Prolyl-4-Hydroxylase α Subunit 2 Promotes Breast Cancer Progression and Metastasis by Regulating Collagen Deposition

BACKGROUND: Increased collagen deposition provides physical and biochemical signals to support tumor growth and invasion during breast cancer development. Therefore, inhibition of collagen synthesis and deposition has been considered a strategy to suppress breast cancer progression. Collagen prolyl-4-hydroxylase α subunit 2 (P4HA2), an enzyme hydroxylating proline residues in -X-Pro-Gly- sequences, is a potential therapeutic target for the disorders associated with increased collagen deposition. However, expression and function of P4HA2 in breast cancer progression are not well investigated. METHODS: Gene co-expression analysis was performed in the published microarray datasets to identify potential regulators of collagen I, III, and IV in human breast cancer tissue. Expression of P4HA2 was silenced by shRNAs, and its activity was inhibited by 1, 4-DPCA, a prolyl-4-hydroxylase inhibitor. Three-dimensional culture assay was used to analyze roles of P4HA2 in regulating malignant phenotypes of breast cancer cells. Reduced deposition of collagen I and IV was detected by Western blotting and immunofluorescence. Control and P4HA2-silenced breast cancer cells were injected into fat pad and tail vein of SCID mice to examine effect of P4HA2 on tumor growth and lung metastasis. RESULTS: Using gene co-expression analysis, we showed that P4HA2 was associated with expression of Col1A1, Col3A1, and Col4A1 during breast cancer development and progression. P4HA2 mRNA levels were significantly upregulated in breast cancer compared to normal mammary tissue. Increased mRNA levels of P4HA2 correlated with poor clinical outcome in breast cancer patients, which is independent of estrogen receptor status. Silencing P4HA2 expression or treatment with the P4HA inhibitor significantly inhibited cell proliferation and suppressed aggressive phenotypes of breast cancer cells in 3D culture, accompanied by reduced deposition of collagen I and IV. We also found that knockdown of P4HA2 inhibited mammary tumor growth and metastasis to lungs in xenograft models. CONCLUSION: These results suggest the critical role of P4HA2 in breast cancer progression and identify P4HA2 as a potential therapeutic target and biomarker for breast cancer progression

Neural Dysfunction Underlying Working Memory Processing at Different Stages of the Illness Course in Schizophrenia:A Comparative Meta-analysis

Schizophrenia (SCZ), as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk (CHR), first-episode psychosis (FEP), and long-term SCZ, using meta-analyses of functional magnetic resonance imaging (fMRI) studies. Following a systematic literature search, fifty-six whole-brain task-based fMRI studies (15 for CHR, 16 for FEP, 25 for long-term SCZ) were included. The separate and pooled neurofunctional mechanisms among CHR, FEP and long-term SCZ were generated by Seed-based d Mapping toolbox. The CHR and FEP groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of SCZ. Individuals with FEP showed lower activation in left inferior parietal lobule than those with long-term SCZ, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course

A Unified Model for Video Understanding and Knowledge Embedding with Heterogeneous Knowledge Graph Dataset

Video understanding is an important task in short video business platforms and it has a wide application in video recommendation and classification. Most of the existing video understanding works only focus on the information that appeared within the video content, including the video frames, audio and text. However, introducing common sense knowledge from the external Knowledge Graph (KG) dataset is essential for video understanding when referring to the content which is less relevant to the video. Owing to the lack of video knowledge graph dataset, the work which integrates video understanding and KG is rare. In this paper, we propose a heterogeneous dataset that contains the multi-modal video entity and fruitful common sense relations. This dataset also provides multiple novel video inference tasks like the Video-Relation-Tag (VRT) and Video-Relation-Video (VRV) tasks. Furthermore, based on this dataset, we propose an end-to-end model that jointly optimizes the video understanding objective with knowledge graph embedding, which can not only better inject factual knowledge into video understanding but also generate effective multi-modal entity embedding for KG. Comprehensive experiments indicate that combining video understanding embedding with factual knowledge benefits the content-based video retrieval performance. Moreover, it also helps the model generate better knowledge graph embedding which outperforms traditional KGE-based methods on VRT and VRV tasks with at least 42.36% and 17.73% improvement in HITS@10

miR-136-5p Regulates the Inflammatory Response by Targeting the IKKβ/NF-κB/A20 Pathway After Spinal Cord Injury

Background/Aims: miR-136-5p participates in recovery after spinal cord injury (SCI) via an unknown mechanism. We investigated the mechanism underlying the involvement of miR-136-5p in the inflammatory response in a rat model of SCI. Methods: Sprague-Dawley rat astrocytes were cultured in vitro to construct a reporter plasmid. Luciferase assays were used to detect the ability of miR-136-5p to target the IKKβ and A20 genes. Next, recombinant lentiviral vectors were constructed, which either overexpressed miR-136-5p or inhibited its expression. The influence of miR-136-5p overexpression and miR-136-5p silencing on inflammation was observed in vivo in an SCI rat model. The expression of IL-1β, IL-6, TNF-α, IFN-α, and related proteins (A20, IKKβ, and NF-κB) was detected. Results: In vitro studies showed that luciferase activity was significantly activated in the presence of the 3’ untranslated region (UTR) region of the IKKβ gene after stimulation of cells with miR-136-5p. However, luciferase activity was significantly inhibited in the presence of the 3’UTR region of the A20 gene. Thus, miR-136-5p may act directly on the 3’UTR regions of the IKKβ and A20 genes to regulate their expression. miR-136-5p overexpression promoted the production of related cytokines and NF-κB in SCI rats and inhibited the expression of A20 protein. Conclusion: Overexpression of miR-136-5p promotes the generation of IL-1β, IL-6, TNF-α, IFN-α, IKKβ, and NF-κB in SCI rats but inhibits the expression of A20. Under these conditions, inflammatory cell infiltration into the rat spinal cord increases and injury is significantly aggravated. Silencing of miR-136-5p significantly reduces the protein expression results described after miR-136-5p overexpression and ameliorates the inflammatory cell infiltration and damage to the spinal cord. Therefore, miR-136-5p might be a new target for the treatment of SCI

On Secrecy Performance of MISO SWIPT Systems With TAS and Imperfect CSI

In this paper, a multiple-input single-output (MISO) simultaneous wireless information and power transfer (SWIPT) system, including one base station (BS) equipped with multiple antennas, one desired single-antenna information receiver (IR), and N (N > 1) single-antenna energy-harvesting receivers (ERs) is considered. Assuming that the information signal to the desired IR may be eavesdropped by ERs if ERs are malicious, we investigate the secrecy performance of the target MISO SWIPT system when imperfect channel state information (CSI) is available and adopted for transmit antenna selection at the BS. Considering that each eavesdropping link experiences independent but not necessarily identically distributed Rayleigh fading, the closed-form expressions for the exact and the asymptotic secrecy outage probability, and the average secrecy capacity are derived and verified by simulations. Furthermore, the optimal power splitting factor is derived for each ER to realize the tradeoff between the energy harvesting and the information eavesdropping. Our results reveal the impact of the imperfect CSI on the secrecy performance of MISO SWIPT systems in the presence of multiple wiretap channels

Acidification oxidation reagent system optimization on coal seams and stimulation effect evaluation

China has abundant coalbed methane (CBM) resources, and most of them are low-permeability and tight reservoirs, with generally low production rate and small recovery factor. Existing technologies face great challenges to meet the demand on CBM in China. It is desirable to develop new methods to improve the production rate and enhance recovery factor. In addition to physical stimulation methods such as hydraulic fracturing and open-hole cave completion, the use of chemical methods to improve physical properties of coal reservoirs has also been a hot research topic in recent years. Coal reservoir acidification and oxidation technology can promote desorption of gas and enlarge permeability of reservoir. But for different coal rank coal reservoirs, the acidification and oxidation agents need to be optimized and their performance evaluated. Laboratory experiments are conducted to compare and analyze the physical properties coal samples from Baode, Mu’ai, and Xinjiang blocks, including coal rank, texture, macroscopic characteristics, quality, porosity, permeability, element, and mineral composition. The optimal concentration of hydrochloric acid is determined through pre-dissolution experiment of coal powder in acid solution. Then a five-factor and three-level orthogonal experiment for acid solution optimization is designed and performed by using Design-Expert software, which identifies the sensitive factors affecting the dissolution. For the coal samples in Baode, Mu’ai, and Xinjiang blocks, the oxidant types and the corresponding acidification and oxidation agent systems are optimized. Applying these acidification and oxidation agent systems to coal samples from Baode, Mu’ai, and Xinjiang blocks, the change of porosity, permeability, and wettability are compared and analyzed. Finally, through numerical simulation, the gas production is predicted for acidification and oxidation in typical well group in Block Mu’ai. Results show that the acid solution has the best dissolution at a concentration of hydrochloric acid of 3 mol/L to 4 mol/L; Top factors played in the experiment are soaking time, acid type, soaking temperature, coal sample type, and acid concentration, in descending order of importance; The optimal oxidant is a hydrogen peroxide solution with a concentration of 3%; the mixed acidification oxidant formula in Baode block is 10% HCl + 2% CH3COOH + 2% HF + 3% H2O2; The optimal mixed acidification oxidant formula in Mu’ai block is 8% HCl + 2% CH3COOH + 4% HF + 3% H2O2; the optimal mixed acidification oxidant formula in Xinjiang block is 12% HCl + 1% CH3COOH + 1% HF + 3% H2O2; The higher the coal rank, the greater the HF content in the optimal acidification oxidant system. Both acidification and oxidation improve the porosity and permeability of coal samples to some extent, and the improvement in low-rank coal is more significant than that in high-rank coal. Acidification and oxidation have different effects on the wettability of coal: Acidification increases the hydrophilicity of coal, whereas oxidation reduce the hydrophilicity of coal; and the hydrophilicity of coal samples treated by the optimized acidification and oxidation system is weakened. Reservoir simulation results show that acidification and oxidation lead to a recovery factor of 64.64% after 10 years of production, which is 19.72% higher than that without acidification and oxidation. The advantage of acidification and oxidation is 0.97% after 18 years of production. However, the acidification and oxidation saved 8 years of production time to achieve a close final recovery factor, which greatly reduces the operating costs. The optimized acidizing oxidation agent systems for CBM reservoirs with low, medium, and high ranks improved the desorption and permeability of the target reservoirs, and increase well production and recovery factor. This research provides technical support for stimulation practices of CBM reservoirs in the aforementioned blocks in China, as well as similar coal reservoirs in the world

Joint Pilot Allocation and Power Control to Enhance Max-Min Spectral Efficiency in TDD Massive MIMO Systems

International audienc

The value of tropical forests to the people who live there: an interview

Abstract Background The integration of DNA methylation and copy number alteration data promises to provide valuable insight into the underlying molecular mechanisms responsible for cancer initiation and progression. However, the generation and processing of these datasets are costly and time-consuming if carried out separately. The Illumina Infinium HumanMethylation450 BeadChip, initially designed for the evaluation of DNA methylation levels, allows copy number variant calling using bioinformatics tools. Results A substantial amount of Infinium HumanMethylation450 data across various cancer types has been accumulated in recent years and is a valuable resource for large-scale data analysis. Here we present MethCNA, a comprehensive database for genomic and epigenomic data integration in human cancer. In the current release, MethCNA contains about 10,000 tumor samples representing 37 cancer types. All raw array data were collected from The Cancer Genome Atlas and NCBI Gene Expression Omnibus database and analyzed using a pipeline that integrated multiple computational resources and tools. The normalized copy number aberration data and DNA methylation alterations were obtained. We provide a user-friendly web-interface for data mining and visualization. Conclusions The Illumina Infinium HumanMethylation450 BeadChip enables the interrogation and integration of both genomic and epigenomic data from exactly the same DNA specimen, and thus can aid in distinguishing driver from passenger mutations in cancer. We expect MethCNA will enable researchers to explore DNA methylation and copy number alteration patterns, identify key oncogenic drivers in cancer, and assist in the development of targeted therapies. MethCNA is publicly available online at http://cgma.scu.edu.cn/MethCNA

Indoor/outdoor relationship of PM2.5 concentration in typical buildings with and without air cleaning in Beijing

Indoor and outdoor particulate matter 2.5 (PM2.5) concentrations were monitored in seven sampling sites: basketball stadium, hotel, shopping centre, research centre, commercial office, apartment building and villa, to determine the indoor and outdoor relationship of PM2.5 mass concentration in the central area of Beijing from February 2014 to March 2014. The influence of four types of ventilation systems on indoor to outdoor (I/O) ratio of PM2.5 concentration was evaluated. The measured results show that the mean I/O ratio of the seven locations was 0.36 when the outdoor PM2.5 concentration was more than 150 mu g/m(3), and 1.1 when the outdoor PM2.5 concentration was less than 100 mu g/m(3), which implies that people&#39;s activities could be the most likely factor rather than outdoor sources for elevated indoor PM2.5 levels. The average I/O ratio was 0.69 for public buildings and 0.94 for residential homes, which illustrates that indoor PM2.5 concentrations could be dominated by outdoor sources for residential homes. Approximately 90% of the outdoor particles were removed in public buildings equipped with fan-coil unit with air cleaning plus fresh air system. The results demonstrate the need to improve indoor air quality by using a proper ventilation system with air cleaning.</p