Search

Abstract Aortic root aneurysm is a potentially life‐threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, this understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete. This knowledge gap has impeded the development of effective targeted therapies. Here, this study performs the first integrative analysis of single‐nucleus multiomic (gene expression and chromatin accessibility) and spatial transcriptomic sequencing data of human aortic root tissue under healthy and MFS conditions. Cell‐type‐specific transcriptomic and cis‐regulatory profiles in the human aortic root are identified. Regulatory and spatial dynamics during phenotypic modulation of vascular smooth muscle cells (VSMCs), the cardinal cell type, are delineated. Moreover, candidate key regulators driving the phenotypic modulation of VSMC, such as FOXN3, TEAD1, BACH2, and BACH1, are identified. In vitro experiments demonstrate that FOXN3 functions as a novel key regulator for maintaining the contractile phenotype of human aortic VSMCs through targeting ACTA2. These findings provide novel insights into the regulatory and spatial dynamics during phenotypic modulation in the aneurysmal aortic root of humans.

Abstract The borylation of unreactive carbon-hydrogen bonds is a valuable method for transforming feedstock chemicals into versatile building blocks. Here, we describe a transition metal-free method for the photoredox-catalyzed borylation of unactivated C(sp3)−H bond, initiated by 1,5-hydrogen atom transfer (HAT). The remote borylation was directed by 1,5-HAT of the amidyl radical, which was generated by photocatalytic reduction of hydroxamic acid derivatives. The method accommodates substrates with primary, secondary and tertiary C(sp3)−H bonds, yielding moderate to good product yields (up to 92%) with tolerance for various functional groups. Mechanistic studies, including radical clock experiments and DFT calculations, provided detailed insight into the 1,5-HAT borylation process.

Congenital heart disease (CHD) is one of the most common causes of major birth defects, with a prevalence of 1%. Although an increasing number of studies have reported the etiology of CHD, the findings scattered throughout the literature are difficult to retrieve and utilize in research and clinical practice. We therefore developed CHDbase, an evidence-based knowledgebase of CHD-related genes and clinical manifestations manually curated from 1114 publications, linking 1124 susceptibility genes and 3591 variations to more than 300 CHD types and related syndromes. Metadata such as the information of each publication and the selected population and samples, the strategy of studies, and the major findings of studies were integrated with each item of the research record. We also integrated functional annotations through parsing ∼ 50 databases/tools to facilitate the interpretation of these genes and variations in disease pathogenicity. We further prioritized the significance of these CHD-related genes with a gene interaction network approach and extracted a core CHD sub-network with 163 genes. The clear genetic landscape of CHD enables the phenotype classification based on the shared genetic origin. Overall, CHDbase provides a comprehensive and freely available resource to study CHD susceptibilities, supporting a wide range of users in the scientific and medical communities. CHDbase is accessible at http://chddb.fwgenetics.org.

Abstract Hypertrophic cardiomyopathy (HCM) is the most common cardiac genetic disorder characterized by cardiomyocyte hypertrophy and cardiac fibrosis. Pathological cardiac remodeling in the myocardium of HCM patients may progress to heart failure. An in-depth elucidation of the lineage-specific changes in pathological cardiac remodeling of HCM is pivotal for the development of therapies to mitigate the progression. Here, we performed single-nucleus RNA-seq of the cardiac tissues from HCM patients or healthy donors and conducted spatial transcriptomic assays on tissue sections from patients. Unbiased clustering of 55,122 nuclei from HCM and healthy conditions revealed 9 cell lineages and 28 clusters. Lineage-specific changes in gene expression, subpopulation composition, and intercellular communication in HCM were discovered through comparative analyses. According to the results of pseudotime ordering, differential expression analysis, and differential regulatory network analysis, potential key genes during the transition towards a failing state of cardiomyocytes such as FGF12, IL31RA, and CREB5 were identified. Transcriptomic dynamics underlying cardiac fibroblast activation were also uncovered, and potential key genes involved in cardiac fibrosis were obtained such as AEBP1, RUNX1, MEOX1, LEF1, and NRXN3. Using the spatial transcriptomic data, spatial activity patterns of the candidate genes, pathways, and subpopulations were confirmed on patient tissue sections. Moreover, we showed experimental evidence that in vitro knockdown of AEBP1 could promote the activation of human cardiac fibroblasts, and overexpression of AEBP1 could attenuate the TGFβ-induced activation. Our study provided a comprehensive analysis of the lineage-specific regulatory changes in HCM, which laid the foundation for targeted drug development in HCM.

Compared with shale gas in north American, it is older, more mature, and significantly difference in China. Taking the Longmaxi Formation of WY block in Sichuan Basin as an example, the quantitative prediction method of sweet spots for high mature shale gas is formed. Firstly, the geophysical response characteristics of shale gas reservoir is studied, and the physical characteristics of the sweet spots are determined. Then, the distributions of reservoir evaluation parameters, such as total organic carbon, brittleness, and others, are obtained by pre-stack simultaneous inversion. Finally, fuzzy neural network method is carried out to predict the distribution of sweet spots and to deploy wells. Shale gas sweet spots in this block vertically concentrate within 30 m above the bottom of the Longmaxi Formation. And two grades of sweet spots are evaluated. The quantitative relationship between the production results of horizontal wells and the evaluation is established with Fuzzy neural network method.

Abstract Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition characterized by medial layer degeneration of the thoracic aorta. A thorough understanding of the regulator changes during pathogenesis is essential for medical therapy development. To delineate the cellular and molecular changes during the development of TAAD, we performed single-cell RNA sequencing of thoracic aortic cells from β-aminopropionitrile-induced TAAD mouse models at three time points that spanned from the early to the advanced stages of the disease. Comparative analyses were performed to delineate the temporal dynamics of changes in cellular composition, lineage-specific regulation, and cell–cell communications. Excessive activation of stress-responsive and Toll-like receptor signaling pathways contributed to the smooth muscle cell senescence at the early stage. Three subpopulations of aortic macrophages were identified, i.e., Lyve1 + resident-like, Cd74 high antigen-presenting, and Il1rn +/Trem1 + pro-inflammatory macrophages. In both mice and humans, the pro-inflammatory macrophage subpopulation was found to represent the predominant source of most detrimental molecules. Suppression of macrophage accumulation in the aorta with Ki20227 could significantly decrease the incidence of TAAD and aortic rupture in mice. Targeting the Il1rn +/Trem1 + macrophage subpopulation via blockade of Trem1 using mLR12 could significantly decrease the aortic rupture rate in mice. We present the first comprehensive analysis of the cellular and molecular changes during the development of TAAD at single-cell resolution. Our results highlight the importance of anti-inflammation therapy in TAAD, and pinpoint the macrophage subpopulation as the predominant source of detrimental molecules for TAAD. Targeting the IL1RN +/TREM1 + macrophage subpopulation via blockade of TREM1 may represent a promising medical treatment.

Hepatocellular carcinoma (HCC) is a malignancy with one of the worst prognoses. Long noncoding RNAs (lncRNAs) may be important in cancer development and may serve as new biomarkers for the diagnosis and treatment of various tumors, according to mounting research. The purpose of this study was to investigate the expression of INKA2-AS1 and clinical importance in HCC patients. The TCGA database was used to obtain the human tumor samples, while the TCGA and GTEx databases were used to gather the human normal samples. We screened differentially expressed genes (DEGs) between HCC and nontumor tissues. Investigations were made into the statistical significance and clinical significance of INKA2-AS1 expression. A single-sample gene set enrichment analysis (ssGSEA) was used to examine potential relationships between immune cell infiltration and INKA2-AS1 expression. In this investigation, we found that HCC specimens had considerably greater levels of INKA2-AS1 expression than nontumor specimens. When utilizing the TCGA datasets and the GTEx database, high INKA2-AS1 expression showed an AUC value for HCC of 0.817 (95% confidence interval: 0.779 to 0.855). Pan-cancer assays revealed that numerous tumor types had dysregulated levels of INKA2-AS1. Gender, histologic grade, and pathologic stage were all substantially correlated with high INKA2-AS1 expression. A survival study indicated that HCC patients with high INKA2-AS1 expression have shorter OS, DSS, and PFI than those with low INKA2-AS1 expression. Multivariate analysis indicated that INKA2-AS1 expression was an independent prognostic factor for OS of patients with HCC. According to immune analysis, the expression of INKA2-AS1 was favorably correlated with T helper cells, Th2 cells, macrophages, TFH, and NK CD56bright cells and negatively correlated with Th17 cells, pDC, cytotoxic cells, DC, Treg, Tgd, and Tcm. The results of this study collectively suggest that INKA2-AS1 has the potential to be a novel biomarker for predicting the prognosis of HCC patients as well as a significant immune response regulator in HCC.

ObjectivesSeveral COVID-19 vaccines list “uncontrolled epilepsy” as a contraindication for vaccination. This consequently restricts vaccination against COVID-19 in patients with epilepsy (PWE). However, there is no strong evidence that COVID-19 vaccination can exacerbate conditions in PWE. This study aims to determine the impact of COVID-19 vaccination on PWE.MethodsPWE were prospectively recruited from 25 epilepsy centers. We recorded the seizure frequency at three time periods (one month before the first vaccination and one month after the first and second vaccinations). A generalized linear mixed-effects model (GLMM) was used for analysis, and the adjusted incidence rate ratio (AIRR) with 95% CI was presented and interpreted accordingly.ResultsOverall, 859 PWE were included in the analysis. Thirty-one (3.6%) and 35 (4.1%) patients were found to have increased seizure frequency after the two doses, respectively. Age had an interaction with time. The seizure frequency in adults decreased by 81% after the first dose (AIRR=0.19, 95% CI:0.11–0.34) and 85% after the second dose (AIRR=0.16, 95% CI:0.08–0.30). In juveniles (

Shahejie marl in the Shulu Sag is a crucial resource for unconventional hydrocarbon exploration in China. Although breakthroughs have been made in tight oil exploration in this area, the mechanisms underlying the formation of this marl reservoir and factors controlling its ‘sweet spots’ have not been thoroughly studied. To understand the pore structure characteristics and factors influencing the marl reservoir, we analyzed core samples from Wells ST1 and ST3. A series of experiments was conducted on the samples, such as X-ray diffraction, focused ion beam scanning electron microscopy, micro-CT, and total organic carbon test. Additionally, the physical properties of different marl rock fabrics were studied with auxiliary tests, such as mercury intrusion capillary pressure analyses, nuclear magnetic resonance, porosity and permeability tests, and thin-section observation. The results revealed that the marl reservoir is characterized by low porosity (1.61%) and low permeability (2.56mD). The porosity and permeability (1.61% and 3.26mD) of laminated marl were better than those (0.92% and 1.68mD) of massive marl. Clay minerals and quartz content in laminated (11.8 and 8.2%) was less than in massive marl (16.2 and 13.3%). The marl pores include intercrystalline pores, dissolution pores, and microfractures. Additionally, the laminated marl pores were primarily distributed along the dark lamina, with good connectivity. A few isolated and uniform holes were observed in the massive marl. Influenced by rock fabric and mineral composition, layered fractures were mainly developed in the laminated marl, while structural fractures were the main type of microfractures in the massive marl. The primary sedimentary mechanism was the main geological action underlying the differences in marl rock fabric; this mechanism affects the physical properties of the marl reservoir, which are key factors to be considered when searching for the marl reservoir ‘sweet spots’. Particular attention should be paid to these factors during tight oil exploration and development in similar sedimentary basins.

BackgroundAlthough many studies reported the effectiveness of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) or surgical resection (SR) in the treatment of hepatocellular carcinoma (HCC), the efficacy of these two strategies remains controversial. Therefore, this meta-analysis aimed to evaluate and compare the efficacy of sequential use of TACE plus RFA (TACE + RFA) and SR alone in treating HCC.MethodsRelevant studies with unmatched and propensity score-matched patients were identified by comprehensive search of MEDLINE, PubMed, EMBASE, Web of Science, and Cochrane electronic databases. Meta-analysis was conducted using Review Manager (RevMan) software version 5.4.1. Finally, 12 eligible studies were included in this study, including 11 case–control studies and 1 randomized controlled trial. The primary outcome of interest for this study was to compare the 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), major complications, 5-year OS in different tumor diameters between the two treatment strategies, and hospital stay time.ResultsHCC patients who received TACE + RFA had a lower incidence of complication rates and shorter hospital stay time than those who received SR alone. Among these studies using propensity score-matched cohorts, SR had better 3- and 5-year OS than TACE + RFA, whereas there were no significant differences between TACE + RFA and SR regarding the 1-, 3-, and 5-year DFS. When the tumor diameter is longer than 3 cm, the 5-year OS rate is better when SR is selected.ConclusionThere was no significant difference in the short-term survival outcomes between TACE + RFA and SR in HCC patients. Moreover, SR is superior to TACE + RFA in terms of long-term beneficial effects but may result in a higher risk of major complications and a longer hospital stay time.

Abstract Background Variants in the gene encoding bone morphogenetic protein receptor type II (BMPR2) are the most common genetic cause of pulmonary arterial hypertension (PAH), whereas biallelic variants in the eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4) are described in pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis (PVOD/PCH). Racial background may influence the clinical characteristics of patients diagnosed with PAH or PVOD/PCH. Here, we compared the clinical characteristics and survival between patients with BMPR2 variants or EIF2AK4 variants in a Chinese population. Methods Heterozygous variants in BMPR2 and homozygous or compound heterozygous biallelic EIF2AK4 variants predicted to be deleterious were identified as potentially causal. Clinical and radiological data were collected and analysed. The primary outcomes were death or lung transplantation. Hazard ratios (HRs) for death or transplantation associated with the presence of BMPR2 or biallelic EIF2AK4 variants were calculated using Cox proportional hazards models to analyse patient survival. Results Two hundred thirty-two patients with PAH were enrolled for genetic testing, and PAH patients with associated conditions were excluded from the study. Forty-five patients with BMPR2 variants and 11 patients with biallelic EIF2AK4 variants were recruited. PAH patients with BMPR2 or biallelic EIF2AK4 variants presented symptoms at the ages of 25.57 ± 10.17 years and 31.6 ± 9.38 years, respectively. The whole group of patients showed female dominance either with BMPR2 variants or biallelic EIF2AK4 variants. Specific radiological abnormalities are more prominent in EIF2AK4 variant carriers but can also be found in some patients with BMPR2 variants. Biallelic EIF2AK4 variant carriers had worse survival than BMPR2 variant carriers (p

Besides biotechnology, nano-CT, the ideal technology, can also be used to observe three-dimensional nanostructures in intact cells as part of research into the characteristics of tight oil characteristics. There are few applications in the process and it is still in the early stage of development, but the advantages shown by 3D nanostructure technology are very strong and have strong applicability. Even in the face of tight oil reservoirs with poor physical properties, rapid decline in oil production after volume fracturing, and low oil recovery, it also shows very strong advantages. In order to promote the study of tight oil characteristics and avoid various problems, this article studies the characteristics of tight oil reservoirs based on nano-CT. The results show that the introduction of nano-CT technology into the study of tight oil reservoir characteristics can meet the market demand of tight oil and increase by 3.54%. It can continuously expand and develop rich oil resources under the condition of protecting geology and reservoirs, providing strong technical support for the next generation of large-scale tight oil storage and efficient growth, and can be used to a certain extent for research. The resulting reservoir characteristics solve the problem of excess resources.

Summary Endometritis, which is usually caused by bacterial infection, is characterized by high levels of pro‐inflammatory cytokines and a high infertility rate. Triggering receptor expressed on myeloid cells‐1 (TREM‐1) has been recognized as a potent amplifier of inflammatory reactions. Studies have demonstrated reduced inflammatory responses and mortality rates of animals with bacterial infection due to the blocking of TREM‐1 expression. However, whether TREM‐1 deficiency could alleviate the inflammatory reaction in bacterial endometritis is still unclear. Here, TREM‐1 knock‐out (Trem‐1−/−) mice were used to inhibit TREM‐1 signalling to evaluate its role in inflammatory reactions after a highly pathogenic LPS infection in mice uteri. The results demonstrated that TREM‐1 deficiency attenuated the inflammation in mice uteri; markedly reduced the number of polymorphonuclear neutrophils; and suppressed interleukin‐1β (IL‐1β), IL‐6, and tumour necrosis factor‐α (TNF‐α) concentrations in serum as well as their production in inflamed uteri after LPS stimulation. Our results illustrate an anticipated pathogenic impact of TREM‐1 on endometritis during LPS infection and indicate that blocking of TREM‐1 in LPS‐induced endometritis holds considerable promise for blunting excessive inflammation.

Abstract Background Variants with known or possible pathogenicity located in genes that are unrelated to primary disease conditions are defined as secondary findings. Secondary findings are not the primary targets of whole exome and genome sequencing (WES/WGS) assay but can be of great practical value in early disease prevention and intervention. The driving force for this study was to investigate the impact of racial difference and disease background on secondary findings. Here, we analyzed secondary findings frequencies in 421 whole exome-sequenced Chinese children who are phenotypically normal or bear congenital heart diseases/juvenile obesity. In total, 421 WES datasets were processed for potential deleterious variant screening. A reference gene list was defined according to the American College of Medical Genetics and Genomics (ACMG) recommendations for reporting secondary findings v2.0 (ACMG SF v2.0). The variant classification was performed according to the evidence-based guidelines recommended by the joint consensus of the ACMG and the Association for Molecular Pathology (AMP). Results Among the 421 WES datasets, we identified 11 known/expected pathogenic variants in 12 individuals, accounting for 2.85% of our samples, which is much higher than the reported frequency in a Caucasian population. In conclusion, secondary findings are not so rare in Chinese children, which means that we should pay more attention to the clinical interpretation of sequencing results.

Abstract Background Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder associated with high pulmonary artery pressure. Genetic testing enables early diagnosis and offers an opportunity for family screening. To identify genetic mutations and help make a precise diagnosis, we performed genetic testing in 191 probands with PAH and tried to analyze the genotype-phenotype correlation. Methods Initially, PAH samples (n = 119) were submitted to BMPR2 screening using Sanger sequencing. Later, we developed a PAH panel test to identify causal mutations in 13 genes related to PAH and tried to call BMPR2 copy number variations (CNVs) with the panel data. Multiplex ligation-dependent probe amplification (MLPA) was used to search for CNVs in BMPR2, ACVRL1 and ENG. Notably, EIF2AK4 gene was also involved in the panel, which allowed to distinguish pulmonary veno-occlusive disease (PVOD)/pulmonary capillary hemangiomatosis (PCH) patients from idiopathic PAH (IPAH). Characteristics of patients were compared using t test for continuous variables. Results Pathogenic BMPR2 mutations were detected most frequently in 32 (17.9%) IPAH and 5 (41.7%) heritable PAH (HPAH) patients by sequencing, and 12 BMPR2 CNVs called from the panel data were all successfully confirmed by MLPA analysis. In addition, homozygous or compound heterozygous EIF2AK4 mutations were identified in 6 patients, who should be corrected to a diagnosis of PVOD/PCH. Genotype-phenotype correlation analysis revealed that PAH patients with BMPR2 mutations were younger at diagnosis (27.2y vs. 31.6y, p = 0.0003) and exhibited more severe pulmonary hemodynamic impairment and a worse cardiac index compared with those without BMPR2 mutations. Conclusions The panel assay represented a highly valuable tool in PAH genetic testing, not only for the detection of small sequence alterations, but also for an indication of BMPR2 CNVs, which had implications for the specific samples to perform further MLPA assay. Analyses of PAH causal genes have a great help to clinical diagnosis and deep implications in disease treatment.

Cyanobacterial taxonomic studies performed by using the modern approaches always lead to creation of many new genera and species. During the field survey for cyanobacterial resources in China, a filamentous cyanobacterial strain was successfully isolated from a microbial mat attached to rock surfaces of the Ganfu Channel, Jiangxi Province, China. This strain was morphologically similar to the cyanobacterial taxa belonging to the genera Microcoleus and Phormidium. The phylogenetic analyses based on 16S rRNA gene sequences showed that this strain formed a well-supported clade, close to the filamentous genera Microcoleus, Tychonema, and Kamptonema. The maximum similarity of 16S rRNA gene sequence of this strain with the related genera was 95.04%, less than the threshold for distinguishing bacterial genus. The ITS secondary structures also distinguish this strain from the related cyanobacterial genera. Therefore, combined with morphology, 16S rRNA gene sequence, and ITS secondary structures, a novel cyanobacterial genus here as Microcoleusiopsis was established, with the species type as Microcoleusiopsis ganfuensis.

Summary: Cardiac outflow tract (OFT) is a major hotspot for congenital heart diseases. A thorough understanding of the cellular diversity, transitions, and regulatory networks of normal OFT development is essential to decipher the etiology of OFT malformations. We performed single-cell transcriptomic sequencing of 55,611 mouse OFT cells from three developmental stages that generally correspond to the early, middle, and late stages of OFT remodeling and septation. Known cellular transitions, such as endothelial-to-mesenchymal transition, have been recapitulated. In particular, we identified convergent development of the vascular smooth muscle cell (VSMC) lineage where intermediate cell subpopulations were found to be involved in either myocardial-to-VSMC trans-differentiation or mesenchymal-to-VSMC transition. Finally, we uncovered transcriptional regulators potentially governing cellular transitions. Our study provides a single-cell reference map of cell states for normal OFT development and paves the way for further studies of the etiology of OFT malformations at the single-cell level. : Liu et al. present single-cell transcriptomes of over 50,000 cells from the developing cardiac outflow tract in mice. They identify convergent development of the vascular smooth muscle cell (VSMC) lineage, with these cells arising either by a myocardial-to-VSMC trans-differentiation or mesenchymal-to-VSMC transition. Keywords: cardiac outflow tract, single-cell RNA-seq, trans-differentiation, vascular smooth muscle, convergent development

The geological features and distribution regularity of the grain shoal reservoirs of the Cretaceous Mishrif Formation in Halfaya Oilfield and their main controlling factors were analyzed based on cored data, 302 pieces of thin sections and 2507 experiment data points. Various types and multiple phases of grain shoal reservoirs are developed in Mishrif Formation, which are dominated by grainstone, followed by wackestone packstone. The formation and distribution of grain shoal reservoirs are mainly controlled by relative sea level change, paleogeomorpholoy and contemporaneous-penecontemporaneous dissolution. Relative sea level change controls the types and development phases of grain shoals. When the sea level falls, rudists, coquina, arene and pelletoids are extensively deposited, among which, rudists clastic shoal and coquina shoal that are deposited at the lowest sea level have the best reservoir properties, with a maximum porosity of 33.94%, maximum permeability of 764.571×10−3 μm2 and an average permeability of 45.81×10−3 μm2. Paleogeomorpholoy controls high-energy facies belt and the dissolution of meteoric water. The submarine paleohigh controls the formation and distribution of high-energy facies belt during depositional period. However, during uplifting and denudation period, the reservoirs in paleohigh are intensively dissolved and represent good reservoir properties, with an average porosity of 14.78% and permeability of 7.849×10−3 μm2. Contemporaneous-penecontemporaneous dissolution results in the formation of most effective pores, which is the key factor for the formation of grain shoal reservoirs in the study area. Key words: grain shoal reservoirs, main controlling factor, relative sea level change, paleogeomorpholoy, dissolution, Mishrif Formation, Halfaya Oilfield, Mesopotamia basin

The objective of this study is to evaluate the rheological properties of SBS/CRP composite modified asphalt under different aging conditions in alpine cold regions. In this study, the styrene-butadiene-styrene (SBS) block copolymer, crumb rubber powder (CRP), softeners and various additives were used to prepare the SBS/CRP composite modified asphalt. The 4.5% SBS modified asphalt and SK90 virgin asphalt were also selected for comparing. The thin film oven test (TFOT) and pressure aging vessel (PAV) aging test were conducted to simulate the different aging conditions. The frequency sensitivity, high-temperature deformation resistance and low-temperature crack resistance of SBS/CRP composite modified asphalt under different aging conditions were studied by the dynamic shear rheometer (DSR) and bending beam rheometer (BBR) test. The results show that the frequency sensitivity of SBS/CRP composite modified asphalt is the lowest. At low and medium temperatures, it has relatively low strength and good flexibility. The master curve of composite modulus for the unaged and aged SBS/CRP composite modified asphalt is in a cluster state. It has strong anti-aging capability, which is less affected by aging conditions. It also has a strong low-temperature relaxation ability, which can meet the requirements of performance at −24 °C in PG classification. The high-temperature deformation resistance of SBS/CRP composite modified asphalt is not much different from SBS modified asphalt’s. Therefore, it can provide the basic support for the application in alpine cold regions under the conditions of low temperature, strong radiation and heavy load.

In the course of the task, the mobile robot should find the shortest and most smooth obstacle-free path to move from the current point to the target point efficiently, which is namely the path planning problem of the mobile robot. After analyzing a large number of planning algorithms, it is found that the combination of traditional planning algorithm and heuristic programming algorithm based on artificial intelligence have outstanding performance. Considering that the basic rapidly exploring random tree algorithm is widely used for some of its advantages, meanwhile there are still defects such as poor real-time performance and rough planned path. So, in order to overcome these shortcomings, this article proposes target bias search strategy and a new metric function taking both distance and angle into account to improve the basic rapidly exploring random tree algorithm, and the neural network is used for curve post-processing to obtain a smooth path. Through simulating in complex environment and comparison with the basic rapidly exploring random tree algorithm, it shows good real-time performance and relatively shorter and smoother planned path, proving that the improved algorithm has good performance in handling path planning problem.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune reactions, and it is an essential mediator of death in sepsis. However, the ligand for TREM-1 has not been fully identified. Previous research identified a natural ligand of TREM-1 distributed on platelets that contributed to the development of sepsis. However, the exact signal for TREM-1 recognition remains to be identified. Here, we identified actin as a TREM-1-interacting protein on platelets and found that recombinant actin could interact with recombinant TREM-1 extracellular domain directly. Furthermore, actin co-localized with TREM-1 on the surface of activated mouse macrophage RAW264.7 cells interacting with platelets. In addition, recombinant actin could enhance the inflammatory response of macrophages from wt mice but not from trem1−/− mice, and the enhancement could be inhibited by LP17 (a TREM-1 inhibitor) in a dose-dependent manner. Importantly, extracellular actin showed co-localization with TREM-1 in lung tissue sections from septic mice, which suggested that TREM-1 recognized actin during activation in sepsis. Therefore, the present study identified actin as a new ligand for TREM-1 signaling, and it also provided a link between both essential regulators of death in sepsis.

The origin, characteristics and geological significance of the collapsed-paleocave systems in the Sinian to Permian carbonate strata in Central Sichuan Basin are studied based on 3D seismic interpretation and attributes analysis, as well as imaging logging and cores. Collapsed-paleocave systems are distributed in the Sinian to Permian carbonate strata vertically and along the ends, releasing offsets and intersections of faults horizontally. On profile, they occur as seismic events push-down. The collapsed-paleocave systems mainly originated from fault movements at three main structural phases, the first stage of Tongwan, the second and third stages of Tongwan and the Early Caledonian, and eventually got into shape at the end of the Permian. The collapsed-paleocave systems are featured by multi-layers, wide distribution and good reservoir quality, in which reservoir space is made up of pre-existing pores, structure genetic fractures and collapsed genetic fractures. According to seismic response characteristics, three types of collapsed-paleocave systems are identified in this area, including multi-layer cave system collapsed complex, multi-layer cave passage collapsed system and intra-bed cave collapsed system. The multi-layer cave system collapsed complex and multi-layer cave passage collapsed system in the overlying deformed layers where fractures are widely distributed may be the favorable targets for future exploration. Key words: collapsed-paleocave systems, collapse mechanism, concentric circular faults, Sinian to Permian, Central Sichuan Basin

BackgroundThis study was aimed to investigate the clinical relevance between glycoprotein Ia (GPIA) rs1126643C/T polymorphism and the outcome of coronary artery disease after coronary artery bypass graft (CABG) surgery and explore the involved potential mechanisms. Methods and ResultsWe genotyped GPIA rs1126643 polymorphism of 1592 patients who underwent CABG and followed up for a median period of 72.8 months. Patients who are GPIA rs1126643 T‐allele carriers have a higher major adverse cardiac or cerebrovascular events risk post‐CABG than those who are CC homozygotes (hazard ratio [HR]=1.29; P=0.022). The clinical association between the risk allele (T) carriage and major adverse cardiac or cerebrovascular events was confirmed in another cohort study, which included 646 CABG patients from various health centers across China. Meanwhile, rs1126643 T allele was also linked with increased risk of major adverse cardiac or cerebrovascular events (HR=1.73; P=0.019). To explore the underlying mechanisms, we prospectively recruited 131 coronary artery disease patients, assessed their platelet aggregation function, and focused on detecting their GPIA mRNA level and protein expression. Results showed that patients with rs1126643 T allele have elevated platelet aggregation activity (P=0.029) when protein expression is increased (P

This paper proposes a twice deployment node balance algorithm (TDNB) which guarantees successful detection of the moving target on road networks. Through dividing the deployment of the sensor nodes into two phases instead of deploying all the sensors at one time, TDNB has a better performance. In the former phase, some of the sensors are deployed on the road at random. In the latter phase, the rest of the sensors are deployed on demand to make the number on each path the same. Due to the equivalence of the node's number, the network will have a prolonged lifetime after inserting nodes into the segment according to this algorithm. TDNB extends the network's lifetime remarkably compared with the former algorithms. Furthermore, TDNB enables us to insert nodes to the segment required in the network instead of all the segments, which reduces the workload to a large extent. In short, without increasing the number of sensors in road network, TDNB has a better performance compared to VISA in terms of network lifetime, which meets the demand for persistent monitoring application.

Normal temperature tensile and fatigue tests were adopted to test the mechanical performance and fatigue life of 2524 aluminum alloy under the three states of T3, artificial aging, and creep aging, and scanning electron microscope and transmission electron microscope were also used to observe the fatigue fracture morphology and aging precipitation features of the alloy under the above three states. Results showed that the alloy treated by creep aging can obtain higher fatigue life, but that treated by artificial aging is lower than T3; T3 alloy is mainly dominated by GPB region. Meanwhile, the crystal boundary displays continuously distributed fine precipitated phases; after artificial aging and creep aging treatment, a large amount of needle-shaped S′ phases precipitate inside the alloy, while there are wide precipitated phases at the crystal boundary. Wide precipitation free zones appear at the crystal boundary of artificial-aging samples, but precipitation free zones at the alloy crystal boundary of creep aging become narrower and even disappear. It can be seen that creep aging can change the precipitation features of the alloy and improve its fatigue life.

By undertakig an aging experiment on 2219 aluminum alloy under different external field and by the method of hardness test, a comparative study on the kinetics of aging generated under different external fields was conducted. Furthermore, the time-temperature-transformation curves (TTT curve) were obtained, and the microstructure and mechanical property of the alloy under the effect of different external fields were tested. Results indicated that the effect of magnetic field postponed the alloy’s aging precipitation process, and slightly reduced its mechanical property; the effects of electric field accelerated the alloy’s aging precipitation, increased its mechanical property and made the precipitated phase of alloy smaller and diffused. In addition, through analysis, it was concluded that the performance of the specimen was even more balanced under the effect of electromagnetic field.

In order to characterize the creep behaviors of 2219 aluminum alloy at different temperatures and stress levels, a RWS-50 Electronic Creep Testing Machine (Zhuhai SUST Electrical Equipment Company, Zhuhai, China) was used for creep experiment at temperatures of 353~458 k and experimental stresses of 130~170 MPa. It was discovered that this alloy displayed classical creep curve characteristics in its creep behaviors within the experimental parameters, and its creep value increased with temperature and stress. Based on the creep equation of hyperbolic sine function, regression analysis was conducted of experimental data to calculate stress exponent, creep activation energy, and other related variables, and a 2219 aluminum alloy creep constitutive equation was established. Results of further analysis of the creep mechanism of the alloy at different temperatures indicated that the creep mechanism of 2219 aluminum alloy differed at different temperatures; and creek characteristics were presented in three stages at different temperatures, i.e., the grain boundary sliding creep mechanism at a low temperature stage (T < 373 K), the dislocation glide creep mechanism at a medium temperature stage (373 K ≤ T < 418 K), and the dislocation climb creep mechanism at a high temperature stage (T ≥ 418 K). By comparative analysis of the fitting results and experiment data, they were found to be in agreement with the experimental data, revealing that the established creep constitutive equation is suitable for different temperatures and stresses.

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined. In the present study, we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation. Specifically, we identify the chemokine CCL2, released by ChP epithelial cells, recruits CCR2+ monocytes to the ChP thereby inciting hydrocephalus pathogenesis. The accumulated ChP macrophages increase the inflammation in ChP epithelial cells through TNF-α/TNFR1/NF-κB signaling cascade, thereby leading to CSF hypersecretion. Strikingly, augmentation of ChP‒CCL2 using an adeno-associated viral approach (AAV) exacerbates macrophage recruitment, activation, and ventriculomegaly in rat PHH models. Systemic application of Bindarit, a specific CCL2 inhibitor, significantly inhibits ChP macrophage infiltration and activation and reduces CSF secretion rate. Furthermore, the administration of CCR2 antagonist (INCB 3284) reduces ChP macrophage accumulation and ventriculomegaly. This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus.