 200 landraces were predicted to carry the Ne1 allele, whereas only 79 (26%) of 301 modern cultivars were predicted to carry Ne1. The significant decrease in Ne1 frequency in modern cultivars indicated that the Ne1 allele had been negatively selected in wheat breeding. This study provides a foundation for marker-assisted selection, gene cloning and functional studies of Ne1 in wheat.


Assuntos
Mapeamento Cromossômico/métodos , Cromossomos de Plantas/genética , Regulação da Expressão Gênica de Plantas , Fenótipo , Proteínas de Plantas/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/genética , Necrose , Melhoramento Vegetal , Proteínas de Plantas/genética
13.
Medicine (Baltimore) ; 100(8): e24882, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33663116

RESUMO

INTRODUCTION: Our aim was to evaluate the safety and efficacy of low-dose mineralocorticoid receptor antagonists (MRAs) in dialysis patients. METHODS: We systematically searched PubMed, EMBASE, and Cochrane libraries for clinical trials on the use of MRAs in dialysis patients. Review Manager 5.3 software was used to analyze relevant data and evaluate the quality of evidence. RESULTS: We identified nine randomized controlled trials including 1128 chronic dialysis patients. In terms of safety, when hyperkalemia was defined as serum potassium level ≥5.5 mmol/L, low-dose MRAs were significantly associated with hyperkalemia (relative risk [RR] 1.76, 95% confidence intervals [CI] 1.07-2.89, P = .02); however, when hyperkalemia was defined as serum potassium level ≥6.0 mmol/L or serum potassium level ≥6.5 mmol/L, no significant association was observed between low-dose MRAs and hyperkalemia (RR 1.40, 95% CI 0.83-2.37, P = .20; RR 1.98, 95% CI 0.91-4.30, P = .09, respectively). Use of low-dose MRAs can reduce cardiovascular mortality by 54% compared with the control group (0.46, 95% CI 0.28-0.76, P = .003). Similarly, the RR of all-cause mortality for the low-dose MRAs group was 0.48 (95% CI 0.33-0.72, P = .0003). CONCLUSION: Low-dose MRAs may benefit dialysis patients without significantly increasing moderate to severe hyperkalemia.


Assuntos
Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Diálise Renal/métodos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Humanos , Hiperpotassemia/induzido quimicamente , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/terapia
14.
Nat Genet ; 53(4): 574-584, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33737755

RESUMO

Rye is a valuable food and forage crop, an important genetic resource for wheat and triticale improvement and an indispensable material for efficient comparative genomic studies in grasses. Here, we sequenced the genome of Weining rye, an elite Chinese rye variety. The assembled contigs (7.74 Gb) accounted for 98.47% of the estimated genome size (7.86 Gb), with 93.67% of the contigs (7.25 Gb) assigned to seven chromosomes. Repetitive elements constituted 90.31% of the assembled genome. Compared to previously sequenced Triticeae genomes, Daniela, Sumaya and Sumana retrotransposons showed strong expansion in rye. Further analyses of the Weining assembly shed new light on genome-wide gene duplications and their impact on starch biosynthesis genes, physical organization of complex prolamin loci, gene expression features underlying early heading trait and putative domestication-associated chromosomal regions and loci in rye. This genome sequence promises to accelerate genomic and breeding studies in rye and related cereal crops.


Assuntos
Mapeamento de Sequências Contíguas/métodos , Produtos Agrícolas/genética , Genoma de Planta , Proteínas de Plantas/genética , Característica Quantitativa Herdável , Secale/genética , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Loci Gênicos , Tamanho do Genoma , Sequenciamento de Nucleotídeos em Larga Escala , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Retroelementos , Amido/biossíntese , Triticum/genética
15.
ACS Appl Mater Interfaces ; 13(8): 9729-9738, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33599495

RESUMO

Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.


Assuntos
Antioxidantes/uso terapêutico , Hemorragia Cerebral/tratamento farmacológico , Sobrecarga de Ferro/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Polímeros/uso terapêutico , Sideróforos/uso terapêutico , Animais , Antioxidantes/síntese química , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Catecóis/síntese química , Catecóis/uso terapêutico , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/complicações , Hemorragia Cerebral/fisiopatologia , Colagenases , Desferroxamina/análogos & derivados , Desferroxamina/uso terapêutico , Ferro/metabolismo , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Neuroprotetores/síntese química , Polímeros/síntese química , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Sideróforos/síntese química
16.
Chem Commun (Camb) ; 57(17): 2192-2195, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33527917

RESUMO

A series of self-assembled 1D nanostructures, including straight and helix nanofibers, nanoribbons, and nanobelts, were fabricated from uniform amphiphilic azobenzene oligomers with tunable molecular weight and side chain functionality, promoted by multiple and cooperative supramolecular interactions. Additionally, the morphological transformation of the nanofibers was achieved during the photoisomerization process.

17.
Carbohydr Polym ; 257: 117598, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33541635

RESUMO

Hydrogels with antioxidative and antibacterial properties have emerged as potential dressings for accelerated wound healing. Herein, a series of reduced polydopamine nanoparticles (rPDA NPs) incorporated oxidized dextran/chitosan hybrid hydrogels have been designed for wound healing due to their excellent antioxidative property and antibacterial activity. The physicochemical properties as well as the antioxidative activities of the hydrogels were carefully characterized. The results demonstrated rPDA NPs have better antioxidative activity than the untreated PDA NPs. And the rPDA NPs incorporated oxidized dextran/chitosan hybrid hydrogels had excellent antioxidative properties to protect cells against external oxidative stress. Besides, the hydrogels also showed antibacterial ability to protect the wound against infections. In vitro and in vivo investigations concluded that rPDA NPs incorporated oxidized dextran/chitosan hybrid hydrogels could be served as an effective dressing for accelerated wound healing.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/química , Quitosana/química , Dextranos/química , Hidrogéis/química , Indóis/química , Polímeros/química , Animais , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bandagens , Compostos de Bifenilo/química , Sequestradores de Radicais Livres , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas In Vitro , Masculino , Camundongos , Nanopartículas , Picratos/química , Polissacarídeos/química , Staphylococcus aureus/efeitos dos fármacos , Suínos , Cicatrização/efeitos dos fármacos
18.
Artigo em Inglês | MEDLINE | ID: mdl-33538165

RESUMO

A solar steam generation method has been widely investigated as a sustainable method to achieve seawater desalination and sewage treatment. However, oil pollutants are usually emitted in real seawater or wastewaters, which can cause serious fouling problems to disturb the solar evaporation performance. In this work, a mussel-inspired, low-cost, polydopamine-filled cellulose aerogel (PDA-CA) has been rationally designed and fabricated with both superhydrophilicity and underwater superoleophobicity. The resulting PDA-CA device could also achieve a high solar evaporation rate of 1.36 kg m-1 h-1 with an 86% solar energy utilize efficiency under 1 sun illumination. In addition, the PDA-CA not only exhibited promising antifouling capacity for long-term water evaporation but also engaged in the effective adsorption of organic dye contaminants. These promising features of PDA-CA may offer new opportunities for developing multifunctional photothermal devices for solar-driven water remediation.

19.
Nat Cell Biol ; 23(2): 160-171, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33462394

RESUMO

The response to poly(ADP-ribose) polymerase inhibitors (PARPi) is dictated by homologous recombination (HR) DNA repair and the abundance of lesions that trap PARP enzymes. It remains unclear, however, if the established role of PARP in promoting chromatin accessibility impacts viability in these settings. Using a CRISPR-based screen, we identified the PAR-binding chromatin remodeller ALC1/CHD1L as a key determinant of PARPi toxicity in HR-deficient cells. ALC1 loss reduced viability of breast cancer gene (BRCA)-mutant cells and enhanced sensitivity to PARPi by up to 250-fold, while overcoming several resistance mechanisms. ALC1 deficiency reduced chromatin accessibility concomitant with a decrease in the association of base damage repair factors. This resulted in an accumulation of replication-associated DNA damage, increased PARP trapping and a reliance on HR. These findings establish PAR-dependent chromatin remodelling as a mechanistically distinct aspect of PARPi responses and therapeutic target in HR-deficient cancers.


Assuntos
Cromatina/metabolismo , DNA Helicases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Recombinação Homóloga/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Proteína BRCA1/genética , Proteína BRCA2/genética , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Aberrações Cromossômicas , DNA Helicases/química , Reparo do DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/química , Epistasia Genética/efeitos dos fármacos , Instabilidade Genômica , Proteínas de Fluorescência Verde/metabolismo , Recombinação Homóloga/efeitos dos fármacos , Humanos , Metanossulfonato de Metila , Mutação/genética , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli Adenosina Difosfato Ribose/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Domínios Proteicos
20.
PLoS One ; 16(1): e0245370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33471852

RESUMO

BACKGROUND: Uremic pruritus (UP) is a common and frustrating symptom in patients receiving hemodialysis (HD). The majority of patients have mild to moderate itching of the skin, and a small percentage have severe itching, which seriously affects their quality of life and survival rate. However, little is known about factors that influence the intensity of itching in patients. METHODS: A cross-sectional study on uremic pruritus in male and female patients receiving HD was conducted in September 2019. This study included 148 eligible patients who received HD at the Blood Purification Center of Xinchang County People's Hospital, Zhejiang Province, China from March 2019 to June 2019. We collected general data consisted of age, sex, body mass index (BMI), place of residence, educational level, diabetes mellitus status and duration of HD; as well as clinical, biochemical indicators, including serum calcium (Ca), serum phosphorus (P), serum albumin (ALB), haemoglobin (Hb), serum intact parathyroid hormone (iPTH), pre-dialysis serum urea nitrogen (BUN), normalized protein catabolic rate (nPCR), urea nitrogen clearance index (KT/V), ferritin (FER) and pre-dialysis serum creatinine (sCR). We also assayed the inflammatory cytokine serum high sensitivity C-reactive protein (hs-CRP). The Five-Dimensional Itching Scale (5DIS) was used to evaluate the degree of skin itching (none, mild, moderate, or severe). We used multiple logistic regression to analyze influencing factors on the degree of skin itching in patients with UP. RESULTS: Of the 148 patients, 60 had uremic pruritus (incidence rate, 40.54%). These included 22 cases of mild skin itching (14.86%), 30 of moderate skin itching (20.27%), and 8 of severe skin itching (5.41%). Compared with uremia patients without skin pruritus, patients with UP had higher levels of iPTH, Hb, BUN, nPCR, and hs-CRP. The composition ratio showed significant differences between urban and rural patients with different degrees of skin itching (P = 0.017); moreover, the difference of iPTH and hs-CRP levels were statistically significant (P = 0.009 and < 0.001, respectively). Using no itching as a reference, multiple logistic regression analysis showed that as hs-CRP level increased, the patient's risks of mild skin itching (odds ratio [OR] = 1.740; 95% confidence interval [CI], 1.061-2.854; P = 0.028), moderate skin itching (OR = 2.8838 95% CI, 1.744-4.718; P < 0.001), and severe skin itching (OR = 9.440; 95% CI, 3.547-25.124; P < 0.001) all increased as well. Compared with urban residents, rural residents have a higher risk of moderate itching (OR = 3.869; 95% CI, 1.099-13.622; P = 0.035). CONCLUSION: Levels of hs-CRP were associated with the intensity of skin itching in patients with UP. Higher hs-CRP levels were closely related to severe skin itching. The relationship between the intensity of skin itching and the environment in maintenance hemodialysis patients needs further clarification.


Assuntos
Prurido/etiologia , Diálise Renal/efeitos adversos , Uremia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/sangue , Fatores de Risco , Uremia/sangue , Adulto Jovem
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