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1.
J Am Chem Soc ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32003979

RESUMO

TDP-43 is a primary pathological hallmark protein of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, which may exist in the form of amyloid inclusions in the cells of patients. In addition to serving as a biomarker for these diseases, TDP-43 can also directly trigger neurodegeneration. We previously determined the amyloidogenic core region of TDP-43 (residues 311-360) and showed by solution NMR that this region includes two α-helices [(321-330) and (335-343)] in solution. We suggested that the helix-to-sheet structural transformation initiates TDP-43 aggregation. In the present study, X-ray diffraction shows that TDP-43 (311-360) aggregates adopt a cross-ß structure. Thioredoxin (Trx)-fused TDP-43 (311-360) can undergo liquid-liquid phase separation (LLPS) before fibrillation, suggesting that phase separation is an intermediate step before amyloid formation. Solid-state NMR (SSNMR), carried out to elucidate the structural changes of TDP-43 (311-360) at the atomic level, indicates five ß-strands of the amyloids formed, with the major two ß-strands contributed by the first helical region in the solution structure. The NMR evidence is also in support of the fibril having a parallel in-register conformation, implying a mechanism in which the helix-helix interactions in LLPS are converted into ß-strand parallel lateral association upon fibrillation. Our studies have assigned many key interresidue interactions that contribute to the stability of the fibril, including F316 with I318 and Q327 and W334 with A325, A326, A329, and S332. SSNMR with 1H detection reveals a unique close interaction between the indole Nε1-Hε1 of W334 and the side-chain carbonyl of Q343. This interaction could be a very important factor in initiating TDP-43 (311-360) folding/misfolding in LLPS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32027112

RESUMO

Bacterial infection is the main cause of implantation-failure worldwide and the importance of antibiotics on medical devices has been undermined due to antibiotic resistance. Antimicrobial hydrogels have emerged as a promising approach to combat infections associated with medical devices and wound healing. However, hydrogel coatings that simultaneously possess both antifouling and antimicrobial attributes are scarce. Herein we report an antimicrobial hydrogel that incorporates adhesion-inhibiting polyethylene glycol (PEG) and colony-suppressing chitosan (CS) as a dressing to combat bacterial infections. These two polymers have important environmentally benign characteristics including low toxicity, low volatility, and biocompatibility. Although hydrogels containing PEG and chitosan have been reported for applications in the fields of wound dressing, tissue repair, water purification, drug delivery and scaffolds for bone regeneration, there still has been no report on the application of CS/PEG hydrogel coatings in dental applications. Herein, this biointerface shows superior activity in early-stage adhesion-inhibition (98.8%, 5 h) and displays remarkably long-lasting colony-suppression activity (93.3%, 7 d). Thus, this novel nanomaterial, which has potential as a dual-functional platform with integrated antifouling and antimicrobial functions with excellent biocompatibility, might be used as a safe and effective antimicrobial coating in biomedical device applications.

3.
Nat Commun ; 11(1): 708, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32024842

RESUMO

The metabolic switch from oxidative phosphorylation to glycolysis is required for tumorigenesis in order to provide cancer cells with energy and substrates of biosynthesis. Therefore, it is important to elucidate mechanisms controlling the cancer metabolic switch. MTR4 is a RNA helicase associated with a nuclear exosome that plays key roles in RNA processing and surveillance. We demonstrate that MTR4 is frequently overexpressed in hepatocellular carcinoma (HCC) and is an independent diagnostic marker predicting the poor prognosis of HCC patients. MTR4 drives cancer metabolism by ensuring correct alternative splicing of pre-mRNAs of critical glycolytic genes such as GLUT1 and PKM2. c-Myc binds to the promoter of the MTR4 gene and is important for MTR4 expression in HCC cells, indicating that MTR4 is a mediator of the functions of c-Myc in cancer metabolism. These findings reveal important roles of MTR4 in the cancer metabolic switch and present MTR4 as a promising therapeutic target for treating HCC.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32039677

RESUMO

Accumulating evidence demonstrates that miRNAs serve as critical biomarkers in various complex human diseases. Thus, identifying potential miRNA-disease associations have become a hot research topic for providing better understanding of disease pathology, including cell carcinoma, cell proliferation and mevalonate pathway. Recently, based on various biological datasets, more and more computational prediction methods have been designed to uncover disease-related miRNAs for further experimental validation. Due to the fact that different limitations exist in previous computational methods, we proposed the model of Decision Template-based MiRNA-Disease Association prediction (DTMDA) to prioritize potential related miRNAs for diseases of interest. By integrating miRNA functional similarity network, miRNA Gaussian interaction profile kernel similarity network, two disease semantic similarity networks and disease Gaussian interaction profile kernel similarity network, we trained five multi-label K nearest neighbors-based core classifiers.

5.
Nat Commun ; 11(1): 875, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32054863

RESUMO

The emerging heterogeneous membranes show unprecedented superiority in harvesting the osmotic energy between ionic solutions of different salinity. However, the power densities are limited by the low interfacial transport efficiency caused by a mismatch of pore alignment and insufficient coupling between channels of different dimensions. Here we demonstrate the use of three-dimensional (3D) gel interface to achieve high-performance osmotic energy conversion through hybridizing polyelectrolyte hydrogel and aramid nanofiber membrane. The ionic diode effect of the heterogeneous membrane facilitates one-way ion diffusion, and the gel layer provides a charged 3D transport network, greatly enhancing the interfacial transport efficiency. When used for harvesting the osmotic energy from the mixing of sea and river water, the heterogeneous membrane outperforms the state-of-the-art membranes, to the best of our knowledge, with power densities of 5.06 W m-2. The diversity of the polyelectrolyte and gel makes our strategy a potentially universal approach for osmotic energy conversion.

6.
Pharm Dev Technol ; : 1-21, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32028816

RESUMO

In this study, RGD coated GEM liposomes were prepared by the emulsification-solvent evaporation method. The in vitro and in vivo characterizations were done to evaluate the feasibility of application. The mean particle size of the prepared liposomes was found to be 165.6 ± 15.7 nm. The entrapment efficiency and drug loading of the formulation were 82.4% ± 7.2% and 10.1% ± 1.4% respectively. The liposomes were negatively charged with a zeta potential of -25.8 mV. The surface morphology of RGD-GEM liposomes was spherical and smooth. After three months of storage at different conditions, lyophilized liposomes appeared to be stable since they showed no collapse or contraction. The Weibull model was the most appropriate kinetic model for RGD-GEM liposomes, showing that the release of GEM from the liposomes was in the manners of both dissolution and diffusion. In vivo, the additive cytotoxicity of RGD-GEM-LPs in our study was caused by the presence of RGD which is more effective in the treatment of breast cancer devoid of toxicity to normal cells. Liposomes could also significantly extend the role of GEM in vivo and showed higher bioavailability than solution.

7.
Sci Adv ; 6(5): eaax1464, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32064332

RESUMO

Many biological organisms can tune their mechanical properties to adapt to environments in multistable modes, but the current synthetic materials, with bistable states, have a limited ability to alter mechanical stiffness. Here, we constructed programmable organohydrogels with multistable mechanical states by an on-demand modular assembly of noneutectic phase transition components inside microrganogel inclusions. The resultant multiphase organohydrogel exhibits precisely controllable thermo-induced stepwise switching (i.e., triple, quadruple, and quintuple switching) mechanics and a self-healing property. The organohydrogel was introduced into the design of soft-matter machines, yielding a soft gripper with adaptive grasping through stiffness matching with various objects under pneumatic-thermal hybrid actuation. Meanwhile, a programmable adhesion of octopus-inspired robotic tentacles on a wide range of surface morphologies was realized. These results demonstrated the applicability of these organohydrogels in lifelike soft robotics in unconstructed and human body environments.

8.
Anal Chim Acta ; 1099: 119-125, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-31986268

RESUMO

γ-Glutamyl transpeptidase (GGT) has attracted considerable attention for its regulatory effect on glutathione metabolism in living organisms; further, its close relationship with physiological dysfunctions such as hepatitis and liver cancers has enhanced its applicability. Therefore, the accurate detection of GGT levels is particularly important for the early diagnosis of diseases. Thus, we herein report the development of a surface-enhanced Raman spectroscopic (SERS) probe, namely bis-s,s'-((s)-4,4'-thiolphenylamide-Glu) (b-(s)-TPA-Glu), that comprises of a γ-glutamyl moiety for detection of the GGT activity. In this system, detection was achieved by observing differences in the SERS spectral profiles of the b-(s)-TPA-Glu probe and its corresponding hydrolysis product that resulted from the catalytic action of GGT. This SERS probe system exhibited a high selectivity toward GGT due to a combination of its specific catalytic action and the distinctive spectroscopic fingerprint of the SERS technique. The developed SERS approach was also found to be approximately linear in the range of 0.2-200 U/L, and a limit of detection of 0.09 U/L was determined. Furthermore, the proposed SERS method was suitable for detection of the GGT activity of clinical serum samples and also for evaluation of the inhibitors of GGT. Consequently, this approach is considered to be a promising diagnostic and drug screening tool for GGT-associated diseases.

9.
Adv Mater ; : e1905298, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967709

RESUMO

2D layered metal-halide perovskites combine efficient exciton radiative recombination in crystal interior with long-distance free-carrier conduction at layer edges, which are promising candidates for realizing high-performance photovoltaic, light-emission and photodetection devices. The anisotropic electrical conductivity in layered perovskites imposes an additional requirement of orientational control for enabling favorable charge transport. However, rational fabrication of single-crystalline nanostructures with pure crystallographic orientation is still elusive. Herein, large-scale pure (101)-orientated 2D-perovskite single-crystalline nanowire arrays are realized by combining solvent engineering with the capillary-bridge lithography technique. Ordered nucleation at liquid-air interface and unidirectional growth along the dewetting direction are demonstrated by fluorescence microscopy and grazing-incidence X-ray scattering in discrete capillary bridges. In consideration of crystal interior exhibiting high resistance arising from the serial insulating organic barriers and ultrafast dissociation of excitons to generate long-lived free carriers at layer edges, ultrasensitive photodetectors are demonstrated with average responsivity exceeding 1.1 × 104 A W-1 and detectivity exceeding 9.1 × 1015 Jones.

10.
Clinics (Sao Paulo) ; 75: e1448, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31994614

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the relationship between the serum levels of calcitonin gene-related peptide (CGRP) and the prognosis of pediatric patients with severe pneumonia. METHODS: Children diagnosed with severe pneumonia (n=76) were stratified into the survival (n=58) and non-survival groups (n=18) according to their 28-day survival status and into the non-risk (n=51), risk (n=17) and high-risk (n=8) categories based on the pediatric critical illness score (PCIS). Demographic data and laboratory results were collected. Serum CGRP levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was generated to determine the cutoff score for high CGRP levels. RESULTS: Serum CGRP levels were significantly higher in the survival group than in the non-survival group and were significantly higher in the non-risk group than in the risk and high-risk groups. The ROC curve for the prognostic potential of CGRP yielded a significant area under the curve (AUC) value with considerable sensitivity and specificity. CONCLUSION: Our findings show that CGRP downregulation might be a diagnostic marker that predicts the prognosis and survival of children with severe pneumonia.

11.
Cell Death Dis ; 11(1): 26, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932578

RESUMO

Mitochondrial dysfunction leads to loss of renal function and structure; however, the precise mechanisms by which mitochondrial function can regulate renal fibrosis remain unclear. Proximal tubular cells (PTCs) prefer fatty acid oxidation as their energy source and dysregulation of lipid metabolism has been linked to tubulointerstitial fibrosis (TIF). Here, we demonstrated that mitochondrial uncoupling protein 2 (UCP2) regulates TIF through the stimulation of lipid deposition and extracellular matrix (ECM) accumulation. We show that UCP2 expression was increased in human biopsy sample and mouse kidney tissues with TIF. Moreover, UCP2-deficient mice displayed mitigated renal fibrosis in I/R-induced mouse model of TIF. Consistent with these results, UCP2 deficiency displayed reduced lipid deposition and ECM accumulation in vivo and in vitro. In UCP2-deficient PTCs, inhibition of TIF resulted from downregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator of lipid metabolism and ECM accumulation. Furthermore, we describe a molecular mechanism by which UCP2 regulates HIF-1α stabilization through regulation of mitochondrial respiration and tissue hypoxia during TIF. HIF-1α inhibition by siRNA suppressed lipid and ECM accumulation by restoration of PPARα and CPT1α, as well as suppression of fibronectin and collagen I expression in PTCs. In conclusion, our results suggest that UCP2 regulates TIF by inducing the HIF-1α stabilization pathway in tubular cells. These results identify UCP2 as a potential therapeutic target in treating chronic renal fibrosis.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31928224

RESUMO

Acute kidney injury (AKI) is a highly prevalent medical syndrome associated with high mortality and morbidity. Several types of cells , including epithelial cells, vascular endothelial cells, pericytes, and macrophages, participate in the development of AKI. Recently, renal fibroblasts were found to play an important role in the regulation of tubular injury, repair, and recovery after AKI. However, the mechanisms underlying fibroblast activation and proliferation during the progression of AKI remain unclear. In this study, we found many activated myo-fibroblasts located in the renal interstitium with an abundance of extracellular matrix (ECM) deposition following folic acid (FA)-induced AKI. The proliferative pattern of tubular epithelial cells and interstitial cells following acute injury was different, indicating that the proliferation of fibroblasts followed the proliferation of tubular epithelial cells. Furthermore, we observed that proliferative tubular epithelial cells preferred aerobic glycolysis as the dominating metabolic pathway in the progress of AKI. Lactate generated from injured tubules was taken up by interstitial fibroblasts in the later stages of AKI, which induced fibroblast activation and proliferation in vitro. Early inhibition of lactate production in tubules by glycolytic inhibitors suppressed fibroblast activation after FA-induced injury. Collectively, these results support the important role of fibroblasts in the development of AKI and suggest that lactate produced by glycolysis in tubular epithelial cells is a novel regulator of fibroblast activation and proliferation.

13.
Nat Protoc ; 15(2): 316-337, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31915388

RESUMO

Current visual biosensing methods, including colorimetric-based, fluorescence-based and chemiluminescence-based methods, are inappropriate for the hundreds of millions of people affected by color blindness and color weakness. Compared with these available methods, a droplet motion-based strategy might be a promising protocol for extension to a wider user base. Here we report a protocol for manipulating the hydrophobicity of DNA, which offers a droplet motion-based biosensing platform for the visual detection of small molecules (ATP), nucleic acids (microRNA) and proteins (thrombin). The protocol starts with target-triggered rolling-circle amplification that can readily generate short single-stranded DNA (ssDNA) fragments or long ssDNA. By exploiting macroscopic wetting behavior and molecular interaction, one can tailor the conformation of ssDNA on the water-oil interface to control the relevant DNA hydrophobicity. The wettability of DNA can be translated into visual signals via reading the sliding speed or the critical sliding angle. The time range for the entire protocol is ∼1 d, and the detection process takes ∼1 min.

14.
Int J Biol Macromol ; 149: 108-115, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31987952

RESUMO

Zedoary turmeric oil (ZTO) has a strong antitumor activity. However, its volatility, insolubility, low bioavailability, and difficulty of medication owing to oily liquid limit its clinical applications. Solid lipid nanoparticles can provide hydrophobic environment to dissolve hydrophobic drug and solidify the oily active composition to decrease the volatility and facilitate the medication. Chitosan has been widely used in pharmaceutics in recent years and coating with chitosan further enhances the internalization of particles by cells due to charge attract. Here, Chitosan (CS)-coated solid lipid nanoparticles (SLN) loaded with ZTO was prepared and characterized using dynamic laser scanner (DLS) and transmission electron microscope (TEM). The uptake and distribution of drug were evaluated in vitro and in vivo. The average sizes of ZTO-SLN and CS-ZTO-SLN were 134.3 ± 3.42 nm and 210.7 ± 4.59 nm, respectively. CS coating inverted the surface charge of particles from -8.93 ± 1.92 mV to +9.12 ± 2.03 mV. The liver accumulation of CS-ZTO-SLN was higher than ZTO-SLN (chitosan-uncoated particles) by analysis of tissue homogenate using HPLC, and the bioavailability of ZTO was also obviously improved. The results suggested that SLN coated with CS improved the features of ZTO formulation and efficiently deliver drug to the liver.

15.
ACS Appl Mater Interfaces ; 12(5): 6309-6318, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31934738

RESUMO

Damage to the responsive superwetting material by external stimuli during the responsive process has been a ticklish question in recent years. We overcome this barrier by imitating a peanut leaf and designing a humidity-responsive MIL-100 (Fe)/octadecylamine-coated stainless steel mesh (HR-MOS). Such a material shows superhydrophilicity when ambient humidity is higher than saturated humidity, while it shows superhydrophobicity and high adhesion to water when ambient humidity is lower than saturated humidity. The peanut leaf-like two-level nanostructure of MIL-100 (Fe) is speculated as the principal factor to bring about the binary synergy wettability of the material. Accordingly, the material can realize humidity-controlled separation of at least 12 types of emulsions along with satisfactory durability. The responsive condition of the material is mild and green, which does lower damage to the material and environment. This strategy is the first to realize humidity-responsive wettability transition and provides a novel approach for manually controlled environmental protection.

16.
Proc Natl Acad Sci U S A ; 117(4): 1890-1894, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31937663

RESUMO

The rapid removal of rain droplets at the leaf apex is critical for leaves to avoid damage under rainfall conditions, but the general water drainage principle remains unclear. We demonstrate that the apex structure enhances water drainage on the leaf by employing a curvature-controlled mechanism that is based on shaping a balance between reduced capillarity and enhanced gravity components. The leaf apex shape changes from round to triangle to acuminate, and the leaf surface changes from flat to bent, resulting in the increase of the water drainage rate, high-dripping frequencies, and the reduction of retention volumes. For wet tropical plants, such as Alocasia macrorrhiza, Gaussian curvature reconfiguration at the drip tip leads to the capillarity transition from resistance to actuation, further enhancing water drainage to the largest degree possible. The phenomenon is distinct from the widely researched liquid motion control mechanisms, and it offers a specific parametric approach that can be applied to achieve the desired fluidic behavior in a well-controlled way.

17.
J Am Chem Soc ; 142(6): 2738-2743, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31984729

RESUMO

The use of photocatalysis for water purification and environmental protection is of key interest. However, the reaction kinetics can be limited by the restricted accessibility of electron acceptor oxygen and the low adsorption of organic compounds-crucial factors underlying photocatalytic performance. Here we simultaneously alleviate these constraints via reaction interface microenvironment design using superhydrophobic (SHB) TiO2 nanoarrays as a model photocatalyst. The low surface energy and rough surface microstructure features of the SHB nanoarrays give the photocatalytic system long-range hydrophobic force and an air-water-solid triphase reaction interface. This simultaneously changes the adsorption model of organic compounds and the access pathway of oxygen, leading to a markedly enhanced adsorption capacity and higher interfacial oxygen levels. These synergistic qualities result in over 30-fold higher reaction kinetics versus a normal diphase system. In addition, this photocatalytic system is stable via repeated cycling. Our findings highlight the importance of reaction interface microenvironment design and reveal an effective path for the development of efficient photocatalysis systems.

18.
ChemSusChem ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31943838

RESUMO

The activity and selectivity of simple photocatalysts for CO2 reduction remain limited by the insufficient photophysics of the catalysts, as well as the low solubility and slow mass transport of gas molecules in/through aqueous solution. In this study, these limitations are overcome by constructing a triphasic photocatalytic system, in which polymeric carbon nitride (CN) is immobilized onto a hydrophobic substrate, and the photocatalytic reduction reaction occurs at a gas-liquid-solid (CO2 -water-catalyst) triple interface. CN anchored onto the surface of a hydrophobic substrate exhibits an approximately 7.2-fold enhancement in total CO2 conversion, with a rate of 415.50 µmol m-2 h-1 under simulated solar light irradiation. This value corresponds to an overall photosynthetic efficiency for full water-CO2 conversion of 0.33 %, which is very close to biological systems. A remarkable enhancement of direct C2 hydrocarbon production and a high CO2 conversion selectivity of 97.7 % are observed. Going from water oxidation to phosphate oxidation, the quantum yield is increased to 1.28 %.

19.
Angew Chem Int Ed Engl ; 59(6): 2465-2472, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-31788929

RESUMO

Multi-wall Sn/SnO2 @carbon hollow nanofibers evolved from SnO2 nanofibers are designed and programable synthesized by electrospinning, polypyrrole coating, and annealing reduction. The synthesized hollow nanofibers have a special wire-in-double-wall-tube structure with larger specific surface area and abundant inner spaces, which can provide effective contacting area of electrolyte with electrode materials and more active sites for redox reaction. It shows excellent cycling stability by virtue of effectively alleviating pulverization of tin-based electrode materials caused by volume expansion. Even after 2000 cycles, the wire-in-double-wall-tube Sn/SnO2 @carbon nanofibers exhibit a high specific capacity of 986.3 mAh g-1 (1 A g-1 ) and still maintains 508.2 mAh g-1 at high current density of 5 A g-1 . This outstanding electrochemical performance suggests the multi-wall Sn/SnO2 @ carbon hollow nanofibers are great promising for high performance energy storage systems.

20.
Adv Mater ; 32(4): e1904351, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793736

RESUMO

Biological ion channels and ion pumps with intricate ion transport functions widely exist in living organisms and play irreplaceable roles in almost all physiological functions. Nanofluidics provides exciting opportunities to mimic these working processes, which not only helps understand ion transport in biological systems but also paves the way for the applications of artificial devices in many valuable areas. Recent progress in the engineering of smart nanofluidic systems for artificial ion channels and ion pumps is summarized. The artificial systems range from chemically and structurally diverse lipid-membrane-based nanopores to robust and scalable solid-state nanopores. A generic strategy of gate location design is proposed. The single-pore-based platform concept can be rationally extended into multichannel membrane systems and shows unprecedented potential in many application areas, such as single-molecule analysis, smart mass delivery, and energy conversion. Finally, some present underpinning issues that need to be addressed are discussed.

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