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1.
Drug Deliv ; 26(1): 989-1001, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31571502

RESUMO

Noninvasive drug delivery is a promising treatment strategy for ocular posterior segment diseases. Many physiological and anatomical barriers of the eye considerably restrict effective diffusion of therapeutics to the target site. To overcome this problem, a novel cyclic arginine-glycine-aspartate (RGD) hexapeptide and penetratin (PEN) co-modified PEGylation polyamidoamine (PAMAM) was designed as a nanocarriers (NCs), and its penetrating and targeting abilities were evaluated. In this study, we show that PAMAM-PEG (reaction molar ratio 1:32) has a relatively high grafting efficiency and low cytotoxicity. The particle size was within the range of 15-20 nm after modification with RGD and PEN. Cellular uptake of RGD-modified NCs involved significant affinity toward integrin αvß3, which validated the targeting of neovasculature. An in vitro permeation study indicated that modification with PEN significantly improved penetration of the NCs (1.5 times higher). In vivo ocular distribution studies showed that, the NCs (modified with PEN or co-modified with RGD and PEN) were highly distributed in the cornea and retina (p < .001), and modification extended retinal retention time for more than 12 h. Therefore, these NCs appear to be a promising noninvasive ocular drug delivery system for ocular posterior segment diseases.

2.
J Am Chem Soc ; 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603326

RESUMO

DNA has been evolved to be a type of unparalleled materials for storing and transmitting genetic information. Much recent attention has been drawn to translate the natural specificity of DNA hybridization reactions for information storage in vitro. In this work, we developed a new type of tubular nucleic acids (TNAs) by condensing DNA chains on the surface of one-dimensional carbon nanotubes (CNTs). We find that DNA interacts with CNTs in a sequence-specific manner, resulting in different conformations including helix, i-motif and G-quadruplex. Atomic force microscopic (AFM) imaging revealed that TNAs exhibit distinct patterns with characteristic height and distance that can be exploited for two-dimensional encoding on CNTs. We further demonstrate the use of TNA-CNT for information storage with visual output. This noncanonical, DNA hybridization-free strategy provides a new route to DNA-based data storage.

3.
J Insect Sci ; 19(5)2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31587064

RESUMO

Rhinoncus sibiricus Faust, a major pest of buckwheat, has invaded the buckwheat cultivation areas of China for years. This pest was first found in Russia in 1940, causing great damage during the entire buckwheat-growing season. In China, there are few records on R. sibiricus, and studies regarding pest damage on buckwheat are unknown. The occurrence and distribution of this species in China is still not clear. We therefore conducted field surveys for 6 yr to identify the distribution range and the degree of pest damage caused by R. sibiricus in the buckwheat-planting areas of China and tested its preference for two Fagopyrum species in common garden experiments. The results showed that R. sibiricus had a larger distribution range in the Northern rather than the Southern part of China, and that pest damage was more serious in northern China. The pest preferred F. tataricum (Tartary buckwheat, Polygonales: Polygonaceae) over F. esculentum (Common buckwheat, Polygonales: Polygonaceae), but caused damage to both, indicating its potential for distribution in southern China. This study clarified the occurrence, distribution, and damage traits of R. sibiricus in the buckwheat cultivation areas of China, which will help explain the pest attack traits and inform strategies for pest control and prediction.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31566428

RESUMO

The transient receptor potential canonical 6 (TRPC6) channel and podocin are co-localized in the glomerular slit diaphragm as an important complex to maintain podocyte function. Gain of TRPC6 function and loss of podocin function induce podocyte injury. We have previously shown that high glucose induces apoptosis of podocytes by activating TRPC6; however, whether the activated TRPC6 can alter podocin expression remains unknown. Western blot, confocal microscopy, and scanning ion conductance microscopy were used to examine both the expression levels of TRPC6, podocin, and nephrin and the morphological change of podocytes in response to high glucose. High glucose increased the expression of TRPC6, but reduced the expression of podocin and nephrin, both in cultured human podocytes and in type 1 diabetic rat kidney. The decreased podocin was diminished in TRPC6 knockdown podocytes. High glucose elevated intracellular calcium in control podocytes, but not in TRPC6 knockdown podocytes. High glucose also elevated the expression of a tight junction protein, zonula occludens-1 (ZO-1) and induced the redistribution of ZO-1 and the loss of podocyte processes. These data together suggest that high glucose reduces the protein levels of podocin by activating TRPC6 and induces morphological changes of cultured podocytes.

5.
Sci Adv ; 5(9): eaau4506, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31598548

RESUMO

Tailored metal nanoclusters have been actively developed to manipulate light at the subwavelength scale for nanophotonic applications. Nevertheless, precise arrangement of molecules in a hot spot with fixed numbers and positions remains challenging. Here, we show that DNA origami metamolecules with Fano resonances (DMFR) can precisely localize single dye molecules and produce quantified surface-enhanced Raman scattering (SERS) responses. To enable tailored plasmonic permutations, we develop a general and programmable method for anchoring a set of large gold nanoparticles (L-AuNPs) on prescribed n-tuple docking sites of super-origami DNA frameworks. A tetrameric nanocluster with four spatially organized 80-nm L-AuNPs exhibits peak-and-dip Fano characteristics. The drastic enhancement at the wavelength of the Fano minimum allows the collection of prominent SERS spectrum for even a single dye molecule. We expect that DMFR provides physical insights into single-molecule SERS and opens new opportunities for developing plasmonic nanodevices for ultrasensitive sensing, nanocircuits, and nanophotonic lasers.

7.
Life Sci Alliance ; 2(5)2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31562192

RESUMO

Metabolic remodelling has emerged as critical for stem cell pluripotency; however, the underlying mechanisms have yet to be fully elucidated. Here, we found that the glycine cleavage system (GCS) is highly activated to promote stem cell pluripotency and during somatic cell reprogramming. Mechanistically, we revealed that the expression of Gldc, a rate-limiting GCS enzyme regulated by Sox2 and Lin28A, facilitates this activation. We further found that the activated GCS catabolizes glycine to fuel H3K4me3 modification, thus promoting the expression of pluripotency genes. Moreover, the activated GCS helps to cleave excess glycine and prevents methylglyoxal accumulation, which stimulates senescence in stem cells and during reprogramming. Collectively, our results demonstrate a novel mechanism whereby GCS activation controls stem cell pluripotency by promoting H3K4me3 modification and preventing cellular senescence.

8.
BMJ Open ; 9(9): e031020, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31481567

RESUMO

OBJECTIVES: This study aimed to investigate the experience of patients with wet age-related macular degeneration (wAMD) in treatment decision-making process. DESIGN: A descriptive qualitative study was designed by using semistructured interviews, and the data analysis was conducted with the thematic analysis approach. PARTICIPANTS AND SETTING: A convenient and purposive sample of 21 participants diagnosed with wAMD was recruited from May 2018 to September 2018. The study was conducted in the Eye Clinic of Southwest Hospital of Army Medical University in Chongqing located in the southwest of China. RESULTS: The mean age of the participants was 64.48 years (ranging 50-81 years), and the duration of the disease ranged from 6 months to 48 months. Four major themes were identified from the original data analysis. These themes included facing the darkness (choosing from light and darkness and living in pain), constraints on decision making (doctor-oriented decision making, inadequacy of options and time), weighing alternatives (family influence, financial burden and maintaining social function) and decision-making support (professional decision-making assistance and peer support). CONCLUSION: This is a qualitative study attempting to explore the patient experience of treatment decision making for wAMD disease in China. Previous literature has focused on treatment effect and symptoms, rather than the individual experience and the wide contexts from a sociocultural perspective. Further studies, such as cross-sectional studies, can be used to describe the status and determine the influencing factors of decision0making process, so as to develop an impact factor model of decision making and to formulate an intervention for patients with wAMD.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31482714

RESUMO

New Recombinant variants is a predominant challenge for preventing the spread of the HIV-1 epidemic. In this study, we confirmed a novel HIV-1 CRF07_BC/CRF55_01B recombinant form for the first time, which was isolated from a male patient in Jiangmen, China. The genomic sequence of the variant with four CRF55_01B segments inserted into the CRF07_BC backbone is 8510bp in length, extending from nucleotides 669 to 9293 according to the HXB2 genome. Specifically, the recombinant strain contains site mutations associated with drug resistance.

10.
Eur J Pharmacol ; 863: 172676, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31542488

RESUMO

Myelodysplastic syndromes (MDSs) are a group of clonal disorders of hematopoietic stem cells, resulting in ineffective hematopoiesis. Previous studies have reported that decitabine (DAC) plays an essential role in cell cycle arrest and cell death induction in multiple cell types. Nevertheless, the effect of decitabine on mesenchymal stromal cells derived from bone marrow of patients with MDSs is not completely clarified. Here, we explored the apoptotic and anti-proliferative effect of DAC on MSCs isolated from patients with MDSs. Treatment with DAC inhibited cell growth in a concentration- and time-dependent manner by inducing apoptosis. We found a positive relationship between cell death triggered by DAC in MSCs and the death receptor family members Fas and FasL mRNA and protein levels (***P < 0.00085), cleaved caspase (-3, -8, and -9) activity, and mitochondrial membrane potential reduction. Additionally, DAC-induced apoptosis was inhibited by Kp7-6, a FasL/Fas antagonist, indicating a crucial role of FasL/Fas, a cell death receptor, in mediating the apoptotic effect of DAC. DAC also induced reactive oxygen species (ROS) generation in MSCs derived from MDSs patients (*P = 0.038). Furthermore, N-acetyl-L-cysteine (NAC), a widely accepted ROS scavenger, efficiently reversed DAC-induced apoptosis by inhibiting ROS generation (***P < 0.00051) in mitochondria and restoring mitochondrial membrane potential. Furthermore, ROS production was found to be a consequence of caspase activation via caspases inhibition. Our data imply that DAC triggers ROS production in human MSCs, which serves as a crucial factor for mitochondrial membrane potential reduction, and DAC induces cell death prior to FasL/Fas stimulation.

11.
Nat Commun ; 10(1): 4130, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511532

RESUMO

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

12.
Anal Chem ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31539227

RESUMO

Ancient Chinese sauce glaze porcelain has recently received growing attention for the discovery of epsilon iron oxide (ε-Fe2O3) crystals in glaze. In this work, we first confirm the presence of ε-Fe2O3 microcrystals, in large quantiteis, in sauce glaze porcelain fired at the Qilizhen kiln in Jiangxi province during the Southern Song dynasty. We then employed focused ion beam scanning electron microscopy (FIB-SEM) to investigate the three-dimensional microstructure of ε-Fe2O3 microcrystals, which revealed three well-separated layers (labeled, respectively, as LY1, LY2, and LY3 from the glaze surface to inside) under the glaze surface. Specifically, LY1 consists of well-defined dendritic fractal structure with high ordered branches at micrometers scale, LY2 has spherical or irregular-shaped particles at nanometers scale, while LY3 consists of dendrites with four, six, or eight primary branches ranging from several nanometers to around 1 µm. Given these findings, we proposed a process for the possible growth of ε-Fe2O3 microcrystals in ancient Chinese sauce glaze.

13.
Nat Neurosci ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527803

RESUMO

The thalamus is the central communication hub of the forebrain and provides the cerebral cortex with inputs from sensory organs, subcortical systems and the cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive transcriptional analyses of retrogradely labeled thalamic neurons in adult mice, we identify three major profiles of thalamic pathways. These profiles exist along a continuum that is repeated across all major projection systems, such as those for vision, motor control and cognition. The largest component of gene expression variation in the mouse thalamus is topographically organized, with features conserved in humans. Transcriptional differences between these thalamic neuronal identities are tied to cellular features that are critical for function, such as axonal morphology and membrane properties. Molecular profiling therefore reveals covariation in the properties of thalamic pathways serving all major input modalities and output targets, thus establishing a molecular framework for understanding the thalamus.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31392819

RESUMO

Pathogen detection is growing in importance in the global health arena because of the high morbidity and mortality associated with bacterial blood stream infections. In this work, we present stochastic DNA walkers in droplets (SDwalker-Drop), a one-step, rapid, and super-multiplex method for ultrahigh-throughput bacterial detection. The SDwalkers, by exploiting cascade signal amplification, endow our analytical platform with fast analysis times and single-cell analysis ability. The autonomous and multiple-step walking behavior of the SDwalkers provides a super-multiplex droplet-encoding strategy by embedding intensity coded barcodes into a sequence of color-multiplexed barcodes. We realized a theoretical coding capacity of 83 -1=511 and achieved 20 distinct patterns for bacterial phenotype detection and identification. Moreover, our SDwalker-Drop platform could be readily integrated with a flow cytometer to afford a general approach for super-multiplexed, high-throughput biological assays and screening.

15.
Zhen Ci Yan Jiu ; 44(7): 476-80, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368276

RESUMO

OBJECTIVE: To investigate the effect of electroacupuncture (EA) plus treadmill exercise on the expression of peroxisome proliferator activated receptor γ coactivator 1α(PGC-1α), Irisin, AMP-activated protein kinase (AMPK) in skeletal muscle of diet-induced obesity (DIO) rats, so as to explore its mechanism underlying body reduction promotion. METHODS: Forty-two male SD rats were divided into normal diet (control, n=10), high fat diet (model), EA, treadmill exercise and EA plus treadmill exercise (combination) groups (n=8 in each of the latter 4 groups). The obesity model was established by feeding the rats with high fat diet. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST36) and "Tianshu" (ST25) for 30 min, 5 times per week for a total of 8 weeks. Rats of the treadmill exercise group were forced to perform exercise on a treadmill (16 m/min) for 30 min, 5 times per week for a total of 8 weeks. Rats in the combination group received the above-mentioned two methods. During the treatment, rats in the control group were fed with normal fodder, rats in other groups were fed with high fat fodder, and their body weight was measured once a week. The expression levels of PGC-1α, fibronectin type Ⅲ domain containing 5 (FNDC5), AMPK mRNA and protein of skeletal muscle were measured by quantitative real-time PCR and Western blot,respectively. RESULTS: After modeling, the body weight was significantly increased (P<0.05), and the expression levels of PGC-1α and FNDC5 mRNA and protein, AMPK mRNA and phosphorylated AMPK (p-AMPK) protein in the skeletal muscle were considerably decreased in the model group relevant to the control group (P<0.05). Following the treatment, the body weight was significantly down-regulated, while the expression levels of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA and p-AMPK protein were obviously up-regulated in the EA, treadmill exercise and combination groups relevant to the model group (P<0.05). The therapeutic effect of EA plus treadmill exercise was significantly superior to those of both simple EA and simple treadmill exercise in down-regulating the body weight, as well as in up-regulating the expression of PGC-1α and FNDC5 mRNAs and proteins, AMPK mRNA, and p-AMPK protein (P<0.05). CONCLUSION: Both EA and treadmill exercise can significantly increase the expression of PGC-1α, FNDC5 and p-AMPK in skeletal muscle of DIO rats, suggesting their efficacy in restoring fatty acid oxidation in skeletal muscle cells and improving mitochondrial function, which may contribute to their function in body reduction. The therapeutic effect of EA plus treadmill exercise is better than that of simple EA and simple treadmill exercise.


Assuntos
Eletroacupuntura , Proteínas Quinases Ativadas por AMP , Animais , Peso Corporal , Fibronectinas , Humanos , Masculino , Músculo Esquelético , Obesidade , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Ratos , Ratos Sprague-Dawley
16.
BMC Nephrol ; 20(1): 309, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390997

RESUMO

BACKGROUND: The benefits and risks of antiplatelet therapy for patients with chronic kidney disease (CKD) remain controversial. We undertook a systematic review and meta-analysis to investigate the effects of antiplatelet therapy on major clinical outcomes. METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library for trials published before April 2019 without language restriction. We included rrandomized controlled trials that involved adults with CKD and compared antiplatelet agents with controls. RESULTS: Fifty eligible trials that included at least one event were identified, providing data for 27773patients with CKD, including 4518 major cardiovascular events and 1962 all-cause deaths. Antiplatelet therapy produced a 15% (OR, 0.85; 95% CI 0.74-0.94) reduction in the odds of major cardiovascular events (P = 0.002), a 48% reduction for access failure events (OR, 0.52; 95% CI, 0.31-0.73), but had no significantly effect on all-cause death (OR, 0.87; 95% CI, 0.71-1.01) or kidney failure events (OR, 0.87; 95% CI, 0.32-1.55). Adverse events were significantly increased by antiplatelet therapy, including major (OR, 1.33; 95% CI, 1.11-1.59) or minor bleeding (OR, 1.66; 95% CI, 1.27-2.05). Among every 1000 persons with CKD treated with antiplatelet therapy for 12 months, 23 major cardiovascular events will be prevented while nine major bleeding events will occur. CONCLUSIONS: Major prevention with antiplatelet agents (cardiovascular events and access failure), might outweigh the risk of bleeding, and there seemed to be an overall net benefit. Individual evaluation and careful monitoring are required.

17.
J Am Chem Soc ; 141(30): 11938-11946, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31287680

RESUMO

The rapidly increasing need for systems biology stimulates the development of supermultiplex (SM) methods for simultaneously labeling multiple biomolecules/cells with distinct colors. Here we report the development of DNA-engineered fractal nanoplasmonic labels with ultrahigh brightness and photostability for SM imaging in single cells. These color-resolvable nanoplasmonic labels have a uniform size of ∼50 nm with an inner hollow gap of ∼1 nm. The outer shell morphology is highly tunable with the tip aspect ratio covering the range of δ = 0.29-1.66, which supports SM plasmonic imaging exceeding the conventional fluorescence multiplexing limit. We demonstrate the use of these SM labels for quantitative imaging of receptor-mediated endocytosis and intracellular transport of multiple protein-NP structures in a single cell in real time. This SM-plasmonic method sheds light on elucidating complex interactions among protein-NPs in nanotoxicology and facilitates the development of novel nanomedicines for diagnosis and therapy.

18.
Nat Protoc ; 14(8): 2416-2436, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31270509

RESUMO

Soft matter can serve as a template to guide the growth of inorganic components with well-controlled structural features. However, the limited design space of conventional organic and biomolecular templates restricts the complexity and accuracy of templated growth. In past decades, the blossoming of structural DNA nanotechnology has provided us with a large reservoir of delicate-framework nucleic acids with design precision down to a single base. Here, we describe a DNA origami silicification (DOS) approach for generating complex silica composite nanomaterials. By utilizing modified silica sol-gel chemistry, pre-hydrolyzed silica precursor clusters can be uniformly coated onto the surface of DNA frameworks; thus, user-defined DNA-silica hybrid materials with ~3-nm precision can be achieved. More importantly, this method is applicable to various 1D, 2D and 3D DNA frameworks that range from 10 to >1,000 nm. Compared to pure DNA scaffolds, a tenfold increase in the Young's modulus (E modulus) of these composites was observed, owing to their soft inner core and solid silica shell. We further demonstrate the use of solidified DNA frameworks to create 3D metal plasmonic devices. This protocol provides a platform for synthesizing inorganic materials with unprecedented complexity and tailored structural properties. The whole protocol takes ~10 d to complete.

19.
ACS Appl Mater Interfaces ; 11(30): 26704-26710, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31264833

RESUMO

Clinical need for treating allergic conjunctivitis (AC) is rapidly increasing. However, AC-relevant anti-inflammatory compounds are generally difficult to solubilize in water, thus limiting their therapeutic potential. Solubility-improved eye drop formulations of these compounds have poor bioavailability and a short retention time in ophthalmic tissues. Herein, we report a DNA/poly(lactic-co-glycolicacid) (PLGA) hybrid hydrogel (HDNA) for water-insoluble ophthalmic therapeutic delivery. PLGA pre-encapsulation enables loading of water-insoluble therapeutics. HDNA's porous structure is capable of sustained delivery of therapeutics. Dexamethasone (DEX), with demonstrated activities in attenuating inflammatory symptom in AC, was used as a model system. The designed HDNA hybrid hydrogels significantly improved the DEX accumulation and mediated the gradual DEX release in ophthalmic cells and tissues. Using the HDNA-DEX complexes, potent efficacy in two animal models of AC was acquired. Given this performance, demonstrable biocompatibility, and biodegradability of DNA hydrogel, the HDNA-based ophthalmic therapeutic delivery system enables novel treatment paradigms, which will have widespread applications in the treatment of various eye diseases.

20.
ACS Appl Mater Interfaces ; 11(34): 30640-30647, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31318203

RESUMO

Engineering biological interfaces represents a powerful means to improve the performance of biosensors. Here, we developed a DNA-engineered nanozyme interface for rapid and sensitive detection of dental bacteria. We employed DNA aptamer as both molecular recognition keys and adhesive substrates to functionalize the nanozyme. Utilizing different immobilization strategies and DNA designs, a range of DNA nanoscale biointerfaces were constructed to modulate enzymatic and biological properties of the nanozyme systems. These functional biointerfaces improved the accessibility of bacteria to the nanozyme surface, providing large signal change range at optimal DNA probe density. The DNA-functionalized nanozymes demonstrate a rapid, label-free, and highly sensitive direct colorimetric detection of Streptococcus mutans, with a detection limit of 12 CFU mL-1, as well as excellent discrimination from other dental bacteria. We demonstrate the use of this biological nanointerface for identifying dental bacteria in salivary samples, showing its potential in clinical prevention and diagnosis of dental diseases.

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