HAO2 inhibits malignancy of clear cell renal cell carcinoma by promoting lipid catabolic process.

Hydroxy acid oxidase 2 (HAO2) has been reported to inhibit tumor progression through metabolic pathway. The current study was designed to evaluate the prognostic significance and probable mechanism of HAO2 in patients with clear cell renal cell carcinoma (ccRCC). The study screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for patients with ccRCC having complete clinical information and HAO2 expression. Low HAO2 was associated with shorter overall survival (OS) and shorter disease-free survival (DFS). Gene set enrichment analysis (GSEA) showed HAO2 was associated with neutral lipid catabolic process, metabolic process, lipid oxidation, epithelial-mesenchymal transition (EMT), and Kirsten rat sarcoma viral oncogene signaling (KRAS). Western blot analysis and immunohistochemistry analysis checked HAO2 expression in ccRCC cancer tissues, normal tissues, and renal cancer cell lines. HAO2 was downregulated in ccRCC cancer tissues and ccRCC cell lines when compared with their control group. Overexpression of HAO2 by plasmid promoted lipid catabolic process, eliminated lipid accumulation, inhibited KRAS expression, controlled the proliferation, migration, and invasion activity of ccRCC tumor cells. Our results indicated that HAO2 inhibits malignancy ccRCC by promoting lipid catabolic process, HAO2 could be an effective molecular marker and treatment for ccRCC

Soil Moisture Determines Horizontal and Vertical Root Extension in the Perennial Grass Lolium perenne L. Growing in Karst Soil

Karst regions are characterized by heterogeneous soil habitats, with shallow wide soil (SW) on hilly slopes and deep narrow soil (DN) in rocky trenches. To make full use of limited water and nutrients, plants have therefore developed a number of root extension strategies. This study investigated the effect of soil moisture on horizontal root extension in SW and vertical root extension in DN by assessing root growth responses, biomass allocation, and root distribution. A full two-way factorial blocked design of soil dimensions by water availability was followed. The perennial grass Lolium perenne L. was grown in SW and DN under high (W100%), moderate (W50%), and low (W30%) water availability, respectively. The main results were as follows: (1) The total biomass of L. perenne was not influenced either by soil habitat or by water application. Root length, root surface area, root biomass and root to shoot ratio all decreased with decreasing water application in SW, but not in DN soil. (2) With decreasing water application, the cumulative percentage of root length, root surface area and root biomass in 4 rings from the center out to 12 cm of SW soil showed a trend of W50% > W30% > W100% in SW, however, the cumulative percentage of root biomass in 4 layers from the surface to a depth of 36 cm was not significantly different between different water treatments in DN. (3) Under all three water treatments, specific root length showed an increase but root length density showed a decreasing trend from the center outward in SW soil or from the surface to bottom in DN soil. Overall, these results suggest that in SW habitat, soil moisture determines horizontal expansion of the roots in L. perenne, although the overall expansion ability was limited in severe drought. However, due to the relatively strong water retention ability, soil moisture changes were less obvious in DN, resulting in no significant vertical extension of the root system. The root response of L. perenne helps our understanding of how herbaceous plants can adjust their belowground morphology to support their growth in harsh karst soil environments

Antimicrobial photodynamic inactivation as an alternative approach to inhibit the growth of Cronobacter sakazakii by fine-tuning the activity of CpxRA two-component system

Cronobacter sakazakii is an opportunistic foodborne pathogen primarily found in powdered infant formula (PIF). To date, it remains challenging to control the growth of this ubiquitous bacterium. Herein, antimicrobial photodynamic inactivation (aPDI) was first employed to inactivate C. sakazakii. Through 460 nm light irradiation coupled with hypocrellin B, the survival rate of C. sakazakii was diminished by 3~4 log. The photokilling effect was mediated by the attenuated membrane integrity, as evidenced by PI staining. Besides, scanning electron microscopy showed the deformed and aggregated cell cluster, and intracellular ROS was augmented by 2~3 folds when light doses increase. In addition to planktonic cells, the biofilm formation of C. sakazakii was also affected, showing an OD590nm decline from 0.85 to 0.25. In terms of molecular aspects, a two-component system called CpxRA, along with their target genes, was deregulated during illumination. Using the knock-out strain of ΔCpxA, the bacterial viability was reduced by 2 log under aPDI, a wider gap than the wildtype strain. Based on the promoted expression of CpxR and OmpC, aPDI is likely to play its part through attenuating the function of CpxRA-OmpC pathway. Finally, the aPDI system was applied to PIF, and C. sakazakii was inactivated under various desiccated or heated storage conditions. Collectively, aPDI serves as an alternative approach to decontaminate C. sakazakii, providing a new strategy to reduce the health risks caused by this prevalent foodborne pathogen

Two novel TSC2 mutations in renal epithelioid angiomyolipoma sensitive to everolimus.

People who suffers renal angiomyolipoma (AML) has a low quality of life. It is widely known that genetic factors including TSC2 mutation contribute to certain populations of renal AML-bearing patients. In this study, we are the first to identify novel TSC2 mutations in one Chinese renal epithelioid AML patient: c.2652C>A; c.2688G>A based on sequencing result from biopsy tissue. These two somatic mutations cause a translational stop of TSC2, which leads to mTORC1 activation. Given the fact that activation of mTORC1 ensures cell growth and survival, we applied its inhibitor, FDA-approved everolimus, to this woman. After months of treatment with everolimus, Computer-Tomography (CT) scan results showed that everolimus successfully reduced tumor growth and distal metastasis and achieved partial response (PR) to everolimu according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Further Blood Routine Examination results showed the concentration of red cell mass, hemoglobin, white blood cell (WBC), platelets and hematocrit (HCT) significantly returned to normal levels indicating patients with these two TSC2 mutations could be effectively treated by everolimus

The feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform

Objective: Recent non-invasive prenatal testing (NIPT) technologies are based on next-generation sequencing (NGS). NGS allows rapid and effective clinical diagnoses to be determined with two common sequencing systems: Illumina and Ion Torrent platforms. The majority of NIPT technology is associated with Illumina platform. We investigated whether fetal trisomy 18 and 21 were sensitively and specifically detectable by semiconductor sequencer: Ion Proton. Methods: From March 2012 to October 2013, we enrolled 155 pregnant women with fetuses who were diagnosed as high risk of fetal defects at Xiamen Maternal & Child Health Care Hospital (Xiamen, Fujian, China). Adapter-ligated DNA libraries were analyzed by the Ion Proton??? System (Life Technologies, Grand Island, NY, USA) with an average 0.3 ?? sequencing coverage per nucleotide. Average total raw reads per sample was 6.5 million and mean rate of uniquely mapped reads was 59.0%. The results of this study were derived from BWA mapping. Z-score was used for fetal trisomy 18 and 21 detection. Results: Interactive dot diagrams showed the minimal z-score values to discriminate negative versus positive cases of fetal trisomy 18 and 21. For fetal trisomy 18, the minimal z-score value of 2.459 showed 100% positive predictive and negative predictive values. The minimal z-score of 2.566 was used to classify negative versus positive cases of fetal trisomy 21. Conclusion: These results provide the evidence that fetal trisomy 18 and 21 detection can be performed with semiconductor sequencer. Our data also suggest that a prospective study should be performed with a larger cohort of clinically diverse obstetrics patients.open2

Improved nucleotide selectivity and termination of 3′-OH unblocked reversible terminators by molecular tuning of 2-nitrobenzyl alkylated HOMedU triphosphates

We describe a novel 3′-OH unblocked reversible terminator with the potential to improve accuracy and read-lengths in next-generation sequencing (NGS) technologies. This terminator is based on 5-hydroxymethyl-2′-deoxyuridine triphosphate (HOMedUTP), a hypermodified nucleotide found naturally in the genomes of numerous bacteriophages and lower eukaryotes. A series of 5-(2-nitrobenzyloxy)methyl-dUTP analogs (dU.I–dU.V) were synthesized based on our previous work with photochemically cleavable terminators. These 2-nitrobenzyl alkylated HOMedUTP analogs were characterized with respect to incorporation, single-base termination, nucleotide selectivity and photochemical cleavage properties. Substitution at the α-methylene carbon of 2-nitrobenzyl with alkyl groups of increasing size was discovered as a key structural feature that provided for the molecular tuning of enzymatic properties such as single-base termination and improved nucleotide selectivity over that of natural nucleotides. 5-[(S)-α-tert-Butyl-2-nitrobenzyloxy]methyl-dUTP (dU.V) was identified as an efficient reversible terminator, whereby, sequencing feasibility was demonstrated in a cyclic reversible termination (CRT) experiment using a homopolymer repeat of ten complementary template bases without detectable UV damage during photochemical cleavage steps. These results validate our overall strategy of creating 3′-OH unblocked reversible terminator reagents that, upon photochemical cleavage, transform back into a natural state. Modified nucleotides based on 5-hydroxymethyl-pyrimidines and 7-deaza-7-hydroxymethyl-purines lay the foundation for development of a complete set of four reversible terminators for application in NGS technologies

Structure modification and constant remelting speed control of a 120-t three-phase electroslag furnace

The traditional large electroslag remelting furnaces have many shortages, such as high short-network impedance and inductance, long maintenance time for electrode replacement, low stiffness of driveline, and low control accuracy of remelting speed. The present research was aimed to solve these problems through structure modification and constant remelting speed control for a 120-t electroslag remelting (ESR) furnace. Based on the technique of three-phase double electrodes in series, the short-network system and the structure of the 120-t ESR furnace were improved; and a continuous feeding system for the self-consumption electrode was proposed. A self-designed fully hydraulic driveline system with three degrees of freedom was successfully applied to the 120-t ESR furnace. An electrode auto-replacement system and the S-style speed-control curve of electrode-feeding system were designed on the basis of the soft measurement/sensing model on the remaining electrode length so as to obtain a high accuracy control system for constant remelting speed. The experiment products showed good surface quality and cross-sectional results, indicating good system control, and verifying the effectiveness of the structure modification of the furnace

Research on Output Signal Controlling of an Asymmetric Hydraulic Cylinder Based on a Flexible Connection

In industrial production, the structures of hydraulic servo system-connecting device-load systems are often simplified as rigid connections for the ease of calculation. However, this simplification is problematic when applied to flexible connections in hydraulic systems, which generally have multivariable and strong couplings; these characteristics affect the control accuracy of the hydraulic servo system and lead to serious distortion of the output waveform, which cannot be ignored. These problems cause greater lag and attenuation of the actual signal than those of the expected signal, leading to lower credibility. Therefore, it is important to study the waveform distortion caused by flexible connections. In this paper, according to the characteristics of a flexible connection, a corresponding mathematical model is established, and an adaptive controller, whose structure is simple and calculation cost is low, is used to adjust the amplitude and phase of the response signal and improve the accuracy of the system response. Treating the change in the response signal as the error value, the algorithm weights are adjusted until the error value is stable. Then, a more accurate output signal is obtained. Finally, the validity and practicability of the adaptive controller are verified by simulation experiments