Rare Copy Number Variants Identify Novel Genes in Sporadic Total Anomalous Pulmonary Vein Connection

Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart anomaly. Several genes have been associated TAPVC but the mechanisms remain elusive. To search novel CNVs and candidate genes, we screened a cohort of 78 TAPVC cases and 100 healthy controls for rare copy number variants (CNVs) using whole exome sequencing (WES). Then we identified pathogenic CNVs by statistical comparisons between case and control groups. After that, we identified altogether eight pathogenic CNVs of seven candidate genes (PCSK7, RRP7A, SERHL, TARP, TTN, SERHL2, and NBPF3). All these seven genes have not been described previously to be related to TAPVC. After network analysis of these candidate genes and 27 known pathogenic genes derived from the literature and publicly database, PCSK7 and TTN were the most important genes for TAPVC than other genes. Our study provides novel candidate genes potentially related to this rare congenital birth defect (CHD) which should be further fundamentally researched and discloses the possible molecular pathogenesis of TAPVC

Optimizing the Mechanical Properties in the Repair Zone of 5Cr5MoV by Controlling Welding Heat Input

The influence of welding heat input on the microstructure and mechanical properties of 5Cr5MoV die steel was studied in order to improve the mechanical properties of the cold working die and extend its service life. Shielded metal arc welding (SMAW) method was used with different heat inputs in the range from 4.2 to 6.61 kJ/cm to repair the 5Cr5MoV die steel. Microhardness and tensile properties were performed to evaluate the repaired quality of the cold working die steel. The microhardness of the weld repaired zone gradually decreased from the weld to the tempering zone. The highest microhardness in the weld repaired zone was 863 HV, and finally, it decreased to about 300 HV. With the increase of heat input, the tensile strength of the weld and the heat affected zone increased; nevertheless, the tensile strength of the tempering zone increased first and then decreased. As a result, 6.6 kJ/cm is the best value of heat input judged from the microhardness distribution and the tensile properties

The Improved WNOFRFs Feature Extraction Method and Its Application to Quantitative Diagnosis for Cracked Rotor Systems

During its operation, a rotor system can be exposed to multiple faults, such as rub-impact, misalignment, cracks and unbalancing. When a crack fault occurs on the rotor shaft, the vibration response signals contain some nonlinear components that are considerably tougher to be extracted through some linear diagnosis methods. By combining the Nonlinear Output Frequency Response Functions weighted contribution rate (WNOFRFs) and Kullback–Leibler (KL) divergence, a novel fault diagnosis method of improved WNOFRFs is proposed. In this method, an index, improved optimal WNOFRFs (IOW), is defined to represent the nonlinearity of the faulty rotor system. This method has been tested through the finite element model of a cracked rotor system and then verified experimentally at the shaft crack detection test bench. The results from the simulation and experiment verified that the proposed method is applicable and effective for cracked rotor systems. The IOW indicator shows high sensitivity to crack faults and can comprehensively represent the nonlinear properties of the system. It can also quantitatively detect the crack fault, and the relationship between the values of IOW and the relative depth of the crack is approximately positively proportional. The proposed method can precisely and quantitatively diagnose crack faults in a rotor system

Immunoinformatic Identification of Multiple Epitopes of gp120 Protein of HIV-1 to Enhance the Immune Response against HIV-1 Infection

Acquired Immunodeficiency Syndrome is caused by the Human Immunodeficiency Virus (HIV), and a significant number of fatalities occur annually. There is a dire need to develop an effective vaccine against HIV-1. Understanding the structural proteins of viruses helps in designing a vaccine based on immunogenic peptides. In the current experiment, we identified gp120 epitopes using bioinformatic epitope prediction tools, molecular docking, and MD simulations. The Gb-1 peptide was considered an adjuvant. Consecutive sequences of GTG, GSG, GGTGG, and GGGGS linkers were used to bind the B cell, Cytotoxic T Lymphocytes (CTL), and Helper T Lymphocytes (HTL) epitopes. The final vaccine construct consisted of 315 amino acids and is expected to be a recombinant protein of approximately 35.49 kDa. Based on docking experiments, molecular dynamics simulations, and tertiary structure validation, the analysis of the modeled protein indicates that it possesses a stable structure and can interact with Toll-like receptors. The analysis demonstrates that the proposed vaccine can provoke an immunological response by activating T and B cells, as well as stimulating the release of IgA and IgG antibodies. This vaccine shows potential for HIV-1 prophylaxis. The in-silico design suggests that multiple-epitope constructs can be used as potentially effective immunogens for HIV-1 vaccine development

The Suitability Assessment of Agricultural Drought Monitoring Indices: A Case Study in Inland River Basin

Drought monitoring is an important scientific basis for drought impact evaluation and the selection of mitigation strategies. Since the drivers of drought vary among regions, there is no universal drought index applicable to different regions. The Shiyang River Basin, an inland river basin, located in Gansu Province, China, has a closed water cycle system. Drought is a dominant nature disaster for the sustainable development of the region. Thus, this is an ideal area to explore the suitability of drought-monitoring indices. Here, we took the Shiyang River Basin as an example, in order to explore suitable indicators for agricultural drought monitoring in inland river basins. This study assessed the twelve different widely used drought indices used for monitoring the impact of drought on crop growth, represented by net primary production (NPP). The results showed that the vegetation status-based drought indices (VCI and NVSWI) had the highest significant correlation (0.6 ≤ |R| ≤ 1, p p < 0.1). These four indices are good indicators for agricultural drought monitoring. Studies based on these four indices showed that agricultural drought has a tendency to slow down from 1982 to 2020. This is inconsistent with the monitoring of drought indices based on the meteorological variables that show a trend of increasing drought. This is mainly due to the increased efficiency of water management and its use in inland river basins. This indicates that other water resource information, such as runoff, should be included to construct an integrated agricultural drought-monitoring indices in management intensive regions, such as in an inland river basin

The Suitability Assessment of Agricultural Drought Monitoring Indices: A Case Study in Inland River Basin

Drought monitoring is an important scientific basis for drought impact evaluation and the selection of mitigation strategies. Since the drivers of drought vary among regions, there is no universal drought index applicable to different regions. The Shiyang River Basin, an inland river basin, located in Gansu Province, China, has a closed water cycle system. Drought is a dominant nature disaster for the sustainable development of the region. Thus, this is an ideal area to explore the suitability of drought-monitoring indices. Here, we took the Shiyang River Basin as an example, in order to explore suitable indicators for agricultural drought monitoring in inland river basins. This study assessed the twelve different widely used drought indices used for monitoring the impact of drought on crop growth, represented by net primary production (NPP). The results showed that the vegetation status-based drought indices (VCI and NVSWI) had the highest significant correlation (0.6 &le; |R| &le; 1, p &lt; 0.05) on NPP, and the integrated drought indices (DSI and ISDI) had the strong significant correlation (0.4 &le; |R| &lt; 0.6, p &lt; 0.1). These four indices are good indicators for agricultural drought monitoring. Studies based on these four indices showed that agricultural drought has a tendency to slow down from 1982 to 2020. This is inconsistent with the monitoring of drought indices based on the meteorological variables that show a trend of increasing drought. This is mainly due to the increased efficiency of water management and its use in inland river basins. This indicates that other water resource information, such as runoff, should be included to construct an integrated agricultural drought-monitoring indices in management intensive regions, such as in an inland river basin

Kinetics of the austenitization in the Fe-Mo-C ternary alloys during continuous heating

The influence of molybdenum on the microstructure and kinetics of the austenization of the Fe-Mo-C ternary alloys is analyzed using differential scanning calorimetry (DSC) and the Johnson-Mehl-Avrami-Kolmogorov model (JMAK) in the temperature range from 293 K to 1373 K. The as-cast microstructure and microstructure after DSC test are obtained using optical microscopy (OM) and scanning electron microscopy (SEM). It was seen that with an increasing Mo concentration, the lamellar pearlite is spherized and the austenite grain size decreases. In addition, both DSC curves and the JMAK model show that the initial (Ac1) and the final (Ac3) temperature of the phase transition increases with an increasing Mo concentration. It was also seen that increasing the Mo concentration, the diffusion activation energy (DAE) increases and the pre-exponential factor of diffusion (DPEF) decreases due to a change in both the austenitic nucleation rate and the diffusion of the elements caused by the introduction of Mo

Fibers by Electrospinning and Their Emerging Applications in Bone Tissue Engineering

Bone tissue engineering (BTE) is an optimized approach for bone regeneration to overcome the disadvantages of lacking donors. Biocompatibility, biodegradability, simulation of extracellular matrix (ECM), and excellent mechanical properties are essential characteristics of BTE scaffold, sometimes including drug loading capacity. Electrospinning is a simple technique to prepare fibrous scaffolds because of its efficiency, adaptability, and flexible preparation of electrospinning solution. Recent studies about electrospinning in BTE are summarized in this review. First, we summarized various types of polymers used in electrospinning and methods of electrospinning in recent work. Then, we divided them into three parts according to their main role in BTE, (1) ECM simulation, (2) mechanical support, and (3) drug delivery system

Surface Engineering of Carbon-Based Microelectrodes for High-Performance Microsupercapacitors

In this research, the enhancement in electrochemical performance of pyrolyzed carbon microelectrodes by surface modification is investigated. For the proposed microfabrication process, pyrolyzed carbon microelectrodes with multi-walled carbon nanotubes (MWCNTs) on their surface are obtained by developing GM-1060 photoresist in mixture of propylene glycol methyl ether acetate (PGMEA) and CNTs, and following pyrolysis of a micropatterned photoresist. Polyvinyl alcohol (PVA)/H2SO4 electrolyte (1 M) was applied to assemble this carbon/CNT microelectrode-based all-solid-state microsupercapacitor (carbon/CNT-MSC). The carbon/CNT-MSC shows a higher electrochemical performance compared with that of pyrolyzed carbon microelectrode-based MSC (carbon-MSC). The specific areal and volumetric capacitances of carbon/CNT-MSC (4.80 mF/cm2 and 32.0 F/cm3) are higher than those of carbon-MSC (3.52 mF/cm2 and 23.4 F/cm3) at the scan rate of 10 mV/s. In addition, higher energy density and power density of carbon/CNT-MSC (2.85 mWh/cm3 and 1.98 W/cm3) than those of carbon-MSC (2.08 mWh/cm3 and 1.41 W/cm3) were also achieved. This facile surface modification and optimization are potentially promising, being highly compatible with modern microfabrication technologies and allowing integration of highly electrically conductive CNTs into pyrolyzed carbon to assemble MSCs with improved electrochemical performance. Moreover, this method can be potentially applied to other high-performance micro/nanostructures and microdevices/systems

Next-generation sequencing identifies novel genes with rare variants in total anomalous pulmonary venous connectionResearch in context

Background: Total anomalous pulmonary venous connection (TAPVC) is recognized as a rare congenital heart defect (CHD). With a high mortality rate of approximately 80%, the survival rate and outcomes of TAPVC patients are not satisfactory. However, the genetic aetiology and mechanism of TAPVC remain elusive. This study aimed to investigate the underlying genomic risks of TAPVC through next-generation sequencing (NGS). Methods: Rare variants were identified through whole exome sequencing (WES) of 78 sporadic TAPVC cases and 100 healthy controls using Fisher's exact test and gene-based burden test. We then detected candidate gene expression patterns in cells, pulmonary vein tissues, and embryos. Finally, we validated these genes using target sequencing (TS) in another 100 TAPVC cases. Findings: We identified 42 rare variants of 7 genes (CLTCL1, CST3, GXYLT1, HMGA2, SNAI1, VAV2, ZDHHC8) in TAPVC cases compared with controls. These genes were highly expressed in human umbilical vein endothelial cells (HUVECs), mouse pulmonary veins and human embryonic hearts. mRNA levels of these genes in human pulmonary vein samples were significantly different between cases and controls. Through network analysis and expression patterns in zebrafish embryos, we revealed that SNAI1, HMGA2 and VAV2 are the most important genes for TAPVC. Interpretation: Our study identifies novel candidate genes potentially related to TAPVC and elucidates the possible molecular pathogenesis of this rare congenital birth defect. Furthermore, SNAI1, HMGA2 and VAV2 are novel TAPVC candidate genes that have not been reported previously in either humans or animals. Fund: National Natural Science Foundation of China. Keywords: Congenital heart defects, Total anomalous pulmonary venous connection, Whole exome sequencing, Target sequencing, Rare variant