Fetal and neonatal outcome in severe alloimmunization managed with intrauterine transfusion: 18-year experience in a tertiary referral hospital in China

BackgroundHemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization, is an important cause of fetal and neonatal morbidity and mortality. However, fetal and neonatal outcome of HDFN managed with intrauterine transfusion (IUT) in China are unknown. In addition, fetal and neonatal outcomes according to the type of maternal red cell alloantibodies involved and outcomes of hydrops fetalis are also unclear.ObjectivesThe objective of this study was to evaluate fetal and neonatal outcomes of severe red-cell alloimmunization treated by IUT, to compare the outcomes according to the type of antibody, and to investigate the perinatal and postnatal outcomes of hydrops fetalis due to red cell alloimmunization.MethodsA retrospective study of pregnancies affected by HDFN and managed with IUT at a tertiary care university hospital in China between January 2001 and December 2018 was performed. Fetal and neonatal outcomes were investigated, and comparison of outcomes depending on the type of antibody and comparison of outcome between hydrops fetalis and fetuses without hydrops were also conducted.Results244 IUTs were performed in 81 fetuses from 80 pregnancies. Anti-RhD was the major etiology of HDFN requiring IUT (71.6%). The fetal survival rate was 90.1%. The survival rate of the hydropic fetuses was significantly lower than those of the non hydropic fetuses (61.2% vs. 95.6%) (P = 0.002**). Compared with non hydropic fetuses, hydropic fetuses had significantly lower gestational age and lower hemoglobin level at first IUT. The neonatal survival rate was 98.6%. Exchange transfusions were required in 26% of the neonates. 30.1% of neonates had late anemia and required top-up transfusions, and hydropic fetuses required more late top-up transfusions than fetuses without hydrops. No significant difference in fetal and neonatal outcomes was found among the four subgroups stratified by the antibody involved.ConclusionOur study demonstrates that IUT is an effective and safe therapy for severe HDFN at our institution. Early detection and treatment of hydrops is critical for perinatal outcomes. Particular attention should be paid to late postnatal anemia in affected neonates and top-up transfusion is still commonly needed

Genetic dissection of grain iron concentration in hexaploid wheat (Triticum aestivum L.) using a genome-wide association analysis method

Iron (Fe) is an essential micronutrient of the body. Low concentrations of bioavailable Fe in staple food result in micronutrient malnutrition. Wheat (Triticum aestivum L.) is the most important global food crop and thus has become an important source of iron for people. Breeding nutritious wheat with high grain-Fe content has become an effective means of alleviating malnutrition. Understanding the genetic basis of micronutrient concentration in wheat grains may provide useful information for breeding for high Fe varieties through marker-assisted selection (MAS). Hence, in the present study, genome-wide association studies (GWAS) were conducted for grain Fe. An association panel of 207 accessions was genotyped using a 660K SNP array and phenotyped for grain Fe content at three locations. The genotypic and phenotypic data obtained thus were used for GWAS. A total of 911 SNPs were significantly associated with grain Fe concentrations. These SNPs were distributed on all 21 wheat chromosomes, and each SNP explained 5.79–25.31% of the phenotypic variations. Notably, the two significant SNPs (AX-108912427 and AX-94729264) not only have a more significant effect on grain Fe concentration but also have the reliability under the different environments. Furthermore, candidate genes potentially associated with grain Fe concentration were predicted, and 10 candidate genes were identified. These candidate genes were related to transport, translocation, remobilization, and accumulationof ironin wheat plants. These findings will not only help in better understanding the molecular basis of Fe accumulation in grains, but also provide elite wheat germplasms to develop Fe-rich wheat varieties through breeding

Auto-tuning MPI Collective Operations on Large-Scale Parallel Systems

MPI libraries are widely used in applications of high performance computing. Yet, effective tuning of MPI colletives on large parallel systems is an outstanding challenge. This process often follows a trial-and-error approach and requires expert insights into the subtle interactions between software and the underlying hardware. This paper presents an empirical approach to choose and switch MPI communication algorithms at runtime to optimize the application performance. We achieve this by first modeling offline, through microbenchmarks, to find how the runtime parameters with different message sizes affect the choice of MPI communication algorithms. We then apply the knowledge to automatically optimize new unseen MPI programs. We evaluate our approach by applying it to NPB and HPCC benchmarks on a 384-node computer cluster of the Tianhe-2 supercomputer. Experimental results show that our approach achieves, on average, 22.7% (up to 40.7%) improvement over the default setting

Chitosan-salvianolic acid B coating on the surface of nickel-titanium alloy inhibits proliferation of smooth muscle cells and promote endothelialization

Introduction: Intracranial stents are of paramount importance in managing cerebrovascular disorders. Nevertheless, the currently employed drug-eluting stents, although effective in decreasing in-stent restenosis, might impede the re-endothelialization process within blood vessels, potentially leading to prolonged thrombosis development and restenosis over time.Methods: This study aims to construct a multifunctional bioactive coating to enhance the biocompatibility of the stents. Salvianolic acid B (SALB), a bioactive compound extracted from Salvia miltiorrhiza, exhibits potential for improving cardiovascular health. We utilized dopamine as the base and adhered chitosan-coated SALB microspheres onto nickel-titanium alloy flat plates, resulting in a multifunctional drug coating.Results: By encapsulating SALB within chitosan, the release period of SALB was effectively prolonged, as evidenced by the in vitro drug release curve showing sustained release over 28 days. The interaction between the drug coating and blood was examined through experiments on water contact angle, clotting time, and protein adsorption. Cellular experiments showed that the drug coating stimulates the proliferation, adhesion, and migration of human umbilical vein endothelial cells.Discussion: These findings indicate its potential to promote re-endothelialization. In addition, the bioactive coating effectively suppressed smooth muscle cells proliferation, adhesion, and migration, potentially reducing the occurrence of neointimal hyperplasia and restenosis. These findings emphasize the exceptional biocompatibility of the newly developed bioactive coating and demonstrate its potential clinical application as an innovative strategy to improve stent therapy efficacy. Thus, this coating holds great promise for the treatment of cerebrovascular disease

Could social robots facilitate children with autism spectrum disorders in learning distrust and deception?

Social robots have been increasingly involved in our daily lives and provide a new environment for children\u27s growth. The current study aimed to examine how children with and without Autism Spectrum Disorders (ASD)learned complex social rules from a social robot through distrust and deception games. Twenty children with ASD between the ages of 5–8 and 20 typically-developing (TD)peers whose age and IQ were matched participated in distrust and deception tasks along with an interview about their perception of the human-likeness of the robot. The results demonstrated that: 1)children with ASD were slower to learn to and less likely to distrust and deceive a social robot than TD children and 2)children with ASD who perceived the robot to appear more human-like had more difficulty in learning to distrust the robot. Besides, by comparing to a previous study the results showed that children with ASD appeared to have more difficulty in learning to distrust a human compared to a robot, particularly in the early phase of learning. Overall, our study verified that social robots could facilitate children with ASD\u27s learning of some social rules and showed that children\u27s perception of the robot plays an important role in their social learning, which provides insights on robot design and its clinical applications in ASD intervention

Association Between Single Nucleotide Polymorphisms in PPARA and EPAS1 Genes and High-Altitude Appetite Loss in Chinese Young Men

Appetite loss is a common symptom that occurs in high altitude (HA) for lowlanders. Previous studies indicated that hypoxia is the initiating vital factor of HA appetite loss. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 play important roles in hypoxic responses. We aimed to explore the association of these hypoxia-related gene polymorphisms with HA appetite loss. In this study, we enrolled 416 young men who rapidly ascended to Lhasa (3700 m) from Chengdu (<500m) by plane. PPARA, EPAS1, EGLN1, HIF1A, HIF1AN, and NFE2L2 were genotyped by MassARRAY. Appetite scores were measured to identify HA appetite loss. Logistic regression and multiple genetic models were tested to evaluate the association between the single nucleotide polymorphisms (SNPs) and risk of HA appetite loss in crude and adjusted (age and SaO2) analysis. Subsequently, Haploview software was used to analyze the linkage disequilibrium (LD), haplotype construction and the association of diverse haplotypes with the risk of HA appetite loss. Our results revealed that allele “A” in PPARA rs4253747 was significantly associated with the increased risk of HA appetite loss. Codominant, dominant, recessive, and log-additive models of PPARA rs4253747 showed the increased risk of HA appetite loss in the crude and adjusted analysis. However, only dominant, overdominant, and log-additive models of EPAS1 rs6756667 showed decreased risk of HA appetite loss in the crude and adjusted analysis. Moreover, the results from haplotype-based test showed that the rs7292407-rs6520015 haplotype “AC” was associated with HA appetite loss in the crude analysis rather than the adjusted analysis. In this study, we first established the association of SNPs in PPARA (rs4253747) and EPAS1 (rs6756667) genes with susceptibility to HA appetite loss in Han Chinese young men. These findings provide novel insights into understanding the mechanisms involved in HA appetite loss

Characterization of the Relationship of CDKL5 with MeCP2 and Dnmt1 in PrimaryRat Cortical Neurons

ABSTRACT Cyclin-dependent kinase-like 5 (CDKL5) is a protein kinase that is homologous to mitogen-activated protein kinases (MAPKs) and cyclin-dependent kinases (CDKs). Mutations in the CDKL5 gene cause X-linked infantile spasms and phenotypes that overlap with that of Rett syndrome, which is a neurodevelopmental disorder caused primarily by mutations in the methyl CpG binding protein 2 gene (MECP2). Previous studies in transfected cell lines showed that CDKL5 interacts with MeCP2 and DNA (cytosine-5)-methyltransferase 1 (Dnmt1). However, little is known about the relationships of CDKL5 with interacting proteins in primary neuronal cultures. In this study, we investigated the expression patterns of CDKL5, MeCP2 and Dnmt1, and their interaction in cultured rat cortical neurons. Using real-time PCR analysis, we found that CDKL5, MeCP2 and Dnmt1 have similar expression patterns at the mRNA level. In contrast, the expression patterns of those proteins at the protein level are different and could be inversely correlated, as shown by western blotting. Using co-immunoprecipitation, we further demonstrated that CDKL5 interacts with MeCP2 and Dnmt1 in primary rat cortical neurons. These data suggest that a functional link exists among CDKL5, MeCP2 and Dnmt1 during neuronal development and may provide further insight into the pathogenesis of Rett syndrome

PERFUME: detection of 8-oxoguanine DNA glycosylase activity based on primer exchange reaction and functionalized hemin/G-quadruplex DNAzyme

Background: 8-oxoguanine DNA glycosylase can maintain genomic stability and integrity. However, it can interfere with the regular DNA damage repair process, possibly leading to the development of cancer and various other human diseases when its activity becomes abnormal. Current methods for detecting 8-oxoguanine DNA glycosylase activity often suffer from low sensitivity, time-consuming procedures, labor-intensive requirements, and the need for specialized equipment and trained professionals for execution. Consequently, there is an urgent need for a portable, user-friendly 8-oxoguanine DNA glycosylase assay that offers swift results and supports real-time testing. Results: We've developed a PERFUME method that combines primer exchange reaction and functionalized G-quadruplex/hemin DNAzyme for sensitive detection of Fpg, a typical 8-oxoguanine DNA glycosylase. Utilizing a single probe and T4 Polynucleotide Kinase (PNK) simplifies the experiment to a one-step reaction at 37 °C in 3 h, reducing sample consumption and improving sensitivity. We chose functionalized hemin cofactors, significantly improving catalytic efficiency and enhancing detection capability. This biosensor detects Fpg activity with a sensitivity as low as 0.11 U mL−1, displaying exceptional sensitivity, selectivity, and interference resistance in human serum and bacterial cell extracts under isothermal conditions. The biosensor demonstrates remarkable selectivity and ability for Fpg inhibitors screening. In addition, this biosensor enables reading the sample's RGB values using a smartphone, facilitating accurate quantification of Fpg activity without the necessity for specialized equipment. Significance: PERFUME simplifies Fpg detection by using a single hairpin and PNK in a one-step process. We utilize FUME to enhance catalytic efficiency, it surpassing the performance of traditional G-quadruplex/hemin DNAzyme methods. This approach excels in analyzing Fpg in human serum and bacterial extracts. It allows quantitative Fpg detection using UV–Vis and smartphones under isothermal conditions, making it valuable for clinical diagnosis

RIP3 dependent NLRP3 inflammasome activation is implicated in acute lung injury in mice

Abstract Background NLRP3 inflammasome is involved in the inflammatory responses during acute lung injury (ALI). RIP3 triggered NLRP3 inflammasome activation independent of necroptosis induction has recently been documented. In this study, the role of RIP3 in the activation of NLRP3 inflammasome in the development of ALI was investigated. Methods A selective RIP3 inhibitor GSK872 was used to investigate the roles of RIP3 in NLRP3 inflammasome activation in the lipopolysaccharide (LPS) induced ALI mouse model. The mechanism of NLRP3 inflammasome activation was investigated in the human monocytic cell line THP-1. NLRP3 inflammasome and necroptosis were measured by flow cytometry or western blot. RIP3–NLRP3 interaction was interrogated using immunoprecipitation and the Duolink® In situ detection. Results Significant upregulation of both necroptosis and NLRP3 inflammasome pathways were observed in the lungs of mice with LPS induced ALI. GSK872 significantly suppressed the activation of necroptosis and NLRP3 activation with reduction of IL-1β and IL-18 production and inflammatory cells infiltration, resulting in a significant amelioration of lung injury. These two processes were shown to be active in interstitial macrophages and CD11b+ monocyte–macrophages/dendritic cells. In THP-1 cells, RIP3 and NLRP3 interaction was enhanced by LPS/ATP stimulation resulting in IL-1β and IL-18 production. This RIP3–NLRP3 interaction was significantly inhibited by GSK872. Conclusion Taking together, these results show that RIP3 participates in the NLRP3 inflammasome activation in infiltrating macrophages in ALI induced by LPS. This process plays a significant pathogenic role in LPS-induced lung injury