The clinical management of advanced hepatocellular carcinoma (HCC) is challenging due to its resistance to chemotherapy. In our work, we demonstrate that an antiparasitic drug atovaquone at clinically relevant concentrations is active against chemoresistant HCC. We show that atovaquone inhibits proliferation and induces apoptosis in not only HCC parental cells but also cells exposed to long time culture of chemotherapeutic agents. Consistently, the combination of atovaquone with cisplatin or doxorubicin achieved remarkably greater efficacy than single drug alone. Mechanistically, atovaquone overcomes HCC chemoresistance via supressing mitochondrial respiration and inducing oxidative stress. Atovaquone but not cisplatin or doxorubicin is ineffective in mitochondrial respiration-deficient rho 0, confirming mitochondria as a specific upstream target of atovaquone. Interestingly, we show that prolonged exposure of HCC cells to chemotherapeutic agents induces higher level of mitochondrial respiration, suggesting that tumors which develop chemoresistance after chemotherapy might be more dependent on mitochondrial respiration than primary tumors and explaining the sensitivity of chemoresistant HCC cells to atovaquone. We further show that atovaquone at tolerable does significantly inhibits chemoresistant HCC growth in mice throughout the duration of treatment. In line with in vitro data, we observe the increased oxidative stress in atovaquone-treated tumors. Our findings highlight the dependency of chemoresistant HCC on mitochondrial respiration and demonstrate that atovaquone is a potential drug to overcome HCC chemoresistance. (C) 2018 Elsevier Inc. All rights reserved.
Waigh, Thomas A.
Lu, Jian Ren
Mixed thermoreversible gels were successfully fabricated by the addition of a thermosensitive polymer, poly(N-isopropylacrylamide) (PNIPAM), to fibrillar nanostructures self-assembled from a short peptide I3K. When the temperature was increased above the lower critical solution temperature of the PNIPAM, the molecules collapsed to form condensed globular particles, which acted as cross-links to connect different peptide nanofibrils and freeze their movements, resulting in the formation of a hydrogel. Since these processes were physically driven, such hydrogels could be reversibly switched between the sol and gel states as a function of temperature. As a model peptide, I3K was formulated with PNIPAM to produce a thermoreversible sol-gel system with a transition temperature of similar to 33 degrees C, which is just below the body temperature. The antibacterial peptide of G(IIKK)(3)I-NH2 could be conveniently encapsulated in the hydrogel by the addition of the solution at lower temperatures in the sol phase and then increasing the temperature to be above 33 degrees C for gelation. The hydrogel gave a sustained and controlled linear release of G(IIKK)(3)I-NH2 over time. Using the peptide nanofibrils as three-dimensional scaffolds, such thermoresponsive hydrogels mimic the extracellular matrix and could potentially be used as injectable hydrogels for minimally invasive drug delivery or tissue engineering.
We demonstrated a novel single molecule - tetrakis(4-carboxyphenyl) porphyrin (TCPP) with a large pi-conjugated system as a high-performance organic anode of lithium batteries. It was found that this TCPP displayed relatively low solubility (<0.1 mg mL(-1)) in a 1 M LiDFOB/PC electrolyte, high reversible specific capacity (ca. 1200 mA h g(-1) at 358 mA g(-1)), excellent rate capability (548.4 mA h g(-1) at 8 A g(-1)) and superior cycling performance (capacity retention of 89% after 2500 cycles at 6 A g(-1)).
Two-dimensional (2D) transition metal dichalcogenides (TMDCs) possess interesting one-dimensional (1D) properties at its edges and inversion domain boundaries, where properties markedly different from the 2D basal plane, such as 1D metallicity and charge density waves, can be observed. Although 2D TMDCs crystals are widely grown by chemical vapor deposition (CVD), the fabrication of 1D TMDCs ribbons is challenging due to the difficulty to confine growth in only one dimension. Here we report the controlled growth of MoSe2 nanoribbons with an aspect ratio >100 by using prepatterned Se reconstructions on Au(100). Using scanning tunneling microscope and spectroscopy (STM/STS), the atomic and electronic structure of MoSe2 nanoribbons are studied. The ultranarrow ribbons show metallic behavior, while wider ribbons show a crossover from metallic to semiconducting behavior going from the edge to the center of the ribbon. The observed conductance modulations of the ultranarrow ribbons are attributed to 1D Moire pattern. Remarkably, it shows a different periodicity compared with the 2D Moire pattern in wider ribbons indicating that the ID system is softened due to the high ratio of edge to basal plane bonds. Further, we demonstrated that the nanoribbons are stable against ambient conditions, which suggests that ID TMDCs can be exploited for further applications.
ldeotype breeding plays a significant role in increasing rice yields. A number of representative plant-type models have been developed based on environmental conditions and yield potential. Identifying the effects of the ecological environment on plant-type models will provide insight into rice ideotype breeding, and will be useful to optimize cultivation management. The aim of this study was to analyze the effects of different ecological conditions on plant-type traits and yields, and to identify the relationships between plant-type models and yield components in different ecological environments. Two populations of filial generations Indica x Japonica rice were grown in Liaoning, Sichuan, Shanghai, and Guangdong in 2012. The grain yield showed a downward trend from high latitude to low latitude. The traits of the plant-types differed markedly among the four regions. Plant height was significantly greater in Sichuan and Liaoning than in Shanghai and Guangdong. Based on panicle length, the four regions were ranked as follows (longest panicle length to shortest) Shanghai > Sichuan > Guangdong > Liaoning. For flag leaf length, the ranking order was as follows (longest to shortest): Shanghai > Guangdong > Sichuan > Liaoning; for flag leaf width (widest to narrowest): Sichuan > Liaoning > Shanghai > Guangdong. The flag leaf angle was larger in Liaoning and Guangdong than in Shanghai and Sichuan. Panicle curvature was significantly influenced by genetic factors. The long-flag-leaf, curved-panicle type with characteristics of the super hybrid plant-type model showed significant vigor in Guangdong, Sichuan, and Shanghai. The short-flag-leaf, erect-panicle plant-type was more adaptable to the environmental conditions in Liaoning. There were strong correlations between some plant-type traits and yield components. However, the strengths and directions of the correlations were not completely consistent because of the different populations in different ecological environments. In ideotype breeding practice, the criteria should be regionalized based on local climatic and cultivation conditions. Such breeding should consider not only traits of "space", but also specific geoecotypes. (C) 2013 Published by Elsevier B.V.
The development of techniques for real-time monitoring of water quality is of great importance for effectively managing inland water resources. In this study, we first analyzed the absorption and fluorescence properties in a large subtropical reservoir and then used a chromophoric dissolved organic matter (CDOM) fluorescence monitoring sensor to predict several water quality parameters including the total nitrogen (TN), total phosphorus (TP), chemical oxygen demand (COD), dissolved organic carbon (DOC), and CDOM fluorescence parallel factor analysis (PARAFAC) components in the reservoir. The CDOM absorption coefficient at 254 nm (a(254)), the humic-like component (C1), and the tryptophan-like component (C3) decreased significantly along a gradient from the northwest to the lake center, northeast, southwest, and southeast region in the reservoir. However, no significant spatial difference was found for the tyrosine-like component (C2), which contributed only four marked peaks. A highly significant linear correlation was found between the a(254) and CDOM concentration measured using the CDOM fluorescence sensor (r(2)=3D 0.865, n =3D 76, p < 0.001), indicating that CDOM concentrations could act as a proxy for the CDOM absorption coefficient measured in the laboratory. Significant correlations were also found between the CDOM concentration and TN, TP, COD, DOC, and the maximum fluorescence intensity of C1, suggesting that the real-time monitoring of CDOM concentrations could be used to predict these water quality parameters and trace the humic-like fluorescence substance in clear aquatic ecosystems with DOC <2 mg/L and total suspended matter (TSM) concentrations <15 mg/L. These results demonstrate that the CDOM fluorescence sensor is a useful tool for on-line water quality monitoring if the empirical relationship between the CDOM concentration measured using the CDOM fluorescence sensor and the water quality parameters is calibrated and validated.=20
In contrast to extensively studied defects in traditional materials, we report here a systematic investigation of the formation mechanism of intrinsic defects in self-assembled peptide nanostructures. The Monte Carlo simulations with our simplified dynamic hierarchical model revealed that the symmetry breaking of layer bending mode at the two ends during morphological transformation is responsible for intrinsic defect formation, whose microscopic origin is the mismatch between layer stacking along the side-chain direction and layer growth along the hydrogen bond direction. Moreover, defect formation does not affect the chirality of the self-assembled structure, which is determined by the initial steps of the peptide self-assembly process. (C) 2015 Author(s).
Climatic changes in Arid Central Asia (ACA) over the past two millennia have been widely concerned. However, less attention has been paid to those in the High Central Asia (HCA), where the Asian water tower nurtures the numerous oases by glacier and/or snow melt. Here, we present a new reconstruction of the temperature and precipitation change over the past two millennia based on grain size of a well-dated glacial lake sediment core in the central of southern Tianshan Mountains. The results show that the glacial lake catchment has experienced cold-wet climate conditions during the Dark Age Cold Period (similar to 300-600 AD; DACP) and the Little Ice Age (similar to 1300-1870 AD; LIA), whereas warm-dry conditions during the Medieval Warm Period (similar to 700-1270 AD; MWP). Integration of our results with those of previously published lake sediment records, stalagmite delta O-18 records, ice core net accumulation rates, tree-ring based temperature reconstructions, and mountain glacier activities suggest that there has a broadly similar hydroclimatic pattern over the HCA areas on centennial time scale during the past two millennia. Comparison between hydroclimatic pattern of the HCA and that of the ACA areas suggests a prevailing 'warm-dry and cold-wet' hydroclimatic pattern over the whole westerlies-dominated central Asia areas during the past two millennia. We argue that the position and intensity of the westerlies, which are closely related to the phase of the North Atlantic Oscillation (NAO), and the strength of the Siberian High pressure (SH), could have jointly modulated the late Holocene central Asia hydroclimatic changes. (C) 2017 Elsevier Ltd and INQUA. All rights reserved.
A series of surfactant-like peptides have been designed for inducing DNA condensation, which are all comprised of the same set of amino acids in different sequences. Results from experiments and molecular dynamics simulations show that the peptide's self-assembly and DNA-interaction behaviors can be well manipulated through sequence variation. With optimized pairing modes between the beta-sheets, the peptide of I(3)V(3)A(3)G(3)K(3) can induce efficient DNA condensation into virus-mimicking structures. The condensation involves two steps; the peptide molecules first bind onto the DNA chain through electrostatic interactions and then self-associate into beta-sheets under hydrophobic interactions and hydrogen bonding. In such condensates, the peptide beta-sheets act as scaffolds to assist the ordered arrangement of DNA, mimicking the very nature of the virus capsid in helping DNA packaging. Such a hierarchy affords an extremely stable structure to attain the highly condensed state and protect DNA against enzymatic degradation. Moreover, the condensate size can be well tuned by the DNA length. The condensates with smaller sizes and narrow size distribution can deliver DNA efficiently into cells. The study helps not only for probing into the DNA packaging mechanism in virus but also delineating the role of peptide self-assembly in DNA condensation, which may lead to development of peptide-based gene vectors for therapeutic applications.
A Quantum Key Distribution (QKD) network can allow multi-user communication via secure key. Moreover, by actively switching communication nodes, one can achieve high key transmission rate for the selected nodes. However, the polarization properties of different fiber path are different and these properties also randomly drift over time. Therefore, polarization recovery after the switching and auto-compensation during key transmission are critical for the QKD network. In this work, we use programmable polarization controllers to implement polarization recovery and auto-compensation in the QKD network. We will also discuss its time limitation and future improvement.
Nanozymes have been extensively investigated to imitate protein enzymes in biomimetic chemistry and the identification of the active site is believed to be the pre-requisite before one can effectively regulate their activity. Herein, ultrathin NiCo LDH nanosheets are synthesized via a fast co-precipitation at room temperature and can be stably dispersed in water without any additives of surfactants or organic solvents. By tuning the ratio between Ni and Co in LDH nanosheets, the activity is tuned and their peroxidase-like activity is determined by Co sites that show higher affinity to both 3,3 ',5,5 '-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) due to the strong Lewis acidity of Co3+ and the low redox potential of Co3+/Co2+. Together with their small crystallite size, ultra-thin thickness and tunable composition, NiCo LDH is used as a nanozyme for highly sensitive colorimetric detection of H2O2 and the limit of detection (LOD) reaches 0.48 mu M.
Strong supramolecular interactions, which induced tight packing and rigid molecules in crystals of cyano substituent oligo(para-phenylene vinylene) (CN-DPDSB), are the key factor for the high luminescence efficiency of its crystals; opposite to its isolated molecules in solution which have very low luminescence efficiency.
We investigated the prevalence of plasmid-mediated quinolone resistance (PMQR) qnr genes by the polymerase chain reaction (PCR) in antibiotic-resistant bacteria isolates collected from aquatic environments in Jinan during 2 years (2008.3-2009.11). Genes were identified to variant level by PCR restriction fragment length polymorphism analysis or sequencing. qnrA1, qnrB2, qnrB4, qnrB6, qnrB9, qnrS1, and the new qnrB variant qnrB26 were detected in 31 strains from six genera (Klebsiella spp., Escherichia coli, Enterobacter spp., Proteus spp., Shigella spp., and Citrobacter spp.), four of which contained double qnr genes. Other PMQR genes, aac(6)-Ib-cr and qepA, were found in 12 (38.7%) and 5 (16.1%) of 31 isolates, respectively; while qepA was found in Shigella spp. for the first time. Eight types of -lactamase genes and eight other types of resistance genes were also present in the 31 qnr-positive isolates. The detection rate for five -lactamase genes (bla(TEM), bla(CTX), ampR, bla(DHA), and bla(SHV)) was >45%. Class 1 integrons and complex class 1 integrons were prevalent in these strains, which contained 15 different gene cassette arrays and 5 different insertion sequence common region 1 (ISCR1)-mediated downstream structures. qnrA1, qnrB2, and qnrB6 were present in three ISCR1-mediated downstream structures: qnrA1-ampR, sapA-like-qnrB2, and sdr-qnrB6. We also analyzed the horizontal transferability of PMQR genes and other resistance determinants. The qnr genes and some integrons and resistance genes from 18 (58.1%) of the 31 qnr-positive strains could be transferred to E. coli J53 Azi(R) or E. coli DH5 recipient strains using conjugation or transformation methods. The results showed that a high number of qnr genes were associated with other resistance genes in aquatic environments in Jinan. This suggests that we should avoid over-using antibiotics and monitor aquatic environments to control the spread of antibiotic resistance genes.
The present study aimed to observe the expression of circadian gene clock circadian regulator (CLOCK) in ovarian cancer cells and the effects of circadian gene CLOCK on cis-dichlorodiamine platinum (cisplatin) resistance in ovarian cancer cells. The expression of CLOCK mRNA and protein in cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were detected by quantitative polymerase chain reaction and western blot assay. Cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were treated with different concentrations of cisplatin for 48 h, and the expression of hCLOCK protein in the two types of cells was detected by western blot assay. RNA interference method was used to knock down the expression of CLOCK in cisplatin-resistant CP70 cells. Subsequently, the cisplatin-resistant CP70 cells were treated with cisplatin. The proliferation of cisplatin-resistant CP70 cells was observed following treatment with cisplatin. The expression of CLOCK mRNA was significantly higher in cisplatin-resistant CP70 cells (1.58 +/- 0.49) compared with cisplatin-sensitive A2780 cells (0.44 +/- 0.13) (P<0.01). Western blot assay results demonstrated that the expression of CLOCK protein was significantly greater in the cisplatin-resistant CP70 cells (1.47 +/- 0.34) compared with the cisplatin-sensitive A2780 cells (0.48 +/- 0.15) (P<0.01). Following the treatment of A2780 and CP70 cells with cisplatin, CLOCK protein expression increased with an increased concentration of cisplatin, in a dose-dependent manner (P<0.01). Following the knockdown of CLOCK in cisplatin-resistant CP70 cells by RNA interference, cisplatin treatment was able to significantly inhibit the proliferation of cells and induce apoptosis (P<0.01). The expression of circadian gene CLOCK in ovarian cancer cells was strongly associated with cisplatin resistance. The upregulation of circadian gene CLOCK in ovarian cancer cells may reduce its sensitivity to cisplatin treatment.
Purpose: Adenoid hypertrophy is a pathological hyperplasia of adenoids and may cause snoring, apnea, and impede breathing during sleep. In clinical practice, radiologists diagnose the severity of adenoid hypertrophy by measuring the ratio of adenoid width (A) to nasopharyngeal width (N) according to the lateral cephalogram, which indicates the locations of four keypoints. The entire diagnostic process is tedious and time-consuming due to the acquisition of A and N. Thus, there is an urgent need to develop computer-aided diagnostic tools for adenoid hypertrophy. Methods: In this paper, we first propose the use of deep learning to solve the problem of adenoid hypertrophy classification. Deep learning driven by big data has developed greatly in the image processing field. However, obtaining a large amount of training data is hard, making the application of deep learning to medical images more difficult. This paper proposes a keypoint localization method to incorporate more prior information to improve the performance of the model under limited data. Furthermore, we design a novel regularized term called VerticalLoss to capture the vertical relationship between keypoints to provide prior information to strengthen the network performance. Results: To evaluate the performance of our proposed method, we conducted experiments with a clinical dataset from the First Affiliated Hospital of Anhui Medical University consisting of a total of 688 patients. As our results show, we obtained a classification accuracy of 95.6%, a macro F1-score of 0.957, and an average AN ratio error of 0.026. Furthermore, we obtained a macro F1-score of 0.89, a classification accuracy of 94%, and an average AN ratio error of 0.027 while using only half of the data for training. Conclusions: The study shows that our proposed method can achieve satisfactory results in the task of adenoid hypertrophy classification. Our approach incorporates more prior information, which is especially important in the field of medical imaging, where it is difficult to obtain large amounts of training data. (C) 2020 American Association of Physicists in Medicine
Waigh, Thomas A.
Lu, Jian R.
Peptide amphiphiles readily self-assemble into a variety of nanostructures, but how molecular architectures affect the size and shape of the nanoaggregates formed is not well understood. From a combined TEM and AFM study of a series of cationic peptide surfactants A(m)K (m = 3, 6, and 9), we show that structural transitions (sheets, fibers/worm-like micelles, and short rods) can be induced by increasing the length of the hydrophobic peptide region. The trend can be interpreted using the molecular packing theory developed to describe surfactant structural transitions, but the entropic gain, decreased CAC, and increased electrostatic interaction associated with increasing the peptide hydrophobic chain need to be taken into account appropriately. Our analysis indicates that the trend in structural transitions observed from A(m)K peptide surfactants is opposite to that obtained from conventional monovalent ionic surfactants. The outcome reflects the dominant role of hydrophobic interaction between the side chains opposed by backbone hydrogen bonding and electrostatic repulsion between lysine side chains.