miR+Pathway: the integration and visualization of miRNA and KEGG pathways.

miRNAs represent a type of noncoding small molecule RNA. Many studies have shown that miRNAs are widely involved in the regulation of various pathways. The key to fully understanding the regulatory function of miRNAs is the determination of the pathways in which the miRNAs participate. However, the major pathway databases such as KEGG only include information regarding protein-coding genes. Here, we redesigned a pathway database (called miR+Pathway) by integrating and visualizing the 8882 human experimentally validated miRNA-target interactions (MTIs) and 150 KEGG pathways. This database is freely accessible at http://www.insect-genome.com/miR-pathway. Researchers can intuitively determine the pathways and the genes in the pathways that are regulated by miRNAs as well as the miRNAs that target the pathways. To determine the pathways in which targets of a certain miRNA or multiple miRNAs are enriched, we performed a KEGG analysis miRNAs by using the hypergeometric test. In addition, miR+Pathway provides information regarding MTIs, PubMed IDs and the experimental verification method. Users can retrieve pathways regulated by an miRNA or a gene by inputting its names.

A New Strategy for Disc Cutter Wear Status Perception Using Vibration Detection and Machine Learning.

Carrying out status monitoring and fault-diagnosis research on cutter-wear status is of great significance for real-time understanding of the health status of Tunnel Boring Machine (TBM) equipment and reducing downtime losses. In this work, we proposed a new method to diagnose the abnormal wear state of the disc cutter by using brain-like artificial intelligence to process and analyze the vibration signal in the dynamic contact between the disc cutter and the rock. This method is mainly aimed at realizing the diagnosis and identification of the abnormal wear state of the cutter, and is not aimed at the accurate measurement of the wear amount. The author believes that when the TBM is operating at full power, the cutting forces are very high and the rock is successively broken, resulting in a complex circumstance, which is inconvenient to vibration signal acquisition and transmission. If only a small thrust is applied, to make the cutters just contact with the rock (less penetration), then the cutters will run more smoothly and suffer less environmental interference, which would be beneficial to apply the method proposed in this paper to detect the state of the cutters. A specific example was to use the frequency-domain characteristics of the periodic vibration waveform during the contact between the cutter and the granite to identify the wear status (including normal wear state, wear failure state, angled wear failure state) of the disc cutter through the artificial neural network, and the diagnosis accuracy rate is 90%.

HnRNPA2B1 promotes the proliferation of breast cancer MCF-7 cells via the STAT3 pathway.

HnRNPA2/B1 is highly expressed in many tumors. However, the role of hnRNPA2/B1 in breast cancer is not clear. In this study, we found the proliferation rate was decreased after knockout of hnRNPA2/B1 by CRISPR-CAS9 in MCF-7 cells, as demonstrated by the reduced expression of CDK4 and p-AKT, and the increased expression of P27. Besides this, the western blot results showed that knockout of hnRNPA2/B1 increased the rate of apoptosis and declined autophagy. By in vivo assay, we found that knockout of hnRNPA2/B1 suppressed tumor growth in a xenograft mouse model. Immunohistochemical staining results confirmed knockout of hnRNPA2/B1 impaired tumor angiogenesis, as illustrated by downregulated expression of VEGF-A. Besides this, interacting proteins with hnRNPA2/B1 were identified by mass spectrometry and the PPI network was constructed. GO analysis suggests that the Interacting proteins are mainly enriched in the Wnt signaling pathway, tumor necrosis factor-mediated signaling pathway, translation, and so on. We then identified hnRNPA2/B1 interacted with signal transducer and activator of transcription 3 (STAT3), as supported by the colocalization of hnRNPA2/B1 and STAT3. Meanwhile, knockout of hnRNPA2/B1 inhibited the phosphorylation of STAT3. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth in vitro and in vivo by activating the STAT3 pathway, regulating apoptosis and autophagy.

A Novel Mass-Producible Capacitive Sensor with Fully Symmetric 3D Structure and Microfluidics for Cells Detection.

Affinity biosensors of interdigitated electrodes have been widely used in cell detection. This research presents a mass-producible and disposable three-dimensional (3D) structure capacitive sensor based on the integrated circuit package lead frames for cell concentration detection. The fully symmetric 3D interdigital electrode structure makes the sensor more homogeneous and sensitive. (3-Aminopropyl) triethoxysilane (APTES) and glutaraldehyde are immobilized onto gold-plated electrodes. By overlaying the microfluidic channels on top, the volume of the solution is kept constant to obtain repeatable measured capacitance values. Moreover, using the upgraded reading and writing functions and circular measurement of the E4980A Data Transfer Program, an automatic multigroup test system is developed. It is shown that the cell concentration and capacitance are inversely correlated, and the cell concentration range of 10³â»106 CFU∙mL-1 is achieved. In addition, the rate of capacitance change matches that of state-of-the-art biosensors reported. A program is developed to find the optimal voltage and frequency for linear fitting between the capacitance change and cell concentration. Future work will employ machine learning-based data analysis to drug resistance sensitivity test of cell lines and cell survival status.

Nucleophosmin Regulates Intracellular Oxidative Stress Homeostasis via Antioxidant PRDX6.

Reactive oxygen species (ROS) play both deleterious and beneficial roles in cancer cells. Nucleophosmin (NPM) is heavily implicated in cancers of diverse origins, being its gene over-expression in solid tumors or frequent mutations in hematological malignancies. However, the role and regulatory mechanism of NPM in oxidative stress are unclear. Here, we found that NPM regulated the expression of peroxiredoxin 6 (PRDX6), a member of thiol-specific antioxidant protein family, consequently affected the level and distribution of ROS. Our data indicated that NPM knockdown caused the increase of ROS and its relocation from cytoplasm to nucleoplasm. In contrast, overexpression or cytoplasmic localization of NPM upregulated PRDX6, and decreased ROS. In addition, NPM knockdown decreased peroxiredoxin family proteins, including PRDX1, PRDX4, and PRDX6. Co-immunoprecipitation further confirmed the interaction between PRDX6 and NPM. Moreover, NSC348884, an inhibitor specifically targeting NPM oligomerization, decreased PRDX6 and significantly upregulated ROS. These observations demonstrated that the expression and localization of NPM affected the homeostatic balance of oxidative stress in tumor cells via PRDX6 protein. The regulation axis of NPM/PRDX/ROS may provide a novel therapeutic target for cancer treatment. J. Cell. Biochem. 118: 4697-4707, 2017. © 2017 Wiley Periodicals, Inc.

Microstructure and Dielectric Properties of Gradient Composite BaxSr1-xTiO3 Multilayer Ceramic Capacitors.

Multilayer ceramic capacitors (MLCCs) prepared using Ba1-xSrxTiO3 (BST) ceramics exhibit high dielectric constants (~1000), low dielectric loss (<0.01), and high breakdown voltage, with particularly significant tunability in dielectric properties (>50%) and with poor temperature stability. Doping-dominated temperature stability improvements often result in unintended loss of dielectric properties. A non-doping method has been proposed to enhance the temperature stability of BST capacitors. The composite gradient multilayer (CGML) ceramic capacitors with BaxSr1-xTiO3, where 0.5 < x < 0.8, as the dielectric, were prepared using a tape-casting method and sintered at 1250 °C. There exists a dense microstructure and continuous interface between the BaxSr1-xTiO3 thick film and the Pt electrodes. CGML ceramic capacitors feature a high dielectric constant at 1270, a low dielectric loss of less than 0.007, and excellent frequency and temperature stability. The capacitor showcases remarkable dielectric properties with a substantial tunability of 68% at 100 kV/cm, along with a notably consistent tunability ranging from 20% to 28% at 15 kV/cm across temperatures spanning from 30 to 100 °C, outperforming single-component BST-MLCCs in dielectric performance.

Effect of Deposition Pressure and Temperature on Tungsten Thin-Film Heater for Phase-Change Switch Applications.

Tungsten (W) film is increasingly utilized in various microheater applications due to its numerous advantages. These advantages include a high melting point, positive constant temperature coefficient of resistance (TCR), good mechanical stability, and compatibility with semiconductor processes. In this paper, deposition parameters for enhancing the properties of W film were investigated, and an optimized microheater was fabricated. It was found that the deposition temperature and pressure can modify the TCR to be negative or positive and the crystalline phase of W films to be alpha phases or mixed with beta phases. A W film deposited under 650 °C with a pressure of 1 pa has a positive TCR and pure alpha phase crystalline structure. We applied this optimized W film as a microheater in an RF phase-change switch (RFPCS), and the maximum voltage of the optimized W microheater increased by at least 48% in this work. By optimizing the microheater, the phase-change switch can be successfully actuated in both on and off states, demonstrated by the Raman results of the phase-change material. A voltage pulse of 20 V/200 ns was enough to turn the switch off with MΩ, and 11 V/3 µs could turn the switch on with 138 Ω. The optimized microheater and device can cycle 500 times without failure. The insertion loss and isolation of the device at 20 GHz was 1.0 dB and 22 dB.

A Review on Material Selection Benchmarking in GeTe-Based RF Phase-Change Switches for Each Layer.

The global demand for radio frequency (RF) modules and components has grown exponentially in recent decades. RF switches are the essential unit in RF front-end and reconfigurable systems leading to the rapid development of novel and advanced switch technology. Germanium telluride (GeTe), as one of the Chalcogenide phase-change materials, has been applied as an RF switch due to its low insertion loss, high isolation, fast switching speed, and low power consumption in recent years. In this review, an in-depth exploration of GeTe film characterization is presented, followed by a comparison of the device structure of directly heated and indirectly heated RF phase-change switches (RFPCSs). Focusing on the prototypical structure of indirectly heated RFPCSs as the reference, the intrinsic properties of each material layer and the rationale behind the material selection is analyzed. Furthermore, the design size of each material layer of the device and its subsequent RF performance are summarized. Finally, we cast our gaze toward the promising future prospects of RFPCS technology.

Synthesis and photophysical properties of 2,5,8,11-tetrakis(5-hexylthiophen-2-yl)tetrathieno[2,3-a:3',2'-c:2'',3''-f:3''',2'''-h]naphthalene.

The title compound, C58H64S8, has been prepared by Pd-catalysed direct C-H arylation of tetrathienonaphthalene (TTN) with 5-hexyl-2-iodothiophene and recrystallized by slow evaporation from dichloromethane. The crystal structure shows a completely planar geometry of the TTN core, crystallizing in the monoclinic space group P2(1)/c. The structure consists of slipped π-stacks and the interfacial distance between the mean planes of the TTN cores is 3.456 (5) Å, which is slightly larger than that of the comparable derivative of tetrathienoanthracene (TTA) with 2-hexylthiophene groups. The packing in the two structures is greatly influenced by both the aromatic core of the structure and the alkyl side chains.

Extracting and Analyzing the S-Parameters of Vertical Interconnection Structures in 3D Glass Packaging.

In order to effectively employ through-glass vias (TGVs) for high-frequency software package design, it is crucial to accurately characterize the S-parameters of vertical interconnection structures in 3D glass packaging. A methodology is proposed for the extraction of precise S-parameters using the transmission matrix (T-matrix) to analyze and evaluate the insertion loss (IL) and reliability of TGV interconnections. The method presented herein enables the handling of a diverse range of vertical interconnections, encompassing micro-bumps, bond-wires, and a variety of pads. Additionally, a test structure for coplanar waveguide (CPW) TGVs is constructed, accompanied by a comprehensive description of the equations and measurement procedure employed. The outcomes of the investigation demonstrate a favorable concurrence between the simulated and measured results, with analyses and measurements conducted up to 40 GHz.

[1,1'-Bis(diphenyl-phosphan-yl)ferrocene-κ(2)P,P'](η(5)-cyclo-penta-dien-yl)(dicyanamido-κN)ruthenium(II) dichloro-methane monosolvate.

The title compound, [FeRu(C(5)H(5))(C(2)N(3))(C(17)H(14)P)(2)], was obtained by reaction of Cp(dppf)RuCl [dppf = 1,1'-bis-(diphenyl-phosphan-yl)ferrocene] with sodium dicyanamide in dichloro-methane. The Ru(II) atom is capped by an η(5)-cyclo-penta-dienyl (Cp) ring, a chelating dppf and a terminal C(2)N(3) unit, giving three-legged piano-stool geometry. The C-N-C angle of the N(CN)(2) ligand [120.8 (6)°] is significantly smaller than that in the corresponding diruthenium complex [127.2 (9)°; Zhang et al. (2003 ▶). Inorg. Chem.42, 633-640] due to steric hindrance between the two {Cp(PPh(3))(2)Ru} building blocks. Disorder was found in the dichloro-methane solvent mol-ecule, which was refined as disordered over two positions, with a site-occupancy ratio of 0.53:0.47 (2).

Multi-Perspective Feature Extraction and Fusion Based on Deep Latent Space for Diagnosis of Alzheimer's Diseases.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to construct functional connectivity (FC) in the brain for the diagnosis and analysis of brain disease. Current studies typically use the Pearson correlation coefficient to construct dynamic FC (dFC) networks, and then use this as a network metric to obtain the necessary features for brain disease diagnosis and analysis. This simple observational approach makes it difficult to extract potential high-level FC features from the representations, and also ignores the rich information on spatial and temporal variability in FC. In this paper, we construct the Latent Space Representation Network (LSRNet) and use two stages to train the network. In the first stage, an autoencoder is used to extract potential high-level features and inner connections in the dFC representations. In the second stage, high-level features are extracted using two perspective feature parses. Long Short-Term Memory (LSTM) networks are used to extract spatial and temporal features from the local perspective. Convolutional neural networks extract global high-level features from the global perspective. Finally, the fusion of spatial and temporal features with global high-level features is used to diagnose brain disease. In this paper, the proposed method is applied to the ANDI rs-fMRI dataset, and the classification accuracy reaches 84.6% for NC/eMCI, 95.1% for NC/AD, 80.6% for eMCI/lMCI, 84.2% for lMCI/AD and 57.3% for NC/eMCI/lMCI/AD. The experimental results show that the method has a good classification performance and provides a new approach to the diagnosis of other brain diseases.

Targeting epiregulin in the treatment-damaged tumor microenvironment restrains therapeutic resistance.

The tumor microenvironment (TME) represents a milieu enabling cancer cells to develop malignant properties, while concerted interactions between cancer and stromal cells frequently shape an "activated/reprogramed" niche to accelerate pathological progression. Here we report that a soluble factor epiregulin (EREG) is produced by senescent stromal cells, which non-cell-autonomously develop the senescence-associated secretory phenotype (SASP) upon DNA damage. Genotoxicity triggers EREG expression by engaging NF-κB and C/EBP, a process supported by elevated chromatin accessibility and increased histone acetylation. Stromal EREG reprograms the expression profile of recipient neoplastic cells in a paracrine manner, causing upregulation of MARCHF4, a membrane-bound E3 ubiquitin ligase involved in malignant progression, specifically drug resistance. A combinational strategy that empowers EREG-specific targeting in treatment-damaged TME significantly promotes cancer therapeutic efficacy in preclinical trials, achieving response indices superior to those of solely targeting cancer cells. In clinical oncology, EREG is expressed in tumor stroma and handily measurable in circulating blood of cancer patients post-chemotherapy. This study establishes EREG as both a targetable SASP factor and a new noninvasive biomarker of treatment-damaged TME, thus disclosing its substantial value in translational medicine.

Identification of a small molecule SR9009 that activates NRF2 to counteract cellular senescence.

The senescence-associated secretory phenotype (SASP) is a striking characteristic of senescence. Accumulation of SASP factors causes a pro-inflammatory response linked to chronic disease. Suppressing senescence and SASP represents a strategy to prevent or control senescence-associated diseases. Here, we identified a small molecule SR9009 as a potent SASP suppressor in therapy-induced senescence (TIS) and oncogene-induced senescence (OIS). The mechanism studies revealed that SR9009 inhibits the SASP and full DNA damage response (DDR) activation through the activation of the NRF2 pathway, thereby decreasing the ROS level by regulating the expression of antioxidant enzymes. We further identified that SR9009 effectively prevents cellular senescence and suppresses the SASP in the livers of both radiation-induced and oncogene-induced senescence mouse models, leading to alleviation of immune cell infiltration. Taken together, our findings suggested that SR9009 prevents cellular senescence via the NRF2 pathway in vitro and in vivo, and activation of NRF2 may be a novel therapeutic strategy for preventing cellular senescence.

A chromosome-level genome assembly of rice leaffolder, Cnaphalocrocis medinalis.

The rice leaffolder, Cnaphalocrocis medinalis Guenée (Crambidae, Lepidoptera), is an important agricultural pest that causes serious losses to rice production in rice-growing regions with high humidity and temperature. However, a lack of genomic resources limits in-depth understanding of its biological characteristics and ecological adaptation. Here, we sequenced the genome of rice leaffolder using the Illumina and PacBio platforms, yielding a genome assembly of 528.3 Mb with a contig N50 of 524.6 kb. A high percentage (96.4%) of Benchmarking Universal Single-Copy Orthologs (BUSCOs) were successfully detected, suggesting high-level completeness of the genome assembly. In total, 39.5% of the genome consists of repeat sequences and 15,045 protein-coding genes were annotated. Comparative phylogenomic analysis showed that some gene families associated with hormone biosynthesis expanded in rice leaffolder. Next, we used the Hi-C technique to produce a chromosome-level genome assembly with a scaffold N50 of 16.1 Mb by anchoring 3,248 scaffolds to 31 chromosomes. The rice leaffolder genome showed high chromosomal synteny with the genome of four other lepidopteran insects. By comparing coverage ratios from the genome resequencing of male and female pupae, we identified near intact Z and W chromosomes. The W chromosome is estimated as 20.75 Mb, which is the most complete known W chromosome in Lepidoptera. The protein-coding genes on the W chromosome were significantly enriched in metabolic pathways. In all, the high-quality genome assembly and the near-intact W chromosome of rice leaffolder should be a useful resource for the fields of insect migration, chromosome evolution and pest control.

Preresection Stained Glue Injection to Localize Pulmonary Small Nodules and Ground-glass Opacities.

OBJECTIVE: We sought to introduce a localization procedure (methylene blue-stained N-butyl cyanoacrylate and N-octyl cyanoacrylate glue) in localizing pulmonary small nodules and ground-glass opacities before thoracoscopic resection, and to evaluate its efficacy. METHODS: A total of 20 patients with pulmonary small nodules and/or ground-glass opacities, who underwent video-assisted thoracoscopic surgery from August 1, 2017 to March 1 2018, were included in the study. RESULTS: A total of 24 lesions in 20 patients underwent blue-stained glue localization. The success rate of localization was 100%, with a mean dose of 0.04±0.01 mL blue dye and 1 mL glue used for each lesion. The average time for the whole localization procedure was 15.4±6.3 minutes. All lesions were intraoperatively localized by visual inspection in combination with palpation. The complications related to the localization procedure included mild pneumothorax occurring in 9 patients and minor pulmonary hematoma in 4 patients. No pain or distress was reported. CONCLUSIONS: Blue-stained glue injection is technically feasible and safe to localize pulmonary small nodules and ground-glass opacities before thoracoscopic resection.

Heterogeneous nuclear ribonucleoprotein A2/B1 is a negative regulator of human breast cancer metastasis by maintaining the balance of multiple genes and pathways.

BACKGROUND: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an important RNA-binding protein that affects the RNA processing, splicing, transport and stability of many genes. hnRNPA2/B1 is expressed during proliferation and metastasis of various cancer types and promotes such processes. However, the precise role and mechanism of hnRNPA2/B1 in breast cancer remain unclear. METHODS: The association of hnRNPA2/B1 with breast cancer metastasis was assessed using tissue chips, mouse models and publicly available data. The role and mechanism of hnRNPA2/B1 in breast cancer metastasis were studied in cell lines and mouse models. FINDINGS: In contrast to other cancer research findings, hnRNPA2/B1 expression was negatively correlated with breast cancer metastasis. hnRNPA2/B1 inhibited MDA-MB-231 triple-negative breast cancer (TNBC) cell metastasis in vitro and in vivo. hnRNPA2/B1 knockout activated ERK-MAPK/Twist and GR-beta/TCF4 pathways but inhibited STAT3 and WNT/TCF4 signalling pathways. Profilin 2 (PFN2) promoted breast cancer cell migration and invasion, whereas hnRNPA2/B1 bound directly to the UAGGG locus in the 3'-untranslated region of PFN2 mRNA and reduced the stability of PFN2 mRNA. INTERPRETATION: Our data supported the role of hnRNPA2/B1 in tumour metastasis risk and survival prediction in patients with breast cancer. The inhibitory role of hnRNPA2/B1 in metastasis was a balance of downstream multiple genes and signalling pathways. PFN2 downregulation by hnRNPA2/B1 might partly explain the inhibitory mechanism of hnRNPA2/B1 in breast cancer metastasis. Therefore, hnRNPA2/B1 might be used as a new prognostic biomarker and valuable molecular target for breast cancer treatments.

Revisiting ovarian cancer microenvironment: a friend or a foe?

Development of ovarian cancer involves the co-evolution of neoplastic cells together with the adjacent microenvironment. Steps of malignant progression including primary tumor outgrowth, therapeutic resistance, and distant metastasis are not determined solely by genetic alterations in ovarian cancer cells, but considerably shaped by the fitness advantage conferred by benign components in the ovarian stroma. As the dynamic cancer topography varies drastically during disease progression, heterologous cell types within the tumor microenvironment (TME) can actively determine the pathological track of ovarian cancer. Resembling many other solid tumor types, ovarian malignancy is nurtured by a TME whose dark side may have been overlooked, rather than overestimated. Further, harnessing breakthrough and targeting cures in human ovarian cancer requires insightful understanding of the merits and drawbacks of current treatment modalities, which mainly target transformed cells. Thus, designing novel and precise strategies that both eliminate cancer cells and manipulate the TME is increasingly recognized as a rational avenue to improve therapeutic outcome and prevent disease deterioration of ovarian cancer patients.

Sustainable inflammation transforms hepatic cells by causing oxidative stress injury and potential epithelial-mesenchymal transition.

The inflammatory microenvironment promotes tumorigenesis. However, the mechanism through which inflammation transforms hepatic cells in precancerous lesions remains unclear. Hepatic cells undergo significant changes in metabolism before carcinogenesis, but the specific alterations in gene expression and cellular functions in response to precancerous inflammation have not been elucidated. In this study, a hepatitis-hepatoma mouse model was successfully established. Label-free quantitative (LFQ) proteomics coupled with bioinformatics analysis was then performed to identify differentially expressed proteins and their functions in hepatic cells with precancerous inflammation. We found that different chemical treatments induced several common changes in the model. Hepatic cells underwent serious oxidative stress injury. Canonical pathway analysis using IPA revealed the activation of signaling pathways, such as integrin signaling, signaling by Rho family GTPases, IL-8 signaling, and ILK signaling, as well as the inhibition of RhoGDI signaling. Analysis of the KEGG pathway indicated alteration in the pathways for focal adhesion and regulation of actin cytoskeleton. Results from western blot analysis demonstrated the upregulation of proteins, including p-STAT3, TWIST, SNAIL, Vimentin, and MMP-9, which are involved in epithelial-mesenchymal transition (EMT). These results indicated that hepatic cells were likely to undergo EMT. Interestingly, the expression of E-cadherin was upregulated, but this observation must be further investigated. In conclusion, the results revealed that notable functional and pathway changes occurred during the precancerous inflammation stage in the liver. Our study contributes to understanding of the roles of inflammation in tumorigenesis and provides a molecular basis for further studies on the tumorigenesis of hepatocellular carcinoma.

Sequential electrophilic and photochemical cyclizations from bis(bithienyl)acetylene to a tetrathienonaphthalene core.

Photoirradiation of bis(bithienyl)acetylenes in the presence of iodine undergoes sequential electrophilic and photochemical cyclizations to produce tetrathienonaphthalenes (TTN) in one pot. The TTN framework is readily transformed into cruciform π-extended derivatives, which form ordered nano/microstructures.