The performance evaluation of NIPT for fetal chromosome microdeletion/microduplication detection: a retrospective analysis of 68,588 Chinese cases.

Background: Chromosomal abnormalities are the main cause of birth defects in newborns. Since the inception of noninvasive prenatal testing (NIPT) technology, it has primarily been applied to the detection of common trisomy (T21, T18, T13). However, the application of NIPT in microdeletion and microduplication detection is still controversial. Methods: This study retrospectively analyzed the data of 68,588 cases that underwent NIPT at Ganzhou Maternal and Child Health Hospital in China. These data were used to evaluate the performance of NIPT in fetal chromosome microdeletion/microduplication detection and to investigate the key factors affecting the NIPT performance. Results: A total of 281 cases (0.41%) had positive NIPT results with copy number variants (CNVs), of which 161 were validated by karyotyping and chromosome microarray analysis (CMA). Among the 161 cases, 92 were confirmed as true positives through karyotyping or CMA, including 61 microdeletion cases and 31 microduplication cases, resulting in a positive predictive value (PPV) of 57.14%. Improvements in library construction methods increased the fraction of cell-free fetal DNA (cffDNA) from 13.76% to 18.44%, leading to a significant improvement in the detection rate (0.47% vs. 0.15%) and PPV (59.86% vs. 28.57%) of NIPT for CNVs. Conclusion: This study proved the robust performance of NIPT for fetal chromosome microdeletion/microduplication detection. In addition, the cffDNA fraction is a key factor influencing NIPT, with increased cffDNA fraction improving the performance of NIPT.

α-Glucosidase Inhibitory Phytochemical Components of Chinese Endemic Plant Whitfordiodendron filipes var. tomentosum.

Whitfordiodendron filipes var. tomentosum is an endemic plant in China. There have been no chemical or pharmacological studies of this plant reported before. In the current research, eight triterpenes and two steroids were obtained. Their structures were established by the analysis of NMR data and comparison with those reported in the literature. These ten structurally diverse compounds comprised five distinct carbon frameworks with different functionalities. The chemotaxonomic significance of these secondary metabolites was discussed, disclosing the common components between the variant W. filipes var. tomentosum and the species W. filipe. Evaluation of α-glucosidase inhibitory activities of these isolates disclosed that compounds 1, 2, 4, and 6 exhibited significant α-glucosidase inhibitory activities (IC50 = 16.6-19.2 µM), which were close in value to the positive control acarbose (IC50 = 11.5 µM). Moreover, the binding modes between the biologically active compounds 1, 2, 4, and 6 and the α-glucosidase protein were preliminarily studied using molecular docking. This study not only showed the chemical and biological profile of the plant W. filipes var. tomentosum but also revealed that these components could be developed as hypoglycemic lead compounds.

Prevalence and genetic analysis of triplicated α-globin gene in Ganzhou region using high-throughput sequencing.

α-globin gene triplication carriers were not anemic in general, while some studies found that α-globin gene triplication coinherited with heterozygous ß-thalassemia may cause adverse clinical symptoms, which yet lacks sufficient evidence in large populations. In this study, we investigated the prevalence and distribution of α-globin gene triplication as well as the phenotypic characteristics of α-globin gene triplication coinherited with heterozygous ß-thalassemia in Ganzhou city, southern China. During 2021-2022, a total of 73,967 random individuals who received routine health examinations before marriage were genotyped for globin gene mutations by high-throughput sequencing. Among them, 1,443 were α-globin gene triplication carriers, with a carrier rate of 1.95%. The most prevalent mutation was αααanti3.7/αα (43.10%), followed by αααanti4.2/αα (38.12%). 42 individuals had coinherited α-globin gene triplication and heterozygous ß-thalassemia. However, they did not differ from the individuals with heterozygous ß-thalassemia and normal α-globin (αα/αα) in terms of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels. In addition, heterogenous clinical phenotypes were found in two individuals with the same genotype. Our study established a database of Ganzhou α-globin gene triplication and provided practical advice for the clinical diagnosis of α-globin gene triplication.

Physiochemical responses of C. elegans under exposure to lanthanum and cerium affected by bacterial metabolism.

The increasing demand for rare earth elements (REEs) in modern applications has drawn significant attention. REEs can be introduced into the environment through REE-containing fertilizers, abandoned REE-rich equipment, and mining, persisting and impacting soil quality, nutrient cycles, and plant growth. Scientists have raised concerns about REEs entering the food chain from the environment and eventually accumulating in organisms. Decades of experimental evidence have shown that these effects include inhibited growth, impaired liver function, and alterations in children's intelligence quotients. However, there exists a paucity of research that has elucidated the metabolic-level biological impacts of REEs. In our study, Caenorhabditis elegans (C. elegans) was used as a model organism to investigate physiological and inherent metabolic changes under exposure to different concentrations of REEs. The diet bacteria of nematodes play a key role in their life and development. Therefore, we investigated the influence of bacterial activity on the nematodes' response to REE exposure. We observed a concentration-dependent accumulation of REEs in nematodes, which consequently led to a reduction in lifespan and alterations in body length. Exposure to a mixed solution of REEs, in comparison to a single REE solution, resulted in greater toxicity toward nematodes. The metabolic results showed that the above changes were closely related to REE-induced amino acid metabolism disorder, membrane disturbance, DNA damage, and oxidative stress. Of note, the presence of living bacteria elicits REE effects in C. elegans. These findings highlight the potential intrinsic metabolic changes occurring in nematodes under REE exposure. Our study raises awareness of the exposure risks associated with REEs, provides valuable insight into the metabolic-level biological impacts of REEs and contributes to the development of effective mitigation strategies to reduce potential risks to human health.

Characterization of a novel HBB:c.194dup variant of the ß-globin gene combined with six alpha genes.

ß-thalassemia (ß-thal) is one of the most prevalent inherited blood disorders in Ganzhou, south China. Next-generation sequencing was used to screen for thalassemia carriers in the general population. During the screening, we identified a novel ß-thal variant in a 46-year-old Chinese man, which was validated by Sanger sequencing. Based on the patient's clinical data, this novel mutation was classified as severe ß0. However, the patient was mildly anemic (hemoglobin, 89 g/L), which was inconsistent with typical ß0 carrier characteristics. On further evaluation, quantitative PCR indicated the presence of six α genes, while molecular analysis and pedigree analysis revealed the coexistence of αααanti3.7 and αααanti4.2. Therefore, we report a novel ß-thal variant combined with six α genes. We describe the patient's clinical phenotype and the process of molecular diagnosis. This case extends the spectrum of thalassemia variants.

Secondary Metabolites from Marine Sponges of the Genus Oceanapia: Chemistry and Biological Activities.

In this review, we summarized the distribution of the chemically investigated Oceanapia sponges, including the isolation and biological activities of their secondary metabolites, covering the literature from the first report in 1989 to July 2019. There have been 110 compounds reported during this period, including 59 alkaloids, 33 lipids, 14 sterols and 4 miscellaneous compounds. Besides their unique structures, they exhibited promising bioactivities ranging from insecticidal to antibacterial. Their complex structural characteristics and diverse biological properties have attracted a great deal of attention from chemists and pharmaceuticals seeking to perform their applications in the treatment of disease.

N-doped three-dimensional needle-like CoS2 bridge connection Co3O4 core-shell structure as high-efficiency room temperature NO2 gas sensor.

The N-doped three-dimensional (3D) needle bridge connection core-shell structure N-CoS2@Co3O4 synthesized in this work was prepared by simple hydrothermal and high-temperature vulcanization methods. The optimized N-CoS2@Co3O4-2 composite response to NO2 is 62.3-100 ppm, a response time of 1.3 s, the recovery time of 17.98 s, the detection limit of 5 ppb and stability of as long as 10 weeks at room temperature (RT). Its excellent NO2 sensing performance is attributed to the unique porous and bridge connection core-shell structure of the N-CoS2@Co3O4-2 with high specific surface area, interconnected internal channels, abundant exposed S edge active sites, and high catalytic performance promoted by N-doping. This simple manufacturing method of high-performance sensing materials paves the way for the design of N-doped bridge connection core-shell structures.

The Soft Coral Sarcophyton trocheliophorum: A Warehouse of Terpenoids with Structural and Pharmacological Diversity.

The soft coral Sarcophyton trocheliophorum, which was frequently encountered on Indo-Pacific and Red Sea coral reefs, furnished a wealth of secondary metabolites. Notably, terpenoids dominated the chemical profile of this species. In this review, we summarized the discovery of 156 terpenoids from the soft coral S. trocheliophorum specimens in different geographical areas. The structures comprised 13 terpenoidal classes with various functionalities. We covered the era from the first report of S. trocheliophorum-derived metabolites in 1976 up to October 2022. The biological effects of these chemical compositions on a vast array of potential pharmacological activities such as protein tyrosine phosphatase 1B (PTP1B) inhibitory, neuroprotective, cytotoxic, anti-inflammatory, antibacterial, antivirus, and immunomodulatory activities were also presented. This review also revealed an immense demand to explore the terpene biosynthetic gene clusters of this species besides the chemo- and bio-investigations.

Thin-layered MoS2 nanoflakes vertically grown on SnO2 nanotubes as highly effective room-temperature NO2 gas sensor.

The unique properties of heterostructure materials make them become a promising candidate for high-performance room-temperature (RT) NO2 sensing. Herein, a p-n heterojunction consisting of two-dimensional (2D) MoS2 nanoflakes vertically grown on one-dimensional (1D) SnO2 nanotubes (NTs) was fabricated via electrospinning and subsequent hydrothermal route. The sulfur edge active sites are fully exposed in the MoS2@SnO2 heterostructure due to the vertically oriented thin-layered morphology features. Moreover, the interface of p-n heterojunction provides an electronic transfer channel from SnO2 to MoS2, which enables MoS2 act as the generous electron donor involved in NO2 gas senor detection. As a result, the optimized MoS2@SnO2-2 heterostructure presents an impressive sensitivity and selectivity for NO2 gas detection at RT. The response value is 34.67 (Ra/Rg) to 100 ppm, which is 26.5 times to that of pure SnO2. It also exhibits a fast response and recovery time (2.2 s, 10.54 s), as well as a low detection limit (10 ppb) and as long as 20 weeks of stability. This simple fabrication of high-performance sensing materials may facilitate the large-scale production of RT NO2 gas sensors.

High-dispersed Fe2O3/Fe nanoparticles residing in 3D honeycomb-like N-doped graphitic carbon as high-performance room-temperature NO2 sensor.

This work illustrates a simple polymer thermal treatment strategy to develop high-dispersed Fe2O3/Fe nanoparticles residing in honeycomb-like N-doped graphitic carbon (Fe2O3/Fe@N-GC). The as-prepared Fe2O3/Fe@N-GC composites consist of three-dimensional (3D) strutted interconnective graphitic carbon frame, which would not only refrain from restacking and facilitate the charge transfer, but also provide more reaction interface between gas molecules and materials. Benefiting from the synergistic merits of Fe2O3/Fe, N-doping graphitic carbon, high surface area and unique 3D architectures, the optimal Fe2O3/Fe@N-GC presents impressive sensitivity and selectivity for NO2 gas detection at room temperature with the response of 25.48-100 ppm, response time of 2.13 s, recovery time of 11.73 s, detection limit of 10 ppb and as long as 60 days of stability. As a result, the present Fe2O3/Fe@N-GC composite with an easy fabrication method and high sensitivity, selectivity, stabitliy towards NO2 at RT would inspire various designs based on the 3D honeycomb structure for more real applications in gas sensors.

Enhanced room-temperature NO2 sensing properties of biomorphic hierarchical mixed phase WO3.

WO3 with a mixed phase (m-WO3 and h-WO3) was synthesized by facile hydrothermal and annealing methods using biomass carbon (Hemp stems) as a sacrificial template. The biomorphic hierarchical structure effectively enhanced the dispersion of WO3 microspheres, which increased the contact area for the target gas molecule. The control of the mixed phase compositions was achieved by space confinement of biomass carbon and heat treatments. The synergistic effect of the mixed phase increased the mobility of carriers and promoted the separation and transport of electrons and holes. Thus, it improved the adsorption-diffusion capacity of NO2 molecules and enhanced the sensor performance at lower operating temperature effectively. The B-WO3-04 (450 °C, 4 h) exhibited an ultra-high response (Ra/Rg = 71.07) towards 100 ppm NO2 gas with excellent repeatability and appreciable long-term stability at room temperature. The significant improvement of B-WO3-04 gas sensing performance was mainly due to its unique hierarchical structure and the optimal proportion of the mixed phase composition.

A novel ß-thalassemia variant at HBB:c.14delC (Codon 4, -C) identified via next-generation sequencing.

OBJECTIVES: ß-Thalassemia (ß-thal) is a genetic disease of the blood caused by mutations in the ß-globin gene. Conventional methods for detecting thalassemia variants often miss rare and novel variants. Identifying the rare and novel ß-thal variants, especially in the high prevalence regions, would enable better disease prevention. METHODS: A Chinese family who had joined the Thalassemia Prevention Program was recruited in this study. The ß-thal carrier screening was performed using next-generation sequencing (NGS), and the results were validated through direct DNA sequencing. Hematological parameters were analyzed, and hemoglobin electrophoresis was performed. Additionally, the presence of thalassemia-associated deletions was determined using gap-polymerase chain reaction. RESULTS: A novel frameshift variant of ß-thal, HBB:c.14delC(Codon 4, -C), was identified in a 31-year-old Chinese man. Subsequent genetic investigation showed that his mother also carried this novel variant. Hematological analysis and clinical evaluation suggested that this variant was present in the heterozygous state and might belong to a severe phenotype of ß-thal. CONCLUSIONS: We identified a novel frameshift variant of ß-thal. NGS has the potential for identifying rare and novel thalassemia variants and broadening the spectrum of thalassemia screening and thus may contribute to effective prevention of thalassemia.

A child with a novel DDX3X variant mimicking cerebral palsy: a case report.

BACKGROUND: Cerebral palsy (CP) is a non-progressive disorder of movement and posture due to a static insult to the brain. In CP, the depth of investigation is guided by the patients' medical history and their clinical examination. Magnetic resonance imaging (MRI) has a high yield and is widely used for investigation in CP. CASE PRESENTATION: In this paper, we report a novel DDX3X variant in a girl afflicted with the X-linked mental retardation-102 (MRX102). The girl had been misdiagnosed with CP in her early life based on a comprehensive clinical evaluation and associated clinical features, such as developmental delay, reduced activities of the arms and legs, and abnormal brain MRI. Subsequently, whole-exome sequencing was applied to better distinguish between CP and actual MRX102 with similar characteristics. CONCLUSIONS: We report on a de novo heterozygous DDX3X variant mimicking cerebral palsy and suggest a thorough and conscientious review during diagnosis of CP.

A 47,XXY Pregnant Woman without the SRY Gene.

Individuals with a 47,XXY karyotype usually present with a male phenotype due to the additional Y chromosome. In this paper, we describe a 47,XXY female who was pregnant with a fetus of the same karyotype based on chromosome analysis of amniotic fluid cells. Further analysis of her Y chromosome indicated that the additional Y chromosome contains no SRY gene on the short arm but carries the azoospermia factor region on the long arm, including azoospermia factor a, b and c (AZFa, AZFb, AZFc). This region may influence her female phenotype. Fertile females with a 47,XXY karyotype and loss of SRY are extremely rare. This paper is the first report of a 47,XXY pregnant woman with a normal phenotype and may enrich our knowledge on 47,XXY individuals.

A Novel ß-Thalassemia Mutation in a Chinese family: IVS-II-203-205 (TCT>CC) (HBB: c.315+203TCT>CC).

ß-Thalassemia (ß-thal) is one of the most common inherited disorders in southern China. More than 300 ß-globin gene mutations around the world have been reported in the HbVar database. In this study, a novel mutation in a 30-year-old Chinese woman [IVS-II-203-205 (TCT>CC), HBB: c.315+203TCT>CC] was first found by direct sequencing. Subsequently, investigation of her parents' genetic codes was completed, and the results showed that her father also carried this mutation. Based on the features observed in clinical practice, this novel mutation was regarded as a mild phenotype of ß-thal.

[Application of next generation sequencing for the detection of chromosomal aneuploidies and copy number variations in abortus tissues].

OBJECTIVE: To detect numerical chromosomal aberrations and copy number variations (CNVs) in abortus tissue samples with a benchtop semiconductor sequencing platform (SSP). METHODS: One hundred and forty patients with early spontaneous abortions at between 7 and 16 weeks were selected. Following DNA extraction, library preparation, high-throughput sequencing was carried out. RESULTS: Chromosomal anomalies were detected in 82 cases (58.57%), which included 67 aneuploidies and 15 CNVs. Trisomies 16, 21, 22, and X/Y were the most common. A significant difference was found in the anomaly rates between women <35 and ≥35 years old (P< 0.01). CONCLUSION: The SSP platform can detect chromosomal aneuploidies and CNVs among abortus tissues. Numerical chromosomal aberration is the main cause of early spontaneous abortion, and advance maternal age is a high risk factor for chromosomal abnormality.

A foetus with 18p11.32-q21.2 duplication and Xp22.33-p11.1 deletion derived from a maternal reciprocal translocation t(X;18)(q13;q21.3).

BACKGROUND: Non-invasive prenatal testing (NIPT) evaluates circulating cell-free DNA (cfDNA) and has been widely applied, with highly accurate results for detecting foetal trisomies 21, 18 and 13. Recently, increasing attention has been paid to the clinical application of the non-invasive detection of foetal sub-chromosomal duplications and deletions beyond common aneuploidies. CASE PRESENTATION: A 32-year-old healthy pregnant woman was referred to the Medical Genetic Centre of Ganzhou Maternal and Child Health Care Hospital. As routine practice, ultrasound examination at a gestational age of 16 weeks showed that the foetus is normal. To avoid invasive prenatal diagnosis procedures, an NIPT was offered to further screen for common foetal chromosomal abnormalities. The result showed that there was an approximately 50.94 Mb duplication in p11.32-q21.2 of chromosome 18 and an approximately 58.46 Mb deletion in p22.33-p11.1 of chromosome X. In addition, the chromosome karyotypes of the parents and foetus were also analysed. Chromosome karyotype analysis results showed that foetal karyotype was 46,X,der(18), the maternal karyotype was 46,XX,t(X;18)(q13;q21.3), and the paternal karyotype revealed no obvious abnormality. CONCLUSION: In this case, we successfully detected a healthy pregnant woman with balanced translocation X;18(q13;q21.3) and described the foetal karyotype as 46,X,der(18)t(X;18)(q11;q21.1)mat. Our report illustrated these cases which present complex X;autosome balance translocation and X;autosome unbalance translocation which may contribute to severe clinical phenotypes. In addition, our report also proved that the interruption of genes in the Xq critical region is not only reason of primary infertility. Finally, we prompted that NIPT might play a role in the first trimester screening of sub-chromosomal rearrangement.