Optimal Modulation Algorithm for Hybrid Clamped Three-Level Inverter

The principle of a three phase hybrid clamped three-level inverter was presented. Taking sixty-four switch states into consideration, the operational states of hybrid clamped three-level inverter and different current circuits in different switch states were detailed derived. Optimal modulation algorithm was proposed based on the neutral small vectors by different combination, which can realize the automatic balancing of the neutral-point voltage with few switching cycles and did not need to measure the voltage of the clamped capacitors. The proposed modulation algorithm was also capable of restraining the turn-off over-voltage of the power switching devices effectively. Simulation results were given to verify the feasibility and correctness. Experimental results obtained by DSP-based implementation of the controller on 1 MW prototype show good performance in terms of DC-bus voltages regulation (small neutral point potential function and low DC ripple coefficient) and good sinusoidal current

Detection of copy number variations based on a local distance using next-generation sequencing data

As one of the main types of structural variation in the human genome, copy number variation (CNV) plays an important role in the occurrence and development of human cancers. Next-generation sequencing (NGS) technology can provide base-level resolution, which provides favorable conditions for the accurate detection of CNVs. However, it is still a very challenging task to accurately detect CNVs from cancer samples with different purity and low sequencing coverage. Local distance-based CNV detection (LDCNV), an innovative computational approach to predict CNVs using NGS data, is proposed in this work. LDCNV calculates the average distance between each read depth (RD) and its k nearest neighbors (KNNs) to define the distance of KNNs of each RD, and the average distance between the KNNs for each RD to define their internal distance. Based on the above definitions, a local distance score is constructed using the ratio between the distance of KNNs and the internal distance of KNNs for each RD. The local distance scores are used to fit a normal distribution to evaluate the significance level of each RDS, and then use the hypothesis test method to predict the CNVs. The performance of the proposed method is verified with simulated and real data and compared with several popular methods. The experimental results show that the proposed method is superior to various other techniques. Therefore, the proposed method can be helpful for cancer diagnosis and targeted drug development

Selection of suitable reference genes for abiotic stress-responsive gene expression studies in peanut by real-time quantitative PCR

Background: Because of its strong specificity and high accuracy, real-time quantitative PCR (RT-qPCR) has been a widely used method to study the expression of genes responsive to stress. It is crucial to have a suitable set of reference genes to normalize target gene expression in peanut under different conditions using RT-qPCR. In this study, 11 candidate reference genes were selected and examined under abiotic stresses (drought, salt, heavy metal, and low temperature) and hormone (SA and ABA) conditions as well as across different organ types. Three statistical algorithms (geNorm, NormFinder and BestKeeper) were used to evaluate the expression stabilities of reference genes, and the comprehensive rankings of gene stability were generated. Results: The results indicated that ELF1B and YLS8 were the most stable reference genes under PEG-simulated drought treatment. For high-salt treatment using NaCl, YLS8 and GAPDH were the most stable genes. Under CdCl2 treatment, UBI1 and YLS8 were suitable as stable reference genes. UBI1, ADH3, and ACTIN11 were sufficient for gene expression normalization in low-temperature experiment. All the 11 candidate reference genes showed relatively high stability under hormone treatments. For organs subset, UBI1, GAPDH, and ELF1B showed the maximum stability. UBI1 and ADH3 were the top two genes that could be used reliably in all the stress conditions assessed. Furthermore, the necessity of the reference genes screened was further confirmed by the expression pattern of AnnAhs. Conclusions: The results perfect the selection of stable reference genes for future gene expression studies in peanut and provide a list of reference genes that may be used in the future

Sirt7 protects against vascular calcification via modulation of reactive oxygen species and senescence of vascular smooth muscle cells

Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. Sirt7, a NAD+-dependent histone deacetylases, plays a crucial role in cardiovascular disease. However, the role of Sirt7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that Sirt7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D3 (vD3). We found that knockdown or inhibition of Sirt7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of Sirt7 had opposite effects. Intriguingly, this protective effect of Sirt7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, Sirt7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of Sirt7 in VSMCs resulted in increased intracellular reactive oxygen species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of Sirt7 on VSMC calcification. Furthermore, we found that knockdown of Sirt7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that Sirt7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. Sirt7 may be a potential therapeutic target for vascular calcification.</p

Traditional Chinese Medicine JianPiHuaTan formula improving quality of life and survival in patients with colorectal cancer through RAS/RAF downstream signaling pathways

ObjectiveJianPiHuaTan Formula (JPHTF), a traditional Chinese medicine (TCM), has been utilized as an adjunctive therapy for colorectal cancer (CRC). The study aims to evaluate the potential clinical benefits of JPHTF and its effectiveness in inhibiting tumor growth.Methods300 stage II/III CRC patients and 412 advanced CRC patients were enrolled to verify the clinical value of JPHTF in CRC treatment. Furthermore, CRC patient-derived xenograft (PDX) mice were utilized to investigate the regulatory mechanisms of JPHTF.ResultsJPHTF significantly improved abdominal distension, shortness of breath, drowsiness, loss of appetite, sleep, and tiredness in stage II/III CRC patients, thereby improving their quality of life. Simultaneously, JPHTF served as a supportive therapy in extending the overall survival (OS) of stage IV CRC patients with RAS/RAF mutations undergoing chemotherapy. Additionally, JPHTF effectively impeded tumor progression in CRC PDX models with RAS mutation, accompanied by a reduction in tumor cell content in the JPHTF group. Transcriptomic analysis revealed the involvement of the Hippo and Hedgehog signaling pathways in JPHTF-mediated CRC inhibition. Furthermore, mice in the JPHTF group exhibited increased immune cell infiltration.ConclusionThese findings suggested that JPHTF may inhibits tumor growth in CRC with RAS mutation by modulating RAS/RAF downstream signaling pathways, specifically the Hippo and Hedgehog signaling, leading to increased immune cell infiltration