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Background Uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). In this work, we defined the precise part of circ_0068481 in PASMC proliferation and migration induced by hypoxia. We hypothesized that circ_0068481 enhanced hypoxia-induced PASMC proliferation, invasion, and migration through the microRNA (miR)-361-3p/Krüppel-like factor 5 (KLF5) pathway. Methods Human PASMCs (hPASMCs) were exposed to hypoxic (3% O2) conditions. Circ_0068481, miR-361-3p, and KLF5 levels were gauged by qRT-PCR and western blot. Cell viability, proliferation, invasion, and migration were detected by XTT, EdU incorporation, transwell, and wound-healing assays, respectively. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were performed to confirm the direct relationship between miR-361-3p and circ_0068481 or KLF5. Results Circ_0068481 expression was increased in the serum of PAH patients and hypoxia-induced hPASMCs. Downregulation of circ_0068481 attenuated hypoxia-induced promotion in hPASMC proliferation, invasion, and migration. Circ_0068481 directly targeted miR-361-3p, and miR-361-3p downregulation reversed the inhibitory effects of circ_0068481 silencing on hypoxia-induced hPASMC proliferation, invasion, and migration. KLF5 was a direct miR-361-3p target, and miR-361-3p upregulation mitigated hypoxia-induced hPASMC proliferation, invasion, and migration by inhibiting KLF5 expression. Moreover, circ_0068481-induced KLF5 expression by binding to miR-361-3p in hypoxic hPASMCs. Conclusions Circ_0068481 knockdown ameliorated hypoxia-induced hPASMC proliferation, invasion, and migration at least in part through the miR-361-3p/KLF5 axis. [ABSTRACT FROM AUTHOR]

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9–99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes. [ABSTRACT FROM AUTHOR]

Background Nucleic acid amplification testing is a critical tool for addressing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Specimen pooling can increase throughput and conserve testing resources but requires validation to ensure that reduced sensitivity does not increase the false-negative rate. We evaluated the performance of a real-time reverse transcription polymerase chain reaction (RT-PCR) test authorized by the US Food and Drug Administration (FDA) for emergency use for pooled testing of upper respiratory specimens. Methods Positive specimens were selected from 3 prevalence groups, 1%–3%, >3%–6%, and >6%–10%. Positive percent agreement (PPA) was assessed by pooling single-positive specimens with 3 negative specimens; performance was assessed using Passing-Bablok regression. Additionally, we assessed the distributions of RT-PCR cycle threshold (Ct) values for 3091 positive specimens. Results PPA was 100% for the 101 pooled specimens. There was a linear relationship between Ct values for pooled and single-tested specimens (r = 0.96–0.99; slope ≈ 1). The mean pooled Ct shifts at 40 cycles were 2.38 and 1.90, respectively, for the N1 and N3 targets. The median Cts for 3091 positive specimens were 25.9 (N1) and 24.7 (N3). The percentage of positive specimens with Cts between 40 and the shifted Ct was 1.42% (N1) and 0.0% (N3). Conclusions Pooled and individual testing of specimens positive for SARS-CoV-2 demonstrated 100% agreement, which demonstrates the viability of pooled specimens for SARS-COV-2 testing using a dual-target RT-PCR system. Pooled specimen testing can help increase testing capacity for SARS-CoV-2 with a low risk of false-negative results. [ABSTRACT FROM AUTHOR]

Since embryonic heart development is a complex process and acquisition of human embryonic specimens is challenging, the mechanism by which the embryonic conduction system develops remains unclear. Herein, we attempt to gain insights into this developmental process through immunohistochemical staining and 3D reconstructions. Expression analysis of T‐box transcription factor 3, cytoskeleton desmin, and nucleoskeleton lamin A protein in human embryos in Carnegie stages 11–20 showed that desmin is preferentially expressed in the myocardium of the central conduction system compared with the peripheral conduction system, and is co‐expressed with T‐box transcription factor 3 in the central conduction system. Further, lamin A was first expressed in the embryonic ventricular trabeculations, where the terminal ramifications of the peripheral conduction system develop, and extended progressively to all parts of the central conduction system. The uncoupled spatiotemporal distribution pattern of lamin A and desmin indicated that the association of cytoskeleton desmin and nucleoskeleton lamin A may be a late event in human embryonic heart development. Compared with model animals, our data provide a direct morphological basis for understanding the arrhythmogenesis caused by mutations in human DES and LMNA genes. [ABSTRACT FROM AUTHOR]

Background: Second heart field cells and neural crest cells have been reported to participate in the morphogenesis of the pharyngeal arch arteries (PAAs); however, how the PAAs grow out and are separated from the aortic sac into left and right sections is unknown. Results: An Isl‐1 positive pharyngeal mesenchyme protrusion in the aortic sac ventrally extends and fuses with the aortic sac wall to form a midsagittal septum that divides the aortic sac. The aortic sac division separates the left and right PAAs to form independent arteries. The midsagittal septum dividing the aortic sac has a different expression pattern from the aortic‐pulmonary (AP) septum in which Isl‐1 positive cells are absent. At 11 days post‐conception (dpc) in a mouse embryo, the Isl‐1 positive mesenchyme protrusion appears as a heart‐shaped structure, in which subpopulations with Isl‐1+ Tbx3+ and Isl‐1+ Nkx2.5+ cells are included. Conclusions: The aortic sac is a dynamic structure that is continuously divided during the migration from the pharyngeal mesenchyme to the pericardial cavity. The separation of the aortic sac is not complete until the AP septum divides the aortic sac into the ascending aorta and pulmonary trunk. Moreover, the midsagittal septum and the AP septum are distinct structures. Key Findings: Isl‐1 positive pharyngeal mesenchyme protrusion.Pharyngeal arch arteries.Aortic sac division. [ABSTRACT FROM AUTHOR]

The hierarchical flower-like CuO nanostructure was synthesized by a facile sol-gel method without template. Indirectly-heated sensors are fabricated by coating the sol-gel on ceramic tubes with signal electrodes and subsequent annealing. The obtained nanostructures are analyzed by X-ray diffraction and scanning electron microscopy. Their gas sensing performances were investigated. The results indicated that the sensor based on hierarchical flower-like CuO exhibited excellent sensing properties towards ethanol, formaldehyde, acetone and dimethylbenzene. The sensor based on the CuO exhibited the optimal gas sensing performance, giving a ppb-level detection limit and a high response (R/R) of 1.378 to 50 ppb formaldehyde at 250 °C. The response and recovery time of the flower-like CuO nanostructure sensor are 11.9 and 8.4 s, respectively. The significantly enhanced sensing properties to formaldehyde could be attributed to the changes in crystallite size and specific surface area. The results indicate that the hierarchical flower-like CuO nanostructure gas sensor can be a simple and useful platform for formaldehyde and other volatile organic compounds sensing application. [ABSTRACT FROM AUTHOR]

To analyse inner- and inter-annual changes, disaster events of 55 countries in Africa from 1990 to 2014 recorded in the International Disaster Database (EM-DAT) were recounted by year and month and were reorganised in five different regions. Thematic maps of flood disasters in Africa between 1990 and 2014 were drawn using ArcGIS 9.3 to research the spatial distribution patterns of average annual flood frequency, total deaths, total affected, and damage. There were eight natural and socio-economic indicators chosen to explore the main factors influencing the spatio-temporal distribution of flood disasters in Africa, including precipitation, ENSO, runoff, forest coverage rate, reservoir capacity, per capita GDP, population, and urbanisation rate. Studies show that seasonal changes of flood disasters in various regions of Africa, except North Africa, are closely related to precipitation. Annual flood frequencies, from 1990 to 2014, showed a fluctuating upward trend and were in good agreement with ENSO years. In terms of spatial distributions, Ethiopia, Kenya, Somalia, Tanzania in eastern Africa, Nigeria in western Africa, and Libya, and Sudan in northern Arica are flood-prone countries, and main factors influencing spatial disparities include runoff, per capita GDP, population, and urbanisation rate. [ABSTRACT FROM AUTHOR]

3D rose-like NiO nanoparticles have been prepared by electrodeposition method. The samples were characterized through X-ray diffraction, scanning electron microscopy, and transmission electron microscopy. The phase and morphology observations showed the formation of rose-like hierarchical structures with an average particle diameter of 400-500 nm. Gas sensing properties of the as-synthesized rose-like NiO nanoparticles were evaluated by the detection of volatile and toxic gases including ethanol, methanol, and acetone. It was found that NiO nanoroses exhibited a highly response to the three gases at 230 °C. Furthermore, at 5 ppm, the NiO nanorose-based sensor gave a higher response to ethanol ( R/ R = 9.11) and methanol ( R/ R = 8.36), in comparison with acetone ( R/ R = 6.44). The results indicated the NiO nanorose-based sensors displayed a rapid response and recovery as well as good reproducibility. [ABSTRACT FROM AUTHOR]

In this study, rose-like nickel oxide nanoparticles (diameter of 400-500nm) were prepared on indium tin oxide (ITO) glass substrates by a simple electrodeposition in NiSO6H2O solution. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and transmission electron microscope (TEM) were used for analysis of the NiO nanoparticles. The effects of operating temperature on the sensor response and the response versus gas concentration properties of the NiO nanorose-based sensors were investigated. We determined the operating temperature of the gas sensors to be 230C, considering the proper sensitivity and a rapid response. In addition, gas-sensing characteristics of rose-like NiO nanoparticles to formaldehyde were investigated. It was shown that the sensors exhibited good response (/) properties to formaldehyde gas at 230C, making them to be promising candidates for practical detectors to formaldehyde gas. 3D rose-like NiO nanoparticles have been prepared by electrodeposition method. Gas sensing properties of the as-synthesized rose-like NiO nanoparticles were evaluated by the detection of formaldehyde gas. It was found that NiO nanoroses exhibited a high response to the formaldehyde gas at 230˚C. At 1000 ppb, the NiO nanorose-based sensors gave a high response ( Rg/ Ra = 3.43) to formaldehyde gas. Therefore, this manifests 3D hierarchical structure may play an important role in enhancing the gas-sensing performs. [ABSTRACT FROM AUTHOR]

In this study, rose-like nickel oxide (NiO) nanoparticles with diameters of 400–500 nm are prepared on ITO glass substrates by simple electrodeposition in NiSO46H2O solution at room temperature followed by oxidation in air. Scanning electron microscopy, x-ray diffraction and a transmission electron microscope are used for analyses of the NiO nanoparticles. The ethanol gas sensitivity of these nanoparticles is studied. The results indicate that the rose-like NiO nanoparticles could be used for the fabrication of ethanol gas sensors to monitor the low concentration of ethanol gas in air. Furthermore, at 5 ppm, the NiO nanorose-based sensors show a high response to ethanol (Rg/Ra = 8.4). [ABSTRACT FROM AUTHOR]

• A novel tyrosinase inhibitory peptide FPY was identified from defatted walnut meal. • The interaction forces between FPY and the receptor were clarified. • The inhibition type of FPY on tyrosinase was competitive and reversible. • The peptide FPY can resist the degradation of digestive enzymes in vitro. Defatted walnut meal protein was hydrolyzed using alcalase to yield tyrosinase inhibitory peptides. After separation by ultrafiltration and Sephadex G-25, the fraction with the highest tyrosinase inhibitory activity was identified using liquid chromatography-tandem mass spectrometry and 606 peptides were obtained. Then, molecular docking was used to screen for tyrosinase inhibitory peptides and to clarify the theoretical interaction mechanism between the peptides and tyrosinase. A peptide with the sequence Phe-Pro-Tyr (FPY, MW: 425.2 Da) was identified and the synthesized peptide inhibited tyrosine monophenolase and diphenolase with IC 50 values of 1.11 ± 0.05 and 3.22 ± 0.09 mM, respectively. The inhibition of tyrosinase by FPY was competitive and reversible. Good stability of FPY toward digestion was observed in an in vitro gastrointestinal digestion simulation experiment. These results indicated that FPY can be used as a potential tyrosinase inhibitor in the food, medicine, and cosmetics industries. [ABSTRACT FROM AUTHOR]