Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.

UHPLC-MS/MS-based central carbon metabolism unveils the biomarkers related to colon cancer.

Even though colon cancer ranks among the leading causes of cancer mortality, early detection dramatically increases survival rates. Many studies have been conducted to determine whether altered metabolite levels may serve as a potential biomarker of cancer that affects key metabolic pathways. The goal of the study was to detect metabolic biomarkers in patients with colon cancer using liquid chromatography-mass spectrometry (LC-MS). This study consisted of 30 patients with colon cancer. An analysis of the metabolomes of cancer samples and para-carcinoma tissues was conducted. We identified a series of important metabolic changes in colon cancer by analyzing metabolites in cancerous tissues compared to their normal counterparts. They are mainly involved in the pentose phosphate pathway, the TCA cycle, glycolysis, galactose metabolism, and butanoate metabolism. As well, we observed dysregulation of AMP, dTMP, fructose, and D-glucose in colon cancer. Additionally, the AUCs for AMP, dTMP, fructose, and D-glucose were greater than 0.7 for the diagnosis of colon cancer. In conclusion, AMP, dTMP, fructose, and D-glucose showed excellent diagnostic performance and could serve as novel disease biomarkers for colon cancer diagnosis.

Formation of Iridium(III) Complexes via Selective Activation of the C-H and N-H Bonds of a Dipyridylpyrrole Ligand.

Treatment of [Ir(PPh3)3Cl] with 2-[5-(pyridin-2-yl)-1H-pyrrol-2-yl]pyridine (Hdpp) in refluxing toluene affords an unexpected pyrrole-metalated iridium(III) hydride complex, [Ir(K2C,N-dpp)(H)(Cl)(PPh3)2] (1), via Cpyrrole-H activation, while the presence of the base KOtBu as the deprotonation reagent produces a pyridine-metalated iridium(III) hydride complex, [Ir(K3C,N,N-dpp)(H)(PPh3)2] (2), via Cpyridine-H activation. Treatment of [Ir(PPh3)3Cl] prepared by a convenient method with Hdpp in the presence of KOtBu under the refluxing mixture solvent toluene/methanol (2:1, v/v) generates the N,N-chelating complex [Ir(K2N,N-dpp)(H)(Cl)(PPh3)2] (3) together with 1 and the N,N-chelating dihydride complex [Ir(K2N,N-dpp)(H)2(PPh3)2] (4). Complex 4 is also readily produced by the reaction of [Ir(PPh3)3Cl] and Hdpp in the presence of KOtBu under refluxing methanol or by the reaction of IrCl3 and PPh3 in refluxing 2-ethoxyethanol. Complexes 1-4 are fully characterized by NMR, IR, and UV-vis spectroscopy and X-ray diffraction analysis. The dpp-/dpp2- ligand shows rich coordination capability, of which pyridine- and pyrrole-cyclometalated coordination modes are first reported. The formation of structural isomers 1 and 3 involved the selective activation of the C-H and N-H bonds of Hdpp is rationalized by theoretical calculations.

[Clinical features and SLC6A8 gene mutations of cerebral creatine deficiency syndrome I: an analysis of two families].

This article reports the clinical and genetic features of two cases of cerebral creatine deficiency syndrome I (CCDSI) caused by SLC6A8 gene mutations. Both children were boys. Boy 1 (aged 2 years and 10 months) and Boy 2 (aged 8 years and 11 months) had the clinical manifestations of delayed mental and motor development, and convulsion. Their older brothers had the same symptoms. The mother of the boy 1 had mild intellectual disability. The genetic analysis showed two novel homozygous mutations, c.200G>A(p.Gly67Asp) and c.626_627delCT(p.Pro209Argfs*87), in the SLC6A8 gene on the X chromosome, both of which came from their mothers. These two novel mutations were rated as possible pathogenic mutations and were not reported in the literature before. This study expands the mutation spectrum of the SLC6A8 gene and has great significance in the diagnosis of boys with delayed development, and epilepsy.

Cube is a good form: Hyperspectral band selection via multi-dimensional and high-order structure preserved clustering.

As an effective strategy for reducing the noisy and redundant information for hyperspectral imagery (HSI), hyperspectral band selection intends to select a subset of original hyperspectral bands, which boosts the subsequent different tasks. In this paper, we introduce a multi-dimensional high-order structure preserved clustering method for hyperspectral band selection, referred to as MHSPC briefly. By regarding original hyperspectral images as a tensor cube, we apply the tensor CP (CANDECOMP/PARAFAC) decomposition on it to exploit the multi-dimensional structural information as well as generate a low-dimensional latent feature representation. In order to capture the local geometrical structure along the spectral dimension, a graph regularizer is imposed on the new feature representation in the lower dimensional space. In addition, since the low rankness of HSIs is an important global property, we utilize a nuclear norm constraint on the latent feature representation matrix to capture the global data structure information. Different to most of previous clustering based hyperspectral band selection methods which vectorize each band as a vector without considering the 2-D spatial information, the proposed MHSPC can effectively capture the spatial structure as well as the spectral correlation of original hyperspectral cube in both local and global perspectives. An efficient alternatively updating algorithm with theoretical convergence guarantee is designed to solve the resultant optimization problem, and extensive experimental results on four benchmark datasets validate the effectiveness of the proposed MHSPC over other state-of-the-arts.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Wastewater treatment and emerging contaminants: Bibliometric analysis.

In recent years, emerging contaminants have been found in the wastewater, surface water, and even drinking water, which should be treated to ensure the safety of our living environment. In this study, we provide a comprehensive summary of wastewater treatment and emerging contaminants research from 1998 to 2021 by using the bibliometric analysis. This study is conducted based on the Web of Science Core Collection Database. The bibliometix R-package, VOSviewer and CiteSpace software are used for bibliometric analysis and science mapping. A dataset of 10, 605 publications has been retrieved. The analysis results show that China has produced the most publications. China and the United States have the closest cooperation. Analysis of the most cited papers reveals that the purification or removal techniques such as ozonation or membrane filtration can effectively remove pharmaceutical compounds from the water environment. We also found that the efficient detection of emerging contaminants and the optimization of removal methods are current challenges. Finally, future research directions are discussed.

Preparation, characterization, and bioactivity evaluation of oligosaccharides from Atractylodes lancea (Thunb.) DC.

Sixteen oligosaccharide monomers with the degree of polymerization 3 to 18 (DP 3 to DP 18) and three active fractions (DP 3-9, DP 8-11, and DP 11-17) were separated from Atractylodes lancea (Thunb.) DC. by optimized fast protein liquid chromatography coupled with refractive index detector (FPLC-RID) and preparation hydrophilic interaction chromatography (Pre-HILIC). Gas chromatography-mass spectrometer (GC-MS), liquid chromatography tandem mass spectrometry (LC-MS/MS), nuclear magnetic resonance (NMR) spectroscopy, and methylation analysis showed that the oligosaccharide in A. lancea was 1-kestose [ß-D-fructofuranosyl-(2 â†’ 1)-ß-D-fructofuranosyl-(2 â†’ 1)-α-D-glucopyranoside] (inulin-type fructooligosaccharides, FOS). Particularly, DP 3-9 showed the best capacity in stimulating phagocytic, NO, and cytokines production on RAW264.7 cells than any other purified oligosaccharide monomers and active fractions. It could also activate T-cells in Peyer's patch cells and enhance the production of colony stimulation factors. Besides, FPLC-RID showed a good capacity for large-scale preparation of DP 3-9 with the recovery of more than 93%. The bioactivity of sixteen FOS monomers (DP 3 to DP 18) and three FOS fractions (DP 3-9, DP 8-11, and DP 11-17) investigated in this study are beneficial for the utilization of FOS as a functional ingredient in novel product development.

Gold-catalyzed oxidation of arylallenes: Synthesis of quinoxalines and benzimidazoles.

A gold-catalyzed oxidation of arylallenes to form α-diketones and aldehydes in good yields is presented. Further directed synthesis of quinoxalines and benzimidazoles, via the condensation of the resulting α-diketones and aldehydes with benzene-1,2-diamine, was achieved in high yields.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.

Identification of Six Novel Variants of ACAD8 in Isobutyryl-CoA Dehydrogenase Deficiency With Increased C4 Carnitine Using Tandem Mass Spectrometry and NGS Sequencing.

Isobutyryl-CoA dehydrogenase deficiency (IBDHD, MIM: #611283) is a rare autosomal recessive hereditary disease, which is caused by genetic mutations of acyl-CoA dehydrogenase (ACAD) 8 and associated with valine catabolism. Here, tandem mass spectrometry (MS/MS) was applied to screen 302,993 neonates for inherited metabolic diseases (IMD) in Ningbo of China from 2017 to 2020. The results suggest that 198 newborns (0.7‰) were initially screened positive for IBDHD with C4-Carnitine, and 27 cases (0.1‰) were re-screened positive. Genetic diagnosis was performed on 21 of the 27 cases. Seven compound heterozygous variations, three biallelic variations, and one heterozygous variation of ACAD8 were found with a pathogenicity rate of 33.3% (7/21). In addition, seven biallelic variations, one heterozygous variation of acyl-CoA dehydrogenase short chain (ACADS), and one biallelic variation of acyl-CoA dehydrogenase short/branched chain (ACADSB) was detected. Further research showed that ACAD8 mutations of 11 IBDHD cases distributed in six different exons with total 14 mutation sites. Five of which were known suspected pathogenic sites (c.286G > A, c.553C > T, c.1000C > T, c.409G > A, c.500del) and six were novel mutation sites: c.911A > T, c.904C > T, c.826G > A, c.995T > C, c.1166G > A, c.1165C > T. This finding enriched the mutation spectrum of ACAD8 in IBDHD.

Oligosaccharide-based quality evaluation of Atractylodis rhizome and a strategy for simplifying its quality control.

BACKGROUND: Atractylodis rhizoma, is the dried rhizomes of Atractylodes lancea (Thunb.) DC. or A. chinensis (DC.) Koidz. Both of two are pharmacologically and economically important, while with differences in efficacy. Therefore, an authentication system is vital for evaluation the quality and discrimination adulteration of Atractylodis rhizoma. Fructooligosaccharides (FOS), which are regarded as functional ingredients in Atractylodis rhizoma, have not been used for quality control of Atractylodis rhizoma for shortage of reference compounds. RESULTS: A HPLC-ELSD method was developed for the quantification of FOS in Atractylodis rhizoma. And chemometrics analysis showed that 2 markers including content of degree of polymerization (DP) 12 and total content of DP 3-15 could be used as the main distinctive elements for quality evaluation of Atractylodis rhizome. Actually, the separation and purification of high DP FOS, such as DP 12, is still a challenge because of high polarity. Then DP 5-based qualification evaluation was investigated for quality control of Atractylodis rhizoma. The results showed that A. lancea and A. chinensis could be clearly separated. CONCLUSIONS: DP 5-based quantification method was credible and effectively adopted for solving the shortage of reference compounds and improving the quality control of Atractylodis rhizoma.

Structural characterization and immunoregulatory activity of two polysaccharides from the rhizomes of Atractylodes lancea (Thunb.) DC.

A neutral polysaccharide (ALP-1) and an acidic polysaccharide (ALP-3) were purified from Atractylodes lancea (Thunb.) DC. ALP-1 exhibited a linear backbone composed of (2 → 1)-linked ß-d-fructofuranose. The backbone of ALP-3 was elucidated as →4)-GalAp-(1 → 3,4)-Rhap-(1→, and with branch chain substituted at O-3 position of →3,4)-Rhap-(1→. The branch chain consists of →3,5)-Araf-(1→, →5)-Araf-(1→, and Araf-(1→. Particularly, ALP-3 could significantly stimulate macrophage proliferation in a dose-dependent manner, and stimulate phagocytic, NO and cytokines production than ALP-1 on RAW264.7 cells. Besides, both ALP-1 and ALP-3 could activate T-cells in Peyer's patch cells and enhance the production of colony stimulation factors. While the ALP-3 also showed better intestinal immune system modulating activity than ALP-1. The result of this study indicated that the structure diversity of polysaccharide is crucial for its bioactivity. And also provided evidence for that carbohydrate polymers in A. lancea definitely contributed to its pharmaceutical effects.

Application of RNA interference methodology to investigate and develop SCMV resistance in maize.

Specific fragments of the sugarcane mosaic virus (SCMV) coat protein gene (cp) were amplified by reverse transcriptionpolymerase chain reaction and used to construct a marker free small interfering RNA complex expression vector against SCMV. In planta transformation was performed on maize (Zea mays) inbred line 8112 mediated by Agrobacterium tumefaciens. PCR and Southern blot analyses demonstrated successful integration of the cp segment into the 8112 genome. The in planta transformation frequency was 0.1%, and the cotransformed frequency with the cp and bar genes was 0.034%. Real-time quantitative PCR of samples from different transgenic plant organs showed that the expression of the cp gene fragment in transgenic plants was variable and that the highest expression level occurred in the tassels and leaves and the lowest expression occurred in the roots. Real-time quantitative PCR was also used to measure how gene expression in transgenic T2 generation plants inoculated with SCMV changes over time. The results showed that the hairpin RNA structure transcribed from the cp gene interfered with SCMV infection and transgenic maize lines were not equally effective in preventing SCMV infection. Our findings provide a valuable tool for controlling plant viruses using RNA interference and the posttranslational gene silencing approach.

Identification and expression analysis of primary auxin-responsive Aux/IAA gene family in cucumber (Cucumis sativus).

Aux/IAA is an important gene family involved in many aspects of growth and development. Aux/IAA proteins are short-lived nuclear proteins that are induced primarily by various phytohormones. In this study, 29 Aux/IAA family genes (CsIAA01-CsIAA29) were identified and characterized in cucumber, including gene structures, phylogenetic relationships, conserved protein motifs and chromosomal locations. These genes show distinct organizational patterns of their putative motifs. The distributions of the genes vary: except for five CsIAA genes in cucumber that were not located, seven CsIAA genes were found on scaffold, while the other 17 CsIAA genes were distributed on seven other chromosomes. Based on a phylogenetic analysis of the Aux/IAA protein sequences from cucumber, Arabidopsis and other plants, the Aux/IAA genes in cucumber were categorized into seven subfamilies. To investigate whether the expression of CsIAA genes is associated with auxin induction, their transcript levels were monitored in seedlings treated with IAA (indole-3-acetic acid), and their expression patterns were analysed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). The results showed that 11/29 CsIAA genes were expressed in leaves whether treated with IAA or not and the time course of processing and compared with the control, five CsIAA genes showed low expression only after 60 min treatment with IAA, while 11 genes showed no expression. These results provide useful information for further functional analysis of Aux/IAA gene family in cucumber.

Antioxidant and antibacterial activity of six edible wild plants (Sonchus spp.) in China.

The total phenolic and flavonoid, antioxidant and antibacterial activities of six Sonchus wild vegetables (Sonchus oleraceus L., Sonchus arvensis L., Sonchus asper (L.) Hill., Sonchus uliginosus M.B., Sonchus brachyotus DC. and Sonchus lingianus Shih) in China were investigated. The results revealed that S. arvensis extract and S. oleraceus extract contained the highest amount of phenolic and flavonoid, respectively. Among the methanol extracts of six Sonchus species, S. arvensis extract exhibited the highest radical (DPPH and ABTS+ scavenging power and lipid peroxidation inhibitory power. It also exhibited the highest reducing power at 500 µg mL⁻¹ by A (700) = 0.80. The results of antibacterial test indicated that the S. oleraceus extract showed higher activity than the other five Sonchus wild vegetables extracts, both in Gram-negative bacteria (Escherichia coli, Salmonella enterica and Vibrio parahaemolyticus) and in a Gram-positive bacterium (Staphylococcus aureus). These results indicate that Sonchus wild food plants might be applicable in natural medicine and healthy food.