Genetic analysis and prenatal diagnosis of a pedigree with developmental retardation due to paternal 8q/18q translocation.

Balanced reciprocal chromosomal translocation carriers will have greater risk to experience recurrent miscarriages, embryonic death, and infertility. We show the pedigree carrying a paternal karyotype which was reported first. This research helps to better understand the clinical manifestations and prognosis of patients with this rare chromosomal abnormality.

The relationship between perceived stress and prolonged grief disorder among Chinese Shidu parents: effects of anxiety and social support.

BACKGROUND: Shidu parents refer to the couple who have lost their only child and have not given birth or adopted another child in China. The number of Shidu parents is increasing annually. The aim of this research was to examine the mediating role of anxiety and the moderating role of social support between perceived stress and prolonged grief disorder (PGD) among Chinese Shidu parents. METHODS: A cross-sectional study was carried out with 505 participants who completed a questionnaire including the Prolonged Grief Questionnair-3 (PG-13), the Perceived Stress Scale-10 (PSS-10), the Self-Rating Anxiety Scale (SAS) and the Duke-UNC Functional Social Support Questionnaire (FSSQ). SPSS PROCESS macro was employed to examine the mediating role of anxiety and the moderating role of social support. RESULTS: The mediation analysis showed anxiety partially mediated the link between perceived stress and PGD, and the proportion of mediation of anxiety was 39.22%. The moderated mediation analysis revealed the second stage of mediating effects of anxiety on the link between perceived stress and PGD was moderated by social support. Specifically, compared with Shidu parents with higher social support, the association between anxiety and PGD was closer for those with lower social support. CONCLUSIONS: The moderated mediation model can broaden our understanding of how and when perceived stress, anxiety and social support work together to affect PGD. The interventions aimed at improving mental health of Chinese Shidu parents need to work on reducing stress and enhancing social support.

Electrochemically-gated graphene broadband microwave waveguides for ultrasensitive biosensing.

Identification of non-amplified DNA sequences and single-base mutations is essential for molecular biology and genetic diagnostics. This paper reports a novel sensor consisting of electrochemically-gated graphene coplanar waveguides coupled with a microfluidic channel. Upon exposure to analytes, propagation of electromagnetic waves in the waveguides is modified as a result of interactions with the fringing field and modulation of graphene dynamic conductivity resulting from electrostatic gating. Probe DNA sequences are immobilised on the graphene surface, and the sensor is exposed to DNA sequences which either perfectly match the probe, contain a single-base mismatch or are unrelated. By monitoring the scattering parameters at frequencies between 50 MHz and 50 GHz, unambiguous and reproducible discrimination of the different strands is achieved at concentrations as low as one attomole per litre (1 aM). By controlling and synchronising frequency sweeps, electrochemical gating, and liquid flow in the microfluidic channel, the sensor generates multidimensional datasets. Advanced data analysis techniques are utilised to take full advantage of the richness of the dataset. A classification accuracy >97% between all three sequences is achieved using different Machine Learning models, even in the presence of simulated noise and low signal-to-noise ratios. The sensor exceeds state-of-the-art sensitivity of field-effect transistors and microwave sensors for the identification of single-base mismatches.

The key role of crystal boron in enhanced degradation of refractory contaminants using heterogeneous Fe3+/SPC system.

An origin Fenton-like system was discussed for the abatement of refractory contaminants. Sodium percarbonate (SPC) was utilized as the source of H2O2 and crystal boron (C-boron) was applied to enhance the activation of H2O2. Under the conditions of 0.50 mM Fe3+, 0.34 mM SPC, and heterogeneous catalysis using 100 mg L-1 C-boron, four target pollutants, at the initial concentrations of 20 µM, could be efficiently degraded by the Fenton-like system, with a degradation rate within 20 min up to 81.1% (aspirin, ASA), 92.8% (nitrobenzene, NB), 94.7% (flunixin meglumine, FMME), and 94.3% (benzoic acid, BA) respectively and total organic carbon removal up to 25.0%. The increase of Fe2+ concentration indicated that the conversion of Fe2+/Fe3+ was remarkably promoted by C-boron. Degradation reactions at acidic pH were comparatively fast, with pH-dependent kobs of 9.9 × 10-2 min-1 (ASA), 1.5 × 10-1 min-1 (NB), 1.7 × 10-1 min-1 (FMME), and 1.9 × 10-1 min-1 (BA), whereas those at neutral and alkaline pH were slower. Furthermore, reactive oxygen species including ·OH, 1O2, and O2·- were identified by in-situ electron paramagnetic resonance tests. The contribution ratios of ·OH turned out to be about 71.3-86.7% for the decomposition of four contaminants. The elimination of natural organic matter and the performance of material recycling highlighted the potential for its application in water treatment. The inhibition rate of Chlorella pyrenoidosa reached 211.9% in the C-boron/Fe3+/SPC system. The relatively high algae toxicity limited its application scope, which requires additional research to resolve.

Study on the Clinical Value of Noninvasive Prenatal Testing in Screening the Chromosomal Abnormalities of the Fetus in the Elderly Pregnant Women.

Introduction: To explore the clinical value of noninvasive prenatal testing (NIPT) in screening the chromosomal abnormalities of the fetus in the elderly pregnant women. Materials and Methods: Between January 2020 and December 2021, 1949 elderly pregnant women underwent NIPT in our hospital. At the same time, 236 elderly pregnant women received invasive prenatal diagnosis, and the pregnancy outcomes were followed-up. Results: When NIPT was used for prenatal screening of fetal chromosomal aneuploidy, its diagnostic coincidence rate for trisomy 21 was the highest, with a coincidence rate of 90.00%, and the diagnostic coincidence rate for other chromosomal abnormalities was the lowest, only 22.22%. The sensitivity, specificity, positive predictive rate, and negative predictive rate for T21 by NIPT were 100%, 99.97%, 94.28%, and 100%; for T18 were 100%, 99.92%, 72.22%, and 100%, respectively; and for T13 were 100%, 99.95%, 50%, and 100%, respectively. Patients with high risks according to NIPT results further received invasive prenatal diagnosis, and 18 cases were excluded from the follow-up. For the remaining 1933 cases in the NIPT group, there was an incidence of 2.28% of adverse pregnancy outcomes. For the remaining 234 cases in the Amniocentesis group, there was an incidence of 1.28% of adverse pregnancy outcomes. There was no significant difference between the two groups (P > 0.05). The diagnostic rate of fetal chromosomal abnormalities in pregnant women under 40 years old was about 0.39-0.79%; however, the risk for people over 40 is relatively high at 1.32-4.44%. Conclusion: The noninvasive prenatal screening of fetal DNA in the second trimester of pregnancy for elderly pregnant women has high application value in the prediction of pregnancy outcome. The high risk of pregnancy can be determined by detecting trisomy 21, 18, and 13 syndromes, and the probability of adverse pregnancy outcome increases.

[Mosaic trisomy 20: discrepancy between cyto-and molecular genetic technologies in prenatal diagnosis].

OBJECTIVE: To provide genetic counseling and prenatal diagnosis for a fetus with mosaic trisomy 20. METHODS: Chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) were carried out for a pregnant woman with advanced maternal age. RESULTS: The karyotype of amniotic fluid sample was 47,XN,+20, whilst the result of CMA was normal. To verify this discrepancy, CMA was performed again with the cultured amniotic fluid, which yielded a result of 47,XN,+20. FISH assay of the amniotic fluid sample was nuc ish(D20Z1)×3[11]/(D20Z1)×2[89], which indicated that about 11% of fetal cells were trisomy 20. After the fetus was born, the karyotype of peripheral blood sample was normal. CONCLUSION: The amniotic fluid sample might be mosaic trisomy 20, and a dominant growth of 47,XN,+20 cells had occurred during the culture process, resulting in alteration of amniotic fluid cell composition. Mosaic trisomy 20 indicated by FISH may be attributed to confined placental mosaicism or somatic mosaicism of trisomy 20.

Modification of Artichoke Dietary Fiber by Superfine Grinding and High-Pressure Homogenization and Its Protection against Cadmium Poisoning in Rats.

This study was carried out to investigate the effects of superfine grinding (SP) and high-pressure homogenization (HPH) on the structural and physicochemical properties of artichoke dietary fiber (ADF), as well as the protective effects against cadmium poisoning in rats. The structural characteristics and physicochemical properties of ADF, HPH-ADF (ADF treated by HPH) and CM-ADF (ADF treated by SP and HPH) were determined, and cadmium chloride (CdCl2) was induced by exposing rats for 7 weeks. The amounts of creatinine and urea; the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum; the quantity of red blood cells, hemoglobin, white blood cells and neutrophil proportion in blood samples; and the activity of glutathione peroxidase (GSH-Px) in liver tissue were analyzed. Hematoxylin-eosin (HE) staining was performed to analyze the tissue structure and pathology of the liver and testis. The results showed that ADF subjected to HPH and SP-HPH exhibited increased content of soluble dietary fiber (SDF) (p < 0.05). HPH and SP-HPH treatments increased oil-holding capacity (OHC), total negative charge (TNC) and heavy metal adsorption capacity (p < 0.05). The CdCl2 intervention led to a significant increase in AST, ALT, creatinine, urea, neutrophil proportion and white blood cell count, as well as a significant decrease in GSH-Px activity, red blood cell count and hemoglobin (HGB) (p < 0.05). In rats fed with ADF, HPH-ADF and CM-ADF significantly reduced creatinine, urea amounts, ALT, AST activity in serum, leukocyte count and the neutrophil ratio in blood and increased GSH-Px activity in the liver, in addition to increasing the erythrocyte count and hemoglobin count in blood (p < 0.05). H&E staining results showed that steatosis in the liver was significantly reduced, whereas testicular tissue edema was improved. These results indicate that ADF exhibited positive activity against cadmium poisoning in rats and that CM-ADF had a better protective effect than ADF and HPH-ADF. ADF has specific potential to be used in health foods or therapeutic drugs, providing a reference for the development and utilization of artichoke waste.

Prenatal diagnosis by whole exome sequencing in a family with a novel TBR1 mutation causing intellectual disability.

OBJECTIVE: To provide prenatal diagnosis for a pregnant woman with genetic history of intellectual disability. CASE REPORT: A Chinese pedigree with intellectual disability was collected in this study. Cytogenetic analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) followed by Sanger validation were conducted to identify the genetic pathogenesis. A novel heterozygous deletion c.370_374delTTCCC in TBR1 gene was identified, leading to a frameshift mutation starting at Phe124 followed by a premature stop codon at position 141 (p.Phe124Valfs∗18). Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. Prenatal diagnosis indicated the absence of this mutation, and the family decided to continue the pregnancy after genetic counseling. CONCLUSION: Our findings demonstrated the significance of genetic testing in the diagnosis of intellectual disability. This work also confirmed the effectiveness of WES in prenatal diagnosis.

LncRNA-MSC-AS1 inhibits the ovarian cancer progression by targeting miR-425-5p.

BACKGROUND: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were reported to be aberrantly expressed and related to the pathogenesis of ovarian cancer. However, the role and regulatory mechanism of MSC-AS1 in ovarian cancer has yet to be fully elucidated. METHODS: Expression of lncRNA MSC-AS1 (MSC-AS1) and microRNA-425-5p (miR-425-5p) in the ovarian cancer tissue samples and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). The functions of MSC-AS1 on ovarian cancer cell proliferation, cell cycle and apoptosis were determined using MTT, colony formation and flow cytometry analyses. The protein expression levels were evaluated using western blot assay. The targeting relationship MSC-AS1 and miR-425-5p was verified via dual-luciferase reporter assay. RESULTS: MSC-AS1 expression level was lowly expressed, while miR-425-5p level was highly in ovarian cancer tissues and cells. Elevation of MSC-AS1 has the ability to significantly inhibit cell proliferation and facilitate cell apoptosis in SKOV3 and A2780 cells. Moreover, MSC-AS1 targeted and negatively modulated miR-425-5p. MiR-425-5p up-regulation has been proved to partially reverse the tumor suppressive function of MSC-AS1 overexpression CONCLUSION: MSC-AS1 sponged miR-425-5p to inhibit the ovarian cancer progression. These findings may provide a promising therapeutic target for the treatment of ovarian cancer.

A prenatal diagnosis case of partial duplication 21q21.1-q21.2 with normal phenotype maternally inherited.

BACKGROUND: Down syndrome is characterized by trisomy 21 or partial duplication of chromosome 21. Extensive studies have focused on the identification of the Down Syndrome Critical Region (DSCR). We aim to provide evidence that duplication of 21q21.1-q21.2 should not be included in the DSCR and it has no clinical consequences on the phenotype. CASE PRESENTATION: Because serological screening was not performed at the appropriate gestational age, noninvasive prenatal testing (NIPT) analysis was performed for a pregnant woman with normal prenatal examinations at 22 weeks of gestation. The NIPT results revealed a 5.8 Mb maternally inherited duplication of 21q21.1-q21.2. To assess whether the fetus also carried this duplication, ultrasound-guided amniocentesis was conducted, and the result of chromosomal microarray analysis (CMA) with amniotic fluid showed a 6.7 Mb duplication of 21q21.1-q21.2 (ranging from position 18,981,715 to 25,707,009). This partial duplication of 21q21.1-q21.2 in the fetus was maternally inherited. After genetic counseling, the pregnant woman and her family decided to continue the pregnancy. CONCLUSION: Our case clearly indicates that 21q21.1-q21.2 duplication is not included in the DSCR and most likely has no clinical consequences on phenotype.

Identification of a novel TP63 mutation causing nonsyndromic cleft lip with or without cleft palate.

BACKGROUND: Cleft lip with or without cleft palate (CL/P) is the most common craniofacial anomaly with a high incidence of live births. The specific pathogenesis of CL/P is still unclear, although plenty of studies have been conducted. Variations of tumor protein 63 (TP63) was reported to be related to the phenotype of CL/P. The case discussed in this report involves a pedigree with mutation at TP63 gene, and the variation was not reported before. CASE PRESENTATION: A Chinese pedigree with CL/P was collected in this study. The proband is a 3-year-old boy with the phenotype of CL/P, while his global development and intelligence are normal. After two CL/P repair operations, he looks almost normal. The proband's uncle and grandmother both have the phenotype of CL/P. Cytogenetic analysis and chromosomal microarray analysis (CMA) were performed, followed by whole exome sequencing (WES) and sanger validation. Analysis of WES revealed a variant of C>T at nucleotide position 1324 (1324C>T) of TP63 gene, possibly producing a truncated protein with a premature stop codon at amino acid position 442 (p.Q442*). This mutation was localized at the oligomerization domain (OD) of TP63 and might impair the capacity of p63 oligomerization. CONCLUSION: The mutation in TP63 was recognized to be the possible cause of the phenotype of CL/P in this pedigree. This report provides some evidence for the clinical diagnosis of CL/P. And our study also provides clinical evidence for the molecular mechanism of TP63 gene causing nonsyndromic cleft lip with or without cleft palate (NSCL/P).

Cobalt doped iron oxychloride as efficient heterogeneous Fenton catalyst for degradation of paracetamol and phenacetin.

Cobalt doped iron oxychloride (Co-FeOCl) was synthesized and employed as catalyst in Fenton degradation of paracetamol (APAP) and phenacetin (PNCT) for the first time. The catalytic performance was evaluated by means of various parameters including catalyst load, hydrogen peroxide (H2O2) dose and pH value. The high removal of APAP (87.5%) and PNCT (76.0%) was obtained under conditions of 0.2 g/L Co-FeOCl and 0.5 mM H2O2 at pH 7.0, with calculated pseudo-first order kinetic constants of 0.031 min-1 for APAP and 0.023 min-1 for PNCT. Particularly, quenching tests and in situ electron spin resonance (ESR) tests were employed for the identification of the reactive oxygen species (ROS) in system. Hydroxyl radical (·OH) and superoxide radical (O2-·) were the primary ROS in Co-FeOCl/H2O2 system. A possible mechanism for H2O2 activation by Co-FeOCl catalyst was proposed as well. Finally, the formation of typical disinfection by-products (DBPs) decreased slightly in Co-FeOCl/H2O2 pre-oxidation. However, stability and reusability of Co-FeOCl were deactivated in the consecutive three cycles.

Immature teratoma arising from uterine corpus in an 11-year-old girl: Case report and review of the literature.

Teratomas are one of the most common germ cell tumors, and they usually occur in ovaries. Extragonadal teratomas are rare, especially immature ones. Only several cases of primary teratomas of the uterus have been reported since 1929. Here, the case of an 11-year-old patient who had a 6-month history of sustained abnormal vaginal discharge is presented. Transabdominal ultrasonography revealed a solid mass in her uterus, resulting in the patient undergoing surgery. Examination of PET-CT scans revealed a mass in the right ovary of the patient 20 days after surgery. The patient underwent a second surgery followed by chemotherapy. This is the youngest case among reported patients of primary immature uterine teratoma, and this patient showed no evidence of recurrence during 2 years of follow-up.

Side chain effects on the solid-state emission behaviours and mechano-fluorochromic activities of 10H-phenothiazinylbenzo[d]imidazoles.

A family of 4-cyanophenyl-substituted 10H-phenothiazinylbenzo[d]imidazoles with different side chains at the 10-position are prepared and their physical properties are studied. The detailed structure-property research demonstrates that the cold crystallization temperature of ground samples and the emission wavelengths of pristine samples are in good accordance with the packing density, conformation distortion and intermolecular interactions, but emission wavelengths of ground samples are slightly chain-dependent. For benzimidazoles with alkyl chains, longer and more branched chains can produce looser packings, which cause pristine samples to display red-shifted emission and reduced MFC activity. For benzimidazoles with a phenyl chain, the emission wavelengths of both the pristine and the ground samples are remarkably red-shifted. Moreover, the degree of conformation distortion is larger, and the cold crystallization temperature is higher. Interestingly, the homologue with the n-hexyl chain displays an intense ML effect that is mainly attributed to the heavy discharge quantity on largely enhanced discharge areas under force stimuli due to the great fragility of this crystal.

Prenatal chromosomal microarray analysis in fetuses with congenital heart disease: a prospective cohort study.

BACKGROUND: Currently, chromosomal microarray analysis is considered the first-tier test in pediatric care and prenatal diagnosis. However, the diagnostic yield of chromosomal microarray analysis for prenatal diagnosis of congenital heart disease has not been evaluated based on a large cohort. OBJECTIVE: Our aim was to evaluate the clinical utility of chromosomal microarray as the first-tier test for chromosomal abnormalities in fetuses with congenital heart disease. STUDY DESIGN: In this prospective study, 602 prenatal cases of congenital heart disease were investigated using single nucleotide polymorphism array over a 5-year period. RESULTS: Overall, pathogenic chromosomal abnormalities were identified in 125 (20.8%) of 602 prenatal cases of congenital heart disease, with 52.0% of them being numerical chromosomal abnormalities. The detection rates of likely pathogenic copy number variations and variants of uncertain significance were 1.3% and 6.0%, respectively. The detection rate of pathogenic chromosomal abnormalities in congenital heart disease plus additional structural anomalies (48.9% vs 14.3%, P < .0001) or intrauterine growth retardation group (50.0% vs 14.3%, P = .044) was significantly higher than that in isolated congenital heart disease group. Additionally, the detection rate in congenital heart disease with additional structural anomalies group was significantly higher than that in congenital heart disease with soft markers group (48.9% vs 19.8%, P < .0001). No significant difference was observed in the detection rates between congenital heart disease with additional structural anomalies and congenital heart disease with intrauterine growth retardation groups (48.9% vs 50.0%), congenital heart disease with soft markers and congenital heart disease with intrauterine growth retardation groups (19.8% vs 50.0%), or congenital heart disease with soft markers and isolated congenital heart disease groups (19.8% vs 14.3%). The detection rate in fetuses with congenital heart disease plus mild ventriculomegaly was significantly higher than in those with other types of soft markers (50.0% vs 15.6%, P < .05). CONCLUSION: Our study suggests chromosomal microarray analysis is a reliable and high-resolution technology and should be used as the first-tier test for prenatal diagnosis of congenital heart disease in clinical practice.

Generation of integration-free induced pluripotent stem cell line (NJMUi001-A) from a phenylketonuria patient.

PKU is a prevalent type of inherited metabolic disease, caused by the defective phenylalanine metabolism. In most PKU cases, mutations in the PAH gene could be found. Dysfunction of this hepatic enzyme will lead to diverse clinical symptoms due to a failure in converting phenylalanine into tyrosine. Here, we report an integration-free human induced pluripotent stem cell line (NJMUi001-A) generated from peripheral blood mononuclear cells of a PKU patient by using Sendai virus. This iPS cell line has characteristics of pluripotent stem cells and can be used as a useful tool for the investigation of this inherited metabolic disease.

Peptidomic Analysis of Fetal Heart Tissue for Identification of Endogenous Peptides Involved in Tetralogy of Fallot.

Tetralogy of fallot (TOF) is one of the most prevalent types of congenital heart diseases. As a category of bioactive molecules, peptides have been proved to participate in various biological processes. However, the role of endogenous peptides in the pathogenesis of TOF has not been studied. In this study, we performed a comparative peptidomic profile in the fetal heart of TOF and the control group for the first time by liquid chromatography-tandem mass spectrometry. Our data demonstrated that a total of 201 peptides derived from 176 precursor proteins were differentially expressed in the heart tissues of TOF fetuses compared with normal controls, including 41 upregulated peptides and 160 downregulated peptides. After analyzing the characteristics of these differentially expressed peptides and their precursor proteins, we found that these peptides were potentially involved in different biological processes, especially cardiogenesis and congenital anomaly of the cardiovascular system. Interestingly, we detected several extracellular matrix-derived peptides involved in our differentially expressed peptidomic profile. In summary, our study constructed a comparative peptidomic profile from the heart tissues of TOF fetuses and normal controls, and it identified a series of peptides that could potentially participate in heart development and TOF formation. The emergence of our peptidomics study indicated a new perspective to explore the pathogenesis of abnormal heart morphology, especially TOF.

Generation of MERRF patient-derived induced pluripotent stem cell line iMERRF-C7.

Human iPSC line iMERRF-C7 was generated from PBMCs of a patient with mitochondrial disorder MERRF. Using Sendai virus, the reprogramming factors Oct3/4, Sox2, Klf4, and cMyc were delivered non-integratively. The resulting iPSCs expressed pluripotency markers, could differentiate into the three germ layers in vivo, had normal genomic structure, and retained the disease-causing m.8344 mutation with similar heteroplasmic level.

Functional analysis of ß-amyrin synthase gene in ginsenoside biosynthesis by RNA interference.

KEY MESSAGE: Down-regulation of ß-amyrin synthase gene expression by RNA interference led to reduced levels of ß-amyrin and oleanane-type ginsenoside as well as up-regulation of dammarane-type ginsenoside level. In the biosynthetic pathway of ginsenosides, ß-amyrin synthase catalyzes the reaction from oxidosqualene to ß-amyrin, the proposed aglycone of oleanane-type saponins. Here, RNAi was employed to evaluate the role of this gene in ginsenoside biosynthesis of Panax ginseng hairy roots. The results showed that RNAi-mediated down-regulation of this gene led to reduced levels of ß-amyrin and oleanane-type ginsenoside Ro as well as increased level of total ginsenosides, indicating an important role of this gene in biosynthesis of ginsenoside. Expression of key genes involved in dammarane-type ginsenoside including genes of dammarenediol synthase and protopanaxadiol and protopanaxatriol synthases were up-regulated in RNAi lines. While expression of squalene synthase genes was not significantly changed, ß-amyrin oxidase gene was down-regulated. This work will be helpful for further understanding ginsenoside biosynthesis pathway.