Super enhancer-associated circRNA-circLrch3 regulates hypoxia-induced pulmonary arterial smooth muscle cells pyroptosis by formation of R-loop with host gene.

BACKGROUND: Pulmonary hypertension (PH) is a complex vascular disorder, characterized by pulmonary vessel remodeling and perivascular inflammation. Pulmonary arterial smooth muscle cells (PASMCs) pyroptosis is a novel pathological mechanism implicated of pulmonary vessel remodeling. However, the involvement of circRNAs in the process of pyroptosis and the underlying regulatory mechanisms remain inadequately understood. METHODS: Western blotting, PI staining and LDH release were used to explore the role of circLrch3 in PASMCs pyroptosis. Moreover, S9.6 dot blot and DRIP-PCR were used to assess the formation of R-loop between circLrch3 and its host gene Lrch3. Chip-qPCR were used to evaluate the mechanism of super enhancer-associated circLrh3, which is transcriptionally activated by the transcription factor Tbx2. RESULTS: CircLrch3 was markedly upregulated in hypoxic PASMCs. CircLrch3 knockdown inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circLrch3 can form R-loop with host gene to upregulate the protein and mRNA expression of Lrch3. Furthermore, super enhancer interacted with the Tbx2 at the Lrch3 promoter locus, mediating the augmented transcription of circLrch3. CONCLUSION: Our findings clarify the role of a super enhancer-associated circLrch3 in the formation of R-loop with the host gene Lrch3 to modulate pyroptosis in PASMCs, ultimately promoting the development of PH.

Joint application of A-InDels and miniSTRs for forensic personal, full and half sibling identifications, and genetic differentiation analyses in two populations from China.

BACKGROUND: Previously, a novel multiplex system of 64 loci was constructed based on capillary electrophoresis platform, including 59 autosomal insertion/deletions (A-InDels), two Y-chromosome InDels, two mini short tandem repeats (miniSTRs), and an Amelogenin gene. The aim of this study is to evaluate the efficiencies of this multiplex system for individual identification, paternity testing and biogeographic ancestry inference in Chinese Hezhou Han (CHH) and Hubei Tujia (CTH) groups, providing valuable insights for forensic anthropology and population genetics research. RESULTS: The cumulative values of power of discrimination (CDP) and probability of exclusion (CPE) for the 59 A-InDels and two miniSTRs were 0.99999999999999999999999999754, 0.99999905; and 0.99999999999999999999999999998, 0.99999898 in CTH and CHH groups, respectively. When the likelihood ratio thresholds were set to 1 or 10, more than 95% of the full sibling pairs could be identified from unrelated individual pairs, and the false positive rates were less than 1.2% in both CTH and CHH groups. Biogeographic ancestry inference models based on 35 populations were constructed with three algorithms: random forest, adaptive boosting and extreme gradient boosting, and then 10-fold cross-validation analyses were applied to test these three models with the average accuracies of 86.59%, 84.22% and 87.80%, respectively. In addition, we also investigated the genetic relationships between the two studied groups with 33 reference populations using population statistical methods of FST, DA, phylogenetic tree, PCA, STRUCTURE and TreeMix analyses. The present results showed that compared to other continental populations, the CTH and CHH groups had closer genetic affinities to East Asian populations. CONCLUSIONS: This novel multiplex system has high CDP and CPE in CTH and CHH groups, which can be used as a powerful tool for individual identification and paternity testing. According to various genetic analysis methods, the genetic structures of CTH and CHH groups are relatively similar to the reference East Asian populations.

Competing Endogenous RNAs Crosstalk in Hippocampus: A Potential Mechanism for Neuronal Developing Defects in Down Syndrome.

Down syndrome (DS) is the most example of aneuploidy, resulting from an additional copy of all or part of chromosome 21. Competing endogenous RNAs (ceRNAs) play important roles in neuronal development and neurological defects. This study aimed to identify hub genes and synergistic crosstalk among ceRNAs in the DS fetal hippocampus as potential targets for the treatment of DS-related neurodegenerative diseases. We profiled differentially expressed long non-coding RNAs (DElncRNAs), differentially expressed circular RNAs (DEcircRNAs), differentially expressed microRNAs (DEmiRNAs), and differentially expressed messenger RNAs (DEmRNAs) in hippocampal samples from patients with or without DS. Functional enrichment analysis and gene set enrichment analysis were performed, and chromosome 21-related ceRNA and protein-protein interaction networks were constructed. Additionally, the correlations between lncRNA-mRNA and miRNA-mRNA expression in the samples and HEK293T cells were validated. Our finding of changes in the expression of some key genes and ncRNAs on chromosome 21 in DS might not fully conform to the gene dosage hypothesis. Moreover, we found that four lncRNAs (MIR99AHG, PLCB4, SNHG14, GIGYF2) and one circRNA (hsa_circ_0061697) may competitively bind with three miRNAs (hsa-miR-548b-5p, miR-730-5p, and hsa-miR-548i) and subsequently regulate five mRNAs (beta-1,3-galactosyltransferase 5 [B3GALT5], helicase lymphoid-specific [HELLS], thrombospondin-2 [THBS2], glycinamide ribonucleotide transformylase [GART], clathrin heavy chain like 1 [CLTCL1]). These RNAs, whether located on chromosome 21 or not, interact with each other and might activate the PI3K/Akt/mTOR and Wnt signaling pathways, which are involved in autophagosome formation and tau hyperphosphorylation, possibly leading to adverse consequences of trisomy 21. These findings provide researchers with a better understanding of the fundamental molecular mechanisms underlying DS-related progressive defects in neuronal development.

HNRNPC mediated m6A methylation of 5-methyltetrahydrofolate-homocysteine methyltransferase and involved in the occurrence of RSA.

N6-methyladenosine methylated modification has been shown to play roles in recurrent spontaneous abortion. We aimed to explore role of heterogeneous nuclear ribonucleoprotein C in the occurrence of recurrent spontaneous abortion. We collected embryonic villous tissues from 3 patients with recurrent spontaneous abortion (RSA group) and 3 normal control pregnancy patients. Methylated RNA immunoprecipitation sequencing, RNA sequencing, methylated RNA immunoprecipitation quantitative PCR were conducted to detect the differentially expressed m6A methylation modification gene and regulatory gene in patients with recurrent spontaneous abortion. Methylated RNA immunoprecipitation sequencing and RNA sequencing results showed that the mRNA expression level of heterogeneous nuclear ribonucleoprotein C significantly decreased in RSA group and mRNA expression level of 5-methyltetrahydrofolate-homocysteine methyltransferase increased. Real-time quantitative PCR confirmed the differential expression of heterogeneous nuclear ribonucleoprotein C and 5-methyltetrahydrofolate-homocysteine methyltransferase. Methylated RNA immunoprecipitation quantitative PCR result showed that mRNA m6A modification level of 5-methyltetrahydrofolate-homocysteine methyltransferase decreased in RSA group. The results of western blotting, real-time quantitative PCR, immunofluorescence, matrigel invasion and wound healing assays indicated that heterogeneous nuclear ribonucleoprotein C might regulate the expression of 5-methyltetrahydrofolate-homocysteine methyltransferase by mediating m6A modification, thereby reducing the proliferation and migration of trophoblast cell line, ultimately leading to the occurrence of recurrent spontaneous abortion.

Construction and evaluation of a novel set of 90 microhaplotypes for forensic applications using NGS technology.

Microhaplotypes (MHs), small sets of linked single nucleotide polymorphisms (SNPs), are becoming a valuable tool for paternity testing, personal identification and other different forensic purposes due to their advantages of both short tandem repeats (STRs) and SNPs. However, only a small part of MHs with small segments have been developed and reported so far. And the current population genetic data of MHs are still insufficient. MHs with small segments possess unique advantages in mixture deconvolution, degradation material identification, noninvasive prenatal paternity testing and even medical tumor diagnostic applications. In the present study, a set of 90 autosomal MHs whose PCR amplicon lengths are from 90-150 bp, of which 58 MHs are less than or equal to 100 bp are selected, and assembled into an amplification multiplex system optimized for Ion S5™ System for forensic application. Genetic diversity study of 90 MHs in the populations from different intercontinental regions shows that the polymorphism information content (PIC) values of 83 MHs are greater than 0.4 in populations from East Asia (EAS), and the average PIC value of 90 MHs is greater than 0.5. A total of EAS populations shows the highest cumulative match probability (CMP) and cumulative probability of exclusion (CPE) values in five intercontinental populations. The CMP and CPE values of 90 MHs in EAS are 1.1688 × 10-54 and 0.999999999998954. The informativeness for assignment (In) values of the 90 MHs are calculated based on data from five intercontinental populations, and the In values of 20 MHs have greater than 0.1, indicating that the 20 MHs are high effectiveness in distinguishing different intercontinental populations, which can be used as candidate ancestry informative markers. Further, we have studied the polymorphisms of the 90 MHs based on 224 unrelated individuals of Henan Han population, China, and obtained the frequency data of the 90 MHs. In the Henan Han population, the effective number of alleles (Ae) of the 90 MHs ranges from 1.7649 (MH45) to 3.9792 (MH50), and the Ae values of 10 MHs reach to 3.0; the Ae values of 80 MHs are greater than 2, and the average Ae value for these MHs is 2.422. The average expected heterozygosity, observed heterozygosity, PIC, matching probability, discrimination power and probability of exclusion values of 90 MHs in the Henan Han population are 0.5788, 0.5851, 0.5039, 0.2608, 0.7392 and 0.2806, respectively. The CMP value of 90 MHs in the study population is less than 10-54, and their CPE value reaches 0.999999999999999923. Moreover, the results of the depth of coverage, allele coverage ratio and noise level indicate that the 90 MH amplification system has well sequencing performance, and the sequencing results are reliable. The results indicate the 90 MHs show higher polymorphisms in the study population. The present panel can be well used in paternity testing and individual identification in the study population and even the populations from EAS.

Construction and application of adenoviral vectors.

Adenoviral vectors have been widely used as vaccine candidates or potential vaccine candidates against infectious diseases due to the convenience of genome manipulation, their ability to accommodate large exogenous gene fragments, easy access of obtaining high-titer of virus, and high efficiency of transduction. At the same time, adenoviral vectors have also been used extensively in clinical research for cancer gene therapy and treatment of diseases caused by a single gene defect. However, application of adenovirus also faces a series of challenges such as poor targeting, strong immune response against the vector itself, and they cannot be used repeatedly. It is believed that these problems will be solved gradually with further research and technological development in related fields. Here, we review the construction methods of adenoviral vectors, including "gutless" adenovirus and discuss application of adenoviral vectors as prophylactic vaccines for infectious pathogens and their application prospects as therapeutic vaccines for cancer and other kinds of chronic infectious disease such as human papillomavirus, hepatitis B virus, and hepatitis C virus.

Identification of novel TMEM231 gene splice variants and pathological findings in a fetus with Meckel Syndrome.

Background: Meckel Syndrome (MKS, OMIM #249000) is a rare and fatal autosomal recessive ciliopathy with high clinical and genetic heterogeneity. MKS shows complex allelism with other related ciliopathies such as Joubert Syndrome (JBTS, OMIM #213300). In MKS, the formation and function of the primary cilium is defective, resulting in a multisystem disorder including occipital encephalocele, polycystic kidneys, postaxial polydactyly, liver fibrosis, central nervous system malformations and genital anomalies. This study aimed to analyze the genotype of MKS patients and investigate the correlation between genotype and phenotype. Methods: A nonconsanguineous couple who conceived four times with a fetus affected by multiorgan dysfunction and intrauterine fetal death was studied. Whole exome sequencing (WES) was performed in the proband to identify the potentially pathogenic variant. Sanger sequencing was performed in family members. In silico tools were used to analyse the pathogenicity of the identified variants. cDNA TA-cloning sequencing was performed to validate the effects of intronic variants on mRNA splicing. Quantitative real-time PCR was performed to investigate the effect of the variants on gene expression. Immunofluorescence was performed to observe pathological changes of the primary cilium in kidney tissue from the proband. Results: Two splice site variants of TMEM231 (NM_001077418.2, c.583-1G>C and c.583-2_588delinsTCCTCCC) were identified in the proband, and the two variants have not been previously reported. The parents were confirmed as carriers. The two variants were predicted to be pathogenic by in silico tools and were classified as pathogenic/likely pathogenic variants according to the American College of Medical Genetics and Genomics guideline. cDNA TA cloning analysis showed that both splice site variants caused a deletion of exon 5. RT-PCR revealed that the expression of TMEM231 was significantly decreased and immunofluorescence showed that the primary cilium was almost absent in the proband's kidney tissue. Conclusion: We reported the clinical, genetic, molecular and histochemical characterisation of a family affected by MKS. Our findings not only extended the mutation spectrum of the TMEM231 gene, but also revealed for the first time the pathological aetiology of primary cilia in humans and provide a basis for genetic counselling of the parents to their offspring.

[Genetic analysis of a Chinese pedigree with Cohen syndrome due to compound heterozygous variants of VPS13B gene].

OBJECTIVE: To investigate the clinical phenotype and genetic characteristics of a Chinese pedigree affected with Cohen syndrome. METHODS: A proband who was admitted to Zhengzhou People's Hospital on June 2, 2021 due to intellectual disability and developmental delay, in addition with her younger sister and other family members, were selected as the study subjects. Clinical data of the proband and her younger sister were collected. Genomic DNA was extracted from peripheral venous blood and chorionic villi samples. Chromosomal abnormalities were detected with chromosomal microarray analysis (CMA). Whole exome sequencing (WES) and Sanger sequencing were carried out to detect candidate variants in the proband. With RNA extracted from the peripheral blood samples, VPS13B gene transcripts and expression were analyzed by PCR and real-time quantitative PCR. Prenatal diagnosis was carried out at 12 weeks' gestation. RESULTS: The proband was a 10-year-old female with clinical manifestations including development delay, obesity, severe myopia and peculiar facial features. Her sister was 3 years old with a similar phenotype. CMA revealed no chromosomal abnormality in the proband, while WES results revealed that the proband and her sister had both harbored compound heterozygous variants of the VPS13B gene, namely c.10076_10077delCA (p.T3359fs*29) and c.6940+1G>T, which were respectively inherited from their mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PS4+PM4+PP1; PVS1+PM2_Supporting+PM3+PP1). In vivo splicing assay confirmed that the c.6940+1G>T variant has produced a frameshift transcript with skipping of exon 38. Compared with the control group, the expression of RNA in the peripheral blood of the proband's parents has decreased to 65% ~ 70% (P < 0.01), whilst that in the proband and her sister has decreased to 40% (P < 0.001). Prenatal diagnosis at 12 weeks of gestation has found that the fetus only harbored the heterozygous c.10076_ 10077delCA variant. CONCLUSION: The c.10076_10077delCA (p.T3359fs*29) frameshift variant and c.6940+1G>T splicing variant probably underlay the Cohen syndrome in this pedigree. Genetic testing has facilitated the diagnosis of this disease.

Fabrication and application of molecularly imprinted polymer doped carbon dots coated silica stationary phase.

Facing the difficulties in chromatographic separation of polar compounds, this investigation devotes to developing novel stationary phase. Molecularly imprinted polymers (MIPs) have aroused wide attention, owing to their outstanding selectivity, high stability, and low cost. In this work, a novel stationary phase based on carbon dots (CDs), MIP layer, and silica beads was synthesized to exploit high selectivity of MIPs, excellent physicochemical property of CDs, and outstanding chromatographic performances of silica microspheres simultaneously. The MIP doped CDs coated silica (MIP-CDs/SiO2) stationary phase was systematically characterized by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) surface area measurement, and carbon elemental analysis. Furthermore, the chromatographic performance of the MIP-CDs/SiO2 column was thoroughly assessed by using a wide variety of compounds (including nucleosides, sulfonamides, benzoic acids, and some other antibiotics). Meanwhile, the separation efficiency of the MIP-CDs/SiO2 stationary phase was superior to other kinds of stationary phases (e.g. nonimprinted NIP-CDs/SiO2, MIP/SiO2, and C18-SiO2). The results demonstrated that MIP-CDs/SiO2 column exhibited best performance in terms of chromatographic separation. For all tested compounds, the resolution value was not less than 1.60, and the column efficiency of MIP-CDs/SiO2 for thymidine was 22,740 plates/m. The results further indicate that the MIP-CDs/SiO2 column can combine the good properties of MIP, CDs, with those of silica microbeads. Therefore, the developed MIP-CDs/SiO2 stationary phase can be applied in the separation science and chromatography-based techniques.

Genomic characteristics and prognosis of lung cancer patients with MSI-H: A cohort study.

BACKGROUND: Microsatellite instability (MSI) is the first pan-cancer biomarker approved to guide immune checkpoint inhibitor therapy for MSI-high (MSI-H) solid tumors. In lung cancer, the MSI-H frequency is very low, and the genetic characteristics and prognosis of lung cancer with MSI-H were rarely reported. METHODS: Next-generation sequencing and immunohistochemistry were used detect MSI status, tumor mutation burden (TMB) and PD-L1 expression. RESULTS: Among 12,484 lung cancer patients screened, 66 were found with MSI-H, the proportion was as low as 0.5%. Compared with Microsatellite stability (MSS), TMB was higher in MSI-H lung cancer patients, while PD-L1 expression showed no considerable difference between MSI-H and MSS. After propensity score matching, compared with MSS, the most common companion mutations in MSI-H were TP53, BRCA2, TGFBR2, PTEN and KMT2C. In MSI-H lung adenocarcinoma with EGFR mutation, TGFBR2 and ERBB2 had higher mutation frequency than in MSS. CONCLUSION: The current study reveals the genetic characteristics of MSI-H lung cancer, which advanced our understanding of MSI-H lung cancer.

Identification of a novel de novo mutation of SETBP1 and new findings of SETBP1 in tumorgenesis.

BACKGROUND: In the past decade, SETBP1 has attracted a lot of interest on that the same gene with different type or level (germline or somatic) of variants could provoke different pathologic consequences such as Schinzel-Giedon syndrome, SETBP1 Haploinsufficiency Disorder (SETBP1-HD) and myeloid malignancies. Whole exome sequencing was conducted to detect the etiology of a pregnant woman with mental retardation. As a new oncogene and potential marker of myeloid malignancies, somatic SETBP1 variants in other cancers were rarely studied. We performed a pan-cancer analysis of SETBP1 gene in different cancers for the first time. RESULTS: A novel heterozygous mutation of the SETBP1 gene (c.1724_1727del, p.D575Vfs*4) was found in the patient and the fetus and the mutation was predicted to result in a truncated protein. Reduced SETBP1 expression was associated with SETBP1-HD. The pan-cancer analysis of SETBP1 showed that SETBP1 overexpression should be given special attention in Bladder Urothelial Carcinoma (BLCA) and Stomach adenocarcinoma (STAD). CONCLUSIONS: The de novo SETBP1 mutation was the genetic cause of SETBP1-HD in the family. BLCA and STAD might be related to SETBP1 overexpression.

Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing.

Pulmonary atresia (PA) is a severe cyanotic congenital heart disease. Although some genetic mutations have been described to be associated with PA, the knowledge of pathogenesis is insufficient. The aim of this research was to use whole-exome sequencing (WES) to determine novel rare genetic variants in PA patients. We performed WES in 33 patients (27 patient-parent trios and 6 single probands) and 300 healthy control individuals. By applying an enhanced analytical framework to incorporate de novo and case-control rare variation, we identified 176 risk genes (100 de novo variants and 87 rare variants). Protein‒protein interaction (PPI) analysis and Genotype-Tissue Expression analysis revealed that 35 putative candidate genes had PPIs with known PA genes with high expression in the human heart. Expression quantitative trait loci analysis revealed that 27 genes that were identified as novel PA genes that could be affected by the surrounding single nucleotide polymorphism were screened. Furthermore, we screened rare damaging variants with a threshold of minor allele frequency at 0.5% in the ExAC_EAS and GnomAD_exome_EAS databases, and the deleteriousness was predicted by bioinformatics tools. For the first time, 18 rare variants in 11 new candidate genes have been identified that may play a role in the pathogenesis of PA. Our research provides new insights into the pathogenesis of PA and helps to identify the critical genes for PA.

Oxygen-Bridged Vanadium Single-Atom Dimer Catalysts Promoting High Faradaic Efficiency of Ammonia Electrosynthesis.

Single-atom catalysts have already been widely investigated for the nitrogen reduction reaction (NRR). However, the simplicity of a single atom as an active center encounters the challenge of modulating the multiple reaction intermediates during the NRR process. Moving toward the single-atom-dimer (SAD) structures can not only buffer the multiple reaction intermediates but also provide a strategy to modify the electronic structure and environment of the catalysts. Here, a structure of a vanadium SAD (V-O-V) catalyst on N-doped carbon (O-V2-NC) is proposed for the electrochemical nitrogen reduction reaction, in which the vanadium dimer is coordinated with nitrogen and simultaneously bridged by one oxygen. The oxygen-bridged metal atom dimer that has more electron deficiency is perceived to be the active center for nitrogen reduction. A loop evolution of the intermediate structure was found during the theoretical process simulated by density functional theory (DFT) calculation. The active center V-O-V breaks down to V-O and V during the protonation process and regenerates to the original V-O-V structure after releasing all the nitrogen species. Thus, the O-V2-NC structure presents excellent activity toward the electrochemical NRR, achieving an outstanding faradaic efficiency (77%) along with the yield of 9.97 µg h-1 mg-1 at 0 V (vs RHE) and comparably high ammonia yield (26 µg h-1 mg-1) with the FE of 4.6% at -0.4 V (vs RHE). This report synthesizes and proves the peculiar V-O-V dimer structure experimentally, which also contributes to the library of SAD catalysts with superior performance.

The covalent organic framework based nylon membrane extraction coupled with UHPLC-MS/MS for highly efficiency determination of hexabromocyclododecanes in environmental water.

Hexabromocyclododecanes (HBCDs) have given their adverse effects on environment and human health, and highly sensitive analysis of HBCDs in water is urgent. In this study, a new method for the determination of trace HBCDs in water was established by covalent organic framework (COF) based nylon membrane extraction (ME) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The COF had been self-assembled onto the nylon membrane in a gentle strategy to fabricate COF nylon membrane. Several important ME parameters including the dosage of COF, pH, eluent condition and salinity were systematically investigated. The limits of detection and quantification were 0.011-0.014 and 0.038-0.047 ng/L for three HBCDs, respectively. The linear ranges were from 0.04 to 20 ng/L, and the relative standard deviations were 5.7-17.8 % (intra-day) and 5.2-14.1 % (inter-day). In addition, density functional theory (DFT) calculations on adsorption energy proved that the introduction of halogen bond (XB) made a key contribution to high extraction efficiency and excellent selectivity of COF nylon membrane for HBCDs. The 500 mL of samples, including tap water and reservoir water, could be extracted only in 23 min. The established method presented highly sensitive for ultra-trace analysis of HBCDs in environmental water.

Sulfamethoxazole degradation by Aeromonas caviae and co-metabolism by the mixed bacteria.

Sulfamethoxazole (SMX) is a frequently detected antibiotic in the environment and has attracted much attention. Aeromonas caviae strain GLB-10 was isolated, which could degrade SMX to Aniline and 3-Amino-5-methylisoxazole. Compared to the single bacteria, the mixed bacteria including stain GLB-10, Vibrio diabolicus strain L2-2, Zobellella taiwanensis, Microbacterium testaceum, Methylobacterium, etc, had an ultrahigh degradation efficiency to SMX, with 250 mg/L SMX being degraded in 3 days. In addition to bioproducts of single bacteria, SMX bioproducts by the mixed bacteria also included acetanilide and hydroquinone which were not detected in the single bacteria. The SMX degradation mechanism of the mixed bacteria was more complicated including acetylation, sulfur reduction 4S pathway, and ipso-hydrolysis. The molecular mechanism of the mixed bacteria degrading SMX was also investigated, revealing that the resistance mechanism related to protein outer membrane protein and catalase peroxidase were overexpressed, meanwhile, 6-hydroxynicotinate 3-monooxygenase and ammonia monooxygenase might be the key proteins in SMX degradation. The mixed bacteria could efficiently degrade SMX in different real environments including tap water, river water, artificial lake water, estuary, and, marine water, and have very great research value in bacterial co-metabolism and biodegradation of sulfonamides antibiotics in the environment.

[Analysis of a fetus with unbalanced translocation derived from a balanced t(6;14) maternal translocation].

OBJECTIVE: To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester. METHODS: Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple. RESULTS: The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple. CONCLUSION: The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.

Mechanism Research of Platelet Core Marker Prediction and Molecular Recognition in Cardiovascular Events.

BACKGROUND: Thrombosis triggered by platelet activation plays a vital role in the pathogenesis of cardiovascular and cerebrovascular diseases. OBJECTIVE: This study aims to find platelet combined biomarkers for cardiovascular diseases and investigate the possibility of Concanavalin A (ConA) acting on platelets as a new pharmacological target. METHODS: High-throughput Technology and bioinformatics analysis were combined and groups of microarray chip gene expression profiles for acute myocardial infarction (AMI) and sickle cell disease (SCD) were obtained using GEO database screening. R language limma package was used to obtain differentially expressed genes (DEGs). GO, KEGG, and other databases were utilized to perform the enrichment analysis of DEGs' functions, pathways, etc. PPI network was constructed using STRING database and Cytoscape software, and MCC algorithm was used to obtain the 200 core genes of the two groups of DEGs. Core targets were confirmed by constructing an intersection area screening. A type of molecular probe, ConA, was molecularly docked with the above core targets on the Zdock, HEX, and 3D-DOCK servers. RESULTS: We found six core markers, CD34, SOCS2, ABL1, MTOR, VEGFA, and SMURF1, which were simultaneously related to both diseases, and the docking effect showed that VEGFA is the best-performing. CONCLUSION: VEGFA is most likely to reduce its expression by binding to ConA, which could affect the downstream regulation of the PI3K/Akt signaling pathway during platelet activation. Some other core targets also have the opportunity to interact with ConA to affect platelet-activated thrombosis and trigger changes in cardiovascular events.

Different effects of maternal homocysteine concentration, MTHFR and MTRR genetic polymorphisms on the occurrence of fetal aneuploidy.

RESEARCH QUESTION: Do maternal homocysteine (Hcy) concentrations, MTHFR and MTRR genes have effects on the occurrence of fetal aneuploidy? DESIGN: A total of 619 aneuploidy mothers and 192 control mothers were recruited in this study. Differences in distributions of maternal MTHFR 677C>T, MTHFR 1298A>C and MTRR 66A>G genetic polymorphisms and maternal Hcy concentrations between aneuploidy mothers and control mothers were analysed. RESULTS: The maternal MTHFR 677C>T polymorphism was found to be a risk factor for the occurrence of many fetal non-mosaic aneuploidies studied here, including trisomies 13, 15, 16, 18, 21, 22, TRA and TS. The maternal MTHFR 1298A>C polymorphism was found to be a risk factor specifically associated with the occurrence of fetal trisomy 15 and fetal TS. The maternal MTRR 66A>G polymorphism was found to be a risk factor only specifically associated with the occurrence of fetal trisomy 21. The Hcy concentrations of mothers of trisomies 22, 21, 18, 16, 15 and TS fetuses were significantly higher than the Hcy concentrations of control mothers. CONCLUSIONS: Overall, data suggested an association between these maternal polymorphisms and the susceptibility of fetal non-mosaic trisomy and Turner syndrome. However, these three maternal polymorphisms had different associations with the susceptibility of different fetal aneuploidies, and the elevated maternal Hcy concentration appeared to be a likely risk factor for fetal Turner syndrome and fetal trisomies.

Unveiling the Protonation Kinetics-Dependent Selectivity in Nitrogen Electroreduction: Achieving 75.05 % Selectivity.

While higher selectivity of nitrogen reduction reaction (NRR) to ammonia (NH3 ) is always achieved in alkali, the selectivity dependence on nitrogen (N2 ) protonation and mechanisms therein are unrevealed. Herein, we profile how the NRR selectivity theoretically relies upon the first protonation that is collectively regulated by proton (H) abundance and adsorption-desorption, along with intermediate-*NNH formation. By incorporating electronic metal modulators (M=Co, Ni, Cu, Zn) in nitrogenase-imitated model-iron polysulfide (FeSx), a series of FeMSx catalysts with tailorable protonation kinetics are obtained. The key intermediates behaviors traced by in situ FT-IR and Raman spectroscopy and operando electrochemical impedance spectroscopy demonstrate the strong protonation kinetics-dependent selectivity that mathematically follows a log-linear Bradley curve. Strikingly, FeCuSx exhibits a record-high selectivity of 75.05 % at -0.1 V (vs. RHE) for NH3 production in 0.1 M KOH electrolyte.

The combined toxic effects of polyvinyl chloride microplastics and di(2-ethylhexyl) phthalate on the juvenile zebrafish (Danio rerio).

Microplastics (MPs) have the characteristics of large specific surface area, high hydrophobicity and surface charge, so they are easy to combine with other pollutants and cause toxic effects on aquatic organisms. Here, we prepared a polyvinyl chloride-microplastics (PVC-MPs) fragmentation model to simulate the real microplastic state, and characterized its composition, morphology, particle size and zeta potential. On this basis, we used single and compound exposure of PVC and di(2-ethylhexyl) phthalate (DEHP) to explore their effects on hatchability and mortality of zebrafish (Danio rerio) embryos and toxicity to oxidative stress and cardiac development in zebrafish larvae. Herein, PVC-MPs slowed down the hatching rate of zebrafish embryos and induced the death of zebrafish, while DEHP could slow down the induced of death, it had no effect on hatching rate. The PVC-MPs/DEHP single pollution could induce the reactive oxygen species (ROS) and activated the antioxidant defense signaling pathway, while the compound group showed the level of feedback autoregulation of NF-E2-related factor 2 (Nrf2) signaling pathway. The single pollution also could inhibit the expression of genes related to cardiac development, while the combined pollution showed an antagonistic effect. This study provided a theoretical basis for the ecotoxicology and biomonitoring of MPs in the natural state.