Construction of oral squamous cell carcinoma organoids in vitro 3D-culture for drug screening.

OBJECTIVE: Patient-derived organoids are potent pre-chemotherapy models. Due to limited research on diverse types of oral squamous cell carcinoma (OSCC) and construction efficiency, our goal was to optimize OSCC organoid models from various sites and assess drug responsiveness. METHODS: We screened and optimized culture media, employing three-dimensional techniques to construct human-derived oral squamous cell carcinoma (OSCC) organoid models in vitro. Morphological validation, immunofluorescence analysis, tissue origin verification, and Short Tandem Repeat (STR) sequencing confirmed the consistency between organoids and source tissues. These organoid models were then subjected to varying concentrations of anticancer drugs, with subsequent assessment of cell viability to calculate IC50 values. RESULTS: Twenty-nine surgical specimens yielded an 86.2% success rate in culturing 25 organoids in vitro. Morphological consistency confirmed nuclear atypia and positive expression of K5, P40, and E-cadherin, indicating squamous epithelial origin. Cultured complex organoids included α-SMA+ tumour-associated fibroblasts and tumour stem cells expressing CD44 and Ki67. STR sequencing affirmed genomic homogeneity between cultured organoids and source tissues. Drug sensitivity testing revealed diverse responses among organoids, highlighting their value for assessing drug sensitivity. CONCLUSIONS: An efficient OSCC organoid culture system for personalized in vitro drug sensitivity screening was established, laying the foundation for precise treatment development.

Rapid identification of potential nonsteroidal anti-inflammatory drug overdose-induced liver toxicity and prediction of follow-up exposure: Integrating bioanalytical and population pharmacokinetic assay.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most frequently used drugs that can cause liver toxicity. The aim of this study was to integrate bioanalytical and population pharmacokinetic (PopPK) assay to rapidly screen and quantify the concentrations of NSAIDs in plasma and monitor clinical safety. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetaminophen (APAP), flurbiprofen (FLB), aspirin (ASP), and ibuprofen (IBP), four commonly used NSAIDs. The PopPK model of the signature toxicant was analyzed based on the published literature. The LC-MS/MS method was successfully validated and applied to determine NSAID concentrations in patient plasma samples. APAP, ASP, and IBP data were best fitted using a one-compartment model, and FLB data were best fitted using a two-compartment model. Bootstrapping and visual predictive checks suggested that a robust and reliable pharmacokinetic model was developed. A fast, simple, and sensitive LC-MS/MS method was developed and validated for determining APAP, FLB, ASP, and IBP in human plasma. Combined with the PopPK model, this method was applied to rapidly analyze the concentrations of NSAIDs in clinical samples from patients presenting to the emergency department with acute liver dysfunction and monitored NSAIDs clinical safety.

Saponins as therapeutic candidates for atherosclerosis.

Drug development for atherosclerosis, the underlying pathological state of ischemic cardiovascular diseases, has posed a longstanding challenge. Saponins, classified as steroid or triterpenoid glycosides, have shown promising therapeutic potential in the treatment of atherosclerosis. Through an exhaustive examination of scientific literature spanning from May 2013 to May 2023, we identified 82 references evaluating 37 types of saponins in terms of their prospective impacts on atherosclerosis. These studies suggest that saponins have the potential to ameliorate atherosclerosis by regulating lipid metabolism, inhibiting inflammation, suppressing apoptosis, reducing oxidative stress, and modulating smooth muscle cell proliferation and migration, as well as regulating gut microbiota, autophagy, endothelial senescence, and angiogenesis. Notably, ginsenosides exhibit significant potential and manifest essential pharmacological attributes, including lipid-lowering, anti-inflammatory, anti-apoptotic, and anti-oxidative stress effects. This review provides a comprehensive examination of the pharmacological attributes of saponins in atherosclerosis, with particular emphasis on their role in the regulation of lipid metabolism regulation and anti-inflammatory effects. Thus, saponins may warrant further investigation as a potential therapy for atherosclerosis. However, due to various reasons such as low oral bioavailability, the clinical application of saponins in the treatment of atherosclerosis still needs further exploration.

The implications of N6-methyladenosine (m6A) modification in esophageal carcinoma.

Esophageal carcinoma (EC) is always diagnosed at advanced stage and its the mortality rate remains high. The patients usually miss the best opportunity for treatment because of non-specific symptoms and the survival rates are low. N6-methyladenosine (m6A) the predominant modification in eukaryotic messenger RNA(mRNA), serves vital roles in numerous bioprocess. This chemical modification is dynamic, reversible and consists of three regulators: m6A methyltransferases (writers), demethylases (erasers) and m6A-binding proteins (readers). Recently, a growing number of evidences have indicated relationships between m6A and EC. Whereas, lacking of cognition about the molecular mechanism of m6A modification in esophageal carcinoma. We will focus on the biological function roles of m6A modification in the tumorigenesis and development of EC. Recent studies showed that immunotherapy had a positive impact on EC. The relationship between m6A and immunotherapy in EC deserves further research and discussion. We will also discuss the potential clinical applications regarding diagnosis, treatment and prognosis of m6A modification for EC and provide perspectives for further studies.

High Throughput Sequencing Analysis of Exosomal miRNA Expressions in Early-Onset Preeclampsia Patients.

BACKGROUND: The goal of this study was to screen for differentially expressed exosomal miRNAs in peripheral blood samples of early-onset preeclampsia and normal pregnant patients using high-throughput sequencing methods and explore their effects on the pathogenesis of preeclampsia. METHODS: Peripheral blood samples from 5 patients with early-onset preeclampsia and 5 normal pregnant women (control group) were enrolled. Then, exosomes were extracted from each sample, and the procedure was replicated three times. An Illumina HiSeq4000 sequencing platform was used to analyze exosomal miRNAs in all samples before comparison. The target genes and signaling pathway predictions and the biological function enrichments of significant and differentially expressed miRNAs were assessed using Miranda and Starbase software, as well as GO and KEGG databases. RESULTS: Compared with the control, patients in the early-onset preeclampsia group had 65 significantly and differentially expressed exosomal miRNAs in their peripheral blood samples. The results have shown that of the 65 differentially expressed miRNAs, 17, including has-miR-6855, has-miR-7151, and has-miR-6777, were up-regulated, and 48, including has-miR-1247, has-miR-29B2, and has-miR-941, were down-regulated (p < 0.05). The Miranda and TargetScanS algorithms predicted a total of 2,231 target genes from the differentially expressed miRNAs. The Go and KEGG analyses showed that the principal biological function of these target genes was the regulation of Ras protein signal transduction, histone modification, GTPase-mediated signal transduction, and transforming growth factor (TGF)-ß. Additionally, the results also showed that the major pathways involved in the regulation of these functions were the PI3K Akt, MAPK, tumor necrosis factor, and EGFR tyrosine kinase inhibition signaling pathways. CONCLUSIONS: There are significant differences in the expression profiles of exosomal miRNAs between early-onset preeclampsia patients and normal pregnant women. These differentially expressed miRNAs may not only play an important regulatory role in the occurrence of early-onset preeclampsia but also participate in its pathophysiological process through genetic regulation of a variety of biological functions and signal pathways.

Therapeutic Role and Potential Mechanism of Resveratrol in Atherosclerosis: TLR4/NF-κB/HIF-1α.

Atherosclerosis, the main pathological basis of cardiovascular disease, is a chronic inflammatory disease that severely affects the quality of human life. Resveratrol (Res) is a natural polyphenol that is a major component of many herbs and foods. The present study analyzed resveratrol from the perspective of visualization and bibliometric analysis and found that resveratrol is closely related to the inflammatory response in cardiovascular diseases (associated with atherosclerosis). To explore the specific molecular mechanism of resveratrol, network pharmacology and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used, in which HIF-1α signaling may be a key pathway in the treatment of AS. Furthermore, we induced the polarization of macrophage RAW264.7 to M1 type to generate inflammatory response by the combination of lipopolysaccharide (LPS) (200 ng/mL) + interferon-γ (IFN-γ) (2.5 ng/mL). LPS and IFN-γ increased the inflammatory factor levels of IL-1ß, TNF-α, and IL-6 in RAW264.7, and the proportion of M1-type macrophages also increased, but the expression of inflammatory factors decreased after resveratrol administration, which confirmed the anti-inflammatory effect of resveratrol in AS. In addition, we found that resveratrol downregulated the protein expression of toll-like receptor 4 (TLR4)/NF-κB/hypoxia inducible factor-1 alpha (HIF-1α). In conclusion, resveratrol has a significant anti-inflammatory effect, alleviates HIF-1α-mediated angiogenesis, and prevents the progression of AS through the TLR4/NF-κB signaling pathway.

Therapeutic Candidates for Alzheimer's Disease: Saponins.

Drug development for Alzheimer's disease, the leading cause of dementia, has been a long-standing challenge. Saponins, which are steroid or triterpenoid glycosides with various pharmacological activities, have displayed therapeutic potential in treating Alzheimer's disease. In a comprehensive review of the literature from May 2007 to May 2023, we identified 63 references involving 40 different types of saponins that have been studied for their effects on Alzheimer's disease. These studies suggest that saponins have the potential to ameliorate Alzheimer's disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. Most intriguingly, ginsenoside Rg1 and pseudoginsenoside-F11 possess these important pharmacological properties and show the best promise for the treatment of Alzheimer's disease. This review provides a summary and classification of common saponins that have been studied for their therapeutic potential in Alzheimer's disease, showcasing their underlying mechanisms. This highlights the promising potential of saponins for the treatment of Alzheimer's disease.

Effects of Genistein on Lipid Metabolism, Antioxidant Activity, and Immunity of Common Carp (Cyprinus carpio L.) Fed with High-Carbohydrate and High-Fat Diets.

A 56-day feeding trial was conducted to investigate the effects of genistein on growth, lipid metabolism, antioxidant capacity, and immunity of common carp fed with high-carbohydrate or high-fat diets. Five diets were used to feed fish: control diet (5% fat; CO), high-fat diet (11% fat; HF), high-carbohydrate diet (45% carbohydrate; HC), and HF or HC diet with 500 mg/kg genistein (FG or CG). Results showed that final body weight (FW) and specific growth rate (SGR) were significantly reduced, but the supplementation with genistein resulted in higher values of FW and SGR than the HF or HC group. Both high carbohydrate and high fat belong to high-energy diets, which may promote lipid deposition. Genistein obviously decreased liver triglyceride (TG) content and alleviated hepatic fat vacuolation in the HF and HC groups. The expression of lipid metabolism genes (cpt-1 and atgl) was markedly higher in the FG group than in the HF group. The lipid synthesis-related genes (fas, acc, and pparγ) were elevated in high-energy diets but recovered to the control level or reduced after genistein treatments. With respect to fatty acid transporter genes, fatp increased in the FG group, and cd36 increased in the CG group. Furthermore, the antioxidant and immune indexes, such as total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), acid phosphatase (ACP), and lysozyme (LZM) activities, were decreased, while malonate aldehyde (MDA) content, activities of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were enhanced in the HF and HC groups. The antioxidant and immunity values could be ameliorated by treatment with genistein. Moreover, the transcript levels of antioxidant-related genes (cat, gr, and nrf2) in the liver and anti-inflammatory factors (tgf-ß and il-10) and lyz in the head kidney tissue were promoted, although the expression levels of proinflammatory factors (tnf-α and il-6) declined in the genistein supplementation group, which confirmed the antioxidant and immune-enhancing effects of genistein. Therefore, 500 mg/kg genistein could ameliorate the negative effects of high-energy diets on immunity.

[Incidence and genetic reproductive characteristics of AZFc microdeletion among patients with azoospermia or severe oligospermia].

OBJECTIVE: To explore the incidence of azoospermia factor c (AZFc) microdeletion among patients with azoospermia or severe oligospermia, its association with sex hormone/chromosomal karyotype, and its effect on the outcome of pregnancy following intracytoplasmic sperm injection (ICSI) treatment. METHODS: A total of 1 364 males with azoospermia or severe oligospermia who presented at the Affiliated Maternity and Child Health Care Hospital of Jiaxing College between 2013 and 2020 were subjected to AZF microdeletion and chromosome karyotyping analysis. The level of reproductive hormones in patients with AZFc deletions was compared with those of control groups A (with normal sperm indices) and B (azoospermia or severe oligospermia without AZFc microdeletion). The outcome of pregnancies for the AZFc-ICSI couples was compared with that of the control groups in regard to fertilization rate, superior embryo rate and clinical pregnancy rate. RESULTS: A total of 51 patients were found to harbor AZFc microdeletion, which yielded a detection rate of 3.74%. Seven patients also had chromosomal aberrations. Compared with control group A, patients with AZFc deletion had higher levels of PRL, FSH and LH (P < 0.05), whilst compared with control group B, only the PRL and FSH were increased (P < 0.05). Twenty two AZFc couples underwent ICSI treatment, and no significant difference was found in the rate of superior embryos and clinical pregnancy between the AZFc-ICSI couples and the control group (P > 0.05). CONCLUSION: The incidence of AZFc microdeletion was 3.74% among patients with azoospermia or severe oligospermia. AZFc microdeletion was associated with chromosomal aberrations and increased levels of PRL, FSH and LH, but did not affect the clinical pregnancy rate after ICSI treatment.

Rapid fabrication of sub-micron scale functional optical microstructures on the optical fiber end faces by DMD-based lithography.

The rapid development of optical fiber application systems puts forward higher requirements for the miniaturization and integration of optical fiber devices. One promising solution is to integrate diffractive optical microstructures on the end faces of optical fibers. However, rapid microfabrication on such tiny and irregular substrates is a challenge. In recent years, Femtosecond laser polymerization technology has become an effective solution to the challenge, which can be flexibly applied for the fabrication of complex 3D microstructures with ultra-high resolution. When the demand for the lithography resolution is not very high, other microfabrication methods with a lower technical threshold may be developed for achieving a balance between fabrication precision, cost and efficiency. In this paper, we report a Digital Micromirror Device (DMD) based lithography method dedicated to the fabrication of functional optical microstructures on the optical fiber end faces. Especially, it's also applicable to single-mode fibers (SMFs). By the projection via a 40x objective lens, the fabrication resolution of 0.405 µm was achieved within an exposure area of 209.92 µm × 157.44 µm. We evaluated the microfabrication results by the photomicrographs and the optical diffraction modulation effects of the functional optical microstructures. This method provides a new idea for fabricating both hybrid optical fiber devices and SMF devices, and it may be an alternative method for resolving the conflict between the precision, the cost and the efficiency.

Identification of novel compound heterozygous mutations of the MYO15A gene with autosomal recessive non-syndromic hearing loss.

BACKGROUND: The most common inheritance pattern responsible for congenital deafness belongs to autosomal recessive non-syndromic hearing loss (ARNSHL) and mutations of the highly heterogeneous MYO15A locus are present in a large proportion of cases. METHODS: One Chinese family with ARNSHL was subjected to clinical evaluation and genetic analysis. We used targeted and whole exome sequencing with Sanger sequencing to identify and characterize mutations. Bioinformatics analysis was conducted to evaluate molecular functions. RESULTS: Three compound heterozygous MYO15A gene variants, including two novel variants, c.6804G > A (p.M2268I), and c.6188_6190delinsGTCA (p.F2063Cfs*60), responsible for deafness were identified. Pathogenicity was assessed by multiple bioinformatics analyses. CONCLUSION: We identified novel mutations of the MYO15A locus associated with ARNSHL in a Chinese family. The current findings expand the MYO15A pathogenic mutation spectrum to assist with genetic counseling and prenatal diagnosis.

Theory-Guided Synthesis of Highly Luminescent Colloidal Cesium Tin Halide Perovskite Nanocrystals.

The synthesis of highly luminescent colloidal CsSnX3 (X = halogen) perovskite nanocrystals (NCs) remains a long-standing challenge due to the lack of a fundamental understanding of how to rationally suppress the formation of structural defects that significantly influence the radiative carrier recombination processes. Here, we develop a theory-guided, general synthetic concept for highly luminescent CsSnX3 NCs. Guided by density functional theory calculations and molecular dynamics simulations, we predict that, although there is an opposing trend in the chemical potential-dependent formation energies of various defects, highly luminescent CsSnI3 NCs with narrow emission could be obtained through decreasing the density of tin vacancies. We then develop a colloidal synthesis strategy that allows for rational fine-tuning of the reactant ratio in a wide range but still leads to the formation of CsSnI3 NCs. By judiciously adopting a tin-rich reaction condition, we obtain narrow-band-emissive CsSnI3 NCs with a record emission quantum yield of 18.4%, which is over 50 times larger than those previously reported. Systematic surface-state characterizations reveal that these NCs possess a Cs/I-lean surface and are capped with a low density of organic ligands, making them an excellent candidate for optoelectronic devices without any postsynthesis ligand management. We showcase the generalizability of our concept by further demonstrating the synthesis of highly luminescent CsSnI2.5Br0.5 and CsSnI2.25Br0.75 NCs. Our findings not only highlight the value of computation in guiding the synthesis of high-quality colloidal perovskite NCs but also could stimulate intense efforts on tin-based perovskite NCs and accelerate their potential applications in a range of high-performance optoelectronic devices.

Cancer-derived IgG involved in cisplatin resistance through PTP-BAS/Src/PDK1/AKT signaling pathway.

OBJECTIVES: This study aimed to explore whether knockdown of cancer-derived IgG (CIgG) could enhance cisplatin-induced anti-cancer effects. MATERIALS AND METHODS: Cancer-derived IgG was knocked down by siRNA or Tet-on shRNA in the absence or presence of cisplatin in WSU-HN6 or CAL27 cells. Cell proliferation, apoptosis, and mobility were evaluated using CCK-8, flow cytometry, and transwell assays, respectively. Molecular events were investigated using real-time PCR and Western blot assays. RESULTS: Knockdown of CIgG significantly promoted cisplatin-induced apoptosis and inhibition of cell proliferation, migration, and invasion. Cisplatin upregulated CIgG expression and phosphorylation of AKT and PDK1, while knockdown of CIgG downregulated phosphorylation of AKT and PDK1, and blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Moreover, knockdown of CIgG blocked cisplatin-induced upregulation of Src phosphorylation, and knockdown of Src blocked cisplatin-induced upregulation of AKT and PDK1 phosphorylation. Overexpression of Src upregulated AKT and PDK1 phosphorylation. Furthermore, knockdown of CIgG upregulated PTP-BAS mRNA and protein expression, whereas cisplatin downregulated PTP-BAS protein, but not mRNA expression; knockdown of PTP-BAS upregulated phosphorylation of Src, PDK1, AKT, and blocked CIgG knockdown-mediated enhancement of cisplatin-induced inhibition of cell proliferation. CONCLUSION: Knockdown of CIgG enhanced the anti-cancer effects of cisplatin through PTP-BAS/Src/PDK1/AKT signaling pathway in oral squamous cell carcinoma.

Genome-wide identification and comparison of differentially expressed profiles of miRNAs and lncRNAs with associated ceRNA networks in the gonads of Chinese soft-shelled turtle, Pelodiscus sinensis.

BACKGROUND: The gonad is the major factor affecting animal reproduction. The regulatory mechanism of the expression of protein-coding genes involved in reproduction still remains to be elucidated. Increasing evidence has shown that ncRNAs play key regulatory roles in gene expression in many life processes. The roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in reproduction have been investigated in some species. However, the regulatory patterns of miRNA and lncRNA in the sex biased expression of protein coding genes remains to be elucidated. In this study, we performed an integrated analysis of miRNA, messenger RNA (mRNA), and lncRNA expression profiles to explore their regulatory patterns in the female ovary and male testis of Pelodiscus sinensis. RESULTS: We identified 10,446 mature miRNAs, 20,414 mRNAs and 28,500 lncRNAs in the ovaries and testes, and 633 miRNAs, 11,319 mRNAs, and 10,495 lncRNAs showed differential expression. A total of 2814 target genes were identified for miRNAs. The predicted target genes of these differentially expressed (DE) miRNAs and lncRNAs included abundant genes related to reproductive regulation. Furthermore, we found that 189 DEmiRNAs and 5408 DElncRNAs showed sex-specific expression. Of these, 3 DEmiRNAs and 917 DElncRNAs were testis-specific, and 186 DEmiRNAs and 4491 DElncRNAs were ovary-specific. We further constructed complete endogenous lncRNA-miRNA-mRNA networks using bioinformatics, including 103 DEmiRNAs, 636 DEmRNAs, and 1622 DElncRNAs. The target genes for the differentially expressed miRNAs and lncRNAs included abundant genes involved in gonadal development, including Wt1, Creb3l2, Gata4, Wnt2, Nr5a1, Hsd17, Igf2r, H2afz, Lin52, Trim71, Zar1, and Jazf1. CONCLUSIONS: In animals, miRNA and lncRNA as master regulators regulate reproductive processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs, lncRNAs, and their targets in P. sinensis might be useful for studying the molecular processes involved in sexual reproduction and genome editing to produce higher quality aquaculture animals. A thorough understanding of ncRNA-based cellular regulatory networks will aid in the improvement of P. sinensis reproductive traits for aquaculture.

[Application of non-invasive prenatal testing for the screening of fetal chromosomal abnormalities in 12 085 cases].

OBJECTIVE: To assess the value of non-invasive prenatal testing (NIPT) for the screening of fetal chromosomal abnormalities. METHODS: For 12 085 pregnant women, the results of NIPT and invasive prenatal diagnosis were compared. RESULTS: The test was successful in 12 067 cases and has detected 179 chromosomal abnormalities, with a positive rate of 1.48%, sensitivity of 98.39% and specificity of 99.02%. Invasive prenatal diagnosis was performed for 3 of 18 patients who had failed NIPT but has detected no karyotypic abnormality. Except for one case of twin Cesarean section which delivered a normal female fetus and a stillbirth of unknown sex, the remainder of the 18 cases all had a normal delivery. The positive rate of NIPT screening for the abnormal ultrasound group was significant higher than that other groups (P< 0.01). Among those with positive results of NIPT, 122 underwent invasive prenatal diagnosis, and 25 trisomy 21, 7 trisomy 18, 3 trisomy 13, 4 aneuploidies of other autosomes, 13 sex chromosomal aneuploidies and 9 microdeletion/microduplications were confirmed, which yielded a positive predictive rate of 86.21%, 50.00%, 23.08%, 21.05%, 46.43%, and 47.36%, respectively. CONCLUSION: NIPT has high sensitivity, specificity and positive predictive value, and is an effective method for prenatal screening. In addition to chromosomes 21, 18 and 13, NIPT has certain predictive value for other autosomal aneuploidies, sex chromosomal aneuploidies, microdeletion/microduplications, and can provide a reference for karyotype analysis and chromosomal microarray verification.

Early Protection by Resveratrol in Rat Lung Transplantation.

BACKGROUND Resveratrol is a multifunctional bioactive substance that has effects in anti-inflammation and prevention of ischemia-reperfusion injury. This study compared the inflammation and expression of related proteins during the early stages after transplantation to explore the effects and mechanisms of resveratrol on transplanted lung. MATERIAL AND METHODS Sprague-Dawley rats were randomized to receive pretreatment of resveratrol suspension (60 mg/kg; RES group), dexamethasone (1 mg/kg; DEM group), or normal saline solution (2 mL/kg; control group) 1 h before lung transplantation. The cytokine concentration in the serum and bronchoalveolar lavage fluid (BALF) of the recipients was determined 24 h after transplantation. Histopathologic evaluation, including lung injury score, and the expression of necroptosis-associated proteins was assessed. RESULTS Histopathologic evaluation showed pneumocyte damage and endothelialitis associated with hemorrhage in the alveoli in the control group, the severity of which was greater than that in the other 2 groups. The levels of interleukin-6 and tumor necrosis factor-a in the serum and BALF of the RES and DEM groups were lower than those in the control group. The expression of necroptosis-associated proteins in the RES group was lower than that in the control group, and was inversely proportional to lung injury. CONCLUSIONS Pretreatment with resveratrol protected rat lung in the early stages after transplantation. We determined a relationship between necroptosis-associated proteins and transplanted lung injury, which suggests that the mechanism of lung transplantation-associated ischemia-reperfusion injury may be related to necroptosis.

Tissue-based transcriptomics of Chionodraco hamatus: Sequencing, de novo assembly, annotation and marker discovery.

Here, we explored the liver, heart and muscle tissue transcriptome of the haemoglobinless Antarctic fish Chionodraco hamatus using the Illumina paired-end RNA sequencing. A total of 114,028 unigenes with a mean length of 794.24 bp was produced. Annotation of these unigenes showed that 29.16% and 35.52% of them had hits in the nucleotide (Nt) and protein (Nr) databases, respectively. In addition, 29.10% and 35.28% unigenes were annotated in the SwissProt and TrEMBL databases while 23.27% and 21.08% of unigenes were annotated in the conserved domain (CCD) and protein family (PFAM) databases, respectively. The results of eukaryotic orthologous groups (KOG) classification analysis showed that around 21.36% of unigenes could be mapped. Differential gene expression analysis indicated that 16,331, 16,291 and 13,262 differentially expressed genes (DEG) could be screened between muscle and heart, muscle and liver and heart and liver, respectively. A significant enrichment analysis of these DEGs revealed their implication in important biological processes, molecular functions, cellular components and diverse pathways. Furthermore, a total of 24,455 simple sequence repeats (SSR) were detected from the generated tissue transcriptome. The transcriptome data produced in this study will constitute an important resource for improving our knowledge of C. hamatus functional genomics and will facilitate future studies regarding this species.

[Prenatal diagnosis of a tetrasomy 18p case using BACs-on-Beads technology and single nucleotide polymorphism array].

OBJECTIVE: To determine the origin of a supernumerary small marker chromosome found in a fetus using prenatal BACs-on-Beads (BoBs) and single nucleotide polymorphism array (SNP-array) assays. METHODS: The fetal sample was subjected to chromosomal karyotyping and BoBs analysis, and the results were validated with genome-wide scanning using a SNP microarray. RESULTS: The fetus was found to have a 47,XX,+mar karyotype. BoBs analysis indicated that there was an amplification between 18p11.32 and 18p11.21, which was verified by the SNP-array assay as a 18.3 Mb duplication occurring at 18p11.32q11.1. CONCLUSION: The karyotype of the fetus was determined as 47,XX,+der18(18p11.32?18q11.1::18q11.1?18p11.32). The duplication has involved important genes including SMCHD1, LPIN2 and TGIF1, which may result in severe malformations in the fetus.

[A case of Wolf-Hirschhorn syndrome diagnosed by single nucleotide polymorphism array].

OBJECTIVE: To explore the genetic causes for a child with multiple congenital malformations and epilepsy through analysis of copy number variations, and to correlate the genotype with the phenotype. METHODS: G-banding karyotyping was performed on the child and her parents. Single nucleotide polymorphisms array (SNP-array) was used to map the exact chromosomal breakpoints in the proband. The result was validated with fluorescence in situ hybridization (FISH). RESULTS: G banding analysis suggested that the proband had a karyotype of 46,XX,del(4)(p15), while both of his parents had a normal karyotype. SNP-array has identified a hemizygous deletion of 13.3 Mb on chromosome 4p16.3p15.33, which has been implicated in Wolf-Hirschhorn syndrome. FISH assay has confirmed the de novo origin of the deletion, with the karyotype and clinical phenotype of both parents taken into consideration. CONCLUSION: A case of Wolf-Hirschhorn syndrome has been diagnosed by clinical manifestation and karyotyping analysis. Compared with conventional karyotyping analysis, SNP-array has greater resolution and accuracy, and can provide useful information for genetic counseling.

Investigation of microplastics in urban rivers of Eastern China in summer: abundance, characteristics and ecological risk assessment.

Microplastics (MPs) are increasingly becoming recognized as worldwide environmental contaminants, exerting a substantial impact on the safety of city rivers. This study explored the abundance and characteristics of MPs in summer 2023, including June and August, representing plum rain and typhoon rain seasons. The Qinhuai River exhibits more spatial fluctuations in six sampling sites with average concentrations of 470 ± 119.56 items per L, and the abundance increases with the water flows in the river. Downstream had the highest MP abundance of 484 ± 121.34 items per L, which were positive with the concentration of suspended solids (SS). Transparent and green MPs were more even in the sampling sites, and the shapes of fragments were predominant in the summer. Interestingly, the proportion of fiber and small-sized (38-75 µm) microplastics was predominant in the plum rain seasons, while the percentage of large-sized (270-5000 µm) and polymers of PE occurred in the typhoon rain seasons. The index of hazard scores of plastic polymers (H) revealed that the studied river had a severe pollution level (IV), which was highly influenced by PVC and PC. Besides, the pollution load index PLI value of different rain seasons was slightly polluted (I), while the PLI in autumn rain seasons was relatively higher than that in other seasons due to the higher variance of MPs. Therefore, the ecological risk of microplastics of PVC and PC in the Qinhuai River during varying seasons should be seriously considered. Our research is expected to provide valuable assistance in improving the management of urban rivers.