Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer and frequently diagnosed at an advanced stage. It is prone to develop unpredictable metastases even with proper treatment. ...Antiangiogenic therapy is the most effective medical treatment for metastatic ccRCC. Thus, exploration of novel approaches to inhibit angiogenesis and metastasis may potentially lead to a better therapeutic option for ccRCC. Among all the types of cancer, renal cancer samples exhibited the maximum upregulation of ApoC1 as referred to in the Oncomine database. The expression of ApoC1 was increased accompanied by ccRCC progression. A high level of ApoC1 was closely related to poor survival time in ccRCC patients. Furthermore, ApoC1 was over-expressed in the highly invasive ccRCC cells as compared to that in the low-invasive ccRCC cells. Besides, ApoC1 promoted metastasis of ccRCC cells via EMT pathway, whereas depletion of ApoC1 alleviated these effects. ApoC1 as a novel pro-metastatic factor facilitates the activation of STAT3 and enhances the metastasis of ccRCC cells. Meanwhile, ApoC1 in the exosomes were transferred from the ccRCC cells to the vascular endothelial cells and promoted metastasis of the ccRCC cells via activating STAT3. Finally, the metastatic potential of the ccRCC cells driven by ApoC1 was suppressed by DPP-4 inhibition. Our study not only identifies a novel ApoC1-STAT3 pathway in ccRCC metastasis but also provides direction for the exploration of novel strategies to predict and treat metastatic ccRCC in the future.
In this paper, we propose a new regular-shaped geometry-based stochastic model (RS-GBSM) for non-isotropic scattering wideband multiple-input multiple-output vehicle-to-vehicle (V2V) Ricean fading ...channels. By correcting the unrealistic assumption widely used in current RS-GBSMs, the proposed model can more practically study the impact of the vehicular traffic density on channel statistics for different time delays. From the proposed model, we derive the Doppler power spectral density (PSD) and find that highly dynamic Doppler spectrum appears for V2V channels. Excellent agreement is achieved between the derived Doppler PSD and measured data, demonstrating the utility of the proposed model. To combat the intercarrier interference (ICI) caused by highly dynamic Doppler spectrum in real orthogonal frequency division multiplexing based V2V systems, this paper proposes a new type of ICI cancellation scheme, named as precoding based cancellation (PBC) scheme. The proposed scheme can be easily implemented into real V2V systems with the same ICI mitigation performance as the current best ICI cancellation scheme that has high complexity. To further improve the performance of the proposed PBC scheme, a new phase rotation aided (PRA) method, namely constant PRA (CPRA) method, is proposed. Compared with the existing PRA method, the CPRA method has better performance and much less implementation complexity. Therefore, the proposed PBC scheme with the CPRA method is the best ICI cancellation scheme for real V2V systems.
Despite more effective chemotherapy combined with limb-salvage surgery for the osteosarcoma treatment, survival rates for osteosarcoma patients have stagnated over the past three decades due to the ...poor prognosis. Osteosarcoma cancer stem cells (OSCs) are responsible for the growth and metastasis of osteosarcoma. The existence of OSCs offers a theoretical explanation for therapeutic failures including tumor recurrence, metastasis, and drug resistance. Understanding the pathways that regulate properties of OSCs may shed light on mechanisms that lead to osteosarcoma and suggest better modes of treatment. In this study, we showed that the expression level of Kruppel-like factor 4 (KLF4) is highly associated with human osteosarcoma cancer stemness. KLF4-overexpressed osteosarcoma cells displayed characteristics of OSCs: increased sphere-forming potential, enhanced levels of stemness-associated genes, great chemoresistance to adriamycin and CDDP, as well as more metastasis potential. Inversely, KLF4 knockdown could reduce colony formation in vitro and inhibit tumorigenesis in vivo, supporting an oncogenic role for KLF4 in osteosarcoma pathogenesis. Furthermore, KLF4 was shown to activate the p38 MAPK signaling pathway to promote cancer stemness. Altogether, our studies uncover an essential role for KLF4 in regulation of OSCs and identify KLF4-p38 MAPK axis as a potential therapeutic target for osteosarcoma treatment.
The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term ...health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chinese on this Pacific island using genotype data of 591,048 SNPs in an initial freeze of 10,801 unrelated TWB participants. In addition to the North-South cline reported in other Han Chinese populations, we find the Taiwanese Han Chinese clustered into three cline groups: 5% were of northern Han Chinese ancestry, 79.9% were of southern Han Chinese ancestry, and 14.5% belonged to a third (T) group. We also find that this T group is genetically distinct from neighbouring Southeast Asians and Austronesian tribes but similar to other southern Han Chinese. Interestingly, high degree of LD between HLA haplotype A*33:03-B*58:01, an MHC allele being of pathological relevance, and SNPs across the MHC region was observed in subjects with T origin, but not in other Han Chinese. This suggested the T group individuals may have experienced evolutionary events independent from the other southern Han Chinese. Based on the newly-discovered population structure, we detect different loci susceptible to type II diabetes in individuals with southern and northern Han Chinese ancestries. Finally, as one of the largest dataset currently available for the Chinese population, genome-wide statistics for the 10,810 subjects are made publicly accessible through Taiwan View (https://taiwanview.twbiobank.org.tw/index; date last accessed October 14, 2016) to encourage future genetic research and collaborations with the island Taiwan.
Zn–iodine (I2) battery, as a promising energy storage device, especially under high I2 loading, is harassed by the shuttle effect of the soluble polyiodide intermediates. Herein, the bifunctional ...role of 2D carbon nanosponge with rich P‐dopant (4.2 at%) and large specific surface area (1966 m2 g−1) in anchoring I2/Ix− (x = 1, 3 or 5) and catalyzing their mutual conversion is reported. Both experiment and computational results reveal the transfer of electrons from the P‐doped site to iodine species, showing strong interfacial interaction. When being used as a host, it possesses high specific capture capacity for I2 (3.34 giodine g−1 or 1.6 mgiodine m−2) and Ix− (6.12 gtriiodide g−1 or 3.1 mgtriiodide m−2), which thus effectively suppresses the shuttle effect, supported by in situ UV–vis and Raman spectra. In addition to the strong interfacial interaction that favors iodine conversion, the P‐doped sites can also catalyze the conversion of I5− to I2, which is the rate‐determining step. Consequently, Zn–I2 batteries under a high I2 content (70 wt%) deliver high specific capacity (220.3 mAh g−1), superior Coulombic efficiency (>99%), and low self‐discharge rate; moreover, they can also operate steadily at 2 A g−1 with ignorable capacity decay for 10 000 cycles.
The movement protein (MP) and coat protein (CP) of tobamoviruses play critical roles in viral cell‐to‐cell and long‐distance movement, respectively. Cucumber green mottle mosaic virus (CGMMV) is a ...member of the genus Tobamovirus. The functions of CGMMV MP and CP during viral infection remain largely unclear. Here, we show that CGMMV MP can interact with CP in vivo, and the amino acids at positions 79–128 in MP are vital for the MP–CP interaction. To confirm this finding, we mutated five conserved residues within the residue 79–128 region and six other conserved residues flanking this region, followed by in vivo interaction assays. The results showed that the conserved threonine residue at the position 107 in MP (MPT107) is important for the MP–CP interaction. Substitution of T107 with alanine (MPT107A) delayed CGMMV systemic infection in Nicotiana benthamiana plants, but increased CGMMV local accumulation. Substitutions of another 10 conserved residues, not responsible for the MP–CP interaction, with alanine inhibited or abolished CGMMV systemic infection, suggesting that these 10 conserved residues are possibly required for the MP movement function through a CP‐independent manner. Moreover, two movement function‐associated point mutants (MPF17A and MPD97A) failed to cause systemic infection in plants without impacting on the MP–CP interaction. Furthermore, we have found that co‐expression of CGMMV MP and CP increased CP accumulation independent of the interaction. MP and CP interaction inhibits the salicylic acid‐associated defence response at an early infection stage. Taken together, we propose that the suppression of host antiviral defence through the MP–CP interaction facilitates virus systemic infection.
Cucumber green mottle mosaic virus movement protein and coat protein interaction facilitates viral systemic infection, possibly via inhibiting the salicylic acid‐associated defence response at an early stage.
To identify changes in brain activation patterns in bipolar disorder (BD) and unipolar depression (UD) patients.
Resting-state fMRI scans of 16 healthy controls, 17 BD and 16 UD patients were ...obtained. T-test of normalized regional homogeneity (ReHo) was performed in a voxel-by-voxel manner. A combined threshold of á = 0.05, minimum cluster volume of V = 10503 mm(3) (389 voxels) were used to determine ReHo differences between groups. In UD group, fMRI revealed ReHo increases in the left middle occipital lobe, right inferior parietal lobule, right precuneus and left convolution; and ReHo decreases in the left parahippocampalgyrus, right precentralgyrus, left postcentralgyrus, left precentralgyrus and left cingulated. In BD group, ReHo increases in the right insular cortex, left middle frontal gyrus, left precuneus, left occipital lobe, left parietal, left superior frontal gyrus and left thalamus; and ReHo decreases in the right anterior lobe of cerebellum, pons, right precentralgyrus, left postcentralgyrus, left inferior frontal gyrus, and right cingulate. There were some overlaps in ReHo profiles between UD and BD groups, but a marked difference was seen in the thalamus of BD.
The resting-state fMRI and ReHo mapping are a promising tool to assist the detection of functional deficits and distinguish clinical and pathophysiological signs of BD and UD.
Water quality prediction plays an important role in environmental monitoring, ecosystem sustainability, and aquaculture. Traditional prediction methods cannot capture the nonlinear and ...non-stationarity of water quality well. In recent years, the rapid development of artificial neural networks (ANNs) has made them a hotspot in water quality prediction. We have conducted extensive investigation and analysis on ANN-based water quality prediction from three aspects, namely feedforward, recurrent, and hybrid architectures. Based on 151 papers published from 2008 to 2019, 23 types of water quality variables were highlighted. The variables were primarily collected by the sensor, followed by specialist experimental equipment, such as a UV-visible photometer, as there is no mature sensor for measurement at present. Five different output strategies, namely Univariate-Input-Itself-Output, Univariate-Input-Other-Output, Multivariate-Input-Other(multi), Multivariate-Input-Itself-Other-Output, and Multivariate-Input-Itself-Other (multi)-Output, are summarized. From results of the review, it can be concluded that the ANN models are capable of dealing with different modeling problems in rivers, lakes, reservoirs, wastewater treatment plants (WWTPs), groundwater, ponds, and streams. The results of many of the review articles are useful to researchers in prediction and similar fields. Several new architectures presented in the study, such as recurrent and hybrid structures, are able to improve the modeling quality of future development.
Cardiovascular and cerebrovascular diseases (CCVD), an abnormal function of the heart, brain or blood vessels, are the biggest cause of deaths worldwide. Traditional Chinese medicine (TCM) holds a ...great promise for preventing such diseases in an integrative and holistic way. However, its systems-level characterization of drug–target associations is still unknown.
Here, we have constructed a computational approach by combining chemical predictors based on chemical structure, chemogenomics data linking compounds with pharmacological information, and a system biology functional data analysis and network reconstruction method.
The pharmacological system generated 58 bioactive ingredients from the Chinese herbal Radix Curcumae formula, and predicted 32 potential targets related to the CCVD. The results indicates that Radix Curcumae share the most common targets with Fructus Gardeniae (15), while less common targets with Moschus and Borneolum (8 and 1, respectively). Further integrated network shows that Radix Curcumae represents the principal component for the prevention of CCVD, and other three medicines serve as adjuvant ones to assist the effects of the principal component, which together probably display synergistic actions.
Our work successfully explains the mechanism of efficiency of Radix Curcumae formula for the prevention of CCVD, and meanwhile, predicts the potential targets of the Chinese medicines, which facilitates to elucidate the compatible mechanism of the complex prescription, i.e., “jun–chen–zuo–shi”, and provides basis for an alternative approach to investigate novel TCM formula on the network pharmacology level.
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Chalcones found in fruits and vegetables have promising cancer chemopreventive properties. This study attempts to identify the anticancer efficacies of chalcone flavokawain B (FKB) in the rhizomes of ...Alpinia pricei Hayata by examining key molecular events in non‐small‐cell lung cancer (A549) cells. Our results indicated that in human A549 cells, FKB (0–15 μg/ml) decreases cell viability and colony formation, dysregulates the Bax:B‐cell lymphoma 2 ratio and increases apoptotic DNA fragmentation. Mitochondrial (caspase‐9/‐3 and poly ADP ribose polymerase PARP) signaling was found to be involved in FKB‐induced apoptosis. In addition, FKB‐induced reactive oxygen species (ROS) generation, and N‐acetylcysteine attenuated FKB‐induced apoptotic cell death. Moreover, FKB triggered autophagy, as evidenced by the improved acidic vesicular organelle formation, lipidated light chain 3 (microtubule‐related light chain 3) accumulation, and ATG7 expression and the decreased mammalian target of rapamycin phosphorylation. Furthermore, FKB suppressed ROS‐mediated ATG4B expression. Inhibiting autophagy using 3‐methyladenine/chloroquine diminished FKB‐induced cell death, indicating that autophagy is triggered as a death mechanism by FKB. In summary, FKB has a crucial role in the execution and propagation of ROS‐mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.
Flavokawain B (FKB)‐induced autophagy was evidenced by a large accumulation of lipidated light chain 3 and acidic vesicular organelles. Mitochondrial (caspase‐9, capase‐3, and PARP) signaling was found to be critically involved in FKB‐induced apoptosis. FKB plays a crucial role in the execution and propagation of ROS‐mediated apoptotic and autophagic cell death of lung adenocarcinoma cells.
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