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Purpose Pulmonary arterial hypertension (PAH) is a disease that the pulmonary artery is abnormally elevated. P2Y12 is an adenosine diphosphate (ADP) receptor and it act as the target of thienopyridine antiplatelet drugs by controlling vascular remodeling. Inhibition of P2Y12 receptor in the process of PAH was explored in this study. Methods The PAH model was established in Sprague-Dawley rats by single subcutaneous injection of 60 mg/kg monocrotaline (MCT). The ticagrelor solution (a selective P2Y12R inhibitor) was intraperitoneally injected into rats at a dose of 14 mg/kg from the time of MCT injection to day 28. Results In the lung tissues of PAH rats, the marked P2Y12R was detected. Treatment with ticagrelor greatly decreased P2Y12R level and efficiently abolished the upregulation of α-SMA as demonstrated by Western blot and RT-PCR. The wall thickness and occlusion score of the pulmonary arterioles showed that blockade of P2Y12R could relieve lung remodeling caused by PAH. The haemodynamic changes at 4 weeks determined that P2Y12R inhibition affected RV pressure and right heart hypertrophy. Conclusions P2Y12R might be involved in the pathogenesis of PAH. Blockade of P2Y12R has potential in treating PAH.

Recently, methyl pentanoate (MPe) has been considered an alternative fuel or additive in gasoline and diesel. Therefore, before its adoption in combustion devices, its combustion characteristics have to be thoroughly understood. Intrinsic flame instability and cellularity are combustion characteristics that influence the performance of combustion devices. In this light, the intrinsic instability and cellularity of MPe/air flames were investigated at the initial pressures of 1, 2, and 4 bar, temperatures of 453 K and 483 K, and equivalence ratios of 0.7-1.4 in a constant volume combustion chamber to understand the various combustion dynamics of MPe. The instability and cellularity were examined using physicochemical characteristics such as the stretch rate, Markstein length, Lewis number, thermal expansion ratio, and flame thickness. There were slight differences in the Markstein length at the various pressures, but generally, according to the Markstein length, MPe flames were unstable at higher pressures. The Lewis number revealed that MPe flames were thermal-diffusively stable, whereas the flame thickness showed MPe flames were more unstable at 483 K and 4 bar. Also, the MPe premixed flame growth rate and stability curves were obtained using theoretical analysis. The stability curves showed that at high initial pressures and temperatures, MPe flame instability occurs early at a smaller flame radius. Moreover, the experimental and theoretical critical radii agreed well. The research results provide a concrete foundation for advancing the knowledge of methyl pentanoate combustion. Refereed/Peer-reviewed

Anti-frustration ability is the ability of individuals to stand up to frustration. The purpose of this study is to develop an anti-frustration ability scale for primary and secondary school students and provide a sound measuring tool for relevant studies. 3168 participants were involved in the study, of which 2488 were formally tested. In the formal test, the samples was randomly divided into 2 groups: Group 1 (n = 1068) was for item analysis and exploratory factor analysis; Group 2 (n = 1420) was for confirmatory factor analysis. The scale consists of 10 items. Item analysis shows that, the item-total correlation of the scale ranges from 0.47 to 0.76; the difference in scores between high and low groups of participants on all items is significant. Exploratory factor analysis shows that, the scale consists of three factors: “frustration endurance”, “frustration mediation” and “growth with frustration”, whose cumulative variance contribution rate is 67.74%. Confirmatory factor analysis shows that the scale had good construct validity (χ2/df = 2.6, GFI = 0.99, AGFI = 0.98, NFI = 0.99, IFI = 0.99, CFI = 0.99, RMR = 0.019, RMSEA = 0.034). The internal consistency coefficient (Cronbach’s alpha) of the scale is 0.83, the Spearman-Brown split-half coefficient is 0.79 and the test-retest coefficient is 0.83. One’s anti-frustration ability is positively correlated with social support (r = 0.49) and self-esteem (r = 0.52). Overall the findings suggest that the Anti-frustration Ability Scale for Primary and Secondary School Students is a reliable and valid tool to measure the anti-frustration ability of primary and secondary school students.

To achieve online multi-target laser ranging in full-waveform light detection and ranging (LiDAR), a multi-target laser ranging method using waveform decomposition is proposed and implemented on a field programmable gate array (FPGA). In this method, an emitted laser pulse and the laser echo scattered from multiple targets are decomposed into a set of Gaussian functions, then the distances between the LiDAR and the targets are obtained using the waveform parameters of Gaussian functions. The waveform decomposition method is modified and implemented on a FPGA for online laser ranging. Simulations and experiments were conducted to verify the ranging performances of the proposed method by the comparition with those of a post-processing Gauss-Newton (post-GN) method. The results of simulations show that the proposed method is more efficient compared with the post-GN method. The time cost reduces 79.8% to 91.1% for a laser echo scattered from three close targets. In experiments, a lab-built full-waveform LiDAR system was used to obtain the waveforms of emitted laser pulses and laser echoes scattered from 1, 2, or 3 targets. The results show that the ranging performances of the proposed method are comparable with those of the post-GN method. The proposed method is capable to distinguish close targets with an equivalent time space of 1.8 times pulse width of an emitted laser pulse and decompose laser echo with a signal-to-noise ratio (SNR) higher than 20 dB. The results show that the proposed method can obtain distances of multiple close targets from a laser echo efficiently and accurately.

Multicomponent heterogeneous Ti

To increase the measurement rate and reduce the ranging error of real-time in-situ laser ranging in full-waveform light detection and ranging (LiDAR), a back propagation (BP) neural network-based online ranging method (BPO) implemented on FPGA is proposed. In BPO, a three-layer BP neural network model is trained and implemented on a Virtex-6 FPGA to estimate the parameters of laser pulses for ranging in real time. The training dataset is generated using the multi-pulse coherent average method combined with the B-spline interpolation method. In the implementation of BPO, the parallel-pipeline architecture is employed to accelerate the computational process. Simulations proved that BPO decreased the time consumption of a single measurement to $2.95~\mu \text{s}$ . The measurement rate was increased to 339 kHz by BPO, which was approximately as 1.2 times as the measurement rate of Gauss-Newton-based online ranging method (GNO). Experiments were conducted by an FPGA-based in-situ ranging system to evaluate the ranging error of BPO. The results revealed that the mean and standard deviation of ranging errors of BPO were 0.8 mm and 1.4 cm for a laser pulse with an SNR of 36.4 dB, respectively. For a laser pulse with an SNR of 21.8 dB, the mean and standard deviation of ranging errors of BPO were 1.7 cm and 5.5 cm, which decreased 0.8 cm and 1.7 cm from those of GNO, implying that the proposed method is capable of mapping the trailing laser pulse and reducing the ranging error caused by the trailing distortion.

Background Congenital hepatic fibrosis (CHF) is a rare autosomal recessive disorder characterized by variable degrees of periportal fibrosis and malformation of bile ducts. CHF is generally accompanied by a variety of conditions or syndromes with other organ involvement. Case summary We report a 5-year-4-month-old Chinese boy with congenital hypothyroidism (CH) diagnosed with CHF. The patient was diagnosed with CH by a newborn screening test and has since been taking levothyroxine. He has developed normally without neurocognitive deficits. Abnormal liver function was observed in the patient at the age of 4 years and 11 mo, and elevated levels of liver function indices were persistent for 5 mo. Radiological imaging indicated hepatospleno-megaly without narrowing of the portal vein but dilated splenic vein. A liver biopsy confirmed the pathological features of CHF. Genetic testing revealed two novel homozygous mutations, namely, c.2141-3T>C variant in PKHD1 related to CHF and c.2921G>A (p.R974H) in DUOX2 related to CH. The patient was treated with compound glycyrrhizin tablet, ursodeoxycholic acid, and levothyroxine after diagnosis. The patient achieved a favorable clinical outcome during a follow-up period of over 2 years. Conclusion Herein, we report the first case of a Chinese boy with comorbidity of CHF and CH, carrying both PKHD1 gene and DUOX2 gene novel mutations. Liver biopsy and genetic testing should be considered for the diagnosis of coexistent liver disease in CH patients with unexplained abnormal liver function.

The thiol redox proteome refers to all proteins whose cysteine thiols are subjected to various redox-dependent posttranslational modifications (PTMs) including S-glutathionylation (SSG), S-nitrosylation (SNO), S-sulfenylation (SOH), and S-sulfhydration (SSH). These modifications can impact various aspects of protein function such as activity, binding, conformation, localization, and interactions with other molecules. To identify novel redox proteins in signaling and regulation, it is highly desirable to have robust redox proteomics methods that can provide global, site-specific, and stoichiometric quantification of redox PTMs. Mass spectrometry (MS)-based redox proteomics has emerged as the primary platform for broad characterization of thiol PTMs in cells and tissues. Herein, we review recent advances in MS-based redox proteomics approaches for quantitative profiling of redox PTMs at physiological or oxidative stress conditions and highlight some recent applications. Considering the relative maturity of available methods, emphasis will be on two types of modifications: 1) total oxidation (i.e., all reversible thiol modifications), the level of which represents the overall redox state, and 2) S-glutathionylation, a major form of reversible thiol oxidation. We also discuss the significance of stoichiometric measurements of thiol PTMs as well as future perspectives toward a better understanding of cellular redox regulatory networks in cells and tissues.

Light detection and ranging (LiDAR) provides a 3-D understanding of environment and plays an important role in autonomous driving. To study the influence of 3-D data quality on the environment perception and provide a theoretical basis for optimizing system design, a multi-beam LiDAR perception assessment model has been established to reveal the relationship between data quality and multi-parameters, including system and motion parameters. A novel ground segmentation algorithm was proposed with a combination of the grid elevation and the neighbor relationship, which was used to validate how the data quality influences the results of environment perception. By the way of down-sampling based on the Karlsruhe Institute of Technology and Toyota Technological Institute (KITTI) dataset, the experimental results showed that the proposed ground segmentation with combination of grid-elevation and neighbor-relationship (GSCGN) method was superior than other general ground segmentation methods in terms of accuracy and efficiency. It should be noted that the mean vertical angular resolution (MVAR), laser repetition frequency, and beam numbers were the dominant influencing parameters on the point density and the accuracy of ground segmentation. Based on the experimental results, the lower limits of system parameters were determined as 16-beam and 4-kHz repetition frequency, with the acceptable recall of 92.2% for ground and 93.5% for object, the accuracy of 92.9% and the runtime of 0.036 s, which can not only provide a reliable environment perception effect, but also reducing the computational burden to satisfy the real-time autonomous driving. This study offers a meaningful investigation to guide LiDAR system design with balancing the contradiction between the optimized system design and the high-degree environment perception.

To investigate the contributions of atmospheric particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5) to heavy air pollution events in Fen-Wei Plain, China and identify their sources, a combination of wavelet analysis and low-atomic number (Z) particle electron probe X-ray microanalysis (EPMA) was utilized in a typical haze episode lasting 10 days (from Nov. 11 to 20, 2016) at Jinzhong, an inland city adjacent to Taiyuan, the capital of Shanxi Province. A 3-layer wavelet decomposition filtration was performed using the daubechies wavelet functions (db6) and the distribution of the real wavelet transformation coefficients and variance of wavelet series for various pollutants within 240 h was plotted. Five dominant periods of PM2.5 in mass concentration were observed, peaking at 101 h, 144 h, 50–51 h, 27–28 h, and 18 h in sequence from high to low in the wavelet variance chart. They were similar to those of PM10, SO2, and CO and partially overlapped with those of NO2, but different from those of O3, implying that PM2.5 have the same sources as PM10, SO2, and CO and have complicated relations with O3 and NO2. It was further found that the chemical compositions of PM2.5 in the dominant periods made great changes compared to the non-dominant periods. The relative number abundance of elemental carbon (EC) and droplets rich in CNOS (likely the mixture of carbonaceous matter with secondary aerosols such as NH4NO3 and (NH4)2SO4/NH4HSO4) in the first and second dominant period were significantly higher than that in other periods. It is concluded that coal and biomass combustion and secondary particles are still the main contributors to the wintertime heavy air pollution events in Fen-Wei Plain, suggesting that the wavelet analysis combined with low-Z particle EPMA is useful in examination of atmospheric particulate matter's origin, evolution, and roles played in haze events.

Cirrhotic cardiomyopathy (CCM) is a common complication of liver cirrhosis. Many patients with cirrhotic livers do not die from liver failure but from abnormal hemodynamics secondary to liver cirrhosis. Liver transplantation is one of the most effective treatments for liver diseases. Recent studies have found that liver transplantation can reverse CCM and improve cardiac function; however, its role and remedial mechanism remain unclear. Circular RNAs (circRNAs) have become an important marker for diagnosing diseases. The differential expression of circRNAs is associated with heart diseases. In this study, we used gene sequencing to detect the circRNA expression profile of patients with CCM before and after liver transplantation and predicted the differential circRNA target genes. The results showed that a total of 1495 circRNAs were dysregulated after liver transplantation, 1319 genes were downregulated, and 176 were upregulated (P 0.05, log2 (fold change) 2.0). The qRT-PCR results showed that circ-ASAP1, circ-N4BP2L2, circ-EXOC6B were significantly downregulated (P 0.05), which were consistent with the RNA sequencing data, and circ-ASAP1 had the most significant difference. Bioinformatics analysis suggested that mTOR and MAPK signaling pathways might be involved in the pathogenesis of CCM. By constructing a circRNA-miRNA-mRNA interaction network, hsa-miR-197-3p, hsa-miR-483-3p, and hsa-miR-885-3p, particularly key miRNA (hsa-miR-483-3p), were found to be the major potential genes involved in CCM regulation. In summary, this study suggested that circRNAs play a crucial regulatory role in the occurrence of CCM before and after liver transplantation, and their potential biological function might be the key to diagnosis and treatment.

Climate models consistently project a significant drying in the Caribbean during climate change, and between 2013 and 2016 the region experienced the worst multiyear drought in the historical period. Although dynamical mechanisms have been proposed to explain drought in the Caribbean, the contributions from mass convergence and advection to precipitation minus evaporation (P − E) anomalies during drought are unknown. Here we analyze the dynamics of contemporaneous droughts in the Caribbean by decomposing the contributions of mass convergence and advection to P − E using observational and simulated data. We find that droughts arise from an anomalous subsidence over the southeastern Caribbean and northeastern South America. Although the contributions from mass convergence and advection vary across the region, it is mass convergence that is the main driver of drought in our study area. A similar dynamical pattern is observed in simulated droughts using the Community Earth System Model (CESM) Large Ensemble (LENS).

Three-dimensional topological insulators are a phase of matter that hosts unique spin-polarized gapless surface states that are protected by time-reversal symmetry. They exhibit unconventional charge and spin transport properties1,2. Intense laser fields can drive ballistic charge dynamics in Dirac bands3,4 or they can coherently steer spin5 and valley pseudospin6. Similarly, high-harmonic generation (HHG) in solids provides insights into the dynamics of the electrons in topological insulators7–13. Despite several theoretical attempts to identify a topological signature in the high-harmonic spectrum14–16, a unique fingerprint has yet to be found experimentally. Here, we observe HHG that arises from topological surface states in the intrinsic topological insulator BiSbTeSe2. The components of the even-order harmonics that are polarized along the pump polarization stem from the spin current in helical surface states, whereas the perpendicular components originate from the out-of-plane spin polarization related to the hexagonal wrapping effect17. The dependence of HHG on surface doping in ambient air also suggests the presence of a Rashba-split two-dimensional electron gas, whose strength can be enhanced by an increase in the intensity of the mid-infrared pump. High-harmonic generation up to the seventh harmonic is observed from the intrinsic three-dimensional topological insulator BiSbTeSe2. The parallel components of the even-order harmonics arise directly from the topological surface states.

The process of domestication has led to dramatic differences in behavioral traits between domestic dogs and gray wolves. Whole-genome research found that a class of putative positively selected genes were related to various aspects of learning and memory, such as long-term potentiation and long-term depression. In this study, we constructed a single-nucleus transcriptomic atlas of the dog hippocampus to illustrate its cell types, cell lineage and molecular features. Using the transcriptomes of 105 057 nuclei from the hippocampus of a Beagle dog, we identified 26 cell clusters and a putative trajectory of oligodendrocyte development. Comparative analysis revealed a significant convergence between dog differentially expressed genes (DEGs) and putative positively selected genes (PSGs). Forty putative PSGs were DEGs in glutamatergic neurons, especially in Cluster 14, which is related to the regulation of nervous system development. In summary, this study provides a blueprint to understand the cellular mechanism of dog domestication.

Sympathetic activation after myocardial infarction (MI) leads to ventricular arrhythmias (VAs), which can result in sudden cardiac death (SCD). The toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factor-kappa B (NF-kB) axis within the hypothalamic paraventricular nucleus (PVN), a cardiac-neural sympathetic nerve centre, plays an important role in causing VAs. An MI rat model and a PVN-TLR4 knockdown model were constructed. The levels of protein were detected by Western blotting and immunofluorescence, and localizations were visualized by multiple immunofluorescence staining. Central and peripheral sympathetic activation was visualized by immunohistochemistry for c-fos protein, renal sympathetic nerve activity (RSNA) measurement, heart rate variability (HRV) analysis and norepinephrine (NE) level detection in serum and myocardial tissue measured by ELISA. The arrhythmia scores were measured by programmed electrical stimulation (PES), and cardiac function was detected by the pressure-volume loop (P-V loop). The levels of TLR4 and MyD88 and the nuclear translocation of NF-kB within the PVN were increased after MI, while sympathetic activation and arrhythmia scores were increased and cardiac function was decreased. However, inhibition of TLR4 significantly reversed these conditions. PVN-mediated sympathetic activation via the TLR4/MyD88/NF-kB axis ultimately leads to the development of VAs after MI.

Dissolved organic phosphorus (DOP) is a key factor in the water eutrophication process because of its high potential bioavailability and inorganic phosphate (Pi) compensation ability through bio- and photo-mineralization. However, the research on the characterization and transformation of DOP is insufficient owing to their complex composition. This study investigates the release of dissolved Pi from DOP photo-mineralization in Lake Dong based on Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis. The results showed that the photo-release of dissolved Pi is spatially heterogeneous in Lake Dong and is consistent with the distribution of DOP concentration. The FT-ICR MS results showed that the simulated irradiation decreased the relative abundance (RA) of the DOP molecular formulae with higher molecular weight (MW) and higher double bond equivalence values (DBE), while the RA of DOP molecular formulae with lower MW and lower DBE value increased or remained. Besides, the total RA of lipid-like formulae increased from 49.09% to 55.90%, while the oxy-aromatic-like formulae decreased from 50.91% to 44.10%, suggesting that simulated irradiation would influence the potential bioavailability of DOP. As the main photolysis medium during DOP photo-mineralization, the hydroxyl radicals (∙OH) are mainly derived from dissolved organic matter (DOM) compared to the nitrate (NO

Taenia pisiformis is one of the most widespread gastrointestinal parasites and its larvae (cysticercosis) causes significant economic loss to rabbit industry. No efficient drug is available for this disease to date. To better understand its genomics, we assembled a 211-Mb high quality genome of T. pisiformis at chromosome level with a scaffold N50 size of 20 Mbp. Totally, 12,097 protein-coding genes was predicted from the genome. Genome-level phylogenetic analysis confirmed the taxonomic affiliations with other tapeworms and revealed that T. pisiformis diverged from its closely related relative T. hydatigena ∼ 14.6 Mya. Comparative genomic analyses revealed that the T. pisiformis genome was characterized by adaptive features of strong positive selection signals from carbohydrate/lipid metabolism and body surface integrity, and of expanded gene families related to metabolism of amino acids and lipids. The high-quality genome of T. pisiformis constitutes a resource for the comparative genomics and for further applications in general parasitology.

The process of dog domestication leads to dramatic differences in behavioral traits compared to grey wolves. A class of putative positively selected genes is related to learning and memory, for instance, long-term potentiation and long-term depression. In this study, we constructed a single-nuclei transcriptomic atlas of the dog hippocampus to illustrate its cell types, cell lineage, and molecular features. Using the transcriptomes of 105,057 single-nuclei from the hippocampus of a Beagle dog, we identified 26 cell clusters and a putative trajectory of oligodendrocyte development. Comparative analysis revealed a significant convergence between dog differentially expressed genes (DEGs) and putative positively selected genes (PSGs). 40 putative PSGs were DEGs in the glutamatergic neurons, especially in the cluster 14, which is related to the regulation of nervous system development. In summary, this study provided a blueprint to understand the cellular mechanism of dog domestication.

This study aims to examine the effects of ambient pressure and injection parameters on the macro-characteristics of air-assisted diesel spray. To illustrate the morphological variation of spray and the formation of vortex ring, the spray diffusion angle was defined. The results indicate that high ambient pressure hinders the radial and axial development of spray and delays the formation of vortex ring. As the ambient pressure increased from 1 bar to 2 bar, the formation of vortex ring was delayed by approximately 0.5 ms. Extending fuel injection duration reduced the spray penetration and increased the far- and near-field spray angles; however, the spray diffusion angle decreased. Increasing fuel injection pressure produces more small-sized droplets owing to enhanced droplet breakup, which decreased the spray penetration and facilitated the lateral diffusion of droplets. Increasing mixture injection duration did not affect the spray penetration; however, the variation of the diffusion angle was slowed down after the mixture injection ended. The insufficient fuel-air interval cannot adequately decelerate the injected fuel droplets, resulting in large penetration and weak lateral diffusion. And there was a critical interval between 1.0 ms − 3.0 ms in this study, after which the fuel droplets could be decelerated sufficiently.

Iron overload is directly associated with diabetes mellitus, loss of islet beta cell, and insulin resistance. Likewise, long noncoding RNA (lncRNA) is associated with type 2 diabetes (T2D). Moreover, lncRNAs could be induced by iron overload. Therefore, we are going to explore the molecular mechanism of lncRNA XIST in iron overload-related T2D. Real-time quantitative PCR and Western blot were used to detect gene and protein levels, respectively. TUNEL and MTT assay were performed to examine cell survival. The glucose test strip, colorimetric analysis kit, ferritin ELISA kit, and insulin ELISA kit were performed to examine the levels of glycolic, iron, and total iron-binding capacity, ferritin, and insulin in serum. Fluorospectrophotometry assay was used to examine labile iron pool level. XIST was higher expressed in T2D and iron overload-related T2D rat tissues and cells, and iron overload-induced promoted XIST expression in T2D. Higher XIST expression was associated with iron overload in patients with T2D. Knockdown of XIST alleviated iron overload and iron overload-induced INS-1 cells injury. Further, we found that XIST can sponge miR-130a-3p to trigger receptor-like kinase 2 (ALK2) expression. Moreover, knockdown of ALK2 alleviated iron overload and iron overload-induced INS-1 cells injury by inhibiting bone morphogenetic protein 6 (BMP6)/ALK2/SMAD1/5/8 axis but reversed with XIST upregulation, which was terminally boosted by overexpression of miR-130a-3p. XIST has the capacity to promote iron overload and iron overload-related T2D initiation and development through inhibition of ALK2 expression by sponging miR-130a-3p, and that targeting this axis may be an effective strategy for treating patients with T2D.