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1.
Soft Robot ; 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31584322

RESUMO

Soft actuators and robotics have been widely researched in recent years mainly due to their compliance to environments and safe interaction with humans. However, the need of tether and low energy efficiency of such actuators/robots has limited their practical applications. This article presents a novel tendon-driven soft actuator concept that has the property of self-pumping, called soft self-pumping actuator (SSPA) in this research. A SSPA is designed by assembling two soft pneumatic actuators (SPAs) face-to-face, whose air chambers are connected by two check valves. Actuation of the SSPA is achieved by tendons that allows precise and untethered control compared with traditional SPAs. The two chambers in the proposed actuators are precharged with air to a desired pressure to enlarge self-stiffness and to facilitate bending. When actuated, one chamber will be compressed and serve as a pump to inject its air into the other chamber, resulting in further bending of the actuator. The airflow involves energy transmission to help the intended actuation, thus improving energy efficiency. In experimental studies, differential chamber air pressure is found to reduce the force in initiating actuator bending. Experimental results have also shown that energy efficiency increase of up to 45% has been achieved compared with the same design but without air transmission. We believe that the proposed concept could lead to more novel designs of controllable and energy saving soft robots.

2.
Biomolecules ; 9(10)2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31547161

RESUMO

The herbicide fomesafen has the advantages of low toxicity and high selectivity, and the target of this compound is protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4). However, this herbicide has a long residual period and can have phytotoxic effects on succeeding crops. To protect maize from fomesafen, a series of thiazole phenoxypyridines were designed based on structure-activity relationships, active substructure combinations, and bioisosterism. Bioassays showed that thiazole phenoxypyridines could improve maize tolerance under fomesafen toxicity stress to varying degrees at a dose of 10 mg·kg-1. Compound 4i exhibited the best effects. After being treated by compound 4i, average recovery rates of growth index exceeded 72%, glutathione content markedly increased by 167% and glutathione S-transferase activity was almost 163% of fomesafen-treated group. More importantly, after being treated by compound 4i, the activity of PPO, the main target enzyme of fomesafen, recovered to 93% of the control level. The molecular docking result exhibited that the compound 4i could compete with fomesafen to bind with the herbicide target enzyme, which consequently attained the herbicide detoxification. The present work suggests that compound 4i could be developed as a potential safener to protect maize from fomesafen.

3.
Transbound Emerg Dis ; 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432620

RESUMO

Although Newcastle disease virus (NDV) has a worldwide distribution, some NDV genotypes have more regional geographical ranges within continents. In this study, we isolated a subgenotype XIIb NDV strain, Goose/CH/GD/E115/2017 (E115), from geese in Guangdong province, Southern China, in 2017. Phylogenetic analysis showed that E115 and six other NDVs from geese in China were grouped under subgenotype XIIb and were distinct from subgenotype XIIa, isolated from chickens in South Africa, and subgenotype XIId, isolated from chickens in Vietnam. To better understand the pathogenicity and transmission of the subgenotype XIIb NDVs from geese in Guangdong province, we inoculated chickens and geese with 106 EID50 of the E115 virus. Eight hours after inoculation, three naïve chickens and three naïve geese were co-housed with the infected chickens or geese to assess intraspecific and interspecific horizontal transmission of the E115 virus. The E115 virus induced significant clinical signs without mortality in chickens, while it was not pathogenic to geese. Intraspecific and interspecific horizontal transmission of the E115 virus was observed among chickens and geese via direct contact. Furthermore, although the current vaccines provided complete protection against disease in chickens after challenging them with the E115 virus, the virus could also be transmitted from vaccinated chickens to naïve contact chickens. Collectively, our findings highlight the need for avoiding the mixing of different bird species to reduce cross-species transmission and for surveillance of NDV in waterfowl.

4.
Ying Yong Sheng Tai Xue Bao ; 30(8): 2691-2698, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418194

RESUMO

Using an approach of spatial sequence instead of temporal succession, we investigated the variation and driving factors of soil microbial biomass and microbial entropy in desert grasslands across four different desertification stages (grassland, fixed dune, semi-fixed dune and mobile dune) in Yanchi County, Ningxia, China. The results showed that soil microbial biomass carbon, nitrogen and phosphorus reduced by 46.1%, 80.8% and 30.0% from grassland to mobile dunes, respectively. The soil microbial entropy (qMBC, qMBN, and qMBP) decreased but soil-microbial stoichiometry imbalance (C:Nimb, C:Pimb and N:Pimb) generally increased with the development of desertification. There were significantly positive relationship between soil microbial biomass nitrogen and C:Nimb, soil microbial biomass phosphorus and C:Pimb, while negative relationship between soil microbial biomass nitrogen and N:Pimb. The RDA result showed that soil ecological stoichiometry (C:N, C:P) had the strongest negative effect on soil microbial entropy carbon (qMBC). Soil microbial biomass and microbial entropy were significantly affected by desertification in desert grassland.


Assuntos
Pradaria , Microbiologia do Solo , Solo , Biomassa , Carbono , China , Conservação dos Recursos Naturais , Clima Desértico , Entropia , Nitrogênio
5.
Bioinspir Biomim ; 14(6): 066008, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31430730

RESUMO

Research on quadrupedal robots inspired by canids or felids have been widely reported and demonstrated. However, none of these legged robots can deal with difficult environments that include water, such as small lakes, streams, rain, mud, flooded terrain, etc. In this paper, we present for the first time a kinematic analysis and a hydrodynamic model of dog paddling motion in a robotic system. The quadrupedal paddling gait of dogs was first analyzed based on underwater video recording. Hydrodynamic drag force analysis in a paddling gait cycle was conducted for a prototype robotic dog. The prototype robotic dog was developed using four pre-charged pneumatics soft actuators with consideration of relative positions of CG (center of gravity) and CB (center of buoyancy) and their dynamic variation in paddling. It was found that such soft actuators have great potential in developing amphibious legged robots, because they are inherently water-tight, anti-rusty, simple in structural design, and have large hydrodynamic advantage due to their mostly hemi-cylindrical shape design. Trotting and paddling of the prototype robotic dog was also demonstrated. It is believed that our findings reported in this research will provide useful guidance in future development of amphibious robotic dogs.

6.
BMC Plant Biol ; 19(1): 302, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31291890

RESUMO

BACKGROUND: Nitrogen (N) and potassium (K) are two important mineral nutrients in regulating leaf photosynthesis. Studying the interactive effects of N and K on regulating N allocation and photosynthesis (Pn) of rice leaves will be of great significance for further increasing leaf Pn, photosynthetic N use efficiency (PNUE) and grain yield. We measured the gas exchange of rice leaves in a field experiment and tested different kinds of leaf N based on N morphology and function, and calculated the interactive effects of N and K on N allocation and the PNUE. RESULTS: Compared with N0 (0 kg N ha- 1) and K0 (0 kg K2O ha- 1) treatments, the Pn was increased by 17.1 and 12.2% with the supply of N and K. Compared with N0K0 (0 kg N and 0 kg K2O ha- 1), N0K120 (0 kg N and 120 kg K2O ha- 1) and N0K180 (0 kg N and 180 kg K2O ha- 1), N supply increased the absolute content of photosynthetic N (Npsn) by 15.1, 15.5 and 10.5% on average, and the storage N (Nstore) was increased by 32.7, 64.9 and 72.7% on average. The relative content of Npsn was decreased by 5.6, 12.1 and 14.5%, while that of Nstore was increased by 8.7, 27.8 and 33.8%. Supply of K promoted the transformation of Nstore to Npsn despite the leaf N content (Na) was indeed decreased. Compared with N0K0, N180K0 (180 kg N and 0 kg K2O ha- 1) and N270K0 (270 kg N and 0 kg K2O ha- 1), K supply increased the relative content of Npsn by 17.7, 8.8 and 7.3%, and decreased the relative content of Nstore by 24.2, 11.4 and 8.7% respectively. CONCLUSIONS: This study indicated the mechanism that K supply decreased the Na but increased the Npsn content and then increased leaf Pn and PNUE from a new viewpoint of leaf N allocation. The supply of K promoted the transformation of Nstore to Npsn and increased the PNUE. The decreased Nstore mainly resulted from the decrease of non-protein N. Combined use of N and K could optimize leaf N allocation and maintain a high leaf Npsn content and PNUE.


Assuntos
Nitrogênio/metabolismo , Oryza/fisiologia , Potássio/metabolismo , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento , Grão Comestível/fisiologia , Oryza/genética , Oryza/crescimento & desenvolvimento , Fotossíntese , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia
7.
J Vis Exp ; (149)2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31329179

RESUMO

Direct control of cellular defined molecular events is important to life science. Recently, studies have demonstrated that femtosecond laser stimulation can simultaneously activate multiple cellular molecular signaling pathways. In this protocol, we show that through coupling femtosecond laser into a confocal microscope, cells can be stimulated precisely by the tightly-focused laser. Some molecular processes that can be simultaneously observed are subsequently activated. We present detailed protocols of the photostimulation to activate extracellular signal regulated kinase (ERK) signaling pathway in Hela cells. Mitochondrial flashes of reactive oxygen species (ROS) and other mitochondrial events can be also stimulated if focusing the femtosecond laser pulse on a certain mitochondrial tubular structure. This protocol includes pretreating cells before photostimulation, delivering the photostimulation by a femtosecond laser flash onto the target, and observing/identifying molecular changes afterwards. This protocol represents an all-optical tool for related biological researches.

8.
Colloids Surf B Biointerfaces ; 181: 379-388, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170644

RESUMO

The study developed a simple, effective and inexpensive strategy for capturing, enriching and detecting circulating tumor cells (CTCs) by using folic acid (FA) as the targeting molecule instead of antibodies. This work constructed magnetic halloysite nanotubes (MHNTs) coated with biocompatible ß-cyclodextrin (CD), and conjugated to FA via a PEG-Ad linker, to specifically capture the FA receptor (FR)-overexpressing cancer cells. The capture efficiencies of MHNTs@ß-CD@Ad-PEG-FA for the Skov3, Hela and A549 cancer cells were 96.3%, 97.0% and 95.6% respectively. In addition, the nanoparticles were able to capture very low numbers of the cancer cells (25-500 cells/mL) from PBS and whole blood, as well as selectively capture the cancer cells over normal HEK 293 T cells. Furthermore, the captured cells were viable and grew normally in vitro, indicating the future potential of downstream analyses. This approach can be adapted for different CTCs, once the tumor-specific surface markers are identified and the efficacy of targeting ligands is established. Taken together, FA-conjugated MHNTs nanoparticles are a highly promising tool for isolating CTCs for the diagnosis and treatment of cancer.

9.
Infect Genet Evol ; 75: 103928, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31226331

RESUMO

Increasing numbers of hepatitis-hydropericardium syndrome (HHS) outbreaks associated with Fowl adenovirus 4 (FAdV-4) have been confirmed in several provinces of China since 2015, mainly affecting 3-5-week-old broiler chicks, resulting in significant losses to the poultry industry. However, little is currently known regarding the molecular epidemiology and host specificity of FAdV-4 associated with HHS in Southern China. In the present study, we isolated 37 FAdV-4 strains from 52 suspected cases of HHS (33 from broilers, one from a layer, two from ducks, and one from a mandarin duck) from Guangdong province during 2016 to 2017. All 37 FAdV-4 strains obtained showed 100% identity of hexon genes at the nucleotide level, and also showed 100% nucleotide sequence identities with strains obtained from other provinces such as Shandong, Zhejiang, and Anhui, which grouped into a FAdV-C cluster. To our knowledge, this represents the first report of an FAdV-4 strain (GZ1) from a mandarin duck with HHS. Experimental infection of the GZ1 strain via intramuscular injection led to a 100% mortality rate in 21-day-old specific pathogen-free chickens. These data indicate the possibility of the cross-species transmission of FAdV-4, highlighting the need for implementing strict biosecurity measures to avoid the mixing of different bird species.

10.
Sci Rep ; 9(1): 8387, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182773

RESUMO

Identifying influential spreaders in complex networks is crucial in understanding, controlling and accelerating spreading processes for diseases, information, innovations, behaviors, and so on. Inspired by the gravity law, we propose a gravity model that utilizes both neighborhood information and path information to measure a node's importance in spreading dynamics. In order to reduce the accumulated errors caused by interactions at distance and to lower the computational complexity, a local version of the gravity model is further proposed by introducing a truncation radius. Empirical analyses of the Susceptible-Infected-Recovered (SIR) spreading dynamics on fourteen real networks show that the gravity model and the local gravity model perform very competitively in comparison with well-known state-of-the-art methods. For the local gravity model, the empirical results suggest an approximately linear relation between the optimal truncation radius and the average distance of the network.

11.
J Med Chem ; 62(13): 6083-6101, 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31250638

RESUMO

Starting from our previously developed c-KIT kinase inhibitor CHMFL-KIT-8140, through a type II kinase inhibitor binding element hybrid design approach, we discovered a novel c-KIT kinase inhibitor compound 18 (CHMFL-KIT-64), which is potent against c-KIT wt and a broad spectrum of drug-resistant mutants with improved bioavailability. 18 exhibits single-digit nM potency against c-KIT kinase and c-KIT T670I mutants in the biochemical assay and displays great potencies against most of the gain-of-function mutations in the juxtamembrane domain, drug-resistant mutations in the ATP binding pocket (except V654A), and activation loops (except D816V). In addition, 18 exhibits a good in vivo pharmacokinetic (PK) profile in different species including mice, rats, and dogs. It also displays good in vivo antitumor efficacy in the c-KIT T670I, D820G, and Y823D mutant-mediated mice models as well as in the c-KIT wt patient primary cells which are known to be imatinib-resistant. The potent activity against a broad spectrum of clinically important c-KIT mutants combining the good in vivo PK/pharmacodynamic properties of 18 indicates that it might be a new potential therapeutic candidate for gastrointestinal stromal tumors.

12.
Colloids Surf B Biointerfaces ; 180: 429-440, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31085461

RESUMO

A novel glutathione-responsive (GSH-responsive) star-like amphiphilic polymer (C12H25)14-ß-CD-(S-S-mPEG)7 (denoted as CCSP) was designed for efficient antitumor drug delivery. The amphiphilic ß-cyclodextrin (ß-CD) self-polymerize in water to form a sphere with a diameter of 40-50 nm. The secondary hydroxyl groups of ß-CD were modified by dodecyl to form a hydrophobic core and the primary hydroxyl groups of ß-CD were decorated with PEG through disulfide bond to form a hydrophilic shell. Since the hydrophobic cavity of ß-CD was maintained, the hydrophobic core formed by dodecyl as well as cavity of ß-CD provided CCSP with a loading content as high as 39.6 wt%. Importantly, DOX@CCSP exhibited low drug leakage and negligible cytotoxicity in non-reductive physiological environment, while it showed rapid release and high cytotoxicity in reductive tumorous environment via the breakage of disulfide bond. In view of the above-mentioned advantages of DOX@CCSP nanocarriers such as high loading content, proper size, favorable stimulus-response release performance and low leakage, it is believed that CCSP may offer great potential to be used as an intelligent nanocarrier for anticancer drug delivery.

13.
Mol Ther Nucleic Acids ; 16: 675-685, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31121479

RESUMO

Dysregulated microRNAs (miRNAs) play crucial roles in the regulation of cancer stem cells (CSCs), and CSCs are closely associated with tumor initiation, metastasis, and recurrence. Here we found that miR-150-5p was significantly downregulated in CSCs of non-small-cell lung cancer (NSCLC) and its expression level was negatively correlated with disease progression and poor survival in patients with NSCLC. Inhibition of miR-150-5p increased the CSC population and sphere formation of NSCLC cells in vitro and stimulated NSCLC cell tumorigenicity and metastatic colonization in vivo. In contrast, miR-150-5p overexpression potently inhibited sphere-formed NSCLC cell tumor formation, metastatic colonization, and recurrence in xenograft models. Furthermore, we identified that miR-150-5p significantly inhibited wingless (Wnt)-ß-catenin signaling by simultaneously targeting glycogen synthase kinase 3 beta interacting protein (GSKIP) and ß-catenin in NSCLC cells. miR-150-5p also targeted high mobility group AT-hook 2 (HMGA2), another regulator of CSCs, and Wnt-ß-catenin signaling. The restoration of HMGA2 and ß-catenin blocked miR-150-5p overexpression-induced inhibition of CSC traits in NSCLC cells. These findings suggest that miR-150-5p functions as a CSC suppressor and that overexpression of miR-150-5p may be a novel strategy to inhibit CSC-induced metastasis and recurrence in NSCLC.

14.
J Med Chem ; 62(10): 5006-5024, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31046271

RESUMO

Gain-of-function mutations of c-KIT kinase play crucial pathological roles for the gastrointestinal stromal tumors (GISTs). Despite the success of imatinib as the first-line treatment of GISTs, dozens of drug-acquired resistant mutations emerge, and c-KIT T670I is one of the most common mutants among them. Although several kinase inhibitors are capable of overcoming the T670I mutant, none of them can achieve the selectivity over the c-KIT wild-type (wt), which also plays important roles in a variety of physiological functions such as hematopoiesis. Starting from axitinib, through fragment hybrid type II kinase inhibitor design approach, we have discovered a novel inhibitor 24, which not only exhibits potent activity to c-KIT T670I mutant but also achieves 12-fold selectivity over c-KIT wt. Compound 24 displays good antiproliferative effects against c-KIT T670I mutant-driven GIST cell lines (GIST-T1/T670I and GIST-5R) and also exhibits suitable in vivo pharmacokinetic profiles as well as dose-dependent antitumor efficacy. This study provides a proof of concept for developing a c-KIT mutant selective inhibitor that theoretically can render a better therapeutic window.

15.
Plant Cell Environ ; 42(7): 2231-2244, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30938459

RESUMO

Typical symptoms of potassium deficiency, characterized as chlorosis or withered necrosis, occur concomitantly with downregulated photosynthesis and impaired leaf water transport. However, the prominent limitations and mechanisms underlying the concerted decreases of leaf photosynthesis and hydraulic conductance are poorly understood. Monocots and dicots were investigated based on responses of photosynthesis and hydraulic conductance and their components and the correlated anatomical determinants to potassium deficiency. We found a conserved pattern in which leaf photosynthesis and hydraulic conductance concurrently decreased under potassium starvation. However, monocots and dicots showed two different hydraulic-redesign strategies: Dicots tended to show a decreased minor vein density, whereas monocots reduced the size of the bundle sheath and its extensions, rather than the minor vein density; both of these strategies may restrain xylem and outside-xylem hydraulic conductance. Additionally, potassium-deprived leaves developed with fewer mesophyll cell-to-cell connections, leading to a reduced area being available for liquid-phase flow. Further quantitative analysis revealed that mesophyll conductance to CO2 and outside-xylem hydraulic resistance were the major contributors to photosynthetic limitation and increased hydraulic resistance, at more than 50% and 60%, respectively. These results emphasize the importance of potassium in the coordinated regulation of leaf photosynthesis and hydraulic conductance through modifications of leaf anatomy.

17.
Nat Genet ; 51(4): 766, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30846878

RESUMO

In the version of this article initially published, the following grant numbers and recipients were missing from the Acknowledgements: XDB19000000 to H.J. and B.Z.; 81430066 and 31621003 to H.J.; 2017YFA0505500 to H.J.; and 15XD1504000 to H.J. The errors have been corrected in the HTML and PDF versions of the article.

18.
Appl Opt ; 58(7): 1855-1861, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30874228

RESUMO

Although the predicted lifetime of the classical 6000 h test given by Energy Star is taken as the normal lifetime of LED products in most research and applications, the aim of this study is to explore the error in lifetime prediction of LED lamps based on the 6000 h test. A non-accelerated aging test with 10 LED lamps is conducted for 20,000 h (from March 2016 to now) under room temperature, which is long enough for this kind of lamp reaching the real lifetime with the normalized luminous flux dropping to 70% naturally. At different aging periods, the correspondent lifetime of each sample is predicted by the lumen degradation, and the median lifetime τ0.5 of 10 samples is obtained by applying the Weibull distribution. Result shows that the τ0.5 of the real lifetime is 16,867 h in this work, and the aging time should be at least 9000 h to make the error in predicting the lifetime less than 3%. On the other hand, the Du'v' values of 0.006, 0.007, and 0.008 are taken as the three thresholds for predicting the lifetime by color shift. For the case of 0.008, the calculated shape parameter of 8.4 in Weibull distribution is similar with that of the real lifetime, which means the Du'v' of 0.008 for this kind of lamp gives the same failure mechanism as that of lumen degradation of 70%.

19.
Ying Yong Sheng Tai Xue Bao ; 30(2): 525-535, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30915805

RESUMO

This study aims to elucidate the effects of soil particle composition and fractal dimension on soil physical and chemical properties following sand-binding revegetation within straw checkerboard in south-eastern Tengger Desert. Three afforested plantations in the year of 2016 (i.e., 1 year), 2013 (i.e., 4 years) and 1987 (i.e., 30 years) were selected as study sites, with the adjacent mobile sand land as control (CK). We measured soil particle composition, soil fractal dimension, and the changes of soil physical and chemical properties. The relationship between soil particle composition, soil fractal dimension, and soil properties was analyzed. The results showed that contents of soil particle with the size of both 100-250 µm and 250-500 µm were greater than that of 50-100 µm, ranging from 42.5% to 80.1% and from 12.5% to 42.2% relative to that ranging from 0.2% to 20.8%. Contents of soil particle with the size of <2 µm and 2-50 µm were remarka-bly lower than that of 100-250 µm, 250-500 µm and 50-100 µm, ranging from 0 to 1.3% and from 0 to 22.7%, respectively. However, contents of soil particle at the size of 500-1000 µm was the lowest occupying <0.3% of soil particle composition. Soil particle with the size of <2 µm and 2-50 µm were found in the 30-year sites only. Soil particle distribution at the size of 50-100 µm, 100-250 µm, and 250-500 µm followed the order of 30 a>1 a>4 a>CK, 4 a>1 a>CK>30 a, and CK>1 a>4 a> 30a, respectively. Soil particle with the size of 500-1000 µm occupied little of soil particle composition, with no significant difference between each site. The fractal dimension of soil particles ranged from 0.54 to 2.59. There was significantly greater soil fractal dimension in 30 a in comparison to 4 a, 1 a and CK, with the intermediate values in 4 a and 1 a, and the lowest values in CK. There was a significantly positive correlation of fractal dimension of soil particles with soil particle content of clay, silt, very fine sand, and a significantly negative correlation of fractal dimension of soil particles with soil particle content of medium sand. Fractal dimension of soil particles was positively correlated with soil electrical conductivity, organic carbon, total nitrogen, and carbon-nitrogen ratio, but with no correlation with soil pH and soil water content. Soil particle content at the size of <2 µm, 2-50 µm, and 50-100 µm had a significant positive correlation with soil electrical conductivity, organic carbon, total nitrogen, and carbon-nitrogen ratio, whereas soil particle content at the size of 250-500 µm had a negative correlation with the former four soil indices and soil water content. In addition, there was a significant negative correlation of soil particle content at the size of 500-1000 µm with soil water content. It was concluded that the sand-binding reve-getation within straw checkerboard in Tengger Desert could facilitate the fine soil particles by ameli-orating stressful soil conditions. Long-term succession of revegetation on mobile sand land could enhance soil clay and silt content as well as soil fractal dimension, thus be beneficial for the improvement of soil physical and chemical properties and desertification control.


Assuntos
Fractais , Solo , China , Conservação dos Recursos Naturais , Tamanho da Partícula
20.
Cancer Biol Ther ; 20(6): 877-885, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894066

RESUMO

BCR fused ABL kinase is the critical driving oncogene for chronic myeloid leukemia (CML) and has been extensively studied as the drug discovery target in the past decade. The successful introduction of tyrosine kinase inhibitors (TKI) such as Imatinib, Dasatinib and Bosutinib has greatly improved the CML patient survival rate. However, upon the chronic treatment, a variety of TKI resistant mutants, such as the V299L mutant which has been found in more and more patients with the high-throughput sequencing technology, are observed, although the incidence is still considered rare compared to the more prevalent gatekeeper T315I mutant. However, with the progress of the precision medicine concept, the rare mutation (or the orphan drug target) has attracted more and more attention. Here we report a novel type II BCR-ABL kinase inhibitor, CHMFL-ABL-039, which not only displayed great potency (IC50: 7.9 nM) and selectivity (S score (1) = 0.02) against native ABL kinase among other kinases in the kinome, but also exhibited great potency (IC50: 27.9 nM) and selectivity against Imatinib-resistant V299L mutant among other frequently observed ABL kinase mutants. CHMFL-ABL-039 has demonstrated greater efficacies than Imatinib regarding to the anti-proliferation, inhibition of the signaling pathway, arrest of cell cycle progression, induction of apoptosis in vitro and suppression of the tumor progression in vivo in the native and V299L mutated BCR-ABL kinase-driven cells/xenograft models. It would be a useful pharmacological tool to study the TKI resistant ABL V299L mutant-mediated pathology and provide a potential precise treatment approach for this orphan CML subtype in the precision medicine era.

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